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OBJECTIVES: To analyze the time between antiretroviral therapy (ART) initiation and the first HIV viral load (VL) test

BackgroundThe primary objective of this study was to retrospectively compare short-term outcomes of intracorporeal versus extracorporeal anastomosis for minimally invasive laparoscopic and robotic-assisted right colectomies for benign and malignant disease. Recent studies suggest potential short-term outcomes advantages for the intracorporeal anastomosis technique.MethodsThis is a multicenter retrospective propensity score-matched comparison of intracorporeal and extracorporeal anastomosis techniques for laparoscopic and robotic-assisted right colectomy between January 11, 2010, and July 21, 2016.ResultsAfter propensity score-matching, there were a total of 1029 minimal invasive surgery cases for analysis-379 right colectomies (335 robotic-assisted and 44 laparoscopic) done with an intracorporeal anastomosis and 650 right colectomies (253 robotic-assisted and 397 laparoscopic) done with an extracorporeal anastomosis. There were no significant differences in any preoperative patient characteristics between groups. The minimally invasive intracorporeal anastomosis group had significantly longer operative times (p

Captive environments trigger the propagation and multiplication of parasites among different reptile species, thus weakening their immune response and causing infections and diseases. Technological advances of convolutional neural networks have opened a new field for detecting and classifying diseases which have shown great potential to overcome the shortcomings of manual detection performed by experts. Therefore, we propose an approach to identify six captive reptiles parasitic agents (Ophionyssus natricis, Blastocystis sp, Oxiurdo egg, Rhytidoides similis, Strongyloides, Taenia) or the absence of such parasites from a microscope stool images dataset. Towards this end, we first use an image segmentation stage to detect the parasite within the image, which combines the Contrast Limited Adaptive Histogram Equalization (CLAHE) technique, the OTSU binarization method, and morphological operations. Then, we carry out a classification stage through MobileNet CNN under a transfer learning scheme. This method was validated on a stool image dataset containing 3616 images data samples and 26 videos from the six parasites mentioned above. The results obtained indicate that our transfer learning-based approach can learn a helpful representation from the dataset. We obtained an average accuracy of 94.26% across the seven classes (i.e., six parasitic agents and the absence of parasites), which statistically outperformed, at a 95% confidence level, a custom CNN trained from scratch.

In this study, we present the results of a genome-wide scan for signatures of positive selection using data from four tribal groups (Kokana, Warli, Bhil, and Pawara) and two caste groups (Deshastha Brahmin and Kunbi Maratha) from West of the Maharashtra State In India, as well as two samples of South Asian ancestry from the 1KG project (Gujarati Indian from Houston, Texas and Indian Telugu from UK). We used an outlier approach based on different statistics, including PBS, xpEHH, iHS, CLR, Tajima's D, as well as two recently developed methods: Graph-aware Retrieval of Selective Sweeps (GRoSS) and Ascertained Sequentially Markovian Coalescent (ASMC). In order to minimize the risk of false positives, we selected regions that are outliers in all the samples included in the study using more than one method. We identified putative selection signals in 107 regions encompassing 434 genes. Many of the regions overlap with only one gene. The signals observed using microarray-based data are very consistent with our analyses using high-coverage sequencing data, as well as those identified with a novel coalescence-based method (ASMC). Importantly, at least 24 of these genomic regions have been identified in previous selection scans in South Asian populations or in other population groups. Our study highlights genomic regions that may have played a role in the adaptation of anatomically modern humans to novel environmental conditions after the out of Africa migration.

Introduction We systematically assessed benefits and harms of tocilizumab (TCZ), which is an antibody blocking IL-6 receptors, in hospitalized COVID-19 patients. Methods Five electronic databases and two preprint webpages were searched until March 4, 2021. Randomized controlled trials (RCTs) and inverse probability treatment weighting (IPTW) cohorts assessing TCZ effects in hospitalized, COVID-19 adult patients were included. Primary outcomes were all-cause mortality, clinical worsening, clinical improvement, need for mechanical ventilation, and adverse events (AE). Inverse variance random-effects meta-analyses were performed with quality of evidence (QoE) evaluated using GRADE methodology. Results Nine RCTs (n = 7,021) and nine IPTW cohorts (n = 7,796) were included. TCZ significantly reduced all-cause mortality in RCTs (RR 0.89, 95%CI 0.81–0.98, p = 0.03; moderate QoE) and non-significantly in cohorts (RR 0.67, 95%CI 0.44–1.02, p = 0.08; very low QoE) vs. control (standard of care [SOC] or placebo). TCZ significantly reduced the need for mechanical ventilation (RR 0.80, 95%CI 0.71–0.90, p = 0.001; moderate QoE) and length of stay (MD -1.92 days, 95%CI -3.46 to -0.38, p = 0.01; low QoE) vs. control in RCTs. There was no significant difference in clinical improvement or worsening between treatments. AEs, severe AEs, bleeding and thrombotic events were similar between arms in RCTs, but there was higher neutropenia risk with TCZ (very low QoE). Subgroup analyses by disease severity or risk of bias (RoB) were consistent with main analyses. Quality of evidence was moderate to very low in both RCTs and cohorts. Conclusions In comparison to SOC or placebo, TCZ reduced all-cause mortality in all studies and reduced mechanical ventilation and length of stay in RCTs in hospitalized COVID-19 patients. Other clinical outcomes were not significantly impacted. TCZ did not have effect on AEs, except a significant increased neutropenia risk in RCTs. TCZ has a potential role in the treatment of hospitalized COVID-19 patients.

Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 infection in children and adolescents primarily causes mild or asymptomatic coronavirus disease 2019 (COVID-19), and severe illness is mainly associated with comorbidities. However, the worldwide prevalence of COVID-19 in this population is only 1%-2%. In Mexico, the prevalence of COVID-19 in children has increased to 10%. As serology-based studies are scarce, we analyzed the clinical features and serological response (SARS-CoV-2 structural proteins) of children and adolescents who visited the Hospital Infantil de México Federico Gómez (October 2020-March 2021). The majority were 9-year-old children without comorbidities who were treated as outpatients and had mild-to-moderate illness. Children aged 6-10 years and adolescents aged 11-15 years had the maximum number of symptoms, including those with obesity. Nevertheless, children with comorbidities such as immunosuppression, leukemia, and obesity exhibited the lowest antibody response, whereas those aged 1-5 years with heart disease had the highest levels of antibodies. The SARS-CoV-2 spike receptor-binding domain-localized peptides and M and E proteins had the best antibody response. In conclusion, Mexican children and adolescents with COVID-19 represent a heterogeneous population, and comorbidities play an important role in the antibody response against SARS-CoV-2 infection.

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.

IntroductionResearchers display an interest in studying aspects like the mental health of high-performance athletes; the dark side of sport, or the earliest attempts to study the so-called dark triad of personality in both initiation and high-performance athletes. Therefore, the objective of this paper is to determine the possible existence and magnitude of negative psychological aspects within a population of competition sailors and from a probabilistic point of view, using Bayesian Network analysis.MethodsThe study was carried out on 235 semi-professional sailors of the 49er Class, aged between 16 and 52 years (M = 24.66; SD = 8.03).ResultsThe results show the existence of a Negative Tetrad-formed by achievement burnout, anxiety due to concentration disruption, amotivation and importance given to error-as a probabilistic product of the psychological variables studied: motivation, anxiety, burnout and fear of error.ConclusionThese results, supported by Bayesian networks, show holistically the influence of the social context on the psychological and emotional well-being of the athlete during competition at sea.

