ALBERT

Description: Background: Preterm birth is the leading cause of mortality and morbidity in newborn infants. Its etiology is multifactorial with genes and environmental factors, including chronic maternal stress, contributing to its risk. Our objective was to investigate whether single nucleotide polymorphisms (SNPs) in genes involved in the stress response are associated with spontaneous preterm birth using a candidate gene approach. Methods: A total of 210 cases (singleton spontaneous preterm birth at

Description: Background: Several studies described the phytochemical constituents of plants in relation with the free radical scavenging property and inhibition of lipid peroxidation. This study investigated the in vitro antioxidant property, and the protective effects of ethanolic and aqueous ethanol extract of the leaves and barks of Afrostyrax lepidophyllus (Huaceae) against ion mediated oxidative damages. Methods: Four extracts (ethanol and aqueous-ethanol) from the leaves and barks of A. lepidophyllus were used in this study. The total phenols content, the antiradical and antioxidant properties were determined using standard colorimetric methods. Results: The plant extracts had a significant scavenging potential on the 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH), nitrite oxide (NO) and 2,2-azinobis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radicals with the IC 50 varied between 47 and 200 µg/mL depending on the part of plant and the type of extract. The ethanol extract of A. lepidophyllus bark (GEE) showed the highest polyphenolic (35.33 ± 0.29) and flavonoid (12.00 ± 0.14) content. All the tested extracts demonstrated a high protective potential with the increased of superoxide dismutase, catalase and peroxidase activities. Conclusion: Afrostyrax lepidophyllus extracts exhibited higher antioxidant potential and significant protective potential on liver enzymes.

Description: Background: With the introduction and implementation of a variety of government programs and policies to encourage adoption of electronic medical records (EMRs), EMRs are being increasingly adopted in North America. We sought to evaluate the completeness of a variety of EMR fields to determine if family physicians were comprehensively using their EMRs and the suitability of use of the data for secondary purposes in Ontario, Canada. Methods: We examined EMR data from a convenience sample of family physicians distributed throughout Ontario within the Electronic Medical Record Administrative data Linked Database (EMRALD) as extracted in the summer of 2012. We identified all physicians with at least one year of EMR use. Measures were developed and rates of physician documentation of clinical encounters, electronic prescriptions, laboratory tests, blood pressure and weight, referrals, consultation letters, and all fields in the cumulative patient profile were calculated as a function of physician and patient time since starting on the EMR. Results: Of the 167 physicians with at least one year of EMR use, we identified 186,237 patients. Overall, the fields with the highest level of completeness were for visit documentations and prescriptions (〉70 %). Improvements were observed with increasing trends of completeness overtime for almost all EMR fields according to increasing physician time on EMR. Assessment of the influence of patient time on EMR demonstrated an increasing likelihood of the population of EMR fields overtime, with the largest improvements occurring between the first and second years. Conclusions: All of the data fields examined appear to be reasonably complete within the first year of adoption with the biggest increase occurring the first to second year. Using all of the basic functions of the EMR appears to be occurring in the current environment of EMR adoption in Ontario. Thus the data appears to be suitable for secondary use.

Description: Background: Recognising the limitations of a paper-based approach to documenting vital sign observations and responding to national clinical guidelines, we have explored the use of an electronic solution that could improve the quality and safety of patient care. We have developed a system for recording vital sign observations at the bedside, automatically calculating an Early Warning Score, and saving data such that it is accessible to all relevant clinicians within a hospital trust. We have studied current clinical practice of using paper observation charts, and attempted to streamline the process. We describe our user-focussed design process, and present the key design decisions prior to describing the system in greater detail. Results: The system has been deployed in three pilot clinical areas over a period of 9 months. During this time, vital sign observations were recorded electronically using our system. Analysis of the number of observations recorded (21,316 observations) and the number of active users (111 users) confirmed that the system is being used for routine clinical observations. Feedback from clinical end-users was collected to assess user acceptance of the system. This resulted in a System Usability Scale score of 77.8, indicating high user acceptability. Conclusions: Our system has been successfully piloted, and is in the process of full implementation throughout adult inpatient clinical areas in the Oxford University Hospitals. Whilst our results demonstrate qualitative acceptance of the system, its quantitative effect on clinical care is yet to be evaluated.

Description: ObjectivesExcess adiposity (obesity and excess gestational weight gain, GWG) during pregnancy (EADP) increases risk for gestational diabetes, preeclampsia, and child and maternal obesity. Personal GWG goals predict total GWG. Some estimates suggest only 30% of pregnant women have personal GWG goals that are congruent with Institute of Medicine GWG recommendations. The primary purpose of this study was to determine the extent to which perceived pre-pregnancy weight status, healthcare provider advice, knowledge of EADP risks, and value for healthy GWG predicted knowledge of GWG recommendations. The secondary purpose was to determine sources of GWG information among pregnant women. Methods: Pregnant women with a confirmed singleton pregnancy completed a one-time survey in obstetric clinic waiting rooms. Logistic regression analysis was used. Results: 246 predominantly African American, low income, overweight/obese women completed surveys. Average age was 25 (SD 5.3) and gestation age ranged from 7 to 40 weeks. Knowledge of pre-pregnancy weight status was the only unique predictor of GWG recommendation knowledge (B = .642, p = .03). The top three sources of GWG information were physicians, internet, and books. The least frequently reported sources of GWG information were other healthcare providers, community programs, and television. Conclusion: In low income diverse overweight/obese pregnant women, accurate pre-pregnancy weight status perception was the only significant unique predictor of knowledge of GWG recommendations. Physicians were the preferred source of GWG information. Clinicians should have frequent, ongoing conversations about weight status with women before, during, and after pregnancy.

Description: Background: In Morocco, families play a major role in caring for elderly cancer patients. Methods: We conducted a prospective descriptive study, in the National Institute of Oncology in Morocco. The study aimed to include family members who are caregivers for patients aged ≥70 years old.FindingsAfter obtaining IRB approval, a total of 150 caregivers responded to the questionnaire. Mean age was 44.7 years. The majority were females (59.3%), living in urban areas (66.7%), and educated (62.7%).Offspring (sons or daughters) represented 56.7, 54% lived with their relatives in the same house. Most of the participants were married and have familial responsibilities. In relatives, anxiety was found in 79.3%, it was related to fear of losing the patient in 57% and resulted in the use of anxiolytics in 10%. Guilt feeling towards patients regarding neglecting their early symptoms was reported in 38%. Depression and anxiety were more frequent among female relatives and among those of urban origin. Obsession of dying from cancer was present in about 30% and fear of contagion was more common among those from rural areas and illiterate. Economic resources were exceeded in 78.7 and 56% have used banking credits, and sale of properties. Work lay-off was recorded in 54%. Relatives participated in treatment making decisions in 86% of patients. Conclusion: Even there was a great impact on elderly cancerous patients relatives, the benefits of caregiving was observed in 80%. More studies have to be conducted, especially in developing countries where the lack of resources majors the impact on family caregivers.

Description: Background: Leptospirosis and dengue are endemic in countries with subtropical or tropical climates and have epidemic potential. The incidence of both these diseases peaks during monsoons and both diseases present with similar clinical manifestations making differentiation of leptospirosis from dengue difficult. It is important to distinguish leptospirosis from dengue as early antibiotic therapy in leptospirosis leads to a favourable outcome, while dengue has no specific treatment, yet early recognition is vital for close monitoring and careful fluid management. Despite the high prevalence of both these infections, co-infection of leptospirosis and dengue has not been reported previously in Sri Lanka. We present the first case of co-infection with leptospirosis and dengue in a Sri Lankan male.Case presentationA 52 year old previously healthy Sri Lankan male was admitted to our facility with a history of fever for 4 days associated with headache, generalized myalgia, reduced urine output. On examination, he was rational, hypotensive, tacycardic, tacypneic and he did not have clinical evidence of fluid leakage or pneumonitis. His serology showed high titre of dengue IgG and IgM and rising titre of leptospirosis antibody. His course of illness was complicated with septic shock, acute renal failure, acute respiratory distress syndrome and disseminated intravascular coagulation and he succumbed to his illness on the eighth day of admission. Conclusion: In areas where both leptospirosis and dengue are endemic, both infections should be include in the differential diagnosis when evaluating patients with acute febrile illness and should consider the possibility of co-infection. Leptospirosis, being a condition having definitive antibiotic therapy, should always be ruled out even if the patient is positive for dengue serology in regions endemic to both these diseases as early initiation of antibiotic therapy can reduce mortality significantly.

Description: Background: Spine surgery is one of the most difficult areas in which to achieve a good clinical outcome and pain medication is often used for a long period of time after surgery. The purpose of this study was to investigate whether pain medication use after spine surgery has been assessed previously with respect to clinical outcome. Methods: A systematic review of PubMed/MEDLINE databases was conducted from Jan 1st 2000 to Dec 31st 2009 using the search key words, “spine surgery” and “clinical outcome.” All publications reporting clinical outcomes were examined and analyzed for outcome measures and data with respect to pain medication use after spine surgery. Results: In total 990 articles met the inclusion criteria. Among them, 56 articles (5.7%) described definitive pain medication use after spine surgery; 98 articles (9.9%) used clinical outcome measures that incorporate pain medication assessment, although only one such study included a definitive description of pain medication use. Conclusions: Pain medication use after spine surgery was assessed in 15.5% of articles published during the last decade. The use of pain medication following spine surgery can affect clinical outcome and, therefore, needs to be taken into consideration for clinical assessment. In future studies, a detailed description of pain medication use and/or clinical outcome measures that incorporate pain medication assessment are advocated when reporting clinical outcomes after spine surgery so that it can be better assessed.

Description: Background: Matrix-metalloproteinases 9 (MMP-9) belongs to the class of matrix metalloproteinases whose main function is to degrade and remodel the extracellular matrix (ECM). MMP-9 has been shown to be an integral part of many diseases where modulation of the ECM is a key step such as cancer, osteoporosis and fibrosis. MMP-9 is secreted as a latent pro-enzyme that requires activation in the extracellular space. Therefore, identifying physiological and molecular contexts, which can activate MMP-9 is important. Results: Acidification of osteoclast-conditioned media to pH 5 resulted in a fragment with a size corresponding to active MMP-9. Also, treatment of recombinant proMMP-9 with recombinant cathepsin K (CTSK) at pH 5 yielded a fragment that corresponded to the molecular weight of active MMP-9, and showed MMP-9 activity. This activation was abrogated in the presence of CTSK inhibitor indicating that CTSK was responsible for the activation of pro-MMP-9. Knocking down CTSK in MDA-MB-231 cells also diminished MMP-9 activity compared to wild type control. Conclusions: Here we provide the first evidence that CTSK can cleave and activate MMP-9 in acidic environments such as seen in tumors and during bone resorption. This finding provides a key link between CTSK expression in tumors and bone and ECM remodeling, through MMP-9 activation. This novel mechanism to activate MMP-9 through extracellular physiological changes elucidated in this study reveals a protease-signaling network involving CTSK and MMP-9 and provides the impetus to explore ECM proteases as physiological markers and pharmacological targets.

Description: Background: Several epidemiologic studies indicate that maternal gestational weight gain (GWG) influences health outcomes in offspring. Any underlying mechanisms have, however, not been established. A recent study of 88 children based on the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort examined the methylation levels at 1,505 Cytosine-Guanine methylation (CpG) loci and found several to be significantly associated with maternal weight gain between weeks 0 and 18 of gestation. Since these results could not be replicated we wanted to examine associations between 0 and 18 week GWG and genome-wide methylation levels using the Infinium HumanMethylation450 BeadChip (450K) platform on a larger sample size, i.e. 729 newborns sampled from the Norwegian Mother and Child Cohort Study (MoBa). Results: We found no CpG loci associated with 0–18 week GWG after adjusting for the set of covariates used in the ALSPAC study (i.e. child’s sex and maternal age) and for multiple testing (q 〉 0.9, both 1,505 and 473,731 tests). Hence, none of the CpG loci linked with the genes found significantly associated with 0–18 week GWG in the ALSPAC study were significant in our study. Conclusions: The inconsistency in the results with the ALSPAC study with regards to the 0–18 week GWG model may arise for several reasons: sampling from different populations, dissimilar methylome coverage, sample size and/or false positive findings.

Description: Background: High disease burden and scarcity of healthcare resources present complex ethical dilemmas for nurses working in developing countries. We assessed nurses’ knowledge in ethics and their perceptions about Continuous Nurses’ Ethics Education (CNEE) for in-service nurses. Methods: Using an anonymous, pre-tested self-administered questionnaire, we assessed nurses’ knowledge in basic ethics concepts at three regional hospitals in Uganda. Adequate knowledge was measured by a score ≥50% in the knowledge assessment test. Nurses’ perceptions on CNEE were assessed using a six-point Likert scale. Results: Of 114 nurses, 91% were female; with mean age 44.7 (SD 10) years. Half were diploma, 47 (41%) certificates, 6 (5%) bachelors’ degrees and one masters’ level training. Overall, 18 (16%) scored ≥50% in the ethics knowledge test. Nurses with diploma or higher level of nursing training were less likely to fail the ethics knowledge than certificate-level nurses (OR 0.14, 95% CI: 0.02–0.7). Only 45% had ever attended at least one CNEE session and up to 93% agreed that CNEE is required to improve nurses’ ethics knowledge and practice. Conclusions: Nurses exhibited low knowledge in ethics and positive attitudes towards CNEE. We recommend structured CNEE programs to address basic concepts in nursing ethics and their application in clinical practice.

Description: Background: Pentalogy of Cantrell is a rare syndrome, first described by Cantrell and co-workers in 1958. The syndrome is characterized by the presence of five major congenital defects involving the diaphragm, abdominal wall, the diaphragmatic pericardium, lower sternum and various congenital intra-cardiac abnormalities. The syndrome has never been reported in Tanzania, although may have been reported from other African countries. Survival rate of the complete form of pentalogy of Cantrell is as low as 20%, but recent studies have reported normal growth achieved by 6 years of age where corrective surgeries were done; showing that surgical repair early in life is essential for survival.Case presentationThe African baby residing in Tanzania was referred from a district hospital on the second day of life. She was noted to have a huge omphalocele and ectopia cordis covered by a thin membrane, with bowels visible through the membrane and the cardiac impulse visible just below the epigastrium. Despite the physical anomaly, she appeared to saturate well in room air and had stable vitals. Her chest X-ray revealed the absence of the lower segments of the sternum and echocardiography showed multiple intra-cardiac defects. Based on these findings, the diagnosis of pentalogy of Cantrell was reached. On her fifth day of life, the neonate was noted to have signs of cardiac failure characterized by easy fatigability and restlessness during feeding. Cardiac failure treatment was initiated and she was discharged on parents’ request on the second week of life. Due to inadequate facilities to undertake this complex corrective surgery, arrangements were being made to refer her abroad. In the meantime, her growth and development was satisfactory until the age of 9 months, when she ran out of the medications and succumbed to death. Her parents could no longer afford transport cost to attend the monthly clinic visits, where the infant was getting free medication refill. Conclusions: The case reported here highlights that in resource limited settings; poor outcome in infants with complex congenital anomalies is a function of multiple factors. However, we believe that surgery would have averted mortality in this 9-month-old female infant. We hope to be able to manage these cases better in future following the recent establishment of cardiac surgery facilities at Muhimbili National Hospital.

Description: Background: Symptom of herpes zoster is sometimes difficult to distinguish from sciatica induced by spinal diseases, including lumbar disc herniation and spinal canal stenosis. Here we report a case of sciatica mimicking lumbar canal stenosis.Case presentationA 74-year-old Chinese male patient visited our hospital for left-sided sciatic pain upon standing or walking for 5 min of approximately 1 month’s duration. At the first visit to our hospital, there were no skin lesions. A magnetic resonance imaging showed spinal canal stenosis between the 4th and 5th lumbar spine. Thus, we diagnosed the patient with sciatica induced by spinal canal stenosis. We considered decompression surgery for the stenosis of 4th and 5th lumbar spine because conservative therapy failed to relieve the patient’s symptom. At that time, the patient complained of a skin rash involving his left foot for several days. A vesicular rash and erythema were observed on the dorsal and plantar surfaces of the great toe and lateral malleolus. The patient was diagnosed with herpes zoster in the left 5th lumbar spinal nerve area based on clinical findings, including the characteristics of the pain and vesicular rash and erythema in the 5th lumbar spinal dermatome. The patient was treated with famciclovir (1,500 mg/day) and non-steroidal anti-inflammatory drugs. After 1 week of medication, the skin rash resolved and pain relief was obtained. Conclusion: In conclusion, spinal surgeons should keep in mind herpes zoster infection as one of the possible differential diagnoses of sciatica, even if there is no typical skin rash.

