Trilobatin contributes to the improvement of myopathy in a mouse model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) occurs due to genetic mutations that lead to a deficiency in dystrophin production and consequent progressive degeneration of skeletal muscle fibres, through oxidative stress and an exacerbated inflammatory process. The flavonoid trilobatin (TLB) demonstrates antioxidant and anti-inflammatory potential. Its high safety profile and effective action make it a potent therapy for the process of dystrophic muscle myonecrosis. Thus, we sought to investigate the action of TLB on damage in a DMD model, the mdx mouse. Eight-week-old male animals were treated with 160 mg/kg/day of trilobatin for 8 weeks. Control animals were treated with saline. Following treatment, muscle strength, serum creatine kinase (CK) levels, histopathology (necrotic myofibres, regenerated fibres/central nuclei, Feret's diameter and inflammatory area) and the levels of catalase and NF-κB (western blotting) of the quadriceps (QUA), diaphragm (DIA) and tibialis anterior (TA) muscles were measured. TLB was able to significantly increase muscle strength and reduce serum CK levels in dystrophic animals. The QUA of mdx mice showed a reduction in catalase and the number of fibres with a centralized nucleus after treatment with TLB. In the DIA of dystrophic animals, TLB reduced the necrotic myofibres, inflammatory area and NF-κB and increased the number of regenerated fibres and the total fibre diameter. In TA, TLB increased the number of regenerated fibres and reduced catalase levels in these animals. It is concluded that in the mdx experimental model, treatment with TLB was beneficial in the treatment of DMD.

Social victimization, default mode network connectivity, and psychotic-like experiences in adolescents.

Social victimization (SV) and altered neural connectivity have been associated with each other and psychotic-like experiences (PLE). However, research has not directly examined the associations between these variables, which may speak to mechanisms of psychosis-risk. Here, we utilized two-year follow-up data from the Adolescent Brain Cognitive Development study to test whether SV increases PLE through two neural networks mediating socio-affective processes: the default mode (DMN) and salience networks (SAN). We find that a latent SV factor was significantly associated with PLE outcomes. Simultaneous mediation analyses indicated that the DMN partially mediated the SV-PLE association while the SAN did not. Further, multigroup testing found that while Black and Hispanic adolescents experienced SV differently than their White peers, the DMN similarly partially mediated the effect of SV on PLE for these racial groups. These cross-sectional results highlight the importance of SV and its potential impact on social cognitive neural networks for psychosis risk.

Training volitional control of the theory of mind network with real-time fMRI neurofeedback.

Is there a way improve our ability to understand the minds of others? Towards addressing this question, here, we conducted a single-arm, proof-of-concept study to evaluate whether real-time fMRI neurofeedback (rtfMRI-NF) from the temporo-parietal junction (TPJ) leads to volitional control of the neural network subserving theory of mind (ToM; the process by which we attribute and reason about the mental states of others). As additional aims, we evaluated the strategies used to self-regulate the network and whether volitional control of the ToM network was moderated by participant characteristics and associated with improved performance on behavioral measures. Sixteen participants underwent fMRI while completing a task designed to individually-localize the TPJ, and then three separate rtfMRI-NF scans during which they completed multiple runs of a training task while receiving intermittent, activation-based feedback from the TPJ, and one run of a transfer task in which no neurofeedback was provided. Region-of-interest analyses demonstrated volitional control in most regions during the training tasks and during the transfer task, although the effects were smaller in magnitude and not observed in one of the neurofeedback targets for the transfer task. Text analysis demonstrated that volitional control was most strongly associated with thinking about prior social experiences when up-regulating the neural signal. Analysis of behavioral performance and brain-behavior associations largely did not reveal behavior changes except for a positive association between volitional control in RTPJ and changes in performance on one ToM task. Exploratory analysis suggested neurofeedback-related learning occurred, although some degree of volitional control appeared to be conferred with the initial self-regulation strategy provided to participants (i.e., without the neurofeedback signal). Critical study limitations include the lack of a control group and pre-rtfMRI transfer scan, which prevents a more direct assessment of neurofeedback-induced volitional control, and a small sample size, which may have led to an overestimate and/or unreliable estimate of study effects. Nonetheless, together, this study demonstrates the feasibility of training volitional control of a social cognitive brain network, which may have important clinical applications. Given the study's limitations, findings from this study should be replicated with more robust experimental designs.

