Genetic Characterization and Population Structure of Drug-Resistant Mycobacterium tuberculosis Isolated from Brazilian Patients Using Whole-Genome Sequencing.

The present study aimed to determine the genetic diversity of isolates of Mycobacterium tuberculosis (Mtb) from presumed drug-resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) was the most frequent phenotypic resistance profile, in addition to an important high frequency of pre-extensive resistance (p-XDR-TB) (9.2%). Using whole-genome sequencing (WGS), we characterized 298 Mtb isolates from Brazil. Besides the analysis of genotype distribution and possible correlations between molecular and clinical data, we determined the performance of an in-house WGS pipeline with other online pipelines for Mtb lineages and drug resistance profile definitions. Sub-lineage 4.3 (52%) was the most frequent genotype, and the genomic approach revealed a p-XDR-TB level of 22.5%. We detected twenty novel mutations in three resistance genes, and six of these were observed in eight phenotypically resistant isolates. A cluster analysis of 170 isolates showed that 43.5% of the TB patients belonged to 24 genomic clusters, suggesting considerable ongoing transmission of DR-TB, including two interstate transmissions. The in-house WGS pipeline showed the best overall performance in drug resistance prediction, presenting the best accuracy values for five of the nine drugs tested. Significant associations were observed between suffering from fatal disease and genotypic p-XDR-TB (p = 0.03) and either phenotypic (p = 0.006) or genotypic (p = 0.0007) ethambutol resistance. The use of WGS analysis improved our understanding of the population structure of MTBC in Brazil and the genetic and clinical data correlations and demonstrated its utility for surveillance efforts regarding the spread of DR-TB, hopefully helping to avoid the emergence of even more resistant strains and to reduce TB incidence and mortality rates.

Restoring the epigenome in Alzheimer's disease: advancing HDAC inhibitors as therapeutic agents.

Current treatment options for Alzheimer's disease (AD) focus on symptom relief rather than halting disease progression. In this context, targeting histone deacetylation emerges as a promising therapeutic alternative. Dysregulation of histone deacetylase (HDAC) activity is present in AD, contributing to cognitive decline. Pharmacological HDAC inhibition has shown benefits in preclinical models, namely reduced amyloid beta plaque formation, lower phosphorylation and aggregation of tau protein, greater microtubule stability, less neuroinflammation, and improved metabolic homeostasis and cell survival. Nonetheless, clinical trials evidenced limitations such as insufficient selectivity or blood-brain barrier penetration. Hence, future innovative strategies are required to enhance their efficacy/safety.

Bioconjugate based on cisplatin and bacterial exopolysaccharide with reduced side effects: A novel proposal for cancer treatment.

BACKGROUND: In the search for alternatives that attenuate the toxicity associated to oncologic treatment with cisplatin (CDDP) and considering the potential health-beneficial properties of exopolysaccharides (EPS) produced by lactic acid bacteria, it was aimed on this study to evaluate the cytotoxic, toxicologic and antitumoral efficacy of a bioconjugate based on CDDP and EPS, on the experimental tumor of sarcoma 180. METHODS: After the synthesis of the cis-[Pt(NH3)2(Cl)2] complex and of the conjugate containing Lactobacillus fermentum exopolysaccharide was tested both in vitro and in vivo for evaluating the acute toxicity. RESULTS: The antitumoral study was performed using mice transplanted with sarcoma 180. The bioconjugate showed low to medium cytotoxicity for the cell lines tested, as well moderated acute toxicity. After determining the LD50, the following experimental groups were established for the antitumor assay: Control (NaCl 0,9%), CDDP (1 mg/kg), EPS and bioconjugate composition (200 mg/kg). The bioconjugate promoted a 38% regression in tumor mass when compared to the control, and a regression of 41% when compared to CDDP. Liver histopathological analysis revealed discrete alterations in animals treated with (CDDP + EPS) when compared to control. The bioconjugate also minimized changes in the renal parenchyma resulting from the tumor. CONCLUSION: Our results indicate that when CDDP is associated with EPS, this composition was more biocompatible, showing itself as a potent chemotherapeutic agent and lower tissue toxicity.

