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Objetivo: Avaliar e comparar o grau de cifose e da força muscular respiratória em mulheres idosas ativas e sedentárias. Métodos: A amostra contou com 30 idosas ativas e sedentárias, com idade entre 60 e 70 anos. Foram realizadas medidas das pressões respiratórias máximas e do grau de cifose. Para a comparação com os valores de pressões respiratórias máximas previstas, foram utilizadas as fórmulas de Black e Hyatt (1969). A análise estatística utilizou o teste t de Student, com índice de significância estabelecido em p < 0,05. Resultados: Participaram do estudo 30 idosas, sendo 15 ativas e 15 sedentárias. A média dos valores de cifose nas ativas foi de 44,4 ± 3,7o e nas participantes sedentárias foi de 56,0 ± 7,2o (p < 0,05). Em relação às pressões respiratórias de ativas e sedentárias, houve diferença estatística entre a pressão expiratória máxima do grupo ativo (43 ± 14,37 cmH2O) e o grupo sedentário (30,80 ± 12,60 cmH2O). Foi verificado que os valores da pressão inspiratória máxima alcançada no grupo ativo e pressões inspiratórias e expiratórias alcançadas no grupo sedentário foram estatisticamente menores que os valores previstos pela equação de Black e Hyatt. Conclusões: A cifose foi menor e a força muscular expiratória maior entre as participantes ativas. A fórmula proposta para predição de valores de pressão inspiratória máxima e pressão expiratória máxima parece não se aplicar à população estudada.

This study investigated serum extracellular vesicles (EVs) in bitches with mammary neoplasms, in order to understand their size, shape, and concentration, as well as their association with tumor malignancy. Thirty bitches were categorized into control (n = 10), mammary tumor grades I and II (GI, n = 13), and grade III (GII, n = 7). Serum was separated from blood collected during mastectomy, and EVs were isolated using size exclusion chromatography. The analysis revealed no significant differences in EV concentrations among groups, with similar concentrations for control, GI, and GII. Ninety-one proteins were identified in EV-enriched samples, with six showing varied abundance across groups. Notably, keratin 18 was highly abundant in GI, while sushi domain-containing protein, EvC ciliary subunit 2, and the joining chain of multimeric IgM and IgA were increased in GII. Additionally, protocadherin 17 and albumin were upregulated in both GI and GII. ROC curves identified potential biomarkers for differentiating tumor grades. Enrichment pathway analysis revealed AFP gene upregulation in the GI. Mass spectrometry proteomics data were deposited in Mendeley Data. The study provides valuable insights into serum EV characterization in bitches, suggesting keratin 18 and protocadherin 17 as potential biomarkers for canine mammary neoplasia, with implications for future diagnostic and therapeutic strategies.

In this article, exact expressions are presented for the probability density function, cumulative distribution function, moment generating function, and higher-order moments of the instantaneous signal-to-noise ratio, considering the product and the sum of the products of $N$ $\alpha$-$\mathcal {F}$ variates with pointing errors. New expressions for the outage probability (OP), bit error probability (BEP), ergodic channel capacity, and the area under the receiver operating characteristics (AUC) are deduced, as well as the asymptotic ones. The obtained expressions are used to assess the influence of various channels and system parameters on the system performance. We analyze a scenario considering dual-hop terahertz links and another regarding reconfigurable intelligent surfaces (RIS)-assisted systems. All expressions derived in this work are new, and Monte Carlo simulations corroborate the analytical curves shown.

The papillary carcinoma is the most prevalent malignant neoplasm of the thyroid gland, representing 85-90% of all cases, and its incidence has been increasing in recent years. It is relatively indolent, however other types poorly differentiated or anaplastic, are more aggressive and usually associated with poor prognosis. Approximately half of these papillary carcinomas harbor a thymine-to-adenine transversion (T1799A) point mutation, in the gene encoding the serine/threonine-kinase B-type Raf kinase (BRAF), with substitution of valine by glutamate (V600E). Mutated BRAF, generates a constitutive activation of the mitogen-activated protein kinases (MAPK) signaling pathway, which plays a critical role in transmitting proliferative signals generated by cell surface receptors and cytoplasmic signaling elements, to the nucleus. BRAF mutation is mutually exclusive with other common genetic alterations, supporting its independent oncogenic role in cell proliferation, survival and tumor de-differentiation. The BRAFV600E occurs exclusively in papillary thyroid carcinoma and papillary carcinoma-derived anaplastic cancer, rising as a specific diagnostic marker for this tumor when identified in cytological / histological exams. This mutation has recently emerged, as a potential prognostic marker for papillary thyroid carcinoma, after several studies have found this mutation to be associated with some clinicopathological characteristics, known to predict tumor recurrence and progression, including, for instance, old patient age, extrathyroidal invasion and lymph node metastasis. It is therefore considered a marker of aggressive disease in these tumors, associated with increased cancer recurrence and even loss of radioiodine avidity. Several studies were not able to confirm these associations. It has become clearer that BRAF mutation will likely have significant impact on the clinical management of papillary thyroid carcinoma.

Introduction: This study aimed to determine whether the administration of antiepileptic drugs (AED) alters the likelihood of detecting epileptiform abnormalities in electroencephalographies (EEG) performed early after a first epileptic seizure. Methods: We performed a retrospective, observational study including patients with a first seizure attended at our centre’s emergency department between July 2014 and November 2019. We collected clinical data, as well as technical data on the acquisition and interpretation of the EEG performed within the first 72 hours after the seizure, and the factors related with seizure recurrence. Results: We recruited 155 patients with a mean (SD) age of 48.6 (22.5) years; 61.3% were men. Regarding seizure type, 51% presented tonic-clonic seizures of unknown onset and 12% presented focal to bilateral tonic-clonic seizures. Thirty-nine patients (25.2%) received AED treatment before the EEG was performed: 33 received a non-benzodiazepine AED and 6 received a benzodiazepine. Epileptiform abnormalities were observed in 29.7% of patients. Previous administration of AEDs was not significantly associated with the probability of detecting interictal epileptiform abnormalities (P = .25) or with the risk of recurrence within 6 months (P = .63). Conclusions: Administration of AEDs before an early EEG following a first seizure does not decrease the likelihood of detecting epileptiform abnormalities. These findings suggest that starting AED treatment immediately in patients with a high risk of early recurrence does not imply a reduction in the diagnostic accuracy of the test. Resumen: Introducción: Determinar si la administración de fármacos antiepilépticos (FAE) puede alterar la probabilidad de encontrar anomalías epileptiformes en EEG realizados de forma precoz tras una primera crisis epiléptica (CE). Método: Estudio observacional retrospectivo en el que se incluyeron los pacientes atendidos en urgencias de nuestro centro por una primera CE entre julio de 2014 y noviembre de 2019. Se recogieron los datos clínicos, las características técnicas de adquisición e interpretación de los EEG efectuados durante las primeras 72 horas tras la CE y los factores relacionados con la recurrencia. Resultados: Se recogieron 155 pacientes; edad media 48,6 ± 22,5 años; 61,3% hombres. El 51% presentaron crisis tónico-clónicas (TC) de inicio desconocido y el 12 % focales con progresión a tónico-clónica bilateral. El 25,2% (39/155) recibieron tratamiento con FAE antes de la realización del EEG; en 33 pacientes se administró un FAE no benzodiacepínico y en 6 una benzodiacepina. Se observaron anomalías epileptiformes en 29,7% de los pacientes. La administración previa de FAE no se asoció de forma significativa ni con la probabilidad de detectar anomalías epileptiformes (p = 0,25) ni con el riesgo de recurrencia a los 6 meses (p = 0,63). Conclusiones: La administración de un FAE previo a la realización del EEG precoz tras una primera CE no disminuye la probabilidad de detectar anomalías epileptiformes. Estos hallazgos sugieren que iniciar un FAE de forma inmediata en aquellos pacientes con alto riesgo de recurrencia precoz no implica un menor rendimiento diagnóstico de dicha prueba.

