Evaluating Seasonal Variations in Human Contact Patterns and Their Impact on the Transmission of Respiratory Infectious Diseases.

BACKGROUND: Human contact patterns are a key determinant driving the spread of respiratory infectious diseases. However, the relationship between contact patterns and seasonality as well as their possible association with the seasonality of respiratory diseases is yet to be clarified. METHODS: We investigated the association between temperature and human contact patterns using data collected through a cross-sectional diary-based contact survey in Shanghai, China, between December 24, 2017, and May 30, 2018. We then developed a compartmental model of influenza transmission informed by the derived seasonal trends in the number of contacts and validated it against A(H1N1)pdm09 influenza data collected in Shanghai during the same period. RESULTS: We identified a significant inverse relationship between the number of contacts and the seasonal temperature trend defined as a spline interpolation of temperature data (p = 0.003). We estimated an average of 16.4 (95% PrI: 15.1-17.5) contacts per day in December 2017 that increased to an average of 17.6 contacts (95% PrI: 16.5-19.3) in January 2018 and then declined to an average of 10.3 (95% PrI: 9.4-10.8) in May 2018. Estimates of influenza incidence obtained by the compartmental model comply with the observed epidemiological data. The reproduction number was estimated to increase from 1.24 (95% CI: 1.21-1.27) in December to a peak of 1.34 (95% CI: 1.31-1.37) in January. The estimated median infection attack rate at the end of the season was 27.4% (95% CI: 23.7-30.5%). CONCLUSIONS: Our findings support a relationship between temperature and contact patterns, which can contribute to deepen the understanding of the relationship between social interactions and the epidemiology of respiratory infectious diseases.

Blood DNA Methylation Analysis Reveals a Distinctive Epigenetic Signature of Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

Vasospasm is a potentially preventable cause of poor prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH). Epigenetics might provide insight on its molecular mechanisms. We aimed to analyze the association between differential DNA methylation (DNAm) and development of vasospasm. We conducted an epigenome-wide association study in 282 patients with aSAH admitted to our hospital. DNAm was assessed with the EPIC Illumina chip (> 850 K CpG sites) in whole-blood samples collected at hospital admission. We identified differentially methylated positions (DMPs) at the CpG level using Cox regression models adjusted for potential confounders, and then we used the DMP results to find differentially methylated regions (DMRs) and enriched biological pathways. A total of 145 patients (51%) experienced vasospasm. In the DMP analysis, we identified 31 CpGs associated with vasospasm at p-value < 10-5. One of them (cg26189827) was significant at the genome-wide level (p-value < 10-8), being hypermethylated in patients with vasospasm and annotated to SUGCT gene, mainly expressed in arteries. Region analysis revealed 13 DMRs, some of them annotated to interesting genes such as POU5F1, HLA-DPA1, RUFY1, and CYP1A1. Functional enrichment analysis showed the involvement of biological processes related to immunity, inflammatory response, oxidative stress, endothelial nitric oxide, and apoptosis. Our findings show, for the first time, a distinctive epigenetic signature of vasospasm in aSAH, establishing novel links with essential biological pathways, including inflammation, immune responses, and oxidative stress. Although further validation is required, our results provide a foundation for future research into the complex pathophysiology of vasospasm.

Accumulation and dietary risks of perfluoroalkyl substances in fish and shellfish: A market-based study in Barcelona.

