Immunosuppression-induced Zika virus reactivation causes brain inflammation and behavioral deficits in mice.

Zika virus (ZIKV) is a neurotropic flavivirus that can persist in several tissues. The late consequences of ZIKV persistence and whether new rounds of active replication can occur, remain unaddressed. Here, we investigated whether neonatally ZIKV-infected mice are susceptible to viral reactivation in adulthood. We found that when ZIKV-infected mice are treated with immunosuppressant drugs, they present increased susceptibility to chemically induced seizures. Levels of subgenomic flavivirus RNAs (sfRNAs) were increased, relative to the amounts of genomic RNAs, in the brains of mice following immunosuppression and were associated with changes in cytokine expression. We investigated the impact of immunosuppression on the testicles and found that ZIKV genomic RNA levels are increased in mice following immunosuppression, which also caused significant testicular damage. These findings suggest that ZIKV can establish new rounds of active replication long after acute stages of disease, so exposed patients should be monitored to ensure complete viral eradication.

TNF-α blockage prevents late neurological consequences of Zika virus infection in mice.

Zika virus (ZIKV) is a neurotropic Orthoflavivirus that causes a myriad of neurological manifestations in newborns exposed in uterus. Despite the devastating consequences of ZIKV on the developing brain, strategies to prevent or treat the consequences of viral infection are not yet available. We previously showed that short-term treatment with the TNF-α neutralizing monoclonal antibody. Infliximab could prevent seizures at acute and chronic stages of ZIKV infection, but had no impact on long-term cognitive and motor dysfunction. Due to the central role of inflammation in ZIKV-neuropathology, we hypothesized that prolonged treatment with the anti-TNF-α monoclonal antibody Infliximab could provide complete rescue of long-term behavioral deficits associated with neonatal ZIKV infection in mice. Here, neonatal (post-natal day 3) Swiss mice were submitted to subcutaneous (s.c.) injection of 106 PFU of ZIKV or mock medium and were then treated with Infliximab (20 µg/day) or sterile saline intraperitoneally (i.p.), for 40 days starting on the day of infection, and behavioral assessment started at 60 days post-infection (dpi). Infliximab prevented ZIKV-induced cognitive and motor impairments in mice. In addition, microgliosis and cell death found in mice following ZIKV infection were partially reversed by TNF-α blockage. Altogether, these results suggest that TNF-α-mediated inflammation is central for late ZIKV-induced behavioral deficits and cell death and strategies targeting this cytokine may be promising approaches to treat subjects exposed to the virus during development.

Depressive symptoms and oral mucositis in children with oncological diseases: a cross-sectional study.

The aim of this study was to investigate the correlation between depressive symptoms and the occurrence of oral mucositis in children with oncological diseases treated at a reference hospital. This was a cross-sectional study conducted with individuals aged 4 to 18 years, diagnosed with primary neoplasms. Data was collected by using a questionnaire that assessed the degree of oral mucositis according to the World Health Organization index, the risk of oral mucositis according to the Child's International Mucositis Evaluation Scale, and depressive symptoms using the Children's Depression Inventory. The data were analyzed and subjected to Spearman's correlation, chi-square test, and Fisher's exact test, considering p<0.05. A statistically significant correlation was observed between depressive symptoms and the degree of oral mucositis (p = 0.044), and also between the "pain" variable within the risk of oral mucositis and depressive symptoms (p = 0.021). Based on the findings, it can be inferred that oral mucositis may be associated with the development of depressive symptoms and may be influenced by the individual's hospitalization, thereby affecting the quality of life of pediatric patients.

Uso de hierro intravenoso en el tratamiento de la anemia ferropénica en niños. A propósito de un caso