Preclinical Effects Of Melatonin On The Development Of Ehrlich's Tumor: A Biochemical, Cognitive, And Molecular Approach.

BACKGROUND: It has already been shown that melatonin is an antitumoral molecule that affects malignant cells via some mechanisms. The benefit played by this hormone on cancer is due to its antioxidant effects. OBJECTIVE: This study aimed to evaluate the preclinical effects of melatonin in mice with the Ehrlich ascites tumor. METHODS: Twenty Balb/ c male mice with Ehrlich tumor were treated with different melatonin doses. Their inflammatory and oxidative stress were accessed by gene expression. Hepatotoxicity and hematological parameters were also evaluated through biochemical analyses. Animal welfare was analysed weekly from the categories guided by the NC3Rs. RESULTS: Gene expression analyses have shown that only Tnfα and Sod1 were expressed in all groups studied. Only the M-3 group showed increased Tnfα expression compared to the control. All groups treated with melatonin showed decreased Sod1 expression compared to the control. No signs of hepatotoxicity were caused by any of the melatonin doses used in the treatment. CONCLUSION: In animals with Ehrlich´s tumor treated with melatonin, a decrease in oxidative stress, an amelioration in welfare and in cognitive tasks could be observed, even if the treatment has not reduced the size of the tumor itself. In parallel with the already patented use of melatonin in the treatment of sleep disorders or chronic kidney disease, our results propose its use to improve the general well-being of breast cancer patients.

Workshops of the Pedagogic Week 2021 of Centro Universitario FMABC / As oficinas da Semana Pedagógica de 2021 do curso de Medicina do Centro Universitário FMABC

INTRODUCTION: Delivering quality medical education is a hot topic. The current discussion essentially addresses content versus competencies. Extensive curricula and matrices, and traditional assessments are against go against the modern concepts of medical education. Remote education stimulated this discussion and brought the opportunity to review the academic load and assessment. REPORT: In January 2021, a pedagogic workshop of the Medicine course of Centro Universitário FMABC was held. It began with a lecture by a visiting professor and coordinator of the medical school accreditation system on remote activities during the pandemic. Next, the person responsible for the Progress Test made a history of the latest assessments, and a professor who is a member of the Accreditation Committee of the Medical Schools presented a summary of the main insufficient points of the last assessment. Afterward, the students presented the last internal evaluations. Finally, the matrices of the course, from the 1st to the 4th year, were presented and compared with those of three other medical schools, and each year coordinator prepared their suggestions for changes to the matrices. Lastly, students, professors, and the course coordination presented a report and proposals, encouraging the integration of the academic community, the reassessment of teaching plans, repetition of content, and recognition of matrices of each year, offering ideas and tools, to reflection on remote learning, and opportunities for change and improvement in teaching, and learning. CONCLUSION: The disciplines showed willingness for integrative activities, extension, and creation of elective disciplines, complementing failures caused by the Pandemic.

INTRODUÇÃO: A entrega da educação médica de qualidade é um tema em ebulição. A discussão atual aborda essencialmente conteúdos versus competências. Currículos e matrizes extensas, e avaliações tradicionais estão na contramão. O ensino remoto estimulou a discussão e a revisão da carga acadêmica e das avaliações. RELATO: Em janeiro de 2021 foi realizada uma oficina pedagógica do Curso de Medicina do Centro Universitário FMABC. Começou com a palestra de um professor convidado e coordenador do sistema de acreditação de escolas médicas, sobre atividades remotas durante a pandemia. A seguir, a responsável pelo Teste do Progresso fez um histórico das últimas avaliações, e um professor membro da comissão de acreditação de escolas médicas apresentaram uma síntese dos principais pontos insuficientes da última avaliação. Na sequência, os discentes apresentaram as últimas avaliações internas. Finalmente, foram apresentadas as matrizes do curso, do 1º ao 4º ano, comparadas com as de mais três escolas médicas, e cada coordenador de ano preparou suas sugestões para alterações de matrizes. Por último, discentes, docentes e a coordenação do curso apresentaram um relatório e propostas, estimulando a integração da comunidade acadêmica, a reavaliação dos planos de ensino, as repetições de conteúdo e o reconhecimento de matrizes de cada ano, oferecendo ideias e ferramentas, para a reflexão sobre o ensino remoto e as oportunidades de mudanças e aprimoramento do ensino e do aprendizado. CONCLUSÃO: As disciplinas mostraram disposição para as atividades integrativas, de extensão e de criação de disciplinas eletivas complementando falhas provocadas pela Pandemia.