Resumen: Introducción: Determinar si la administración de fármacos antiepilépticos (FAE) puede alterar la probabilidad de encontrar anomalías epileptiformes en EEG realizados de forma precoz tras una primera crisis epiléptica (CE). Método: Estudio observacional retrospectivo en el que se incluyó a los pacientes atendidos en urgencias de nuestro centro por una primera CE entre julio del 2014 y noviembre del 2019. Se recogieron los datos clínicos, las características técnicas de adquisición e interpretación de los EEG efectuados durante las primeras 72 h tras la CE y los factores relacionados con la recurrencia. Resultados: Se recogieron 155 pacientes; edad media 48,6 ±22,5 años; 61,3% hombres. El 51% presentó crisis tónico-clónicas de inicio desconocido y el 12% focales con progresión a tónico-clónica bilateral. El 25,2% (39/155) recibió tratamiento con FAE antes de la realización del EEG; en 33 pacientes se administró un FAE no benzodiacepínico y en 6 una benzodiacepina. Se observaron anomalías epileptiformes en 29,7% de los pacientes. La administración previa de FAE no se asoció de forma significativa ni con la probabilidad de detectar anomalías epileptiformes (p = 0,25) ni con el riesgo de recurrencia a los 6 meses (p = 0,63). Conclusiones: La administración de un FAE previo a la realización del EEG precoz tras una primera CE no disminuye la probabilidad de detectar anomalías epileptiformes. Estos hallazgos sugieren que iniciar un FAE de forma inmediata en aquellos pacientes con alto riesgo de recurrencia precoz no implica un menor rendimiento diagnóstico de dicha prueba. Abstract: Introduction: This study aimed to determine whether the administration of antiepileptic drugs (AED) alters the likelihood of detecting epileptiform abnormalities in electroencephalographies (EEG) performed early after a first epileptic seizure. Method: We performed a retrospective, observational study including patients with a first seizure attended at our centre's emergency department between July 2014 and November 2019. We collected clinical data, as well as technical data on the acquisition and interpretation of the EEG performed within the first 72 hours after the seizure, and the factors related with seizure recurrence. Results: We recruited 155 patients with a mean (SD) age of 48.6 (22.5) years; 61.3% were men. Regarding seizure type, 51% presented tonic-clonic seizures of unknown onset and 12% presented focal to bilateral tonic-clonic seizures. Thirty-nine patients (25.2%) received AED treatment before the EEG was performed: 33 received a non-benzodiazepine AED and 6 received a benzodiazepine. Epileptiform abnormalities were observed in 29.7% of patients. Previous administration of AEDs was not significantly associated with the probability of detecting interictal epileptiform abnormalities (P=.25) or with the risk of recurrence within 6 months (P=.63). Conclusions: Administration of AEDs before an early EEG following a first seizure does not decrease the likelihood of detecting epileptiform abnormalities. These findings suggest that starting AED treatment immediately in patients with a high risk of early recurrence does not imply a reduction in the diagnostic accuracy of the test.

Thrombotic microangiopathy (TMA) is an anatomopathological lesion mediated by endothelial dysfunction and characterized by the creation of microthrombi in small vessels. In patients with cancer, it may be due to toxicity secondary to chemotherapy, tumor embolization, or hematopoietic progenitor transplantation. Cancer-associated TMA is an underestimated entity that generally appears in the final stages of the disease, although it may also be the initial manifestation of an underlying cancer. Support treatment is necessary in all cases and, depending on the cause, different targeted therapies may be used. The prognosis is very poor. In this article we present a comprehensive review of the existing literature on the physiological mechanisms of cancer-associated TMA. Afterwards, five clinical cases will be presented of patients who developed TMA and were diagnosed in our Department in 2023. We present a discussion of the different causes that triggered the condition, the possible reasons behind the underestimation of this pathology, and the measures that may be adopted.

O objetivo desse artigo é partir de uma visão geral dos principais processos educativos presentes no Brasil colonial para contrastá-los com dinâmicas específicas vivenciadas numa região singular, a capitania de Minas Gerais, indicando as principais tendências investigativas sobre o tema. Essa abordagem permite vislumbrar as ações das instituições dominantes no cenário colonial, isto é, o Estado português e a Igreja Católica, e o envolvimento de diferentes grupos sociais e indivíduos em atividades educativas, mesmo que distanciadas daquelas instituições. Tendo em vista o desvendamento dos mecanismos envolvidos nas diferentes formas de relação com a educação em seus diversos entendimentos sobre ela, desde que se instalaram as primeiras instituições educativas e se iniciaram processos escolares e não escolares no Brasil, utiliza-se a abordagem que considera as diferentes escalas de análise, transitando dos processos gerais para as dinâmicas particulares, numa perspectiva orientada pela micro-história e suas propostas metodológicas, a fim de realçar sua pertinência para uma compreensão mais refinada da história da educação brasileira em seus tempos iniciais.

