Thousands of induced germline mutations affecting immune cells identified by automated meiotic mapping coupled with machine learning.

Forward genetic studies use meiotic mapping to adduce evidence that a particular mutation, normally induced by a germline mutagen, is causative of a particular phenotype. Particularly in small pedigrees, cosegregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the identification of mutations causing immune phenotypes in mice by creating Candidate Explorer (CE), a machine-learning software program that integrates 67 features of genetic mapping data into a single numeric score, mathematically convertible to the probability of verification of any putative mutation-phenotype association. At this time, CE has evaluated putative mutation-phenotype associations arising from screening damaging mutations in ∼55% of mouse genes for effects on flow cytometry measurements of immune cells in the blood. CE has therefore identified more than half of genes within which mutations can be causative of flow cytometric phenovariation in Mus musculus The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.

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.

Alteration in glucose metabolism in the brain associated with tamoxifen treatment: Study in postmenopausal animal model.

Tamoxifen is an effective breast cancer therapy in postmenopausal women. However, it can induce hyperglycemia through different mechanisms, such as the impairment of mitochondrial metabolism. Quercetin, a flavonoid with antioxidant potential, has beneficial effects on tamoxifen-induced adverse effects. Therefore, this study aimed to (1) investigate glucose concentration in blood, cerebrospinal fluid, cerebellum, cortex, and hippocampus of tamoxifen-treated ovariectomized female rats, non-treated and treated with quercetin; and (2) establish the metabolic profile of these regions. For that purpose, ovariectomized female rats were divided into four groups: canola oil 1 mL/kg (CONT); tamoxifen 5 mg/kg (TAM); quercetin 22.5 mg/kg (QUER); and tamoxifen 5 mg/kg + quercetin 22.5 mg/kg (TAM + Q); and were treated for 14 days orally. Subsequently, glucose levels were measured in blood, cerebrospinal fluid, cerebellum, cortex, and hippocampus. Pyruvate and lactate concentrations were analyzed in the three brain regions. Tamoxifen-induced hyperglycemia significantly increased glucose concentrations in the cerebrospinal fluid, cortex, and hippocampus, as well as lactate production in the hippocampus. Quercetin significantly prevented the tamoxifen-induced increase in glucose concentrations in all analyzed samples. Besides, quercetin decreased cortical pyruvate production. The copper content decreased only in the hippocampus of group TAM + Q animals. In addition, it is important to highlight that this study also observed that fourteen days of tamoxifen treatment strongly affects brain glucose metabolism, potentially disrupting normal brain functions. Therefore, this drug might represent a risk factor for postmenopausal women undergoing chemoprevention. Meanwhile, quercetin represents a potential intervention to promote metabolic regulation of glucose in tamoxifen-treated women.

Alterations in neuromuscular junctions and oxidative stress of the soleus muscle of obese Wistar rats caused by vibratory platform training.

OBJECTIVES: evaluate the effects that whole-body vibration (WBV) causes on the neuromuscular junctions and oxidative stress of the soleus muscle of obese Wistar rats. METHODS: 32 male Wistar rats were used, 16 of which were obesity induced by monosodium glutamate, randomized into four groups: control (GC), control with WBV (GCP), obese (GO) and obese with WBV (GOP). At the 70 days old, the training on WBV was started, performed 3 times a week, during 8 consecutive weeks. At the 130 days old, the animals were euthanized and the soleus muscles were collected. RESULTS: Regarding the analysis of the neuromuscular junctions, the obese groups had lower mean size when compared to the control groups. On the other hand, the WBV presented higher averages when compared to the groups that did not perform the training. Regarding the oxidative stress, for the lipid peroxidation there was a significant difference between obese and non-obese animals, however, there was no difference between the animals WBV and those who did not. CONCLUSION: WBV promotes beneficial changes such as increased measurements of the structures of the neuromuscular junctions, but is not able to promote changes in the concentration of the cholinesterase enzyme in the synaptic cleft.

eHealth Literacy in German Skin Cancer Patients.

The global incidence of skin cancer has steadily increased in recent years, and malignant melanoma still has one of the fastest-growing incidence rates among all malignant tumors in the western world. Thus, newly diagnosed patients have an increased need for health information concerning their disease. Using a standardized questionnaire, our study aims to investigate our patients' primary sources of health-related information as well as their self-proclaimed eHealth literacy. We received 714 questionnaires. Regardless of age, the primary source of information was the treating dermato-oncologist, followed by the treating general practitioner and the Internet. However, with increasing age, the usage of the Internet decreased. Hence, younger participants were better equipped to find health-related information while using the Internet. Additionally, comprehending health-related information and gaining medical knowledge was significantly increased in better-educated participants. Overall, our study shows that with increased use of eHealth services, accessing web-based information increased, correlating with a better eHealth literacy of our patients. eHealth technologies are increasingly becoming more prevalent as a primary source of information in our modern health care system. Thus, it is crucial to educate cancer patients in eHealth literacy to make autonomous, informed decisions and gain more confidence in dealing with their disease.