High Prevalence of a c.5979dupA Variant in the Dysferlin Gene (DYSF) in Individuals from a Semiarid Region of Brazil.

Background: Dysferlinopathies represent a group of limb girdle or distal muscular dystrophies with an autosomal-recessive inheritance pattern resulting from the presence of pathogenic variants in the dysferlin gene (DYSF). Objective: In this work, we describe a population from a small city in Brazil carrying the c.5979dupA pathogenic variant of DYSF responsible for limb girdle muscular dystrophy type 2R and distal muscular dystrophy. Methods: Genotyping analyses were performed by qPCR using customized probe complementary to the region with the duplication under analysis in the DYSF. Results: A total of 104 individuals were examined. c.5979dupA was identified in 48 (46.15%) individuals. Twenty-three (22%) were homozygotes, among whom 13 (56.5%) were female. A total of 91.3% (21) of homozygous individuals had a positive family history, and seven (30.4%) reported consanguineous marriages. Twenty-five (24%) individuals were heterozygous (25.8±16 years) for the same variant, among whom 15 (60%) were female. The mean CK level was 697 IU for homozygotes, 140.5 IU for heterozygotes and 176 IU for wild-type homo-zygotes. The weakness distribution pattern showed 17.3% of individuals with a proximal pattern, 13% with a distal pattern and 69.6% with a mixed pattern. Fatigue was present in 15 homozygotes and one heterozygote. Conclusion: The high prevalence of this variant in individuals from this small community can be explained by a possible founder effect associated with historical, geographical and cultural aspects.

Social cognition training improves recognition of distinct facial emotions and decreases misattribution errors in healthy individuals.

Facial emotion recognition is a key component of social cognition. Impaired facial emotion recognition is tied to poor psychological wellbeing and deficient social functioning. While previous research has demonstrated the potential for social cognition training to improve overall facial emotion recognition, questions remain regarding what aspects of emotion recognition improve. We report results from a randomized controlled trial that evaluates whether computerized social cognition training can improve recognition of distinct facial emotions in healthy participants. This investigation was designed to better understand the therapeutic potential of social cognition training for individuals with neuropsychiatric disorders. Fifty-five healthy adult participants were randomly assigned to an internet-based intervention during which they either completed social cognition training (SCT) or played control computer games (CON) for 10.5 h over 2-3 weeks. Facial emotion recognition was measured with the Penn ER-40, which was conducted before and after training. The following variables were collected and analyzed: facial emotion recognition accuracy for each emotion (i.e., anger, fear, happy, neutral (no emotional expression), and sad), reaction times for each emotion, and response error types (i.e., frequency of an emotion being chosen incorrectly, frequency of an emotion being missed, and frequency of an emotion being confused for another particular emotion). ANOVAs and t-tests were used to elucidate intervention effects both within and between groups. Results showed that the SCT group improved their accuracy for angry and neutral faces. They also improved their reaction times for neutral, fearful, and sad faces. Compared to the CON group, the SCT group had significantly faster reaction times to neutral faces after training. Lastly, the SCT group decreased their tendency to confuse angry faces for no emotional expression and to confuse no emotional expression for sad faces. In contrast, the CON group did not significantly improve their accuracy or reaction times on any emotional expression, and they did not improve their response error types. We conclude that social cognition training can improve recognition of distinct emotions in healthy participants and decrease response error patterns, suggesting it has the potential to improve impaired emotion recognition and social functioning in individuals with facial emotion recognition deficits.