BackgroundResidents of Nursing Homes (NHs) have suffered greater impacts from the COVID-19 pandemic. However, the rates of COVID-19 in these institutions are heterogeneously distributed. Describing and understanding the structural, functional, and socioeconomic differences between NHs is extremely important to avoid new outbreaks.ObjectivesAnalyze inequalities in the cumulative incidences (CIs) and in the mortality rates (MRs) due to COVID-19 in the NHs of Barcelona based on the characteristics of the NHs.MethodsExploratory ecological study of 232 NHs. The dependent variables were the cumulative incidence and mortality rate due to COVID-19 in NHs between March and June 2020. Structural variables of the NHs were evaluated such as neighborhood socioeconomic position (SEP), isolation and sectorization capacity, occupancy, overcrowding and ownership.ResultsThe cumulative incidence and mortality rate were higher in the low SEP neighborhoods and lower in those of high SEP neighborhoods. Regarding the isolation and sectorization capacity, Type B NHs had a higher risk of becoming infected and dying, while Type C had a lower risk of dying than Type A. Greater overcrowding was associated with greater morbidity and mortality, and higher occupancy was associated with higher incidence. The risk of becoming infected and dying in public NHs was significantly higher than for-profit NH.ConclusionsThe social components together with the functional and infrastructure characteristics of the NHs influence the cumulative incidence and the mortality rate by COVID-19. It is necessary to redefine the care model in the NHs to guarantee the health of the residents.

Despite increasing evidence that plant intra- and inter-specific diversity increases primary productivity, and that such effect may in turn cascade up to influence herbivores, there is little information about plant diversity effects on plant anti-herbivore defenses, the relative importance of different sources of plant diversity, and the mechanisms for such effects. For example, increased plant growth at high diversity may lead to reduced investment in defenses via growth-defense trade-offs. Alternatively, positive effects of plant diversity on plant growth may lead to increased herbivore abundance which in turn leads to a greater investment in plant defenses. The magnitude of trait variation underlying diversity effects is usually greater among species than among genotypes within a given species, so plant species diversity effects on resource use by producers as well as on higher trophic levels should be stronger than genotypic diversity effects. Here we compared the relative importance of plant genotypic and species diversity on anti-herbivore defenses and whether such effects are mediated indirectly via diversity effects on plant growth and/or herbivore damage. To this end, we performed a large-scale field experiment where we manipulated genotypic diversity of big-leaf mahogany (Swietenia macrophylla) and tree species diversity, and measured effects on mahogany growth, damage by the stem-boring specialist caterpillar Hypsipyla grandella, and defensive traits (polyphenolics and condensed tannins in stem and leaves). We found that both forms of plant diversity had positive effects on stem (but not leaf) defenses. However, neither source of diversity influenced mahogany growth, and diversity effects on defenses were not mediated by either growth-defense trade-offs or changes in stem-borer damage. Although the mechanism(s) of diversity effects on plant defenses are yet to be determined, our study is one of the few to test for and show producer diversity effects on plant chemical defenses.

The spaceflight environment is relevant to conditions encountered by pathogens during the course of infection and induces novel changes in microbial pathogenesis not observed using conventional methods. It is unclear how microbial cells sense spaceflight-associated changes to their growth environment and orchestrate corresponding changes in molecular and physiological phenotypes relevant to the infection process. Here we report that spaceflight-induced increases in Salmonella virulence are regulated by media ion composition, and that phosphate ion is sufficient to alter related pathogenesis responses in a spaceflight analogue model. Using whole genome microarray and proteomic analyses from two independent Space Shuttle missions, we identified evolutionarily conserved molecular pathways in Salmonella that respond to spaceflight under all media compositions tested. Identification of conserved regulatory paradigms opens new avenues to control microbial responses during the infection process and holds promise to provide an improved understanding of human health and disease on Earth.

Chromosome shaping and individualization are necessary requisites to warrant the correct segregation of genomes in either mitotic or meiotic cell divisions. These processes are mainly prompted in vertebrates by three multiprotein complexes termed cohesin and condensin I and II. In the present study we have analyzed by immunostaining the appearance and subcellular distribution of condensin I in mouse mitotic and meiotic chromosomes. Our results demonstrate that in either mitotically or meiotically dividing cells, condensin I is loaded onto chromosomes by prometaphase. Condensin I is detectable as a fuzzy axial structure running inside chromatids of condensed chromosomes. The distribution of condensin I along the chromosome length is not uniform, since it preferentially accumulates close to the chromosome ends. Interestingly, these round accumulations found at the condensin I axes termini colocalized with telomere complexes. Additionally, we present the relative distribution of the condensin I and cohesin complexes in metaphase I bivalents. All these new data have allowed us to propose a comprehensive model for meiotic chromosome structure.

Influenza and respiratory syncytial virus (RSV) cause acute infections of the respiratory tract. Since the viruses both cause illnesses with similar symptoms, researchers often try to apply knowledge gleaned from study of one virus to the other virus. This can be an effective and efficient strategy for understanding viral dynamics or developing treatment strategies, but only if we have a full understanding of the similarities and differences between the two viruses. This study used mathematical modeling to quantitatively compare the viral kinetics of in vitro RSV and influenza virus infections. Specifically, we determined the viral kinetics parameters for RSV A2 and three strains of influenza virus, A/WSN/33 (H1N1), A/Puerto Rico/8/1934 (H1N1), and pandemic H1N1 influenza virus. We found that RSV viral titer increases at a slower rate and reaches its peak value later than influenza virus. Our analysis indicated that the slower increase of RSV viral titer is caused by slower spreading of the virus from one cell to another. These results provide estimates of dynamical differences between influenza virus and RSV and help provide insight into the virus-host interactions that cause observed differences in the time courses of the two illnesses in patients.

Videos and commercials produced for large audiences can elicit mixed opinions. We wondered whether this diversity is also reflected in the way individuals watch the videos. To answer this question, we presented 65 commercials with high production value to 25 individuals while recording their eye movements, and asked them to provide preference ratings for each video. We find that gaze positions for the most popular videos are highly correlated. To explain the correlations of eye movements, we model them as "interactions" between individuals. A thermodynamic analysis of these interactions shows that they approach a "critical" point such that any stronger interaction would put all viewers into lock-step and any weaker interaction would fully randomise patterns. At this critical point, groups with similar collective behaviour in viewing patterns emerge while maintaining diversity between groups. Our results suggest that popularity of videos is already evident in the way we look at them, and that we maintain diversity in viewing behaviour even as distinct patterns of groups emerge. Our results can be used to predict popularity of videos and commercials at the population level from the collective behaviour of the eye movements of a few viewers.

