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Detecting epistatic drivers of human phenotypes is a considerable challenge. Traditional approaches use regression to sequentially test multiplicative interaction terms involving pairs of genetic variants. For higher-order interactions and genome-wide large-scale data, this strategy is computationally intractable. Moreover, multiplicative terms used in regression modeling may not capture the form of biological interactions. Building on the Predictability, Computability, Stability (PCS) framework, we introduce the epiTree pipeline to extract higher-order interactions from genomic data using tree-based models. The epiTree pipeline first selects a set of variants derived from tissue-specific estimates of gene expression. Next, it uses iterative random forests (iRF) to search training data for candidate Boolean interactions (pairwise and higher-order). We derive significance tests for interactions, based on a stabilized likelihood ratio test, by simulating Boolean tree-structured null (no epistasis) and alternative (epistasis) distributions on hold-out test data. Finally, our pipeline computes PCS epistasis p-values that probabilisticly quantify improvement in prediction accuracy via bootstrap sampling on the test set. We validate the epiTree pipeline in two case studies using data from the UK Biobank: predicting red hair and multiple sclerosis (MS). In the case of predicting red hair, epiTree recovers known epistatic interactions surrounding MC1R and novel interactions, representing non-linearities not captured by logistic regression models. In the case of predicting MS, a more complex phenotype than red hair, epiTree rankings prioritize novel interactions surrounding HLA-DRB1, a variant previously associated with MS in several populations. Taken together, these results highlight the potential for epiTree rankings to help reduce the design space for follow up experiments.

Clinical testing typically relies on invasive blood draws and biopsies. Alternative methods of sample collection are continually being developed to improve patient experience; swabbing the skin is one of the least invasive sampling methods possible. To show that skin swabs in combination with untargeted mass spectrometry (metabolomics) can be used for non-invasive monitoring of an oral drug, we report the kinetics and metabolism of diphenhydramine in healthy volunteers (n = 10) over the course of 24 hours in blood and three regions of the skin. Diphenhydramine and its metabolites were observed on the skin after peak plasma levels, varying by compound and skin location, and is an illustrative example of how systemically administered molecules can be detected on the skin surface. The observation of diphenhydramine directly from the skin supports the hypothesis that both parent drug and metabolites can be qualitatively measured from a simple non-invasive swab of the skin surface. The mechanism of the drug and metabolites pathway to the skin's surface remains unknown.

In recent years, different laboratories have provided evidence on the role of miRNAs in regulation of corneal epithelial metabolism, permeability and wound healing, as well as their alteration after surgery and in some ocular pathologies. We searched the available databases reporting miRNA expression in the human eye, looking for miRNAs highly expressed in central cornea, which could be crucial for maintenance of the epithelial phenotype. Using the rabbit RCE1(5T5) cell line as a model of corneal epithelial differentiation, we describe the participation of miR-141-3p as a possible negative regulator of the proliferative/migratory phenotype in corneal epithelial cells. The expression of miR-141-3p followed a time course similar to the differentiation-linked KRT3 cytokeratin, being delayed 24-48 hours relative to PAX6 expression; such result suggested that miR-141-3p only regulates the expression of terminal phenotype. Inhibition of miR-141-3p led to increased cell proliferation and motility, and induced the expression of molecular makers characteristic of an Epithelial Mesenchymal Transition (EMT). Comparison between the transcriptional profile of cells in which miR-141-3p was knocked down, and the transcriptomes from proliferative non-differentiated and differentiated stratified epithelia suggest that miR-141-3p is involved in the expression of terminal differentiation mediating the arrest of cell proliferation and inhibiting the EMT in highly motile early differentiating cells.

Genome and transcriptome examinations have become more common due to Next-Generation Sequencing (NGS), which significantly increases throughput and depth coverage while reducing costs and time. Mitochondrial DNA (mtDNA) is often the marker of choice in degraded samples from archaeological and forensic contexts, as its higher number of copies can improve the success of the experiment. Among other sequencing strategies, amplicon-based NGS techniques are currently being used to obtain enough data to be analyzed. There are some pipelines designed for the analysis of ancient mtDNA samples and others for the analysis of amplicon data. However, these pipelines pose a challenge for non-expert users and cannot often address both ancient and forensic DNA particularities and amplicon-based sequencing simultaneously. To overcome these challenges, a user-friendly bioinformatic tool was developed to analyze the non-coding region of human mtDNA from degraded samples recovered in archaeological and forensic contexts. The tool can be easily modified to fit the specifications of other amplicon-based NGS experiments. A comparative analysis between two tools, MarkDuplicates from Picard and dedup parameter from fastp, both designed for duplicate removal was conducted. Additionally, various thresholds of PMDtools, a specialized tool designed for extracting reads affected by post-mortem damage, were used. Finally, the depth coverage of each amplicon was correlated with its level of damage. The results obtained indicated that, for removing duplicates, dedup is a better tool since retains more non-repeated reads, that are removed by MarkDuplicates. On the other hand, a PMDS = 1 in PMDtools was the threshold that allowed better differentiation between present-day and ancient samples, in terms of damage, without losing too many reads in the process. These two bioinformatic tools were added to a pipeline designed to obtain both haplotype and haplogroup of mtDNA. Furthermore, the pipeline presented in the present study generates information about the quality and possible contamination of the sample. This pipeline is designed to automatize mtDNA analysis, however, particularly for ancient samples, some manual analyses may be required to fully validate results since the amplicons that used to be more easily recovered were the ones that had fewer reads with damage, indicating that special care must be taken for poor recovered samples.

Black Sigatoka is the most widespread banana disease worldwide. It is caused by Pseudocercospora fijiensis, a fungal pathogen known for developing resistance to fungicides such as thiabendazole. Despite the increasing costs associated with the use of chemicals to control this disease, the pathogen's mechanisms for fungicide resistance are not fully understood. The metabolite profiles of P. fijiensis isolates with different levels of resistance to thiabendazole were characterized by GC-MS. A total of 33 isolates were obtained from symptomatic banana plants and the sensitivity of each isolate to thiabendazole was assessed at 0, 1, 10, 100, 1000, and 10000 μg.mL-1. Then, the metabolite profile of each isolate was assessed using GC-MS. Metabolites such as hexadecanoic acid, tetradecanoic acid, octadecadienoic acid and octadecanoic acid were significantly over-accumulated in the presence of thiabendazole at 10 μg.mL-1. Phosphoric acid, L-proline, and D-allose increased in concentration with time in the presence of 100 μg.mL-1 of thiabendazole, and mannonic acid, 1-hexadecanol, D-sorbitol and tetracosanoic acid were only detected in the presence of the fungicide. Metabolic pathways including that of fructose, mannose metabolism, the biosynthesis of unsaturated fatty acids, and ABC transporters were upregulated in resistant isolates. Our findings show an increment of tetracosanoic (myristic) acid suggesting a possible β-tubulin-compensation mechanism in resistant isolates. The presence of myristic acid promoted the generation of diacylglycerol kinase δ which facilitated the production of β-tubulin in other studies. Additionally, important changes in the metabolite profiles were observed as soon as six hours after exposure to the fungicide showing an early response of the pathogen. To the best of our knowledge, this is the first report that describes the changes in the metabolite profile of P. fijiensis resistant to thiabendazole when exposed to the fungicide.

