Using Acanthamoeba spp. as a cell model to evaluate Leishmania infections.

Leishmaniasis represents a severe global health problem. In the last decades, there have been significant challenges in controlling this disease due to the unavailability of licensed vaccines, the high toxicity of the available drugs, and an unrestrained surge of drug-resistant parasites, and human immunodeficiency virus (HIV)-Leishmania co-infections. Leishmania spp. preferentially invade macrophage lineage cells of vertebrates for replication after subverting cellular functions of humans and other mammals. These early events in host-parasite interactions are likely to influence the future course of the disease. Thus, there is a continuing need to discover a simple cellular model that reproduces the in vivo pathogenesis. Acanthamoeba spp. are non-mammalian phagocytic amoeba with remarkable similarity to the cellular and functional aspects of macrophages. We aimed to assess whether the similarity reported between macrophages and Acanthamoeba spp. is sufficient to reproduce the infectivity of Leishmania spp. Herein, we analyzed co-cultures of Acanthamoeba castellanii or Acanthamoeba polyphaga with Leishmania infantum, Leishmania amazonensis, Leishmania major, and Leishmania braziliensis. Light and fluorescence microscopy revealed that the flagellated promastigotes attach to the A. castellanii and/or A. polyphaga in a bipolar and or random manner, which initiates their uptake via pseudopods. Once inside the cells, the promastigotes undergo significant changes, which result in the obligatory amastigote-like intracellular form. There was a productive infection with a continuous increase in intracellular parasites. However, we frequently observed intracellular amastigotes in vacuoles, phagolysosomes, and the cytosol of Acanthamoeba spp. Our findings corroborate that Leishmania spp. infects Acanthamoeba spp. and replicates in them but does not cause their rapid degeneration or lysis. Overall, the evidence presented here confirms that Acanthamoeba spp. have all prerequisites and can help elucidate how Leishmania spp. infect mammalian cells. Future work exposing the mechanisms of these interactions should yield novel insights into how these pathogens exploit amoebae.

Mechanistic studies of mycobacterial glycolipid biosynthesis by the mannosyltransferase PimE.

Tuberculosis (TB), exceeded in mortality only by COVID-19 among global infectious diseases, is caused by Mycobacterium tuberculosis (Mtb). The pathogenicity of Mtb is largely attributed to its complex cell envelope, which includes a class of glycolipids called phosphatidyl-myo-inositol mannosides (PIMs), found uniquely in mycobacteria and its related corynebacterineae. These glycolipids maintain the integrity of the mycobacterial cell envelope, regulate its permeability, and mediate host-pathogen interactions. PIMs consist of a phosphatidyl-myo-inositol core decorated with one to six mannose residues and up to four acyl chains. The mannosyltransferase PimE catalyzes the transfer of the fifth PIM mannose residue from a polyprenyl phosphate-mannose (PPM) donor. This step in the biosynthesis of higher-order PIMs contributes to the proper assembly and function of the mycobacterial cell envelope; however, the structural basis for substrate recognition and the catalytic mechanism of PimE remain poorly understood. Here, we present the cryo-electron microscopy (cryo-EM) structures of PimE from Mycobacterium abscessus captured in its apo form and in a product-bound complex with the reaction product Ac1PIM5 and the by-product polyprenyl phosphate (PP), determined at 3.0 Å and 3.5 Å, respectively. The structures reveal the active site within a distinctive binding cavity that accommodates both donor and acceptor substrates/products. Within the cavity, we identified residues involved in substrate coordination and catalysis, which we confirmed through in vitro enzymatic assays and further validated by in vivo complementation experiments. Molecular dynamics simulations were applied to identify the access pathways and the dynamics involved in substrate binding. Integrating structural, biochemical, genetic, and computational experiments, our study provides comprehensive insights into how PimE functions, opening potential avenues for development of novel anti-TB therapeutics.

Enhancing Transcriptome Mapping with Rapid PRO-seq Profiling of Nascent RNA.

Precision nuclear run-on (PRO) sequencing (PRO-seq) is a powerful technique for mapping polymerase active sites with nucleotide resolution and measuring newly synthesized transcripts at both promoters and enhancer elements. The current PRO-seq protocol is time-intensive, technically challenging, and requires a large amount of starting material. To overcome these limitations, we developed rapid PRO-seq (rPRO-seq) which utilizes pre-adenylated single-stranded DNAs (AppDNA), a dimer blocking oligonucleotide (DBO), on-bead 5' RNA end repair, and column-based purification. These modifications enabled efficient transcriptome mapping within a single day (∼12 hours) increasing ligation efficiency, abolished adapter dimers, and reduced sample loss and RNA degradation. We demonstrate the reproducibility of rPRO-seq in measuring polymerases at promoters, gene bodies, and enhancers as compared to original PRO-seq protocols. Additionally, rPRO-seq is scalable, allowing for transcriptome mapping with as little as 25,000 cells. We apply rPRO-seq to study the role of Integrator in mouse hematopoietic stem and progenitor cell (mHSPC) homeostasis, identifying Ints11 as an essential component of transcriptional regulation and RNA processing in mHSPC homeostasis. Overall, rPRO-seq represents a significant advance in the field of nascent transcript analyses and will be a valuable tool for generating patient-specific genome-wide transcription profiles with minimal sample requirements.

Neuronal differentiation requires BRAT1 complex to remove REST from chromatin.