Molecular alterations leading progression of asymptomatic CLL-like high-count monoclonal B lymphocytosis (hiMBL) to chronic lymphocytic leukemia (CLL) remain poorly understood. Recently, genome-wide association studies have found 6p21.3, where the human leukocyte antigen (HLA) system is coded, to be a susceptibility risk region for CLL. Previous studies have produced discrepant results regarding the association between HLA and CLL development and outcome, but no studies have been performed on hiMBL.We evaluated the role of HLA class I (-A, -B and -C) and class II (-DRB1 and -DQB1) in hiMBL/CLL susceptibility, hiMBL progression to CLL, and treatment requirement in a large series of 263 patients diagnosed in our center with hiMBL (n = 156) or Binet A CLL (n = 107).No consistent association between HLA specificities and hiMBL or CLL susceptibility was found. With a median follow-up of 7.7 years, 48/156 hiMBLs (33%) evolved to asymptomatic CLLs, while 16 hiMBLs (10%) and 44 CLLs (41%) required treatment. No HLA specificities were found to be significantly associated with hiMBL progression or treatment in the whole cohort. However, within antigen-experienced immunoglobulin heavy-chain (IGHV)-mutated hiMBLs, which represents the highest proportion of hiMBL cases (81%), the presence of HLA-DQB1*03 showed a trend to a higher risk of progression to CLL (60% vs. 26%, P = 0.062). Moreover, HLA-DQB1*02 specificity was associated with a lesser requirement for 15-year treatment (10% vs. 36%, P = 0.012).In conclusion, our results suggest a role for HLA in IGHV-mutated hiMBL prognosis, and are consistent with the growing evidence of the influence of 6p21 on predisposition to CLL. Larger non-biased series are required to enable definitive conclusions to be drawn.

The composition of ecological assemblages depends on a variety of factors including environmental filtering, biotic interactions and dispersal limitation. By evaluating the phylogenetic pattern of assemblages, we gain insight into the relative contribution of these mechanisms to generating observed assemblages. We address some limitations in the field of community phylogenetics by using simulations, biologically relevant null models, and cost distance analysis to evaluate simultaneous mechanisms leading to observed patterns of co-occurrence. Building from past studies of phylogenetic community structure, we applied our approach to hummingbird assemblages in the Northern Andes. We compared the relationship between relatedness and co-occurrence among predicted assemblages, based on estimates of suitable habitat and dispersal limitation, and observed assemblages. Hummingbird co-occurrence peaked at intermediate relatedness and decreased when a closely-related species was present. This result was most similar to simulations that included simultaneous effects of phylogenetic conservatism and repulsion. In addition, we found older sister taxa were only weakly more separated by geographic barriers, suggesting that time since dispersal is unlikely to be the sole factor influencing co-occurrence of closely related species. Our analysis highlights the role of multiple mechanisms acting simultaneously, and provides a hypothesis for the potential importance of competition at regional scales.

Several microorganisms produce nosocomial infections (NIs), among which Pseudomonas aeruginosa stands out as an opportunist pathogen with the capacity to develop multiresistance to first-choice antibiotics. From 2007 to 2013, forty-six NIs produced by P. aeruginosa were detected at a pediatric tertiary care hospital in Mexico with a significant mortality rate (17.39%). All isolates (n = 58/46 patients) were characterized by evaluating their response to several antibiotics as panresistant (PDR), extensively resistant (XDR), multiresistant (MDR) or sensitive (S). In addition, all isolates were typified through multilocus sequencing of seven genes: acsA, aroE, guaA, mutL, nuoD, ppsA and trpE. Furthermore, to establish the genetic relationships among these isolates, we carried out a phylogenetic inference analysis using maximum likelihood to construct a phylogenetic network. To assess evolutionary parameters, recombination was evaluated using the PHI test, and the ratio of nonsynonymous to synonymous substitutions was determined. Two of the strains were PDR (ST1725); 42 were XDR; four were MDR; and ten were S. Twenty-one new sequence types were detected. Thirty-three strains exhibited novel sequence type ST1725. The ratio of nonsynonym to synonym substitutions was 1:1 considering all genes. Phylogenetic analysis showed that the genetic relationship of the PDR, XDR and MDR strains was mainly clonal; however, the PHI test and the phylogenetic network suggest that recombination events occurred to produce a non-clonal population. This study aimed not only to determine the genetic diversity of clinical P. aeruginosa but also to provide a warning regarding the identification and spreading of clone ST1725, its ability to cause outbreaks with high mortality rates, and to remain in the hospital environment for over seven years. These characteristics highlight the need to identify clonal outbreaks, especially where high resistance to most antibiotics is observed, and control measures are needed. This study also represents the first report of the PDR ST1725.

OBJECTIVES:Vascular calcification is a frequent complication in chronic haemodialysis patients and is associated with adverse outcomes. Serum calcium and phosphate levels and imbalances in calcification regulators are thought to contribute to the process. In this regard, the dialysate calcium concentration is a modifiable tool for modulating the risk of vascular calcification. We explored pre- and post-dialysis phosphate and calcium concentrations in stable chronic haemodialysis patients treated by dialysis with the KDIGO-suggested 1.5 mmol/L calcium dialysate to investigate the effects on ex vivo calcification of rat aortic rings. APPROACH AND RESULTS:At the end of haemodialysis, mean serum calcium levels were increased in 88% of paired pre-/post-dialysis samples, while mean serum phosphate and parathyroid hormone levels were decreased. Rat aortic ring cultures grown at the same calcium and phosphate concentrations revealed that pre- and post-dialysis resulted in a similar degree of calcification. By contrast, haemodialysis with unchanged serum calcium resulted in a 5-fold reduction in calcium deposition. CONCLUSION:Dialysis with the widely prescribed 1.5 mmol/L calcium dose results in persistent high serum calcification potential in a sizable proportion of patients, driven by increased post-dialysis calcium concentration. This could potentially be mitigated by individualising dialysate calcium dosage based on pre-dialysis serum calcium levels.

Bioconjugate preparation is a fundamental step for antibody generation and immunoassay development to small chemical compounds. For analytical targets holding in their structure an aryl halogen atom, cross-coupling reactions may be a simple and efficient way to obtain functionalized derivatives; thus offering great potential to elicit robust and selective immune responses after being coupled to immunogenic carrier proteins. However, substitution of the halogen atom by an aliphatic chain might eventually compromise the affinity and specificity of the resulting antibodies. In order to address this issue, proquinazid, a new-generation fungicide with outstanding performance, was chosen as model analyte. Two functionalized derivatives differing in spacer arm rigidity were synthesized by Sonogashira cross-coupling chemistry. These haptens were covalently coupled to bovine serum albumin and the resulting immunoconjugates were employed for rabbit vaccination. Antibodies were tested for proquinazid recognition by direct and indirect competitive immunoassay, and IC50 values in the low nanomolar range were found, thus demonstrating the suitability of this straightforward synthetic strategy for the generation of immunoreagents to compounds bearing an aryl halide. Following antibody characterization, competitive immunoassays were developed and employed to determine proquinazid residues in grape musts, and their analytical performance was satisfactorily validated by comparison with GC-MS. Besides having described the development of the first immunochemical method for proquinazid analysis, an efficient functionalization approach for analytes comprising aryl halides is reported.

