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Background: Violence against women has a negative impact on multiple dimensions of women's health. During the Covid-19 pandemic, intimate partner violence against women has continued, and in some contexts has intensified. The aim of this study was to identify the prevalence of intimate partner violence against women during covid-19 pandemic and its association with socioeconomic, behavioral, and life-experience factors., Methods and Findings: Cross-sectional, population-based study conducted in the municipality of Vitória, state of Espírito Santo, from January to May 2022, where 1,086 women aged 18 years and over were interviewed. The World Health Organization (WHO) instrument on violence against women was used to screen outcomes. The prevalence of violence during the pandemic (psychological, physical, and sexual) and bivariate analysis with sociodemographic, behavioral, family, and life history characteristics of women were estimated. The multivariate analysis was carried out for each type of violence, the Poisson regression model was performed with an estimate of robust variance, inserting the variables of interest with (p<0.20). Those with p<0.05 remained in the adjusted model., Results: The prevalence of violence psychological against women perpetrated by an intimate partner during the pandemic was the most frequent (20.2%), followed by physical (9.0%) and sexual violence (6.5%). Women with less schooling and who were single had a higher prevalence of physical and psychological violence, as did those with a history of sexual abuse in childhood and whose mothers had been beaten by their intimate partners. Sexual violence was more prevalent among non-white, with up to eight years of schooling, whose mothers had a history of intimate partner violence, and who consumed alcohol during four days or more (p<0.01)., Conclusion: Psychological, physical, and sexual violence perpetrated by the intimate partner during the pandemic presented high magnitude among women living in Vitória. Sociodemographic, behavioral factors, and personal and maternal experiences of violence were associated with the phenomenon., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Leite et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Newborns with one-or-more adverse birth outcomes (ABOs) are at greater risk of mortality or long-term morbidity with health impacts into adulthood. Hence, identifying ABO-associated factors is crucial for devising relevant interventions. For this study, ABOs were defined as prematurity (PTB) for gestational age <37 weeks, low birth weight (LBW) <2.5 kg, macrosomia >4 kg, asphyxia for a 5-minute Apgar score <7, congenital anomalies, and neonatal sepsis. This study aimed to assess factors associated with ABOs among babies delivered at the only hospital of Sao Tome & Principe (STP), a resource-constrained sub-Saharan-Central African country., Methods: A hospital-based unmatched case‒control study was conducted among newborns from randomly selected mothers. Newborns with one-or-more ABO were the cases (ABO group), while healthy newborns were the controls (no-ABO group). Data were collected by a face-to-face interview and abstracted from antenatal care (ANC) pregnancy cards and medical records. Multivariable logistic regression analysis was performed to identify ABO-associated factors considering a level of significance of α = 0.05., Results: A total of 519 newborns (176 with ABO and 343 no-ABO) were enrolled. The mean gestational age and birthweight of cases and controls were 36 (SD = 3.7) weeks with 2659 (SD = 881.44) g and 39.6 (SD = 1.0) weeks with 3256 (SD = 345.83) g, respectively. In the multivariable analysis, twin pregnancy [aOR 4.92, 95% CI 2.25-10.74], prolonged rupture of membranes [aOR 3.43, 95% CI 1.69-6.95], and meconium- fluid [aOR 1.59, 95% CI 0.97-2.62] were significantly associated with ABOs. Eight or more ANC contacts were found to be protective [aOR 0.33, 95% CI 0.18-0.60, p<0.001]., Conclusion: Modifiable factors were associated with ABOs in this study and should be considered in cost-effective interventions. The provision of high-quality ANC should be a priority. Twin pregnancies and intrapartum factors such as prolonged rupture of membranes and meconium-stained amniotic fluid are red flags for ABOs that should receive prompt intervention and follow-up., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Vasconcelos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Cytokines induced by SARS-CoV-2 infection play a crucial role in the pathophysiology of COVID-19 and hyperinflammatory responses have been associated with poor clinical outcomes, with progression to severe conditions or long-term subacute complications named as long-COVID-19., Methods: In this cross-sectional study, we aimed to evaluate a set of antigen-specific inflammatory cytokines in blood from recovered COVID-19 individuals or who suffered a post-acute phase of SARS-CoV-2 infection compared to healthy individuals with no history of COVID-19 exposition or infection. Interferon-gamma (IFN-γ), IFN-γ-induced protein 10 (IP-10), tumor necrosis factor (TNF), IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, and IL-17A were quantified by multiplex cytometric bead assay and enzyme-linked immunosorbent assay after stimulation of whole blood with recombinant Spike protein from SARS-CoV-2. Additionally, all participants have evaluated for anti-(S) protein-specific IgG antibodies. Clinical specimens were collected within two months of COVID-19 diagnosis., Results: A total of 47 individuals were enrolled in the study, a median age of 43 years (IQR = 14.5), grouped into healthy individuals with no history of infection or exposure to SARS-CoV-2 (unexposed group; N = 21); and patients from the Health Complex of the Rio de Janeiro State University (UERJ), Brazil, who were SARS-CoV-2 positive by RT-PCR (COVID-19 group)-categorized as recovered COVID-19 (N = 11) or long-COVID-19 (N = 15). All COVID-19 patients presented at least one signal or symptom during the first two weeks of infection. Six patients were hospitalized and required invasive mechanical ventilation. Our results showed that COVID-19 patients had significantly higher levels of IFN-γ, TNF, IL-1β, IL-2, IL-6, IL-8, and IP-10 than the unexposed group. The long-COVID-19 group has presented significantly high levels of IL-1β and IL-6 compared to unexposed individuals, but not from recovered COVID-19. A principal-component analysis demonstrated 84.3% of the total variance of inflammatory-SARS-CoV-2 response in the first two components, and it was possible to stratify IL-6, TNF, IL-1β, IL-10, and IL-2 as the top-five cytokines which are candidates to discriminate COVID-19 group (including long-COVID-19 subgroup) and healthy unexposed individuals., Conclusion: We revealed important S protein-specific differential biomarkers in individuals affected by COVID-19, bringing new insights into the inflammatory status or SARS-CoV-2 exposition determination., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gomes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Workplace violence in healthcare settings has long been studied in scientific literature, particularly in the nursing profession. Research has explored mostly user violence probably for its high prevalence and impact on health and job satisfaction. Yet this focus may overshadow another dangerous type of workplace violence: coworker violence. Exerted by co-workers with similar status, lateral violence differs from that yielded by a co-worker with a higher rank, known as vertical. This study aims to deepen the knowledge about lateral violence perceived by nurses and its interaction with other variables commonly associated with workplace violence in healthcare: burnout, job satisfaction, and self-perceived health., Method: A random block sampling was performed, prompting a total sample of 925 nursing professionals from 13 public hospitals located in the southeast of Spain. The sample distribution (mean and standard deviation) and the response percentages according to the study variables of the ad-hoc questionnaire were analyzed and classified with cluster analysis., Results: Through the cluster analysis, two subgroups were obtained: Cluster 1, composed of 779 participants, with low scores in the variables used for the classification, high levels of both extrinsic and intrinsic satisfaction, low levels of emotional exhaustion and cynicism, and low rates of somatization, anxiety, social dysfunction and depression; and Cluster 2, composed of 115 participants and characterized by moderate-high scores in the variables used for the classification, moderate extrinsic satisfaction, and low intrinsic satisfaction, high emotional exhaustion and cynicism and lower somatization, anxiety, social dysfunction, and depression scores. Excluded cases amounted to 31., Conclusion: Nursing professionals who experience lateral violence reveal a lower intrinsic satisfaction, feeling less self-accomplished in their job, and less positive work experience. Emotional exhaustion rises as a concerning progressive and long-term outcome of experiencing this type of violence., Competing Interests: The authors have declared that no competing interests exist.

