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The hydroclimate of South America is characterized by the South American summer monsoon (SASM), a tropical atmospheric circulation that induces a summer precipitation regime, and the Southern Hemisphere Westerlies (SHW), an extratropical atmospheric circulation that induces a winter precipitation regime. Stretched between these two systems is a NW-SE-oriented region dominated by descending air masses, resulting in the South American subtropical dry zone (SASDZ), also known as the arid diagonal. We investigated the Cerro Tuzgle cushion peatland (CTP) located on the Argentine Altiplano, north of the present-day SASDZ. Previous work revealed that the CTP was consistently in the SASM regime during the last 2900 cal yr BP. Here, we extend the CTP record to the middle Holocene covering the last 7200 cal yr BP to gain further knowledge of the Holocene development of the SASM and potential modulations of the SASDZ. The prominent feature of the entire record is a distinct and lasting transition centred around 3100 cal yr BP characterized by declining minerogenic content, increasing organic carbon content, rising stable carbon isotope values of organic matter and cellulose, and increasing stable oxygen isotope values of cellulose. We interpret this specific proxy pattern as a hydroclimatic transition towards less arid conditions at the CTP after 3100 cal yr BP. The transition corresponds with the end of the continuous Holocene strengthening of the SASM between 3500 cal yr BP and 3000 cal yr BP indicated by proxy records from north and east of the CTP. The CTP does not reflect this strengthening of the SASM and rather exhibits a threshold response indicating the effective establishment of the SASM summer precipitation regime at 24°S. This suggests that moisture supply during a more arid middle Holocene was provided by isotopically depleted precipitation, while moisture supply after the transition originated from isotopically enriched SASM summer precipitation. Concurrent hydroclimatic changes in the SHW winter precipitation regime south of the SASDZ are documented in a distinct lake level rise of Laguna Aculeo (33°50´S) around 3200 cal yr BP. These coinciding hydrological changes of the SASM and the SHW precipitation regimes indicate larger scale reorganisations of atmospheric circulation components, potentially connected to major modulations of the SASDZ. Thus, our CTP record sheds light on the middle to late Holocene development of the SASM at its southern limit and corroborates connections between the tropical and extratropical hydroclimate of South America.

Achalasia is a disease characterized by the inability to relax the esophageal sphincter due to a degeneration of the parasympathetic ganglion cells located in the wall of the thoracic esophagus. Achalasia has been associated with extraesophageal dysmotility, suggesting alterations of the autonomic nervous system (ANS) that extend beyond the esophagus. The purpose of the present contribution is to investigate whether achalasia may be interpreted as the esophageal manifestation of a more generalized disturbance of the ANS which includes alterations of heart rate and/or blood pressure. Therefore simultaneous non-invasive records of the heart inter-beat intervals (IBI) and beat-to-beat systolic blood pressure (SBP) of 14 patients (9 female, 5 male) with achalasia were compared with the records of 34 rigorously screened healthy control subjects (17 female, 17 male) in three different conditions: supine, standing up, and controlled breathing at 0.1 Hz, using a variety of measures in the time and spectral domains. Significant differences in heart rate variability (HRV) and blood pressure variability (BPV) were observed which seem to be due to cardiovagal damage to the heart, i.e., a failure of the ANS, as expected according to our hypothesis. This non-invasive methodology can be employed as an auxiliary clinical protocol to study etiology and evolution of achalasia, and other pathologies that damage ANS.

The world is facing a major pulse of ecological and social changes that may favor the risk of zoonotic outbreaks. Such risk facilitation may occur through the modification of the host's community diversity and structure, leading to an increase in pathogen reservoirs and the contact rate between these reservoirs and humans. Here, we examined whether anthropization alters the relative abundance and richness of zoonotic reservoir and non-reservoir rodents in three Socio-Ecological Systems. We hypothesized that anthropization increases the relative abundance and richness of rodent reservoirs while decreasing non-reservoir species. We first developed an Anthropization index based on 15 quantitative socio-ecological variables classified into five groups: 1) Vegetation type, 2) Urbanization degree, 3) Water quality, 4) Potential contaminant sources, and 5) Others. We then monitored rodent communities in three regions of Northwestern Mexico (Baja California, Chihuahua, and Sonora). A total of 683 rodents of 14 genera and 27 species were captured, nine of which have been identified as reservoirs of zoonotic pathogens (359 individuals, 53%). In all regions, we found that as anthropization increased, the relative abundance of reservoir rodents increased; in contrast, the relative abundance of non-reservoir rodents decreased. In Sonora, reservoir richness increased with increasing anthropization, while in Baja California and Chihuahua non-reservoir richness decreased as anthropization increased. We also found a significant positive relationship between the anthropization degree and the abundance of house mice (Mus musculus) and deer mice (Peromyscus maniculatus), the most abundant reservoir species in the study. These findings support the hypothesis that reservoir species of zoonotic pathogens increase their abundance in disturbed environments, which may increase the risk of pathogen exposure to humans, while anthropization creates an environmental filtering that promotes the local extinction of non-reservoir species. [ABSTRACT FROM AUTHOR]

Plants in arid zones are constantly exposed to drought stress. The ASR protein family (Abscisic, Stress, Ripening) -a subgroup of the late embryogenesis abundant superfamily- is involved in the water stress response and adaptation to dry environments. Tomato ASR1, as well as other members of this family, is an intrinsically disordered protein (IDP) that functions as a transcription factor and a chaperone. Here we employed different biophysical techniques to perform a deep in vitro characterization of ASR1 as an IDP and showed how both environmental factors and in vivo targets modulate its folding. We report that ASR1 adopts different conformations such as α-helix or polyproline type II in response to environmental changes. Low temperatures and low pH promote the polyproline type II conformation (PII). While NaCl increases PII content and slightly destabilizes α-helix conformation, PEG and glycerol have an important stabilizing effect of α-helix conformation. The binding of Zn2+in the low micromolar range promotes α-helix folding, while extra Zn2+ results in homo-dimerization. The ASR1-DNA binding is sequence specific and dependent on Zn2+. ASR1 chaperone activity does not change upon the structure induction triggered by the addition of Zn2+. Furthermore, trehalose, which has no effect on the ASR1 structure by itself, showed a synergistic effect on the ASR1-driven heat shock protection towards the reporter enzyme citrate synthase (CS). These observations prompted the development of a FRET reporter to sense ASR1 folding in vivo. Its performance was confirmed in Escherichia coli under saline and osmotic stress conditions, representing a promising probe to be used in plant cells. Overall, this work supports the notion that ASR1 plasticity is a key feature that facilitates its response to drought stress and its interaction with specific targets.