Genetically modified ZIKA virus as a microRNA-sensitive oncolytic virus against central nervous system tumors.

Here we introduce a first-in-class microRNA-sensitive oncolytic Zika virus (ZIKV) for virotherapy application against central nervous system (CNS) tumors. The described methodology produced two synthetic modified ZIKV strains that are safe in normal cells, including neural stem cells, while preserving brain tropism and oncolytic effects in tumor cells. The microRNA-sensitive ZIKV introduces genetic modifications in two different virus sites: first, in the established 3'UTR region, and secondly, in the ZIKV protein coding sequence, demonstrating for the first time that the miRNA inhibition systems can be functional outside the UTR RNA sites. The total tumor remission in mice bearing human CNS tumors, including metastatic tumor growth, after intraventricular and systemic modified ZIKV administration, confirms the promise of this virotherapy as a novel agent against brain tumors-highly deadly diseases in urgent need of effective advanced therapies.

Metabolic Myopathies: Experience of a Reference Center of Inherited Metabolic Diseases.

INTRODUCTION: Metabolic myopathies (MM) are a heterogeneous group of genetic disorders affecting metabolic pathways involved in energy production during rest, exercise and physiologic stress (fever, fasting, …). Impairments in the pathways of glycolysis/ glycogenolysis, fatty acid transport/oxidation or in the mitochondrial respiratory chain present primarily with exercise intolerance, myalgias, weakness, cramps, or rhabdomyolysis. Depending on aetiology, the diagnosis can be made through neonatal screening, pre-symptomatic or in the set of clinical manifestations for which a high level of suspicion is important. METHODS: Retrospective descriptive study of the clinical, biochemical, and molecular features of patients with a confirmed diagnosis of MM followed by the multidisciplinary team of the Reference Center of Inherited Metabolic Diseases of Centro Hospitalar Universitário de Lisboa Central from 2009 to 2022. RESULTS: Twenty-three patients with MM were included: 9 (39%) glycogen storage diseases (7 McArdle and 2 Pompe), 7 (30%) fatty acid oxidation disorders (3 CPT2, 3 LCHAD and 1 MAD deficiencies), 6 (26%) mitochondrial disease with significant muscle involvement (2 Pearson, 1 Kearns Sayre, 1 VARS2, 1 SUCLA2 and 1 MT-TL1 deficiencies), and 1 myoadenylate deaminase deficiency. Ages varied from 15 months to 35 years. Eighteen (78%) patients were diagnosed by clinical symptoms, 3 by newborn screening (LCHAD) and 2 were asymptomatic (1 Pompe and 1 McArdle). Frequent symptoms were rhabdomyolysis triggered by illness or exercise 12 (52%), fatigue 11 (48%), exercise intolerance 10 (43%), and myalgia 9 (43%). Eight (35%) patients (LCHAD and mitochondrial) had multisystemic involvement. In 20 (87%) patients, the diagnosis was confirmed by biochemical and/or genetic analysis and 3 (McArdle) by muscle biopsy. CONCLUSION: MM are a heterogeneous set of disorders, but a careful history may guide the differential diagnosis among biochemical pathways and other etiologies. Nowadays, molecular testing has become a powerful tool for diagnosis confirmation, surpassing muscular biopsy in most cases. Accurate diagnosis is important to identify who may benefit from specific therapeutic options, such as enzyme replacement therapy, restricted diets, emergency regime and cofactors. All patients benefit from adequate lifestyle modifications, individualized exercise prescription, nutritional intervention, and genetic counselling.

Cardioprotective effect of the quercetin on cardiovascular remodeling and atherosclerosis in rodents fed a high-fat diet: A systematic review.

