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T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy originating from T progenitor cells. It accounts for 15% of childhood and 25% of adult ALL cases. GNE-987 is a novel chimeric molecule developed using proteolysis-targeting chimeras (PROTAC) technology for targeted therapy. It consists of a potent inhibitor of the bromodomain and extraterminal (BET) protein, as well as the E3 ubiquitin ligase Von Hippel-Lindau (VHL), which enables the effective induction of proteasomal degradation of BRD4. Although GNE-987 has shown persistent inhibition of cell proliferation and apoptosis, its specific antitumor activity in T-ALL remains unclear. In this study, we aimed to investigate the molecular mechanisms underlying the antitumor effect of GNE-987 in T-ALL. To achieve this, we employed technologies including RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq) and CUT&Tag. The degradation of BET proteins, specifically BRD4, by GNE-987 has a profound impact on T-ALL cell. In in vivo experiments, sh-BRD4 lentivirus reduced T-ALL cell proliferation and invasion, extending the survival time of mice. The RNA-seq and CUT&Tag analyses provided further insights into the mechanism of action of GNE-987 in T-ALL. These analyses revealed that GNE-987 possesses the ability to suppress the expression of various genes associated with super-enhancers (SEs), including lymphoblastic leukemia 1 (LCK). By targeting these SE-associated genes, GNE-987 effectively inhibits the progression of T-ALL. Importantly, SE-related oncogenes like LCK were identified as critical targets of GNE-987. Based on these findings, GNE-987 holds promise as a potential novel candidate drug for the treatment of T-ALL.
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Apoptose , Proliferação de Células , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Fatores de Transcrição , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Animais , Camundongos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Elementos Facilitadores Genéticos , Proteínas que Contêm BromodomínioRESUMO
Background/Study Context: Adjustments of posture in response to balance challenges may lead to subsequent increases in conscious posture processing. If cognitive resources are stretched by conscious processing of postural responses fewer resources will be available to attend to environmental trip or fall hazards. The objective of the study was to explore brain activity related to conscious processing of posture as a function of movement specific reinvestment and fear of falling. Method: Forty-three older adults (M = 71.4, SD = 4.1) stood with a wide or narrow stance on a force-plate while neural coherence between verbal-analytical (T3) and motor planning (Fz) regions of the brain was assessed using electroencephalography. The propensity for movement specific reinvestment was assessed using the Chinese version Movement Specific Reinvestment Scale (MSRS-C) and fear of falling was assessed using the Chinese version Fall Efficacy Scale International (FES-I[CH]). Results: Scores from the MSRS-C were negatively correlated with changes in T3-Fz coherence that occurred when participants shifted from wide to narrow stance. Together, MSRS-C and FES-I(CH) uniquely predicted the percentage change in T3-Fz coherence between the two stance conditions. Conclusion: Presented with two postural tasks of different complexities, participants with a lower propensity for conscious control of their movements (movement specific reinvestment) exhibited larger changes in real-time brain activity (neural coherence) associated with conscious postural processing.
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Envelhecimento/fisiologia , Encéfalo/fisiologia , Postura/fisiologia , Acidentes por Quedas , Idoso , Eletroencefalografia , Medo/fisiologia , Feminino , Humanos , Masculino , Movimento/fisiologia , Equilíbrio Postural/fisiologiaRESUMO
BACKGROUND: There is little evidence considering the relationship between movement-specific reinvestment (a dimension of personality which refers to the propensity for individuals to consciously monitor and control their movements) and working memory during motor skill performance. Functional near-infrared spectroscopy (fNIRS) measuring oxyhemoglobin demands in the frontal cortex during performance of virtual reality (VR) psychomotor tasks can be used to examine this research gap. OBJECTIVE: The aim of this study was to determine the potential relationship between the propensity to reinvest and blood flow to the dorsolateral prefrontal cortices of the brain. A secondary aim was to determine the propensity to reinvest and performance during 2 dental tasks carried out using haptic VR simulators. METHODS: We used fNIRS to assess oxygen demands in 24 undergraduate dental students during 2 dental tasks (clinical, nonclinical) on a VR haptic simulator. We used the Movement-Specific Reinvestment Scale questionnaire to assess the students' propensity to reinvest. RESULTS: Students with a high propensity for movement-specific reinvestment displayed significantly greater oxyhemoglobin demands in an area associated with working memory during the nonclinical task (Spearman correlation, rs=.49, P=.03). CONCLUSIONS: This small-scale study suggests that neurophysiological differences are evident between high and low reinvesters during a dental VR task in terms of oxyhemoglobin demands in an area associated with working memory.