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

Adolescence is a period of increased risk-taking behavior, thought to be driven, in part, by heightened reward sensitivity. One challenge of studying reward processing in the field of developmental neuroscience is finding a task that activates reward circuitry, and is short, not too complex, and engaging for youth of a wide variety of ages and socioeconomic backgrounds. In the present study, we tested a brief child-friendly reward task for activating reward circuitry in two independent samples of youth ages 7-19 years old enriched for poverty (study 1: n = 464; study 2: n = 27). The reward task robustly activated the ventral striatum, with activation decreasing from early to mid-adolescence and increasing from mid- to late adolescence in response to reward. This response did not vary by gender, pubertal development, or income-to-needs ratio, making the task applicable for a wide variety of populations. Additionally, ventral striatum activation to the task did not differ between youth who did and did not expect to receive a prize at the end of the task, indicating that an outcome of points alone may be enough to engage reward circuitry. Thus, this reward task is effective for studying reward processing in youth from different socioeconomic backgrounds., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Dry eye is a common, complex, and multifactorial disease of the ocular surface and tear film that results in discomfort and visual disturbances. Prevalence rates vary and largely rely on studies involving older populations. This study sought to evaluate dry eye among a sample of young students in Brazil., Methods: Cross-sectional survey included 2,140 students using 2 self-applicable questionnaires of dry eye symptoms: the Ocular Surface Disease Index (OSDI) and the Women's Health Study (WHS) questionnaire and a list of risk factors associated with dry eye. Participants with dry eye symptoms underwent a clinical evaluation., Results: Participants were 23.4±5.2 years of age, 56.1% female and 43.9% male, 34.4% had an OSDI score greater than 22, and 23.5% had dry eye according to the WHS. Dry eye frequency differed consistently between the sexes: 42.6% women and 24.0% men based on the OSDI, and 27.1% women and 18.5% men based on the WHS. Univariate and multivariate analyses demonstrated that female sex, contact lens wear, the screen use for more than 6 hours per day, less than 6 hours of sleep a night, and certain medications were relevant related risk factors for dry eye. Despite symptoms, clinical evaluations demonstrated mild signs of dry eye., Conclusions: Dry eye symptoms were found to be a prevalent condition among Brazilian undergraduate students. Compared to the rates of dry eye among the general Brazilian population over 40 years of age, students present at higher dry eye symptoms rates and distinct odds for related risk factors were identified., Competing Interests: The authors have declared that no competing interests exist.

