Nurses' workload during the COVID-19 pandemic: potential for experiences of moral distress.

OBJECTIVES: to understand nurses' experiences of moral distress related to work overload during the COVID-19 pandemic in Brazil. METHODS: qualitative research, whose data collection occurred through individual interviews with 19 nurses who worked on the front line of COVID-19 in health services in southeastern Brazil. Data were analyzed using thematic content analysis. RESULTS: work overload proved to be a powerful source of experiences of moral distress due to excessive working hours during vaccination, double working hours, a troubled relationship due to pressure from managers and the population and physical and mental exhaustion, which prevented nurses from act according to their judgment. FINAL CONSIDERATIONS: nurses' work overload reflects on quality patient care and prevents nurses from acting in accordance with their moral principles, generating moral distress in nurses.

KSRP improves pancreatic beta cell function and survival.

Impaired insulin production and/or secretion by pancreatic beta cells can lead to high blood glucose levels and type 2 diabetes (T2D). Therefore, investigating new proteins involved in beta cell response to stress conditions could be useful in finding new targets for therapeutic approaches. KH-type splicing regulatory protein (KSRP) is a protein usually involved in gene expression due to its role in post-transcriptional regulation. Although there are studies describing the important role of KSRP in tissues closely related to glucose homeostasis, its effect on pancreatic beta cells has not been explored so far. Pancreatic islets from diet-induced obese mice (C57BL/6JUnib) were used to determine KSRP expression and we also performed in vitro experiments exposing INS-1E cells (pancreatic beta cell line) to different stressors (palmitate or cyclopiazonic acid-CPA) to induce cellular dysfunction. Here we show that KSRP expression is reduced in all the beta cell dysfunction models tested. In addition, when manipulated to knock down KSRP, beta cells exhibited increased death and impaired insulin secretion, whereas KSRP overexpression prevented cell death and increased insulin secretion. Taken together, our findings suggest that KSRP could be an important target to protect beta cells from impaired functioning and death.

First report of coexistence of blaKPC-2 and blaNDM-1 in carbapenem-resistant clinical isolates of Klebsiella aerogenes in Brazil.

Klebsiella aerogenes is an important opportunistic pathogen with the potential to develop resistance against last-line antibiotics, such as carbapenems, limiting the treatment options. Here, we investigated the antibiotic resistance profiles of 10 K. aerogenes strains isolated from patient samples in the intensive-care unit of a Brazilian tertiary hospital using conventional PCR and a comprehensive genomic characterization of a specific K. aerogenes strain (CRK317) carrying both the blaKPC-2 and blaNDM-1 genes simultaneously. All isolates were completely resistant to ß-lactam antibiotics, including ertapenem, imipenem, and meropenem with differencing levels of resistance to aminoglycosides, quinolones, and tigecycline also observed. Half of the strains studied were classified as multidrug-resistant. The carbapenemase-producing isolates carried many genes of interest including: ß-lactams (blaNDM-1, blaKPC-2, blaTEM-1, blaCTX-M-1 group, blaOXA-1 group and blaSHVvariants in 20-80% of the strains), aminoglycoside resistance genes [aac(6')-Ib and aph(3')-VI, 70 and 80%], a fluoroquinolone resistance gene (qnrS, 80%), a sulfonamide resistance gene (sul-2, 80%) and a multidrug efflux system transporter (mdtK, 70%) while all strains carried the efflux pumps Acr (subunit A) and tolC. Moreover, we performed a comprehensive genomic characterization of a specific K. aerogenes strain (CRK317) carrying both the blaKPC-2 and blaNDM-1 genes simultaneously. The draft genome assembly of the CRK317 had a total length of 5,462,831 bp and a GC content of 54.8%. The chromosome was found to contain many essential genes. In silico analysis identified many genes associated with resistance phenotypes, including ß-lactamases (blaOXA-9, blaTEM-1, blaNDM-1, blaCTX-M-15, blaAmpC-1, blaAmpC-2), the bleomycin resistance gene (bleMBL), an erythromycin resistance methylase (ermC), aminoglycoside-modifying enzymes [aac(6')-Ib, aadA/ant(3")-Ia, aph(3')-VI], a sulfonamide resistance enzyme (sul-2), a chloramphenicol acetyltransferase (catA-like), a plasmid-mediated quinolone resistance protein (qnrS1), a glutathione transferase (fosA), PEtN transferases (eptA, eptB) and a glycosyltransferase (arnT). We also detected 22 genomic islands, eight families of insertion sequences, two putative integrative and conjugative elements with a type IV secretion system, and eight prophage regions. This suggests the significant involvement of these genetic structures in the dissemination of antibiotic resistance. The results of our study show that the emergence of carbapenemase-producing K. aerogenes, co-harboring blaKPC-2 and blaNDM-1, is a worrying phenomenon which highlights the importance of developing strategies to detect, prevent, and control the spread of these microorganisms.