Cardiovascular diseases (CVD) are the leading cause of death globally, estimated at 17.9 million premature deaths. Several risk factors contribute to the development of CVD, including unhealthy diet rich in saturated fat. Quercetin (Q) is a important natural flavonoid with cardioprotective effect. However, it is crucial to understand and clarify which dosages and intervention times quercetin promotes better cardioprotective effects when exposed to a High-Fat Diet (HFD). We aim was to carry out a review to identify and compare experimental studies that investigated the quercetin effect on cardiac parameters in rodents fed a HFD. This literature search was performed through the specialized databases PubMed, Embase, Web of Science and Lilacs in May 2022. The following information was collected and assessed: Species of animals, dietary fat content, intervention protocol (quercetin), and main results of alterations associated with cardiac change. A total of 116 articles were selected from the database and 30 articles were included in this study. The administration form of quercetin was used in the diet supplemented in 73.4% (n = 22) of the studies. The dosage ranged between 10 and 100 mg/kg, 0.01%-0.36%, and 4-8 g/kg diet. The treatment time ranged between 14 and 63 days in 48.4% studies and most of the selected studies observed changes in the: Serum concentrations of lipids (60%, n = 18) mainly decrease in TC and TG, left ventricle (LV) (16.13%, n = 5) includes attenuation of the cardiac hypertrophy; inhibition of atherosclerotic progression (32%, n = 10) with decrease in lesions and plaque formation; improvement in the expression of gene and protein associated with cardiac functionality and oxidative stress (51.6%; n = 16). Quercetin supplementation at different concentrations/doses promotes important cardioprotective effects in experimental models exposed to a HFD. The supplemented diet was shown to be the better administration option. The methodological variation presented in the articles selected in this review proves that the most appropriate intervention protocol, as well as the most effective route of administration, promotes these effects.

Translocating Lactobacillus torments tumors via tryptophan catabolism.

Variability in the efficacy of immune checkpoint inhibitors in cancer patients is associated with the human gut microbiota. However, detailed mechanisms are unclear. In this issue of Cell, Bender et al. uncovered that a probiotic Lactobacillus strain translocates into murine tumors to enhance immunotherapy via the tryptophan metabolite indole-3-aldehyde (I3A).

Effects of a high-fat diet on the bone structure of Wistar rats: a systematic review.

CONTEXT: Saturated fats found in diets known as high-fat, cafeteria, or Western diets appear to have a negative effect on bone structure; however, few studies have focused on investigating this association, and the data available in the literature remain controversial. OBJECTIVE: The aim of the current review was to investigate the effects of a high-fat dietary intake on the bone structure of Wistar rats. DATA SOURCES: A search for articles was carried out in the Pubmed/MEDLINE, Web of Science, Embase, and Scopus databases. DATA EXTRACTION: In total, 447 articles were found in the initial search; 5 articles were included in the systematic review, after application of the exclusion criteria. DATA ANALYSIS: The review was guided by the PICOS strategy and based on the PRISMA protocol for animal reviews. CONCLUSION: High-fat diets appear to affect bone structure of Wistar rats. Diet composition and exposure time are the factors determining the strength of the effect.

Role of synthetical amynoquinone ethyl 2-(1,4-dioxo-1,4-dihydronaphthalen-2-ylamino) acetate in inhibition of Ehrlich's tumor.

