Evidence-Based Tools for Dietary Assessments in Nutrition Epidemiology Studies for Dementia Prevention

Increasing evidence proposes diet as a notable modifiable factor and viable target for the reduction of Alzheimer’s Disease risk and age-related cognitive decline. However, assessment of dietary exposures is challenged by dietary capture methods that are prone to misreporting and measurement errors. The utility of -omics technologies for the evaluation of dietary exposures has the potential to improve reliability and offer new insights to pre-disease indicators and preventive targets in cognitive aging and dementia. In this review, we present a focused overview of metabolomics as a validation tool and framework for investigating the immediate or cumulative effects of diet on cognitive health.

A tale of two plasmids: contributions of plasmid associated phenotypes to epidemiological success among Shigella

Dissemination of antimicrobial resistance (AMR) genes by horizontal gene transfer (HGT) mediated through plasmids is a major global concern. Genomic epidemiology studies have shown varying success of different AMR plasmids during outbreaks, but the underlying reasons for these differences are unclear. Here, we investigated two Shigella plasmids (pKSR100 and pAPR100) that circulated in the same transmission network but had starkly contrasting epidemiological outcomes to identify plasmid features that may have contributed to the differences. We used plasmid comparative genomics to reveal divergence between the two plasmids in genes encoding AMR, SOS response alleviation, and conjugation. Experimental analyses revealed that these genomic differences corresponded with reduced conjugation rates for the epidemiologically successful pKSR100, but more extensive AMR, reduced fitness costs, and a reduced SOS response in the presence of antimicrobials, compared with the less successful pAPR100. The discrepant phenotypes between the two plasmids are consistent with the hypothesis that plasmid associated phenotypes contribute to determining the epidemiological outcome of AMR HGT and suggest that phenotypes relevant in responding to antimicrobial pressure and fitness impact may be more important than those around conjugation in this setting. Plasmid phenotypes could thus be valuable tools in conjunction with genomic epidemiology for predicting AMR dissemination.

A framework for research into continental ancestry groups of the UK Biobank

The UK Biobank is a large prospective cohort, based in the United Kingdom, that has deep phenotypic and genomic data on roughly a half a million individuals. Included in this resource are data on approximately 78,000 individuals with "non-white British ancestry". Whilst most epidemiology studies have focused predominantly on populations of European ancestry, there is an opportunity to contribute to the study of health and disease for a broader segment of the population by making use of the UK Biobank's "non-white British ancestry" samples. Here we present an empirical description of the continental ancestry and population structure among the individuals in this UK Biobank subset. Reference populations from the 1000 Genomes Project for Africa, Europe, East Asia, and South Asia were used to estimate ancestry for each individual. Those with at least 80% ancestry in one of these four continental ancestry groups were taken forward (N=62,484). Principal component and K-means clustering analyses were used to identify and characterize population structure within each ancestry group. Of the approximately 78,000 individuals in the UK Biobank that are of "non-white British" ancestry, 50,685, 6,653, 2,782, and 2,364 individuals were associated to the European, African, South Asian, and East Asian continental ancestry groups, respectively. Each continental ancestry group exhibits prominent population structure that is consistent with self-reported country of birth data and geography. Methods outlined here provide an avenue to leverage UK Biobank's deeply phenotyped data allowing researchers to maximise its potential in the study of health and disease in individuals of non-white British ancestry.

Epidemiology of Concussions in National Collegiate Athletic Association (NCAA) Sports: 2014/15-2018/19