Since the 1940s, per- and polyfluoroalkyl substances (PFAS) have been widely produced and used in various applications due to their unique properties. Consequently, the principal exposure routes of PFAS have been broadly studied, leading to the conclusion that dietary exposure (more specifically, the consumption of fish and seafood) was one of their main contributors. Thus, developing an analytical method that determines the level of PFAS in fish and seafood has become a relevant subject. In this work, a previous analytical method has been optimized to determine 12 PFAS in fish muscle from salmon, tuna, cod, hake, sardine, anchovy, and sole, as well as in seven different seafood species (i.e., cuttlefish, octopus, squid, shrimp, Norway lobster, prawn, and mussel) by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Subsequently, the PFAS profile of the different species was studied to determine if it was consistent with that previously reviewed in the literature and to know the most relevant contribution of PFAS for each species. Finally, human exposure to PFAS through their consumption was estimated by the daily intake for seven different age/gender groups. PFAS were obtained from 0.014 to 0.818 ng g-1 wet weight in fish samples. Sardines, anchovies, and soles presented the highest PFAS levels. However, cod samples also showed some PFAS traces. Regarding seafood, PFAS levels range from 0.03 to 36.7 ng g-1 dry weight for the studied species. A higher concentration of PFAS has been found in the cephalopods' spleens and the crustaceans' heads. PFOS and PFBS were the predominant compounds in each seafood species, respectively. On the other hand, in the case of mussels, which are the less polluted species of the study, contamination by longer-chained PFAS was also observed. Finally, the total intake of PFAS due to fish and shellfish consumption for the Spanish adult population was estimated at 17.82 ng day-1. Nevertheless, none of the analyzed samples exceeded the European Food Safety Authority (EFSA) risk value for the supervised PFAS in any age/gender group reviewed.

UV-Vis absorption spectrophotometry and LC-DAD-MS-ESI(+)-ESI(-) coupled to chemometrics analysis of the monitoring of sulfamethoxazole degradation by chlorination, photodegradation, and chlorination/photodegradation.

Sulfamethoxazole (SMX) is one of the most widely used antibiotics worldwide and has been detected at high concentrations in wastewater treatment plant effluents and river waters. In this study, the SMX degradation process combining the simultaneous chlorine oxidation and UV photodegradation is assessed and compared with both photodegradation and chlorine oxidation processes individually. Photodegradation and Chlorine/UV tests were performed using Suntest CPS equipment. Different experimental techniques, including UV-Visible spectrophotometry and liquid chromatography coupled to a diode array detector and positive and negative ionization mass spectrometry (LC-DAD-MS-ESI(+)-ESI(-)), were used to evaluate the degradation reaction of SMX. All the analytical data generated have been processed with the Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) method to monitor, resolve, and identify the several transformation products generated during the studied degradation processes. A new data fusion analysis strategy is proposed to examine the three processes simultaneously (with only photodegradation, only chlorination, and simultaneous chlorination+photodegradation). Combined with the analysis of different analytical techniques individually (spectrophotometry, LC-DAD, and LC-MS), the fusion of all generated data improved the description of the degradation processes. Detection using DAD allowed a better correspondence among the species monitored spectrophotometrically (UV-Vis) with those analyzed chromatographically. On the other side, detection using MS in both positive and negative acquisition modes allowed resolving a larger number of chemical compounds (specially SMX degradation subproducts) that could not be detected by UV-Vis spectrometry. The results obtained permitted the comparison of the effects produced by the three different degradation processes.

Latino Mortality Paradox Found (Again): COVID-19 Mortality a Tale of Two Years.

Objectives: This study examines the resiliency of the Latino Mortality paradox during the COVID-19 pandemic. Methods: Data from the Centers for Disease Control and Prevention are used to compute the ratio of Latino-to-white all-causes death rates for adults aged 45 and older, nationally and among 13 U.S. states with Latino populations greater than one million. Results: Nationally, the Latino mortality paradox persisted in 2020 and 2021. However, there was significant variation across states. We document three distinct patterns of COVID-19 mortality across 13 U.S. states: 1) the disappearance of the Latino mortality paradox, 2) the persistence of the Latino mortality paradox, and 3) the disappearance in 2020 and reemergence in 2021 of the Latino mortality paradox. Discussion: COVID-19 Mortality has disproportionately affected mid- and late-life Latinos, although the disparities relative to whites have narrowed. We discuss the dynamics influencing the waning and waxing of the Latino mortality paradox.

Mediterranean Sea heatwaves jeopardize greater amberjack's (Seriola dumerili) aquaculture productivity through impacts on the fish microbiota.

