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Traditional pastures in temperate regions face limitations such as reduced growth and nutritional quality during the summer season. Plantain (P. lanceolata L.) offers advantages like increased yield and decreased nitrogen losses from grazing ruminants. Effective grazing management is essential for pasture health, and defoliation frequency and intensity play a pivotal role. This study aimed to evaluate plantain's regrowth, yield, and morpho-physiological and chemical responses under different defoliation frequencies and intensities, with the goal of enhancing its management in pastures. The study was conducted in pots within a controlled-environment growth chamber, examining the impact of three defoliation frequencies (based on extended leaf length: 15, 25 and 35 cm) and two defoliation intensities (5 and 8 cm of residual heights) with four replicates (24 pots as experimental units). The variables of interest were morphological characteristics, dry matter (DM) accumulation, herbage chemical composition, growth rate traits, and photosynthetic parameters. Defoliation frequency affected plantain's growth and nutritional composition. More frequent cuts (15 cm) resulted in lower DM yield per cut and lower stem content, while less frequent cuts (35 cm) produced higher values. Defoliation intensity influenced the proportion of leaves and stems in the total DM, with 5 cm cuts favoring leaves. Nutrient content was also affected by defoliation frequency, with less frequent cuts (35 cm) showing lower crude protein concentration and metabolizable energy content but higher neutral detergent fiber and water-soluble carbohydrate concentration. Plantain's growth rate variables were mainly influenced by defoliation frequency, with less frequent cuts promoting faster leaf appearance and growth of new leaves. The basal fluorescence variables and chlorophyll content were affected by cutting frequency, being highest when cut less frequently (35 cm), while no differences were found in the actual quantum efficiency among different defoliation frequencies and intensities. The fraction of light dedicated to non-photochemical quenching was highest when cut less frequently and more intensively. Overall, defoliation at 25 cm of extended leaf length balanced plantain forage quality and regrowth capacity.

Background/objectivesGermline genetic testing is recommended for younger patients with idiopathic pancreatitis but there has been a lack of consensus in recommendations for those over age 35. We aimed to analyze the results of genetic testing among subjects of varying ages.MethodsIndividuals who underwent germline multigene testing for pancreatitis susceptibility genes (CASR, CFTR, CPA1, CTRC, PRSS1, SPINK1) through a large commercial laboratory between 2017 and 2022 were included. Test results and information collected from test requisition forms were evaluated. Multivariable logistic regression models were performed to identify factors associated with a positive pancreatitis panel (pathogenic, likely pathogenic, and/or increased risk variants) in pancreatitis-related genes.ResultsOverall, 2,468 subjects with primary indication of acute pancreatitis (AP) (n = 401), chronic pancreatitis (CP) (n = 631), pancreatic cancer (n = 128), or other indications (n = 1,308) completed germline testing. Among patients with AP or CP, the prevalence of any positive result for those ConclusionsThe highest prevalence of pathogenic variants is seen in younger individuals with a positive family history of pancreatitis. However, clinically meaningful results are identified in older subjects, suggesting that genetic counseling and testing should be considered for all age groups.

Intolerance of Uncertainty (IU) is thought to lead to maladaptive behaviours and dysfunctional decision making, both in the clinical and healthy population. The seminal study reported by Luhmann and collaborators in 2011 showed that IU was negatively associated with choosing a delayed, but more certain and valuable, reward over choosing an immediate, but less certain and valuable, reward. These findings have been widely disseminated across the field of personality and individual differences because of their relevance to understand the role of IU in maladaptive behaviours in anxiety-related disorders. We conducted a study to replicate and extend Luhmann et al.'s results with a sample of 313 participants, which exceeded the size necessary (N = 266) to largely improve the statistical power of the original study by using the small telescopes approach. The results of our well powered study strongly suggest that the relationship between IU and the tendency to prefer an immediate, but less certain and less valuable reward is virtually negligible. Consequently, although this relationship cannot be definitely discarded, we conclude that it cannot be detected with Luhmann et al.'s (2011) decision-making task.

PKD1 is the most commonly mutated gene causing autosomal dominant polycystic kidney disease (ADPKD). It encodes Polycystin-1 (PC1), a putative membrane protein that undergoes a set of incompletely characterized post-transcriptional cleavage steps and has been reported to localize in multiple subcellular locations, including the primary cilium and mitochondria. However, direct visualization of PC1 and detailed characterization of its binding partners remain challenging. We now report a new mouse model with HA epitopes and eGFP knocked-in frame into the endogenous mouse Pkd1 gene by CRISPR/Cas9. Using this model, we sought to visualize endogenous PC1-eGFP and performed affinity-purification mass spectrometry (AP-MS) and network analyses. We show that the modified Pkd1 allele is fully functional but the eGFP-tagged protein cannot be detected without signal amplification by secondary antibodies. Using nanobody-coupled beads and large quantities of tissue, AP-MS identified an in vivo PC1 interactome, which is enriched for mitochondrial proteins and components of metabolic pathways. These studies suggest this mouse model and interactome data will be useful to understand PC1 function, but that new methods and brighter tags will be required to track endogenous PC1.

Fibropapillomatosis (FP) is a disease characterized by epithelial tumors that can impede life-sustaining activities of sea turtles, especially green turtles (Chelonia mydas). FP is caused by a herpesvirus, but environmental factors are also thought to play a role in triggering FP tumor growth. In this study, we evaluate the epidemiology of FP tumors in green turtles along the coast of Espírito Santo, Brazil, a region where juvenile green turtles are known to aggregate with high FP prevalence. A dataset comprising 2024 beach-cast green turtles recorded through daily beach surveys on 400 km of coastline from 2018 to 2021 (inclusive) was evaluated. FP tumors were recorded in 40.9% of the individuals in this dataset, and presence of FP tumors was predicted by individual variables (presence of marine leeches, stranding code, curved carapace length, body mass-size residual) and characteristics of the stranding site (distance to nearest metallurgical plant, mean sea surface salinity (SSS), annual range of sea surface temperature (SST)). Additionally, a second dataset comprising detailed information about the size and anatomical distribution of tumors in 271 green turtles with FP from the same region was evaluated. Hierarchical clustering analysis revealed these turtles could be classified in three groups according to the anatomical distribution of their tumors, and in turn the group to which each turtle was assigned could be predicted by the study period (2010-2014 vs. 2018-2022) and by characteristics of the stranding/capture site (green turtle stranding density, mean sea surface chlorophyll-a concentration, mean SSS, mean SST, annual range of SST). These results corroborate that individual and environmental factors play a significant role driving FP epidemiology. Furthermore, the results suggest that rather than behaving as a single entity, FP may be seen as a mosaic of distinct anatomical patterns that are not necessarily driven by the same environmental factors.