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Encéfalo/fisiologia , Simulação por Computador/estatística & dados numéricos , Odontologia/normas , Imageamento por Ressonância Magnética/métodos , Destreza Motora/fisiologia , Adulto , Competência Clínica , Feminino , Humanos , Masculino , Realidade VirtualRESUMO
We describe a pediatric cystic fibrosis patient who developed a pulmonary exacerbation due to two multidrug-resistant (MDR) Pseudomonas aeruginosa isolates. In addition to these MDR organisms, the case was further complicated by ß-lactam allergy. Despite the MDR phenotype, both isolates were susceptible to an antimicrobial combination.
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Antibacterianos/uso terapêutico , Fibrose Cística/complicações , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Adolescente , Amicacina/uso terapêutico , Antibacterianos/efeitos adversos , Ciprofloxacina/uso terapêutico , Fibrose Cística/microbiologia , Hipersensibilidade a Drogas/etiologia , Quimioterapia Combinada , Feminino , Humanos , Testes de Sensibilidade Microbiana , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/uso terapêutico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/patogenicidade , Tazobactam , beta-Lactamas/efeitos adversosRESUMO
BACKGROUND: A defining characteristic of expertise is automated performance of skills, which frees attentional capacity to better cope with some common intraoperative stressors. There is a paucity of research on how best to foster automated performance by surgical trainees. This study examined the use of a multitask training approach to promote automated, robust laparoscopic skills. METHODS: Eighty-one medical students completed training of a fundamental laparoscopic task in either a traditional single-task training condition or a novel multitask training condition. Following training, participants' laparoscopic performance was tested in a retention test, two stress transfer tests (distraction and time pressure) and a secondary task test, which was included to evaluate automaticity of performance. The laparoscopic task was also performed as part of a formal clinical examination (OSCE). RESULTS: The training groups did not differ in the number of trials required to reach task proficiency (p = .72), retention of skill (ps > .45), or performance in the clinical examination (p = .14); however, the groups did differ with respect to the secondary task (p = .016). The movement efficiency (number of hand movements) of single-task trainees, but not multitask trainees, was negatively affected during the secondary task test. The two stress transfer tests had no discernable impact on the performance of either training group. CONCLUSION: Multitask training was not detrimental to the rate of learning of a fundamental laparoscopic skill and added value by providing resilience in the face of a secondary task load, indicative of skill automaticity. Further work is needed to determine the extent of the clinical utility afforded by multitask training.
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Educação de Graduação em Medicina/métodos , Laparoscopia/educação , Competência Clínica , Avaliação Educacional , Feminino , Humanos , Masculino , Retenção Psicológica , Estudantes de Medicina , Adulto JovemRESUMO
Direct electric measurement via small contacting pads on individual quasi-one-dimensional nanoentities, such as nanowires and carbon nanotubes, are usually required to access its electronic properties. We show in this work that 1D nanoentities in suspension can be driven to rotation by AC electric fields. The chirality of the resultantrotation unambiguously reveals whether the nanoentities are metal, semiconductor, or insulator due to the dependence of the Clausius-Mossotti factor on the material conductivity and frequency. This contactless method provides rapid and parallel identification of the electrical characteristics of 1D nanoentities.
