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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.

[This corrects the article DOI: 10.1371/journal.pone.0239291.].

BackgroundKetamine has recently attracted considerable attention for its rapid effects on patients with major depressive disorder, including treatment-resistant depression (TRD). Despite ketamine's promising results in treating depression, a significant number of patients do not respond to the treatment, and predicting who will benefit remains a challenge. Although its antidepressant effects are known to be linked to its action as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, the precise mechanisms that determine why some patients respond and others do not are still unclear.ObjectiveThis study aims to understand the computational mechanisms underlying changes in the auditory mismatch negativity (MMN) response following treatment with intravenous ketamine. Moreover, we aim to link the computational mechanisms to their underlying neural causes and use the parameters of the neurocomputational model to make individual treatment predictions.MethodsThis is a prospective study of 30 patients with TRD who are undergoing intravenous ketamine therapy. Prior to 3 out of 4 ketamine infusions, EEG will be recorded while patients complete the auditory MMN task. Depression, suicidality, and anxiety will be assessed throughout the study and a week after the last ketamine infusion. To translate the effects of ketamine on the MMN to computational mechanisms, we will model changes in the auditory MMN using the hierarchical Gaussian filter, a hierarchical Bayesian model. Furthermore, we will employ a conductance-based neural mass model of the electrophysiological data to link these computational mechanisms to their neural causes.ConclusionThe findings of this study may improve understanding of the mechanisms underlying response and resistance to ketamine treatment in patients with TRD. The parameters obtained from fitting computational models to EEG recordings may facilitate single-patient treatment predictions, which could provide clinically useful prognostic information.Trial registrationClinicaltrials.gov NCT05464264. Registered June 24, 2022.

The temporal variability of fish habitat utilization is poorly understood in tropical deltaic systems due to high water turbidity, which limits visual censuses, and to the lack of long-term data incorporating climate variability events. We aimed to assess the influence of body size and El Niño Southern Oscillation (ENSO) variability on the cross-habitat utilization rate of 14 fish species of commercial relevance in the Ciénaga Grande de Santa Marta (CGSM). We estimated the utilization of mangroves and coastal lagoons based on relative catch frequencies from encircling gillnets used within a long-term catch monitoring program, and then tested for significant changes in each species' habitat utilization as a function of body size and climate variability. Six species showed a high dependence on mangroves and four on coastal lagoons for most body size classes (including juveniles) and ENSO conditions. One species (Elops smithi) showed a high utilization of mangroves in some ENSO phases and body size classes, while three species showed a high utilization of both mangroves and coastal lagoons. Mangrove utilization by six species (Megalops atlanticus, E. smithi, Centropomus undecimalis, Mugil incilis, Mugil liza, and Ariopsis canteri) increased in larger body sizes at low depths, which usually occurs under dry ENSO conditions, when predatory risk is higher in coastal lagoons. Another species (Caquetaia kraussi) increased its mangrove utilization from the body size at which its feeding habits change. Mangroves and coastal lagoons are important nurseries and habitats for adults of the main commercial fish species in the CGSM. Seascape habitats and fringe/riverine mangroves must be conserved in tropical deltas to promote not only nurseries but also fish lifecycles.

BackgroundAir pollution contains a mixture of different pollutants from multiple sources. However, the interaction of these pollutants with other environmental exposures, as well as their harmful effects on children under five in tropical countries, is not well known.ObjectiveThis study aims to characterize the external exposome (ambient and indoor exposures) and its contribution to clinical respiratory and early biological effects in children.Materials and methodsA cohort study will be conducted on children under five (n = 500) with a one-year follow-up. Enrolled children will be followed monthly (phone call) and at months 6 and 12 (in person) post-enrolment with upper and lower Acute Respiratory Infections (ARI) examinations, asthma development, asthma control, and genotoxic damage. The asthma diagnosis will be pediatric pulmonologist-based and a standardized protocol will be used. Exposure, effect, and susceptibility biomarkers will be measured on buccal cells samples. For environmental exposures PM2.5 will be sampled, and questionnaires, geographic information, dispersion models and Land Use Regression models for PM2.5 and NO2 will be used. Different statistical methods that include Bayesian and machine learning techniques will be used for the ambient and indoor exposures-and outcomes. This study was approved by the ethics committee at Universidad Pontificia Bolivariana.Expected study outcomes/findingsTo estimate i) The toxic effect of particulate matter transcending the approach based on pollutant concentration levels; ii) The risk of developing an upper and lower ARI, based on different exposure windows; iii) A baseline of early biological damage in children under five, and describe its progression after a one-year follow-up; and iv) How physical and chemical PM2.5 characteristics influence toxicity and children's health.

Background Employment is a key social determinant of health. People living with HIV (PLWH) have higher unemployment rates than the general population. Vocational rehabilitation services have been shown to have significant and positive impact on employment status for PLWH. Understanding whether integrating vocational rehabilitation with health care services is acceptable, from the perspectives of PLWH and their health care providers, is an area that is understudied. Methods We conducted a qualitative study and collected data from focus groups and interviews to understand the perspectives of stakeholders regarding the potential for vocational rehabilitation and health care integration. We completed five focus groups with 45 health care providers and one-to-one interviews with 23 PLWHs. Participants were sampled from infectious disease, primary care clinics, and AIDS Service Organizations in Toronto and Ottawa, Canada. Interviews were audio-recorded and transcribed. We conducted a reflexive thematic analysis of the transcripts. Findings We found health care providers have little experience assisting patients with employment and PLWH had little experience receiving employment interventions from their health care team. This lack of integration between health care and vocational services was related to uncertainties around drug coverage, physician role and living with an episodic disability. Health care providers thought that there is potential for a larger role for health care clinics in providing employment interventions for PLWH however patients were divided. Some PLWH suggest that health care providers could provide advice on the disclosure of status, work limitations and act as advocates with employers. Interpretation Health care providers and some PLWH recognize the importance of integrating health services with vocational services but both groups have little experience with implementing these types of interventions. Thus, there needs to be more study of such interventions, including the processes entailed and outcomes they aim to achieve.

ObjectivesSome studies show an increased risk of gestational diabetes mellitus for ABO blood groups. Others find a lower risk or do not identify any association. Inconsistencies may be due to the heterogeneity in the control for confounding variables. We determined the association between ABO blood groups and gestational diabetes mellitus in Mexican women, controlling for gravidity and age, pre-pregnancy body mass index, fasting glucose at the first trimester, and first-degree relative with diabetes.MethodsThis case-control study was conducted from February 2019 to December 2021 in Monterrey, Mexico, with 185 cases (women with gestational diabetes mellitus) and 530 controls. ABO blood groups and other variables were obtained from the clinical records. A multivariate binary logistic regression was used for estimating association. Two models were run, one for primigravidae and another for non-primigravidae. A p-value < 0.05 was significant.ResultsThe ABO blood groups were O (69.4%), A (22.2%), B (6.7%), and AB (1.7%), with no differences between cases and controls (p = 0.884). No association was found between ABO blood groups and gestational diabetes mellitus, in primigravidae or non-primigravidae.ConclusionABO blood groups were not associated with an increased risk of gestational diabetes mellitus in Mexican women, independent of gravidity and well-known risk factors.

