Hypothermia Does Not Boost the Neuroprotection Promoted by Umbilical Cord Blood Cells in a Neonatal Hypoxia-Ischemia Rat Model.

Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of death and long-term disability in the perinatal period. Currently, therapeutic hypothermia is the standard of care for this condition with modest efficacy and strict enrollment criteria. Therapy with umbilical cord blood cells (UCBC) has come forward as a strong candidate for the treatment of neonatal HIE, but no preclinical studies have yet compared the action of UCBC combined with hypothermia (HT) with the action of each therapy by itself. Thus, to evaluate the potential of each therapeutic approach, a hypoxic-ischemic brain lesion was induced in postnatal day ten rat pups; two hours later, HT was applied for 4 h; and 24, 48, and 72 h post-injury, UCBC were administered intravenously. The neonatal hypoxic-ischemic injury led to a brain lesion involving about 48% of the left hemisphere that was not improved by HT (36%) or UCBC alone (28%), but only with the combined therapies (25%; p = 0.0294). Moreover, a decrease in glial reactivity and improved functional outcomes were observed in both groups treated with UCBC. Overall, these results support UCBC as a successful therapeutic approach for HIE, even when treatment with therapeutic hypothermia is not possible.

Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy: A Systematic Review of Preclinical Studies.

Neonatal hypoxic-ischemic encephalopathy (HIE) is an important cause of mortality and morbidity in the perinatal period. This condition results from a period of ischemia and hypoxia to the brain of neonates, leading to several disorders that profoundly affect the daily life of patients and their families. Currently, therapeutic hypothermia (TH) is the standard of care in developing countries; however, TH is not always effective, especially in severe cases of HIE. Addressing this concern, several preclinical studies assessed the potential of stem cell therapy (SCT) for HIE. With this systematic review, we gathered information included in 58 preclinical studies from the last decade, focusing on the ones using stem cells isolated from the umbilical cord blood, umbilical cord tissue, placenta, and bone marrow. Outstandingly, about 80% of these studies reported a significant improvement of cognitive and/or sensorimotor function, as well as decreased brain damage. These results show the potential of SCT for HIE and the possibility of this therapy, in combination with TH, becoming the next therapeutic approach for HIE. Nonetheless, few preclinical studies assessed the combination of TH and SCT for HIE, and the existent studies show some contradictory results, revealing the need to further explore this line of research.

[Telehealth as state response strategy: systematic reviewLa telesalud como estrategia de respuesta del Estado: revisión sistemática]. / A telessaúde como estratégia de resposta do Estado: revisão sistemática.

OBJECTIVE: To identify telehealth initiatives described in the literature as a strategy for national health policies. METHOD: A systematic review was performed to identify articles focusing on the use of telehealth as a state response strategy to health problems or needs. The Virtual Health Library, PubMed, and Google Scholar were searched using the following keywords: "telessaude politicas", "implantacao telessaude", "telehealth policy", "telehealth America", "telehealth Asia", "telehealth Antartida", "telehealth Europe", "telehealth Africa", "telehealth Oceania". Data collection was performed from March 2016 to February 2017. RESULTS: Twenty-one articles describing telehealth initiatives in various countries, published in Portuguese, Spanish, and English, were analyzed. Concentration of studies on specific areas or regions was not detected. Most articles were published from 2014 to 2017. Telehealth initiatives have been used mainly to decrease health costs, for continued education of health care professionals, consultations between health care professionals, to strengthen primary health care, and to improve the access to health care in remote areas. CONCLUSIONS: Telehealth is used as state policy across the five continents, with variations in the degree of implementation. The main differences in telehealth among countries refer to infrastructure, financing, engagement of patients and caretakers, and position of the state regarding the role of telehealth.