Social affective forecasting and social anhedonia in schizophrenia-spectrum disorders: a daily diary study.

Social anhedonia (SA) is a trait-like phenomenon observed across schizophrenia-spectrum disorders (SSDs). While in-the-moment social pleasure experiences are intact in SSDs, anticipatory pleasure experiences may be disrupted. Thus, the prediction of future emotions in social situations, or social affective forecasting (SAF), may play a role in SA. Therefore, we utilized daily diary methods to examine SAF in SSD and the association between SAF and SA in 34 SSD and 43 non-SSD individuals. SAF was calculated as the absolute difference between anticipatory and consummatory ratings of 13 positive and negative emotions for daily social interactions reported across eight days. Results suggest that individuals with SSDs are less accurate in forecasting negative, but not positive emotions, for future social interactions. Further, poorer forecasting accuracy of negative emotions were associated with elevated levels of SA and lower social pleasure. Together, these data suggest that inaccuracies in forecasting negative emotions may be a worthwhile intervention target for reducing SA in SSDs.

Explaining the Association Between Urbanicity and Psychotic-Like Experiences in Pre-Adolescence: The Indirect Effect of Urban Exposures.

Urban living is a growing worldwide phenomenon with more than two-thirds of people expected to live in cities by 2050. Although there are many benefits to living in an urban environment, urbanicity has also been associated with deleterious health outcomes, including increased risk for psychotic outcomes particularly when the urban exposure occurs in pre-adolescence. However, the mechanisms underlying this association is unclear. Here, we utilize one-year follow-up data from a large (N=7,979), nationwide study of pre-adolescence in the United States to clarify why urbanicity (i.e., census-tract population density) might impact psychotic-like experiences (PLE) by looking at the indirect effect of eight candidate urbanicity-related physical (e.g., pollution) and social (e.g., poverty) exposures. Consistent with other work, we found that of the evaluated exposures related to urbanicity, several were also related to increased number of PLE: PM2.5, proximity to roads, census-level homes at-risk for exposure to lead paint, census-level poverty, and census-level income-disparity. These same urban-related exposures were also related to the persistence of PLE after 1 year, but not new onset of PLE. Mediation analysis revealed that a substantial proportion the urbanicity-PLE association (number and persistence) could be explained by PM2.5 (23-44%), families in poverty (68-93%), and income disparity (67-80%). Together, these findings suggest that specific urban-related exposures contribute to the existence and maintenance, but not onset of PLE, which might help to explain why those in urban environments are disproportionately at-risk for psychosis and point toward areas for public health intervention.

Early mobilization in victims of traumatic brain injury / Mobilização precoce em vítimas de traumatismo cranioencefálico

INTRODUCTION: Several studies have shown that early mobilization is safe and beneficial for patients admitted to the intensive care units (ICUs), especially for those with mechanical ventilation (MV). OBJECTIVE: To investigate the benefits of early mobilization physiotherapeutic techniques applied to patients who suffered craniocerebral trauma (CCT). METHODS: This is an experimental study that evaluated clinical data from 27 patients. In sedated patients, mobilization and passive stretching were performed on the upper and lower limbs; in those without sedation, active-assisted, free and resisted exercises were included. RESULTS: The experimental group was composed of 51.8% of the participants and the control group by 48.2%, the majority being male (81.5%) with a median age of 43 years. The patients in the experimental group had an average of 9.5 days (2.2-14.7) of mechanical ventilation (MV), and those belonging to the control group, of 17 days (7-21.7) with MV (p=0.154). The patients in the experimental group had an average of 13.5 days in the ICU, against an average of 17 days in the control group (p=0.331), and an average of 20.5 days in hospital against 24 days in the control group (p=0.356). CONCLUSION: Early mobilization should be applied to critically ill patients as it can decrease the length of stay in the ICU and the hospital.