Whole-Body Vibration Promotes Skeletal Muscle Restructuring and Reduced Obesogenic Effect of MSG in Wistar Rats.

The negative changes of obesity to the locomotor system are a major concern in the current scenario, where obesity and metabolic syndrome are recurrent in Western societies. A physical exercise is an important tool as a way to rehabilitate obesity, highlighting whole-body vibration, as it is an easy-access modality with few restrictions. In this sense, we sought to evaluate the effect of whole-body vibration on the extensor digitorum longus muscle on a monosodium glutamate-induced obesity model. The main findings of the present study are related to the ability of the treatment with vibration to reduce the obesogenic characteristics and slow down the dyslipidemic condition of the animals. Likewise, the vibration promoted by the vibrating platform was essential in the recovery of the muscle structure, as well as the recovery of the muscle's oxidative capacity, initially compromised by obesity.

Morality is relative: Anger, disgust, and aggression as contingent responses to sibling versus acquaintance harm.

Angry reactions to moral violations should be heightened when wrongs befall oneself in comparison with when wrongs befall acquaintances, as prior research by Molho, Tybur, Güler, Balliet, and Hofmann (2017) demonstrates, because aggressive confrontation is inherently risky and therefore only incentivized by natural selection to curtail significant fitness costs. Here, in 3 preregistered studies, we extend this sociofunctional perspective to cases of wrongs inflicted on siblings. We observed equivalently heightened anger in response to transgressions against either oneself or one's sibling relative to transgressions against acquaintances across studies, whereas transgressions against acquaintances evoked greater disgust and/or fear (both associated with social avoidance) in 2 of the 3 studies. Studies 2 and 3, which incorporated measures of tendencies to confront the transgressor, confirmed that the elevated anger elicited by self or sibling harm partially mediated heightened inclinations toward direct aggression. Finally, in Study 3 we compared tendencies to experience anger and to directly aggress on behalf of siblings and close friends. Despite reporting greater affiliative closeness for friends than for siblings, harm to friends failed to evoke heightened anger relative to acquaintance harm, and participants were inclined to directly aggress against those who had harmed their sibling to a significantly greater extent than when the harm befell their friend. These overall results broadly replicate Molho et al.'s (2017) findings and theoretically extend the sociofunctionalist account of moral emotions to kinship. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Has the COVID-19 Pandemic Accelerated the Future of Work or Changed Its Course? Implications for Research and Practice.

The COVID-19 pandemic is a unique transboundary crisis which has disrupted people's way of life more dramatically than any event in generations. Given the ambiguity surrounding the end of the COVID-19 pandemic and its enduring negative effects, it is important to understand how this has affected important future of work trends. The aim of the current paper is to assess the impact of the COVID-19 pandemic on commonly discussed future of work trends relevant to occupational safety and health priority areas. These topics include work arrangements, compensation and benefits, and the organization of work. For each topic, we assess trends leading up to the COVID-19 pandemic, discuss the impact of the pandemic on these trends, and conclude with implications for research and practice. Overall, the pandemic appears to have both accelerated and disrupted various trends associated with future of work topic areas. These effects are discussed in terms of implications for both policymakers and organizations.

Whole-body vibration promotes lipid mobilization in hypothalamic obesity rat.

OBJECTIVES: This study aimed to analyze the effect of whole-body vibration (WBV) on metabolic parameters using the monosodium l-glutamate (MSG) model of obesity. METHOD: MSG-obese rats that were exposed to WBV on a vibrating platform with 60 Hz frequency, 2 mm amplitude, three times/week, 10 min/day, during eight weeks (from postnatal day (PN) 80 to PN136). Blood glucose, creatine kinases (CK and CK-MB) and lipid profile through plasma and liver levels of lipids and lipoproteins were evaluated. Morphology and oxidative stress of adipose and hepatic tissues were further evaluated. RESULTS: When performing a WBV exercise, animals showed contrasting metabolic responses. Vibration Control group (CTL-WBV) presented a reduction in CK and liver triacylglycerol, an increase in glucose, lactate, total cholesterol, liver cholesterol, and LDL while MSG Vibration group (MSG-WBV) showed an increase in total triacylglycerol, VLDL, lactate, CK, liver cholesterol, additional liver lipid peroxidation and LDL, total cholesterol and CKMB reduction. CONCLUSION: Even although the MSG is a model of impacting injury, the metabolic demand of WBV exercise was able to induce mobilization of substrates, highlighting the lipid mobilization in obese animals, it should be used as a metabolic rehabilitation tool in patients with metabolic diseases, such as obesity and diabetes.