Introducción: el déficit de hierro es la causa más común de anemia debido a carencia nutricional. Su tratamiento consiste en proporcionar alimentos ricos en hierro biodisponible junto con la administración de hierro oral. En circunstancias definidas puede utilizarse el hierro intravenoso. Objetivo: describir el abordaje diagnóstico y terapéutico de un niño portador de anemia ferropénica severa secundaria a mala adherencia al hierro oral en el que se utilizó hierro intravenoso. Caso clínico: niño de 21 meses, raza blanca. Antecedente de anemia ferropénica severa, con repercusión hemodinámica que a los 14 meses requirió transfusión de sangre desplasmatizada. Sin controles de hemoglobina posteriores. Sin adherencia a profilaxis con hierro vía oral. Alto consumo de leche de vaca y bajo consumo de alimentos ricos en hierro. En el contexto de infección respiratoria aguda baja se constata anemia clínica con marcado decaimiento y anorexia, sin repercusión hemodinámica. Se confirma la anemia microcítica, hipocrómica severa, con ancho de distribución eritrocitaria elevado, con metabolismo de hierro alterado. Recibe hierro sacarato, intravenoso, por seis días con buena tolerancia y evolución. Discusión: se identificaron múltiples factores de riesgo para anemia ferropénica. La pobre respuesta al tratamiento con hierro oral debido a efectos adversos y olvidos de administración, junto al antecedente de anemia ferropénica severa, que requirió transfusión de sangre desplasmatizada, motivaron la indicación de hierro intravenoso. Su administración fue programada y monitorizada, sin complicaciones. Es necesario fortalecer la prevención en todos los controles pediátricos y abordar este problema de salud desde una mirada interdisciplinaria.

Summary: Introduction: iron deficiency is the most common cause of anemia due to nutritional deficiency. Its treatment consists of providing bioavailable iron rich food together with oral iron. In specific circumstances, intravenous iron may be used. Objective: of this study is to describe the diagnostic and therapeutic approach used with a child with severe iron deficiency anemia secondary to poor adherence to oral iron, in which intravenous iron was used. Clinical case: 21 month-old white patient. History of severe iron deficiency anemia, with hemodynamic repercussions that at 14 months of age required transfusion of deplasmatized blood. Without subsequent hemoglobin controls. No adherence to oral iron prophylaxis. High consumption of cow's milk and low of iron-rich foods. Within the context of acute lower respiratory infection, a clinical anemia with marked decline and anorexia were observed, without hemodynamic repercussions. Severe hypochromic microcytic anemia was confirmed, with an elevated erythrocyte distribution width and altered iron metabolism. He received iron saccharate, intravenously for 6 days with good tolerance and evolution. Discussion: multiple risk factors for iron deficiency anemia were identified. The poor response to treatment with oral iron resulting from adverse effects and lack of proper administration, together with a history of severe iron deficiency anemia, which required transfusion of deplasmatized blood, led to the prescription of intravenous iron. This administration was scheduled and monitored, occurring without complications. It is necessary to strengthen prevention of this condition in all pediatric check-ups and address this health problem from an interdisciplinary perspective.

Introdução: a deficiência de ferro é a causa mais comum de anemia por deficiência nutricional. Seu tratamento consiste no fornecimento de alimentos ricos em ferro biodisponível, juntamente com a administração de ferro por via oral. Em circunstâncias especificas, pode ser utilizado ferro intravenoso. Objetivo: descrever a abordagem diagnóstica e terapêutica de uma criança com anemia ferropriva grave secundária a sua má adesão ao ferro oral, e o uso de ferro intravenoso. Caso clínico: 21 meses, raça branca. História de anemia ferropriva grave, com repercussão hemodinâmica que requiriu de transfusão de sangue desplasmatizada aos 14 meses. Não houve nenhum controle de hemoglobina subsequente. Nenhuma adesão à profilaxia oral com ferro. Alto consumo de leite de vaca e baixo consumo de alimentos ricos em ferro. No contexto de infecção respiratória inferior aguda, observa-se anemia clínica com acentuado emagrecimento e anorexia, sem repercussões hemodinâmicas. É confirmada anemia microcítica e hipocrômica grave, com largura de distribuição eritrocitária elevada e metabolismo alterado do ferro. Recebeu sacarose férrica intravenosa por 6 dias com boa tolerância e evolução. Discussão: foram identificados múltiplos fatores de risco para anemia ferropriva. A má resposta ao tratamento com ferro oral devido aos efeitos adversos e ao esquecimento da administração, aliás da história de anemia ferropriva grave, que exigiu transfusão de sangue desplasmatizada, motivaram a indicação do ferro intravenoso. Sua administração foi programada e monitorada, e aconteceu sem intercorrências. É preciso fortalecer a prevenção em todos os controles pediátricos e abordar este problema de saúde numa persectiva interdisciplinar.

