A case report of BIA-ALCL: Diagnostic, treatment, and mammary reconstruction.

INTRODUCTION AND IMPORTANCE: BIA-ALCL is a non-Hodgkin lymphoma occurring primarily in women with textured breast implants, typically presenting as late seroma. Diagnosis involves ultrasound-guided fine-needle aspiration or core needle biopsy, followed by cytologic and immunohistochemical evaluation. Positive results show CD30 cell expression and lack ALK expression. Treatment includes removing breast implants and the periprosthetic capsule. If the lymphoma has spread, en bloc capsulectomy, immunotherapy, and chemotherapy are required. Reconstruction can be done with smooth implants or autologous tissue. PRESENTATION OF CASE: We present here the case of a woman with a 12-year history of microtextured breast implants, without any cancer family background, who presented with peri-implant effusion in the left breast, which tested positive for BIA-ALCL at stage IA. The patient underwent breast implant removal with total capsulectomy and posterior successful autologous tissue reconstruction, demonstrating that outcomes can be satisfactory when properly treated. CLINICAL DISCUSSION: Paying attention to signs in women with breast implants, beyond imaging tests, can aid in the early diagnosis of BIA-ALCL and ensure a not aggressive treatment. This approach allows the reconstruction with autologous tissue without the need of further implants. CONCLUSION: BIA-ALCL is a rare disease, further studies about this lymphoma can help with early diagnosis and potential prevention.

Similar hypothyroid and sepsis circulating mRNA expression could be useful as a biomarker in nonthyroidal illness syndrome: a pilot study

ABSTRACT Objective: Based on hypothetical hypothyroidism and nonthyroidal illness syndrome (NTIS) gene expression similarities, we decided to compare the patterns of expression of both as models of NTIS. The concordant profile between them may enlighten new biomarkers for NTIS challenging scenarios. Materials and methods: We used Ion Proton System next-generation sequencing to build the hypothyroidism transcriptome. We selected two databanks in GEO2 platform datasets to find the differentially expressed genes (DEGs) in adults and children with sepsis. The ROC curve was constructed to calculate the area under the curve (AUC). The AUC, chi-square, sensitivity, specificity, accuracy, kappa and likelihood were calculated. We performed Cox regression and Kaplan-Meier analyses for the survival analysis. Results: Concerning hypothyroidism DEGs, 70.42% were shared with sepsis survivors and 61.94% with sepsis nonsurvivors. Some of them were mitochondrial gene types (mitGenes), and 95 and 88 were related to sepsis survivors and nonsurvivors, respectively. BLOC1S1, ROMO1, SLIRP and TIMM8B mitGenes showed the capability to distinguish sepsis survivors and nonsurvivors. Conclusion: We matched our hypothyroidism DEGs with those in adults and children with sepsis. Additionally, we observed different patterns of hypothyroid-related genes among sepsis survivors and nonsurvivors. Finally, we demonstrated that ROMO1, SLIRP and TIMM8B could be predictive biomarkers in children's sepsis.

APOL1 in an ethnically diverse pediatric population with nephrotic syndrome: implications in focal segmental glomerulosclerosis and other diagnoses.

BACKGROUND: APOL1 high-risk genotypes (HRG) are associated with increased risk of kidney disease in individuals of African ancestry. We analyzed the effects of APOL1 risk variants on an ethnically diverse Brazilian pediatric nephrotic syndrome (NS) cohort. METHODS: Multicenter study including 318 NS patients, categorized as progressors to advanced CKD [estimated glomerular filtration rate (eGFR)] < 30 mL/min/1.73 m2] and slow/non-progressors (eGFR > 30 mL/min/1.73 m2 through the study). We employed Cox regression with progression time as the outcome and APOL1 genotype as the independent variable. We tested this association in the entire cohort and three subgroups; (1) focal segmental glomerulosclerosis (FSGS), (2) steroid-resistant NS (SRNS), and (3) those who underwent kidney biopsy. RESULTS: Nineteen patients (6%) had an HRG. Of these, 47% were self-reported White. Patients with HRG manifested NS at older ages and presented higher frequencies of FSGS and SRNS. HRG patients progressed to advanced CKD more often than low-risk-genotype (LRG) children in the whole NS cohort (p = 0.001) and the three subgroups. In SRNS and biopsied patients, a single risk variant was associated with trends of higher CKD progression risk. CONCLUSIONS: Novel discoveries include a substantial prevalence of HRG among patients self-reported White, worse kidney outcomes in HRG versus LRG children in the FSGS subgroup, and a trend of higher CKD progression risk associated with a single risk variant in the SRNS cohort. These findings suggest APOL1-associated NS extends beyond patients self-reported non-White, the HRG effect is independent of FSGS, and a single risk variant may have a detrimental impact in children with NS.

Fabry disease: GLA deletion alters a canonical splice site in a family with neuropsychiatric manifestations.