Repressor element-1 silencing transcription factor (REST) is required for the formation of mature neurons. REST dysregulation underlies a key mechanism of neurodegeneration associated with neurological disorders. However, the mechanisms leading to alterations of REST-mediated silencing of key neurogenesis genes are not known. Here, we show that BRCA1 Associated ATM Activator 1 (BRAT1), a gene linked to neurodegenerative diseases, is required for the activation of REST-responsive genes during neuronal differentiation. We find that INTS11 and INTS9 subunits of Integrator complex interact with BRAT1 as a distinct trimeric complex to activate critical neuronal genes during differentiation. BRAT1 depletion results in persistence of REST residence on critical neuronal genes disrupting the differentiation of NT2 cells into astrocytes and neuronal cells. We identified BRAT1 and INTS11 co-occupying the promoter region of these genes and pinpoint a role for BRAT1 in recruiting INTS11 to their promoters. Disease-causing mutations in BRAT1 diminish its association with INTS11/INTS9, linking the manifestation of disease phenotypes with a defect in transcriptional activation of key neuronal genes by BRAT1/INTS11/INTS9 complex. Finally, loss of Brat1 in mouse embryonic stem cells leads to a defect in neuronal differentiation assay. Importantly, while reconstitution with wild-type BRAT1 restores neuronal differentiation, the addition of a BRAT1 mutant is unable to associate with INTS11/INTS9 and fails to rescue the neuronal phenotype. Taken together, our study highlights the importance of BRAT1 association with INTS11 and INTS9 in the development of the nervous system.

Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors.

This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients (n = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and AFF3, the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered.

Sex and body mass index impact on digit circumference for Leeds Dactylitis Index calculation.

OBJECTIVES: To estimate digit circumference and the impact of sex and body mass index (BMI) for the calculation of the Leeds Dactylitis Index (LDI) in psoriatic arthritis (PsA) patients with bilateral dactylitis. METHODS: Digit circumference of the hands and the foot were measured with a dactylometer and were studied according to sex and BMI (divided in 4 weight categories) in healthy Portuguese subjects, using Student's t-test and One-way ANOVA, respectively. The effect size of sex and BMI were calculated using Cohen's d test and Eta squared, respectively. Multiple linear regression was used to calculate the effect of sex and BMI, as well as their interaction, to create a formula to predict digit circumference. RESULTS: Fifty-nine participants (33 women, 26 men) with a mean BMI of 24.8 were included. Men's mean digit circumferences were statistically higher than those of women (p<0.001), with a large sex effect size in most of the digits. Differences in the mean circumference between the four BMI categories were statistically significant (p<0.05) for all digits, with a large BMI effect size. Sex and BMI were independent variables to predict mean digit circumference (p<0.001). A new tool (based on regression analysis) allowing to estimate the circumference of digits for males and females of different BMIs is presented. CONCLUSIONS: Our data allows the calculation of digit circumference for males and females of different BMIs in the Portuguese population; and shows that BMI influences digital circumference supporting BMI inclusion in LDI references tables.

Caracterización de recién nacidos con síndrome de Down: experiencia de cuatro años en el Servicio de Neonatología del Centro Hospitalario Pereira Rossell, Montevideo, Uruguay / Characterization of newborns with Down syndrome: 4-year experience at the Pereira Rossell Hospital's Neonatology Department, Montevideo, Uruguay / Caracterização de recém-nascidos com síndrome de Down: experiência de 4 anos no serviço de neonatologia do Centro Hospitalar Pereira Rossell, Montevidéu, Uruguai

Introducción: la trisomía 21 o síndrome de Down (SD) es la alteración cromosómica más frecuente, con una incidencia general de 1 en 600 a 800 recién nacidos vivos. Su diagnóstico es de sospecha clínica y confirmación citogenética. Las cardiopatías congénitas y las malformaciones gastrointestinales son frecuentes, al igual que las alteraciones hematológicas y desórdenes tiroideos. Material y método: estudio descriptivo con el objetivo de detallar las características fenotípicas, genéticas, malformaciones y morbilidades asociadas en los pacientes con trisomía 21 nacidos en el Servicio de Neonatología del Centro Hospitalario Pereira Rossell entre el 1 de julio de 2017 y el 1 de julio de 2021. Resultados: se incluyeron 56 pacientes, 30/56 fueron de sexo masculino, la media de edad gestacional fue de 37 semanas. Un total de 17 pacientes fue pretérmino. De los pacientes estudiados, 45/56 presentaron trisomía libre en el cariotipo. La hipotonía fue el signo más frecuentemente observado en el examen clínico. El defecto congénito más frecuente, en 34 pacientes, fue la cardiopatía congénita. La más frecuente fue la comunicación interauricular (CIA), seguida de la comunicación interventricular (CIV) en segundo lugar y el canal atrioventricular (canal AV) en tercer lugar. Se encontraron 23 pacientes con alteraciones en el hemograma, siendo la plaquetopenia la alteración más observada. A nueve pacientes se les realizó diagnóstico de hipotiroidismo y la mortalidad global durante la internación fue de 1,78%. Conclusiones: se destaca la alta prevalencia de prematurez y de defectos congénitos asociados, siendo la cardiopatía congénita la más frecuente.

Introduction: trisomy 21 or Down Syndrome is the most frequent chromosomal alteration, with a general incidence of 1 in 600 to 800 live newborns. Diagnosis is based on clinical suspicion and cytogenetic confirmation. Congenital heart disease and gastrointestinal malformations are frequent, as are hematological abnormalities and thyroid disorders. Materials and Methods: descriptive study with the objective of describing the phenotypic and genetic characteristics, malformations and associated morbidities in patients with trisomy 21 born in the neonatology service of the Pereira Rossell Hospital between July 1, 2017 and July 1, 2021. Results: 56 patients were included, 30/56 were male, the mean gestational age was 37 weeks. A total of 17 patients were preterm. Of the patients studied, 45/56 presented free trisomy in the karyotype. Hypotonia was the most frequently observed sign on clinical examination. The most common birth defect, in 34 patients, was congenital heart disease. Among them, the most frequent defect was interatrial septal defect (CIA), followed by interventricular septal defect (VSD) and thirdly, atrioventricular canal (AV canal). Twenty-three patients with alterations in the complete blood count were found, being thrombocytopenia the most observed alteration. Nine patients were diagnosed with hypothyroidism and overall mortality during hospitalization was 1.78%. Conclusions: we must highlight the high prevalence of prematurity and associated congenital defects, being congenital heart disease the most frequent.