Depressive symptoms and oral mucositis in children with oncological diseases: a cross-sectional study

Abstract The aim of this study was to investigate the correlation between depressive symptoms and the occurrence of oral mucositis in children with oncological diseases treated at a reference hospital. This was a cross-sectional study conducted with individuals aged 4 to 18 years, diagnosed with primary neoplasms. Data was collected by using a questionnaire that assessed the degree of oral mucositis according to the World Health Organization index, the risk of oral mucositis according to the Child's International Mucositis Evaluation Scale, and depressive symptoms using the Children's Depression Inventory. The data were analyzed and subjected to Spearman's correlation, chi-square test, and Fisher's exact test, considering p<0.05. A statistically significant correlation was observed between depressive symptoms and the degree of oral mucositis (p = 0.044), and also between the "pain" variable within the risk of oral mucositis and depressive symptoms (p = 0.021). Based on the findings, it can be inferred that oral mucositis may be associated with the development of depressive symptoms and may be influenced by the individual's hospitalization, thereby affecting the quality of life of pediatric patients.

Factors Associated with Periodontitis in Patients with and without HIV.

Purpose: The aim of this study was to compare clinical periodontal conditions in HIV-positive people on HAART with an HIV-negative group, in addition to investigating factors associated with periodontitis in the entire sample. Methods: This was a cross-sectional study. Data were collected by oral clinical examination for the diagnosis of periodontitis, review of medical records, and application of a questionnaire containing personal data, deleterious habits, and oral hygiene habits for the other variables. The results were analyzed by Pearson's χ 2 test and Student's t-test. A logistic regression model was constructed for the multivariate analysis and periodontitis was defined as a dependent variable. The analysis was performed on the entire sample (HIV+ and HIV-) and also on the group consisting of only people living with HIV. Results: Individuals older than 43 years old and with HIV were more likely to develop moderate and severe periodontitis (47.80 and 4.84 times, respectively). When analyzing only HIV+, in addition to age (OR = 2.795; CI = 1.080-7.233), the use of nonnucleoside reverse transcriptase inhibitors (NNRTIs) (OR = 2.841; CI = 1.135-7.112) was also associated with moderate and severe periodontitis. Conclusion: It was possible to observe a higher prevalence of periodontitis among individuals with HIV, showing an association between the virus, advanced age, and moderate or severe periodontitis.

Imperfect diet choice reduces the performance of a predatory mite.

Two mutually unexclusive hypotheses prevail in the theory of nutritional ecology: the balanced diet hypothesis states that consumers feed on different food items because they have complementary nutrient and energy compositions. The toxin-dilution hypothesis poses that consumers feed on different food items to dilute the toxins present in each. Both predict that consumers should not feed on low-quality food when ample high-quality food forming a complete diet is present. We investigated the diet choice of Phytoseiulus persimilis, a predatory mite of web-producing spider mites. It can develop and reproduce on single prey species, for example the spider mite Tetranychus urticae. A closely related prey, T. evansi, is of notorious bad quality for P. persimilis and other predator species. We show that juvenile predators feeding on this prey have low survival and do not develop into adults. Adults stop reproducing and have increased mortality when feeding on it. Feeding on a mixed diet of the two prey decreases predator performance, but short-term effects of feeding on the low-quality prey can be partially reversed by subsequently feeding on the high-quality prey. Yet, predators consume low-quality prey in the presence of high-quality prey, which is in disagreement with both hypotheses. We suggest that it is perhaps not the instantaneous reproduction on single prey or mixtures of prey that matters for the fitness of predators, but that it is the overall reproduction by a female and her offspring on an ephemeral prey patch, which may be increased by including inferior prey in their diet.

Pleiotropic antifibrotic actions of aspirin-triggered resolvin D1 in the lungs.

