Search

Background: Racial and ethnic minorities have borne a disproportionate burden from coronavirus disease 2019 (COVID-19). Certain essential occupations, including food processing and farm work, employ large numbers of Hispanic migrant workers and have been shown to carry an especially high risk of infection., Methods: This observational cohort study measured the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and assessed the risk factors for seropositivity among food processing and farm workers, and members of their households, in North Carolina, USA. Participants completed questionnaires, blood samples were collected, and an enzyme-linked immunosorbent assay was used to assess SARS-CoV-2 seropositivity. Univariate and multi-variate analyses were undertaken to identify risk factors associated with seropositivity, using generalized estimating equations to account for household clustering., Findings: Among the 218 participants, 94.5% were Hispanic, and SARS-CoV-2 seropositivity was 50.0%. Most seropositive individuals did not report a history of illness compatible with COVID-19. Attending church, having a prior history of COVID-19, having a seropositive household member, and speaking Spanish as one's primary language were associated with SARS-CoV-2 seropositivity, while preventive behaviours were not., Interpretation: These findings underscore the substantial burden of COVID-19 among a population of mostly Hispanic essential workers and their households in rural North Carolina. This study contributes to a large body of evidence showing that Hispanic Americans have suffered a disproportionate burden of COVID-19. This study also highlights the epidemiologic importance of viral transmission within the household., Competing Interests: None declared., (© 2023 The Author(s).)

Meat packing, produce processing, and farm workers are known to have an elevated risk of COVID-19, but occupational risk factors in this population are unclear. We performed an observational cohort study of meat packing, produce processing, and farm workers in North Carolina in fall 2020. Blood, saliva, and nasal turbinate samples were collected to assess for SARS-CoV-2 seropositivity. Risk factors for SARS-CoV-2 seropositivity were investigated using chi-square tests, two-sample t-tests, and adjusted risk ratio analyses. Among 118 enrolled workers, the baseline SARS-CoV-2 seroprevalence was 50.0%. Meat packing plant workers had the highest SARS-CoV-2 seroprevalence (64.6%), followed by farm workers (45.0%) and produce processing workers (10.0%), despite similar sociodemographic characteristics. Compared to SARS-CoV-2 seronegative workers, seropositive workers were more likely to work in loud environments that necessitated yelling to communicate (RR: 1.83, 95% CI: 1.25-2.69), work in cold environments (RR: 1.58, 95% CI: 1.12-2.24), or continue working despite developing symptoms at work (RR: 1.63, 95% CI: 1.14-2.32). After adjusting for age and working despite symptoms, high occupational noise levels were associated with a 1.72 times higher risk of SARS-CoV-2 seropositivity (95% CI: 1.16-2.55). Half of food processing workers showed evidence of past SARS-CoV-2 infection, a prevalence five times higher than most of the United States population at the time of the study. Work environments with loud ambient noise may pose elevated risks for SARS-CoV-2 transmission. Our findings also highlight the disproportionate burden of COVID-19 among underserved and economically disadvantaged Latinx communities in the United States., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Klein et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Lipids represent an important source of nutrition for infecting mycobacteria, accumulating within the necrotic core of granulomas and present in foamy macrophages associated with mycobacterial infection. In order to better understand the timing, process and importance of lipid accumulation, we developed methods for direct in vivo visualization and quantification of this process using the zebrafish-M. marinum larval model of infection. We find that neutral lipids accumulate cell-autonomously in mycobacterium-infected macrophages in vivo during early infection, with detectable levels of accumulation by two days post-infection. Treatment with ezetimibe, an FDA-approved drug, resulted in decreased levels of free cholesterol and neutral lipids, and a reduction of bacterial growth in vivo. The effect of ezetimibe in reducing bacterial growth was dependent on the mce4 operon, a key bacterial determinant of lipid utilization. Thus, in vivo, lipid accumulation can occur cell-autonomously at early timepoints of mycobacterial infection, and limitation of this process results in decreased bacterial burden., Competing Interests: The authors have declared that no competing interests exist.