Fabry disease (FD) is a rare X-linked glycosphingolipidosis caused by mutations in GLA, a gene responsible for encoding α-galactosidase A, an enzyme required for degradation of glycosphingolipids, mainly globotriaosylceramide (Gb3) in all cells of the body. FD patients present a broad spectrum of clinical phenotype and many symptoms are shared with other diseases, making diagnosis challenging. Here we describe a novel GLA variant located in the 5' splice site of the intron 3, in four members of a family with neuropsychiatric symptoms. Analysis of the RNA showed the variant promotes alteration of the wild type donor site, affecting splicing and producing two aberrant transcripts. The functional characterization showed absence of enzymatic activity in cells expressing both transcripts, confirming their pathogenicity. The family presents mild signs of FD, as angiokeratoma, cornea verticillata, acroparesthesia, tinnitus, vertigo, as well as accumulation of plasma lyso-Gb3 and urinary Gb3. Interestingly, the man and two women present psychiatric symptoms, as depression or schizophrenia. Although psychiatric illnesses, especially depression, are frequently reported in patients with FD and studies have shown that the hippocampus is an affected brain structure in these patients, it is not clear whether the Gb3 accumulation in the brain is responsible for these symptoms or they are secondary. Therefore, new studies are needed to understand whether the accumulation of Gb3 could produce neuronal alterations leading to psychiatric symptoms.

Cathepsin L in COVID-19: From Pharmacological Evidences to Genetics.

The coronavirus disease 2019 (COVID-19) pandemics is a challenge without precedent for the modern science. Acute Respiratory Discomfort Syndrome (ARDS) is the most common immunopathological event in SARS-CoV-2, SARS-CoV, and MERS-CoV infections. Fast lung deterioration results of cytokine storm determined by a robust immunological response leading to ARDS and multiple organ failure. Here, we show cysteine protease Cathepsin L (CatL) involvement with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 from different points of view. CatL is a lysosomal enzyme that participates in numerous physiological processes, including apoptosis, antigen processing, and extracellular matrix remodeling. CatL is implicated in pathological conditions like invasion and metastasis of tumors, inflammatory status, atherosclerosis, renal disease, diabetes, bone diseases, viral infection, and other diseases. CatL expression is up-regulated during chronic inflammation and is involved in degrading extracellular matrix, an important process for SARS-CoV-2 to enter host cells. In addition, CatL is probably involved in processing SARS-CoV-2 spike protein. As its inhibition is detrimental to SARS-CoV-2 infection and possibly exit from cells during late stages of infection, CatL could have been considered a valuable therapeutic target. Therefore, we describe here some drugs already in the market with potential CatL inhibiting capacity that could be used to treat COVID-19 patients. In addition, we discuss the possible role of host genetics in the etiology and spreading of the disease.

Percepções das gestantes quanto à escolha da via de parto / Perceptions of pregnant women regarding the choice of the route of deliver

Esta pesquisa teve como objetivo conhecer as percepções das gestantes quanto à escolha da via de parto. Trata-se de um estudo descritivo com abordagem qualitativa, realizado com gestantes de um município da região noroeste do Estado do Paraná. Os dados foram coletados por meio de entrevistas semiestruturadas, audiogravadas. Para o tratamento dos dados, adotou-se o discurso do sujeito coletivo. Participaram 20 gestantes, das quais 13 realizaram o parto cesárea. De acordo com as respostas das entrevistas foram geradas 25 expressões-chaves e delas originaram-se cinco ideias centrais: A ­ "Preferência pelo parto normal", na qual metade das gestantes optou inicialmente por essa via de parto; B ­ "Indicação da via de parto cesárea", escolhida por nove gestantes (45%) com indicação médica, a despeito da preferência prévia pelo parto normal; C ­ "Escolha de via de parto cesárea", com quatro (20%) mulheres que escolheram essa via por medo da dor; D ­ "Satisfação com via de parto realizada", via pela qual todas as mulheres (35%) que realizaram parto normal expressaram satisfação; e E ­ "Dualidade entre satisfação e sofrimento com a via de parto realizada", misto de sentimento vivenciado por todas mulheres que realizaram cesárea. Concluiu-se que metade das gestantes tem preferência pelo parto normal, mas a maioria acabou por realizar o parto cesárea. Na percepção das entrevistadas, as escolhas da via de parto cesáreo foram decorrentes de indicação médica, medo, insegurança e desejo pela laqueadura. Sugerem-se ações educativas esclarecedoras para diminuir inseguranças nas decisões das gestantes e possibilitar autonomia na escolha consciente quanto à via de parto.

This study aimed to know the perceptions of pregnant women regarding the choice of the route of delivery. Descriptive study with a qualitative approach was conducted with pregnant women from a municipality in the Northwest region of the State of Paraná. Data were collected through semi-structured, audio-recorded interviews. For data treatment, the discourse of the collective subject was adopted. Participants were twenty pregnant women, 13 of whom undergoing cesarean delivery. According to the responses to the interviews, 25 key expressions were generated and five central ideas were originated: A ­ "Preference for vaginal childbirth", in which half of the pregnant women initially opted for this route of delivery; B ­ "Indication for cesarean section", with nine pregnant women (45%) with medical indication, despite the previous preference for vaginal delivery; C ­ "Choice for cesarean section", with four (20%) women who chose this route due to fear of labor pain; D ­ "Satisfaction with the route of delivery performed", in which all women (35%) undergoing vaginal delivery expressed satisfaction with this route; E ­ "Duality between satisfaction and suffering with the childbirth performed", in which all women who underwent cesarean section experienced this mixed feeling. This study concluded that half of the pregnant women have a preference for vaginal delivery, but the majority had a cesarean delivery. In the perception of pregnant women, the choices for cesarean delivery were due to medical indication, fear, insecurity and desire for sterilization. Educational actions are suggested to reduce insecurities in the decisions of pregnant women and enable autonomy in the conscious choice regarding the route of delivery.

