Upper respiratory Streptococcus pneumoniae colonization among working-age adults with prevalent exposure to overcrowding.

Most pneumococcal disease occurs among infants and older adults and is thought to be driven by the transmission of Streptococcus pneumoniae from young children to these vulnerable age groups. However, pneumococcal disease outbreaks also affect non-elderly adults living or working in congregate, close-contact settings. Little is known about pneumococcal carriage in such populations. From July to November 2020, we collected saliva from low-income adult farmworkers in Monterey County, California, and tested for pneumococcal carriage following culture enrichment via quantitative PCR assays targeting the pneumococcal lytA and piaB genes. Participants were considered to carry pneumococci if lytA and piaB cycle threshold values were both below 40. Among 1,283 participants enrolled in our study, 117 (9.1%) carried pneumococci. Carriers tended more often than non-carriers to be exposed to children aged <5 years [odds ratio (OR) = 1.45 (0.95-2.20)] and overcrowding [OR = 1.48 (0.96-2.30) and 2.84 (1.20-6.73), respectively, for participants in households with >2-4 and >4 persons per bedroom vs ≤2 persons per bedroom]. Household overcrowding remained associated with increased risk of carriage among participants not exposed to children aged <5 years [OR = 2.05 (1.18-3.59) for participants living in households with >2 vs ≤2 persons per bedroom]. Exposure to children aged <5 years and overcrowding were each associated with increased pneumococcal density among carriers [piaB cT difference of 2.04 (0.36-3.73) and 2.44 (0.80-4.11), respectively]. While exposure to young children was a predictor of pneumococcal carriage, associations of overcrowding with increased prevalence and density of carriage in households without young children suggest that transmission also occurs among adults in close-contact settings.IMPORTANCEAlthough infants and older adults are the groups most commonly affected by pneumococcal disease, outbreaks are known to occur among healthy, working-age populations exposed to overcrowding, including miners, shipyard workers, military recruits, and prisoners. Carriage of Streptococcus pneumoniae is the precursor to pneumococcal disease, and its relation to overcrowding in adult populations is poorly understood. We used molecular methods to characterize pneumococcal carriage in culture-enriched saliva samples from low-income adult farmworkers in Monterey County, CA. While exposure to children in the household was an important risk factor for pneumococcal carriage, living in an overcrowded household without young children was an independent predictor of carriage as well. Moreover, participants exposed to children or overcrowding carried pneumococci at higher density than those without such exposures, suggesting recent transmission. Our findings suggest that, in addition to transmission from young children, pneumococcal transmission may occur independently among adults in overcrowded settings.

Childhood exposure to organophosphate pesticides: Functional connectivity and working memory in adolescents.

BACKGROUND: Early life exposure to organophosphate (OP) pesticides is linked with adverse neurodevelopment and brain function in children. However, we have limited knowledge of how these exposures affect functional connectivity, a measure of interaction between brain regions. To address this gap, we examined the association between early life OP pesticide exposure and functional connectivity in adolescents. METHODS: We administered functional near-infrared spectroscopy (fNIRS) to 291 young adults with measured prenatal or childhood dialkylphosphates (DAPs) in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal study of women recruited during pregnancy and their offspring. We measured DAPs in urinary samples collected from mothers during pregnancy (13 and 26 weeks) and children in early life (ages 6 months, 1, 2, 3, and 5 years). Youth underwent fNIRS while they performed executive function and semantic language tasks during their 18-year-old visit. We used covariate-adjusted regression models to estimate the associations of prenatal and childhood DAPs with functional connectivity between the frontal, temporal, and parietal regions, and a mediation model to examine the role of functional connectivity in the relationship between DAPs and task performance. RESULTS: We observed null associations of prenatal and childhood DAP concentrations and functional connectivity for the entire sample. However, when we looked for sex differences, we observed an association between childhood DAPs and functional connectivity for the right interior frontal and premotor cortex after correcting for the false discovery rate, among males, but not females. In addition, functional connectivity appeared to mediate an inverse association between DAPs and working memory accuracy among males. CONCLUSION: In CHAMACOS, a secondary analysis showed that adolescent males with elevated childhood OP pesticide exposure may have altered brain regional connectivity. This altered neurofunctional pattern in males may partially mediate working memory impairment associated with childhood DAP exposure.