Description: Background: Cost-effectiveness analyses provide insight in the use of lifestyle interventions. To evaluate the cost-effectiveness of a lifestyle intervention compared to usual care in people with Familial Hypercholesterolemia, 340 people with FH were randomized to the intervention or control group. LDL cholesterol, quality of life and costs were measured at 0 and 12 months. Cost-effectiveness analyses were performed from a healthcare perspective using bootstrapping techniques. Results: Non-significant decreases in LDL cholesterol and quality of life were found. The mean between-group difference in costs was €−237 (95% CI −1,386 to 130). The incremental cost-effectiveness ratios were 1,729 per 1 mmol/l LDL cholesterol and 145,899 per QALY gained. Assumed that the small non-significant decrease in LDL cholesterol is attributed to the intervention, the probability of cost-effectiveness of the intervention compared to usual care was 91% per 1 mmol/l LDL cholesterol reduction and 75% per QALY gained at a ceiling ratio of €20,000. Conclusions: The intervention is not cost-effective.Trial registration: NTR1899, date 07-07-2009.

Description: Background: ‘Flare phenomenon’ after initial luteinizing hormone-releasing hormone agonist administration is a widely approved concept in the treatment of prostate cancer. In most guidelines, concomitant therapy with anti-androgens is recommended to prevent this flare phenomenon. However, there are few reports describing serum prostate-specific antigen transitions after hormonal therapy. Here, we present a case of a man who experienced the biochemical and clinical flare phenomenon despite prior anti-androgen use and who has detailed data.Case presentationA 70-year-old Asian man with metastatic prostate cancer (multiple bone) was referred to our hospital. He was treated with prior anti-androgens and luteinizing hormone-releasing hormone agonist. Regardless of prior use of anti-androgens, his low back pain caused by bone metastases was deteriorated and serum prostate-specific antigen level was raised from 974.8 ng/mL to 2,555.5 ng/mL within 3 weeks. Then, his serum prostate specific antigen level started to decrease along with the pain. The nadir reached 1.0 ng/mL and remained for 6 months. Because the serum level of prostate-specific antigen then began to increase again, anti-androgen was discontinued for anti-androgen withdrawal syndrome. Then the serum level decreased again to less than 0.1 ng/mL. Until now, his serum prostate-specific antigen level has been maintained at less than 0.1 ng/mL for more than 30 months without any clinical progressions. Conclusion: We present the case of a patient in whom a clinical flare caused by an leuteinizing hormone-releasing hormone agonist was not prevented by prior anti-androgen administration. In addition, the nadir level of prostate-specific antigen when he received leuteinizing hormone-releasing hormone monotherapy was ten times lower than when he received concomitant therapy, and period of anti-androgen withdrawal syndrome was longer than usual. In this case, anti-androgen was probably not effective from the initial administration. Awareness of the possibility of ineffectiveness of anti-androgens is important in the treatment of symptomatic metastatic prostate cancer. Leuteinizing hormone-releasing hormone antagonist and surgical castration is a more reliable clinical approach for the prostate cancer patients with symptomatic metastatic disease.

Description: Background: According to the World Health Organization 130–150 million (according to WHO) of people globally are chronically infected with hepatitis C virus. The virus is responsible for chronic hepatitis that ultimately may cause liver cirrhosis and death. The disease is progressive, however antiviral treatment may slow down or stop its development. Therefore, it is important to estimate the severity of liver fibrosis for diagnostic, therapeutic and prognostic purposes.Liver biopsy provides a high accuracy diagnosis, however it is painful and invasive procedure. Recently, we witness an outburst of non-invasive tests (biological and physical ones) aiming to define severity of liver fibrosis, but commonly used FibroTest®, according to an independent research, in some cases may have accuracy lower than 50 %. In this paper a data mining and classification technique is proposed to determine the stage of liver fibrosis using easily accessible laboratory data. Methods: Research was carried out on archival records of routine laboratory blood tests (morphology, coagulation, biochemistry, protein electrophoresis) and histopathology records of liver biopsy as a reference value. As a result, the granular model was proposed, that contains a series of intervals representing influence of separate blood attributes on liver fibrosis stage. The model determines final diagnosis for a patient using aggregation method and voting procedure. The proposed solution is robust to missing or corrupted data. Results: The results were obtained on data from 290 patients with hepatitis C virus collected over 6 years. The model has been validated using training and test data. The overall accuracy of the solution is equal to 67.9 %. The intermediate liver fibrosis stages are hard to distinguish, due to effectiveness of biopsy itself. Additionally, the method was verified against dataset obtained from 365 patients with liver disease of various etiologies. The model proved to be robust to new data. What is worth mentioning, the error rate in misclassification of the first stage and the last stage is below 6.5 % for all analyzed datasets. Conclusions: The proposed system supports the physician and defines the stage of liver fibrosis in chronic hepatitis C. The biggest advantage of the solution is a human-centric approach using intervals, which can be verified by a specialist, before giving the final decision. Moreover, it is robust to missing data. The system can be used as a powerful support tool for diagnosis in real treatment.

Description: Background: Treatment of a multi-drug resistant tuberculosis (MDR-TB) patient is clinically challenging, requiring a minimum of 18 months of therapy. Its occurrence in a systemic lupus erythromatosus (SLE) patient may complicate management of both MDR-TB and SLE. This is the first descriptive report of MDR-TB in an SLE patient.Case presentationA 19-year old female receiving long-term prednisolone for SLE was diagnosed with MDR-TB. She was started on MDR-TB treatment regimen and prednisolone was replaced with azathioprine. After an initial response to therapy, patient experienced a flare of lupus symptoms. Imaging studies revealed avascular necrosis of right femoral head. She was then treated with intravenous methyl-prednisolone, followed by maintenance corticosteroid. Azathioprine was discontinued due to hematological toxicity and failure to control SLE. Her symptoms of lupus regressed and did not re-occur for the duration of her MDR-TB treatment. Patient was declared cured of MDR-TB after 18 months of ATT. She is currently scheduled for a total hip replacement surgery. Conclusions: This case highlights the challenges of simultaneously managing MDR-TB and SLE in a patient due to their over-lapping signs and symptoms, drug–drug interactions, and the need for use of immunomodulatory agents in the absence of standard guidelines and documented previous experiences. Our experience underscores the importance of appropriate selection of treatment regimens for both MDR-TB and SLE.

Description: Background: Exercise capacity is evaluated using the 6-minute walk test in various diseases. Variety in the distances walked was also shown in healthy subjects. Moreover, age-related influences on cardiac hemodynamic response to the 6-minute walk test have not been clarified. The purpose of this study was thus to investigate the hemodynamic response to the 6-minute walk test and to detect factors related to the distance walked in healthy subjects. Methods: Thirteen young adults (age 20.5 ± 0.7 years, BMI 22.0 ± 4.3) and 26 elderly individuals (age 60.2 ± 6.1 years, BMI 21.7 ± 2.2) were enrolled to measure real-time hemodynamic responses using non-invasive impedance cardiography during the 6-minute walk test. Results: Stroke volume was higher in the young than in the elderly and reached a plateau within 30 s of starting to walk in all subjects. An increase in heart rate took more than 1 min in the elderly, while it took less than 30 s in the young, which resulted in slower increases in cardiac output and cardiac index in the elderly. There was no difference in the distance in the 6-minute walk test between the young and the elderly. The distance walked was correlated with heart rate, cardiac output, and cardiac index, but not with stroke volume, at the end of the 6-minute walk test. Conclusions: The distance walked appeared to depend on increased cardiac output based on heart rate, but did not appear to be limited by stroke volume, in healthy subjects.

Description: Background: Genetic alterations of mucin genes, such as MUC2 and MUC4, were previously identified to be associated with endometriosis and related infertility. Additionally, gene expression profiling has confirmed MUC17 to be overexpressed in mucinous ovarian carcinoma; however, its associated risk for endometriosis remains unclear. This study was focused on the potential impact of genetic variations in MUC17 on endometriosis development and associated clinical features. Methods: The study subjects included 189 female Taiwanese patients with pathology-proven endometriosis and 191 healthy Taiwanese women as controls. Five single-nucleotide polymorphisms (rs4729645, rs10953316, rs74974199, rs4729655, and rs4729656) within the MUC17 gene were selected and genotyped using the Taqman genotyping assay to examine the allele frequency and genotype distributions of MUC17 polymorphisms. Results: Genotyping revealed that the A allele at rs10953316 in MUC17 was a protective genetic factor in endometriosis development (p = 0.008; OR = 0.53; 95 % CI: 0.36-0.79). Genetic variation of rs4729655 protected patients against endometriosis-induced infertility, but was associated with a higher cancer antigen 125 (CA125) level. Base-pairing analysis, called MaxExpect, predicted an additional loop in the mRNA structure caused by rs10953316 polymorphism, possibly influencing ribosome sliding and translation efficiency. Such predictions were confirmed by immunohistochemistry that patients with AA genotype at rs10953316 showed low MUC17 levels in their endometrium, patients with GA genotype showed moderate levels, and strong staining could be found in patients with GG genotype. Conclusions: MUC17 polymorphisms are involved in endometriosis development and the associated infertility in the Taiwanese population.

Description: Background: Health decision-making requires evidence from high-quality data. As one example, the Discharge Abstract Database (DAD) compiles data from the majority of Canadian hospitals to form one of the most comprehensive and highly regarded administrative health databases available for health research, internationally. However, despite the success of this and other administrative health data resources, little is known about their history or the factors that have led to their success. The purpose of this paper is to provide an historical overview of Canadian administrative health data for health research to contribute to the institutional memory of this field. Methods: We conducted a qualitative content analysis of approximately 20 key sources to construct an historical narrative of administrative health data in Canada. Specifically, we searched for content related to key events, individuals, challenges, and successes in this field over time. Results: In Canada, administrative health data for health research has developed in tangent with provincial research centres. Interestingly, the lessons learned from this history align with the original recommendations of the 1964 Royal Commission on Health Services: (1) standardization, and (2) centralization of data resources, that is (3) facilitated through governmental financial support. Conclusions: The overview history provided here illustrates the need for longstanding partnerships between government and academia, for classification, terminology and standardization are time-consuming and ever-evolving processes. This paper will be of interest to those who work with administrative health data, and also for countries that are looking to build or improve upon their use of administrative health data for decision-making.

Description: Background: The characteristics of glaucoma patients and their response to therapy may differ by institution, region and country. Therefore, clinicians should understand the distinctiveness of their patients. Here, we profile primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) patients at a major university hospital in Japan. Methods: This study included 523 eyes from 523 POAG and NTG patients who underwent full clinical ophthalmologic evaluations at Tohoku University Hospital. Clinical characteristics such as age, sex, visual acuity, intraocular pressure, Humphrey field analyzer-measured mean deviation (MD) and MD slope were collected retrospectively. MD slope was calculated from MD data that included the first baseline measurement of MD and 4 subsequent, consecutive, reliable measurements of MD. Refractive error was analyzed in a subgroup with no history of refractive surgery, including intraocular lens implantation. Patient characteristics were analyzed separately in the groups of patients with low (

Description: Background: Genotype imputation is an important procedure in current genomic analysis such as genome-wide association studies, meta-analyses and fine mapping. Although high quality tools are available that perform the steps of this process, considerable effort and expertise is required to set up and run a best practice imputation pipeline, particularly for larger genotype datasets, where imputation has to scale out in parallel on computer clusters. Results: Here we present MOLGENIS-impute, an ‘imputation in a box’ solution that seamlessly and transparently automates the set up and running of all the steps of the imputation process. These steps include genome build liftover (liftovering), genotype phasing with SHAPEIT2, quality control, sample and chromosomal chunking/merging, and imputation with IMPUTE2. MOLGENIS-impute builds on MOLGENIS-compute, a simple pipeline management platform for submission and monitoring of bioinformatics tasks in High Performance Computing (HPC) environments like local/cloud servers, clusters and grids. All the required tools, data and scripts are downloaded and installed in a single step. Researchers with diverse backgrounds and expertise have tested MOLGENIS-impute on different locations and imputed over 30,000 samples so far using the 1,000 Genomes Project and new Genome of the Netherlands data as the imputation reference. The tests have been performed on PBS/SGE clusters, cloud VMs and in a grid HPC environment. Conclusions: MOLGENIS-impute gives priority to the ease of setting up, configuring and running an imputation. It has minimal dependencies and wraps the pipeline in a simple command line interface, without sacrificing flexibility to adapt or limiting the options of underlying imputation tools. It does not require knowledge of a workflow system or programming, and is targeted at researchers who just want to apply best practices in imputation via simple commands. It is built on the MOLGENIS compute workflow framework to enable customization with additional computational steps or it can be included in other bioinformatics pipelines. It is available as open source from: https://github.com/molgenis/molgenis-imputation.

Description: Background: A third of the world population is infected with tuberculosis (TB) bacilli. TB accounts for 25 % of all avoidable deaths in developing countries. The objective of the study was to assess impact of directly observed treatment short-course (DOTS) strategy on new tuberculosis case finding and treatment outcomes in Somali Regional State, Ethiopia from 2003 up to 2012 and from 2004 up to 2013, respectively. Methods: A health facility based retrospective study was employed. Quarterly reports were collected using World Health Organization (WHO) reporting format for TB case finding and treatment outcome from all zones in the region to the Federal Ministry of Health. Results: A total of 31, 198 all types of new TB cases were registered and reported during the period from 2003 up to 2012, in the region. Out of these, smear positive pulmonary TB cases were 12,466 (40 %), and 10,537 (33.8 %) and 8195 (26.2 %) for smear negative pulmonary TB and extra-pulmonary TB cases, respectively. An average case detection rate (CDR) of 19.1 % (SD 3.6) and treatment success rate (TSR) of 85.5 % (SD 5.0) for smear positive pulmonary TB were reported for the specified years period. For the overall study period, trend chi-squire analysis for CDR was X 2  = 2.1; P 〉 0.05 and X 2  = 5.64; P 

Description: Background: Hepatitis C virus (HCV) genotypes have been shown to be differently distributed between distinct geographical areas. Libya is a large country has the longest coast in the Mediterranean basin. Information regarding hepatitis C genotypes and subtypes circulating in Libya are not well known. The objectives of this study were to determine the frequency of various HCV genotypes cross Libya and the demographic and attributable risk factors associated with HCV transmission among Libyan population. Methods: A cross-sectional study was carried out on patients with recently confirmed HCV infection. A total of 3,227 serum samples enrolled at 19 collection center cross Libya. 1,756 belonged to Tripoli region, 452 to West region 355 to North region, 181 South regions and 483 East region. The samples were tested by type specific genotyping assay and correlated with demographic and potential risk factors within the studied populations. Results: A total of 20 discrete genotypes and subtypes were identified among the Libyan population ranging from 11.5 to 0.3 % cross the country. Genotype 1 was the most frequent among all regions (19.7–40.5 %), reaching the highest value in Tripoli region, followed by genotype 4 which was more prevalent in the South (49.3 %) and West (40.0 %) regions. Genotype 3, was higher in Tripoli (21.3 %) and East (15.9 %) regions while genotype 2, common in North (23.6 %) and South (22.5 %) regions. However, we found evidence that there is a changing relative prevalence of HCV genotypes in relation to age, gender and the mode of transmission which is reflected in the predominance of certain genotypes among Libyan population. Conclusions: Different HCV genotypes were isolated form Libyan population including newly emerged ones. The prevalence of the genotypes varied by geographic region and influenced by demographic and risk factors. Knowing the frequency and distribution of the genotypes would provide key information on understanding the spread of HCV in Libya and this could be greatly reflected on national plans and future strategies for infection prevention.

Description: Interactions between modular domains and short linear motifs (3–10 amino acids peptide stretches) are crucial for cell signaling. The motifs typically reside in the disordered regions of the proteome and the interactions are often transient, allowing for rapid changes in response to changing stimuli. The properties that make domain-motif interactions suitable for cell signaling also make them difficult to capture experimentally and they are therefore largely underrepresented in the known protein-protein interaction networks. Most of the knowledge on domain-motif interactions is derived from low-throughput studies, although there exist dedicated high-throughput methods for the identification of domain-motif interactions. The methods include arrays of peptides or proteins, display of peptides on phage or yeast, and yeast-two-hybrid experiments. We here provide a survey of scalable methods for domain-motif interaction profiling. These methods have frequently been applied to a limited number of ubiquitous domain families. It is now time to apply them to a broader set of peptide binding proteins, to provide a comprehensive picture of the linear motifs in the human proteome and to link them to their potential binding partners. Despite the plethora of methods, it is still a challenge for most approaches to identify interactions that rely on post-translational modification or context dependent or conditional interactions, suggesting directions for further method development.