Cyperus prophyllatus, an endangered new species of Cyperus (Cyperaceae) from an aquatic ecosystem of the Atlantic Forest, Espírito Santo State, southeastern Brazil, is described and illustrated. The spikelet morphology of Cyperus prophyllatus is unique among the c. 950 species of Cyperus in having both a conspicuous spikelet prophyll and a corky rachilla articulation, which remain persistent at the base of the spikelet after disarticulation. Our molecular phylogenetic data support the placement of C. prophyllatus in the C3 Cyperus Grade and more precisely in the clade representing Cyperus sect. Oxycaryum, which also includes C. blepharoleptos and C. gardneri. Anatomical and (micro)morphological analyses corroborate the phylogenetic results, provide a better understanding of ecology and taxonomy, as well as reveal compatibility of structures with survival and dispersion in aquatic environments. A distribution map, table with distinctive characters of allied species, and conservation status are made available., Competing Interests: The authors have declared that no competing interests exist.

The Human Immunodeficiency Virus Type I (HIV-1) subtype B comprises approximately 10% of all HIV infections in the world. The HIV-1 subtype B epidemic comprehends a pandemic variant (named BPANDEMIC) disseminated worldwide and non-pandemic variants (named BCAR) that are mostly restricted to the Caribbean. The goal of this work was the identification of amino acid signatures (AAs) characteristic to the BCAR and BPANDEMIC variants. To this end, we analyzed HIV-1 subtype B full-length (n = 486) and partial (n = 814) genomic sequences from the Americas classified within the BCAR and BPANDEMIC clades and reconstructed the sequences of their most recent common ancestors (MRCA). Analysis of contemporary HIV-1 sequences revealed 13 AAs between BCAR and BPANDEMIC variants (four on Gag, three on Pol, three on Rev, and one in Vif, Vpu, and Tat) of which only two (one on Gag and one on Pol) were traced to the MRCA. All AAs correspond to polymorphic sites located outside essential functional proteins domains, except the AAs in Tat. The absence of stringent AAs inherited from their ancestors between modern BCAR and BPANDEMIC variants support that ecological factors, rather than viral determinants, were the main driving force behind the successful spread of the BPANDEMIC strain., Competing Interests: The authors have declared that no competing interests exist.