ObjectivesTo determine the clinical, laboratory, and hospital factors associated with preoperative complications in older adults with hip fractures.MethodologyAnalytical observational retrospective cohort study, whose population was older adults with a diagnosis of hip fracture treated in a hospital in northern Peru, during 2017-2019.Results432 patients with a median age of 83 years (RIC: 77-88) were evaluated, with the female gender being the most prevalent (60.9%). The most common comorbidities included cardiovascular disease (68%) and diabetes (17.6%), and multimorbidity was observed in 47.2% of cases. The median number of geriatric syndromes was 2 (RIC: 1-5). The overall mortality rate was 3.2% (1.7-5.3). Analysis with the Poisson regression model found a significant association with MRC scale 3-5 degree (RR = 1.60), glucose on admission (RR = 1.01), and minimally significantly female sex (RR = 2.41).ConclusionsThe most commonly observed complications were infectious in nature, including pneumonia, sepsis, and urinary tract infections. The MRC scale from 3 to 5 degrees increases the risk of developing a preoperative complication; the glucose levels upon admission show a clinically irrelevant association; and in females, there is a minimally significant association in older adults with hip fractures.

We examined a natural history of opioid overdose deaths from 1999-2021 in the United States to describe state-level spatio-temporal heterogeneity in the waves of the epidemic. We obtained overdose death counts by state from 1999-2021, categorized as involving prescription opioids, heroin, synthetic opioids, or unspecified drugs. We developed a Bayesian multivariate multiple change point model to flexibly estimate the timing and magnitude of state-specific changes in death rates involving each drug type. We found substantial variability around the timing and severity of each wave across states. The first wave of prescription-involved deaths started between 1999 and 2005, the second wave of heroin-involved deaths started between 2010 and 2014, and the third wave of synthetic opioid-involved deaths started between 2014 and 2021. The severity of the second and third waves was greater in states in the eastern half of the country. Our study highlights state-level variation in the timing and severity of the waves of the opioid epidemic by presenting a 23-year natural history of opioid overdose mortality in the United States. While reinforcing the general notion of three waves, we find that states did not uniformly experience the impacts of each wave.

Cervical cancer has high incidence and mortality rates, especially in less-developed countries. Prevention methods are well established, but there are still barriers preventing some Brazilian women from undergoing a Pap sample. The objective of the study was to evaluate the acceptance, preferences and completion of four screening methods. This has an experimental design (community trial). A total of 164 participants who had never had a Pap sample or had not had one for more than three years were included. The city's urban area was stratified by census tracts and divided according to income and education levels. Women belonging to the lower-income strata were considered in the study. Random blocks were numbered into five intervention groups (Group 1- Pap sample at the hospital; Group 2- Pap sample in the mobile unit; Group 3- urine self-collection; Group 4- vaginal self-collection; Group 5- woman's choice). Only 164 women met all of the eligibility criteria (15.3%). Most of them accepted the assigned method (92%), but only 84% of the women completed the collection step. The acceptance rates were as follows: Group 1 (100%), Group 2 (64.5%), Group 3 (100%) and Group 4 (91.4%). In Group 5, the women's preferences were distributed as follows: examination performed at the hospital, 13 women (33.3%); examination performed at the mobile unit, 11 women (28.2%); urine self-collection, 11 women (28.2%); and vaginal self-collection, 4 women (10.3%). This study suggests that methods that allow cervical sampling collected near the women's domicile might improve the acceptance and completion of preventive tests. This finding is relevant for the development of new cervical cancer screening strategies.

The mountain region of central Veracruz, Mexico hosts a large system of karst and volcanic caves that are unexplored. In particular, the vertebrates that inhabit these subterranean ecosystems are unknown. This study evaluated the diversity of mammals, birds, reptiles, amphibians, and fish in three environments (euphotic, disphotic, and aphotic) of 16 caves of different geological origin (12 karst caves and 4 volcanic caves) distributed along an altitudinal gradient (300-2400 m a.s.l.). We found a richness of 242 vertebrate species (184 birds, 30 mammals, 15 reptiles, 12 amphibians, and 1 fish) and an abundance of a total of 11,323 individuals (4,969 mammals, 6,483 birds, 36 reptiles, 27 amphibians, and 5 fish). The richness of all vertebrate classes was higher in karst than in volcanic caves. Vertebrate diversity was also higher at mid-altitudes between 600-899 m a.s.l. Diversity varied between environments, where bird and reptile richness was higher in the euphotic environment, while mammal and amphibian diversity was higher in the aphotic environment. The similarity in the composition of vertebrate species does not depend on the distance between karstic and volcanic caves. Volcanic and karst caves shared on average up to 70% and 55% of vertebrate species, which indicates that only 30% and 45% of species, respectively, is different in each cave type. Given the vulnerability and fragility of these subterranean ecosystems, as well as the important diversity that they contain, we recommend including the caves of the central region of Veracruz in the conservation agenda of local governments and communities. Community-based conservation can help ensure the presence of vertebrate species in the caves of this region.

The Big Five personality traits have shown associations with symptoms of depression and anxiety among college students, but it is unclear which factors mediate these relationships. Past research suggests that psychological distress is closely related to difficulties in affect regulation (e.g., low distress tolerance). Therefore, the present study examined the associations between personality traits and depression and anxiety via emotion regulation and distress tolerance. Participants were 694 (81.4% females; Mean age = 23.12 [SD 2.75]) Argentinian college students who completed an online survey examining mental health and personality variables. A sizeable percentage of students endorsed moderate to severe symptoms of depression (45.1%) or anxiety (25.9%). Utilizing path analyses, we found that appraisal, a dimension of distress tolerance, atemporally mediated the association between emotional stability and symptoms of depression/anxiety (i.e., higher levels of emotional stability → higher appraisal distress tolerance → fewer symptoms of depression/anxiety). Further, expressive suppression (a dimension of emotion regulation) significantly mediated the associations between personality traits (i.e., agreeableness and extraversion) and symptoms of depression (higher levels of agreeableness/extraversion → lower use of expressive suppression → fewer symptoms of depression). Taken together, the results suggest that higher levels of emotional stability, extraversion and agreeableness could protect students from the development of symptoms of depression/anxiety via lower maladaptive emotion regulation strategies and higher distress tolerance (particularly appraisal). These findings highlight the relevance of intervention strategies specifically tailored to improve distress tolerance and emotion regulation for those students undergoing mental health problems.

[This corrects the article DOI: 10.1371/journal.pone.0302465.].

BackgroundThe COVID-19 pandemic has prompted a transformation of medical training. Although there were obvious medical education and social interaction challenges, e-learning presented some advantages, which may have generated medical curricula innovation and adjustments to novel technological methodologies. This study aims to generate consensuses among medical students regarding medical education provided during the pandemic in the resource-limited context of a Global South university.MethodsThe implementation of a participatory Delphi method included a recruitment campaign, training, constitution of Delphi panels and questions, and development of the Delphi exercises. Students from the second to the sixth year of medicine of a university in Quito, Ecuador, constituted two Delphi panels, developed questions about the education received during the pandemic, and answered them over 3.5 rounds.FindingsTwenty-two medical students participated in the Delphi exercises about their perception of medical education during the COVID-19 pandemic. The analysis consisted of a total of 22 Delphi questions divided into five distinct categories: adaptations and innovations, curriculum and assessment changes, virtual clinical practice, time management, and mental health. The authors established high, medium, and low consensuses for analysis.ConclusionsConsensuses were reached based on students' academic year and focused on the changes in lecture delivery, the usage of new technologies, patient care skills, the impact of the educational routine, and the mental health of the COVID-19 pandemic. The way the pandemic affected medical education in the Global South set the stage for the need for a comprehensive review of tools, skills, and curricula for students from culturally diverse backgrounds. This study offers a highly replicable methodology to generate consensuses and introduce students to academic research.