Malaria remains a major global public health problem with an estimated 200 million cases detected in 2012. Although the most advanced candidate malaria vaccine (RTS,S) has shown promise in clinical trials, its modest efficacy and durability have created uncertainty about the impact of RTS,S immunization (when used alone) on global malaria transmission. Here we describe the development and characterization of a novel modified vaccinia virus Ankara (MVA)-based malaria vaccine which co-expresses the Plasmodium yoelii circumsporozoite protein (CSP) and IL-15. Vaccination/challenge studies showed that C57BL/6 mice immunized with the MVA-CSP/IL15 vaccine were protected significantly better against a P. yoelii 17XNL sporozoite challenge than either mice immunized with an MVA vaccine expressing only CSP or naïve controls. Importantly, the levels of total anti-CSP IgG were elevated about 100-fold for the MVA-CSP/IL15 immunized group compared to mice immunized with the MVA-CSP construct that does not express IL-15. Among the IgG subtypes, the IL-15 expressing MVA-CSP vaccine induced levels of IgG1 (8 fold) and IgG2b (80 fold) higher than the MVA-CSP construct. The significantly enhanced humoral responses and protection detected after immunization with the MVA-CSP/IL15 vaccine suggest that this IL-15 expressing MVA construct could be considered in the development of future malaria immunization strategies.

disease is one of the most neglected tropical diseases in the world, affecting nearly 15 million people, primarily in Latin America. Only two drugs are used for the treatment of this disease, nifurtimox and benznidazole. These drugs have limited efficacy and frequently induce adverse effects, limiting their usefulness. Consequently, new drugs must be found. In this study, we demonstrated the in vitro trypanocidal effects of a series of four gallic acid derivatives characterized by a gallate group linked to a triphenylphosphonium (TPP(+)) moiety (a delocalized cation) via a hydrocarbon chain of 8, 10, 11, or 12 atoms (TPP(+)-C8, TPP(+)-C10, TPP(+)-C11, and TPP(+)-C12, respectively). We analyzed parasite viability in isolated parasites (by MTT reduction and flow cytometry) and infected mammalian cells using T. cruzi Y strain trypomastigotes. Among the four derivatives, TPP(+)-C10 and TPP(+)-C12 were the most potent in both models, with EC50 values (in isolated parasites) of 1.0 ± 0.6 and 1.0 ± 0.7 μM, respectively, and were significantly more potent than nifurtimox (EC50 = 4.1 ± 0.6 μM). At 1 μM, TPP(+)-C10 and TPP(+)-C12 induced markers of cell death, such as phosphatidylserine exposure and propidium iodide permeabilization. In addition, at 1 μM, TPP(+)-C10 and TPP(+)-C12 significantly decreased the number of intracellular amastigotes (TPP(+)-C10: 24.3%, TPP(+)-C12: 19.0% of control measurements, as measured by DAPI staining) and the parasite's DNA load (C10: 10%, C12: 13% of control measurements, as measured by qPCR). Based on the previous mode of action described for these compounds in cancer cells, we explored their mitochondrial effects in isolated trypomastigotes. TPP(+)-C10 and TPP(+)-C12 were the most potent compounds, significantly altering mitochondrial membrane potential at 1 μM (measured by JC-1 fluorescence) and inducing mitochondrial transition pore opening at 5 μM. Taken together, these results indicate that the TPP(+)-C10 and TPP(+)-C12 derivatives of gallic acid are promising trypanocidal agents with mitochondrial activity.

Studies of pharmacogenomics-related traits are increasingly being performed to identify loci that affect either drug response or susceptibility to adverse drug reactions. However, the effect of the polymorphisms can differ in magnitude or be absent depending on the population being assessed. We used the Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus array to characterize the distribution of polymorphisms of pharmacogenetics and pharmacogenomics (PGx) relevance in two samples from the most populous Latin American countries, Brazil and Mexico. The sample from Brazil included 268 individuals from the southeastern state of Rio de Janeiro, and was stratified into census categories. The sample from Mexico comprised 45 Native American Zapotecas and 224 self-identified Mestizo individuals from 5 states located in geographically distant regions in Mexico. We evaluated the admixture proportions in the Brazilian and Mexican samples using a panel of Ancestry Informative Markers extracted from the DMET array, which was validated with genome-wide data. A substantial variation in ancestral proportions across census categories in Brazil, and geographic regions in Mexico was identified. We evaluated the extent of genetic differentiation (measured as FST values) of the genetic markers of the DMET Plus array between the relevant parental populations. Although the average levels of genetic differentiation are low, there is a long tail of markers showing large frequency differences, including markers located in genes belonging to the Cytochrome P450, Solute Carrier (SLC) and UDP-glucuronyltransferase (UGT) families as well as other genes of PGx relevance such as ABCC8, ADH1A, CHST3, PON1, PPARD, PPARG, and VKORC1. We show how differences in admixture history may have an important impact in the distribution of allele and genotype frequencies at the population level.

Immunity contributes to arterial inflammation during atherosclerosis. Oxidized low-density lipoproteins induce an autoimmune response characterized by specific antibodies and immune complexes in atherosclerotic patients. We hypothesize that specific Fcγ receptors for IgG constant region participate in atherogenesis by regulating the inflammatory state of lesional macrophages. In vivo we examined the role of activating Fcγ receptors in atherosclerosis progression using bone marrow transplantation from mice deficient in γ-chain (the common signaling subunit of activating Fcγ receptors) to hyperlipidemic mice. Hematopoietic deficiency of Fcγ receptors significantly reduced atherosclerotic lesion size, which was associated with decreased number of macrophages and T lymphocytes, and increased T regulatory cell function. Lesions of Fcγ receptor deficient mice exhibited increased plaque stability, as evidenced by higher collagen and smooth muscle cell content and decreased apoptosis. These effects were independent of changes in serum lipids and antibody response to oxidized low-density lipoproteins. Activating Fcγ receptor deficiency reduced pro-inflammatory gene expression, nuclear factor-κB activity, and M1 macrophages at the lesion site, while increasing anti-inflammatory genes and M2 macrophages. The decreased inflammation in the lesions was mirrored by a reduced number of classical inflammatory monocytes in blood. In vitro, lack of activating Fcγ receptors attenuated foam cell formation, oxidative stress and pro-inflammatory gene expression, and increased M2-associated genes in murine macrophages. Our study demonstrates that activating Fcγ receptors influence the macrophage phenotypic balance in the artery wall of atherosclerotic mice and suggests that modulation of Fcγ receptor-mediated inflammatory responses could effectively suppress atherosclerosis.

Recently, studies of adaptive color variation have become popular as models for examining the genetics of natural selection. We examined color pattern polymorphism and genetic variation in a population of side-blotched lizards (Uta stansburiana) that is found in habitats with both dark (lava) and light colored (granite) substrates. We conducted a limited experiment for adult phenotypic plasticity in laboratory conditions. We recorded both substrate and lizard color patterns in the field to determine whether lizards tended to match their substrate. Finally we examined genetic variation in a gene (melanocortin 1 receptor) that has been shown to affect lizard color in other species and in a presumably neutral gene (mitochondrial cytochrome b). Populations were sampled in the immediate area of the lava flows as well as from a more distant site to examine the role of population structure. Our captive Uta did not change color to match their background. We show that side-blotched lizards tend to match the substrate on which it was caught in the field and that variation in the melanocortin 1 receptor gene does not correlate well with color pattern in this population. Perhaps the most remarkable result is that this population of side-blotched lizards shows extremely high levels of variation at both genetic markers, in the sense of allele numbers, with relatively low levels of between-allele sequence variation. Genetic variation across this small region was as great or greater than that seen in samples of pelagic fish species collected worldwide. Statistical analysis of genetic variation suggests rapid population expansion may be responsible for the high levels of variation.