While we are performing a demanding cognitive task, not only do we have a sense of cognitive effort, we are also subjectively aware that we are initiating, executing and controlling our thoughts and actions (i.e., sense of agency). Previous studies have shown that cognitive effort can be both detrimental and facilitative for the experienced sense of agency. We hypothesized that the reason for these contradictory findings might lie in the use of differential time windows in which cognitive effort operates. The current study therefore examined the effect of cognitive effort exerted on the current trial, on the previous trial or across a block of trials on sense of agency, using implicit (Experiment 1) and explicit (Experiment 2) measures of sense of agency. We showed that the exertion of more cognitive control on current trials led to a higher explicit sense of agency. This surprising result was contrasted to previous studies to establish potential reasons for this surprising finding and to formulate recommendations for future studies., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To analyze how ocular surface parameters correlate to presence of pterygium and investigate the possible impact of pterygia on tear film findings and meibomian glands findings., Methods: We investigated objective parameters of the ocular surface such as conjunctival hyperemia, tear film stability and volume, meibomian gland dysfunction, dry eye disease, corneal topography comparing healthy individuals and correlating with the pterygium clinical presentation., Results: A total of 83 patients were included. Corneal astigmatism induction was 2.65 ± 2.52 D (0.4-11.8). The impact of pterygium on the ocular surface parameters compared to matched controls was seen in: conjunctival hyperemia (control 1.55±0.39/pterygium 2.14±0.69; p = 0.0001), tear meniscus height (control 0.24±0.05 mm/pterygium 0.36±0.14mm; p 0.0002), meiboscore lower eyelid (control 0.29±0.64/pterygium 1.38±0.95; p 0.0001) and meiboscore upper eyelid (control 0.53±0.62/pterygium 0.98±0.75; p = 0.0083). We found a high number of pterygium patients (88%) presented meibomian gland alterations. Interestingly, meibomian gland loss was coincident to the localization of the pterygium in 54% of the upper and 77% lower lids., Conclusion: Pterygium greatly impacts on ocular surface by inducing direct alterations in the pattern of meibomian glands besides corneal irregularities, conjunctival hyperemia and lacrimal film alterations, inducing significant symptoms and potential signs of dysfunction., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Dry Eye Disease (DED) is part of several conditions, including Sjögren's syndrome (SS) and no single test to diagnosis DED. The present study intends to evaluate whether a set of signs and symptoms of DED can distinguish: a) SS from other non-overlapping systemic diseases related to DED; b) primary and secondary SS., Methods: 182 consecutive patients with DED were evaluated under five groups: SS, graft-versus-host disease (GVHD), Graves' orbitopathy (GO), diabetes mellitus (DM), glaucoma under treatment with benzalkonium chloride medications (BAK). Twenty-four healthy subjects were included as control group (CG). The evaluation consisted of Ocular Surface Disease Index (OSDI), Schirmer test (ST), corneal fluorescein staining (CFS) and tear film break up time (TFBUT). Indeed, a subset of DED patients (n = 130), classified as SS1, SS2 and nonSS (NSS) by the American-European Criteria were compared. Quadratic discriminant analysis (QDA) classified the individuals based on variables collected. The area under Receiver Operating Characteristics (ROC) curve evaluated the classification performance in both comparisons., Results: Comparing SS with other diseases, QDA showed that the most important variable for classification was OSDI, followed by TFBUT and CFS. Combined, these variables were able to correctly classify 62.6% of subjects in their actual group. At the discretion of the area under the ROC curve, the group with better classification was the control (97.2%), followed by DM (95.5%) and SS (92.5%). DED tests were different among the NSS, SS1 and SS2 groups. The analysis revealed that the combined tests correctly classified 54.6% of the patients in their groups. The area under the ROC curve better classified NSS (79.5%), followed by SS2 (74.4%) and SS1 (69.4%)., Conclusions: Diseases that causes DED, and also SS1, SS2 and NSS are distinguishable conditions, however a single ocular tools was not able to detect the differences among the respective groups., Competing Interests: The authors have declared that no competing interests exist.

Background: Pleural tuberculosis (PlTB) is the most common extrapulmonary manifestation of this infectious disease which still presents high mortality rates worldwide. Conventional diagnostic tests for PlTB register multiple limitations, including the lack of sensitivity of microbiological methods on pleural specimens and the need of invasive procedures such as pleural biopsy performance. In this scenario, the search for biological markers on pleural fluid (PF) has been the target of several studies as a strategy to overcome the limitations of PlTB diagnosis. This study aims to evaluate the use either isolated or in combination with adenosine deaminase (ADA), interferon-gamma (IFN-γ), interferon-gamma inducible protein of 10-kD (IP-10) levels on PF in order to guide an accurate anti-TB treatment in microbiologically non-confirmed cases., Methods and Findings: Eighty patients presenting pleural effusion under investigation were enrolled in a cross-sectional study conducted at Pedro Ernesto University Hospital, Rio de Janeiro, RJ, Brazil. Peripheral blood (PB) and PF samples collected from all patients were applied to the commercial IFN-γ release assay, QuantiFERON-TB Gold In-Tube, and samples were analyzed for IFN-γ and IP-10 by immunoassays. ADA activity was determined on PF by the colorimetric method. Based on microbiological and histological criteria, patients were categorized as follow: confirmed PlTB (n = 16), non-confirmed PlTB (n = 17) and non-PlTB (n = 47). The Mycobacterium tuberculosis antigen-specific production of IFN-γ and IP-10 on PB or PF did not show significant differences. However, the basal levels of these biomarkers, as well as the ADA activity on PF, were significantly increased in confirmed PlTB in comparison to non-PlTB group. Receiver operating characteristics curves were performed and the best cut-off points of these three biomarkers were estimated. Their either isolated or combined performances (sensitivity [Se], specificity [Sp], positive predictive value [PPV], negative predictive value [NPV] and accuracy [Acc]) were determined and applied to Venn's diagrams among the groups. Based on the confirmed PlTB cases, IFN-γ showed the best performance of them at a cut-off point of 2.33 IU/mL (Se = 93.8% and Sp = 97.9%) followed by ADA at a cut-off of 25.80 IU/L (Se = 100% and Sp = 84.8%) and IP-10 (Cut-point = 4,361.90 pg/mL, Se = 75% and Sp = 82.6%). IFN-γ plus ADA (cut-point: 25.80 IU/L) represent the most accurate biomarker combination (98.4%), showing Se = 93.7%, Sp = 100%, PPV = 100% and NPV = 97.9%. When this analysis was applied in non-confirmed PlTB, 15/17 (88.2%) presented at least two positive biomarkers in combination., Conclusion: IFN-γ, IP-10, and ADA in PlTB effusions are significantly higher than in non-PlTB cases. IFN-γ is an excellent rule-in and rule-out test compared to IP-10 and ADA. The combination of IFN-γ and ADA, in a reviewed cut-off point, showed to be particularly useful to clinicians as their positive results combined prompts immediate treatment for TB while both negative results suggest further investigation., Competing Interests: The authors have declared that no competing interests exist.