Description: Background: Digoxin intoxication results in predominantly digestive, cardiac and neurological symptoms. This case is outstanding in that the intoxication occurred in a nonagenarian and induced severe, extensively documented visual symptoms as well as dysphagia and proprioceptive illusions. Moreover, it went undiagnosed for a whole month despite close medical follow-up, illustrating the difficulty in recognizing drug-induced effects in a polymorbid patient.Case presentationDigoxin 0.25 mg qd for atrial fibrillation was prescribed to a 91-year-old woman with an estimated creatinine clearance of 18 ml/min. Over the following 2–3 weeks she developed nausea, vomiting and dysphagia, snowy and blurry vision, photopsia, dyschromatopsia, aggravated pre-existing formed visual hallucinations and proprioceptive illusions. She saw her family doctor twice and visited the eye clinic once until, 1 month after starting digoxin, she was admitted to the emergency room. Intoxication was confirmed by a serum digoxin level of 5.7 ng/ml (reference range 0.8–2 ng/ml). After stopping digoxin, general symptoms resolved in a few days, but visual complaints persisted. Examination by the ophthalmologist revealed decreased visual acuity in both eyes, 4/10 in the right eye (OD) and 5/10 in the left eye (OS), decreased color vision as demonstrated by a score of 1/13 in both eyes (OU) on Ishihara pseudoisochromatic plates, OS cataract, and dry age-related macular degeneration (ARMD). Computerized static perimetry showed non-specific diffuse alterations suggestive of either bilateral retinopathy or optic neuropathy. Full-field electroretinography (ERG) disclosed moderate diffuse rod and cone dysfunction and multifocal ERG revealed central loss of function OU. Visual symptoms progressively improved over the next 2 months, but multifocal ERG did not. The patient was finally discharged home after a 5 week hospital stay. Conclusion: This case is a reminder of a complication of digoxin treatment to be considered by any treating physician. If digoxin is prescribed in a vulnerable patient, close monitoring is mandatory. In general, when facing a new health problem in a polymorbid patient, it is crucial to elicit a complete history, with all recent drug changes and detailed complaints, and to include a drug adverse reaction in the differential diagnosis.

Description: Background: In family-based association analysis, each family is typically ascertained from a single proband, which renders the effects of ascertainment bias heterogeneous among family members. This is contrary to case–control studies, and may introduce sample or ascertainment bias. Statistical efficiency is affected by ascertainment bias, and careful adjustment can lead to substantial improvements in statistical power. However, genetic association analysis has often been conducted using family-based designs, without addressing the fact that each proband in a family has had a great influence on the probability for each family member to be affected.MethodWe propose a powerful and efficient statistic for genetic association analysis that considered the heterogeneity of ascertainment bias among family members, under the assumption that both prevalence and heritability of disease are available. With extensive simulation studies, we showed that the proposed method performed better than the existing methods, particularly for diseases with large heritability. Results: We applied the proposed method to the genome-wide association analysis of Alzheimer’s disease. Four significant associations with the proposed method were found. Conclusion: Our significant findings illustrated the practical importance of this new analysis method.

Description: Background: Leukoencephalopathy with Vanishing White Matter (VWM) is an autosomal recessive disorder caused by germline mutations in the genes EIF2B1-5, which encode the 5 subunits of the eukaryotic translation initiation factor eIF2B. To date, analysis of the biochemical effects of mutations in the EIF2B2-5 genes has been carried out, but no study has been performed on mutations in the EIF2B1 gene. This gene encodes eIF2Bα, the smallest subunit in eIF2B which has an important role in both the structure and regulation of the eIF2B complex. Methods: eIF2B subunits were overexpressed in HEK293 cells and isolated from the resulting cell lysates by affinity chromatography. Formation of the eIF2B complex and binding of its substrate, eIF2, was assessed by western blot. Assays of the guanine nucleotide exchange (GEF) activity were also carried out. Results: Of the 5 eIF2Bα mutations studied, we found 3 that showed loss or reduction of binding of eIF2Bα to the rest of the complex, one with increased GEF activity, and one where no effects on activity or complex formation were observed. Conclusions: This is the first study on eIF2Bα VWM mutations. We show that some mutations cause expected decreases in GEF activity or complex formation, similar to a majority of observed VWM mutations. However, we also observe some unexpected changes which hint at other effects of these mutations on as yet undescribed functions of eIF2B.

Description: Background: Ataxia with oculomotor apraxia type 1 is an autosomal-recessive neurodegenerative disorder characterized by a childhood onset of slowly progressive cerebellar ataxia, followed by oculomotor apraxia and a severe primary motor peripheral axonal motor neuropathy. Ataxia with oculomotor apraxia type 1 is caused by bi-allelic mutations in APTX (chromosome 9p21.1).Case presentationOur patient has a clinical presentation that is typical for ataxia with oculomotor apraxia type 1 with no particularly severe phenotype. Multiplex Ligation-dependent Probe Amplification analysis resulted in the identification of a homozygous deletion of all coding APTX exons (3 to 9). SNP array analysis using the Illumina Infinium CytoSNP-850 K microarray indicated that the deletion was about 62 kb. Based on the SNP array results, the breakpoints were found using direct sequence analysis: c.-5 + 1225_*44991del67512, p.0?. Both parents were heterozygous for the deletion. Homozygous complete APTX deletions have been described in literature for two other patients. We obtained a sample from one of these two patients and characterized the deletion (156 kb) as c.-23729_*115366del155489, p.0?, including the non-coding exons 1A and 2 of APTX. The more severe phenotype reported for this patient is not observed in our patient. It remains unclear whether the larger size of the deletion (156 kb vs 62 kb) plays a role in the phenotype (no extra genes are deleted). Conclusion: Here we described an ataxia with oculomotor apraxia type 1 patient who has a homozygous deletion of the complete coding region of APTX. In contrast to the patient with the large deletion, our patient does not have a severe phenotype. More patients with deletions of APTX are required to investigate a genotype-phenotype effect.

Description: Background: Appropriate utilization and compliance of Surgical Safety Checklist reduces occurrence of perioperative surgical complications and improve patient outcomes. However, data on compliance of surgical checklists are scarce in the study area. Therefore, the aim of this study was to evaluate compliance of checklist completion and its barrier for utilization at University of Gondar Hospital, Northwest Ethiopia. Methods: A prospective observational study was conducted among 282 patients undergoing elective and emergency surgery from January to March 2013. Compliance and completeness rate with implementation of Sign-in, Time-out, and Sign-out domains was computed with SPSS 20 package. Results: A total of 282 operations were performed and checklists were utilized in 39.7 % (112/282) of cases. Among these, most checklists were employed during emergency procedures (61.6 %) that need general anesthesia (75.9 %) in department of surgery (58.9 %). The overall compliance and completeness rate were 39.7 and 63.4 % respectively. The sign-in, time-out and sign-out were missed in 30.5 % (273/896), 35.4 % (436/1,232) and 45.7 % (307/672) respectively. The main reasons cited for non-user were lack of previous training (45.1 %) and lack of cooperation among surgical team members (21.6 %).Conclusions and recommendationsThe completeness rate was satisfactory but the overall compliance rate was suboptimal. An instrument that is used 40 % of the time has been a fairly basic introduction without significant reinforcement training. Moreover, frequent use of the checklist during emergency cases has been deemed to be of value by clinicians. Supplementary training and attention to actual checklist use would be indicated to ensure that this valuable tool could be used more routinely and improve communication. Conducting regular audit of checklist utilization is also recommended.

Description: Background: Hospital accreditation programs are internationally widespread and consume increasingly scarce health resources. However, we lack tools to consistently identify suitable indicators to assess and monitor accreditation outcomes. We describe the development and validation of such a tool. Results: Using Australian accreditation standards as our reference point we: reviewed the research evidence for potential indicators; looked for links with existing external indicators; and assessed relevant state and federal policies. We allocated provisional scores, on a five point Likert scale, to the five accountability criteria in the tool: research; accuracy; proximity; no adverse effects; and specificity. An expert panel validated the use of the purpose designed indicator assessment tool. The panel identified hand hygiene compliance rates as a suitable process indicator, and hospital acquired Staphylococcus aureus infection (SAB) rates as an outcome indicator, with the hypothesis that improved hand hygiene compliance rates and lower SAB rates would correlate with accreditation performance. Conclusions: This new tool can be used to identify, analyse, and compare accreditation indicators. Using infection control indicators such as hand hygiene compliance and SAB rates to measure accreditation effectiveness has merit, and their efficacy can be determined by comparing accreditation scores with indicator outcomes. To verify the tool as a robust instrument, testing is needed in other health service domains, both in Australia and internationally. This tool provides health policy makers with an important means for assessing the accreditation programs which form a critical part of the national patient safety and quality framework.

Description: Background: Recently, a lot of energy devices in the surgical field, especially in the liver surgery, have been developed, and a fine tip LigaSure™, Dolphin Tip Sealer/Divider (DT-SD) also has been used frequently to dissect liver parenchyma as well as ultrasonically activated device (USAD). However, the utility of this instrument for liver dissection (LD) is still unknown. Moreover, to reduce bleeding during LD, a half-grip technique (HGT) was contrived. We herein report an experimental study in swine model to evaluate the feasibility and effectiveness of HGT using DT-SD for LD. Methods: The swine model experiment was carried out under general anesthesia by veterinarians. LD was performed repeatedly by DT-SD with the HGT (Group A, n = 6), or the conventional clamp-crush technique (CCT) (Group B, n = 6), and by variable mode USAD (Group C, n = 6). The dissection length and depth (cm) as well as bleeding volume (g) were measured carefully, and the dissection area (cm 2 ) and speed (cm 2 /min) were calculated precisely. Histological examinations of the dissection surfaces were also executed. Mann–Whitney’s U test was used for Statistical analyses with variance at a significance level of 0.05. Results: Among the three groups, the three averages of dissection lengths were unexpectedly equalized to 8.3 cm. The dissection area (cm 2 ) was 9.9 ± 5.1 in Group A, 9.8 ± 4.7 in Group B, and 9.9 ± 4.5 in Group C. The mean blood loss during LD was 10.6 ± 14.8 g in Group A, 41.4 ± 39.2 g in Group B, and 34.3 ± 39.2 g in Group C. For Group A, the bleeding rate was the least, 0.9 ± 1.0 g/cm 2 , and the average depth of coagulation was the thickest, 1.47 ± 0.29 mm, among the three groups (p 

Description: Background: Body fluids such as saliva and tears from patients with hepatitis B virus (HBV) infection are known as infectious agents. The infectivity of feces from patients with HBV infection has not been established. The aim of this study was to determine whether feces from HBV carriers can be a source of HBV infection. Methods: Thirty-three children and 17 adults (ages 0–49 years, median age 13 years) who were chronically infected with HBV were enrolled. The levels of HBV DNA in the feces from these patients were quantified by real-time PCR, and the levels of fecal HBsAg were measured. Isolated human hepatocytes from chimeric mice with humanized livers were co-cultured with serum, tears and feces from the HBV carriers. Four chimeric mice were inoculated intravenously with sterilized feces from HBV carriers. Results: HBV DNA was detected in the feces of 37 (74 %) of the 50 patients. The fecal HBV DNA levels ranged from 2.8 to 8.4 log copies/mL (mean ± SD  =  5.6 ± 1.2 log copies/mL). A significant correlation was observed in the levels of HBV DNA between serum and feces (r  =  0.54, p 

Description: Background: There is general consensus that appropriate development and use of information and communication technologies (ICT) are crucial in the delivery of effective primary care (PC). Several countries are defining policies to support and promote a structural change of the health care system through the introduction of ICT. This study analyses the state of development of basic ICT in PC systems of 31 European countries with the aim to describe the extent of, and main purposes for, computer use by General Practitioners (GPs) across Europe. Additionally, trends over time have been analysed. Methods: Descriptive statistical analysis was performed on data from the QUALICOPC (Quality and Costs of Primary Care in Europe) survey, to describe the geographic differences in the general use of computer, and in specific computerized clinical functions for different health-related purposes such as prescribing, medication checking, generating health records and research for medical information on the Internet. Results: While all the countries have achieved a near-universal adoption of a computer in their primary care practices, with only a few countries near or under the boundary of 90 %, the computerisation of primary care clinical functions presents a wide variability of adoption within and among countries and, in several cases (such as in the southern and central-eastern Europe), a large room for improvement. Conclusions: At European level, more efforts could be done to support southern and central-eastern Europe in closing the gap in adoption and use of ICT in PC. In particular, more attention seems to be need on the current usages of the computer in PC, by focusing policies and actions on the improvement of the appropriate usages that can impact on quality and costs of PC and can facilitate an interconnected health care system. However, policies and investments seem necessary but not sufficient to achieve these goals. Organizational, behavioural and also networking aspects should be taken in consideration.

Description: Background: It remains unclear to what extent midgut rotation determines human intestinal topography and pathology. We reinvestigated the midgut during its looping and herniation phases of development, using novel 3D visualization techniques. Results: We distinguished 3 generations of midgut loops. The topography of primary and secondary loops was constant, but that of tertiary loops not. The orientation of the primary loop changed from sagittal to transverse due to the descent of ventral structures in a body with a still helical body axis. The 1 st secondary loop (duodenum, proximal jejunum) developed intraabdominally towards a left-sided position. The 2 nd secondary loop (distal jejunum) assumed a left-sided position inside the hernia before returning, while the 3 rd and 4 th secondary loops retained near-midline positions. Intestinal return into the abdomen resembled a backward sliding movement. Only after return, the 4 th secondary loop (distal ileum, cecum) rapidly “slid” into the right lower abdomen. The seemingly random position of the tertiary small-intestinal loops may have a biomechanical origin. Conclusions: The interpretation of “intestinal rotation” as a mechanistic rather than a descriptive concept underlies much of the confusion accompanying the physiological herniation. We argue, instead, that the concept of “en-bloc rotation” of the developing midgut is a fallacy of schematic drawings. Primary, secondary and tertiary loops arise in a hierarchical fashion. The predictable position and growth of secondary loops is pre-patterned and determines adult intestinal topography. We hypothesize based on published accounts that malrotations result from stunted development of secondary loops.

Description: Background: All organisms must synthesize the enzymatic cofactor coenzyme A (CoA) from the precursor pantothenate. Most bacteria can synthesize pantothenate de novo by the condensation of pantoate and β-alanine. The synthesis of β-alanine is catalyzed by l-aspartate-α-decarboxylase (PanD), a pyruvoyl enzyme that is initially synthesized as a zymogen (pro-PanD). Active PanD is generated by self-cleavage of pro-PanD at Gly24-Ser25 creating the active-site pyruvoyl moiety. In Salmonella enterica, this cleavage requires PanM, an acetyl-CoA sensor related to the Gcn5-like N-acetyltransferases. PanM does not acetylate pro-PanD, but the recent publication of the three-dimensional crystal structure of the PanM homologue PanZ in complex with the PanD zymogen of Escherichia coli provides validation to our predictions and provides a framework in which to further examine the cleavage mechanism. In contrast, PanD from bacteria lacking PanM efficiently cleaved in the absence of PanM in vivo. Results: Using phylogenetic analyses combined with in vivo phenotypic investigations, we showed that two classes of bacterial l-aspartate-α-decarboxylases exist. This classification is based on their posttranslational activation by self-cleavage of its zymogen. Class I l-aspartate-α-decarboxylase zymogens require the acetyl-CoA sensor PanM to be cleaved into active PanD. This class is found exclusively in the Gammaproteobacteria. Class II l-aspartate-α-decarboxylase zymogens self cleave efficiently in the absence of PanM, and are found in a wide number of bacterial phyla. Several members of the Euryarchaeota and Crenarchaeota also contain Class II l-aspartate-α-decarboxylases. Phylogenetic and amino acid conservation analyses of PanM revealed a conserved region of PanM distinct from conserved regions found in related Gcn5-related acetyltransferase enzymes (Pfam00583). This conserved region represents a putative domain for interactions with l-aspartate-α-decarboxylase zymogens. This work may inform future biochemical and structural studies of pro-PanD-PanM interactions. Conclusions: Experimental results indicate that S. enterica and C. glutamicum l-aspartate-α-decarboxylases represent two different classes of homologues of these enzymes. Class I homologues require PanM for activation, while Class II self cleave in the absence of PanM. Computer modeling of conserved amino acids using structure coordinates of PanM and l-aspartate-α-decarboxylase available in the protein data bank (RCSB PDB) revealed a putative site of interactions, which may help generate models to help understand the molecular details of the self-cleavage mechanism of l-aspartate-α-decarboxylases.

