ALBERT

Description: Our aim is to explore general practitioners’ (GPs’) knowledge about EMF, and to assess whether different knowledge structures are related to the GPs’ concern about EMF. Random samples were drawn from lists of GPs in Germany in 2008. Knowledge about EMF was assessed by seven items. A latent class analysis was conducted to identify latent structures in GPs’ knowledge. Further, the GPs’ concern about EMF health risk was measured using a score comprising six items. The association between GPs’ concern about EMF and their knowledge was analysed using multiple linear regression. In total 435 (response rate 23.3%) GPs participated in the study. Four groups were identified by the latent class analysis: 43.1% of the GPs gave mainly correct answers; 23.7% of the GPs answered low frequency EMF questions correctly; 19.2% answered only the questions relating EMF with health risks, and 14.0% answered mostly “don’t know”. There was no association between GPs’ latent knowledge classes or between the number of correct answers given by the GPs and their EMF concern, whereas the number of incorrect answers was associated with EMF concern. Greater EMF concern in subjects with more incorrect answers suggests paying particular attention to misconceptions regarding EMF in risk communication.

Description: This study aims to explore the efficiency of using online education as an intervention measure to prevent occupational hazards in a clinical nursing setting. The subjects were 320 female nursing staff from two hospitals in Taiwan. The questionnaire results indicated that the subjects primarily experienced human factor occupational hazards, as well as psychological and social hazards. Specifically, 73.1% and 69.8% of the subjects suffered from poor sleep quality and low back pain, respectively. After web-based learning, the experimental group had higher post-test scores than the control group in terms of knowledge, attitudes, and practices (KAP). However, there was only a significant difference (p 〈 0.05) in their knowledge about the prevention of occupational hazards. It is suggested that an online discussion may enhance nursing staff’s participation in web-based learning, and further facilitate their comments on negative factors. The findings can highly promote nursing staff’s attitudes and practices toward preventing occupational hazards through web-based learning.

Description: Ambient particulate matters and temperature were reported to have additive effects over the respiratory disease hospital admissions and deaths. The purpose of this study is to discuss the interactive pulmonary toxicities of cold stress and fine particulate matter (PM2.5) exposure by estimating inflammation and oxidative stress responses. 48 Wistar male rats, matched by weight and age, were randomly assigned to six groups, which were treated with cold stress alone (0 °C, 10 °C, and 20 °C (Normal control)) and cold stresses plus PM2.5 exposures respectively. Cold stress alone groups were intratracheal instillation of 0.25 mL normal saline, while cold stress plus PM2.5 exposure groups were intratracheal instillation of 8 mg/0.25 mL PM2.5. These procedures were carried out for three times with an interval of 48 hours for each treatment. All rats were sacrificed after 48 hours of the third treatment. The bronchoalveolar lavage fluid (BALF) was collected for analyzing inflammatory cells and cytokines, and lung homogenate MDA was determined for oxidative stress estimation. Results showed higher level of total cell and neutrophil in the BALF of PM2.5 exposed groups (p 〈 0.05). Negative relationships between cold stress intensity and the level of tumor necrosis factor alpha (TNF-a), C-reactive protein (CRP) interleukin-6 (IL-6) and interleukin-8 (IL-8) in BALF were indicated in PM2.5 exposure groups. Exposure to cold stress alone caused significant increase of inflammatory cytokines and methane dicarboxylic aldehyde (MDA) and decline of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity only in 0 °C exposure group (p 〈 0.05). The two-way ANOVA found significant interactive effects between PM2.5 exposure and cold stress in the level of neutrophil, IL-6 and IL-8 and SOD activity (p 〈 0.05). These data demonstrated that inflammation and oxidative stress involved in the additive effect of PM2.5 exposure and cold stress on pulmonary toxicity, providing explanation for epidemiological studies on the health effect of ambient PM2.5 and cold stress.

Description: This paper presents a detailed description of an approach designed to investigate the application of the Health Impact Assessment (HIA) framework to assess the potential health impacts of climate change. A HIA framework has been combined with key climate change terminology and concepts. The fundamental premise of this framework is an understanding of the interactions between people, the environment and climate. The diversity and complexity of these interactions can hinder much needed action on the critical health issue of climate change. The objectives of the framework are to improve the methodology for understanding and assessing the risks associated with potential health impacts of climate change, and to provide decision-makers with information that can facilitate the development of effective adaptation plans. While the process presented here provides guidance with respect to this task it is not intended to be prescriptive. As such, aspects of the process can be amended to suit the scope and available resources of each project. A series of working tables has been developed to assist in the collation of evidence throughout the process. The framework has been tested in a number of locations including Western Australia, Solomon Islands, Vanuatu and Nauru.

Description: Background: The transcription factor Nrf2, encoded by the NFE2L2 gene, is an important regulator of the cellular protection against oxidative stress. Parkinson?s disease is a neurodegenerative disease highly associated with oxidative stress. In a previously published study, we reported associations of NFE2L2 haplotypes with risk and age at onset of idiopathic Parkinson?s disease in a Swedish discovery material and a Polish replication material. Here, we have extended the replication study and performed meta-analyses including the Polish material and four new independent European patient-control materials. Furthermore, all SNPs included in the haplotype windows were investigated individually for associations with Parkinson?s disease in meta-analyses including all six materials. Methods: Totally 1038 patients and 1600 control subjects were studied. Based on previous NFE2L2 haplotype associations with Parkinson?s disease, five NFE2L2 tag SNPs were genotyped by allelic discrimination and three functional NFE2L2 promoter SNPs were genotyped by sequencing. The impact of individual SNPs and haplotypes on risk and age at onset of Parkinson?s disease were investigated in each material individually and in meta-analyses of the obtained results. Results: Meta-analyses of NFE2L2 haplotypes showed association of haplotype GAGCAAAA, including the fully functional promoter haplotype AGC, with decreased risk (OR?=?0.8 per allele, p?=?0.012) and delayed onset (+1.1?years per allele, p?=?0.048) of Parkinson?s disease. These results support the previously observed protective effect of this haplotype in the first study. Further, meta-analyses of the SNPs included in the haplotypes revealed four NFE2L2 SNPs associated with age at onset of Parkinson?s disease (rs7557529 G?〉?A, ?1.0?years per allele, p?=?0.042; rs35652124 A?〉?G, ?1.1?years per allele, p?=?0.045; rs2886161 A?〉?G, ?1.2?years per allele, p?=?0.021; rs1806649 G?〉?A, +1.2?years per allele, p?=?0.029). One of these (rs35652124) is a functional SNP located in the NFE2L2 promoter. No individual SNP was associated with risk of Parkinson?s disease. Conclusion: Our results support the hypothesis that variation in the NFE2L2 gene, encoding a central protein in the cellular protection against oxidative stress, may contribute to the pathogenesis of Parkinson?s disease. Functional studies are now needed to explore these results further.

Description: Background: Most PCR-based diagnostics are still considered time- and labor-intensive due to disparate purification, amplification, and detection steps. Advancements in PCR enzymes and buffer chemistry have increased inhibitor tolerance, facilitating PCR directly from crude samples. Obviating the need for DNA purification, while lacking a concentration step, these direct sample methods are particularly apt for human genetic testing. However, direct PCR protocols have traditionally employed thermal cyclers with slow ramp rates and conservative hold times that significantly increase an assay?s time-to-result. For this proof-of-principle study, our objective was to significantly reduce sample preparation and assay time for a PCR-based genetic test, for myotonic dystrophy type 1 (DM1), by pairing an inhibitor-resistant enzyme mix with a rapid thermal cycler to analyze samples directly in whole blood. Methods: DM1 genetic screening was done with an adapted conventional PCR approach that employed the Streck Philisa? Thermal Cycler, the inhibitor-resistant NEBNext? High-Fidelity 2X PCR Master Mix, and agarose gel electrophoresis or an Agilent 2100 Bioanalyzer for detection. The Gene Link? Myotonic Dystrophy Genemer? Kit was used as a reference assay kit to evaluate the rapid assay. Results: In this work, a rapid and direct PCR assay testing 10% whole blood as template has been developed as an exclusionary screening assay for DM1, a triple-repeat genetic disorder. PCR amplification was completed in 15 minutes using 30 cycles, including in situ hot-start/cell lysis. Out of the 40 donors screened, this assay identified 23 (57.5%) as DM1 negative suggesting no need for further testing. These data are 100% concordant with data collected using the commercially available Gene Link Genemer? Kit per the kit-specific PCR protocol. Conclusions: The PCR assay described in this study amplified DM1 short tandem repeats in 15 minutes. By eliminating sample purification and slower conventional PCR protocols, we demonstrated how adaptation of current PCR technology and chemistries can produce a simple-to-use exclusionary screening assay that is independent of up-front sample prep, improving a clinical lab technician?s time-to-result. We envision this direct and rapid methodology could be applied to other conventional PCR-based genetic tests and sample matrices where genomic DNA is targeted for analysis within a given molecular diagnostic platform.

Description: Background: Marburg viruses have been responsible for a number of outbreaks throughout sub-Saharan Africa, as well as a number of laboratory infections. Despite many years of experience with the viruses, little is known about several important epidemiologic parameters relating to the development of Marburg virus disease. The analysis uses pooled data from all Marburg cases between 1967 and 2008 to develop estimates for the incubation period and the clinical onset serial interval (COSI). Methods: Data were obtained from original outbreak investigation forms (n = 406) and from published data (n = 45). Incubation periods were calculated for person-to-person exposure, for laboratory-acquired infections, and for presumed zoonotic exposures. Similar analysis was conducted for COSI, using only cases with unambiguous person-to-person transmission where both the primary and the secondary case patients had well-defined illness onsets. Results: Seventy-six cases were retained for the incubation period analysis. Incubation periods ranged from a minimum of 2 days in the case of two laboratory workers to a maximum of at least 26 days for a person-to-person household transmission. Thirty-eight cases were retained for COSI analysis. The median COSI was 11 days, with an interquartile range of 8 to 15. Conclusions: This study extends the maximum known incubation period of Marburg virus disease to 26 days. The analysis was severely hampered by a lack of completeness in epidemiologic data. It is necessary to prioritize obtaining more accurate epidemiologic data in future outbreaks; greater use of COSI may facilitate an improved understanding of outbreak dynamics in Marburg and other diseases.

Description: Climate change will increase the frequency and magnitude of extreme weather events and create risks that will impact health care facilities. Health care facilities will need to assess climate change risks and adopt adaptive management strategies to be resilient, but guidance tools are lacking. In this study, a toolkit was developed for health care facility officials to assess the resiliency of their facility to climate change impacts. A mixed methods approach was used to develop climate change resiliency indicators to inform the development of the toolkit. The toolkit consists of a checklist for officials who work in areas of emergency management, facilities management and health care services and supply chain management, a facilitator’s guide for administering the checklist, and a resource guidebook to inform adaptation. Six health care facilities representing three provinces in Canada piloted the checklist. Senior level officials with expertise in the aforementioned areas were invited to review the checklist, provide feedback during qualitative interviews and review the final toolkit at a stakeholder workshop. The toolkit helps health care facility officials identify gaps in climate change preparedness, direct allocation of adaptation resources and inform strategic planning to increase resiliency to climate change.

Description: The World Health Organization defines social determinants of health as “complex, integrated, and overlapping social structures and economic systems” that are responsible for most health inequities. Similar to the individual-level risk factors such as behavioral and biological risk factors that influence disease, we consider social determinants of health such as the distribution of income, wealth, influence and power as risk factors for risk of disease. We operationally define health inequity in a disease within a population due to a risk factor that is unfair and avoidable as the difference between the disease outcome with and without the risk factor in the population. We derive expressions for difference in health inequity between two populations due to a risk factor that is unfair and avoidable for a given disease. The difference in heath inequity between two population groups due to a risk factor increases with increasing difference in relative risks and the difference in prevalence of the risk factor in the two populations. The difference in health inequity could be larger than the difference in health outcomes between the two populations in some situations. Compared to health disparities which are typically measured and monitored using absolute or relative disparities of health outcomes, the methods presented in this manuscript provide a different, yet complementary, picture because they parse out the contributions of unfair and avoidable risk factors.