Defatting of donor transplant livers during normothermic perfusion-a randomised clinical trial: study protocol for the DeFat study.

BACKGROUND: Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes. METHODS: In the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months). DISCUSSION: This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths. TRIAL REGISTRATION: ISRCTN ISRCTN14957538. Registered in October 2022.

Association of pesticide exposure with respiratory health outcomes and rhinitis in avocado farmworkers from Michoacán, Mexico.

BACKGROUND: A growing literature suggests associations between occupational pesticide exposure and respiratory health. In this study, we aimed to examine the association of exposure to insecticides, fungicides, and herbicides, individually and as a mixture, with respiratory health outcomes and rhinitis in avocado farmworkers from Michoacán, Mexico. MATERIAL AND METHODS: We conducted a cross-sectional study of 105 avocado farmworkers between May and August 2021. We quantified 12 insecticide, fungicide, and herbicide metabolites in urine samples collected during two study visits (8-10 weeks apart). We collected survey data on self-reported pesticide use during the 12 months prior to the baseline survey and estimated annual exposure-intensity scores (EIS) using a semi-quantitative exposure algorithm. We also assessed respiratory symptoms, including wheezing, chest tightness, wheezing after exercise, and night cough. We used generalized linear regression models to examine associations of individual urinary metabolite concentrations and annual EIS with respiratory health outcomes and rhinitis. Mixture effects were assessed using Bayesian Weighted Quantile Sum (BWQS) regression. RESULTS: After adjusting for multiple comparisons, we observed mostly null associations of individual pesticide metabolite concentrations and annual EIS with the outcomes of interest. However, in BWQS analyses, we found evidence of a mixture association of urinary pesticide metabolites with increased odds of night cough (OR: 5.34, 95 % CrI: 1.67, 20.62). Pyrethroid metabolites 3-phenoxybenzoic acid and cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid were the main contributors to this association (43 %). CONCLUSIONS: Our findings indicate that exposure to a mixture of pesticides, particularly pyrethroid insecticides, may be associated with night cough in avocado farmworkers.

FOXK2 targeting by the SCF-E3 ligase subunit FBXO24 for ubiquitin mediated degradation modulates mitochondrial respiration.

FOXK2 is a crucial transcription factor implicated in a wide array of biological activities and yet understanding of its molecular regulation at the level of protein turnover is limited. Here, we identify that FOXK2 undergoes degradation in lung epithelia in the presence of the virulent pathogens Pseudomonas aeruginosa and Klebsiella pneumoniae through ubiquitin-proteasomal processing. FOXK2 through its carboxyl terminus (aa 428-478) binds the Skp-Cullin-F-box ubiquitin E3 ligase subunit FBXO24 that mediates multisite polyubiquitylation of the transcription factor resulting in its nuclear degradation. FOXK2 was detected within the mitochondria and targeted depletion of the transcription factor or cellular expression of FOXK2 mutants devoid of key carboxy terminal domains significantly impaired mitochondrial function. In experimental bacterial pneumonia, Fbxo24 heterozygous mice exhibited preserved mitochondrial function and Foxk2 protein levels compared to WT littermates. The results suggest a new mode of regulatory control of mitochondrial energetics through modulation of FOXK2 cellular abundance.

Estimating geographic variation of infection fatality ratios during epidemics.