Mycobacterium tuberculosis (Mtb) is still one of the primary pathogens of humans causing tuberculosis (TB) disease. Mtb embraces nine well-defined phylogenetic lineages with biological and geographical disparities. The lineage L4 is the most globally widespread of all lineages and was introduced to America with European colonization. Taking advantage of many genome projects available in public repositories, we undertake an evolutionary and comparative genomic analysis of 522 L4 Latin American Mtb genomes. Initially, we performed careful quality control of public read datasets and applied several thresholds to filter out low-quality data. Using a genome de novo assembly strategy and phylogenomic methods, we spotted novel south American clades that have not been revealed yet. Additionally, we describe genomic deletion profiles of these strains from an evolutionary perspective and report Mycobacterium tuberculosis L4 sublineages signature-like gene deletions, some of the novel. One is a specific deletion of 6.5 kbp that is only present in sublineage 4.1.2.1. This deletion affects a complex group of 10 genes with putative products annotated, among others, as a lipoprotein, transmembrane protein, and toxin/antitoxin system proteins. The second novel deletion spans for 4.9 kbp and specific of a particular clade of the 4.8 sublineage and affects 7 genes. The last novel deletion affects 4 genes, extends for 4.8 kbp., and is specific to some strains within the 4.1.2.1 sublineage that are present in Colombia, Peru and Brasil.

Traditional pastures in temperate regions face limitations such as reduced growth and nutritional quality during the summer season. Plantain (P. lanceolata L.) offers advantages like increased yield and decreased nitrogen losses from grazing ruminants. Effective grazing management is essential for pasture health, and defoliation frequency and intensity play a pivotal role. This study aimed to evaluate plantain's regrowth, yield, and morpho-physiological and chemical responses under different defoliation frequencies and intensities, with the goal of enhancing its management in pastures. The study was conducted in pots within a controlled-environment growth chamber, examining the impact of three defoliation frequencies (based on extended leaf length: 15, 25 and 35 cm) and two defoliation intensities (5 and 8 cm of residual heights) with four replicates (24 pots as experimental units). The variables of interest were morphological characteristics, dry matter (DM) accumulation, herbage chemical composition, growth rate traits, and photosynthetic parameters. Defoliation frequency affected plantain's growth and nutritional composition. More frequent cuts (15 cm) resulted in lower DM yield per cut and lower stem content, while less frequent cuts (35 cm) produced higher values. Defoliation intensity influenced the proportion of leaves and stems in the total DM, with 5 cm cuts favoring leaves. Nutrient content was also affected by defoliation frequency, with less frequent cuts (35 cm) showing lower crude protein concentration and metabolizable energy content but higher neutral detergent fiber and water-soluble carbohydrate concentration. Plantain's growth rate variables were mainly influenced by defoliation frequency, with less frequent cuts promoting faster leaf appearance and growth of new leaves. The basal fluorescence variables and chlorophyll content were affected by cutting frequency, being highest when cut less frequently (35 cm), while no differences were found in the actual quantum efficiency among different defoliation frequencies and intensities. The fraction of light dedicated to non-photochemical quenching was highest when cut less frequently and more intensively. Overall, defoliation at 25 cm of extended leaf length balanced plantain forage quality and regrowth capacity. [ABSTRACT FROM AUTHOR]

Background/Objectives: Germline genetic testing is recommended for younger patients with idiopathic pancreatitis but there has been a lack of consensus in recommendations for those over age 35. We aimed to analyze the results of genetic testing among subjects of varying ages. Methods: Individuals who underwent germline multigene testing for pancreatitis susceptibility genes (CASR, CFTR, CPA1, CTRC, PRSS1, SPINK1) through a large commercial laboratory between 2017 and 2022 were included. Test results and information collected from test requisition forms were evaluated. Multivariable logistic regression models were performed to identify factors associated with a positive pancreatitis panel (pathogenic, likely pathogenic, and/or increased risk variants) in pancreatitis-related genes. Results: Overall, 2,468 subjects with primary indication of acute pancreatitis (AP) (n = 401), chronic pancreatitis (CP) (n = 631), pancreatic cancer (n = 128), or other indications (n = 1,308) completed germline testing. Among patients with AP or CP, the prevalence of any positive result for those <35 versus ≥35 years of age was 32.1% and 24.5% (p = 0.007), and the prevalence of a clinically meaningful result was 10.8% and 5.4%, respectively (p = 0.001). Positive family history of pancreatitis was associated with increased odds ratio (OR) of 8.59 (95% confidence interval (CI) 2.92–25.25) for a clinically significant panel result while each 5-year increase in age at test completion had lower odds (OR 0.89, 95% CI 0.83–0.95). Conclusions: The highest prevalence of pathogenic variants is seen in younger individuals with a positive family history of pancreatitis. However, clinically meaningful results are identified in older subjects, suggesting that genetic counseling and testing should be considered for all age groups. [ABSTRACT FROM AUTHOR]

Intolerance of Uncertainty (IU) is thought to lead to maladaptive behaviours and dysfunctional decision making, both in the clinical and healthy population. The seminal study reported by Luhmann and collaborators in 2011 showed that IU was negatively associated with choosing a delayed, but more certain and valuable, reward over choosing an immediate, but less certain and valuable, reward. These findings have been widely disseminated across the field of personality and individual differences because of their relevance to understand the role of IU in maladaptive behaviours in anxiety-related disorders. We conducted a study to replicate and extend Luhmann et al.'s results with a sample of 313 participants, which exceeded the size necessary (N = 266) to largely improve the statistical power of the original study by using the small telescopes approach. The results of our well powered study strongly suggest that the relationship between IU and the tendency to prefer an immediate, but less certain and less valuable reward is virtually negligible. Consequently, although this relationship cannot be definitely discarded, we conclude that it cannot be detected with Luhmann et al.'s (2011) decision-making task. [ABSTRACT FROM AUTHOR]

In this paper we present the design of an open-source and low-cost buoy prototype for remote monitoring of water quality variables in fish farming. The designed battery-powered system periodically measures temperature, pH and dissolved oxygen, transmitting the information locally through a low-power wide-area network protocol to a gateway connected to a cloud service for data storage and visualization. We provide a novel buoy design that can be easily constructed with off-the-shelf materials, delivering a stable anchored float for the IoT device and the probes immersed in the water pond. The prototype was tested at an operating fish farm, showing promising results for a low-cost remote monitoring tool that enables automatic data acquisition and storage in fish farming scenarios. All the elements of this design, including hardware and software designs, are freely available under permissive licenses as an open-source project.