The temporal variability of fish habitat utilization is poorly understood in tropical deltaic systems due to high water turbidity, which limits visual censuses, and to the lack of long-term data incorporating climate variability events. We aimed to assess the influence of body size and El Niño Southern Oscillation (ENSO) variability on the cross-habitat utilization rate of 14 fish species of commercial relevance in the Ciénaga Grande de Santa Marta (CGSM). We estimated the utilization of mangroves and coastal lagoons based on relative catch frequencies from encircling gillnets used within a long-term catch monitoring program, and then tested for significant changes in each species' habitat utilization as a function of body size and climate variability. Six species showed a high dependence on mangroves and four on coastal lagoons for most body size classes (including juveniles) and ENSO conditions. One species (Elops smithi) showed a high utilization of mangroves in some ENSO phases and body size classes, while three species showed a high utilization of both mangroves and coastal lagoons. Mangrove utilization by six species (Megalops atlanticus, E. smithi, Centropomus undecimalis, Mugil incilis, Mugil liza, and Ariopsis canteri) increased in larger body sizes at low depths, which usually occurs under dry ENSO conditions, when predatory risk is higher in coastal lagoons. Another species (Caquetaia kraussi) increased its mangrove utilization from the body size at which its feeding habits change. Mangroves and coastal lagoons are important nurseries and habitats for adults of the main commercial fish species in the CGSM. Seascape habitats and fringe/riverine mangroves must be conserved in tropical deltas to promote not only nurseries but also fish lifecycles. [ABSTRACT FROM AUTHOR]

Background: Ketamine has recently attracted considerable attention for its rapid effects on patients with major depressive disorder, including treatment-resistant depression (TRD). Despite ketamine's promising results in treating depression, a significant number of patients do not respond to the treatment, and predicting who will benefit remains a challenge. Although its antidepressant effects are known to be linked to its action as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, the precise mechanisms that determine why some patients respond and others do not are still unclear. Objective: This study aims to understand the computational mechanisms underlying changes in the auditory mismatch negativity (MMN) response following treatment with intravenous ketamine. Moreover, we aim to link the computational mechanisms to their underlying neural causes and use the parameters of the neurocomputational model to make individual treatment predictions. Methods: This is a prospective study of 30 patients with TRD who are undergoing intravenous ketamine therapy. Prior to 3 out of 4 ketamine infusions, EEG will be recorded while patients complete the auditory MMN task. Depression, suicidality, and anxiety will be assessed throughout the study and a week after the last ketamine infusion. To translate the effects of ketamine on the MMN to computational mechanisms, we will model changes in the auditory MMN using the hierarchical Gaussian filter, a hierarchical Bayesian model. Furthermore, we will employ a conductance-based neural mass model of the electrophysiological data to link these computational mechanisms to their neural causes. Conclusion: The findings of this study may improve understanding of the mechanisms underlying response and resistance to ketamine treatment in patients with TRD. The parameters obtained from fitting computational models to EEG recordings may facilitate single-patient treatment predictions, which could provide clinically useful prognostic information. Trial registration: Clinicaltrials.gov NCT05464264. Registered June 24, 2022. [ABSTRACT FROM AUTHOR]

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

BackgroundValproic acid (VPA) has shown beneficial effects in vitro against SARS-CoV-2 infection, but no study has analyzed its efficacy in the clinical setting.MethodsThis multicenter, retrospective study included 165 adult patients receiving VPA at the time of admission to hospital, and 330 controls matched for sex, age and date of admission. A number of clinical, outcome and laboratory parameters were recorded to evaluate differences between the two groups. Four major clinical endpoints were considered: development of lung infiltrates, in-hospital respiratory worsening, ICU admissions and death.ResultsVPA-treated patients had higher lymphocyte (PConclusionsVPA-treated patients seem to develop less serious COVID-19 than control patients, according to diverse clinical endpoints and laboratory markers.

Entamoeba are amoeboid extracellular parasites that represent an important group of organisms for which the regulatory networks must be examined to better understand how genes and functional processes are interrelated. In this work, we inferred the gene regulatory networks (GRNs) in four Entamoeba species, E. histolytica, E. dispar, E. nuttalli, and E. invadens, and the GRN topological properties and the corresponding biological functions were evaluated. From these analyses, we determined that transcription factors (TFs) of E. histolytica, E. dispar, and E. nuttalli are associated mainly with the LIM family, while the TFs in E. invadens are associated with the RRM_1 family. In addition, we identified that EHI_044890 regulates 121 genes in E. histolytica, EDI_297980 regulates 284 genes in E. dispar, ENU1_120230 regulates 195 genes in E. nuttalli, and EIN_249270 regulates 257 genes in E. invadens. Finally, we identified that three types of processes, Macromolecule metabolic process, Cellular macromolecule metabolic process, and Cellular nitrogen compound metabolic process, are the main biological processes for each network. The results described in this work can be used as a basis for the study of gene regulation in these organisms.

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

Objective To determine the gene expression profile in individuals with new latent tuberculosis infection (LTBI), and to compare them with people with active tuberculosis (TB) and those exposed to TB but not infected. Design A prospective cohort study. Recruitment and follow-up were conducted between September 2016 to December 2018. Gene expression and data processing and analysis from April 2019 to April 2021. Setting Two male Colombian prisons. Participants 15 new tuberculin skin test (TST) converters (negative TST at baseline that became positive during follow-up), 11 people that continued with a negative TST after two years of follow-up, and 10 people with pulmonary ATB. Main outcome measures Gene expression profile using RNA sequencing from PBMC samples. The differential expression was assessed using the DESeq2 package in Bioconductor. Genes with |logFC| >1.0 and an adjusted p-value < 0.1 were differentially expressed. We analyzed the differences in the enrichment of KEGG pathways in each group using InterMiner. Results The gene expression was affected by the time of incarceration. We identified group-specific differentially expressed genes between the groups: 289 genes in people with a new LTBI and short incarceration (less than three months of incarceration), 117 in those with LTBI and long incarceration (one or more years of incarceration), 26 in ATB, and 276 in the exposed but non-infected individuals. Four pathways encompassed the largest number of down and up-regulated genes among individuals with LTBI and short incarceration: cytokine signaling, signal transduction, neutrophil degranulation, and innate immune system. In individuals with LTBI and long incarceration, the only enriched pathway within up-regulated genes was Emi1 phosphorylation. Conclusions Recent infection with MTB is associated with an identifiable RNA pattern related to innate immune system pathways that can be used to prioritize LTBI treatment for those at greatest risk for developing active TB.