A clear understanding of the structural foundations underlying protein aggregation is an elusive goal of central biomedical importance. A step toward this aim is exemplified by the β-barrel motif represented by the intestinal fatty acid binding protein (IFABP) and two abridged all-β sheet forms (Δ98Δ and Δ78Δ). At odds with the established notion that a perturbation of the native fold should necessarily favor a buildup of intermediate forms with an enhanced tendency to aggregate, the intrinsic stability (ΔG°H2O) of these proteins does not bear a straightforward correlation with their trifluoroethanol (TFE)-induced aggregation propensity. In view of this fact, we found it more insightful to delve into the connection between structure and stability under sub-aggregating conditions (10% TFE). In the absence of the co-solvent, the abridged variants display a common native-like region decorated with a disordered C-terminal stretch. Upon TFE addition, an increase in secondary structure content is observed, assimilating them to the parent protein. In this sense, TFE perturbs a common native like region while exerting a global compaction effect. Importantly, in all cases, fatty acid binding function is preserved. Interestingly, energetic as well as structural diversity in aqueous solution evolves into a common conformational ensemble more akin in stability. These facts reconcile apparent paradoxical findings related to stability and rates of aggregation. This scenario likely mimics the accrual of aggregation-prone species in the population, an early critical event for the development of fibrillation.

Emerging evidence has highlighted the pivotal role of microvasculature injury in the development and progression of renal fibrosis. Angiopoietin-1 (Ang-1) is a secreted vascular growth factor that binds to the endothelial-specific Tie2 receptor. Ang-1/Tie2 signaling is critical for regulating blood vessel development and modulating vascular response after injury, but is dispensable in mature, quiescent vessels. Although dysregulation of vascular endothelial growth factor (VEGF) signaling has been well studied in renal pathologies, much less is known about the role of the Ang-1/Tie2 pathway in renal interstitial fibrosis. Previous studies have shown contradicting effects of overexpressing Ang-1 systemically on renal tubulointerstitial fibrosis when different engineered forms of Ang-1 are used. Here, we investigated the impact of site-directed expression of native Ang-1 on the renal fibrogenic process and peritubular capillary network by exploiting a conditional transgenic mouse system [Pax8-rtTA/(TetO)7 Ang-1] that allows increased tubular Ang-1 production in adult mice. Using a murine unilateral ureteral obstruction (UUO) fibrosis model, we demonstrate that targeted Ang-1 overexpression attenuates myofibroblast activation and interstitial collagen I accumulation, inhibits the upregulation of transforming growth factor β1 and subsequent phosphorylation of Smad 2/3, dampens renal inflammation, and stimulates the growth of peritubular capillaries in the obstructed kidney. Our results suggest that Ang-1 is a potential therapeutic agent for targeting microvasculature injury in renal fibrosis without compromising the physiologically normal vasculature in humans.

Most societies prohibit some market transactions based on moral concerns, even when the exchanges would benefit the parties involved and would not create negative externalities. A prominent example is given by payments for human organs for transplantation, banned virtually everywhere despite long waiting lists and many deaths of patients who cannot find a donor. Recent research, however, has shown that individuals significantly increase their stated support for a regulated market for human organs when provided with information about the organ shortage and the potential beneficial effects a price mechanism. In this study we focused on payments for human organs and on another "repugnant" transaction, indoor prostitution, to address two questions: (A) Does providing general information on the welfare properties of prices and markets modify attitudes toward repugnant trades? (B) Does additional knowledge on the benefits of a price mechanism in a specific context affect attitudes toward price-based transactions in another context? By answering these questions, we can assess whether eliciting a market-oriented approach may lead to a relaxation of moral opposition to markets, and whether there is a cross-effect of information, in particular for morally controversial activities that, although different, share a reference to the "commercialization" of the human body. Relying on an online survey experiment with 5,324 U.S. residents, we found no effect of general information about market efficiency, consistent with morally controversial markets being accepted only when they are seen as a solution to a specific problem. We also found some cross-effects of information about a transaction on the acceptance of the other; however, the responses were mediated by the gender and (to a lesser extent) religiosity of the respondent--in particular, women exposed to information about legalizing prostitution reduced their stated support for regulated organ payments. We relate these findings to prior research and discuss implications for public policy.

In previous studies we demonstrated the immunohistochemical expression of aromatase in pituitary cells. In order to determine whether pituitary aromatase is involved in the paracrine regulation of prolactin-producing pituitary cells and the physiological relevance of pituitary aromatase in the control of these cells, an in vivo and in vitro immunocytochemical and morphometric study of prolactin-positive pituitary cells was carried out on the pituitary glands of adult male rats treated with the aromatase antagonist fadrozole. Moreover, we analyzed the expression of mRNA for the enzyme in pituitary cells of male adult rats by in situ hybridization. The aromatase-mRNA was seen to be located in the cytoplasm of 41% of pituitary cells and was well correlated with the immunocytochemical staining. After in vivo treatment with fadrozole, the size (cellular and nuclear areas) of prolactin cells, as well as the percentage of prolactin-positive cells and the percentage of proliferating-prolactin cells, was significantly decreased. Moreover, fadrozole decreased serum prolactin levels. In vitro, treatment with fadrozole plus testosterone induced similar effects on prolactin-positive cells, inhibiting their cellular proliferation. Our results suggest that under physiological conditions aromatase P450 exerts a relevant control over male pituitary prolactin-cells, probably transforming testosterone to estradiol in the pituitary gland.

Aging enhances frequency of chronic diseases like cardiovascular diseases or periodontitis. Here we reproduced an age-dependent model of the periodontium, a fully physiological approach to periodontal conditions, to evaluate the impact of dietary fat type on gingival tissue of young (6 months old) and old (24 months old) rats.Animals were fed life-long on diets based on monounsaturated fatty acids (MUFA) as virgin olive oil, n-6 polyunsaturated fatty acids (n-6PUFA), as sunflower oil, or n-3PUFA, as fish oil. Age-related alveolar bone loss was higher in n-6PUFA fed rats, probably as a consequence of the ablation of the cell capacity to adapt to aging. Gene expression analysis suggests that MUFA or n-3PUFA allowed mitochondria to maintain an adequate turnover through induction of biogenesis, autophagy and the antioxidant systems, and avoiding mitochondrial electron transport system alterations.The main finding is that the enhanced alveolar bone loss associated to age may be targeted by an appropriate dietary treatment. The mechanisms involved in this phenomenon are related with an ablation of the cell capacity to adapt to aging. Thus, MUFA or n-3PUFA might allow mitochondrial maintaining turnover through biogenesis or autophagy. They might also be able to induce the corresponding antioxidant systems to counteract age-related oxidative stress, and do not inhibit mitochondrial electron transport chain. From the nutritional and clinical point of view, it is noteworthy that the potential treatments to attenuate alveolar bone loss (a feature of periodontal disease) associated to age could be similar to some of the proposed for the prevention and treatment of cardiovascular diseases, a group of pathologies recently associated with age-related periodontitis.

