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Recurrent exposures to a pathogenic antigen remodel the CD8+ T cell compartment and generate a functional memory repertoire that is polyclonal and complex. At the clonotype level, the response to the conserved influenza antigen, M158–66 has been well characterized in healthy individuals, but not in patients receiving immunosuppressive therapy or with aberrant immunity, such as those with juvenile idiopathic arthritis (JIA). Here we show that patients with JIA have a reduced number of M158–66 specific RS/RA clonotypes, indicating decreased clonal richness and, as a result, have lower repertoire diversity. By using a rank-frequency approach to analyze the distribution of the repertoire, we found several characteristics of the JIA T cell repertoire to be akin to repertoires seen in healthy adults, including an amplified RS/RA-specific antigen response, representing greater clonal unevenness. Unlike mature repertoires, however, there is more fluctuation in clonotype distribution, less clonotype stability, and more variable IFNy response of the M158–66 specific RS/RA clonotypes in JIA. This indicates that functional clonal expansion is altered in patients with JIA on immunosuppressive therapies. We propose that the response to the influenza M158–66 epitope described here is a general phenomenon for JIA patients receiving immunosuppressive therapy, and that the changes in clonal richness and unevenness indicate a retarded and uneven generation of a mature immune response.

ABSTRACTSome studies have shown that the betel nut Areca catechu L and “binahong” leaves Anredera cordifolia (Ten) Steenis have anti-parasite and wound healing properties. This study evaluated the effect of A. catechu nut and A. cordifolia leaves powder supplementation on faecal parasite number and type, histopathology of the intestine, caecum, associated organs, some serum biochemistry, and egg production of laying hens. Twenty-four 54-week-old ISA-brown laying hens from local layer farmers were assigned randomly into 4-treatment groups: 1) without supplementation (T0), 2) supplemented with 0.25% (T0.25%), 3) 0.5% (T0.5%), 4) 1.0% (T1.0%). We carried out the supplementation for 18 days by administering A. catechu nut powder for 3-days, and subsequently, A. cordifolia leaves powder for another 3-days for 3-rounds to control the parasite larvae. Faecal parasite count and type were enumerated at the beginning and end of treatment. Egg production was recorded daily during the 18 days experiment. Blood was sampled at the end of the experiment to determine serum albumin, globulin, and transaminases. The intestinal tract, liver, and spleen samples were collected at the end of the study for histopathological examination. Faecal Ascaridia galli in control hens increased by 87.5% after 18 days of the experiment, while A. catechu nut and A. cordifolia leaves powder supplementation prevented such an increase. Supplemented hens have a better reduction of Railentina cesticillus compared to control birds. Supplementation improved intestinal and other tissue histopathology, especially in the caecum (free of erosion), improving serum albumin and transaminases without affecting egg production.

No abstract available.

Abstract Objective In sub-Saharan Africa, 45% of the rural population uses boreholes (BHs). Despite recent gains in improved water access and coverage, parallel use of unimproved sources persists. Periodic infrastructure disrepair contributes to non-exclusive use of BHs. Our study describes functionality of BHs in 2014, 2015, and 2016 in 15 rural towns in the Eastern Region of Ghana sourced from three groundwater quality clusters (high iron, high salinity, and control). We also assess factors affecting cross-sectional and longitudinal functionality using logistic regression. Results BH functionality rates ranged between 81 and 87% and were similar across groundwater quality clusters. Of 51 BHs assessed in all three years, 34 (67%) were consistently functional and only 3 (6%) were consistently broken. There was a shift toward proactive payment for water over the course of the study in the control and high-salinity clusters. Payment mechanism, population served, presence of nearby alternative water sources, and groundwater quality cluster were not significant predictors of cross-sectional or longitudinal BH functionality. However, even in the high iron cluster, where water quality is poor and no structured payment mechanism for water exists, BHs are maintained, showing that they are important community resources.