Due to the dramatic reduction of sea cucumber Isostichopus badionotus populations in the Yucatan Peninsula by overfishing and poaching, aquaculture has been encouraged as an alternative to commercial catching and restoring wild populations. However, the scarcity of broodstock, the emergence of a new disease in the auricularia larvae stage, and the development of skin ulceration syndrome (SUS) in the culture have limited aquaculture development. This study presents the changes in the intestine and skin microbiota observed in early and advanced stages of SUS disease in cultured juvenile I. badionotus obtained during an outbreak in experimental culture through 16S rRNA gene sequencing and histological evidence. Our results showed inflammation in the intestines of juveniles at both stages of SUS. However, more severe tissue damage and the presence of bacterial clusters were detected only in the advanced stages of SUS. Differences in the composition and structure of the intestinal and skin bacterial community from early and advanced stages of SUS were detected, with more evident changes in the intestinal microbial communities. These findings suggest that SUS was not induced by a single pathogenic bacterium. Nevertheless, a decrease in the abundance of Vibrio and an increase in Halarcobacter (syn. Arcobacter) was observed, suggesting that these two bacterial groups could be keystone genera involved in SUS disease.

We present the results of the excavations and analyses of the diverse and exceptional archaeological assemblage of Taguatagua 3, a new late Pleistocene site located in the ancient Tagua Tagua lake in Central Chile (34°S). The anthropogenic context is constrained in a coherently dated stratigraphic deposit which adds new information about the mobility, subsistence strategies, and settlement of the early hunter-gatherers of southern South America. The age model constructed, as well as radiocarbon dates obtained directly from a combustion structure, indicate that the human occupation occurred over a brief time span around 12,440-12,550 cal yr BP. Considering taphonomic, geoarchaeological, lithic, archaeobotanical, and zooarchaeological evidence, as well as the spatial distribution combined with ethnographic data, we interpret Taguatagua 3 as a logistic and temporary camp associated mainly with gomphothere hunting and butchering. Nevertheless, several other activities were carried out here as well, such as hide and/or bone preparation, small vertebrate and plant processing and consumption, and red ochre grinding. Botanical and eggshell remains suggest that the anthropic occupation occurred during the dry season. Considering the contemporaneous sites recorded in the basin, we conclude that the ancient Tagua Tagua lake was a key location along the region's early hunter-gatherer mobility circuits. In this context, it acted as a recurrent hunting/scavenging place during the Late Pleistocene due to its abundant, diverse, and predictable resources.

The innovative performance of manufacturing and service companies can be impacted by the existing relationship between open innovation (OI) and the generation of confidentiality agreements (NDAs) as a tool for the protection of intellectual property. Based on the analysis of a cross-sectional sample of 6,798 industrial companies (2019-2020) and 9,304 companies in the service sector (2017-2019) that are part of the directory of the National Administrative Department of Statistics (DANE) in its Technological Innovation and Development Survey (EDIT and EDITS), it can be suggested that the interaction of these two variables (OI and NDAs) generate positive effects for the manufacturing industry but negative ones for the service sector. It could be deduced that the positive effect is due to the greater tradition of OI in the manufacturing industry and the negative effect to the caution that the service sector presents when collaborating with external actors.

Detecting epistatic drivers of human phenotypes is a considerable challenge. Traditional approaches use regression to sequentially test multiplicative interaction terms involving pairs of genetic variants. For higher-order interactions and genome-wide large-scale data, this strategy is computationally intractable. Moreover, multiplicative terms used in regression modeling may not capture the form of biological interactions. Building on the Predictability, Computability, Stability (PCS) framework, we introduce the epiTree pipeline to extract higher-order interactions from genomic data using tree-based models. The epiTree pipeline first selects a set of variants derived from tissue-specific estimates of gene expression. Next, it uses iterative random forests (iRF) to search training data for candidate Boolean interactions (pairwise and higher-order). We derive significance tests for interactions, based on a stabilized likelihood ratio test, by simulating Boolean tree-structured null (no epistasis) and alternative (epistasis) distributions on hold-out test data. Finally, our pipeline computes PCS epistasis p-values that probabilisticly quantify improvement in prediction accuracy via bootstrap sampling on the test set. We validate the epiTree pipeline in two case studies using data from the UK Biobank: predicting red hair and multiple sclerosis (MS). In the case of predicting red hair, epiTree recovers known epistatic interactions surrounding MC1R and novel interactions, representing non-linearities not captured by logistic regression models. In the case of predicting MS, a more complex phenotype than red hair, epiTree rankings prioritize novel interactions surrounding HLA-DRB1, a variant previously associated with MS in several populations. Taken together, these results highlight the potential for epiTree rankings to help reduce the design space for follow up experiments.

Chia (Salvia hispanica L.) seed (CS) and Pumpkin (Cucurbita moschata) seed (PS) are used in ruminant diets as energy sources. The current experiment studied the impact of dietary inclusion of CS and PS on nutrient intake and digestibility, milk yield, and milk composition of dairy sheep. Twelve primiparous Texel × Suffolk ewes [70 ± 5 days in milk (DIM); 0.320 ± 0.029 kg milk yield] were distributed in a 4 × 3 Latin square design and fed either a butter-based control diet [CON; 13 g/kg dry matter] or two diets with 61 g/kg DM of either CS or PS. Dietary inclusion of CS and PS did not alter live weight (p >0.1) and DM intake (p >0.1). However, compared to the CON, dietary inclusion of both CS and PS increased the digestibility of neutral detergent fiber (p 0.05) and C18:3n3 (p > 0.05). Overall short-term feeding of CS and/or PS (up to 6.1% DM of diet) not only maintains the production performance and digestibility of nutrients but also positively modifies the milk FA composition.

BackgroundForced alcohol (ethanol, EtOH) exposure has been shown to cause significant impairments on reversal learning, a widely-used assay of cognitive flexibility, specifically on fully-predictive, deterministic versions of this task. However, previous studies have not adequately considered voluntary EtOH consumption and sex effects on probabilistic reversal learning. The present study aimed to fill this gap in the literature.MethodsMale and female Long-Evans rats underwent either 10 weeks of voluntary intermittent 20% EtOH access or water only (H2O) access. Rats were then pretrained to initiate trials and learn stimulus-reward associations via touchscreen response, and subsequently required to select between two visual stimuli, rewarded with probability 0.70 or 0.30. In the final phase, reinforcement contingencies were reversed.ResultsWe found significant sex differences on several EtOH-drinking variables, with females reaching a higher maximum EtOH consumption, exhibiting more high-drinking days, and escalating their EtOH at a quicker rate compared to males. During early abstinence, EtOH drinkers (and particularly EtOH-drinking females) made more initiation omissions and were slower to initiate trials than H2O drinking controls, especially during pretraining. A similar pattern in trial initiations was also observed in discrimination, but not in reversal learning. EtOH drinking rats were unaffected in their reward collection and stimulus response times, indicating intact motivation and motor responding. Although there were sex differences in discrimination and reversal phases, performance improved over time. We also observed sex-independent drinking group differences in win-stay and lose-shift strategies specific to the reversal phase.ConclusionsFemales exhibit increased vulnerability to EtOH effects in early learning: there were sex-dependent EtOH effects on attentional measures during pretraining and discrimination phases. We also found sex-independent EtOH effects on exploration strategies during reversal. Future studies should aim to uncover the neural mechanisms for changes in attention and exploration in both acute and prolonged EtOH withdrawal.