This paper analyses COVID-19 patients' dynamics during the first wave in the region of Castilla y León (Spain) with around 2.4 million inhabitants using multi-state competing risk survival models. From the date registered as the start of the clinical process, it is assumed that a patient can progress through three intermediate states until reaching an absorbing state of recovery or death. Demographic characteristics, epidemiological factors such as the time of infection and previous vaccinations, clinical history, complications during the course of the disease and drug therapy for hospitalised patients are considered as candidate predictors. Regarding risk factors associated with mortality and severity, consistent results with many other studies have been found, such as older age, being male, and chronic diseases. Specifically, the hospitalisation (death) rate for those over 69 is 27.2% (19.8%) versus 5.3% (0.7%) for those under 70, and for males is 14.5%(7%) versus 8.3%(4.6%)for females. Among patients with chronic diseases the highest rates of hospitalisation are 26.1% for diabetes and 26.3% for kidney disease, while the highest death rate is 21.9% for cerebrovascular disease. Moreover, specific predictors for different transitions are given, and estimates of the probability of recovery and death for each patient are provided by the model. Some interesting results obtained are that for patients infected at the end of the period the hazard of transition from hospitalisation to ICU is significatively lower (p < 0.001) and the hazard of transition from hospitalisation to recovery is higher (p < 0.001). For patients previously vaccinated against pneumococcus the hazard of transition to recovery is higher (p < 0.001). Finally, internal validation and calibration of the model are also performed.

Estimating and projecting population trends using population viability analysis (PVA) are central to identifying species at risk of extinction and for informing conservation management strategies. Models for PVA generally fall within two categories, scalar (count-based) or matrix (demographic). Model structure, process error, measurement error, and time series length all have known impacts in population risk assessments, but their combined impact has not been thoroughly investigated. We tested the ability of scalar and matrix PVA models to predict percent decline over a ten-year interval, selected to coincide with the IUCN Red List criterion A.3, using data simulated for a hypothetical, short-lived organism with a simple life-history and for a threatened snail, Tasmaphena lamproides. PVA performance was assessed across different time series lengths, population growth rates, and levels of process and measurement error. We found that the magnitude of effects of measurement error, process error, and time series length, and interactions between these, depended on context. We found that high process and measurement error reduced the reliability of both models in predicted percent decline. Both sources of error contributed strongly to biased predictions, with process error tending to contribute to the spread of predictions more than measurement error. Increasing time series length improved precision and reduced bias of predicted population trends, but gains substantially diminished for time series lengths greater than 10-15 years. The simple parameterization scheme we employed contributed strongly to bias in matrix model predictions when both process and measurement error were high, causing scalar models to exhibit similar or greater precision and lower bias than matrix models. Our study provides evidence that, for short-lived species with structured but simple life histories, short time series and simple models can be sufficient for reasonably reliable conservation decision-making, and may be preferable for population projections when unbiased estimates of vital rates cannot be obtained.

Ovarian cancer is the fifth leading cause of cancer death in women. Ovarian cancers display a high degree of complex genetic alterations involving many oncogenes and tumor suppressor genes. Analysis of the association between genetic alterations and clinical endpoints such as survival will lead to improved patient management via genetic stratification of patients into clinically relevant subgroups. In this study, we aim to define subgroups of high-grade serous ovarian carcinomas that differ with respect to prognosis and overall survival. Genome-wide DNA copy number alterations (CNAs) were measured in 72 clinically annotated, high-grade serous tumors using high-resolution oligonucleotide arrays. Two clinically annotated, independent cohorts were used for validation. Unsupervised hierarchical clustering of copy number data derived from the 72 patient cohort resulted in two clusters with significant difference in progression free survival (PFS) and a marginal difference in overall survival (OS). GISTIC analysis of the two clusters identified altered regions unique to each cluster. Supervised clustering of two independent large cohorts of high-grade serous tumors using the classification scheme derived from the two initial clusters validated our results and identified 8 genomic regions that are distinctly different among the subgroups. These 8 regions map to 8p21.3, 8p23.2, 12p12.1, 17p11.2, 17p12, 19q12, 20q11.21 and 20q13.12; and harbor potential oncogenes and tumor suppressor genes that are likely to be involved in the pathogenesis of ovarian carcinoma. We have identified a set of genetic alterations that could be used for stratification of high-grade serous tumors into clinically relevant treatment subgroups.

Archaea represent a diverse phylogenetic group that includes free-living, extremophile, mesophile, symbiont, and opportunistic organisms. These prokaryotic organisms share a high significant similarity with the basal transcriptional machinery of Eukarya, and they share regulatory mechanisms with Bacteria, such as operonic organization and DNA-binding transcription factors (TFs). In this work, we identified the repertoire of TFs in 415 archaeal genomes and compared them with their counterparts in bacterial genomes. The comparisons of TFs, at a global level and per family, allowed us to identify similarities and differences between the repertoires of regulatory proteins of bacteria and archaea. For example, 11 of 62 families are more highly abundant in archaea than bacteria, and 13 families are abundant in bacteria but not in archaea and 38 families have similar abundances in the two groups. In addition, we found that archaeal TFs have a lower isoelectric point than bacterial proteins, i.e., they contain more acidic amino acids, and are smaller than bacterial TFs. Our findings suggest a divergence occurred for the regulatory proteins, even though they are common to archaea and bacteria. We consider that this analysis contributes to the comprehension of the structure and functionality of regulatory proteins of archaeal organisms.

Background Chronic Chagas Cardiomyopathy (CCM) is a unique form of cardiomyopathy compared to other etiologies of heart failure. In CCM, risk prediction based on biomarkers has not been well-studied. We assessed the prognostic value of a biomarker panel to predict a composite outcome (CO), including the need for heart transplantation, use of left ventricular assist devices, and mortality. Methods Prospective cohort study of 100 adults with different stages of CCM. Serum concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), neutrophil gelatinase-associated lipocalin (NGAL), high sensitivity troponin T (hs-cTnT), soluble (sST2), and cystatin-C (Cys-c) were measured. Survival analyses were performed using Cox proportional hazard models. Results During a median follow-up of 52 months, the mortality rate was 20%, while the CO was observed in 25% of the patients. Four biomarkers (NT-proBNP, hs-cTnT, sST2, and Cys-C) were associated with the CO; concentrations of NT-proBNP and hs-cTnT were associated with the highest AUC (85.1 and 85.8, respectively). Combining these two biomarkers above their selected cut-off values significantly increased risk for the CO (HR 3.18; 95%CI 1.31–7.79). No events were reported in the patients in whom the two biomarkers were under the cut-off values, and when both levels were above cut-off values, the CO was observed in 60.71%. Conclusion The combination of NT-proBNP and hs-TnT above their selected cut-off values is associated with a 3-fold increase in the risk of the composite outcome among CCM patients. The use of cardiac biomarkers may improve prognostic evaluation of patients with CCM.

BackgroundThe Chronic Pain Coping Inventory (CPCI) has been widely used to measure coping with pain, however, the psychometric properties of the Brazilian CPCI are unknown.AimTo verify the validity and reliability of the CPCI-Brazilian version.Materials and methodsA sample of 705 outpatients with chronic pain participated in the study. Cronbach's alpha, corrected item-total correlations, and confirmatory factor analysis were performed, using the method of Diagonally Weighted Least Squares.ResultsConstruct validity was supported with a factor loading range of 0.36-0.90 (9 factors) corroborating original loads. The final model had adequate fit with items 42 and 54 excluded, D.F = 2174, TLI = 0.96; CFI = 0.96 and RMSEA = 0.051(p = 0.067). Eight of the nine CPCI scales showed satisfactory reliability (Cronbach's alpha ranged from 0.70 to 0.92). The Relaxation scale obtained a low alpha value (0.53).ConclusionThe CPCI-Brazilian version, after exclusion of items 42 and 54, is valid to measure chronic pain coping in Brazilian adults.

