Mitochondrial function in skeletal muscle contributes to reproductive endothermy in tegu lizards (Salvator merianae).

AIM: In cyclic climate variations, including seasonal changes, many animals regulate their energy demands to overcome critical transitory moments, restricting their high-demand activities to phases of resource abundance, enabling rapid growth and reproduction. Tegu lizards (Salvator merianae) are ectotherms with a robust annual cycle, being active during summer, hibernating during winter, and presenting a remarkable endothermy during reproduction in spring. Here, we evaluated whether changes in mitochondrial respiratory physiology in skeletal muscle could serve as a mechanism for the increased thermogenesis observed during the tegu's reproductive endothermy. METHODS: We performed high-resolution respirometry and calorimetry in permeabilized red and white muscle fibers, sampled during summer (activity) and spring (high activity and reproduction), in association with citrate synthase measurements. RESULTS: During spring, the muscle fibers exhibited increased oxidative phosphorylation. They also enhanced uncoupled respiration and heat production via adenine nucleotide translocase (ANT), but not via uncoupling proteins (UCP). Citrate synthase activity was higher during the spring, suggesting greater mitochondrial density compared to the summer. These findings were consistent across both sexes and muscle types (red and white). CONCLUSION: The current results highlight potential cellular thermogenic mechanisms in an ectothermic reptile that contribute to transient endothermy. Our study indicates that the unique feature of transitioning to endothermy through nonshivering thermogenesis during the reproductive phase may be facilitated by higher mitochondrial density, function, and uncoupling within the skeletal muscle. This knowledge contributes significant elements to the broader picture of models for the evolution of endothermy, particularly in relation to the enhancement of aerobic capacity.

Assessment of the musculoskeletal discomfort scale for upper limb among workers in inner Brazil.

BACKGROUND: Work-related musculoskeletal disorders for upper limbs (UL-WMSDs) form a complex of occupational diseases common to many professions worldwide. UL-WMSDs are manifested in most cases by pain, resulting in musculoskeletal discomfort. OBJECTIVE: This research aimed to evaluate the perception of musculoskeletal discomfort in workers from the interior of the Brazilian states of Alagoas and Bahia through the construction of a scale to assess musculoskeletal discomfort for upper limb. METHODS: The discomfort assessment scale was constructed from self-reported pain symptoms by 420 workers from the inner regions of the Brazilian states of Alagoas and Bahia. The reliability and dimensionality of the collected data were analyzed by McDonald's Omega and exploratory factor analysis, respectively. Item Response Theory (IRT) was used to create parameters for the discomfort scale. RESULTS: The musculoskeletal discomfort metric was constructed from the workers' response with six levels (varying from minimum discomfort to maximum discomfort). At the lowest level of the scale, workers indicated symptoms in the shoulders and wrists were rare. At the highest level of the scale, daily pain symptoms are reported in all regions of the upper limbs. The shoulders are the last region to develop extreme pain symptoms. CONCLUSION: The metric was created to present satisfactory psychometric properties and capable measurement of the workers' level of musculoskeletal discomfort based on self-reported pain symptoms. Therefore, the metric can support measuring discomfort, contributing to decisions that improve a healthier occupational environment for the worker.

Neural processing without O2 and glucose delivery: from the pond to the clinic.

Neuronal activity requires a large amount of ATP, leading to a rapid collapse of brain function when aerobic respiration fails. Here, we summarize how rhythmic motor circuits in the brainstem of adult frogs, which normally have high metabolic demands, transform to produce proper output during severe hypoxia associated with emergence from hibernation. We suggest that general principles underlying plasticity in brain bioenergetics may be uncovered by studying non-mammalian models that face extreme environments, yielding new insights to combat neurological disorders involving dysfunctional energy metabolism.

Pepsin Inhibitors Prevent Inflammation and Loss of Laryngeal Barrier Function in Mice with Gastroesophageal Reflux.