PurposeThe COVID-19 pandemic has spread worldwide, and almost 396 million people have been infected around the globe. Latin American countries have been deeply affected, and there is a lack of data in this regard. This study aims to identify the clinical characteristics, in-hospital outcomes, and factors associated with ICU admission due to COVID-19. Furthermore, to describe the functional status of patients at hospital discharge after the acute episode of COVID-19.Material and methodsThis was a prospective, multicenter, multinational observational cohort study of subjects admitted to 22 hospitals within Latin America. Data were collected prospectively. Descriptive statistics were used to characterize patients, and multivariate regression was carried out to identify factors associated with severe COVID-19.ResultsA total of 3008 patients were included in the study. A total of 64.3% of patients had severe COVID-19 and were admitted to the ICU. Patients admitted to the ICU had a higher mean (SD) 4C score (10 [3] vs. 7 [3)], pConclusionsThis study confirms that patients with SARS CoV-2 in the Latin American population had a lower mortality rate than previously reported. Systemic complications are frequent in patients admitted to the ICU due to COVID-19, as previously described in high-income countries.

Rapid tests for SARS-COV-2 infection are important tools for pandemic control, but current rapid tests are based on proprietary designs and reagents. We report clinical validation results of an open-access lateral flow assay (OA-LFA) design using commercially available materials and reagents, along with RT-qPCR and commercially available comparators (BinaxNOW® and Sofia®). Adult patients with suspected COVID-19 based on clinical signs and symptoms, and with symptoms ≤7 days duration, underwent anterior nares (AN) sampling for the OA-LFA, Sofia®, BinaxNOW ™, and RT-qPCR, along with nasopharyngeal (NP) RT-qPCR. Results indicate a positive predictive agreement with NP sampling as 69% (60% -78%) OA-LFA, 74% (64% - 82%) Sofia®, and 82% (73% - 88%) BinaxNOW™. The implication for these results is that we provide an open-access LFA design that meets the minimum WHO target product profile for a rapid test, that virtually any diagnostic manufacturer could produce.

Inexpensive, simple, rapid diagnostics are necessary for efficient detection, treatment, and mitigation of COVID-19. Assays for SARS-CoV2 using reverse transcription polymerase chain reaction (RT-PCR) offer good sensitivity and excellent specificity, but are expensive, slowed by transport to centralized testing laboratories, and often unavailable. Antigen-based assays are inexpensive and can be rapidly mass-produced and deployed at point-of-care, with lateral flow assays (LFAs) being the most common format. While various manufacturers have produced commercially available SARS-Cov2 antigen LFAs, access to validated tests remains difficult or cost prohibitive in low-and middle-income countries. Herein, we present a visually read open-access LFA (OA-LFA) using commercially-available antibodies and materials for the detection of SARS-CoV-2. The LFA yielded a Limit of Detection (LOD) of 4 TCID50/swab of gamma irradiated SARS-CoV-2 virus, meeting the acceptable analytical sensitivity outlined by in World Health Organization target product profile. The open-source architecture presented in this manuscript provides a template for manufacturers around the globe to rapidly design a SARS-CoV2 antigen test.

Intolerance of Uncertainty (IU) is thought to lead to maladaptive behaviours and dysfunctional decision making, both in the clinical and healthy population. The seminal study reported by Luhmann and collaborators in 2011 [1] showed that IU was negatively associated with choosing a delayed, but more probable and valuable, reward over choosing an immediate, but less probable and valuable, reward. These findings have been widely disseminated across the field of personality and individual differences because of their relevance for the understanding of the role of IU in the development and maintenance of anxiety-related disorders. Given their importance it would be desirable to have replications of this study, but none have been carried out so far. The current study has been designed to replicate and extend Luhmann et al.'s results. Our sample will include 266 healthy participants (more than five times the sample size used by Luhmann et al.) to detect with a power of 95% the effect size that can be detected with a power of 33% in the original study. To increase our chances of getting such a sample size, the experiment will be conducted online, To increase our chances of getting such a sample size, the experiment will be conducted online, adding check trials to the original decision-making task to monitor participants' engagement. Additionally, we will explore the role of impulsivity in the relationship between IU and willingness to wait. This study will add empirical evidence about the role of IU in decision making and, in case of replication of Luhmann et al.'s results, will support the hypothesis that high-IU individuals may engage in inefficient or costly behaviour in exchange for less time enduring an uncertain situation.

In this paper, we propose a hierarchical statistical model for a single repairable system subject to several failure modes (competing risks). The paper describes how complex engineered systems may be modelled hierarchically by use of Bayesian methods. It is also assumed that repairs are minimal and each failure mode has a power-law intensity. Our proposed model generalizes another one already presented in the literature and continues the study initiated by us in another published paper. Some properties of the new model are discussed. We conduct statistical inference under an objective Bayesian framework. A simulation study is carried out to investigate the efficiency of the proposed methods. Finally, our methodology is illustrated by two practical situations currently addressed in a project under development arising from a partnership between Petrobras and six research institutes.

Changes in the cholesterol (Chol) content of biological membranes are known to alter the physicochemical properties of the lipid lamella and consequently the function of membrane-associated enzymes. To characterize these changes, we used steady-state and time resolved fluorescence spectroscopy and two photon-excitation microscopy techniques. The membrane systems were chosen according to the techniques that were used: large unilamellar vesicles (LUVs) for cuvette and giant unilamellar vesicles (GUVs) for microscopy measurements; they were prepared from dipalmitoyl phosphatidylcholine (DPPC) and dioctadecyl phosphatidylcholine (DOPC) in mixtures that are well known to form lipid domains. Two fluorescent probes, which insert into different regions of the bilayer, were selected: 1,6-diphenyl-1,3,5-hexatriene (DPH) was located at the deep hydrophobic core of the acyl chain regions and 2-dimethylamino-6-lauroylnaphthalene (Laurdan) at the hydrophilic-hydrophobic membrane interface. Our spectroscopy results show that (i) the changes induced by cholesterol in the deep hydrophobic phospholipid acyl chain domain are different from the ones observed in the superficial region of the hydrophilic-hydrophobic interface, and these changes depend on the state of the lamella and (ii) the incorporation of cholesterol into the lamella induces an increase in the orientation dynamics in the deep region of the phospholipid acyl chains with a corresponding decrease in the orientation at the region close to the polar lipid headgroups. The microscopy data from DOPC/DPPC/Chol GUVs using Laurdan generalized polarization (Laurdan GP) suggest that a high cholesterol content in the bilayer weakens the stability of the water hydrogen bond network and hence the stability of the liquid-ordered phase (Lo).

