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Sexual dimorphism is common throughout the animal kingdom, leading to sex-specific phenotypic differences. The common whitetail skimmer dragonfly, Plathemis lydia (Drury, 1773), is sexually dichromatic, where males of this species display a conspicuous white abdomen and females display a dark brown abdomen. Differences in abdomen conspicuousness between male and female P. lydia are likely attributed to differences in selective pressure where males use their white conspicuous abdomen during male-male territorial chases. We hypothesized that male P. lydia would exhibit wing morphology adaptations to better offset the costs of predation and territoriality and that these adaptations would differ from females. We used field-collected images to quantify differences in body length, wing length, wing area, wing shape, and wing loading between male and female P. lydia. Our results show that male P. lydia have significantly shorter fore and hind wings relative to body size with a higher wing loading when compared to females. We also found that male P. lydia have narrower and pointier fore and hind wings compared to females. These results are consistent with the idea that males are adapted for faster flight, specifically higher acceleration capacity, and higher agility whereas females are adapted for higher maneuverability.

Neural crest cell genes control the migration of neural crest cells to multiple parts of developing vertebrate embryos. A recent hypothesis posits that the "domestication syndrome" characteristic of domesticated animals is driven by selection for tameness acting on neural crest cell genes, particularly those affecting cell migration. This is posited to explain why this syndrome involves many disparate phenotypic effects. These effects can be connected to deficits in neural crest cell migration. This hypothesis predicts that patterns of selection on these neural crest cell genes will differ between domesticated species and related wild species. Specifically, it predicts higher levels of positive selection on these genes in domesticated species, relative to closely related wild species. Here we test this prediction in a comparative framework. We obtained DNA sequences from a public database (NCBI) for eleven key neural crest cell genes from a set of thirty domesticated vertebrates and matched close relatives that remain wild. We used the program Contrast-FEL in the software suite HyPhy to compare the number of sites under positive selection (as measured by non-synonymous to synonymous nucleotide substitution rates across codons) between these two types of taxa in a phylogenetic framework. We found that domesticated lineages showed a consistently higher level of positive selection on these key genes, relative to their closely related wild counterparts. In addition, we found support for relaxation of selection and purifying selection. We argue that this result is consistent with an important role for these genes in the domestication syndrome.

BackgroundDespite the great progress made over the last decades, stronger structural interventions are needed to end the HIV/AIDS pandemic in Low and Middle-Income Countries (LMIC). Brazil is one of the largest and data-richest LMIC, with rapidly changing socioeconomic characteristics and an important HIV/AIDS burden. Over the last two decades Brazil has also implemented the world's largest Conditional Cash Transfer programs, the Bolsa Familia Program (BFP), and one of the most consolidated Primary Health Care (PHC) interventions, the Family Health Strategy (FHS).ObjectiveWe will evaluate the effects of socioeconomic determinants, BFP exposure and FHS coverage on HIV/AIDS incidence, treatment adherence, hospitalizations, case fatality, and mortality using unprecedently large aggregate and individual-level longitudinal data. Moreover, we will integrate the retrospective datasets and estimated parameters with comprehensive forecasting models to project HIV/AIDS incidence, prevalence and mortality scenarios up to 2030 according to future socioeconomic conditions and alternative policy implementations.Methods and analysisWe will combine individual-level data from all national HIV/AIDS registries with large-scale databases, including the "100 Million Brazilian Cohort", over a 19-year period (2000-2018). Several approaches will be used for the retrospective quasi-experimental impact evaluations, such as Regression Discontinuity Design (RDD), Random Administrative Delays (RAD) and Propensity Score Matching (PSM), combined with multivariable Poisson regressions for cohort analyses. Moreover, we will explore in depth lagged and long-term effects of changes in living conditions and in exposures to BFP and FHS. We will also investigate the effects of the interventions in a wide range of subpopulations. Finally, we will integrate such retrospective analyses with microsimulation, compartmental and agent-based models to forecast future HIV/AIDS scenarios.ConclusionThe unprecedented datasets, analyzed through state-of-the-art quasi-experimental methods and innovative mathematical models will provide essential evidences to the understanding and control of HIV/AIDS epidemic in LMICs such as Brazil.

BackgroundCOVID-19 vaccine coverage in the Latinx community depends on delivery systems that overcome barriers such as institutional distrust, misinformation, and access to care. We hypothesized that a community-centered vaccination strategy that included mobilization, vaccination, and "activation" components could successfully reach an underserved Latinx population, utilizing its social networks to boost vaccination coverage.MethodsOur community-academic-public health partnership, "Unidos en Salud," utilized a theory-informed approach to design our "Motivate, Vaccinate, and Activate" COVID-19 vaccination strategy. Our strategy's design was guided by the PRECEDE Model and sought to address and overcome predisposing, enabling, and reinforcing barriers to COVID-19 vaccination faced by Latinx individuals in San Francisco. We evaluated our prototype outdoor, "neighborhood" vaccination program located in a central commercial and transport hub in the Mission District in San Francisco, using the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework during a 16-week period from February 1, 2021 to May 19, 2021. Programmatic data, city-wide COVID-19 surveillance data, and a survey conducted between May 2, 2021 and May 19, 2021 among 997 vaccinated clients ≥16 years old were used in the evaluation.ResultsThere were 20,792 COVID-19 vaccinations administered at the neighborhood site during the 16-week evaluation period. Vaccine recipients had a median age of 43 (IQR 32-56) years, 53.9% were male and 70.5% were Latinx, 14.1% white, 7.7% Asian, 2.4% Black, and 5.3% other. Latinx vaccinated clients were substantially more likely than non-Latinx clients to have an annual household income of less than $50,000 a year (76.1% vs. 33.5%), be a first-generation immigrant (60.2% vs. 30.1%), not have health insurance (47.3% vs. 16.0%), and not have access to primary care provider (62.4% vs. 36.2%). The most frequently reported reasons for choosing vaccination at the site were its neighborhood location (28.6%), easy and convenient scheduling (26.9%) and recommendation by someone they trusted (18.1%); approximately 99% reported having an overall positive experience, regardless of ethnicity. Notably, 58.3% of clients reported that they were able to get vaccinated earlier because of the neighborhood vaccination site, 98.4% of clients completed both vaccine doses, and 90.7% said that they were more likely to recommend COVID-19 vaccination to family and friends after their experience; these findings did not substantially differ according to ethnicity. There were 40.3% of vaccinated clients who said they still knew at least one unvaccinated person (64.6% knew ≥3). Among clients who received both vaccine doses (n = 729), 91.0% said that after their vaccination experience, they had personally reached out to at least one unvaccinated person they knew (61.6% reached out to ≥3) to recommend getting vaccinated; 83.0% of clients reported that one or more friends, and/or family members got vaccinated as a result of their outreach, including 18.9% who reported 6 or more persons got vaccinated as a result of their influence.ConclusionsA multi-component, "Motivate, Vaccinate, and Activate" community-based strategy addressing barriers to COVID-19 vaccination for the Latinx population reached the intended population, and vaccinated individuals served as ambassadors to recruit other friends and family members to get vaccinated.

