Colombo Twin and Singleton Study (CoTASS): A description of a population based twin study of mental disorders in Sri Lanka

Background: The Sri Lankan twin registry is one of the first to be established in a developing country, and its design has ensured sampling from a wide range of environmental conditions. It thus has great potential to examine environmental and genetic influences on diverse phenotypes, including psychiatric disorders, in the context of a diversity of environmental exposures, which may not have been fully explored in previous twin studies in developed countries. This paper presents the rationale for the study, describes its context, and the methods for twin ascertainment and data collection. Methods: A population-based twin register was established in the Colombo district of Sri Lanka using infrastructure designed to periodically update the electoral register. We invited a subsample from this register to participate in the project on common mental disorders, using random ascertainment. A separate non-twin sample was randomly selected from the geographical areas where twins were found. Home interviewers collected diagnostic information on common mental disorders, as well as environmental exposures including life events, socio-economic conditions, and the impact of the civil war and the Tsunami of 2004. Results: We identified 19,302 individuals in the creation of the population based twin register. We randomly selected a subsample, of whom 4,387 were eligible to participate and 4,024 agreed to be interviewed ( including data on 1,954 complete pairs of twins and 5 sets of triplets). Those who refused consent had a similar mean age and sex ratio to those who were interviewed. We invited 2,485 singletons to participate and 2,019 were interviewed. Conclusion: Initial exploration of the data suggests the samples are very representative of the Colombo district of Sri Lanka, so we have created a unique resource for understanding the influences on mental disorders in developing countries, and to compare to the influences found in developed countries

Analysing Dynamical Behavior of Cellular Networks via Stochastic Bifurcations

The dynamical structure of genetic networks determines the occurrence of various biological mechanisms, such as cellular differentiation. However, the question of how cellular diversity evolves in relation to the inherent stochasticity and intercellular communication remains still to be understood. Here, we define a concept of stochastic bifurcations suitable to investigate the dynamical structure of genetic networks, and show that under stochastic influence, the expression of given proteins of interest is defined via the probability distribution of the phase variable, representing one of the genes constituting the system. Moreover, we show that under changing stochastic conditions, the probabilities of expressing certain concentration values are different, leading to different functionality of the cells, and thus to differentiation of the cells in the various types

Prevention of Cytotoxic T Cell Escape Using a Heteroclitic Subdominant Viral T Cell Determinant

High affinity antigen-specific T cells play a critical role during protective immune responses. Epitope enhancement can elicit more potent T cell responses and can subsequently lead to a stronger memory pool; however, the molecular basis of such enhancement is unclear. We used the consensus peptide-binding motif for the Major Histocompatibility Complex molecule H-2Kb to design a heteroclitic version of the mouse hepatitis virus-specific subdominant S598 determinant. We demonstrate that a single amino acid substitution at a secondary anchor residue (Q to Y at position 3) increased the stability of the engineered determinant in complex with H-2Kb. The structural basis for this enhanced stability was associated with local alterations in the pMHC conformation as a result of the Q to Y substitution. Recombinant viruses encoding this engineered determinant primed CTL responses that also reacted to the wildtype epitope with significantly higher functional avidity, and protected against selection of virus mutated at a second CTL determinant and consequent disease progression in persistently infected mice. Collectively, our findings provide a basis for the enhanced immunogenicity of an engineered determinant that will serve as a template for guiding the development of heteroclitic T cell determinants with applications in prevention of CTL escape in chronic viral infections as well as in tumor immunity

Applied CAL on Problem Based Learning Using Gagne’s Instructional Design

Abstract— In the Problem-Based Learning (PBL) model, students are expected to study independently. One of the methods that can improve the ability or skill of learners is using Computer Assisted Learning (CAL). Implementation of CAL in PBL should be able to create Self-Directed Learning (SDL) culture through appropriate instructional design and interesting modules. In this paper, the CAL software is developed using multimedia learning principles, convenient appearance, and user-friendly navigation. The CAL’s learning content is designed using Gagne's instructional design. The experiment proved the CAL was able to give effect size 0.89 and developed self-directed learning culture. From the interviews, students were very glad and interested to use the CAL modules because they can learn anytime and can reach the course objectives without a lecturer