Invasive alien species are a major threat to native insular species. Eradicating invasive mammals from islands is a feasible and proven approach to prevent biodiversity loss. We developed a conceptual framework to identify globally important islands for invasive mammal eradications to prevent imminent extinctions of highly threatened species using biogeographic and technical factors, plus a novel approach to consider socio-political feasibility. We applied this framework using a comprehensive dataset describing the distribution of 1,184 highly threatened native vertebrate species (i.e. those listed as Critically Endangered or Endangered on the IUCN Red List) and 184 non-native mammals on 1,279 islands worldwide. Based on extinction risk, irreplaceability, severity of impact from invasive species, and technical feasibility of eradication, we identified and ranked 292 of the most important islands where eradicating invasive mammals would benefit highly threatened vertebrates. When socio-political feasibility was considered, we identified 169 of these islands where eradication planning or operation could be initiated by 2020 or 2030 and would improve the survival prospects of 9.4% of the Earths most highly threatened terrestrial insular vertebrates (111 of 1,184 species). Of these, 107 islands were in 34 countries and territories and could have eradication projects initiated by 2020. Concentrating efforts to eradicate invasive mammals on these 107 islands would benefit 151 populations of 80 highly threatened vertebrates and make a major contribution towards achieving global conservation targets adopted by the worlds nations.

Predictions of hospital beds occupancy depends on hospital admission rates and the length of stay (LoS) according to bed type (general ward -GW- and intensive care unit -ICU- beds). The objective of this study was to describe the LoS of COVID-19 hospital patients in Colombia during 2020-2021. Accelerated failure time models were used to estimate the LoS distribution according to each bed type and throughout each bed pathway. Acceleration factors and 95% confidence intervals were calculated to measure the effect on LoS of the outcome, sex, age, admission period during the epidemic (i.e., epidemic waves, peaks or valleys, and before/after vaccination period), and patients geographic origin. Most of the admitted COVID-19 patients occupied just a GW bed. Recovered patients spent more time in the GW and ICU beds than deceased patients. Men had longer LoS than women. In general, the LoS increased with age. Finally, the LoS varied along epidemic waves. It was lower in epidemic valleys than peaks, and decreased after vaccinations began in Colombia. Our study highlights the necessity of analyzing local data on hospital admission rates and LoS to design strategies to prioritize hospital beds resources during the current and future pandemics.

Attention Deficit Hyperactivity Disorder (ADHD) is an increasingly prevalent neuropsychiatric disorder characterized by hyperactivity, inattention, and impulsivity. Symptoms emerge from underlying deficiencies in neurocircuitry, and recent research has suggested a role played by the gut microbiome. The gut microbiome is an ecosystem of interdependent taxa involved in an exponentially complex web of interactions, plus host gene and reaction pathways, some of which involve neurotransmitters with roles in ADHD neurocircuitry. Studies have analyzed the ADHD gut microbiome using macroscale metrics such as diversity and differential abundance, and have proposed several taxa as elevated or reduced in ADHD compared to Control. Few studies have delved into the complex underlying dynamics ultimately responsible for the emergence of such metrics, leaving a largely incomplete, sometimes contradictory, and ultimately inconclusive picture. We aim to help complete this picture by venturing beyond taxa abundances and into taxa relationships (i.e. cooperation and competition), using a publicly available gut microbiome dataset (targeted 16S, v3-4 region, qPCR) from an observational, case-control study of 30 Control (15 female, 15 male) and 28 ADHD (15 female, 13 male) undergraduate students. We first perform the same macroscale analyses prevalent in ADHD gut microbiome literature (diversity, differential abundance, and composition) to observe the degree of correspondence, or any new trends. We then estimate two-way ecological relationships by producing Control and ADHD Microbial Co-occurrence Networks (MCNs), using SparCC correlations (p ≤ 0.01). We perform community detection to find clusters of taxa estimated to mutually cooperate along with their centroids, and centrality calculations to estimate taxa most vital to overall gut ecology. We finally summarize our results, providing conjectures on how they can guide future experiments, some methods for improving our experiments, and general implications for the field.

Agave potatorum Zucc. locally known as Tobalá, is an important species for mezcal production. It is a perennial species that takes 10 to 15 years to reach reproductive age. Because of high demand of Tobalá mezcal and the slow maturation of the plants, its wild populations have been under intense anthropogenic pressure. The main objective of this study was to estimate the genome-wide diversity in A. potatorum and determine if the type of management has had any effect on its diversity, inbreeding and structure. We analyzed 174 individuals (105 wild, 42 cultivated and 27 from nurseries) from 34 sites with a reduced representation genomic method (ddRADseq), using 14,875 SNPs. The diversity measured as expected heterozygosity was higher in the nursery and wild plants than in cultivated samples. We did not find private alleles in the cultivated and nursery plants, which indicates that the individuals under management recently derived from wild populations, which was supported by higher gene flow estimated from wild populations to the managed plants. We found low but positive levels of inbreeding (FIS = 0.082), probably related to isolation of the populations. We detected low genetic differentiation among populations (FST = 0.0796), with positive and significant isolation by distance. The population genetic structure in the species seems to be related to elevation and ecology, with higher gene flow among populations in less fragmented areas. We detected an outlier locus related to the recognition of pollen, which is also relevant to self-incompatibility protein (SI). Due to seed harvest and long generation time, the loss of diversity in A. potatorum has been gradual and artificial selection and incipient management have not yet caused drastic differences between cultivated and wild plants. Also, we described an agroecological alternative to the uncontrolled extraction of wild individuals.

Swine dysentery (SD) is a worldwide production-limiting disease of growing-finishing pigs in commercial farms. The importance of the large intestinal microbiota in the swine dysentery pathogenesis has been established, but not well characterized. The objective of this study was to characterize the fecal bacterial microbiota of pigs immediately prior to developing clinical signs of swine dysentery. A total of 60 fecal samples were collected from 15 pigs with SD. Sampling times included a time point prior to SD (d0, n=15), 2 days before mucohaemorrhagic diarrhea was observed (d-2SD, n=15), 1 day before mucohaemorrhagic diarrhea was observed (d-1SD, n=15), and the day when pigs developed mucohemorragic diarrhea (MHD, n=15). Sequencing of cpn60 amplicons was used to profile the microbiome, and analyses were performed on QIIME2. Increased Chao1 index in d-1SD and MHD samples when compared to the d0 was the only change observed in alpha diversity. No differences between sampling times on beta diversity (Bray-Curtis dissimilarity) were found. Although a small sample size was investigated, differential abundance analysis revealed that Alistipes dispar and Parabacteroides gordonii were increased in MHD fecal samples when compared to d-2SD and d-1SD. It is suggested that these taxa may play a role in the pathogenesis of SD, which is known to require the presence of Brachyspira spp. and an anaerobe for severe disease development.

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.

The release of vast quantities of sulfide from the sediment into the water column, known as a sulfidic event, has detrimental consequences on fish catches, including downstream effects on other linked element cycles. Despite being frequent occurrences in marine upwelling regions, our understanding of the factors that moderate sulfidic event formation and termination are still rudimentary. Here, we examined the biogeochemical and hydrodynamic conditions that underpinned the formation/termination of one of the largest sulfur plumes to be reported in the Peruvian upwelling zone. Consistent with previous research, we find that the sulfur-rich plume arose during the austral summer when anoxic conditions (i.e., oxygen and nitrate depletion) prevailed in waters overlying the upper shelf. Furthermore, the shelf sediments were organically charged and characterized by low iron-bound sulfur concentrations, further enabling the diffusion of benthic-generated sulfide into the water column. While these biogeochemical conditions provided a predicate to sulfidic event formation, we highlight that attenuations in local wind intensity served as an event trigger. Namely, interruptions in local wind speed constrained upwelling intensity, causing increased stratification over the upper shelf. Moreover, disturbances in local wind patterns likely placed additional constraints on wind-driven mesoscale eddy propagation, with feedback effects on coastal elemental sulfur plume (ESP) formation. We suggest ESP development occurs as a result of a complex interaction of biogeochemistry with regional hydrodynamics.