Objectives: We aim to estimate geographic variability in total numbers of infections and infection fatality ratios (IFR; the number of deaths caused by an infection per 1,000 infected people) when the availability and quality of data on disease burden are limited during an epidemic. Methods: We develop a noncentral hypergeometric framework that accounts for differential probabilities of positive tests and reflects the fact that symptomatic people are more likely to seek testing. We demonstrate the robustness, accuracy, and precision of this framework, and apply it to the United States (U.S.) COVID-19 pandemic to estimate county-level SARS-CoV-2 IFRs. Results: The estimators for the numbers of infections and IFRs showed high accuracy and precision; for instance, when applied to simulated validation data sets, across counties, Pearson correlation coefficients between estimator means and true values were 0.996 and 0.928, respectively, and they showed strong robustness to model misspecification. Applying the county-level estimators to the real, unsimulated COVID-19 data spanning April 1, 2020 to September 30, 2020 from across the U.S., we found that IFRs varied from 0 to 44.69, with a standard deviation of 3.55 and a median of 2.14. Conclusions: The proposed estimation framework can be used to identify geographic variation in IFRs across settings.

Single Cell MALDI-MS Imaging of Lipids and Proteins in Senescent Fibroblasts.

In this study, we evaluate the lipidomic and proteomic profiles of human lung fibroblasts (hLFs) to interrogate changes occurring due to senescence. To study single cell populations, a comparison of cell adhered onto slides utilizing poly-D-lysine versus centrifugal force deposition was first analyzed to determine whether specific alterations were observed between preparations. The poly-D-lysine approach was than utilized to interrogate the lipidome of the cell populations and further evaluate potential applications of the MALDI-IHC platform for single-cell level analyses. Altogether, our results show the ability to detect lipids implicated in senescence and alterations to protein expression between normal and senescent fibroblast populations. This report is the first time that the MALDI-IHC system has been utilized at a single-cell level for analyzing the expression of proteins.

Pesticide exposure, birth size, and gestational age in the ISA birth cohort, Costa Rica.

Purpose: To examine associations of prenatal biomarkers of pesticide exposure with birth size measures and length of gestation among newborns from the Infants' Environmental Health (ISA) birth cohort, Costa Rica. Methods: We included 386 singleton liveborn newborns with data on birth size measures, length of gestation, and maternal urinary biomarkers of chlorpyrifos, synthetic pyrethroids, mancozeb, pyrimethanil, and 2, 4-D during pregnancy. We associated biomarkers of exposure with birth outcomes using multivariate linear regression and generalized additive models. Results: Concentrations were highest for ethylene thiourea (ETU, metabolite of mancozeb), median = 3.40; p10-90 = 1.90-6.79 µg/L, followed by 3,5,6-trichloro-2-pyridinol (TCP, metabolite of chlorpyrifos) p50 = 1.76 p10-90 = 0.97-4.36 µg/L, and lowest for 2,4-D (p50 = 0.33 p10-90 = 0.18-1.07 µg/L). Among term newborns (≥37 weeks), higher prenatal TCP was associated with lower birth weight and smaller head circumference (e.g., ß per 10-fold-increase) during the second half of pregnancy = -129.6 (95% confidence interval [CI] = -255.8, -3.5) grams, and -0.61 (95% CI = -1.05, -0.17) centimeters, respectively. Also, among term newborns, prenatal 2,4-D was associated with lower birth weight (ß per 10-fold-increase = -125.1; 95% CI = -228.8, -21.5), smaller head circumference (ß = -0.41; 95% CI = -0.78, -0.03), and, during the second half of pregnancy, with shorter body length (ß = -0.58; 95% CI = -1.09, -0.07). Furthermore, ETU was nonlinearly associated with head circumference during the second half of pregnancy. Biomarkers of pyrethroids and pyrimethanil were not associated with birth size, and none of the biomarkers explained the length of gestation. Conclusions: Prenatal exposure to chlorpyrifos and 2,4-D, and, possibly, mancozeb/ETU, may impair fetal growth.

Phenotypic Heterogeneity of Cancer Associated Fibroblasts in Cervical Cancer Progression: FAP as a Central Activation Marker.