OBJETIVO: Determinar las acciones de telesalud descritas en las publicaciones pertinentes como estrategia en materia de políticas nacionales de salud. MÉTODO: Se realizó un estudio de revisión sistemática de la producción científica sobre la utilización de la telesalud como estrategia de respuesta del Estado a los problemas o a las necesidades de salud de la población, en el cual se emplearon las bases de datos de la Biblioteca Virtual de Salud (BVS), PubMed y Google Académico. Los términos utilizados en la búsqueda fueron "telesalud política", "implantación telesalud", "telehealth policy", "telehealth America", "telehealth Asia", "telehealth Antarctica", "telehealth Europe", "telehealth Africa" y "telehealth Oceania". Los datos se recopilaron entre marzo del 2016 y febrero del 2017. RESULTADOS: Se analizaron 21 artículos en español, inglés y portugués sobre telesalud en distintos países. No hubo ninguna concentración importante de artículos por lugar ni región. El mayor número de publicaciones se registró entre el 2014 y el 2017. La estrategia de telesalud se ha puesto en práctica para reducir los costos de la atención de salud, fomentar la educación permanente de los profesionales de salud y facilitar las consultas entre ellos, fortalecer la atención primaria de salud y ampliar el acceso a los servicios de salud en las zonas remotas. CONCLUSIONES: La estrategia de telesalud se utiliza como política pública en África, América, Asia y Europa, pero existen variaciones con respecto a la fase de implantación. Las principales diferencias en materia de telesalud observadas en los distintos países correspondieron a infraestructura, financiamiento, compromiso de los enfermos y prestadores de cuidado, y postura del Estado frente al papel de la telesalud.

Reading in Autism Spectrum Disorders: A Literature Review.

OBJECTIVE: To review what the literature says about reading abilities of children on the autism spectrum (autism spectrum disorders, ASD) as well as to assess the results of intervention proposals. The broad ASD diagnosis used in the last decades and the resulting changes in the prevalence of these disorders have led to a relevant increase in the number of children diagnosed with ASD in the school system. The purpose of this review is to identify the different profiles of reading abilities shown by children with ASD described in the recent literature and the results of reported intervention methods. METHODS: A review of the literature was conducted in the Web of Sciences and PubMed databases with the keywords 'autism' AND 'read*' and the filter 2010-2015. All articles published in the last 5 years focusing on description of and intervention for reading abilities in individuals with ASD were included. Review articles were excluded. RESULTS: The selected 58 articles were divided into those that described reading abilities in individuals with ASD (n = 27) and those that reported intervention procedures for reading development (n = 31). CONCLUSIONS: Direct comparisons and associations were prevented due to different inclusion criteria and lack of detailed information about intervention processes. We propose tentative conclusions that should be confirmed by further studies.

Single laboratory evaluation of umbilical cord blood units processing methodologies for banking.

OBJECTIVE: To compare the efficiency of 3 different processing methods (Sepax, AutoXpress [AXP], and manual processing with hydroxyethyl starch [HES] sedimentation) used at Stemlab during a 10-year period. METHODS: Historical data were compiled and the analytical results obtained for the 3 different methods were compared. RESULTS: The manual processing (HES) method yielded the highest level of total nucleated cell recovery after processing, and the AXP system yielded the highest CD34+ cell number. The red blood cell reduction was also significantly higher with the HES method. Also, HES showed comparable results to Toticyte technology for umbilical cord blood (UCB) processing. CONCLUSION: These results show that the HES method is as effective as automated technologies for UCB volume reduction; hence, it is a suitable methodology for private and public UCB banks. The HES method also proved to be superior to Toticyte technology for medical applications, with higher recovery yields of total nucleated cells after thawing and equivalent CD34+ cell recovery and functionality.

"ZARPAR"-Educational Program for Cognitive and Behavioral Development: Results of an Experiment to Evaluate Its Impact on Antisocial and Pro-Social Behavior.

Using an experimental design and a multi-measure and multi-informant approach, the current study sought to evaluate the impact of the early developmental prevention program "ZARPAR"-an intervention designed as a social and cognitive skills training program, that seeks to promote children's behavioral adjustment. A sample of elementary school children (experimental group n = 37; control group n = 66), attending Portuguese schools, was assessed before and 6 months after the intervention on the program's key-dimensions: behavioral problems, social skills, and executive functioning. Based on parent and teacher reports, the results largely suggested that the intervention had no effect or, for some dimensions, even the existence of negative outcomes. Possible reasons for these results are discussed. The current study highlights that, despite the overwhelmingly positive message about developmental prevention programs, not all interventions work, thus reinforcing the need for rigorous evaluations, in order to enhance the success of future interventions.