For most secretory pathway proteins, crossing the endoplasmic reticulum (ER) membrane is an irreversible process. However, in some cases this flow can be reversed. For instance, misfolded proteins retained in the ER are retrotranslocated to the cytosol to be degraded by the proteasome. This mechanism, known as ER associated degradation (ERAD), is exploited by several bacterial toxins to gain access to the cytosol. Interestingly, some ER resident proteins can also be detected in the cytosol or nucleus, calreticulin (CRT) being the most studied. Here we show that in Trypanosoma cruzi a minor fraction of CRT localized to the cytosol. ER calcium depletion, but not increasing cytosolic calcium, triggered the retrotranslocation of CRT in a relatively short period of time. Cytosolic CRT was subsequently degraded by the proteasome. Interestingly, the single disulfide bridge of CRT is reduced when the protein is located in the cytosol. The effect exerted by ER calcium was strictly dependent on the C-terminal domain (CRT-C), since a CRT lacking it was totally retained in the ER, whereas the localization of an unrelated protein fused to CRT-C mirrored that of endogenous CRT. This finding expands the regulatory mechanisms of protein sorting and may represent a new crossroad between diverse physiological processes.

Participation in technical/research internships may improve undergraduate graduation rates and persistence in science, technology, engineering, and mathematics (STEM), yet little is known about the benefits of these activities a) for community college students, b) when hosted by national laboratories, and c) beyond the first few years after the internship. We applied Social Cognitive Career Theory (SCCT) to investigate alumni perspectives about how CCI at Lawrence Berkeley National Laboratory (LBNL) impacted their academic/career activities. We learned that alumni had low confidence and expectations of success in STEM as community college students. Participation in CCI increased their professional networks, expectations of success, and STEM skills, identity, and self-efficacy/confidence. Hispanic/Latinx alumni recalled the positive impact of mentors who prioritized personal connections, and women valued "warm" social environments. We propose several additions to the SCCT model, to better reflect the supports and barriers to STEM persistence for community college students., Competing Interests: No potential conflict of interest was reported by the authors, with respect to the research, authorship, and/or publication of this work., (Copyright: © 2025 Coté et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Ischemia-reperfusion injury (IRI) inevitably occurs during kidney transplantation and extended ischemia is associated with delayed graft function and poor outcomes. Remote ischemic preconditioning (RIPC) is a simple, noninvasive procedure aimed at reducing IRI and improving graft function. Experimental studies have implicated the kynurenine pathway as a protective mechanism behind RIPC., Methods: First, paired biopsies from 11 living kidney donors were analyzed to characterize the acute transcriptomic response to IRI. Second, 16 living kidney donors were subjected to either RIPC (n = 9) or no pretreatment (n = 7) to evaluate the impact of RIPC on the transcriptomic response to IRI. Finally, the effect of RIPC on plasma metabolites was analyzed in 49 healthy subjects., Results: There was a robust immediate response to IRI in the renal transcriptomes of living-donor kidney transplantation, including activation of the mitogen-activated protein kinase (MAPK) and epidermal growth factor receptor (EGFR) pathways. Preconditioning with RIPC did not significantly alter the transcriptomic response to IRI or the concentration of plasma metabolites., Conclusions: The present data validate living-donor kidney transplantation as a suitable model for mechanistic studies of IRI in human kidneys. The failure of RIPC to alter transcriptomic responses or metabolites in the kynurenine pathway raises the question of the robustness of the standard procedure used to induce RIPC, and might explain the mixed results in clinical trials evaluating RIPC as a method to attenuate IRI., Competing Interests: J.S.R. reports funding from GSK and Sanofi and fees from Travere Therapeutics and Astex. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development, or marketed products associated with this research to declare., (Copyright: © 2024 Nordström et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Computing Lagrangian trajectories with ocean circulation models is a powerful way to infer larval dispersal pathways and connectivity. Defining release areas and timing of particles to represent larval habitat realistically is critical to obtaining representative dispersal pathways. However, it is challenging due to spatial and temporal variability in larval density. Forward-tracking particle experiments were conducted to study larval connectivity of four species (neritic or mesopelagic) in the Gulf of Mexico's (GoM) deep-water region. A seasonal climatology coupled with predicted potential larval habitat models based on generalized additive models was used to delimit the particle dispersal origin. Two contrasting mesoscale circulation patterns were examined: (1) high Loop Current (LC) intrusion, absence of recently detached LC anticyclonic eddies (LC-ACE), and no interaction between LC-ACEs and the semi-permanent cyclonic eddy (CE) in the Bay of Campeche (BoC), and (2) limited LC intrusion, a recently detached LC-ACE, and interaction between LC-ACEs and the BoC's CE. To simulate larval transport, virtual larvae were randomly released in the potential habitats and advected for 30 days with the velocity fields of the HYbrid Coordinate Ocean Model with hourly-resolution assimilation. Potential habitat location and size played a major role in dispersal and connectivity. A greater percentage of particles were retained in potential habitats restricted to the southern BoC, suggesting lower connectivity with other GoM regions than those encompassing most of the BoC or the central Gulf. Mesoscale feature interactions in the western GoM and BoC led to greater dispersion along the western basin. By contrast, the absence of ACE-CE interaction in the BoC led to greater retention and less connectivity between the southern and northern GoM. Under high LC intrusion, particles seeded north of the Yucatan Shelf were advected through the Florida Straits and dispersed within the GoM. Coupling potential habitat models with particle experiments can help characterize the dispersal and connectivity of fish larvae in oceanic systems., Competing Interests: No authors have competing interests., (Copyright: © 2024 Daudén-Bengoa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Previous literature suggests that mindfulness meditation can have positive effects on mental health, however, its mechanisms of action are still unclear. In this pre-registered study, we investigate the effects of mindfulness training on lapses of attention (and their associated neural correlates) during meditation practice. For this purpose, we recorded Electroencephalogram (EEG) during meditation practice before and after 8 weeks of mindfulness training (or waitlist) in 41 participants (21 treatment and 20 controls). In order to detect lapses of attention and characterize their EEG correlates, we interrupted participants during meditation to report their level of focus and drowsiness. First, we show that self-reported lapses of attention during meditation practice were associated to an increased occurrence of theta oscillations (3-6 Hz), which were slower in frequency and more spatially widespread than theta oscillations occurring during focused attention states. Then, we show that mindfulness training did not reduce the occurrence of lapses of attention nor their associated EEG correlate (i.e. theta oscillations) during meditation. Instead, we find that mindfulness training was associated with a significant slowing of alpha oscillations in frontal electrodes during meditation. Crucially, frontal alpha slowing during meditation practice has been reported in experienced meditators and is thought to reflect relative decreases in arousal levels. Together, our findings provide insights into the EEG correlates of mindfulness meditation, which could have important implications for the identification of its mechanisms of action and/or the development of neuromodulation protocols aimed at facilitating meditation practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rodriguez-Larios et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The aim of this present clinical trial is to evaluate the effectiveness of a multicomponent prehabilitation programme administered through educational videos versus another programme based on written exercise recommendations, in patients scheduled for lumbar radiculopathy surgery. This study will be a multicentre, controlled, randomised, parallel clinical trial. One hundred participants undergoing lumbar radiculopathy surgery who meet the established inclusion criteria will be recruited at different Spanish hospitals. The experimental group will follow a 4-week prehabilitation programme combining therapeutic exercise, back care education, and pain neuroscience education delivered through videos designed for consumption at home. The control group will be provided with written instructions to perform therapeutic exercises during the same prehabilitation time period. The primary outcome of the study will be disability, assessed using the Spanish version of the Oswestry Disability Index. The secondary outcomes will be pain perception, health-related quality of life, fear avoidance, kinesiophobia, catastrophising, anxiety, depression, physical activity, and the treatment satisfaction of the patients. This study will provide evidence for the effectiveness of a home-based multicomponent prehabilitation programme that addresses some already identified barriers to patient attendance in face-to-face programmes. Understanding the medium and long-term effects of pre-surgery lumbar muscle training and pain neuroscience education administered via instructional videos watched by patients at home, will help improve the design of prehabilitation programmes in this population while also improving the cost-effectiveness of such interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Arguisuelas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Complete revascularization (CR) in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD), is associated with a reduction in major adverse cardiovascular events (MACE). However, there is uncertainty about whether nonculprit-lesion revascularization should be performed, during index hospitalization or delayed, especially regarding health care resources utilization. In this study, we aimed to evaluate the impact of in-hospital nonculprit-lesion revascularization vs. delayed (after discharge) revascularization on the length of index hospitalization., Methods: In this single-center study, we randomly assigned patients with STEMI and MVD who underwent successful culprit-lesion PCI to a strategy of either CR during in-hospital admission or a delayed CR after discharge. The first primary endpoint was the length of hospital stay. The second endpoint was the composite of cardiovascular death, myocardial infarction or ischemia-driven revascularization at 12 months (MACE)., Results: From January 2018 to December 2022, we enrolled 258 patients (131 allocated to CR during in-hospital admission and 127 to an after-discharge CR). We found a significant reduction in the length of hospital stay in those assigned to after-discharge CR strategy [4 days (3-5) versus 7 days (5-9); p = 0.001]. At 12-month of follow-up, no differences were found in the occurrence of MACE, 7 (5.34%) patients in in-hospital CR and 4 (3.15%) in after-discharge CR strategy; (hazard ratio, 0.59; 95% confidence interval, 0.17 to 2.02; p = 0.397)., Conclusions: In STEMI patients with MVD, an after-discharge CR strategy reduces the length of index hospitalization without an increased risk of MACE after 12 months of follow-up., Trial Registration: ClinicalTrials.gov number: NCT04743154., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rumiz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Peru's holds the highest COVID death rate per capita worldwide. Key to this outcome is the lack of robust, rapid, and accurate molecular tests to circumvent the elevated costs and logistics of SARS-CoV-2 detection via RT-qPCR. To facilitate massive and timely COVID-19 testing in rural and socioeconomically deprived contexts, we implemented and validated RCSMS, a rapid and sensitive CRISPR-Cas12a test for the molecular detection of SARS-CoV-2 from saliva. RCSMS uses the power of CRISPR-Cas technology and lateral flow strips to easily visualize the presence of SARS-CoV-2 even in laboratories with limited equipment. We show that a low-cost thermochemical treatment with TCEP/EDTA is sufficient to inactivate viral particles and cellular nucleases in saliva, eliminating the need to extract viral RNA with commercial kits, as well as the cumbersome nasopharyngeal swab procedure and the requirement of biosafety level 2 laboratories for molecular analyses. Notably, RCSMS performed outstandingly in a clinical validation done with 352 patients from two hospitals in Lima, detecting as low as 50 viral copies per 10 μl reaction in 40 min, with sensitivity and specificity of 96.5% and 99.0%, respectively, relative to RT-qPCR. The negative and positive predicted values obtained from this field validation indicate that RCSMS can be confidently deployed in both high and low prevalence settings. Like other CRISPR-Cas-based biosensors, RCSMS can be easily reprogrammed for the detection of new SARS-CoV-2 variants. We conclude that RCSMS is a fast, efficient and inexpensive alternative to RT-qPCR for expanding COVID-19 testing capacity in Peru and other low- and middle-income countries with precarious healthcare systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abugattas-Núñez del Prado et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Batrachochytrium dendrobatidis (Bd) is a lethal fungal species that parasitizes vertebrates and is associated with the worldwide decline of amphibian populations. The development of sensitive, rapid detection methods, particularly DNA-based techniques, is critical for effective management strategies. This study evaluates the efficacy of DNA extraction and a portable PCR device in a mountable field laboratory setup for detecting Bd near the habitats of three critically endangered Atelopus toad species in Ecuador. We collected skin swabs from Atelopus balios, A. nanay, and A. bomolochos, and environmental DNA (eDNA) samples from streams in Andean and coastal regions of Ecuador. For eDNA, a comparison was made with duplicates of the samples that were processed in the field and in a standard university laboratory. Our findings revealed Bd detection in eDNA and swabs from 6 of 12 water samples and 10 of 12 amphibian swab samples. The eDNA results obtained in the field laboratory were concordant with those obtained under campus laboratory conditions. These findings highlight the potential of field DNA-based monitoring techniques for detecting Bd in amphibian populations and their aquatic habitats, particularly in remote areas. Furthermore, this research aligns with the National Action Plan for the Conservation of Ecuadorian Amphibians and contributes to the global effort to control this invasive and deadly fungus., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Riascos-Flores et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Religious leaders have the potential to play a significant role in the identification and referral of individuals with mental health problems., Objective: This study sought to understand the perceptions of religious leaders in regards to identifying and referring parishioners with mental health issues to healthcare professionals, in Chimbote, Peru., Methods: We performed a cross-sectional study that covered religious leaders of different religious groups in Chimbote. The leaders completed a survey that assessed their characteristics, past experiences of detecting and referring those with mental health problems to healthcare professionals, and perceptions of four clinical cases (for which we used the Clergy's Perception of Mental Illness Survey instrument)., Results: We included 109 religious' leaders of four religious groups (11 Catholics, 70 Evangelicals, 21 Mormons, and 7 Adventists). Of these, 50.5% had received at least one request for help with mental health issues from a parishioner in the previous month, over 85% expressed a desire for training in identifying mental health problems, and 22-30% reported receiving any training. While the majority of leaders were able to correctly identify cases of depression, alcohol dependence, and drug problems, only 62% correctly classified a case of schizophrenia. Despite this, 80% stated that they would refer their parishioners to healthcare professionals., Conclusion: Parishioners tend to consult their religious leaders regarding their mental health and approximately 80% stated they would refer such cases to a healthcare professional. However, less than one-third of the leaders had received training to detect mental health problems. These results suggest that there is a need for training programs to improve the ability of religious leaders to identify and refer individuals with mental health issues., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cjuno et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