INTRODUCTION: Obesity is a worldwide public health issue. Since the epidemiological behaviour of this disease is not well established in our country, the purpose of this study was to determinate its prevalence in the Maracaibo City, Zulia State- Venezuela. MATERIALS AND METHODS: A cross-sectional study was undertaken using the data set from the Maracaibo City Metabolic Syndrome Prevalence Study. The sample consists of 2108 individuals from both genders and randomly selected: 1119 (53.09%) women and 989 (46.91%) men. The participants were interrogated for a complete clinical history and anthropometric measurements. To classify obesity, the WHO criteria for Body Mass Index (BMI), and Waist Circumference (WC) from the IDF/NHLBI/AHA/WHF/IAS/IASO-2009 (IDF-2009) and ATPIII statements were applied. RESULTS: For BMI, obesity had an overall prevalence of 33.3% (n = 701), and according to gender women had 32.4% (n = 363) and men had 34.2% (n = 338). Overweight had a prevalence of 34.8% (n = 733), Normal weight had 29.8% (n = 629), and Underweight had 2.1% (n = 45). Adding Obesity and Overweight results, the prevalence of elevated BMI (>25 Kg/m(2)) was 68.1%. Using the IDF-2009 WC's cut-off, Obesity had 74.2% prevalence, compared to 51.7% using the ATPIII parameters. CONCLUSIONS: These results show a high prevalence of abdominal obesity in our locality defined by the WHO, IDF-2009 and ATPIII criteria, which were not designed for Latin-American populations. We suggest further investigation to estimate the proper values according to ethnicity, genetic background and sociocultural aspects.

A current concern in genetic epidemiology studies in admixed populations is that population stratification can lead to spurious results. The Brazilian census classifies individuals according to self-reported "color", but several studies have demonstrated that stratifying according to "color" is not a useful strategy to control for population structure, due to the dissociation between self-reported "color" and genomic ancestry. We report the results of a study in a group of Brazilian siblings in which we measured skin pigmentation using a reflectometer, and estimated genomic ancestry using 21 Ancestry Informative Markers (AIMs). Self-reported "color", according to the Brazilian census, was also available for each participant. This made it possible to evaluate the relationship between self-reported "color" and skin pigmentation, self-reported "color" and genomic ancestry, and skin pigmentation and genomic ancestry. We observed that, although there were significant differences between the three "color" groups in genomic ancestry and skin pigmentation, there was considerable dispersion within each group and substantial overlap between groups. We also saw that there was no good agreement between the "color" categories reported by each member of the sibling pair: 30 out of 86 sibling pairs reported different "color", and in some cases, the sibling reporting the darker "color" category had lighter skin pigmentation. Socioeconomic status was significantly associated with self-reported "color" and genomic ancestry in this sample. This and other studies show that subjective classifications based on self-reported "color", such as the one that is used in the Brazilian census, are inadequate to describe the population structure present in recently admixed populations. Finally, we observed that one of the AIMs included in the panel (rs1426654), which is located in the known pigmentation gene SLC24A5, was strongly associated with skin pigmentation in this sample.

The spaceflight environment is relevant to conditions encountered by pathogens during the course of infection and induces novel changes in microbial pathogenesis not observed using conventional methods. It is unclear how microbial cells sense spaceflight-associated changes to their growth environment and orchestrate corresponding changes in molecular and physiological phenotypes relevant to the infection process. Here we report that spaceflight-induced increases in Salmonella virulence are regulated by media ion composition, and that phosphate ion is sufficient to alter related pathogenesis responses in a spaceflight analogue model. Using whole genome microarray and proteomic analyses from two independent Space Shuttle missions, we identified evolutionarily conserved molecular pathways in Salmonella that respond to spaceflight under all media compositions tested. Identification of conserved regulatory paradigms opens new avenues to control microbial responses during the infection process and holds promise to provide an improved understanding of human health and disease on Earth.

BackgroundOne of the most important pillars of action to achieve the elimination of trachoma and soil-transmitted helminth infections as a public health problem is the mass administration, at regular intervals, of azithromycin and anthielmintics, respectively, to a high proportion of the eligible population in endemic areas.ObjectiveThe objective of the study was to identify access barriers and facilitators for achieving coverage goals in the mass drugs administration, azithromycin and albendazole, in the department of Amazonas, Colombia.MethodologyImplementation research was used, combining three types of qualitative research methodologies to collect information about access barriers and facilitators already described; These were individual and group interviews, focus group discussions and face-to-face intercultural dialogues. We design, validate and apply different instruments with questions adapted to the context and role of the participants, and recorded and transcribed the sessions and analyzed them in qualitative analysis software. We used the Consolidated Framework for Implementation Research (CFIR) to complement the above instrument questions, to guide data analysis, and apply the Consolidated Criteria for Reporting Qualitative Research (COREQ).ResultsRecords of 159 participants were included; 21 individual and 3 group interviews, 6 focus group discussions and 4 intercultural dialogues were carried out. 21 strong, 30 weak, 6 neutral barriers as well as 5 weak and 11 strong facilitators were identified. 62% of the strong barriers and 40% of the weak ones were concentrated in the "Outer Setting Domain". Only 16 facilitators were identified, 44% in the "Innovation" domain.ConclusionsMultiple political, administrative, geographical, logistical and cultural access barriers, as well as external and internal migration of the population, explain low coverage in mass administration of azithromycin and albendazole. It is necessary to review them individually to implement an improvement plan that also recognizes the identified facilitators.

PurposeHER2-low has garnered significant attention for the treatment of HER2-negative breast cancer. We aimed to determine the prevalence of HER2-low expression in Hispanic/Latino women with breast cancer (BC).MethodsWe searched in Embase, LILACS, and Medline databases for articles reporting the expression of HER2 immunohistochemistry with scores reported as 0, 1+, 2+, or 3+, with equivocal cases (2+) confirmed through in situ hybridization (ISH).ResultsA total of 12 articles were finally included, comprising 73,467 individuals. The prevalence of HER2-zero, HER2-low and HER2 positive cases among all BC (0, 1+, 2+/ISH-, 2+/ISH+ and 3+), was 45.0%, 32.0%, and 23.0%, respectively. The prevalence of HER2-zero and HER2-low expression among negative cases (0, 1+ and 2+/ISH-), was 53.0% and 47.0%, respectively.ConclusionThere is an important percentage of Hispanic/Latino individuals who would benefit from HER2-targeted therapies, even in HER2 negative cases. Additional research on the prevalence of HER2-low tumors across a wider range of Latin American countries is required to better understand the molecular epidemiology of this biomarker within the Hispanic/Latino population.

[This corrects the article DOI: 10.1371/journal.pone.0292727.].

[This corrects the article DOI: 10.1371/journal.pone.0240200.].