Biomarkers of hypoxic-ischemic encephalopathy: a systematic review.

BACKGROUND: Current diagnostic criteria for hypoxic-ischemic encephalopathy in the early hours lack objective measurement tools. Therefore, this systematic review aims to identify putative molecules that can be used in diagnosis in daily clinical practice (PROSPERO ID: CRD42021272610). DATA SOURCES: Searches were performed in PubMed, Web of Science, and Science Direct databases until November 2020. English original papers analyzing samples from newborns > 36 weeks that met at least two American College of Obstetricians and Gynecologists diagnostic criteria and/or imaging evidence of cerebral damage were included. Bias was assessed by the Newcastle-Ottawa Scale. The search and data extraction were verified by two authors separately. RESULTS: From 373 papers, 30 met the inclusion criteria. Data from samples collected in the first 72 hours were extracted, and increased serum levels of neuron-specific enolase and S100-calcium-binding protein-B were associated with a worse prognosis in newborns that suffered an episode of perinatal asphyxia. In addition, the levels of glial fibrillary acidic protein, ubiquitin carboxyl terminal hydrolase isozyme-L1, glutamic pyruvic transaminase-2, lactate, and glucose were elevated in newborns diagnosed with hypoxic-ischemic encephalopathy. Moreover, pathway analysis revealed insulin-like growth factor signaling and alanine, aspartate and glutamate metabolism to be involved in the early molecular response to insult. CONCLUSIONS: Neuron-specific enolase and S100-calcium-binding protein-B are potential biomarkers, since they are correlated with an unfavorable outcome of hypoxic-ischemic encephalopathy newborns. However, more studies are required to determine the sensitivity and specificity of this approach to be validated for clinical practice.

Umbilical-Cord-Derived Mesenchymal Stromal Cells Modulate 26 Out of 41 T Cell Subsets from Systemic Sclerosis Patients.

Systemic sclerosis (SSc) is an immune-mediated disease wherein T cells are particularly implicated, presenting a poor prognosis and limited therapeutic options. Thus, mesenchymal-stem/stromal-cell (MSC)-based therapies can be of great benefit to SSc patients given their immunomodulatory, anti-fibrotic, and pro-angiogenic potential, which is associated with low toxicity. In this study, peripheral blood mononuclear cells from healthy individuals (HC, n = 6) and SSc patients (n = 9) were co-cultured with MSCs in order to assess how MSCs affected the activation and polarization of 58 different T cell subsets, including Th1, Th17, and Treg. It was found that MSCs downregulated the activation of 26 out of the 41 T cell subsets identified within CD4+, CD8+, CD4+CD8+, CD4-CD8-, and γδ T cells in SSc patients (HC: 29/42) and affected the polarization of 13 out of 58 T cell subsets in SSc patients (HC: 22/64). Interestingly, SSc patients displayed some T cell subsets with an increased activation status and MSCs were able to downregulate all of them. This study provides a wide-ranging perspective of how MSCs affect T cells, including minor subsets. The ability to inhibit the activation and modulate the polarization of several T cell subsets, including those implicated in SSc's pathogenesis, further supports the potential of MSC-based therapies to regulate T cells in a disease whose onset/development may be due to immune system's malfunction.

Rab10 regulates phagosome maturation and its overexpression rescues Mycobacterium-containing phagosomes maturation.