OBJECTIVE: This study aimed to evaluate the role of pepsin inhibitors in the inflammatory response and their effects on laryngeal mucosal integrity during gastroesophageal reflux (GERD) under in vivo conditions. METHODS: A surgical model of GERD was used, in which mice were treated with pepstatin (0.3 mg/kg) or darunavir (8.6 mg/kg) for 3 days. On the third day after the experimental protocol, the laryngeal samples were collected to assess the severity of inflammation (wet weight and myeloperoxidase activity) and mucosal integrity (transepithelial electrical resistance and paracellular epithelial permeability to fluorescein). RESULTS: The surgical GERD model was reproduced. It showed features of inflammation and loss of barrier function in the laryngeal mucosa. Pepstatin and darunavir administration suppressed laryngeal inflammation and preserved laryngeal mucosal integrity. CONCLUSION: Pepsin inhibition by the administration of pepstatin and darunavir improved inflammation and protected the laryngeal mucosa in a mouse experimental model of GERD. LEVEL OF EVIDENCE: NA Laryngoscope, 134:3080-3085, 2024.

Plasticity in the Functional Properties of NMDA Receptors Improves Network Stability during Severe Energy Stress.

Brain energy stress leads to neuronal hyperexcitability followed by a rapid loss of function and cell death. In contrast, the frog brainstem switches into a state of extreme metabolic resilience that allows them to maintain motor function during hypoxia as they emerge from hibernation. NMDA receptors (NMDARs) are Ca2+-permeable glutamate receptors that contribute to the loss of homeostasis during hypoxia. Therefore, we hypothesized that hibernation leads to plasticity that reduces the role of NMDARs within neural networks to improve function during hypoxia. To test this, we assessed a circuit with a large involvement of NMDAR synapses, the brainstem respiratory network of female bullfrogs, Lithobates catesbeianus Contrary to our expectations, hibernation did not alter the role of NMDARs in generating network output, nor did it affect the amplitude, kinetics, and hypoxia sensitivity of NMDAR currents. Instead, hibernation strongly reduced NMDAR Ca2+ permeability and enhanced desensitization during repetitive stimulation. Under severe hypoxia, the normal NMDAR profile caused network hyperexcitability within minutes, which was mitigated by blocking NMDARs. After hibernation, the modified complement of NMDARs protected against hyperexcitability, as disordered output did not occur for at least one hour in hypoxia. These findings uncover state-dependence in the plasticity of NMDARs, whereby multiple changes to receptor function improve neural performance during metabolic stress without interfering with their normal role during healthy conditions.

Comparison between general obesity and abdominal adiposity to estimate cardiovascular disease prevalence in individuals with chronic kidney disease: results from NHANES 2005-2016.

Abdominal obesity, regardless of overall obesity, is associated with metabolic abnormalities and with direct impact on cardiovascular risk. The aim of this study was to compare body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) to estimate cardiovascular disease (CVD) prevalence in individuals with chronic kidney disease (CKD). The data analyzed is from 2005-2016 cycles of the NHANES. A total of 2,825 participants with CKD were included in this study, and most of them had a high BMI, 66.1%, to be exact (BMI ≥ 25.0 kg/m² if age <65 or >27.0 if age ≥ 65). The prevalence rates of high WC (≥102 cm for men or ≥88 cm for women) and high WHtR (WHtR>0.5) in the study population were 70.0% and 91.0%, respectively. The results of this study suggest that BMI is a good indicator of the risk of CVDs in individuals with CKD. In addition, the results show that WC and WHtR are associated with CVDs in non-overweight individuals of both sexes. These results indicate that the assessment of abdominal fat is essential even in non-overweight patients because the risk of CVDs cannot be identified in this subpopulation using only BMI.

The new missense G376V-TDP-43 variant induces late-onset distal myopathy but not amyotrophic lateral sclerosis.