The Hawaiian hoary bat (Lasiurus semotus; Chiroptera: Vespertilionidae), commonly and locally known as 'ōpe'ape'a, is a solitary, insectivorous, and foliage-roosting species distributed across a wide range of habitats in lowland and montane environments. The species, as with many others in the Hawaiian archipelago, are facing a suite of challenges due to habitat loss and degradation, introduced predators and pests, and climate change. An understanding of the roost requirements of foliage-roosting tree bats is critical to their conservation as these habitats provide several important benefits to survival and reproduction. Because little is known about 'ōpe'ape'a roost ecology and considerable effort is needed to capture and track bats to roost locations, we examined resource selection at multiple spatial scales-perch location within a roost tree, roost tree, and forest stand. We used a discrete choice modeling approach to investigate day-roost selection and describe attributes of roost trees including those used as maternity roosts. 'Ōpe'ape'a were found roosting in 19 tree species and in an assortment of landcover types including native and non-native habitats. Our results are largely consistent with findings of other studies of foliage-roosting, insectivorous tree bats where bats selected roost locations that may offer protection and thermoregulatory benefits.

IntroductionCOVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread worldwide, becoming a long-term pandemic.ObjectivesTo analyze the factors associated with mortality in patients hospitalized for COVID-19 in a tertiary hospital in the Lambayeque region of Peru.MethodsA retrospective cohort study of patients with a diagnosis of COVID-19, hospitalized in a hospital in northern Peru, was conducted from March to September 2020.ResultsOf the 297 patients studied, 69% were women, the mean age was 63.99 years (SD = ±15.33 years). Hypertension was the most frequent comorbidity (36.67%), followed by diabetes mellitus (24.67%) and obesity (8.33%). The probability of survival at 3 days of ICU stay was 65.3%, at 7 days 24.2%, and 0% on day 14. Risk factors associated with mortality in patients hospitalized for COVID-19 are age, male sex, tachypnea, low systolic blood pressure, low peripheral oxygen saturation, impaired renal function, elevated IL-6 and elevated D-dimer.ConclusionsMortality in hospitalized patients with COVID-19 was 51.18 per 100 persons, Mortality was found to be associated with hypertension, type of infiltrating, and sepsis.

In humans, the pituitary gland is covered by a fibrous capsule and is considered a continuation of the meningeal sheath. However, in rodents some studies concluded that only the pars tuberalis (PT) and pars nervosa (PN) are enwrapped by the pia mater, while others showed that the whole gland is covered by this sheath. At PT the median eminence subarachnoid drains cerebrospinal fluid (CSF) to its cisternal system representing a pathway to the hypothalamus. In the present study we examined the rat pituitary capsule to elucidate its configuration, its physical interaction with the pituitary border and its relationship with the CSF. Furthermore, we also revisited the histology of the pituitary cleft and looked whether CSF drained in it. To answer such questions, we used scanning and transmission electron microscopy, intracerebroventricular infusion of Evan´s blue, fluorescent beads, and sodium fluorescein. The latter was measured in the pars distalis (PD) and various intracranial tissues. We found a pituitary capsule resembling leptomeninges, thick at the dorsal side of the pars intermedia (PI) and PD, thicker at the level of PI in contiguity with the PN and thinner at the rostro-ventral side as a thin membrane of fibroblast-like cells embedded in a fibrous layer. The capsule has abundant capillaries on all sides. Our results showed that the CSFs bathe between the capsule and the surface of the whole gland, and ciliate cells are present in the pituitary border. Our data suggest that the pituitary gland intercommunicates with the central nervous system (CNS) through the CSF.

BackgroundColombia is currently the world's main recipient country for Venezuelan migrants, and women represent a high proportion of them. This article presents the first report of a cohort of Venezuelan migrant women entering Colombia through Cúcuta and its metropolitan area. The study aimed to describe the health status and access to healthcare services among Venezuelan migrant women in Colombia with irregular migration status, and to analyze changes in those conditions at a one-month follow-up.MethodsWe carried out a longitudinal cohort study of Venezuelan migrant women, 18 to 45 years, who entered Colombia with an irregular migration status. Study participants were recruited in Cúcuta and its metropolitan area. At baseline, we administered a structured questionnaire including sociodemographic characteristics, migration history, health history, access to health services, sexual and reproductive health, practice of early detection of cervical cancer and breast cancer, food insecurity, and depressive symptoms. The women were again contacted by phone one month later, between March and July 2021, and a second questionnaire was applied.ResultsA total of 2,298 women were included in the baseline measurement and 56.4% could be contacted again at the one-month follow-up. At the baseline, 23.0% of the participants reported a self-perceived health problem or condition in the past month and 29.5% in the past 6 months, and 14.5% evaluated their health as fair or poor. A significant increase was found in the percentage of women who reported a self-perceived health problem during the past month (from 23.1% to 31.4%; pConclusionThis report presents initial information on the health status of Venezuelan migrant women in Colombia, and is a starting point for further longer longitudinal follow-ups to assess changes over time in health conditions.

IntroductionAn electronic nose (eNose) device has shown a high specificity and sensitivity to diagnose or rule out tuberculosis (TB) in the past. The aim of this study was to evaluate its performance in patients referred to INERAM.MethodsPatients aged ≥15 years were included. A history, physical examination, chest radiography (CRX) and microbiological evaluation of a sputum sample were performed in all participants, as well as a 5-minute breath test with the eNose. TB diagnosis was preferably established by the gold standard and compared to the eNose predictions. Univariate and multivariate logistic regression analyses were performed to assess potential risk factors for erroneous classification results by the eNose.Results107 participants with signs and symptoms of TB were enrolled of which 91 (85.0%) were diagnosed with TB. The blind eNose predictions resulted in an accuracy of 50%; a sensitivity of 52.3% (CI 95%: 39.6-64.7%) and a specificity of 36.4% (CI 95%: 12.4-68.4%). Risk factors for erroneous classifications by the eNose were older age (multivariate analysis: OR 1.55, 95% CI 1.10-2.18, p = 0.012) and antibiotic use (multivariate analysis: OR 3.19, 95% CI 1.06-9.66, p = 0.040).ConclusionIn this study, the accuracy of the eNose to diagnose TB in a tertiary referral hospital was only 50%. The use of antibiotics and older age represent important factors negatively influencing the diagnostic accuracy of the eNose. Therefore, its use should probably be restricted to screening in high-risk communities in less complex healthcare settings.

Light chain (AL) amyloidosis is a form of systemic amyloidosis, causing organ dysfunction, mainly affecting the heart and kidney. Patient-tailored and risk-adapted decision making is critical in AL amyloidosis management. There is limited real-world evidence data from Argentina and Latin America regarding the treatment approaches for AL amyloidosis. This retrospective cohort study aimed to describe the treatment patterns and outcomes in adult patients (>18 years) diagnosed with AL amyloidosis at the Hospital Italiano in Buenos Aires, Argentina, using a 10-yearfollow-up data (June 1, 2010 to May 31, 2019) from the institutional registry of amyloidosis (IRA). The study population had a mean age of 63 years and 54.4% weremale. Heart and kidney were the most frequently affected organs. Of the 90 eligible patients included in the study, 70underwent treatment. Bortezomib-based regimen was the preferred first-line treatment (75.7% patients). Overall,54.4% of the patients presented a deep response (complete or very good partial response). Median overall survival (OS) was 5years, the 1-year OS and progression free survival rates were 80% (95% confidence interval [CI]: 68-87) and 80% (95%CI 68-87)), respectively. This study provides vital real-world evidence for the long-term treatment patterns and survival in a large cohort of AL amyloidosis patients in Argentina.