Introdução: a Trissomia do 21 ou Síndrome de Down é a alteração cromossômica mais frequente, com incidência geral de 1 em 600 a 800 recém-nascidos vivos. Seu diagnóstico é baseado na suspeita clínica e na confirmação citogenética. Doenças cardíacas congênitas e malformações gastrointestinais são frequentes, assim como anomalias hematológicas e distúrbios da tireoide. Materiais e métodos: estudo descritivo com objetivo de descrever as características fenotípicas e genéticas, malformações e morbidades associadas em pacientes com trissomia dos 21 nascidos no serviço de Neonatologia do Hospital Pereira Rossell entre 1º de julho de 2017 e 1º de julho de 2021. Resultados: foram incluídos 56 pacientes, 30/56 do sexo masculino, idade gestacional média de 37 semanas. Um total de 17 pacientes foram prematuros. Dos pacientes estudados, 45/56 apresentavam trissomia livre no cariótipo. A hipotonia foi o sinal mais frequentemente observado no exame clínico. O defeito congênito mais comum, em 34 pacientes, foi a cardiopatia congênita. Dentre eles, o mais frequente foi a comunicação interatrial (CIA), seguida pela comunicação interventricular (CIV) em segundo lugar e pelo canal atrioventricular (canal AV) em terceiro lugar. Foram encontrados 23 pacientes com alterações no hemograma completo, sendo a trombocitopenia a alteração mais observada. Nove pacientes foram diagnosticados com hipotireoidismo e a mortalidade geral durante a internação foi de 1,78%. Conclusões: destaca-se a alta prevalência de prematuridade e defeitos congênitos associados, sendo as cardiopatias congênitas as mais frequentes.

Cycling versus swapping strategies in psoriatic arthritis: results from the rheumatic diseases Portuguese register.

OBJECTIVE: To compare the 2-year retention rate between a second tumor necrosis factor alpha inhibitor (TNFi) and secukinumab (SEK) or ustekinumab (UST), in Psoriatic Arthritis (PsA) patients with previous inadequate response to their first TNFi. METHODS: Prospective longitudinal cohort study with a follow-up period of 2 years using the Nationwide Portuguese Reuma.pt database. Patients with a clinical diagnosis of PsA who also fulfill the CASPAR classification criteria, with previous treatment failure to a first-line TNFi and having started a second biotechnological drug (TNFi, SEK or UST) were included. The Cycling group was defined as switching from a first TNFi to a second TNFi, and the Swapping group as switching from a first TNFi to SEK or UST. Sociodemographic data, disease characteristics, disease activity scores and physical function at baseline and after 6, 12 and 24 months were recorded. Cox-proportional hazards regression was used to compare retention rates between Cycling and Swapping groups. To obtain a predictor model of 2-year discontinuation, a multivariable Cox regression model was performed. RESULTS: In total, 439 patients were included, 58% were female, with a mean age (standard deviation) of 49 (12) years. Globally, 75.6% initiated a second TNFi (Cycling group), and 24.4% started SEK/UST (Swapping group). The retention rates after 6, 12 and 24 months were 72%/66%/59% in the Cycling group; and 77%/66%/59% in the Swapping group. There were no significant differences in retention rates between both strategies (HR: 1.06, 95% CI 0.72-1.16). After 2 years of follow-up, 34.4% of patients discontinued their second biologic, mainly due to inefficacy (72.8%), with no differences found between groups. Baseline treatment with glucocorticoids was the only predictor of discontinuation after 2 years of follow-up (HR:1.668, 95% CI 1.154-2.409). CONCLUSIONS: After failure of a first TNF inhibitor, Cycling and Swapping strategies result in similar retention rates suggesting that both are acceptable in the management of patients with psoriatic arthritis.

Determinants of health-related quality of life and global functioning and health in axSpA, pSpA, and PsA: results from the ASAS-PerSpA study.

OBJECTIVES: We aim to identify determinants of health-related quality of life (HRQoL) and global functioning and health (GH) in axial spondyloarthritis (axSpA), peripheral spondyloarthritis (pSpA), and psoriatic arthritis (PsA). METHODS: ASAS-perSpA study data were analyzed. Models for the three patient groups were performed separately to explore factors associated with HRQoL and GH, assessed by EQ-5D and ASAS-HI, respectively. RESULTS: The analyses included 4185 patients: 2719 with axSpA, 433 with pSpA, and 1033 with PsA.In axSpA, disease activity (DA) (ß=-0.061), physical function (ß=-0.041), female sex (ß=-0.019), and fibromyalgia (ß=-0.068) were associated with worse HRQoL; age (ß = 0.001) and university education (ß = 0.014) with better HRQoL. In pSpA, DA (ß=-0.04) and physical function (ß=-0.054) were associated with worse HRQoL. In PsA, DA (ß=-0.045), physical function (ß=-0.053), axial disease (ß=-0.041), and female sex (ß=-0.028) were associated with worse HRQoL.In axSpA, DA (ß = 0.889), physical function (ß = 0.887), peripheral disease (ß = 0.564), female sex (ß = 0.812) and fibromyalgia (ß = 1.639) were associated with worse GH; age (ß=-0.013) and university education (ß=-0.274) with better GH. In pSpA, physical function (ß = 1.142), and female sex (ß = 1.060) were associated with worse GH; university education (ß=-0.611) with better GH. In PsA, DA (ß = 0.703), physical function (ß = 1.025), axial involvement (ß = 0.659), female sex (ß = 0.924), and fibromyalgia (ß = 1.387) were associated with worse GH; age (ß=-0.024) and university education (ß=-0.856) with better GH. CONCLUSIONS: DA and physical function are major HRQoL and GH determinants across spondyloarthritis types, and clinical characteristics and sociodemographic factors play an important role, highlighting the importance of a holistic approach for individual patients.