Description: Background: Heterochromatin is essential for chromosome segregation, gene silencing and genome integrity. The fission yeast Schizosaccharomyces pombe contains heterochromatin at centromeres, subtelomeres, and mating type genes, as well as at small islands of meiotic genes dispersed across the genome. This heterochromatin is generated by partially redundant mechanisms, including the production of small interfering RNAs (siRNAs) that are incorporated into the RITS protein complex (RNAi-Induced Transcriptional Silencing). The assembly of heterochromatin islands requires the function of the RNA-binding protein Mmi1, which recruits RITS to its mRNA targets and to heterochromatin islands. In addition, Mmi1 directs its targets to an exosome-dependent RNA elimination pathway. Results: Ccr4-Not is a conserved multiprotein complex that regulates gene expression at multiple levels, including RNA degradation and translation. We show here that Ccr4-Not is recruited by Mmi1 to its RNA targets. Surprisingly, Ccr4 and Caf1 (the mRNA deadenylase catalytic subunits of the Ccr4-Not complex) are not necessary for the degradation or translation of Mmi1 RNA targets, but are essential for heterochromatin integrity at Mmi1-dependent islands and, independently of Mmi1, at subtelomeric regions. Both roles require the deadenylase activity of Ccr4 and the Mot2/Not4 protein, a ubiquitin ligase that is also part of the complex. Genetic evidence shows that Ccr4-mediated silencing is essential for normal cell growth, indicating that this novel regulation is physiologically relevant. Moreover, Ccr4 interacts with components of the RITS complex in a Mmi1-independent manner. Conclusions: Taken together, our results demonstrate that the Ccr4-Not complex is required for heterochromatin integrity in both Mmi1-dependent and Mmi1-independent pathways.

Description: Background: Bone resorption takes place within the basic multicellular units (BMU), and the surface to be resorbed is isolated from adjacent bone surfaces by a sealing zone between osteoclast membrane and bone matrix, which defines the limits of the resorption lacuna. Considering that the extracellular fluid (ECF) in both BMU and the resorption lacuna can be isolated from its surroundings, I hypothesize that flow and ion composition of the bone ECF in these sites might contribute to the regulation of osteoclast H + secretion. To investigate this hypothesis, I evaluated the H + secretion properties of individual osteoclasts and osteoclast-like cells (OCL-cells) and investigated whether changes in flow or chloride content of the extracellular solution modify the H + secretion properties in vitro. Results: The results show that 1) osteoclasts are unable to secrete H + and regulate intracellular pH (pH i ) under continuous flow conditions and exhibit progressive intracellular acidification; 2) the cessation of flow coincides with the onset of H + secretion and subsequent progressive intracellular alkalinization of osteoclasts and OCL-cells; 3) osteoclasts exhibit spontaneous rhythmic oscillations of pH i in non-flowing ECF, 4) pH i oscillations are not abolished by concanamycin, NPPB, or removal of extracellular Na + or Cl − ; 5) extracellular Cl − removal modifies the pattern of oscillations, by diminishing H + secretion; 6) pH i oscillations are abolished by continuous flowing of ECF over osteoclasts and OCL-cells. Conclusions: The data suggest, for the first time, that ECF flow and Cl − content have direct effects on osteoclast H + secretion and could be part of a mechanism determining the onset of osteoclast H + secretion required for bone resorption.

Description: Background: Mounting evidence shows that smartphone usage heavily disrupts our work life and social activities. Moreover, it is possible that overuse could resemble addictive tendencies. A key contributing factor to smartphone overuse seems to be usage of the messaging application WhatsApp. Although WhatsApp is one of the most commonly used communication applications on smartphones, research in this area is scarce. Given the huge societal debate on the impact of smartphone usage on our daily lives, the present study undertook a large-scale investigation in order to provide numbers on smartphone usage generally—and use of WhatsApp in particular, with the aim of providing a basis for a scientific debate. Methods: In a large sample of N = 2,418 users, we recorded WhatsApp behaviour over a 4 week period. Results: Our data show that use of WhatsApp accounted for 19.83% (= 32.11 min) of all smartphone behaviour (compare: Facebook only 9.38% = 15.19 min). The mean of general daily smartphone usage was 161.95 min. Females used WhatsApp for significantly longer periods of time than males and younger age was associated with longer duration of WhatsApp use. While the personality trait Extraversion was positively associated with daily WhatsApp use, Conscientiousness showed an inverse correlation with the length of daily WhatsApp use. Conclusions: The numbers on smartphone usage in the present study show that the smartphone dominates our daily life. In particular WhatsApp is a driving force, here. Given the length of daily smartphone and WhatsApp usage, more studies need to be conducted to better understand smartphone usage.

Description: Background: Bangladesh is facing serious shortage of trained health professionals. In the pluralistic healthcare system of Bangladesh, formal health care providers constitute only 5 % of the total workforce; the rest are informal health care providers. Information Communication Technologies (ICTs) are increasingly seen as a powerful tool for linking the community with formal healthcare providers. Our study assesses an intervention that linked village doctors (a cadre of informal health care providers practising modern medicine) to formal doctors through call centres from the perspective of the village doctors who participated in the intervention. Methods: The study was conducted in Chakaria, a remote rural area in south-eastern Bangladesh during April–May 2013. Twelve village doctors were selected purposively from a pool of 55 village doctors who participated in the mobile health (mHealth) intervention. In depth interviews were conducted to collect data. The data were manually analysed using themes that emerged.ResultThe village doctors talked about both business benefits (access to formal doctors, getting support for decision making, and being entitled to call trained doctors) and personal benefits (both financial and non-financial). Some of the major barriers mentioned were technical problems related to accessing the call centre, charging consultation fees, and unfamiliarity with the call centre physicians. Conclusion: Village doctors saw many benefits to having a business relationship with the trained doctors that the mHealth intervention provided. mHealth through call centres has the potential to ensure consultation services to populations through existing informal healthcare providers in settings with a shortage of qualified healthcare providers.

Description: Background: Choosing the most appropriate family physician (FP) for the individual, plays a fundamental role in primary care. The aim of this study is to determine the selection criteria for the patients in choosing their family doctors and priority ranking of these criteria by using the multi-criteria decision-making method of the Analytic Hierarchy Process (AHP) model. Methods: The study was planned and conducted in two phases. In the first phase, factors affecting the patients’ decisions were revealed with a qualitative research. In the next phase, the priorities of FP selection criteria were determined by using AHP model. Criteria were compared in pairs. 96 patient were asked to fill the information forms which contains comparison scores in the Family Health Centres. Results: According to the analysis of focus group discussions FP selection criteria were congregated in to five groups: Individual Characteristics, Patient-Doctor relationship, Professional characteristics, the Setting, and Ethical Characteristics.For each of the 96 participants, comparison matrixes were formed based on the scores of their information forms. Of these, models of only 5 (5.2 %) of the participants were consistent, in other words, they have been able to score consistent ranking. The consistency ratios (CR) were found to be smaller than 0.10. Therefore the comparison matrix of this new model, which was formed based on the medians of scores only given by these 5 participants, was consistent (CR = 0.06 

Description: Background: About 1,000 endangered Patagonian huemul deer (Hippocamelus bisulcus) remain in Chile and 350–500 in Argentina. Most groups (〉100) are not recovering, and prevalence of osteopathology in Argentina was at least 57%. Here I describe relevant cases of osteopathology from a Chilean population which, however, recently also provided data on trace mineral status, supporting the initial hypothesis that nutrition may be a primary etiologic factor. Additionally, recent data on bone chemical composition of Argentine cases and soil analyses are discussed. Results: Fluoride levels in Argentine cases with osteopathology were low and fluorosis was discarded as an etiological factor. Selenium deficiency occurred in 73% of huemul from the Chilean population which exhibited several cases with osteopathology. The pathophysiognomy included extensive erosion; tooth loss; porosification; perforations of palate, maxillar and mandibular bone with frequent exposure of tooth roots; and fractured mandibula. Areas currently used by remaining huemul have mainly acidic volcanic soils, which reduces selenium bioavailability: mean soil selenium levels from areas typically used by extant huemul were very deficient (0.19 ppm), corroborating documented overt selenium deficiency in local livestock and plants. The area of extant huemul is known to result in primary iodine deficiency in livestock which is aggravated by selenium deficiency. Conclusions: Currently the most parsimonious explanation for frequent osteopathology and lack of numerical recovery are the combined effects of selenium and iodine deficiencies based on: osteopathology in a population of selenium deficient huemul; selenium deficient livestock, plants and soils; acidic soils; and regional primary iodine deficiency. The nexus between mineral nutrition and population dynamics of huemul may be due to constraints on their movements to fertile lowlands, including the elimination of historic migratory traditions, and concomitant elimination of source populations.

Description: Background: In recent years the emergence of multidrug resistant Klebsiella pneumoniae strains has been an increasingly common event. This opportunistic species is one of the five main bacterial pathogens that cause hospital infections worldwide and multidrug resistance has been associated with the presence of high molecular weight plasmids. Plasmids are generally acquired through horizontal transfer and therefore is possible that systems that prevent the entry of foreign genetic material are inactive or absent. One of these systems is CRISPR/Cas. However, little is known regarding the clustered regularly interspaced short palindromic repeats and their associated Cas proteins (CRISPR/Cas) system in K. pneumoniae. The adaptive immune system CRISPR/Cas has been shown to limit the entry of foreign genetic elements into bacterial organisms and in some bacteria it has been shown to be involved in regulation of virulence genes. Thus in this work we used bioinformatics tools to determine the presence or absence of CRISPR/Cas systems in available K. pneumoniae genomes. Results: The complete CRISPR/Cas system was identified in two out of the eight complete K. pneumoniae genomes sequences and in four out of the 44 available draft genomes sequences. The cas genes in these strains comprises eight cas genes similar to those found in Escherichia coli, suggesting they belong to the type I-E group, although their arrangement is slightly different. As for the CRISPR sequences, the average lengths of the direct repeats and spacers were 29 and 33 bp, respectively. BLAST searches demonstrated that 38 of the 116 spacer sequences (33%) are significantly similar to either plasmid, phage or genome sequences, while the remaining 78 sequences (67%) showed no significant similarity to other sequences. The region where the CRISPR/Cas systems were located is the same in all the Klebsiella genomes containing it, it has a syntenic architecture, and is located among genes encoding for proteins likely involved in metabolism and resistance to antibiotics. Conclusions: The CRISPR/Cas system is not widely distributed in K. pneumoniae genomes, those present most likely belong to type I-E with few differences from the arrangement of the cse3 gene and most of the spacers have not been are not described yet. Given that the CRISPR/Cas system is scarcely distributed among K. pneumoniae genomes it is not clear whether it is involved in either immunity against foreign genetic material or virulence. We consider that this study represents a first step to understand the role of CRISPR/Cas in K. pneumoniae.

Description: Background: Gorham’s syndrome is a rare illness of unknown etiology. It is characterized by a local proliferation of blood or lymphatic vessels that in bones leads to progressive resorption and destruction. The cause of the disease is not elucidated, and therapeutic options remain limited.Case presentationWe report herein the case of a young female Caucasian patient aged 18 years with diffuse Gorham syndrome. In tissue specimens angiogenesis and massive lymphangiogenesis as well as the expression of vascular endothelial growth factor-A (VEGF-A) and neuropilins was observed. Lymphangiogenesis is a prominent feature of the disease and a number of lymphatic markers were found to be expressed, however only VEGF-A, but not vascular endothelial growth factor-C (VEGF-C) was found to be elevated in the circulation. Circulating levels of soluble VEGF receptor-1 were also not elevated. Furthermore, the patient responded favorably and the disease was stabilized following treatment with the beta-blocking agent Propranolol alone which acts on VEGF-A alone, but not on soluble VEGF receptor-1 levels. Conclusion: This suggests that the disease is dependent on VEGF-A, but on neither VEGF-C, the major driver of lymphangiogenesis, nor FLT1. Furthermore, Propranolol acts on VEGF-A but not FLT1 expression.

Description: Background: Equations based on single-frequency bioelectrical impedance analysis at 50 kHz for determination of total body water content (TBW) have been previously validated in healthy non-sedated beagle dogs. We investigated whether these equations are predictive of TBW in various canine breeds by comparing the results of these equations with TBW values evaluated directly by deuterium oxide (D 2 O) dilution. Methods: Total body water content of 13 healthy adult pet dogs of various breeds was determined directly using D 2 O dilution and indirectly using previous equations based on values obtained with a portable bioelectric impedance device. Paired Student’s t-tests were used to compare TBW obtained by single-frequency bioelectrical impedance analysis and D 2 O dilution. A p-value of

Description: Background: Mitochondria are key regulators of apoptosis. In response to stress, BH3-only proteins activate pro-apoptotic Bcl2 family proteins Bax and Bak, which induce mitochondrial outer membrane permeabilization (MOMP). While the large-scale mitochondrial release of pro-apoptotic proteins activates caspase-dependent cell death, a limited release results in sub-lethal caspase activation which promotes tumorigenesis. Mitochondrial autophagy (mitophagy) targets dysfunctional mitochondria for degradation by lysosomes, and undergoes extensive crosstalk with apoptosis signaling, but its influence on apoptosis remains undetermined. The BH3-only protein Bnip3 integrates apoptosis and mitophagy signaling at different signaling domains. Bnip3 inhibits pro-survival Bcl2 members via its BH3 domain and activates mitophagy through its LC3 Interacting Region (LIR), which is responsible for binding to autophagosomes. Previously, we have shown that Bnip3-activated mitophagy prior to apoptosis induction can reduce mitochondrial activation of caspases, suggesting that a reduction to mitochondrial levels may be pro-survival. An outstanding question is whether organelle dynamics and/or recently discovered subcellular variations of protein levels responsible for both MOMP sensitivity and crosstalk between apoptosis and mitophagy can influence the cellular apoptosis decision event. To that end, here we undertook a systems biology analysis of mitophagy-apoptosis crosstalk at the level of cellular mitochondrial populations. Results: Based on experimental findings, we developed a multi-scale, hybrid model with an individually adaptive mitochondrial population, whose actions are determined by protein levels, embedded in an agent-based model (ABM) for simulating subcellular dynamics and local feedback via reactive oxygen species signaling. Our model, supported by experimental evidence, identified an emergent regulatory structure within canonical apoptosis signaling. We show that the extent of mitophagy is determined by levels and spatial localization of autophagy capacity, and subcellular mitochondrial protein heterogeneities. Our model identifies mechanisms and conditions that alter the mitophagy decision within mitochondrial subpopulations to an extent sufficient to shape cellular outcome to apoptotic stimuli. Conclusion: Overall, our modeling approach provides means to suggest new experiments and implement findings at multiple scales in order to understand how network topologies and subcellular heterogeneities can influence signaling events at individual organelle level, and hence, determine the emergence of heterogeneity in cellular decisions due the actions of the collective intra-cellular population.

Description: Background: Pulmonary tuberculosis is caused by Mycobacterium tuberculosis and its manifestations may include parenchymal, airway, vascular, pleural, mediastinal and chest wall lesions. Hemoptysis is a common complication of the disease. Massive hemoptysis occurs in about 8 % of cases; with associated mortality ranging from 5 to 25 % Massive hemoptysis secondary to pulmonary artery aneurysm rupture is a rare phenomenon presenting unique challenges in airway management and stabilization of oxygenation, ventilation and blood pressure.Case historyWe present a case of a patient with necrotizing pulmonary tuberculosis complicated by a ruptured pulmonary artery “Rasmussen” aneurysm requiring emergent intubation and embolization. Conclusion: Massive hemoptysis should be treated as a medical emergency requiring the coordinated care of multiple specialists including intensivists, interventional radiologists, anesthesiologists, and surgeons. Airway management and stabilization of cardiorespiratory status should be the highest priority, followed by timely diagnostic procedures to localize the site and cause of the bleeding.

Description: Background: Antenatal care has several benefits for expecting mothers and birth outcomes; yet many mothers do not utilise this service in Nepal. Mass media may play an important role in increasing the use of antenatal care and other maternal health services. However, the effect of mass media on increasing health service utilisation has remained an under studied area in Nepal. The aim of this study was to investigate the impact of mass media on the utilisation of antenatal care services in rural Nepal. Methods: A community-based cross-sectional study was conducted in Sinurjoda Village Development Committee of Dhanusha District, Nepal. A total of 205 mothers of children aged under 1 year were selected using systematic random sampling. Logistic regression was employed to examine the association between selected antenatal care services and mass media exposure after adjusting for other independent variables. Results: A majority of mothers were exposed to mass media. Radio was accessible to most (60.0 %) of the participants followed by television (43.41 %). Mothers exposed to mass media were more likely to attending antenatal visits [Odds ratio (OR) 6.28; 95 % CI (1.01–38.99)], taking rest and sleep during pregnancy [OR 2.65; 95 % CI (1.13–6.26)], and receiving TT immunization [OR 5.12; 95 % CI (1.23–21.24)] than their non-exposed counterparts. Conclusions: The study reported a positive influence of mass media on the utilisation of antenatal care services in Nepal. Therefore, further emphasis should be given to increase awareness of women of rural Nepal through mass media to improve utilisation of antenatal care services in Nepal.