Competências gerenciais na perspectiva de enfermeiros do contexto hospitalar / Management competencies in the perspective of nurses in the hospital context

Objetivo: Descrever a percepção de enfermeiros acerca das competências gerenciais no contexto hospitalar. Método: Estudo descritivo realizado em um hospital no noroeste do Paraná, com dados coletados junto a 25 enfermeiros. Utilizou-se instrumento composto por questões de caracterização sociodemográfica e voltadas à percepção acerca da importância das competências gerenciais na prática do enfermeiro. As respostas foram dispostas em escala do tipo Likert, em que, quanto maior o escore mais indispensável era considerada a competência. Os dados foram analisados utilizando estatística descritiva. Resultados: 76% dos participantes eram do sexo feminino, com idade media de 35 anos. O domínio liderança obteve escore de 44,84 (DP±0,8), comunicação de 14,52 (DP±1,32), tomada de decisão de 16,12 (DP±3,2) e o planejamento e organização de 17,24 (DP±1,56). Todos os domínios obtiveram pontuação próxima ao escore máximo. Conclusão: Os enfermeiros percebem como indispensáveis as competências gerenciais determinadas para a formação, em sua prática profissional no contexto hospitalar. (AU)

Objective: To describe the perception of nursesabout managerial competencies in the hospital context. Method: A descriptive study performed in a hospital in the northwest of Paraná, Brazil, with data collected from 25 nurses. It was used an instrument composed of questions of sociodemographic characterization and focused on the perception about the importance of managerial competences in nurses' practice, being they leadership, communication, decision making and planning and organization. The answers were arranged in a Likert scale, in which the higher the score, the more indispensable the competence was considered. Data were analyzed using descriptive statistics. Results: 76% of the participants were female, with a mean age of 35 years. The leadership domain obtained a score of 44.84 (SD ± 0.8), communication of 14.52 (SD ± 1.32), decision making of 16.12 (SD ± 3.2) and planning and organization of 17.24 (SD ± 1.56). All domains scored near the maximum score. Conclusion: Nurses perceive as indispensable the managerial competences determined for the training, in their professional practice in the hospital context. (AU)

Objetivos: Describir la percepción de enfermeros acerca de las competencias gerenciales en el contexto hospitalario. Método: Estudio descriptivo realizado en un hospital en el noroeste de Paraná, Brasil, con datos recogidos junto a 25 enfermeros. Se utilizó instrumento compuesto por cuestiones de caracterización sociodemográfica y orientadas a la percepción acerca de la importancia de las competencias gerenciales en la práctica del enfermero, ya sean liderazgo, comunicación, toma de decisiones y planificación y organización. Las respuestas fueron dispuestas a escala del tipo Likert, en que, cuanto mayor el puntaje más indispensable era considerada la competencia. Los datos fueron analizados utilizando estadística descriptiva. Resultados: 76% de los participantes eran del sexo femenino, con edad media de 35 años. El dominio de liderazgo obtuvo una puntuación de 44,84 (DP ± 0,8), comunicación de 14,52 (DP ± 1,32), toma de decisión de 16,12 (DP ± 3,2) y la planificación y organización de 17,24 (DP ± 1,56). Todos los dominios obtuvieron una puntuación cercana a la puntuación máxima. Conclusión: Los enfermeros perciben como indispensables las competencias gerenciales determinadas para la formación, en su práctica profesional en el contexto hospitalario. (AU)

Exomes of Ductal Luminal Breast Cancer Patients from Southwest Colombia: Gene Mutational Profile and Related Expression Alterations.

Cancer is one of the leading causes of mortality worldwide. Breast cancer is the most frequent cancer in women, and in recent years it has become a serious public health problem in Colombia. The development of large-scale omic techniques allows simultaneous analysis of all active genes in tumor cells versus normal cells, providing new ways to discover the drivers of malignant transformations. Whole exome sequencing (WES) was obtained to provide a deep view of the mutational genomic profile in a set of cancer samples from Southwest Colombian women. WES was performed on 52 tumor samples from patients diagnosed with invasive breast cancer, which in most cases (33/52) were ductal luminal breast carcinomas (IDC-LM-BRCA). Global variant call was calculated, and six different algorithms were applied to filter out false positives and identify pathogenic variants. To compare and expand the somatic tumor variants found in the Colombian cohort, exome mutations and genome-wide expression alterations were detected in a larger set of tumor samples of the same breast cancer subtype from TCGA (that included DNA-seq and RNA-seq data). Genes with significant changes in both the mutational and expression profiles were identified, providing a set of genes and mutations associated with the etiology of ductal luminal breast cancer. This set included 19 single mutations identified as tumor driver mutations in 17 genes. Some of the genes (ATM, ERBB3, ESR1, TP53) are well-known cancer genes, while others (CBLB, PRPF8) presented driver mutations that had not been reported before. In the case of the CBLB gene, several mutations were identified in TCGA IDC-LM-BRCA samples associated with overexpression of this gene and repression of tumor suppressive activity of TGF-ß pathway.