INTRODUÇÃO: Diversos estudos têm mostrado que a mobilização precoce é segura e benéfica para pacientes internados em unidades de terapia intensiva (UTIs), especialmente para aqueles com ventilação mecânica (VM). OBJETIVO: Investigar os benefícios das técnicas fisioterapêuticas de mobilização precoce aplicada aos pacientes que sofreram traumatismo cranioencefálico (TCE). MÉTODOS: Trata-se de um estudo quasi-randomizado, que incluiu 27 com TCE divididos em dois grupos: controle (n=13) e experimental (n=14) pacientes. No grupo experimental, os pacientes sedados foram submetidos à mobilização e alongamentos passivos nos membros superiores e inferiores; naqueles sem sedação, foram incluídos exercícios ativo-assistidos, livres e resistidos. RESULTADOS: O grupo experimental foi composto por 51,8% dos participantes da pesquisa e o grupo controle por 48,2%, sendo a maioria do sexo masculino (81,5%) com mediana de idade de 43 anos. Os pacientes do grupo experimental apresentaram média de 9,5 dias (2,2-14,7) de ventilação mecânica, e os pertencentes ao grupo controle, de 17 dias (7-21,7) com de VM (p=0,154). Os pacientes do grupo experimental apresentaram média de 13,5 dias de internação em UTI, contra média de 17 dias do grupo controle (p=0,331), e média de 20,5 dias de internação hospitalar contra 24 dias do grupo controle (p=0,356). CONCLUSÃO: A mobilização precoce é uma técnica que deve ser aplicada em pacientes críticos dentro das UTIs, pois pode diminuir o tempo de internação na UTI e hospitalar.

Stroke Hospital Admissions during the COVID-19 Outbreak in São Paulo, Brazil.

BACKGROUND: Globally, stroke remains an important cause of death and long-term disability, and the impact of coronavirus disease (COVID-19) on the health system may have impaired stroke care. Previous studies suggest significant reduction in hospital admissions for stroke after COVID-19 onset as patients may hesitate seeking medical help due to fear of exposure. METHODS: This cross-sectional study included cases of hospital admissions for stroke, identified from the Hospital Information System of the Unified Health System (Sistema Único de Saúde), which contains official and public data in Brazil. Data were collected in duplicate, then categorized according to the International Classification of Diseases, tenth revision (ICD-10), considering codes I60-I69. Linear regression was used to estimate the variation in hospital admissions for stroke in the city of São Paulo (SP) - the largest and most populous city in Brazil and Latin America, between January and June of each analyzed year (2017-2020). The percentage variation between June and January 2020 was also compared. The level of significance was set at 5%, and the statistical program used was Stata, version 14.0. RESULTS: In the city of SP, during the first wave of COVID-19, from January to June 2020, there were registered decreases in absolute numbers and mean monthly admissions for stroke. Compared to January 2020, data from June 2020 showed 17% reduction in hospitalizations for intracerebral hemorrhage, 32% for cerebral infarction, 26% for stroke unspecified, and 47% for other cerebrovascular diseases. CONCLUSION: We argue for policies aimed at improving stroke care and developing awareness campaigns regarding the importance of early diagnosis and treatment, as even in less severe presentations, stroke can trigger an increase in mortality, cost, and long-term disability.

Ursolic acid increases strength in mdx mice model and may decrease fibrosis deposition by tgf-ß downregulation / El ácido ursólico aumenta la resistencia en el modelo de ratones mdx y podría disminuir la deposición de fibrosis mediante la regulación decreciente de tgf-ß

SUMMARY: Dystrophin disfunction results in sarcolemma destabilization, leading muscle cell damage by continuous degeneration cycles and limited regeneration. In muscle dystrophy, caused by dystrophin dysfunction, inflammation, necrosis and fibrosis are pathophysiological muscle function loss characteristics. As a genetic disease, this muscle dystrophy has no cure, however, advances in drug therapy using glucocorticoids can decrease the disease progression. Subsequently, alternative therapies were studied, such as ursolic acid (UA), that inhibits muscle atrophy and increases muscle mass and strength. Herein, we used 10 mg/kg daily supplementation in mdx mice for 4 weeks to evaluate serum creatine phosphokinase (CPK), muscle strength (Kondziela test), muscular organization (histology) and expression of fibrosis related genes (TGF-ß, TNF-α, mstn and ostn). UA supplementation increased muscle morphological organization, motor strength and decreased muscular TGF-ß expression. Altogether, the gene expression profile, histological organization and strength could suggest that UA treatment did not stop the fibrogenesis but decreased its progress.