Climate change is dramatically increasing the frequency and severity of marine heatwaves (MHWs) in the Mediterranean basin, strongly affecting marine food production systems. However, how it will shape the ecology of aquaculture systems, and the cascading effects on productivity, is still a major knowledge gap. The present work aims to increase our understanding of future impacts, caused by raising water temperatures, on the interaction between water and fish microbiotas, and consequential effects upon fish growth. Thus, the bacterial communities present in the water tanks, and mucosal tissues (skin, gills and gut), of greater amberjack farmed in recirculatory aquaculture systems (RAS), at three different temperatures (24, 29 and 33 °C), were characterized in a longitudinal study. The greater amberjack (Seriola dumerili) is a teleost species with high potential for EU aquaculture diversification due to its fast growth, excellent flesh quality and global market. We show that higher water temperatures disrupt the greater amberjack's microbiota. Our results demonstrate the causal mediation exerted by this bacterial community shifts on the reduction of fish growth. The abundance of members of the Pseudoalteromonas is positively correlated with fish performance, whereas members of the Psychrobacter, Chryseomicrobium, Paracoccus and Enterovibrio are suggested as biomarkers for dysbiosis, at higher water temperatures. Hence, opening new evidence-based avenues for the development of targeted microbiota-based biotechnological tools, designed to increase the resilience and adaptation to climate change of the Mediterranean aquaculture industry.

The neighborhood context and all-cause mortality among older adults in Puerto Rico.

Background: Recent efforts have been made to collect data on neighborhood-level attributes and link them to longitudinal population-based surveys. These linked data have allowed researchers to assess the influence of neighborhood characteristics on the health of older adults in the US. However, these data exclude Puerto Rico. Because of significantly differing historical and political contexts, and widely ranging structural factors between the island and the mainland, it may not be appropriate to apply current knowledge on neighborhood health effects based on studies conducted in the US to Puerto Rico. Thus, we aim to (1) examine the types of neighborhood environments older Puerto Rican adults reside in and (2) explore the association between neighborhood environments and all-cause mortality. Methods: We linked data from the 2000 US Census to the longitudinal Puerto Rican Elderly Health Conditions Project (PREHCO) with mortality follow-up through 2021 to examine the effects of the baseline neighborhood environment on all-cause mortality among 3,469 participants. Latent profile analysis, a model-based clustering technique, classified Puerto Rican neighborhoods based on 19 census block group indicators related to the neighborhood constructs of socioeconomic status, household composition, minority status, and housing and transportation. The associations between the latent classes and all-cause mortality were assessed using multilevel mixed-effects parametric survival models with a Weibull distribution. Results: A five-class model was fit on 2,477 census block groups in Puerto Rico with varying patterns of social (dis)advantage. Our results show that older adults residing in neighborhoods classified as Urban High Deprivation and Urban High-Moderate Deprivation in Puerto Rico were at higher risk of death over the 19-year study period relative to the Urban Low Deprivation cluster, controlling for individual-level covariates. Conclusions: Considering Puerto Rico's socio-structural reality, we recommend that policymakers, healthcare providers, and leaders across industries to (1) understand how individual health and mortality is embedded within larger social, cultural, structural, and historical contexts, and (2) make concerted efforts to reach out to residents living in disadvantaged community contexts to understand better what they need to successfully age in place in Puerto Rico.

The outcome of boosting mitochondrial activity in alcohol-associated liver disease is organ-dependent.

BACKGROUND AND AIMS: Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one of the earliest manifestations of alcohol-induced injury, restoring mitochondrial activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as a mediator for ALD progression and hypothesize that targeting MCJ may help in recovering mitochondrial fitness without collateral oxidative damage. APPROACH AND RESULTS: C57BL/6 mice [wild-type (Wt)] Mcj knockout and Mcj liver-specific silencing (MCJ-LSS) underwent the NIAAA dietary protocol (Lieber-DeCarli diet containing 5% (vol/vol) ethanol for 10 days, plus a single binge ethanol feeding at day 11). To evaluate the impact of a restored mitochondrial activity in ALD, the liver, gut, and pancreas were characterized, focusing on lipid metabolism, glucose homeostasis, intestinal permeability, and microbiota composition. MCJ, a protein acting as an endogenous negative regulator of mitochondrial respiration, is downregulated in the early stages of ALD and increases with the severity of the disease. Whole-body deficiency of MCJ is detrimental during ALD because it exacerbates the systemic effects of alcohol abuse through altered intestinal permeability, increased endotoxemia, and dysregulation of pancreatic function, which overall worsens liver injury. On the other hand, liver-specific Mcj silencing prevents main ALD hallmarks, that is, mitochondrial dysfunction, steatosis, inflammation, and oxidative stress, as it restores the NAD + /NADH ratio and SIRT1 function, hence preventing de novo lipogenesis and improving lipid oxidation. CONCLUSIONS: Improving mitochondrial respiration by liver-specific Mcj silencing might become a novel therapeutic approach for treating ALD.