Background: Exercise has proved effective in attenuating the unfavourable response normally associated with postprandial hypertriglyceridemia (PHTG) and accompanying oxidative stress. Yet, the acute effects of prior exercise and PHTG on DNA damage remains unknown. The purpose of this study was to examine if walking alters PHTG-induced oxidative damage and the interrelated inflammatory mechanisms., Methods: Twelve apparently healthy, recreationally active, male participants (22.4 ± 4.1 years; 179.2 ± 6 cm; 84.2 ± 14.7 kg; 51.3 ± 8.6 ml·kg - 1 ·min - 1 ) completed a randomised, crossover study consisting of two trials: (1) a high-fat meal alone (resting control) or (2) a high-fat meal immediately following 1 h of moderate exercise (65% maximal heart rate). Venous blood samples were collected at baseline, immediately post-exercise or rest, as well as at 2, 4 and 6 h post-meal. Biomarkers of oxidative damage (DNA single-strand breaks, lipid peroxidation and free radical metabolism) and inflammation were determined using conventional biochemistry techniques., Results: DNA damage, lipid peroxidation, free radical metabolism and triglycerides increased postprandially (main effect for time, p < 0.05), regardless of completing 1 h of preceding moderate intensity exercise. Plasma antioxidants (α-tocopherol and γ-tocopherol) also mobilised in response to the high-fat meal (main effect for time, p < 0.05), but no changes were detected for retinol-binding protein-4., Conclusion: The ingestion of a high fat meal induces postprandial oxidative stress, inflammation and a rise in DNA damage that remains unaltered by one hour of preceding exercise.

Purpose: Oxidative stress is associated with tissue cytokine secretion although the precise mechanism(s) underpinning this relationship during high intensity intermittent exercise remains unclear. This study investigates the acute response to a bout of high intensity intermittent walking (HIIW), compared to continuous moderate intensity walking (CMW), on various cytokines and biomarkers of oxidative stress., Methods: Seventeen (n = 17) apparently healthy male participants (aged 22.6 ± 4.6 years; [Formula: see text]: 53.7 ± 7.1 ml kg -1  min -1 ) undertook a randomised crossover study consisting of two exercise trials: (1) HIIW requiring 3 × 5 min bursts at 80% [Formula: see text] (each separated by 5 min of walking at 30% [Formula: see text]) and (2) CMW (60% [Formula: see text] for 30 min). Each trial was separated by 7 days. Venous blood samples were obtained pre-exercise, post-exercise and at 2, 4, 24 and 48 h post-exercise for determination of systemic inflammation (IL-6 and TNF-α), lipid soluble antioxidants and oxidative stress (LOOH, H 2 O 2 and the ascorbyl free radical)., Results: Both IL-6 and TNF-α increased immediately post exercise, regardless of intensity and remained elevated until at least 4 h (main effect for time; p < 0.05). While there was no change in either lipid peroxidation or free radical metabolism (Asc· and H 2 O 2 ), α-tocopherol increased (pooled HIIW and CMW, p < 0.05), whereas lycopene decreased at 2 h post HIIW (p < 0.05)., Conclusion: Bouts of both HIIW and CMW promote cytokine secretion post exercise, and this seems to be independent of oxidative stress. Further investigation is required to assess how such changes may underpin some of the transient health benefits of exercise.

Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi ( S Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility to S Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulates Salmonella invasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches., Competing Interests: The authors declare no conflict of interest.

Macrophages play a central role in mycobacterial pathogenesis. Recent work has highlighted the importance of diverse macrophage types and phenotypes that depend on local environment and developmental origins. In this review, we highlight how distinct macrophage phenotypes may influence disease progression in tuberculosis. In addition, we draw on work investigating specialized macrophage populations important in cancer biology and atherosclerosis in order to suggest new areas of investigation relevant to mycobacterial pathogenesis. Understanding the mechanisms controlling the repertoire of macrophage phenotypes and behaviors during infection may provide opportunities for novel control of disease through modulation of macrophage form and function., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cardiovascular disease (CVD) is the leading cause of global mortality. Although the incidence may be reduced with regular exercise, the health benefits of a single bout of exercise on selected CVD risk factors are not well understood. The primary objective of this review is to consider the transient effects of exercise on immune (neutrophil count) and inflammatory (interleukin-6 [IL-6], C-reactive protein [CRP]) markers in untrained adults., Methods: MEDLINE, EMBASE, CINAHL, Sports Discus and Cochrane were searched for relevant studies published from January 1946 to May 2013. Randomised controlled or crossover studies which measured any of these parameters in untrained but otherwise healthy participants in the 48 h following about of exercise, less than 1 h in duration were included., Results: Ten studies met the inclusion criteria. The results indicate a single bout of aerobic or resistance exercise of moderate to high intensity promotes an increase in IL-6 (145 %) and neutrophil counts (51 %). It appears that 30-60 min of moderate to high intensity exercise is necessary to elicit such changes although variables such as the mode, intensity and pattern of exercise also affect the response. The acute response of CRP within the included studies is equivocal., Conclusions: Although responses to CRP are inconsistent, a single bout of exercise can increase the activity of both circulating IL-6 and neutrophil counts in untrained adults. These immune and inflammatory responses to a single bout of exercise may be linked to a range of health benefits.