TDP-43-positive inclusions in neurons are a hallmark of several neurodegenerative diseases including familial amyotrophic lateral sclerosis (fALS) caused by pathogenic TARDBP variants as well as more common non-Mendelian sporadic ALS (sALS). Here we report a G376V-TDP-43 missense variant in the C-terminal prion-like domain of the protein in two French families affected by an autosomal dominant myopathy but not fulfilling diagnostic criteria for ALS. Patients from both families presented with progressive weakness and atrophy of distal muscles, starting in their 5th-7th decade. Muscle biopsies revealed a degenerative myopathy characterized by accumulation of rimmed (autophagic) vacuoles, disruption of sarcomere integrity and severe myofibrillar disorganization. The G376 V variant altered a highly conserved amino acid residue and was absent in databases on human genome variation. Variant pathogenicity was supported by in silico analyses and functional studies. The G376 V mutant increased the formation of cytoplasmic TDP-43 condensates in cell culture models, promoted assembly into high molecular weight oligomers and aggregates in vitro, and altered morphology of TDP-43 condensates arising from phase separation. Moreover, the variant led to the formation of cytoplasmic TDP-43 condensates in patient-derived myoblasts and induced abnormal mRNA splicing in patient muscle tissue. The identification of individuals with TDP-43-related myopathy but not ALS implies that TARDBP missense variants may have more pleiotropic effects than previously anticipated and support a primary role for TDP-43 in skeletal muscle pathophysiology. We propose to include TARDBP screening in the genetic work-up of patients with late-onset distal myopathy. Further research is warranted to examine the precise pathogenic mechanisms of TARDBP variants causing either a neurodegenerative or myopathic phenotype.

THE WATER-SOLUBLE CONTRAST FOR ADHESIVE SMALL BOWEL OBSTRUCTION: ARE THERE ADVANTAGES?

BACKGROUND: Adhesive small bowel obstruction is one of the most common causes of surgical emergencies, representing about 15% of hospital admissions. Defining the need and timing of surgical intervention still remains a challenge. AIMS: To report the experience of using meglumine-based water-soluble contrast in a tertiary hospital in southern Brazil, comparing with the world literature. METHODS: Patients suspected of having adhesive small bowel obstruction, according to their clinical conditions, underwent an established protocol, consisting of the administration of water-soluble contrast, followed by plain abdominal radiograph within 12 hours and by a new clinical evaluation. The protocol was initiated after starting conservative management, including fasting and placement of a nasogastric tube, as well as intravenous fluid reposition. RESULTS: A total of 126 patients were submitted to the protocol. The water-soluble contrast test sensitivity and specificity after the first radiograph were 94.6 and 91.0%, respectively; after the second radiograph, these values were 92.3 and 100%. The general test values for sensitivity and specificity were 91.9 and 100%, respectively. CONCLUSIONS: The measure parameters evaluated in this study were similar to those found in the literature, contributing to endorse the importance of this test in the evaluation of patients with adhesive small bowel obstruction. The particular relevance of this study was the similar results that were found using a different type of meglumine-based contrast, which is available in Brazil.

Cuidado de crianças e adolescentes em tratamento oncológico na pandemia da COVID-19: experiência de familiares / Care of children and adolescents undergoing cancer treatment in the COVID-19 pandemic: experience of family members / Atención de niños y adolescentes en tratamiento oncológico en la pandemia de COVID-19: experiencia de familiares

RESUMO Objetivo: descrever as experiências vivenciadas por familiares de crianças e adolescentes com câncer, em tratamento oncológico, durante a pandemia da COVID-19. Método: estudo qualitativo, exploratório e descritivo, com 20 familiares de crianças e adolescentes em tratamento oncológico em um ambulatório de oncopediatria. Foram realizadas entrevistas semiestruturadas em setembro e outubro de 2020 e posterior análise de conteúdo. Resultados: as experiências vivenciadas pelos familiares no cuidado à criança e ao adolescente durante a pandemia revelam repercussões e formas de enfrentamento advindas das preocupações e inseguranças relacionadas à COVID-19, das mudanças na rotina e da reorganização das programações terapêuticas para a continuidade do tratamento oncológico. Conclusão: tanto as crianças e os adolescentes quanto seus familiares redobraram as precauções que estavam habituados antes da pandemia. Observou-se a necessidade de reorganização e reagendamentos de consultas, procedimentos e internações, mas sem prejuízos para a terapêutica programada. A insegurança e a ansiedade foram os sentimentos mais presentes, relacionados à evolução da COVID-19(AU)