Cervical cancer (CC) is the fourth leading cancer among women and is one of the principal gynecological malignancies. In the tumor microenvironment, cancer-associated fibroblasts (CAFs) play a crucial role during malignant progression, exhibiting a variety of heterogeneous phenotypes. CAFs express phenotypic markers like fibroblast activation protein (FAP), vimentin, S100A4, α-smooth muscle actin (αSMA), and functional markers such as MMP9. This study aimed to evaluate the protein expression of vimentin, S100A4, αSMA, FAP, and MMP9 in mesenchymal stem cells (MSC)-CAF cells, as well as in cervical cancer samples. MSC cells were stimulated with HeLa and SiHa tumor cell supernatants, followed by protein evaluation and cytokine profile to confirm differentiation towards a CAF phenotype. In addition, automated immunohistochemistry (IHQa) was performed to evaluate the expression of these proteins in CC samples at different stages. Our findings revealed a high expression of FAP in stimulated MSC cells, accompanied by the secretion of pro/anti-inflammatory cytokines. In the other hand, CC samples were observed to have high expression of FAP, vimentin, αSMA, and MMP9. Most importantly, there was a high expression of their activation proteins αSMA and FAP during the different stages. In the early stages, a myofibroblast-like phenotype (CAFs αSMA+ FAP+), and in the late stages a protumoral phenotype (CAF αSMA- FAP+). In summary, FAP has a crucial role in the activation of CAFs during cervical cancer progression.

Predators of the sea urchin Diadema mexicanum (Diadematoida: Diadematidae) at the Eastern Tropical Pacific coral reefs / Depredadores del erizo de mar Diadema mexicanum (Diadematoida: Diadematidae) en los arrecifes de coral del Pacífico Tropical Oriental

Abstract Introduction: The coral reefs of Isla del Coco National Park are some of the most pristine ecosystems on Earth. The sea urchin Diadema mexicanum (Diadematoida: Diadematidae) is a common inhabitant with a pivotal role in the ecology of this unique ecosystem. Objective: In this study, we identified the predominant predators of D. mexicanum and estimated the predatory consumption rates. We also determined predation rates at different sea urchin sizes and at sites with contrasting refuge availability. Methods: We use field video recording observations and tethering experiments. Results: The balistid Sufflamen verres and the labrid Bodianus diplotaenia were identified as predators of small and medium size D. mexicanum; the labrids Thalassoma grammaticum and B. diplotaenia (juvenile) and the tetraodontid Arothron meleagris were attempted predators; and Canthigaster punctatissima and Holacanthus passer were scavengers. Larger sea urchins (> 30 mm) were also preyed upon during the tethering experiments. Furthermore, a clear effect of the site on survival of the different sea urchins' sizes was noted. No difference in the sea urchin predator biomass was found among sites, which highlights the importance of site complexity on survival. At high and medium complexity sites, large individuals had better survival, while at the low complexity site, there was almost no differences in survival rates among the three size classes. Our results also show that a high abundance of these predatory fishes, above 0.04 ind m-2, guarantees a low sea urchin density. Below this threshold, a higher variability in sea urchin density is observed Despite not being registered with the video recordings, lobsters were observed once preying upon a large sea urchin individual. Conclusions: This study identifies a keystone fish guild with high predation rate for Diadema in the National Park, which suggests that protective actions have positively benefited predatory fish and lobster populations.

Resumen Introducción: Los arrecifes de coral del Parque Nacional Isla del Coco son uno de los ecosistemas más prístinos de la Tierra. El erizo de mar Diadema mexicanum (Diadematoida: Diadematidae) es un habitante común con un papel ecológico esencial en este ecosistema único. Objetivo: En este estudio, identificamos los depredadores predominantes de D. mexicanum y estimamos las tasas de consumos predatorias. También determinamos las tasas predatorias de diferentes tamaños de erizo de mar en sitios con disponibilidad de refugio contrastante. Métodos: Utilizamos grabaciones de video de campo y experimentos de marcaje. Resultados: El pez ballesta Sufflamen verres y el lábrido Bodianus diplotaenia fueron identificados como depredadores de tamaños pequeños y medianos de D. Mexicanum; los lábridos Thalassoma grammaticum y B. diplotaenia (juvenil) y el tetraodóntido Arothron meleagris fueron intento de depredadores; y Canthigaster punctatissima y Holacanthus passer fueron carroñeros. Los erizos de mar de gran tamaño (> 30 mm) también fueron depredados durante el experimento de marcaje. Además, se encontró un efecto claro del sitio en la supervivencia de los diferentes tamaños de erizo de mar. No se encontraron diferencias en la biomasa de los depredadores del erizo de mar entre sitios, lo que señala la importancia de la complejidad del sitio en la supervivencia. En sitios con complejidad estructural alta y media, los individuos grandes tuvieron mejor supervivencia, mientras que en sitios de complejidad baja apenas hubo diferencias en las tasas de supervivencia entre los tres tamaños. Nuestros resultados también muestran que una alta abundancia de peces depredadores, por encima de 0.04 ind m-2, asegura bajas densidades de erizos de mar. A pesar de no ser registrado durante las grabaciones de video, se observó en una ocasión a una langosta depredando sobre un erizo de gran tamaño. Conclusiones: Este estudio identifica el grupo de peces clave con grandes tasas de depredación sobre Diadema en el Parque Nacional, lo que sugiere que las medidas de protección han beneficiado positivamente las poblaciones de peces depredadores y langostas.