Research on human immunology has been hindered by the lack of optimal small animal models, given that the protective immune responses of human and non-human species show significant differences. However, due to ethical constraints[1] and the high cost of clinical trials, it is urgent to improve the current animal models that can mimic faithfully human physiology, particularly the human immune system (HIS). HIS mice had been generated recently by engrafting human hematopoietic stem cells (hHSCs) or human peripheral mononuclear cells (hPBMCs) into highly immuno-deficient mice such as NSG, NOG or NRG mice. However, a major experimental drawback for studies using these models is the rapid onset of Graft-versus-Host Disease (GvHD). In the present study, we overcome this limitation by generating new immuno-deficient mice named "HUMAMICE" (HLA-A2+/+/DR1+/+/H-2-β2m-/-/IAβ-/-/Rag2-/-/IL2rγ-/-/Perf-/- mice), which expressed human HLA molecules instead of mouse MHC molecules (H-2), and whose immuno-deficient status was reversed by transferring functional HLA-matched PBMCs thus producing mice with an immuno-competent status with a functional human immune system. We showed that in this HLA-matched context, the hPBMC-transfer led to high lymphocytes engraftment rates without GvHD over three months in this novel mouse model. Furthermore, to evaluate the utility of the hPBMC-HUMAMICE, we immunized them with commercial vaccine of Hepatitis B virus (HBsAg, Hepvac@) which resulted in robust and reproducible production of high levels of HBsAg-specific antibodies, implying that both transferred T and B lymphocytes were functional in HUMAMICE. These responses are comparable to those observed in human clinical trials with this identical vaccine. In conclusion, these findings indicated that the HLA-matched-hPBMC-HUMAMICE represents a promising model for dissecting human immune responses in various human diseases, including infectious diseases, cancers and tumors, and to facilitate the development of novel vaccines and cellular therapies.

BackgroundThe prevalence and role of human papillomavirus (HPV) in the aetiology of oesophageal squamous cell carcinoma is uncertain. Based on the presence of HPV in the oral cavity and its causal association with squamous cell carcinoma of the oropharynx, we hypothesised that HPV is more strongly associated with proximal than distal oesophageal squamous cell carcinoma.MethodsA population-based study comparing HPV infection in relation to tumour site in patients diagnosed with oesophageal squamous cell carcinomas in the Stockholm County in 1999-2006. Multiplex polymerase chain reaction genotyping (PCR) with Luminex was conducted on pre-treatment endoscopic biopsies to identify type specify HPV. Carcinogenic activity of HPV was assessed by p16(INK4a) expression. Multivariable logistic regression was used to calculate odds ratios and 95% confidence intervals.ResultsAmong 204 patients, 20 (10%) had tumours harbouring HPV DNA, almost all (90%) of HPV high-risk type, mainly HPV16. Tumours containing HPV were not overrepresented in the upper compared to the middle or lower third of the oesophagus (odds ratio 0.6, 95% confidence interval 0.2-1.9). P16(INK4a) expression was similarly common (24% and 16%) in the HPV-positive and HPV-negative groups.ConclusionThis study found a limited presence of HPV in oesophageal squamous cell carcinoma of uncertain oncogenic relevance and did not demonstrate that HPV was more strongly associated with proximal than distal tumours.

In a clinical context, conventional optical microscopy is commonly used for the visualization of biological samples for diagnosis. However, the availability of molecular techniques and rapid diagnostic tests are reducing the use of conventional microscopy, and consequently the number of experienced professionals starts to decrease. Moreover, the continuous visualization during long periods of time through an optical microscope could affect the final diagnosis results due to induced human errors and fatigue. Therefore, microscopy automation is a challenge to be achieved and address this problem. The aim of the study is to develop a low-cost automated system for the visualization of microbiological/parasitological samples by using a conventional optical microscope, and specially designed for its implementation in resource-poor settings laboratories. A 3D-prototype to automate the majority of conventional optical microscopes was designed. Pieces were built with 3D-printing technology and polylactic acid biodegradable material with Tinkercad/Ultimaker Cura 5.1 slicing softwares. The system's components were divided into three subgroups: microscope stage pieces, storage/autofocus-pieces, and smartphone pieces. The prototype is based on servo motors, controlled by Arduino open-source electronic platform, to emulate the X-Y and auto-focus (Z) movements of the microscope. An average time of 27.00 ± 2.58 seconds is required to auto-focus a single FoV. Auto-focus evaluation demonstrates a mean average maximum Laplacian value of 11.83 with tested images. The whole automation process is controlled by a smartphone device, which is responsible for acquiring images for further diagnosis via convolutional neural networks. The prototype is specially designed for resource-poor settings, where microscopy diagnosis is still a routine process. The coalescence between convolutional neural network predictive models and the automation of the movements of a conventional optical microscope confer the system a wide range of image-based diagnosis applications. The accessibility of the system could help improve diagnostics and provide new tools to laboratories worldwide.

Despite the common belief that police presence reduces crime, there is mixed evidence of such causal effects in major Latin America cities. In this work we identify the casual relationship between police presence and criminal events by using a large dataset of a randomized controlled police intervention in Bogotá D.C., Colombia. We use an Instrumental Variables approach to identify the causal effect of interest. Then we consistently estimate a Conditional Logit discrete choice model with aggregate data that allow us to identify agents' utilities for crime location using Two Stage Least Squares. The estimated parameters allow us to compute the police own and cross-elasticities of crime for each of the spatial locations and to evaluate different police patrolling strategies. The elasticity of crime to police presence is, on average across spatial locations, -0.26 for violent crime, -0.38 for property crime and -0.38 for total crime, all statistically significant. Estimates of cross-elasticities are close to zero; however, spillover effects are non-negligible. Counterfactual analysis of different police deployment strategies show, for an optimal allocating algorithm, an average reduction in violent crime of 7.09%, a reduction in property crimes of 8.48% and a reduction in total crimes of 5.15% at no additional cost. These results show the potential efficiency gains of using the model to deploy police resources in the city without increasing the total police time required.

ObjectiveTo estimate the baseline to measure one of the three indicators of the World Health Organization (WHO) End TB strategy (2015-2035), measure the costs incurred by patients affected by tuberculosis (TB) during a treatment episode and estimate the proportion of households facing catastrophic costs (CC) and associated risk factors, in Colombia, 2021.Material and methodsA nationally representative cross-sectional survey was conducted among participants on TB treatment in Colombia, using telephone interviews due to the exceptional context of the COVID-19 pandemic. The survey collected household costs (direct [medical and non-medical out-of-pocket expenses] and indirect) over an episode of TB, loss of time, coping measures, self-reported income, and asset ownership. Total costs were expressed as a proportion of annual household income and analyzed for risk factors of CC (defined as costs above 20% annual household income).ResultsThe proportion of TB-affected households incurring in costs above 20% annual household income (CC) was 51.7% (95%CI: 45.4-58.0) overall, 51.3% (95%CI: 44.9-57.7) among patients with drug-sensitive (DS) TB, and 65.0% (95%CI: 48.0-82.0) among drug-resistant (DR). The average patient cost of a TB case in Colombia was $1,218 (95%CI 1,106-1,330) including $860.9 (95%CI 776.1-945.7) for non-medical costs, $339 (95%CI 257-421) for the indirect costs, and $18.1 (95%CI 11.9-24.4) for the medical costs. The factors that influenced the probability of facing CC were income quintile, job loss, DR-TB patient, and TB type.ConclusionMain cost drivers for CC were non-medical out-of-pocket expenses and income loss (indirect costs). Current social protection programs ought to be expanded to mitigate the proportion of TB-affected households facing CC in Colombia, especially those with lower income levels.