The immunologic significance of cross-reactivity of TCR recognition of peptide:MHC complexes is still poorly understood. We have described TCR cross-reactivity in a system involving polyclonal CD8 T cell recognition of the well characterized influenza viral M158-66 epitope. While M158-66 is generally conserved between influenza A isolates, error-prone transcription generates stable variant RNA during infection which could act as novel epitopes. If packaged and viable, variant genomic RNA generates an influenza quasispecies. The stable RNA variants would generate a new transmissible epitope that can select a specific repertoire, which itself should have cross-reactive properties. We tested two candidate peptides in which Thr65 is changed to Ala (A65) or Ser (S65) using recall responses to identify responding T cell clonotypes. Both peptides generated large polyclonal T cell repertoires of their own with repertoire characteristics and cross-reactivity patterns like that observed for the M158-66 repertoire. Both substitutions could be present in viral genomes or mRNA at sufficient frequency during an infection to drive immunity. Peptides from the resulting protein would be a target for CD8 cells irrespective of virus viability or transmissibility. These data support the hypothesis that cross-reactivity is important for immunity against RNA virus infections.

Abstract For several decades, the World Health Organization has collected, maintained, and distributed invaluable country-specific disease surveillance data that allow experts to develop new analytical tools for disease tracking and forecasting. To capture the extent of available data within these sources, we proposed a completeness metric based on the effective time series length. Using FluNet records for 29 Pan-American countries from 2005 to 2019, we explored whether completeness was associated with health expenditure indicators adjusting for surveillance system heterogeneity. We observed steady improvements in completeness by 4.2–6.3% annually, especially after the A(H1N1)-2009 pandemic, when 24 countries reached > 95% completeness. Doubling in decadal health expenditure per capita was associated with ~ 7% increase in overall completeness. The proposed metric could navigate experts in assessing open access data quality and quantity for conducting credible statistical analyses, estimating disease trends, and developing outbreak forecasting systems.

Abstract Background Lifelong healthy habits developed during childhood may prevent chronic diseases in adulthood. Interventions to promote these habits must begin early. The BONES (Beat Osteoporosis – Nourish and Exercise Skeletons) project assessed whether early elementary school children participating in a multifaceted health behavior change, after-school based intervention would improve bone quality and muscular strength and engage in more bone-strengthening behaviors. Methods The 2-year BONES (B) intervention included bone-strengthening physical activity (85 min/week), educational materials (2 days/week), and daily calcium-rich snacks (380 mg calcium/day) delivered by after-school program leaders. BONES plus Parent (B + P) included an additional parent education component. From 1999 to 2004, n = 83 after-school programs (N = 1434 children aged 6–9 years) in Massachusetts and Rhode Island participated in a group randomized trial with two intervention arms (B only, n = 25 programs; B + P, n = 33) and a control arm (C, n = 25). Outcome measures (primary: bone quality (stiffness index of the calcaneus) and muscular strength (grip strength and vertical jump); secondary: bone-strengthening behaviors (calcium-rich food knowledge, preference, and intake; and physical activity level (metabolic equivalent time (MET) score, and weight-bearing factor (WBF) score)) were recorded at baseline, and after years one and two. Analyses followed an intent-to-treat protocol, and focused on individual subjects’ trajectories along the three time points adjusting for baseline age and race via a mixed-effects regression framework. Analyses were performed with and without sex stratification. Results Children in B + P increased bone stiffness compared to C (p = 0.05); No significant changes were observed in muscle strength, food knowledge, or vertical jump. Children in B + P showed significant improvement in their MET and WBF scores compared to C (p