Phagosome maturation follows a defined biochemical program and, in the vast majority of cases, the microbe inside the phagosome is killed and digested. Although, an important number of pathogens, including Mycobacterium tuberculosis, which kills around two million people every year, have acquired the ability to survive, and even replicate by arresting phagosomal maturation. To identify more of the machinery involved in phagocytosis and phagosomal maturation, we investigated the function of Rab10 in engulfment and maturation of inert particles and Mycobacterium bovis bacille Calmette-Guérin (BCG). We showed that Rab10 association with phagosomes is transient and confocal microscopy revealed detectible levels of Rab10 on phagosomal membranes at very early time-points, occurring even before Rab5 acquisition. Rab10 recruitment had strong functional consequence, as the knockdown of endogenous Rab10 by RNA interference or overexpression of Rab10 dominant-negative mutant delayed maturation of phagosomes of IgG-opsonized latex beads or heat killed-mycobacteria. These results can be explained, at least in part, by the involvement of Rab10 in recycling of some phagosomal components. More importantly, overexpression of the constitutively active mutant of Rab10 partially rescued live-Mycobacterium-containing phagosomes maturation. Indeed, we found that the membrane harbouring Mycobacterium acquired early endosome antigen 1 (EEA-1), a marker excluded from phagosomes in control cells. Altogether these results indicate that Rab10, acting upstream of Rab5, plays a prominent role in phagolysosome formation and can modulate Mycobacterium-containing phagosomes maturation.

Cisplatin impairs rat liver mitochondrial functions by inducing changes on membrane ion permeability: prevention by thiol group protecting agents.

Cisplatin (CisPt) is the most important platinum anticancer drug widely used in the treatment of head, neck, ovarian and testicular cancers. However, the mechanisms by which CisPt induces cytotoxicity, namely hepatotoxicity, are not completely understood. The goal of this study was to investigate the influence of CisPt on rat liver mitochondrial functions (Ca(2+)-induced mitochondrial permeability transition (MPT), mitochondrial bioenergetics, and mitochondrial oxidative stress) to better understand the mechanism underlying its hepatotoxicity. The effect of thiol group protecting agents and some antioxidants against CisPt-induced mitochondrial damage was also investigated. Treatment of rat liver mitochondria with CisPt (20nmol/mg protein) induced Ca(2+)-dependent mitochondrial swelling, depolarization of membrane potential (DeltaPsi), Ca(2+) release, and NAD(P)H fluorescence intensity decay. These effects were prevented by cyclosporine A (CyA), a potent and specific inhibitor of the MPT. In the concentration range of up to 40nmol/mg protein, CisPt slightly inhibited state 3 and stimulated state 2 and state 4 respiration rates using succinate as respiratory substrate. The respiratory indexes, respiratory control ratio (RCR) and ADP/O ratios, the DeltaPsi, and the ADP phosphorylation rate were also depressed. CisPt induced mitochondrial inner membrane permeabilization to protons (proton leak) but did not induce significant changes on mitochondrial H(2)O(2) generation. All the effects induced by CisPt on rat liver mitochondria were prevented by thiol group protecting agents namely, glutathione (GSH), dithiothreitol (DTT), N-acetyl-L-cysteine (NAC) and cysteine (CYS), whereas superoxide-dismutase (SOD), catalase (CAT) and ascorbate (ASC) were without effect. In conclusion, the anticancer drug CisPt: (1) increases the sensitivity of mitochondria to Ca(2+)-induced MPT; (2) interferes with mitochondrial bioenergetics by increasing mitochondrial inner membrane permeabilization to H(+); (3) does not significantly affect H(2)O(2) generation by mitochondria; (4) its mitochondrial damaging effects are protected by thiol group protecting agents. Based on these conclusions, it is possible to hypothesise that small changes on the redox-status of thiol groups, affecting membrane permeability to cations (Ca(2+) and H(+)) underlie CisPt-induced liver mitochondrial damage, putatively responsible for its hepatotoxicity. Therefore, we propose that CisPt-induced mitochondrial damage and consequent hepatotoxicity could be prevented by using thiol group protecting agents as therapeutic adjuvants.

Speech and language pathology and autistic spectrum.