Background: An imbalance in the excitatory/inhibitory systems in the pain networks may explain the persistent chronic pain after hallux valgus surgery. Thus, to contra-regulate this dysfunction, the use of transcranial direct current stimulation (tDCS) becomes attractive., Objective: We tested the hypothesis that two preoperative active(a)-tDCS sessions compared with sham(s)-tDCS could improve the postoperative pain [as indexed by Visual Analogue Scale (VAS) at rest and during walking (primary outcomes)]. To assess their effect on the change in the Numerical Pain Scale (NPS0-10) during Conditioned Pain Modulation (CPM-task), disability related to pain (DRP) and analgesic consumption (secondary outcomes). Also, we assessed if the brain derived neurotrophic factor (BDNF) in the cerebral spinal fluid (CSF) after tDCS could predict the intervention's effect on the DRP., Methods: It is a prospective, double blind, sham-controlled, randomized single center, 40 women (18-70 years-old) who had undergone hallux valgus surgery were randomized to receive two sessions (20 minutes each) of anodal a-tDCS or s-tDCS on the primary motor cortex at night and in the morning before the surgery. To assess the DRP was used the Brazilian Profile of Chronic Pain: Screen (B-PCP:S)., Results: A-tDCS group showed lower scores on VAS at rest and during walking (P<0.001). At rest, the difference between groups was 2.13cm (95%CI = 1.59 to 2.68) while during walking was 1.67cm (95%CI = 1.05 to 2.28). A-tDCS, when compared to s-tDCS reduced analgesic doses in 73.25% (P<0.001), produced a greater reduction in B-PCP:S (mean difference of 9.41 points, 95%CI = 0.63 to 18.21) and higher function of descending pain modulatory system (DPMS) during CPM-task., Conclusion: A-tDCS improves postoperative pain, the DRP and the function of DPMS. Also, the CSF BDNF after a-tDCS predicted the improvement in the DRP. In overall, these findings suggest that a-tDCS effects may be mediated by top-down regulatory mechanisms associated with the inhibitory cortical control., Trial Registration: ClinicalTrials.gov NCT02360462.

Brazil has a concentrated HIV epidemic and men who have sex with men (MSM) are disproportionately affected. Yet, no data is available on the HIV care cascade for this population. This study aimed to assess the HIV care cascade among MSM newly diagnosed through innovative testing strategies in Rio de Janeiro. Data from 793 MSM and travestites/transgender women (transwomen) tested for HIV at a non-governmental LGBT organization and a mobile testing unit located at a gay friendly venue were analyzed. A 12-month-after-HIV-diagnosis-censored cohort was established using CD4, viral load and combination antiretroviral therapy (cART) longitudinal data from those diagnosed with HIV. A cross-sectional HIV care cascade was built using this data. The relative risks of achieving each cascade-stage were estimated using generalized linear models according to age, self-declared skin-color, education, history of sexually transmitted diseases (STD), drug use and prior HIV testing. From Jan-2013 to Jan-2014, 793 MSM and transwomen were tested, 131 (16.5%) were HIV-infected. As of January 2015, 95 (72.5%) were linked to HIV care, 90 (68.7%) were retained in HIV care, 80 (61.1%) were on cART, and 50 (38.2%) were virally suppressed one year after HIV diagnosis. Being non-white (Relative risk [lower bound; upper bound of 95% confidence interval] = 1.709 [1.145; 2.549]) and having a prior HIV-test (1.954 [1.278; 2.986]) were associated with an HIV-positive diagnosis. A higher linkage (2.603 [1.091; 6.211]) and retention in care (4.510 [1.880; 10.822]) were observed among those who were older than 30 years of age. Using community-based testing strategies, we were able to access a high-risk MSM population and a small sample of transwomen. Despite universal care coverage and the test-and-treat policy adopted in Brazil, the MSM cascade of care indicates that strategies to increase linkage to care and prompt cART initiation targeted to these populations are critically needed. Interventions targeting non-white and young MSM should be prioritized.

