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Objectives: Environmental factors such as physical activity induce epigenetic modifications, with exercise-responsive DNA methylation changes occurring in skeletal muscle. To determine the skeletal muscle DNA methylation signature of endurance swim training, we used whole-genome methylated DNA immunoprecipitation (MeDIP) sequencing. Methods: We utilized endurance-trained rats, cultured L6 myotubes, and human skeletal muscle cells, employing MeDIP sequencing, gene silencing, and palmitate oxidation assays. Additional methods included promoter luciferase assays, fluorescence microscopy, and RNA/DNA analysis to investigate exercise-induced molecular changes. Results: Gene set enrichment analysis (GSEA) of differentially methylated promoter regions identified an enrichment of four gene sets, including those linked to lipid metabolic processes, with hypermethylated or hypomethylated promoter regions in skeletal muscle of exercise-trained rats. Bisulfite sequencing confirmed hypomethylation of CpGs in the Serhl2 (Serine Hydrolase Like 2) transcription start site in exercise-trained rats. Serhl2 gene expression was upregulated in both exercise-trained rats and an ''exercise-in-a-dish'' model of L6 myotubes subjected to electrical pulse stimulation (EPS). Serhl2 promoter activity was regulated by methylation and EPS. A Nr4a binding motif in the Serhl2 promoter, when deleted, reduced promoter activity and sensitivity to methylation in L6 myotubes. Silencing Serhl2 in L6 myotubes reduced intracellular lipid oxidation and triacylglycerol synthesis in response to EPS. Conclusions: Exercise-training enhances intracellular lipid metabolism and phenotypic changes in skeletal muscle through epigenomic modifications on Serhl2. Hypomethylation of the Serhl2 promoter influences Nr4a transcription factor binding, promoter activity, and gene expression, linking exercise-induced epigenomic regulation of Serhl2 to lipid oxidation and triacylglycerol synthesis.

RESUMO Objetivo Investigar se há diferença na classificação da hipernasalidade de fala de ouvintes não experientes usando escalas ordinais distintas; verificar a concordância dos ouvintes nas análises ao empregar estas escalas e verificar se a ordem de apresentação das escalas influencia os resultados. Método Vinte acadêmicos em Fonoaudiologia classificaram os graus de hipernasalidade de 40 amostras (orais) de pacientes com fissura labiopalatina. Dez realizaram as classificações utilizando escala de 4 pontos (ausente, leve, moderada e grave) e, após duas semanas, utilizando escala de 3 pontos (ausente, pouco hipernasal e muito hipernasal). Outros dez alunos realizaram as mesmas classificações, porém em ordem inversa. As classificações foram feitas de forma remota e documentadas em um formulário. Resultados A porcentagem média de respostas corretas dos alunos, em relação ao padrão-ouro, foi significativamente maior para a escala de 3 pontos. Não houve interação significativa entre ordem de apresentação e escala para o percentual de acerto das classificações. A concordância dos alunos em relação à avaliação padrão-ouro foi regular (escala de 3 pontos) e moderada (escala de 4 pontos). A porcentagem média de concordância das análises intra-avaliador foi significativamente maior para a escala de 3 pontos. Não houve interação significativa entre ordem de apresentação e escala para o percentual das classificações intra-avaliadores. O índice de coeficiente Kappa mostrou concordância intra-avaliador mais favorável para a escala reduzida. Conclusão A escala reduzida favoreceu a classificação da hipernasalidade de fala pelos ouvintes e pode ser considerada uma importante estratégia para favorecer as avaliações iniciais de acadêmicos em Fonoaudiologia durante sua formação.