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Eletrônica , Nanoestruturas , Modelos TeóricosRESUMO
BACKGROUND: Super-enhancers (SEs) typically govern the expression of critical oncogenes and play a fundamental role in the initiation and progression of cancer. Focusing on genes that are abnormally regulated by SE in cancer may be a new strategy for understanding pathogenesis. In the context of this investigation, we have identified a previously unreported SE-driven gene IRF2BP2 in neuroblastoma (NB). METHODS: The expression and prognostic value of IRF2BP2 were detected in public databases and clinical samples. The effect of IRF2BP2 on NB cell growth and apoptosis was evaluated through in vivo and in vitro functional loss experiments. The molecular mechanism of IRF2BP2 was investigated by the study of chromatin regulatory regions and transcriptome sequencing. RESULTS: The sustained high expression of IRF2BP2 results from the activation of a novel SE established by NB master transcription factors MYCN, MEIS2 and HAND2, and they form a new complex that regulates the gene network associated with the proliferation of NB cell populations. We also observed a significant enrichment of the AP-1 family at the binding sites of IRF2BP2. Remarkably, within NB cells, AP-1 plays a pivotal role in shaping the chromatin accessibility landscape, thereby exposing the binding site for IRF2BP2. This orchestrated action enables AP-1 and IRF2BP2 to collaboratively stimulate the expression of the NB susceptibility gene ALK, thereby upholding the highly proliferative phenotype characteristic of NB. CONCLUSION: Our findings indicate that SE-driven IRF2BP2 can bind to AP-1 to maintain the survival of tumor cells via regulating chromatin accessibility of NB susceptibility gene ALK.
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Super enhancers (SEs) are genomic regions comprising multiple closely spaced enhancers, typically occupied by a high density of cell-type-specific master transcription factors (TFs) and frequently enriched in key oncogenes in various tumors, including neuroblastoma (NB), one of the most prevalent malignant solid tumors in children originating from the neural crest. Cyclin-dependent kinase 5 regulatory subunit-associated protein 3 (CDK5RAP3) is a newly identified super-enhancer-driven gene regulated by master TFs in NB; however, its function in NB remains unclear. Through an integrated study of publicly available datasets and microarrays, we observed a significantly elevated CDK5RAP3 expression level in NB, associated with poor patient prognosis. Further research demonstrated that CDK5RAP3 promotes the growth of NB cells, both in vitro and in vivo. Mechanistically, defective CDK5RAP3 interfered with the UFMylation system, thereby triggering endoplasmic reticulum (ER) phagy. Additionally, we provide evidence that CDK5RAP3 maintains the stability of MEIS2, a master TF in NB, and in turn, contributes to the high expression of CDK5RAP3. Overall, our findings shed light on the molecular mechanisms by which CDK5RAP3 promotes tumor progression and suggest that its inhibition may represent a novel therapeutic strategy for NB.
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Proteínas de Ciclo Celular , Regulação Neoplásica da Expressão Gênica , Neuroblastoma , Fatores de Transcrição , Animais , Humanos , Camundongos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Retículo Endoplasmático/metabolismo , Elementos Facilitadores Genéticos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos Nus , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neuroblastoma/genética , Neuroblastoma/patologia , Neuroblastoma/metabolismo , Prognóstico , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
Traveler's diarrhea is the most common travel disease in both children and adults. Adult guidelines for traveler's diarrhea have been established, but significant gaps persist in guidance for the evaluation and management of pediatric traveler's diarrhea. Adult guidelines are not necessarily applicable in children, and it is essential for clinicians to account for the differences in pediatric pathophysiology, clinical presentations, and treatment recommendations when evaluating and managing pediatric traveler's diarrhea.
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Diarreia/diagnóstico , Diarreia/terapia , Viagem , Adolescente , Anti-Infecciosos/uso terapêutico , Infecções Bacterianas/epidemiologia , Criança , Pré-Escolar , Desidratação/epidemiologia , Diarreia/epidemiologia , Hidratação/métodos , Humanos , Doenças Parasitárias/epidemiologia , Fatores de Risco , Viroses/epidemiologia , Adulto JovemRESUMO
Purpose of Review: Due to the rapidly changing landscape of COVID-19, the purpose of this review is to provide a concise and updated summary of pediatric COVID-19 diagnosis and management. Recent Findings: The relative proportion of pediatric cases have significantly increased following the emergence of the Omicron variant (from < 2% in the early pandemic to 25% from 1/27 to 2/3/22). While children present with milder symptoms than adults, severe disease can still occur, particularly in children with comorbidities. There is a relative paucity of pediatric data in the management of COVID-19 and the majority of recommendations remain based on adult data. Summary: Fever and cough remain the most common clinical presentations, although atypical presentations such as "COVID toes," anosmia, and croup may be present. Children are at risk for post-infectious complications such as MIS-C and long COVID. Nucleic acid amplification tests through respiratory PCR remain the mainstay of diagnosis. The mainstay of management remains supportive care and prevention through vaccination is highly recommended. In patients at increased risk of progression, interventions such as monoclonal antibody therapy, PO Paxlovid, or IV remdesivir × 3 days should be considered. In patients with severe disease, the use of remdesivir, dexamethasone, and immunomodulatory agents (tocilizumab, baricitinib) is recommended. Children can be at risk for thrombosis from COVID-19 and anticoagulation is recommended in children with markedly elevated D-dimer levels or superimposed clinical risk factors for hospital associated venous thromboembolism.