This study tested the usability of a home-based self-administration transcranial direct current stimulation (tDCS) device designed specifically for women's health needs. This is a single center triple blinded clinical usability study for a new wireless, Bluetooth-controlled wearable tDCS device for women's health. The study aims to evaluate the usability and effective blinding of a home-based tDCS system. A total of forty-nine women of reproductive age were randomly allocated (1:1) to receive one session of active tDCS (n = 24) or sham tDCS (n = 25) over the motor and dorsolateral prefrontal cortex. Each participant self-administered one 20-minute session without supervision following guidance on a software application alone. The System Usability Scale (SUS) and the Patient Global Impression of Change (PGIC) were used to evaluate the usability of the system. Regardless of sham or active conditions, all users found the system easy to use without the support of researchers. Usability scores were considered to be "excellent" in both groups and no significant difference was found between sham and active groups showing effective blinding of the device (Active group: 93.7 (83.1-97.5); Sham group 90 (86.2-95) p = 0.79) and PGIC (Active group: 2 (1-2.75); Sham group 2 (1-2) p = 0.99) using an unpaired t-test or non-parametric statistical tests accordingly. The new Bluetooth-controlled wearable tDCS device is easy, safe to use and completely controlled by a smartphone app. This device is focused on women's health and will be tested as an alternative treatment for chronic pelvic pain and mood disturbance associated with menstrual cycles in further research.

Understanding habitat extension that limits species distribution is a crucial tool for management and conservation, in which habitat mapping plays a pivotal role. The mesovoid shallow substratum (MSS) is a type of shallow subterranean habitat with an important conservation value for invertebrate communities, functioning as climatic/reproductive refuge, biogeographic corridor and/or permanent habitat. Methodologies to map the mesovoid shallow substratum (MSS) are currently lacking. We propose a novel method for colluvial MSS habitat mapping, combining geographic information systems, geological maps, and geological knowledge on the habitat genesis. We tested and validated the efficiency of the method using the Arrábida karst area (Portugal) as a model. The method allowed the remote detection of MSS habitats suitable for invertebrate communities ex situ within the study area, and enabled the estimation of habitat extent. The faunal communities sampled in the selected location were dominated by arthropods, especially insects, showcasing the efficacy of this mapping method to detect suitable MSS habitats. The use of this method considerably reduces the in situ scouting area, providing a more efficient way of locating these habitats. The MSS is protected under EU legislation concerning floral communities and geological features, completely neglecting its faunal communities. This method also allows to estimate potential MSS habitat extension in several lithologies, facilitating the implementation of invertebrate prospections, and the establishment of more effective conservation measures.

Background: Vaccination is one of the most important measures to contain the COVID-19 pandemic, especially for frail patients. VACCINATE is a multicentre prospective observational study promoted by the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET) aimed at assessing the long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases (rcCTDs) in terms of efficacy and safety. Methods: Adult rcCTDs patients were eligible for recruitment. Demographic, clinical and vaccination data were collected at enrolment. Follow-up visits were scheduled 4, 12, 24, 36 and 48 weeks after completion of the first vaccination cycle; data on adverse events, disease exacerbations and the occurrence of new SARS-CoV-2 infections were collected at these time-points. Findings: 365 rcCTDs patients (87 % female, mean age 51.8 ± 14.6 years) were recruited. Overall, 200 patients (54.8 %) experienced at least one adverse event, generally mild and in most cases occurring early after the vaccination. During follow-up, 55 disease exacerbations were recorded in 39 patients (10.7 %), distributed over the entire observation period, although most frequently within 4 weeks after completion of the vaccination cycle. The incidence of new SARS-CoV-2 infections was 8.9 per 1000 person-months, with no cases within 12 weeks from vaccine administration and an increasing trend of infections moving away from the primary vaccination cycle. Only one case of severe COVID-19 was reported during the study period. Interpretation: COVID-19 vaccination seems effective and safe in rcCTDs patients. The rate of new infections was rather low and serious infections were uncommon in our cohort. No increased risk of disease flares was observed compared to previous disease history; however, such exacerbations may be potentially severe, emphasising the need for close monitoring of our patients.

Abstract The relationship between brain diffusion microstructural changes and disability in multiple sclerosis (MS) remains poorly understood. We aimed to explore the predictive value of microstructural properties in white (WM) and grey matter (GM), and identify areas associated with mid-term disability in MS patients. We studied 185 patients (71% female; 86% RRMS) with the Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), and Symbol Digit Modalities Test (SDMT) at two time-points. We used Lasso regression to analyse the predictive value of baseline WM fractional anisotropy and GM mean diffusivity, and to identify areas related to each outcome at 4.1 years follow-up. Motor performance was associated with WM (T25FW: RMSE = 0.524, R2 = 0.304; 9HPT dominant hand: RMSE = 0.662, R2 = 0.062; 9HPT non-dominant hand: RMSE = 0.649, R2 = 0.139), and SDMT with GM diffusion metrics (RMSE = 0.772, R2 = 0.186). Cingulum, longitudinal fasciculus, optic radiation, forceps minor and frontal aslant were the WM tracts most closely linked to motor dysfunction, and temporal and frontal cortex were relevant for cognition. Regional specificity related to clinical outcomes provide valuable information that can be used to develop more accurate predictive models that could improve therapeutic strategies.

PURPOSEEarly integration of pediatric palliative care (PPC) for children with cancer is critical to improving the quality of life of both the patient and family. Understanding physician perceptions of palliative care and perceived barriers to early integration is necessary to develop PPC in Brazil.METHODSThe Assessing Doctors' Attitudes on Palliative Treatment survey was modified for use in Brazil. The survey was open from January 2022 to June 2022 and distributed to physicians of all specialties from participating institutions who treat children with cancer. Statistical analysis was complemented by qualitative analysis of open-ended responses.RESULTSA total of 272 respondents participated. Most respondents reported access to PPC experts for consultation (77.2%) and 34.5% indicated previous palliative care training. Physician knowledge of PPC was generally aligned with WHO guidance (median alignment, 93.0%; range, 80.5%-98.2%). However, about half (53.3%) felt comfortable addressing physical needs of patients receiving PPC, 35.3% addressing emotional needs, 25.8% addressing spiritual needs, and 33.5% addressing grief and bereavement needs. Most respondents (65.4%) felt palliative care should be involved from diagnosis, but only 10.3% stated that this occurred in their setting. The most important barriers identified were physician discomfort (89.0%), limited physician knowledge (88.6%), and lack of home-based services (83.8%).CONCLUSIONDespite a strong understanding of the role of palliative care, physicians in Brazil reported low confidence delivering PPC to children with cancer. Additionally, physicians generally believed that PPC should be integrated earlier in the disease trajectory of children with cancer. This work will direct educational and capacity building initiatives to ensure greater access to high-quality PPC for children with cancer in Brazil to address patient and family suffering.