Nurses' workload during the COVID-19 pandemic: potential for experiences of moral distress / Carga de trabajo de las enfermeras durante la pandemia de COVID-19: potencial para experiencias de sufrimiento moral / Sobrecarga de trabalho de enfermeiros na pandemia de COVID-19: potência para vivências de sofrimento moral

ABSTRACT Objectives: to understand nurses' experiences of moral distress related to work overload during the COVID-19 pandemic in Brazil. Methods: qualitative research, whose data collection occurred through individual interviews with 19 nurses who worked on the front line of COVID-19 in health services in southeastern Brazil. Data were analyzed using thematic content analysis. Results: work overload proved to be a powerful source of experiences of moral distress due to excessive working hours during vaccination, double working hours, a troubled relationship due to pressure from managers and the population and physical and mental exhaustion, which prevented nurses from act according to their judgment. Final Considerations: nurses' work overload reflects on quality patient care and prevents nurses from acting in accordance with their moral principles, generating moral distress in nurses.

RESUMEN Objetivos: comprender las experiencias de angustia moral de los enfermeros relacionadas con la sobrecarga de trabajo durante la pandemia de COVID-19 en Brasil. Métodos: investigación cualitativa, cuya recolección de datos ocurrió a través de entrevistas individuales con 19 enfermeros que actuaron en la primera línea de COVID-19 en servicios de salud de la región Sudeste de Brasil. Los datos fueron analizados mediante análisis de contenido temático. Resultados: la sobrecarga de trabajo resultó ser una poderosa fuente de experiencias de sufrimiento moral por exceso de jornada durante la vacunación, doble jornada laboral, relaciones conflictivas por presiones de los directivos y la población y agotamiento físico y mental, lo que impidió al enfermero actuar según su criterio. Consideraciones Finales: la sobrecarga de trabajo de las enfermeras se refleja en la calidad de la atención al paciente e impide que las enfermeras actúen de acuerdo con sus principios morales, generando sufrimiento moral en las enfermeras.

RESUMO Objetivos: compreender vivências de sofrimento moral de enfermeiros relacionadas à sobrecarga de trabalho durante a pandemia de COVID-19 no Brasil. Métodos: pesquisa qualitativa, cuja coleta de dados ocorreu através de entrevistas individuais com 19 enfermeiros que atuaram na linha de frente da COVID-19 em serviços de saúde da região Sudeste do Brasil. Os dados foram analisados mediante análise temática de conteúdo. Resultados: a sobrecarga de trabalho mostrou-se potente fonte para vivências de sofrimento moral devido à jornada de trabalho excessiva na vacinação, à dupla jornada de trabalho, à relação conturbada por pressão de gestores e população e ao esgotamento físico e mental, os quais impediam o enfermeiro de agir conforme o seu julgamento. Considerações Finais: a sobrecarga de trabalho dos enfermeiros reflete na assistência de qualidade ao paciente, e impede que os enfermeiros atuem conforme os seus princípios morais, gerando sofrimento moral nos enfermeiros.

Vertical sleeve gastrectomy improves glucose-insulin homeostasis by enhancing ß-cell function and survival via FGF15/19.