BRAT1 associates with INTS11/INTS9 heterodimer to regulate key neurodevelopmental genes.

Integrator is a multi-subunits protein complex involved in regulation of gene expression. Several Integrator subunits have been found to be mutated in human neurodevelopmental disorders, suggesting a key role for the complex in the development of nervous system. BRAT1 is similarly linked with neurodegenerative diseases and neurodevelopmental disorders such as rigidity and multifocal-seizure syndrome. Here, we show that INTS11 and INTS9 subunits of Integrator complex interact with BRAT1 and form a trimeric complex in human HEK293T cells as well as in pluripotent human embryonal carcinoma cell line (NT2). We find that BRAT1 depletion disrupts the differentiation of NT2 cells into astrocytes and neural cells. Loss of BRAT1 results in inability to activate many neuronal genes that are targets of REST, a neuronal silencer. We identified BRAT1 and INTS11 co-occupying the promoter region of these genes and pinpoint a role for BRAT1 in recruiting INTS11 to their promoters. Disease-causing mutations in BRAT1 diminish its association with INTS11/INTS9, linking the manifestation of disease phenotypes with a defect in transcriptional activation of key neuronal genes by BRAT1/INTS11/INTS9 complex. Highlights: Integrator subunits INTS9 and INTS11 tightly interact with BRAT1 Depletion of BRAT1 causes a dramatic delay in human neural differentiation BRAT1 and INTS11 module targets the promoters of neural marker genes and co-regulates their expression. The recruitment of INTS11 to these sites is BRAT1-dependent. Pathogenic E522K mutation in BRAT1 disrupts its interaction with INTS11/INTS9 heterodimer.

Characteristics associated with poor COVID-19 outcomes in people with psoriasis, psoriatic arthritis and axial spondyloarthritis: data from the COVID-19 PsoProtect and Global Rheumatology Alliance physician-reported registries.

OBJECTIVES: To investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). METHODS: Demographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death. ORs were estimated using multivariable ordinal logistic regression. RESULTS: Of 5045 cases, 18.3% had PsO, 45.5% PsA and 36.3% axSpA. Most (83.6%) were not hospitalised, 14.6% were hospitalised and 1.8% died. Older age was non-linearly associated with COVID-19 severity. Male sex (OR 1.54, 95% CI 1.30 to 1.83), cardiovascular, respiratory, renal, metabolic and cancer comorbidities (ORs 1.25-2.89), moderate/high disease activity and/or glucocorticoid use (ORs 1.39-2.23, vs remission/low disease activity and no glucocorticoids) were associated with increased odds of severe COVID-19. Later pandemic time periods (ORs 0.42-0.52, vs until 15 June 2020), PsO (OR 0.49, 95% CI 0.37 to 0.65, vs PsA) and baseline exposure to TNFi, IL17i and IL-23i/IL-12+23i (OR 0.57, 95% CI 0.44 to 0.73; OR 0.62, 95% CI 0.45 to 0.87; OR 0.67, 95% CI 0.45 to 0.98; respectively; vs no disease-modifying antirheumatic drug) were associated with reduced odds of severe COVID-19. CONCLUSION: Older age, male sex, comorbidity burden, higher disease activity and glucocorticoid intake were associated with more severe COVID-19. Later pandemic time periods, PsO and exposure to TNFi, IL17i and IL-23i/IL-12+23i were associated with less severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with PsO, PsA and axSpA during COVID-19 waves or similar future respiratory pandemics.

Oxidized mC modulates synthetic lethality to PARP inhibitors for the treatment of leukemia.

TET2 haploinsufficiency is a driving event in myeloid cancers and is associated with a worse prognosis in patients with acute myeloid leukemia (AML). Enhancing residual TET2 activity using vitamin C increases oxidized 5-methylcytosine (mC) formation and promotes active DNA demethylation via base excision repair (BER), which slows leukemia progression. We utilize genetic and compound library screening approaches to identify rational combination treatment strategies to improve use of vitamin C as an adjuvant therapy for AML. In addition to increasing the efficacy of several US Food and Drug Administration (FDA)-approved drugs, vitamin C treatment with poly-ADP-ribosyl polymerase inhibitors (PARPis) elicits a strong synergistic effect to block AML self-renewal in murine and human AML models. Vitamin-C-mediated TET activation combined with PARPis causes enrichment of chromatin-bound PARP1 at oxidized mCs and γH2AX accumulation during mid-S phase, leading to cell cycle stalling and differentiation. Given that most AML subtypes maintain residual TET2 expression, vitamin C could elicit broad efficacy as a PARPi therapeutic adjuvant.

Incidencia de endocarditis infecciosa en un servicio de neonatología centro de referencia nacional en el período 2009-2019 / Incidence of infective endocarditis in a national reference neonatology department in 2009-2019 / Incidência de endocardite infecciosa no departamento de neonatologia de referência nacional no período 2009-2019

La endocarditis infecciosa es una enfermedad rara en pediatría, principalmente en la etapa neonatal pero con una importante morbimortalidad. Existen factores de riesgo definidos, sin embargo el diagnóstico, principalmente en recién nacidos, continúa siendo un desafío. En este trabajo se presenta un relevamiento en 10 años, 5 casos de endocarditis infecciosa confirmada en recién nacidos y se analizan las características clínicas, estudios paraclínicos, agentes infeccioso, tratamiento realizado y asociación con factores de riesgo en esta población.