"Flow experience" is a term used to describe the state of being fully immersed in what you are doing. The Flow State Scale (FSS-2) was developed to assess how people feel when they are in the flow state while participating in certain sports activities. The goal of this study was to obtain a short adapted version of the FSS-2 for the Brazilian-Portuguese language and for general activities (FSS-BR-S). To do this, we translated it both ways (forwards and backwards) and verified that the translation was accurate. Methods: After getting answers from 396 Brazilian participants, we performed (1) the construct validity of the FSS-BR-S and (2) the psychometric item quality analysis. The confirmatory factorial analysis shows that a FSS-BR-S factorial model is the best fit for the data (χ2 = 44.36, p = .023, df = 27, χ2/df = 1.64, CFI = 0.99, TLI = 0.98, and RMSEA = 0.04). Reliability tests done in this structure show that the FSS-BR-S (which only has nine items) has good internal consistency. The item quality analysis reveals that its difficulty and differentiating parameters are good for estimating the overall flow state. The test information curve for the short version demonstrates that it is very useful for estimating the flow states of each disposition. Discussion and Conclusions: Based on these findings, we can conclude that the FSS-BR-S has demonstrated sufficient validity to be used with Brazilians., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bittencourt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study assessed the seroprevalence of SARS-CoV-2 in 496 asymptomatic individuals from Mato Grosso do Sul, located in Dourados, the largest periurban indigenous area in Brazil, from January 25 to February 4, 2021. The volunteers participated before receiving their first dose of the CoronaVac inactivated vaccine. For screening, blood samples were collected and analyzed using SARS-CoV-2 rapid tests and the enzyme-linked immunosorbent assay (ELISA). We observed varying trends in total anti-SARS-CoV-2 antibodies across different variables. Seropositivity among the participants tested was 63.70% (316/496) using the rapid test and 52.82% (262/496) were positive using the ELISA method. The majority of participants identified with the Guarani-Kaiowá ethnic group, with 66.15% (217/328), and other ethnic groups with 58.84% (193/328). The median age of the subjects was 30.5 years, with 79.57% (261/328) being femaleThis research showed the elevated seroprevalence of SARS-CoV-2 antibodies in asymptomatic Brazilians. The findings indicate a high seropositivity rate among the asymptomatic indigenous population of Midwest Brazil. This underscores the overlooked status of these communities and underscores the need for targeted national initiatives that emphasize the protection of vulnerable ethnic groups in the fight against COVID-19., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 de Oliveira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The effect of 20% high degree polymerized agave fructans (HDPAF) on the induction of the defense system in avocado fruits was investigated by transcriptomic analysis at 1, 24 and 72 h after treatment, and the effect of HDPAF on respiration rate and ethylene production was also analyzed. Transcriptomic profiling revealed 5425 differentially expressed genes (DEGs), 55 of which were involved in the pathways related to plant defense response to pathogens. Key genes were associated with phenylpropanoid biosynthesis, mitogen-activated protein signaling, plant hormone signaling, calcium ion signal decoding, and pathogenesis-related proteins. Dysregulated genes involved in ethylene biosynthesis were also identified, and the reduction in ethylene production by HDPAF was corroborated by gas chromatography, where three days of delayed peak production was observed compared to that in water-treated fruits. These results help to understand the mechanism of induction of the avocado defense system by applying HDPAF and support the application of HDPAF as an efficient postharvest treatment to extend the shelf life of the fruit., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cuéllar-Torres et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: There is a sparsity of knowledge of the specific mechanisms through which financial and non-financial incentives impact the performance of health teams. This study aims to address this knowledge gap by examining an in-kind incentives program for healthcare teams implemented in three districts in Belize (2012-2022) as part of the Salud Mesoamerica Initiative, which aimed to improve healthcare quality., Methods: We performed a qualitative study to understand the mechanisms through which the in-kind incentive program supported quality improvement in Belize. We conducted key informant interviews (April-June 2021) remotely on a sample of former and current healthcare workers from Belize's Ministry of Health and Wellness familiar with the program. We analyzed responses using qualitative content analysis. We used open coding to identify patterns and themes., Results: We conducted eight key informant interviews from a pool of thirty potential informants. Our analysis of the interviews yielded a total of 11 major themes with 27 subthemes. Most informants reported that in-kind incentives were not the primary motivation for improving their performance, though they did acknowledge that incentives had increased their attention on the quality of care provided. Conversely, we found that quarterly measurements and supportive supervision by national level authorities offered an external validation mechanism and instilled frontline staff with a sense of shared responsibility towards improving their performance. The majority of informants conveyed positive opinions about the in-kind incentives program., Conclusions: Our study contributes to the understanding of how in-kind incentives can enhance performance. We found that in-kind incentives created extrinsic motivation, leading to an increased focus on quality. Standardized measurements and supportive supervision improved intrinsic motivation and formed a stronger commitment to quality of care. Rather than focusing on tangible incentives, explicitly incorporating standardized measurements and supportive supervision in the routine work of the Ministry of Health could have longer lasting effects on quality improvement., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rios-Zertuche et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: An association of ABO blood group and COVID-19 remains controversial., Methods: Following STROBE guidance for observational research, we explored the distribution of ABO blood group in patients hospitalized for acute COVID-19 and in those with Long COVID. Contingency tables were made and risk factors were explored using crude and adjusted Mantle-Haentzel odds ratios (OR and 95% CI)., Results: Up to September 2022, there were a total of 5,832 acute COVID-19 hospitalizations in our hospital, corresponding to 5,503 individual patients, of whom blood group determination was available for 1,513 (27.5%). Their distribution by ABO was: 653 (43.2%) group 0, 690 (45.6%) A, 113 (7.5%) B, and 57 (3.8%) AB, which corresponds to the expected frequencies in the general population. In parallel, of 676 patients with Long COVID, blood group determination was available for 135 (20.0%). Their distribution was: 60 (44.4%) from group 0, 61 (45.2%) A, 9 (6.7%) B, and 5 (3.7%) AB. The distribution of the ABO system of Long COVID patients did not show significant differences with respect to that of the total group (p ≥ 0.843). In a multivariate analysis adjusting for age, sex, ethnicity, and severity of acute COVID-19 infection, subgroups A, AB, and B were not significantly associated with developing Long COVID with an OR of 1.015 [0.669-1.541], 1.327 [0.490-3.594] and 0.965 [0.453-2.058], respectively. The effect of the Rh+ factor was also not significant 1,423 [0.772-2,622] regarding Long COVID., Conclusions: No association of any ABO blood subgroup with COVID-19 or developing Long COVID was identified., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Soriano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The COVID-19 pandemic remains the pre-eminent global health problem, and yet after more than three years there is still no prophylactic agent against the disease aside from vaccines. The objective of this study was to evaluate whether pre-existing, outpatient medications approved by the US Food and Drug Administration (FDA) reduce the risk of hospitalization due to COVID-19. This was a retrospective cohort study of patients from across the United States infected with COVID-19 in the year 2020. The main outcome was adjusted odds of hospitalization for COVID-19 amongst those positive for the infection. Outcomes were adjusted for known risk factors for severe disease. 