Vertical sleeve gastrectomy (VSG) restores glucose homeostasis in obese mice and humans. In addition, the increased fibroblast growth factor (FGF)15/19 circulating level postsurgery has been implicated in this effect. However, the impact of FGF15/19 on pancreatic islets remains unclear. Using a diet-induced obese mice model, we demonstrate that VSG attenuates insulin hypersecretion in isolated pancreatic islets, likely due to morphological alterations in the endocrine pancreas such as reduction in islet, ß-cell, and α-cell mass. In addition, VSG relieves gene expression of endoplasmic reticulum (ER) stress and inflammation markers in islets from obese mice. Incubation of INS-1E ß-cells with serum from obese mice induced dysfunction and cell death, whereas these conditions were not induced with serum from obese mice submitted to VSG, implicating the involvement of a humoral factor. Indeed, VSG increased FGF15 circulating levels in obese mice, as well as the expression of FGF receptor 1 (Fgfr1) and its coreceptor ß-klotho (Klb), both in pancreatic islets from VSG mice and in INS-1E cells treated with the serum from these mice. Moreover, exposing INS-1E cells to an FGFR inhibitor abolished the effects of VSG serum on insulin secretion and cell death. Also, recombinant FGF19 prevents INS-1E cells from dysfunction and death induced by serum from obese mice. These findings indicate that the amelioration of glucose-insulin homeostasis promoted by VSG is mediated, at least in part, by FGF15/19. Therefore, approaches promoting FGF15/19 release or action may restore pancreatic islet function in obesity.NEW & NOTEWORTHY Vertical sleeve gastrectomy (VSG) decreases insulin secretion, endoplasmic reticulum (ER) stress, and inflammation in pancreatic islets from obese mice. In addition, VSG increased fibroblast growth factor (FGF)15 circulating levels in obese mice, as well as the expression of FGF receptor 1 (Fgfr1) and its coreceptor ß-klotho (Klb), both in pancreatic islets from VSG mice and in INS-1E ß-cells treated with the serum from these mice. Serum from operated mice protects INS-1E cells from dysfunction and apoptosis, which was mediated by FGF15/19.

Perfil medicamentoso e frequência de polifarmácia em idosos de uma Unidade Básica de Saúde / Drug profile and frequency of polypharmacy in elderly people in a Primary Care Unit / Perfil farmacológico y frecuencia de polifarmacia en ancianos en una Unidad Básica de Salud

Objetivo: identificar o perfil medicamentoso e a frequência de polifarmácia em idosos cadastrados e que fazem acompanhamento em uma unidade básica de saúde. Método: estudo observacional e retrospectivo, realizado em uma unidade básica de saúde de um município do Triângulo Mineiro, Minas Gerais. Foi realizada amostragem aleatória e estratificada para coleta de dados de prontuários físicos e eletrônicos de idosos atendidos nos anos de 2019 e 2020, analisados por meio de estatística descritiva. Resultados: entre 448 prontuários foram analisados, porém somente 208 (46,4%) foram válidos. Os medicamentos mais prescritos foram losartana (n=72; 34,6%), sinvastatina (n=60; 28,8%) e metformina (n=51; 24,5%). Observou-se 24,0% de frequência de polifarmácia (n=51), maior frequência de mulheres (n=42; 30,2%) e com significativa associação com diabetes mellitus (p=0,034). Conclusão: a polifarmárcia foi detectada, mais presente nas mulheres, sendo que medicamentos mais utilizados foram relacionados à hipertensão arterial, dislipidemias e diabetes mellitus. Destaca-se a incompletude de informações nos prontuários analisados.

Objective: to identify the medication profile and frequency of polypharmacy in registered elderly people who are followed up at a primary care unit. Method: observational and retrospective study, carried out in a primary care unit in a municipality in Triângulo Mineiro, Minas Gerais. Random and stratified sampling was carried out to collect data from the physical and electronic medical records of the elderly assisted in the years 2019 and 2020, analyzed using descriptive statistics. Results: among 448 medical records analyzed, 208 (46.4%) were considered valid for inclusion in the study. The most prescribed drugs were losartan (n=72; 34.6%), simvastatin (n=60; 28.8%) and metformin (n=51; 24.5%). There was a 24.0% frequency of polypharmacy (n=51), a higher frequency of wome (n=42; 30.2%) and with a significant association with diabetes mellitus (p=0.034). Conclusion: polypharmacy was detected, more present in women, and the most used drugs were related to arterial hypertension, dyslipidemia and diabetes mellitus. The incompleteness of information in the analyzed medical records stands out. Descriptors: Health of the Elderly; Aged; Primary Health Care; Polypharmacy.

Objetivo: identificar el perfil farmacológico y frecuencia de polifarmacia en ancianos registrados en seguimiento en una unidad básica de salud. Método: estudio observacional y retrospectivo, realizado en una unidad básica de salud de un municipio del Triângulo Mineiro, Minas Gerais. Se realizó un muestreo aleatorio y estratificado para recolectar datos de las historias clínicas físicas y electrónicas de los ancianos atendidos en los años 2019 y 2020, analizados mediante estadística descriptiva. Resultados: de 448 historias clínicas analizadas, 208 (46,4%) fueron consideradas válidas para su inclusión en el estudio. Los fármacos más prescritos fueron Losartán (n=72; 34,6%), Simvastatina (n=60; 28,8%) y Metformina (n=51; 24,5%). La frecuencia de polifarmacia estuvo en el 24,0% (n=51), mayor frecuencia de mujeres (n=42; 30,2%) y con asociación significativa con diabetes mellitus (p=0,034). Conclusión: se detectó la polifarmacia, más presente en las mujeres; los fármacos más utilizados estuvieron relacionados con hipertensión arterial, dislipidemia y diabetes mellitus. Se destaca la incompletitud de la información en las historias clínicas analizadas.