Infective endocarditis is a rare disease in pediatrics, mainly in neonates, even though it involves significant morbidity and mortality. There are defined risk factors; however, regarding diagnosis and mainly for the case of newborns, it continues to be a challenge. In this paper, we present a 10-year research and follow-up of 5 confirmed cases of infective endocarditis in newborns and their clinical characteristics, paraclinical studies, infectious agents, treatment and association with risk factors in this population

A endocardite infecciosa é uma doença rara em pediatria, principalmente na fase neonatal, mas apresenta significativa morbidade e mortalidade. Existem fatores de risco definidos, porém o diagnóstico, principalmente em recém-nascidos, continua sendo um desafio. Este paper apresenta uma pesquisa de 10 anos de 5 casos de endocardite infecciosa confirmada em recém-nascidos e analisa as suas características clínicas, estudos para clínicos, agentes infecciosos, tratamento e associação com fatores de risco nesta população.

Asistencia del recién nacido con hernia diafragmática congénita / Care of newborns with congenital diaphragmatic hernia / Cuidados ao recém-nascido com hérnia diafragmática congênita

La hernia diafragmática congénita es un defecto en el diafragma que lleva a la herniación del contenido abdominal a la cavidad torácica durante el período intrauterino. La morbimortalidad está determinada por la asociación con otras malformaciones, el grado de hipoplasia pulmonar y la presencia de hipertensión pulmonar secundaria. Presenta una incidencia estimada de 1 cada 2.500-3.000 recién nacidos vivos, constituyendo en un 60% una malformación aislada. Es una patología evolutiva que puede ser diagnosticada a partir de la semana 20-24, la ubicación más habitual es la posterolateral izquierda. Se trata de una patología que requiere ingreso a cuidados intensivos al nacimiento y luego de lograda la estabilización del paciente es de sanción quirúrgica. Los objetivos de este trabajo son conocer las características generales de la patología para sistematizar el manejo logrando así un óptimo asesoramiento de los padres a nivel prenatal y seguimiento postnatal del recién nacido.

Congenital diaphragmatic hernia is a defect in the diaphragm that leads to herniation of theabdominal contents of the thoracic cavity during the intrauterine period. Morbidity and mortality are determined by the association with other malformations, the degree ofpulmonary hypoplasia and the presence of secondary pulmonary hypertension.It has an estimated incidence of 1 every 2,500-3,000 live newborns, and in 60% of the cases it is an isolated malformation. It is an evolutionary pathology that can be diagnosed from week 20-24; it is most commonly located in the left posterolateral. It is a pathology that requires intensive care at birth and after delivery and once the patient has been stabilized, surgical action is required. The objectives of this work are to understand the general characteristics of the pathology in order to refine its manipulation and achieve optimal counseling for parents at the newborn's prenatal and postnatal stages.

A hérnia diafragmática congênita é um defeito no diafragma que leva à herniação doconteúdo abdominal para a cavidade torácica durante o período intrauterino. A morbimortalidade é determinada pela associação com outras malformações, pelo grau de hipoplasia pulmonar e pela presença de hipertensão pulmonar secundária. Apresenta uma incidência estimada de 1 a cada 2.500-3.000 nascidos vivos, constituindo-se em 60% uma malformação isolada. É uma patologia evolutiva que pode ser diagnosticada a partir da semana 20-24 e a localização mais comum é o póstero-lateral esquerdo. É uma patologia que requer internação em terapia intensiva ao nascimento e após o parto. Uma vez que o paciente for estabilizado, é necessária ação cirúrgica. Os objetivos deste paper são conhecer as características gerais da patologia para melhorar o seu manejo, obtendo assim um aconselhamento ideal para os pais no nível pré-natal e no acompanhamento do crescimento pós-natal do recém-nascido.

Inclusão ou ilusão da identidade de gênero no país com o maior número de assassinatos de transgêneros: um ensaio crítico brasileiro / Inclusión o ilusión de la identidad de gênero en el país con el mayor número de asesinatos transgêneros: ensayo crítico brasileño / Inclusion or illusion of gender identity in the country with the highest transgender murders: a Brazilian critical essay

Resumo Objetivo refletir sobre as implicações e os riscos associados ao novo registro de identificação do Brasil para a população trans. Método trata-se de estudo reflexivo que explora o conceito de identidade social como um fenômeno complexo, fundamentado nos princípios da autodeterminação e da dignidade humana. São consideradas perspectivas feministas pós-humanistas e críticas, que desafiam o essencialismo biológico dos indivíduos, com foco especial na teoria de Judith Butler. Resultados o Brasil está atualmente implementando um registro nacional de identificação capaz de reconhecer a identidade de gênero das pessoas trans. Este estudo aborda as implicações do novo sistema nacional de identificação, incluindo possíveis retrocessos e avanços na luta pelos direitos das pessoas trans. Para proteger a identidade e a segurança dessas pessoas, este artigo defende a criação de um novo sistema de identificação emitido pelo governo que armazene informações pessoais em bancos de dados, exibindo apenas o nome social e o marcador de gênero no cartão. Considerações finais e implicações para a prática as altas taxas de violência contra pessoas trans no Brasil destacam a necessidade urgente do novo sistema. O reconhecimento precoce e o respeito pela identidade de gênero são fundamentais para promover o sucesso do novo sistema.

Resumen Objetivo reflexionar sobre las implicaciones y los riesgos asociados con el nuevo registro de identificación de Brasil para la población trans. Método este es un estudio reflexivo que explora el concepto de identidad social como un fenómeno complejo, fundamentado en los principios de autodeterminación y dignidad humana. Se consideran perspectivas feministas poshumanistas, que desafían el esencialismo biológico, con un enfoque particular en la teoría de Judith Butler. Resultados Brasil se encuentra implementando un registro nacional de identificación que puede reconocer la identidad de género entre personas trans. Este estudio aborda las implicaciones del nuevo sistema nacional de identificación, incluyendo posibles retrocesos y avances en la lucha por los derechos de las personas trans. Para proteger la identidad y la seguridad de estas personas, este artículo aboga por la creación de un nuevo sistema de identificación emitido por el gobierno que almacene información personal en bases de datos, mostrando solo el nombre social y el marcador de género en la tarjeta. Consideraciones finales e implicaciones para la práctica las altas tasas de violencia contra personas trans en Brasil enfatizan la necesidad urgente del nuevo sistema. El reconocimiento temprano y el respeto por la identidad de género son fundamentales para promover el éxito del nuevo sistema nacional de identificación.