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Blastomyces dermatitidis is a fungus endemic to the Ohio and Mississippi river valley region and great lakes region. Exposure is typically associated with outdoor activities near streams, rivers, or moist soil. Pulmonary disease is the main manifestation, whereas dissemination is more frequently observed in immunosuppressed individuals. We herein report an uncommon case of B. dermatitidis causing invasive fungal sinusitis in a patient with well-controlled type 2 diabetes mellitus in the absence of conventional higher-risk environmental exposures. This case highlights the importance of a broad differential for invasive fungal infections in patients with diabetes, including those in endemic areas without classical exposures.
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Blastomicose , Diabetes Mellitus Tipo 2 , Sinusite , Adolescente , Blastomyces , Blastomicose/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diplopia , Humanos , Sinusite/tratamento farmacológicoRESUMO
PURPOSE: The current study investigated the therapeutic potential of transcranial direct current stimulation (tDCS) on speech intelligibility, speech-related physiological and vocal functions among post-stroke dysarthric patients. METHOD: Nine chronic post-stroke dysarthric patients were randomly assigned to the stimulation or sham group. The stimulation group received 2mA of anodal tDCS over the left inferior primary motor cortex for 15 minutes, while the sham group received 30s of stimulation under the same settings. All the participants received 10 daily 15 minutes of individualized speech therapy targeting their dominant phonological process or phonemes with the greatest difficulty. The outcome measures included (1) perceptual analysis of single words, passage reading and diadochokinetic rate, (2) acoustic analysis of a sustained vowel, and (3) kinematic analysis of rapid syllable repetitions and syllable production in sentence, conducted before and after the treatment. RESULTS: The results revealed that both the stimulation and sham groups had improved perceptual speech intelligibility at the word level, reduced short rushes of speech during passage reading, improved rate during alternating motion rate, AMR-kha1, and improved articulatory kinematics in AMR-tha1 and syllables /tha1/ and /kha1/ production in sentence. Compared to the sham group, the stimulation group showed significant improvement in articulatory kinematics in AMR-kha1 and syllable /kha1/ production in sentence. The findings also showed that anodal stimulation led to reduced shimmer value in sustained vowel /a/ phonation, positive changes in articulatory kinematics in AMR-tha1 and syllables /pha1/ and /kha1/ production in sentence at the post treatment measure. In addition to positive effects on articulatory control, reduced perturbation of voice amplitude documented in the stimulation group post treatment suggests possible tDCS effects on the vocal function. CONCLUSIONS: The current study documented the beneficial effects of anodal tDCS over the primary motor cortex on speech production and suggested that combined tDCS and speech therapy may promote recovery from post-stroke dysarthria.