Introduction: Pulmonary fibrosis is a destructive, progressive disease that dramatically reduces life quality of patients, ultimately leading to death. Therapeutic regimens for pulmonary fibrosis have shown limited benefits, hence justifying the efforts to evaluate the outcome of alternative treatments. Methods: Using a mouse model of bleomycin (BLM)-induced lung fibrosis, in the current work we asked whether treatment with pro-resolution molecules, such as pro-resolving lipid mediators (SPMs) could ameliorate pulmonary fibrosis. To this end, we injected aspirin-triggered resolvin D1 (7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E19Z-docosahexaenoic acid; ATRvD1; i.v.) 7 and 10 days after BLM (intratracheal) challenge and samples were two weeks later. Results and discussion: Assessment of outcome in the lung tissues revealed that ATRvD1 partially restored lung architecture, reduced leukocyte infiltration, and inhibited formation of interstitial edema. In addition, lung tissues from BLM-induced mice treated with ATRvD1 displayed reduced levels of TNF-α, MCP-1, IL-1-ß, and TGF-ß. Of further interest, ATRvD1 decreased lung tissue expression of MMP-9, without affecting TIMP-1. Highlighting the beneficial effects of ATRvD1, we found reduced deposition of collagen and fibronectin in the lung tissues. Congruent with the anti-fibrotic effects that ATRvD1 exerted in lung tissues, α-SMA expression was decreased, suggesting that myofibroblast differentiation was inhibited by ATRvD1. Turning to culture systems, we next showed that ATRvD1 impaired TGF-ß-induced fibroblast differentiation into myofibroblast. After showing that ATRvD1 hampered extracellular vesicles (EVs) release in the supernatants from TGF-ß-stimulated cultures of mouse macrophages, we verified that ATRvD1 also inhibited the release of EVs in the bronco-alveolar lavage (BAL) fluid of BLM-induced mice. Motivated by studies showing that BLM-induced lung fibrosis is linked to angiogenesis, we asked whether ATRvD1 could blunt BLM-induced angiogenesis in the hamster cheek pouch model (HCP). Indeed, our intravital microscopy studies confirmed that ATRvD1 abrogates BLM-induced angiogenesis. Collectively, our findings suggest that treatment of pulmonary fibrosis patients with ATRvD1 deserves to be explored as a therapeutic option in the clinical setting.

Lycopene induces bone marrow lymphopoiesis and differentiation of peritoneal IgA-producing cells.

Lycopene is a hydrocarbon-carotenoid commonly found in red fruits intake with major function correlated to antioxidative capacity in several pathological conditions, including cancer and cardiovascular diseases. Recently, lycopene has been associated with hematopoiesis, although the effects on B lymphocyte differentiation and antibody production are poorly understood. In this work, the principal aim was to investigate whether lycopene affects B lymphopoiesis and terminal differentiation into plasma cells. Distinct in vivo and in vitro strategies based on lycopene supplementation were used direct in Balb/c mice or in culture systems with cells derived of these mice. In the bone marrow, lycopene expanded B220+IgM- progenitor B cells and B220+IgM+ immature B lymphocytes. In the spleen, lycopene induced terminal CD138+ plasma cell generation. In the blood, we found prominent IgA and low IgM levels after lycopene administration. Interestingly, the pattern of peritoneal IgM+ and IgA+ B cells indicated a significant IgM-to-IgA class switching after lycopene injection. These data indicated that lycopene induces B cell differentiation into IgA-producing plasma cells. Thus, a new cellular function has been attributed to lycopene for B lymphocyte biology and possibly associated with humoral responses and mucosal immunity.

Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice.

RoundUp® (RUp) is a comercial formulation containing glyphosate (N-(phosphono-methyl) glycine), and is the world's leading wide-spectrum herbicide used in agriculture. Supporters of the broad use of glyphosate-based herbicides (GBH) claim they are innocuous to humans, since the active compound acts on the inhibition of enzymes which are absent in human cells. However, the neurotoxic effects of GBH have already been shown in many animal models. Further, these formulations were shown to disrupt the microbiome of different species. Here, we investigated the effects of a lifelong exposure to low doses of the GBH-RUp on the gut environment, including morphological and microbiome changes. We also aimed to determine whether exposure to GBH-RUp could harm the developing brain and lead to behavioral changes in adult mice. To this end, animals were exposed to GBH-RUp in drinking water from pregnancy to adulthood. GBH-RUp-exposed mice had no changes in cognitive function, but developed impaired social behavior and increased repetitive behavior. GBH-Rup-exposed mice also showed an activation of phagocytic cells (Iba-1-positive) in the cortical brain tissue. GBH-RUp exposure caused increased mucus production and the infiltration of plama cells (CD138-positive), with a reduction in phagocytic cells. Long-term exposure to GBH-RUp also induced changes in intestinal integrity, as demonstrated by the altered expression of tight junction effector proteins (ZO-1 and ZO-2) and a change in the distribution of syndecan-1 proteoglycan. The herbicide also led to changes in the gut microbiome composition, which is also crucial for the establishment of the intestinal barrier. Altogether, our findings suggest that long-term GBH-RUp exposure leads to morphological and functional changes in the gut, which correlate with behavioral changes that are similar to those observed in patients with neurodevelopmental disorders.