ObjectivesTo analyze the time between antiretroviral therapy (ART) initiation and the first HIV viral load (VL) test MethodsThis was a cohort study with data from a linkage of national HIV databases, following a previously published procedure. Two types of variables were examined: individual-level (sex, age group, race/skin color, education, baseline CD4 cell count and VL, initial ART regimen, adherence, ART regimen change and number of VL tests until suppression) and facility-level (national and metropolitan region, caseload). Multilevel parametric accelerated failure time survival models were used. Fixed and random effects were analyzed through null, sociodemographic, combined sociodemographic and clinical, and facility-related variables, adjusted for the number of VL tests until suppression. Likelihood, interquartile range, and proportion of change in variance were used for comparisons.ResultsOf 132,540 participants, 89.4% (114,696) achieved viral suppression: 20.8% within three months, and 56.4% within six months. Median TS was 161 days, varying from 31 to 1,426 days, depending on the time interval between initiation and VL testing. Among those who had VL testing within 66 days, median TS was 55 days. All individual and facility-related variables were associated with TS, explaining the 16.2% and 13.2% variability, respectively.ConclusionsThis was the first Brazilian nationwide cohort to analyze TS. It is also one of the largest operational cohorts globally to assess healthcare facility characteristics. The findings indicated that both individual and facility-related characteristics contribute to TS. Strengthening VL monitoring should be included as part of a coordinated effort to improve the quality of care provided for people living with HIV/AIDS in Brazil.

Major clusters of Guillain-Barré Syndrome (GBS) emerged during the Zika virus (ZIKV) outbreaks in the South Pacific and the Americas from 2014 to 2016. The factors contributing to GBS susceptibility in ZIKV infection remain unclear, although considerations of viral variation, patient susceptibility, environmental influences, and other potential factors have been hypothesized. Studying the role of viral genetic factors has been challenging due to the low viral load and rapid viral clearance from the blood after the onset of Zika symptoms. The prolonged excretion of ZIKV in urine by the time of GBS onset, when the virus is no longer present in the blood, provides an opportunity to unravel whether specific ZIKV mutations are related to the development of GBS in certain individuals. This study aimed to investigate the association between specific ZIKV genotypes and the development of GBS, taking advantage of a unique collection of ZIKV-positive urine samples obtained from GBS cases and controls during the 2016 ZIKV outbreak in Colombia. Utilizing Oxford-Nanopore technology, we conducted complete genome sequencing of ZIKV in biological samples from 15 patients with GBS associated with ZIKV and 17 with ZIKV infection without neurological complications. ZIKV genotypes in Colombia exhibited distribution across three clades (average bootstrap of 90.9±14.9%), with two clades dominating the landscape. A comparative analysis of ZIKV genomes from GBS and non-neurological complications, alongside 1368 previously reported genomes, revealed no significant distinctions between the two groups. Both genotypes were similarly distributed among observed clades in Colombia. Furthermore, no variations were identified in the amino acid composition of the viral genome between the two groups. Our findings suggest that GBS in ZIKV infection is perhaps associated with patient susceptibility and/or other para- or post-infectious immune-mediated mechanisms rather than with specific ZIKV genome variations.

Contact tracing played a crucial role in minimizing the onward dissemination of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in the recent pandemic. Previous studies had also shown the effectiveness of preventive measures such as mask-wearing, physical distancing, and exposure duration in reducing SARS-CoV-2 transmission. However, there is still a lack of understanding regarding the impact of various exposure settings on the spread of SARS-CoV-2 within the community, as well as the most effective preventive measures, considering the preventive measures adherence in different daily scenarios. We aimed to evaluate the effect of individual protective measures and exposure settings on the community transmission of SARS-CoV-2. Additionally, we aimed to investigate the interaction between different exposure settings and preventive measures in relation to such SARS-CoV-2 transmission. Routine SARS-CoV-2 contact tracing information was supplemented with additional data on individual measures and exposure settings collected from index patients and their close contacts. We used a case-control study design, where close contacts with a positive test for SARS-CoV-2 were classified as cases, and those with negative results classified as controls. We used the data collected from the case-control study to construct a Bayesian network (BN). BNs enable predictions for new scenarios when hypothetical information is introduced, making them particularly valuable in epidemiological studies. Our results showed that ventilation and time of exposure were the main factors for SARS-CoV-2 transmission. In long time exposure, ventilation was the most effective factor in reducing SARS-CoV-2, while masks and physical distance had on the other hand a minimal effect in this ventilation spaces. However, face masks and physical distance did reduce the risk in enclosed and unventilated spaces. Distance did not reduce the risk of infection when close contacts wore a mask. Home exposure presented a higher risk of SARS-CoV-2 transmission, and any preventive measures posed a similar risk across all exposure settings analyzed. Bayesian network analysis can assist decision-makers in refining public health campaigns, prioritizing resources for individuals at higher risk, and offering personalized guidance on specific protective measures tailored to different settings or environments.

The agricultural sector of Colombia supports the national economy and food security due to the rich lands for cultivation. Although Colombia has a vast hydrological basin, climate change can impact agricultural productivity, generating economic and social adverse effects. For this, we evaluated the impact of some environmental variables on the production of the most sold crops using production, climatic, and hydrological data of the 1121 municipalities from 2007 to 2020. We modeled the production of coffee, rice, palm oil, sugarcane, and corn, adopting a Bayesian spatio-temporal model that involved a set of environmental variables: average temperature, minimum temperature, maximum temperature, evapotranspiration, precipitation, runoff, soil moisture, vapor pressure, radiation, and wind speed. We found that increases in the average temperatures can affect coffee (-0.2% per °C), rice (-3.76% per °C), and sugarcane (-0.19% per °C) production, meanwhile, these increases can boost palm oil (+2.55% per °C) and corn (+1.28% per °C) production in Colombia. This statement implies that the agricultural sector needs to substitute land use, promoting the production of palm oil and corn. Although our results did not find a significant effect of hydrological variables in any crop, suggesting that the abundance of water in Colombia might balance the impact of these variables. The increases in vapor pressure impact all the crops negatively (between -11.2% to -0.43% per kPa), except rice, evidencing that dry air conditions affect agricultural production. Colombia must manage the production location of the traditional products and implement agro-industrial technologies to avoid the climate change impact on crops.

IntroductionThe COVID-19 pandemic has become a significant health crisis, marked by high mortality rates on a global scale, with mortality from the disease being notably concentrated among the elderly due to various factors.ObjectiveThis study aims to investigate the biological and non-biological factors associated with COVID-19 mortality rates among the elderly worldwide.MethodsThe following databases will be consulted: PubMed, Scopus, EMBASE, Web of Science and ScienceDirect. Longitudinal observational studies (cohort and case-control-risk factors) will be included. The risk of bias, defined as low, moderate, high, will be assessed using the National Heart, Lung and Blood Institute (NHLBI) Quality Assessment Tool for observational cohort and cross-sectional studies. Two independent authors will conduct the searches, and any possible disagreements will be resolved by a third author. Heterogeneity between study results will be assessed using a standard X2 test with a significance level of 0.05, and an I2 value will be calculated to further assess heterogeneity. The random effects model for meta-analyses will be adopted to distribute the weight between the studies and standardize their contributions. The meta-analyses will be conducted using RevMan software.DiscussionDespite the numerous publications on COVID-19 mortality among the elderly, there is still a gap in knowledge, as there is no systematic review and meta-analysis that summarizes the main biological and non-biological associated factors globally.ConclusionThe results of this study will consolidate the latest evidence and address gaps in the overall understanding of biological or non-biological associated factors. This knowledge will facilitate the development of appropriate health strategies for this demographic group and pave the way for further research.Trial registrationPROSPERO (CRD42023400873).