Description: Background: Non-adherence to Antiretroviral Treatment (ART) is strongly associated with virologic rebound and drug resistance. Studies have shown that the most frequently mentioned reason for missing ART doses is the forgetfulness of patients to take their medications on time. Therefore using communication devices as reminder tools, for example alarms, pagers, text messages and telephone calls could improve adherence to ART. The aim of this study is to measure access to cellphones, willingness to receive text message medication reminders and to identify associated factors of ART patients at the University of Gondar Hospital, in North West Ethiopia. Methods: An institution based cross sectional quantitative study was conducted among 423 patients on ART during April 2014. Data were collected using structured interviewer-administered questionnaires. Data entry and analysis were done using Epi-Info version 7 and SPSS version 20 respectively. Descriptive statistics and multivariable logistic regression analysis were used to describe the characteristic of the sample and identify factors associated with the willingness to receive text message medication reminders. Results: A total of 415 (98 % response rate) respondents participated in the interview. The majority of respondents 316 (76.1 %) owned a cellphone, and 161(50.9 %) were willing to receive text message medication reminders. Positively associated factors to the willingness were the following: Younger age group (AOR = 5.18, 95 % CI: [1.69, 15.94]), having secondary or higher education (AOR = 4.61, 95 % CI: [1.33, 16.01]), using internet (AOR = 3.94, 95 % CI: [1.67, 9.31]), not disclosing HIV status to anyone other than HCP (Health Care Provider) (AOR = 3.03, 95 % CI: [1.20, 7.61]), availability of radio in dwelling (AOR = 2.74 95 % CI: [1.27, 5.88]), not answering unknown calls (AOR = 2.67, 95 % CI: [1.34, 5.32]), use of cellphone alarm as medication reminder (AOR = 2.22, 95%CI [1.09, 4.52]), and forgetting to take medications (AOR = 2.13, 95 % CI: [1.14, 3.96]). Conclusions: A high proportion of respondents have a cell phone and are willing to use it as medication reminders. Age, educational status and using internet were the main factors that are significantly associated with the willingness of patients to receive text message medication reminders.

Description: Background: Neurogenic thoracic outlet syndrome is an underestimated cause of brachial weakness and pain. The subclavius posticus muscle (SPM) is an aberrant muscle originating from the medial aspect of the first rib reaching to superior border of the scapula, which may cause, depending on its activation, dynamic compression of the brachial plexus.Case presentationIn the present study, we report about a 32-year-old male caucasian patient with weakness in radial deviation of his left hand. An isolated macrodactyly of his left middle finger had been operated twice. Electroneurography showed a carpal-tunnel-syndrome (CTS) on the left side. MRI of the brachial plexus revealed an additional muscle in the costoclavicular space, identified as SPM. To our knowledge, this is the second case report of a neurogenic thoracic outlet syndrome due to SPM, and the first case described with isolated macrodactyly and CTS in the same patient. Conclusion: If complaints about hand weakness are only reported in cases of distinct hand positions, a dynamic compression of the brachial plexus by SPM may be the cause. A neurogenic thoracic outlet syndrome may facilitate the development of CTS.

Description: Background: Tetanus in newborns, is an under-reported public health problem and a major cause of mortality in developing countries. This study aimed to determine the predictors and outcome of tetanus in newborn infants in the slums of Bin-Qasim town, Karachi, Pakistan. Methods: We conducted a case–control study at primary health care centers of slums of Bin-Qasim town, area located adjacent to Bin Qasim seaport in Karachi, from January 2003 to December 2013. Cases were infants aged ≤30 days with tetanus, as defined by the World Health Organization. Controls were newborn infants aged ≤30 days without Tetanus, who were referred for a checkup or minor illnesses. The case to control ratio was 1:2. Results: We analyzed 26 cases and 52 controls. The case fatality was 70.8%. We identified four independent predictors of Tetanus in newborns: maternal education (only religious education with no formal education OR 51.95; 95% CI 3.69–731), maternal non-vaccination (OR 24.55; 95% CI 1.01–131.77), lack of a skilled birth attendant (OR 44.00; 95% CI 2.30–840.99), and delivery at home (OR 11.54; 95% CI 1.01–131.77). Conclusions: We identified several potentially modifiable socio-demographic risk factors for Tetanus in newborns, including maternal education and immunization status, birth site, and lack of a skilled birth attendant. Prioritization of these risk factors could be useful for planning preventive and cost-effective measures.

Description: Background: The 12-lead electrocardiographic screening for the prevention of sudden cardiac death in young competitive athletes is not cost-effective and thus not routinely recommended. We investigate whether a less expensive wireless electrocardiographic transmission device can be used to screen for the prevention of sudden cardiac death in this population. Methods: During pre-participation screening, twenty college football players underwent two electrocardiograms: a conventional 12-lead electrocardiogram and a wireless 9-lead electrocardiogram. We compared several electrocardiographic parameters (QRS duration, left ventricular hypertrophy using the Cornell voltage criteria and the Sokolow–Lyon criteria, ST deviation and corrected QT interval) to determine the correlation. Results: The QRS duration, left ventricular hypertrophy using the Cornell voltage criteria and the Sokolow–Lyon criteria and corrected QT interval exhibited significant correlation between the two types of electrocardiograms (correlation coefficient 0.878, 0.630, 0.770 and 0.847, respectively with P values of 0.01, 0.003, 0.01 and 0.01, respectively). ST deviation in V1 was weakly correlated between the two types of electrocardiograms without statistical significance (correlation coefficient 0.360 with a P value of 0.119). Conclusions: Our newly developed wireless 9-lead electrocardiogram demonstrated significant correlations with a conventional 12-lead electrocardiogram in terms of QRS duration, left ventricular hypertrophy and corrected QT interval.

Description: Background: Stroke is a common cause of morbidity and mortality around the world. Intracranial large artery atherosclerosis (ICAD) is a frequent etiology of stroke in the South Asian population. There is a need for widely available screening tools to identify patients that are at high risk of stroke due to ICAD for aggressive risk management. This study describes the experience of using the transcranial Doppler (TCD) as a screening tool for this purpose at a tertiary care hospital in a developing country. Methods: 86 Patients admitted with stroke due to ICAD underwent TCD for six arteries (Right and left middle cerebral arteries, right and left anterior cerebral arteries, right and left posterior cerebral arteries) in addition to the magnetic resonance angiography (MRA) that is done routinely at the stroke center. Arteries were labeled with either 50% stenosis by TCD using two separate criteria. These findings were compared with those from the MRA which was used as the gold standard. The proportion of patients that had complete exams (all six arteries insonated by TCD) was reported. The success rate of each TCD criteria in detecting arteries with 〉50% stenosis was also calculated. Results: There was an attempt to visualize 516 arteries (86 patients with 6 arteries each) of which 375 (72.7%) were successfully insonated. 38 of the 86 (55.8%) patients had complete examinations. MRA reported 43 (8.3%) arteries as stenosed 〉50%. The TCD did not categorize any artery as stenosed using either criterion and hence failed to classify any stenosed artery correctly. The positive predictive and sensitivity was 0 for this study and the negative predictive value was 93.3%. Conclusions: This study indicates the poor sensitivity of TCD to be a reliable screening tool for the presence of ICAD in the South Asian population in a real life clinical setting.

Description: Background: This study aims at verifying relationships between the perception of medico-legal risks involved in the professional activity of Italian otolaryngologists, defensive medical behaviour and their understanding of professional liability insurance in matters of civil liability. One hundred specialists replied to a questionnaire pertaining to the psychological impact of medico-legal issues and to specific queries regarding insurance coverage, either privately stipulated or provided by the employer. Statistic analysis was carried out by χ 2 test and ANOVA multiple variance regression test, assuming P = 0.05 as the value of minimum statistical significance. Results: It was found that in 50 % of cases the behaviour of the doctor towards the patient had been decidedly influenced by concerns over medico-legal implications. In 29 % of the sample these concerns had “often to always” influenced the choice of diagnostic procedures or treatment options, in order to safeguard themselves in case of legal dispute. The data obtained showed a statistically significant correlation between the level of concern (regarding potential medico-legal disputes) experienced by specialists on the one hand and variations in the doctor/patient relationship (P 

Description: No description available

Description: Background: Hyperinsulinaemic hypoglycaemia (HH) is a group of clinically and genetically heterogeneous disorders characterized by unregulated insulin secretion. Abnormalities in nine different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A, UCP2 and HNF1A) have been reported in HH, the most common being ABCC8 and KCNJ11. We describe the genetic aetiology and phenotype of Iranian patients with HH. Methods: Retrospective clinical, biochemical and genetic information was collected on 23 patients with biochemically confirmed HH. Mutation analysis was carried out for the ATP-sensitive potassium (K ATP ) channel genes (ABCC8 and KCNJ11), GLUD1, GCK, HADH and HNF4A. Results: 78 % of the patients were identified to have a genetic cause for HH. 48 % of patients had mutation in HADH, whilst ABCC8/KCNJ11 mutations were identified in 30 % of patients. Among the diazoxide-responsive patients (18/23), mutations were identified in 72 %. These include two novel homozygous ABCC8 mutations. Of the five patients with diazoxide-unresponsive HH, three had homozygous ABCC8 mutation, one had heterozygous ABCC8 mutation inherited from an unaffected father and one had homozygous KCNJ11 mutation. 52 % of children in our cohort were born to consanguineous parents. Patients with ABCC8/KCNJ11 mutations were noted to be significantly heavier than those with HADH mutation (p = 0.002). Our results revealed neurodevelopmental deficits in 30 % and epilepsy in 52 % of all patients. Conclusions: To the best of our knowledge, this is the first study of its kind in Iran. We found disease-causing mutations in 78 % of HH patients. The predominance of HADH mutation might be due to a high incidence of consanguineous marriage in this population. Further research involving a larger cohort of HH patients is required in Iranian population.

Description: Background: Doorknobs are inevitable points of hand contact. We monitored doorknob contamination in a university hospital using an ATP bioluminescence assay and stamp agar method. We selected grip-, lever-, push-, insert-, and two-pull-type doorknobs in staff lavatories and break rooms, a linen closet, dirty utility rooms, a newborn care unit, clinical lavatories and examination rooms, dressing rooms for radiological tests, and lavatories for health examination, as monitoring points in wards and clinics. Sequential monitoring with an ATP assay (six times) and culture (once) were performed at the same time of day in autumn, winter, and summer. We provided contamination data to appropriate healthcare providers and housekeepers, and queried the staff regarding decontamination of doorknobs. Results: When comparing ATP values on the same type of doorknobs, significant differences in contamination were demonstrated among several clinical rooms and several rooms in wards during all three seasons. No correlation was observed between ATP values on clinical-examination-room doorknobs and outpatient numbers, or between ATP values at any monitoring point and microbial colony-forming units. ATP values on clinical-examination-room doorknobs were reduced after cleaning according to instructions. Conclusions: ATP assay is useful for measuring baseline doorknob contamination in clinical rooms. Our findings confirm the need to improve routine decontamination in clinical departments. We need to analyze further the relationship between hospital-acquired infections and doorknob contamination, as assessed by ATP assay in clinics.

Description: Background: Few studies investigated the association between basal metabolic rate (BMR) and indicators of pulmonary function. This study was conducted to estimate BMR in overweight/obese and non-obese healthy subjects using four commonly used predictive equations and to investigate its relation to the indicators of lung function tests (LFT). A cross sectional study was conducted in Tabuk University, Tabuk, Saudi Arabia. A total of 201 students (98 males and 103 females) participated in the study. Four different values of BMR were calculated for each participant using four different predictive equations (Harris-Benedict, Mifflin, FAO/WHO/UNU and Henry-Rees). A portable All-flow spirometer (Clement Clarke International, Harlow, UK) was used for measurements of LFT. Results: Significantly higher values of spirometric indicators (p 

Description: Background: Warfarin is widely used for the prevention and treatment of cardiac, thromboembolic and hypercoagulable diseases. Since warfarin is a narrow therapeutic index medicine, it requires close monitoring when used in the outpatient setting and on long term basis. Warfarin has been found to be associated with a number of complications especially bleeding. Patients’ knowledge on warfarin can improve anticoagulation control with decrease in adverse drug reaction and other associated complications. The objective was to assess knowledge level of warfarin therapy among its users and to provide adequate education and counseling to the patients. Methods: In the present cross sectional study, 34 patients on warfarin were interviewed. Patients’ knowledge on warfarin was assessed using a validated Anticoagulation Knowledge Assessment (AKA) questionnaire comprising 29 questions. Each correct answer scored 3.45 points whereas an incorrect answer scored zero point. Patient who answered at least 21 questions correctly or scored (21 × 3.45 = 72.4 %) was considered to have adequate level of knowledge or have obtained a passing score. Association between independent variables and AKA score was assessed using Pearson Chi square test or Fisher’s exact test for categorical variables. Patients were counseled regarding proper warfarin use by the researcher pharmacists at the end of each data collection schedule. Results: Of the 34 patients, only 5.8 % (n = 2) achieved a passing score whereas 94.1 % (n = 32) failed to achieve the passing score. 67.6 % of the patients (n = 23) achieved a score below 50 %. More than 50 % of the patients incorrectly answered 15 questions in the questionnaire. None of the patients scored 100 %. No significant association was found between age, gender of patients and total warfarin score. A significant association (p 

Description: Background: A decline in clinical skills of medical students and junior doctors is well documented. We aim to determine how the 32 UK medical schools utilise simulated heart sounds to develop medical students’ cardiac auscultation skills. Methods: Representatives of all 32 UK medical schools were contacted with a survey questionnaire. Data analysis was carried out using SPSS. Continuous variables e.g. teaching group size were described using median and interquartile range (IQR). Results: 27 Medical schools use a form of simulated heart sounds as a teaching method (2 representatives were unsure, 3 did not respond). This teaching is mandatory in 17 schools. Simulation-based teaching tends to be offered during 3rd year of medical training [median = 3rd year, interquartile range (IQR) 2–3]. Seven medical schools offered simulation teaching more than once. The median number of students in each session was 7.5 [IQR = 5.5–9.5]. One medical school reported that they were unsure how best to implement the heart sound simulation into the medical undergraduate curriculum. Conclusion: The results of our survey of all the UK medical schools suggest that heart sound simulation are used mainly as an introduction to heart murmurs rather than a tool for repetitive practice, complementing clinical experience. Most medical schools do not measure the impact of such teaching on clinical examination.

Description: Background: Human African Trypanosomiasis (HAT) is a neglected tropical disease affecting poor rural communities living in tsetse-infested regions of sub-Saharan Africa. In Zambia, sporadic cases of HAT have been reported mainly in the old foci along the tsetse-infested Luangwa river valley in north-eastern part of the country. In such places where malaria is the major endemic febrile disease, with possibilities of co-infections of HAT and malaria and where the levels of alertness to the presence of HAT among health care personnel (HCP) is low, there is a high chance of misdiagnosing HAT for malaria because of their similarities in clinical presentation. This study, conducted in Zambia’s tsetse-infested rural health centres (RHCs) of Chama and Mambwe districts, was designed to investigate the staffing levels, the HCP levels of alertness to the occurrence of HAT and their capacity to detect the disease. Methods: Structured questionnaires were used to collect information pertaining to HAT alertness and the capacity to detect the disease from 101 HCP in a cross sectional study of 23 RHCs drawn from Zambia’s Chama and Mambwe districts between April and July 2013. The data collected were analyzed using Stata/SE version 11.0. Results: Participants from both Chama and Mambwe district RHCs reported similar very low levels of qualified HCP and laboratory technicians, and that they had similar basic tools for HAT diagnosis. Although not statistically significant, respondents from Chama (~89 %) tended to be more aware about the occurrence of HAT compared to their Mambwe counterparts (~78 %). Whereas ~40 % of the HCP from Chama district (n = 52) claimed to have encountered at least one case of HAT, only ~4 % of their Mambwe counterparts (n = 49) had similar experiences (P = 0.000). Conclusion: Health care personnel in RHCs from Chama tended to be more alert to the occurrence of HAT than the HCP from Mambwe district. The extremely low levels of categorized HCP, general absence of functional laboratories, coupled with absence of national HAT surveillance and control programs, are among some of the serious challenges that Zambia’s Chama and Mambwe districts face to control/eliminate HAT.

Description: Background: Influenza virus pandemics vary dramatically in their severity and mortality. Thus, it is very important to identify populations with high risks of developing severe illness to reduce mortality in future pandemics. The purpose was to determine the mortality-associated risk factors in hospitalized Mexican patients infected with influenza A/H1N1. Results: The risk factors associated with mortality were: male sex [odds ratio (OR) = 5.25, confidence interval (CI) = 1.22–28.95], medical attention delayed 〉3 days (OR = 9.9, CI = 1.51–64.52), anti-flu therapy delayed 〉3 days (OR = 10.0, CI = 1.07–93.43), admission to intensive care unit (ICU) (OR = 9.9, CI = 1.51–64.52) and creatinine levels 〉1.0 mg/dL when admitted to hospital (OR = 11.2, CI = 1.05–120.32). After adjusting for the effects of potentially confounding variables in a logistic regression model, delayed medical attention (OR = 13.91, CI = 1.09–41.42, p = 0.044) and ICU hospitalization (OR = 11.02, CI = 1.59–76.25, p = 0.015) were the only predictors of mortality. Conclusion: Early medical attention is essential for reducing the mortality risk in patients with influenza A/H1N1, while a requirement for ICU management increases the risk.