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Córtex Motor , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Projetos Piloto , Inteligibilidade da Fala , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Estimulação Transcraniana por Corrente Contínua/métodosRESUMO
BACKGROUND: An understanding of differences in expert and novice neural behavior can inform surgical skills training. Outside the surgical domain, electroencephalographic (EEG) coherence analyses have shown that during motor performance, experts display less coactivation between the verbal-analytic and motor planning regions than their less skilled counterparts. Reduced involvement of verbal-analytic processes suggests greater neural efficiency. The authors tested the utility of an implicit motor learning intervention specifically devised to promote neural efficiency by reducing verbal-analytic involvement in laparoscopic performance. METHODS: In this study, 18 novices practiced a movement pattern on a laparoscopic trainer with either conscious awareness of the movement pattern (explicit motor learning) or suppressed awareness of the movement pattern (implicit motor learning). In a retention test, movement accuracy was compared between the conditions, and coactivation (EEG coherence) was assessed between the motor planning (Fz) region and both the verbal-analytic (T3) and the visuospatial (T4) cortical regions (T3-Fz and T4-Fz, respectively). RESULTS: Movement accuracy in the conditions was not different in a retention test (P = 0.231). Findings showed that the EEG coherence scores for the T3-Fz regions were lower for the implicit learners than for the explicit learners (P = 0.027), but no differences were apparent for the T4-Fz regions (P = 0.882). CONCLUSIONS: Implicit motor learning reduced EEG coactivation between verbal-analytic and motor planning regions, suggesting that verbal-analytic processes were less involved in laparoscopic performance. The findings imply that training techniques that discourage nonessential coactivation during motor performance may provide surgeons with more neural resources with which to manage other aspects of surgery.
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Competência Clínica , Laparoscopia/educação , Aprendizagem , Destreza Motora , Adulto , Conscientização , Simulação por Computador , Instrução por Computador , Eficiência , Eletroencefalografia , Sincronização de Fases em Eletroencefalografia , Lobo Frontal/fisiologia , Humanos , Curva de Aprendizado , Retenção Psicológica , Comportamento Espacial , Análise e Desempenho de Tarefas , Lobo Temporal/fisiologia , Adulto JovemRESUMO
PURPOSE OF REVIEW: Provide an updated review of the clinical management and diagnosis of Kawasaki disease with inclusion of potential diagnostic difficulties with multisystem inflammatory syndrome in children (MIS-C) given the ongoing COVID-19 pandemic. RECENT FINDINGS: Adjunctive corticosteroid therapy has been shown to reduce the rate of coronary artery dilation in children at high risk for IVIG resistance in multiple Japanese clinical studies (most notably RAISE study group). Additional adjunctive therapies (etanercept, infliximab, cyclosporin) may also provide limited benefit, but data is limited to single studies and subgroups of patients with cardiac abnormalities. The efficacy of other agents (atorvastatin, doxycycline) is currently being investigated. MIS-C is a clinically distinct entity from KD with broad clinical manifestations and multiorgan involvement (cardiac, GI, hematologic, dermatologic, respiratory, renal). MIS-C with Kawasaki manifestations is more commonly seen in children < 5 years of age. SUMMARY: The 2017 American Heart Association (AHA) treatment guidelines have included changes in aspirin dosing (including both 80-100 mg/kg/day and 30-50 mg/kg/day treatment options), consideration of the use of adjuvant corticosteroid therapy in patients at high risk of IVIG resistance, and the change in steroid regimen for refractory KD to include both pulse-dose IVMP and longer course of prednisolone with an oral taper. A significant proportion of children diagnosed with MIS-C, a post-infectious syndrome of SARS-CoV-2 infection, meet criteria for Kawasaki disease. Further investigation is warranted to further delineate these conditions and optimize treatment of these conditions given the ongoing COVID-19 pandemic.
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Depression is a common psychiatric illness affecting over 300 million people globally. Acupuncture has been reported to be a safe complementary treatment for depression. This study is aimed to investigate the efficacy and mechanism of combining acupuncture with antidepressants in treating depression compared to the sole use of antidepressants. Seventy depression patients were randomly assigned to the treatment group (n = 50) and control group (n = 20). The treatment group received acupuncture combined antidepressants treatment for 3 weeks, while the control group took antidepressants monotherapy for 3 weeks. Among the 70 patients, 40 participants (20 control; 20 treatment) were randomized for studying functional connectivity (FC) of the dorsolateral prefrontal cortex (DLPFC) measured by the functional near-infrared spectroscopy. The primary outcome was HAMD-17 and secondary outcomes were PHQ-9, and the relationships of resting-state FC (rsFC) with the depression severity. PHQ-9 and HAMD-17 scores in the treatment group were significantly lower than those in the control group at Week 3 (p = 0.01) with effect sizes of -0.4 and -0.61 respectively. The rsFC in F1, F3, AF3, AF7, FC3, FC5 (left DLPFC, 10-20 system), AF8, and F6 (right DLPFC) in the treatment group had significant temporal correlation (p < 0.05, FDR corrected) in DLPFC compared to the channels in the control group. No significant correlation was found between the changes of rsFC and depression severity. In conclusion, depressed patients receiving acupuncture combined with antidepressants have improvement of depressive symptoms and the stronger rsFC in the DLPFC compared to those using antidepressants alone.