The Hodgkin-Huxley model, decades after its first presentation, is still a reference model in neuroscience as it has successfully reproduced the electrophysiological activity of many organisms. The primary signal in the model represents the membrane potential of a neuron. A simple representation of this signal is presented in this paper. The new proposal is an adapted Frequency Modulated Möbius multicomponent model defined as a signal plus error model in which the signal is decomposed as a sum of waves. The main strengths of the method are the simple parametric formulation, the interpretability and flexibility of the parameters that describe and discriminate the waveforms, the estimators' identifiability and accuracy, and the robustness against noise. The approach is validated with a broad simulation experiment of Hodgkin-Huxley signals and real data from squid giant axons. Interesting differences between simulated and real data emerge from the comparison of the parameter configurations. Furthermore, the potential of the FMM parameters to predict Hodgkin-Huxley model parameters is shown using different Machine Learning methods. Finally, promising contributions of the approach in Spike Sorting and cell-type classification are detailed.

BackgroundIn February 2016, the World Health Organization (WHO) declared the epidemic of the ZIKA virus (ZIKV) in Latin America to be a public health emergency. In Colombia, 11,944 pregnant women registered a ZIKV infection during the epidemic. So far, little is known about the experiences of women infected with ZIKV during their pregnancy, especially those relating to the provision of health services during the period of the epidemic.ObjectiveTo explore the experiences of pregnant women diagnosed with ZIKV infection about the provision of health services in two Colombian cities, considering the perspective of sexual and reproductive rights.MethodsQualitative study under the grounded theory approach, which uses semi-structured interviews as tools to explore the biographical experience of mothers during their gestation process and ZIKV infection, dividing the interview into two broad categories: before and during pregnancy.ResultsTwenty-two women were interviewed, 10 in Cali and 12 in Villavicencio. The average age at the time of pregnancy was 27.6 years. Most women were not planning at the time of pregnancy and the pregnancy was unwanted. Most campaigns focused on mosquito eradication rather than on sexual and reproductive health campaigns. The quality of health care was not sufficient, adequate, or appropriate. Also, the breakdown of the health system to deal with the pandemic was also noted. Some women were treated with disrespect by health professionals. Voluntary termination of pregnancy was inadequately advised, and women lost autonomy regarding decisions about their health.ConclusionsIn the health care of ZIKV epidemics, it is necessary to include the gender perspective, more specifically, sexual and reproductive rights. In addition, these epidemics must be addressed through a comprehensive, appropriate, and not fragmented health system, in which sexual and reproductive rights must be mainstreamed in all health promotion and prevention programs.

We study the health trajectories of the population aged over 60, comparing between one European and two Latin American countries (Spain, Chile and Costa Rica) which have similar longevity patterns. Our focus is on functional limitation and mortality risks, considering differences by gender, education and social participation. Data come from national panel surveys (EPS, CRELES, SHARE). Multistate modelling is used to estimate transition probabilities between two health states: healthy to unhealthy, unhealthy to healthy as well as the transition to death from healthy or unhealthy states, to estimate the duration of stay in a specific state (computing healthy and unhealthy life expectancies) and the effect of the selected covariates. Results show that older Costa Ricans have the smallest gender gap in life expectancy but women have a lower healthy life expectancy compared to those in Chile and Spain. Participation in social activities leads to higher healthy life expectancy among the elderly in Costa Rica and Spain, whilst there were no relevant educational differences observed in longevity in the analysed countries. To conclude: despite the different patterns observed in health transitions and survival across the three countries, social participation is associated with greater health and longevity among people of old age, with little effect coming from educational attainment. Public policies should therefore be aimed at reducing unhealthy life years and dependency at advanced ages by promoting more engagement in social activities, especially among vulnerable groups who are more likely to experience impairment from a younger age.

Information such as the prevalence and frequency of criminal behaviour is difficult to estimate using standard survey techniques because of the tendency of respondents to withhold or misrepresent information. Social desirability bias is a significant threat to the validity of self-reported data, especially when supplied by persons such as sexual offenders or those convicted of theft or substance abuse. The randomized response approach is an alternative to the standard interview method and offers great potential for researchers in the field of criminal justice. By means of a survey of 792 prison inmates, incorporating both indirect and direct response techniques, we investigate if the prison population also has problems recognizing their participation in criminal acts such as theft, illicit drug use, violence against property, reckless driving and arson. Our research findings suggest that self-reported criminal behaviour among a prison population is affected by social desirability bias and that the behaviour considered is significantly associated with the severity of obsessive-compulsive symptoms. The results also demonstrate the inadequacy of traditional, yet widely used, direct questioning methods, and the great potential for indirect questioning techniques to advance policy formation and evaluation in the field of criminal behaviour.

IntroductionWe hypothesize that high altitudes could have an adverse effect on neonatal health outcomes, especially among at-risk neonates. The current study aims to assess the association between higher altitudes on survival time among at-risk neonates.MethodsRetrospective survival analysis. Setting: Ecuadorian neonates who died at ≤28 days of life. Patients: We analyzed the nationwide dataset of neonatal deaths from the Surveillance System of Neonatal Mortality of the Ministry of Public Health of Ecuador, registered from 126 public and private health care facilities, between January 2014 to September 2017. Main outcome measures: We retrospectively reviewed 3016 patients. We performed a survival analysis by setting the survival time in days as the primary outcome and fixed and mixed-effects Cox proportional hazards models to estimate hazard ratios (HR) for each altitude stratum of each one of the health care facilities in which those neonates were attended, adjusting by individual variables (i.e., birth weight, gestational age at birth, Apgar scale at 5 minutes, and comorbidities); and contextual variables (i.e., administrative planning areas, type of health care facility, and level of care).ResultsAltitudes of health care facilities ranging from 80 to ConclusionHigher altitudes are independently associated with shorter survival time, as measured by days among at-risk neonates. Altitude should be considered when assessing the risk of having negative health outcomes during neonatal period.

In this work, we performed an analysis of the networks of interactions between drugs and their targets to assess how connected the compounds are. For our purpose, the interactions were downloaded from the DrugBank database, and we considered all drugs approved by the FDA. Based on topological analysis of this interaction network, we obtained information on degree, clustering coefficient, connected components, and centrality of these interactions. We identified that this drug-target interaction network cannot be divided into two disjoint and independent sets, i.e., it is not bipartite. In addition, the connectivity or associations between every pair of nodes identified that the drug-target network is constituted of 165 connected components, where one giant component contains 4376 interactions that represent 89.99% of all the elements. In this regard, the histamine H1 receptor, which belongs to the family of rhodopsin-like G-protein-coupled receptors and is activated by the biogenic amine histamine, was found to be the most important node in the centrality of input-degrees. In the case of centrality of output-degrees, fostamatinib was found to be the most important node, as this drug interacts with 300 different targets, including arachidonate 5-lipoxygenase or ALOX5, expressed on cells primarily involved in regulation of immune responses. The top 10 hubs interacted with 33% of the target genes. Fostamatinib stands out because it is used for the treatment of chronic immune thrombocytopenia in adults. Finally, 187 highly connected sets of nodes, structured in communities, were also identified. Indeed, the largest communities have more than 400 elements and are related to metabolic diseases, psychiatric disorders and cancer. Our results demonstrate the possibilities to explore these compounds and their targets to improve drug repositioning and contend against emergent diseases.