Description: Background: Vitamin D (vitD) deficiency is linked to many disease states including rickets and cancer, and vitD supplementation to improve response to cancer therapy has been explored. Supplementation may be most appropriate for dogs with suboptimal vitD concentrations. In dogs, the primary source of vitD is diet (predominantly via commercial dog food). Our goal was to determine how food source and supplements affect 25(OH)D concentrations, the storage form of vitD. Serum was collected from clinically healthy dogs, and pet owners were surveyed about food source and supplements. Serum 25(OH)D concentration was measured using a quantitative chemiluminescent assay (LIASON, DiaSorin, Stillwater, MN). Results: Dogs (n = 320) were tested for serum 25(OH)D concentrations (range 9.5–249.2 ng/mL). Dogs were fed commercial diets from forty different manufactures (n = 292); additionally some dogs were fed homemade diets (n = 18) or a combination of commercial and homemade diets (n = 10). Median serum 25(OH)D concentrations in dogs fed commercial foods ranged from 47.4 to 100.1 ng/mL with an overall median of 67.9 ng/ml (CV 29 %). Analysis for differences among manufacturers was significant (P = 0.0006). Serum 25(OH)D concentrations amongst dogs fed homemade diets had the largest range (9.5–129 ng/mL) and the lowest value (9.5 ng/mL). Dogs receiving salmon oil as a supplement (n = 22) had significantly higher serum 25(OH)D (on average a 19.6 ng/mL increase) than those not receiving a supplement (P = 0.007). Conclusions: Serum 25(OH)D concentrations in dogs vary widely which likely reflects varying dietary vitD content. Notable differences exist among manufacturers and brands and may reflect differences in proprietary formulations. Given the variability of measured serum 25(OH)D concentrations in dogs and the importance vitD appears to have on health status, dietary vitD content should be optimized.

Description: Background: Determinants of waterpipe use in adolescents are believed to differ from those for other tobacco products, but there is a lack of studies of possible social, cultural, or psychological aspects of waterpipe use in this population. This study applied a socioecological model to explore waterpipe use, and its relationship to other tobacco use in Swedish adolescents. Methods: A total of 106 adolescents who attended an urban high-school in northern Sweden responded to an anonymous questionnaire. Prevalence rates for waterpipe use were examined in relation to socio-demographics, peer pressure, sensation seeking behavior, harm perception, environmental factors, and depression. Results: Thirty-three percent reported ever having smoked waterpipe (ever use), with 30 % having done so during the last 30 days (current use). Among waterpipe ever users, 60 % had ever smoked cigarettes in comparison to 32 % of non-waterpipe smokers (95 % confidence interval 1.4–7.9). The odds of having ever smoked waterpipe were three times higher among male high school seniors as well as students with lower grades. Waterpipe ever users had three times higher odds of having higher levels of sensation-seeking (95 % confidence interval 1.2–9.5) and scored high on the depression scales (95 % confidence interval 1.6–6.8) than non-users. The odds of waterpipe ever use were four times higher for those who perceived waterpipe products to have pleasant smell compared to cigarettes (95 % confidence interval 1.7–9.8). Waterpipe ever users were twice as likely to have seen waterpipe use on television compared to non-users (95 % confidence interval 1.1–5.7). The odds of having friends who smoked regularly was eight times higher for waterpipe ever users than non-users (95 % confidence interval 2.1–31.2). Conclusion: The current study reports a high use of waterpipe in a select group of students in northern Sweden. The study adds the importance of looking at socioecological determinants of use, including peer pressure and exposure to media marketing, as well as mental health among users.

Description: Background: Kaposi’s Sarcoma is the most common sarcoma and second most prevalent cancer seen in Tanzania. Little is known about Kaposi’s sarcoma in our setting as there is paucity of recent published data regarding this condition. This study describes the clinicopathological pattern and treatment outcome of Kaposi’s sarcoma at Bugando Medical Centre, a tertiary care hospital in northwestern Tanzania. Methods: This was a prospective study of histologically confirmed Kaposi’s sarcoma that was conducted at Bugando Medical Center between July 2004 and June 2014. Results: A total of 248 patients (M:F = 1.4:1) representing 2.4 % of all malignancies during the study period were enrolled into the study. The median age at presentation was 36 years. Females were younger than males (p = 0.04). Out of 248 patients, 122 (49.2 %) were HIV positive. Of these, 46 (37.7 %) were males and 76 (62.3 %) females. AIDS-related Kaposi’s sarcoma were younger than HIV negative Kaposi’s sarcoma patients (p = 0.011). Median duration of symptoms was 6 months. Kaposi’s sarcoma was the AIDS defining disease in 82 (67.2 %) patients while in the remaining 40 (32.8 %) it was diagnosed between 1 and 14 months after the initial diagnosis of AIDS. The lower limb was most frequently involved site in 28.9 % of patient. Females had more disseminated lesions compared with more localized lesions in the males (p = 0.001). The treatment modalities in this study included chemotherapy, radiotherapy, surgery and highly active antiretroviral therapy. Overall 126 (53.4 %) patients had significant improvement in quality of life at the end of 1 year follow up. Treatment related complication and mortality rates were 25.8 and 24.2 % respectively. Poor ACTG stage, CD4+ count

Description: Background: In Ontario, Canada, we conducted an evaluation of rotavirus (RV) vaccine on hospitalizations and Emergency Department (ED) visitations for acute gastroenteritis (AGE). In our original analysis, any one of the International Classification of Disease, Version 10 (ICD-10) codes was used for outcome ascertainment: RV-specific- (A08.0), viral- (A08.3, A08. 4, A08.5), and unspecified infectious- gastroenteritis (A09). Annual age-specific rates per 10,000 population were calculated.FindingsThe average monthly rate of AGE hospitalization for children under age two increased from 0.82 per 10,000 from January 2003 to March 2009, to 2.35 over the period of April 2009 to March 31, 2013. Similar trends were found for ED consultations and in other age groups. A rise in events corresponding to the A09 code was found when the outcome definition was disaggregated by ICD-10 code. Documentation obtained from the World Health Organization confirmed that a change in directive for the classification of unspecified gastroenteritis occurred with the release of ICD-10 in April 2009. AGE events previously classified under the code K52.9, are now classified under code A09.9. Conclusions: Based on change in the classification of unspecified gastroenteritis we modified our outcome definition to also include unspecified non-infectious-gastroenteritis (K52.9). We recommend other investigators consider using both A09.9 and K52.9 ICD-10 codes for outcome ascertainment in future rotavirus vaccine impact studies to ensure that all unspecified cases of AGE are captured, especially if the study period spans 2009.

Description: Recent studies have identified epithelial stem and progenitor cell populations of the lung. We are just beginning to understand the mechanisms that regulate their homeostatic, regenerative and maladaptive behaviors. Here, we discuss evidence of regulatory niches for epithelial stem cells of the lung.

Description: Background: Medication errors (MEs) are important problems in all hospitalized populations, especially in intensive care unit (ICU). Little is known about the prevalence of medication prescribing errors in the ICU of hospitals in Ethiopia. The aim of this study was to assess medication prescribing errors in the ICU of Tikur Anbessa Specialized Hospital using retrospective cross-sectional analysis of patient cards and medication charts. Results: About 220 patient charts were reviewed with a total of 1311 patient-days, and 882 prescription episodes. 359 MEs were detected; with prevalence of 40 per 100 orders. Common prescribing errors were omission errors 154 (42.89 %), 101 (28.13 %) wrong combination, 48 (13.37 %) wrong abbreviation, 30 (8.36 %) wrong dose, wrong frequency 18 (5.01 %) and wrong indications 8 (2.23 %). Conclusions: The present study shows that medication errors are common in medical ICU of Tikur Anbessa Specialized Hospital. These results suggest future targets of prevention strategies to reduce the rate of medication error.

Description: Background: Mitochondrial biogenesis and adequate energy production are important for embryogenesis and placentation. Previous studies documented alterations in maternal blood mitochondrial DNA (mtDNA) copy number—a marker of mitochondrial dysfunction—in pregnancies complicated by placental abruption. To further understand the role of mitochondrial dysfunction in the pathogenesis of placental abruption, we conducted a pilot study using placental specimen collected from 103 placental abruption cases and 102 non-abruption controls. Real-time quantitative polymerase chain reaction (PCR) was used to assess the relative copy number of mtDNA in DNA extracted from placental samples collected immediately after delivery. Logistic regression procedures were used to estimate adjusted odds ratios (OR) and 95 % confidence intervals (CI). Results: Higher odds of placental abruption was observed with increasing mtDNA copy number (p value for trend = 0.05). The odds of placental abruption was elevated among women who delivered placentas with higher mtDNA copy number (≥120.5, the median) as compared with those with lower values (

Description: Background: Evidence is lacking for what defines post-intubation hypotension in the intensive care unit (ICU). If a valid definition could be used, the potential exists to evaluate possible risk factors and thereby improve post-intubation. Thus, our objectives were to arrive at the best surrogate for post-intubation hypotension that accurately predicts both in-hospital and 90-day mortality in a population of ICU patients and to report mortality rates between the exposed and unexposed cohorts. Methods: We conducted a retrospective cohort study of emergent endotracheal intubations in a medical-surgical ICU from January 1, 2010 to December 31, 2011 to evaluate surrogates for post-intubation hypotension that would predict in-hospital and 90-day mortality followed by an analysis of exposed versus unexposed using our best surrogate. Patients were ≥18 years of age, underwent emergent intubation during their first ICU admission, and did not meet any of the surrogates 60 min pre-intubation. Results: The six surrogates evaluated 60 min post-intubation were those with any systolic blood pressures ≤90 mmHg, any mean arterial pressures ≤65 mmHg, reduction in median systolic blood pressures of ≥20 %, any vasopressor administration, any non-sinus rhythm and, fluid administration of ≥30 ml/kg. A total of 147 patients were included. Of the six surrogates, only the administration of any vasopressor 60 min post-intubation remained significant for mortality. Twenty-nine patients were then labeled as hemodynamically unstable and compared to the 118 patients labeled as hemodynamically stable. After adjusting for confounders, the hemodynamically unstable group had a significantly higher in-hospital and 90-day mortality [OR (95 % CI); 3.84 (1.31–11.57) (p value = 0.01) and 2.37 (1.18–4.61) (p-value = 0.02)]. Conclusions: Emergently intubated patients manifesting hemodynamic instability after but not before intubation, as measured by vasoactive administration 60 min post-intubation, have a higher association with in-hospital and 90-day mortality.

Description: Background: Insulinomas are rare pancreatic endocrine tumors. Most are benign and solitary. However, the nonspecific symptoms and small size of these tumors led to difficulties of diagnosis and localization.Case presentationWe present two Arab patients with pancreatic long-standing insulinoma. Both patients presented episodic hypoglycemic symptoms respectively during 10 and 2 years. Biochemical and morphological workup detected localized pancreatic insulinoma. Open procedure surgery was done for the two patients and insulinomas were successfully removed by enucleation. Conclusion: Insulinoma remains a diagnostic challenge to practitioners. Diagnosis of suspected cases is easily confirmed by standard endocrine tests, especially the supervised fasting test. Accurate preoperative localization is essential for more effective and safest surgery.

Description: Background: In this study, we hypothesized that TB co-infection independently increases the risk of poor treatment outcomes in such patients even if they are on antiretroviral therapy (ART). Therefore, this study was aimed at investigating this hypothesis among cohort of adult PLWHs in South West Ethiopia.MethodologyCohort study comparing the immunologic and clinical outcomes of 130 HIV/TB co-infected and 520 only HIV patients starting ART was enrolled. Chi square and student t test were used to compare outcome variables and logistic regression was used to assess the effect of TB on treatment failure. Results: In this study, TB co-infection didn’t increase immunologic failure even in univariate analysis at both 6 [OR, 1.10 (0.59–1.69), P = 0.85] and 12 months [OR, 1.06 (0.58–1.93), P = 0.89] of ART initiation. However, it increased the risk of clinical failure at both 6 [Adjusted Odd Ratio (AOR), 2.90 (1.41–6.09), P = 0.028] and 12 months [AOR, 2.93 (1.41–6.09), P = 0.004] of ART initiation. Conclusion: This study showed that TB co-infection didn’t adversely affect the immunologic outcomes, weight and hemoglobin responses even though it increased the risk of clinical failure nearly three times. Therefore, beside the concern given for TB prevention and treatment, several patient and policy related factors need to be addressed to maximally benefit from highly active antiretroviral therapy rollout in resource limited settings.

Description: Background: Endocytosis of activated EGF receptor (EGFR) to specific endocytic compartments is required to terminate EGF signaling. Trafficking of EGFR relies on microtubule tracks that transport the cargo vesicle to their intermediate and final destinations and can be modulated through posttranslational modification of tubulin including acetylation. Na,K-ATPase maintains intracellular sodium homeostasis, functions as a signaling scaffold and interacts with EGFR. Na,K-ATPase also binds to and is regulated by acetylated tubulin but whether there is a functional link between EGFR, Na,K-ATPase and tubulin acetylation is not known. Results: EGF-induced sodium influx regulates EGFR trafficking through increased microtubule acetylation. Increased sodium influx induced either by sodium ionophores or Na,K-ATPase blockade mimicked the EGF-induced effects on EGFR trafficking through histone deacetylase (HDAC) 6 inactivation and accumulation of acetylated tubulin. In turn, blocking sodium influx reduced tubulin acetylation and EGF-induced EGFR turnover. Knockdown of HDAC6 reversed the effect of sodium influx indicating that HDAC6 is necessary to modulate sodium-dependent tubulin acetylation. Conclusions: These studies provide a novel regulatory mechanism to attenuate EGFR signaling in which EGF modulates EGFR trafficking through intracellular sodium-mediated HDAC6 inactivation and tubulin acetylation.

Description: Background: Earlier studies suggest that knowledge about Autism Spectrum Disorder (ASD) among healthcare workers in Nigeria is low. This present study assessed the knowledge of Nigerian final year medical students about symptoms of ASD and some other aspects of ASD. This is a cross sectional descriptive study that drew a total of seven hundred and fifty-seven (757) final year medical students from ten (10) randomly selected fully accredited medical schools out of a total of twenty-seven (27) fully accredited medical schools in Nigeria. Sociodemographic and Knowledge about Childhood Autism among Health Workers (KCAHW) questionnaires were used to assess knowledge of final year medical students about ASD and obtain demographic information. Results: Only few, 218 (28.8 %) of the 757 final year medical students had seen and participated in evaluation and management of at least a child with ASD during their clinical postings in pediatrics and psychiatry. Knowledge and recognition of symptoms of ASD is observed to be better among this group of final year medical students as shown by higher mean scores in the four domains of KCAHW questionnaire. Knowledge about ASD varies across gender and regions. Misconceptions about ASD were also observed among the final year medical students. Conclusions: More focus needs to be given to ASD in the curriculum of Nigerian undergraduate medical students, especially during their psychiatry and pediatric clinical postings.

Description: Background: Recently United States (US) medical schools have implemented curricular reforms to address issues of character in medical education. Very few studies have examined students’ opinions about the importance of character development in medical school. This cross-sectional study assessed US medical students’ opinions regarding character-focused education and their experiences receiving character feedback from educators. We mailed a questionnaire to 960 third year medical students from 24 medical schools. Respondents received a second questionnaire during their fourth year. Students answered three items that assessed their opinions regarding character development in medical education. They also indicated the frequency of positive/negative feedback regarding their character traits. We also tested associations between these opinions and various demographic, religious and spiritual characteristics. We used the χ 2 test to examine bivariate associations between each demographic/religious characteristic and students’ opinions on character development or feedback. Results: Excluding 41 ineligible respondents, the adjusted response rate for the first questionnaire was 61 % (n = 564/919) and 84 % (n = 474/564) for the follow-up questionnaire. Twenty-eight percent of students agreed that one could be a good physician without being a good person; 39 % agreed that educators should focus on science instead of students’ characters; 72 % agreed that it was educators’ responsibility to train students to have good character; 1 % of students reported no positive feedback from faculty regarding character traits; 50 % reported no negative feedback. Conclusions: US students in clinical clerkships receive predominately positive feedback from educators regarding character traits. A majority of medical students, regardless of demographic and religious characteristics, are receptive to the role of character development in medical education. This finding suggests that character-based approaches toward ethics and professionalism training may find renewed receptivity among medical students despite recent “professionalism movement” fatigue.