Correlation between GLA variants and alpha-Galactosidase A profile in dried blood spot: an observational study in Brazilian patients.

BACKGROUND: Fabry disease is a rare X-linked inherited disorder caused by deficiency of α-Galactosidase A. Hundreds of mutations and non-coding haplotypes in the GLA gene have been described; however, many are variants of unknown significance, prompting doubts about the diagnosis and treatment. The α-Galactosidase A enzymatic activity in dried blood spot (DBS) samples are widely used for screening purposes; however, even when values below the normal are found, new tests are required to confirm the diagnosis. Here we describe an analysis of GLA variants and their correlation with DBS α-Galactosidase A enzymatic activity in a large Brazilian population with Fabry disease symptoms. RESULTS: We analyzed GLA variants by DNA sequencing of 803 male patients with suspected Fabry disease or belonging to high-risk populations; in 179 individuals, 58 different exonic variants were detected. From these, 50 are variants described as pathogenic and eight described as variants of unknown significance. The other individuals presented complex non-coding haplotypes or had no variants. Interestingly, the enzymatic activity in DBS was different among pathogenic variants and the other genotypes, including variants of unknown significance; the first presented mean of 12% of residual activity, while the others presented levels above 70% of the activity found in healthy controls. CONCLUSION: The activity of α-Galactosidase A in DBS was markedly reduced in males with known pathogenic variants when compared with subjects presenting variants of unknown significance, non-coding haplotypes, or without variants, indicating a possible non-pathogenic potential of these latter genotypes. These findings bring a better understanding about the biochemical results of α-Galactosidase A in DBS samples, as well as the possible non-pathogenic potential of non-coding haplotypes and variants of unknown significance in GLA gene. These results certainly will help clinicians to decide about the treatment of patients carrying variants in the gene causing this rare but life-threatening disease.

Functional Characterization and Pharmacological Evaluation of a Novel GLA Missense Mutation Found in a Severely Affected Fabry Disease Family.

BACKGROUND: Fabry disease (FD) is a rare X-linked storage disorder resulting from the deficient activity of the lysosomal hydrolase α-galactosidase A (α-Gal A). Here we describe a 23-year-old man with FD possessing a novel mutation in the GLA gene, the evaluation of his family, and the functional characterization of the novel variant. METHODS: Two generations of a family were screened for FD by clinical symptoms and low enzymatic activity. This step was followed by DNA sequencing that showed a novel GLA missense mutation. To confirm the pathogenicity potential of the mutation, we employed site-directed polymerase chain reaction mutagenesis. GLA wild-type and mutant plasmids were transfected into mammalian cells; RNA and proteins were extracted for expression and analysis of enzymatic activity. RESULTS: The patient presents the variant p.Asn34Asp in the GLA and had several manifestations of FD since adolescence. The investigation of the deficiency of α-Gal A was initiated due to stage 4 of chronic kidney disease. All family members carrying the novel mutation presented early symptoms, including index case's mother, who received a renal transplant when she was 35 years old. In silico and in vitro analysis confirmed the pathogenic potential of the mutation p.Asn34Asp showing that the enzyme had only 4% of residual activity due to protein misfolding. The ability of the pharmacological chaperone 1-deoxygalactonojirimycin to recover the mutant was confirmed, producing 37.5% of residual activity. CONCLUSION: In this work, we present a novel missense mutation in GLA that leads to the production of a catalytically competent α-Gal A, which is degraded before its delivery to the lysosome, promoting severe manifestations of FD, with a very similar disease course in affected men and women.

Macrophage immunomodulation: An indispensable tool to evaluate the performance of wound dressing biomaterials.

A major burden of the healthcare system resides in providing proper medical treatment for all types of chronic wounds, which are usually treated with dressings to induce a faster regeneration. Hence, to reduce healing time and improve the patient's quality of life, it is extremely important to select the most appropriate constituent material for a specific wound dressing. A wide range of wound dressings exist but their mechanisms of action are poorly explored, especially concerning the immunomodulatory effects that occur from the interactions between immune cells and the biomaterial. Tissue-resident and monocyte-derived recruited macrophages are key regulators of wound repair. These phagocytic immune cells exert specific functions during the different stages of wound healing. The recognition of the substantial role of macrophages in the outcome of the wound healing process requires specific understanding of the immunomodulatory effects of commercially available or newly developed wound dressings. For a precise intervention, it is necessary to obtain more knowledge on macrophage polarization in different phases of wound healing in the presence of the dressings. The main purpose of this review is to collect clinical cases in which macrophage immunomodulation was taken into consideration as an indicator of the performances of novel or mainstream wound dressing materials, including those provided with antimicrobial properties.

Chemotherapy-induced fatigue is associated with changes in gene expression in the peripheral blood mononuclear cell fraction of patients with locoregional breast cancer.