Prenatal current-use pesticide exposure and children's neurodevelopment at one year of age in the Infants' Environmental Health (ISA) birth cohort, Costa Rica.

BACKGROUND: Pesticide exposure may affect young children's neurodevelopment, but only few cohort studies have addressed possible effects of non-organophosphate pesticides. OBJECTIVE: We evaluated associations between prenatal current-use pesticide exposure and neurodevelopmental outcomes among 1-year-old children from the Infants' Environmental Health (ISA) birth cohort. METHODS: To determine prenatal pesticide exposure, we measured biomarkers of pyrimethanil, chlorpyrifos, synthetic pyrethroids, and 2,4-D in urine samples among 355 women, 1-3 times during pregnancy. One-year post-partum, we evaluated children's neurodevelopment with the Bayley Scales of Infant and Toddler Development 3rd edition (BSID-III). We assessed associations between exposures and neurodevelopmental outcomes (composite and z-scores) using single-chemical linear regression models adjusted for possible confounders (maternal education, parity, sex, gestational age at birth, child age, HOME-score, location of assessment, biomarkers of mancozeb), and studied effect-modification by sex. We evaluated non-linear associations of multiple pesticide exposures with Bayesian kernel machine regression (BKMR). RESULTS: We found higher prenatal urinary 2,4-D concentrations were associated with lower language (ßper ten-fold increase = -2.0, 95 % confidence interval (CI) = -3.5, -0.5) and motor (ßper ten-fold increase = -2.2, 95 %CI = -4.2, -0.1) composite scores among all children. Also, higher chlorpyrifos exposure [measured as urinary 3,5,6-trichloro-2-pyridinol (TCPy)] was associated with lower cognitive composite scores (ßper ten-fold increase = -1.9, 95 %CI = -4.7, 0.8), and lower motor composite scores among boys (ßper ten-fold increase = -3.8, 95 % CI = -7.7, 0.1) but not girls (ßper ten-fold increase = 2.3, 95 %CI = -1.6, 6.3, pINT = 0.11). Finally, higher pyrimethanil was associated with lower language abilities among girls, but not boys. Pyrethroid metabolite concentrations did not explain variability in BSID-III composite scores. Associations were similar for BSID-III z-scores, and we found no evidence for non-linear associations or mixture effects. DISCUSSION: Prenatal exposure to common-use pesticides may affect children's neurodevelopment at 1-year of age, some effects may be sex-specific.

Association of pesticide exposure with neurobehavioral outcomes among avocado farmworkers in Mexico.

