ALBERT

Description: Background: Acute liver failure (ALF) is marked by a sudden loss of hepatic function and is associated with a high mortality rate in children. The etiology of ALF is shown to vary geographically. This study assessed the frequency of hepatotropic viruses as etiological agents of ALF in Indian children. Methods: This retrospective study enrolled children aged 0–18 years with confirmed ALF admitted to Christian Medical College, Vellore and King Edward Memorial Hospital and Research Center, Pune between January 2003 and December 2005. The frequency of hepatotropic viruses as etiological agents in children with ALF aged ≤18 years was calculated with 95 % confidence interval (CI). Descriptive analyses of demographic characteristics, clinical signs and symptoms of ALF, choice of treatment and outcomes were performed. Results: Of 76 children enrolled, 54 were included in the per-protocol analyses. Mean age of children with ALF was 5.43 years (standard deviation = 3.62); 51.9 % (28/54) were female. The percentage of children positive for anti-hepatitis A virus (HAV) IgM and hepatitis B surface antigen was 65.9 % (27/41; 95 % CI 49.4–79.9) and 15.9 % (7/44; 95 % CI 6.6–30.1), respectively. The final cause of ALF was HAV (36.3 %) followed by hepatitis B virus (HBV; 8.8 %). Before and during admission, encephalopathy was observed in 77.8 % (42/54) and 63.0 % (34/54) of children, respectively. A high number of children (46/54; 85.2 %) required intensive care and ALF was fatal in 24.1 % (13/54). The proportion of deaths due to HAV and HBV was 18.5 % (5/27) and 57.1 % (4/7), respectively. Conclusions: HAV and HBV were the most common etiological agents of ALF in Indian children. Primary prevention by vaccination against HAV and HBV in young children may be useful in the prevention of ALF due to viral hepatitis in India.

Description: Visceral obesity and metabolic syndrome are commonly associated with non-alcoholic fatty liver disease (NAFLD). The progression of steatosis to NASH depends on a number of metabolic and patient-related factors...

Description: Background: The CornealL GrAft Thickness Evaluation (COLGATE) system was recently developed to facilitate the evaluation of corneal graft thickness from OCT images. Graft thickness measurement are a surrogate indicator for detecting graft failure or success. The purpose of this study was to determine the reproducibility of the COLGATE system in measuring DSAEK graft area between two observers. Methods: This was a prospective case series in which 50 anterior segment OCT images of patients who had undergone DSAEK in either eye were analysed. Two observers (MW, AC) independently obtained the image analysis for the graft area using both semi automated and automated method. One week later, each observer repeated the analysis for the same set of images. Bland-Altman analysis was performed to analyze inter and intra observer agreement. Results: There was strong intraobserver correlation between the 2 semi automated readings obtained by both observers. (r=0.936 and r=0.962). Intraobserver ICC for observer 1 was 0.936 (95% CI 0.890 to 0.963) and 0.967 (95% CI 0.942 to 0.981) for observer 2. Likewise, there was also strong interobserver correlation (r=0.913 and r=0.969). The interobserver ICC for the first measurements was 0.911 (95% CI 0.849 to 0.949) and 0.968 (95% CI 0.945 to 0.982) for the second. There was statistical difference between the automatic and the semi automated readings for both observers (p=0.006, p=0.003). The automatic readings gave consistently higher values than the semi automated readings especially in thin grafts. Conclusion: The analysis from the COLGATE programme can be reproducible between different observers. Care must be taken when interpreting the automated analysis as they tend to over estimate measurements.

Description: Background: Comparative genomics is a formidable tool to identify functional elements throughout a genome. In the past ten years, studies in the budding yeast Saccharomyces cerevisiae and a set of closely related species have been instrumental in showing the benefit of analyzing patterns of sequence conservation. Increasing the number of closely related genome sequences makes the comparative genomics approach more powerful and accurate. Results: Here, we report the genome sequence and analysis of Saccharomyces arboricolus, a yeast species recently isolated in China, that is closely related to S. cerevisiae. We obtained high quality de novo sequence and assemblies using a combination of next generation sequencing technologies, established the phylogenetic position of this species and considered its phenotypic profile under multiple environmental conditions in the light of its gene content and phylogeny. Conclusions: We suggest that the genome of S. arboricolus will be useful in future comparative genomics analysis of the Saccharomyces sensu stricto yeasts.