PURPOSE: Chemotherapy-induced fatigue (CIF) is a frequent symptom that impairs patient functioning and quality of life. We aimed to evaluate whether systemic chemotherapy can induce a specific gene expression profile in peripheral blood mononuclear cells (PBMNC) of patients with locoregional breast cancer (LRBC) who develop CIF. METHODS: PBMNC were collected from 3 patients who developed CIF before and after their initial cycle of chemotherapy, and RNA-seq was performed in an Ion Torrent™ System. A total of 12.345 transcripts were sequenced, of which 26 were selected out of 71 that had significantly different expression before and after chemotherapy. The RNA-seq results were validated by RT-qPCR in a different group of 28 patients with LRBC who developed CIF after their first cycle of chemotherapy and in six patients who also received chemotherapy but did not develop CIF (controls). We assessed CIF according the BFI and Chalder Questionnaires. RESULTS: We observed a significant increase in expression of DUSP18 and RHOBTB1 and decreased expression of NCAN and RAET1G in patients who developed CIF after chemotherapy. Control patients only exhibited a significant decrease in NCAN expression. CONCLUSION: CIF induces specific changes in gene expression in the PBMNC of LRBC patients. Some of these changes, such as downregulation of NCAN expression, may reflect direct effects of chemotherapy since they are also observed in the controls. Furthermore, CIF may involve downregulation of skeletal muscle genes (RHOBT1, DUSP18) and immune systems (RAETG1), whereas NCAN downregulation may underlie the adverse cognitive effects of chemotherapy.

Hospitalization during pregnancy according to childbirth financial coverage: a population-based study. / Hospitalização durante a gravidez segundo financiamento do parto: um estudo de base populacional.

Objective To analyze the occurrence, profile and main causes of hospitalization during pregnancy according to the type of childbirth financial coverage. Method A cross-sectional population-based study carried out with puerperal women through a stratified sample, calculated according to the hospital and the type of childbirth financial coverage source: public sector (SUS) or private (not SUS). The sociodemographic profile, the rate of obstetric complications and the causes of hospitalization were analyzed, coded according to International Classification of Diseases. Results A total of 928 postpartum women were interviewed, of whom 32.2% reported at least one hospitalization during pregnancy. Those with childbirth covered by SUS were less favored because they were the majority among hospitalized women (57.2%), with a higher percentage of adolescents (18.1%), lower education level (91.8%), low family income (39.3%) and fewer prenatal consultations (25.3%). The most frequent causes of hospitalization were "other maternal diseases that complicate pregnancy" (24.6%) (with emphasis on anemia and influenza), urinary tract infection (13.1%), preterm labor (8.7%) and hypertension (7.2%). Conclusion Anemia, influenza, urinary tract infection, preterm labor and hypertension should especially be prevented and treated to avoid hospital admissions during pregnancy, especially among pregnant women covered by SUS.

Hospitalização durante a gravidez segundo financiamento do parto: um estudo de base populacional / Hospitalización durante el embarazo según la financiación del parto: un estudio de base poblacional / Hospitalization during pregnancy according to childbirth financial coverage: a population-based study

RESUMO Objetivo Analisar a ocorrência, o perfil e as principais causas de internação na gravidez por financiamento do parto. Método Estudo transversal de base populacional, realizado com puérperas, por meio de amostra estratificada, calculada segundo o hospital e a fonte de financiamento do parto: setor público (SUS) e privado (não SUS). Foram analisados o perfil sociodemográfico, as taxas de intercorrência obstétrica e as causas de internação, codificadas de acordo com normas da Classificação Internacional de Doenças. Resultados Foram entrevistadas 928 puérperas, das quais 32,2% relataram pelo menos uma internação na gestação. Aquelas com parto SUS mostraram-se menos favorecidas por ser maioria entre as internadas (57,2%), com maior percentual de adolescentes (18,1%), menor escolaridade (91,8%), baixa renda familiar (39,3%) e menor número de consultas pré-natal (25,3%). As causas mais frequentes de internação foram as "outras doenças da mãe que complicam a gravidez" (24,6%) (com destaque para anemia e influenza), infecção do trato urinário (13,1%), trabalho de parto prematuro (8,7%) e hipertensão (7,2%). Conclusão Deve-se prevenir e tratar especialmente anemia, influenza, infecção urinária, trabalho de parto prematuro e hipertensão para evitar internações hospitalares na gravidez, principalmente para gestantes do SUS.

RESUMEN Objetivo Analizar la ocurrencia, el perfil y las principales causas de ingreso hospitalario en el embarazo por financiación del parto. Método Estudio transversal de base poblacional, realizado con puérperas, mediante muestra estratificada, calculada según el hospital y la fuente de financiación del parto: sector público (SUS) y privado (no SUS). Fueron analizados el perfil sociodemográfico, las tasas de alteraciones obstétricas y las causas de hospitalización, codificadas de acuerdo con las normas de la Clasificación Internacional de Enfermedades. Resultados Fueron entrevistadas 928 puérperas, de las que el 32,2% relataron por lo menos una hospitalización en la gestación. Las con parto SUS se mostraron menos favorecidas al ser mayoría entre las hospitalizadas (57,2%), con mayor porcentual de adolescentes (18,1%), menor escolaridad (91,8%), bajos ingresos familiares (39,3%) y menor número de consultas pre natal (25,3%). Las causas más frecuentes de hospitalización fueron las "otras enfermedades de la madre que complican el embarazo" (24,6%) (con énfasis para anemia e influenza), infección del tracto urinario (13,1%), trabajo de parto prematuro (8,7%) e hipertensión (7,2%). Conclusión Se debe prevenir y tratar especialmente anemia, influenza, infección urinaria, trabajo de parto prematuro e hipertensión para evitar ingresos hospitalarios en el embarazo, destacándose las gestantes del SUS.