Diabetes mellitus is a chronic disease that affects over 382 million people worldwide. Type-1 Diabetes (T1D) is classified as an autoimmune disease that results from pancreatic β-cell destruction and insulin deficiency. Type-2 Diabetes (T2D) is characterized principally by insulin resistance in target tissues followed by decreased insulin production due to β-cell failure. It is challenging to identify immunological markers such as inflammatory molecules that are triggered in response to changes during the pathogenesis of diabetes. APRIL is an important member of the TNF family and has been linked to chronic inflammatory processes of various diseases since its discovery in 1998. Therefore, this study aimed to evaluate APRIL serum levels in T1D and T2D. For this, we used the ELISA assay to measure serum APRIL levels of 33 T1D and 30 T2D patients, and non-diabetic subjects as control group. Our data showed a decrease in serum APRIL levels in T1D patients when compared with healthy individuals. The same pattern was observed in the group of T2D patients when compared with the control. The decrease of serum APRIL levels in diabetic patients suggests that this cytokine has a role in T1D and T2D. Diabetes is already considered as an inflammatory condition with different cytokines being implicated in its physiopathology. Our data suggest that APRIL can be considered as a potential modulating cytokine in the inflammatory process of diabetes.

The paralytic disease botulism is caused by botulinum neurotoxins (BoNT), multi-domain proteins containing a zinc endopeptidase that cleaves the cognate SNARE protein, thereby blocking acetylcholine neurotransmitter release. Antitoxins currently used to treat botulism neutralize circulating BoNT but cannot enter, bind to or neutralize BoNT that has already entered the neuron. The light chain endopeptidase domain (LC) of BoNT serotype A (BoNT/A) was targeted for generation of monoclonal antibodies (mAbs) that could reverse paralysis resulting from intoxication by BoNT/A. Single-chain variable fragment (scFv) libraries from immunized humans and mice were displayed on the surface of yeast, and 19 BoNT/A LC-specific mAbs were isolated by using fluorescence-activated cell sorting (FACS). Affinities of the mAbs for BoNT/A LC ranged from a KD value of 9.0×10-11 M to 3.53×10-8 M (mean KD 5.38×10-9 M and median KD 1.53×10-9 M), as determined by flow cytometry analysis. Eleven mAbs inhibited BoNT/A LC catalytic activity with IC50 values ranging from 8.3 ~73×10-9 M. The fine epitopes of selected mAbs were also mapped by alanine-scanning mutagenesis, revealing that the inhibitory mAbs bound the α-exosite region remote from the BoNT/A LC catalytic center. The results provide mAbs that could prove useful for intracellular reversal of paralysis post-intoxication and further define epitopes that could be targeted by small molecule inhibitors.

Canine Visceral Leishmaniasis (CVL) shares many aspects with the human disease and dogs are considered the main urban reservoir of L. infantum in zoonotic VL. Infected dogs develop progressive disease with a large clinical spectrum. A complex balance between the parasite and the genetic/immunological background of the host are decisive for infection evolution and clinical outcome. This study comprised 92 Leishmania infected mongrel dogs of various ages from Mato Grosso, Brazil. Spleen samples were collected for determining parasite load, humoral response, cytokine mRNA expression and histopathology alterations. By real-time PCR for the ssrRNA Leishmania gene, two groups were defined; a low (lowP, n = 46) and a high parasite load groups (highP, n = 42). When comparing these groups, results show variable individual humoral immune response with higher specific IgG production in infected animals but with a notable difference in CVL rapid test optical densities (DPP) between highP and lowP groups. Splenic architecture disruption was characterized by disorganization of white pulp, more evident in animals with high parasitism. All cytokine transcripts in spleen were less expressed in highP than lowP groups with a large heterogeneous variation in response. Individual correlation analysis between cytokine expression and parasite load revealed a negative correlation for both pro-inflammatory cytokines: IFNγ, IL-12, IL-6; and anti-inflammatory cytokines: IL-10 and TGFβ. TNF showed the best negative correlation (r2 = 0.231; p<0.001). Herein we describe impairment on mRNA cytokine expression in leishmania infected dogs with high parasite load associated with a structural modification in the splenic lymphoid micro-architecture. We also discuss the possible mechanism responsible for the uncontrolled parasite growth and clinical outcome.