The COVID-19 pandemic has created unprecedented challenges for health care systems globally. This study aimed to explore the presence of mental illness in a Spanish cohort of COVID-19-infected population and to evaluate the association between the presence of specific mental health conditions and the risk of death and hospitalization. This is a retrospective cohort study including all individuals with confirmed infection by SARS-CoV-2 from the PRECOVID (Prediction in COVID-19) Study (Aragon, Spain). Mental health illness was defined as the presence of schizophrenia and other psychotic disorders, anxiety, cognitive disorders, depression and mood disorders, substance abuse, and personality and eating disorders. Multivariable logistic regression models were used to examine the likelihood of 30-day all-cause mortality and COVID-19 related hospitalization based on baseline demographic and clinical variables, including the presence of specific mental conditions, by gender. We included 144,957 individuals with confirmed COVID-19 from the PRECOVID Study (Aragon, Spain). The most frequent diagnosis in this cohort was anxiety. However, some differences were observed by sex: substance abuse, personality disorders and schizophrenia were more frequently diagnosed in men, while eating disorders, depression and mood, anxiety and cognitive disorders were more common among women. The presence of mental illness, specifically schizophrenia spectrum and cognitive disorders in men, and depression and mood disorders, substance abuse, anxiety and cognitive and personality disorders in women, increased the risk of mortality or hospitalization after COVID-19, in addition to other well-known risk factors such as age, morbidity and treatment burden. Identifying vulnerable patient profiles at risk of serious outcomes after COVID-19 based on their mental health status will be crucial to improve their access to the healthcare system and the establishment of public health prevention measures for future outbreaks.

ObjectiveTo end the AIDS epidemic by 2030, despite the increasing poverty and inequalities, policies should be designed to deal with population heterogeneity and environmental changes. Bottom-up designs, such as the Agent-Based Model (ABM), can model these features, dealing with such complexity. HIV/AIDS has a complex dynamic of structural factors, risk behaviors, biomedical characteristics and interventions. All embedded in unequal, stigmatized and heterogeneous social structure. To understand how ABMs can model this complexity, we performed a scoping review of HIV applications, highlighting their potentialities.MethodsWe searched on PubMed, Web of Science, and Scopus repositories following the PRISMA extension for scoping reviews. Our inclusion criteria were HIV/AIDS studies with an ABM application. We identified the main articles using a local co-citation analysis and categorized the overall literature aims, (sub)populations, regions, and if the papers declared the use of ODD protocol and limitations.ResultsWe found 154 articles. We identified eleven main papers, and discussed them using the overall category results. Most studies model Transmission Dynamics (37/154), about Men who have sex with Men (MSM) (41/154), or individuals living in the US or South Africa (84/154). Recent studies applied ABM to model PrEP interventions (17/154) and Racial Disparities (12/154). Only six papers declared the use of ODD Protocol (6/154), and 34/154 didn't mention the study limitations.ConclusionsWhile ABM is among the most sophisticated techniques available to model HIV/AIDS complexity. Their applications are still restricted to some realities. However, researchers are challenged to think about social structure due model characteristics, the inclusion of these features is still restricted to case-specific. Data and computational power availability can enhance this feature providing insightful results.

This work aimed at creating a psychosocial intervention based on growth mindset theory and implementation intention strategies, in order to reduce alcohol consumption among users in the general population, and the clinical population of individuals with alcohol use disorder. A mixed method approach was used, combining qualitative and quantitative research methods among both populations. Four focus groups were first conducted to extract arguments in favor of a malleable view of alcohol consumption (study 1A), situations that trigger the desire to drink alcohol, as well as strategies used by people to counteract this need (study 1B). Data were analyzed using reflective thematic analysis in line with the scientific literature on alcohol consumption. The results were used to create a questionnaire scoring the relevance of each argument, situation and strategy (study 2). The 20 best scored arguments, situations and strategies were selected to create the intervention. The created intervention consisted in a popularized scientific article describing alcohol consumption as malleable, including the selected arguments and followed by two internalization exercises. Then, a volitional help sheet included the selected situations and solutions was presented, allowing forming up to three plans. The discussion focused on the added value of the created material compared to pre-existing tools in the literature, and presents plans to test the intervention in a future study.

Cellular senescence and low-grade inflammation favor the acceleration of aging. The liver is an essential metabolic organ because changes related to its function are related to age-related diseases. The objective of this study was to evaluate the effects of maraviroc (MVC) and/or rapamycin (RAPA) on liver tissue in an experimental model of frailty syndrome in mice, since MVC and RAPA are two molecules able to decrease CCR5 expression, which is overexpressed in patients with frailty. Methods: Eighty male homozygous IL10KO mice were randomly assigned to one of 4 groups (n = 20): i) IL10KO group; ii) MVC group, iii) RAPA group, and iv) MVC-RAPA group. Liver samples were analyzed. Gene expression quantification and western blotting were also performed. The proinflammatory cytokines IL-6 and IL-18 were decreased in MVC and MVC/RAPA groups, IL-12 was decreased in RAPA and MVC/RAPA groups and TNF-α was decreased in all therapeutic groups. P21 was decreased in RAPA and MVC/RAPA groups, Galactosidase beta-1, was also significantly reduced in all therapeutic groups, as were NF-kB1, NF-kB2 and STAT3. In all groups, mTOR and CCL5 were significantly reduced. CCR5 expression was decreased in the MVC and MVC/RAPA groups. Conclusion: MVC and RAPA may protect against some factors involved in liver aging. More studies will be necessary to verify their clinical applications.

Animal rehabilitation centres provide a unique opportunity to study the microbiome of wild animals because subjects will be handled for their treatment and can therefore be sampled longitudinally. However, rehabilitation may have unintended consequences on the animals' microbiome because of a less varied and suboptimal diet, possible medical treatment and exposure to a different environment and human handlers. Our study describes the gut microbiome of two large seal cohorts, 50 pups (0-30 days old at arrival) and 23 weaners (more than 60 days old at arrival) of stranded harbour seals admitted for rehabilitation at the Sealcentre Pieterburen in the Netherlands, and the effect of rehabilitation on it. Faecal samples were collected from all seals at arrival, two times during rehabilitation and before release. Only seals that did not receive antimicrobial treatment were included in the study. The average time in rehabilitation was 95 days for the pups and 63 days for the weaners. We observed that during rehabilitation, there was an increase in the relative abundance of some of the Campylobacterota spp and Actinobacteriota spp. The alpha diversity of the pups' microbiome increased significantly during their rehabilitation (p-value

IntroductionThe diagnosis of acute respiratory distress syndrome (ARDS) includes the ratio of pressure arterial oxygen and inspired oxygen fraction (P/F) ≤ 300, which is often adjusted in locations more than 1,000 meters above sea level (masl) due to hypobaric hypoxemia. The main objective of this study was to develop a prediction model for in-hospital mortality among patients with ARDS due to coronavirus disease 2019 (COVID-19) (C-ARDS) at 2,600 masl with easily available variables at patient admission and to compare its discrimination capacity with a second model using the P/F adjusted for this high altitude.MethodsThis study was an analysis of data from patients with C-ARDS treated between March 2020 and July 2021 in a university hospital located in the city of Bogotá, Colombia, at 2,600 masl. Demographic and laboratory data were extracted from electronic records. For the prediction model, univariate analyses were performed to screen variables with p ResultsA total of 2,210 subjects were included in the final analysis. The final model included 11 variables without interaction terms or nonlinear functions. The coefficients are presented excluding influential observations. The final equation for the model fit was g(x) = age(0.04819)+weight(0.00653)+height(-0.01856)+haemoglobin(-0.0916)+platelet count(-0.003614)+ creatinine(0.0958)+lactate dehydrogenase(0.001589)+sodium(-0.02298)+potassium(0.1574)+systolic pressure(-0.00308)+if moderate ARDS(0.628)+if severe ARDS(1.379), and the probability of in-hospital death was p (x) = e g (x)/(1+ e g (x)). The AUC of the ROC curve was 0.7601 (95% confidence interval (CI) 0.74-0, 78). The second model with the adjusted P/F presented an AUC of 0.754 (95% CI 0.73-0.77). No statistically significant difference was found between the AUC curves (p value = 0.6795).ConclusionThis study presents a prediction model for patients with C-ARDS at 2,600 masl with easily available admission variables for early stratification of in-hospital mortality risk. Adjusting the P/F for 2,600 masl did not improve the predictive capacity of the model. We do not recommend adjusting the P/F for altitude.