ABSTRACT Objective To analyze the occurrence, profile and main causes of hospitalization during pregnancy according to the type of childbirth financial coverage. Method A cross-sectional population-based study carried out with puerperal women through a stratified sample, calculated according to the hospital and the type of childbirth financial coverage source: public sector (SUS) or private (not SUS). The sociodemographic profile, the rate of obstetric complications and the causes of hospitalization were analyzed, coded according to International Classification of Diseases. Results A total of 928 postpartum women were interviewed, of whom 32.2% reported at least one hospitalization during pregnancy. Those with childbirth covered by SUS were less favored because they were the majority among hospitalized women (57.2%), with a higher percentage of adolescents (18.1%), lower education level (91.8%), low family income (39.3%) and fewer prenatal consultations (25.3%). The most frequent causes of hospitalization were "other maternal diseases that complicate pregnancy" (24.6%) (with emphasis on anemia and influenza), urinary tract infection (13.1%), preterm labor (8.7%) and hypertension (7.2%). Conclusion Anemia, influenza, urinary tract infection, preterm labor and hypertension should especially be prevented and treated to avoid hospital admissions during pregnancy, especially among pregnant women covered by SUS.

The Challenge of Diagnosis and Indication for Treatment in Fabry Disease

Abstract Fabry disease, caused by deficient alpha-galactosidase A lysosomal enzyme activity, remains challenging to health-care professionals. Laboratory diagnosis in males is carried out by determination of alpha-galactosidase A activity; for females, enzymatic activity determination fails to detect the disease in about two-thirds of the patients, and only the identification of a pathogenic mutation in the GLA gene allows for a definite diagnosis. The hurdle to be overcome in this field is to determine whether a mutation that has never been described determines a ''classic'' or ''nonclassic'' phenotype, because this will have an impact on the decision-making for treatment initiation. Besides the enzymatic determination and GLA gene mutation determination, researchers are still searching for a good biomarker, and it seems that plasma lyso-Gb3 is a useful tool that correlates to the degree of substrate storage in organs. The ideal time for treatment initiation for children and nonclassic phenotype remains unclear.

Pregnancy complications in Brazilian puerperal women treated in the public and private health systems / Intercorrências na gravidez em puérperas brasileiras atendidas nos sistemas público e privado de saúde / Alteraciones durante el embarazo en mujeres brasileras que han dado a luz siendo atendidas en los sistemas públicos y privados de salud

ABSTRACT Objective: to analyze the prevalence of pregnancy complications and sociodemographic profile of puerperal patients with complications, according to the form of financing of the childbirth service. Method: cross-sectional study with interview of 928 puerperal women whose childbirth was financed by the Unified Health System, health plans and private sources (other sources than the Unified Health System). The sample was calculated based on the births registered in the Information System on Live Births, stratified by hospital and form of financing of the childbirth service. Data were analyzed using the chi-square and Fisher's exact tests. Results: the prevalence was 87.8% for all puerperal women, with an average of 2.4 complications per woman. In the case of deliveries covered by the Unified Health System, urinary tract infection (38.2%), anemia (26.0%) and leucorrhea (23.5%) were more frequent. In turn, vaginal bleeding (26.4%), urinary tract infection (23.9%) and leucorrhoea (23.7%) were prevalent in deliveries that were not covered by the Unified Health System. Puerperal women that had their delivery covered by the Unified Health System reported a greater number of intercurrences related to infectious diseases, while women who used health plans and private sources reported intercurrences related to chronic diseases. A higher frequency of puerperal adolescents, non-white women, and women without partner among those assisted in the Unified Health System (p < 0.001). Conclusion: the high prevalence of complications indicates the need for monitoring and preventing diseases during pregnancy, especially in the case of pregnant women with unfavorable sociodemographic characteristics.

RESUMO Objetivo: analisar a prevalência de intercorrências na gravidez e o perfil sociodemográfico das puérperas com intercorrências segundo financiamento do parto. Métodos: estudo transversal com entrevistas a 928 puérperas com partos financiados pelo Sistema Único de Saúde (SUS) e convênios e particulares (não SUS). A amostra foi calculada a partir dos nascimentos registrados no Sistema de Informações sobre Nascidos Vivos, estratificados por hospital e tipo de financiamento do parto. Os dados foram analisados por meio do teste Qui-quadrado e Exato de Fisher. Resultados: para todas puérperas, a prevalência foi 87,8%, com média de 2,4 intercorrências por mulher. Para partos SUS, infecção do trato urinário (38,2%), anemia (26,0%) e leucorreia (23,5%) foram mais frequentes. Para partos não SUS houve maior prevalência de sangramento vaginal (26,4%), infecção do trato urinário (23,9%) e leucorreia (23,7%). Puérperas que realizaram parto pelo SUS relataram maior número de intercorrências relacionadas às doenças infecciosas e as atendidas por convênios e particulares, as relacionadas a doenças crônicas. Observou-se maior frequência de puérperas adolescentes, não brancas e sem companheiro entre aquelas com parto SUS (p<0,001). Conclusão: a elevada prevalência de intercorrências indica necessidade de monitoramento e prevenção dos agravos na gestação, principalmente para gestantes com características sociodemográficas desfavoráveis.