The aim of this study was to identify variations from different language therapy processes times in two groups of children with autistic spectrum disorders. 8 subjects, from 3 to 17 years old, participated of this study and they were divided in two groups: Group 1: 4 subjects, in language therapy for 12 months, with therapist change after 6 months; Group 2: 4 subjects, also in language therapy for 12 months, but without therapist change in this period. Data was collected from two videotapes recordings: initial and final and all the recordings had fifteen minutes of duration. The analysis was done according to the criteria proposed by Fernandes (2004a), for functional evaluation of language and the statistical analysis were done with the Wilcoxon signed ranks test and the Mann-Whitney test, with 5% of significance. The results showed no difference between the two groups. This outcome may be related to the small size of the groups or to the duration of the study. Nevertheless, a better functional profile of communication was noted on group 2, with had no therapist change. This outcome was represented by the improving of the communicational acts and the use of the communicative space, it was also noted an increasing of the utilization of the verbal mean and decreasing of the vocal mean, besides a greater utilization of the more interactive functions.

Development of RT-qPCR and semi-nested RT-PCR assays for molecular diagnosis of hantavirus pulmonary syndrome.

Hantavirus Pulmonary Syndrome is an, often fatal, emerging zoonotic disease in the Americas caused by hantaviruses (family: Hantaviridae). In Brazil, hantavirus routine diagnosis is based on serology (IgM-ELISA) while RT-PCR is often used to confirm acute infection. A Semi-nested RT-PCR and an internally controlled RT-qPCR assays were developed for detection and quantification of four hantaviruses strains circulating in the Brazilian Amazon: Anajatuba (ANAJV) and Castelo dos Sonhos (CASV) strains of Andes virus (ANDV) species; and Rio Mamoré (RIOMV) and Laguna Negra (LNV) strains of LNV species. A consensus region in the N gene of these hantaviruses was used to design the primer sets and a hydrolysis probe. In vitro transcribed RNA was diluted in standards with known concentration. MS2 bacteriophage RNA was detected together with hantavirus RNA as an exogenous control in a duplex reaction. RT-qPCR efficiency was around 100% and the limit of detection was 0.9 copies/µL of RNA for RT-qPCR and 10 copies/µL of RNA for Semi-nested RT-PCR. There was no amplification of either negative samples or samples positive to other pathogens. To assess the protocol for clinical sensitivity, specificity and general accuracy values, both assays were used to test two groups of samples: one comprising patients with disease (n = 50) and other containing samples from healthy individuals (n = 50), according to IgM-ELISA results. A third group of samples (n = 27) infected with other pathogens were tested for specificity analysis. RT-qPCR was more sensitive than semi-nested RT-PCR, being able to detect three samples undetected by conventional RT-PCR. RT-qPCR clinical sensitivity, specificity and general accuracy values were 92.5%, 100% and 97.63%, respectively. Thus, the assays developed in this study were able to detect the four Brazilian Amazon hantaviruses with good specificity and sensitivity, and may become powerful tools in diagnostic, surveillance and research applications of these and possibly other hantaviruses.

STROKE34 Study Protocol: A Randomized Controlled Phase IIa Trial of Intra-Arterial CD34+ Cells in Acute Ischemic Stroke.

RATIONALE/AIM: Despite the increasing efficacy of recanalization therapies for acute ischemic stroke, a large number of patients are left with long-term functional impairment, devoid of efficacious treatments. CD34+ cells comprise a subset of bone marrow-derived mononuclear cells with the capacity to promote angiogenesis in ischemic lesions and have shown promising results in observational and in vitro studies. In this study, we aim to assess the efficacy of an autotransplant of CD34+ cells in acute ischemic stroke. SAMPLE SIZE ESTIMATES: 30 patients will be randomized for a power of 90% and alpha of 0.05 to detect a difference in 3 months infarct volume. METHODS AND DESIGN: We will screen 18-80 years old patients with acute ischemic stroke due to occlusion of a middle cerebral artery (MCA) for randomization. Persistent arterial occlusions, contra-indications to magnetic resonance imaging (MRI), premorbid dependency, or other severe diseases will be excluded. Treatment will involve bone marrow aspiration, selection of CD34+ cells, and their administration intra-arterially in the symptomatic MCA by angiography. Patients will be randomized for treatment at 7 (±2) days, 20 (±5 days) or sham procedure, 10 in each group. STUDY OUTCOMES: The primary outcome will be infarct volume in MRI performed at 3 months. Secondary outcomes will include adverse events and multidimensional functional and neurological measures. DISCUSSION/CONCLUSION: STROKE34 is a PROBE design phase IIa clinical trial to assess the efficacy of intra-arterial administration of CD34+ cells 7 and 20 days after acute ischemic stroke. TRIAL REGISTRATION EU CLINICAL TRIALS REGISTER: 2017-002456-88.