The casts of Pompeii bear witness to the people who died during the Vesuvius 79 AD eruption. However, studies on the cause of death of these victims have not been conclusive. A previous important step is the understanding of the post-depositional processes and the impact of the plaster in bones, two issues that have not been previously evaluated. Here we report on the anthropological and the first chemical data obtained from the study of six casts from Porta Nola area and one from Terme Suburbane. A non-invasive chemical analysis by portable X-ray fluorescence was employed for the first time on these casts of Pompeii to determine the elemental composition of the bones and the plaster. Elemental profiles were determined providing important data that cross-referenced with anthropological and stratigraphic results, are clearly helpful in the reconstruction of the perimortem and post-mortem events concerning the history of these individuals. The comparative analyses carried out on the bone casts and other collections from burned bones of the necropolis of Porta Nola in Pompeii and Rome Sepolcreto Ostiense, and buried bones from Valencia (Spain), reveal the extent of high temperature alteration and post-depositional plaster contamination. These factors make bioarchaeological analyses difficult but still allow us to support asphyxia as the likely cause of death.

Zika virus (ZIKV) was first isolated in 1947. From its isolation until 2007, symptoms of ZIKV-caused disease were limited (e.g., fever, hives, and headache); however, during the epidemic in Brazil in 2014, ZIKV infection caused Guillain-Barré syndrome in adults and microcephaly in fetuses and infants of women infected during pregnancy. The neurovirulence of ZIKV has been studied using neural progenitor cells (NPCs), brain organoids, neurons, and astrocytes. NPCs and astrocytes appear to be the most susceptible cells of the Central Nervous System to ZIKV infection. In this work, we aimed to develop a culture of astrocytes derived from a human NPC cell line. We analyze how ZIKV affects human astrocytes and demonstrate that 1) ZIKV infection reduces cell viability, increases the production of Reactive Oxygen Species (ROS), and results in high viral titers; 2) there are changes in the expression of genes that facilitate the entry of the virus into the cells; 3) there are changes in the expression of genes involved in the homeostasis of the glutamatergic system; and 4) there are ultrastructural changes in mitochondria and lipid droplets associated with production of virions. Our findings reveal new evidence of how ZIKV compromises astrocytic functionality, which may help understand the pathophysiology of ZIKV-associated congenital disease.

University students constitute a population that is highly vulnerable to developing mental health problems, such as distress. The role of different variables associated with the development of states of stress has been studied in order to identify potential risk and protective factors. This study explored whether mindfulness, self-compassion, and experiential avoidance, while controlling for specific sociodemographic and academic variables, were potential significant protective or risk factors explaining perceived stress in a sample of 589 Spanish university students (81.2% female, age range 18-48 years). A hierarchical multiple regression analysis was performed using an exploratory cross-sectional design. Higher experiential avoidance, lower self-compassion, lower mindfulness, not perceiving family support, higher total study hours per week, having a partner (vs. being single), being female (vs. being male), and being older were significantly associated with higher levels of perceived stress. In conclusion, perceived stress in our sample was positively associated with experiential avoidance, which could be regarded as a potential psychological risk variable. In contrast, perceived stress was negatively correlated with self-compassion and mindfulness, which, in turn, could be seen as protective factors. Accordingly, it is concluded that programmes aimed at reducing stress and at improving well-being among university students should include experiential avoidance, self-compassion, and mindfulness as therapeutic targets.

Given the ever-increasing prevalence of type 2 diabetes and obesity, the pressure on global healthcare is expected to be colossal, especially in terms of blindness. Electroretinogram (ERG) has long been perceived as a first-use technique for diagnosing eye diseases, and some studies suggested its use for preventable risk factors of type 2 diabetes and thereby diabetic retinopathy (DR). Here, we show that in a non-evoked mode, ERG signals contain spontaneous oscillations that predict disease cases in rodent models of obesity and in people with overweight, obesity, and metabolic syndrome but not yet diabetes, using one single random forest-based model. Classification performance was both internally and externally validated, and correlation analysis showed that the spontaneous oscillations of the non-evoked ERG are altered before oscillatory potentials, which are the current gold-standard for early DR. Principal component and discriminant analysis suggested that the slow frequency (0.4-0.7 Hz) components are the main discriminators for our predictive model. In addition, we established that the optimal conditions to record these informative signals, are 5-minute duration recordings under daylight conditions, using any ERG sensors, including ones working with portative, non-mydriatic devices. Our study provides an early warning system with promising applications for prevention, monitoring and even the development of new therapies against type 2 diabetes.

Knowledge gaps exist in the socio-ecological systems of small touristic islands in Latin America. Understanding tourists’ perceptions of their environmental knowledge can help plan actions to prevent natural capital loss necessary for local economies. Tourists’ perceptions of a touristic hotspot, Holbox Island, were documented. Surveys demonstrated that tourists are aware of their environmental impacts and are interested in minimizing these. Results were compared with results on Bocas del Toro, Panama. Tourists’ perceptions had similarities among sites driven by similarities in tourists’ populations with a common geographic origin. Tourists lack site-specific knowledge to steer them towards environmentally conscious decisions in both regions. Findings suggest the need to promote local actions to gain tourists’ understanding about their destination and support education programs on island conservation. Addressing these needs can help build resilience to overcome the adverse socio-environmental effects of tourism, environmental disasters, and health crises as COVID-19 on small islands.

BackgroundCOVID-19 has resulted in over 1 million deaths in the U.S. as of June 2022, with continued surges after vaccine availability. Information on related attitudes and behaviors are needed to inform public health strategies. We aimed to estimate the prevalence of COVID-19, risk factors of infection, and related attitudes and behaviors in a racially, ethnically, and socioeconomically diverse urban population.MethodsThe DFW COVID-19 Prevalence Study Protocol 1 was conducted from July 2020 to March 2021 on a randomly selected sample of adults aged 18-89 years, living in Dallas or Tarrant Counties, Texas. Participants were asked to complete a 15-minute questionnaire and COVID-19 PCR and antibody testing. COVID-19 prevalence estimates were calculated with survey-weighted data.ResultsOf 2969 adults who completed the questionnaire (7.4% weighted response), 1772 (53.9% weighted) completed COVID-19 testing. Overall, 11.5% of adults had evidence of COVID-19 infection, with a higher prevalence among Hispanic and non-Hispanic Black persons, essential workers, those in low-income neighborhoods, and those with lower education attainment compared to their counterparts. We observed differences in attitudes and behaviors by race and ethnicity, with non-Hispanic White persons being less likely to believe in the importance of mask wearing, and racial and ethnic minorities more likely to attend social gatherings.ConclusionOver 10% of an urban population was infected with COVID-19 early during the pandemic. Differences in attitudes and behaviors likely contribute to sociodemographic disparities in COVID-19 prevalence.