Quinones are naturally or synthetically occurring secondary metabolites that have various bio-dynamics, highlighting their antitumor potential. This has been explored through their selective cytotoxicity, and studies in medicinal chemistry about the relation between biological activity versus chemical structure may lead to the solution of the toxicity problems associated with quinones. In this context, the antitumor effect of a synthetic naphthoquinone, named Ethyl 2-(1,4-Dioxo-1,4-Dihydronaphthalen-2-Ylamino) Acetate, was tested using mice transplanted with Ehrlich ascitic tumor as an experimental model. The acute toxicity test was performed using 30 mice that received the aminoquinone at doses of 100, 200, 300, and 600 mg/kg. After evaluation of the clinical findings in the spontaneous activity tests, the LD50 calculation for the test substance showed low levels of toxicity at doses lower than 244.11 ± 23.29 mg/kg. Thus, three experimental groups were established, where animals transplanted with tumor cells received NaCl vehicle solution (control, n = 6), and the others were treated with 71.7 mg/kg of Methotrexate (n = 6) or 20 mg/kg of Aminoquinone (n = 6). All administrations were intraperitoneal, in a single dose. Three days after the implantation of the tumor cells the animals were weighed daily and evaluated for tumor biometry and development. The treatments occurred five days after the implantation of the tumor cells and were extended for 7 more days. At the end of the 12-day experimental period, all animals were euthanized for biochemical and histopathological analyses of the tumors and vital organs. The spontaneous activity test showed that the amount of responses associated with the nervous system tends to increase with the increase in dosage, highlighting the excitatory effect on the central nervous system in almost all dosages employed, followed by depressant activities on this system. There was a significant tumor reduction, both in animals treated with methotrexate (71.7 %) and in those treated with aminoquinone (91.6 %) in the control group. There was no significant difference in tumor volume between the animals treated with aminoquinone or methotrexate. The histopathological analysis revealed that in both treatments there were fewer mitoses in the tumor mass compared to the control group. However, there was apparent toxicity to the liver, heart, and left kidney in the treatment with methotrexate compared to aminoquinone. The significant capacity for tumor reduction presented by aminoquinone allows pointing it as a promising alternative for the development of a more efficient drug to control tumor development, being necessary for the development of new studies to deepen the knowledge about its mechanisms of action.

Evolving concepts of host-pathobiont interactions in autoimmunity.

Autoimmune diseases are complex, multifactorial diseases with a polygenic trait and diverse environmental factors that contribute to triggering and exacerbating each disorder. The human microbiome is increasingly implicated in the multistep pathogenesis of autoimmune diseases. We summarize here the latest developments in the field of how the microbiota interacts with the host on a cellular and molecular level. We review how pathobionts evolve within the gut of autoimmune-prone hosts to translocate to secondary lymphoid tissues. On mucosal sites and in non-gut tissues, pathobionts trigger autoimmune pathways through various mechanisms, including cross-reactivity with autoantigens and secretion of metabolites that alter immune functions. A better understanding of these mechanisms will hasten the development of unconventional therapeutic approaches for autoimmune diseases.

Perinatal and post-weaning exposure to a high-fat diet causes histomorphometric, neuroplastic, and histopathological changes in the rat ileum.

Exposure to a diet with a high saturated fat content can influence the characteristics of the gastrointestinal tract, causing losses in the absorption of nutrients and favoring the appearance of diseases. The objective was to assess the effects of a high-fat diet (HFD) in the perinatal (pregnancy and lactation) and post-weaning period on the histomorphometry, neuroplasticity, and histopathology of the ileum. Wistar rats were divided into four subgroups: Control/Control (CC, n = 10) rats fed a control diet (C) throughout the trial period; Control/HFD (CH, n = 9) rats fed diet C (perinatal) and HFD after weaning; HFD/Control (HC, n = 10) rats fed HFD (perinatal) and diet C (post-weaning); HFD/HFD (HH, n = 9) rats fed HFD throughout the experimental period. There was atrophy of the Ileum wall with a reduction in the muscular tunic, submucosa, and mucosa thickness in the HH group of 37%, 28%, and 46%, respectively (p < 0.0001). The depth of the crypts decreased by 29% (p < 0.0001) and height increased by 5% (p < 0.0013). Villus height decreased by 41% and 18% in HH and HC groups (p < 0.0001) and width decreased by 11% in the HH (p < 0.0001). The height of the enterocytes decreased by 18% in the HH (p < 0.0001). There was a decrease in the area of the myenteric and submucosal plexus ganglia in the HH and HC groups (p < 0.0001). The number, occupation, and granules of Paneth cells increased in the HH and HC groups (p < 0.0001). Intraepithelial lymphocytes (IELs) increased in all groups exposed to the HFD. Goblet cells decreased in groups CH and HH (p < 0.0001). The evidence from this study suggests that the HFD had altered the histomorphometry, neuroplasticity, and histopathology of the ileum of the rats.