BACKGROUND AND AIM: To date, few studies have focused on the health effects of pesticide exposure among avocado farmworkers. We examined the association of exposure to insecticides, fungicides, and herbicides with cognitive and mental health outcomes among these avocado workers from Michoacan, Mexico. MATERIALS AND METHODS: We conducted a cross-sectional study of 105 avocado farmworkers between May and August 2021. We collected data on self-reported pesticide use during the 12 months prior to the baseline survey and estimated annual exposure-intensity scores (EIS) using a semi-quantitative exposure algorithm. We calculated specific gravity adjusted average concentrations of 12 insecticide, fungicide, or herbicide metabolites measured in urine samples collected during two study visits (8-10 weeks apart). We assessed participants' cognitive function and psychological distress using the NIH Toolbox Cognition Battery and the Brief Symptom Inventory 18 (BSI-18), respectively. We examined individual associations of EIS and urinary pesticide metabolites with neurobehavioral outcomes using generalized linear regression models. We also implemented Bayesian Weighted Quantile Sum (BWQS) regression to evaluate the association between a pesticide metabolite mixture and neurobehavioral outcomes. RESULTS: In individual models, after adjusting for multiple comparisons, higher concentrations of hydroxy-tebuconazole (OH-TEB, metabolite of fungicide tebuconazole) were associated with higher anxiety (IRR per two-fold increase in concentrations = 1.26, 95% CI:1.08, 1.48) and Global Severity Index (GSI) (IRR = 1.89, 95% CI:1.36, 2.75) scores, whereas higher concentrations of 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of chlorpyrifos) were associated with lower GSI scores (IRR = 0.69, 95% CI: 0.56, 0.85). In BWQS analyses, we found evidence of a mixture association of urinary pesticide metabolites with higher anxiety (IRR = 1.72, 95% CrI: 1.12, 2.55), depression (IRR = 4.60, 95% CrI: 2.19, 9.43), and GSI (IRR = 1.99, 95% CrI: 1.39, 2.79) scores. OH-TEB and hydroxy-thiabendazole (metabolite of fungicide thiabendazole) combined contributed 54%, 40%, and 54% to the mixture effect in the anxiety symptoms, depression symptoms, and overall psychological distress models, respectively. CONCLUSIONS: We found that exposure to tebuconazole and thiabendazole, fungicides whose effects have been rarely studied in humans, may be associated with increased psychological distress among avocado farmworkers. We also observed that exposure to chlorpyrifos may be associated with decreased psychological distress.

SARS-CoV-2 infection and long COVID among California farmworkers.

PURPOSE: The purpose of this cross-sectional study was to determine the prevalence of long COVID and identify its clinical manifestations among farmworkers in California. METHODS: We collected data on sociodemographic characteristics, anthropometrics, clinical chemistries and anti-SARS-CoV-2 immunoglobulin G antibodies, self-reported SARS-CoV-2 infection history, and standardized health tests and scales from 297 farmworkers in California between February and July 2022. RESULTS: Most participants were born in Mexico or Central America, had less than a high school diploma, and were overweight or obese. The prevalence of long COVID (defined as self-reported SARS-CoV-2 infection with symptoms >28 days) among farmworkers with a suspected or test-confirmed infection was 61.8%. Participants with long COVID had higher mean [95% CI] body mass index (32.9 [31.6-34.1]) and high-sensitivity C-reactive protein levels (4.8 [3.7, 6.0]) than those with no COVID-19 history (30.5 [29.3-31.7], and 3.3 [2.2, 4.3], respectively). Farmworkers with long COVID also reported greater fatigue, dyspnea, taste and smell problems, and overall poorer mental and physical health, than those with no COVID-19 history. Farmworkers with long COVID had increased odds of functional limitations compared to those with a self-reported SARS-CoV-2 infection with symptoms ≤28 days (OR [95% CI]: 7.46 [3.26, 17.09]). CONCLUSIONS: A significant proportion of farmworkers experience long COVID with persistent symptoms that limit their ability to perform their work. A comprehensive approach that addresses the unique needs and challenges of farmworkers is warranted given this population's high prevalence of long COVID and the essential nature of their work.