Description: Background: Statin intolerance is often due to myalgias. Severe vitamin D deficiency is characterized by musculoskeletal pain. We hypothesized that statin-intolerance is associated with vitamin D deficiency.ObjectivesTo determine whether there is an association between statin-intolerance and vitamin D deficiency in a retrospective observational analysis. Methods: We evaluated 20 female patients with prior myalgia-related daily dose statin intolerance on an alternative day statin dosing protocol of twice weekly for 4 weeks followed by advancement to daily dosing, as tolerated. Fasting baseline and follow-up lipid and 25-hydroxy-vitamin D (25-OHD) levels were obtained by chart review. Results: The group median age was 61 ± 13 years old and BMI was 27 ± 7 kg/m 2 . Women who remained on alternative day statin dosing (n = 16) compared to women on daily dosing (n = 4) had a significantly lower group mean 25-OHD (mean 29 ± 11.23 vs. 47.5 ± 23.53 ng/ml p = 0.0307 respectively). Conclusions: In women with prior myalgia-related statin intolerance, vitamin D levels were significantly lower in women who remained on alternative day dosing compared to those who were tolerant of daily dosing.

Description: Background: Meningitis means an inflammation of the meninges, or the membrane around the brain and spinal cord. It might be caused by a number of factors, but infectious meningitis is due to multiplication of fungal, viral or bacterial organisms. A number of studies showed that the diagnosis and treatment management of meningitis is a complex and common problem and a special attention is demanded. In this work, our attention primarily has focused on the process of making decisions in medical domain by using Fuzzy Cognitive Map, to model physicians-experts' behavior in the decision task related to this life threatening disease. Methods: Fuzzy cognitive mapping (FCM) is a method for analysing and depicting human perception of a given system. The method produces a conceptual model which is not limited by exact values and measurements, and thus is well suited to represent relatively unstructured knowledge and causalities expressed in imprecise forms. A team of doctors (physicians), comprising of four paediatricians, has been formed to define the number and types of sign/symptoms and other life-style related factors used in deciding the presence and absence of meningitis disease. The FCM model, consisting of 20 concepts nodes, has been designed by the team paediatricians after through deliberations. The 19 concepts are the symptoms and risks taken under consideration for the decision on disease. Results: The paediatricians were supplied with a form containing various input parameters to be filled at the time of diagnosing meningitis among infants and children. The paediatricians supplied back the cases of forty different children with age ranging from 2 months through 7 years. The physicians' decision was available for each of the cases as whether treated for meningitis disease or not. The physicians' opinions were used as "gold standard" for the model evaluation. The system predicted the outcome in all forty cases with an accuracy of 95%, thus showing its functionality and demonstrating that the use of the FCMs as dynamic models is reliable and good. Conclusions: This work elaborates the development of the knowledge based system, using the formalization of FCMs for meningitis diagnosis in children and infants. The results have shown that the suggested FCM-based tool gives a front-end decision on diagnosing meningitis and could be considered as helpful reference for physicians and patients.

Description: Background: To assess repeatability of the Zhongshan Assessment Program (ZAP) software measurement of Anterior Segment Optical Coherence Tomography (ASOCT) images and correlate with graft trephine diameter following Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) Methods: Retrospectively evaluated interventional case series. 121 consecutive eyes undergoing DSAEK over a 26 month period underwent ASOCT imaging 1 month after their surgery. ASOCT images were processed using ZAP software which measured the graft and cornea parameters including anterior and posterior graft arc length and cord length, posterior cornea arc length (PCAL) and anterior chamber width. Results: The graft measurements showed good repeatability on ASOCT using ZAP with high intraclass coefficient and small variation in the coefficient of variation. On ASOCT, the mean recipient PCAL was 12.99+/-0.69 mm and the anterior chamber width was 11.16+/-0.57 mm. The mean Graft anterior arc length was 9.69+/-0.66 mm and the mean Graft anterior cord length was 8.92+/-2.94 mm. The mean graft posterior arc length was 9.24+/-0.75mm and the mean graft posterior cord length was 8.15+/-0.57mm. Graft posterior arc length (rho=0.788, p