Objectives The main goal of this study was to characterise the frequency and phenotype of B, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in peripheral blood and the cytokine environment present in circulation in children with extended oligoarticular juvenile idiopathic arthritis (extended oligo JIA) and polyarticular JIA (poly JIA) when compared with healthy controls, children with persistent oligoarticular JIA (persistent oligo JIA) and adult JIA patients.Methods Blood samples were collected from 105 JIA patients (children and adults) and 50 age-matched healthy individuals. The frequency and phenotype of B, Tfh and Tfr cells were evaluated by flow cytometry. Serum levels of APRIL, BAFF, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-17A, IL-21, IL-22, IFN-γ, PD-1, PD-L1, sCD40L, CXCL13 and TNF were measured by multiplex bead-based immunoassay and/or ELISA in all groups included.Results The frequency of B, Tfh and Tfr cells was similar between JIA patients and controls. Children with extended oligo JIA and poly JIA, but not persistent oligo JIA, had significantly lower frequencies of plasmablasts, regulatory T cells and higher levels of Th17-like Tfh cells in circulation when compared with controls. Furthermore, APRIL, BAFF, IL-6 and IL-17A serum levels were significantly higher in paediatric extended oligo JIA and poly JIA patients when compared with controls. These immunological alterations were not found in adult JIA patients in comparison to controls.Conclusions Our results suggest a potential role and/or activation profile of B and Th17-like Tfh cells in the pathogenesis of extended oligo JIA and poly JIA, but not persistent oligo JIA.

The Green Bank 820 MHz pulsar survey covers ≃173 deg ^2 in the Cygnus X region of the Galaxy, centered on l = 84.°5 and b = 1.°5. Significant star formation is present in this region, and lines of sight pass through three arms of the Galaxy (Orion–Cygnus, Perseus, and an outer arm). Using the Green Bank Telescope, we recorded 200 MHz of bandwidth for 4.5 minutes at 81.92 μ s resolution for each of 3457 observed survey pointings during 2016 and 2017, covering about two-thirds of the total area. We searched these data for pulsars and report the discovery of six new pulsars—PSRs J2016+3820, J2016+4231, J2019+3810, J2035+3538, J2035+3655, and J2041+4551—and the codiscovery of PSR J2057+4701. PSR J2035+3655 is in a short (4.5 hr) binary orbit; we report the full binary solution and weakly constrain the mass of the pulsar via a marginal (2 σ ) detection of the Shapiro delay. We also searched the survey data for known pulsars to estimate the survey’s sensitivity and measured 820 MHz pulse widths and flux density for 20 detected sources. For sources that were also detected in the Green Bank North Celestial Cap survey at 350 MHz, we measure scattering parameters and compare to expectations for the region. With these results, we revisit the population estimates that motivated this survey and consider the impact of the survey’s yield on their underlying models. We note an apparent underestimate in dispersion measure predictions from typical Galactic electron density models in the survey region, and discuss future observation strategies.

The Australian, Chinese, European, Indian, and North American pulsar timing array (PTA) collaborations recently reported, at varying levels, evidence for the presence of a nanohertz gravitational-wave background (GWB). Given that each PTA made different choices in modeling their data, we perform a comparison of the GWB and individual pulsar noise parameters across the results reported from the PTAs that constitute the International Pulsar Timing Array (IPTA). We show that despite making different modeling choices, there is no significant difference in the GWB parameters that are measured by the different PTAs, agreeing within 1 σ . The pulsar noise parameters are also consistent between different PTAs for the majority of the pulsars included in these analyses. We bridge the differences in modeling choices by adopting a standardized noise model for all pulsars and PTAs, finding that under this model there is a reduction in the tension in the pulsar noise parameters. As part of this reanalysis, we “extended” each PTA’s data set by adding extra pulsars that were not timed by that PTA. Under these extensions, we find better constraints on the GWB amplitude and a higher signal-to-noise ratio for the Hellings–Downs correlations. These extensions serve as a prelude to the benefits offered by a full combination of data across all pulsars in the IPTA, i.e., the IPTA’s Data Release 3, which will involve not just adding in additional pulsars but also including data from all three PTAs where any given pulsar is timed by more than a single PTA.

We present a framework for modeling astrophysical pulses from radio pulsars and fast radio bursts (FRBs). This framework, called fitburst , generates synthetic representations of dynamic spectra that are functions of several physical and heuristic parameters; the heuristic parameters can nonetheless accommodate a vast range of distributions in spectral energy. fitburst is designed to optimize the modeling of features induced by effects that are intrinsic and extrinsic to the emission mechanism, including the magnitude and frequency dependence of pulse dispersion and scatter broadening. fitburst removes intrachannel smearing through two-dimensional upsampling, and can account for phase-wrapping of “folded” signals that are typically acquired during pulsar-timing observations. We demonstrate the effectiveness of fitburst in modeling data containing pulsars and FRBs observed with the Canadian Hydrogen Intensity Mapping Experiment telescope.

The Green Bank North Celestial Cap survey is one of the largest and most sensitive searches for pulsars and transient radio objects. Observations for the survey have finished; priorities have shifted toward long-term monitoring of its discoveries. In this study, we have developed a pipeline to handle large data sets of archival observations and connect them to recent, high-cadence observations taken using the Canadian Hydrogen Intensity Mapping Experiment telescope. This pipeline handles data for 128 pulsars and has produced measurements of spin, positional, and orbital parameters that connect data over observation gaps as large as 2000 days. We have also measured glitches in the timing residuals for five of the pulsars included and proper motion for 19 sources (13 new). We include updates to orbital parameters for 19 pulsars, including nine previously unpublished binaries. For two of these binaries, we provide updated measurements of post-Keplerian binary parameters, which result in much more precise estimates of the total masses of both systems. For PSR J0509+3801, the much improved measurement of the Einstein delay yields much improved mass measurements for the pulsar and its companion, 1.399(6) M _⊙ and 1.412(6) M _⊙ , respectively. For this system, we have also obtained a measurement of the orbital decay due to the emission of gravitational waves, ${\dot{P}}_{{\rm{B}}}=-1.37(7)\times {10}^{-12}$ , which is in agreement with the rate predicted by general relativity for these masses.