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Terapia por Acupuntura , Espectroscopia de Luz Próxima ao Infravermelho , Antidepressivos/uso terapêutico , Terapia Combinada , Humanos , Imageamento por Ressonância MagnéticaRESUMO
A key driver of patients' well-being and clinical trials for Parkinson's disease (PD) is the course that the disease takes over time (progression and prognosis). To assess how genetic variation influences the progression of PD over time to dementia, a major determinant for quality of life, we performed a longitudinal genome-wide survival study of 11.2 million variants in 3,821 patients with PD over 31,053 visits. We discover RIMS2 as a progression locus and confirm this in a replicate population (hazard ratio (HR) = 4.77, P = 2.78 × 10-11), identify suggestive evidence for TMEM108 (HR = 2.86, P = 2.09 × 10-8) and WWOX (HR = 2.12, P = 2.37 × 10-8) as progression loci, and confirm associations for GBA (HR = 1.93, P = 0.0002) and APOE (HR = 1.48, P = 0.001). Polygenic progression scores exhibit a substantial aggregate association with dementia risk, while polygenic susceptibility scores are not predictive. This study identifies a novel synaptic locus and polygenic score for cognitive disease progression in PD and proposes diverging genetic architectures of progression and susceptibility.
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Cognição , Progressão da Doença , Loci Gênicos , Estudo de Associação Genômica Ampla , Herança Multifatorial/genética , Doença de Parkinson/genética , Doença de Parkinson/patologia , Sinapses/genética , Apolipoproteína E4/genética , Transtornos Cognitivos/genética , Predisposição Genética para Doença , Glucosilceramidase/genética , Humanos , Estudos Longitudinais , Mutação/genética , Doença de Parkinson/fisiopatologia , Modelos de Riscos Proporcionais , Fatores de Risco , Análise de SobrevidaRESUMO
OBJECTIVE: Implicit motor learning, which is a non-conscious form of learning characterized by motor performance improvement with practice, plays an essential role in various daily activities. Earlier study using neurofeedback training (NFT), a type of brain-computer interaction that enables the user to learn self-regulating his/her own brain activity, demonstrated that down-regulating alpha over primary motor cortex by NFT could immediately facilitate the implicit motor learning in a relatively simple motor task. However, detailed effects on EEG and implicit motor learning due to NFT especially in a more complex motor task are still unclear. APPROACH: We designed a single-blind sham-controlled between-subject study to examine whether alpha down-regulation NFT could facilitate implicit motor learning and also its consolidation in a more difficult and motor predominant task. At left primary motor cortex (C3) in two days, the alpha NFT group received alpha down-regulation training through auditory feedback while the sham-control group received random beta NFT. At the end of NFT, all participants performed the continuous tracking task with their dominant (right) hand to evaluate the implicit motor learning immediately. Finally, the continuous tracking task was performed again on the next day to assess consolidation effects. MAIN RESULTS: The alpha NFT group successfully decreased alpha amplitude during NFT, whereas the sham-control group maintained alpha at a relatively stable level. There was unfortunately no statistical evidence proving that the alpha NFT group significantly enhanced the implicit motor learning at the end of NFT and the consolidation on the next day compared to the sham-control group. Nevertheless, a significant correlation was found between the alpha change trend during NFT and the implicit motor learning for all participants, suggesting that faster alpha down-regulation was associated with better implicit motor learning. SIGNIFICANCE: The findings suggested a close link between implicit motor learning and alpha change induced by NFT.