Background: Updated epidemiology studies examining sports-related concussions (SRCs) are critical in evaluating recent efforts aimed at reducing the incidence of SRCs in National Collegiate Athletic Association (NCAA) sports. Purpose: To describe the epidemiology of SRCs in 23 NCAA sports during the 2014/15-2018/19 academic years. Study Design: Descriptive epidemiology study. Methods: SRC and exposure data collected in the NCAA Injury Surveillance Program were analyzed. Injury counts, rates, and proportions were used to describe injury characteristics by sport, event type (practices, competitions), injury mechanism (player contact, surface contact, equipment/apparatus contact), and injury history (new, recurrent). Injury rate ratios (IRRs) were used to examine differential injury rates, and injury proportion ratios (IPRs) were used to examine differential distributions. Results: A total of 3497 SRCs from 8,474,400 athlete-exposures (AEs) were reported during the study period (4.13 per 10,000 AEs); the competition-related SRC rate was higher than was the practice-related SRC rate (IRR, 4.12; 95% CI, 3.86-4.41). The highest SRC rates were observed in men’s ice hockey (7.35 per 10,000 AEs) and women’s soccer (7.15 per 10,000 AEs); rates in women’s soccer and volleyball increased during 2015/16-2018/19. Player contact was the most prevalently reported mechanism in men’s sports (77.0%), whereas equipment/apparatus contact was the most prevalently reported mechanism in women’s sports (39.2%). Sex-related differences were observed in soccer, basketball, softball/baseball, and swimming and diving. Most SRCs reported in men’s sports (84.3%) and women’s sports (81.1%) were reported as new injuries. Conclusion: Given the increasing SRC rates observed in women’s soccer and volleyball during the latter years of the study, these results indicate the need to direct further attention toward trajectories of SRC incidence in these sports. The prevalence of equipment/apparatus contact SRCs in women’s sports also suggests that SRC mechanisms in women’s sports warrant further investigation. As most SRCs during the study period were reported as new injuries, the prevalence of recurrent SRCs in men’s and women’s ice hockey is also noteworthy.

Multilocus Genotyping of Pneumocystis jirovecii from Deceased Cuban AIDS Patients Using Formalin-Fixed and Paraffin-Embedded Tissues

The results of the genotypic characterization of Pneumocystis jirovecii are described in lung tissue samples from 41 Cubans who died of AIDS with pneumocystosis between 1995 and 2008. Histological sections of the lung preserved as formalin-fixed and paraffin-embedded tissue were examined. PCR amplification and nucleotide sequencing of the two mitochondrial genes (large and small) of the pathogen allowed verification of a predominance of genotype 3 (85T/248C) of the large mitochondrial gene and genotype 3 (160A/196T) of the small mitochondrial gene over a period of 14 years (1995–2008). These results suggest that the 85T/248C//160A/196T genotype circulates with the highest frequency (81.3%) among AIDS patients in Cuba. Multilocus analysis indicates a limited circulation of pathogen genotypes on the island with the existence of a clonal genotype with an epidemic structure. Furthermore, it appears that circulating strains of P. jirovecii have not developed mutations related to sulfonamide resistance. Taken together, the data in this study revealed important elements about pneumocystosis in Cuban patients dying of AIDS and the usefulness of formalin-fixed and paraffin-embedded samples to carry out molecular epidemiology studies of P. jirovecii.

Evaluating Smartphone App Based Dietary Tracking in a Military Population: Validation Study (Preprint)

BACKGROUND Collecting dietary intake data is a key component for a majority of nutritional epidemiology studies. Smartphone technology advancements allow researchers to use health and nutrition apps as alternatives to currently available tools (food frequency questionnaires, 24-hour recalls, and food diaries). Service Members (SM) can greatly benefit from the always-available information and easily accessible nature of smartphones to track their intake. Clinicians working with military units can help provide these SM with the skills to evaluate their intake for performance benefits. Understanding the accuracy of these apps is important to determine their effectiveness for use in clinical and research settings. OBJECTIVE This study evaluated the relative validity of self-reported intake with the HealthWatch 360 (HW 360) app compared to the Automated Self-Administered 24-hour Dietary Assessment (ASA24). METHODS Recruitment targeted Army and Air Force SM from Joint Base Lewis-McChord, WA and Joint Base San Antonio-Lackland, TX who currently or previously failed to meet body composition standards. Participants (n=53) completed a demographic questionnaire, baseline anthropometric measurements, and recorded daily intake on the HW 360 app. They returned approximately two weeks later to complete a 24-hour recall using the ASA24. Agreement and relative validity were evaluated using Bland-Altman plots and two one-sided tests at a ± 10% equivalency range of ASA24 mean nutrient intake values between HW 360 and ASA24 data. Multilinear regressions analyzed relationships between participant demographics and relative validity. RESULTS HW 360 was not significantly equivalent to the ASA24. Large levels of underreporting were found in total energy (Mean Difference (Mdiff) = -503.3 kcal, 90% CI: -649.8 to -356.7 kcal), carbohydrates (Mdiff = -52.2 g, 90% CI: -70.4 to -34.1 g), protein (Mdiff = -20.4 g, 90% CI: -29.4 to -11.3 g), and fat (Mdiff = -24.6 g, 90% CI: -32.5 to -16.7 g). Bland-Altman plots failed to illustrate agreement. No significant correlations existed for demographic variables and relative validity. CONCLUSIONS Differences between all variables tested were above clinically significant values and limit the usage of this application in research and clinical settings. Further research is needed to determine the potential causes of underreporting and evaluate methods to minimize this effect. Understanding these effects allows the implementation of a tailored app for use with SM. It has the potential to be an invaluable asset for this population due the unpredictable nature of deployments and training exercises. CLINICALTRIAL ClinicalTrials.gov NCT04959318; https://clinicaltrials.gov/ct2/show/NCT04959318

Enterotoxigenic Escherichia coli degrades the host MUC2 mucin barrier to facilitate critical pathogen-enterocyte interactions in human small intestine.