Description: Background: Asthma is an inflammatory disease of the airways, but in clinical practice inflammation is rarely monitored. The aim of this study was to assess the level of airway inflammation in steroid naive adult and pediatric patients with intermittent asthma over one year. Methods: 54 children and 50 adults with intermittent asthma (GINA step 1) were included. On up to 6 visits lung function, airway hyperresponsiveness to methacholine (PC20FEV1), sputum eosinophils and exhaled nitric oxide (FeNO) were assessed. Results: 36 pediatric and 34 adult patients were able to produce at least three adequate sputum samples over the study period and were included into the analysis.In 8 children (22%) the percentage of sputum eosinophils was always below 2.5%. A higher level of eosinophils (〉2.5%) was found on at least one visit in 16 (44%) and always 〉2.5% in 12 children (33%). In the adult group the respective numbers were 14 patients (41%) with always low (

Description: Background: Tests for the evolutionary conservation of associations between genes coding for transcription factors (TFs) and other genes have been limited to a few model organisms due to the lack of experimental information of functional associations in other organisms. We aimed at surmounting this limitation by using the most co-occurring gene pairs as proxies for the most conserved functional interactions available for each gene in a genome. We then used genes predicted to code for TFs to compare their most conserved interactions against the most conserved interactions for the rest of the genes within each prokaryotic genome available. Results: We plotted profiles of phylogenetic profiles, p-cubic, to compare the maximally scoring interactions of TFs against those of other genes. In most prokaryotes, genes coding for TFs showed lower co-occurrences when compared to other genes suggesting that transcriptional regulation evolves quickly in most, if not all prokaryotes. We also show that genes coding for TFs tend to have lower Codon Adaptation Indexes compared to other genes further suggesting quick gene exchange and rewiring of transcriptional regulation across prokaryotes.Keywordstranscription factors; interactome; evolvability; comparative genomics; phylogenetic profiles; regulatory interactions

Description: The effects of aflatoxin B1 (AFB1) exposure and sodium selenite supplementation on cell apoptosis of jejunum in broilers were studied. A total of 240 one-day-old male AA broilers were randomly assigned four dietary treatments containing 0 mg/kg of AFB1 (control), 0.3 mg/kg AFB1 (AFB1), 0.4 mg/kg supplement Se (+ Se) and 0.3 mg/kg AFB1 + 0.4 mg/kg supplement Se (AFB1 + Se), respectively. Compared with the control broilers, the number of apoptotic cells, the expression of Bax and Caspase-3 mRNA were significantly increased, while the expression of Bcl-2 mRNA and the Bcl-2/Bax ratio were significantly decreased in AFB1 broilers. The number of apoptotic cells and the expression of Caspase-3 mRNA in AFB1 + Se broilers were significantly higher than those in the control broilers, but significantly lower than those in AFB1 broilers. There were no significant changes in the expression of Bax mRNA between AFB1 + Se and control broilers; the expression of Bcl-2 mRNA and the Bcl-2/Bax ratio in AFB1 + Se broilers were significantly lower than those in the control broilers, but significantly higher than those in AFB1 broilers. In conclusion, 0.3 mg/kg AFB1 in the diet can increase cell apoptosis, decrease Bcl-2 mRNA expression, and increase of Bax and Caspase-3 mRNA expression in broiler’s jejunum. However, supplementation of dietary sodium selenite at the concentration of 0.4 mg/kg Se may ameliorate AFB1-induced apoptosis by increasing Bcl-2 mRNA expression, and decreasing Bax and Caspase-3 mRNA expression.

Description: Background: Through a review of three cases, the etiopathogenetic, clinical-diagnostic, and therapeutic aspects of ectopic thyroid tissue are herein discussed to highlight the main presentations of this polymorphous disease.Case presentations: The first case involved an ectopic thyroid gland in the lingual area in a 45-year-old Caucasian woman who presented with dysphagia and midline swelling at the base of the tongue. The second case involved a 22-year-old Caucasian woman with a submandibular mass comprising ectopic thyroid tissue. The third case involved a 33-year-old Caucasian man with a typical thyroglossal duct cyst characterized by the presence of thyroid tissue upon histological analysis. Conclusion: Surgery seems to be the most appropriate treatment for patients with ectopic thyroid tissue showing clinical signs of upper airway obstruction or when the lesion shows signs of infection or malignant degeneration. When a site of ectopic thyroid tissue is the only such site in the body, removal of this tissue will usually lead to hypothyroidism that requires medical thyroid hormone replacement.

Description: Background: Otolaryngologists encounter cases of various foreign bodies in the oral and pharyngeal regions. One commonly found foreign body is a fish bone, ingested in most cases by carelessness or an accident. These foreign materials are removed by endoscopy or through a simple procedure. However, hypopharyngeal damage is rarely caused by a foreign body in the pharynx following the swallowing of a toothbrush.Case presentationA 44-year-old Asian male visited the emergency room with chief complaints of intraoral pain and dysphagia that had started on the same day. The patient had paranoid-type schizophrenia that began 10 years ago; he had been hospitalized and was being treated at another clinic, and was transferred to the emergency room by the medical staff after swallowing a toothbrush. We successfully removed a toothbrush located within the pharynx of a patient with a history of a psychologic disorder via surgery and conservative treatment. Conclusion: The case with this patient, and a rapid diagnosis as well as treatment is imperative. The presence and state of a foreign body must be determined through a careful physical examination and imaging, followed by the immediate removal of the foreign body, all while keeping in mind the possibility of accompanying damage to nearby tissues.

Description: Many city governments choose to supply more developable land and transportation infrastructure with the hope of attracting people and businesses to their cities. However, like those in Taiwan, major cities worldwide suffer from traffic congestion. This study applies the system thinking logic of the causal loops diagram (CLD) model in the System Dynamics (SD) approach to analyze the issue of traffic congestion and other issues related to roads and land development in Taiwan’s cities. Comparing the characteristics of development trends with yearbook data for 2002 to 2013 for all of Taiwan’s cities, this study explores the developing phenomenon of unlimited city sprawl and identifies the cause and effect relationships in the characteristics of development trends in traffic congestion, high-density population aggregation in cities, land development, and green land disappearance resulting from city sprawl. This study provides conclusions for Taiwan’s cities’ sustainability and development (S&D). When developing S&D policies, during decision making processes concerning city planning and land use management, governments should think with a holistic view of carrying capacity with the assistance of system thinking to clarify the prejudices in favor of the unlimited developing phenomena resulting from city sprawl.

Description: This study assessed the feasibility of community-based comprehensive intervention on Type 2 diabetes mellitus (T2DM) on a large population in China. An intervention study was conducted on 7200 T2DM patients within one year and consisted of six lectures on health issues, and four times face-to-face lifestyle counseling delivered by general health practitioners, at local primary health centers (PHCs). A “knowledge, attitude and practice” (KAP) survey and fasting plasma glucose (FPG) measurement were conducted at baseline and after the intervention, respectively. A total of 6586 T2DM patients completed the intervention. After one year intervention, patients’ KAP level improved significantly (p 〈 0.001) and the average FPG has decreased from 8.53 mmol/L (standard deviation: 2.84) to 7.11 mmol/L (standard deviation: 1.34) (p 〈 0.001). Patients in rural areas and with lower education level showed higher FPG and poorer KAP level both before and after the intervention. In conclusion, community-based comprehensive intervention for T2DM is feasible on a large population. Improving and repeating the comprehensive strategy is greatly recommended in order to sustain the impact, especially in rural areas and for patients with lower education levels.

Description: Background: Crescentic glomerulonephritis is a rare condition in children and is typically associated with renal insufficiency. Dysfunction of the alternative complement pathway is an unusual aetiology with an unknown mechanism.Case presentationWe report a case of a previously healthy 12-year-old Caucasian girl who was examined on emergency owing to an asymptomatic gross haematuria. An active urinary sediment and nephrotic-range proteinuria were identified, and serologic examination showed a decreased serum C3 concentration not associated with any immunologic or infectious cause. Oedema, hypertension, and renal insufficiency were not observed. A renal biopsy was performed, and crescentic glomerulonephritis associated with C3 glomerulonephritis was diagnosed. Prompt treatment with intravenous steroids resulted in complete resolution of the gross haematuria. Further examination did not detect any underlying acquired cause. A combination of oral steroids and cyclophosphamide, followed by mycophenolate mofetil, was maintained and resulted in clinical remission during an 8-month follow-up. Conclusion: The presence of severe injury such as crescentic glomerulonephritis secondary to C3 glomerulonephritis is extremely unusual in children. This is the first known case of paediatric crescentic glomerulonephritis secondary to C3 glomerulonephritis that presented with gross haematuria and was treated early and effectively with immunosuppressive therapy based on its severe histologic features.

Description: Background: Ophthalmic infections cause significant morbidity in Cambodian children but aetiologic data are scarce. We investigated the causes of acute eye infections in 54 children presenting to the ophthalmology clinic at Angkor Hospital for Children, Siem Reap between March and October 2012.FindingsThe median age at presentation was 3.6 years (range 6 days – 16.0 years). Forty two patients (77.8%) were classified as having an external eye infection, ten (18.5%) as ophthalmia neonatorum, and two (3.7%) as intra-ocular infection. Organisms were identified in all ophthalmia neonatorum patients and 85.7% of patients with an external eye infection. Pathogens were not detected in either of the intra-ocular infection patients. Most commonly isolated bacteria were Staphylococcus aureus (23 isolates), coagulase-negative staphylococci (13), coliforms (7), Haemophilus influenzae/parainfluenzae (6), Streptococcus pneumoniae (4), and Neisseria gonorrhoeae (2). Chlamydia trachomatis DNA was detected in 60% of swabs taken from ophthalmia neonatorum cases. Conclusions: This small study demonstrates the wide range of pathogens associated with common eye infections in Cambodian children. The inclusion of molecular assays improved the spectrum of detectable pathogens, most notably in neonates.

Description: Background: Cardiac hypertrophy is characterized by alterations in both cardiac bioenergetics and insulin sensitivity. Insulin promotes glucose uptake by cardiomyocytes and its use as a substrate for glycolysis and mitochondrial oxidation in order to maintain the high cardiac energy demands. Insulin stimulates Ca2+ release from the endoplasmic reticulum, however, how this translates to changes in mitochondrial metabolism in either healthy or hypertrophic cardiomyocytes is not fully understood. Results: In the present study we investigated insulin-dependent mitochondrial Ca2+ signaling in normal and norepinephrine or insulin like growth factor?1-induced hypertrophic cardiomyocytes. Using mitochondrion-selective Ca2+-fluorescent probes we showed that insulin increases mitochondrial Ca2+ levels. This signal was inhibited by the pharmacological blockade of either the inositol 1,4,5-triphosphate (Camila) receptor or the mitochondrial Ca2+ uniporter, as well as by siRNA-dependent mitochondrial Ca2+ uniporter knockdown. Norepinephrine-stimulated cardiomyocytes showed a significant decrease in endoplasmic reticulum-mitochondrial contacts compared to either control or insulin like growth factor?1-stimulated cells. This resulted in a reduction in mitochondrial Ca2+ uptake, Akt activation, glucose uptake and oxygen consumption in response to insulin. Blocking mitochondrial Ca2+ uptake was sufficient to mimic the effect of norepinephrine-induced cardiomyocyte hypertrophy on insulin signaling. Conclusions: Mitochondrial Ca2+ uptake is a key event in insulin signaling and metabolism in cardiomyocytes.

Description: Background: Malaria still remains the leading cause of childhood morbidity and mortality in Uganda. Interventions like malaria vaccines which reduce the malaria burden are needed in malaria endemic communities. There is need to establish baseline characteristics in vaccine trial study sites. This study determined the following baseline malariometric indices: spleen rates, bed net use, malaria parasitaemia and malaria episodes in an inception cohort of children aged 12 -60 months in Iganga district, Uganda. Methods: In a longitudinal cohort study, 748 children were enrolled with 397 in an active follow up arm and 351 in a passive arm. The children in the two arms were followed for 6 months to determine the incidence of malaria episodes. Results: The overall baseline spleen rate was 8.2% (61/748) among the study participants. Of the households surveyed, about 36% reported using bed nets and almost 30% of the users had insecticide-treated nets. 274 (36.6%) of the study participants had a history of fever in the past 24 hrs at the time of the baseline survey. All participants had a peripheral blood smear for malaria parasites done at enrollment with 76.8% having the asexual form of malaria parasites. The malaria episodes per child per year were 1.5 and 0.79 in the active and passive follow up arms respectively. Conclusions: There is a high prevalence of malaria asexual parasitaemia in children below five years. The bed net usage still remains low among this population. These baseline malariometric indices have important implication for malaria control interventions.

Description: Background: The disease progression following hepatitis B virus (HBV) infection is associated with single-nucleotide polymorphisms (SNPs). However, the role of SNPs in chronic HBV infection in children remains unclear. Here, we investigate the association between SNPs and early spontaneous hepatitis B e antigen (HBeAg) seroconversion in children with chronic hepatitis B infection. Methods: This was a retrospective cohort study. We genotyped seven SNPs in the following genes, interleukin (IL)-10 (rs1800871 and rs1800872), human leukocyte antigen (HLA)-DPA1 (rs3077), HLA-DPB1 (rs9277535), HLA-DQB2 (rs7453920), HLA-DQB1 (rs2856718), and IL28B (rs8099917), in patients with chronic HBV infection using PCR and sequencing. These variants were analyzed for an association with early HBeAg seroconversion in children. Results: Of 225 Japanese patients with chronic hepatitis B virus infection (male/female: 105/120, median age at initial visit: 6 years; range 0–44 years), 52 achieved spontaneous HBeAg seroconversion at the age of 10 years or younger (G1: early seroconversion group), and 57 did not achieve spontaneous HBeAg seroconversion under the age of 20 years (G2: late or no seroconversion group). Of the seven SNPs, only the HLA-DPA1 SNP displayed a low p-value (P = 0.070), but not significant, to have early HBeAg seroconversion in the dominant model and in the allele model (P =  0.073) using the chi-square test. The association study found a low p-value, but not significant, to have early HBeAg seroconversion in the dominant model for HLA-DPA1 (genotype TC + TT vs. CC, P = 0.070, odds ratio: 2.016, 95% confidence interval: 0.940-4.323) using a logistic regression model. Conclusion: Although the HLA-DPA1 SNP did not show a statistically significant association with early HBeAg seroconversion in this study, the HLA-DPA1 SNP might increase the likelihood of achieving early spontaneous HBeAg seroconversion in children.

