Early life adversity shapes social subordination and cell type-specific transcriptomic patterning in the ventral hippocampus.

Adverse events in early life can modulate the response to additional stressors later in life and increase the risk of developing psychiatric disorders. The underlying molecular mechanisms responsible for these effects remain unclear. Here, we uncover that early life adversity (ELA) in mice leads to social subordination. Using single-cell RNA sequencing (scRNA-seq), we identified cell type-specific changes in the transcriptional state of glutamatergic and GABAergic neurons in the ventral hippocampus of ELA mice after exposure to acute social stress in adulthood. These findings were reflected by an alteration in excitatory and inhibitory synaptic transmission induced by ELA in response to acute social stress. Finally, enhancing the inhibitory network function through transient diazepam treatment during an early developmental sensitive period reversed the ELA-induced social subordination. Collectively, this study significantly advances our understanding of the molecular, physiological, and behavioral alterations induced by ELA, uncovering a previously unknown cell type-specific vulnerability to ELA.

Multimodal learning in clinical proteomics: enhancing antimicrobial resistance prediction models with chemical information.

MOTIVATION: Large-scale clinical proteomics datasets of infectious pathogens, combined with antimicrobial resistance outcomes, have recently opened the door for machine learning models which aim to improve clinical treatment by predicting resistance early. However, existing prediction frameworks typically train a separate model for each antimicrobial and species in order to predict a pathogen's resistance outcome, resulting in missed opportunities for chemical knowledge transfer and generalizability. RESULTS: We demonstrate the effectiveness of multimodal learning over proteomic and chemical features by exploring two clinically relevant tasks for our proposed deep learning models: drug recommendation and generalized resistance prediction. By adopting this multi-view representation of the pathogenic samples and leveraging the scale of the available datasets, our models outperformed the previous single-drug and single-species predictive models by statistically significant margins. We extensively validated the multi-drug setting, highlighting the challenges in generalizing beyond the training data distribution, and quantitatively demonstrate how suitable representations of antimicrobial drugs constitute a crucial tool in the development of clinically relevant predictive models. AVAILABILITY AND IMPLEMENTATION: The code used to produce the results presented in this article is available at https://github.com/BorgwardtLab/MultimodalAMR.

miRNAs associated with endoplasmic reticulum stress and unfolded protein response during decidualization.

RESEARCH QUESTION: Do microRNAs (miRNAs) play a role in regulating endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) in decidualized cells and endometrium associated with reproductive failures? DESIGN: Endometrial stromal cell line St-T1b was decidualized in vitro with 8-Br-cAMP over 5 days, or treated with the ERS inducer thapsigargin. Expression of ERS sensors, UPR markers and potential miRNA regulators was analysed by quantitative PCR. Endometrial biopsies from patients with recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) were investigated for the location of miRNA expression. RESULTS: Decidualization of St-T1b cells resulted in increased expression of ERS sensors including ATF6α, PERK and IRE1α, and the UPR marker, CHOP. TXNIP, which serves as a link between the ERS pathway and inflammation, as well as inflammasome NLRP3 and interleukin 1ß expression increased in decidualized cells. An in-silico analysis identified miR-17-5p, miR-21-5p and miR-193b-3p as miRNAs potentially involved in regulation of the ERS/UPR pathways and inflammation associated with embryo implantation. Their expression decreased significantly (P ≤ 0.0391) in non-decidualized cells in the presence of thapsigargin. Finally, expression of the selected miRNAs was localized by in-situ hybridization in stromal and glandular epithelial cells in endometrial samples from patients with RPL and RIF. Expression in stroma cells from patients with RPL was lower in comparison with stroma cells from patients with RIF. CONCLUSIONS: Decidualization in St-T1b cells is accompanied by ERS/UPR processes, associated with an inflammatory response that is potentially influenced by miR-17-5p, miR-21-5p and miR-193b-3p. These miRNAs are expressed differentially in stromal cells from patients with RPL and RIF, indicating an alteration in regulation of the ERS/UPR pathways.

Automatically annotated motion tracking identifies a distinct social behavioral profile following chronic social defeat stress.