Enterotoxigenic Escherichia coli (ETEC) are a genetically diverse pathologic variant of E. coli defined by the production of heat-labile (LT) and/or heat-stable (ST) toxins. ETEC are estimated to cause hundreds of millions of cases of diarrheal illness annually. However, it is not clear that all strains are equally equipped to cause disease and asymptomatic colonization with ETEC is common in low-middle income regions lacking basic sanitation and clean water where ETEC are ubiquitous. Recent molecular epidemiology studies have revealed a significant association between strains which produce EatA, a secreted autotransporter protein, and the development of symptomatic infection. Here, we demonstrate that LT stimulates production of MUC2 mucin by goblet cells in human small intestine, enhancing the protective barrier between pathogens and enterocytes. In contrast, using explants of human small intestine as well as small intestinal enteroids, we show that EatA counters this host defense by engaging and degrading the MUC2 mucin barrier to promote bacterial access to target enterocytes and ultimately toxin delivery suggesting that EatA plays a crucial role in the molecular pathogenesis of ETEC. These findings may inform novel approaches to prevention of the acute diarrheal illness as well as the sequelae associated with ETEC and other pathogens that rely on EatA and similar proteases for efficient interaction with their human hosts.

Statins mediate anti- and pro-tumourigenic functions in lung adenocarcinoma development by remodelling the tumour microenvironment

Anti-cancer properties of statins are controversial, and possibly context-dependent. Recent pathology/epidemiology studies of human lung adenocarcinoma showed reduced protumourigenic macrophages associated with a shift to lower grade tumours amongst statin users but, paradoxically, worse survival compared to non-users. To investigate the mechanisms involved, we have characterised mouse lung adenoma/adenocarcinoma models treated with atorvastatin. Here we show that atorvastatin suppresses premalignant disease by inhibiting the recruitment of protumourigenic macrophages to the tumour microenvironment, manifested in part by suppression of Rac-mediated CCR1 ligand secretion. However, prolonged atorvastatin treatment leads to drug resistance and progression of lung adenomas into invasive disease. Pathological progression is not driven by acquisition of additional driver mutations or immunoediting/evasion but is associated with stromal changes including the development of desmoplastic stroma containing Gr1+ myeloid cells and tertiary lymphoid structures (TLS). These findings show that any chemopreventive functions of atorvastatin in lung adenocarcinoma are overridden by stromal remodelling in the long term, thus providing mechanistic insight into the poor survival of lung adenocarcinoma patients with statin use.

The Rain Forest Environment and Oil Palm Fatal Yellowing

Oil palm produces the most consumed vegetable oil in the world. In addition to being economically viable and having multiple uses, the crop has a strong ecological appeal, given its high level of carbon sequestration, its low environmental impact, and a low mechanization level in the harvest process, generating income and financial sustainability for the inhabitants of that biome. However, despite the large areas suitable for cultivation in harmony with the forest in Brazil, oil palm production has been limited by a disease known as fatal Yellowing (FY). In 30 years of research to determine the causal agent of this disease, many epidemiology studies with insects and plant pathogens have been performed, but there is no consensus on its cause. Abiotic factors have also started to be considered a possible cause of these symptoms. Therefore, to clarify the relationship of this disease to environmental variables, we studied the nutritional status of the plant, the soil class and fertility, the climatic variables and attempted to verify the set of proteins and their isoforms expressed in diseased palms showing FY symptoms and healthy palms. FY occurred under constant rain and in clay soils; consequently, the roots of these palm trees suffered anoxia, which caused nutritional problems and the accumulation of stress-related proteins. Under these conditions, the usually observed symptom was yellowing, which can lead to the death of the plant, giving the disease its name. In other words, the symptomatic picture is not associated with only a biotic cause. Thus, a pedological survey of the area, planting in soils not subject to waterlogging or with good drainage conditions, and the correct maintenance of soil fertility and plant nutrition may certainly contribute to the management of and reduction in fatal yellowing without the use of agrochemicals.