The role of virtual ligand screening in modern drug discovery is to mine large chemical collections and to prioritize for experimental testing a comparatively small and diverse set of compounds with expected activity against a target. Several studies have pointed out that the performance of virtual ligand screening can be improved by taking into account receptor flexibility. Here, we systematically assess how multiple crystallographic receptor conformations, a powerful way of discretely representing protein plasticity, can be exploited in screening protocols to separate binders from non-binders. Our analyses encompass 36 targets of pharmaceutical relevance and are based on actual molecules with reported activity against those targets. The results suggest that an ensemble receptor-based protocol displays a stronger discriminating power between active and inactive molecules as compared to its standard single rigid receptor counterpart. Moreover, such a protocol can be engineered not only to enrich a higher number of active compounds, but also to enhance their chemical diversity. Finally, some clear indications can be gathered on how to select a subset of receptor conformations that is most likely to provide the best performance in a real life scenario.

IntroductionBoth recessive and dominant genetic forms of Parkinson's disease have been described. The aim of this study was to assess the contribution of several genes to the pathophysiology of early onset Parkinson's disease in a cohort from central Spain.Methods/patientsWe analyzed a cohort of 117 unrelated patients with early onset Parkinson's disease using a pipeline, based on a combination of a next-generation sequencing panel of 17 genes previously related with Parkinson's disease and other Parkinsonisms and CNV screening.ResultsTwenty-six patients (22.22%) carried likely pathogenic variants in PARK2, LRRK2, PINK1, or GBA. The gene most frequently mutated was PARK2, and p.Asn52Metfs*29 was the most common variation in this gene. Pathogenic variants were not observed in genes SNCA, FBXO7, PARK7, HTRA2, DNAJC6, PLA2G6, and UCHL1. Co-occurrence of pathogenic variants involving two genes was observed in ATP13A2 and PARK2 genes, as well as LRRK2 and GIGYF2 genes.ConclusionsOur results contribute to the understanding of the genetic architecture associated with early onset Parkinson's disease, showing both PARK2 and LRRK2 play an important role in Spanish Parkinson's disease patients. Rare variants in ATP13A2 and GIGYF2 may contribute to PD risk. However, a large proportion of genetic components remains unknown. This study might contribute to genetic diagnosis and counseling for families with early onset Parkinson's disease.

DNA-binding Transcription Factors (TFs) play a central role in regulation of gene expression in prokaryotic organisms, and similarities at the sequence level have been reported. These proteins are predicted with different abundances as a consequence of genome size, where small organisms contain a low proportion of TFs and large genomes contain a high proportion of TFs. In this work, we analyzed a collection of 668 experimentally validated TFs across 30 different species from diverse taxonomical classes, including Escherichia coli K-12, Bacillus subtilis 168, Corynebacterium glutamicum, and Streptomyces coelicolor, among others. This collection of TFs, together with 111 hidden Markov model profiles associated with DNA-binding TFs collected from diverse databases such as PFAM and DBD, was used to identify the repertoire of proteins putatively devoted to gene regulation in 1321 representative genomes of Archaea and Bacteria. The predicted regulatory proteins were posteriorly analyzed in terms of their genomic context, allowing the prediction of functions for TFs and their neighbor genes, such as genes involved in virulence, enzymatic functions, phosphorylation mechanisms, and antibiotic resistance. The functional analysis associated with PFAM groups showed diverse functional categories were significantly enriched in the collection of TFs and the proteins encoded by the neighbor genes, in particular, small-molecule binding and amino acid transmembrane transporter activities associated with the LysR family and proteins devoted to cellular aromatic compound metabolic processes or responses to drugs, stress, or abiotic stimuli in the MarR family. We consider that with the increasing data derived from new technologies, novel TFs can be identified and help improve the predictions for this class of proteins in complete genomes. The complete collection of experimentally characterized and predicted TFs is available at http://web.pcyt.unam.mx/EntrafDB/.

The pretreatment of biomass remains a critical requirement for bio-renewable fuel production from lignocellulose. Although current processes primarily involve chemical and physical approaches, the biological breakdown of lignin using enzymes and microorganisms is quickly becoming an interesting eco-friendly alternative to classical processes. As a result, bioprospection of wild fungi from naturally occurring lignin-rich sources remains a suitable method to uncover and isolate new species exhibiting ligninolytic activity. In this study, wild species of white rot fungi were collected from Colombian forests based on their natural wood decay ability and high capacity to secrete oxidoreductases with high affinity for phenolic polymers such as lignin. Based on high activity obtained from solid-state fermentation using a lignocellulose source from oil palm as matrix, we describe the isolation and whole-genome sequencing of Dictyopanus pusillus, a wild basidiomycete fungus exhibiting ABTS oxidation as an indication of laccase activity. Functional characterization of a crude enzymatic extract identified laccase activity as the main enzymatic contributor to fungal extracts, an observation supported by the identification of 13 putative genes encoding for homologous laccases in the genome. To the best of our knowledge, this represents the first report of an enzymatic extract exhibiting laccase activity in the Dictyopanus genera, offering means to exploit this species and its enzymes for the delignification process of lignocellulosic by-products from oil palm.

Coxiella burnetii causes Q fever in humans and coxiellosis in animals. In humans, it causes acute febrile illnesses like influenza, pneumonia, hepatitis, and chronic illnesses such as endocarditis, vascular infection, and post-infectious fatigue syndrome. It is widely distributed worldwide, and its main reservoirs are sheep, goats, and cattle. This study aimed to determine the frequency of C. burnetii infection using molecular detection and to identify the associated factors in livestock farmers and cattle from the Magdalena Medio region of Antioquia, Colombia. Using real-time polymerase chain reaction (PCR), molecular detection was performed for the IS1111 insertion sequence of C. burnetii using genomic DNA collected from the peripheral blood of 143 livestock farmers and 192 cattle from 24 farms located in Puerto Berrío, Puerto Nare, and Puerto Triunfo. To confirm the results, bidirectional amplicon sequencing of 16S rRNA was performed in four of the positive samples. Additionally, factors associated with C. burnetii were identified using a Poisson regression with cluster effect adjustment. Real-time PCR showed positive results in 25.9% and 19.5% of livestock farmer samples and cattle samples, respectively. For livestock farmers, factors associated with C. burnetii were the area where the farm was located [Puerto Berrío, adjusted prevalence ratio (aPR): 2.13, 95% confidence interval (CI): 1.10-4.11], presence of hens (aPR: 1.47, 95% CI: 1.21-1.79), horses (aPR: 1.61, 95% CI: 1.54-1.67), and ticks (aPR: 2.36, 95% CI: 1.03-5.42) in the residence, and consumption of raw milk (aPR: 1.47, 95% CI: 1.26-1.72). For cattle, the factors associated with Coxiella genus were municipality (Puerto Nare; aPR: 0.39, 95% CI: 0.37-0.41) and time of residence on the farm (≥49 months; aPR: 2.28, 95% CI: 1.03-5.20). By analyzing sequences of the 16S rRNA molecular marker, C. burnetii infection was confirmed in livestock farmers. However, in cattle, only the presence of Coxiella-type bacteria was identified. Further research is necessary to determine the potential role that these types of bacteria have as etiological agents for disease in livestock farmers and cattle from the study area.