3,974,272 patients aged 18 or older with a diagnosis of COVID-19 in 2020 met our inclusion criteria and were included in the analysis. Mean age was 50.7 (SD 18). Of this group, 290,348 patients (7.3%) were hospitalized due to COVID-19, similar to the CDC's reported estimate (7.5%). Four drugs showed protective effects against COVID-19 hospitalization: rosuvastatin (aOR 0.91, p = 0.00000024), empagliflozin-metformin (aOR 0.69, p = 0.003), metformin (aOR 0.97, p = 0.017), and enoxaparin (aOR 0.88, p = 0.0048). Several pre-existing medications for outpatient use may reduce severity of disease and protect against COVID-19 hospitalization. Well-designed clinical trials are needed to assess the efficacy of these agents in a therapeutic or prophylactic setting., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sandhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Multidirectional jumping and repeated sprint ability are crucial performance factors in basketball. The main aim of this investigation was to examine the neuromuscular performance and body balance adaptations following basketball-specific combined training programs based on drop jump and multidirectional repeated sprint versus multidirectional plyometric training. Forty-two professional basketball male players participated in the current investigation and were randomly assigned to three groups: a combined group (COMB; n = 14), a multidirectional jump group (MJG; n = 14) and an active control group (CON; n = 14). The COMB and the MJG groups completed the 8-week training programs with two weekly sessions while the CON continued their usual training. The static and dynamic balance tests, the repeated sprint ability test (IRSA5COD), the T-change of direction (CoD) test, the vertical jump tests, the five time-jump test (FJT) were performed by participants before and after the intervention period. The results showed a significant main effect of time with remarkable improvements at the end of the intervention (P < 0.001, effect size small/moderate) except the physiological parameters for IRSA5COD. Only, significant group × time interactions for body balance, T-CoD test, IRSA5COD (total time and best time), and jump tests were found (P < 0.001, effect size from trivial to moderate). Bonferroni corrected post-hoc tests revealed significantly greater improvement in favor of COMB compared to MJG for body balance, CoD and IRSA5COD (P < 0.005, effect size small/moderate). Otherwise, no significant differences between COMB and MJG concerning jump performances were found. Combined drop jump and multidirectional repeated sprint training program lead to significantly better neuromuscular performance, body balance and CoD in professional basketball players when compared with an usual training., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Brini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We conducted research to understand online trade in jaguar parts and develop tools of utility for jaguars and other species. Our research took place to identify potential trade across 31 online platforms in Spanish, Portuguese, English, Dutch, French, Chinese, and Vietnamese. We identified 230 posts from between 2009 and 2019. We screened the images of animal parts shown in search results to verify if from jaguar; 71 posts on 12 different platforms in four languages were accompanied by images identified as definitely jaguar, including a total of 125 jaguar parts (50.7% posts in Spanish, 25.4% Portuguese, 22.5% Chinese and 1.4% French). Search effort varied among languages due to staff availability. Standardizing for effort across languages by dividing number of posts advertising jaguars by search time and number of individual searches completed via term/platform combinations changed the proportions the rankings of posts adjusted for effort were led by Portuguese, Chinese, and Spanish. Teeth were the most common part; 156 posts offered at least 367 teeth and from these, 95 were assessed as definitely jaguar; 71 of which could be linked to a location, with the majority offered for sale from Mexico, China, Bolivia, and Brazil (26.8, 25.4, 16.9, and 12.7% respectively). The second most traded item, skins and derivative items were only identified from Latin America: Brazil (7), followed by Peru (6), Bolivia (3), Mexico (2 and 1 skin piece), and Nicaragua and Venezuela (1 each). Whether by number of posts or pieces, the most commonly parts were: teeth, skins/pieces of skins, heads, and bodies. Our research took place within a longer-term project to assist law enforcement in host countries to better identify potential illegal trade and presents a snapshot of online jaguar trade and methods that also may have utility for many species traded online., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Polisar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Noguez Imm et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Low temperature and sodium butyrate (NaBu) are two of the most used productivity-enhancing strategies in CHO cell cultures during biopharmaceutical manufacturing. While these two approaches alter the balance in the reciprocal relationship between cell growth and productivity, we do not fully understand their mechanisms of action beyond a gross cell growth inhibition. Here, we used continuous culture to evaluate the differential effect of low temperature and NaBu supplementation on CHO cell performance and gene expression profile. We found that an increase in cell-productivity under growth-inhibiting conditions was associated with the arrest of cells in the G1/G0 phase. A transcriptome analysis revealed that the molecular mechanisms by which low temperature and NaBu arrested cell cycle in G1/G0 differed from each other through the deregulation of different cell cycle checkpoints and regulators. The individual transcriptome changes in pattern observed in response to low temperature and NaBu were retained when these two strategies were combined, leading to an additive effect in arresting the cell cycle in G1/G0 phase. The findings presented here offer novel molecular insights about the cell cycle regulation during the CHO cell bioprocessing and its implications for increased recombinant protein production. This data provides a background for engineering productivity-enhanced CHO cell lines for continuous manufacturing., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Avello et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: In 2010, British Columbia (BC) implemented HIV Treatment as Prevention (TasP) as policy. We examined trends in virologic suppression and determinants of significant viremia among a prospective biobehavioural cohort of men who have sex with men (gbMSM) in Vancouver from 2012-2017., Methods: Respondent-driven sampling was used to recruit sexually active gbMSM (≥16 years) who completed biannual study visits with a computer-assisted self-interview and clinical CD4 and viral load (VL) testing. We linked participant data with the BC HIV Drug Treatment Program to obtain antiretroviral dispensing and VL data. We conducted a trend analysis of VL suppression using univariable generalized estimating equation (GEE) multi-level modelling and multivariable GEE to identify factors associated with episodes of VL ≥200 copies/mL., Results: Of 774 participants, 223 were living with HIV at baseline and 16 were diagnosed during follow-up (n = 239). We observed a significant trend towards reduced levels of unsuppressed VL (>200 copies/mL) from 22% (07/2012-12/2012) to 12% (07/2016-12/2016) (OR:0.87; 95%CI:0.83-0.91 for each 6-month period). Among those with at least one follow-up visit, (n = 178, median follow-up = 3.2 years, median age = 46.9 years), younger age (aOR:0.97; 95%CI:0.94-0.99, per year), ecstasy use (aOR:1.69; 95%CI:1.13-2.53), crystal methamphetamine use (aOR:1.71; 95%CI:1.18-2.48), seeking sex via websites (aOR:1.46; 95%CI:1.01-2.12), and lower HIV treatment optimism (aOR:0.94; 95%CI:0.90-0.97) were associated with episodes of elevated viremia., Conclusions: During a period when TasP policy was actively promoted, we observed a significant trend towards reduced levels of unsuppressed VL. Continued efforts should promote HIV treatment optimism and engagement, especially among younger gbMSM and those who use ecstasy and crystal methamphetamine., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Momentum is funded through the National Institute on Drug Abuse (R01DA031055-01A1) and the Canadian Institutes for Health Research (MOP-107544, FDN-143342, PJT-153139). HLA was supported by a Postdoctoral Fellowship Award from the Canadian Institutes of Health Research (Grant # MFE-152443). NJL was supported by a CANFAR/CTN Postdoctoral Fellowship Award. DMM and NJL are supported by Scholar Awards from the Michael Smith Foundation for Health Research (#5209, #16863). KGC is supported by a Canadian HIV Trials Network / Canadian Foundation for AIDS Research Postdoctoral Fellowship award, a Michael Smith Foundation for Health Research Trainee award, and a Canadian Institutes of Health Research Health Systems Impact Fellowship award. JMS is supported by a Michael Smith Foundation for Health Research Trainee award and a CTN CIHR Canadian HIV/AIDS Trials Network postdoctoral fellowship award.JM is supported with grants paid to his institution by the British Columbia Ministry of Health and by the US National Institutes of Health (R01DA036307). He has also received limited unrestricted funding, paid to his institution, from Abbvie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. The remaining authors report no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The British Columbia Centre for Excellence in HIV/AIDS (BC-CfE) may, upon meeting all legislative and policy obligations, provide de-identified data used in the manuscript for external research use. Identifiable data will not be provided to external researchers. Requests for access to the research dataset must be directed to the Data Analysis Team using the BC-CfE Data Analysis Research Form. The Data Analysis Team and the Privacy Officer will review external data access requests and if approved, the de-identified research dataset will be provided via Secure File Transfer Protocol to the researcher.