Attachment is an innate human relational mechanism that develops progressively from early childhood, influences individuals' representations and behaviors, shapes relationships, and affects the social and cultural environment. Parental bonding refers to the ability of parents to be emotionally and behaviorally available to the child during infancy. Attachment style refers to the individual's relational attitude in close relationships that influences adult love, bonding, handling relationships, and social exploration. The role of intergenerational, cultural and developmental factors influencing the relationship between the attachment style in adulthood and the parental bonding style recalled during childhood has been debated. This study explores the relationships between recalled parental bonding, adult attachment style, and cultural background in a sample of Spanish, Italian, and Japanese adults using a cross-sectional and cross-cultural design. For this purpose, the validated versions of the Experience in Close Relationship Scale and the Parental Bonding Instrument were administered to a non-clinical population of three hundred and five participants in the three countries. Results show that the most frequent adult attachment style is the secure style, followed by the dismissing-avoidant, the preoccupied, and the fearful-avoidant style. The dismissing-avoidant style was the most frequent insecure attachment style in the Japanese sample whereas the preoccupied style was the most frequent insecure attachment style in the Italians and Spaniards. Japanese are more anchored to the memory of maternal and paternal overprotection, which is related to more avoidance in actual close relationships. Spaniard's current relationships are mildly independent of recalled parental bonding, showing an association between lower current avoidance to primary parental care. In the Italian sample, there is no significant relationship between current adult close relationships and recalled parental bonding. These results suggest that different cultural models influence adult attachment representations differently, in terms of the weight placed on attachment-related avoidance, attachment-related anxiety, care, and overprotection in infant and adult relationships.

[This corrects the article DOI: 10.1371/journal.pone.0240933.].

BackgroundDiacutaneous fibrolysis is a non-invasive instrumental physiotherapeutic technique, used to treat mechanical or inflammatory pain and normalize function in the musculoskeletal system. Different studies have reported positive effects on range of motion, strength or function in musculoskeletal disorders, mainly in the upper extremity. The incidence and recurrence rates of hamstring injuries are high in many sports. However, there are no studies assessing these parameters in the hamstring and gluteus maximus in athletes. Objective. To evaluate the immediate and 30 minutes post-treatment effects of a single diacutaneous fibrolysis session on hamstring length, flexibility, muscle strength, myoelectrical activity and lower limb performance in athletes with hamstring shortening.MethodsA randomized within-participant clinical trial. Sixty-six athletes with hamstring shortening were recruited. A single session of diacutaneous fibrolysis was applied following the cetripetal protocol to the gluteus maximus, biceps femoris and semitendinosus of for the experimental lower limb, whereas the control limb was not treated. Hamstring length (Passive knee extension test), hamstring and low back flexibility (Modified back saver sit and reach test), hamstring and gluteus maximus strength and electrical activity (dynamometry and surface electromyography, respectively) and lower limb performance (Countermovement Jump) were tested before treatment (T0), after treatment (T1), and 30 minutes post-treatment (T2).ResultsWe only found a statistically significant difference between T0-T2 for the hamstring length favouring the experimental limbs (p0.05).ConclusionsA single session of diacutaneous fibrolysis in athletes with hamstring shortening, following the centripetal protocol for the posterior part of the thigh, produces improvements in hamstring length 30 minutes after, and in gluteus maximus strength immediately and 30 minutes after the treatment. It seems to have no effects on the overall hamstring and lower back flexibility or myoelectric activity. Importantly, the lower limb performance was not impaired after the treatment.

Cocoa cultivation is of considerable economic and social importance to the Amazonas region and is commonly associated with forest species in the region. However, the diversification level and composition of cacao agroforestry systems in Peru are poorly understood. The objective of this study is, therefore, to describe the diversity of tree species in cocoa AFS by plantation age. Accordingly, the number of species of 15 plots covering a total of 1.5 hectares was recorded. Moderately low levels of tree species diversity were reported (H´ ranged 0.89–1.45). In total 17 species were reported throughout the study area. The most abundant botanical family was represented by a single Musa sp. species. The dissimilarity indices show a moderate similarity between the age ranges evaluated (over 62%). Additionally, the IVI indicates that the most important species are used for food and timber apart from providing shade, additionally major of this species are introduced intentionally for the farmers. Based on the observations, it may be concluded that the farmer’s interest in obtaining further benefits from the plot, mostly economic benefits affect the diversification of cocoa agroforestry systems.

The Baja California Pacific Islands (BCPI) is a seabird hotspot in the southern California Current System supporting 129 seabird breeding populations of 23 species and over one million birds annually. These islands had a history of environmental degradation because of invasive alien species, human disturbance, and contaminants that caused the extirpation of 27 seabird populations. Most of the invasive mammals have been eradicated and colonies have been restored with social attraction techniques. We have recorded the number of breeding pairs annually for most of the colonies since 2008. To assess population trends, we analyzed these data and show results for 19 seabird species on ten island groups. The maximum number of breeding pairs for each nesting season was used to estimate the population growth rate (λ) for each species at every island colony. We performed a moving block bootstrap analysis to assess whether seabird breeding populations are increasing or decreasing. San Benito, Natividad, and San Jerónimo are the top three islands in terms of abundance of breeding pairs. The most widespread species is Cassin's Auklet (Ptychoramphus aleuticus) with 14 colonies. Thirty-one populations of 14 species are significantly increasing while eleven populations of seven species are decreasing. We did not find statistical significance for 19 populations, however, 15 have λ>1 which suggest they are growing. Twelve of the 18 species for which we estimated a regional population trend are significantly increasing, including seven surface-nesting species: Brandt's Cormorant (Phalacrocorax penicillatus), Brown Pelican (Pelecanus occidentalis), Caspian Tern (Hydroprogne caspia), Double-crested Cormorant (P. auritus), Elegant Tern (Thalasseus elegans), Laysan Albatross (Phoebastria immutabilis) and Western Gull (Larus occidentalis), and five burrow-nesting species: Ainley's (Hydrobates cheimomnestes), Ashy (H. homochroa) and Townsend's (H. socorroensis) Storm-Petrels, and Craveri's (Synthliboramphus craveri) and Guadalupe (S. hypoleucus) Murrelets. The BCPI support between 400,000 and 1.4 million breeding individuals annually. Our results suggest that these islands support healthy and growing populations of seabirds that have shown to be resilient to extreme environmental conditions such as the "Blob", and that such resilience has been strengthen from conservation and restoration actions such as the eradication of invasive mammals, social attraction techniques and island biosecurity.

Objective To describe the impact of different doses of corticosteroids on the evolution of patients with COVID-19 pneumonia, based on the potential benefit of the non-genomic mechanism of these drugs at higher doses. Methods Observational study using data collected from the SEMI-COVID-19 Registry. We evaluated the epidemiological, radiological and analytical scenario between patients treated with megadoses therapy of corticosteroids vs low-dose of corticosteroids and the development of complications. The primary endpoint was all-cause in-hospital mortality according to use of corticosteroids megadoses. Results Of a total of 14,921 patients, corticosteroids were used in 5,262 (35.3%). Of them, 2,216 (46%) specifically received megadoses. Age was a factor that differed between those who received megadoses therapy versus those who did not in a significant manner (69 years [IQR 59–79] vs 73 years [IQR 61–83]; p < .001). Radiological and analytical findings showed a higher use of megadoses therapy among patients with an interstitial infiltrate and elevated inflammatory markers associated with COVID-19. In the univariate study it appears that steroid use is associated with increased mortality (OR 2.07 95% CI 1.91–2.24 p < .001) and megadose use with increased survival (OR 0.84 95% CI 0.75–0.96, p 0.011), but when adjusting for possible confounding factors, it is observed that the use of megadoses is also associated with higher mortality (OR 1.54, 95% CI 1.32–1.80; p < .001). There is no difference between megadoses and low-dose (p .298). Although, there are differences in the use of megadoses versus low-dose in terms of complications, mainly infectious, with fewer pneumonias and sepsis in the megadoses group (OR 0.82 95% CI 0.71–0.95; p < .001 and OR 0.80 95% CI 0.65–0.97; p < .001) respectively. Conclusion There is no difference in mortality with megadoses versus low-dose, but there is a lower incidence of infectious complications with glucocorticoid megadoses.