INTRODUCTION:Adolescents have a higher incidence of sexually transmitted infections (STIs) than persons of older age groups. The WHO emphasises the need to adopt specific and comprehensive prevention programmes aimed at this age group. The objective of this work was to analyse the prevalence of HIV/STIs among adolescents and to identify the sociodemographic, clinical and behavioural markers associated with these infections, in order to promote specific preventive strategies. METHODOLOGY:Retrospective descriptive study of adolescents, aged 10-19 years, who were attended to for the first consultation between 2016 and 2018 in a reference STI clinic in Madrid. All adolescents were given a structured epidemiological questionnaire where information on sociodemographic, clinical and behavioural characteristics was collected. They were screened for human inmmunodeficiency virus (HIV) and other sexually transmitted infections (STIs). The processing and analysis of the data was done using the STATA 15.0 statistical package. RESULTS:The frequency of HIV/STIs detected among all adolescents was: gonorrhoea 21.7%, chlamydia 17.1%, syphilis 4.8% and HIV 2.4%. After conducting a multivariate analysis, the independent and statistically significant variables related to the presence of an STI were having first sexual relations at a young age and having a history of STIs. Latin American origin was just below the level of statistical significance (p = 0.066). DISCUSSION/CONCLUSIONS:Adolescents who begin sexual relations at an early age or those who have a history of HIV/STIs are at higher risk of acquiring STIs. Comprehensive prevention programmes aimed specifically at adolescents should be implemented, especially before the age of 13 years.

BACKGROUND:Cardiovascular disease (CVD) is the leading cause of death in women worldwide. The cardiovascular risk profile deteriorates after women enter menopause. By definition, women diagnosed with premature ovarian insufficiency (POI) experience menopause before 40 years of age, which may render these women even more susceptible to develop CVD later in life. However, prospective long-term follow up data of well phenotyped women with POI are scarce. In the current study we compare the CVD profile and risk of middle aged women previously diagnosed with POI, to a population based reference group matched for age and BMI. METHODS AND FINDINGS:We compared 123 women (age 49.0 (± 4.3) years) and diagnosed with POI 8.1 (IQR: 6.8-9.6) years earlier, with 123 population controls (age 49.4 (± 3.9) years). All women underwent an extensive standardized cardiovascular screening. We assessed CVD risk factors including waist circumference, BMI, blood pressure, lipid profile, pulse wave velocity (PWV), and the prevalence of diabetes mellitus, metabolic syndrome (MetS) and carotid intima media thickness (cIMT), in both women with POI and controls. We calculated the 10-year CVD Framingham Risk Score (FRS) and the American Heart Association's suggested cardiovascular health score (CHS). Waist circumference (90.0 (IQR: 83.0-98.0) versus 80.7 (IQR: 75.1-86.8), p < 0.01), waist-to-hip ratio (0.90 (IQR: 0.85-0.93) versus 0.79 (IQR: 0.75-0.83), p < 0.01), systolic blood pressure (124 (IQR 112-135) versus 120 (IQR109-131), p < 0.04) and diastolic blood pressure (81 (IQR: 76-89) versus 78 (IQR: 71-86), p < 0.01), prevalence of hypertension (45 (37%) versus 21 (17%), p < 0.01) and MetS (19 (16%) versus 4 (3%), p < 0.01) were all significantly increased in women with POI compared to healthy controls. Other risk factors, however, such as lipids, glucose levels and prevalence of diabetes were similar comparing women with POI versus controls. The arterial stiffness assessed by PWV was also similar in both populations (8.1 (IQR: 7.1-9.4) versus 7.9 (IQR: 7.1-8.4), p = 0.21). In addition, cIMT was lower in women with POI compared to controls (550 μm (500-615) versus 684 μm (618-737), p < 0.01). The calculated 10-year CVD risk was 5.9% (IQR: 3.7-10.6) versus 6.0% (IQR: 3.9-9.0) (p = 0.31) and current CHS was 6.1 (1.9) versus 6.5 (1.6) (p = 0.07), respectively in POI versus controls. CONCLUSIONS:Middle age women with POI presented with more unfavorable cardiovascular risk factors (increased waist circumference and a higher prevalence of hypertension and MetS) compared to age and BMI matched population controls. In contrast, the current study reveals a lower cIMT and similar 10-year cardiovascular disease risk and cardiovascular health score. In summary, neither signs of premature atherosclerosis nor a worse cardiovascular disease risk or health score were observed among middle age women with POI compared to population controls. Longer-term follow-up studies of women of more advanced age are warranted to establish whether women with POI are truly at increased risk of developing CVD events later in life. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02616510.

Many persons living with HIV (PLWH) either reduced their employment capacity or stopped work completely due to disease progression. With the advent of effective antiretroviral therapy, some PLWH were able to return to the workforce and many are now transitioning into retirement. We examined the histories of employment, retirement and disability status on depression among 1,497 Participants living with HIV from 1997 to 2015 in the Multicenter AIDS Cohort Study. Data were collected on depressive symptoms, employment, retirement, disability status as well as HIV-related and sociodemographic characteristics. Employment, retirement and disability status were lagged 2 years to assess whether the risk of depression at a given observation were temporally predicted by each respective status, adjusting for prior depressive symptoms and covariates. Being employed (aOR: 0.76; 95% CI: 0.71–0.82) had lower odds of depression risk two years later compared to those unemployed. There were higher odds of depression risk associated with disability (aOR: 1.43; 95% CI: 1.32–1.54) versus those not on disability. Retirement status was not associated with the risk of depressive symptoms. These findings could help inform policies and employment programs to facilitate the return to work for PLWH who are willing and able to work.

Modern survey methods may be subject to non-observable bias, from various sources. Among online surveys, for example, selection bias is prevalent, due to the sampling mechanism commonly used, whereby participants self-select from a subgroup whose characteristics differ from those of the target population. Several techniques have been proposed to tackle this issue. One such is Propensity Score Adjustment (PSA), which is widely used and has been analysed in various studies. The usual method of estimating the propensity score is logistic regression, which requires a reference probability sample in addition to the online nonprobability sample. The predicted propensities can be used for reweighting using various estimators. However, in the online survey context, there are alternatives that might outperform logistic regression regarding propensity estimation. The aim of the present study is to determine the efficiency of some of these alternatives, involving Machine Learning (ML) classification algorithms. PSA is applied in two simulation scenarios, representing situations commonly found in online surveys, using logistic regression and ML models for propensity estimation. The results obtained show that ML algorithms remove selection bias more effectively than logistic regression when used for PSA, but that their efficacy depends largely on the selection mechanism employed and the dimensionality of the data.