RAB7 deficiency impairs pulmonary artery endothelial function and promotes pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a devastating and progressive disease with limited treatment options. Endothelial dysfunction plays a central role in the development and progression of PAH, yet the underlying mechanisms are incompletely understood. The endosome-lysosome system is important to maintain cellular health, and the small GTPase RAB7 regulates many functions of this system. Here, we explored the role of RAB7 in endothelial cell (EC) function and lung vascular homeostasis. We found reduced expression of RAB7 in ECs from patients with PAH. Endothelial haploinsufficiency of RAB7 caused spontaneous pulmonary hypertension (PH) in mice. Silencing of RAB7 in ECs induced broad changes in gene expression revealed via RNA-Seq, and RAB7-silenced ECs showed impaired angiogenesis and expansion of a senescent cell fraction, combined with impaired endolysosomal trafficking and degradation, suggesting inhibition of autophagy at the predegradation level. Furthermore, mitochondrial membrane potential and oxidative phosphorylation were decreased, and glycolysis was enhanced. Treatment with the RAB7 activator ML-098 reduced established PH in rats with chronic hypoxia/SU5416. In conclusion, we demonstrate for the first time to our knowledge the fundamental impairment of EC function by loss of RAB7, causing PH, and show RAB7 activation to be a potential therapeutic strategy in a preclinical model of PH.

Prenatal and childhood exposure to organophosphate pesticides and functional brain imaging in young adults.

BACKGROUND: Early life exposure to organophosphate (OP) pesticides has been linked with poorer neurodevelopment from infancy to adolescence. In our Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort, we previously reported that residential proximity to OP use during pregnancy was associated with altered cortical activation using functional near infrared spectroscopy (fNIRS) in a small subset (n = 95) of participants at age 16 years. METHODS: We administered fNIRS to 291 CHAMACOS young adults at the 18-year visit. Using covariate-adjusted regression models, we estimated associations of prenatal and childhood urinary dialkylphosphates (DAPs), non-specific OP metabolites, with cortical activation in the frontal, temporal, and parietal regions of the brain during tasks of executive function and semantic language. RESULTS: There were some suggestive associations for prenatal DAPs with altered activation patterns in both the inferior frontal and inferior parietal lobes of the left hemisphere during a task of cognitive flexibility (ß per ten-fold increase in DAPs = 3.37; 95% CI: -0.02, 6.77 and ß = 3.43; 95% CI: 0.64, 6.22, respectively) and the inferior and superior frontal pole/dorsolateral prefrontal cortex of the right hemisphere during the letter retrieval working memory task (ß = -3.10; 95% CI: -6.43, 0.22 and ß = -3.67; 95% CI: -7.94, 0.59, respectively). We did not observe alterations in cortical activation with prenatal DAPs during a semantic language task or with childhood DAPs during any task. DISCUSSION: We observed associations of prenatal OP concentrations with mild alterations in cortical activation during tasks of executive function. Associations with childhood exposure were null. This is reasonably consistent with studies of prenatal OPs and neuropsychological measures of attention and executive function found in CHAMACOS and other birth cohorts.

Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

[Alzheimer's disease. Current evidence on the preventive role of nutrition]. / Enfermedad de Alzheimer. Evidencia actual sobre el papel preventivo de la nutrición.

Introduction: Introduction: in the last decades, a significant increase in the incidence of Alzheimer's disease (AD) has been observed. Currently, there are no effective pharmacological treatments available, which makes preventive measures particularly important. Objective: to analyze the available scientific evidence on nutritional and dietary factors and their association with AD prevention. Methods: a review of nutritional and dietary factors related to the prevention of AD was conducted. Results: several dietary components have been positively associated with AD prevention, including intake of complex carbohydrates, fiber, omega-3, plant-based proteins, vitamins (folates, choline, vitamin D, C, B6 and B9), zinc, some bioactive compounds such as flavonols and probiotics. Following the Mediterranean, Dietary Approaches to Stop Hypertension (DASH) y Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets has been associated with a lower risk of developing the disease. Conclusion: nutrition may have a protective role against AD, although further studies are needed in this regard.