The role played by certain domestic species such as dogs as a translational model in comparative oncology shows great interest to develop new therapeutic strategies in brain tumors. Gliomas are a therapeutic challenge that represents the most common form of malignant primary brain tumors in humans and the second most common form in dogs. Gene-directed enzyme/prodrug therapy using adipose mesenchymal stem cells (Ad-MSCs) expressing the herpes simplex virus thymidine kinase (TK) has proven to be a promising alternative in glioblastoma therapy, through its capacity to migrate and home to the tumor and delivering local cytotoxicity avoiding other systemic administration. In this study, we demonstrate the possibility for canine Ad-MSCs (cAd-MSCs) to be genetically engineered efficiently with a lentiviral vector to express TK (TK-cAd-MSCs) and in combination with ganciclovir (GCV) prodrug demonstrated its potential antitumor efficacy in vitro and in vivo in a mice model with the human glioblastoma cell line U87. TK-cAd-MSCs maintained cell proliferation, karyotype stability, and MSCs phenotype. Genetic modification significantly affects its secretory profile, both the analyzed soluble factors and exosomes. TK-cAd-MSCs showed a high secretory profile of some active antitumor immune response cytokines and a threefold increase in the amount of secreted exosomes, with changes in their protein cargo. We also found that the prodrug protein is not released directly into the culture medium by TK-cAd-MSCs. We believe that our work provides new perspectives for glioblastoma gene therapy in dogs and a better understanding of this therapy in view of its possible implantation in humans.

BackgroundInfection by the SARS-Cov-2 virus produces in humans a disease of highly variable and unpredictable severity. The presence of frequent genetic single nucleotide polymorphisms (SNPs) in the population might lead to a greater susceptibility to infection or an exaggerated inflammatory response. SARS-CoV-2 requires the presence of the ACE2 protein to enter in the cell and ACE2 is a regulator of the renin-angiotensin system. Accordingly, we studied the associations between 8 SNPs from AGTR1, ACE2 and ACE genes and the severity of the disease produced by the SARS-Cov-2 virus.Methods318 (aged 59.6±17.3 years, males 62.6%) COVID-19 patients were grouped based on the severity of symptoms: Outpatients (n = 104, 32.7%), hospitalized on the wards (n = 73, 23.0%), Intensive Care Unit (ICU) (n = 84, 26.4%) and deceased (n = 57, 17.9%). Comorbidity data (diabetes, hypertension, obesity, lung disease and cancer) were collected for adjustment. Genotype distribution of 8 selected SNPs among the severity groups was analyzed.ResultsFour SNPs in ACE2 were associated with the severity of disease. While rs2074192 andrs1978124showed a protector effectassuming an overdominant model of inheritance (G/A vs. GG-AA, OR = 0.32, 95%CI = 0.12-0.82; p = 0.016 and A/G vs. AA-GG, OR = 0.37, 95%CI: 0.14-0.96; p = 0.038, respectively); the SNPs rs2106809 and rs2285666were associated with an increased risk of being hospitalized and a severity course of the disease with recessive models of inheritance (C/C vs. T/C-T/T, OR = 11.41, 95% CI: 1.12-115.91; p = 0.012) and (A/A vs. GG-G/A, OR = 12.61, 95% CI: 1.26-125.87; p = 0.0081). As expected, an older age (OR = 1.47), male gender (OR = 1.98) and comorbidities (OR = 2.52) increased the risk of being admitted to ICU or death vs more benign outpatient course. Multivariable analysis demonstrated the role of the certain genotypes (ACE2) with the severity of COVID-19 (OR: 0.31, OR 0.37 for rs2074192 and rs1978124, and OR = 2.67, OR = 2.70 for rs2106809 and rs2285666, respectively). Hardy-Weinberg equilibrium in hospitalized group for I/D SNP in ACE was not showed (pConclusionsDifferent genetic variants in ACE2 were associated with a severe clinical course and death groups of patients with COVID-19. ACE2 common SNPs in the population might modulate severity of COVID-19 infection independently of other known markers like gender, age and comorbidities.

Neural crest cell genes control the migration of neural crest cells to multiple parts of developing vertebrate embryos. A recent hypothesis posits that the "domestication syndrome" characteristic of domesticated animals is driven by selection for tameness acting on neural crest cell genes, particularly those affecting cell migration. This is posited to explain why this syndrome involves many disparate phenotypic effects. These effects can be connected to deficits in neural crest cell migration. This hypothesis predicts that patterns of selection on these neural crest cell genes will differ between domesticated species and related wild species. Specifically, it predicts higher levels of positive selection on these genes in domesticated species, relative to closely related wild species. Here we test this prediction in a comparative framework. We obtained DNA sequences from a public database (NCBI) for eleven key neural crest cell genes from a set of thirty domesticated vertebrates and matched close relatives that remain wild. We used the program Contrast-FEL in the software suite HyPhy to compare the number of sites under positive selection (as measured by non-synonymous to synonymous nucleotide substitution rates across codons) between these two types of taxa in a phylogenetic framework. We found that domesticated lineages showed a consistently higher level of positive selection on these key genes, relative to their closely related wild counterparts. In addition, we found support for relaxation of selection and purifying selection. We argue that this result is consistent with an important role for these genes in the domestication syndrome.

Background Despite the great progress made over the last decades, stronger structural interventions are needed to end the HIV/AIDS pandemic in Low and Middle-Income Countries (LMIC). Brazil is one of the largest and data-richest LMIC, with rapidly changing socioeconomic characteristics and an important HIV/AIDS burden. Over the last two decades Brazil has also implemented the world’s largest Conditional Cash Transfer programs, the Bolsa Familia Program (BFP), and one of the most consolidated Primary Health Care (PHC) interventions, the Family Health Strategy (FHS). Objective We will evaluate the effects of socioeconomic determinants, BFP exposure and FHS coverage on HIV/AIDS incidence, treatment adherence, hospitalizations, case fatality, and mortality using unprecedently large aggregate and individual-level longitudinal data. Moreover, we will integrate the retrospective datasets and estimated parameters with comprehensive forecasting models to project HIV/AIDS incidence, prevalence and mortality scenarios up to 2030 according to future socioeconomic conditions and alternative policy implementations. Methods and analysis We will combine individual-level data from all national HIV/AIDS registries with large-scale databases, including the “100 Million Brazilian Cohort”, over a 19-year period (2000–2018). Several approaches will be used for the retrospective quasi-experimental impact evaluations, such as Regression Discontinuity Design (RDD), Random Administrative Delays (RAD) and Propensity Score Matching (PSM), combined with multivariable Poisson regressions for cohort analyses. Moreover, we will explore in depth lagged and long-term effects of changes in living conditions and in exposures to BFP and FHS. We will also investigate the effects of the interventions in a wide range of subpopulations. Finally, we will integrate such retrospective analyses with microsimulation, compartmental and agent-based models to forecast future HIV/AIDS scenarios. Conclusion The unprecedented datasets, analyzed through state-of-the-art quasi-experimental methods and innovative mathematical models will provide essential evidences to the understanding and control of HIV/AIDS epidemic in LMICs such as Brazil.

The load in tasks planned for sports teaching in physical education classes has received little attention. The purpose of this study was therefore to analyze the external load, eTL, in the tasks designed by physical education teachers from the in-service and pre-service stages, for teaching handball in primary education, and to compare them with the tasks included in the lesson plans designed for handball using the tactical games teaching model. An associative, comparative and cross-sectional methodology was used. Twenty-three teachers, five in the in-service phase and eighteen in the pre-service phase, designed lesson plans for teaching handball, which were compared with lesson plans validated by a panel of experts. The analysis was performed on 1,232 tasks or analysis units. eTL was categorized using the Integrated analysis system of training tasks (SIATE) instrument. A descriptive and associative analysis was made of the variables that make up the eTL and an inferential analysis of the eTL using non-parametric tests. The total eTL of the tasks planned by the in-service and pre-service teachers was low, and significantly lower than the tasks planned using the tactical games model, which showed a high level.