Abstract Objective to reflect on the implications and risks associated with Brazil's new identification registry for the trans population. Method this is a reflective study that explores the concept of social identity as a complex phenomenon, grounded in the principles of self-determination and human dignity. To accomplish this, it draws upon feminist post-humanist and critical perspectives, challenging individuals' biological essentialism, with a particular focus on Judith Butler's theory. Results Brazil is currently implementing a national identification registry that can recognize trans individuals' gender identity. This manuscript addresses the implications of the new national identification system, including potential setbacks and advances in the struggle for trans rights. To safeguard people's identity and safety, this article advocates for a novel national government-issued identification system that stores personal information in central databases for linking purposes, displaying only the preferred name and gender marker on the identification card. Final considerations and implication for practice the high rates of anti-trans violence in Brazil emphasize the urgent need for the new system. Early recognition and respect for gender identity are integral to promoting the success of the new national identification system.

Sífilis gestacional y congénita en el Centro Hospitalario Pereira Rossell, 2020-2021 / Gestational and congenital syphilis at a children Hospital Center Pereira Rossell, 2020-2021 / Sifilis gestacional e congênita no Centro Hospitalar Pereira Rossell, 2020-2021

Introducción: la sífilis congénita es una entidad grave, que ocurre en recién nacidos de gestantes con sífilis no tratada o tratada inadecuadamente, que puede conducir a resultados adversos en el feto como abortos, óbitos, partos prematuros, bajo peso al nacer, infecciones sistémicas graves y muerte. Constituye un importante problema de salud pública a pesar de la disponibilidad de intervenciones costo-efectivas para evitar la transmisión materno fetal. Objetivos: determinar la prevalencia de sífilis gestacional e incidencia de sífilis congénita en el Centro Hospitalario Pereira Rossell en el periodo marzo 2020 - marzo 2021, año en el que se declaró la pandemia por COVID-19. Material y métodos: se realizó un estudio observacional, descriptivo en al cual fueron incluidas las mujeres embarazadas con diagnóstico de sífilis gestacional y neonatos con sífilis congénita. Resultados: se registró una prevalencia de sífilis gestacional de 27,5/1000 embarazadas y una incidencia de sífilis congénita de 1,37/1000 nacidos vivos. De los 161 recién nacidos 78 (48,4%) fueron considerados de alto riesgo de sífilis connatal por lo cual recibieron tratamiento y su internación se prolongó. Se observó un alto porcentaje de embarazos mal controlados y un bajo nivel de tratamiento a las parejas sexuales. Conclusiones: la prevalencia de sífilis gestacional en el Centro Hospitalario Pereira Rossell, en el período marzo 2020-marzo 2021, año de la pandemia por COVID-19; fue de 27,5/1000 embarazadas. Se confirmó aumento de la prevalencia con respecto al 20,8% reportado anteriormente. La incidencia de SC fue de 1,37/1000 nacidos vivos. Concomitante se observó una disminución en el control del embarazo y escaso tratamiento de las parejas sexuales. Se constata que aumentó el porcentaje de neonatos con alto riesgo de padecer sífilis connatal.

Introduction: syphilis is a preventable and treatable sexually transmitted disease that is a major public health problem. Transmission to the fetus, congenital syphilis, is serious and it is also the cause of abortions and deaths. Early and timely maternal diagno sis is a fundamental prevention tool. Objectives: to determine the prevalence of gestational syphilis and the incidence of congenital syphilis in the Pereira Rossell Hospital Center in the period March 2020-March 2021, the year in which the COVID-19 pandemic was declared. Material and Methods: an observational, descriptive study was carried out in which pregnant women diagnosed with gestational syphilis and neonates with congenital syphilis were included. Results: a prevalence of gestational syphilis of 27.5/1000 pregnant women and an incidence of congenital syphilis of 1.37/1000 live births were recorded of the 161 newborns, 78 (48.4%) of the neonates were considered to be at high risk of connatal syphilis, for which they received treatment and their hospital stay was prolonged. A high percentage of poorly controlled pregnancies and a low level of treatment for sexual partners were observed. Conclusions: the prevalence of gestational syphilis maintained an upward trend at the Pereira Rossell Hospital Center during the first year of the COVID-19 pandemic, mainly due to a significant decrease in pregnancy control, poor treatment of sexual partners and a high percentage of patients at high risk of unconfirmed connatal syphilis. After the first year of the COVID-19 Pandemic this rising trend still remains.

Introduccción: a sífilis é uma doença sexualmente transmissível, prevenível e tratável, que constitui um importante problema de saúde pública. Sua transmissão para o feto constitui uma entidade grave, a sífilis congênita, que é a causa de abortos e mortes. O diagnóstico materno precoce e oportuno é uma ferramenta fundamental de prevenção. Objetivos: determinar a prevalência de sífilis gestacional e incidência de sífilis congênita no Centro Hospitalar Pereira Rossell no período de março de 2020 a março de 2021, ano em que foi declarada a pandemia de COVID-19. Materiais e métodos: foi realizado um estudo observacional, descritivo, no qual foram incluídas gestantes com diagnóstico de sífilis gestacional e neonatos com sífilis congênita. Resultados: houve prevalência de sífilis gestacional de 27,5/1000 gestantes e incidência de sífilis congênita de 1,37/1000 nascidos vivos. Dos 161 recém nascidos, 78 (48,4%) dos neonatos foram considerados de alto risco para sífilis conatal para os quais receberam tratamento e sua internação foi prolongada. Observouse elevado percentual de gestações mal controladas e baixo nível de tratamento dos parceiros sexuais. Conclusões: a prevalência de sífilis gestacional no Centro Hospitalar Pereira Rossell no primeiro ano da pandemia de COVID-19 manteve a tendência ascendente, maiormente devido à diminuição significativa do controle da gravidez, mau tratamento dos parceiros sexuais e alta porcentagem de pacientes com alto risco de sífilis congênita não confirmada. A tendência ascendente ainda continua depois do primeiro ano da pandemia.