Coastal wetlands are ecosystems associated with intense carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) recycling, modulated by salinity and other environmental factors that influence the microbial community involved in greenhouse gases production and consumption. In this study, we evaluated the influence of environmental factors on GHG concentration and benthic microbial community composition in coastal wetlands along the coast of the semiarid region. Wetlands were situated in landscapes along a south-north gradient of higher aridity and lower anthropogenic impact. Our results indicate that wetlands have a latitudinal variability associated with higher organic matter content at the north, especially in summer, and higher nutrient concentration at the south, predominantly in winter. During our sampling, wetlands were characterized by positive CO2 μM and CH4 nM excess, and a shift of N2O nM excess from negative to positive values from the north to the south. Benthic microbial communities were taxonomically diverse with > 60 phyla, especially in low frequency taxa. Highly abundant bacterial phyla were classified into Gammaproteobacteria (Betaproteobacteria order), Alphaproteobacteria and Deltaproteobacteria, including key functional groups such as nitrifying and methanotrophic bacteria. Generalized additive model (GAM) indicated that conductivity accounted for the larger variability of CH4 and CO2, but the predictions of CH4 and CO2 concentration were improved when latitude and pH concentration were included. Nitrate and latitude were the best predictors to account for the changes in the dissolved N2O distribution. Structural equation modeling (SEM), illustrated how the environment significantly influences functional microbial groups (nitrifiers and methane oxidizers) and their resulting effect on GHG distribution. Our results highlight the combined role of salinity and substrates of key functional microbial groups with metabolisms associated with both carbon and nitrogen, influencing dissolved GHG and their potential exchange in natural and anthropogenically impacted coastal wetlands., Competing Interests: The authors have declared that no competing interests exist.