A study of 82 extended HLA haplotypes in HFE-C282Y homozygous hemochromatosis subjects: relationship to the genetic control of CD8+ T-lymphocyte numbers and severity of iron overload.

BACKGROUND: It has been recently demonstrated that CD8+ T-lymphocyte numbers are genetically transmitted in association with the MHC class I region. The present study was designed with the objective of narrowing the region associated with the setting of CD8+ T-lymphocyte numbers in a population of C282Y homozygous hemochromatosis subjects, in whom a high prevalence of abnormally low CD8+ T-lymphocyte counts has been described. METHODS: The study includes 43 C282Y homozygous subjects fully characterized both phenotypically and genotypically. Clinical characterization includes measurements of iron parameters at diagnosis (transferrin saturation and serum ferritin), total body iron stores and T-cell immunophenotyping determined by flow cytometry. Genetic characterization includes HLA class I alleles (A, B and C) and four additional microsatellite markers (D6S265, D6S2222, D6S105 and D6S2239) spanning 5 Megabases in the 6p21.3 region. RESULTS: Eighty-two extended C282Y carrying haplotypes were defined. Single-locus analysis revealed that the HLA-A region was associated with CD8+ T-cell numbers. Multivariate analysis showed that the combinations of the most common HLA-A alleles (HLA-A*03, -A*02 and -A*01) were associated with significantly lower numbers of CD8+ T-lymphocytes (0.30 +/- 0.14 x 106/ml), in comparison with subjects carrying only one copy of those alleles (0.46 +/- 0.19 x 106/ml) and subjects without any copy of those alleles (0.79 +/- 0.15 x 106/ml;p = 0.0001). No differences were observed in CD8+ T-cell counts among control subjects carrying the same combinations of HLA-A alleles (0.47 +/- 0.14; 0.45 +/- 0.21 and 0.41 +/- 0.17 x 106/ml, respectively), therefore not supporting a direct effect of HLA specificity but rather an indirect association with a locus close to HLA-A. Multivariate analysis showed that the combination of the most common HLA-A alleles also have an impact on the clinical expression of HH in terms of iron stores, in males(p = 0.0009). CONCLUSION: The present study provides evidence supporting an inextricable link between extended HLA haplotypes, CD8+ T-lymphocyte numbers and severity of iron overload in hereditary hemochromatosis(HH). It gives additional information to better define a candidate region involved in the regulation of CD8+ T-lymphocyte numbers. A new evolutionary hypothesis concerning the inheritance of the phenotype of low CD8+ T-lymphocyte numbers associated with particular ancestral HLA haplotypes carrying the C282Y mutation and its implication on the clinical heterogeneity of HH is discussed.

[Relation between social cognitive aspects and the functional communicative profile in a group of adolescents of the autistic spectrum]. / Relação entre os aspectos sócio cognitivos e perfil funcional da comunicação em um grupo de adolescentes do espectro autístico.

BACKGROUND: Issues concerning language development and their relation with social cognitive aspects give direction to the clinical practice when assisting the population with the diagnosis within the autistic spectrum. The deficits or differences in this development can result in different ways of analyzing and counseling this population. Adolescence becomes a question mark in this analysis since, in most cases, researches address only early childhood. The speech pathologist must assess the relationship between language abilities and communicative competence. Language abilities refer to the possibilities to understand and formulate spoken or written symbolic systems, whereas the communicative competence refers to the ability to use language as an effective tool to interact with other people in several social contexts. PURPOSE: To verify the development of the functional communicative profile and of the social cognitive aspects of adolescents, who attend a specialized institution and who have a psychiatric diagnosis within the autistic spectrum in three different situations of communication during a 12 months period and to study the relation between these variables in the same situations, during the same period of time. METHOD: Subjects of this study were five adolescents with ages between 12 and 17 years. Two recording sets, with a 12 month interval, were obtained for each subject. Each recording set was composed by three 30 minutes videotaped situations of different interactive contexts: Situation I--individual language therapy; Situation II--child in a group with coordinator; Situation III--child in a group without coordinator. RESULTS: Differences exist between the subjects in the three studied situations regarding the social cognitive performance and the functional communicative profile. CONCLUSION: There is a relationship between the development of the social cognitive aspects and the functional communicative profile in the three situations of communication for the studied period.