Contributory Factors to Caregiver Burden in Parkinson's Disease.

Background: Although there is growing recognition of the relevancy of informal caregivers there is scarce information on the contributory factors of caregiver burden in Parkinson's Disease (PD). Objective: To identify the main associated factors to caregivers' burden in people caring for a person with PD. Methods: We analyzed the data set from a multinational online survey the Parkinson's real-world impact assesSMent (PRISM) focusing on medication use, comorbidities, health-related quality of life, relationship changes and the use of healthcare and supportive care resources by people with PD and their carers. Structured questionnaires including the Parkinson's disease quality of life questionnaire (PDQ-39), non-motor symptoms questionnaire (NMSQuest) and the Questionnaire for impulsive-compulsive disorder in Parkinson's disease (QUIP) were applied. Caregiver burden was assessed by the Zarit Burden Interview (ZBI). Results: In a cohort of 245 dyads (patient and respective caregiver), caregivers reported a mild to moderate burden. Carers' perception of PD impact in partnership, financial burden, hours of care, patient's age, hypersexuality and health-related quality of life (HRQoL) were found to be significant contributory factors to caregiver burden. Taken together these variables explained 66.8% of the variance in the Interpretation of the ZBI total score. Conclusions: Caring for a person with PD entails substantial burden, particularly when the caregiver perceives greater changes in partnership dynamics, dedicates more time to caregiving tasks, has financial burden, and when the patient is older, reports worst HRQoL and has sexual compulsive urges.

Multigenerational effects of co-exposure to dimethylarsinic acid and polystyrene microplastics on the nematode Caenorhabditis elegans.

In the current study, we assessed the impact of DMA (dimethylarsinic acid) and MPs (microplastics) interactions in C. elegans over the course of five generations. We found that the redox state of the organisms changed over generations as a result of exposure to both pollutants. From the third generation onward, exposure to MPs reduced GST activity, indicating reduced detoxifying abilities of these organisms. Additionally, dimethylarsinic exposure decreased the growth of organisms in the second, fourth, and fifth generations. In comparison to isolated pollutants, the cumulative effects of co-exposure to DMA and MPs seem to have been more harmful to the organisms, as demonstrated by correlation analysis. These findings demonstrate that DMA, despite being considered less hazardous than its inorganic equivalents, can still have toxic effects on species at low concentrations and the presence of MPs, can worsen these effects.

Butyrate restores the fat/lean mass ratio balance and energy metabolism and reinforces the tight junction-mediated intestinal epithelial barrier in prediabetic mice independently of its anti-inflammatory and epigenetic actions.

Tissue/cellular actions of butyrate on energy metabolism and intestinal barrier in normal metabolic conditions or prediabetes are still unclear. In this work, we investigated the beneficial effect of dietary supplementation with sodium butyrate on energy metabolism, body mass composition, and intestinal epithelial barrier mediated by tight junction (TJ) in chow diet-fed normal and high-fat diet (HF)-fed prediabetic mice, considering the well-known butyrate action as an epigenetic and inflammatory regulator. Butyrate significantly reduced the fat/lean mass ratio, slightly ameliorated dyslipidemia, restored oral glucose tolerance, and increased basal energy expenditure in prediabetic HF-fed mice but had no effect on control animals. Such effects were observed in the absence of significant alterations in the hypothalamic expression of orexigenic and anorexigenic genes and motor activity. Also, butyrate suppressed the whitening effect of HF on brown adipose tissue but did not affect cell bioenergetics in immortalized UCP1-positive adipocytes in vitro. Butyrate reinforced the intestinal epithelial barrier in HF-fed mice and in Caco-2 monolayers, which involved higher trafficking of TJ proteins to the cell-cell contact region of the intestinal epithelia, without affecting TJ gene expression or the acetylation level of histones H3 and H4 in vivo. All metabolic and intestinal effects of butyrate in prediabetic mice occurred in the absence of detectable changes in systemic or local inflammation, or alterations in endotoxemia markers. Butyrate has no effect on chow diet-fed mice but, in the context of HF-induced prediabetes, it prevents metabolic and intestinal dysfunctions independently of its anti-inflammatory and epigenetic actions.