Abstract Background The maintenance of skeletal muscle plasticity upon changes in the environment, nutrient supply, and exercise depends on regulatory mechanisms that couple structural and metabolic adaptations. The mechanisms that interconnect both processes at the transcriptional level remain underexplored. Nr2f6, a nuclear receptor, regulates metabolism and cell differentiation in peripheral tissues. However, its role in the skeletal muscle is still elusive. Here, we aimed to investigate the effects of Nr2f6 modulation on muscle biology in vivo and in vitro. Methods Global RNA‐seq was performed in Nr2f6 knockdown C2C12 myocytes (N = 4–5). Molecular and metabolic assays and proliferation experiments were performed using stable Nr2f6 knockdown and Nr2f6 overexpression C2C12 cell lines (N = 3–6). Nr2f6 content was evaluated in lipid overload models in vitro and in vivo (N = 3–6). In vivo experiments included Nr2f6 overexpression in mouse tibialis anterior muscle, followed by gene array transcriptomics and molecular assays (N = 4), ex vivo contractility experiments (N = 5), and histological analysis (N = 7). The conservation of Nr2f6 depletion effects was confirmed in primary skeletal muscle cells of humans and mice. Results Nr2f6 knockdown upregulated genes associated with muscle differentiation, metabolism, and contraction, while cell cycle‐related genes were downregulated. In human skeletal muscle cells, Nr2f6 knockdown significantly increased the expression of myosin heavy chain genes (two‐fold to three‐fold) and siRNA‐mediated depletion of Nr2f6 increased maximal C2C12 myocyte's lipid oxidative capacity by 75% and protected against lipid‐induced cell death. Nr2f6 content decreased by 40% in lipid‐overloaded myotubes and by 50% in the skeletal muscle of mice fed a high‐fat diet. Nr2f6 overexpression in mice resulted in an atrophic and hypoplastic state, characterized by a significant reduction in muscle mass (15%) and myofibre content (18%), followed by an impairment (50%) in force production. These functional phenotypes were accompanied by the establishment of an inflammation‐like molecular signature and a decrease in the expression of genes involved in muscle contractility and oxidative metabolism, which was associated with the repression of the uncoupling protein 3 (20%) and PGC‐1α (30%) promoters activity following Nr2f6 overexpression in vitro. Additionally, Nr2f6 regulated core components of the cell division machinery, effectively decoupling muscle cell proliferation from differentiation. Conclusions Our findings reveal a novel role for Nr2f6 as a molecular transducer that plays a crucial role in maintaining the balance between skeletal muscle contractile function and oxidative capacity. These results have significant implications for the development of potential therapeutic strategies for metabolic diseases and myopathies.

ABSTRACT Objective: To compare the knowledge of Dental and Speech-Language Pathology undergraduate students about prosthesis treatment of velopharyngeal dysfunction in cases of cleft lip and palate before and after using educational multimedia material. Methods: The sample comprised 58 students (38 from the Dental program, and 20 from the Speech-Language Pathology program). A questionnaire on prosthesis treatment of velopharyngeal dysfunction in cases of cleft lip and palate was administered to a group of Dental and Speech-Language Pathology undergraduate students before and after they had access to educational multimedia (video) material on the topic approached in this study. Inferential statistics were used to investigate the significance of differences in correct answers before and after the Dental and Speech-Language Pathology undergraduate students had access to the multimedia/video material. Results: Before having access to the multimedia/video material, Speech-Language Pathology students had more correct answers (Dental: 4.89±1.31; SLP: 6.30±0.57). After having access to the material, the difference in correct answers between the students of both programs decreased (Dental: 6.00±0.66; SLP: 6.45±0.51), as Dental students’ knowledge of the research topic increased. The comparison of the total sample before and after applying the multimedia/video material also demonstrated an increase in correct answers. Conclusion: Speech-Language Pathology students proved to have greater previous knowledge of palatal prostheses used for velopharyngeal dysfunction in cases of cleft lip and palate. Moreover, using the multimedia material possibly increased both Dental and Speech-Language Pathology students’ knowledge of this topic.

RESUMO Objetivo Caracterizar e comparar a audição e o estado da orelha média na fissura labiopalatina nas condições com ou sem história de tubo de ventilação. Métodos Estudo retrospectivo de 463 prontuários de pacientes com fissura transforame unilateral não sindrômica, operados. Foram analisadas otoscopia, imitanciometria, audiometria e história de TV ao longo de dez anos. Resultados Dos 440 prontuários incluídos no estudo, 254 (58%) apresentaram história de TV, enquanto 186 (42%) não apresentaram. As alterações encontradas nos exames de otoscopia foram mais frequentes nas orelhas com história de TV, e o resultado estatístico revelou associação significativa entre presença de TV e ocorrência de fluido (p

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia.

The transcriptional coactivator PGC-1α has been implicated in the regulation of multiple metabolic processes. However, the previously reported metabolic phenotypes of mice deficient in PGC-1α have been inconsistent. PGC-1α exists as multiple isoforms, including variants transcribed from an alternative first exon. We show here that alternative PGC-1α variants are the main entity that increases PGC-1α during exercise. These variants, unlike the canonical isoform of PGC-1α, are robustly upregulated in human skeletal muscle after exercise. Furthermore, the extent of this upregulation correlates with oxygen consumption. Mice lacking these variants manifest impaired energy expenditure during exercise, leading to the development of obesity and hyperinsulinemia. The alternative variants are also upregulated in brown adipose tissue in response to cold exposure, and mice lacking these variants are intolerant of a cold environment. Our findings thus indicate that an increase in PGC-1α expression, attributable mostly to upregulation of alternative variants, is pivotal for adaptive enhancement of energy expenditure and heat production and thereby essential for the regulation of whole-body energy metabolism.