Although zoophilic dermatophytes remain the predominant cause of tinea capitis in Spain, an increase due to anthropophilic species has been reported. We report a retrospective observational study that included twenty-four children, who were diagnosed with tinea capitis due to anthropophilic species between 2004 and 2019. 75% of the patients were males with a mean age of 4,88 years. We observed 83,3% of cases from Africa, 4,2% from South America and 12,5% from Spain. Clinically, 70,8% of the patients presented scaly patches and non-scaring alopecia. Trichophyton soudanense was the main dermatophyte of the series (45,8%), followed by Microsporum audouinii (20,8%), Trichophyton tonsurans (12,5%) and Trichophyton violaceum (12,5%). Although this pattern of infection appears to be linked to immigration from Africa, we saw three native cases. The easier transmission of anthropophilic rather than zoophilic dermatophytes could predict a rise in the incidence of tinea capitis and a public health problem. Resumen: Aunque los dermatofitos zoófilos son aparentemente aún la causa principal de tinea capitis en España, se está observando un repunte por especies antropófilas. Presentamos un estudio observacional retrospectivo de veinticuatro niños con tinea capitis antropófila, diagnosticados en nuestro centro entre 2004 y 2019. El 75% de los pacientes fueron varones con una media de edad de 4,88 años. El 83,3% eran africanos, el 4,2% de América del Sur y el 12,5% de España. Clínicamente, en el 70,8% de los casos se observaron parches descamativos con alopecia no cicatricial. Trichophyton soudanense fue el dermatofito más aislado (45,8%), seguido de Microsporum audouinii (20,8%), Trichophyton tonsurans (12,5%) y Trichophyton violaceum (12,5%). Aunque este patrón parece estar relacionado con la inmigración africana, observamos 3 casos nativos. La facilidad de transmisión de los dermatofitos antropófilos permite predecir un aumento en la incidencia de la tinea capitis y un potencial problema de salud pública.

Introduction Network analysis has been used to explore the interplay between psychopathology and functioning in psychosis, but no study has used dedicated statistical techniques to focus on the bridge symptoms connecting these domains. Objectives The current study aims to estimate the network of depressive, negative, and positive symptoms, general psychopathology, and real-world functioning in people with first-episode schizophrenia or schizophreniform disorder, focusing on bridge nodes. Methods Baseline data from the OPTiMiSE trial were analysed. The sample included 446 participants (age 40.0±10.9 years, 70% males). The network was estimated with a Gaussian graphical model (GGM), using scores on individual items of the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS), and the Personal and Social Performance (PSP) scale. Stability, strength centrality, expected influence (EI), predictability, and bridge centrality statistics were computed. The top 20% scoring nodes on bridge strength were selected as bridge nodes. Results Nodes from different rating scales assessing similar psychopathological and functioning constructs tended to cluster together in the estimated network (Fig. 1). The most central nodes (EI) were Delusions, Emotional Withdrawal, Depression, and Depressed Mood. Bridge nodes included Depression, Conceptual Disorganisation, Active Social Avoidance, Delusions, Stereotyped Thinking, Poor Impulse Control, Guilty Feelings, Unusual Thought Content, and Hostility. Most of the bridge nodes belonged to the general psychopathology subscale of the PANSS. Depression (G6) was the bridge node with the highest value. Image: Conclusions The current study provides novel insights for understanding the complex phenotype of psychotic disorders and the mechanisms underlying the development and maintenance of comorbidity and functional impairment after psychosis onset. Disclosure of Interest None Declared

Nesse artigo pretende-se analisar o processo de expansão do ensino régio na América portuguesa destacando a atuação dos governadores e suas relações com o poder central, respondendo conforme as especificidades de cada capitania aos esforços de centralização e uniformização da coroa portuguesa. O objetivo é reunir elementos para uma análise comparada e contribuir para a compreensão dos processos iniciais de implantação do ensino público no Brasil, com destaque para o confronto entre as ações administrativas do poder central e as experiências vividas no cotidiano do gerenciamento do ensino público no período colonial.

Objectives: To analyze the characteristics and the predictive factors of the use of rituximab and belimumab in daily practice in patients from the inception cohort Registro Español de Lupus (RELES). Material and methods: The study included 518 patients. We considered patients treated with biologics who received at least one dose of rituximab or belimumab, and possible indications of those manifestations registered at the same time or in the previous 2 months of the start of the therapy. Results: In our cohort, 37 (7%) patients received at least one biological treatment. Rituximab was prescribed in 26 patients and belimumab in 11. Rituximab was mainly prescribed for hemolytic anemia or thrombocytopenia (11 patients, 42%), lupus nephritis and neuropsychiatric lupus (5 patients each, 19%). Belimumab was mostly used for arthritis (8 patients, 73%). In the univariate analysis, the predictive factors at diagnosis for the use of biologic therapy were younger age (p = 0.022), a higher SLEDAI (p = 0.001) and the presence of psychosis (p = 0.011), organic mental syndrome (SOCA) (p = 0.006), hemolytic anemia (p = 0.001), or thrombocytopenia (p = 0.01). In the multivariant model, only younger age, psychosis, and hemolytic anemia were independent predictors of the use of biologics. Conclusions: Rituximab is usually given to patients with hematological, neuropsychiatric and renal involvement and belimumab for arthritis. Psychosis, hemolytic anemia and age at the diagnosis of lupus were independent predictive factors of the use of biological agents. Their global effects are beneficial, with a significant reduction in SLE activity and a low rate of side effects.

Background: Although biological therapies have transformed the outlook for those with rheumatoid arthritis, there is a lack of any meaningful response in approximately 40% of patients. The role of B cells in rheumatoid arthritis pathogenesis is well recognised and is supported by the clinical efficacy of the B-cell-depleting agent rituximab (MabThera, F. Hoffman La-Roche Ltd, Basel, Switzerland). Rituximab is licensed for use in rheumatoid arthritis following failure of conventional synthetic disease-modifying antirheumatic drugs and tumour necrosis factor inhibitor therapy. However, over 50% of patients show low/absent synovial B-cell infiltration, suggesting that, in these patients, inflammation is driven by alternative cell types. This prompted us to test the hypothesis that, in synovial biopsy B-cell-poor patients, tocilizumab (RoActemra, F. Hoffman La-Roche Ltd, Basel, Switzerland) (targeting interleukin 6) is superior to rituximab (targeting CD20+/B cells). Design: The R4–RA (A Randomised, open-labelled study in anti-TNFalpha inadequate responders to investigate the mechanisms for Response, Resistance to Rituximab versus Tocilizumab in Rheumatoid Arthritis patients) trial is a 48-week Phase IV, open-label, randomised controlled trial conducted in 19 European centres that recruited patients failing on or intolerant to conventional synthetic disease-modifying antirheumatic drug therapy and at least one tumour necrosis factor inhibitor. Participants: Synovial tissue was obtained at trial entry and classified histologically as B-cell rich or B-cell poor to inform balanced stratification. Patients were randomised on a 1 : 1 basis to receive standard therapy with rituximab or tocilizumab. B-cell-poor/-rich molecular classification was also carried out. The study was powered to test the superiority of tocilizumab over rituximab at 16 weeks in the B-cell-poor population. Main outcome measures: The primary end point was defined as an improvement in the Clinical Disease Activity Index (CDAI) score of ≥ 50% from baseline. In addition, patients were considered to be non-responders if they did not reach an improvement in CDAI score of ≥ 50% and a CDAI score of