Abstract Progress on the nutrition Sustainable Development Goals has been slow. More attention is needed on the ‘sustainable’ part, focused on impact lasting beyond programme implementation. To determine sustained impact of a multisectoral nutrition intervention that provided water, sanitation, hygiene, livelihood, health and nutrition support (2013–2015) in eastern Chad, we utilize longitudinal household data collected 2 years (2017) after the intervention ended. Between 2013 and 2015, children (6–59 months) in the multisectoral intervention were less likely to be severely wasted, underweight and had a higher weight‐for‐height z‐score (WHZ) compared with the control. To measure sustained programme impact, we use data on six nutrition indicators from 517 children between 2015 and 2017. We ran three models: a generalized linear model on cross‐sectional child cohorts; a mixed‐effects model on household panel data; and a mixed‐effects model on child panel data. For children who were born during the programme, we saw significant improvement in underweight, weight for age z‐scores (WAZs) and height‐for‐age z‐scores (HAZs). Boys 6–23 months born after the end of the programme, on the other hand, were significantly more likely to be underweight or wasted and had lower WHZ and WAZ compared with boys born during the programme and girls born during and after the programme. Corresponding to the literature from sub‐Saharan Africa, boys appear to be more vulnerable to malnutrition, which might be why they are more sensitive to programme cessation. Future monitoring, evaluations and research need to consider impact sustainability and that it might not be homogeneous across age and gender.

Background The US population is aging, with concurrent increases in cardiovascular disease (CVD) burdens; however, spatiotemporal and demographic trends in CVD incidence in the US elderly have not been investigated in detail. This study aims to characterize trends from 1991 to 2014 in CVD hospitalizations among US Medicare beneficiaries, aged 65+ years, by single year of age/sex/race/state using records from the US Centers for Medicare & Medicaid, covering 98% of older Americans. Methods and Results We abstracted 181 202 758 US Centers for Medicare & Medicaid hospitalization records indicating CVD in any of 10 diagnosis codes; tabulated total cases of CVD by sex, age, race, state, and calendar year (1991–2014); and normalized hospitalization counts to standardize over data batches. Stratum‐specific hospitalization rates were calculated using US Centers for Medicare & Medicaid records and US Census population counts; a cubic polynomial function was fit to year‐specific distributions of rates by single year of age. Nationwide, CVD‐related hospitalization rates increased from 1991 to 2014. Differences between hospitalization rates at age 65 and 66 years, representing magnitude of healthcare deferral until Medicare onset, increased by 7.49 per 100 people 1991 to 2006 overall, and were largest among blacks and Native Americans. Rates of CVD hospitalizations were consistently highest in the Midwest/Deep South. Evidence of misclassification of race/ethnicity in US Centers for Medicare & Medicaid hospitalization records in the 1990s was noted. Conclusions Trends in CVD‐related hospitalization rates among older Americans highlight the essential need for targeted policies to reduce CVD burdens, to improve reporting of race/ethnicity in large administrative databases, and to enhance access to affordable healthcare.

T-cell memory to pathogens can be envisioned as a receptor-based imprint of the pathogenic environment on the naïve repertoire of clonotypes. Recurrent exposures to a pathogen inform and reinforce memory, leading to a mature state. The complexity and temporal stability of this system in man is only beginning to be adequately described. We have been using a rank-frequency approach for quantitative analysis of CD8 T cell repertoires. Rank acts as a proxy for previous expansion, and rank-frequency, the number of clonotypes at a particular rank, as a proxy for abundance, with the relation of the two estimating the diversity of the system. Previous analyses of circulating antigen-experienced cytotoxic CD8 T-cell repertoires from adults have shown a complex two-component clonotype distribution. Here we show this is also the case for circulating CD8 T cells expressing the BV19 receptor chain from five adult subjects. When the repertoire characteristic of clonotype stability is added to the analysis, an inverse correlation between clonotype rank frequency and stability is observed. Clonotypes making up the second distributional component are stable; indicating that the circulation can be a depot of selected clonotypes. Temporal repertoire dynamics was further examined for influenza-specific T cells from children, middle-aged, and older adults. Taken together, these analyses describe a dynamic process of system development and aging, with increasing distributional complexity, leading to a stable circulating component, followed by loss of both complexity and stability.