Description: Background: The diagnosis of Marked First Degree Atrioventricular Block is made with electrocardiogram when PR interval 〉=0.30s. A PR interval of up to 0.48 s had been reported in literature. Data is sparse on an extremely prolonged PR interval associated with Atrioventricular Dissociation and Pseudo-Pacemaker Syndrome. Electrocardiogram with this type of uncommon features poses diagnostic and management challenges in clinical practice.Case presentationWe report a case of a 22 year old Nigerian male from Igbo ethnic group who presented himself for medical screening with a history of exercise intolerance, occasional palpitation and fainting spells. He has no history of cough, orthopnoea, paroxysmal nocturnal dyspnoea nor body swelling. A physical examination revealed that the patient has a pulse rate of 64 beats per minute, blood pressure of 110/70 mmHg and soft heart sounds. Standard 12-lead electrocardiogram showed an uncommon Marked First Degree Atrioventricular Block with an extremely prolonged PR interval of 0.56 s. Long rhythm strips of the electrocardiogram showed extremely prolonged PR interval associated with Atrioventricular Dissociation and variable degrees of Atrioventricular Block (Mobitz type I and II). Conclusions: An extremely prolonged PR interval may occur in First Degree Atrioventricular Block and it may be associated with Atrioventricular Dissociation and Pseudo-Pacemaker Syndrome which may pose diagnostic and management challenges. This suggests that not all cases of First Degree Atrioventricular Block are benign and so should be sub-classified based on degree of PR interval prolongation and associated electrical abnormalities.

Description: Background: In the Wnt pathway, the secreted frizzled-related protein 2 (SFRP2) is thought to act as one of the several competitive inhibitors of Wnt. However, the precise role of SFRP2 is still poorly understood especially in B lymphocytes. Here, we investigated the function of SFRP2, comparing the SFRP2 defective as well as normal B lymphocytes in mice. Results: We demonstrated that calcium influx from extracellular to intracellular space in splenic B cells was clearly affected by the defect of SFRP2. In addition, the phosphorylation of phospholipase Cgamma2 was observed to be reduced in SFRP2 defective splenic B cells with B cell receptor stimulation. Conclusions: SFRP2 is suggested to modulate the influx from extracellular calcium in the B cell receptor signaling pathway.

Description: Background: Lymphoepithelioma-like carcinoma is an undifferentiated carcinoma with histological features similar to undifferentiated, non-keratinizing carcinoma of the nasopharynx. Lymphoepithelioma-like carcinoma of the urinary bladder is uncommon with a reported incidence of 0.3%- 1.3% of all bladder cancer. We report a Japanese case of predominant lymphoepithelioma-like carcinoma of the urinary bladder and review all of the English literature after performing a pooled analysis of the cases including the present one.Case presentationAn 83-year-old Japanese man was introduced to our department with the chief complaint of macroscopic hematuria. Cystoscopy demonstrated a thumb tip-sized bladder tumor at the trigone. The patient underwent a transurethral resection of the bladder tumor. The pathological examination showed predominant lymphoepithelioma-like carcinoma of the urinary bladder with urothelial carcinoma. The patient was diagnosed with muscle invasive lymphoepithelioma-like carcinoma of the urinary bladder and was treated with concurrent chemoradiotherapy. The patient is under observation with regular clinical follow-up and remains well after 12 months, with no evidence of disease recurrence. The reports of 93 patients including the present one of lymphoepithelioma-like carcinoma of the urinary bladder from the English literature were collected between 1991 and 2014. Patients were evaluated for clinicopathological findings. Outcome resulted as follows: 59 patients (67%) did not show evidence of disease, 14 (17%) died of disease, 5 (6%) was alive with metastases, and 9 (10%) died for causes unrelated to the primary disease. Cause-specific survival rate resulted 83%. The overall patients were divided into three groups (pure, predominant and focal) according to the lymphoepithelioma-like carcinoma of the urinary bladder classification of Amin et al. Conclusions: Because lymphoepithelioma-like carcinoma of the urinary bladder is more sensitive to both chemotherapy and radiotherapy than conventional urothelial carcinoma, radical cystectomy may not be necessary for all patients with muscle invasive lymphoepithelioma-like carcinoma of the urinary bladder. Therefore, pathological information may be useful in selecting patients suitable for bladder-preservation treatment. On the other hand, the apparently more aggressive nature of focal lymphoepithelioma-like carcinoma of the urinary bladder suggests that these patients are probably best managed with radical cystectomy and adjuvant treatment.

Description: Background: Understanding the distribution and abundance of pathogens can provide insight into the evolution and ecology of their host species. Previous research in kokanee, the freshwater form of sockeye salmon (Oncorhynchus nerka), found evidence that populations spawning in streams may experience a greater pathogen load compared with populations that spawn on beaches. In this study we tested for differences in the abundance and diversity of the gram-negative bacteria, Flavobacterium spp., infecting tissues of kokanee in both of these spawning habitats (streams and beaches). Molecular assays were carried out using primers designed to amplify a ~200 nucleotide region of the gene encoding the ATP synthase alpha subunit (AtpA) within the genus Flavobacterium. Using a combination of DNA sequencing and quantitative PCR (qPCR) we compared the diversity and relative abundance of Flavobacterium AtpA amplicons present in DNA extracted from tissue samples of kokanee collected from each spawning habitat. Results: We identified 10 Flavobacterium AtpA haplotypes among the tissues of stream-spawning kokanee and seven haplotypes among the tissues of beach-spawning kokanee, with only two haplotypes shared between spawning habitats. Haplotypes occurring in the same clade as F. psychrophilum were the most prevalent (92% of all reads, 60% of all haplotypes), and occurred in kokanee from both spawning habitats (streams and beaches). Subsequent qPCR assays did not find any significant difference in the relative abundance of Flavobacterium AtpA amplicons between samples from the different spawning habitats. Conclusions: We confirmed the presence of Flavobacterium spp. in both spawning habitats and found weak evidence for increased Flavobacterium diversity in kokanee sampled from stream-spawning sites. However, the quantity of Flavobacterium DNA did not differ between spawning habitats. We recommend further study aimed at quantifying pathogen diversity and abundance in population-level samples of kokanee combined with environmental sampling to better understand the ecology of pathogen infection in this species.

Description: Background: The Gibberellin Stimulated-Like (GSL) or Snakin peptides from higher plants are cysteine-rich, with broad spectrum activity against a range of bacterial and fungal pathogens. To detect GSL peptides in applications such as western blot analysis and enzyme-linked immunosorbent assays (ELISA), specific antibodies that recognise GSL peptides are required. However, the intrinsic antimicrobial activity of these peptides is likely to prevent their expression alone in bacterial or yeast expression systems for subsequent antibody production in animal hosts. Results: To overcome this issue we developed an Escherichia coli expression strategy based on the expression of the GSL1 peptide as a His-tagged thioredoxin fusion protein. The DNA sequence for the mature GSL1 peptide from potato (Solanum tuberosum L.) was cloned into the pET-32a expression vector to produce a construct encoding N-terminally tagged his6-thioredoxin-GSL1. The fusion protein was overexpressed in E. coli to produce soluble non-toxic protein. The GSL1 fusion protein could be easily purified by using affinity chromatography to yield ~1.3 mg of his6-thioredoxin-GSL1 per L of culture. The fusion protein was then injected into rabbits for antibody production. Western blot analysis showed that the antibodies obtained from rabbit sera specifically recognised the GSL1 peptide that had been expressed in a wheat germ cell-free expression system. Conclusion: We present here the first report of a GSL1 peptide expressed as a fusion protein with thioredoxin that has resulted in milligram quantities of soluble protein to be produced. We have also demonstrated that a wheat germ system can be used to successfully express small quantities of GSL1 peptide useful as positive control in western blot analysis. To our knowledge this is the first report of antibodies being produced against GSL1 peptide. The antibodies will be useful for analysis of GSL1peptides in western blot, localization by immunohistochemistry (IHC) and quantitation by ELISA.

Description: A simple and inexpensive method based on solvent extraction followed by low temperature clean-up was applied for determination of seven pyrethroids residues in bovine raw milk using gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) and gas chromatography with electron-capture detector (GC-ECD). Sample extraction procedure was established through the evaluation of seven different extraction protocols, evaluated in terms of analyte recovery and cleanup efficiency. Sample preparation optimization was based on Doehlert design using fifteen runs with three different variables. Response surface methodologies and polynomial analysis were used to define the best extraction conditions. Method validation was carried out based on SANCO guide parameters and assessed by multivariate analysis. Method performance was considered satisfactory since mean recoveries were between 87% and 101% for three distinct concentrations. Accuracy and precision were lower than ±20%, and led to no significant differences (p 〈 0.05) between results obtained by GC-ECD and GC-MS/MS techniques. The method has been applied to routine analysis for determination of pyrethroid residues in bovine raw milk in the Brazilian National Residue Control Plan since 2013, in which a total of 50 samples were analyzed.

Description: Background: The development of the craniofacial skeleton from embryonic mesenchyme is a complex process that is not yet completely understood, particularly for intramembranous bones. This study investigates the development of the neural crest derived infraorbital (IO) bones of the zebrafish (Danio rerio) skull. Located under the orbit, the IO bones ossify in a set sequence and are closely associated with the lateral line system. We conducted skeletogenic condensation and neuromast laser ablation experiments followed by shape analyses in order to investigate the relationship between a developing IO bone and the formation of the IO series as well as to investigate the highly debated inductive potential of neuromasts for IO ossification. Results: We demonstrate that when skeletogenic condensations recover from laser ablation, the resulting bone differs in shape compared to controls. Interestingly, neighbouring IO bones in the bone series are unaffected. In addition, we show that the amount of canal wall mineralization is significantly decreased following neuromast laser ablation at juvenile and larval stages. Conclusions: These results highlight the developmental robustness of the IO bones and provide direct evidence that canal neuromasts play a role in canal wall development in the head. Furthermore, we provide evidence that the IO bones may be two distinct developmental modules. The mechanisms underlying developmental robustness are rarely investigated and are important to increase our understanding of evolutionary developmental biology of the vertebrate skull.

Description: Background: Inherited thrombocytopenias (IT) are a heterogeneous group of rare diseases characterized by a reduced number of blood platelets. The frequency of IT is probably underestimated because of diagnostic difficulties and because not all the existing forms have as yet been identified, with some patients remaining without a definitive diagnosis. Exome Sequencing has made possible the identification of almost all variants in the coding regions of protein-coding genes, thereby providing the opportunity to identify the disease causing gene in a number of patients with indefinite diagnoses, specifically in consanguineous families.Case presentationFamilial thrombocytopenia with small size platelets was present in several members of a highly consanguineous family from Northern Iraq. Genotyping of all affected, their unaffected siblings and parents, followed by exome sequencing revealed a strong candidate loss of function variant in a homozygous state: a frameshift mutation in the FYB gene. The protein encoded by this gene is known to be a cytosolic adaptor molecule expressed by T, natural killer (NK), myeloid cells and platelets, and is involved in platelet activation and controls the expression of interleukin-2. Knock-out mice were reported to show isolated thrombocytopenia. Conclusion: Inherited thrombocytopenias differ in their presentation, associated features, and molecular etiologies. An accurate diagnosis is needed to provide appropriate management as well as counseling for the individuals and their family members. Exome sequencing may become a first diagnostic tool to identify the molecular basis of undiagnosed familial IT. In this report, the clinical evaluation combined with the power and efficiency of genomic analysis defined the FYB gene as the possible underlying cause of autosomal recessive thrombocytopenia with small platelet size. This is the first report linking pathogenic variants in FYB and thrombocytopenia in humans.

Description: Background: The degree of cardiovascular function impairment parallels the degree of obesity and obese subjects have abnormal changes on the electrocardiogram (ECG). Early ECG changes in obesity have not been previously studied. The objective of the present study was to determine the early ECG changes in obese rats and their relationship with anthropometric measurements.FindingsAt seven weeks all rats in the experimental were obese and in sinus rhythm. In the experimental resting heart rate was increased (364 +/- 13 vs. 313 +/- 12 bpm, P

Description: Patients with limited English proficiency have known limitations accessing health care, but differences in hospital outcomes once access is obtained are unknown. We investigate inpatient mortality rates and obstetric trauma for self-reported speakers of English, Spanish, and languages of Asia and the Pacific Islands (API) and compare quality of care by language with patterns by race/ethnicity. Data were from the United States Agency for Healthcare Research and Quality, Healthcare Cost and Utilization Project, 2009 State Inpatient Databases for California. There were 3,757,218 records. Speaking a non-English principal language and having a non-White race/ethnicity did not place patients at higher risk for inpatient mortality; the exception was significantly higher stroke mortality for Japanese-speaking patients. Patients who spoke API languages or had API race/ethnicity had higher risk for obstetric trauma than English-speaking White patients. Spanish-speaking Hispanic patients had more obstetric trauma than English-speaking Hispanic patients. The influence of language on obstetric trauma and the potential effects of interpretation services on inpatient care are discussed. The broader context of policy implications for collection and reporting of language data is also presented. Results from other countries with and without English as a primary language are needed for the broadest interpretation and generalization of outcomes.