BackgroundMost patients with COVID-19 receive antibiotics despite the fact that bacterial co-infections are rare. This can lead to increased complications, including antibacterial resistance. We aim to analyze risk factors for inappropriate antibiotic prescription in these patients and describe possible complications arising from their use.MethodsThe SEMI-COVID-19 Registry is a multicenter, retrospective patient cohort. Patients with antibiotic were divided into two groups according to appropriate or inappropriate prescription, depending on whether the patient fulfill any criteria for its use. Comparison was made by means of multilevel logistic regression analysis. Possible complications of antibiotic use were also identified.ResultsOut of 13,932 patients, 3047 (21.6%) were prescribed no antibiotics, 6116 (43.9%) were appropriately prescribed antibiotics, and 4769 (34.2%) were inappropriately prescribed antibiotics. The following were independent factors of inappropriate prescription: February-March 2020 admission (OR 1.54, 95%CI 1.18-2.00), age (OR 0.98, 95%CI 0.97-0.99), absence of comorbidity (OR 1.43, 95%CI 1.05-1.94), dry cough (OR 2.51, 95%CI 1.94-3.26), fever (OR 1.33, 95%CI 1.13-1.56), dyspnea (OR 1.31, 95%CI 1.04-1.69), flu-like symptoms (OR 2.70, 95%CI 1.75-4.17), and elevated C-reactive protein levels (OR 1.01 for each mg/L increase, 95% CI 1.00-1.01). Adverse drug reactions were more frequent in patients who received ANTIBIOTIC (4.9% vs 2.7%, p < .001).ConclusionThe inappropriate use of antibiotics was very frequent in COVID-19 patients and entailed an increased risk of adverse reactions. It is crucial to define criteria for their use in these patients. Knowledge of the factors associated with inappropriate prescribing can be helpful.

PurposeTo analyze the relationship between intraoperative cultures and the development of surgical site infection (SSI) in women undergoing laparotomy for gynecological surgery.MethodsProspective observational cohort study. Over a six-year period, women who underwent elective laparotomy at our hospital were included. Patients' demographics, underlying co-morbidities, surgical variables, type and etiology of postoperative surgical site infections were collected. Skin and subcutaneous samples were taken just prior to skin closure and processed for microbiological analysis. Univariate and multivariate analyses (logistic regression model) were conducted to explore the association of the studied variables with SSIs.Results284 patients were included in our study, of which 20 (7%) developed surgical site infection, including 11 (55%) superficial and nine (45%) organ-space. At univariate analysis, length of surgery, colon resection, transfusion and positive intraoperative culture were associated with surgical site infection occurrence. Skin and subcutaneous cultures were positive in 25 (8.8%) and 20 (7%) patients, respectively. SSI occurred in 35% of women with positive subcutaneous culture and in 20% of those with positive skin cultures. Using multivariate analysis, the only independent factor associated with surgical site infection was a positive subcutaneous culture (OR 10.4; 95% CI 3.5-30.4; PConclusionIntraoperative subcutaneous cultures before skin closure may help early prediction of surgical site infection in open gynecological procedures.

Rheumatoid arthritis (RA) has been associated with insulin resistance (IR). Due to an excess in storage of white adipose tissue, IR has an inflammatory process that overlaps with RA. This is performed by the activation/migration of monocytes carried out by the CCR2/CCL2 and CMKLR1/RvE1 chemokines systems. Furthermore, these can potentiate chronic inflammation which is the central axis in the immunopathogenesis of RA. We evaluated the association between the relative expression of CCR2 and CMKLR1 and the serum levels of their ligands CCL2 and RvE1, in the context of adiposity status with IR as a comorbidity in RA. We studied 138 controls and 138 RA-patients classified with and without IR. We evaluated adiposity, RA activity, IR status and immunometabolic profiles by routine methods. Insulin, CCL2 and RvE1 serum levels were determined by ELISA. Relative expression of CCR2, CMKLR1 and RPS28 as constitutive gene by SYBR green RT-qPCR and 2-ΔΔCT method. Increased measurements were observed of body adiposity and metabolic status as follows: RA with IR>control group with IR>RA without IR> control group without IR. CCR2 and CMKLR1 relative expression was increased in RA without IR versus control without IR. CCR2: 2.3- and 1.3-fold increase and CMKLR1: 3.5- and 2.7-fold increase, respectively. Whereas, CCR2 expression correlates with CMKLR1 expression (rho = 0.331) and IR status (rho = 0.497 to 0.548). CMKLR1 expression correlates with inflammation markers (rho = 0.224 to 0.418). CCL2 levels were increased in the RA groups but levels of RvE1 were increased in RA without IR. We conclude that in RA with IR, the chemokine receptors expression pattern showed a parallel increase with their respective ligands. RA and IR in conjunction with the pathological distribution of body fat mass might exacerbate chronic inflammation. These results suggest that high CCL2 levels and compensatory RvE1 levels might not be enough to resolve the inflammation by themselves.

BackgroundThe inadequacy of HIV viraemia and resistance monitoring in Africa leads to uncontrolled circulation of HIV strains with drug resistance mutations (DRM), compromising antiretroviral therapy (ART) effectiveness. This study describes the DRM prevalence and its therapeutic impact in HIV-infected pediatric patients from Kinshasa (Democratic Republic of Congo, DRC).MethodsFrom 2016-2018, dried blood were collected from 71 HIV-infected children and adolescents under ART in two hospitals in Kinshasa for HIV-1 DRM pol analysis, predicted ARV-susceptibility by Stanford and phylogenetic characterization.ResultsHIV-1 sequences were recovered from 55 children/adolescents with 14 years of median-age. All had received nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTI, NNRTI), 9.1% protease inhibitors (PI) and only one integrase inhibitor (INI). Despite the use of ART, 89.1% showed virological failure and 67.3% carried viruses with major-DRM to one (12.7%), two (47.3%), or three (5.5%) ARV-families. Most children/adolescents harbored DRM to NNRTI (73.5%) or NRTI (61.2%). Major-DRM to PI was present in 8.3% and minor-DRM to INI in 15%. Dual-class-NRTI+NNRTI resistance appeared in 53.1% of patients. Viruses presented high/intermediate resistance to nevirapine (72.9% patients), efavirenz (70.9%), emtricitabine/lamivudine (47.9%), rilpivirine (41.7%), etravirine (39.6%), doravidine (33.3%), zidovudine (22.9%), among others. Most participants were susceptible to INI and PI. Great diversity of variants was found, with a high rate (40%) of unique recombinants.ConclusionThe high DRM prevalence observed among HIV-infected children and adolescents in Kinshasa could compromise the 95-95-95-UNAIDS targets in the DRC. It also reinforces the need for routine resistance monitoring for optimal rescue therapy election in this vulnerable population to control the spread of resistant HIV in the country.