ABSTRACT Objective: to describe the experience of family members of children and adolescents with cancer undergoing cancer treatment, during the COVID-19 pandemic. Method: qualitative, exploratory and descriptive study, with 20 family members of children and adolescents undergoing cancer treatment in a pediatric oncology outpatient clinic. Semi-structured interviews were carried out in September and October 2020 and subsequent content analysis. Results: the experiences lived by family members in the care of children and adolescents during the pandemic reveal repercussions and ways of coping arising from concerns and insecurities related to COVID-19, changes in routine and the reorganization of therapeutic programs for the continuity of cancer treatment. Conclusion: both children and adolescents and their families redoubled the precautions they were used to before the pandemic. There was a need for reorganization and rescheduling of consultations, procedures and hospitalizations, but without prejudice to the planned therapy. Insecurity and anxiety were the most present feelings related to the evolution of COVID-19(AU)

RESUMEN Objetivo: describir las vivencias de familiares de niños y adolescentes con cáncer, en tratamiento oncológico, durante la pandemia de COVID-19. Método: estudio cualitativo, exploratorio y descriptivo, junto a 20 familiares de niños y adolescentes en tratamiento oncológico en un ambulatorio de oncología pediátrica. Se realizaron entrevistas semiestructuradas en septiembre y octubre y posterior análisis de contenido. Resultados: las experiencias vividas por los familiares en el cuidado de niños y adolescentes durante la pandemia revelan repercusiones y formas de enfrentamiento derivadas de las preocupaciones e inseguridades relacionadas con el COVID-19, los cambios de rutina y la reorganización de los programas terapéuticos para la continuidad del tratamiento oncológico. Conclusión: tanto los niños y los adolescentes como sus familiares redoblaron las precauciones a las que estaban acostumbrados antes de la pandemia. Hubo necesidad de reorganización y reprogramación de consultas, procedimientos y hospitalizaciones, pero sin perjuicio de la terapia prevista. La inseguridad y la ansiedad fueron los sentimientos más presentes relacionados con la evolución del COVID-19(AU)

Segurança do paciente sob a ótica de enfermeiros da estratégia saúde da família / Patient safety from the perspective of family health strategy nurses / La seguridad del paciente en la perspectiva de los enfermeros de la estrategia de salud de la familia

Objetivo: identificar o conhecimento dos enfermeiros que atuam na Estratégia Saúde da Família quanto à segurança do paciente. Método: estudo qualitativo exploratório, descritivo, realizado com 20 enfermeiros da Estratégia Saúde da Família de um município paranaense. A coleta de dados foi realizada entre julho e dezembro de 2021 com entrevistas semiestruturadas. Os dados foram categorizados e analisados com auxílio do software Iramuteq. Resultados: os enfermeiros relataram dificuldades no processo de trabalho e aspectos que influenciavam nas ações relacionadas à segurança do paciente: falta de profissionais, sobrecarga de trabalho, falhas na comunicação, trabalho em equipe e processo de formação, impacto da pandemia contra COVID-19, eventos adversos e cultura de notificação. Considerações finais: o estudo demonstrou a fragilidade dos enfermeiros em relação à segurança do paciente na Atenção Primária à Saúde e a necessidade de o tema ser amplamente discutido entre todos os componentes das equipes da Estratégia Saúde da Família(AU)

Objective: to identify the knowledge of nurses who work in the Family Health Strategy regarding patient safety. Method: exploratory, descriptive qualitative research, carried out with 20 nurses from the Family Health Strategy in a municipality in Paraná. Data collection was carried out from July to December 2021 with semi-structured interviews. Data was categorized and analyzed using the Iramuteq software. Results: nurses reported difficulties in the work process that potentially jeopardize patient safety. The following factors contribute to the patient safety concerns: shortage of professiomals, work overload, communication failures, teamwork and training process, impact of the pandemic against COVID-19, adverse events and reporting culture. Final considerations: the study demonstrated the fragility of nurses in relation to patient safety in Primary Health Care and the need for the topic to be widely discussed among all components of the Family Health Strategy teams(AU)