Purpose: This study compares signs, symptoms and predictive tools used to diagnose dry eye disease (DED) and ocular surface disorders in six systemic well-defined and non-overlapping diseases. It is well known that these tests are problematic because of a lack of agreement between them in identifying these conditions. Accordingly, we provide here a comparative clinical profile analysis of these different diseases., Methods: A spontaneous and continuous sample of patients with Sjögren's syndrome (SS) (n=27), graft-versus-host-disease (GVHD) (n=28), Graves orbitopathy (n=28), facial palsy (n=8), diabetes mellitus without proliferative retinopathy (n=14) and glaucoma who chronically received topical drugs preserved with benzalkonium chloride (n=20) were enrolled. Evaluation consisted of a comprehensive protocol encompassing: (1) structured questionnaire - Ocular Surface Disease Index (OSDI); (2) tear osmolarity (TearLab Osmolarity System - Ocusense); (3) tear film break-up time (TBUT); (4) fluorescein and lissamine green staining; (5) Schirmer test and (6) severity grading., Results: One hundred and twenty five patients (aged 48.8 years-old ± 14.1, male:female ratio=0.4) were enrolled in the study, along with 24 age and gender matched controls. Higher scores on DED tests were obtained in Sjögren Syndrome (P<0.05), except for tear film osmolarity that was higher in diabetics (P<0.001) and fluorescein staining, that was higher in facial palsy (P<0.001). TFBUT and OSDI correlated better with other tests. The best combination of diagnostic tests for DED was OSDI, TBUT and Schirmer test (sensitivity 100%, specificity 95% and accuracy 99.3%)., Conclusions: DED diagnostic test results present a broad range of variability among different conditions. Vital stainings and TBUT correlated best with one another whereas the best test combination to detect DED was: OSDI/TBUT/Schirmer.

Background: Although high aerobic capacity is associated with effective cardiac function, the effect of aerobic capacity on atrial function, especially in terms of cellular mechanisms, is not known. We aimed to investigate whether rats with low inborn maximal oxygen uptake (VO2 max) had impaired atrial myocyte contractile function when compared to rats with high inborn VO2 max., Methods and Results: Atrial myocyte function was depressed in Low Capacity Runners (LCR) relative to High Capacity Runners (HCR) which was associated with impaired Ca(2+) handling. Fractional shortening was 52% lower at 2 Hz and 60% lower at 5 Hz stimulation while time to 50% relengthening was 43% prolonged and 55% prolonged, respectively. Differences in Ca(2+) amplitude and diastolic Ca(2+) level were observed at 5 Hz stimulation where Ca(2+) amplitude was 70% lower and diastolic Ca(2+) level was 11% higher in LCR rats. Prolonged time to 50% Ca(2+) decay was associated with reduced sarcoplasmic reticulum (SR) Ca(2+) ATPase function in LCR (39%). Na(+)/Ca(2+) exchanger activity was comparable between the groups. Diastolic SR Ca(2+) leak was increased by 109%. This could be partly explained by increased ryanodine receptors phosphorylation at the Ca(2+)-calmodulin-dependent protein kinase-II specific Ser-2814 site in LCR rats. T-tubules were present in 68% of HCR cells whereas only 33% LCR cells had these structures. In HCR, the significantly higher numbers of cells with T-tubules were combined with greater numbers of myocytes where Ca(2+) release in the cell occurred simultaneously in central and peripheral regions, giving rise to faster and more spatial homogenous Ca(2+)-signal onset., Conclusion: This data demonstrates that contrasting for low or high aerobic capacity leads to diverse functional and structural remodelling of atrial myocytes, with impaired contractile function in LCR compared to HCR rats.