Description: Large private sector investments in low- and middle-income countries are often critically evaluated with regards to their environmental, social, human rights, and health impacts. A health impact assessment, including a baseline health survey, was commissioned by the Addax Bioenergy Sierra Leone project in 2010. As part of the monitoring, a follow-up survey was conducted three years later. A set of health indicators was assessed at six impacted and two control sites. Most of these indices improved, particularly at the impacted sites. The prevalences of stunting, wasting, and Plasmodium falciparum in children under five years of age decreased significantly at impacted sites (all p 〈 0.05) and non-significantly at control sites. Anemia in children and in women of reproductive age (15–49 years) decreased significantly at impacted and control sites (p 〈 0.05 and p 〈 0.001, respectively). Health facility-based deliveries increased significantly at the impacted sites (p 〈 0.05). The prevalences of helminth infections in children aged 10–15 years remained approximately at the same levels, although focal increases at the impacted sites were noted. Access to improved sanitation decreased significantly (p 〈 0.05) at control and non-significantly at impacted sites. Water quality remained poor without significant changes. The epidemiologic monitoring of a bioenergy project provides a useful contribution for evidence-based decision-making.

Description: Elderly persons’ perceived accessibility to railway traveling depends on their functional limitations/diseases, their functional abilities and their travel behaviors in interaction with the barriers encountered during whole trips. A survey was conducted on a random sample of 1000 city residents (65–85 years old; 57% response rate). The travels were perceived least accessible by respondents with severely reduced functional ability and by those with more than one functional limitation/disease (e.g., restricted mobility and chronic pain). Those who traveled “often”, perceived the accessibility to be better than those who traveled less frequently. For travelers with high functional ability, the main barriers to more frequent traveling were travel costs and low punctuality. For those with low functional ability, one’s own health was reported to be the main barrier. Our results clarify the links among existing functional limitations/functional abilities, the barriers encountered, the travel behavior, and the overall accessibility to traveling. By operationalizing the whole-trip concept as a chain of events, we deliver practical knowledge on vulnerable groups for decision-making to improve the transport environment for all.

Description: Background: The MedSeq Project is a randomized clinical trial developing approaches to assess the impact of integrating genome sequencing into clinical medicine. To facilitate the return of results of potential medical relevance to physicians and patients participating in the MedSeq Project, we sought to develop a reporting approach for the effective communication of such findings. Methods: Genome sequencing was performed on the Illumina HiSeq platform. Variants were filtered, interpreted, and validated according to methods developed by the Laboratory for Molecular Medicine and consistent with current professional guidelines. The GeneInsight software suite, which is integrated with the Partners HealthCare electronic health record, was used for variant curation, report drafting, and delivery. Results: We developed a concise 5?6 page Genome Report (GR) featuring a single-page summary of results of potential medical relevance with additional pages containing structured variant, gene, and disease information along with supporting evidence for reported variants and brief descriptions of associated diseases and clinical implications. The GR is formatted to provide a succinct summary of genomic findings, enabling physicians to take appropriate steps for disease diagnosis, prevention, and management in their patients. Conclusions: Our experience highlights important considerations for the reporting of results of potential medical relevance and provides a framework for interpretation and reporting practices in clinical genome sequencing.

Description: Background: Management of diabetes mellitus is complex and involves controlling multiple risk factors that may lead to complications. Given that patients provide most of their own diabetes care, patient self-management training is an important strategy for improving quality of care. Web-based interventions have the potential to bridge gaps in diabetes self-care and self-management. The objective of this study was to determine the effect of a web-based patient self-management intervention on psychological (self-efficacy, quality of life, self-care) and clinical (blood pressure, cholesterol, glycemic control, weight) outcomes. Methods: For this cohort study we used repeated-measures modelling and qualitative individual interviews. We invited patients with type 2 diabetes to use a self-management website and asked them to complete questionnaires assessing self-efficacy (primary outcome) every three weeks for nine months before and nine months after they received access to the website. We collected clinical outcomes at three-month intervals over the same period. We conducted in-depth interviews at study conclusion to explore acceptability, strengths and weaknesses, and mediators of use of the website. We analyzed the data using a qualitative descriptive approach and inductive thematic analysis. Results: Eighty-one participants (mean age 57.2?years, standard deviation 12) were included in the analysis. The self-efficacy score did not improve significantly more than expected after nine months (absolute change 0.12; 95% confidence interval ?0.028, 0.263; p?=?0.11), nor did clinical outcomes. Website usage was limited (average 0.7 logins/month). Analysis of the interviews (n?=?21) revealed four themes:1) mediators of website use; 2) patterns of website use, including role of the blog in driving site traffic; 3) feedback on website; and 4) potential mechanisms for website effect. Conclusions: A self-management website for patients with type 2 diabetes did not improve self-efficacy. Website use was limited. Although its perceived reliability, availability of a blog and emailed reminders drew people to the website, participants? struggles with type 2 diabetes, competing priorities in their lives, and website accessibility were barriers to its use. Future interventions should aim to integrate the intervention seamlessly into the daily routine of end users such that it is not seen as yet another chore.

Description: Background: To report a case of non-typical Pseudomonas aeruginosa keratitis that was misdiagnosed as fungal keratitis by in vivo confocal microscopy.Case presentationA 37-year-old Chinese woman presented with a 2-week history of increasing pain and redness of the right eye. She was started on hourly topical fortified tobramycin and levofloxacin by the referring doctor without improvement. She denied any improvement of her symptoms and signs. On examination, she had a large central corneal ulcer extending to the peripheral cornea. Further symptoms included a satellite lesion, intense conjunctival injection and marked corneal oedema. The corneal scrape was not performed initially because of the deep infiltrate in the stroma. The patient was examined by in vivo confocal microscopy. Confocal microscopy images showed hyper-reflective, thin, and branching interlocking linear structures in the stroma that were 5-8 mum in width and 200-400 mum in length. The morphology was consistent with that of fungus. However, the histopathological examination, Gram stain, and culture of the cornea only confirmed the presence of a Pseudomonas species within the deep strom. No fungal element was found. The pathogen was sensitive to ciprofloxacin, gentamicin, levofloxacin, tobramycin and amikacin. Conclusion: This case reports the potential for a false positive finding of fungus in Pseudomonas aeruginosa keratitis and emphasizes the importance of bacterial culture and antibiotic susceptibility testing in the management of microbial keratitis.

Description: Background: Cerebral palsy (CP) is a heterogeneous neurodevelopmental disorder associated with intellectual disability in one-third of cases. Recent findings support Mendelian inheritance in subgroups of patients with the disease. The purpose of this study was to identify a novel genetic cause of paraplegic CP with intellectual disability in a consanguineous Pakistani family. Methods: We performed whole-exome sequencing (WES) in two brothers with CP and intellectual disability. Analysis of AP4M1 mRNA was performed using quantitative real-time PCR on total RNA from cultured fibroblasts. The brothers were investigated clinically and by MRI. Results: We identified a novel homozygous AP4M1 mutation c.194_195delAT, p.Y65Ffs*50 in the affected brothers. Quantitative RT-PCR analysis showed markedly reduced AP4M1 mRNA levels suggesting partial non-sense mediated mRNA decay. Several clinical and MRI features were consistent with AP-4 complex deficiency. However, in contrast to previously reported cases with AP4M1 mutations our patients show an aggressive behavior and a relatively late onset of disease. Conclusion: This study shows an AP4M1 mutation associated with aggressive behavior in addition to mild dysmorphic features, intellectual disability, spastic paraparesis and reduced head circumference. Our findings expand the clinical spectrum associated with AP-4 complex deficiency and the study illustrates the importance of MRI and WES in the diagnosis of patients with CP and intellectual disability.

Description: Chlorpyrifos (CPF) is a commonly used organophosphate insecticide (OP). In adults, exposure to OPs has been inconsistently associated with reduced lung function. OP exposure and lung function has not been assessed in adolescents. The objective of this study was to assess CPF exposure and lung function among Egyptian adolescents. We conducted a 10-month study of male adolescent pesticide applicators (n = 38) and non-applicators of similar age (n = 24). Urinary 3,5,6-trichloro-2-pyridinol (TPCy), a CPF-specific metabolite, was analyzed in specimens collected throughout the study. Spirometry was performed twice after pesticide application: day 146, when TCPy levels were elevated and day 269, when TCPy levels were near baseline. Applicators had higher levels of TCPy (mean cumulative TCPy day 146 = 33,217.6; standard deviation (SD) = 49,179.3) than non-applicators (mean cumulative TCPy day 146 = 3290.8; SD = 3994.9). Compared with non-applicators, applicators had higher odds of reporting wheeze, odds ratio = 3.41 (95% CI: 0.70; 17.41). Cumulative urinary TCPy was inversely associated with spirometric measurements at day 146, but not at day 269. Although generally non-significant, results were consistent with an inverse association between exposure to CPF and lung function.

Description: Diatoms are a highly diversified group of algae that are widely distributed in aquatic ecosystems, and various species have different nutrient and temperature requirements for optimal growth. Here, we describe unusual psychrophilic diatoms of Cymbella in a travertine deposition environment in southwestern China in winter season. Travertine surfaces are colonized by these psychrophilic diatoms, which form biofilms of extracellular polysaccharide substances (EPS) with active metabolic activities in extremely cold conditions. The travertine in Huanglong, is a typical single crystalline calcite with anisotropic lattice distortions of unit cell parameters along axes of a and c, and this structure is suggestive of some level of metabolic mediation on mineralization. Near-edge X-ray absorption fine structure spectroscopy (NEXAFS) results further confirmed the occurrence of biogenic distortion of the crystal lattice of travertine calcite. Overall, our results imply that the metabolic influence of psychrophilic diatoms may be particularly important for promoting formation and dissolution of travertine in extremely cold environments of Huanglong. The EPS of psychrophilic diatoms will protect travertine from HCO3− etching and provide template for forming travertine when water re-flowing, in warm season.

Description: Background: In this study we assessed the mediation role of the gestational age on the effect of the infant's congenital heart defects (CHD) on birth-weight. Methods: We used secondary data from the Baltimore-Washington Infant Study (1981-1989). Mediation analysis was employed to investigate whether gestational age acted as a mediator of the association between CHD and reduced birth-weight. We estimated the mediated effect, the mediation proportion, and their corresponding 95% confidence intervals (CI) using several methods. Results: There were 3362 CHD cases and 3564 controls in the dataset with mean birth-weight of 3071 (SD = 729) and 3353 (SD = 603) grams, respectively; the mean gestational age was 38.9 (SD = 2.7) and 39.6 (SD = 2.2) weeks, respectively. After adjusting for covariates, the estimated mediated effect by gestational age was 113.5 grams (95%CI, 92.4-134.2) and the mediation proportion was 40.7% (95%CI, 34.7%-46.6%), using the bootstrap approach. Conclusions: Gestational age may account for about 41% of the overall effect of heart defects on reduced infant birth-weight. Improved prenatal care and other public health efforts that promote full term delivery, particularly targeting high-risk families and mothers known to be carrying a fetus with CHD, may therefore be expected to improve the birth-weight of these infants and their long term health.

Description: The aim of this study is to investigate the relationships between road traffic noise exposure, annoyance caused by different noise sources and validated health indicators in a cohort of 1375 adults from the region of Basel, Switzerland. Road traffic noise exposure for each study participant was determined using modelling, and annoyance from various noise sources was inquired by means of a four-point Likert scale. Regression parameters from multivariable regression models for the von Zerssen score of somatic symptoms (point symptom score increase per annoyance category) showed strongest associations with annoyance from industry noise (2.36, 95% CI: 1.54, 3.17), neighbour noise (1.62, 95% CI: 1.17, 2.06) and road traffic noise (1.53, 95% CI: 1.09, 1.96). Increase in modelled noise exposure by 10 dB(A) resulted in a von Zerssen symptom score increase of 0.47 (95% CI: −0.01, 0.95) units. Subsequent structural equation modelling revealed that the association between physical noise exposure and health-related quality of life (HRQOL) is strongly mediated by annoyance and sleep disturbance. This study elucidates the complex interplay of different factors for the association between physical noise exposure and HRQOL.

Description: Background: Lead is a pervasive pollutant, associated at low levels to many adverse health effects. Objective: To investigate lead levels, exposure pathways and intervention possibilities in school children from Alpuyeca, in Morelos, Mexico. Methods: Blood lead concentrations (BPb) were measured in 226 children in 2011. Exposure pathways were assessed through a questionnaire, lead measurements in different environmental matrices and spatial aggregation analysis of lead concentrations. Results: BPb ranged from 1.5 to 36.5 µg/dL, with a mean (SD) of 7.23 (4.9) µg/dL. Sixty-four and 18% of the children had BPb > 5 µg/dL and > 10 µg/dL, respectively. The use of lead glazed ceramics was reported in almost half of the households; it was the main BPb determinant and it was associated with an increased risk of having BPb > 5 g/dL by 2.7 times (p = 0.001). Environmental samples were within US EPA’s lead recommended limits, and blood lead levels were randomly distributed in the community. Conclusions: Lead remains a public health problem in Alpuyeca, Mexico. Unlike other local pollutants, lead exposure prevention can be achieved inexpensively and in a short term. Interventions should make mothers aware of lead’s health effects and empower them to safeguard their children’s health by avoiding the culturally ingrained use of lead glazed pottery.Background: Lead is a pervasive pollutant, associated at low levels to many adverse health effects. Objective: To investigate lead levels, exposure pathways and intervention possibilities in school children from Alpuyeca, in Morelos, Mexico. Methods: Blood lead concentrations (BPb) were measured in 226 children in 2011. Exposure pathways were assessed through a questionnaire, lead measurements in different environmental matrices and spatial aggregation analysis of lead concentrations. Results: BPb ranged from 1.5 to 36.5 µg/dL, with a mean (SD) of 7.23 (4.9) µg/dL. Sixty-four and 18% of the children had BPb > 5 µg/dL and > 10 µg/dL, respectively. The use of lead glazed ceramics was reported in almost half of the households; it was the main BPb determinant and it was associated with an increased risk of having BPb > 5 g/dL by 2.7 times (p = 0.001). Environmental samples were within US EPA’s lead recommended limits, and blood lead levels were randomly distributed in the community. Conclusions: Lead remains a public health problem in Alpuyeca, Mexico. Unlike other local pollutants, lead exposure prevention can be achieved inexpensively and in a short term. Interventions should make mothers aware of lead’s health effects and empower them to safeguard their children’s health by avoiding the culturally ingrained use of lead glazed pottery.

