High incidence of rapid telomere loss in telomerase-deficient Caenorhabditis elegans

Telomerase is essential to maintain telomere length in most eukaryotes. Other functions for telomerase have been proposed but molecular mechanisms remain unclear. We studied Caenorhabditis elegans with a mutation in the trt-1 telomerase reverse transcriptase gene. Mutant animals showed a progressive decrease in brood size and typically failed to reproduce after five generations. Using PCR analysis to measure the length of individual telomere repeat tracks on the left arm of chromosome V we observed that trt-1 mutants lost ∼125bp of telomeric DNA per generation. Chromosome fusions involving complex recombination reactions were observed in late generations. Strikingly, trt-1 mutant animals displayed a high frequency of telomeres with many fewer repeats than average. Such outlying short telomeres were not observed in mrt-2 mutants displaying progressive telomere loss very similar to trt-1 mutants. We speculate that, apart from maintaining the average telomere length, telomerase is required to prevent or repair sporadic telomere truncations that are unrelated to the typical ‘end-replication’ problems

Valve interstitial cells induce donor-specific T-cell anergy

AbstractObjectives: Valve allografts produce an immune response, which can influence their performance. The exact role of the interaction between recipient T cells and the different cellular components of the donor valve in stimulating an immune response is not known. Therefore the T-cell response to valve endothelial and interstitial cells was investigated in vitro. Methods: Valve endothelial and interstitial cells were characterized for cell-surface molecules before and after interferon γ treatment by means of a panel of specific monoclonal antibodies and flow cytometry. The proliferative response of highly purified T lymphocytes was used to assess the immunogenicity of cultured valve endothelial and interstitial cells. This was further investigated by using a 2-step tolerance-induction protocol. Results: Valve endothelial and interstitial cells express similar levels of human leukocyte antigens and adhesion and costimulatory molecules, which are either induced or upregulated after interferon γ treatment. T-cell responses to endothelial cells were detected after interferon γ treatment, but responses to interferon γ–treated interstitial cells were not detected. This lack of response resulted in the induction of T-cell anergy, which was reversed by the presence of the costimulatory molecule B7-1. Conclusions: Although valve endothelial and interstitial cells express a similar range of cell-surface molecules, it is only the endothelial cells that are immunogenic. In addition, we have shown that these 2 cell types interact in a donorspecific manner to orchestrate the immune response and therefore may have clinical relevance in the allogeneic response of the heart valve recipients.J Thorac Cardiovasc Surg 2001;122:129-3

Knowledge, attitude, and practice regarding COVID-19 pandemic among medical students of Ernakulam, India

Background: COVID – 19 infection is a serious pandemic the world is now facing. This study aimed to assess the knowledge, attitude, and practice regarding COVID-19 infection among medical students at a private medical college in central Kerala.  Methods: A cross-sectional web-based study was conducted during April-May 2020 in a private medical college in Ernakulam District using the Universal sampling technique. The study tool was a semi-structured validated questionnaire containing sociodemographic details and questions on knowledge, attitude, and practice (KAP) regarding COVID-19 infection. Data were analyzed using SPSS version 20 software. Results: A total of 288 students were included in the study, with a mean age of 21±1.4. The male-to-female ratio was 2.75:1. Medical students showed adequate knowledge (81.6%), attitude (91.3%), and practice (84.7%) towards the COVID-19 pandemic, respectively. The main symptoms of COVID-19 infection were known to at least 83% of the participants. The majority (85.4%) were aware that there is no specific treatment for COVID-19 infection and 90% were aware of the main modes of the disease transmission. The majority (99%) of the medical students believed that COVID-19 infection could be prevented through social distancing, wearing masks, and the practice of self-hygiene. About 75.6% believed that government measures for prevention are adequate. Steam inhalation, saline gargling, and consumption of vitamin C-rich foodstuffs were the main specific measures adopted. Older age and female gender were found to be associated with better knowledge. Conclusion: Adequate KAP levels among medical students in this study are attributable to the current lockdown and the strict government measures to contain the infection

Prevalence and correlates of geriatric depression in a rural community in Kerala, India