Pedro Paulo Chieffi,1 Susana Angelica Zevallos Lescano,2 Gabriela Rodrigues e Fonseca,3 Sergio Vieira dos Santos1 1Department of Pathological Sciences, Santa Casa Medical School, São Paulo, Brazil; 2Laboratory of Helminthology, Institute for Tropical Medicine of São Paulo, University of São Paulo, São Paulo, Brazil; 3Department of Infectious and Parasitic Diseases, Faculty of Medicine, University of São Paulo, São Paulo, BrazilCorrespondence: Pedro Paulo ChieffiDepartamento de Ciências Patológicas, Faculdade de Ciências Médicas da Santa Casa de São Paulo, Rua Cesário Mota Junior, 112, São Paulo, CEP01221-020, BrasilTel +5511-33677722Email pchieffi@usp.brAbstract: This is a review of the published contributions made by Brazilian researchers between 2010 and 2020 on the natural history of human toxocariasis and the effects of human toxocariasis on nonhuman paratenic hosts.Keywords: Toxocara, Toxocara canis, toxocariasis, visceral larva migrans syndrome, Brazilian contribution

Introduction The use of internet among children and adolescent has risen in the last decade. In addition, suicide is the second cause of death among adolescents. Previous research have indicated the relation between Problematic Internet Use (PIU) and different mental health problems. Nonetheless there is a lack of studies analyzing the relation between suicide behaviour and PIU Objectives The main objective of the present work was to analyze the relation between Problematic Internet Use and suicide behaviour and depression in adolescents Methods A total of 1036 adolescents (450 males) were randomly selected. Mean age was 15,21 (SD = 1,23). The Adolescent Behavioural Suicide Scale SENTIA, The Reynolds Adolescent Depression Scale Short Form (RADS-SF), and The Compulsive Internet Use Scale (CIUS) were used. A Manova was performed with two groups (risk and non-risk to PIU) as independent variables and suicide and depression scores as dependent variables Results The results revealed a statiscally signifficant association between PIU and both depression and suicide behaviour (λ = 0.245, F(2,81,000) = 15.549, P ≤ 0.001, η² = 0.116). In particular, adolescents at a higher risk for PIU obtained higher scores on suicide behaviours and depression. Conclusions Results found in the present study reveal that adolescents have moderate prevalence rates for PIU. Also adolescents at risk for PIU with a total of more than 3 hour sof internet use everyday were at a higher risk for suicide. Prevention strategies should be devote to intervene in internet use as it maybe a variable affecting suicide behaviour. Disclosure No significant relationships.

Introduction PIU has not yet been recognized by diagnostic classification systems, but it has received increasing research and clinical attention. It is defined as a generalized and compulsive use of the Internet associated with a loss of control and negative consequences for the individual Objectives The main goal was to analyze the relation between problematic Internet Use and wellbeing in adolescents Methods The sample included a total of 1059 adolescents (47% were males). Age range was between 14 and 18 years old (M = 15,12; SD = 1,03). We used the Compulsive Internet Use Scale to assess Problematic Internet Use and the Strengths and Difficulties Questionnaire to screen for psychological difficulties and prosocial behaviour. Results The results found in the ANOVA revealed that problematic internet use was statistically significant associated with psychological difficulties and prosocial capabilities (λ = 0.475, F(3,83,000) = 25.569, P ≤ 0.001, η² = 0.215).Adolescents with higher levels of Problematic Internet Use revealed more emotional and behavioural difficulties. In addition. those adolescents with higher levels of prosocial ablities were at a lower risk for Problematic Internet Use. Conclusions Previous research have revealed that the use of Internet has almost doubled in the last decade among adolescents across different European countries. Results revealed statistically significant correlations between Problematic Internet Use and indicators of well-being such as emotional difficulties and behavioral problems, as well as prosocial behaviours. Prevention strategies should focus on detecting problematic internet use among adolescents, as it is a variable related with different psychological difficulties that are diminishing adolescents’ well-being. Disclosure No significant relationships.

Abstract Background The vasculitides are a group of rare diseases with different manifestations and outcomes. New therapeutic options have led to the need for long-term registries. The Rheumatic Diseases Portuguese Register, Reuma.pt, is a web-based electronic clinical record, created in 2008, which currently includes specific modules for 12 diseases and > 20,000 patients registered from 79 rheumatology centres. On October 2014, a dedicated module for vasculitis was created as part of the European Vasculitis Society collaborative network, enabling prospective collection and central storage of encrypted data from patients with this condition. All Portuguese rheumatology centres were invited to participate. Data regarding demographics, diagnosis, classification criteria, assessment tools, and treatment were collected. We aim to describe the structure of Reuma.pt/vasculitis and characterize the patients registered since its development. Results A total of 687 patients, with 1945 visits, from 13 centres were registered; mean age was 53.4 ± 19.3 years at last visit and 68.7% were females. The most common diagnoses were Behçet’s disease (BD) (42.5%) and giant cell arteritis (GCA) (17.8%). Patients with BD met the International Study Group criteria and the International Criteria for BD in 85.3 and 97.2% of cases, respectively. Within the most common small- and medium-vessel vasculitides registered, median [interquartile range] Birmingham Vasculitis Activity Score (BVAS) at first visit was highest in patients with ANCA-associated vasculitis (AAV) (17.0 [12.0]); there were no differences in the proportion of patients with AAV or polyarteritis nodosa who relapsed (BVAS≥1) or had a major relapse (≥1 major BVAS item) during prospective assessment (p = 1.00, p = 0.479). Biologic treatment was prescribed in 0.8% of patients with GCA, 26.7% of patients with AAV, and 7.6% of patients with BD. There were 34 (4.9%) deaths reported. Conclusions Reuma.pt/vasculitis is a bespoke web-based registry adapted for routine care of patients with this form of rare and complex diseases, allowing an efficient data-repository at a national level with the potential to link with other international databases. It facilitates research, trials recruitment, service planning and benchmarking.