Molecular BCR::ABL1 Quantification and ABL1 Mutation Detection as Essential Tools for the Clinical Management of Chronic Myeloid Leukemia Patients: Results from a Brazilian Single-Center Study.

Chronic myeloid leukemia (CML) is a well-characterized oncological disease in which virtually all patients possess a translocation (9;22) that generates the tyrosine kinase BCR::ABL1 protein. This translocation represents one of the milestones in molecular oncology in terms of both diagnostic and prognostic evaluations. The molecular detection of the BCR::ABL1 transcription is a required factor for CML diagnosis, and its molecular quantification is essential for assessing treatment options and clinical approaches. In the CML molecular context, point mutations on the ABL1 gene are also a challenge for clinical guidelines because several mutations are responsible for tyrosine kinase inhibitor resistance, indicating that a change may be necessary in the treatment protocol. So far, the European LeukemiaNet and the National Comprehensive Cancer Network (NCCN) have presented international guidelines on CML molecular approaches, especially those related to BCR::ABL1 expression. In this study, we show almost three years' worth of data regarding the clinical treatment of CML patients at the Erasto Gaertner Hospital, Curitiba, Brazil. These data primarily comprise 155 patients and 532 clinical samples. BCR::ABL1 quantification by a duplex-one-step RT-qPCR and ABL1 mutations detection were conducted. Furthermore, digital PCR for both BCR::ABL1 expression and ABL1 mutations were conducted in a sub-cohort. This manuscript describes and discusses the clinical importance and relevance of molecular biology testing in Brazilian CML patients, demonstrating its cost-effectiveness.

Optical switching a photon-avalanche-like mechanism in NdAl3(BO3)4 particles excited at 1064 nm by an auxiliary beam at 808 nm.

In recent years, an unconventional excitation of trivalent neodymium ions (N d 3+) at 1064 nm, not resonant with ground-state transitions, has been investigated with the unprecedented demonstration of a photon-avalanche-like (PA-like) mechanism, in which the temperature increase plays a fundamental role. As a proof-of-concept, N d A l 3(B O 3)4 particles were used. A consequence of the PA-like mechanism is the absorption enhancement of excitation photons providing light emission at a broad range covering the visible and near-infrared spectra. In the first study, the temperature increase was due to intrinsic nonradiative relaxations from the N d 3+ and the PA-like mechanism ensued at a given excitation power threshold (P t h ). Subsequently, an external heating source was used to trigger the PA-like mechanism while keeping the excitation power below P t h at room temperature. Here, we demonstrate the switching on of the PA-like mechanism by an auxiliary beam at 808 nm, which is in resonance with the N d 3+ ground-state transition 4 I 9/2→{4 F 5/2,2 H 9/2}. It comprises the first, to the best of our knowledge, demonstration of an optical switched PA, and the underlying physical mechanism is the additional heating of the particles due to the phonon emissions from the N d 3+ relaxation pathways when exciting at 808 nm. The present results have potential applications in controlled heating and remote temperature sensing.

Biochemical and physiological effects of multigenerational exposure to spheric polystyrene microplastics in Caenorhabditis elegans.

Although studies have already shown the effects of exposure to microplastics (MP) in different species, the effects over generations in these individuals remain poorly understood. Therefore, the present study aimed to evaluate the effect of polystyrene MP (spherical, 1 µm) on the responses of the free-living nematode Caenorhabditis elegans in a multigenerational approach over five subsequent generations. MP concentrations of both 5 and 50 µg/L induced a detoxification response, increasing glutathione S-transferase (GST) activity and inducing the generation of reactive oxygen species (ROS) and lipid peroxidation (TBARS). MP also demonstrated the ability to accumulate in the animal's body during the 96 h of each generational exposure, and possibly, this constant interaction was the main reason for the decreased response in physiological parameters as in the exploratory behavior (body bending) of nematodes, and in the reproduction, being this last parameter most negatively affected during the five exposed generations, with a reduction of almost 50% in the last generation. These results emphasize the importance of multigenerational approaches, highlighting their advantage in the assessment of environmental contaminants.

Brevundimonas brasiliensis sp. nov.: a New Multidrug-Resistant Species Isolated from a Patient in Brazil.