On the Occurrence of Dangerous Problem Behavior during Functional Analysis: An Evaluation of 30 Applications.

Functional analyses are often conducted by behavior analysts to understand the environmental variables contributing to an individual's problem behavior to better inform treatment implementation. While functional analyses are integral for designing function-based interventions, they often arrange contingencies to evoke and reinforce dangerous problem behavior. In Study 1 we reviewed 22 functional analyses with open-contingency classes including non-dangerous topographies of problem behavior and we found that participants were more likely to exhibit the non-dangerous behavior in 82% of the applications. We then conducted a single-subject comparison of closed and open-contingency classes with four additional participants in Study 2. Our results suggest that the functional analyses with the open-contingency class reduced the likelihood of observing dangerous problem behavior.

Prion protein complexed to a DNA aptamer induce behavioral and synapse dysfunction in mice.

Conversion of the cellular prion protein (PrPC) into the scrapie form (PrPSc) is the leading step to the development of transmissible spongiform encephalopathies (TSEs), still incurable neurodegenerative disorders. Interaction of PrPC with cellular and synthetic ligands that induce formation of scrapie-like conformations has been deeply investigated in vitro. Different nucleic acid (NA) sequences bind PrP and convert it to ß-sheet-rich or unfolded species; among such NAs, a 21-mer double-stranded DNA, D67, was shown to induce formation of PrP aggregates that were cytotoxic. However, in vivo effects of these PrP-DNA complexes were not explored. Herein, aggregates of recombinant full-length PrP (rPrP23-231) induced by interaction with the D67 aptamer were inoculated into the lateral ventricle of Swiss mice and acute effects were investigated. The aggregates had no influence on emotional, locomotor and motor behavior of mice. In contrast, mice developed cognitive impairment and hippocampal synapse loss, which was accompanied by intense activation of glial cells in this brain region. Our results suggest that the i.c.v. injection of rPrP:D67 aggregates is an interesting model to study the neurotoxicity of aggregated PrP in vivo, and that glial cell activation may be an important step for behavioral and cognitive dysfunction in prion diseases.

Prevalência e previsibilidade de caninos impactados em pacientes à procura de tratamento dentário no sudoeste da Bahia, Brasil / Prevalence and predictability of impacted maxillary canines in dental in patients seeking dental treatment in southwest Bahia, Brazil

Resumo Objetivo: identificar a prevalência e determinar a previsibilidade de impactação de caninos superiores permanentes com base em uma amostra de radiografias panorâmicas na região Sudoeste da Bahia, Brasil. Métodos: realizou-se um estudo epidemiológico transversal retrospectivo, em que foram analisadas 5.611 radiografias panorâmicas. No primeiro estudo, houve análise de 4.987 radiografias de pacientes com idades entre 15 a 54 anos, em fase de dentadura permanente, para identificar a prevalência de caninos impactados. O segundo estudo contou com 624 indivíduos em fase de dentadura mista, entre 8 e 14 anos, em que método empregado foi a localização de caninos impactados a partir da determinação da previsibilidade. Foram realizados cálculo amostral e análise estatística descritiva, através do teste qui-quadrado. Resultados: foram encontrados 53 casos de caninos impactados com rizogênese completa dentro do estudo de prevalência, assim como uma média de idade de 27,4 anos entre o sexo feminino (60,3%) e o masculino (39,7%). Foram encontrados 46 casos de uma possível impactação em indivíduos com idade média de 11,7 anos, sendo 54,3% do sexo masculino e 45,7% do feminino. Após o teste qui-quadrado pôde-se perceber relevância estatística entre a faixa de idade de 11 e 12 anos com a previsibilidade da anomalia, em contrapartida, não se percebeu a mesma relação com o aumento da idade do indivíduo. Conclusão: com base nos resultados, foi possível determinar a prevalência de caninos impactados em 1,06% e a taxa de previsibilidade foi de 6,05%. (AU)