Experiência do município de São Paulo na implantação de Serviços de Saúde Integral para Lésbicas, Gays, Bissexuais, Travestis, Transexuais, Intersexos, Assexuais e Pessoas com Vivência de Variabilidade de Gênero ­ LGBTIA+ / Experience of the Municipality of Sao Paulo in the Implementation of Comprehensive Health Services for Lesbians, Gays, Bisexuals, Travestis, Transsexuals, Intersex, Asexuals and People with Experience of Gender Variability - LGBTIA+

Historicamente a população LGBTIA+ sempre foi excluída nos serviços de saúde. As dificuldades de acesso são legítimas e decorrentes do estigma e discriminação. Era necessário fortalecer o acesso e a qualidade do atendimento em saúde. As pessoas LGBTIA+ precisavam ser melhor acolhidas, ter garantido atendimento integral e ter seus direitos básicos respeitados. Era necessário ampliar a rede de serviços de hormonização, rever sistemas de informação (nome social/gênero/orientação sexual) e investir na capacitação dos profissionais de saúde. Para resolver esses problemas, foi desenhado pela Área Técnica de Saúde Integral da População LGBTIA+ da Secretaria Municipal de Saúde de São Paulo um plano de ações e estratégias de cuidado em conjunto com as seis interlocutoras regionais LGBTIA+. O principal resultado foi a implementação de unidades na Rede SAMPA Trans, de 28 unidades para 45 em 2022, com 3.346 pessoas trans em acompanhamento. Isso permitiu dar maior visibilidade a essa população, aprimorar o acolhimento, ofertar acompanhamento de qualidade desde a utilização de hormônios, até as cirurgias de transformação corporal. A SMS conta hoje com um modelo de rede de atenção à saúde integral da população LGBTIA+ inédito no estado de São Paulo e no Brasil.

Metodologia ativa na educação permanente para abordar ética e bioética / Active methodology in continuing education to address ethics and bioethics / Metodología activa en la educación permanente para abordar la ética y la bioética

Resumo Mediante pesquisa qualitativa com a técnica do discurso do sujeito coletivo, este estudo analisa a educação à distância como metodologia ativa na educação permanente de equipe de enfermagem de hospital universitário de Minas Gerais. Coletados por meio de questionário e de grupo focal, os dados foram organizados conforme três ideias centrais que emergiram nas reuniões. Para os participantes da pesquisa, a modalidade à distância pode ser considerada uma metodologia ativa de ensino que possibilita intervenções no trabalho, desde que haja infraestrutura necessária para o desenvolvimento do processo de trabalho e realização das capacitações no ambiente laboral. Para concluir, ressalta-se a importância do trabalhador da enfermagem ser sujeito ativo do seu processo de ensino-aprendizagem, utilizando a educação permanente em saúde para prestar assistência aos usuários do Sistema Único de Saúde de forma integral, ética e segura.

Abstract This qualitative research, based on the discourse of the collective subject, analyzes distance education as an active methodology in the continuing education of a nursing team at a university hospital in Minas Gerais. Data were collected by means of a questionnaire and a focus group, and organized according to three central ideas that emerged in the meetings. Research participants see distance education as an active teaching methodology that enables interventions at work, provided that there is necessary infrastructure for developing the work process and implementing training in the work environment. The analysis also emphasizes the importance of nursing workers being an active subject in their teaching-learning process, using continuing health education to provide integral, ethical, and safe care to the Unified Health System users.

Resumen Desde una investigación cualitativa con la técnica del discurso del sujeto colectivo, este estudio analiza la educación a distancia como metodología activa en la formación permanente del equipo de enfermería de un hospital universitario de Minas Gerais (Brasil). Se recopilaron los datos mediante un cuestionario y un grupo focal para organizarlos de acuerdo con tres ejes centrales que surgieron en las reuniones. Para los participantes de la investigación, la modalidad a distancia puede ser una metodología de enseñanza activa que posibilita intervenciones en el trabajo, siempre que exista la infraestructura necesaria para el desarrollo del proceso de trabajo y la realización de capacitaciones en el ambiente laboral. Es importante que el profesional enfermero sea un sujeto activo en su proceso de enseñanza-aprendizaje al usar la educación permanente en salud para brindar asistencia integral, ética y segura a los usuarios del Sistema Único de Salud.