Description: Crotamine is one of the main constituents of the venom of the South American rattlesnake Crotalus durissus terrificus. Here we sought to investigate the inflammatory and toxicological effects induced by the intrahippocampal administration of crotamine isolated from Crotalus whole venom. Adult rats received an intrahippocampal infusion of crotamine or vehicle and were euthanized 24 h or 21 days after infusion. Plasma and brain tissue were collected for biochemical analysis. Complete blood count, creatinine, urea, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), creatine-kinase (CK), creatine kinase-muscle B (CK-MB) and oxidative parameters (assessed by DNA damage and micronucleus frequency in leukocytes, lipid peroxidation and protein carbonyls in plasma and brain) were quantified. Unpaired and paired t-tests were used for comparisons between saline and crotamine groups, and within groups (24 h vs. 21 days), respectively. After 24 h crotamine infusion promoted an increase of urea, GOT, GPT, CK, and platelets values (p ≤ 0.01), while red blood cells, hematocrit and leukocytes values decreased (p ≤ 0.01). Additionally, 21 days after infusion crotamine group showed increased creatinine, leukocytes, TBARS (plasma and brain), carbonyl (plasma and brain) and micronucleus compared to the saline-group (p ≤ 0.01). Our findings show that crotamine infusion alter hematological parameters and cardiac markers, as well as oxidative parameters, not only in the brain, but also in the blood, indicating a systemic pro-inflammatory and toxicological activity. A further scientific attempt in terms of preserving the beneficial activity over toxicity is required.

Description: Background: Epidemiological studies have suggested that variants on adiponectin (ADIPOQ) and its receptor ADIPOR1 (adiponectin receptor 1) are associated with colorectal cancer (CRC) risk; however, the results were inconclusive. The aim of the study was to evaluate the associations between the variants on ADIPOQ and ADIPOR1 and the CRC risk with a hospital-based case-control study in the Chinese population along with meta-analysis of available epidemiological studies. Methods: With a hospital-based case-control study of 341 cases and 727 controls, the associations between the common variants on ADIPOQ (rs266729, rs822395, rs2241766 and rs1501299) and ADIPOR1 (rs1342387 and rs12733285) and CRC susceptibility were evaluated. Meta-analysis of the published epidemiological studies was performed to investigate the associations between the variants and CRC risk. Results: For the population study, we found that variant rs1342387 of ADIPOR1 was associated with a reduced risk for CRC [adjusted odds ratio (OR)?=?0.74, 95% confidential intervals (95% CI)?=?0.57-0.97; CT/TT vs. CC]. The meta-analysis also suggested a significant association for rs1342387 and CRC risk; the pooled OR was 0.79 (95% CI?=?0.66-0.95) for the CT/TT carriers compared to CC homozygotes under the random-effects model (Q?=?8.06, df?=?4, P?=?0.089; I2?=?50.4%). The case-control study found no significant association for variants rs266729, rs822395, rs2241766, and rs1501299 on ADIPOQ or variant rs12733285 on ADIPOR1 and CRC susceptibility, which were consistent with results from the meta-analysis studies. Conclusions: These data suggested that variant rs1342387 on ADIPOR1 may be a novel CRC susceptibility factor.

Description: Background: High blood pressure levels have been associated with elevated atherogenic blood lipid fraction, but epidemiological surveys often give inconsistent results across population sub-groups. To determine the extent to which there are differences in lipid profile based on blood pressure levels, we assessed lipid profile of subjects with high-normal blood pressure and compared with those of hypertensives and optimally normal blood pressure. Methods: The study was a cross-sectional comparative study conducted at Aminu Kano Teaching Hospital, Kano, Nigeria. Fasting lipid levels were examined among randomly selected patients with optimally normal blood pressure (group 1), high - normal blood pressure (group 2) and those with hypertension (group 3). Optimal blood pressure was defined as systolic blood pressure (SBP) of 〈 120 mmHg / or diastolic blood pressure (DBP) of 〈 80 mmHg; and high- normal blood pressure as SBP of 130 - 139 mmHg / or DBP of 85 - 89 mmHg. Results: A total of 300 subjects were studied, 100 in each group. The mean age of subjects in group 1 was 27.32 +/- 8.20 years and 60% were female, while that of group 2 was 34.04 +/- 6.25 years, and 53% were female, and that for group 3 was 52.81 +/- 13.3 years and 56% were female. The mean total cholesterol (TC) for subjects in group1 (3.96 +/- 0.40 mmol/L) was significantly lower than levels in group2 (4.55 +/- 1.01 mmol/L); P = 5.2 mmol/L) was absent in group1, but found among 11% of group2 subjects and 40% of those in group 3 (P-value for trend 0.05 for groups 2 Vs 1 and p

Description: Global climate change is affecting health and mortality, particularly in vulnerable populations. High ambient temperatures decrease blood pressure (BP) in young and middle aged adults and may lead to orthostatic hypotension, increasing the risk of falls in older adults. The aim of this study was to evaluate the feasibility of a test protocol to investigate BP response and aerobic capacity of older adults in a hot indoor environment. BP response and aerobic capacity were assessed in 26 community-dwelling older women (median age 75.5 years) at a room temperature of either 20 °C or 30 °C. The protocol was well tolerated by all participants. In the 30 °C condition systolic and diastolic BP (median difference 10 and 8 mmHg, respectively) and distance walked in 6 min (median difference 29.3 m) were lower than in the 20 °C condition (all p 〈 0.01). Systolic BP decreased after standing up from a lying position in the 30 °C (17.4 mmHg) and 20 °C (14.2 mmHg) condition (both p 〈 0.001). In conclusion, the protocol is feasible in this cohort and should be repeated in older adults with poor physical performance and impaired cardio-vascular response mechanisms. Furthermore, aerobic capacity was reduced after exposure to hot environmental temperatures, which should be considered when recommending exercise to older people during the summer months.

Description: Background: Online cancer information can support patients in making treatment decisions. However, such information may not be adequately tailored to the patient?s perspective, particularly if healthcare professionals do not sufficiently engage patient groups when developing online information. We applied qualitative user testing during the development of a patient information website on stereotactic ablative radiotherapy (SABR), a new guideline-recommended curative treatment for early-stage lung cancer. Methods: We recruited 27 participants who included patients referred for SABR and their relatives. A qualitative user test of the website was performed in 18 subjects, followed by an additional evaluation by users after website redesign (N?=?9). We primarily used the `thinking aloud? approach and semi-structured interviewing. Qualitative data analysis was performed to assess the main findings reported by the participants. Results: Study participants preferred receiving different information that had been provided initially. Problems identified with the online information related to comprehending medical terminology, understanding the scientific evidence regarding SABR, and appreciating the side-effects associated with SABR. Following redesign of the website, participants reported fewer problems with understanding content, and some additional recommendations for better online information were identified. Conclusions: Our findings indicate that input from patients and their relatives allows for a more comprehensive and usable website for providing treatment information. Such a website can facilitate improved patient participation in treatment decision-making for cancer.

Description: Background: The parameters that characterize the intricate water diffusion in tumors may also reveal their distinct pathology. Specifically, characterization of breast cancer could be aided by diffusion magnetic resonance.The present in vitro study aimed to discover connections between the NMR biexponential diffusion parameters [fast diffusion phase (DFDP ), slow diffusion phase (DSDP ), and spin population of fast diffusion phase (P1)] and the histological constituents of nonmalignant (control) and malignant human breast tissue. It also investigates whether the diffusion coefficients indicate tissue status. Methods: Post-surgical specimens of control (mastopathy and peritumoral tissues) and malignant human breast tissue were placed in an NMR spectrometer and diffusion sequences were applied. The resulting decay curves were analyzed by a biexponential model, and slow and fast diffusion parameters as well as percentage signal were identified. The same samples were also histologically examined and their percentage composition of several tissue constituents were measured: parenchyma (P), stroma (St), adipose tissue (AT), vessels (V) , pericellular edema (PCE), and perivascular edema (PVE). Correlations between the biexponential model parameters and tissue types were evaluated for different specimens. The effects of tissue composition on the biexponential model parameters, and the effects of histological and model parameters on cancer probability, were determined by non-linear regression. . Results: Meaningful relationships were found among the in vitro data. The dynamic parameters of water in breast tissue are stipulated by the histological constituents of the tissues (P, St, AT, PCE, and V). High coefficients of determination (R 2) were obtained in the non-linear regression analysis: DFDP (R2 = 0.92), DSDP (R2 = 0.81), and P1(R2 = 0.93).In the cancer probability analysis, the informative value (R2) of the obtained equations of cancer probability in distinguishing tissue malignancy depended on the parameters input to the model. In order of increasing value, these equations were: cancer probability (P, St, AT, PCE, V) (R2 = 0.66), cancer probability (DFDP, DSDP)(R 2 = 0.69), cancer probability (DFDP, DSDP, P1) (R2 = 0.85). Conclusion: Histological tissue components are related to the diffusion biexponential model parameters. From these parameters, the relative probability of cancer in a given specimen can be determined with some certainty.

Description: Background: Aggregatibacter bacteria are a rare cause of endocarditis in adults. They are part of a group of organisms known as HACEK - Haemophilus, Aggregatibacter, Cardiobacter, Eikenella, and Kingella. Among these organisms, several Haemophilus species have been reclassified under the genus Aggregatibacter. Very few cases of Aggregatibacter endocarditis in patients with pacemaker devices have been reported.Case presentationWe present here what we believe to be the first case of Aggregatibacter aphrophilus pacemaker endocarditis. A 62-year-old African American male with a medical history significant for dual-chamber pacemaker placement in 1996 for complete heart block with subsequent lead manipulation in 2007, presented to his primary care doctor with fever, chills, night sweats, fatigue, and ten-pound weight loss over a four-month period. Physical examination revealed a new murmur and jugular venous distension which prompted initiation of antibiotics for suspicion of endocarditis. Both sets of initial blood cultures were positive for A. aphrophilus. Transesophageal echocardiogram revealed vegetations on the tricuspid valve and the right ventricular pacemaker lead (Figure 1). This case highlights the importance of identifying rare causes of endocarditis and recognizing that treatment may not differ from the standard treatment for typical presentations. The patient received intravenous ceftriaxone for his endocarditis for a total of six weeks. Upon device removal, temporary jugular venous pacing wires were placed. After two weeks of antibiotic treatment and no clinical deterioration, a new permanent pacemaker was placed and the patient was discharged home. Conclusions: This is the first case of A. aphrophilus endocarditis in a patient with a permanent pacemaker. Our patient had no obvious risk factors other than poor dentition and a history of repeated pacemaker lead manipulation. This suggests that valvulopathies secondary to repeated lead manipulation can be clinically significant factors in morbidity and mortality in this patient population.

Description: Background: Mitochondrial DNA maintenance disorders are an important cause of hereditary ataxia syndrome, and the majority are associated with mutations in the gene encoding the catalytic subunit of the mitochondrial DNA polymerase (DNA polymerase gamma), POLG. Mutations resulting in the amino acid substitutions A467T and W748S are the most common genetic causes of inherited cerebellar ataxia in Europe. Methods: We report here a POLG mutational screening in a family with a mitochondrial ataxia phenotype. To evaluate the likely pathogenicity of each of the identified changes, a 3D structural analysis of the PolG protein was carried out, using the Alpers mutation clustering tool reported previously. Results: Three novel nucleotide changes and the p.Q1236H polymorphism have been identified in the affected members of the pedigree. Computational analysis suggests that the p.K601E mutation is likely the major contributing factor to the pathogenic phenotype. Conclusions: Computational analysis of the PolG protein suggests that the p.K601E mutation is likely the most significant contributing factor to a pathogenic phenotype. However, the co-occurrence of multiple POLG alleles may be necessary in the development an adult-onset mitochondrial ataxia phenotype.