Severe stress exposure increases the risk of stress-related disorders such as major depressive disorder (MDD). An essential characteristic of MDD is the impairment of social functioning and lack of social motivation. Chronic social defeat stress is an established animal model for MDD research, which induces a cascade of physiological and behavioral changes. Current markerless pose estimation tools allow for more complex and naturalistic behavioral tests. Here, we introduce the open-source tool DeepOF to investigate the individual and social behavioral profile in mice by providing supervised and unsupervised pipelines using DeepLabCut-annotated pose estimation data. Applying this tool to chronic social defeat in male mice, the DeepOF supervised and unsupervised pipelines detect a distinct stress-induced social behavioral pattern, which was particularly observed at the beginning of a novel social encounter and fades with time due to habituation. In addition, while the classical social avoidance task does identify the stress-induced social behavioral differences, both DeepOF behavioral pipelines provide a clearer and more detailed profile. Moreover, DeepOF aims to facilitate reproducibility and unification of behavioral classification by providing an open-source tool, which can advance the study of rodent individual and social behavior, thereby enabling biological insights and, for example, subsequent drug development for psychiatric disorders.

Advancing social behavioral neuroscience by integrating ethology and comparative psychology methods through machine learning.

Social behavior is naturally occurring in vertebrate species, which holds a strong evolutionary component and is crucial for the normal development and survival of individuals throughout life. Behavioral neuroscience has seen different influential methods for social behavioral phenotyping. The ethological research approach has extensively investigated social behavior in natural habitats, while the comparative psychology approach was developed utilizing standardized and univariate social behavioral tests. The development of advanced and precise tracking tools, together with post-tracking analysis packages, has recently enabled a novel behavioral phenotyping method, that includes the strengths of both approaches. The implementation of such methods will be beneficial for fundamental social behavioral research but will also enable an increased understanding of the influences of many different factors that can influence social behavior, such as stress exposure. Furthermore, future research will increase the number of data modalities, such as sensory, physiological, and neuronal activity data, and will thereby significantly enhance our understanding of the biological basis of social behavior and guide intervention strategies for behavioral abnormalities in psychiatric disorders.

Increasing resolution in stress neurobiology: from single cells to complex group behaviors.

Stress can have severe psychological and physiological consequences. Thus, inappropriate regulation of the stress response is linked to the etiology of mood and anxiety disorders. The generation and implementation of preclinical animal models represent valuable tools to explore and characterize the mechanisms underlying the pathophysiology of stress-related psychiatric disorders and the development of novel pharmacological strategies. In this commentary, we discuss the strengths and limitations of state-of-the-art molecular and computational advances employed in stress neurobiology research, with a focus on the ever-increasing spatiotemporal resolution in cell biology and behavioral science. Finally, we share our perspective on future directions in the fields of preclinical and human stress research.

Self-reported health conditions, quality of Primary Health Care and associated factors according to sexual and gender minorities / Condições de saúde autorreferidas, qualidade da Atenção Primária à Saúde e fatores associados segundo minorias sexuais e de gênero

Introduction: Lesbians, gays, bisexuals, transvestites, transsexuals, transgenders, queers, intersexes, asexuals, pansexuals, and other sexual and gender minorities constitute a population that has been little studied regarding the use and care of health services. Objective: From this perspective, the general objective of this study was to evaluate the quality of Primary Health Care according to members of sexual and gender minorities. Methods: This is evaluative research, with a cross-sectional and descriptive-analytical design and a quantitative approach, performed by a web survey in Brazil. The script for data collection addressed sociodemographic characteristics, sexual orientation, gender identity, self-reported health conditions, and the 23 items of the Primary Care Assessment Tool, a reduced version for adult users. Results: The results represent 314 LGBTQIAP+ people, predominantly young, white, cisgender, homosexual, and bisexual, from the five Brazilian regions, highlighting the states of Minas Gerais and São Paulo. The use of alcoholic beverages and other substances, weight change, and the presence of mental diseases were the most frequent self-reported health conditions. Primary health care was mainly evaluated with low overall scores, thus indicating low quality. The attributes "community guidance" and "coordination" (care integration) were marked by unfavorable evaluations, indicating small extensions. People belonging to sexual and gender minorities who worked had kidney problems, had been hospitalized recently, and that had their gender identity and sexual orientation known by health professionals were more likely to evaluate the Primary Health Care as good. Conclusion: This work points out weaknesses in the care of the LGBTQIAP+ population the following attributes: family guidance, accessibility, longitudinality, and available services, which can be prioritized to improve the quality of Primary Health Care in the Brazilian Unified Health System. (AU)