Resumen: Aunque los dermatofitos zoófilos son aparentemente aún la causa principal de tinea capitis en España, se está observando un repunte por especies antropófilas. Presentamos un estudio observacional retrospectivo de 24 niños con tinea capitis antropófila, diagnosticados en nuestro centro entre 2004 y 2019. El 75% de los pacientes fueron varones con una media de edad de 4,88 años. El 83,3% eran africanos, el 4,2% de América del Sur y el 12,5% de España. Clínicamente, en el 70,8% de los casos se observaron parches descamativos con alopecia no cicatricial. Trichophyton soudanense fue el dermatofito más aislado (45,8%), seguido de Microsporum audouinii (20,8%), Trichophyton tonsurans (12,5%) y Trichophyton violaceum (12,5%). Aunque este patrón parece estar relacionado con la inmigración africana, observamos 3 casos nativos. La facilidad de transmisión de los dermatofitos antropófilos permite predecir un aumento en la incidencia de la tinea capitis y un potencial problema de salud pública. Abstract: Although zoophilic dermatophytes remain the predominant cause of tinea capitis in Spain, an increase due to anthropophilic species has been reported. We report a retrospective observational study that included 24 children, who were diagnosed with tinea capitis due to anthropophilic species between 2004 and 2019. 75% of the patients were males with a mean age of 4,88 years. We observed 83,3% of cases from Africa, 4,2% from South America and 12,5% from Spain. Clinically, 70,8% of the patients presented scaly patches and non-scaring alopecia. Trichophyton soudanense was the main dermatophyte of the series (45,8%), followed by Microsporum audouinii (20,8%), Trichophyton tonsurans (12,5%) and Trichophyton violaceum (12,5%). Although this pattern of infection appears to be linked to immigration from Africa, we saw three native cases. The easier transmission of anthropophilic rather than zoophilic dermatophytes could predict a rise in the incidence of tinea capitis and a public health problem.

We present timing solutions for 21 pulsars discovered in 350 MHz surveys using the Green Bank Telescope (GBT). All were discovered in the Green Bank North Celestial Cap pulsar survey, with the exception of PSR J0957−0619, which was found in the GBT 350 MHz Drift-scan pulsar survey. The majority of our timing observations were made with the GBT at 820 MHz. With a spin period of 37 ms and a 528 days orbit, PSR J0032+6946 joins a small group of five other mildly recycled wide binary pulsars, for which the duration of recycling through accretion is limited by the length of the companion’s giant phase. PSRs J0141+6303 and J1327+3423 are new disrupted recycled pulsars. We incorporate Arecibo observations from the NANOGrav pulsar timing array into our analysis of the latter. We also observed PSR J1327+3423 with the Long Wavelength Array, and our data suggest a frequency-dependent dispersion measure. PSR J0957−0619 was discovered as a rotating radio transient, but is a nulling pulsar at 820 MHz. PSR J1239+3239 is a new millisecond pulsar (MSP) in a 4 days orbit with a low-mass companion. Four of our pulsars already have published timing solutions, which we update in this work: the recycled wide binary PSR J0214+5222, the noneclipsing black widow PSR J0636+5128, the disrupted recycled pulsar J1434+7257, and the eclipsing binary MSP J1816+4510, which is in an 8.7 hr orbit with a redback-mass companion.

We search for gravitational-wave (GW) transients associated with fast radio bursts (FRBs) detected by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst Project, during the first part of the third observing run of Advanced LIGO and Advanced Virgo (2019 April 1 15:00 UTC–2019 October 1 15:00 UTC). Triggers from 22 FRBs were analyzed with a search that targets both binary neutron star (BNS) and neutron star–black hole (NSBH) mergers. A targeted search for generic GW transients was conducted on 40 FRBs. We find no significant evidence for a GW association in either search. Given the large uncertainties in the distances of our FRB sample, we are unable to exclude the possibility of a GW association. Assessing the volumetric event rates of both FRB and binary mergers, an association is limited to 15% of the FRB population for BNS mergers or 1% for NSBH mergers. We report 90% confidence lower bounds on the distance to each FRB for a range of GW progenitor models and set upper limits on the energy emitted through GWs for a range of emission scenarios. We find values of order 10 ^51 –10 ^57 erg for models with central GW frequencies in the range 70–3560 Hz. At the sensitivity of this search, we find these limits to be above the predicted GW emissions for the models considered. We also find no significant coincident detection of GWs with the repeater, FRB 20200120E, which is the closest known extragalactic FRB.

Fast radio bursts (FRBs) display a confounding variety of burst properties and host-galaxy associations. Repeating FRBs offer insight into the FRB population by enabling spectral, temporal, and polarimetric properties to be tracked over time. Here, we report on the polarized observations of 12 repeating sources using multiyear monitoring with the Canadian Hydrogen Intensity Mapping Experiment (CHIME) over 400–800 MHz. We observe significant rotation measure (RM) variations from many sources in our sample, including RM changes of several hundred radians per square meter over month timescales from FRBs 20181119A, 20190303A, and 20190417A, and more modest RM variability (ΔRM ≲ few tens of radians per square meter) from FRBs 20181030A, 20190208A, 20190213B, and 20190117A over equivalent timescales. Several repeaters display a frequency-dependent degree of linear polarization that is consistent with depolarization via scattering. Combining our measurements of RM variations with equivalent constraints on DM variability, we estimate the average line-of-sight magnetic field strength in the local environment of each repeater. In general, repeating FRBs display RM variations that are more prevalent and/or extreme than those seen from radio pulsars in the Milky Way and the Magellanic Clouds, suggesting repeating FRBs and pulsars occupy distinct magnetoionic environments.

Fast radio burst (FRB) source FRB 20180916B exhibits a 16.33-day periodicity in its burst activity. It is as of yet unclear what proposed mechanism produces the activity, but polarization information is a key diagnostic. Here we report on the polarization properties of 44 bursts from FRB 20180916B detected between 2018 December and 2021 December by CHIME/FRB, the FRB project on the Canadian Hydrogen Intensity Mapping Experiment. In contrast to previous observations, we find significant variations in the Faraday rotation measure (RM) of FRB 20180916B. Over the 9-month period 2021 April and 2021 December we observe an apparent secular increase in RM of ∼50 rad m ^−2 (a fractional change of over 40%) that is accompanied by a possible drift of the emitting band to lower frequencies. This interval displays very little variation in the dispersion measure (ΔDM ≲ 0.8 pc cm ^−3 ), which indicates that the observed RM evolution is likely produced from coherent changes in the Faraday-active medium’s magnetic field. Burst-to-burst RM variations appear unrelated to the activity cycle phase. The degree of linear polarization of our burst sample (≳80%) is consistent with the negligible depolarization expected for this source in the 400–800 MHz bandpass of CHIME. FRB 20180916B joins other repeating FRBs in displaying substantial RM evolution. This is consistent with the notion that repeater progenitors may be associated with young stellar populations by their preferential occupation of dynamic magnetized environments commonly found in supernova remnants, in pulsar wind nebulae, or near high-mass stellar companions.