Periodontal diseases are initiated primarily by Gram-negative, tooth-associated microbial biofilms that elicit a host response that causes osseous and soft tissue destruction. Carvedilol is a β-blocker used as a multifunctional neurohormonal antagonist that has been shown to act not only as an anti-oxidant but also as an anti-inflammatory drug. This study evaluated whether Carvedilol exerted a protective role against ligature-induced periodontitis in a rat model and defined how Carvedilol affected metalloproteinases and RANKL/RANK/OPG expression in the context of bone remodeling. Rats were randomly divided into 5 groups (n = 10/group): (1) non-ligated (NL), (2) ligature-only (LO), and (3) ligature plus Carvedilol (1, 5 or 10 mg/kg daily for 10 days). Periodontal tissue was analyzed for histopathlogy and using immunohistochemical analysis characterized the expression profiles of MMP-2, MMP-9, COX-2, and RANKL/RANK/OPG and determined the presence of IL-1β, IL-10 and TNF-α, myeloperoxidase (MPO), malonaldehyde (MDA) and, glutathione (GSH). MPO activity in the group with periodontal disease was significantly increased compared to the control group (p<0.05). Rats treated with 10 mg/kg Carvedilol presented with significantly reduced MPO and MDA concentrations (p<0.05) in addition to presenting with reduced levels of the pro-inflammatory cytokines IL-1 β and TNF-α (p<0.05). IL-10 levels in Carvedilol-treated rats remained unaltered. Immunohistochemical analysis demonstrated reduced expression of MMP-2, MMP-9, RANK, RANKL, COX-2, and OPG in rats treated with 10 mg/kg Carvedilol. This study demonstrated that Carvedilol affected bone formation/destruction and anti-inflammatory activity in a rat model of periodontitis.

Herein, we performed microarray experiments in Schwann cells infected with live M. leprae and identified novel differentially expressed genes (DEG) in M. leprae infected cells. Also, we selected candidate genes associated or implicated with leprosy in genetic studies and biological experiments. Forty-seven genes were selected for validation in two independent types of samples by multiplex qPCR. First, an in vitro model using THP-1 cells was infected with live Mycobacterium leprae and M. bovis bacillus Calmette-Guérin (BCG). In a second situation, mRNA obtained from nerve biopsies from patients with leprosy or other peripheral neuropathies was tested. We detected DEGs that discriminate M. bovis BCG from M. leprae infection. Specific signatures of susceptible responses after M. leprae infection when compared to BCG lead to repression of genes, including CCL2, CCL3, IL8 and SOD2. The same 47-gene set was screened in nerve biopsies, which corroborated the down-regulation of CCL2 and CCL3 in leprosy, but also evidenced the down-regulation of genes involved in mitochondrial metabolism, and the up-regulation of genes involved in lipid metabolism and ubiquitination. Finally, a gene expression signature from DEG was identified in patients confirmed of having leprosy. A classification tree was able to ascertain 80% of the cases as leprosy or non-leprous peripheral neuropathy based on the expression of only LDLR and CCL4. A general immune and mitochondrial hypo-responsive state occurs in response to M. leprae infection. Also, the most important genes and pathways have been highlighted providing new tools for early diagnosis and treatment of leprosy.

Real-time reverse transcription PCR (RT-qPCR) has emerged as an accurate and widely used technique for expression profiling of selected genes. However, obtaining reliable measurements depends on the selection of appropriate reference genes for gene expression normalization. The aim of this work was to assess the expression stability of 15 candidate genes to determine which set of reference genes is best suited for transcript normalization in citrus in different tissues and organs and leaves challenged with five pathogens (Alternaria alternata, Phytophthora parasitica, Xylella fastidiosa and Candidatus Liberibacter asiaticus). We tested traditional genes used for transcript normalization in citrus and orthologs of Arabidopsis thaliana genes described as superior reference genes based on transcriptome data. geNorm and NormFinder algorithms were used to find the best reference genes to normalize all samples and conditions tested. Additionally, each biotic stress was individually analyzed by geNorm. In general, FBOX (encoding a member of the F-box family) and GAPC2 (GAPDH) was the most stable candidate gene set assessed under the different conditions and subsets tested, while CYP (cyclophilin), TUB (tubulin) and CtP (cathepsin) were the least stably expressed genes found. Validation of the best suitable reference genes for normalizing the expression level of the WRKY70 transcription factor in leaves infected with Candidatus Liberibacter asiaticus showed that arbitrary use of reference genes without previous testing could lead to misinterpretation of data. Our results revealed FBOX, SAND (a SAND family protein), GAPC2 and UPL7 (ubiquitin protein ligase 7) to be superior reference genes, and we recommend their use in studies of gene expression in citrus species and relatives. This work constitutes the first systematic analysis for the selection of superior reference genes for transcript normalization in different citrus organs and under biotic stress.