Introdução: Lésbicas, gays, bissexuais, travestis, transexuais, transgêneros, queer, intersexos, assexuais, pansexuais e outras minorias sexuais e de gênero constituem uma população pouco estudada no que se refere ao uso e atendimento em serviços de saúde. Objetivo: Nessa perspectiva, o objetivo geral deste estudo foi avaliar a qualidade da Atenção Primária à Saúde segundo integrantes de minorias sexuais e de gênero. Método: Trata-se de uma pesquisa avaliativa, com delineamento transversal, descritivo-analítico, de abordagem quantitativa, por meio de web survey no Brasil. O roteiro de coleta abordou características sociodemográficas, de orientação sexual, identidade de gênero, condições de saúde autorreferidas e os 23 itens do instrumento Primary Care Assessment Tool, versão reduzida para usuários adultos. Resultados: Os resultados representam 314 pessoas LGBTQIAP+, predominantemente jovens, brancos, cisgêneros, homossexuais e bissexuais, provenientes das cinco regiões brasileiras, com destaque para os estados de Minas Gerais e São Paulo. O uso de bebidas alcoólicas e outras substâncias, a alteração ponderal e a presença de doenças mentais foram as condições de saúde autorreferidas que mais se destacaram. A atenção primária à saúde foi majoritariamente avaliada com baixa pontuação geral, indicando baixa qualidade. Assinalam-se os atributos orientação comunitária e coordenação (integração de cuidados) pelas avaliações negativas, indicando pequena extensão. As pessoas de minorias sexuais e de gênero que trabalhavam, possuíam problema renal, haviam sido internadas recentemente e sua identidade de gênero e orientação sexual eram conhecidas pelos profissionais de saúde apresentaram mais chance de avaliar bem a Atenção Primária à Saúde. Conclusão: Este trabalho aponta como fragilidades no cuidado da população LGBTQIAP+ os atributos de orientação familiar, acessibilidade, longitudinalidade e serviços disponíveis que podem ser priorizadas para a melhoria da qualidade da Atenção Primária à Saúde do Sistema Único de Saúde brasileiro. (AU)

Oclusão do cateter intravascular para hemodiálise: um relato de experiência dos cuidados de enfermagem / Intravascular catheter occlusion for hemodialysis: a nursing care experience reportoclusión de catéter / Intravascular para hemodiálisis: relato de una experiencia de atención de enfermería

Objetivo: Relatar os cuidados de enfermagem em pacientes com obstrução de cateter venoso central para hemodiálise. Método: Trata-se de um estudo descritivo do tipo relato de experiência, desenvolvido durante a participação em um projeto de extensão universitária em serviços de nefrologia na região Nordeste do Brasil. As atividades ocorreram durante os meses de outubro e novembro do ano de 2021, em uma unidade de nefrologia ambulatorial e uma unidade de diálise de um hospital geral. Resultados: Os resultados e discussões foram organizados e apresentados em três subtópicos: Avaliação do cateter venoso central para hemodiálise; Manutenção do cateter venoso central para hemodiálise e Manejo frente a oclusão do cateter venoso central para hemodiálise. Considerações finais: A prática assistencial do enfermeiro é essencial para o desenvolvimento de cuidados que visam a segurança do paciente em hemodiálise, especificamente na avaliação, manutenção e prevenção da oclusão do cateter intravascular, através de cuidados de baixo custo, não invasivos e eficazes, baseados em evidências científicas.

Systematic Review of Functional MRI Applications for Psychiatric Disease Subtyping.