Objetivo: identificar el conocimiento de los enfermeros que actúan en la Estrategia Salud de la Familia en cuanto a la seguridad del paciente. Método: Investigación cualitativa, descriptiva, exploratoria, realizada con 20 enfermeros de la Estrategia Salud de la Familia en un municipio de Paraná. La recolección de datos se realizó entre julio y diciembre de 2021 por medio de entrevistas semiestructuradas. Los datos fueron categorizados y analizados utilizando el software Iramuteq. Resultados: los enfermeros declararon dificultades en el proceso de trabajo y aspectos que influyeron en las acciones relacionadas con la seguridad del paciente: falta de profesionales, sobrecarga de trabajo, fallas en la comunicación, trabajo en equipo y proceso de capacitación, impacto de la pandemia frente a la COVID-19, eventos adversos y cultura de notificación. Consideraciones finales: el estudio demostró la fragilidad de los enfermeros respecto a la seguridad del paciente en la Atención Primaria de Salud y la necesidad de que el tema sea ampliamente discutido entre todos los componentes de los equipos de la Estrategia Salud de la Familia(AU)

Targeting the glycine-rich domain of TDP-43 with antibodies prevents its aggregation in vitro and reduces neurofilament levels in vivo.

Cytoplasmic aggregation and concomitant nuclear clearance of the RNA-binding protein TDP-43 are found in ~ 90% of cases of amyotrophic lateral sclerosis and ~ 45% of patients living with frontotemporal lobar degeneration, but no disease-modifying therapy is available. Antibody therapy targeting other aggregating proteins associated with neurodegenerative disorders has shown beneficial effects in animal models and clinical trials. The most effective epitopes for safe antibody therapy targeting TDP-43 are unknown. Here, we identified safe and effective epitopes in TDP-43 for active and potential future passive immunotherapy. We prescreened 15 peptide antigens covering all regions of TDP-43 to identify the most immunogenic epitopes and to raise novel monoclonal antibodies in wild-type mice. Most peptides induced a considerable antibody response and no antigen triggered obvious side effects. Thus, we immunized mice with rapidly progressing TDP-43 proteinopathy ("rNLS8" model) with the nine most immunogenic peptides in five pools prior to TDP-43ΔNLS transgene induction. Strikingly, combined administration of two N-terminal peptides induced genetic background-specific sudden lethality in several mice and was therefore discontinued. Despite a strong antibody response, no TDP-43 peptide prevented the rapid body weight loss or reduced phospho-TDP-43 levels as well as the profound astrogliosis and microgliosis in rNLS8 mice. However, immunization with a C-terminal peptide containing the disease-associated phospho-serines 409/410 significantly lowered serum neurofilament light chain levels, indicative of reduced neuroaxonal damage. Transcriptomic profiling showed a pronounced neuroinflammatory signature (IL-1ß, TNF-α, NfκB) in rNLS8 mice and suggested modest benefits of immunization targeting the glycine-rich region. Several novel monoclonal antibodies targeting the glycine-rich domain potently reduced phase separation and aggregation of TDP-43 in vitro and prevented cellular uptake of preformed aggregates. Our unbiased screen suggests that targeting the RRM2 domain and the C-terminal region of TDP-43 by active or passive immunization may be beneficial in TDP-43 proteinopathies by inhibiting cardinal processes of disease progression.

Imunoterapia de dessensibilização para Malassezia spp. - Relato de caso experimental / Desensitization immunotherapy for Malassezia spp: experimental case report

A pitiríase versicolor (PV) consiste em uma infecção fúngica ocasionada por leveduras de Malassezia spp., que apesar de manejo simples, é uma doença com elevadas chances de recidiva e cronificação, além da pouca variedade de terapias efetivas para tratar cepas resistentes. Existem relatos na literatura sobre utilização de dessensibilização para Malassezia spp., mas para o tratamento de dermatite atópica e não PV, conferindo caráter inovador ao relato em questão. O caso apresentado consiste em um paciente de 28 anos, do sexo masculino, com manifestações típicas de PV em região de face, cervical, dorsal e axilar, há 4 anos, com resistência aos esquemas terapêuticos tópicos e sistêmicos. Uma vez identificada a ineficácia das terapias tradicionais, foi iniciado o tratamento com dessensiblização para Malassezia spp., em aplicações semanais, com aumento progressivo da dosagem e posterior aumento no intervalo das aplicações. Após onze meses de realização do novo tratamento, o paciente evoluiu com melhora completa das lesões. Conclui-se que a utilização de técnicas imunoterápicas para o tratamento de PV foi considerado eficaz no caso relatado, apesar de ainda não haver evidências que amparem sua utilização em maior escala.