To increase knowledge on Brevundimonas pathogens, we conducted in-depth genomic and phenotypic characterization of a Brevundimonas strain isolated from the cerebrospinal fluid of a patient admitted in a neonatal intensive care unit. The strain was identified as a member of the genus Brevundimonas based on Vitek 2 system results and 16S rRNA gene sequencing and presented a multidrug resistance profile (MDR). Several molecular and biochemical tests were used to characterize and identify the species for in-depth results. The draft genome assembly of the isolate has a total length of 3,261,074 bp and a G+C of 66.86%, similar to other species of the genus. Multilocus sequence analysis, Type (Strain) Genome Server, digital DNA-DNA hybridization, and average nucleotide identity confirmed that the Brevundimonas sp. studied represents a distinct species, for which we propose the name Brevundimonas brasiliensis sp. nov. In silico analysis detected antimicrobial resistance genes (AMRGs) mediating resistance to ß-lactams (penP, blaTEM-16, and blaBKC-1) and aminoglycosides [strA, strB, aac(6')-Ib, and aac(6')-Il]. We also found AMRGs encoding the AcrAB efflux pump that confers resistance to a broad spectrum of antibiotics. Colistin and quinolone resistance can be attributed to mutation in qseC and/or phoP and GyrA/GyrB, respectively. The Brevundimonas brasiliensis sp. nov. genome contained copies of type IV secretion system (T4SS)-type integrative and conjugative elements (ICEs); integrative mobilizable elements (IME); and Tn3-type and IS3, IS6, IS5, and IS1380 families, suggesting an important role in the development and dissemination of antibiotic resistance. The isolate presented a range of virulence-associated genes related to biofilm formation, adhesion, and invasion that can be relevant for its pathogenicity. Our findings provide a wealth of data to hinder the transmission of MDR Brevundimonas and highlight the need for monitoring and identifying new bacterial species in hospital environments. IMPORTANCE Brevundimonas species is considered an opportunistic human pathogen that can cause multiple types of invasive and severe infections in patients with underlying pathologies. Treatment of these pathogens has become a major challenge because many isolates are resistant to most antibiotics used in clinical practice. Furthermore, there are no consistent therapeutic results demonstrating the efficacy of antibacterial agents. Although considered a rare pathogen, recent studies have provided evidence of the emergence of Brevundimonas in clinical settings. Hence, we identified a novel pathogenic bacterium, Brevundimonas brasiliensis sp. nov., that presented a multidrug resistance (MDR) profile and carried diverse genes related to drug resistance, virulence, and mobile genetic elements. Such data can serve as a baseline for understanding the genomic diversity, adaptation, evolution, and pathogenicity of MDR Brevundimonas.

Predicting factors of neurodevelopmental performance in children with phenylketonuria.

In phenylketonuria (PKU), high phenylalanine (Phe) levels hamper neurodevelopment impairing executive function later in life. While the second has been more studied, fewer data exist on predictors of PKU patients' development in specific populations. To contribute to the field, we performed a retrospective analysis of predictors of neurodevelopment in PKU patients in a Portuguese cohort. We analyzed the retrospective data on the metabolic control of 89 patients, as their health and familial features. Griffith's Mental Development Scale performance at age 6 (GMDS6) was used to assess neurodevelopment. Our cohort included 14 GMDS6low and 75 GMDS6high patients. In a multivariate analysis, the better predictors of neurodevelopment were the metabolic control at age 3 and year of birth (n = 87, ß0  = -121, ß1  = -1.77, ß2  = 0.06, LRchi2(2) = 13.61, Prob > chi2 = 0.001, Pseudo R2 = 0.1773). With this model, it was possible to define a safety cut-off of 7.8 mg/dL for the Phe level at age 3 (sensitivity = 72.6%, specificity = 78.6%), confirming the safety of the cut-off of 6 mg/dL already used in the clinical practice. Our study supports the relevance of metabolic control to predict the neurodevelopment of PKU patients, in the historical context of the disease management.

An Early and Sustained Inflammatory State Induces Muscle Changes and Establishes Obesogenic Characteristics in Wistar Rats Exposed to the MSG-Induced Obesity Model.

The model of obesity induced by monosodium glutamate cytotoxicity on the hypothalamic nuclei is widely used in the literature. However, MSG promotes persistent muscle changes and there is a significant lack of studies that seek to elucidate the mechanisms by which damage refractory to reversal is established. This study aimed to investigate the early and chronic effects of MSG induction of obesity upon systemic and muscular parameters of Wistar rats. The animals were exposed to MSG subcutaneously (4 mg·g-1 b.w.) or saline (1.25 mg·g-1 b.w.) daily from PND01 to PND05 (n = 24). Afterwards, in PND15, 12 animals were euthanized to determine the plasma and inflammatory profile and to assess muscle damage. In PND142, the remaining animals were euthanized, and samples for histological and biochemical analyses were obtained. Our results suggest that early exposure to MSG reduced growth, increased adiposity, and inducted hyperinsulinemia and a pro-inflammatory scenario. In adulthood, the following were observed: peripheral insulin resistance, increased fibrosis, oxidative distress, and a reduction in muscle mass, oxidative capacity, and neuromuscular junctions, increased fibrosis, and oxidative distress. Thus, we can conclude that the condition found in adult life and the difficulty restoring in the muscle profile is related to the metabolic damage established early on.