People with Parkinson’s disease (PD) often experience a decrease in their facial expressivity, but little is known about how the coordinated movements across regions of the face are impaired in PD. The face has neurologically independent regions that coordinate to articulate distinct social meanings that others perceive as gestalt expressions, and so understanding how different regions of the face are affected is important. Using the Facial Action Coding System, this study comprehensively measured spontaneous facial expression across 600 frames for a multiple case study of people with PD who were rated as having varying degrees of facial expression deficits, and created correlation matrices for frequency and intensity of produced muscle activations across different areas of the face. Data visualization techniques were used to create temporal and correlational mappings of muscle action in the face at different degrees of facial expressivity. Results showed that as severity of facial expression deficit increased, there was a decrease in number, duration, intensity, and coactivation of facial muscle action. This understanding of how regions of the parkinsonian face move independently and in conjunction with other regions will provide a new focus for future research aiming to model how facial expression in PD relates to disease progression, stigma, and quality of life.

One area of food system research that remains overlooked in terms of making urban-rural distinctions explicit is the private emergency food system of food banks, food pantries, soup kitchens, and emergency shelters that exists throughout the United States. This system is an important one for millions of food-insecure individuals and today serves nearly as many individuals as public food assistance. In this article, we present an exploratory case that presents findings from research looking at the private emergency food system of a rural county in northern New England, U.S. Specifically, we examine the history of this national network to contextualize our findings and then discuss possibilities for collaboration between this private system and the local food movement (on behalf of both the public and the state). These collaborations present an opportunity in the short term to improve access to high quality local foods for insecure populations, and in the long term to challenge the systemic income and race-based inequalities that increasingly define the modern food system and are the result of prioritizing market-based reforms that re-create inequality at the local and regional levels. We propose alternatives to these approaches that emphasize the ability to ensure adequate food access for vulnerable populations, as well as the right to define, structure, and control how food is produced beyond food consumerism (i.e., voting with our dollars), but through efforts increasingly aligned with a food sovereignty agenda.

We show that the microsporidian fungus Enterocytozoon bieneusi is associated with lower rates of weight gain in children in Uganda with persistent diarrhea. This relationship remained after controlling for HIV and concurrent cryptosporidiosis. Children with microsporidiosis were predicted to weigh 1.3 kg less than children without microsporidiosis at 5 years of age.

We used the Temporal Exposure Response Surfaces modeling technique to examine the association between gastroenteritis-related emergency room visits and hospitalizations in the elderly and drinking water turbidity before and during the 1993 Milwaukee waterborne Cryptosporidium outbreak. Before the outbreak, the rate of such events increased with age in the elderly (p

Existing climate classification has not been designed for an efficient handling of public health scenarios. This work aims to design an objective spatial climate regionalization method for assessing health risks in response to extreme weather. Specific climate regions for the conterminous United States of America (USA) were defined using satellite remote sensing (RS) data and compared with the conventional Köppen-Geiger (KG) divisions. Using the nationwide database of hospitalisations among the elderly (≥65 year olds), we examined the utility of a RS-based climate regionalization to assess public health risk due to extreme weather, by comparing the rate of hospitalisations in response to thermal extremes across climatic regions. Satellite image composites from 2002-2012 were aggregated, masked and compiled into a multi-dimensional dataset. The conterminous USA was classified into 8 distinct regions using a stepwise regionalization approach to limit noise and collinearity (LKN), which exhibited a high degree of consistency with the KG regions and a well-defined regional delineation by annual and seasonal temperature and precipitation values. The most populous was a temperate wet region (10.9 million), while the highest rate of hospitalisations due to exposure to heat and cold (9.6 and 17.7 cases per 100,000 persons at risk, respectively) was observed in the relatively warm and humid south-eastern region. RS-based regionalization demonstrates strong potential for assessing the adverse effects of severe weather on human health and for decision support. Its utility in forecasting and mitigating these effects has to be further explored.