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors, with insulin resistance as a critical component for its development. Insulin signaling in the heart leads to Akt (also known as PKB) activation, a serine/threonine protein kinase, which regulates cardiac glucose metabolism and growth. Cardiac metabolic inflexibility, characterized by impaired insulin-induced glucose uptake and oxidation, has been reported as an early and consistent change in the heart of different models of MetS and diabetes; however, the evaluation of Akt activation has yielded variable results. Here we report in cardiomyocytes of MetS rats, diminished insulin-induced glucose uptake and Akt activation, evaluated by its impaired mobilization towards the plasma membrane and phosphorylation, and reflected in a re-distribution of its interacting proteins, assessed by label-free mass spectrometry (data are available via ProteomeXchange with identifier PXD013260). We report 45 proteins with diminished abundance in Akt complex of MetS cardiomyocytes, mainly represented by energy metabolism-related proteins, and also, 31 Akt-interacting proteins with increased abundance, which were mainly related to contraction, endoplasmic reticulum stress, and Akt negative regulation. These results emphasize the relevance of Akt in the regulation of energy metabolism in the heart and highlight Akt-interacting proteins that could be involved in the detrimental effects of MetS in the heart.

Bilingualism was implemented in the Community of Madrid (Spain) more than ten years ago, through the incorporation of the English language in the teaching methods of certain schools. Since that time, various research projects have been carried out, with the objective of comparing the academic performance of students in bilingual schools with those in non-bilingual schools. The present paper makes use of primary education data from the Department of Education and Research for the Community of Madrid in an effort to analyze whether or not bilingualism results in the relative improvement of educational outcomes achieved in primary schools in the Region of Madrid, in Spain. More specifically, the data used is from sixth grade classrooms, given that, generally speaking, in this grade all schools give a standardized test which measures academic performance in Math, Science and Technology, Spanish Language Arts and English Language Arts. Our assessment makes use of a multinomial logit model, and includes the most common variables found in the research on the determination of educational outcomes (variables related to whether or not schools are bilingual, which is the main focus of this paper), as well as other less common variables considered to be relevant. These include absenteeism, satisfaction levels among families and students, and the percentage of students in second chance programs. The results show that bilingualism does not lower children performance in the subjects taught in English or in the subjects taught in Spanish. Academic performance in Mathematics, Science and Technology, and Spanish Language Arts is similar with respect to those schools which are not bilingual. However, results in English are significantly higher in bilingual schools when compared to non-bilingual schools.

BACKGROUND & AIM:Worldwide, measures are being implemented to eradicate hepatitis B (HBV) and C (HCV) viruses, which can be transmitted from the mother during childbirth. This study aims to determine the prevalence of HBV and HCV in pregnant women in Spain, focusing on country of origin, epidemiological factors and risk of vertical transmission (VT). METHODOLOGY:Multicentre open-cohort study performed during 2015. HBV prevalence was determined in 21870 pregnant women and HCV prevalence in 7659 pregnant women. Epidemiological and risk factors for VT were analysed in positive women and differences between HBV and HCV cases were studied. RESULTS:HBV prevalence was 0.42% (91/21870) and HCV prevalence was 0.26% (20/7659). Of the women with HBV, 65.7% (44/67) were migrants. The HBV transmission route to the mother was unknown in 40.3% of cases (27/67) and VT in 31.3% (21/67). Among risk factors for VT, 67.7% (42/62) of the women had viraemia and 14.5% (9/62) tested HBeAg-positive. All of the neonates born to HBV-positive mothers received immunoprophylaxis, and none contracted infection by VT. In 80% (16/20) of the women with HCV, the transmission route was parenteral, and nine were intravenous drug users. Viraemia was present in 40% (8/20) of the women and 10% (2/20) were HIV-coinfected. No children were infected. Women with HCV were less likely than women with HBV to breastfeed their child (65% vs. 86%). CONCLUSIONS:The prevalences obtained in our study of pregnant women are lower than those previously documented for the general population. Among the women with HBV, the majority were migrants and had a maternal family history of infection, while among those with HCV, the most common factor was intravenous drug use. Despite the risk factors observed for VT, none of the children were infected. Proper immunoprophylaxis is essential to prevent VT in children born to HBV-positive women.

Tuberculosis (TB) is a major global public health problem with high mortality and morbidity. In low-middle income countries (LMIC) a large number of respiratory symptomatic cases that require TB screening per year demands more accurate, fast and affordable testing for TB diagnostics. Sputum smear is the initial screening test in LMICs, however, its sensitivity is limited in patients with low sputum bacilli load. The same limitation is observed in the currently available molecular tests. We designed, standardized and evaluated an electrochemical biosensor that detects the highly specific DNA insertion element 6110 (IS6110). A PCR amplified DNA product is hybridized on the surface of the working electrode built on FTO-Glass with immobilized specific DNA probes, after which cyclic voltammetry is performed with an Ag/AgCl reference electrode and a platinum counter electrode. The response of the sensor was measured by the ratio (cathodic peak current of the hybridized sensor) / (cathodic peak current of the non-hybridized sensor). We tested the biosensor, using positive hybridization control sequences, genomic DNA extracted from M. tuberculosis strains and sputum of TB patients, and extracted DNA from the urine of healthy controls spiked with M. tuberculosis DNA. This biosensor was effective for the detection of M. tuberculosis DNA with a detection limit of 16 fM in sputum sample and 1 fM in spiked urine samples. The low cost and the relatively brief duration of the assay make this an important TB screening tool in the fight against tuberculosis.

This research-on-research study describes efforts to develop non-Cochrane systematic reviews (SRs) by analyzing demographical and time-course collaborations between international institutions using protocols registered in the International Prospective Register of Systematic Reviews (PROSPERO) or published in scientific journals. We have published an a priori protocol to develop this study. Protocols published in scientific journals were searched using the MEDLINE and Embase databases; the query terms "Systematic review" [Title] AND "protocol" [Title] were searched from February 2011 to December 2017. Protocols registered at PROSPERO during the same period were obtained by web scraping all non-Cochrane records with a Python script. After excluding protocols that had a fulfillment or duplication rate of less than 90%, they were classified as published "only in PROSPERO", "only in journals", or in "journals and PROSPERO". Results of data and metadata extraction using text mining processes were curated by two reviewers. These Datasets and R scripts are freely available to facilitate reproducibility. We obtained 20,814 protocols of non-Cochrane SRs. While "unique protocols" by reviewers' institutions from 60 countries were the most frequent, a median of 6 (2-150) institutions from 130 different countries were involved in the preparation of "collaborative protocols". The highest Ranked countries involved in overall protocol production were the UK, the U.S., Australia, Brazil, China, Canada, the Netherlands, Germany, and Italy. Most protocols were registered only in PROSPERO. However, the number of protocols published in scientific journals (924) or in both PROSPERO and journals (807) has increased over the last three years. Syst Rev and BMJ Open published more than half of the total protocols. While the more productive countries were involved in "unique" and "collaborative protocols", less productive countries only participated in "collaborative protocols" that were mainly published in PROSPERO. Our results suggest that, although most countries were involved in solitary production of protocols for non-Cochrane SRs during the study period, it would be useful to develop new strategies to promote international collaborations, especially with less productive countries.