Pityriasis versicolor is a infection caused by Malassezia yeast species, which, despite simple management, involves a high risk of recurrence and chronicity, and there are few effective therapies for resistant strains. Desensitization for Malassezia spp. has been reported in the literature, but for atopic dermatitis, rather than pityriasis versicolor, making this an innovative report. The case presented herein is of a 28-year-old man who had typical manifestations of pityriasis versicolor in the face, cervical, dorsal, and axillary region for 4 years that were resistant to topical and systemic therapies. Once the ineffectiveness of traditional therapies had been determined, weekly Malassezia desensitization sessions were begun, progressively increasing first in dosage and then in frequency. After 11 months, the lesions had improved completely. In this case, immunotherapeutic techniques effectively treated pityriasis versicolor, although the evidence is as yet insufficient to support large-scale use.

Necessidades humanas básicas afetadas e diagnósticos de enfermagem da nanda-i para pacientes graves com covid-19 / Necesidades humanas básicas afectadas y diagnósticos de enfermería de nanda-i para pacientes graves con covid-19 / Basic human needs affected and nanda-i nursing diagnoses for severe patients with covid-19

Objetivo: Identificar as Necessidades Humanas Básicas Psicobiológicas e os Diagnósticos de Enfermagem da NANDA-I para pacientes com covid-19 internados em unidade de terapia intensiva. Método: estudo descritivo, documental, transversal e quantitativo, realizado em uma unidade de terapia intensiva para pacientes com diagnóstico de covid-19, utilizando como fonte de dados o prontuário eletrônico do paciente. Para análise dos dados utilizou-se estatística descritiva, sendo avaliado frequência absoluta e relativa, média e desvio padrão. Resultados: foram identificadas sete Necessidades Humanas Básicas Psicobiológicas e 15 Diagnósticos de Enfermagem mais frequentes. Conclusão: o uso da Sistematização da Assistência de Enfermagem e a operacionalização do Processo de Enfermagem auxilia no planejamento individualizado do cuidado voltado à pacientes críticos com covid-19 internados em unidades de terapia intensiva. A identificação dessas necessidades contribui para o gerenciamento do cuidado e melhora a qualidade da assistência de enfermagem.

Objective: Identify Psychobiological Basic Human Needs and NANDA-I Nursing Diagnoses for patients with COVID-19 admitted to an intensive care unit. Method: descriptive, documentary, cross-sectional and quantitative study, carried out in an intensive care unit for patients diagnosed with COVID-19, using the patient's electronic medical record as a data source. Descriptive statistics were used for data analysis, with absolute and relative frequency, mean and standard deviation being evaluated. Results: seven Psychobiological Basic Human Needs and 15 most frequent Nursing Diagnoses were identified. Conclusion: the use of the Systematization of Nursing Care and the operationalization of the Nursing Process helps in the individualized planning of care aimed at critical patients with COVID-19 hospitalized in intensive care units. Identifying these needs contributes to the management of care and improves the quality of nursing care.

Objetivo: Identificar las Necesidades Humanas Básicas psicobiológicas y los Diagnósticos de Enfermería de NANDA-I para pacientes con covid-19 que ingresaron en una unidad de cuidados intensivos. Método: estudio descriptivo, documental, transversal y cuantitativo realizado en una unidad de cuidados intensivos para pacientes con diagnóstico de covid-19, utilizando como fuente de datos la historia clínica electrónica del paciente. Para el análisis de los datos se utilizó estadística descriptiva, que evaluó la frecuencia absoluta y relativa, la media y la desviación estándar. Resultados: se identificaron siete Necesidades Humanas Básicas Psicobiológicas y 15 Diagnósticos de Enfermería más frecuentes. Conclusión: el uso de la Sistematización de la Atención de Enfermería y la puesta en marcha del Proceso de Enfermería ayuda en la planificación individualizada de la atención dirigida a pacientes críticos con covid-19 hospitalizados en las unidades de cuidados intensivos. La identificación de esas necesidades contribuye a la gestión del cuidado y la mejora de la calidad de la atención de enfermería.