Racial and Ethnic Differences in Sleep Duration Life Expectancies among Men and Women in Mid-to-Late Life.

This analysis documents U.S. racial/ethnic and gender differences in life expectancies with different self-reported sleep durations among adults aged 50 and older. We used self-reported sleep duration and linked mortality information from the 2004-2015 National Health Interview Survey (n = 145,015) to calculate Sullivan Method Lifetables for life expectancies with different self-reported sleep duration states: short (≤6 hours), optimal (seven to 8 hours), and long (≥9 hours) sleep duration per-day by race/ethnicity and gender. Non-Hispanic Black men (35.8%, 95% CI: 34.8%-36.8%) and women (36.5%, 95% CI: 35.7%-37.1%) exhibited the highest proportion of years lived with short sleep duration followed by Hispanic men (31.1%, 95% CI: 29.9%-32.3%) and women (34.1%, 95% CI: 33.1%-35.1%) and Non-Hispanic White men (25.8%, 95% CI: 25.4%-26.2%) and women (27.4%, 95% CI: 27.0%-27.7%). These results highlight how race/ethnic inequality in sleep duration and life expectancy are intertwined among older adults in the U.S.

Caregiving for Foreign-Born Older Adults With Dementia.

OBJECTIVES: This study examines how nativity, dementia classification, and age of migration (AOM) of older foreign-born (FB) adults are associated with caregiver psychological well-being and care burden. METHODS: We used linked data from Round 1 and Round 5 of the National Health and Aging Trends Study and Round 5 of the National Study of Caregiving for a sample of nondementia caregivers (n = 941), dementia caregivers (n = 533), and matched care recipients. Ordinary least squares regression models were estimated, adjusting for caregiver characteristics. RESULTS: Relative to nondementia caregivers, dementia caregivers were more likely to provide care for an older FB adult (8.69% vs. 26.70%), reported more assistance with caregiving activities, worse quality of relationship with care recipients, and higher care burden than nondementia caregivers. In adjusted models, interactions of nativity status × dementia and AOM × dementia revealed that overall, caregivers of older FB adults with dementia who migrated in late life (50+) reported lower psychological well-being than those caring for older FB older adults who migrated at (20-49 years) and (0-19 years). Moderating effects of AOM on the link between dementia caregiving and care burden were not observed. DISCUSSION: Age of migration of older FB adults with probable dementia may have unique effects on the caregiver's psychological well-being. Our results underscore the importance of considering sociocultural factors of FB adults beyond nativity and the need for research to develop culturally appropriate interventions to enhance psychological well-being and reduce the care burden among dementia caregivers.

Components of event-related potentials and borderline personality disorder: a meta-analysis.

Background: Borderline personality disorder (BPD) is characterized by symptoms associated with difficulties in emotion regulation, altered self-image, impulsivity, and instability in personal relationships. A relationship has been found between BPD symptoms and altered neuropsychological processes. Studies of event-related potentials (ERP) measured with electroencephalogram (EEG) have found neural correlates related to BPD symptoms. Of note is the P300 component, considered a potential mental health biomarker for trauma-associated disorders. However, no meta-analysis has been found to demonstrate this relationship.Objectives: To evaluate the relationship between the P300 component and BPD symptoms. To evaluate the relationship of other ERP components with BPD symptoms.Methods: The method and procedure were adjusted to the PRISMA checklist. The search was performed in three databases: WOS, Scopus and PubMed. A Random Effects Model was used to perform the analysis of the studies. In addition, a meta-regression was performed with % women, Gini and GDP. Finally, a descriptive analysis of the main results found between P300, other ERP components (LPP, P100 and ERN/Ne) and BPD symptoms was performed.Results: From a review of 485 articles, a meta-analysis was performed with six articles that met the inclusion criteria. A moderate, positive relationship was found between the P300 component and BPD symptoms (REM = .489; p < .001). It was not possible to perform meta-analyses for other ERP components (LPP, P100 and ERN/Ne) due to the low number of articles found.Conclusion: The idea that P300 could be considered for use as a biomarker to identify altered neural correlates in BPD is reinforced. In addition, a moderating effect of inequality (Gini) was detected.