RESUMEN Objetivo: analizar la prevalencia de alteraciones durante el embarazo y el perfil socio-demográfico de los partos con alteraciones, según financiamiento del parto. Método: estudio transversal, con entrevistas a 928 mujeres que han dado a luz siendo financiado tanto por el Sistema Único de Salud como por convenios y particulares (no pertenecientes al Sistema Único de Salud). La muestra fue calculada a partir de los nacimientos registrados en el Sistema de Informaciones sobre Nacidos Vivos, estratificados por hospital y tipo de financiamiento del parto. Los datos fueron analizados por medio del test chi-cuadrado y exacto de Fisher. Resultados: para todas las puérperas, la prevalencia fue 87,8%, con media de 2,4 alteraciones por mujer. Para partos financiados por el Sistema Único de Salud, infección del tracto urinario (38,2%), anemia (26,0%) y leucorrea (23,5%) fueron las más frecuentes. Para partos no realizados por medio del Sistema Único de Salud hubo mayor prevalencia de sangramiento vaginal (26,4%), infección del tracto urinario (23,9%) y leucorrea (23,7%). Las que realizaron parto por el Sistema Único de Salud relataron mayor número de alteraciones relacionadas a las enfermedades infecciosas, mientras que las atendidas por convenios y particulares, las relacionadas a enfermedades crónicas. Se observó mayor frecuencia de adolescentes, no blancas y sin compañero entre aquellas con parto por el Sistema Único de Salud (p<0,001). Conclusión: la elevada prevalencia de alteraciones indica necesidad de monitoramiento y prevención de los agravios en la gestación, principalmente para gestantes con características sociodemográficas desfavorables.

Morbidade materna grave identificada no Sistema de Informações Hospitalares do Sistema Único de Saúde, no estado do Paraná, 2010 / Morbilidad materna severa identificada en el Sistema de Información Hospitalaria del Sistema Nacional de Salud, en el Estado de Paraná, 2010 / Severe maternal morbidity identified in the Hospital Information System of the Brazilian National Health System in Paraná State, Brazil, 2010

OBJETIVO: descrever a morbidade materna grave (near miss) entre mulheres no estado do Paraná, Brasil, em 2010. MÉTODOS: estudo descritivo com dados do Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH/SUS); foram incluídas todas as internações com diagnóstico principal contemplado no Capítulo XV da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde - 10a Revisão - e/ou com registro de procedimentos obstétricos indicativos de near miss; utilizaram-se três critérios definidores de morbidade materna grave. RESULTADOS: foram identificadas 4.890 internações por morbidade materna grave, à taxa de 52,9 internações/1.000 partos, sendo 69,8/1.000 para mulheres de 35 a 39 e 356,6/1.000 para mulheres de 44 a 49 anos; as principais causas de internação foram pré-eclâmpsia (28,2%), hemorragia grave (23,7%) e disfunção do sistema imunológico (14,0%). CONCLUSÃO: evidenciou-se a necessidade de dispensar maior atenção às gestantes a partir de 35 anos de idade que apresentaram maiores taxas de near miss.

OBJETIVOS: describir la morbilidad materna severa (near miss) entre mujeres en el estado de Paraná, Brasil, en 2010. MÉTODOS: estudio descriptivo, transversal con datos del Sistema de Información Hospitalaria (SIH/SUS), fueron incluidas todas las internaciones con diagnóstico principal contemplado en el Capítulo XV de la Clasificación Internacional de Enfermedades - 10a Revisión -, y/o registro de procedimientos indicativos de near miss; se utilizaron tres criterios para la morbilidad materna severa. RESULTADOS: se identificaron 4890 internaciones con morbilidad materna grave, tasa de 52,9 hospitalizaciones/1.000 partos, siendo 69,8/1000 para mujeres entre 35-39 años de edad, y 356.6/1.000 para mujeres entre 44-49 años; las principales causas de hospitalización fueron pre-eclampsia (28,2%), hemorragia grave (23,7%) y disfunción del sistema inmune (14,0%). CONCLUSIÓN: los resultados indican la necesidad de prestar mayor atención a las mujeres en grupos de mayor edad, ya que tenían tasas más altas de near miss.

OBJECTIVE: to describe near miss maternal morbidity among women living in Paraná State, Brazil, in 2010. METHODS: this was a descriptive study using Brazilian National Hospital Information System (SIH/SUS) data on all hospital admissions with primary diagnosis falling under Chapter XV of the International Statistical Classification of Diseases and Related Health Problems 10th Revision and/or with records of obstetric procedures indicative of near misses; three criteria were used to define severe maternal morbidity. RESULTS: 4,890 admissions owing to near miss were identified, with a rate of 52.9 hospitalizations per 1,000 births, a rate of 69.8/1,000 among women aged 35-39 and a rate of 356.6/1,000 among women aged 44-49; the leading causes of hospitalization were preeclampsia (28.2%), haemorrhage (23.7%) and immune system dysfunction (14.0%). CONCLUSION: the results indicate the need to pay greater attention to women aged 35 and over since they had higher rates of near miss.