Description: Background: Plant receptor-like kinase (RLK/Pelle) family regulates growth and developmental processes and interaction with pathogens and symbionts.Platanaceae is one of the earliest branches of Eudicots temporally located before the split which gave rise to Rosids and Asterids. Thus investigations into the RLK family in Platanus can provide information on the evolution of this gene family in the land plant.Moreover RLKs are good candidate for finding genes that are able to confer resistance to Platanus pathogens. Results: Degenerate oligonucleotide primers targeting the kinase domain of stress-related RLKs were used to isolate for the first time 111 RLK gene fragments in Platanus x acerifolia. Sequences were classified as candidates of the following subfamilies: CrRLK1L, LRR XII, WAK-like, and LRR X-BRI1 group. All the structural features typical of the RLK kinase domain were identified, including the non-RD motif which marks potential pathogen recognition receptors (PRRs). The LRR XII candidates, whose counterpart in Arabidopsis and rice comprises non-RD PRRs, were mostly non-RD kinases, suggesting a group of PRRs. Region-specific signatures of a relaxed purifying selection in the LRR XII candidates were also found, which is novel for plant RLK kinase domain and further supports the role of LRR XII candidates as PRRs. As we obtained CrRLK1L candidates using primers designed on Pto of tomato, we analysed the phylogenetic relationship between CrRLK1L and Pto-like of plant species. We thus classified all non-solanaceous Pto-like genes as CrRLK1L and highlighted for the first time the close phylogenetic vicinity between CrRLK1L and Pto group. The origins of Pto from CrRLK1L is proposed as an evolutionary mechanism. Conclusions: The signatures of relaxed purifying selection highlight that a group of RLKs might have been involved in the expression of phenotypic plasticity and is thus a good candidate for investigations into pathogen resistance.Search of Pto-like genes in Platanus highlighted the close relationship between CrRLK1L and Pto group. It will be exciting to verify if sensu strictu Pto are present in taxonomic groups other than Solanaceae, in order to further clarify the evolutionary link with CrRLK1L.We obtained a first valuable resource useful for an in-depth study on stress perception systems.

Description: Background: Analyzing the microarray data of different conditions, one can identify the conserved and condition-specific genes and gene modules, and thus can infer the underlying cellular activities. All the available tools based on Bioconductor and R packages differ in how they extract differential coexpression and at what level they study. There is a need for a user-friendly, flexible tool which can start analysis using raw or preprocessed microarray data and can report different levels of useful information. Findings: We present a GUI software, No3CoGP: Non-Conserved and Conserved Coexpressed Gene Pairs which takes Affymetrix microarray data (.CEL files or log2 normalized .txt files) along with annotation file (.csv file), Chip Definition File (CDF file) and probe file as inputs, utilizes the concept of network density cut-off and Fisher's z-test to extract biologically relevant information. It can identify four possible types of gene pairs based on their coexpression relationships. These are (i) gene pair showing coexpression in one condition but not in the other, (ii) gene pair which is positively coexpressed in one condition but negatively coexpressed in the other condition, (iii) positively and (iv) negatively coexpressed in both the conditions. Further, it can generate modules of coexpressed genes. Conclusion: Easy-to-use GUI interface enables researchers without knowledge in R language to use No3CoGP. Utilization of one or more CPU cores, depending on the availability, speeds up the program. The output files stored in the respective directories under the user-defined project offer the researchers to unravel condition-specific functionalities of gene, gene sets or modules.

Description: Background: IRAK-M is an inhibitor of Toll-like receptor signaling that acts by re-directing IRAK-4 activity to TAK1 independent NF-?B activation and by inhibition of IRAK-1/IRAK-2 activity. IRAK-M is expressed in monocytes/macrophages and lung epithelial cells. Lack of IRAK-M in mice greatly improves the resistance to nosocomial pneumonia and lung tumors, which entices IRAK-M as a potential therapeutic target. IRAK-M consists of an N-terminal death domain (DD), a dysfunctional kinase domain and unstructured C-terminal domain. Little is known however on IRAK-M?s structure-function relationships. Results: Since death domains provide the important interactions of IRAK-1, IRAK-2 and IRAK-4 molecules, we generated a 3D structure model of the human IRAK-M-DD (residues C5-G119) to guide mutagenesis studies and predict protein-protein interaction points. First we identified the DD residues involved in the endogenous capacity of IRAK-M to activate NF-?B that is displayed upon overexpression in 293T cells. W74 and R97, at distinct interfaces of the IRAK-M-DD, were crucial for this endogenous NF-?B activating capacity, as well as the C-terminal domain (S445-E596) of IRAK-M. Resulting anti-inflammatory A20 and pro-inflammatory IL-8 transcription in 293T cells was W74 dependent, while IL-8 protein expression was dependent on R97 and the TRAF6 binding motif at P478. The IRAK-M-DD W74 and R97 binding interfaces are predicted to interact with opposite sides of IRAK-4-DD?s. Secondly we identified DD residues important for the inhibitory action of IRAK-M by stable overexpression of mutants in THP-1 macrophages and H292 lung epithelial cells. IRAK-M inhibited TLR2/4-mediated cytokine production in macrophages in a manner that is largely dependent on W74. R97 was not involved in inhibition of TNF production but was engaged in IL-6 down-regulation by IRAK-M. Protein-interactive residues D19-A23, located in between W74 and R97, were also observed to be crucial for inhibition of TLR2/4 mediated cytokine induction in macrophages. Remarkably, IRAK-M inhibited TLR5 mediated IL-8 production by lung epithelial cells independent of W74 and R97, but dependent on D19-A23 and R70, two surface-exposed regions that harbor predicted IRAK-2-DD interaction points of IRAK-M. Conclusion: IRAK-M employs alternate residues of its DD to inhibit the different inflammatory mediators induced by varying TLRs and cells.

Description: TGFβ1 (Transforming Growth Factor-beta1) is a versatile regulator of T cell immune responses. Depending on its context in the immunological environment, TGFβ1 guides T cells toward specific activation programs including TH17 and regulatory T cell activities. Moreover, TGFβ signals function in immune homeostasis by directly attenuating T cell effector activities. We uncovered a novel context under which TGFβ1 stringently and reversibly silences activation responses of resting human T cells to TCR/CD28 stimulating surfaces:Using ligand-presenting beads, TGFβ1 and TCR/CD28-activating signals were directed into defined plasma membrane domains of T cells. Selective targeting of TGFβ1 cytokine into TCR/CD28 signalling plasma membrane domains held back early response of TCR-proximal tyrosine phosphorylation and bead engulfment at activation sites. Consequently, downstream induction of proliferation and cytokine secretion were stringently attenuated. After extended incubation with TGFβ1-presenting beads, silenced T cells became receptive again to activation by renewed TCR/CD28-stimuli, indicating that the unresponsive state of T cells was reverted and did not reflect long-lasting anergy or decrease in T cell viability. These findings outline a new strategy of physically linking TGFβ1 and TCR-activating functions for the treatment of disease and pathological conditions which are caused by unwanted T cell activity.

Description: Avoiding or minimizing potential environmental impact is the driving idea behind protecting a population’s health via Environmental Impact Assessments (EIAs) and Strategic Environmental Assessments (SEAs). However, both are often carried out without any systematic approach. This paper describes the findings of a review of HIA, EIA and SEA experiences carried out by the authors, who act as institutional competent subjects at the national and regional levels in Italy. The analysis of how health is tackled in EIA and SEA procedures could support the definition of a protocol for the integration of HIA with EIA and SEA. Although EIA and SEA approaches include the aim of protecting health, significant technical and methodological gaps are present when assessing health systematically, and their basic principles regarding assessment are unsatisfactory for promoting and addressing healthcare concepts stated by the WHO. HIA is still poorly integrated into the decision-making process, screening and monitoring phases are only occasionally implemented, and operational details are not well-defined. The collaborative approach of institutions involved in environment and health is a core element in a systematic advancement toward supporting effective decisions and effective protection of the environment and health. At the Italian national level, the definition of guidelines and tools for HIA, also in relation with EIA and SEA, is of great interest.

Description: There is expedient evidence showing that differences in adolescent alcohol consumption and other risk-behaviour depend on both family structure and family member drunkenness exposure. Data were obtained among adolescents (N = 12,115, mean age 14.9 ± 0.89) in Austria, Estonia, France, Germany, Hungary, Ireland, Israel, Italy, Romania, Slovenia and Spain within the European Union’s 7th Framework Programme funded project, ‘Saving and Empowering Young Lives in Europe (SEYLE)’. The current study reveals how adolescents’ alcohol consumption patterns are related to their family structure and having seen their family member drunk. The results revealed statistically significant differences in adolescent alcohol consumption depending on whether the adolescent lives in a family with both birth parents, in a single-parent family or in a family with one birth parent and one step-parent. The study also revealed that the abstaining from alcohol percentage among adolescents was greater in families with both birth parents compared to other family types. The study also showed that the more often adolescents see their family member drunk the more they drink themselves. There is no difference in adolescent drinking patterns whether they see their family member drunk once a month or once a week. This study gives an insight on which subgroups of adolescents are at heightened risk of alcohol abuse and that decrease of family member drunkenness may have positive effects on the drinking habits of their children.

Description: Background: The percentage of time during which the patients have the INR within the target values (i.e. Time in Therapeutic Range [TTR]) is a quality measure of anticoagulation with Vitamin K Antagonists (VKA). To evaluate the quality of anticoagulation using TTR according to the Rosendaal method, we performed an observational, retrospective study. We included all outpatients who attended the cardiology anticoagulation clinic of a Portuguese hospital (2011-2013), whose target INR was 2.0-3.0. Results: 377 VKA-treated patients were evaluated. Of these, 72.4% had non-valvular atrial fibrillation. Patients were followed for a mean period of 471 days. The mean TTR was 60.3% (SD 19.3%) and 44.3% of the patients had a mean TTR 〈 60%. Patients were at high risk of bleeding (INR 〉 4.5) and at high thrombotic risk (INR 〈 1.5) during, respectively, 1.7% and 4.7% of the time. Conclusions: Anticoagulation control needs to be improved. These results are informative for all stakeholders: patients, health care professionals, and policymakers.

Description: Background: The ever-expanding rollout of antiretroviral therapy in poor resource settings without routine virological monitoring has been accompanied with development of drug resistance that has resulted in limited treatment success. Methods: A cross-sectional study with one time viral load was conducted during the period between 2012 and 2013 to determine treatment failure and drug resistance mutations among adults receiving first-line (44) (3TC_d4T/AZT_NVP/EFV) and second-line (20) (3TC/AZT/LPV/r) in Nairobi, Kenya. HIV-1 pol-RT genotyping for drug resistance was performed using an in-house protocol. Results: A total of 64 patients were recruited (mean age 36.9 yrs.) during the period between 2012 and 2013 of the 44 adult patients failing first-line 24 (40.9%) had drug resistance mutations. Eight (8) patients had NRTI resistance mutations with NAMS M184V (54.2%) and K65R (8.4%) mutations being the highest followed by TAMs T215Y and K70R (12.5%). In addition, among patients failing second-line (20), six patients (30%) had NNRTI resistance; two patients on K103N and G190A mutations while V106A, Y184V, A98G, Y181C mutations per patient were also detected. However, for NRTI two patients had TAM T215Y. M184V mutation occurred in one patient. Conclusions: The study findings showed that HIV-1 drug resistance was significantly high in the study population. The detected accumulated resistance strains show that emergence of HIV drug resistance will continue to be a big challenge and should be given more attention as the scale up of treatment in the country continues.

Description: Background: During the Hajj season, respiratory symptoms are very common among pilgrims. Here, we investigated the viable bacterial population in air samples collected around the slaughterhouses used during the Hajj.Methods and results: We collected air samples on three days from four different sites: slaughterhouses at Al-Kakia, Al-Meaisim and Al-Sharaia, and from a waste disposal area designated for the remnants of slaughter. Samples were cultured on blood agar plates for 48 h, and bacterial isolates were identified using MALDI-TOF MS. A dendrogram using the spectra of the unidentified bacterial species was constructed, and PCR amplification and sequencing of the 16S rRNA gene was performed for one isolate per cluster. In total, 2500 colonies appeared on the nutrient agar plates, and 244 were purified for further analysis. Good identification was obtained for 202 (83%) isolates by MALDI-TOF MS. The most common genera were Bacillus (n = 94, 45%) and Staphyloccocus (n = 55, 26%). Poor identification was obtained for 42 (17%) isolates, and their spectra clustering revealed that these isolates belonged to 10 species. Four of these were considered to be new species. Conclusions: During the Hajj, the air was contaminated by many environmental bacterial agents, and MALDI-TOF MS was successfully adapted for their rapid identification.

Description: In urban Maroua, Cameroon, improved drinking water sources are available to a large majority of the population, yet this water is frequently distributed through informal distribution systems and stored in home containers (canaries), leaving it vulnerable to contamination. We assessed where contamination occurs within the distribution system, determined potential sources of environmental contamination, and investigated potential pathogens. Gastrointestinal health status (785 individuals) was collected via health surveys. Drinking water samples were collected from drinking water sources and canaries. Escherichia coli and total coliform levels were evaluated and molecular detection was performed to measure human-associated faecal marker, HF183; tetracycline-resistance gene, tetQ; Campylobacter spp.; and Staphylococcus aureus. Statistical analyses were performed to evaluate the relationship between microbial contamination and gastrointestinal illness. Canari samples had higher levels of contamination than source samples. HF183 and tetQ were detected in home and source samples. An inverse relationship was found between tetQ and E. coli. Presence of tetQ with lower E. coli levels increased the odds of reported diarrhoeal illness than E. coli levels alone. Further work is warranted to better assess the relationship between antimicrobial-resistant bacteria and other pathogens in micro-ecosystems within canaries and this relationship’s impact on drinking water quality.

Description: The authors wish to add the following amendment and correction on their paper published in IJERPH [1]: Page 6139, Line 3 in Paragraph 3: “…Israel, [17,18],…” should read “…Israel and Palestine [17,18]…”. [...]