In order to identify common and specific enzymatic activities associated with the metabolism of the three cellular domains of life, the conservation and variations between the enzyme contents of Bacteria, Archaea, and Eukarya organisms were evaluated. To this end, the content of enzymes belonging to a particular pathway and their abundance and distribution in 1507 organisms that have been annotated and deposited in the KEGG database were assessed. In addition, we evaluated the consecutive enzymatic reaction pairs obtained from metabolic pathway reactions and transformed into sequences of enzymatic reactions, with catalytic activities encoded in the Enzyme Commission numbers, which are linked by a substrate. Both analyses are complementary: the first considers individual reactions associated with each organism and metabolic map, and the second evaluates the functional associations between pairs of consecutive reactions. From these comparisons, we found a set of five enzymatic reactions that were widely distributed in all the organisms and considered here as universal to Bacteria, Archaea, and Eukarya; whereas 132 pairs out of 3151 reactions were identified as significant, only 5 of them were found to be widely distributed in all the taxonomic divisions. However, these universal reactions are not widely distributed along the metabolic maps, suggesting their dispensability to all metabolic processes. Finally, we found that universal reactions are also associated with ancestral domains, such as those related to phosphorus-containing groups with a phosphate group as acceptor or those related to the ribulose-phosphate binding barrel, triosephosphate isomerase, and D-ribose-5-phosphate isomerase (RpiA) lid domain, among others. Therefore, we consider that this analysis provides clues about the functional constraints associated with the repertoire of enzymatic functions per organism.

INTRODUCTION:Active tuberculosis (TB) and latent tuberculosis infection (LTBI) are a public health threat in prisons around the world. The objectives of the study were to estimate the prevalence of LTBI and TB as well as to investigate TB transmission inside one prison, in Colombia. METHODS:A Cross-sectional study was conducted in inmates who agreed to participate. Inmates with respiratory symptoms (RS) of any duration underwent to medical evaluation and three sputum samples were taken for smear microscopy and culture for TB diagnosis. Drug susceptibility was analyzed using BACTEC MGIT 960 and GenoType MTBDRplus. Molecular genotyping of Mycobacterium tuberculosis isolates was performed by 24-Locus MIRU-VNTR and spoligotyping. LTBI was evaluated according to the result of the tuberculin skin test (TST). Close contact investigation was conducted inside the prison for inmates that shared the cell with the index TB case. RESULTS:Among 301/2,020 (15%) inmates with RS of any duration, 8% were diagnosed with active TB. The prevalence of active TB was 1,026 cases/100,000 inmates. We isolated M. tuberculosis in 19/24 (79%) TB cases, 94.7% were susceptible to first line drugs and only one was monoresistant to isoniazid. The most prevalent sub-lineage was Haarlem (68.4%), followed by LAM (26.3%) and T superfamily (5.3%). 24-Locus MIRU-VNTR typing results alone or in combination with spoligotyping identified three clusters containing two isolates each. Two clusters corresponded to inmates that shared the same cell, but each one was located in different blocks of the prison. Inmates from the last cluster were in the same block in nearby cells. TST reading was performed in 95.6% inmates, and 67.6% had a positive reaction. CONCLUSIONS:The prevalence of LTBI and TB was higher in prison than in the general population. Molecular genotyping suggests that TB in this prison is mainly caused by strains imported by inmates or endogenous reactivation.

Ikakogi is a behaviorally and morphologically intriguing genus of glassfrog. Using tadpole morphology, vocalizations, and DNA, a new species is described from the Sierra Nevada de Santa Marta (SNSM), an isolated mountain range in northern Colombia. The new taxon is the second known species of the genus Ikakogi and is morphologically identical to I. tayrona (except for some larval characters) but differs by its genetic distance (14.8% in mitochondrial encoded cytochrome b MT-CYB; ca. 371 bp) and by the dominant frequency of its advertisement call (2928-3273 Hz in contrast to 2650-2870 Hz in I. tayrona). They also differ in the number of lateral buccal floor papillae, and the position of the buccal roof arena papillae. Additionally, the new species is differentiated from all other species of Centrolenidae by the following traits: tympanum visible, vomerine teeth absent, humeral spines present in adult males, bones in life white with pale green in epiphyses, minute punctuations present on green skin dorsum, and flanks with lateral row of small, enameled dots that extend from below eye to just posterior to arm insertion. We describe the external and internal larval morphology of the new species and we redescribe the larval morphology of Ikakogi tayrona on the basis of field collected specimens representing several stages of development from early to late metamorphosis. We discuss the relevance of larval morphology for the taxonomy and systematics of Ikakogi and other centrolenid genera. Finally, we document intraspecific larval variation in meristic characters and ontogenetic changes in eye size, coloration, and labial tooth-rows formulas, and compare tadpoles of related species. Ikakogi tayrona has been proposed as the sister taxon of all other Centrolenidae; our observations and new species description offers insights about the ancestral character-states of adults, egg clutches, and larval features in this lineage of frogs.

HIV and pneumonia infections have both been shown to negatively impact lung function. However, evidence of the role of inflammation on lung dysfunction in HIV and pneumonia co-infected individuals remains limited. We aimed to systematically review the association of inflammatory markers and lung abnormalities in HIV and pneumonia co-infected individuals. This systematic review was registered with the International Prospective Register of Systematic Reviews on August 15, 2017 (registration number CRD42017069254) and used 4 databases (Cochrane Central Register of Controlled Trials, PubMed Central, Clinical Trials.gov and Google Scholar). All clinical trial, observational, and comparative studies targeting adult (> 18 years old) populations with HIV, pneumonia, or both, that report on immune response (cytokine, chemokine, or biomarker), and lung abnormality as an outcome were eligible. Data selection, risk of bias and extraction were performed independently by 2 blinded reviewers. Due to heterogeneity among the articles, a qualitative synthesis was performed. Our search strategy identified 4454 articles of which, 7 met our inclusion criteria. All of the studies investigated the ability of circulating biomarkers to predict lung damage in HIV. None of the articles included patients with both HIV and pneumonia, nor pneumonia alone. Markers of inflammation (IL-6, TNF-α, CRP), innate defense (cathelicidin), monocyte and macrophage activation (sCD14, sCD163 and, IL-2sRα), endothelial dysfunction (ET-1) and general immune health (CD4/CD8 ratio) were associated with lung abnormalities in HIV. This review highlights the lack of available information regarding the impact of inflammatory mediators on lung function in HIV and pneumonia populations, therefore opportunities to prevent lung damage with available anti-inflammatory treatment or to investigate new ones still remain.