Background: Psychiatric disorders have been historically classified using symptom information alone. Recently, there has been a dramatic increase in research interest not only in identifying the mechanisms underlying defined pathologies but also in redefining their etiology. This is particularly relevant for the field of personalized medicine, which searches for data-driven approaches to improve diagnosis, prognosis, and treatment selection for individual patients. Methods: This review aims to provide a high-level overview of the rapidly growing field of functional magnetic resonance imaging (fMRI) from the perspective of unsupervised machine learning applications for disease subtyping. Following the PRISMA guidelines for protocol reproducibility, we searched the PubMed database for articles describing functional MRI applications used to obtain, interpret, or validate psychiatric disease subtypes. We also employed the active learning framework ASReview to prioritize publications in a machine learning-guided way. Results: From the 20 studies that met the inclusion criteria, five used functional MRI data to interpret symptom-derived disease clusters, four used it to interpret clusters derived from biomarker data other than fMRI itself, and 11 applied clustering techniques involving fMRI directly. Major depression disorder and schizophrenia were the two most frequently studied pathologies (35% and 30% of the retrieved studies, respectively), followed by ADHD (15%), psychosis as a whole (10%), autism disorder (5%), and the consequences of early exposure to violence (5%). Conclusions: The increased interest in personalized medicine and data-driven disease subtyping also extends to psychiatric disorders. However, to date, this subfield is at an incipient exploratory stage, and all retrieved studies were mostly proofs of principle where further validation and increased sample sizes are craved for. Whereas results for all explored diseases are inconsistent, we believe this reflects the need for concerted, multisite data collection efforts with a strong focus on measuring the generalizability of results. Finally, whereas functional MRI is the best way of measuring brain function available to date, its low signal-to-noise ratio and elevated monetary cost make it a poor clinical alternative. Even with technology progressing and costs decreasing, this might incentivize the search for more accessible, clinically ready functional proxies in the future.

C-doping anisotropy effects on borophene electronic transport.

The electronic transport anisotropy for different C-doped borophene polymorphs (ß12andχ3) was investigated theoretically combining density functional theory and non-equilibrium Green's function. The energetic stability analysis reveals that B atoms replaced by C is more energetically favorable forχ3phase. We also verify a directional character of the electronic band structure on C-doped borophene for both phases. Simulated scanning tunneling microscopy and also total density of charge confirm the directional character of the bonds. The zero bias transmission forß12phase atE-EF= 0 shows that C-doping induces a local current confinement along the lines of doped sites. TheI-Vcurves show that C-doping leads to an anisotropy amplification in theß12than in theχ3. The possibility of confining the electronic current at an specific region of the C-doped systems, along with the different adsorption features of the doped sites, poses them as promising candidates to highly sensitive and selective gas sensors.

Comprehensive Identification of Pathogenic Gene Variants in Patients With Neuroendocrine Disorders.

PURPOSE: Congenital hypopituitarism (CH) can present in isolation or with other birth defects. Mutations in multiple genes can cause CH, and the use of a genetic screening panel could establish the prevalence of mutations in known and candidate genes for this disorder. It could also increase the proportion of patients that receive a genetic diagnosis. METHODS: We conducted target panel genetic screening using single-molecule molecular inversion probes sequencing to assess the frequency of mutations in known hypopituitarism genes and new candidates in Argentina. We captured genomic deoxyribonucleic acid from 170 pediatric patients with CH, either alone or with other abnormalities. We performed promoter activation assays to test the functional effects of patient variants in LHX3 and LHX4. RESULTS: We found variants classified as pathogenic, likely pathogenic, or with uncertain significance in 15.3% of cases. These variants were identified in known CH causative genes (LHX3, LHX4, GLI2, OTX2, HESX1), in less frequently reported genes (FOXA2, BMP4, FGFR1, PROKR2, PNPLA6) and in new candidate genes (BMP2, HMGA2, HNF1A, NKX2-1). CONCLUSION: In this work, we report the prevalence of mutations in known CH genes in Argentina and provide evidence for new candidate genes. We show that CH is a genetically heterogeneous disease with high phenotypic variation and incomplete penetrance, and our results support the need for further gene discovery for CH. Identifying population-specific pathogenic variants will improve the capacity of genetic data to predict eventual clinical outcomes.

The Transcription Factor NF-κB Mediates Thyrotropin-Stimulated Expression of Thyroid Differentiation Markers.