We present timing solutions for 12 pulsars discovered in the Green Bank North Celestial Cap 350 MHz pulsar survey, including six millisecond pulsars (MSPs), a double neutron star (DNS) system, and a pulsar orbiting a massive white dwarf companion. Timing solutions presented here include 350 and 820 MHz Green Bank Telescope data from initial confirmation and follow-up, as well as a dedicated timing campaign spanning 1 ryr PSR J1122−3546 is an isolated MSP, PSRs J1221−0633 and J1317−0157 are MSPs in black widow systems and regularly exhibit eclipses, and PSRs J2022+2534 and J2039−3616 are MSPs that can be timed with high precision and have been included in pulsar timing array experiments seeking to detect low-frequency gravitational waves. PSRs J1221−0633 and J2039−3616 have Fermi Large Area Telescope gamma-ray counterparts and also exhibit significant gamma-ray pulsations. We measure proper motions for three of the MSPs in this sample and estimate their space velocities, which are typical compared to those of other MSPs. We have detected the advance of periastron for PSR J1018−1523 and therefore measure the total mass of the DNS system, m _tot = 2.3 ± 0.3 M _⊙ . Long-term pulsar timing with data spanning more than 1 yr is critical for classifying recycled pulsars, carrying out detailed astrometry studies, and shedding light on the wealth of information in these systems post-discovery.

O artigo analisa eventos educativos ocorridos na América portuguesa setecentista, na capitania de Minas Gerais, inscritos nas práticas pedagógicas e civilizadoras do estado e da igreja em duas dimensões: na atuação das famílias quanto à construção de estratégias para a educação das crianças e jovens, por meio de seus capitais econômicos e culturais; nas ações pedagógicas para a conformação social da população mestiça, foco nas pretensões civilizadoras e de controle. As análises valem-se de fontes que, embora já bem conhecidas da historiografia colonial, são relativamente recentes no corpus documental das pesquisas sobre a história da educação no Brasil nos séculos XVIII e XIX: os testamentos, os inventários post mortem e os processos eclesiásticos.

Objectives: To identify ultrasound (US) features associated with the presence of shoulder complaints.Methods: This observational, case-control study, compared US findings between participants with and without shoulder complaints, matched for age, sex, and dominancy. Data was collected from February 2018 to June 2020. Two-tailed Fisher's and Mann-Whitney U-tests were used, with p-values < 0.05 considered significant.Results: A total of 202 participants were enrolled (median age 56 years, range 18–70, 155 women), comprising 140 cases and 62 controls. A calcification size ≥6 mm, when age < 56 (p = 0.02), and a distance to tendon insertion ≥6 mm, when age ≥56 (p = 0.009), were only found in symptomatic shoulders. Color Doppler in rotator cuff (RC) tendons predominated in the presence of symptoms (26/140 vs. 2/62, p = 0.003). An algorithm also combining the number of calcifications, tendon echotexture and insertional thickening, osseous irregularity, cuff tears, and subacromial effusion showed a 92% (57/62) specificity for shoulder pain on this study sample.Conclusion: Calcification diameter of 6 mm or more is associated with shoulder pain in patients younger than 56 years. A distance from calcification to tendon insertion of 6 mm or more is related to pain in older patients. Doppler signal also is associated with shoulder pain. An algorithm based on a set of specific ultrasonographic criteria have a strong association with the presence of symptoms.

We aimed to validate the association of 28 GWAS-identified genetic variants for response to TNF inhibitors (TNFi) in a discovery cohort of 1361 rheumatoid arthritis (RA) patients monitored in routine care and ascertained through the REPAIR consortium and DANBIO registry. We genotyped selected markers and evaluated their association with response to TNFi after 6 months of treatment according to the change in disease activity score 28 (ΔDAS28). Next, we confirmed the most interesting results through meta-analysis of our data with those from the DREAM cohort that included 706 RA patients treated with TNFi. The meta-analysis of the discovery cohort and DREAM registry including 2067 RA patients revealed an overall association of the LINC02549rs7767069 SNP with a lower improvement in DAS28 that remained significant after correction for multiple testing (per-allele ORMeta=0.83, PMeta=0.000077; PHet=0.61). In addition, we found that each copy of the LRRC55rs717117G allele was significantly associated with lower improvement in DAS28 in rheumatoid factor (RF)-positive patients (per-allele ORMeta=0.67, P=0.00058; PHet=0.06) whereas an opposite but not significant effect was detected in RF-negative subjects (per-allele ORMeta=1.38, P=0.10; PHet=0.45; PInteraction=0.00028). Interestingly, although the identified associations did not survive multiple testing correction, the meta-analysis also showed overall and RF-specific associations for the MAFBrs6071980 and CNTN5rs1813443 SNPs with decreased changes in DAS28 (per-allele ORMeta_rs6071980 = 0.85, P=0.0059; PHet=0.63 and ORMeta_rs1813443_RF+=0.81, P=0.0059; PHet=0.69 and ORMeta_rs1813443_RF-=1.00, P=0.99; PHet=0.12; PInteraction=0.032). Mechanistically, we found that subjects carrying the LINC02549rs7767069T allele had significantly increased numbers of CD45RO+CD45RA+ T cells (P=0.000025) whereas carriers of the LINC02549rs7767069T/T genotype showed significantly increased levels of soluble scavengers CD5 and CD6 in serum (P=0.00037 and P=0.00041). In addition, carriers of the LRRC55rs717117G allele showed decreased production of IL6 after stimulation of PBMCs with B burgdorferi and E coli bacteria (P=0.00046 and P=0.00044), which suggested a reduced IL6-mediated anti-inflammatory effect of this marker to worsen the response to TNFi. In conclusion, this study confirmed the influence of the LINC02549 and LRRC55 loci to determine the response to TNFi in RA patients and suggested a weak effect of the MAFB and CNTN5 loci that need to be further investigated.

Background: Sporotrichosis has recently emerged as an important mycosis worldwide, with diverse transmission and epidemiologic profiles. For instance, in Brazil most cases are related to zoonotic transmission from naturally infected cats, and the majority of cases in China are due to external injury with environmental materials. Publications on sporotrichosis and on its etiologic agent may guide the direction of the research in this field. It can also define priorities for future studies. Methods: In this study, we evaluated the trends of global research in Sporothrix and sporotrichosis, based on publications records retrieved from Scopus and Web of Science databases for the period of 1945 to 2018. The overall productivity in the field, its geographical and temporal distribution, research themes, co-authorship networks, funding sources, and if audience and research findings are addressed in the abstracts. Results: A total of 4,007 unique publications involving 99 countries were retrieved, most of them published after 2000. Authors based on institutions from the United States of America and Brazil accounted for 57.4% of the publications. Brazil was the leading country in terms of research collaboration and networking, with co-authorship with 45 countries. The thematic mapping revealed a temporal shift from clinical to applied research. Despite the large number of countries publishing in this field, most of funded studies came from Brazil, Mexico, China, South Africa, or the United States of America. The analysis of content identified few specific public health recommendations for prevention, case-management, or research. Moreover, most papers do not have a clearly defined intended audience. Conclusion: As the research in this field is emerging in several countries, with the generation of a large amount of data, it is necessary that scientists strengthen efforts to translate the research results into practice to curb this neglected infection.