Bilateral proprioception includes the ability to sense the position and motion of one hand relative to the other, without looking. This sensory ability allows us to perform daily activities seamlessly, and its impairment is observed in various neurological disorders such as cerebral palsy and stroke. It can undergo experience-dependent plasticity, as seen in trained piano players. If its neural correlates were better understood, it would provide a useful assay and target for neurorehabilitation for people with impaired proprioception. We designed a non-invasive electroencephalography-based paradigm to assess the neural features relevant to proprioception, especially focusing on bilateral proprioception, i.e., assessing the limb distance from the body with the other limb. We compared it with a movement-only task, with and without the visibility of the target hand. Additionally, we explored proprioceptive accuracy during the tasks. We tested eleven Controls and nine Skilled musicians to assess whether sensorimotor event-related spectral perturbations in μ (8-12Hz) and low-β (12-18Hz) rhythms differ in people with musical instrument training, which intrinsically involves a bilateral proprioceptive component, or when new sensor modalities are added to the task. The Skilled group showed significantly reduced μ and low-β suppression in bilateral tasks compared to movement-only, a significative difference relative to Controls. This may be explained by reduced top-down control due to intensive training, despite this, proprioceptive errors were not smaller for this group. Target visibility significantly reduced proprioceptive error in Controls, while no change was observed in the Skilled group. During visual tasks, Controls exhibited significant μ and low-β power reversals, with significant differences relative to proprioceptive-only tasks compared to the Skilled group-possibly due to reduced uncertainty and top-down control. These results provide support for sensorimotor μ and low-β suppression as potential neuromarkers for assessing proprioceptive ability. The identification of these features is significant as they could be used to quantify altered proprioceptive neural processing in skill and movement disorders. This in turn can be useful as an assay for pre and post sensory-motor intervention research.

The fall armyworm (Spodoptera frugiperda) is one of the most destructive pests of corn. New infestations have been reported in the East Hemisphere, reaching India, China, Malaysia, and Australia, causing severe destruction to corn and other crops. In Puerto Rico, practical resistance to different mode of action compounds has been reported in cornfields. In this study, we characterized the inheritance of resistance to chlorantraniliprole and flubendiamide and identified the possible cross-resistance to cyantraniliprole and cyclaniliprole. The Puerto Rican (PR) strain showed high levels of resistance to flubendiamide (RR50 = 2,762-fold) and chlorantraniliprole (RR50 = 96-fold). The inheritance of resistance showed an autosomal inheritance for chlorantraniliprole and an X-linked inheritance for flubendiamide. The trend of the dominance of resistance demonstrated an incompletely recessive trait for H1 (♂ SUS × ♀ PR) × and an incompletely dominant trait for H2 (♀ SUS × ♂ PR) × for flubendiamide and chlorantraniliprole. The PR strain showed no significant presence of detoxification enzymes (using synergists: PBO, DEF, DEM, and VER) to chlorantraniliprole; however, for flubendiamide the SR = 2.7 (DEM), SR = 3.2 (DEF) and SR = 7.6 (VER) indicated the role of esterases, glutathione S- transferases and ABC transporters in the metabolism of flubendiamide. The PR strain showed high and low cross-resistance to cyantraniliprole (74-fold) and cyclaniliprole (11-fold), respectively. Incomplete recessiveness might lead to the survival of heterozygous individuals when the decay of diamide residue occurs in plant tissues. These results highlight the importance of adopting diverse pest management strategies, including insecticide rotating to manage FAW populations in Puerto Rico and other continents.

Environmental Impact Assessment is the process of evaluating the effects caused by a project on the environment. The outcomes generated by this assessment can lead to a reduction of the negative effects and an increase in the positive effects caused by mine projects. The present study was conducted to evaluate the environmental impact assessment of the Goliran Coal Mine in northern Iran. In the descriptive-analytical study, to achieve the objectives, observatory surveys were conducted around the coal mine using a checklist, which was about the positive and negative effects of a coal mine. Then the data were entered into the RIAM and the positive and negative effects were ranked and the most important effects were determined. In RIAM, one point is assigned to each component. 17 important activities for environmental impacts were identified using a checklist. Among the activities carried out at the coal mine site, the major ones included tunnel excavation, construction of the rail line collection and disposal of coal mine effluent, coal transportation, collection and disposal of mine tailings, and technical defects and leakage. The scores of each environmental factor were based on the four environmental components: physical/chemical, biological/ecological, social/cultural, and economic/operational. The results of the present study showed that the most negatively affected environmental components are the physical/chemical components derived from three activities; the construction of the underground tunnel; the construction of a coal transport rail line; and the actual transportation of coal extracts. The scores of each environmental factor based on the four components at the Goliran coal mine in northern Iran indicate that the highest negative score was -64, corresponding to the physical/chemical component, and was assigned to air pollution. On the other hand, the highest positive score corresponds to the economic/operational component with +54, assigned to the income that employees earn from the mine. Overall results showed that the coal mine in northern Iran had negative effects on the environment but the effects were not severe. It is suggested that for future research, corrective measures should be taken in the form of an environmental management plan to reduce the negative effects caused by coal mining, and then prospective research should be done to check the extent of reducing the negative effects.

The threat of population declines caused by pelagic longline fisheries in the Atlantic has increased the concern to find strategies that minimize the bycatch and mortality of non-target marine animals. Gear modification, such as the use of circle hooks instead of conventional J-hooks, has been identified as an effective bycatch reduction strategy in different pelagic longline fisheries around the world. This study aimed to verify the effectiveness of the use of circle hooks by quantifying catch rates, relative size selectivity, and anatomical hooking position for the most common target species (swordfish, Xiphias gladius, and blue shark, Prionace glauca), and some bycatch species (loggerhead sea turtles, Caretta caretta, and shortfin mako, Isurus oxyrinchus) caught by the Azorean longline fishing fleet. The trial was conducted for five consecutive years (2000-2004) using eight different types of hooks. In general, the blue shark catches using circle hooks were significantly higher compared to J (Mustad 9/0). The circle hooks also showed high probabilities of catching juvenile blue sharks. Conversely, the circle hooks were efficient in reducing the loggerhead sea turtle bycatch and were related to fewer catches of small sea turtle individuals. The use of circle hooks was also associated with reduced swordfish catches compared to J (Mustad 9/0), and the effect of hook types on length at capture was only significant for Circle (L. & P. 18/0-CLP18) and Ringed Tuna (RT). No significant differences were observed comparing hook type to either catch rates or size selectivity for shortfin mako. Additionally, circle hooks were more likely to lodge in the mouth than in deeper anatomical positions, when compared to J (Mustad 9/0), for the four species analysed. The present study demonstrated that the use of circle hooks could mitigate the impact of the pelagic longline fisheries in the Azores by decreasing the bycatch of sea turtles and reducing animal injuries caused by deep hooking.