The P300 component of event-related potentials could be considered for use as a possible biomarker to identify altered neural correlates in Borderline Personality Disorder.There is support for the proposition that an altered P300 would be present in disorders related to exposure to traumatic events.P300 could be used to evaluate the therapeutic processes associated with the clinical symptoms of Borderline Personality Disorder.

Multiomics signatures of type 1 diabetes with and without albuminuria.

Aims/hypothesis: To identify novel pathophysiological signatures of longstanding type 1 diabetes (T1D) with and without albuminuria we investigated the gut microbiome and blood metabolome in individuals with T1D and healthy controls (HC). We also mapped the functional underpinnings of the microbiome in relation to its metabolic role. Methods: One hundred and sixty-one individuals with T1D and 50 HC were recruited at the Steno Diabetes Center Copenhagen, Denmark. T1D cases were stratified based on levels of albuminuria into normoalbuminuria, moderate and severely increased albuminuria. Shotgun sequencing of bacterial and viral microbiome in stool samples and circulating metabolites and lipids profiling using mass spectroscopy in plasma of all participants were performed. Functional mapping of microbiome into Gut Metabolic Modules (GMMs) was done using EggNog and KEGG databases. Multiomics integration was performed using MOFA tool. Results: Measures of the gut bacterial beta diversity differed significantly between T1D and HC, either with moderately or severely increased albuminuria. Taxonomic analyses of the bacterial microbiota identified 51 species that differed in absolute abundance between T1D and HC (17 higher, 34 lower). Stratified on levels of albuminuria, 10 species were differentially abundant for the moderately increased albuminuria group, 63 for the severely increased albuminuria group while 25 were common and differentially abundant both for moderately and severely increased albuminuria groups, when compared to HC. Functional characterization of the bacteriome identified 23 differentially enriched GMMs between T1D and HC, mostly involved in sugar and amino acid metabolism. No differences in relation to albuminuria stratification was observed. Twenty-five phages were differentially abundant between T1D and HC groups. Six of these varied with albuminuria status. Plasma metabolomics indicated differences in the steroidogenesis and sugar metabolism and circulating sphingolipids in T1D individuals. We identified association between sphingolipid levels and Bacteroides sp. abundances. MOFA revealed reduced interactions between gut microbiome and plasma metabolome profiles albeit polar metabolite, lipids and bacteriome compositions contributed to the variance in albuminuria levels among T1D individuals. Conclusions: Individuals with T1D and progressive kidney disease stratified on levels of albuminuria show distinct signatures in their gut microbiome and blood metabolome.

Gender, Age of Migration, and Cognitive Life Expectancies Among Older Latinos: Evidence From the Health and Retirement Study.

OBJECTIVES: Migration and gender are important factors that differentiate the Latino immigrant experience in the United States. We investigate the association between nativity status, age of migration, and cognitive life expectancies among a nationally representative sample of Latino adults aged 50 and older to explore whether age of migration and gender influence cognitive aging across the life course. METHODS: This study used data from the Health and Retirement Study (1998-2016) to estimate Sullivan-based life tables of cognitive life expectancies by nativity, age of migration, and gender for older Latino adults. Cognitive status was based on the Langa-Weir algorithm. We test for both within-group (i.e., nativity and age of migration) and gender differences to explore the overall burden of disease among this rapidly growing population. RESULTS: Foreign-born Latinos, regardless of age of migration or gender, spend a greater number of years after age 50 with cognitive impairment/no dementia than U.S.-born Latinos. However, the number of years spent with dementia varied by subgroup with midlife immigrant men and late-life immigrant men and women exhibiting a significant disadvantage relative to the U.S.-born. Furthermore, we document a gender disadvantage for all Latino women, regardless of immigrant status. DISCUSSION: The robust relationship between nativity, age of migration, and cognitive aging suggests that older foreign-born Latinos experiencing cognitive decline may place serious burdens on families. Future research should target the needs of different subgroups of older Latinos who are entering their last decades of life to develop culturally appropriate long-term care programs.

microRNA-based signatures obtained from endometrial fluid identify implantative endometrium.