RESUMEN: La disfunción de la distrofina resulta en la desestabilización del sarcolema, llevando al daño de las células musculares por ciclos continuos de degeneración y regeneración limitada. En la distrofia muscular, debido a la disfunción de la distrofina, la inflamación, la necrosis y la fibrosis, son características fisiopatológicas de la pérdida de la función muscular. Como enfermedad genetica no es possible remediar esta distrofia muscular, sin embargo, los avances en la terapia de medicamentos con glucocorticoides pueden disminuir la progresión de la enfermedad. Se estudiaron terapias alternativas, como el ácido ursólico (UA), que inhibe la atrofia muscular y aumenta la masa y la fuerza muscular. En este estudio, utilizamos una suplementación diaria de 10 mg / kg en ratones mdx durante 4 semanas para evaluar la creatina fosfoquinasa (CPK) sérica, la fuerza muscular (prueba de Kondziela), la organización muscular (histología) y la expresión de genes relacionados con la fibrosis (TGF-ß, TNF- α, mstn y ostn). La suplementación con AU aumentó la organización morfológica muscular, la fuerza motora y la disminución de la expresión muscular de TGF-ß. El perfil de expresión génica, la organización histológica y la fuerza simultáneamente podrían sugerir que el tratamiento con AU no detuvo la fibrogénesis sino que disminuyó su progreso.

Comparative Study on the Effects of Paullinia cupana, PC-18 and Magnesium Chloride on Solid Ehrlich Tumor.

New perspectives arise in the therapeutic practice for cancer, with the objective to not only treat patients, but also improve their quality of life. Guarana, a plant from Brazilian Amazon presents a wide range of pharmacological actions. This study evaluated the effect of Guarana (Paullinia cupana) extract, pure and dry Guarana (PC-18) extract and magnesium chloride (MgCl2) in mice of the Balb/c strain inoculated with the Ehrlich tumor regarding gene expression of inflammatory markers transforming growth factor-ß1 and tumor necrosis factor alpha and oxidative stress (OS) and fatigue, superoxide dismutase, catalase, and glutathione peroxidase 4 and analyzed myelotoxicity and hepatotoxicity. After euthanasia, blood was collected to analyze the complete blood count and measured the levels of liver enzymes (alanine aminotransferase and aspartate aminotransferase). Hepatoprotective actions of the crude extract of P. cupana and PC-18 extract were noticed. The PC-18 and MgCl2 group showed the best result regarding animal welfare. There were no associations between compounds and gene expression regarding fatigue and OS. PC-18 reduced the tumor and may have an antitumor action. The crude extract of Guarana presented hepatoprotective action.

The Neural Basis of Social Cognition in Typically Developing Children and Its Relationship to Social Functioning.

Theory of mind (ToM), the ability to think about the perspectives, beliefs, and feelings of another, develops throughout childhood and adolescence and is an important skill for social interactions. This study examines neural activity in typically developing children during a novel ToM task - the Movie Mentalizing Task- and tests its relations to ToM behavioral performance and social functioning. In this fMRI task, children ages 8-13years (N=25) watched a brief movie clip and were asked to predict a character's mental state after a social interaction. Engaging in the Movie Mentalizing Task activated the ToM neural network. Moreover, greater neural activity in the ToM network, including the superior temporal gyrus and inferior frontal gyrus, was associated with better behavioral performance on independent ToM tasks and was related to better social functioning, though these results do not survive correction for multiple comparisons. Results offer a new affective theory of mind task for children in the scanner that robustly recruits activity in theory of mind regions.