Description: Longitudinal data enables detecting the effect of aging/time, and as a repeated measures design is statistically more efficient compared to cross-sectional data if the correlations between repeated measurements are not large. In particular, when genotyping cost is more expensive than phenotyping cost, the collection of longitudinal data can be an efficient strategy for genetic association analysis. However, in spite of these advantages, genome-wide association studies (GWAS) with longitudinal data have rarely been analyzed taking this into account. In this report, we calculate the required sample size to achieve 80% power at the genome-wide significance level for both longitudinal and cross-sectional data, and compare their statistical efficiency. Furthermore, we analyzed the GWAS of eight phenotypes with three observations on each individual in the Korean Association Resource (KARE). A linear mixed model allowing for the correlations between observations for each individual was applied to analyze the longitudinal data, and linear regression was used to analyze the first observation on each individual as cross-sectional data. We found 12 novel genome-wide significant disease susceptibility loci that were then confirmed in the Health Examination cohort, as well as some significant interactions between age/sex and SNPs.

Description: To mitigate climate change, city authorities are developing policies in areas such as transportation, housing and energy use, to reduce greenhouse gas emissions. In addition to their effects on greenhouse gas emissions, these policies are likely to have consequences for the wellbeing of their populations for example through changes in opportunities to take physical exercise. In order to explore the potential consequences for wellbeing, we first explore what ‘wellbeing’ is and how it can be operationalised for urban planners. In this paper, we illustrate how wellbeing can be divided into objective and subjective aspects which can be measured quantitatively; our review of measures informs the development of a theoretical model linking wellbeing to policies which cities use to reduce greenhouse gas emissions. Finally, we discuss the extent to which the links proposed in the conceptual model are supported by the literature and how cities can assess wellbeing implications of policies.

Description: Aluminum absorption leads to deposits in several tissues. In this study, we have investigated, to our knowledge for the first time, aluminum deposition in the salivary glands in addition to the resultant cellular changes in the parotid and submandibular salivary glands in a model of chronic intoxication with aluminum citrate in rats. Aluminum deposits were observed in the parotid and submandibular glands. Immunohistochemical evaluation of cytokeratin-18 revealed a decreased expression in the parotid gland with no changes in the submandibular gland. A decreased expression of α-smooth muscle actin was observed in the myoepithelial cells of both glands. The expression of metallothionein I and II (MT-I/II), a group of metal-binding proteins, which are useful indicators for detecting physiological responses to metal exposure, was higher in both glands. In conclusion, we have shown that at a certain time and quantity of dosage, aluminum citrate promotes aluminum deposition in the parotid and submandibular glands, leads to an increased expression of MT-I/II in both the glands, damages the cytoskeleton of the myoepithelial cells in both glands, and damages the cytoskeleton of the acinar/ductal cells of the parotid glands, with the submandibular glands showing resistance to the toxicity of the latter.

Description: Compensatory health beliefs (CHBs) are beliefs that an unhealthy behavior can be compensated with a healthy behavior. In line with the CHBs model, the aim of this study was twofold. First, the study investigated the relationship between autonomous motivation and CHBs that physical inactivity can be compensated by taking the stairs instead of the elevator. Second, the study focused on the associations between CHBs and readiness to use the stairs more often and stair and elevator use. Thus, a cross-sectional online questionnaire was designed that was filled out by 135 participants. Path analysis showed that individuals with stronger autonomous motivation to use the stairs strongly agreed that sedentary behavior could be compensated by taking the stairs instead of the elevator. Moreover, CHBs were positively related to readiness to change behavior, but not to self-reported stair and elevator use. Even though future research is necessary to replicate these findings, autonomous motivation seems to have a positive impact on CHBs which, in turn, might boost an intended behavior change. Thus, promoting possible compensation of physical inactivity might foster the readiness to change the unhealthy behavior.

Description: Climate change puts pressure on existing health vulnerabilities through higher frequency of extreme weather events, changes in disease vector distribution or exacerbated air pollution. Climate change adaptation policies may hold potential to reduce societal inequities. We assessed the role of public health and social justice in European climate change adaptation using a three-fold approach: a document analysis, a critical discourse analysis of a subgroup of strategies, and a ranking of strategies against our social justice framework. The ranking approach favored planning that includes various adaptation types, social issues and infrastructure changes. Themes on values identified in the five subgroup documents showed that risks are perceived as contradictory, technology is viewed as savior, responsibilities need to be negotiated, and social justice is advocated by only a few countries. Of 21 strategy documents assessed overall, those from Austria, England and Sweden received the highest scores in the ranking. Our qualitative assessment showed that in European adaptation planning, progress could still be made through community involvement into adaptation decisions, consistent consideration of social and demographic determinants, and a stronger link between infrastructural adaptation and the health sector. Overall, a social justice framework can serve as an evaluation guideline for adaptation policy documents.

Description: Cervical cancer remains a significant cause of morbidity and mortality for women in developing countries, despite the fact that inexpensive, simple and effective screening methods are available. Visual inspection of the cervix with acetic acid (VIA) can be used as part of a “reen and treat” program to identify precancerous lesions for cryotherapy treatment. This case report details how the VIA screening test was incorporated into the care of a patient presenting to a maternal health clinic in Thomonde, Haiti which was staffed by doctors and medical students from Emory University School of Medicine in collaboration with Haiti Medishare. As demonstrated here, the VIA test requires minimal materials, can be efficiently incorporated into a physical exams, provides immediate results, and is easily demonstrated to and performed by local healthcare providers. The straightforward and sensitive VIA technique is an ideal cervical cancer screening method for resource poor areas.

Description: Background: Evolutionary psychologists hypothesized that men are more upset by sexual infidelity than women are, whereas women are more upset by emotional infidelity than men are. On the other hand, the sexual imagination hypothesis states that gender differences in infidelity responses are derived from explicit men's sexual imagery. Based on the latter hypothesis, we hypothesized that although men would report being more distressed by sexual infidelity than women who were not in a committed relationship (NCR), no gender difference would be reported in a committed relationship (CR).FindingsThese two hypotheses were tested with 598 participants in a CR and 1,643 participants in a NCR. No significant gender difference was found sexual infidelity response in the CR group (d = 0.008, a power of .956), whereas men were more upset than women about sexual infidelity in the NCR group. Moreover, a significant interaction between gender and infidelity type was found in the NCR, whereas no significant interaction between gender and infidelity type was observed in the CR group (partial eta2 = 0.005, a power of .943). Conclusions: Our findings supported the sexual imagination hypothesis but were inconsistent with the EJM hypothesis.

Description: Background: Somatic cell cloning by nuclear transfer (SCNT) in pig is clearly of great benefit for basic research and biomedical applications. Even though cloned offspring have been successfully produced in pig, SCNT is struggling with the low efficiency. Results: In the present study, we investigated differentially expressed proteins of the extraembryonic tissue from pig SCNT fetus compared to control (normal) fetus. We obtained the extraembryonic tissue from embryos at day 35 of pregnancy and examined the protein expression profiles using two-dimensional electrophoresis (2-D) and Western blotting. The extraembryonic tissue of fetus in control pregnancy was compared to the extraembryonic tissue of SCNT fetus, which showed an abnormally small size and shape as well as exhibited abnormal placental morphology compared to control fetus. A proteomic analysis showed that the expression of 33 proteins was significantly increased or decreased in the extraembryonic tissue of SCNT fetus compared to control fetus. The differentially expressed proteins in the extraembryonic tissue of SCNT fetus included ATP or lipid binding proteins, antioxidant proteins, translation elongation factors, and transcription factors. Western blotting analysis indicated that antioxidant enzymes and anti-apoptotic proteins were down-regulated; however, the expression levels of apoptotic proteins, Bax and Hsp27, were increased in the extraembryonic tissue of SCNT fetus. Moreover, immunohistochemical analysis also showed that the expression of the catalase or GPX genes was decreased in the extraembryonic tissue with SCNT fetus compared to those with control fetus. In addition, we observed a significant decrease in DNA methytransferase1 (Dnmt1) expression in SCNT extraembryonic tissue, and the expression levels of Dnmt3a and Dnmt3b were abnormally higher in SCNT fetus compared to control fetus. Moreover, a marked increase in the frequency of TUNEL-positive cells was observed in the extraembryonic tissue in SCNT fetus. Conclusion: These results demonstrated that pig SCNT fetus showed abnormal protein expression in the extraembryonic tissue, and extensive apoptosis occurred in the extraembryonic tissue of the SCNT fetus due to an increase in apoptotic protein expression or a decrease in antioxidant protein expression.

Description: Background: Brain abscess are uncommon childhood infection. Brain abscess caused by Panton-Valentine Leokocidin positive Community acquired Methicillin Resistant Staphylococcal aureus have never been reported in the United Kingdom.Case presentationWe report a case of a previously well 11-month old boy of Indian origin who developed a parietal lobe abscess from PVL positive CA-MRSA. Conclusion: This case is one of the few described cases of brain abscess caused by PVL CA-MRSA in children. The unusual (insidious) presentation, the absence of a clear staphylococcal focus and the unexpected finding of a CA-MRSA in this patient highlight the challenges of managing such cases in clinical settings and the potential future risk to public health.

Description: Background: Influenza B viruses are classified into two main lineages: Yamagata-like and Victoria-like, which differ antigenically and phylogenetically. To understand the evolution of influenza B viruses in South East Asia as well as to determine the vaccine efficacy, we genetically characterised gene segments 4, 6 and 8 from non-tissue culture adapted influenza B viruses detected in Singapore from 2004 to 2009. Methods: vRNA were extracted from the nasopharygeal swabs or nasal washes of SAF servicemen displaying febrile and respiratory symptoms, and subjected to PCR assay to test for the presence of influenza B virus. The PCR-positive specimens were next subjected to sequencing of the full gene segments 4 (HA), 6 (NA/NB) and 8 (NS1/NEP). The nucleotide sequences were aligned together with that of other specimens isolated from South East Asia as well as the vaccine strains. Phylogenetic trees of each gene segment were constructed and the amino acid alignments were analysed. Results: A majority of the Singaporean specimens analysed in this study, from 2004-2009, had gene segment 4 from the Victoria-like lineage and gene segment 6 from Yamagata-like lineage. Some of these specimens had both gene segments from the Yamagata lineage and this resulted in several vaccine mismatches. Gene segment 8 from majority of these specimens clustered separately from both the Yamagata and Victoria strains. The HA protein of the most of Singaporean specimens isolated post 2000 contained a glycosylation site at position 211, which was not dominant prior to 2000. No amino acid substitution conferring drug-resistance was found in either the HA or NA proteins. Conclusions: The presence of both lineages co-circulating post 2000, suggests that a trivalent vaccine is not enough to confer immunity to the general public, strongly endorsing the inclusion of both lineages in the vaccine. Several amino acid substitutions were observed, prompting in depth functional analyses.

Description: Background: Dengue is an important worldwide public health problem, and continues to spread in Brazil. This article presents the first Brazilian case report of the death of an indigenous child by dengue fever.Case presentationIn August 2013, a child aged 2 years and from the Tremembé ethnic group, who was previously healthy with no complaints, suddenly presented intense crying, precordial pain, and general malaise. A few minutes after these non-specific symptoms, the patient started tonic–clonic convulsions and had cyanosis, a substantial increase in body temperature to the touch, cold sudoresis, sphincter relaxation, and unconsciousness. This situation remained for 15 minutes, progressing to respiratory insufficiency, with consequent absence of peripheral pulses. Death was confirmed approximately 40 minutes after the first symptoms. An autopsy was performed using the usual techniques. Immunohistochemistry was positive for dengue, and microscopic examination indicated micro perivascular edema and cerebral hemorrhage. Conclusion: Considering that the death occurred during the major endemic seasonal period for dengue fever, primary clinical evidence suggestive of viral infection presenting with sudden and quick death, and positive immunohistochemistry results, the case was closed as severe dengue fever. Clinicians must consider dengue as a diagnostic hypothesis among the indigenous population in Brazil.

Description: Background: Epithelial-to-mesenchymal transition (EMT) induced by TGF-?1 is one of well-recognized factors contributing to renal fibrosis. However, the underlying molecular mechanisms of EMT are not fully understood. Brachyury, an evolutionarily conserved transcription factor, was recently identified as an important factor promoting EMT in human carcinoma cell lines. There is no evidence that Brachyury is involved in renal tubular EMT. Results: Our results demonstrated that Brachyury was prominently induced in TGF-?1-treated human proximal tubular epithelial (HK-2) cells and that this induction was accompanied by changes characteristic of EMT. Blockage of Brachyury expression by short interfering RNA (siRNA) in HK-2 cells effectively reversed the TGF-?1-induced EMT phenotype. Brachyury induction repressed E-cadherin transcription; the E-cadherin promoter contains a Brachyury binding site, and decreased expression of E-cadherin occurred in Brachyury-overexpressing cells when they were transfected with reporter constructs using the promoter. This effect was partially mediated by Slug and Snail, as knockdown of Snail and Slug by siRNA effectively reversed Brachyury-mediated EMT and partially restored E?cadherin expression. The expression of Brachyury also presented in a rat model of obstructive nephropathy and in tubulointerstitial fibrosis tissues of IgA nephropathy, suggesting that it may have a role in EMT and renal fibrosis in vivo. Conclusion: Our results demonstrate for the first time that Brachyury plays an important role in regulating TGF-?1?mediated renal EMT and could be an attractive target for progression of renal disease therapies.