ASSESSMENT OF HEALTH-RELATED QUALITY OF LIFE AND RISK FACTORS ASSOCIATED WITH PANCREATITIS IN A TERTIARY CARE HOSPITAL

Objective: The objective of the study was to measure the health-related quality of life (HRQoL) in pancreatitis and to appraise the risk factors associated with the pancreatitis. Methods: A prospective observational study was performed with admitted cases of pancreatitis over 6 month’s period. A total of 150 patients were selected for the study. All data concerning risk factors were recorded and Short-Form-36 (SF-36) questionnaire was applied and quality of life (QOL) was analyzed in all patients with in study group. Results: All domains of (HRQoL) were assessed; it shows highest effect on role limitations due to physical health (36%), role limitations due to emotional problems (29%), role limitations due to physical health, and role limitations due to emotional problems (10%). Finally, our study revealed that there is a profound deterioration in physical components of QOL. The risk factors that majorly influence the QOL in association with disease were found to be alcohol consumption and smoking (70%). Conclusion: Pancreatitis remarkably diminishes the patient’s HRQoL which predominantly shows negative impact on physical health

A non-enzymatic urea sensor based on the nickel sulfide / graphene oxide modified glassy carbon electrode

Here, a non-enzymatic graphene stabilized nickel sulphide is used for electrochemical based device for detecting urea is carried out. NiS was used as electron distribution on the compound helps in selective interaction with analytes. However, since neat NiS is unstable during the interaction, stabilization of the compound is very critical. Hence, nickel sulfide/graphene oxide (NiS/GO) was synthesized via the superficial hydrothermal method. The synthesized functionalized GO nanoparticles were characterized for size, surface area, and morphology for tuning to the specific application. This compound nickel sulfide/graphene oxide was used to modify glassy carbon electrode (NiS/GO/MGCE). Detection capabilities of this modified electrode to urea in water was evaluated in both electrochemical and electrochemical impedance spectroscopy (EIS) modes. Results suggests that the NiS/GO nanocomposite modified electrode exhibited a very low limit of detection and the electrode process was identified to be diffusion-controlled. In addition, selectivity, interference, long-term stability and practical applicability of the developed sensor were evaluated. Hence, the developed NiS/GO/MGCE displayed excellent electrocatalytic behaviour towards the sensing of urea with good sensitivity, selectivity, and reproducibility

Direct benefit transfer for nutritional support of patients with TB in India—analysis of national TB program data of 3.7 million patients, 2018–2022

Abstract Background Patients with TB have additional nutritional requirements and thus additional costs to the household. Ni-kshay Poshan Yojana(NPY) is a Direct Benefit Transfer (DBT) scheme under the National Tuberculosis Elimination Programme(NTEP) in India which offers INR 500 monthly to all notified patients with TB for nutritional support during the period of anti-TB treatment. Five years after its implementation, we conducted the first nationwide evaluation of NPY. Methods In our retrospective cohort study using programmatic data of patients notified with TB in nine randomly selected Indian states between 2018 and 2022, we estimated the proportion of patients who received at least one NPY instalment and the median time to receive the first instalment. We determined the factors associated (i) with non-receipt of NPY using a generalised linear model with Poisson family and log link and (ii) with time taken to receive first NPY benefit in 2022 using quantile regression at 50th percentile. Results Overall, 3,712,551 patients were notified between 2018 and 2022. During this period, the proportion who received at least one NPY instalment had increased from 56.9% to 76.1%. Non-receipt was significantly higher among patients notified by private sector (aRR 2.10;2.08,2.12), reactive for HIV (aRR 1.69;1.64,1.74) and with missing/undetermined diabetic status (aRR 2.02;1.98,2.05). The median(IQR) time to receive the first instalment had reduced from 200(109,331) days in 2018 to 91(51,149) days in 2022. Patients from private sector(106.9;106.3,107.4days), those with HIV-reactive (103.7;101.8,105.7days), DRTB(104.6;102.6,106.7days) and missing/undetermined diabetic status (115.3;114,116.6days) experienced longer delays. Conclusions The coverage of NPY among patients with TB had increased and the time to receipt of benefit had halved in the past five years. Three-fourths of the patients received at least one NPY instalment, more than half of whom had waited over three months to receive the first instalment. NTEP has to focus on timely transfer of benefits to enable patients to meet their additional nutritional demands, experience treatment success and avoid catastrophic expenditure