The evolution of the remarkably complex primate brain has been a topic of great interest for decades. Multiple factors have been proposed to explain the comparatively larger primate brain (relative to body mass), with recent studies indicating diet has the greatest explanatory power. Dietary specialisations also correlate with dental adaptations, providing a potential evolutionary link between brain and dental morphological evolution. However, unambiguous evidence of association between brain and dental phenotypes in primates remains elusive. Here we investigate the effect of diet on variation in primate brain and dental morphology and test whether the two anatomical systems coevolved. We focused on the primate suborder Strepsirrhini, a living primate group that occupies a very wide range of dietary niches. By making use of both geometric morphometrics and dental topographic analysis, we extend the study of brain-dental ecomorphological evolution beyond measures of size. After controlling for allometry and evolutionary relatedness, differences in brain and dental morphology were found between dietary groups, and brain and dental morphologies were found to covary. Historical trajectories of morphological diversification revealed a strong integration in the rates of brain and dental evolution and similarities in their modes of evolution. Combined, our results reveal an interplay between brain and dental ecomorphological adaptations throughout strepsirrhine evolution that can be linked to diet.

The concentrations of trace elements including As, Zn, Cu, Se, Pb, Hg and Cd, were determined in the blood of nesting Kemp's ridley turtles (Lepidochelys kempii) at Rancho Nuevo sanctuary, Tamaulipas, Mexico during 2018-2020. The sequential concentrations analyzed were Zn> Se> Cu> As> Pb; while Cd and Hg concentrations were below the limits of detection (0.01 μg g-1). No significant differences were observed between the concentrations of trace elements (p> 0.05) by year, except Se levels, possibly resulting from recorded seasonal differences in turtle size. No relationships among turtle size vs elements concentration were observed. In conclusion, essential and toxic trace elements concentrations in the blood of nesting Kemp's ridley turtles may be a reflex of the ecosystem in which the turtles develop, that is, with low bioavailability of elements observed in the trophic webs in the Gulf of Mexico.

Clinical testing typically relies on invasive blood draws and biopsies. Alternative methods of sample collection are continually being developed to improve patient experience; swabbing the skin is one of the least invasive sampling methods possible. To show that skin swabs in combination with untargeted mass spectrometry (metabolomics) can be used for non-invasive monitoring of an oral drug, we report the kinetics and metabolism of diphenhydramine in healthy volunteers (n = 10) over the course of 24 hours in blood and three regions of the skin. Diphenhydramine and its metabolites were observed on the skin after peak plasma levels, varying by compound and skin location, and is an illustrative example of how systemically administered molecules can be detected on the skin surface. The observation of diphenhydramine directly from the skin supports the hypothesis that both parent drug and metabolites can be qualitatively measured from a simple non-invasive swab of the skin surface. The mechanism of the drug and metabolites pathway to the skin’s surface remains unknown.

It is well known that the presence of comorbidities and age-related health issues may hide biochemical and metabolic features triggered by SARS-CoV-2 infection and other diseases associated to hypoxia, as they are by themselves chronic inflammatory conditions that may potentially disturb metabolic homeostasis and thereby negatively impact on COVID-19 progression. To unveil the metabolic abnormalities inherent to hypoxemia caused by COVID-19, we here applied gas chromatography coupled to mass spectrometry to analyze the main metabolic changes exhibited by a population of male patients less than 50 years of age with mild/moderate and severe COVID-19 without pre-existing comorbidities known to predispose to life-threatening complications from this infection. Several differences in serum levels of particular metabolites between normal controls and patients with COVID-19 as well as between mild/moderate and severe COVID-19 were identified. These included increased glutamic acid and reduced glutamine, cystine, threonic acid, and proline levels. In particular, using the entire metabolomic fingerprint obtained, we observed that glutamine/glutamate metabolism was associated with disease severity as patients in the severe COVID-19 group presented the lowest and higher serum levels of these amino acids, respectively. These data highlight the hypoxia-derived metabolic alterations provoked by SARS-CoV-2 infection in the absence of pre-existing co-morbidities as well as the value of amino acid metabolism in determining reactive oxygen species recycling pathways, which when impaired may lead to increased oxidation of proteins and cell damage. They also provide insights on new supportive therapies for COVID-19 and other disorders that involve altered redox homeostasis and lower oxygen levels that may lead to better outcomes of disease severity.

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.

In this study, we conducted the translation and validation of the K-SF-42 in Japan (Figueredo, 2017). The K-SF-42 is a new short form of the Arizona Life History Battery. We obtained empirical evidence that the original seven-factor structure could be applied to the Japanese translated version of K-SF-42 (K-SF-42-J). We also observed good internal consistency of the seven scales of K-SF-42-J. The multi-group confirmatory factor analysis findings suggest that the K-SF-42-J can be used in both sexes and diverse age groups. The K-SF-42-J scales showed similar correlates as the English original, with higher scores of other life history strategy measurement, trait emotional intelligence, well-being, and cultural and social resources in childhood. Use of the K-SF-42-J will allow researchers with Japanese speaking samples to integrate their findings with the existing life history strategy research literature. The brevity of the K-SF-42-J will be appealing to researchers who are concerned about taxing the time and motivation of their participants.

Cassava (Manihot esculenta Crantz) biofortification with provitamin A carotenoids is an ongoing process that aims to alleviate vitamin A deficiency. The moderate content of provitamin A carotenoids achieved so far limits the contribution to providing adequate dietary vitamin A levels. Strategies to increase carotenoid content focused on genes from the carotenoids biosynthesis pathway. In recent years, special emphasis was given to ORANGE protein (OR), which promotes the accumulation of carotenoids and their stability in several plants. The aim of this work was to identify, characterize and investigate the role of OR in the biosynthesis and stabilization of carotenoids in cassava and its relationship with phytoene synthase (PSY), the rate-limiting enzyme of the carotenoids biosynthesis pathway. Gene and protein characterization of OR, expression levels, protein amounts and carotenoids levels were evaluated in roots of one white (60444) and two yellow cassava cultivars (GM5309-57 and GM3736-37). Four OR variants were found in yellow cassava roots. Although comparable expression was found for three variants, significantly higher OR protein amounts were observed in the yellow varieties. In contrast, cassava PSY1 expression was significantly higher in the yellow cultivars, but PSY protein amount did not vary. Furthermore, we evaluated whether expression of one of the variants, MeOR_X1, affected carotenoid accumulation in cassava Friable Embryogenic Callus (FEC). Overexpression of maize PSY1 alone resulted in carotenoids accumulation and induced crystal formation. Co-expression with MeOR_X1 led to greatly increase of carotenoids although PSY1 expression was high in the co-expressed FEC. Our data suggest that posttranslational mechanisms controlling OR and PSY protein stability contribute to higher carotenoid levels in yellow cassava. Moreover, we showed that cassava FEC can be used to study the efficiency of single and combinatorial gene expression in increasing the carotenoid content prior to its application for the generation of biofortified cassava with enhanced carotenoids levels.

Background Peru is the country with the world’s highest COVID-19 death rate per capita. Characteristics associated with increased mortality among adult patients with COVID-19 pneumonia in this setting are not well described. Methods Retrospective, single-center cohort study including 1537 adult patients hospitalized with a diagnosis of SARS-CoV-2 pneumonia between May 2020 and August 2020 at a national hospital in Lima, Peru. The primary outcome measure was in-hospital mortality. Results In-hospital mortality was 49.71%. The mean age was 60 ± 14.25 years, and 68.38% were males. We found an association between mortality and inflammatory markers, mainly leukocytes, D-dimer, lactate dehydrogenase, C-reactive protein and ferritin. A multivariate model adjusted for age, hypertension, diabetes mellitus, and corticosteroid use demonstrated that in-hospital mortality was associated with greater age (RR: 2.01, 95%CI: 1.59–2.52) and a higher level of oxygen requirement (RR: 2.77, 95%CI: 2.13–3.62). Conclusions: In-hospital mortality among COVID-19 patients in Peru is high and is associated with greater age and higher oxygen requirements.