Description: Background: In the Dutch 2007–2009 Q fever outbreak Coxiella burnetii was transmitted aerogenically from dairy goat farms to those living in the surrounding areas. Relatively few children were reported. The true number of pediatric infections is unknown. In this study, we estimate the expected number of acute and chronic childhood infections. Methods: As Coxiella was transmitted aerogenic to those living near infected dairy goat farms, we could use adult seroprevalence data to estimate infection risk for inhabitants, children and adults alike. Using Statistics Netherlands data we estimated the number of children at (high) risk for developing chronic Q fever. Literature was reviewed for childhood (0–15 years) Q fever reports and disease rates. We compared this with Dutch reported and our estimated data for 2007–2009. Results: In The Netherlands epidemic, 44 children were reported (1.2 % of total notifications). The childhood incidence was 0.15 compared to 2.6 per 10,000 inhabitants for adults. No complications were reported. Based on the expected similarity in childhood and adult exposure we assume that 9.8 % of children in the high-risk area had Q fever infection, resulting in 1562 acute infections during the Q fever epidemic interval. Based on the prevalence of congenital heart disease, at least 13 children are at high risk for developing chronic Q fever. In medical literature, 42 case reports described 140 childhood Q fever cases with a serious outcome (four deaths). In chronic Q fever, cardiac infections were predominant. Four outbreaks were reported involving children, describing 11 childhood cases. 36 National and/or regional studies reported seroprevalences varying between 0 and 70 %. Conclusion: In the 3-year Dutch epidemic, few childhood cases were reported, with pulmonary symptoms leading, and none with a serious presentation. With an estimated 13 high-risk children for chronic infection in the high exposure area, and probably forty in the whole country, we may expect several chronic Q fever complications in the coming years in paediatric practice.

Description: Background: Workplace health promotion is focussed on improving the health and wellbeing of workers. Although quantifiable effectiveness and economic evidence is variable, workplace health promotion is recognised by both government and business stakeholders as potentially beneficial for worker health and economic advantage. Despite the current debate on whether conclusive positive outcomes exist, governments are investing, and business engagement is necessary for value to be realised. Practical tools are needed to assist decision makers in developing the business case for workplace health promotion programs. Our primary objective was to develop an evidence-based, simple and easy-to-use resource (calculator) for Australian employers interested in workplace health investment figures. Results: Three phases were undertaken to develop the calculator. First, evidence from a literature review located appropriate effectiveness measures. Second, a review of employer-facilitated programs aimed at improving the health and wellbeing of employees was utilised to identify change estimates surrounding these measures, and third, currently available online evaluation tools and models were investigated. We present a simple web-based calculator for use by employers who wish to estimate potential annual savings associated with implementing a successful workplace health promotion program. The calculator uses effectiveness measures (absenteeism and staff turnover rates) and change estimates sourced from 55 case studies to generate the annual savings an employer may potentially gain. Australian wage statistics were used to calculate replacement costs due to staff turnover. The calculator was named the Workplace Health Savings Calculator and adapted and reproduced on the Healthy Workers web portal by the Australian Commonwealth Government Department of Health and Ageing. Conclusion: The Workplace Health Savings Calculator is a simple online business tool that aims to engage employers and to assist participation, development and implementation of workplace health promotion programs.

Description: Background: Vitamin B 12 deficiency is often diagnosed with hematological manifestations of megaloblastic macrocytic anemia, which is usually the initial presentation. Neurological symptoms are often considered to be late manifestations and usually occur after the onset of anemia. Sub acute combined cord degeneration, which is a rare cause of myelopathy is however the commonest neurological manifestation of vitamin B 12 deficiency.Case presentationWe present a case of a 66 year old Sinhalese Sri Lankan female, who is a strict vegetarian, presenting with one month’s history suggestive of Sub-acute combined cord degeneration in the absence of haematological manifestations of anaemia. Her Serum B 12 levels were significantly low, after which she was treated with hydroxycobalamine supplementation, showing marked clinical improvement of symptoms, with normalization of serum B 12 levels. Hence, the diagnosis of vitamin B 12 deficiency was confirmed retrospectively. Conclusion: Vitamin B 12 deficiency could rarely present with neurological manifestations in the absence of anaemia. Therefore a high index of suspicion is necessary for the early diagnosis and prompt treatment in order to reverse neurological manifestations, as the response to treatment is inversely proportionate to the severity and duration of the disease.

Description: Background: Recent data suggest that the prevalence of obesity and its associate cardiometabolic risks are increasing in Bangladesh. Published data of obesity in Bangladeshi industry workers is scarce. The purpose of this study was to assess the prevalence of general and central obesity in Bangladeshi factory workers and their associations with diabetes and hypertension. Methods: A total of 791 male factory workers aged ≥20 years in capital Dhaka city of Bangladesh were investigated in a population-based cross-sectional survey. According to the International Association for the Study of Obesity and the International Obesity Task Force guidelines for Asian population, general obesity was defined as body mass index (BMI) ≥25 kg/m 2 , central obesity was defined as a waist circumference (WC) of ≥90 cm and waist hip ratio (WHR) of ≥0.90. Pearson’s correlation coefficient and logistic regression analysis were used to observe the association between anthropometric indices (BMI, WC and WHR) and cardiometabolic risk indicators (FBG, 2hBG, SBP and DBP). Results: The prevalence of overweight (BMI 23–24.9 kg/m 2 ) and general obesity (BMI ≥25 kg/m 2 ) in this study population was 29.8 and 43.5 % respectively. Central obesity defined by WC and WHR was 35.3 and 78.3 % respectively. Both general and central obesity were found to be significantly associated with diabetes and hypertension in separate logistic regression analyses. Conclusion: The prevalence of general and central obesity in Bangladeshi factory workers was high, and it was associated with diabetes and hypertension.

Description: Background: Venous access, a prerequisite for anesthesiological and surgical intervention in pediatric patients, is often difficult to establish and potentially painful. AV300 uses near infrared laser light to improve visibility of peripheral veins and could help cannulating them. The aim of this study was to examine if use of Accuvein ® AV300 vein viewer could facilitate venous cannulation in children. Methods: From January to March 2011, 238 consecutive pediatric patients (0–17 years) preceding surgical interventions were included. All participants including newborns, infants and children were allocated to groups [control group (124 patients) and intervention group (114 patients)] in a non-random way. Randomization was not feasible because data was acquired retrospectively from a clinical quality management project. In control group, peripheral IV cannulation was performed without supporting device, in intervention group with support of AV300. Time and number of attempts until successful venous cannulation were defined as primary end points. Results: Median time until successful cannulation was 2 min (range 0.1–20, quartiles: 25 %: 1; 75 %: 5) in the intervention group and 1 min (range 0.1–18, quartiles: 25 %: 0.2; 75 %: 2) in the control group (p 

Description: Background: Recent advances in molecular genetics have enabled to determine the genetic causes of non-syndromic hearing loss, and more than 100 genes have been related to the phenotype. Due to this extraordinary genetic heterogeneity, a large percentage of patients remain without any molecular diagnosis. This condition imply the need for new methodological strategies in order to detect a greater number of mutations in multiple genes. In this work, we optimized and tested a panel of 86 mutations in 17 different genes screened using a high-throughput genotyping technology to determine the molecular etiology of hearing loss. Methods: The technology used in this work was the MassARRAY iPLEX® platform. This technology uses silicon chips and DNA amplification products for accurate genotyping by mass spectrometry of previous reported mutations. The generated results were validated using conventional techniques, as direct sequencing, multiplex PCR and RFLP-PCR. Results: An initial genotyping of control subjects, showed failures in 20 % of the selected alterations. To optimize these results, the failed tests were re-designed and new primers were synthesized. Then, the specificity and sensitivity of the panel demonstrated values above 97 %. Additionally, a group of 180 individuals with NSHL without a molecular diagnosis was screened to test the diagnostic value of our panel, and mutations were identified in 30 % of the cases. In 20 % of the individuals, it was possible to explain the etiology of the HL. Mutations in GJB2 gene were the most prevalent, followed by other mutations in in SLC26A4, CDH23, MT-RNR1, MYO15A, and OTOF genes. Conclusions: The MassARRAY technology has the potential for high-throughput identification of genetic variations. However, we demonstrated that optimization is required to increase the genotyping success and accuracy. The developed panel proved to be efficient and cost-effective, being suitable for applications involving the molecular diagnosis of hearing loss.

Description: Background: Prenatal screening tests for Down syndrome (DS) are routine in many developed countries and new tests are rapidly becoming available. Decisions about prenatal screening are increasingly complex with each successive test, and pregnant women need information about risks and benefits as well as clarity about their values. Decision aids (DAs) can help healthcare providers support women in this decision. Using an environmental scan, we aimed to identify publicly available DAs focusing on prenatal screening/diagnosis for Down syndrome that provide effective support for decision making. Methods: Data sources searched were the Decision Aids Library Inventory (DALI) of the Ottawa Patient Decision Aids Research Group at the Ottawa Health Research Institute; Google searches on the internet; professional organizations, academic institutions and other experts in the field; and references in existing systematic reviews on DAs. Eligible DAs targeted pregnant women, focused on prenatal screening and/or diagnosis, applied to tests for fetal abnormalities or aneuploidies, and were in French, English, Spanish or Portuguese. Pairs of reviewers independently identified eligible DAs and extracted characteristics including the presence of practical decision support tools and features to aid comprehension. They then performed quality assessment using the 16 minimum standards established by the International Patient Decision Aids Standards (IPDASi v4.0). Results: Of 543 potentially eligible DAs (512 in DALI, 27 from experts, and four on the internet), 23 were eligible and 20 were available for data extraction. DAs were developed from 1996 to 2013 in six countries (UK, USA, Canada, Australia, Sweden, and France). Five DAs were for prenatal screening, three for prenatal diagnosis and 12 for both). Eight contained values clarification methods (personal worksheets). The 20 DAs scored a median of 10/16 (range 6–15) on the 16 IPDAS minimum standards.DiscussionNone of the 20 included DAs met all 16 IPDAS minimum standards, and few included practical decision support tools or aids to comprehension. Conclusions: Our results indicate there is a need for DAs that effectively support decision making regarding prenatal testing for Down syndrome, especially in light of the recently available non-invasive prenatal screening tests.

Description: Background: Self-rating instruments which require a large number of repeated assessments over time are increasingly popular in psychiatry. They are well suited to describing variations in mental states, especially in order to investigate effects of behaviour and events on functioning and mood. For bipolar disorder, the self-rating instrument ‘NIMH daily life chart’ was developed to assess the course of the illness. This instrument has been validated in the customary ways, yet information about data quality (e.g. completeness, consistency, construct validity, reactivity) was lacking. The goal of this study was to develop several data quality indicators computed from data, in order to be able to detect respondents that provide less valid or reliable data. Methods: During approximately 1 year on average, 137 patients with DSM-IV diagnosed bipolar disorder rated their mood, functioning and number of alcohol units consumed on a daily basis. Three kinds of quality indicators were developed: (1) compliance (i.e. completeness of recording on a daily basis), (2) the association between conceptually related variables—construct validity—and (3) reactivity: any changes in alcohol-drinking behaviour due to the assessments themselves. Relations were measured with Spearman’s rho. Results: A relation was found between data quality and illness severity: respondents with lower data quality, according to our operationalisations, were more strongly affected by the illness, as expressed in the number of ill days, than respondents with higher data quality. Conclusion: The more affected patients are by the illness, the lower the data quality to be expected in life chart reports.

Description: Background: Three equine influenza viruses, A/equine/Nador/1/1997(H3N8), A/equine/Essaouira/2/2004(H3N8), and A/equine/Essaouira/3/2004(H3N8), were isolated from different Equidae during local respiratory disease outbreaks in Morocco in 1997 and 2004. Their non-structural (NS) genes were amplified and sequenced. Results: The results show high homology of NS nucleotide sequences of A/equine/Nador/1/1997 with European strains (i.e., A/equine/newmarket/2/93 and A/equine/Grobois/1/1998) and clustered into the European lineage. However, NS gene of A/equine/Essaouira/2/2004(H3N8) and A/equine/Essaouira/3/2004(H3N8) strains indicated high homology with equine influenza strains that had circulated before 1990 (A/equine/Fontainbleu/1/1979(H3N8), which belonged to a pre-divergent phase Amino acid sequence comparison of the NS1 protein with reference strain A/equine/Miami/1963(H3N8) shows that the A/equine/Nador/1/1997(H3N8) strain has 12 substitutions at the residues D/24/N, R/44/K, S/48/I, R/67/Q, A/86/V, E/139/K, A/112/T, E/186/K, L/185/F, A/223/E, S/213/T and S/228/P. In both A/equine/Essaouira/2/2004(H3N8) and A/equine/Essaouira/3/2004(H3N8) strains, the NS1 sequences present one common mutation at the residue: S/228/P. Conclusion: It seems that all of these substitutions are not produced at the key residues of the RNA-binding domain (RBD) and the effector domain (ED). Consequently, we can suppose that they will not affect the potency of inhibition of cellular defences, and the virulence of the Moroccan equine strains will be maintained.

Description: Background: Childhood cancer becomes a public health problem in developing countries which aggravates the burden of childhood mortality by infectious diseases and malnutrition. In poor countries, the death rate for most pediatric cancers is almost 100 %. This study attempts to determine the magnitude, patterns and trends of pediatric malignancies in the study area which is important in re-evaluating existing services and in improving facilities and patient care. Methods: A retrospective study of 3 year period were carried out among all children aged below 15 years old admitted into the pediatric wards of Gondar University Hospital, Northwest Ethiopia. The charts of all children aged below 15 years old admitted in the pediatric wards due to cancer were reviewed by using the data collection format. Data were entered and analyzed using SPSS version 20 statistical package.ResultA total of 71 cancer cases were diagnosed and admitted to the pediatrics ward during the study period. More than two-third of the study subjects 50 (70.4 %) were males. The mean age of study subjects was 7 ± 4 year where majority 26 (36.6 %) of the study subjects were ≥10 years. Of all, 43 (60.6 %) were hematological malignancy followed by Wilms tumor 13 (18.3 %), Neuroblastoma 5 (7 %), Rhabdomyosarcoma 3 (4.2 %), Brain tumor 3 (4.2 %), Hepatoblastoma 2 (2.8 %). More than two-third of cases were found to be concomitantly malnourished being stunted, wasted and under weight. Nearly half of patients had not received chemotherapy and majority of those started chemotherapy did not complete all the treatment cycles. Shortage and absence of safe and affordable chemotherapy drugs were the major reasons for therapy interruption. Conclusion: The study shows increasing childhood cancer cases over the years. Hematological malignancy takes the leading prevalence followed by Wilms tumor and Neuroblastoma. The majority of cases were also discharged without any clinical change that had the only death option. Therefore, the government and the hospital should give emphasis to establish cancer therapy centers and insure accessibility and affordability of chemotherapy drugs.

Description: Background: Retrorectal tumors in adults are very rare and little known condition. These tumors, often misdiagnosed or mistreated, should be completely excised because of the potential for malignancy or infection. A suitable operative approach is the key to the successful surgical management.Case presentationWe report the case of a 45-year-old Arab male who presented with chronic pelvic pain accompanied by straining to defecate and dysuria. The clinical examination showed a painless mass in the left perineal area. Pelvic magnetic resonance imaging and computed tomography scan demonstrated a huge and well-limited pelvic mass causing displacement and compression of the rectum and bladder. Although the large size of the mass (〉7 cm in the greater diameter), it was successfully and completely excised through only perineal approach without undertaking coccygectomy or sacrectomy. The histopathological study revealed a low-grade leiomyosarcoma. The patient is currently in 4-years follow-up with no signs of recurrence or metastasis. Conclusion: Even large retro-rectal tumors may be successfully excised by the perineal approach especially in carefully selected patients, but require extensive knowledge of pelvic anatomy and expertise in pelvic surgery.

Description: Background: To investigate significant association between various clinical and extra-clinical factors brought out the activities of Consultation-Liaison Service. Methods: Data from all psychiatric consultations for patients admitted to the Perugia General Hospital and carried out over a 1-year period (from July the 1st 2009 to June the 30th 2010) were collected by a structured clinical report including: socio-demographic features, features of referrals, features of back-referrals. T-test, Mann–Whitney U-test, χ 2 -test and Fischer’s were statistically used. Results: 1098 consultations were performed. The consultations carried out the Emergency Unit were excluded from the study. The type and the reasons for the referrals were discussed such as the ICD-10 diagnosis and the liaison interventions too. Significant associations emerged between gender and: social status and occupation (p 

Description: Background: In times of rapidly increasing numbers of immunological approaches entering the clinics, antigen delivery becomes a pivotal process. The genuine way of rendering antigen presenting cells (APC) antigen specific, largely influences the outcome of the immune response. Short peptides bear the demerit of HLA restriction, whereas the proper way of delivery for long peptide sequences is currently a matter of debate. Electroporation is a reliable method for antigen delivery, especially using nucleic acids. The nucleofection process is based on this approach with the twist of further ensuring delivery also into the nucleus. Beside the form of antigen, the type of APC used for immune response induction may be crucial. Dendritic cells (DC) are by far the most commonly used APC; however B cells have entered this field as well and have gained wide acceptance. Results: In this study, we compared B cells to DC with regard to nucleofection efficiency and intensity of resulting antigen expression. APC were transfected either with plasmid DNA containing the reporter gene green fluorescent protein (GFP) or directly with in vitro-transcribed (IVT) GPF mRNA as a surrogate antigen. Out of nearly 100 different nucleofection programs tested, the top five for each cell type were identified and validated using cells from cancer patients. Flow cytometric analyses of transfected cells determining GFP expression and viability revealed a reverse correlation of efficiency and viability. Finally, donor dependant variances were analyzed. Conclusion: In summary, nucleofection of both DC and B cells is feasible with plasmid DNA and IVT mRNA. And no differences with regard to nucleofectability were observed between the two cell types. Using IVT mRNA omits the danger of genomic integration and plasmid DNA constructs permit a more potent and longer lasting antigen expression.