Background: Cinnamon has been shown to delay gastric emptying of a high-carbohydrate meal and reduce postprandial glycemia in healthy adults. However, it is dietary fat which is implicated in the etiology and is associated with obesity, type 2 diabetes and cardiovascular disease. We aimed to determine the effect of 3 g cinnamon (Cinnamomum zeylanicum) on GE, postprandial lipemic and glycemic responses, oxidative stress, arterial stiffness, as well as appetite sensations and subsequent food intake following a high-fat meal., Methods: A single-blind randomized crossover study assessed nine healthy, young subjects. GE rate of a high-fat meal supplemented with 3 g cinnamon or placebo was determined using the 13C octanoic acid breath test. Breath, blood samples and subjective appetite ratings were collected in the fasted and during the 360 min postprandial period, followed by an ad libitum buffet meal. Gastric emptying and 1-day fatty acid intake relationships were also examined., Results: Cinnamon did not change gastric emptying parameters, postprandial triacylglycerol or glucose concentrations, oxidative stress, arterial function or appetite (p < 0.05). Strong relationships were evident (p < 0.05) between GE Thalf and 1-day palmitoleic acid (r = -0.78), eiconsenoic acid (r = -0.84) and total omega-3 intake (r = -0.72). The ingestion of 3 g cinnamon had no effect on GE, arterial stiffness and oxidative stress following a HF meal., Conclusions: 3 g cinnamon did not alter the postprandial response to a high-fat test meal. We find no evidence to support the use of 3 g cinnamon supplementation for the prevention or treatment of metabolic disease. Dietary fatty acid intake requires consideration in future gastrointestinal studies., Trial Registration Number: at http://www.clinicaltrial.gov: NCT01350284.

Previous studies of Plasmodium vivax transmission to Anopheles spp. mosquitoes have not been able to predict mosquito infectivity on the basis of microscopic or molecular quantification of parasites (total parasites in the sample or total number of gametocytes) in infected blood. Two methods for production of P. vivax ookinete cultures in vitro, with yields of 10(6) macrogametocytes, 10(4) zygotes, and 10(3) ookinetes, respectively, per 10 mL of P. vivax-infected patient blood with approximately 0.01% parasitemia, were used to study P. vivax sexual stage development. The quantity of gametocytes, determined by counting Giemsa-stained blood smears, and quantity and type of gametocyte as determined by quantitative reverse transcriptase-polymerase chain reaction for Pvalpha tubulin II and macrogametocyte-specific pvg377 did not predict ookinete yield. Factors that affect the efficiency of in vitro P. vivax ookinete transformation remain poorly understood.

There is a paucity of research examining the influence of acute exercise on pulse wave velocity (PWV) and oxidative stress. The purpose of this study was to examine the effects of acute moderate aerobic exercise on PWV and oxidative stress in healthy males. Eight apparently healthy males (age 23.6 ± 2.8 yrs; stature 181.4 ± 8.1 cm; weight 83.4 ± 16.2 kg; all data mean ±SD) participated in a randomized crossover design consisting of (i) a one hour bout of moderate aerobic exercise and (ii) a control trial of one hour rest. Pre- and post-exercise blood samples were drawn for the determination of lipid hydroperoxides (LOOHs) and lipid-soluble antioxidants (lycopene, retinol, and β-carotene). Exercise had no effect on stiffness and LOOHs (P > 0.05). Retinol and lycopene were increased following exercise (P < 0.05). These findings suggest that acute moderate exercise has no effect on PWV and LOOHs, but it can increase systemic antioxidants, which may be of benefit to health.

Previous reports have described obtaining mature Plasmodium vivax ookinetes in vitro using blood from infected patients using a simplified, field-based protocol. Here, we report protocols that produce improved P. vivax ookinete yields and morphological development. Optimal conditions included induction of gametogenesis using 10 mM Tris, 170 mM NaCl, 10 mM glucose, 25 mM NaHCO(3), and 100 μM xanthurenic acid for 90 minutes at pH 8.0-8.2, followed by culture in RPMI-1640, 50 mg/mL hypoxanthine, 25 mM HEPES, 29 mM NaHCO(3), 2 mM L-glutamine, and 20% fetal bovine serum at pH 8.4 for 36 hours. Ookinetes were produced in 86% (18/21) of optimized in vitro cultures; yields ranged from 6.5 × 10(4) to 2.8 × 10(6); percent gametocyte conversion ranged from 1.4% to 4.7%. This improved method is suitable for preparation of P. vivax ookinetes in quantities sufficient for biochemical, molecular, and cell biological analysis where basic laboratory facilities are in proximity to patients with vivax malaria.