Phonatory effects of airway dehydration: preliminary evidence for impaired compensation to oral breathing in individuals with a history of vocal fatigue.

PURPOSE: Airway drying is detrimental to phonation and is posited to exacerbate vocal fatigue. However, limited research has demonstrated the adverse phonatory effects of dehydration in speakers reporting vocal fatigue. We compared the negative phonatory consequences of short-term oral breathing at low, moderate, and high humidity in individuals reporting a history of vocal fatigue and control participants. METHOD: Females reporting a history of vocal fatigue (N = 8) and matched controls (N = 8) participated in a repeated-measures design over 3 different days. RESULTS: Oral breathing at low and moderate humidity increased phonation threshold pressure (PTP) to a greater extent in individuals reporting a history of vocal fatigue as compared to controls. Conversely, PTP did not increase in either participant group after oral breathing in a humid environment. Perceived phonatory effort (PPE) ratings were poorly correlated with PTP. CONCLUSIONS: The emergence of between-group differences in PTP at low and moderate but not high ambient humidity demonstrates that drying challenges might be detrimental to voice production in individuals with a history of vocal fatigue. Based on the phonatory effects of dehydration, we suggest that individuals reporting vocal fatigue may demonstrate impaired compensation to airway drying induced by short-term oral breathing.

Avaliação comportamental de ratos treinados em natação forçada / Behavioral assessment of rats through the forced-swimming test

Objetivos: O exercício físico regular tem diversos efeitos benéficos, contudo, há relatos de aumento na concentração de corticosteroides endógenos, os quais podem inibir a neurogênese e piorar as funções cognitivas, sendo este um aspecto dúbio do exercício físico. O objetivo deste estudo foi avaliar, por meio de testes comportamentais, o efeito do exercício crônico por natação forçada com e sem sobrecarga, sobre parâmetros de ansiedade em ratos Wistar.Métodos: Foram utilizados 24 ratos Wistar, separados em três grupos: Grupo Controle - submetido apenas a avaliações e contato com a água; Grupo Natação - composto por animais submetidos à natação com tempo progressivo; Grupo Natação com Sobrecarga - composto por animais submetidos à natação com sobrecarga de 10% do peso corporal. O exercício ocorreu três vezes por semana, no período vespertino, com aumento no tempo a cada duas semanas (20, 30 e 40 minutos), totalizando seis semanas. Foi realizado em um tanque de água circular de 200 litros, com profundidade de 50 cm e temperatura da água mantida entre 30 e 32º C. A ansiedade dos animais foi avaliada pelos testes Labirinto em Cruz Elevado e Campo Aberto.Resultados: Não houve diferenças significativas em qualquer dos testes comportamentais, comparando os três grupos.Conclusões: Não houve alteração no padrão comportamental de ratos Wistar submetidos a diferentes protocolos de exercício (natação forçada com e sem sobrecarga) quando comparados ao grupo controle não submetido a exercícios.

Aims: Regular exercise has several beneficial effects. However, reports show increasing concentrations of endogenous corticosteroids, which may inhibit neurogenesis and deteriorate cognitive functions, thus raising doubts as to the benefits of physical exercise. The objective of this study was to evaluate, through behavioral tests, the effect of chronic forced swimming with and without overload on anxiety parameters in Wistar rats. Methods: Twenty-four Wistar rats, divided into three groups, were assessed: Control Group - subjected only to evaluations and contact with water; Swimming Group - consisting of animals submitted to progressive swimming time; Weight-loaded Swimming Group - consisting of animals submitted to swimming with loads in excess of 10% of their body weight. The exercise was performed three times a week in the afternoon, with swimming time increases every two weeks (20, 30, and 40 minutes), during six weeks, A 200-liter circular water tank, filled to a depth of 50 cm, was used, and the water temperature was kept between 30º and 32º C. The animals' anxiety was assessed by the Elevated Plus Maze and Open Field tests. Results: No significant differences between the three groups were detected by any of the behavioral tests.Conclusions: No changes were observed in the behavioral pattern of Wistar rats submitted to different exercise protocols (forced swimming with and without overload) compared to the control group.