Preventive and modeling approaches to address the COVID-19 pandemic have been primarily based on the age or occupation, and often disregard the importance of heterogeneity in population contact structure and individual connectivity. To address this gap, we developed models based on Erdős-Rényi and a power law degree distribution that first incorporate the role of heterogeneity and connectivity and then can be expanded to make assumptions about demographic characteristics. Results demonstrate that variations in the number of connections of individuals within a population modify the impact of public health interventions such as lockdown or vaccination approaches. We conclude that the most effective strategy will vary depending on the underlying contact structure of individuals within a population and on timing of the interventions., Competing Interests: The authors have declared that no competing interests exist.

Background: The COVID-19 pandemic in Brazil has been showing a pattern of distribution of related deaths associated with individual socioeconomic status (SES). However, little is known about the role of SES in the distribution of the mortality rate in different population, from an ecological perspective., Objective: The objective of this study was to evaluate the role of socioeconomic factors in the distribution of the COVID-19-related mortality rate among Brazilian municipalities in 2020., Methods: We conducted a retrospective, cross-sectional, observational, population-wide, and ecological study, using data of COVID-19-related deaths from the Influenza Epidemiological Surveillance Information System database (SIVEP-Gripe) and SES from the Social Vulnerability Index (SVI), the Human Development Index (HDI), the Geographic Index of the Socioeconomic Context and Social Studies (GeoSES), and 2010 Demographic Census (IBGE/Brazil). We computed crude, age- and sex-standardized, and the latter offset by the time of exposure to the epidemic mortality rates. To determine socioeconomic factors associated with mortality rates we used log-linear models with state codes as a random effect and Haversine variance-covariance matrix., Results: 191,528 deaths were related to COVID-19 and distributed in 4,928 (88.55%) Brazilian municipalities. Whatever the socioeconomic indexes used, the R2 were very small to explain SMRT. Consistent across all socioeconomic indexes used, high-income, more educated, and well infrastructure municipalities generally had higher mortality rates., Conclusion: Excluding the effect of demographic structure and pandemic timing from mortality rates, the contribution of SES to explain differences in COVID-19-related mortality rates among municipalities in Brazil became very low. The impact of SES on COVID-19-related mortality may vary across levels of aggregation. Urban infrastructure, which includes mobility structures, more complex economic activities and connections, may have influenced the average municipal death rate., Competing Interests: The authors have declared that no competing interests exist.