Swine dysentery is causally associated with Brachyspira hampsonii and B. hyodysenteriae infection. Given the importance of transmission models in understanding re-emergent diseases and developing control strategies such as vaccines, the objective of this experiment was to evaluate two experimental natural transmission (seeder pig) models in grower pigs, each with 24 animals. Seeder pigs were intragastrically inoculated using broth cultures of either B. hampsonii strain 30446 (genomovar II) or B. hyodysenteriae strain G44. In trial 1, three seeder pigs were placed into two pens containing nine susceptible contact pigs creating a 1:3 seeder:contact ratio. This was sufficient to achieve natural B. hampsonii infection of 13/18 (72%) contact pigs, however, the incidence of mucoid or mucohemorrhagic diarrhea (MMHD) in contact pigs differed significantly between pens (4/9 versus 9/9; P = 0.03). In trial 2, eight seeder pigs inoculated intragastrically with B. hampsonii did not develop MMHD but when re-inoculated with B. hyodysenteriae 14 days later, all developed mucohemorrhagic diarrhea within 13 days of re-inoculation. Two seeder pigs were placed into each of 4 contact pens each containing 4 pigs. This 1:2 seeder:contact ratio resulted in natural infection of 14/16 (87%) contact pigs with incubation period ranging from 9–15 days. There were no significant differences among pens in incubation period, duration, clinical period or severity of diarrhea. These trials demonstrated that a 1:2 seeder:contact ratio with groups of six grower pigs per pen sustained natural transmission of B. hyodysenteriae G44 with greater consistency in the incidence of MMHD among pens compared to a B. hampsonii 30446 transmission model using 1:3 seeder:contact ratio in pens of 12. Understanding why B. hampsonii intragastric inoculation failed in one experiment warrants additional research.

Our knowledge about the structure and function of Andean forests at regional scales remains limited. Current initiatives to study forests over continental or global scales still have important geographical gaps, particularly in regions such as the tropical and subtropical Andes. In this study, we assessed patterns of structure and tree species diversity along ~ 4000 km of latitude and ~ 4000 m of elevation range in Andean forests. We used the Andean Forest Network (Red de Bosques Andinos, https://redbosques.condesan.org/) database which, at present, includes 491 forest plots (totaling 156.3 ha, ranging from 0.01 to 6 ha) representing a total of 86,964 identified tree stems ≥ 10 cm diameter at breast height belonging to 2341 identified species, 584 genera and 133 botanical families. Tree stem density and basal area increases with elevation while species richness decreases. Stem density and species richness both decrease with latitude. Subtropical forests have distinct tree species composition compared to those in the tropical region. In addition, floristic similarity of subtropical plots is between 13 to 16% while similarity between tropical forest plots is between 3% to 9%. Overall, plots ~ 0.5-ha or larger may be preferred for describing patterns at regional scales in order to avoid plot size effects. We highlight the need to promote collaboration and capacity building among researchers in the Andean region (i.e., South-South cooperation) in order to generate and synthesize information at regional scale.

Heightened fear of breast cancer (FBC) has been linked to increased distress following breast cancer diagnosis and to avoidance of mammography screening. To our knowledge, however, no studies have examined the nature of FBC exclusively among young females, even though they are overrepresented in media stories of breast cancer. Given that no instruments are available to assess FBC in the Spanish language, we sought to 1) evaluate the psychometric properties and factor structure of the Champion Breast Cancer Fear Scale (CBCFS), and 2) offer preliminary data on the nature of FBC among young women. Participants (N = 442, mean age = 21.17, range 17-35) completed the translated CBCFS (CBCFS-es) and the Spanish version of the Short Health Anxiety Inventory. The CBCFS-es demonstrated good concurrent validity, internal consistency, and test-retest reliability. Confirmatory factor analysis showed adequate fit to a one-factor solution. The majority of participants reported considerably high levels of FBC, as 25.34% and 59.73% of them scored above the moderate- and high-FBC cut-offs, respectively. Moreover, FBC could not be explained by general concerns regarding health and illness, given that levels of health anxiety were low. Implications for health education, research, and clinical practice are discussed.

AimThis report presents phenotypic and genetic data on the prevalence and characteristics of extended-spectrum β-lactamases (ESBLs) and representative carbapenemases-producing Gram-negative species in Mexico.Material and methodsA total of 52 centers participated, 43 hospital-based laboratories and 9 external laboratories. The distribution of antimicrobial resistance data for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, Acinetobacter baumannii complex, and Pseudomonas aeruginosa in selected clinical specimens from January 1 to March 31, 2020 was analyzed using the WHONET 5.6 platform. The following clinical isolates recovered from selected specimens were included: carbapenem-resistant Enterobacteriaceae, ESBL or carbapenem-resistant E. coli, and K. pneumoniae, carbapenem-resistant A. baumannii complex, and P. aeruginosa. Strains were genotyped to detect ESBL and/or carbapenemase-encoding genes.ResultsAmong blood isolates, A. baumannii complex showed more than 68% resistance for all antibiotics tested, and among Enterobacteria, E. cloacae complex showed higher resistance to carbapenems. A. baumannii complex showed a higher resistance pattern for respiratory specimens, with only amikacin having a resistance lower than 70%. Among K. pneumoniae isolates, blaTEM, blaSHV, and blaCTX were detected in 68.79%, 72.3%, and 91.9% of isolates, respectively. Among E. coli isolates, blaTEM, blaSHV, and blaCTX were detected in 20.8%, 4.53%, and 85.7% isolates, respectively. For both species, the most frequent genotype was blaCTX-M-15. Among Enterobacteriaceae, the most frequently detected carbapenemase-encoding gene was blaNDM-1 (81.5%), followed by blaOXA-232 (14.8%) and blaoxa-181(7.4%), in A. baumannii was blaOXA-24 (76%) and in P. aeruginosa, was blaIMP (25.3%), followed by blaGES and blaVIM (13.1% each).ConclusionOur study reports that NDM-1 is the most frequent carbapenemase-encoding gene in Mexico in Enterobacteriaceae with the circulation of the oxacillinase genes 181 and 232. KPC, in contrast to other countries in Latin America and the USA, is a rare occurrence. Additionally, a high circulation of ESBL blaCTX-M-15 exists in both E. coli and K. pneumoniae.

Objective To compare the completeness and quality of information about diabetic retinopathy on Wikipedia in the world’s leading spoken languages in 2020. Design and methods An observational, descriptive, cross-sectional study. The information on diabetic retinopathy obtained from the free encyclopedia Wikipedia® was assessed in languages with one hundred million or more total speakers. The term "diabetic retinopathy" was accessed in the corresponding Wikipedia entry in English, while the "more languages" function gives access to other languages. The information on the sites was collected by three ophthalmologist observers. A database was created with the most important subtopics for the education of patients with diabetic retinopathy in any of its classifications, based on a 25-question survey. The results were stratified on a scale from 0 to 4. A confirming correlation was found in the statistical analysis among the observers. Results No language achieved the label “excellent”; 2 languages were rated as “fair “; 4 languages qualified as “substandard”; and 7 languages were scored as “poor.” No information could be found in five languages. Conclusions As would be expected, the quality of content is variable across different languages. However, if anyone can edit Wikipedia, health professionals can do so as well to improve the quality and quantity of information for patients.