Foot rotation asymmetry in Down syndrome and the relationship with crawling and walking onset: a cross-sectional study / A marcha de base alargada na síndrome de Down e a relação com o engatinhar e os primeiros passos: um estudo transversal

INTRODUCTION: Down syndrome individuals have different gait patterns, which include specific characteristics such as foot rotation asymmetryOBJECTIVE: The aim of this study was to analyze the relationship between this asymmetry and the hands-and-knees crawling pattern before gait acquisition in Down syndrome children, as well as the possible association of this gait to gender, ethnicity, comorbidities, physiotherapy, and occupational therapy interventionsMETHODS: In this cross-sectional study, 361 children with or without foot rotation asymmetry were selected. An online questionnaire was administered to the parents or guardians of those childrenRESULTS: Hands-and-knees crawling decreased the prevalence of foot rotation asymmetry in Down syndrome children. The longer it took for walking onset, the higher the prevalence of this asymmetry. Indeed, for each month of delay, there was a 7% increase in prevalence. There was a significant relationship between orthopedic alterations in knees or flat feet and foot rotation asymmetry. There was no significance related to gender, ethnicity, other comorbidities, physiotherapy, or occupational therapy interventionsCONCLUSION: The findings in this study revealed that foot rotation asymmetry might be related to the acquisition of motor skills, hands-and-knees crawling and the walking onset

INTRODUÇÃO: As pessoas com síndrome de Down (SD) apresentam diferentes padrões de marcha, incluindo algumas características específicas como a marcha de base alargadaOBJETIVO: O objetivo deste estudo foi analisar a relação entre a marcha de base alargada e a aquisição motora engatinhar em quatro apoios adquiridas antes da marcha em crianças com SD, bem como a provável associação desta marcha com gênero, etnia, comorbidades e tratamentos de fisioterapia e terapia ocupacionalMÉTODO: Neste estudo transversal, foram selecionados 361 indivíduos que apresentaram ou não marcha de base alargada. Um questionário on-line foi administrado para pais / responsáveis destas criançasRESULTADOS: O engatinhar em quatro apoios diminuiu a prevalência da marcha de base alargada em crianças com SD. Quanto maior o tempo em meses para os primeiros-passos, maior a prevalência de base alargada, sendo que, a cada mês de atraso, a prevalência aumenta em 7%. Foi observada significância entre as alterações ortopédicas em joelhos e pés planos e a marcha de base alargada. Não foi encontrada significância relacionada a gênero, etnia, outras comorbidades, fisioterapia ou terapia ocupacionalCONCLUSÃO: Os achados deste estudo mostraram que o aparecimento da base alargada pode estar relacionado às aquisições motoras, engatinhar em quatro apoios, e aos primeiros passos

Cognitive dysfunction and psychosis: expanding the phenotype of SPG7.

Spastic paraplegia type 7 (SPG7) is one of the most common forms of autosomal recessive hereditary spastic paraplegia, which can lead to a hybrid spastic-ataxic phenotype. Recently, novel complicated forms of SPG7, including cognitive and social impairment phenotypes, have been reported. We present a SPG7 case with two pathogenic variants in compound heterozygosity in the SPG7 gene, featuring a cerebellar cognitive affective syndrome with psychosis not yet described in the literature.

The representation of mental state information in schizophrenia and first-degree relatives: a multivariate pattern analysis of fMRI data.

Individuals with a schizophrenia-spectrum disorder (SSD) and those at familial high risk (FHR) for SSDs experience social difficulties that are related to neural abnormalities in the network of brain regions recruited during theory of mind (ToM). Prior work with these groups has focused almost exclusively on characterizing the involvement of these regions in ToM. Here, we examine the representational content of these regions using multivariate pattern analysis. We analyzed two previously collected datasets of SSD, FHR and control participants who, while undergoing functional magnetic resonance imaging, completed the false-belief task in which they read stories describing beliefs or physical representations (e.g. photographs). Univariate and multivariate analyses were performed in regions of interest to evaluate group differences in task-based activation and representational content, respectively. Compared to non-SSDs, SSDs showed reduced decoding accuracy for the category of mental states in the right temporo-parietal junction-which was related to false-belief accuracy-and the dorsal medial prefrontal cortex (DMPFC) and reduced involvement of DMPFC for mental state understanding. FHR showed no differences in decoding accuracy or involvement compared to non-FHR. Given prior studies of disrupted neural involvement in FHR and the lack of decoding differences observed here, the onset of illness may involve processes that corrupt how mental state information is represented.