Newborn Skin Maturity Medical Device Validation for Gestational Age Prediction: Clinical Trial.

BACKGROUND: Early access to antenatal care and high-cost technologies for pregnancy dating challenge early neonatal risk assessment at birth in resource-constrained settings. To overcome the absence or inaccuracy of postnatal gestational age (GA), we developed a new medical device to assess GA based on the photobiological properties of newborns' skin and predictive models. OBJECTIVE: This study aims to validate a device that uses the photobiological model of skin maturity adjusted to the clinical data to detect GA and establish its accuracy in discriminating preterm newborns. METHODS: A multicenter, single-blinded, and single-arm intention-to-diagnosis clinical trial evaluated the accuracy of a novel device for the detection of GA and preterm newborns. The first-trimester ultrasound, a second comparator ultrasound, and data regarding the last menstrual period (LMP) from antenatal reports were used as references for GA at birth. The new test for validation was performed using a portable multiband reflectance photometer device that assessed the skin maturity of newborns and used machine learning models to predict GA, adjusted for birth weight and antenatal corticosteroid therapy exposure. RESULTS: The study group comprised 702 pregnant women who gave birth to 781 newborns, of which 366 (46.9%) were preterm newborns. As the primary outcome, the GA as predicted by the new test was in line with the reference GA that was calculated by using the intraclass correlation coefficient (0.969, 95% CI 0.964-0.973). The paired difference between predicted and reference GAs was -1.34 days, with Bland-Altman limits of -21.2 to 18.4 days. As a secondary outcome, the new test achieved 66.6% (95% CI 62.9%-70.1%) agreement with the reference GA within an error of 1 week. This agreement was similar to that of comparator-LMP-GAs (64.1%, 95% CI 60.7%-67.5%). The discrimination between preterm and term newborns via the device had a similar area under the receiver operating characteristic curve (0.970, 95% CI 0.959-0.981) compared with that for comparator-LMP-GAs (0.957, 95% CI 0.941-0.974). In newborns with absent or unreliable LMPs (n=451), the intent-to-discriminate analysis showed correct preterm versus term classifications with the new test, which achieved an accuracy of 89.6% (95% CI 86.4%-92.2%), while the accuracy for comparator-LMP-GA was 69.6% (95% CI 65.3%-73.7%). CONCLUSIONS: The assessment of newborn's skin maturity (adjusted by learning models) promises accurate pregnancy dating at birth, even without the antenatal ultrasound reference. Thus, the novel device could add value to the set of clinical parameters that direct the delivery of neonatal care in birth scenarios where GA is unknown or unreliable. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2018-027442.

Reduced dopaminergic neuron degeneration and global transcriptional changes in Parkinson's disease mouse brains engrafted with human neural stems during the early disease stage.

INTRODUCTION: Current stem cell therapies for Parkinson's disease (PD) focus on a neurorestorative approach that aims to repair the CNS during the symptomatic phase. However, the pleiotropic and supportive effects of human neural stem cells (hNSCs) may make them effective for PD treatment during the disease's earlier stages. In the current study, we investigated the therapeutic effects of transplanting hNSCs during the early stages of PD development when most dopaminergic neurons are still present and before symptoms appear. Previous studies on hNSCs in Parkinson's disease focus on the substantia nigra and its immediate surroundings, but other brain structures are affected in PD as well. Here, we investigated the therapeutic effects of hNSCs on the entire PD-afflicted brain transcriptome using RNA sequencing (RNA-seq). METHODS: PD was induced with a single intranasal infusion of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and hNSCs were transplanted unilaterally into the striatum one week later. The timepoint for hNSC transplantation coincided with upregulation of endogenous proinflammatory cytokines in the CNS, which play a role in stem cell migration. At 3 weeks post-transplantation (4 weeks post-MPTP), we assessed motor symptoms through behavioral tests, quantified dopaminergic neurons in the substantia nigra, and performed global transcriptional profiling to understand the mechanism underlying the effect of hNSCs on dopaminergic neuron degeneration. RESULTS: We found that early hNSC engraftment mitigated motor symptoms induced by MPTP, and also reduced MPTP-induced loss of dopaminergic neurons. In this study, we uniquely presented the first comprehensive analysis of the effect of hNSC transplantation on the transcriptional profiling of PD mouse brains showing decreased expression of 249 and increased expression of 200 genes. These include genes implicated in mitochondrial bioenergetics, proteostasis, and other signaling pathways associated with improved PD outcome following hNSC transplantation. CONCLUSION: These findings indicate that NSC transplantation during the asymptomatic phase of PD may limit or halt the progression of this neurodegenerative disorder. Transcriptional profiling of hNSC-engrafted PD mouse brains provides mechanistic insight that could lead to novel approaches to ameliorating degeneration of dopaminergic neurons and improving behavioral dysfunction in PD.