Sweet's syndrome complicating ulcerative colitis: a rare association.

Sweet's syndrome (SS) is a neutrophilic dermatosis disorder of unknown aetiology, characterised by acute fever, neutrophilia, painful erythematous papules, nodules and plaques, and an infiltrate consisting predominantly of mature neutrophils in the upper dermis. Classical SS is a rare extra-intestinal manifestation of inflammatory bowel disease (IBD). It is more common in Crohn's disease than in ulcerative colitis (UC). There is a predilection for women, and for patients with colonic disease and active IBD. We report the case of a 39-year-old woman with a flare of moderate severity UC treated with mesalazine who presented with a 5-day history of acute fever, painful papules and plaques on forearms and legs, episcleritis and cervical pain. Skin biopsies showed papillary dermis inflammatory cell infiltration composed mainly of neutrophils, without evidence of leukocytoclastic vasculitis or panniculitis, compatible with SS. The patient had an excellent response to systemic corticosteroids. Symptoms promptly improved and skin lesions resolved after 7 weeks.

Nasal closure for the treatment of epistaxis secondary to hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT), also known by the eponym Osler-Weber-Rendu syndrome, is an autosomal dominant disorder characterised by the presence of multiple arteriovenous malformations (AVMs) affecting multiple organs. Many procedures have been used for epistaxis control in patients with this disorder. The objective of this study was to report the treatment of severe HHT-related epistaxiswith the modified Young's procedure. MATERIALS AND METHODS: We describe the treatment of 4 patients with severe blood-transfusion-dependent epistaxis who underwent a modified Young's procedure in a tertiary hospital. The nasal closure was bilateral and complete in all cases. All patients were followed for 12 months or longer. RESULTS: The procedure was well tolerated and complete cessation of bleeding was achieved in all the patients. CONCLUSION: Young's technique is a safe surgical procedure, well tolerated by patients with severe epistaxis and HHT.

Multicenter survey on the use of device-assisted enteroscopy in Portugal.

BACKGROUND: Device-assisted enteroscopies (DAEs) are recent endoscopic techniques that enable direct endoscopic small-bowel evaluation. OBJECTIVE: The objective of this article is to evaluate the implementation of DAEs in Portugal and assess the main indications, diagnoses, diagnostic yield, therapeutic yield and complication rate. METHODS: We conducted a multicenter retrospective series using a national Web-based survey on behalf of the Portuguese Small-Bowel Study Group. Participants were asked to fill out two online databases regarding procedural data, indications, diagnoses, endoscopic therapy and complications using prospectively collected institutional data records. RESULTS: A total of eight centers were enrolled in the survey, corresponding to 1411 DAEs. The most frequent indications were obscure gastrointestinal bleeding (OGIB), inflammatory bowel disease and small-bowel tumors. The pooled diagnostic yield was 63%. A relation between the diagnostic yield and the indications was clear, with a diagnostic yield for OGIB of 69% (p = 0.02) with a 52% therapeutic yield. Complications occurred in 1.2%, with a major complication rate of 0.57%. Perforations occurred in four patients (0.28%). CONCLUSION: DAEs are safe and effective procedures, with complication rates of 1.2%, the most serious of which is perforation. Most procedures are performed in the setting of OGIB. Diagnostic and therapeutic yields are dependent on the indication, hence appropriate patient selection is crucial.