Aims: A Markov model was adapted to assess the real-world cost-effectiveness of rivaroxaban, dabigatran and apixaban. Each of these non-vitamin K antagonist oral anticoagulants was compared with vitamin K antagonist for stroke prevention in patients with non-valvular atrial fibrillation in Spain., Methods: All inputs were derived from real-world studies: baseline patient characteristics, clinical event rates, as well as persistence rates for the vitamin K antagonist treatment option. A meta-analysis of real-world studies provided treatment effect and persistence data for rivaroxaban, dabigatran and apixaban, each compared with vitamin K antagonist therapy. The model considered 3-month cycles over a lifetime horizon. The model outcomes included different costs, quality-adjusted life years and life-years gained. Sensitivity analyses were performed to test the robustness of the model., Results: When compared with vitamin K antagonist, rivaroxaban incurred incremental costs of €77 and resulted in incremental quality-adjusted life years of 0.08. The incremental cost per quality-adjusted life year was €952. For the same comparison, the incremental cost per quality-adjusted life year for dabigatran was €4,612. Finally, compared with vitamin K antagonist, the incremental cost per quality-adjusted life year for apixaban was €32,015. The sensitivity analyses confirmed the robustness of the base case results. The probabilities to be cost-effective versus vitamin K antagonist were 94%, 86% and 35%, respectively, for rivaroxaban, dabigatran and apixaban, considering a willingness-to-pay threshold of €22,000 per quality-adjusted life year gained, based on a cost-effectiveness study of the Spanish National Health System., Conclusion: These results suggest that rivaroxaban and dabigatran are cost-effective versus vitamin K antagonist for stroke prevention in non-valvular atrial fibrillation, from the Spanish National Health System perspective., Competing Interests: Kevin Bowrin is an employee of Bayer plc, Jean-Baptiste Briere is an employee of Bayer AG. Aurélie Millier and Jean Tardu are employees of Creativ-Ceutical, which received funding from Bayer AG. Mondher Toumi is a consultant for Creativ-Ceutical. Carlos Escobar Cervantes, Julio Martí-Almor and Alejandro Pérez Cabeza received consulting fees for their critical inputs on study design and results interpretation. C. Escobar reports personal fees from Bayer, Boehringer, Bristol Myers Squibb, Daiichi Sankyo and Pfizer outside the submitted work. J. Martí-Almor reports personal fees from Bayer, Daiichi Sankyo, Pfizer and Boehringer outside the submitted work. A. Pérez Cabeza reports personal fees from Bayer, Boehringer, Bristol Myers Squibb, Daiichi Sankyo and Pfizer outside the submitted work.

Background: Reported cases of COVID-19 may be underestimated due to mild or asymptomatic cases and a low testing rate in the general population., Research Question: What is the seroprevalence of SARS-CoV-2 infection in the general population and how it compares with the data on SARS-CoV-2 cases reported by a national health surveillance system (SNVS 2.0)., Study Design and Methods: This was a population-based, seroepidemiological, cross-sectional study in the city of Puerto Madryn, a middle size city in the Province of Chubut, Argentina. The study period was between March 3 and April 17, 2021. The sample size was calculated using the technique of calculation of confidence intervals for a proportion. Participants were selected using stratified and cluster probability sampling. A total of 1405 subjects were invited to participate in the study. Participants were divided into the following four age groups: 1) 0 to 14, 2) 15 to 39, 3) 40 to 64, and 4) 65 or older. After informed consent was obtained, a blood sample was taken by puncture of the fingertip, and a structured questionnaire was administered to evaluate demographics, socioeconomic status, level of education, comorbidities and symptoms suggestive of COVID-19. COVID-19 seroprevalence was documented using an immunoenzymatic test for the in vitro detection of IgG antibodies specific to the spike protein of SARS-CoV-2., Results: A total of 987 participants completed the survey. Seropositivity in the full study population was 39,2% and in those under 15 years of age, 47.1%. Cases reported by the SNSV 2.0 amounted to 9.35% of the total population and 1.4% of those under 15 years of age., Interpretation: The prevalence of COVID-19 infection in the general population is four times higher than the number of cases reported by the SNVS 2.0 in the city of Puerto Madryn. For each child under the age of 15 identified by the SNVS 2.0 with COVID-19, there are more than 30 unrecognized infections. Seroepidemiological studies are important to define the real extent of SARS-CoV-2 infection in a particular community. Children may play a significant role in the progression of the current pandemic., Competing Interests: The authors have declared that no competing interests exist.

The membrane protein M of the Porcine Epidemic Diarrhea Virus (PEDV) is the most abundant component of the viral envelope. The M protein plays a central role in the morphogenesis and assembly of the virus through protein interactions of the M-M, M-Spike (S) and M-nucleocapsid (N) type. The M protein is known to induce protective antibodies in pigs and to participate in the antagonistic response of the cellular antiviral system coordinated by the type I and type III interferon pathways. The 3D structure of the PEDV M protein is still unknown. The present work exposes a predicted 3D model of the M protein generated using the Robetta protocol. The M protein model is organized into a transmembrane and a globular region. The obtained 3D model of the PEDV M protein was compared with 3D models of the SARS-CoV-2 M protein created using neural networks and with initial machine learning-based models created using trRosetta. The 3D model of the present study predicted four linear B-cell epitopes (RSVNASSGTG and KHGDYSAVSNPSALT peptides are noteworthy), six discontinuous B-cell epitopes, forty weak binding and fourteen strong binding T-cell epitopes in the CV777 M protein. A high degree of conservation of the epitopes predicted in the PEDV M protein was observed among different PEDV strains isolated in different countries. The data suggest that the M protein could be a potential candidate for the development of new treatments or strategies that activate protective cellular mechanisms against viral diseases., Competing Interests: The authors have declared that no competing interests exist.

Background: Valproic acid (VPA) has shown beneficial effects in vitro against SARS-CoV-2 infection, but no study has analyzed its efficacy in the clinical setting., Methods: This multicenter, retrospective study included 165 adult patients receiving VPA at the time of admission to hospital, and 330 controls matched for sex, age and date of admission. A number of clinical, outcome and laboratory parameters were recorded to evaluate differences between the two groups. Four major clinical endpoints were considered: development of lung infiltrates, in-hospital respiratory worsening, ICU admissions and death., Results: VPA-treated patients had higher lymphocyte (P<0.0001) and monocyte (P = 0.0002) counts, and lower levels of diverse inflammatory parameters, including a composite biochemical severity score (P = 0.016). VPA patients had shorter duration of symptoms (P<0.0001), were more commonly asymptomatic (P = 0.016), and developed less commonly lung infiltrates (65.8%/88.2%, P<0.0001), respiratory worsening (20.6%/30.6%, P = 0.019) and ICU admissions (6.1%/13.0%, P = 0.018). There was no difference in survival (84.8%/88.8%, P = 0.2), although death was more commonly related to non-COVID-19 causes in the VPA group (36.0%/10.8%, P = 0.017). The cumulative hazard for developing adverse clinical endpoints was higher in controls than in the VPA group for infiltrates (P<0.0001), respiratory worsening (P<0.0001), and ICU admissions (P = 0.001), but not for death (0.6). Multivariate analysis revealed that VPA treatment was independently protective for the development of the first three clinical endpoints (P = 0.0002, P = 0.03, and P = 0.025, respectively), but not for death (P = 0.2)., Conclusions: VPA-treated patients seem to develop less serious COVID-19 than control patients, according to diverse clinical endpoints and laboratory markers., Competing Interests: The authors have declared that no competing interests exist.