Malignant T Cell Activation by a Bacillus Species Isolated from Cutaneous T-Cell Lymphoma Lesions.

Cutaneous T-cell lymphoma (CTCL) is a life-debilitating malignancy of lymphocytes homing to the skin. Although CTCL is thought to arise from a combination of genetic, epigenetic, and environmental factors, specific triggers are unclear. The skin is colonized by a unique microbiota and is heavily influenced by its interactions. We hypothesized that adaptive immune responses to skin commensals lead to clonal T-cell proliferation and transformation in the appropriate genetic background. We therefore collected lesional and nonlesional skin microbiota from patients with CTCL to study T cell interactions using skin T cell explants and peripheral, skin-homing CD4+ T cells. By various methods, we identified Bacillus safensis in CTCL lesions, a rare human commensal in healthy skin, and showed that it can induce malignant T cell activation and cytokine secretion. Taken together, our data suggest microbial triggers in the skin microbiota of patients with CTCL as potential instigators of tumorigenesis.

Familial Amyloid Polyneuropathy Misdiagnosed as Systemic Sclerosis.

We present the case of a 53-year-old woman of Portuguese ancestry with a diagnosis of progressive systemic sclerosis (SSc), proposed for haematopoietic stem cell transplantation (HSCT). Clinical re-evaluation when assessing eligibility for the procedure led to the alternative diagnosis of familial amyloid polyneuropathy (FAP). We discuss the clinical presentations of FAP and SSc, focusing on their overlapping and distinguishing features. We emphasize the need for a high level of suspicion in order to establish an early diagnosis of FAP in the absence of a family history, and provide prognostic and genetic counselling. LEARNING POINTS: It is important to review diagnoses, especially when the clinical course is atypical.Cutaneous involvement is a commonly unrecognized feature of familial amyloid polyneuropathy.Hereditary conditions should be included in the differential diagnosis of multisystemic diseases, even in the absence of a family history.

Skin Deep: The Role of the Microbiota in Cutaneous Autoimmunity.

The skin microbiota is thought to possibly contribute to the pathogenesis of skin autoimmune diseases. The gut microbiota affects systemically the development and function of the immune system, thereby potentially influencing cutaneous autoimmunity as well. In this paper, we review the role of the gut and skin microbiota in cutaneous autoimmune diseases. Besides direct inflammatory effects at the skin barrier, microbiota may contribute to the pathogenesis of skin autoimmune diseases by metabolites, recall immune cell responses, and permeation of antigens to the subepidermal space. Skin and gut barrier dysfunction may represent a common pathophysiologic process allowing microbiota or its particles to promote autoimmune diseases at barrier surfaces.

Retenção de objetos intracavitários em procedimentos cirúrgicos: ações de segurança propostas por enfermeiros especialistas / Retention of intracavitary objects in surgical procedures: safety actions proposed by specialist nurses / Retención de objetos intracavitarios en procedimientos quirúrgicos: acciones de seguridad propuestas por enfermeros especialistas