Gastos públicos em serviços ambulatoriais de Fonoaudiologia no Brasil entre 2009 e 2018: bases de dados do DATASUS / Public spending on outpatient speech therapy services in Brazil between 2009 and 2018: DATASUS databases

RESUMO Objetivo Analisar os gastos públicos em saúde destinados aos serviços ambulatoriais em Fonoaudiologia nas cinco Regiões Federativas do Brasil. Métodos Trata-se de um estudo ecológico realizado por meio da busca de dados secundários disponíveis em uma plataforma virtual de domínio público, DATASUS (Departamento de Informática do Sistema Único de Saúde). Os dados coletados referiram-se aos valores aprovados para os procedimentos da Fonoaudiologia no período de 2009 a 2018 nas cinco Regiões Federativas. Adotou-se análise descritiva dos dados e exposição dos resultados em valores absolutos, relativos e taxas de crescimento. Resultados Verificou-se que o investimento médio em reais (R$), por ano, nos serviços de Fonoaudiologia no Brasil foi de, aproximadamente, R$ 223.952.639.232,00; sendo 47,2% dos recursos destinados à Região Sudeste. Dentre as grandes áreas de especialização, a Audiologia foi responsável por 95,4% do investimento, seguida pelas áreas da Linguagem (4,0%), Motricidade Orofacial (0,5%) e Voz (0,1%). Conclusão Os serviços fonoaudiológicos demandam considerável parcela dos recursos públicos, sendo a área da Audiologia responsável por quase metade desses gastos, seguida pelas grandes áreas da Linguagem, Motricidade Orofacial e Voz.

ABSTRACT Purpose To analyze public spending on health services to outpatient services in Speech Therapy in the five federative regions of Brazil. Methods This is an ecological study carried out through the search for secondary data available on a public domain virtual platform, DATASUS. The collected data refer to the values ​​approved for the Speech Therapy procedures in the period from 2009 to 2018 in the five federative regions. Descriptive analysis of data and exposure of results in absolute and relative values ​​and growth rates were adopted. Results It was found that the average investment in reais, per year, in speech therapy services in Brazil was approximately R$ 223,952,639,232.00, with 47.2% of the resources destined for the Southeast region. Among the major areas of specialization, Audiology accounted for 95.4% of the investment, followed by Language (4.0%), Orofacial Motricity (0.5%) and Voice (0.1%). Conclusion The findings indicate that speech therapy services demand a considerable portion of public resources, with the area of ​​Audiology being responsible for almost half of these expenses, followed by the large area of ​​Language, Orofacial Motricity and Voice.

Androgen- and estrogen-dependent regulation of insulin-degrading enzyme in subcellular fractions of rat prostate and uterus.

Innumerous data support the fact that insulin-degrading enzyme (IDE) is the primary enzymatic mechanism for initiating and controlling cellular insulin degradation. Nevertheless, insulin degradation is unlikely to be the only cellular function of IDE, because it appears that some cellular effects of insulin are mediated by IDE as a regulatory protein. Insulin-degrading enzyme shows a significant correlation with various cellular functions, such as cellular growth and differentiation, and the expression of IDE is developmentally regulated. Besides insulin, other substrates are also degraded by IDE, including various growth-promoting peptides. It has also been shown that IDE enhances the binding of androgen to DNA in the nuclear compartment. It is also known that the androgen hormones have a stimulatory effect on prostate growth, and that estradiol stimulates uterine growth. To establish whether IDE is regulated by a cellular prostate/uterine growth stimulus, the present study assessed whether IDE was modified in quantity and activity during proliferative conditions (castration + testosterone in the male rat, or castration + estradiol or the proestrus phase of the estrous cycle in the female rat) and autolysis (castration or the metestrus phase of the estrous cycle) using cytosolic and nuclear fractions of rat prostate and cytosolic fractions of rat uterus. The activity and amount of IDE decreased in the cytosolic fraction with castration and during metestrus, and increased with testosterone or estradiol treatment and during proestrus. In the nuclear fraction, the quantity of the IDE followed the same pattern observed in the cytosolic fraction, although without degradative activity. The data presented here suggest that IDE may participate in prostatic and uterine growth and that the testosterone or estradiol and/or prostate and uterus insulin-like growth factors may be important factors for the expression and regulation of IDE in the prostate and uterus.