ObjectivesWith the purpose of reducing the well-known negative impact of late presentation (LP) on people living with HIV (PLWH), guidelines on early HIV diagnosis were published in 2014 in Spain, but since then no data on LP prevalence have been published. To estimate prevalence and risk factors of LP and to evaluate their impact on the development of clinical outcomes in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) during 2004-2018.MethodsCoRIS is an open prospective multicenter cohort of PLWH, adults, naive to ART at entry. LP was defined as HIV diagnosis with CD4 count ≤350 cells/μL or an AIDS defining event (ADE). Multivariable Poisson regression models were used to estimate both prevalence ratios (PR) for the association of potential risk factors with LP and Incidence rate ratios (IRRs) for its impact on the development of the composite endpoint (first ADE, first serious non-AIDS event [SNAE] or overall mortality).Results14,876 individuals were included. Overall, LP prevalence in 2004-2018 was 44.6%. Risk factors for LP included older age, having been infected through injection drug use or heterosexual intercourse, low educational level and originating from non-European countries. LP was associated with an increased risk of the composite endpoint (IRR: 1.34; 95%CI 1.20, 1.50), ADE (1.39; 1.18, 1.64), SNAE (1.22; 1.01, 1.47) and mortality (1.71; 1.41, 2.08).ConclusionsLP remains a health problem in Spain, mainly among certain populations, and is associated with greater morbidity and mortality. Public policies should be implemented to expand screening and early diagnosis of HIV infection, for a focus on those at greatest risk of LP.

Multi-drug resistant (MDR) non-typhoidal Salmonella (NTS) is a public health concern globally. This study reports the phenotypic and genotypic antimicrobial resistance (AMR) profiles of NTS isolates from bovine lymph nodes (n = 48) and ground beef (n = 29). Furthermore, we compared genotypic AMR data of our isolates with those of publicly available NTS genomes from Mexico (n = 2400). The probability of finding MDR isolates was higher in ground beef than in lymph nodes:χ2 = 12.0, P = 0.0005. The most common resistant phenotypes involved tetracycline (40.3%), carbenicillin (26.0%), amoxicillin-clavulanic acid (20.8%), chloramphenicol (19.5%) and trimethoprim-sulfamethoxazole (16.9%), while more than 55% of the isolates showed decreased susceptibility to ciprofloxacin and 26% were MDR. Conversely, resistance to cephalosporins and carbapenems was infrequent (0-9%). MDR phenotypes were strongly associated with NTS serovar (χ2 = 24.5, P

Emotional stability-Neuroticism is a complex construct influenced by genetics and environmental factors. Women tend to exhibit higher neuroticism scores than men, which may be associated with an increased risk of suffering from some common mental conditions. Some authors have pointed out the influence of sex hormones, since they induce sexual differentiation of the brain that can lead to sex-specific behaviors. 2D:4D digit ratio is commonly used as a marker of prenatal sex hormones. In this study we analyzed whether there was an association between 2D:4D and personality measured through the BFQ in a homogeneous sample of 101 young women college students. We found a positive association between 2D:4D and emotional stability, as well as with its subdimensions emotion control and impulse control. This association could be quadratic and nonlinear. However, no association was found with the other four dimensions. We also measured anxiety, depression and global life satisfaction, variables related to neuroticism. We observed that emotional stability is positively associated to social desirability and global life satisfaction, and negatively related to anxiety and depression. On the other hand, we did not find any association between 2D:4D and anxiety, depression, and global life satisfaction. These results can be linked to other aspects such as subjective well-being and psychopathological symptoms. This study may help to better understand how these constructs are related and could lead to future projects to elucidated how these variables influence personality.

RORγt is an isoform of RORC, preferentially expressed in Th17 cells, that functions as a critical regulator of type 3 immunity. As murine Th17-driven inflammatory disease models were greatly diminished in RORC knock-out mice, this receptor was prioritised as an attractive therapeutic target for the treatment of several autoimmune diseases. Human genetic studies indicate a significant contributory role for RORC in several human disease conditions. Furthermore, genome-wide association studies (GWAS) report a significant association between inflammatory bowel disease (IBD) and the RORC regulatory variant rs4845604. To investigate if the rs4845604 variant may affect CD4+ T cell differentiation events, naïve CD4+ T cells were isolated from eighteen healthy subjects homozygous for the rs4845604 minor (A) or major (G) allele). Isolated cells from each subject were differentiated into distinct T cell lineages by culturing in either T cell maintenance medium or Th17 driving medium conditions for six days in the presence of an RORC inverse agonist (to prevent constitutive receptor activity) or an inactive diastereomer (control). Our proof of concept study indicated that genotype had no significant effect on the mean number of naïve CD4 T cells isolated, nor the frequency of Th1-like and Th17-like cells following six days of culture in any of the four culture conditions. Analysis of the derived RNA-seq count data identified genotype-driven transcriptional effects in each of the four culture conditions. Subsequent pathway enrichment analysis of these profiles reported perturbation of metabolic signalling networks, with the potential to affect the cellular detoxification response. This investigation reveals that rs4845604 genotype is associated with transcriptional effects in CD4+ T cells that may perturb immune and metabolic pathways. Most significantly, the rs4845604 GG, IBD risk associated, genotype may be associated with a differential detoxification response. This observation justifies further investigation in a larger cohort of both healthy and IBD-affected individuals.

Background Clinical outcomes among COVID-19 patients vary greatly with age and underlying comorbidities. We aimed to determine the demographic and clinical factors, particularly baseline chronic conditions, associated with an increased risk of severity in COVID-19 patients from a population-based perspective and using data from electronic health records (EHR). Methods Retrospective, observational study in an open cohort analyzing all 68,913 individuals (mean age 44.4 years, 53.2% women) with SARS-CoV-2 infection between 15 June and 19 December 2020 using exhaustive electronic health registries. Patients were followed for 30 days from inclusion or until the date of death within that period. We performed multivariate logistic regression to analyze the association between each chronic disease and severe infection, based on hospitalization and all-cause mortality. Results 5885 (8.5%) individuals showed severe infection and old age was the most influencing factor. Congestive heart failure (odds ratio -OR- men: 1.28, OR women: 1.39), diabetes (1.37, 1.24), chronic renal failure (1.31, 1.22) and obesity (1.21, 1.26) increased the likelihood of severe infection in both sexes. Chronic skin ulcers (1.32), acute cerebrovascular disease (1.34), chronic obstructive pulmonary disease (1.21), urinary incontinence (1.17) and neoplasms (1.26) in men, and infertility (1.87), obstructive sleep apnea (1.43), hepatic steatosis (1.43), rheumatoid arthritis (1.39) and menstrual disorders (1.18) in women were also associated with more severe outcomes. Conclusions Age and specific cardiovascular and metabolic diseases increased the risk of severe SARS-CoV-2 infections in men and women, whereas the effects of certain comorbidities are sex specific. Future studies in different settings are encouraged to analyze which profiles of chronic patients are at higher risk of poor prognosis and should therefore be the targets of prevention and shielding strategies.

Anopheles albitarsis F is a putative species belonging to the Albitarsis Complex, recognized by rDNA, mtDNA, partial white gene, and microsatellites sequences. It has been reported from the island of Trinidad, Venezuela and Colombia, and incriminated as a vector of malaria parasites in the latter. This study examined mitochondrially encoded cytochrome c oxidase I (MT-CO1) sequences of An. albitarsis F from malaria-endemic areas in Colombia and Venezuela to understand its relations with other members of the Complex, revised and update the geographical distribution and bionomics of An. albitarsis F and explore hypotheses to explain its phylogenetic relationships and geographical expansion. Forty-five MT-CO1 sequences obtained in this study were analyzed to estimate genetic diversity and possible evolutionary relationships. Sequences generated 37 haplotypes clustered in a group where the genetic divergence of Venezuelan populations did not exceed 1.6% with respect to Colombian samples. Anopheles albitarsis F (π = 0.013) represented the most recent cluster located closer to An. albitarsis I (π = 0.009). Barcode gap was detected according to Albitarsis Complex lineages previously reported (threshold 0.014-0.021). Anopheles albitarsis F has a wide distribution in northern South America and might play an important role in the transmission dynamics of malaria due to its high expansion capacity. Future studies are required to establish the southern distribution of An. albitarsis F in Venezuela, and its occurrence in Guyana and Ecuador.