Background: The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factor is a key regulator of cell survival, proliferation, and gene expression. Although activation of NF-κB signaling in thyroid follicular cells after thyrotropin (TSH) receptor (TSHR) engagement has been reported, the downstream signaling leading to NF-κB activation remains unexplored. Here, we sought to elucidate the mechanisms that regulate NF-κB signaling activation in response to TSH stimulation. Methods: Fisher rat-derived thyroid cell lines and primary cultures of NF-κB essential modulator (NEMO)-deficient mice thyrocytes were used as models. Signaling pathways leading to the activation of NF-κB were investigated by using chemical inhibitors and phospho-specific antibodies. Luciferase reporter gene assays and site-directed mutagenesis were used to monitor NF-κB-dependent gene transcriptional activity and the expression of thyroid differentiation markers was assessed by reverse transcription quantitative polymerase chain reaction and Western blot, respectively. Chromatin immunoprecipitation (ChIP) was carried out to investigate NF-κB subunit p65 DNA binding, and small interfering RNA (siRNA)-mediated gene knockdown approaches were used for studying gene function. Results: Using thyroid cell lines, we observed that TSH treatment leads to protein kinase C (PKC)-mediated canonical NF-κB p65 subunit nuclear expression. Moreover, TSH stimulation phosphorylated the kinase TAK-1, and its knockdown abolished TSH-induced NF-κB transcriptional activity. TSH induced the transcriptional activity of the NF-κB subunit p65 in a protein kinase A (PKA)-dependent phosphorylation at Ser-276. In addition, p65 phosphorylation at Ser-276 induced acetyl transferase p300 recruitment, leading to its acetylation on Lys-310 and thereby enhancing its transcriptional activity. Evaluation of the role played by NF-κB in thyroid physiology demonstrated that the canonical NF-κB inhibitor BAY 11-7082 reduced TSH-induced expression of thyroid differentiation markers. The involvement of NF-κB signaling in thyroid physiology was confirmed by assessing the TSH-induced gene expression in primary cultures of NEMO-deficient mice thyrocytes. ChIP and the knockdown experiments revealed that p65 is a nuclear effector of TSH actions, inducing the transcripcional expression of thyroid differentiation markers. Conclusions: Taken together, our results point to NF-κB being a pivotal mediator in the TSH-induced thyroid follicular cell differentiation, a relevant finding with potential physiological and pathophysiological implications.

Toxoplasmose congênita na atenção primária à saúde: importância da prevenção no controle de uma doença negligenciada / Congenital toxoplasmosis in primary health care: the importance of prevention in the control of a neglected disease / Toxoplasmosis congénita en la atención primaria de salud: importancia de la prevención en el control de una enfermedad desatendida

Justificativa e Objetivos: a toxoplasmose é uma doença com grande impacto na saúde pública, responsável por causar sequelas em recém-nascidos com a infecção, apesar de ainda ser negligenciada no Brasil. A doença é potencialmente grave quando há transmissão congênita. O diagnóstico da toxoplasmose durante a gestação é complexo e o tratamento da doença em gestantes não é totalmente eficaz. O presente estudo objetivou realizar um levantamento sobre o conhecimento de gestantes atendidas nas unidades básicas de saúde do município de Jataí/GO sobre a toxoplasmose. Métodos: promover ações educativas com gestantes sobre a doença e formas de prevenção. As ações foram realizadas por acadêmicos do curso de medicina da Universidade Federal de Jataí com 64 gestantes. Resultados: observou-se que faltam informações sobre a doença e formas de prevenção, sendo que 86% das gestantes não conheciam todas as formas de transmissão da toxoplasmose. As participantes relataram também não ter recebido instruções sobre a doença durante o acompanhamento pré-natal. Conclusão: o trabalho evidenciou a falta de informações sobre a toxoplasmose congênita por parte das gestantes, indicando que essas ações na atenção primária à saúde são extremamente valiosas para a prevenção da doença, além de contribuir para a formação de acadêmicos do curso de medicina.(AU)

Background and Objectives: toxoplasmosis is a disease with a great impact on public health, causing sequelae to infected newborns, however, this disease remains neglected in Brazil. The disease is potentially serious when there is congenital transmission. Toxoplasmosis diagnosis during pregnancy is complex and the treatment of the disease in pregnant women is not fully effective. This study aimed at surveying the knowledge of toxoplasmosis in pregnant women cared for at Basic Health Units in the city of Jataí/GO. Methods: to promote educational actions with pregnant women on the disease and forms of prevention. The actions were conducted by medical students from the Universidade Federal de Jataí and includes 64 pregnant women. Results: we observed a lack of information about the disease and its prevention, and 86% of them did not know all forms of transmission of toxoplasmosis. It was also evident that pregnant women report not receiving instructions about the disease during prenatal care. Conclusion: our study evidenced the lack of information on congenital toxoplasmosis in pregnant women, indicating that these actions in primary care are extremely valuable to prevent the disease, in addition to contributing to the training of medical students.(AU)