STUDY QUESTION: Is it possible to use free and extracellular vesicle-associated microRNAs (miRNAs) from human endometrial fluid (EF) samples as non-invasive biomarkers for implantative endometrium? SUMMARY ANSWER: The free and extracellular vesicle-associated miRNAs can be used to detect implantative endometrium in a non-invasive manner. WHAT IS KNOWN ALREADY: miRNAs and extracellular vesicles (EVs) from EF have been described as mediators of the embryo-endometrium crosstalk. Therefore, the analysis of miRNA from this fluid could become a non-invasive technique for recognizing implantative endometrium. This analysis could potentially help improve the implantation rates in ART. STUDY DESIGN, SIZE, DURATION: In this prospective study, we first optimized different protocols for EVs and miRNA analyses using the EF of a setup cohort (n = 72). Then, we examined differentially expressed miRNAs in the EF of women with successful embryo implantation (discovery cohort n = 15/validation cohort n = 30) in comparison with those for whom the implantation had failed (discovery cohort n = 15/validation cohort n = 30). Successful embryo implantation was considered when pregnancy was confirmed by vaginal ultrasound showing a gestational sac 4 weeks after embryo transfer (ET). PARTICIPANTS/MATERIALS, SETTING, METHODS: The EF of the setup cohort was obtained before starting fertility treatment during the natural cycle, 16-21 days after the beginning of menstruation. For the discovery and validation cohorts, the EF was collected from women undergoing frozen ET on Day 5, and the samples were collected immediately before ET. In this study, we compared five different methods; two of them based on direct extraction of RNA and the other three with an EV enrichment step before the RNA extraction. Small RNA sequencing was performed to determine the most efficient method and find a predictive model differentiating between implantative and non-implantative endometrium. The models were confirmed using quantitative PCR in two sets of samples (discovery and validation cohorts) with different implantation outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: The protocols using EV enrichment detected more miRNAs than the methods based on direct RNA extraction. The two most efficient protocols (using polymer-based precipitation (PBP): PBP-M and PBP-N) were used to obtain two predictive models (based on three miRNAs) allowing us to distinguish between an implantative and non-implantative endometrium. The first Model 1 (PBP-M) (discovery: AUC = 0.93; P-value = 0.003; validation: AUC = 0.69; P-value = 0.019) used hsa-miR-200b-3p, hsa-miR-24-3p and hsa-miR-148b-3p. Model 2 (PBP-N) (discovery: AUC = 0.92; P-value = 0.0002; validation: AUC = 0.78; P-value = 0.0002) used hsa-miR-200b-3p, hsa-miR-24-3p and hsa-miR-99b-5p. Functional analysis of these miRNAs showed strong association with key implantation processes such as in utero embryonic development or transforming growth factor-beta signaling. LARGE SCALE DATA: The FASTQ data are available in the GEO database (access number GSE178917). LIMITATIONS, REASONS FOR CAUTION: One important factor to consider is the inherent variability among the women involved in the trial and among the transferred embryos. The embryos were pre-selected based on morphology, but neither genetic nor molecular studies were conducted, which would have improved the accuracy of our tests. In addition, a limitation in miRNA library construction is the low amount of input RNA. WIDER IMPLICATIONS OF THE FINDINGS: We describe new non-invasive protocols to analyze miRNAs from small volumes of EF. These protocols could be implemented in clinical practice to assess the status of the endometrium before attempting ET. Such evaluation could help to avoid the loss of embryos transferred to a non-implantative endometrium. STUDY FUNDING/COMPETING INTEREST(S): J.I.-P. was supported by a predoctoral grant from the Basque Government (PRE_2017_0204). This study was partially funded by the Grant for Fertility Innovation (GFI, 2011) from Merck (Darmstadt, Germany). It was also supported by the Spanish Ministry of Economy and Competitiveness MINECO within the National Plan RTI2018-094969-B-I00, the European Union's Horizon 2020 research and innovation program (860303), the Severo Ochoa Centre of Excellence Innovative Research Grant (SEV-2016-0644) and the Instituto de Salud Carlos III (PI20/01131). The funding entities did not play any role in the study design, collection, analysis and interpretation of data, writing of the report or the decision to submit the article for publication. The authors declare no competing interests.