Lmna(-/-) mice display multiple tissue defects and die by 6-8 weeks of age reportedly from dilated cardiomyopathy with associated conduction defects. We sought to determine whether restoration of lamin A in cardiomyocytes improves cardiac function and extends the survival of Lmna(-/-) mice. We observed increased total desmin protein levels and disorganization of the cytoplasmic desmin network in ~20% of Lmna(-/-) ventricular myocytes, rescued in a cell-autonomous manner in Lmna(-/-) mice expressing a cardiac-specific lamin A transgene (Lmna(-/-); Tg). Lmna(-/-); Tg mice displayed significantly increased contractility and preservation of myocardial performance compared to Lmna(-/-) mice. Lmna(-/-); Tg mice attenuated ERK1/2 phosphorylation relative to Lmna(-/-) mice, potentially underlying the improved localization of connexin43 to the intercalated disc. Electrocardiographic recordings from Lmna(-/-) mice revealed arrhythmic events and increased frequency of PR interval prolongation, which is partially rescued in Lmna(-/-); Tg mice. These findings support our observation that Lmna(-/-); Tg mice have a 12% median extension in lifespan compared to Lmna(-/-) mice. While significant, Lmna(-/-); Tg mice only have modest improvement in cardiac function and survival likely stemming from the observation that only 40% of Lmna(-/-); Tg cardiomyocytes have detectable lamin A expression. Cardiomyocyte-specific restoration of lamin A in Lmna(-/-) mice improves heart-specific pathology and extends lifespan, demonstrating that the cardiac pathology of Lmna(-/-) mice limits survival. The expression of lamin A is sufficient to rescue certain cellular defects associated with loss of A-type lamins in cardiomyocytes in a cell-autonomous fashion.

BACKGROUND:There is a correlation between the endocannabinoid system and hepatic fibrosis based on the activation of CB1 and CB2 receptors; where CB1 has profibrogenic effects. Gene therapy with a plasmid carrying a shRNA for CB1 delivered by hydrodynamic injection has the advantage of hepatic tropism, avoiding possible undesirable effects of CB1 pharmacological inhibition. OBJECTIVE:To evaluate hydrodynamics-based liver transfection in an experimental model of liver cirrhosis of a plasmid with the sequence of a shRNA for CB1 and its antifibrogenic effects. METHODS:Three shRNA (21pb) were designed for blocking CB1 mRNA at positions 877, 1232 and 1501 (pshCB1-A, B, C). Sequences were cloned in the pENTR™/U6. Safety was evaluated monitoring CB1 expression in brain tissue. The silencing effect was determined in rat HSC primary culture and CCl4 cirrhosis model. Hydrodynamic injection in cirrhotic liver was through iliac vein and with a dose of 3mg/kg plasmid. Serum levels of liver enzymes, mRNA levels of TGF-β1, Col IA1 and α-SMA and the percentage of fibrotic tissue were analyzed. RESULTS:Hydrodynamic injection allows efficient CB1 silencing in cirrhotic livers and pshCB1-B (position 1232) demonstrated the main CB1-silencing. Using this plasmid, mRNA level of fibrogenic molecules and fibrotic tissue considerably decrease in cirrhotic animals. Brain expression of CB1 remained unaltered. CONCLUSION:Hydrodynamics allows a hepatotropic and secure transfection in cirrhotic animals. The sequence of the shCB1-B carried in a plasmid or any other vector has the potential to be used as therapeutic strategy for liver fibrosis.

The small Neotropical finches called capuchinos are outstanding because they have experienced one of the most recent and explosive avian radiations ever documented for birds. Despite very low morphological and niche divergence among species, many of them are reproductively isolated when in sympatry due to strong sexual selection in plumage traits. However, a specific pair of mostly parapatric species, the Pearly-bellied, Sporophila pileata, and the Copper Seedeaters, S. bouvreuil, has confounded taxonomists because individuals with intermediate color patterns can be found. By analyzing diagnostic COI mtDNA sequences and adult male plumage we provide evidence for hybridization. Paternity tests using microsatellites also indicated that representatives with intermediate plumage pattern can be fertile. Our findings are consistent with the classification of S. bouvreuil and S. pileata as distinct taxa, but we demonstrate that the sexual selection mechanisms involved in the isolation of other reproductively sympatric capuchinos are not applicable to this pair of species, likely because of reduced barriers to mate recognition.

Helicobacter pylori is a Gram-negative bacterium that causes chronic atrophic gastritis and peptic ulcers and it has been associated with the development of gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT). One of the more remarkable characteristics of H. pylori is its ability to survive in the hostile environment of the stomach. H. pylori regulates the expression of specific sets of genes allowing it to survive high acidity levels and nutrient scarcity. In the present study, we determined the expression of virulence associated protein D (VapD) of H. pylori inside adenocarcinoma gastric (AGS) cells and in gastric biopsies. Using qRT-PCR, VapD expression was quantified in intracellular H. pylori-AGS cell cultures at different time points and in gastric mucosa biopsies from patients suffering from chronic atrophic gastritis, follicular gastritis, peptic ulcers, gastritis precancerous intestinal metaplasia and adenocarcinoma. Our results show that vapD of H. pylori presented high transcription levels inside AGS cells, which increased up to two-fold above basal values across all assays over time. Inside AGS cells, H. pylori acquired a coccoid form that is metabolically active in expressing VapD as a protection mechanism, thereby maintaining its permanence in a viable non-cultivable state. VapD of H. pylori was expressed in all gastric biopsies, however, higher expression levels (p = 0.029) were observed in gastric antrum biopsies from patients with follicular gastritis. The highest VapD expression levels were found in both antrum and corpus gastric biopsies from older patients (>57 years old). We observed that VapD in H. pylori is a protein that is only produced in response to interactions with eukaryotic cells. Our results suggest that VapD contributes to the persistence of H. pylori inside the gastric epithelial cells, protecting the microorganism from the intracellular environment, reducing its growth rate, enabling long-term infection and treatment resistance.

Alterations in the cortico-cerebellar-thalamic-cortical circuit might underlie the diversity of symptoms in schizophrenia. However, molecular changes in cerebellar neuronal circuits, part of this network, have not yet been fully determined. Using LC-MS/MS, we screened altered candidates in pooled grey matter of cerebellum from schizophrenia subjects who committed suicide (n = 4) and healthy individuals (n = 4). Further validation by immunoblotting of three selected candidates was performed in two cohorts comprising schizophrenia (n = 20), non-schizophrenia suicide (n = 6) and healthy controls (n = 21). We found 99 significantly altered proteins, 31 of them previously reported in other brain areas by proteomic studies. Transport function was the most enriched category, while cell communication was the most prevalent function. For validation, we selected the vacuolar proton pump subunit 1 (VPP1), from transport, and two EF-hand calcium-binding proteins, calmodulin and parvalbumin, from cell communication. All candidates showed significant changes in schizophrenia (n = 7) compared to controls (n = 7). VPP1 was altered in the non-schizophrenia suicide group and increased levels of parvalbumin were linked to antipsychotics. Further validation in an independent cohort of non-suicidal chronic schizophrenia subjects (n = 13) and non-psychiatric controls (n = 14) showed that parvalbumin was increased, while calmodulin was decreased in schizophrenia. Our findings provide evidence of calcium-binding protein dysregulation in the cerebellum in schizophrenia, suggesting an impact on normal calcium-dependent synaptic functioning of cerebellar circuits. Our study also links VPP1 to suicide behaviours, suggesting a possible impairment in vesicle neurotransmitter refilling and release in these phenotypes.