Sleeve Gastrectomy-Induced Weight Loss Increases Insulin Clearance in Obese Mice.

Sleeve gastrectomy (SG) successfully recovers metabolic homeostasis in obese humans and rodents while also resulting in the normalization of insulin sensitivity and insulinemia. Reduced insulin levels have been attributed to lower insulin secretion and increased insulin clearance in individuals submitted to SG. Insulin degradation mainly occurs in the liver in a process controlled, at least in part, by the insulin-degrading enzyme (IDE). However, research has yet to explore whether liver IDE expression or activity is altered after SG surgery. In this study, C57BL/6 mice were fed a chow (CTL) or high-fat diet (HFD) for 10 weeks. Afterward, the HFD mice were randomly assigned to two groups: sham-surgical (HFD-SHAM) and SG-surgical (HFD-SG). Here, we confirmed that SG improves glucose-insulin homeostasis in obese mice. Additionally, SG reduced insulinemia by reducing insulin secretion, assessed by the analysis of plasmatic C-peptide content, and increasing insulin clearance, which was evaluated through the calculation of the plasmatic C-peptide:insulin ratio. Although no changes in hepatic IDE activity were observed, IDE expression was higher in the liver of HFD-SG compared with HFD-SHAM mice. These results indicate that SG may be helpful to counteract obesity-induced hyperinsulinemia by increasing insulin clearance, likely through enhanced liver IDE expression.

Missense MED12 variants in 22 males with intellectual disability: From nonspecific symptoms to complete syndromes.

We describe the phenotype of 22 male patients (20 probands) carrying a hemizygous missense variant in MED12. The phenotypic spectrum is very broad ranging from nonspecific intellectual disability (ID) to the three well-known syndromes: Opitz-Kaveggia syndrome, Lujan-Fryns syndrome, or Ohdo syndrome. The identified variants were randomly distributed throughout the gene (p = 0.993, χ2 test), but mostly outside the functional domains (p = 0.004; χ2 test). Statistical analyses did not show a correlation between the MED12-related phenotypes and the locations of the variants (p = 0.295; Pearson correlation), nor the protein domain involved (p = 0.422; Pearson correlation). In conclusion, establishing a genotype-phenotype correlation in MED12-related diseases remains challenging. Therefore, we think that patients with a causative MED12 variant are currently underdiagnosed due to the broad patients' clinical presentations.

Genetic counseling and carrier screening in candidates for gamete donation at a Portuguese center.

OBJECTIVE: Genetic counseling and carrier screening are part of the gamete donation process by healthy individuals. We aim to review the findings of genetic counseling and carrier screening of a cohort of candidates at our public gametes bank. METHODS: Thirty-four male and 64 female candidates had genetic counseling with a medical geneticist before donation. Of these, one female candidate voluntarily dropped-out. Thirty-four males and 63 females performed karyotype and screening for the more common pathogenic variants for CFTR-related cystic fibrosis and spinal muscular atrophy (SMN1) in the Portuguese population. In addition, all females also performed Fragile X expansion screening (FMR1). Thirty candidates with known or assumed African ancestry performed hemoglobinopathies screening. RESULTS: Six candidates were definitely or temporarily withheld from the donation process given their family or personal history that required further investigation. Of 97 candidates tested, 16.5% presented anomalous laboratory results (16/97): ten candidates were carriers for an autosomal recessive disorder - cystic fibrosis (5/97), sickle cell anemia (3/30), and spinal muscular atrophy (2/97). One female was an FMR1 pre-mutation carrier (1/63). One female candidate presented with triple X mosaicism: 47,XXX[2]/46,XX[50]. Two candidates presented with chromosomal instability of unknown origin. In one candidate, a mosaic for the Philadelphia chromosome was detected, revealing the diagnosis of chronic myeloid leukemia. CONCLUSIONS: From a cohort of 97 candidates, 21.7% had a family/personal history or an anomalous laboratory result that required additional genetic counseling, stressing the importance of performing pre-donation genetic counseling in this population.