A Comprehensive Metabolomics Analysis of Fecal Samples from Advanced Adenoma and Colorectal Cancer Patients.

Accurate diagnosis of colorectal cancer (CRC) still relies on invasive colonoscopy. Noninvasive methods are less sensitive in detecting the disease, particularly in the early stage. In the current work, a metabolomics analysis of fecal samples was carried out by ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS). A total of 1380 metabolites were analyzed in a cohort of 120 fecal samples from patients with normal colonoscopy, advanced adenoma (AA) and CRC. Multivariate analysis revealed that metabolic profiles of CRC and AA patients were similar and could be clearly separated from control individuals. Among the 25 significant metabolites, sphingomyelins (SM), lactosylceramides (LacCer), secondary bile acids, polypeptides, formiminoglutamate, heme and cytidine-containing pyrimidines were found to be dysregulated in CRC patients. Supervised random forest (RF) and logistic regression algorithms were employed to build a CRC accurate predicted model consisting of the combination of hemoglobin (Hgb) and bilirubin E,E, lactosyl-N-palmitoyl-sphingosine, glycocholenate sulfate and STLVT with an accuracy, sensitivity and specificity of 91.67% (95% Confidence Interval (CI) 0.7753-0.9825), 0.7 and 1, respectively.

"Many people have no idea": a qualitative analysis of healthcare barriers among Yazidi refugees in the Midwestern United States.

BACKGROUND: The COVID-19 pandemic has shed new light on inequities in healthcare access faced by immigrant and refugee communities. To address ongoing disparities, there is an urgent need for ecological approaches to better understand the barriers that hinder and resources that facilitate access to healthcare. This study investigates barriers to healthcare system access faced by Yazidi refugees in the Midwestern United States. METHODS: Informed by the Interpretative Phenomenological Approach, three focus group meetings with a community advisory board were conducted between September 2019 and January 2020. The nine-member focus group included social workers, healthcare providers, and members of the Yazidi community. Meeting recordings were transcribed into English, coded for themes, and validated. RESULTS: We describe themes related to specific barriers to healthcare access; analyze the influence of relational dynamics in the focus group; explore experiential themes related to healthcare access in the Yazidi community, and finally interpret our findings through a social-ecological lens. CONCLUSION: Community agencies, healthcare organizations, policymakers, and other stakeholders must work together to develop strategies to reduce systemic barriers to equitable care. Community representation in priority-setting and decision-making is essential to ensure relevance, acceptability, and utilization of developed strategies.

Ascites and resistance to immune checkpoint inhibition in dMMR/MSI-H metastatic colorectal and gastric cancers.

BACKGROUND: Despite unprecedented benefit from immune checkpoint inhibitors (ICIs) in patients with mismatch repair deficient (dMMR)/microsatellite instability high (MSI-H) advanced gastrointestinal cancers, a relevant proportion of patients shows primary resistance or short-term disease control. Since malignant effusions represent an immune-suppressed niche, we investigated whether peritoneal involvement with or without ascites is a poor prognostic factor in patients with dMMR/MSI-H metastatic colorectal cancer (mCRC) and gastric cancer (mGC) receiving ICIs. METHODS: We conducted a global multicohort study at Tertiary Cancer Centers and collected clinic-pathological data from a cohort of patients with dMMR/MSI-H mCRC treated with anti-PD-(L)1 ±anti-CTLA-4 agents at 12 institutions (developing set). A cohort of patients with dMMR/MSI-high mGC treated with anti-PD-1 agents±chemotherapy at five institutions was used as validating dataset. RESULTS: The mCRC cohort included 502 patients. After a median follow-up of 31.2 months, patients without peritoneal metastases and those with peritoneal metastases and no ascites had similar outcomes (adjusted HR (aHR) 1.15, 95% CI 0.85 to 1.56 for progression-free survival (PFS); aHR 0.96, 95% CI 0.65 to 1.42 for overall survival (OS)), whereas inferior outcomes were observed in patients with peritoneal metastases and ascites (aHR 2.90, 95% CI 1.70 to 4.94; aHR 3.33, 95% CI 1.88 to 5.91) compared with patients without peritoneal involvement. The mGC cohort included 59 patients. After a median follow-up of 17.4 months, inferior PFS and OS were reported in patients with peritoneal metastases and ascites (aHR 3.83, 95% CI 1.68 to 8.72; aHR 3.44, 95% CI 1.39 to 8.53, respectively), but not in patients with only peritoneal metastases (aHR 1.87, 95% CI 0.64 to 5.46; aHR 2.15, 95% CI 0.64 to 7.27) when compared with patients without peritoneal involvement. CONCLUSIONS: Patients with dMMR/MSI-H gastrointestinal cancers with peritoneal metastases and ascites should be considered as a peculiar subgroup with highly unfavorable outcomes to current ICI-based therapies. Novel strategies to target the immune-suppressive niche in malignant effusions should be investigated, as well as next-generation ICIs or intraperitoneal approaches.