Introducción: Introducción: en las últimas décadas, se ha observado un incremento significativo en la incidencia de la enfermedad de Alzheimer (EA). En la actualidad, no se dispone de tratamientos farmacológicos efectivos, lo que hace que las medidas preventivas sean particularmente importantes. Objetivo: analizar la evidencia científica disponible sobre factores nutricionales y dietéticos y su asociación con la prevención de la EA. Métodos: se llevó a cabo una revisión de la literatura científica sobre factores nutricionales y dietéticos relacionados con la prevención de la EA. Resultados: diversos componentes de la dieta se han asociado positivamente con la prevención de la EA. Estos incluyen hidratos de carbono complejos, fibra, omega-3, proteínas de origen vegetal, vitaminas (folatos, colina, vitamina D, C, B6 y B9), zinc y algunos compuestos bioactivos como los flavonoles, y los probióticos. El seguimiento de las dietas mediterránea, Dietary Approaches to Stop Hypertension (DASH) y Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) se ha asociado con un menor de riesgo de desarrollar la enfermedad. Conclusión: la nutrición podría tener un papel protector frente a la EA, aunque se requieren más estudios al respecto.

[Cardiometabolic effects of intermittent fasting in women]. / Efectos cardiometabólicos del ayuno intermitente en la mujer.

Introduction: Intermittent fasting is a dietary pattern characterized by alternating periods of total or partial fasting and ad libitum food consumption. During prolonged fasting, the body uses the ketone bodies formed from lipolysis of body fat, which also leads to some metabolic modifications with positive effects on health. In this sense, nocturnal intermittent fasting could contribute to properly synchronize the circadian system making the physiological, hormonal, energetic and metabolic processes work correctly and keeping to the individual in homeostasis. Thus, according to the results of different studies, intermittent fasting, in the short-medium term, seems to improve body composition, as well as the values of several cardiometabolic parameters such as insulin and HOMA-IR index, among others. These effects have been observed in both pre- and postmenopausal women (no differences have been found between both states) and are similar to those found in interventions with caloric restriction diets.

Introducción: El ayuno intermitente es un patrón dietético caracterizado por la alternancia de periodos de ayuno, totales o parciales, y de consumo de alimentos ad libitum. Durante el ayuno prolongado, el organismo utiliza los cuerpos cetónicos que se forman a partir de la lipolisis de la grasa del organismo, lo que también da lugar a algunas modificaciones metabólicas con efectos positivos para la salud. En este sentido, el ayuno intermitente nocturno podría contribuir a sincronizar adecuadamente el sistema circadiano, haciendo que los procesos fisiológicos, hormonales, energéticos y metabólicos funcionen correctamente y mantengan al individuo en homeostasis. Así, de acuerdo con los resultados de diferentes estudios, el ayuno intermitente, a corto-medio plazo, parece mejorar la composición corporal, así como los valores de diversos parámetros cardiometabólicos como la insulina y el índice HOMA-IR, entre otros. Estos efectos se han observado tanto en mujeres premenopáusicas como postmenopáusicas, sin hallar diferencias entre ambos estados y son similares a los encontrados con intervenciones con dietas con restricción calórica.

Association between Mineral Intake and Cognition Evaluated by Montreal Cognitive Assessment (MoCA): A Cross-Sectional Study.

BACKGROUND: Mineral intake may protect against cognitive impairment (CI) and all-cause dementia, which affects a large number of adults worldwide. The aim of this study was to investigate the association between mineral intake and Montreal Cognitive Assessment (MoCA), which is a sensitive and specific test. METHODS: In total, 201 adults were included in a cross-sectional study. They completed a three-day dietary record to estimate their average daily intake of minerals. Contributions to dietary reference intakes (DRIs) were also calculated. The participants were divided into tertiles according to their mineral intake. CI classifications were determined via the MoCA (score < 26). Apolipoprotein E (APOE) genotyping was carried out, and the patients' anthropometric measurements and physical activity, health and personal data were collected. RESULTS: The prevalence of CI in this selective sample was 54.2% (34.3% females and 19.9% males). In women, being in the third tertiles of iron and manganese intake was associated with lower odds of having CI (OR [95% CI]: 0.32 [0.11 ± 0.93]; 0.33 [0.12 ± 0.93], p < 0.05). No significant differences were observed for any of the nutrients studied in men. CONCLUSIONS: These findings suggest that a low mineral intake, especially low iron and manganese intake in women, is associated with a worse cognition as assessed by MoCA.