Justificación y Objetivos: la toxoplasmosis es una enfermedad con un gran impacto en la salud pública, causante de secuelas en recién nacidos con esta infección, a pesar de que todavía se descuida en Brasil. La enfermedad es potencialmente grave cuando hay transmisión congénita. El diagnóstico de toxoplasmosis durante el embarazo es complejo, y el tratamiento de la enfermedad en mujeres embarazadas no es totalmente efectivo. Este estudio tuvo como objetivo llevar a cabo una encuesta sobre el conocimiento de la toxoplasmosis en mujeres embarazadas atendidas en las unidades básicas de salud en la ciudad de Jataí, estado de Góias (Brasil). Métodos: promover acciones educativas sobre la enfermedad con mujeres embarazadas y las formas de prevención. Las acciones fueron realizadas por estudiantes de medicina de la Universidade Federal de Jataí con 64 mujeres embarazadas. Resultados: existe una falta de información sobre la enfermedad y las formas de prevenirla, y el 86% de ellas no conocían todas las formas de transmisión de toxoplasmosis. También fue evidente que las mujeres embarazadas informaron que no recibieron instrucciones sobre la enfermedad durante la atención prenatal. Conclusión: el estudio puso de manifiesto la falta de información sobre la toxoplasmosis congénita por parte de las mujeres embarazadas, lo que indica que estas acciones en atención primaria son muy valiosas para prevenir la enfermedad, además de contribuir a la formación de estudiantes de medicina.(AU)

Acetic Acid Fermentation of Soybean Molasses and Characterisation of the Produced Vinegar.

Soybean molasses is a by-product from the production of protein concentrate from soybean meal that predominantly contains sugars, with sucrose as the major component. In Brazil, soybean molasses is used for animal feed or it is discarded, although some industries use it to produce ethanol. This study aims to evaluate the parameters required for the acetic acid fermentation of soybean molasses, and characterise the resultant vinegar. To study the most suitable parameters for the acetic acid fermentation, vinegar was produced from the alcohol fermentation of soybean molasses through eight fermentation cycles: five for adaptation and three for production. The average acidity of the acetic acid fermentation product was 50.60 g/L, with an acetic acid fermentation yield, total yield of acetic acid in broth and productivity 65.01%, 92.76% and 0.033 g/(L·h), respectively. The vinegar produced from soybean molasses has an acidity of 5.07% (m/V), residual ethanol content 0.17% (m/V), sugars 7.86% (m/V), dry extract 14.67% (m/V), ash 2.27% (m/V) and a density of 1.023 g/cm3. The contents of total phenolics and isoflavones decreased after the alcohol and acetic acid fermentations. Moreover, the isoflavones profile of the fermented product comprised only three forms: daidzein, glycitin and genistin. According to our results, 3460 L of vinegar can be produced for every tonne of soy molasses, with an acetic acid concentration of 40 g/L, the minimum required by the legislation on vinegar production. Thus, these findings demonstrate that soy molasses represents a useful raw material for the production of vinegar.

Menuria como presentación de fístula vesicouterina / Menouria as vesicouterine fistula presentation

Introducción: las fístulas vesicouterinas son entidades poco frecuentes representando entre el 1 y el 4% de todas las fístulas urogenitales. En el 83% de las ocasiones se establece el antecedente de cesárea segmentaria trans-versa. La clínica es variable, pudiéndose asociar la presencia de incontinencia de orina, menuria y amenorrea. Caso clínico: el caso descrito en este artículo resulta de especial interés debido al diagnóstico pasados dos años del antecedente de cesárea junto con la presencia de incontinencia urinaria y menuria. Como tratamiento se optó por la cirugía vía laparoscópica con reparación vesical e histerectomía por deseos genésicos cumplidos. Discusión: según la bibliografía revisada sobre esta patología el diagnóstico se realiza mediante técnicas de imagen como la cistografía e histeroscopia con azul de metileno. El tratamiento quirúrgico con reparación de la fístula se sabe que presenta resultados satisfactorios; se puede optar por el tratamiento conservador en los casos de fístulas de pequeño tamaño y diagnosticadas precozmente