Rural/urban dwelling across the life-course and late-life cognitive ability in Mexico.

BACKGROUND: Urban advantages in older adults' cognitive function have been observed. Less is known about early-life urban dwelling and late-life cognition. We evaluate how rural/urban dwelling throughout life and rural to urban shifts in life relate with cognition in Mexico, a country experiencing aging and urbanization. METHODS: Data came from the 2003 and 2012 Mexican Health and Aging Study (n = 12,238 adults age 50+). Early-life urban dwelling was self-reported. Late-life urban dwelling was based on population size of respondents' community of residence (community 2500+ people) at the time of survey. Cognitive function was measured across several cognitive tasks. We assess differences in baseline cognitive function and nine-year decline across groups using a latent change score model. RESULTS: Cross-sectionally, compared to always rural dwellers, rural-urban transitions were associated with cognitive benefits, though individuals residing in urban areas continuously through life exhibited the highest levels of cognitive function (ß = 0.89, 95% CI: 0.83, 0.96) even after adjusting for SES, health, and health behaviors (ß = 0.28, 95% CI: 0.22, 0.35). Longitudinally, always urban dwellers exhibited slower decline than always rural dwellers when adjusting for baseline cognition (ß = 0.11, 95% CI: 0.03, 0.18), though faster decline when baseline cognition was not adjusted (ß = -0.11, 95% CI: -0.18, -0.04). No differences were observed for cognitive change across comparison groups after adjusting for potential mechanisms. CONCLUSIONS: Early- and late-life urban dwelling may result in cognitive advantages for older Mexican adults. Clinicians should consider where individuals resided throughout life to better understand a patient's likelihood of experiencing poor cognitive outcomes.

Demographic and Health Characteristics of Older Latino Birth Cohorts in the Health and Retirement Study.

OBJECTIVES: Latinos are the fastest aging racial/ethnic minority group in the United States. One limitation to understanding the diverse experiences of older Latinos is the lack of nationally representative data necessary to examine factors contributing to changes in population-level health over time. This is needed to provide a more comprehensive picture of the demographic characteristics that influence the health and well-being of older Latinos. METHODS: We utilized the steady-state design of the Health and Retirement Study (HRS) from 1992 to 2016 to examine the demographic and health characteristics of five entry birth cohorts of older Latinos aged 51-56 years (n = 2,882). Adjusted Wald tests were used to assess statistically significant differences in demographic and health characteristics across the HRS birth cohorts. RESULTS: Cross-cohort comparisons of demographic and health characteristics of older Latinos indicate significant change over time, with later-born HRS birth cohorts less likely to identify as Mexican-origin, more likely to identify as a racial "other," and more likely to be foreign-born. In addition, we find that later-born cohorts are more educated and exhibit a higher prevalence of hypertension, diabetes, and obesity. DISCUSSION: Increasing growth and diversity among the older U.S. Latino population make it imperative that researchers document changes in the demographic composition and health characteristics of this population as it will have implications for researchers, policymakers, health care professionals, and others seeking to anticipate the needs of this rapidly aging population.