Aquatic macroinvertebrates play a crucial role in freshwater ecosystems, but their diversity remains poorly known, particularly in the tropics. This "taxonomic void" limits our understanding of biodiversity patterns and processes in freshwater ecosystems, and the scale at which they operate. We used DNA barcoding to estimate lineage diversity (and the diversity of unique haplotypes) in 224 specimens of freshwater macroinvertebrates at a small spatial scale within the Panama Canal Watershed (PCW). In addition, we compiled available barcoding data to assess macroinvertebrate diversity at a broader spatial scale spanning the Isthmus of Panama. Consistently across two species delimitation algorithms (i.e., ABGD and GMYC), we found high lineage diversity within the PCW, with ~ 100-106 molecular operational taxonomic units (MOTUs) across 168 unique haplotypes. We also found a high lineage diversity along the Isthmus of Panama, but this diversity peaked within the PCW. However, our rarefaction/extrapolation approach showed that this diversity remains under-sampled. As expected, these results indicate that the diversity of Neotropical freshwater macroinvertebrates is higher than previously thought, with the possibility of high endemicity even at narrow spatial scales. Consistent with previous work on aquatic insects and other freshwater taxa in this region, geographic isolation is likely a main factor shaping these patterns of diversity. However, other factors such as habitat variability and perhaps local adaptation might be reshaping these patterns of diversity at a local scale. Although further research is needed to better understand the processes driving diversification in freshwater macroinvertebrates, we suggest that Neotropical streams hold a high proportion of hidden biodiversity. Understanding this diversity is crucial in the face of increasing human disturbance.

IntroductionInterfacility transfers may reflect a time delay of definitive surgical care, but few studies have examined the prevalence of interfacility transfers in the urban low- and middle-income (LMIC) setting. The aim of this study was to determine the number of interfacility transfers required for surgical and obstetric conditions in an urban MIC setting to better understand access to definitive surgical care among LMIC patients.MethodsA retrospective analysis of public interfacility transfer records was conducted from April 2015 to April 2016 in Cali, Colombia. Data were obtained from the single municipal ambulance agency providing publicly funded ambulance transfers in the city. Interfacility transfers were defined as any patient transfer between two healthcare facilities. We identified the number of transfers for patients with surgical conditions and categorized transfers based on patient ICD-9-CM codes. We compared surgical transfers from public vs. private healthcare facilities by condition type (surgical, obstetric, nonsurgical), transferring physician specialty, and transfer acuity (code blue, emergent, urgent and nonurgent) using logistic regression.Results31,659 patient transports occurred over the 13-month study period. 22250 (70.2%) of all transfers were interfacility transfers and 7777 (35%) of transfers were for patients with surgical conditions with an additional 2,244 (10.3%) for obstetric conditions. 49% (8660/17675) of interfacility transfers from public hospitals were for surgical and obstetric conditions vs 32% (1466/4580) for private facilities (PConclusionSurgical and obstetric conditions account for nearly half of all urban interfacility ambulance transfers. The most common reasons for transfer are basic surgical conditions with public healthcare facilities transferring a greater proportion of patient with surgical conditions than private facilities. Timely access to an initial healthcare facility may not be a reliable surrogate of definitive surgical care given the substantial need for interfacility transfers.

BackgroundEfficacy and safety of treatments for hospitalized COVID-19 are uncertain. We systematically reviewed efficacy and safety of remdesivir for the treatment of COVID-19.MethodsStudies evaluating remdesivir in adults with hospitalized COVID-19 were searched in several engines until August 21, 2020. Primary outcomes included all-cause mortality, clinical improvement or recovery, need for invasive ventilation, and serious adverse events (SAEs). Inverse variance random effects meta-analyses were performed.ResultsWe included four randomized controlled trials (RCTs) (n = 2296) [two vs. placebo (n = 1299) and two comparing 5-day vs. 10-day regimens (n = 997)], and two case series (n = 88). Studies used intravenous remdesivir 200mg the first day and 100mg for four or nine more days. One RCT (n = 236) was stopped early due to AEs; the other three RCTs reported outcomes between 11 and 15 days. Time to recovery was decreased by 4 days with remdesivir vs. placebo in one RCT (n = 1063), and by 0.8 days with 5-days vs. 10-days of therapy in another RCT (n = 397). Clinical improvement was better for 5-days regimen vs. standard of care in one RCT (n = 600). Remdesivir did not decrease all-cause mortality (RR 0.71, 95%CI 0.39 to 1.28, I2 = 43%) and need for invasive ventilation (RR 0.57, 95%CI 0.23 to 1.42, I2 = 60%) vs. placebo at 14 days but had fewer SAEs; 5-day decreased need for invasive ventilation and SAEs vs. 10-day in one RCT (n = 397). No differences in all-cause mortality or SAEs were seen among 5-day, 10-day and standard of care. There were some concerns of bias to high risk of bias in RCTs. Heterogeneity between studies could be due to different severities of disease, days of therapy before outcome determination, and how ordinal data was analyzed.ConclusionsThere is paucity of adequately powered and fully reported RCTs evaluating effects of remdesivir in hospitalized COVID-19 patients. Until stronger evidence emerges, we cannot conclude that remdesivir is efficacious for treating COVID-19.

The application of artificial intelligence (AI) and machine learning (ML) in biomedical research promises to unlock new information from the vast amounts of data being generated through the delivery of healthcare and the expanding high-throughput research applications. Such information can aid medical diagnoses and reveal various unique patterns of biochemical and immune features that can serve as early disease biomarkers. In this report, we demonstrate the feasibility of using an AI/ML approach in a relatively small dataset to discriminate among three categories of samples obtained from mice that either rejected or tolerated their pancreatic islet allografts following transplant in the anterior chamber of the eye, and from naïve controls. We created a locked software based on a support vector machine (SVM) technique for pattern recognition in electropherograms (EPGs) generated by micellar electrokinetic chromatography and laser induced fluorescence detection (MEKC-LIFD). Predictions were made based only on the aligned EPGs obtained in microliter-size aqueous humor samples representative of the immediate local microenvironment of the islet allografts. The analysis identified discriminative peaks in the EPGs of the three sample categories. Our classifier software was tested with targeted and untargeted peaks. Working with the patterns of untargeted peaks (i.e., based on the whole pattern of EPGs), it was able to achieve a 21 out of 22 positive classification score with a corresponding 95.45% prediction accuracy among the three sample categories, and 100% accuracy between the rejecting and tolerant recipients. These findings demonstrate the feasibility of AI/ML approaches to classify small numbers of samples and they warrant further studies to identify the analytes/biochemicals corresponding to discriminative features as potential biomarkers of islet allograft immune rejection and tolerance.