Introduction: Vesicouterine fistulas are a rare entity, representing between 1 and 4 % of all the urogenital fistulas. In up to 83% of cases there is a previous segmental transverse cesarean section. Clinical manifestations are diverse, and might simultaneously comprise urinary incontinence, menouria and amenorrhea. Case report: The case reported in this article is of special interest due to the delayed diagnosis, two years after the cesarean section, presenting symptoms being urinary incontinence and menouria. The patient was treated with laparoscopic bladder reparation and hysterectomy due to fulfilled reproductive expectations. Discussion: Based on a literature review of the topic diagnosis is established with imaging techniques, such as cystography and hysteroscopy with methylene blue. Surgical repair shows good results, although a conservative approach might be preferred for small and early-diagnosed fistulas

Physicochemical Characterization and Skin Permeation of Cationic Transfersomes Containing the Synthetic Peptide PnPP-19.

BACKGROUND: PnPP-19 is a 19-amino-acid synthetic peptide previously described as a novel drug for the treatment of erectile dysfunction. OBJECTIVE: The aim of this work was to evaluate the physicochemical properties of cationic transfersomes containing PnPP-19 and the skin permeation of free PnPP-19 and PnPP-19-loaded transfersomes. METHODS: Three different liposomal preparation methods were evaluated. Cationic transfersomes contained egg phosphatidyl choline: stearylamine (9:1 w/w) and Tween 20 (84.6:15.4 lipid:Tween, w/w). Lipid concentration varied from 20 to 40 mM. We evaluated the entrapment percentage, mean diameter, zeta potential and stability at 4 °C of the formulations. The skin permeation assays were performed with abdominal human skin using Franz diffusion cell with 3 cm2 diffusion area at 32 °C and a fluorescent derivative of the peptide, containing 5-TAMRA, bound to PnPP-19 C-terminal region, where an extra lysine was inserted. RESULTS: Our results showed variable entrapment efficiencies, from 6% to 30%, depending on the preparation method and the lipid concentration used. The reverse phase evaporation method using a total lipid concentration equal to 40 mM led to the best entrapment percentage (30.2 + 4.5%). Free PnPP-19 was able to permeate skin at a rate of 10.8 ng/cm2/h. However, PnPP-19 was specifically hydrolyzed by skin proteases, generating a fragment of 15 amino acid residues. Encapsulated PnPP-19 permeated the skin at a rate of 19.8 ng/cm2/h. CONCLUSION: The encapsulation of PnPP-19 in cationic transfersomes protected the peptide from degradation, favoring its topical administration.

Aflatoxins and ochratoxin A in different cocoa clones (Theobroma cacao L.) developed in the southern region of Bahia, Brazil.

Brazil is the sixth largest producer of cocoa beans in the world, after Côte d'Ivoire, Ghana, Indonesia, Nigeria and Cameroon. The southern region of Bahia stands out as the country's largest producer, accounting for approximately 60% of production. Due to damage caused by infestation of the cocoa crop with the fungus Moniliophthora perniciosa, which causes 'witch's broom disease', research in cocoa beans has led to the cloning of species that are resistant to the disease; however, there is little information about the development of other fungal genera in these clones, such as Aspergillus, which do not represent a phytopathogenicity problem but can grow during the pre-processing of cocoa beans and produce mycotoxins. Thus, the aim of this work was to determine the presence of aflatoxin (AF) and ochratoxin A (OTA) in cocoa clones developed in Brazil. Aflatoxin and ochratoxin A contamination were determined in 130 samples from 13 cocoa clones grown in the south of Bahia by ultra-performance liquid chromatography with a fluorescence detector. The method was evaluated for limit of detection (LOD) (0.05-0.90 µg kg-1), limit of quantification (0.10-2.50 µg kg-1) and recovery (RSD) (89.40-95.80%) for AFB1, AFB2, AFG1, AFG2 and OTA. Aflatoxin contamination was detected in 38% of the samples in the range of