Description: Background: Zinc deficiency is a major public health problem in many developing countries including Nepal. The present study was designed to assess the prevalence of zinc deficiency and to study the association of zinc deficiency with anthropometric and socio-demographic variables, in school children of eastern Nepal. Methods: This cross-sectional study included total 125 school children of age group 6–12 years from Sunsari and Dhankuta districts of eastern Nepal. Plasma zinc level was estimated by Flame Atomic Absorption Spectroscopy. Results: The Median interquartile range (IQR) values of zinc in the two districts Sunsari and Dhankuta were 5.9 (4.4, 7.9) μmol/L and 5.8 (4.3, 8.4) μmol/L respectively. A total of 55 children (87.3%) in Sunsari and 52 (83.9%) in Dhankuta had zinc deficiency, no significant difference was observed in the Median (IQR) plasma zinc levels (p = 0.9) and zinc deficiency patterns (p = 0.3) of the two districts. Significant differences were observed in the plasma zinc levels (p = 0.02) and zinc deficiency patterns (p = 0.001), of the school children having age groups 6–8 years than in 9–10 and 11–12 years of age, and zinc deficiency patterns between male and female school children (p = 0.04) respectively. Conclusions: The present study showed higher prevalence of zinc deficiency among school children in eastern Nepal. In our study, zinc deficiency was associated with both sex and age. The findings from the present study will help to populate data for policy implementation regarding consumption and supplementation of zinc.

Description: Background: The high-mobility-group (HMG) proteins are the most abundant non-histone chromatin-associated proteins. HMG proteins are present at high levels in various undifferentiated tissues during embryonic development and their levels are strongly reduced in the corresponding adult tissues, where they have been implicated in maintaining and activating stem/progenitor cells. Here we deciphered the role of the high mobility group AT-hook protein 2 (HMGA2) during lung development by analyzing the lung of Hmga2 deficient mice (Hmga2-/-). Results: We found that Hmga2 is expressed in the mouse embryonic lung at the distal airways. Analysis of Hmga2-/- mice showed that Hmga2 is required for proper cell proliferation and distal epithelium differentiation during embryonic lung development. Hmga2 knockout (KO) led to enhanced canonical WNT signaling due to an increased expression of secreted WNT glycoproteins Wnt2b, Wnt7b and Wnt11 as well as a reduction of the WNT signaling antagonizing proteins GATA6 (GATA binding protein 6) and FZD2 (frizzled homolog 2). Analysis of siRNA mediated loss-of-function (LOF) experiments in embryonic lung explant culture confirmed the role of Hmga2 as a key regulator of distal lung epithelium differentiation and supported the causal involvement of enhanced canonical WNT signaling in mediating the effect of Hmga2-LOF. Finally, we found that HMGA2 directly regulates Gata6 and thereby modulates Fzd2 expression. Conclusions: Our results support that Hmga2 regulates canonical WNT signaling at different points of the pathway. Increased expression of the secreted WNT glycoproteins might explain a paracrine effect by which Hmga2-KO enhanced cell proliferation in the mesenchyme of the developing lung. In addition, HMGA2-mediated direct regulation of Gata6 is crucial for fine-tuning the activity of WNT signaling in the airway epithelium. Our results are the starting point for future studies in which the relevance of Hmga2 mediated regulation of WNT signaling might be investigated in the adult lung within the context of proper balance between differentiation and self-renewal of lung stem/progenitor cells during lung regeneration in both homeostatic turnover and repair after injury.

Description: Background: A net-based, decision support system for diagnostic assessment and management of psychiatric disorders, developed as part of a telepsychiatry service, which aims to deliver mental health care to underserved population of remote areas in India is described. This paper presents the development and preliminary results of diagnostic validation of the application, intended for use among adult patients. The bilingual (English and Hindi) diagnostic tool consists of a core diagnostic section comprising a screening sub-module and criteria-based diagnostic sub-modules for 18 adult psychiatric disorders, and additional sections covering background information. The diagnostic tool of the application was examined among 100 consecutive consenting adult outpatients, by comparing it with detailed semi-structured clinical assessments led by a consultant psychiatrist, on accuracy of diagnoses generated, and examining the feasibility of its use. Results: The screening sub-module had high sensitivity and high specificity, low positive predictive values, but high negative predictive values for most disorders. For the diagnostic sub-modules, there was moderate (kappa = 0.4-0.6), to substantial agreement (kappa 〉 0.6) between diagnoses generated by the tool and consultants' diagnoses, for all the disorders except dysthymia. Sensitivity was high barring a few disorders. Specificity was high for all the disorders, positive predictive values were acceptable to high for most disorders, and negative predictive values were consistently high. Completion rate was 100%; average time taken was five minutes for screening alone, and 30 minutes for complete assessment with screening and criteria-based evaluation. A majority of the patients, their relatives, and interviewers were satisfied with the interview. Conclusions: The preliminary results indicated that despite some limitations, the new diagnostic system was reasonably comprehensive, time-efficient and feasible, with an acceptable level of diagnostic accuracy. Hence, it appeared to be suitable for use as a telepsychiatric application.