Objetivo: Descrever ações de segurança para mitigar o risco de retenção de objetos intracavitários em procedimentos cirúrgicos, na opinião de enfermei-ros especialistas em assistência perioperatória. Método: Estudo qualitativo. Dados oriundos de reunião científica realizada durante o 14o Congresso da Associação Brasileira de Enfermagem em Centro Cirúrgico, em 2019, em São Paulo. Participaram enfermeiros especialistas em enfermagem perioperatória, divididos alea-toriamente em cinco grupos. Indisponibilidade para participar da reunião na íntegra considerou-se critério de exclusão. Compuseram o corpus de dados: gra-vação da reunião e registros dos grupos. Procedeu-se à análise de conteúdo para avaliar os dados. Seguiu-se a Resolução no 466/2012 do Conselho Nacional de Saúde (CNS). Resultados: Participaram 19 enfermeiros de seis estados brasileiros, a maioria mulheres. Ações propostas pelos participantes do estudo, visando a diminuir a retenção de objetos intracavitários: promover educação permanente e multiprofissional; estabelecer e seguir boas práticas institucionais; seguir proto-colo de cirurgia segura; atuar de forma integrada à equipe do serviço de esterilização; usar processos e tecnologias que contribuem para ampliar a segurança do paciente; contar instrumental e materiais cirúrgicos; e fortalecer o trabalho interdisciplinar. Conclusão: Ações para reduzir a retenção de objetos intracavitários incluem educação permanente, trabalho interdisciplinar e multissetorial, seguimento de fluxos e protocolos que visem à segurança do paciente.

Aims: This study aimed to describe the safety actions to mitigate the risk of retention of intracavitary objects in surgical procedures, in the opinion of perioperative care specialist nurses. Methods: This is a qualitative study. Data from a scientific meeting held during the 14th Congress of the Brazilian Association of Nursing in the Surgical Centre, in 2019, in São Paulo. Participants were nurses specialized in perioperative nursing, randomly divided into five groups. Unavailability to participate in the meeting in full was considered an exclusion criterion. The data corpus comprised meeting recording and group records. Content analysis was used to evaluate the data. Resolution no. 466/2012 of the National Health Council (CNS) was follo-wed. Results: A total of 19 nurses, mostly female, from six Brazilian states participated in this study. Actions proposed by the study participants to reduce the retention of intracavitary objects included promoting continuing and multidisciplinary education; establishing and following good institutional prac-tices; following the safe surgery protocol; integrating with the sterilization service team; using processes and technologies that contribute to increasing patient safety; counting surgical instruments and materials; and strengthening interdisciplinary work. Conclusion: Actions to reduce retention of intra-cavitary objects include permanent education, interdisciplinary work, and multisectoral work, following flows and protocols aimed at patient safety.

Objetivo: describir acciones de seguridad para mitigar el riesgo de retención de objetos intracavitarios en procedimientos quirúrgicos, según la opinión de enfermeros especialistas en cuidados perioperatorios. Método: estudio cualitativo. Datos de una reunión científica realizada durante el 14o Congreso de la Asociación Brasileña de Enfermería del Centro Quirúrgico, en 2019, en São Paulo. Participaron enfermeros especialistas en enfermería perioperatoria, divididos aleatoriamente en cuatro grupos. La falta de disponibilidad para participar en la reunión en su totalidad se consideró un criterio de exclusión. El corpus de datos estuvo compuesto por: grabación de la reunión y actas de los grupos. Se realizó un análisis de contenido para analizar los datos. A esto le siguió la Resolución no 466/2012 del Consejo Nacional de Salud (CNS). Resultados: Participaron 19 enfermeros de seis estados brasileños, la mayoría mujeres. Acciones propuestas por los participantes del estudio, con el objetivo de reducir la retención de objetos intracavitarios: promover la educación permanente y multiprofesional; establecer y seguir buenas prácticas institucionales; seguir un protocolo de cirugía seguro; actuar de manera integrada con el equipo del servicio de esterilización; hacer uso de procesos y tecnologías que contribuyan a aumentar la seguridad del paciente; realizar el conteo de instrumentos y material quirúrgico; fortalecer el trabajo interdisciplinario. Conclusión: las acciones para reducir la retención de objetos intraca-vitarios incluyen educación permanente, trabajo interdisciplinario y multisectorial, monitoreo de flujos y protocolos dirigidos a la seguridad del paciente.