Telomere-length dependent T-cell clonal expansion:A model linking ageing to COVID-19 T-cell lymphopenia and mortality

BACKGROUND: Severe COVID-19 T-cell lymphopenia is more common among older adults and entails poor prognosis. Offsetting the decline in T-cell count during COVID-19 demands fast and massive T-cell clonal expansion, which is telomere length (TL)-dependent. METHODS: We developed a model of TL-dependent T-cell clonal expansion capacity with age and virtually examined the relation of T-cell clonal expansion with COVID-19 mortality in the general population. FINDINGS: The model shows that an individual with average hematopoietic cell TL (HCTL) at age twenty years maintains maximal T-cell clonal expansion capacity until the 6th decade of life when this capacity rapidly declines by more than 90% over the next ten years. The collapse in the T-cell clonal expansion capacity coincides with the steep increase in COVID-19 mortality with age. INTERPRETATION: Short HCTL might increase vulnerability of many older adults, and some younger individuals with inherently short HCTL, to COVID-19 T-cell lymphopenia and severe disease. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section

Short Telomeres and a T-Cell Shortfall in COVID-19:The Aging Effect

The slow pace of global vaccination and the rapid emergence of SARS-CoV-2 variants suggest recurrent waves of COVID-19 in coming years. Therefore, understanding why deaths from COVID-19 are highly concentrated among older adults is essential for global health. Severe COVID-19 T-cell lymphopenia is more common among older adults, and it entails poor prognosis. Much about the primary etiology of this form of lymphopenia remains unknown, but regardless of its causes, offsetting the decline in T-cell count during SARS-CoV-2 infection demands fast and massive T-cell clonal expansion, which is telomere length (TL)-dependent. We have built a model that captures the effect of age-dependent TL shortening in hematopoietic cells and its effect on T-cell clonal expansion capacity. The model shows that an individual with average hematopoietic cell TL (HCTL) at age twenty years maintains maximal T-cell clonal expansion capacity until the 6th decade of life when this capacity plummets by more than 90% over the next ten years. The collapse coincides with the steep increase in COVID-19 mortality with age. HCTL metrics may thus explain the vulnerability of older adults to COVID-19. That said, the wide inter-individual variation in HCTL across the general population means that some younger adults with inherently short HCTL might be at risk of severe COVID-19 lymphopenia and mortality from the disease. SIGNIFICANCE STATEMENT: Declining immunity with advancing age is a general explanation for the increased mortality from COVID-19 among older adults. This mortality far exceeds that from viral illnesses such as the seasonal influenza, and it thus requires specific explanations. One of these might be diminished ability with age to offset the development of severe T-cell lymphopenia (a low T-cell count in the blood) that often complicates COVID-19. We constructed a model showing that age-dependent shortening of telomeres might constrain the ability of T-cells of some older COVID-19 patients to undertake the massive proliferation required to clear the virus that causes the infection. The model predicts that individuals with short telomeres, principally seniors, might be at a higher risk of death from COVID-19

Severity and persistence of asthma and mental health: a birth cohort study

Background. The goal of the current study was to investigate asthma and mental health among youth in the community, and to consider the role of asthma severity and persistence in this link

Identification of patients with recent-onset psychosis in KwaZulu Natal, South Africa:a pilot study with traditional health practitioners and diagnostic instruments

There is considerable variation in epidemiology and clinical course of psychotic disorders across social and geographical contexts. To date, very little data are available from low- and middle-income countries. In sub-Saharan Africa, most people with psychoses remain undetected and untreated, partly due to lack of formal health care services. This study in rural South Africa aimed to investigate if it is possible to identify individuals with recent-onset psychosis in collaboration with traditional health practitioners (THPs)

Socioeconomic differences in cancer survival: The Norwegian Women and Cancer Study

<p>Abstract</p> <p>Background</p> <p>Cancer survival has been observed to be poorer in low socioeconomic groups, but the knowledge about the underlying causal factors is limited. The purpose of this study was to examine how cancer survival varies by socioeconomic status (SES) among women in Norway, and to identify factors that explain this variation. SES was measured by years of education and gross household income, respectively.</p> <p>Methods</p> <p>We used data from The Norwegian Women and Cancer Study, a prospective cohort study including 91 814 women who responded to an extensive questionnaire between 1996 and 1998. A total of 3 899 incident cancer cases were diagnosed during follow-up, of whom 1 089 women died, 919 of them from cancer. Cox Proportional Hazards Model was used to calculate relative risks (RR) of mortality and 95% confidence intervals.</p> <p>Results</p> <p>We observed an overall negative socioeconomic gradient in cancer survival, which was most evident in the site specific analyses for survival of ovarian cancer by years of education. For colorectal cancer, mortality increased with years of education, but not with income. After adjustment for household size, marital status, disease stage, and smoking status the SES variation in cancer survival became non-significant. We found that the unequal socioeconomic distribution of smoking status prior to diagnosis contributed considerably to the poorer survival in low SES groups.</p> <p>Conclusion</p> <p>We found an overall negative socioeconomic gradient in cancer survival when SES is measured as years of education or gross household income. Smoking status prior to diagnosis was an important predictive factor for socioeconomic variation in survival.</p