Miocene deposits of South America have yielded several species-rich assemblages of caviomorph rodents. They are mostly situated at high and mid- latitudes of the continent, except for the exceptional Honda Group of La Venta, Colombia, the faunal composition of which allowed to describe the late middle Miocene Laventan South American Land Mammal Age (SALMA). In this paper, we describe a new caviomorph assemblage from TAR-31 locality, recently discovered near Tarapoto in Peruvian Amazonia (San Martín Department). Based on mammalian biostratigraphy, this single-phased locality is unambiguously considered to fall within the Laventan SALMA. TAR-31 yielded rodent species found in La Venta, such as the octodontoid Ricardomys longidens Walton, 1990 (nom. nud.), the chinchilloids Microscleromys paradoxalis Walton, 1990 (nom. nud.) and M. cribriphilus Walton, 1990 (nom. nud.), or closely-related taxa. Given these strong taxonomic affinities, we further seize the opportunity to review the rodent dental material from La Venta described in the Ph.D. volume of Walton in 1990 but referred to as nomina nuda. Here we validate the recognition of these former taxa and provide their formal description. TAR-31 documents nine distinct rodent species documenting the four extant superfamilies of Caviomorpha, including a new erethizontoid: Nuyuyomys chinqaska gen. et sp. nov. These fossils document the most diverse caviomorph fauna for the middle Miocene interval of Peruvian Amazonia to date. This rodent discovery from Peru extends the geographical ranges of Ricardomys longidens, Microscleromys paradoxalis, and M. cribriphilus, 1,100 km to the south. Only one postcranial element of rodent was unearthed in TAR-31 (astragalus). This tiny tarsal bone most likely documents one of the two species of Microscleromys and its morphology indicates terrestrial generalist adaptations for this minute chinchilloid.

Objective To analyze the performance of adenosine deaminase in pleural fluid combined with other parameters routinely measured in clinical practice and assisted by machine learning algorithms for the diagnosis of pleural tuberculosis in a low prevalence setting, and secondly, to identify effusions that are non-tuberculous and most likely malignant. Patients and methods We prospectively analyzed 230 consecutive patients diagnosed with lymphocytic exudative pleural effusion from March 2013 to June 2020. Diagnosis according to the composite reference standard was achieved in all cases. Pre-test probability of pleural tuberculosis was 3.8% throughout the study period. Parameters included were: levels of adenosine deaminase, pH, glucose, proteins, and lactate dehydrogenase, red and white cell counts and lymphocyte percentage in pleural fluid, as well as age. We tested six different machine learning-based classifiers to categorize the patients. Two different classifications were performed: a) tuberculous/non-tuberculous and b) tuberculous/malignant/other. Results Out of a total of 230 patients with pleural effusion included in the study, 124 were diagnosed with malignant effusion and 44 with pleural tuberculosis, while 62 were given other diagnoses. In the tuberculous/non-tuberculous classification, and taking into account the validation predictions, the support vector machine yielded the best result: an AUC of 0.98, accuracy of 97%, sensitivity of 91%, and specificity of 98%, whilst in the tuberculous/malignant/other classification, this type of classifier yielded an overall accuracy of 80%. With this three-class classifier, the same sensitivity and specificity was achieved in the tuberculous/other classification, but it also allowed the correct classification of 90% of malignant cases. Conclusion The level of adenosine deaminase in pleural fluid together with cell count, other routine biochemical parameters and age, combined with a machine-learning approach, is suitable for the diagnosis of pleural tuberculosis in a low prevalence scenario. Secondly, non-tuberculous effusions that are suspected to be malignant may also be identified with adequate accuracy.

Mycobacterium tuberculosis (M. tuberculosis) was the pathogen responsible for the highest number of deaths from infectious diseases in the world, before the arrival of the COVID-19 pandemic. Whole genome sequencing (WGS) has contributed to the understanding of genetic diversity, the mechanisms involved in drug resistance and the transmission dynamics of this pathogen. The object of this study is to use WGS for the epidemiological and molecular characterization of M. tuberculosis clinical strains from Chinchiná, Caldas, a small town in Colombia with a high incidence of TB. Sputum samples were obtained during the first semester of 2020 from six patients and cultured in solid Löwenstein-Jensen medium. DNA extraction was obtained from positive culture samples and WGS was performed with the Illumina HiSeq 2500 platform for subsequent bioinformatic analysis. M. tuberculosis isolates were typified as Euro-American lineage 4 with a predominance of the Harlem and LAM sublineages. All samples were proven sensitive to antituberculosis drugs by genomic analysis, although no phenotype antimicrobial tests were performed on the samples, unreported mutations were identified that could require further analysis. The present study provides preliminary data for the construction of a genomic database line and the follow-up of lineages in this region.

Hypertensive disorders in pregnancy (HDP) are associated with increased risk of offspring neurodevelopmental disorders, suggesting long-term adverse impacts on fetal brain development. However, the relationship between HDP and deficits in general child development is unclear. Our objective was to assess the association between HDP and motor and cognitive developmental delay in children at 36 months of age. We analyzed data from the All Our Families community-based cohort study (n = 1554). Diagnosis of HDP-gestational or chronic hypertension, preeclampsia, or eclampsia-was measured through medical records. Child development was measured by maternal-report on five domains of the Ages and Stages Questionnaire (ASQ-3). Standardized cut-off scores were used to operationalize binary variables for any delay, motor delay, and cognitive delay. We calculated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) using logistic regression, sequentially controlling for potential confounders followed by factors suspected to lie on the causal pathway. Overall, 8.0% of women had HDP and hypertension-exposed children had higher prevalence of delay than unexposed children. Hypertension-exposed children had elevated risk for developmental delay, but CIs crossed the null. The aRRs quantifying the fully adjusted effect of HDP on child development were 1.19 (95% CI 0.92, 1.53) for any delay, 1.18 (95% CI 0.86, 1.61) for motor delay, and 1.24 (95% CI 0.83, 1.85) for cognitive delay. We did not find a statistically significant association between HDP and developmental delay. Confidence intervals suggest that children exposed to HDP in utero have either similar or slightly elevated risk of any, motor, and cognitive delay at 36 months after controlling for maternal and obstetric characteristics. The observed direction of association aligns with evidence of biological mechanisms whereby hypertensive pathology can disrupt fetal neurodevelopment; however, more evidence is needed. Findings may have implications for early developmental monitoring and intervention following prenatal hypertension exposure.

The Antillean manatee (Trichechus manatus manatus), a subspecies of the West Indian manatee, inhabits fresh, brackish, and warm coastal waters distributed along the eastern border of Central America, the northern coast of South America, and throughout the Wider Caribbean Region. Threatened primarily by human encroachment, poaching, and habitat degradation, Antillean manatees are listed as endangered by the International Union for the Conservation of Nature. The impact of disease on population viability remains unknown in spite of concerns surrounding the species' ability to rebound from a population crash should an epizootic occur. To gain insight on the baseline health of this subspecies, a total of 191 blood samples were collected opportunistically from wild Antillean manatees in Belize between 1997 and 2009. Hematologic and biochemical reference intervals were established, and antibody prevalence to eight pathogens with zoonotic potential was determined. Age was found to be a significant factor of variation in mean blood values, whereas sex, capture site, and season contributed less to overall differences in parameter values. Negative antibody titers were reported for all pathogens surveyed except for Leptospira bratislava, L. canicola, and L. icterohemorrhagiae, Toxoplasma gondii, and morbillivirus. As part of comprehensive health assessment in manatees from Belize, this study will serve as a benchmark aiding in early disease detection and in the discernment of important epidemiologic patterns in the manatees of this region. Additionally, it will provide some of the initial tools to explore the broader application of manatees as sentinel species of nearshore ecosystem health.