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Neurorretroalimentação , Encéfalo , Regulação para Baixo , Feminino , Mãos , Humanos , Masculino , Método Simples-CegoRESUMO
BACKGROUND: Dry-electrode-based transcranial direct current stimulation is a new type of non-invasive brain stimulation system which relieves chronic low back pain and improves related muscle movement, in a way that overcomes the drawback of conventional systems. OBJECTIVE: To investigate the effectiveness of dry-electrode-based transcranial direct current stimulation in relieving chronic low back pain and altering pain-related low back muscles movement, by using pain assessment tool and surface electromyographic topography. METHODS: We conducted a prospective, double-blind, randomized, sham-controlled study. 60 patients with non-specific chronic low back pain were randomly and evenly allocated into tDCS and sham groups. Each group accepted a single 20-minute stimulation at 2âmA on the primary motor cortex. Numeric rating scale for pain intensity assessment and root-mean-square difference parameter from surface electromyographic topography were measured before and after stimulation. The current direction in brain using finite element method was simulated to verify the current distribution under dry stimulation electrode. RESULTS: After stimulation, the pain intensity in the tDCS group significantly decreased, while it did not show evident change in the sham group. However, change of root-mean-square difference parameters between tDCS and sham groups showed no significant difference. Simulation results based on finite element method showed most of current focused on primary motor cortex while peak value of current density was 0.225âA/m2. CONCLUSIONS: Dry-electrode-based transcranial direct current stimulation can lower pain perception in patients with chronic low back pain. The analgesic mechanism can affect the top-down modulation pathway of pain.
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Músculos do Dorso/cirurgia , Eletrodos , Dor Lombar/terapia , Estimulação Transcraniana por Corrente Contínua , Adulto , Analgésicos , Músculos do Dorso/inervação , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiologia , Córtex Motor/cirurgia , Medição da Dor/métodos , Estimulação Transcraniana por Corrente Contínua/métodos , Resultado do TratamentoRESUMO
Understanding the role that children play in the clinical burden and propagation of severe acute respiratory syndrome coronavirus 2, responsible for coronavirus disease 2019 (COVID-19) infections, is emerging. While the severe manifestations and acute clinical burden of COVID-19 have largely spared children compared with adults, understanding the epidemiology, clinical presentation, diagnostics, management, and prevention opportunities and the social and behavioral impacts on child health is vital. Foremost is clarifying the contribution of asymptomatic and mild infections to transmission within the household and community and the clinical and epidemiologic significance of uncommon severe post-infectious complications. Here, we summarize the current knowledge, identify resources, and outline research opportunities. Pediatric infectious diseases clinicians have a unique opportunity to advocate for the inclusion of children in epidemiological, clinical, treatment, and prevention studies to optimize their care as well as to represent children in the development of guidance and policy during pandemic response.
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Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Doenças Assintomáticas , COVID-19 , Teste para COVID-19 , Criança , Serviços de Saúde da Criança , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/prevenção & controle , Transmissão Vertical de Doenças Infecciosas , Pandemias/prevenção & controle , Pediatria , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Pneumonia Viral/transmissão , Guias de Prática Clínica como Assunto , Gravidez , Complicações Infecciosas na Gravidez , SARS-CoV-2RESUMO
PURPOSE: The present study aimed to explore the short-term effect of anodal transcranial direct current stimulation (tDCS) on tongue twister production. METHOD: Thirty healthy native Cantonese adult speakers were randomly assigned to the anodal tDCS group or the sham tDCS group. Anodal tDCS of 2 mA was applied over the Broca's area of the brain. The stimulation lasted for 20 min for the anodal tDCS group and 30 s for the sham tDCS group. The participants were instructed to produce a list of tongue twisters before, immediately after and 4 h after tDCS. RESULT: Speech rate and response accuracy measured immediately after stimulation were significantly faster and higher, respectively, than before stimulation. Although there was no change in speech rate measured at 4 h after stimulation, response accuracy at that time point was significantly lower than that measured immediately after stimulation. However, there were no significant differences between the anodal tDCS and sham tDCS groups in either speech rate or response accuracy. CONCLUSION: The findings revealed that a single session of anodal tDCS over the Broca's area did not significantly improve speech production during tongue twister production.