We investigated the mechanisms of excitation-contraction (EC) coupling in human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and fetal ventricular myocytes (hFVMs) using patch-clamp electrophysiology and confocal microscopy. We tested the hypothesis that Ca(2+) influx via voltage-gated L-type Ca(2+) channels activates Ca(2+) release from the sarcoplasmic reticulum (SR) via a local control mechanism in hESC-CMs and hFVMs. Field-stimulated, whole-cell [Ca(2+)](i) transients in hESC-CMs required Ca(2+) entry through L-type Ca(2+) channels, as evidenced by the elimination of such transients by either removal of extracellular Ca(2+) or treatment with diltiazem, an L-type channel inhibitor. Ca(2+) release from the SR also contributes to the [Ca(2+)](i) transient in these cells, as evidenced by studies with drugs interfering with either SR Ca(2+) release (i.e. ryanodine and caffeine) or reuptake (i.e. thapsigargin and cyclopiazonic acid). As in adult ventricular myocytes, membrane depolarization evoked large L-type Ca(2+) currents (I(Ca)) and corresponding whole-cell [Ca(2+)](i) transients in hESC-CMs and hFVMs, and the amplitude of both I(Ca) and the [Ca(2+)](i) transients were finely graded by the magnitude of the depolarization. hESC-CMs exhibit a decreasing EC coupling gain with depolarization to more positive test potentials, "tail" [Ca(2+)](i) transients upon repolarization from extremely positive test potentials, and co-localized ryanodine and sarcolemmal L-type Ca(2+) channels, all findings that are consistent with the local control hypothesis. Finally, we recorded Ca(2+) sparks in hESC-CMs and hFVMs. Collectively, these data support a model in which tight, local control of SR Ca(2+) release by the I(Ca) during EC coupling develops early in human cardiomyocytes.

[This corrects the article DOI: 10.1371/journal.pone.0222145.].

The aim was to evaluate the effect of different feed additives on intake, performance, and fecal consistency index (FCI) of dairy calves from 6-60 d of age and its residual effect 15 d after weaning. Fifty Holstein calves (38 ± 1.0 kg BW) were fed 5 L/d of milk plus starter feed until weaning, and corn silage and concentrate after weaning. The treatments were: control (CON), monensin (MON; 30 mg/kg of starter), probiotic E. faecium (PROB; 70 mg/kg of starter), essential oils (EO; 300 mg/kg of starter), or PROB + EO (EOPROB). Fecal score and dry matter intake (DMI) were measured daily, and animals were weighed every 15 d. A DNA extraction from feces was performed to identify the presence of microorganisms (E. coli, Hafnia, Shiguella, Lactobacillus spp, Enterococcus spp, and Enterococcus faecium NCIMB 10415) by PCR. Two 72-h digestibility trials were performed at days 20-28 and 50-56, by total fecal collection. The DMI before weaning was greater for EO (903.0 g/d) compared with MON (794.3 g/d) and EOPROB (783.1 g/d). The FCI decreased during pre-weaning for EO and MON. Average daily gain (ADG) and feed efficiency (FE) did not differ among treatments before weaning. After weaning, DMI and FCI did not differ among treatments. The EO had greater ADG (917.5 g/d) compared with CON (615.8 g/d) and PROB (592.6 g/d). The FE improved with EO (0.72 g/g) over CON (0.36 g/g), MON (0.49 g/g), and PROB (0.36 g/g). The PCR results showed absence of E. faecium NCIMB 10415 in animals fed PROB and CON. Animals fed PROB had greater intake of CP and NDF than animals fed EOPROB. The EO can be added to the dairy calf ration to improve fecal score and increase DMI. The pre-weaning FCI decrease with MON and increase with PROB.

OBJECTIVES:To test the hypothesis that transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) influences performance in a 20-min time-trial self-paced exercise and electroencephalographic (EEG) oscillatory brain activity in a group of trained male cyclists. DESIGN:The study consisted of a pre-registered (https://osf.io/rf95j/), randomised, sham-controlled, single-blind, within-subject design experiment. METHODS:36 trained male cyclists, age 27 (6.8) years, weight 70.1 (9.5) Kg; VO2max: 54 (6.13) ml.min-1.kg-1, Maximal Power output: 4.77 (0.6) W/kg completed a 20-min time-trial self-paced exercise in three separate sessions, corresponding to three stimulation conditions: anodal, cathodal and sham. tDCS was administered before each test during 20-min at a current intensity of 2.0 mA. The anode electrode was placed over the DLPFC and the cathode in the contralateral shoulder. In each session, power output, heart rate, sRPE and EEG (at baseline and during exercise) was measured. RESULTS:There were no differences (F = 0.31, p > 0.05) in power output between the stimulation conditions: anodal (235 W [95%CI 222-249 W]; cathodal (235 W [95%CI 222-248 W] and sham (234 W [95%CI 220-248 W]. Neither heart rate, sRPE nor EEG activity were affected by tDCS (all Ps > 0.05). CONCLUSION:tDCS over the left DLFC did not affect self-paced exercise performance in trained cyclists. Moreover, tDCS did not elicit any change on oscillatory brain activity either at baseline or during exercise. Our data suggest that the effects of tDCS on endurance performance should be taken with caution.

The microbiome plays a key role in the biology, ecology and evolution of arthropod vectors of human pathogens. Vector-bacterial interactions could alter disease transmission dynamics through modulating pathogen replication and/or vector fitness. Nonetheless, our understanding of the factors shaping the bacterial community in arthropod vectors is incomplete. Using large-scale 16S amplicon sequencing, we examine how habitat disturbance structures the bacterial assemblages of field-collected whole-body hematophagous arthropods that vector human pathogens including mosquitoes (Culicidae), sand flies (Psychodidae), biting midges (Ceratopogonidae) and hard ticks (Ixodidae). We found that all comparisons of the bacterial community among species yielded statistically significant differences, but a difference was not observed between adults and nymphs of the hard tick, Haemaphysalis juxtakochi. While Culicoides species had the most distinct bacterial community among dipterans, tick species were composed of entirely different bacterial OTU's. We observed differences in the proportions of some bacterial types between pristine and disturbed habitats for Coquillettidia mosquitoes, Culex mosquitoes, and Lutzomyia sand flies, but their associations differed within and among arthropod assemblages. In contrast, habitat quality was a poor predictor of differences in bacterial classes for Culicoides biting midges and hard tick species. In general, similarities in the bacterial communities among hematophagous arthropods could be explained by their phylogenetic relatedness, although intraspecific variation seems influenced by habitat disturbance.