Description: Background: Management of late relapse of a testicular germ cell tumor is difficult because few cases have been reported and the tumors are intractable to chemotherapy. Here we present a case with a single brain metastasis from late relapse of a testicular germ cell tumor. This is the first report of a brain metastasis that was treated successfully only by surgery.Case presentationA 19-year-old Japanese man presented with breathing difficulties and left testis enlargement and he was diagnosed with a yolk sac tumor following a left orchiectomy. At the time of diagnosis, multiple lung metastases were apparent on computed tomography, and serum alpha-fetoprotein level was elevated to 10,245 ng/ml. The patient received three postoperative courses of bleomycin, etoposide and cisplatin and etoposide and cisplatin respectively and a complete response was obtained. Four years after surgery, the patient was admitted to the hospital due to a sudden seizure. High alpha-fetoprotein levels (539 ng/ml) were evident and magnetic resonance imaging suggested a 45-mm single brain tumor in the right parietal lobe, for which surgery was performed. The pathological diagnosis was yolk sac tumor. The alpha-fetoprotein level remained normal at 2 months after operation. There was no recurrence 24 months post-operation. Conclusion: Chemoresistance and late neurotoxicity are concerns in treating brain metastasis with chemotherapy or cerebral radiotherapy. Surgery is believed to be the optimal treatment choice if the size of the brain metastasis is larger than 35-mm and the late relapse area is surgically accessible.

Description: and projection. Although China is the world's most populous country with approximately a fifth of the world's population, none of the empirical tables from mainland China were used in calibrating the existing models. In this paper, we applied recent three model life table systems with different inputs to China mortality data to investigate whether or not these systems truly reflect Chinese mortality epidemiological patterns and whether or not system biases exist. The resulting residuals show that, in most cases, the male infant mortality rate (1q0), adult mortality rate (45q15) and old age mortality rate (20q60) have a strong bias towards being overestimated and the life expectancy at birth (e0) bias is underestimated. We also give the detailed results for each case. Furthermore, we found that the average relative errors (AREs) for females are more than those for males for e0, 45q15 and 20q60, but for 1q0, males have larger AREs in the Wilmoth and Murray systems. We also found that the urban population has more errors than the rural population in almost all cases. Finally, by comparing the AREs with 10 other countries, we found the errors for China are more than those for other countries in most cases. It is concluded that these existing model life table systems cannot accurately reflect Chinese mortality epidemiological situations and trajectories. Therefore, model life tables should be used with caution when applied to China on the basis of 5q0.

Description: Objective: To assess the impact of different smoking behaviors of caregivers on environmental tobacco smoke (ETS) exposure in children aged 5–6 years in Changsha, China. Methods: We conducted a cross-sectional, random digit-dial telephone survey of caregivers (n = 543) between August and October 2013. Caregivers’ smoking behaviors were collected by a questionnaire. Exposure assessment was based upon determination of urinary cotinine levels in children employing gas chromatography–triple quadrupole mass spectrometry (GC-MS/MS). Results: In children not living with a smoker, children living with one smoker, and children living with more than one smoker at home, median urinary cotinine concentrations (ng/mL) were 0.72, 2.97, and 4.46, respectively. For children living with one smoker, median urinary cotinine levels of children exposed to ETS were associated with caregiver smoking behaviors, i.e., if a caregiver consumed more cigarettes (>20 compared with ≤10; 7.73 versus 2.29 ng/mL, respectively). Conclusions: The magnitude of ETS exposure in children is correlated with the smoking behaviors of the caregiver. Counseling for smoking cessation and educational interventions are needed urgently for smoking caregivers to increase their awareness about ETS exposure and to encourage smoking cessation at home or to take precautions to protect children’s health.

Description: Lentinus edodes, a functional food, was evaluated as a potential antidote for adsorption/removal of cadmium ion from simulated gastrointestinal fluids. An adsorption/removal capacity of 65.12 mg/g was achieved by L. edodes in solutions with a pH ranging from 2.5 to 6.0, while little if any adsorption was observed in solutions with a pH under 2.5. In solutions with pH 6.0, 84% of the cadmium adsorption by L. edodes occurred in the first minute. Scanning electronic microscopic examination showed that the cell wall polysaccharides of L. edodes provided a rough sponge-like surface for effective cadmium adsorption. FTIR indicated that the carboxyl, hydroxyl and –NH groups of the cell wall polysaccharides and proteins were the primary functional groups that chemically bind with cadmium ions. The energy dispersive spectrometry further revealed that cation exchange might be attributed to cadmium biosorption. These results suggested that L. edodes was effective for cadmium detoxication, especially in low concentration.

Description: This study set out to explore the relationship between female media use behavior and agreement with agenda-specific publicly promoted health messages. A random digit dial telephone cross-sectional survey was conducted using a nationally representative sample of female residents aged 25 and over. Respondents’ agreement with health messages was measured by a six-item Health Information Scale (HIS). Data were analyzed using chi-square tests and multiple logistic regression. This survey achieved a response rate of 86% (n = 1074). In this study the longest duration of daily television news watching (OR = 2.32), high self-efficacy (OR = 1.56), and greater attention to medical and health news (OR = 5.41) were all correlates of greater agreement with the selected health messages. Surprisingly, Internet use was not significant in the final model. Many women that public health interventions need to be targeting are not receptive to health information that can be accessed through Internet searches. However, they may be more readily targeted by television campaigns. Agenda-specific public health campaigns aiming to empower women to serve as nodes of information transmission and achieve efficient trickle down through the family unit might do better to invest more heavily in television promotion.

Description: Background: Adenovirus co-infections in HIV patients cause wide-spread morbidity in sub-Saharan Africa, but little research has documented the burden and distribution of these pathogens. This study was conducted between December, 2010 and March, 2011 to investigate the prevalence of Adenovirus Respiratory Tract and HIV co-infections in Patients attending the University of Ilorin Teaching Hospital Ilorin, Nigeria.MethodOne Hundred and Eighty Four (184) patients were recruited with confirmed HIV positive status. Investigation was done by serology using the Human Adenovirus IgG ELISA Kit to test for the presence of the Immunoglobulin G (antibody) against the virus. This was conducted and juxtaposed simultaneously with responses received from the questionnaires provided to each participant to correlate the relationship of the co-infections to their socio-demographic factors (Age, Gender, Occupation and location of residence), risk factors (Average hours of exposure per day (time spent outdoor daily), proximity of their apartments to livestock settlements), recent occurrence of respiratory tract infections/conjunctivitis and their ART status. Results: This study recorded a prevalent rate of 38% (70 patients) to the co-infections. Nevertheless, 62% (114 patients) tested negative to the co-infections. Conclusion: There was statistical significance between the ages of HIV patients and Adenovirus co-infection (p 〈 0.05). However, there was no significance with respect to gender of the subjects (p 〉 0.05). The findings also showed that there were statistical significance for all the risk factors; Occupation, Location and Proximity to Livestock settlement, recent respiratory tract infection/conjunctivitis, and ART status in relation to Adenovirus and HIV co-infections (p 〈 0.05).

Description: Public fitness centers and exercise facilities have been implicated as possible sources for transmitting community-acquired bacterial infections. However, the overall diversity of the bacterial community residing on the surfaces in these indoor environments is still unknown. In this study, we investigated the overall bacterial ecology of selected fitness centers in a metropolitan area (Memphis, TN, USA) utilizing culture-independent pyrosequencing of the 16S rRNA genes. Samples were collected from the skin-contact surfaces (e.g., exercise instruments, floor mats, handrails, etc.) within fitness centers. Taxonomical composition revealed the abundance of Firmicutes phyla, followed by Proteobacter and Actinobacteria, with a total of 17 bacterial families and 25 bacterial genera. Most of these bacterial genera are of human and environmental origin (including, air, dust, soil, and water). Additionally, we found the presence of some pathogenic or potential pathogenic bacterial genera including Salmonella, Staphylococcus, Klebsiella, and Micrococcus. Staphylococcus was found to be the most prevalent genus. Presence of viable forms of these pathogens elevates risk of exposure of any susceptible individuals. Several factors (including personal hygiene, surface cleaning and disinfection schedules of the facilities) may be the reasons for the rich bacterial diversity found in this study. The current finding underscores the need to increase public awareness on the importance of personal hygiene and sanitation for public gym users.

Description: Background: Shiga toxin-producing Escherichia coli (STEC) is the causative agent of hemolytic uremic syndrome (HUS). Colloidal bismuth hydroxide gel (CBHG) is an anti-diarrheal and antisecretory compound, which does not inhibit gastrointestinal motility and reaches an in vivo gut concentration of 10.8 mg/ml of bismuth. Its action on bacteria has not been studied. We analyzed its inhibitory effects on STEC, as well as the deactivation of the Shiga toxin (Stx) and its ability to block the spread of genes encoding Stx. We determined a minimum inhibitory concentration and bactericidal concentration for the STEC O157:H7 strain (EDL933), with CBHG and Chobet(R) bismuth cream with pectin (CBCHP). We analyzed its effect on Stx by means of cytotoxicity assay and ELISA, as well as its effect on the free 933 W Stx phage. Results: Effect on the EDL933 strain: CBHG: MIC 10 mg/ml of bismuth. CBCHP: MIC 6 mg/ml and MBC 15 mg/ml of bismuth. Effect on EDL933 virulence factors: significant decrease in active Stx and 933 W Stx phage titer. ELISA did not find significant differences with treatment. Conclusions: The results obtained may be useful in the development of new therapeutic strategies based on the use of CBHG to prevent or improve the prognosis of HUS, as it can be used to control STEC infections.

Description: Tobacco use, the leading cause of preventable death in the U.S., can be reduced through state-level tobacco prevention and cessation programs. In the absence of research about how to communicate the need for these programs to policymakers, this qualitative study aimed to understand the motivations and priorities of policymakers in North Carolina, a state that enacted a strong tobacco control program from 2003–2011, but drastically reduced funding in recent years. Six former legislators (three Democrats, three Republicans) and three lobbyists for health organizations were interviewed about their attitudes towards tobacco use, support of state-funded programs, and reactions to two policy briefs. Five themes emerged: (1) high awareness of tobacco-related health concerns but limited awareness of program impacts and funding, (2) the primacy of economic concerns in making policy decisions, (3) ideological differences in views of the state’s role in tobacco control, (4) the impact of lobbyist and constituent in-person appeals, and (5) the utility of concise, contextualized data. These findings suggest that building relationships with policymakers to communicate ongoing program outcomes, emphasizing economic data, and developing a constituent advocacy group would be valuable to encourage continued support of state tobacco control programs.

Description: Background: Early recognition of severe sepsis and septic shock is challenging. The aim of this study was to determine the diagnostic accuracy of an electronic alert system in detecting severe sepsis or septic shock among emergency department (ED) patients. Methods: An electronic sepsis alert system was developed as a part of a quality-improvement project for severe sepsis and septic shock. The system screened all adult ED patients for a combination of systemic inflammatory response syndrome and organ dysfunction criteria (hypotension, hypoxemia or lactic acidosis). This study included all patients older than 14?years who presented to the ED of a tertiary care academic medical center from Oct. 1, 2012 to Jan. 31, 2013. As a comparator, emergency medicine physicians or the critical care physician identified the patients with severe sepsis or septic shock.In the ED, vital signs were manually entered into the hospital electronic heath record every hour in the critical care area and every two hours in other areas. We also calculated the time from the alert to the intensive care unit (ICU) referral. Results: Of the 49,838 patients who presented to the ED, 222 (0.4%) were identified to have severe sepsis or septic shock. The electronic sepsis alert had a sensitivity of 93.18% (95% CI, 88.78% - 96.00%), specificity of 98.44 (95% CI, 98.33% ? 98.55%), positive predictive value of 20.98% (95% CI, 18.50% ? 23.70%) and negative predictive value of 99.97% (95% CI, 99.95% ? 99.98%) for severe sepsis and septic shock. The alert preceded ICU referral by a median of 4.02?hours (Q1 - Q3: 1.25?8.55). Conclusions: Our study shows that electronic sepsis alert tool has high sensitivity and specificity in recognizing severe sepsis and septic shock, which may improve early recognition and management.

Description: The present cohort study examined how lifestyle, household environment, and caries activity test score of Japanese children at age 1.5 years affected their dental caries incidence at age 3. Inclusion criteria were 1.5-year-old children with no dental caries. Dental examinations were performed for 33,655 children who participated in routine dental examinations at 1.5 years of age, and the exam was repeated approximately 21 months later (at age 3) at the Kobe City Public Health Center in Japan. After excluding 622 children who had caries at age 1.5 and 1831 children with missing lifestyle and household environment data in the questionnaires, the final data analysis was performed on a total of 31,202 children (16,052 boys, 15,150 girls).The multivariate logistic regression analysis indicated a strong association of the consumption of sugar-sweetened beverages/snacks, less frequent tooth brushing by the parents, lack of fluoride varnish, family history of smoking, with the risk of developing dental caries. A child’s late bedtime is also one of the major risk factors for dental caries development. Further investigation is needed to examine whether the short duration or the irregularity of the sleep-wake cycle would affect early childhood oral health and whether there is a relationship between late bedtime and late night snack intake.