There is mounting evidence that the cerebellum impacts hippocampal functioning, but the impact of the cerebellum on hippocampal interneurons remains obscure. Using miniscopes in freely behaving male and female mice, we found optogenetic stimulation of Purkinje cells alters the calcium activity of a large percentage of CA1 interneurons. This includes both increases and decreases in activity. Remarkably, this bidirectional impact occurs in a coordinated fashion, in line with interneurons' functional properties. Specifically, CA1 interneurons activated by cerebellar stimulation are commonly locomotion-active, while those inhibited by cerebellar stimulation are commonly rest-active interneurons. We additionally found that subsets of CA1 interneurons show altered activity during object investigations. Importantly, these interneurons also show coordinated modulation by cerebellar stimulation: CA1 interneurons that are activated by cerebellar stimulation are more likely to be activated, rather than inhibited, during object investigations, while interneurons that show decreased activity during cerebellar stimulation show the opposite profile. We examined two different stimulation locations (IV/V vermis or simplex) and two different stimulation approaches (7 Hz or a single 1 s light pulse)--in all cases, the cerebellum induces similar coordinated CA1 interneuron changes congruent with an explorative state. Overall, our data show that CA1 interneurons are impacted by cerebellar manipulation in a bidirectional and coordinated fashion and are therefore likely to play an important role in cerebello-hippocampal communication. [ABSTRACT FROM AUTHOR]

Achieving temporally precise, noninvasive control over specific neural cell types in the deep brain would advance the study of nervous system function. Here we use the potent channelrhodopsin ChRmine to achieve transcranial photoactivation of defined neural circuits, including midbrain and brainstem structures, at unprecedented depths of up to 7 mm with millisecond precision. Using systemic viral delivery of ChRmine, we demonstrate behavioral modulation without surgery, enabling implant-free deep brain optogenetics.

BackgroundEndoscopic endonasal approaches pose the potential risk of olfactory loss. Loss of olfaction and potentially taste can be permanent and greatly affect patients' quality of life. Treatments for olfactory loss have had limited success. Omega-3 supplementation may be a therapeutic option with its effect on wound healing and nerve regeneration.ObjectiveTo evaluate the impact on olfaction in patients treated with omega-3 supplementation following endoscopic skull base tumor resection.MethodsIn this multi-institutional, prospective, randomized controlled trial, 110 patients with sellar or parasellar tumors undergoing endoscopic resection were randomized to nasal saline irrigations or nasal saline irrigations plus omega-3 supplementation. The University of Pennsylvania Smell Identification Test (UPSIT) was administered preoperatively and at 6 wk, 3 mo, and 6 mo postoperatively.ResultsEighty-seven patients completed all 6 mo of follow-up (41 control arm, 46 omega-3 arm). At 6 wk postoperatively, 25% of patients in both groups experienced a clinically significant loss in olfaction. At 3 and 6 mo, patients receiving omega-3 demonstrated significantly less persistent olfactory loss compared to patients without supplementation (P = .02 and P = .01, respectively). After controlling for multiple confounding variables, omega-3 supplementation was found to be protective against olfactory loss (odds ratio [OR] 0.05, 95% CI 0.003-0.81, P = .03). Tumor functionality was a significant independent predictor for olfactory loss (OR 32.7, 95% CI 1.15-929.5, P = .04).ConclusionOmega-3 supplementation appears to be protective for the olfactory system during the healing period in patients who undergo endoscopic resection of sellar and parasellar masses.

Introduction: Data mining techniques expand access to important information for the decision-making process during health care. The objective the study proposes using data mining techniques to identify variables (surgical treatment protocols, patient characteristics, post-surgical complications) associated with fistulas after primary palatoplasty in patients with unilateral transforamen incisor cleft (UTIC). Method: A data set of 222 patients with UTIC without syndromes, operated by four surgeons with Furlow’s or von Langenbeck’s primary palatoplasty techniques, was analyzed for this study. Two models for detecting the outcome of surgery were induced using data mining techniques (Decision Tree and Apriori). Results: Five rules were selected from a decision tree pointing to some variables as predictors of fistulas associated with primary palatoplasty: infection, cough, hypernasality, and surgeon. Analysis of the model indicates that it correctly classifies 95.9% of occurrences between the absence and presence of fistulas. The second model indicates that the absence of post-surgical complications (infection and fever) and normal speech results (absent hypernasality, without suggestive of velopharyngeal dysfunction) are related to the absence of fistulas. Regarding surgical procedures, the Furlow technique and the Vomer flap were more frequent in patients with fistulas. Conclusion: Data mining techniques, as applied in the present study, pointed to infection and cough, hypernasality, and surgeon and surgical techniques as predictors of fistulas related to primary palatoplasty.