Perfil sociodemográfico e fragilidade de prontuários de idosos atendidos em uma unidade básica de saúde / Sociodemographic profile and fragility of medical records of elderly people treated at a basic health unit / Perfil sociodemográfico y fragilidad de los prontuarios de ancianos en una unidad básica de salud

Objetivo: identificar o perfil sociodemográfico de idosos de uma Unidade Básica de Saúde e detectar o provimento de informações nos prontuários da unidade. Métodos: Estudo quantitativo, descritivo, retrospectivo, realizado em uma Unidade Básica de Saúde de um município do Triângulo Sul de Minas Gerais. A coleta de dados ocorreu de abril a agosto de 2021, após amostragem probabilista com prontuários físicos e eletrônicos de idosos atendidos em 2019/2020. Foi utilizado instrumento validado por juízes contendo variáveis sociodemográficas e realizado análise descritiva. Resultados: A amostra foi composta por 448 prontuários, predominaram mulheres, brancas, aposentadas, casadas/com companheiro(a), com ensino fundamental incompleto, que não faziam uso de bebida alcoólica e não fumantes. Na maioria destas variáveis, havia ausência de informações nos prontuários. Conclusões: A falta de dados chama a atenção ao reconhecer fragilidades no provimento de informações de saúde da população nos prontuários desta unidade.

Objective: to identify the sociodemographic profile of the elderly in a Basic Health Unit and detect the provision of information in the unit's medical records. Methods: Quantitative, descriptive, retrospective study, carried out in a Basic Health Unit in a municipality in the Southern Triangle of Minas Gerais. Data collection took place from April to August 2021, after probabilistic sampling with physical and electronic medical records of elderly people assisted in 2019/2020. An instrument validated by judges containing sociodemographic variables was used and a descriptive analysis was performed. Results: The sample consisted of 448 medical records, predominantly women, white, retired, married/with a partner, with incomplete primary education, who did not use alcohol and non-smokers. In most of these variables, there was no information in the medical records. Conclusions: The lack of data draws attention when recognizing weaknesses in the provision of health information to the population in the medical records of this unit.

Objetivo: identificar el perfil sociodemográfico de los ancianos en una Unidad Básica de Salud y detectar la provisión de información en los prontuarios de la unidad. Métodos: Estudio cuantitativo, descriptivo, retrospectivo, realizado en una Unidad Básica de Salud de un municipio del Triángulo Sur de Minas Gerais. La recolección de datos ocurrió de abril a agosto de 2021, después de un muestreo probabilístico con prontuario físico y electrónico de ancianos atendidos en 2019/2020. Se utilizó un instrumento validado por jueces que contiene variables sociodemográficas y se realizó un análisis descriptivo. Resultados: La muestra estuvo constituida por 448 historias clínicas, predominantemente mujeres, blancas, jubiladas, casadas/con pareja, con instrucción primaria incompleta, que no consumieran alcohol y no fumadoras. En la mayoría de estas variables no había información en las historias clínicas. Conclusiones: Llama la atención la falta de datos al reconocer debilidades en la provisión de información de salud a la población en las historias clínicas de esta unidad.

The bile acid TUDCA reduces age-related hyperinsulinemia in mice.

Aging is associated with glucose metabolism disturbances, such as insulin resistance and hyperinsulinemia, which contribute to the increased prevalence of type 2 diabetes (T2D) and its complications in the elderly population. In this sense, some bile acids have emerged as new therapeutic targets to treat TD2, as well as associated metabolic disorders. The taurine conjugated bile acid, tauroursodeoxycholic acid (TUDCA) improves glucose homeostasis in T2D, obesity, and Alzheimer's disease mice model. However, its effects in aged mice have not been explored yet. Here, we evaluated the actions of TUDCA upon glucose-insulin homeostasis in aged C57BL/6 male mice (18-month-old) treated with 300 mg/kg of TUDCA or its vehicle. TUDCA attenuated hyperinsulinemia and improved glucose homeostasis in aged mice, by enhancing liver insulin-degrading enzyme (IDE) expression and insulin clearance. Furthermore, the improvement in glucose-insulin homeostasis in these mice was accompanied by a reduction in adiposity, associated with adipocyte hypertrophy, and lipids accumulation in the liver. TUDCA-treated aged mice also displayed increased energy expenditure and metabolic flexibility, as well as a better cognitive ability. Taken together, our data highlight TUDCA as an interesting target for the attenuation of age-related hyperinsulinemia and its deleterious effects on metabolism.