BackgroundProsthetic valve endocarditis (PVE) is a serious infection associated with high mortality that often requires surgical treatment.MethodsStudy on clinical characteristics and prognosis of a large contemporary prospective cohort of prosthetic valve endocarditis (PVE) that included patients diagnosed between January 2008 and December 2020. Univariate and multivariate analysis of factors associated with in-hospital mortality was performed.ResultsThe study included 1354 cases of PVE. The median age was 71 years with an interquartile range of 62-77 years and 66.9% of the cases were male. Patients diagnosed during the first year after valve implantation (early onset) were characterized by a higher proportion of cases due to coagulase-negative staphylococci and Candida and more perivalvular complications than patients detected after the first year (late onset). In-hospital mortality of PVE in this series was 32.6%; specifically, it was 35.4% in the period 2008-2013 and 29.9% in 2014-2020 (p = 0.031). Variables associated with in-hospital mortality were: Age-adjusted Charlson comorbidity index (OR: 1.15, 95% CI: 1.08-1.23), intracardiac abscess (OR:1.78, 95% CI:1.30-2.44), acute heart failure related to PVE (OR: 3. 11, 95% CI: 2.31-4.19), acute renal failure (OR: 3.11, 95% CI:1.14-2.09), septic shock (OR: 5.56, 95% CI:3.55-8.71), persistent bacteremia (OR: 1.85, 95% CI: 1.21-2.83) and surgery indicated but not performed (OR: 2.08, 95% CI: 1.49-2.89). In-hospital mortality in patients with surgical indication according to guidelines was 31.3% in operated patients and 51.3% in non-operated patients (pConclusionsNot performing cardiac surgery in patients with PVE and surgical indication, according to guidelines, has a significant negative effect on in-hospital mortality. Strategies to better discriminate patients who can benefit most from surgery would be desirable.

Masculinities and femininities are often characterized by social inequalities and mainly studied from the perspectives of adult, heterosexual and non-activist people. This study explores the discourses on masculinities and femininities of young cisgender men and women, involved or not in feminist activism and of different sexual orientations (heterosexual, bisexual and homosexual) in Spain. Between 2019 and 2020, we conducted a qualitative study with 20 semi-structured interviews and 8 discussion groups in which 73 people participated. A socially dominant gender discourse was identified, which establishes a dichotomous understanding of masculinity in constant confrontation with femininity, as well as of heterosexuality against homosexuality, in a heteronormative context. Young people discursively position themselves differently from said discourse according to their sexual orientation and involvement in feminist activism. We encounter discursive positions that reproduce the socially dominant gender discourse, especially detected among non-activist heterosexuals. We also observe others that try to transgress it, mainly among activists of all sexual orientations and non-activist homosexuals and bisexuals. This study empirically adds to the knowledge of the configuration of inequalities in gender relations and how interactions with sexuality take place. The results also provide guidance for future gender-transformative interventions to promote gender equality and social justice.

The tumor immune infiltrate has an impact on cancer control and progression, additionally a growing body of evidence has proposed the role of neoadjuvant chemotherapy in modulating the contexture of the tumor immune infiltrate. Here, we performed a systematic review to evaluate the effect of chemotherapy in the immune infiltration of breast cancer tumors. We systematically searched Pubmed/MEDLINE, EMBASE, CENTRAL, and BVS databases with a cutoff date of 11/06/2022. Studies in patients with pathological diagnosis of BC, whose first line of treatment was only NAC, were included. Only published experimental studies that measured tumor immune infiltrate before and after NAC by hematoxylin and eosin (H&E) staining, immunohistochemistry (IHQ), or transcriptome were included. Reviews, studies with animal models and in-vitro models were excluded. Studies in which BC was not the primary tumor or studies with patients who received other types of neoadjuvant therapy were also excluded. The NIH quality assessment tool for before and after studies without control was used. We included 32 articles that evaluated the proximal tumor microenvironment before and after neoadjuvant chemotherapy in 2072 patients who received NAC as first line of treatment and who were evaluated for immune infiltrate in the pre- and post-chemotherapy tumor sample. Results were divided into two major categories immune cells and in-situ expression of immune checkpoints and cytokines. Qualitative synthesis was performed with the 32 articles included, and in nine of them a quantitative analysis was achieved, resulting in six meta-analyses. Despite high heterogeneity among the articles regarding treatment received, type of tumor reported, and techniques used to evaluate immune infiltrate, we found a significant decrease of TILs and FoxP3 expression after neoadjuvant chemotherapy. The study protocol was registered in PROSPERO 2021 (Protocol ID: CRD42021243784) on 6/29/2021.

IntroductionMentalization or reflective functioning (RF) is the capacity to interpret oneself or the others in terms of internal mental states. Its failures have been linked to several mental disorders and interventions improving RF have a therapeutic effect. Mentalizing capacity of the parents influences the children's attachment. The Reflective Functioning Questionnaire (RFQ-8) is a widely used tool for the assessment of RF. No instrument is available to assess general RF in Spanish-speaking samples. The aim of this study is to develop a Spanish version of the RFQ-8 and to evaluate its reliability and validity in the general population and in individuals with personality disorders.Methods602 non-clinical and 41 personality disordered participants completed a Spanish translation of the RFQ and a battery of self-reported questionnaires assessing several RF related constructs (alexithymia, perspective taking, identity diffusion and mindfulness), psychopathology (general and specific) and interpersonal problems. Temporal stability was tested in a non-clinical sub-sample of 113 participants.ResultsExploratory and confirmatory factor analyses suggested a one-factor structure in the Spanish version of the RFQ-8. RFQ-8 understood as a single scale was tested, with low scorings reflecting genuine mentalizing, and high scorings uncertainty. The questionnaire showed good internal consistence in both samples and moderate temporal stability in non-clinical sample. RFQ correlated significantly with identity diffusion, alexithymia, and general psychopathology in both samples; and with mindfulness, perspective taking, and interpersonal problems in clinical sample. Mean values of the scale were significantly higher in the clinical group.DiscussionThis study provides evidence that the Spanish version of the RFQ-8, understood as a single scale, has an adequate reliability and validity assessing failures in reflective functioning (i.e., hypomentalization) in general population and personality disorders.

Objective observation of pedestrian behavior on the street has traditionally been difficult due to intensive commitment of time and resources with spatial analysis of pedestrian locations encountering additional problems. Recently, Unmanned Aerial Vehicles (UAVs) have gained popularity due to the significant improvements they offer over other conventional observation systems, such as their ability to cover larger surface areas in less time. This study tests the performance of UAV-based observation techniques in measuring pedestrian activity in two comparative settings in Santiago de Chile. The study develops an alternative technique adapting the behavioral mapping methodology that allows acquiring information about the people's activities and the places where they are carried out. In this study a set of streets in the city of Santiago de Chile was selected as a case study, and the reliability of those observations was tested among raters in a population sample. Further, the use of a Geographic Information System (GIS) in the data coding process is detailed and exemplified using some of its spatial analysis tools. The results show high levels of inter-rater reliability in the different categories of recorded data. Finally, we discuss the advantages and limitations in observing pedestrian behavior using this technology and observation technique.