Description: Background: Kikuchi–Fujimoto disease is so named because Kikuchi and Fujimoto were the first scientists to describe it in Japan in 1972. Although the disease has been reported from all over the world and more so from Asia, it is rare. To date only eight cases have been reported from Nepal. Cervical lymphadenopathy, fever and raised Erythrocyte Sedimentation Rate are usual presenting features of this disease. We describe a case which presented with thrombocytopenia and axillary lymphadenopathy in addition to the usual features. Out of the total eight cases that have been reported from Nepal so far, no patients had thrombocytopenia and only one patient had axillary lymphadenopathy.Case presentationA 24-year-old Nepali female presented with a 3-week history of low-grade fever, headache, and painful, discrete, unilateral left-sided cervical and axillary lymphadenopathy. Among the multitude of tests that were carried out, Erythrocyte Sedimentation Rate was raised and there was thrombocytopenia while other tests were normal. Painful lymphadenopathy pointed to bacterial lymphadenitis while chronic low-grade fever suggested tuberculosis. A cervical lymph node was excised for histopathological examination to reach an accurate diagnosis. On the basis of pathognomonic features viz., paracortical foci composed of various types of histiocytes including crescentic type in the background of abundant apoptotic karyorrhectic debris, a diagnosis of Kikuchi–Fujimoto disease was made. On follow-up evaluation after 6 weeks, the patient had no systemic symptoms, enlarged lymph nodes had regressed in size significantly, and Erythrocyte Sedimentation Rate and platelet count had become normal. Conclusion: Kikuchi–Fujimoto disease should be kept in the differential diagnosis of lymphadenopathy in young patients, female or male even in tuberculosis-endemic countries and even in patients who have unusual features; for example thrombocytopenia and involvement of axillary lymph nodes in addition to cervical lymph nodes as in this case.

Description: Background: Gastrointestinal stromal tumors (GIST) recently have been recognized as a genetically and biologically heterogeneous disease. In addition to KIT or PDGFRA mutated GIST, mutational inactivation of succinate dehydrogenase (SDH) subunits has been detected in the KIT/PDGFRA wild-type subgroup, referred to as SDH deficient (dSDH). Even though most dSDH GIST harbor mutations in SDHx subunit genes, some are SDHx wild type.Epigenetic regulation by DNA methylation of CpG islands recently has been found to be an alternative mechanism underlying the lack of SDH complex in GIST.Case presentationWe report a particular case of dSDH GIST, previously analyzed with microarrays and next-generation sequencing, for which no molecular pathogenetic events have been identified. Gene expression analysis showed remarkable down-modulation of SDHC mRNA with respect to all other GIST samples, both SDHA-mutant and KIT/PDGFRA-mutant GIST. By a bisulfite methylation assay targeted to 2 SDHC CpG islands, we detected hypermethylation of the SDHC promoter. Conclusion: Herein we report an additional case of dSDH GIST without SDHx mutation but harboring hypermethylation in the SDHC promoter, thus confirming the complexity of the molecular background of this subtype of GIST.

Description: Background: Familial hypercholesterolemia (FH) is one of the commonest monogenic disorders, predominantly inherited as an autosomal dominant trait. When untreated, it results in early coronary heart disease. The vast majority of FH remains undiagnosed in Latvia. The identification and early treatment of affected individuals remain a challenge worldwide. Most cases of FH are caused by mutations in one of four genes, APOB, LDLR, PCSK9, or LDLRAP1. The spectrum of disease-causing variants is very diverse and the variation detection panels usually used in its diagnosis cover only a minority of the disease-causing gene variants. However, DNA-based tests may provide an FH diagnosis for FH patients with no physical symptoms and with no known family history of the disease. Here, we evaluate the use of targeted next-generation sequencing (NGS) to identify cases of FH in a cohort of patients with coronary artery disease (CAD) and individuals with abnormal low-density lipoprotein–cholesterol (LDL–C) levels. Methods: We used targeted amplification of the coding regions of LDLR, APOB, PCSK9, and LDLRAP1, followed by NGS, in 42 CAD patients (LDL–C, 4.1–7.2 mmol/L) and 50 individuals from a population-based cohort (LDL–C, 5.1–9.7 mmol/L). Results: In total, 22 synonymous and 31 nonsynonymous variants, eight variants in close proximity (10 bp) to intron–exon boundaries, and 50 other variants were found. We identified four pathogenic mutations (p.(Arg3527Gln) in APOB, and p.(Gly20Arg), p.(Arg350*), and c.1706–10G 〉 A in LDLR) in seven patients (7.6 %). Three possible pathogenic variants were also found in four patients. Conclusion: NGS-based methods can be used to detect FH in high-risk individuals when they do not meet the defined clinical criteria.

Description: Background: In Ethiopia, where malaria and schistosomiasis are co-endemic, co-infections are expected to be high. However, data about the prevalence of malaria-schistosomiasis co-infection and their clinical correlation is lacking. Therefore, the aim of this study was to assess prevalence of Schistosoma mansoni co-infection and associated clinical correlates in malaria patients. Methods: A cross-sectional study was conducted in 2013 at Chwahit Health Center, in northwest Ethiopia. Blood film positive malaria patients (N = 205) were recruited for the study. Clinical, parasitological, hematological, and biochemical parameters were assessed from every study participant. Stool samples were also collected and processed with Kato-Katz technique to diagnose and classify intensity of Schistosoma mansoni. Results: The prevalence of Schistosoma mansoni and malaria co-infection was 19.5 %. The age group of 16–20 years old was significantly associated with co-infection. Co-infected patients with a moderate-heavy egg burden of Schistosoma mansoni had significantly high mean Plasmodium parasitemia. On the other hand, age group of 6–10 years old and moderate-heavy Schistosoma mansoni co-infection were significantly associated with severe malaria. Conclusions: Prevalence of malaria and Schistosoma mansoni co-infection in the study area was considerably high. Severity of malaria and parasitemia of Plasmodium were associated with certain age groups and intensity of concurrent Schistosoma mansoni. Further study is needed to explore the underlying mechanisms of interaction between malaria and Schistosoma mansoni.

Description: Background: A plethora of publicly available biomedical resources do currently exist and are constantly increasing at a fast rate. In parallel, specialized repositories are been developed, indexing numerous clinical and biomedical tools. The main drawback of such repositories is the difficulty in locating appropriate resources for a clinical or biomedical decision task, especially for non-Information Technology expert users. In parallel, although NLP research in the clinical domain has been active since the 1960s, progress in the development of NLP applications has been slow and lags behind progress in the general NLP domain.The aim of the present study is to investigate the use of semantics for biomedical resources annotation with domain specific ontologies and exploit Natural Language Processing methods in empowering the non-Information Technology expert users to efficiently search for biomedical resources using natural language. Methods: A Natural Language Processing engine which can “translate” free text into targeted queries, automatically transforming a clinical research question into a request description that contains only terms of ontologies, has been implemented. The implementation is based on information extraction techniques for text in natural language, guided by integrated ontologies. Furthermore, knowledge from robust text mining methods has been incorporated to map descriptions into suitable domain ontologies in order to ensure that the biomedical resources descriptions are domain oriented and enhance the accuracy of services discovery. The framework is freely available as a web application at (http://calchas.ics.forth.gr/). Results: For our experiments, a range of clinical questions were established based on descriptions of clinical trials from the ClinicalTrials.gov registry as well as recommendations from clinicians. Domain experts manually identified the available tools in a tools repository which are suitable for addressing the clinical questions at hand, either individually or as a set of tools forming a computational pipeline. The results were compared with those obtained from an automated discovery of candidate biomedical tools. For the evaluation of the results, precision and recall measurements were used. Our results indicate that the proposed framework has a high precision and low recall, implying that the system returns essentially more relevant results than irrelevant. Conclusions: There are adequate biomedical ontologies already available, sufficiency of existing NLP tools and quality of biomedical annotation systems for the implementation of a biomedical resources discovery framework, based on the semantic annotation of resources and the use on NLP techniques. The results of the present study demonstrate the clinical utility of the application of the proposed framework which aims to bridge the gap between clinical question in natural language and efficient dynamic biomedical resources discovery.

Description: Background: The endogenous ability to dedifferentiate, re-pattern, and re-differentiate adult cells to repair or replace damaged or missing structures is exclusive to only a few tetrapod species. The Mexican axolotl is one example of these species, having the capacity to regenerate multiple adult structures including their limbs by generating a group of progenitor cells, known as the blastema, which acquire pattern and differentiate into the missing tissues. The formation of a limb regenerate is dependent on cells in the connective tissues that retain memory of their original position in the limb, and use this information to generate the pattern of the missing structure. Observations from recent and historic studies suggest that blastema cells vary in their potential to pattern distal structures during the regeneration process; some cells are plastic and can be reprogrammed to obtain new positional information while others are stable. Our previous studies showed that positional information has temporal and spatial components of variation; early bud (EB) and apical late bud (LB) blastema cells are plastic while basal-LB cells are stable. To identify the potential cellular and molecular basis of this variation, we compared these three cell populations using histological and transcriptional approaches. Results: Histologically, the basal-LB sample showed greater tissue organization than the EB and apical-LB samples. We also observed that cell proliferation was more abundant in EB and apical-LB tissue when compared to basal-LB and mature stump tissue. Lastly, we found that genes associated with cellular differentiation were expressed more highly in the basal-LB samples. Conclusions: Our results characterize histological and transcriptional differences between EB and apical-LB tissue compared to basal-LB tissue. Combined with our results from a previous study, we hypothesize that the stability of positional information is associated with tissue organization, cell proliferation, and pathways of cellular differentiation.

Description: Background: Photosynthesis is the key process for plant growth and development. The determination of chlorophyll fluorescence kinetics allows the quantification of effects on photosynthetic processes triggered by environmental stress factors such as, e.g., the infection by fungal phytopathogens. The technique is non-invasive, rapid and well suited for experimental field work. Results: Healthy and Uromyces-infected plants of Euphorbia cyparissias were monitored directly in situ in the field using rapid fluorescence kinetics. Non-infected healthy plants show a typical maximum value for the relative variable fluorescence F v /F m of around 0.8 with occasional variation between the leaves from the plant top towards the base, while infected plants exhibited a strong gradient to low values at the base. The photosynthetic performance index (PI) showed a higher heterogeneity within the leaves in both plant types. Conclusions: The non-invasive and rapid measurement of chlorophyll fluorescence induction allows characterizing the photosynthetic capacity of healthy and infected plants and of parts of them directly in the field. The PI, is highly sensitive not only concerning infection, but also towards other local environmental influences.

Description: Background: Phagocytosis activity of peripheral blood leukocytes in smokers or chronic obstructive pulmonary disease patients was found to be controversial and dependent on the phagocytic stimulus. Results: We demonstrated that long-term exposure to cigarette smoke in mice clearly suppressed the phagocytosis of granulocytes and monocytes from peripheral blood. Conclusions: Impaired phagocytosis activity of peripheral blood leukocytes may have a systemic effect and potentially contribute to smoking-associated diseases such as pneumonia and lung cancer.

Description: Background: Bilateral posterior fracture-dislocation of the shoulders is an uncommon complication of grand mal seizures. We report a case of bilateral posterior dislocation of the shoulders with proximal humeral fractures following epileptic seizures. A posterior fracture-dislocation of the shoulder is very rare and can be caused by epileptic seizures, trauma, electrocution or electroconvulsive therapy.Case presentationA 62-year-old Sri Lankan male was admitted to our medical unit following four repeated generalized tonic–clonic convulsions, each lasting for several minutes. Following the second seizure he reported an inability to move both upper arms due to intense pain. There was no history of fall during the episodes of convulsions however but the bystanders have forcibly restrained his movements during the tonic–clonic convulsions. Clinical examination revealed severely restricted range of movement in both shoulders, with associated swelling and bruising of the shoulder joints and upper arms. Radiographs of the shoulders confirmed fractures at the level of surgical neck with posterior dislocation. Conclusion: Bilateral posterior fracture-dislocation of shoulders complicating epileptic seizures are rare. Forcible restraining of the patient’s upper limbs during seizures is the likely cause for the fracture dislocations in our patient and this had not been reported before.

Description: Background: The exacerbation of HIV-1 associated dyslipidemia seen in a subset of patients receiving anti-retroviral therapy suggests that genetic factors put these individuals at greater risk of cardiovascular disease. Single nucleotide polymorphisms (SNPs) within genes of and influencing the reverse cholesterol transport (RCT) pathway are associated with lipid levels but little is known regarding their copy number variation (CNV). This form of quantitative genetic variation has the potential to alter the amount of gene product made, thereby also influencing lipid metabolism. Results: To examine if CNV in RCT pathway genes was associated with altered serum lipid profiles in HIV-positive individuals receiving therapy, we designed a custom multiplex ligation-dependent probe amplification assay to screen 16 RCT genes within a subset of individuals from the Multicenter AIDS Cohort Study who show extreme lipid phenotypes. Verification of CNV was performed using a custom NanoString assay, and the Illumina HT-12 mRNA expression microarray was used to determine the influence of copy number on gene expression. Among the RCT genes, CNV was observed to be extremely rare. The only CNV seen was in the CETP gene, which showed a loss of copy in 1 of the 320 samples (0.3 %) in our study. The genes in our study showed little variation in expression between individuals, and the variation seen was not related to any detected CNV. Conclusions: Whole gene CNV is uncommon in RCT pathway genes, and not a major factor in the development of highly active antiretroviral therapy (HAART) associated dyslipidemia.

Description: Background: There is evidence that physicians’ prescription behavior is negatively affected by the extent of their interactions with pharmaceutical companies. In order to develop and implement policies and interventions for better management of interactions, we need to understand physicians’ perspectives on this issue. Surveys addressing physicians’ interactions with pharmaceutical companies need to use validated tools to ensure the validity of their findings.ObjectiveTo assess the validity of tools used in surveys of physicians about the extent and nature of their interactions with pharmaceutical companies, and about their knowledge, beliefs and attitudes towards such interactions; and to identify those tools that have been formally validated. Methods: We developed a search strategy with the assistance of a medical librarian. We electronically searched MEDLINE and EMBASE databases in September 2015. Teams of two reviewers conducted data selection and data abstraction. They identified eligible studies in one table and then abstracted the relevant data from the studies with validated tools in another table. Tables were piloted and standardized. Results: We identified one validated questionnaire out of the 11 assessing the nature and extent of the interaction, and three validated questionnaires out of the 47 assessing knowledge, beliefs and attitudes of physicians toward the interaction. None of these validated questionnaires were used in more than one survey. Conclusion: The available supporting evidence of the issue of physicians’ interaction with pharmaceutical company is of low quality. There is a need for research to develop and validate tools to survey physicians about their interactions with pharmaceutical companies.

Description: Background: The transcription factor 7-like 2 (TCF7L2) is one of the genes that have been identified as possible determinants of diabetes which is associated with obesity. Data on the genetic causes of obesity in sub-Saharan African populations are very scares. The aim of this study was to assess the association between the transcription factor 7-like 2 (TCF7L2) gene polymorphism (rs12255372 G/T) and obesity and weight-related traits in a Cameroonian population. Methods: A case–control study was conducted on 35 obese and 30 non-obese Cameroonian adults. TCF7L2 rs12255372 genotypes were determined using PCR–RFLP and correlated with BMI and weight-related traits. Results: No significant association was observed between the rs12255372 T allele (χ 2  = 0.0684, p = 0.79) or the TT genotype (χ 2  = 0.372, p = 0.54) of the TCF7L2 gene and obesity in the Cameroonian population. However, amongst the weight-related traits, triglycerides were significantly associated with the T risk allele of the TCF7L2 gene (p = 0.012). Conclusion: This study on Cameroonian subjects replicates the absence of association between the TCF7L2 rs12255372 variant and obesity as observed in European and American populations.