Construction and validation of an instrument to assess the comfort of adolescents undergoing chemotherapy.

OBJECTIVE: To build and validate a self-report instrument to assess the comfort of adolescents with cancer undergoing chemotherapy. METHODS: This methodological study was developed in five stages: scoping review; qualitative study to characterize comfort from the perspective of adolescents with cancer undergoing chemotherapy; instrument construction; instrument content validation by experts; pre-test with a group of adolescents. RESULTS: In the scoping review, 20 comfort changes were identified; regarding the perspective of comfort for adolescents, it was possible to identify the effects on their daily lives and the impact on chemotherapy; in content validation, the index was 0.96 and Cronbach's Alpha 0.87. In the pre-test, the instrument obtained the final version with 37 items and Cronbach's Alpha 0.94. CONCLUSIONS: The constructed and validated self-report instrument showed good reliability related to satisfactory psychometric parameters and can be used by nurses in clinical practice to assess and evidence comfort changes.

Molecular profiling of CO2/pH-sensitive neurons in the locus coeruleus of bullfrogs reveals overlapping noradrenergic and glutamatergic cell identity.

Locus coeruleus (LC) neurons regulate breathing by sensing CO2/pH. Neurons within the vertebrate LC are the main source of norepinephrine within the brain. However, they also use glutamate and GABA for fast neurotransmission. Although the amphibian LC is recognized as a site involved in central chemoreception for the control of breathing, the neurotransmitter phenotype of these neurons is unknown. To address this question, we combined electrophysiology and single-cell quantitative PCR to detect mRNA transcripts that define norepinephrinergic, glutamatergic, and GABAergic phenotypes in LC neurons activated by hypercapnic acidosis (HA) in American bullfrogs. Most LC neurons activated by HA had overlapping expression of noradrenergic and glutamatergic markers but did not show strong support for GABAergic transmission. Genes that encode the pH-sensitive K+ channel, TASK2, and acid-sensing cation channel, ASIC2, were most abundant, while Kir5.1 was present in 1/3 of LC neurons. The abundance of transcripts related to norepinephrine biosynthesis linearly correlated with those involved in pH sensing. These results suggest that noradrenergic neurons in the amphibian LC also use glutamate as a neurotransmitter and that CO2/pH sensitivity may be linkedto the noradrenergic cell identity.

Synaptic modifications transform neural networks to function without oxygen.

BACKGROUND: Neural circuit function is highly sensitive to energetic limitations. Much like mammals, brain activity in American bullfrogs quickly fails in hypoxia. However, after emergence from overwintering, circuits transform to function for approximately 30-fold longer without oxygen using only anaerobic glycolysis for fuel, a unique trait among vertebrates considering the high cost of network activity. Here, we assessed neuronal functions that normally limit network output and identified components that undergo energetic plasticity to increase robustness in hypoxia. RESULTS: In control animals, oxygen deprivation depressed excitatory synaptic drive within native circuits, which decreased postsynaptic firing to cause network failure within minutes. Assessments of evoked and spontaneous synaptic transmission showed that hypoxia impairs synaptic communication at pre- and postsynaptic loci. However, control neurons maintained membrane potentials and a capacity for firing during hypoxia, indicating that those processes do not limit network activity. After overwintering, synaptic transmission persisted in hypoxia to sustain motor function for at least 2 h. CONCLUSIONS: Alterations that allow anaerobic metabolism to fuel synapses are critical for transforming a circuit to function without oxygen. Data from many vertebrate species indicate that anaerobic glycolysis cannot fuel active synapses due to the low ATP yield of this pathway. Thus, our results point to a unique strategy whereby synapses switch from oxidative to exclusively anaerobic glycolytic metabolism to preserve circuit function during prolonged energy limitations.