Plasmodium vivax causes 25-40% of malaria cases worldwide, yet research on this human malaria parasite has been neglected. Nevertheless, the recent publication of the P. vivax reference genome now allows genomics and systems biology approaches to be applied to this pathogen. We show here that whole-genome analysis of the parasite can be achieved directly from ex vivo-isolated parasites, without the need for in vitro propagation. A single isolate of P. vivax obtained from a febrile patient with clinical malaria from Peru was subjected to whole-genome sequencing (30× coverage). This analysis revealed over 18,261 single-nucleotide polymorphisms (SNPs), 6,257 of which were further validated using a tiling microarray. Within core chromosomal genes we find that one SNP per every 985 bases of coding sequence distinguishes this recent Peruvian isolate, designated IQ07, from the reference Salvador I strain obtained in 1972. This full-genome sequence of an uncultured P. vivax isolate shows that the same regions with low numbers of aligned sequencing reads are also highly variable by genomic microarray analysis. Finally, we show that the genes containing the largest ratio of nonsynonymous-to-synonymous SNPs include two AP2 transcription factors and the P. vivax multidrug resistance-associated protein (PvMRP1), an ABC transporter shown to be associated with quinoline and antifolate tolerance in Plasmodium falciparum. This analysis provides a data set for comparative analysis with important potential for identifying markers for global parasite diversity and drug resistance mapping studies.

Background: Up to 40% of the world's population is at risk for Plasmodium vivax malaria, a disease that imposes a major public health and economic burden on endemic countries. Because P. vivax produces latent liver forms, eradication of P. vivax malaria is more challenging than it is for P. falciparum. Genetic analysis of P. vivax is exceptionally difficult due to limitations of in vitro culture. To overcome the barriers to traditional molecular biology in P. vivax, we examined parasite transcriptional changes in samples from infected patients and mosquitoes in order to characterize gene function, define regulatory sequences and reveal new potential vaccine candidate genes., Principal Findings: We observed dramatic changes in transcript levels for various genes at different lifecycle stages, indicating that development is partially regulated through modulation of mRNA levels. Our data show that genes involved in common biological processes or molecular machinery are co-expressed. We identified DNA sequence motifs upstream of co-expressed genes that are conserved across Plasmodium species that are likely binding sites of proteins that regulate stage-specific transcription. Despite their capacity to form hypnozoites we found that P. vivax sporozoites show stage-specific expression of the same genes needed for hepatocyte invasion and liver stage development in other Plasmodium species. We show that many of the predicted exported proteins and members of multigene families show highly coordinated transcription as well., Conclusions: We conclude that high-quality gene expression data can be readily obtained directly from patient samples and that many of the same uncharacterized genes that are upregulated in different P. vivax lifecycle stages are also upregulated in similar stages in other Plasmodium species. We also provide numerous examples of how systems biology is a powerful method for determining the likely function of genes in pathogens that are neglected due to experimental intractability.

Background: Individuals with impaired glucose tolerance (IGT) have a greater risk of developing diabetes and cardiovascular disease compared with those with normal glycemic control. The aim of this study was to examine the effects of acute aerobic exercise on glycemia, regional arterial stiffness, and oxidative stress in obese subjects with IGT., Design: Twelve obese subjects (7 men and 5 women; 48.0±9.4 years; body mass index 32.4±7.0kg/m(2)) with IGT participated in a 30-minute bout of walking at 65% of maximum predicted heart rate. Pulse wave velocity (PWV, for determination of arterial stiffness) and blood pressure were examined before and after exercise, whereas venous blood samples were drawn for the determination of glucose, blood lipids, and indices of oxidative stress and inflammation (lipid hydroperoxides; superoxide dismutase; high-sensitivity C-reactive protein)., Results: After exercise PWV (9.1±1.2m/s vs. 8.6±1.0m/s), glucose (5.7±0.6 mmol·L(-1) vs. 5.4±0.6 mmol·L(-1)), and diastolic blood pressure (94±14mm Hg vs. 86±13mm Hg) decreased, respectively (P < .05). A correlation was observed between PWV and glucose (r=0.544, P < .05). There were no changes in lipid hydroperoxides, superoxide dismutase, high-sensitivity C-reactive protein, or blood lipids (P > .05)., Conclusions: These findings suggest that acute aerobic exercise can reduce regional arterial stiffness in obese subjects with IGT by possibly improving glucose metabolism, independent of changes in oxidative stress.