Ixazomib, an oral proteasome inhibitor, exhibits potential effect in dystrophin-deficient mdx mice.

Dystrophin deficiency makes the sarcolemma fragile and susceptible to degeneration in Duchenne muscular dystrophy. The proteasome is a multimeric protease complex and is central to the regulation of cellular proteins. Previous studies have shown that proteasome inhibition improved pathological changes in mdx mice. Ixazomib is the first oral proteasome inhibitor used as a therapy in multiple myeloma. This study investigated the effects of ixazomib on the dystrophic muscle of mdx mice. MDX mice were treated with ixazomib (7.5 mg/kg/wk by gavage) or 0.2 mL of saline for 12 weeks. The Kondziela test was performed to measure muscle strength. The tibialis anterior (TA) and diaphragm (DIA) muscles were used for morphological analysis, and blood samples were collected for biochemical measurement. We observed maintenance of the muscle strength in the animals treated with ixazomib. Treatment with ixazomib had no toxic effect on the mdx mouse. The morphological analysis showed a reduction in the inflammatory area and fibres with central nuclei in the TA and DIA muscles and an increase in the number of fibres with a diameter of 20 µm2 in the DIA muscle after treatment with ixazomib. There was an increase in the expression of dystrophin and utrophin in the TA and DIA muscles and a reduction in the expression of osteopontin and TGF-ß in the DIA muscle of mdx mice treated with ixazomib. Ixazomib was thus shown to increase the expression of dystrophin and utrophin associated with improved pathological and functional changes in the dystrophic muscles of mdx mice.

The efficacy of real-time functional magnetic resonance imaging neurofeedback for psychiatric illness: A meta-analysis of brain and behavioral outcomes.

Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) has gained popularity as an experimental treatment for a variety of psychiatric illnesses. However, there has yet to be a quantitative review regarding its efficacy. Here, we present the first meta-analysis of rtfMRI-NF for psychiatric disorders, evaluating its impact on brain and behavioral outcomes. Our literature review identified 17 studies and 105 effect sizes across brain and behavioral outcomes. We find that rtfMRI-NF produces a medium-sized effect on neural activity during training (g = .59, 95 % CI [.44, .75], p < .0001), a large-sized effect after training when no neurofeedback is provided (g = .84, 95 % CI [.37, 1.31], p = .005), and small-sized effects for behavioral outcomes (symptoms g = .37, 95 % CI [.16, .58], p = .002; cognition g = .23, 95 % CI [-.33, .78], p = .288). Mixed-effects analyses revealed few moderators. Together, these data suggest a positive impact of rtfMRI-NF on brain and behavioral outcomes, although more research is needed to determine how rtfMRI-NF works, for whom, and under what circumstances.

Comparability of social anhedonia across epidemiological dimensions: A multinational study of measurement invariance of the Revised Social Anhedonia Scale.

Social anhedonia, or the loss of motivation in and pleasure from social engagement, is an important feature in understanding the etiology and outcome of various psychopathologies. While the Revised Social Anhedonia Scale (RSAS) represents one of the most commonly used self-report measures of social anhedonia, little is known regarding the construct comparability across populations. We examined measurement invariance of the full and brief RSAS in a diverse, international sample of 14,064 participants across nine epidemiological dimensions, including gender, age, ethnicity, education, community income, continent, migrant status, ethnic density, and urbanicity. Both the full and brief RSAS, as represented by a three-factor structure, achieved metric invariance for all dimensions. The full version showed considerable scalar noninvariance for ethnicity and continent, which was significantly reduced in the brief version. These findings suggest that while the scales measure the same construct across diverse groups, mean comparisons are only appropriate for the brief, and not the full, version. Future research may consider using the brief RSAS to ensure cross-national comparability. (PsycInfo Database Record (c) 2021 APA, all rights reserved).