Maternal pre-pregnancy body mass index, gestational weight gain and child weight during the first 2 years of life in an Amazonian birth cohort.

BACKGROUND: In socially vulnerable populations, evidence is needed regarding the role of maternal nutritional status on child weight during the first 2 years of life. OBJECTIVES: We aimed to assess the association of pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with offspring BMI-for-age z-scores (BAZs) during the first 2 years of life. METHODS: A population-based birth cohort study was conducted with 900 mother-child pairs. Pre-pregnancy weight and weight at delivery were collected from medical records, and anthropometric data were measured at birth and at 6-month, 1-year and 2-year follow-up visits. Linear regression and linear mixed-effect models assessed associations with pre-pregnancy BMI, GWG and BAZ during the first 2 years of life. RESULTS: Pre-pregnancy overweight and obesity and excessive GWG were positively associated with BAZ at birth and at 1- and 2-year follow-up visits. There were no significant additional BAZ changes per year based on the exposures up to age 2 years. CONCLUSIONS: Elevated maternal pre-pregnancy BMI and GWG were associated with a child's higher BAZ at birth, and these differences remained constant throughout the first 2 years of life in Amazonian children. These findings highlight the importance of promoting adequate maternal weight before pregnancy and during prenatal care also in socially vulnerable populations.

Synthesis by Microwave Irradiation, Molecular Structural Analysis and Trypanocidal Activity of Novel Pyrazole-tetrahydropyrimidine Derivatives.

BACKGROUND: A series of new eight 2-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1,4,5,6-tetrahydropyrimidines 1(a-h) were synthesized by microwave irradiation technique. In vitro phenotypic screening was performed to evaluate the effect of these compounds on intracellular amastigotes forms of Trypanosoma cruzi, the etiological agent of Chagas disease. METHODS: Compounds 1(a-h) were synthesized from pyrazole-carbonitriles 2(a-h) employing microwave irradiation (50W) for 10-20 minutes. Physicochemical properties were calculated using OSIRIS DataWarrior. The toxic effect on mammalian cells (Vero Cells) and the trypanocidal activity against Trypanosoma cruzi (Dm28c-Luc) were also evaluated. RESULTS: Compounds 1(a-h) were obtained in 24-94% yields. They were completely characterized by Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR) and High-Resolution Mass Spectrometry (HRMS) analyses. The derivatives showed low trypanocidal activity, with IC50 ranging from 47.16 to > 100 µM, with lower activity than benznidazole (1.93 µM) used as reference drug. CONCLUSION: The attractive features of this synthetic methodology are mild conditions, short reaction time, and low power. All derivatives showed low toxicity in mammalian cells, good oral bioavailability, and did not violate Lipinski´s rule of 5.

Plasticity in the functional properties of NMDA receptors improves network stability during severe energy stress.

Brain energy stress leads to neuronal hyperexcitability followed by a rapid loss of function and cell death. In contrast, the frog brainstem switches into a state of extreme metabolic resilience that allows them to maintain motor function during hypoxia as they emerge from hibernation. NMDA receptors (NMDARs) are Ca2+-permeable glutamate receptors that contribute to the loss of homeostasis during hypoxia. Therefore, we hypothesized that hibernation leads to plasticity that reduces the role of NMDARs within neural networks to improve function during energy stress. To test this, we assessed a circuit with a large involvement of NMDAR synapses, the brainstem respiratory network of female bullfrogs, Lithobates catesbeianus. Contrary to our expectations, hibernation did not alter the role of NMDARs in generating network output, nor did it affect the amplitude, kinetics, and hypoxia sensitivity of NMDAR currents. Instead, hibernation strongly reduced NMDAR Ca2+ permeability and enhanced desensitization during repetitive stimulation. Under severe hypoxia, the normal NMDAR profile caused network hyperexcitability within minutes, which was mitigated by blocking NMDARs. After hibernation, the modified complement of NMDARs protected against hyperexcitability, as disordered output did not occur for at least one hour in hypoxia. These findings uncover state-dependence in the plasticity of NMDARs, whereby multiple changes to receptor function improve neural performance during energy stress without interfering with its normal role during healthy activity.