Abstract Objective: to identify the prevalence and to determine the predictability of permanent superior canine impaction based on a panoramic radiographic sample in the Southwestern region of Bahia, Brazil. Methods: A retrospective cross-sectional epidemiological study which analyzed 5,611 panoramic radiographs was performed. In the first study, 4,987 radiographs of patients whose ages were between 15 to 54 years old in permanent dentition phase were analyzed to identify the prevalence of impacted canines. The second study included 624 individuals in the mixed dentition phase, between 8 and 14 years old, in which the method used was impacted canines localization based on predictability determination. The sample calculation and descriptive statistical analysis have been performed using the chi-square test. Results: we have found 53 cases of canines impacted with complete rhizogenesis within the prevalence study, as well as a mean age of 27.4 years between female (60.3%) and male (39.7%). We have found 46 cases of a possible impaction in individuals with a mean age of 11.7 years, 54.3% of males and 45.7% of females. After the chi-square test, it was possible to perceive statistical significance between the age group between 11 and 12 years with predictability of the anomaly, in contrast, the same relationship with the increase of the individuals age has not been perceived. Conclusion: based on the results, it was possible to determine the prevalence of impacted canines in 1.06% and the rate of predictability was 6.05%.(AU)

ATRvD1 Attenuates Renal Tubulointerstitial Injury Induced by Albumin Overload in Sepsis-Surviving Mice.

Novel strategies for the prevention and treatment of sepsis-associated acute kidney injury and its long-term outcomes have been required and remain a challenge in critical care medicine. Therapeutic strategies using lipid mediators, such as aspirin-triggered resolvin D1 (ATRvD1), can contribute to the resolution of acute and chronic inflammation. In this study, we examined the potential effect of ATRvD1 on long-term kidney dysfunction after severe sepsis. Fifteen days after cecal ligation and puncture (CLP), sepsis-surviving BALB/c mice were subjected to a tubulointerstitial injury through intraperitoneal injections of bovine serum albumin (BSA) for 7 days, called the subclinical acute kidney injury (subAKI) animal model. ATRvD1 treatment was performed right before BSA injections. On day 22 after CLP, the urinary protein/creatinine ratio (UPC), histologic parameters, fibrosis, cellular infiltration, apoptosis, inflammatory markers levels, and mRNA expression were determined. ATRvD1 treatment mitigated tubulointerstitial injury by reducing proteinuria excretion, the UPC ratio, the glomerular cell number, and extracellular matrix deposition. Pro-fibrotic markers, such as transforming growth factor ß (TGFß), type 3 collagen, and metalloproteinase (MMP)-3 and -9 were reduced after ATRvD1 administration. Post-septic mice treated with ATRvD1 were protected from the recruitment of IBA1+ cells. The interleukin-1ß (IL-1ß) levels were increased in the subAKI animal model, being attenuated by ATRvD1. Tumor necrosis factor-α (TNF-α), IL-10, and IL-4 mRNA expression were increased in the kidney of BSA-challenged post-septic mice, and it was also reduced after ATRvD1. These results suggest that ATRvD1 protects the kidney against a second insult such as BSA-induced tubulointerstitial injury and fibrosis by suppressing inflammatory and pro-fibrotic mediators in renal dysfunction after sepsis.

Características epidemiológicas y clínicas de los menores de 18 años con hemofilia asistidos en el Centro Hospitalario Pereira Rossell. 2016 - 2018 / Epidemiologic and clinical characteristics of hemophilic patients of under 18 years of age assisted at the Pereira Rossell Hospital Center. 2016-2018 / Características epidemiológicas e clínicas de menores de 18 anos com hemofilia assistidos no Centro Hospitalar Pereira Rossell. 2016 - 2018