The carboxysome is a bacterial micro-compartment (BMC) subtype that encapsulates enzymatic activities necessary for carbon fixation. Carboxysome shells are composed of a relatively complex cocktail of proteins, their precise number and identity being species dependent. Shell components can be classified in two structural families, the most abundant class associating as hexamers (BMC-H) that are supposed to be major players for regulating shell permeability. Up to recently, these proteins were proposed to associate as homo-oligomers. Genomic data, however, demonstrated the existence of paralogs coding for multiple shell subunits. Here, we studied cross-association compatibilities among BMC-H CcmK proteins of Synechocystis sp. PCC6803. Co-expression in Escherichia coli proved a consistent formation of hetero-hexamers combining CcmK1 and CcmK2 or, remarkably, CcmK3 and CcmK4 subunits. Unlike CcmK1/K2 hetero-hexamers, the stoichiometry of incorporation of CcmK3 in associations with CcmK4 was low. Cross-interactions implicating other combinations were weak, highlighting a structural segregation of the two groups that could relate to gene organization. Sequence analysis and structural models permitted the localization of interactions that would favor formation of CcmK3/K4 hetero-hexamers. The crystallization of these CcmK3/K4 associations conducted to the elucidation of a structure corresponding to the CcmK4 homo-hexamer. Yet, subunit exchange could not be demonstrated in vitro. Biophysical measurements showed that hetero-hexamers are thermally less stable than homo-hexamers, and impeded in forming larger assemblies. These novel findings are discussed within the context of reported data to propose a functional scenario in which minor CcmK3/K4 incorporation in shells would introduce sufficient local disorder as to allow shell remodeling necessary to adapt rapidly to environmental changes.

IntroductionAssociation between parent's Body Mass Index (BMI) and their children, has been widely documented. Individual, familiar and structural factors play a role in this relation. We analyzed the association between maternal BMI change during the first year post-partum and their offspring's growth-trajectories and energy intake in their first five years of life.ObjectiveCompare growth-trajectories and children's caloric intake according to post-partum mother´s BMI classification.MethodsThe anthropometric assessment was taken in 935 mother-child pairs along the study period. Mothers were classified into four groups according to their BMI-trajectories in the post-partum. Children's weight for height z-scores (WHZ) was compared among groups using random-effects regression models. A longitudinal comparison of children's caloric intake by the maternal group was carried out.ResultsAt 42 months of age, infants from mothers that remained overweight during the first year post-partum had, on average, 0.61 SD higher WHZ than those from mothers who remained in a recommended BMI group (R-BMI) in the same period. At 60 months of age, children´s prevalence of obesity was almost twice in the maternal overweight group vs R-BMI group (14.2% and 7.3% respectively). Chances for a child of having an over caloric intake were 36.5% (95% IC: 6.6%, 74.8%) and significantly higher among children from overweight mothers than those from R-BMI mothers. The difference in children's WHZ trajectory remained significant after adjusting for caloric intake, suggesting that contextual factors play a role in shaping children's obesity. A concurrent ethnographic study with the study subjects provides suggestions as to what these factors might be, including changes in the food landscape.ConclusionChildren from overweight mothers tended to have a more caloric diet yielding a higher propensity to obesity. Contextual factors such as food landscape might contribute to childhood obesity beyond having an overweight mother. Pregnancy and post-partum is a window of opportunity for interventions to decrease the incidence of children's overweight.

Antimicrobial resistance (AMR) represents a serious threat to global health. The development of new drugs to combat infections caused by bacteria resistant to multiple or even all available antibiotics is urgent. Most antibiotics used up to date have been identified from soil microorganisms. The marine environment represents an alternative source with great potential for the identification of microorganisms that produce bioactive molecules, including antibiotics. In this study, we analyzed the antibacterial activity of a collection of 82 bacterial strains isolated from marine water and sediment samples collected from the Southwestern Gulf of Mexico. Eight of the marine isolates inhibited the growth of different pathogenic bacteria, seven of which were identified as presumptive Pseudomonas aeruginosa. Interestingly, genome sequencing and phylogenetic analysis revealed that the remaining marine isolate showing antibacterial activity is a novel Pseudomonas species that we denominated Pseudomonas sp. GOM7, which was not pathogenic in the Galleria mellonella infection model in the conditions tested. Notably, Pseudomonas sp. GOM7 inhibited the growth of multidrug and methicillin-resistant strains of the priority pathogen Staphylococcus aureus. Our results show that the anti-S. aureus compound(s) produced by Pseudomonas sp. GOM7 can be extracted from the culture supernatant of this bacterium with the organic solvent ethyl acetate. Annotation of the Pseudomonas sp. GOM7 genome revealed the presence of several biosynthetic gene clusters predicted to code for possible antimicrobial compounds. Our results further highlight the potential of bacteria from the Gulf of Mexico as a source of novel antimicrobials. [ABSTRACT FROM AUTHOR]

The human skeleton undergoes constant remodeling throughout the lifetime. Processes occurring on microscopic and molecular scales degrade bone and replace it with new, fully functional tissue. Multiple bone remodeling events occur simultaneously, continuously and independently throughout the body, so that the entire skeleton is completely renewed about every ten years.Bone remodeling is performed by groups of cells called Bone Multicellular Units (BMU). BMUs consist of different cell types, some specialized in the resorption of old bone, others encharged with producing new bone to replace the former. These processes are tightly regulated so that the amount of new bone produced is in perfect equilibrium with that of old bone removed, thus maintaining bone microscopic structure.To date, many regulatory molecules involved in bone remodeling have been identified, but the precise mechanism of BMU operation remains to be fully elucidated. Given the complexity of the signaling pathways already known, one may question whether such complexity is an inherent requirement of the process or whether some subset of the multiple constituents could fulfill the essential role, leaving functional redundancy to serve an alternative safety role. We propose in this work a minimal model of BMU function that involves a limited number of signals able to account for fully functional BMU operation. Our main assumptions were i) at any given time, any cell within a BMU can select only one among a limited choice of decisions, i.e. divide, die, migrate or differentiate, ii) this decision is irreversibly determined by depletion of an appropriate internal inhibitor and iii) the dynamics of any such inhibitor are coupled to that of specific external mediators, such as hormones, cytokines, growth factors. It was thus shown that efficient BMU operation manifests as an emergent process, which results from the individual and collective decisions taken by cells within the BMU unit in the absence of any external planning.