Explanatory pluralism in the medical sciences: theory and practice

Explanatory pluralism is the view that the best form and level of explanation depends on the kind of question one seeks to answer by the explanation, and that in order to answer all questions in the best way possible, we need more than one form and level of explanation. In the first part of this article, we argue that explanatory pluralism holds for the medical sciences, at least in theory. However, in the second part of the article we show that medical research and practice is actually not fully and truly explanatory pluralist yet. Although the literature demonstrates a slowly growing interest in non-reductive explanations in medicine, the dominant approach in medicine is still methodologically reductionist. This implies that non-reductive explanations often do not get the attention they deserve. We argue that the field of medicine could benefit greatly by reconsidering its reductive tendencies and becoming fully and truly explanatory pluralist. Nonetheless, trying to achieve the right balance in the search for and application of reductive and non-reductive explanations will in any case be a difficult exercise

Health system outcomes and determinants amenable to public health in industrialized countries: a pooled, cross-sectional time series analysis

BACKGROUND: Few studies have tried to assess the combined cross-sectional and temporal contributions of a more comprehensive set of amenable factors to population health outcomes for wealthy countries during the last 30 years of the 20(th )century. We assessed the overall ecological associations between mortality and factors amenable to public health. These amenable factors included addictive and nutritional lifestyle, air quality, public health spending, healthcare coverage, and immunizations. METHODS: We used a pooled cross-sectional, time series analysis with corrected fixed effects regression models in an ecological design involving eighteen member countries of the Organisation for Economic Cooperation and Development during the period 1970 to 1999. RESULTS: Alcohol, tobacco, and fat consumption, and sometimes, air pollution were significantly associated with higher all-cause mortality and premature death. Immunizations, health care coverage, fruit/vegetable and protein consumption, and collective health expenditure had negative effects on mortality and premature death, even after controlling for the elderly, density of practicing physicians, doctor visits and per capita GDP. However, tobacco, air pollution, and fruit/vegetable intake were sometimes sensitive to adjustments. CONCLUSION: Mortality and premature deaths could be improved by focusing on factors that are amenable to public health policies. Tackling these issues should be reflected in the ongoing assessments of health system performance

A geographical population analysis of dental trauma in school-children aged 12 and 15 in the city of Curitiba-Brazil

<p>Abstract</p> <p>Background</p> <p>The study presents a geographical analysis of dental trauma in a population of 12 and 15 year-old school-children, in the city of Curitiba, Brazil (n = 1581), using a database obtained in the period 2005-2006. The main focus is to analyze dental trauma using a geographic information system as a tool for integrating social, environmental and epidemiological data.</p> <p>Methods</p> <p>Geostatistical analysis of the database and thematic maps were generated showing the distribution of dental trauma cases according to Curitiba's Health Districts and other variables of interest. Dental trauma spatial variation was assessed using a generalized additive model in order to identify and control the individual risk-factors and thus determine whether spatial variation is constant or not throughout the Health Districts and the place of residence of individuals. In addition, an analysis was made of the coverage of dental trauma cases taking the spatial distribution of Curitiba's primary healthcare centres.</p> <p>Results</p> <p>The overall prevalence of dental trauma was 37.1%, with 53.1% in males and 46.7% in females. The spatial analysis confirms the hypothesis that there is significant variation in the occurrence of dental trauma, considering the place of residence in the population studied (Monte Carlo test, p = 0,006). Furthermore, 28.7% of cases had no coverage by the primary healthcare centres.</p> <p>Conclusions</p> <p>The effect of the place of residence was highly significant in relation to the response variable. The delimitation of areas, as a basis for case density, enables the qualification of geographical territories where actions can be planned based on priority criteria. Promotion, control and rehabilitation actions, applied in regions of higher prevalence of dental trauma, can be more effective and efficient, thus providing healthcare refinement.</p