Resumen: Introducción: la hemofilia es una enfermedad hereditaria, ligada al cromosoma X, debida al déficit de factor VIII (tipo A) o IX (tipo B). La prevalencia estimada al nacimiento es de 24,6 casos cada 100.000 varones para hemofilia A y 5 casos cada 100.000 para hemofilia B. El Departamento de Medicina Transfusional (DMT) del Centro Hospitalario Pereira Rossell (CHPR) es el Centro de Referencia Nacional (CDRN) para los menores de 18 años. El abordaje integral, inter-disciplinario del paciente con hemofilia en un centro especializado disminuye la morbi-mortalidad y contribuye a mejorar la calidad de vida. Objetivo: describir las características epidemiológicas y clínicas de los menores de 18 años con hemofilia asistidos en el DMT-CHPR entre el 1 enero de 2016 y el 31 de diciembre de 2018. Metodología: estudio descriptivo, retrospectivo, de todos los menores de 18 años con hemofilia. Se describió: edad y circunstancias del diagnóstico, tipo y severidad de la hemofilia, controles en salud, estudios complementarios, complicaciones, frecuencia y motivos de hospitalización, tratamiento. El protocolo de estudio fue aprobado por el Comité de Ética Institucional. Resultados: se asistieron 67 pacientes, 57 con hemofilia A y 10 con hemofilia B. La mediana de edad fue 8 años. Presentaban hemofilia severa 61 pacientes, moderada 2 y leve 4. Presentaban antecedentes familiares de coagulopatía 41. La mediana de edad al diagnóstico fue 2 meses. Se diagnosticaron en el período neonatal 24 de los pacientes con hemofilia A y 5 con hemofilia B. Desarrollaron inhibidores 7 pacientes, todos con hemofilia severa. Conclusiones: en esta serie, predominaron los pacientes con hemofilia A, severa, antecedentes familiares conocidos de coagulopatía, en tratamiento profiláctico con factores de la coagulación. Esta comunicación aporta información valiosa sobre las características de estos pacientes, lo que contribuye a la gestión clínica y a planificar estrategias de mejora de la calidad asistencial.

Summary: Introduction: hemophilia is a hereditary disease, linked to chromosome X and caused by the deficit of factor VIII (type A) and IX (type B). Estimated prevalence at birth is 24.6 cases every 100,000 boys for hemophilia A and 5 cases every 100,000 cases for hemphilia B. The Transfusion Medical Department (TMD) of the Pereira Rossell Children's Hospital Center (CHPR, acronym in Spanish) is the national reference center (NRC) for patients under 18 years of age. A comprehensive, inter-disciplinary approach to hemophilic patients at a specialized center decreases morbidity and mortality and contributes to improving quality of life. Objective: to describe the epidemiologic, clinical and progression characteristics of hemophilic patients of under 18 years of age assisted at the TMD-CHPR between January 1st 2016 and December 31st, 2018. Methodology: descriptive, retrospective study of all hemophilic patients of under 18 years of age. Variables described: age, circumstances of diagnosis, type and severity of hemophilia, health check-ups, tests, complications, frequency and reasons for hospital admittance, treatment. The study protocol was approved by the Institutional Ethics Committee. Results: 67 patients were assisted, 57 with hemophilia A and 10 with hemophilia B. Median age was 8 years. Severe hemophilia was present in 61 patients, moderate in 2 and mild in 4. 41 had a family history of coagulopathy. Median age at diagnosis was 2 months. 24 patients with hemophilia A and 5 patients with hemophilia B were diagnosed during the neonatal period. 7 patients developed inhibitors, all of them with severe hemophilia. Conclusions: in this study there is a predominance of patients with severe hemophilia A, known family history of coagulopathy, under prophylactic treatment with coagulation factors. This study provides valuable information about the characteristics of these patients, which contributes to improved clinical management and planning strategies to improve their quality of care.