Exploring NAD+ metabolism in host-pathogen interactions.

Nicotinamide adenine dinucleotide (NAD(+)) is a vital molecule found in all living cells. NAD(+) intracellular levels are dictated by its synthesis, using the de novo and/or salvage pathway, and through its catabolic use as co-enzyme or co-substrate. The regulation of NAD(+) metabolism has proven to be an adequate drug target for several diseases, including cancer, neurodegenerative or inflammatory diseases. Increasing interest has been given to NAD(+) metabolism during innate and adaptive immune responses suggesting that its modulation could also be relevant during host-pathogen interactions. While the maintenance of NAD(+) homeostatic levels assures an adequate environment for host cell survival and proliferation, fluctuations in NAD(+) or biosynthetic precursors bioavailability have been described during host-pathogen interactions, which will interfere with pathogen persistence or clearance. Here, we review the double-edged sword of NAD(+) metabolism during host-pathogen interactions emphasizing its potential for treatment of infectious diseases.

Perfil obstétrico de usuárias do Sistema Único de Saúde após implantação da Rede Mãe Paranaense / Obstetric profile of public health system users after implantation of the Network Mother from the State of Paraná-Brazil

Este estudo teve por objetivo descrever o perfil sociodemográfico e obstétrico das puérperas residentes em Maringá, atendidas pela Rede Mãe Paranaense. Estudo descritivo realizado com 592 puérperas por meio de entrevista, consulta ao cartão da gestante e prontuário hospitalar, entre 2013 e 2014.Encontraram-se, em sua maior parte, mulheres pardas (44,8%), com ensino médio completo (46,1%), a maioria em união estável (86,3%), e ocupação remunerada (52,0%). Das entrevistadas, 67,8% iniciaram precocemente o pré-natal e 74,0% realizaram sete ou mais consultas. Entretanto, apenas 35,3% planejaram a gravidez, 38,3% participaram de grupos de gestantes e 67,7% foram classificadas quanto ao risco gestacional. Das intercorrências na gestação, a infecção do trato urinário (37,3%), anemia (27,2%) e hipertensão arterial (19,3%) foram as mais frequentes. Devido à alta prevalência de gravidez na adolescência (17,2%), parto cesáreo (57,3%), nascimento prematuro (13,7%), e uso de drogas de abuso durante a gestação (20,6%), evidenciou-se a necessidade de direcionamento da atenção, com vistas à promoção da saúde do binômio mãe-filho.

This study aimed to describe the sociodemographic and obstetric profile of resident mothers in the municipality of Maringa, attended by Network Mother from the State of Paraná. This is a descriptive study conducted with 592 postpartum women through interviews, the pregnant woman's card to the consultation and hospital records, between 2013 and 2014. There have been found mostly brown women (44.8%), had completed high school (46.1%), in stable union (86.3%), and exercising gainful occupation (52.0%). Of those interviewed, 67.8% started early prenatal care, 74.0% had seven or more visits, only 35.3% planned their pregnancy, 38,3% participated in groups of pregnant women and 67.7% were classified according to gestational risk. Of complications in pregnancy, urinary tract infection (37.3%), anemia (27.2 %) and hypertension (19.3%) were the most frequent. Given the high prevalence of adolescents (17.2%), cesarean delivery (57.3%), preterm birth (13.7%), and drug abuse during pregnancy (20.6%), showed the need the direction of attention, with a view to promoting the health of both mother and child.

Chronic light deprivation inhibits appetitive associative learning induced by ethanol and its respective c-Fos and pCREB expression.

To address the role of mixed anxiety/mood disorder on appetitive associative learning, we verify whether previous chronic light deprivation changes ethanol-induced conditioned place preference and its respective expression of c-Fos and pCREB, markers of neuronal activity and plasticity. The experimental group was maintained in light deprivation for 24 h for a period of 4 wk. Subsequently, it was adapted to a standard light-dark cycle for 1 wk. As a control, some mice were maintained in standard cycle for a period of 4 wk (Naïve group). Then, all animals were submitted to behavioral tests to assess emotionality: elevated plus maze; open field; and forced swim. After that, they were submitted to ethanol-induced conditioned place preference. Ninety minutes after the place preference test, they were perfused, and their brains processed for c-Fos and pCREB immunohistochemistry. Light deprivation induced anxiety-like trait (elevated plus maze), despair (forced swim), and hyperlocomotion (open field), common features seen in other animal models of depression. Ethanol-induced conditioned place preference was accompanied by increases on c-Fos and pCREB in the hippocampus, prefrontal cortex and striatum. Interestingly, mice previously submitted to light deprivation did not develop either acquisition and/or expression of ethanol-induced conditioned place preference or increases in c-Fos and pCREB. Therefore, chronic light deprivation mimics several behavioral aspects of other animal models of depression. Furthermore, it could be useful to study the neurochemical mechanisms involved in the dual diagnosis. However, given its likely deleterious effects on appetitive associative memory, it should be used with caution to investigate the cognitive aspects related to the dual diagnosis.