Prevención de hipoglicemia neonatal en recién nacidos con factores de riesgo mediante la administración bucal de una dosis de gel de dextrosa al 40%: ensayo clínico aleatorizado / Prevention of neonatal hypoglycemia in newborns with risk factors by buccal administration of a dose of 40% dextrose gel: randomized clinical trial / Prevenção da hipoglicemia neonatal em recém-nascidos com fatores de risco através da ingestão bucal de gel de dextrose no 40%: ensaio clínico randomizado

Introducción: la hipoglicemia neonatal es un trastorno metabólico frecuente en neonatos, con mayor incidencia en aquellos con factores de riesgo como ser hijos de madre diabética, pequeño para la edad gestacional y pretérmino tardíos. Material y métodos: se realizó un ensayo analítico aleatorizado, controlado por placebo para evaluar la eficacia de la administración de gel de dextrosa al 40% para la prevención de hipoglicemia neonatal en esta población. Se reclutaron un total de 120 pacientes. Resultados: se encontró una menor incidencia de hipoglicemia neonatal al compararla con la incidencia reportada en la literatura internacional. No se encontraron diferencias estadísticamente significativas en cuanto al número de ingresos a áreas de internación para tratamiento de hipoglicemia ni en la alimentación a pecho directo exclusivo al alta entre los grupos. Conclusiones: el gel de dextrosa al 40% en recién nacidos podría ser un tratamiento alternativo para profilaxis de hipoglicemia en recién nacidos con factores de riesgo.

Introduction: neonatal hypoglycemia is a frequent metabolic disorder in neonates, with a higher incidence in those with risk factors such as being children of diabetic mothers, small for gestational age, and late preterm. Methodology: a randomized, placebo controlled analytic trial was conducted to evaluate the efficacy of 40% dextrose gel administration for the prevention of neonatal hypoglycemia in this population. A total of 120 patients were recruited. Results: a lower incidence of neonatal hypoglycemia was found when compared to the incidence reported in the international literature. No statistically significant differences were found in terms of the number of admissions to inpatient areas for hypoglycemia treatment or exclusive direct breastfeeding at discharge between the groups. Conclusions: 40% dextrose gel in newborns could be an alternative treatment for hypoglycemia prophylaxis in newborns with risk factors.

Introdução: a hipoglicemia neonatal é um disturbio metabólico comum em neonatos, com maior incidencia naqueles que apresentam fatores de risco, tais como filhos de mães diabéticas, pequenos para a idade gestacional e prematuros tardios. Metodologia: foi realizado um ensaio analítico randomizado e controlado por placebo para avaliar a eficácia da administração de gel de dextrose a 40% para prevenção de hipoglicemia neonatal nesta população. Um total de 120 pacientes foram recrutados. Resultados: foi encontrada menor incidência de hipoglicemia neonatal quando comparada com a incidência relatada na literatura internacional. Não foram encontradas diferenças estatisticamente significativas relativas ao número de internações em áreas de internação para tratamento de hipoglicemia ou aleitamento materno direto exclusivo para descarga entre os grupos. Conclusões: o gel de dextrose a 40% em recém nascidos pode ser uma alternativa de tratamento para profilaxia de hipoglicemia em recém nascidos com fatores de risco.

Theoretical-methodological essay on gender identity information validity in epidemiological surveillance of violence / Ensayo teórico-metodológico sobre la validez de la información de identidad de género en el seguimiento epidemiológico de la violencia / Ensaio teórico-metodológico sobre validade da informação da identidade de gênero no monitoramento epidemiológico da violência

ABSTRACT The inclusion of the "gender identity" field in the Brazilian violence surveillance system, although representing a step forward, still has limitations that may compromise epidemiological data validity. Existing response options for victims' identities do not adequately cover the diversity of this analysis category, resulting in classification biases. Additionally, the absence of options for cisgender identities reflects an approach that naturalizes these identities, while trans identities are considered deviant and subject to surveillance. To overcome these limitations, it is imperative to adopt a broader understanding of gender as a social and performative construction. This requires a reassessment of social structures and data collection instruments. In this context of discussion, this theoretical-methodological essay aims to reflect on gender identity measurement in the Reporting Diseases System interpersonal and self-inflicted violence surveillance system, taking as frameworks the theoretical conceptions about gender as a performative act and the foundations of validity in epidemiological investigations.

RESUMEN La inclusión del campo de la "identidad de género" en el sistema brasileño de vigilancia de la violencia, aunque representa un paso adelante, todavía tiene limitaciones que pueden comprometer la validez de los datos epidemiológicos. Las opciones de respuesta existentes para las identidades de las víctimas no cubren adecuadamente la diversidad de esta categoría de análisis, lo que genera sesgos de clasificación. Además, la ausencia de opciones para las identidades cisgénero refleja un enfoque que naturaliza estas identidades, mientras que las identidades trans se consideran desviadas y sujetas a seguimiento. Para superar estas limitaciones, es imperativo adoptar una comprensión más amplia del género como una construcción social y performativa. Esto requiere una reevaluación de las estructuras sociales y de los instrumentos de recolección de datos. En este contexto de discusión, este ensayo teórico-metodológico tiene como objetivo reflexionar sobre la medición de la identidad de género en el sistema de vigilancia de la violencia interpersonal y autoinfligida del Sistema de Enfermedades de Declaración Obligatoria, tomando como referentes las concepciones teóricas sobre el género como acto performativo y los fundamentos de validez en las investigaciones epidemiológicas.