Background: Elderly constitutes a vulnerable group for depression, as they are especially prone to suffer adverse consequences of a depressive episode and have greater rates of completed suicides. This study aims to estimate the prevalence and determinants of geriatric depression.  Methods: A cross-sectional study was done among 250 elderlies from 1st January 2019 to 1st January 2020 in the different rural blocks of Ernakulam district, India. The multistage sampling technique and the Geriatric Depression Scale (GDS-30) were used to collect the data. A score of 0 9 is considered "normal", 10 19 is labeled as "mildly depressed", and 20 30 as "severely depressed". Statistical analysis was performed using the IBM SPSS software. The Chi-square test /Fisher's exact test was used to study the association between the socio-demographic and behavioral variables with depression. Results: The mean age was 69.33 ± 7.41years and male: female ratio was 0.55: 1.The overall prevalence of depression was 52.4%. Advanced age over 70years [OR=2.04;95% CI, 1.227 – 3.394; P=0.006], female gender[OR=2.844;95% CI,1.663-4.865; P =<0.001], lack of gainful employment [OR=3.504; 95% CI, 1.833–6.699; P =<0.001], physical dependence [OR=0.365;95% CI,0.162–0.821; P =0.012], financial dependence [OR=0.388; 95% CI, 0.219–0.687; P =<0.001], presence of medical co morbidities [OR=0.428; 95% CI, 0.212–0.866; P =0.016],poor lifestyle including the lack of regular exercise [OR =2.020; 95% CI,1.174–3.473; P =0.010], addiction to alcohol [OR=4.932;95%CI,1.600-15.208; P =0.004] and addiction to tobacco smoking [OR=2.905;95%CI,1.273-6.628; P =0.009] and poor family support [OR= 5.180;95% CI,716–15.636; P = 0.002] were found to be significantly associated with depression. Conclusion: The prevalence of depression among the elderlies was high, and hence early diagnosis and prompt treatment are essential to reduce its burden in the community

Mental health in UK Biobank: development, implementation and results from an online questionnaire completed by 157 366 participants

Background UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors. Aims An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders. Method An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders. Results 157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation. Conclusions The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health

RCRA Monitoring Database Development Project

published or submitted for publicationis peer reviewedOpe

CLAYmb: The Development and Assessment of an Interactive Learning Application for Pottery Making

This study aimed to design and develop an interactive learning application called CLAYmb, utilizing the phases of the SDLC, and evaluated its technical and quality aspects using ISO 25010 software standards. The study utilized a developmental research design, with IT experts and end-users as respondents, and the results demonstrated that the SDLC model was suitable for developing the system, and the respondents highly accepted it. The study's recommendations include conducting further research to evaluate the long-term effectiveness of CLAYmb, involving a more diverse set of respondents, and improving the system's usability through user testing and feedback analysis. Valuable insights into the development and evaluation of interactive learning applications using SDLC and ISO 25010 software standards are presented in this study. It emphasizes the significance of involving users in the design and development process and underscores the need for continuous evaluation and enhancement of such systems. These findings can serve as a basis for improving the technical quality and quality of using interactive learning applications in the future

The Caenorhabditis elegans vab-10 spectraplakin isoforms protect the epidermis against internal and external forces

Morphogenesis of the Caenorhabditis elegans embryo is driven by actin microfilaments in the epidermis and by sarcomeres in body wall muscles. Both tissues are mechanically coupled, most likely through specialized attachment structures called fibrous organelles (FOs) that connect muscles to the cuticle across the epidermis. Here, we report the identification of new mutations in a gene known as vab-10, which lead to severe morphogenesis defects, and show that vab-10 corresponds to the C. elegans spectraplakin locus. Our analysis of vab-10 reveals novel insights into the role of this plakin subfamily. vab-10 generates isoforms related either to plectin (termed VAB-10A) or to microtubule actin cross-linking factor plakins (termed VAB-10B). Using specific antibodies and mutations, we show that VAB-10A and VAB-10B have distinct distributions and functions in the epidermis. Loss of VAB-10A impairs the integrity of FOs, leading to epidermal detachment from the cuticle and muscles, hence demonstrating that FOs are functionally and molecularly related to hemidesmosomes. We suggest that this isoform protects against forces external to the epidermis. In contrast, lack of VAB-10B leads to increased epidermal thickness during embryonic morphogenesis when epidermal cells change shape. We suggest that this isoform protects cells against tension that builds up within the epidermis