Works requiring taxonomic knowledge face several challenges, such as arduous identification of many taxa and an insufficient number of taxonomists to identify a great deal of collected organisms. Machine learning tools, particularly convolutional neural networks (CNNs), are then welcome to automatically generate high-performance classifiers from available data. Supported by the image datasets available at the largest online database on ant biology, the AntWeb (www.antweb.org), we propose here an ensemble of CNNs to identify ant genera directly from the head, profile and dorsal perspectives of ant images. Transfer learning is also considered to improve the individual performance of the CNN classifiers. The performance achieved by the classifiers is diverse enough to promote a reduction in the overall classification error when they are combined in an ensemble, achieving an accuracy rate of over 80% on top-1 classification and an accuracy of over 90% on top-3 classification.

New effective compounds for tuberculosis treatment are needed. This study evaluated the effects of a series of quinoxaline-derived chalcones against laboratorial strains and clinical isolates of M. tuberculosis. Six molecules, namely N5, N9, N10, N15, N16, and N23 inhibited the growth of the M. tuberculosis H37Rv laboratorial strain. The three compounds (N9, N15 and N23) with the lowest MIC values were further tested against clinical isolates and laboratory strains with mutations in katG or inhA genes. From these data, N9 was selected as the lead compound for further investigation. Importantly, this chalcone displayed a synergistic effect when combined with moxifloxacin. Noteworthy, the anti-tubercular effects of N9 did not rely on inhibition of mycolic acids synthesis, circumventing important mechanisms of resistance. Interactions with cytochrome P450 isoforms and toxic effects were assessed in silico and in vitro. The chalcone N9 was not predicted to elicit any mutagenic, genotoxic, irritant, or reproductive effects, according to in silico analysis. Additionally, N9 did not cause mutagenicity or genotoxicity, as revealed by Salmonella/microsome and alkaline comet assays, respectively. Moreover, N9 did not inhibit the cytochrome P450 isoforms CYP3A4/5, CYP2C9, and CYP2C19. N9 can be considered a potential lead molecule for development of a new anti-tubercular therapeutic agent.

This study examines whether the relationship between the employees' perceived job autonomy may be prone to the contextual influence of supervisor support and presenteeism climate in explaining the attendance behaviors of presenteeism-the employees' decision to attend work despite being ill or not feeling well. Does work context play a role on presenteeism climate and the specific act of presenteeism? This study includes 213 health care employees (e.g., nurses, doctors) working in one private hospital in Lebanon. We used the ordinary least squared (OLS) regressions path analytical framework and bootstrapping methods to estimate the hypothesized moderated-mediation models. Our findings indicate that healthcare job resources (job autonomy) is correlated with the presenteeism climate and the occurrence of presenteeism attendance behaviors. We also found that this relationship is mediated by presenteeism climate and that supervisor support moderates the observed indirect relationship. This study extends the organizational attendance research domain to presenteeism climate by explaining for both doctors and nurses how contextual variables explains the relationship between jobs resources and presenteeism attendance behaviors. Supervisor support plays an important role in encouraging task autonomy and thus allowing employees increase their perception of empowerment to manage their actions at work. Overall, healthcare managers should ensure that employees understand their roles and duties and have an up-to-date, clearly defined role (e.g., job description) so that they can meet their organizations' goals.

BACKGROUND:Bacteremia is common in severe urinary infections, but its influence on the outcomes is not well established. The aim of this study was to assess the association of bacteremia with outcomes in elderly patients admitted to hospital with pyelonephritis or urinary sepsis. METHODS:This prospective muticenter observational study was conducted at 5 Spanish hospitals. All patients aged >65 years with pyelonephritis or urinary sepsis admitted to the departments of internal medicine and with urine and blood cultures obtained at admission to hospital were eligible. Transfer to ICU, length of hospital stay, hospital mortality and all cause 30-day mortality in bacteremic and non-bacteremic groups were compared. Risk factors for all cause 30-day mortality was also estimated. RESULTS:Of the 424 patients included in the study 181 (42.7%) had bacteremia. Neither transfer to ICU (4.4% vs. 2.9%, p = 0.400), nor length of hospital stay (9.7±4.6 days vs. 9.0±7.3 days, p = 0.252), nor hospital mortality (3.3% vs. 6.2%, p = 0.187), nor all cause 30-day mortality (9.4% vs. 13.2%, p = 0.223) were different between bacteremic and non-bacteremic groups. By multivariate analysis, risk factors for all cause 30-day mortality were age (OR 1.05, 95% CI 1.00-1.10), McCabe index ≥2 (OR 10.47, 95% CI 2.96-37.04) and septic shock (OR 8.56, 95% CI 2.86-25.61); whereas, bacteremia was inversely associated with all cause 30-day mortality (OR 0.33, 95% CI 0.15-0.71). CONCLUSIONS:In this cohort, bacteremia was not associated with a worse prognosis in elderly patients with pyelonephritis or urinary sepsis.

The conservation of many endangered taxa relies on hybrid identification, and when hybrids become morphologically indistinguishable from the parental species, the use of molecular markers can assign individual admixture levels. Here, we present the puzzling case of the extinct in the wild Alagoas Curassow (Pauxi mitu), whose captive population descends from only three individuals. Hybridization with the Razor-billed Curassow (P. tuberosa) began more than eight generations ago, and admixture uncertainty affects the whole population. We applied an analysis framework that combined morphological diagnostic traits, Bayesian clustering analyses using 14 microsatellite loci, and mtDNA haplotypes to assess the ancestry of all individuals that were alive from 2008 to 2012. Simulated data revealed that our microsatellites could accurately assign an individual a hybrid origin until the second backcross generation, which permitted us to identify a pure group among the older, but still reproductive animals. No wild species has ever survived such a severe bottleneck, followed by hybridization, and studying the recovery capability of the selected pure Alagoas Curassow group might provide valuable insights into biological conservation theory.

OBJECTIVES:Vitamin D (VD) enhances the immune response against Mycobacterium tuberculosis in vitro, and VD deficiency has been described in patients with active tuberculosis (TB). However, the role of hypovitaminosis D in the pathogenesis of early TB infection acquisition is unclear. We aimed to evaluate the association of VD deficiency, season of the year, and latent TB infection in household contacts (HHC), given that this is a potentially modifiable condition often related to nutritional deficiencies and lack of sun exposure. METHODS:We prospectively enrolled new pulmonary TB cases (n = 107) and their HHC (n = 144) over a 2-year period in Santiago, Chile. We compared plasma 25-hydroxycholecalciferol (25OHD) levels and examined the influence of season, ethnic background, living conditions, and country of origin. RESULTS:Over 77% of TB cases and 62.6% of HHC had VD deficiency (