Resumo: Introdução: o Departamento de Medicina Transfusional (DMT) do Centro Hospitalar Pereira Rossell (CHPR) é o Centro Nacional de Referência (CNR) para menores de 18 anos de idade. A abordagem abrangente e interdisciplinar do paciente com hemofilia em um centro especializado reduz a morbimortalidade e contribui para a melhoria da qualidade de vida. Objetivo: descrever as características epidemiológicas, clínicas e evolutivas em crianças menores de 18 anos com hemofilia atendidas no DMT-CHPR entre 1 de janeiro de 2016 e 31 de dezembro de 2018. Metodologia: estudo descritivo, retrospectivo, de todos os menores de 18 anos com hemofilia. Descrevemos: idade e circunstâncias do diagnóstico, tipo e gravidade da hemofilia, controles de saúde, estudos complementares, complicações, frequência e motivos de hospitalização, tratamento. O protocolo do estudo foi aprovado pelo Comitê de Ética Institucional. Resultados: 67 pacientes foram atendidos, 57 com hemofilia A e 10 com hemofilia B. A media de idade foi de 8 anos. Houve 61 pacientes com hemofilia grave, moderada 2 e leve 4. 41 tiveram história familiar de coagulopatia. A media de idade no diagnóstico foi de 2 meses. 24 dos pacientes com hemofilia A e 5 com hemofilia B foram diagnosticados no período neonatal e 7 desenvolveram inibidores, todos com hemofilia grave. Conclusões: neste estudo, predominaram pacientes com hemofilia A grave, história familiar conhecida de coagulopatia, em tratamento profilático com fatores de coagulação. O estudo fornece informações valiosas sobre as características desses pacientes, o que contribui para o manejo clínico e estratégias de planejamento para melhorar a qualidade do atendimento deles.

Adenosine Diphosphate Improves Wound Healing in Diabetic Mice Through P2Y12 Receptor Activation.

Chronic wounds are a public health problem worldwide, especially those related to diabetes. Besides being an enormous burden to patients, it challenges wound care professionals and causes a great financial cost to health system. Considering the absence of effective treatments for chronic wounds, our aim was to better understand the pathophysiology of tissue repair in diabetes in order to find alternative strategies to accelerate wound healing. Nucleotides have been described as extracellular signaling molecules in different inflammatory processes, including tissue repair. Adenosine-5'-diphosphate (ADP) plays important roles in vascular and cellular response and is immediately released after tissue injury, mainly from platelets. However, despite the well described effect on platelet aggregation during inflammation and injury, little is known about the role of ADP on the multiple steps of tissue repair, particularly in skin wounds. Therefore, we used the full-thickness excisional wound model to evaluate the effect of local ADP application in wounds of diabetic mice. ADP accelerated cutaneous wound healing, improved new tissue formation, and increased both collagen deposition and transforming growth factor-ß (TGF-ß) production in the wound. These effects were mediated by P2Y12 receptor activation since they were inhibited by Clopidogrel (Clop) treatment, a P2Y12 receptor antagonist. Furthermore, P2Y1 receptor antagonist also blocked ADP-induced wound closure until day 7, suggesting its involvement early in repair process. Interestingly, ADP treatment increased the expression of P2Y12 and P2Y1 receptors in the wound. In parallel, ADP reduced reactive oxygen species (ROS) formation and tumor necrosis factor-α (TNF-α) levels, while increased IL-13 levels in the skin. Also, ADP increased the counts of neutrophils, eosinophils, mast cells, and gamma delta (γδ) T cells (Vγ4+ and Vγ5+ cells subtypes of γδ+ T cells), although reduced regulatory T (Tregs) cells in the lesion. In accordance, ADP increased fibroblast proliferation and migration, myofibroblast differentiation, and keratinocyte proliferation. In conclusion, we provide strong evidence that ADP acts as a pro-resolution mediator in diabetes-associated skin wounds and is a promising intervention target for this worldwide problem.

Humeral Head Osteonecrosis: Outcomes of Hemiarthroplasty After Minimum 10-Year Follow-Up.

Objective To analyze long-term functional and radiographic results of partial shoulder replacement for humeral head osteonecrosis. Methods Retrospective review of thirteen cases, with a mean postoperative follow-up of 17 years (range 10 to 26 years). The findings from the last follow-up were compared to those in which the patients had one year of postoperative follow-up. Functional assessment consisted of shoulder movement measurements and application of the University of California, Los Angeles (UCLA) shoulder score. All patients underwent radiographic examination to measure glenoid erosion, proximal humeral migration and lateral glenohumeral dislocation. Results Glenoid erosion increased over time significantly ( p < 0.05). Paradoxically, all active shoulder movements also improved ( p < 0.05), while UCLA scores remained the same. Radiographic deterioration was not correlated with clinical function. We had an 84.7% survival rate for arthroplasties after a mean time of 16 years. Conclusions Early functional outcomes were maintained in the long run and do not correlate with radiographic deterioration (increased erosion of the glenoid).