RESUMO A inclusão do campo "identidade de gênero" no sistema de vigilância de violências brasileiro, embora tenha representando um avanço, ainda apresenta limitações que podem comprometer a validade dos dados epidemiológicos. As opções de resposta existentes para as identidades das vítimas não abrangem adequadamente a diversidade dessa categoria de análise, resultando em vieses de classificação. Adicionalmente, a ausência de opções para as identidades cisgênero reflete uma abordagem que naturaliza essas identidades, enquanto as identidades trans são consideradas desviantes e passíveis de monitoramento. Para superar essas limitações, é imprescindível adotar uma compreensão mais ampla do gênero como uma construção social e performativa. Isso requer uma reavaliação das estruturas sociais e dos instrumentos de coleta de dados. Nesse contexto de discussão, este ensaio teórico-metodológico tem como objetivo refletir sobre a aferição da identidade de gênero no sistema de vigilância de violências interpessoais e autoprovocadas do Sistema de Agravos de Notificação, tomando como referenciais as concepções teóricas sobre gênero como ato performativo e os fundamentos da validade em investigações epidemiológicas.

Incidencia y características de los pacientes portadores de defectos congénitos en el Servicio de Neonatología del Centro Hospitalario Pereira Rossell 2016-2020: 5 años de experiencia / Incidence and characteristics of patients with congenital defects at the Pereira Rossell Hospital's Neonatology Department in 2016-2020: 5 years experience / Incidência e características dos pacientes com defeitos congênitos no Serviço de Neonatologia do Centro Hospitalar Pereira Rossell 2016-2020: 5 anos de experiencia

Los defectos congénitos son alteraciones morfológicas que se originan durante la vida intrauterina que se presentan hasta en un 5% de los recién nacidos vivos. Tienen múltiples etiologías, siendo esta multifactorial en el 90% de los casos. Se realizó un estudio observacional, prospectivo, descriptivo incluyendo a todos los recién nacidos portadores de defectos congénitos en el período 2016-2020. El objetivo de este trabajo es determinar la incidencia de defectos congénitos en recién nacidos del Centro Hospitalario Pereira Rossell en el período mencionado, así como conocer su distribución por aparatos y sistemas, las características demográficas de esta población, la prevalencia de diagnóstico prenatal y la exposición materna a factores de riesgo durante la organogénesis. Se obtuvo una incidencia de 1,7% (423 recién nacidos afectados en 24.870 nacimientos), de los cuales el 34,98% contaba con diagnóstico prenatal. El sistema cardiovascular fue el que presentó una mayor frecuencia de alteraciones, y el defecto congénito más frecuentemente observado individualmente fue la gastrosquisis, con una incidencia de 15,28 cada 10.000 nacidos vivos. La diabetes gestacional se presentó en el 17,25% de las gestantes. Este trabajo nos permitió conocer la incidencia de defectos congénitos, así como su distribución por aparatos y sistemas. Este tipo de sistemas de vigilancia resultan fundamentales para identificar elementos a mejorar, que permitan disminuir la morbilidad y mortalidad de estos pacientes y también identificar precozmente factores de riesgo que aumenten estas patologías de forma significativa.

Congenital birth defects are morphological disturbances originated during gestation and present in up to 5% of live births. They have multiple etiologies, in 90% of cases of multifactorial origin. A longitudinal, prospective, observational study was carried out and it included all patients with congenital birth defects in 2016-2020. The main objective of this study was to determine the incidence of newborns with congenital birth defects between 2016 and 2020, to determine their distribution by organ, to describe their demographic characteristics, to calculate the prevalence of prenatal diagnosis and to identify maternal risk factors. We obtained an incidence of 1,7% (423 affected newborns in 24870 live births), 34,98% had prenatal diagnoses. The cardiovascular system was the most frequently affected and when classified by individual birth defect, the most frequently observed was gastroschisis with 15.28 cases in 10,000 live births. Gestational diabetes was the maternal risk factor most frequently observed with 17, 25%. This study enabled us to know the incidence of congenital birth defects and their distribution by different organs at our center. These surveillance systems are key to identify areas of potential improvement that might enable us to mitigate morbidity and mortality in this group of patients.

Os defeitos congênitos são alterações morfológicas que se originam durante a vida intrauterina e ocorrem em até 5% dos recém-nascidos vivos. Possuem múltiplas etiologias, sendo multifatoriais em 90% dos casos. Realizou-se um estudo observacional, prospectivo e descritivo incluindo todos os recém-nascidos com defeitos congênitos no período 2016-2020. O objetivo deste trabalho foi determinar a incidência de defeitos congênitos em recém-nascidos do Centro Hospitalar Pereira Rossell no período 2016-2020, bem como conhecer sua distribuição por órgãos e sistemas, as características demográficas dessa população, a prevalência de diagnóstico pré-natal e exposição materna a fatores de risco durante a organogênese. Obteve-se uma incidência de 1,7% (423 recém-nascidos afetados em 24.870 nascimentos), dos quais 34,98% tiveram diagnóstico pré-natal. O sistema cardiovascular foi o que apresentou maior frequência de alterações, e o defeito congênito mais observado individualmente foi a gastrosquise com incidência de 15,28 em cada 10.000 nascidos vivos. O diabetes gestacional ocorreu em 17,25% das gestantes. Este paper permitiu conhecer a incidência de defeitos congênitos, bem como sua distribuição por órgãos e sistemas. Estes tipos de sistemas de vigilância são essenciais para identificar elementos a melhorar, que permitam reduzir a morbilidade e mortalidade desses pacientes e também identificar precocemente fatores de risco que aumentam significativamente essas patologias.