Discursos de profesionales de la salud y de mujeres sobre el aborto voluntario / Discourses of health professionals and voluntary women about abortion

El presente artículo indaga los significados del aborto voluntario desde el discurso de los profesionales sanitarios involucrados en ello y de mujeres que han experimentado una interrupción voluntaria del embarazo. Se toma como referencia la ley aprobada en España en el año 2010 y el objetivo es conocer como los sujetos implicados en este proceso social y de salud resignifican la ley con sus propios discursos en función de sus parámetros culturales y su rol en dicho proceso. Surgen así nomenclaturas, adjetivos y condicionantes sociales variados a pesar de encontrarnos ante un proceso que parece estar unificado, consensuado y aceptado ante la legislación, la sociedad y el modelo médico hegemónico (AU)

This article examines the different meanings of voluntary abortion which are given not only by the health professionals but also by women who have been involved in this situation. In this way, the last law approved in Spain in 2010 is taken as a reference. The aim is to know how the subjects involved in this social and health process resignify the law via their own point of view related to their cultural parameters and their role in the abortion process. For instance, it seems to be unified and approved by consensus with the legislation, society and the hegemonic medical model. However, although this matter is involved in a standard process, this issue arises many nomenclatures, adjectives and varied social conditions (AU)

Púrpura trombocitopénica trombótica puerperal / Postpartum thrombotic thrombocytopenic purpura

La púrpura trombocitopénica trombótica es una enfermedad multisistémica de etiología desconocida. Se han observado diversas circunstancias que pueden actuar como factores predisponentes: la gestación, un proceso infeccioso, los anticonceptivos orales y la cirugía. Las mujeres embarazadas o en el período posparto representan un 10% de los casos de púrpura trombocitopénica trombótica, con una incidencia aproximada de un caso de cada 25.000 partos. Presentamos un caso clínico de una mujer que desarrolló púrpura trombocitopénica trombótica a los 6 días de habérsele realizado una cesárea, sin otros hallazgos significativos, enfatizando la importancia de reconocer esta afección en vista de la similitud con otras enfermedades durante el embarazo (AU)

Thrombotic thrombocytopenic purpura is a multisystem disease of unknown etiology. There are various predisposing factors, such as pregnancy, an infectious process, oral contraceptives, and surgery. Pregnant or postpartum women represent 10% of cases of thrombotic thrombocytopenic purpura, with an approximate incidence of one in 25,000 births. We report the case of a woman who developed thrombotic thrombocytopenic purpura 6 days after undergoing a caesarean section without other significant findings, emphasizing the importance of distinguishing this disease from other, highly similar illnesses during pregnancy (AU)

Embolización de las arterias uterinas en hematoma disecante de la episiotomía / Uterine artery embolization in dissecting hematoma after episiotomy

Antecedentes. La hemorrragia posparto es una complicación potencialmente grave, siendo de vital importancia que el diagnóstico y el tratamiento tengan lugar de forma precoz. Dentro de los sangrados posparto cabe mencionar los hematomas del canal del parto. Caso. Presentamos un caso grave de hematoma del canal del parto que requirió técnica de embolización selectiva tras el fracaso del tratamiento quirúrgico local, con shock hipovolémico y coagulación intravascular diseminada. Conclusión. Hay que tener en cuenta que la embolización precisa de una infraestuctura y tecnología que se encuentran en hospitales de tercer nivel; la premura en el diagnóstico y una paciente estable hemodinámicamente permitirán el abordaje mediante técnicas de embolización. La embolización de las arterias uterinas en manos expertas permitirá preservar la fertilidad futura de la paciente con escasas complicaciones (AU)

Background. Postpartum hemorrhage is a potentially serious complication and includes bruising of the birth canal. It is vitally important that the diagnosis and treatment take place at an early stage. Case. We report a serious case of bruising of the birth canal that required selective embolization after unsuccessful local surgical treatment, with hypovolemic shock and disseminated intravascular coagulation. Conclusion. Embolization requires an infrastructure and technology that are available in tertiary care hospitals. Early diagnosis allows embolization to be performed in hemodynamically stable patients. Uterine artery embolization in expert hands enables future fertility to be preserved with few complications (AU)