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The genome-wide perturbation of transcriptional networks with CRISPR-Cas technology has primarily involved systematic and targeted gene modulation. Here, we developed PRISM (Perturbing Regulatory Interactions by Synthetic Modulators), a screening platform that uses randomized CRISPR-Cas transcription factors (crisprTFs) to globally perturb transcriptional networks. By applying PRISM to a yeast model of Parkinson's disease (PD), we identified guide RNAs (gRNAs) that modulate transcriptional networks and protect cells from alpha-synuclein (αSyn) toxicity. One gRNA identified in this screen outperformed the most protective suppressors of αSyn toxicity reported previously, highlighting PRISM's ability to identify modulators of important phenotypes. Gene expression profiling revealed genes differentially modulated by this strong protective gRNA that rescued yeast from αSyn toxicity when overexpressed. Human homologs of top-ranked hits protected against αSyn-induced cell death in a human neuronal PD model. Thus, high-throughput and unbiased perturbation of transcriptional networks via randomized crisprTFs can reveal complex biological phenotypes and effective disease modulators.
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Sistemas CRISPR-Cas , Redes Reguladoras de Genes , RNA Guia de Cinetoplastídeos/genética , Fatores de Transcrição/genética , Transcrição Gênica , alfa-Sinucleína/genética , Linhagem Celular Tumoral , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ensaios de Triagem em Larga Escala , Humanos , Modelos Biológicos , Neurônios/metabolismo , Neurônios/patologia , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Fenótipo , RNA Guia de Cinetoplastídeos/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/metabolismo , Transgenes , alfa-Sinucleína/antagonistas & inibidores , alfa-Sinucleína/metabolismoRESUMO
OBJECTIVE: To identify the frequency and relative importance of symptoms experienced by adults with fibromyalgia (FM) and determine factors associated with a higher disease burden. METHODS: We conducted semistructured interviews with 15 participants with FM, collecting 1479 quotes regarding the symptomatic burden of FM. We then performed an international cross-sectional study involving 1085 participants with FM to determine the prevalence and relative importance (scale 0-4) of 149 symptoms representing 14 symptomatic themes. We performed subgroup analysis to determine how age, sex, disease duration, medication use, employment status, change in employment status, missing work due to FM, and ability level are related to symptomatic theme prevalence. RESULTS: The symptomatic themes with the highest prevalence in FM were pain (99.8%), muscle tenderness (99.8%), and fatigue (99.3%). The symptomatic themes that had the greatest effect on patients' lives were related to fatigue (2.88), pain (2.85), muscle tenderness (2.79), and impaired sleep and daytime sleepiness (2.70). Symptomatic theme prevalence was most strongly associated with the modified Rankin Scale level of disability, disability status, and change in employment status (on disability vs not on disability). CONCLUSION: Participants with FM identify a variety of symptoms that significantly affect their daily lives. Many of these symptoms, such as fatigue, sleep disturbance, and activity limitation, are life-altering and not related to traditional diagnostic criteria. Symptom prevalence in this population varies across subgroups based on demographic categories and disability status.
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Fadiga , Fibromialgia , Humanos , Fibromialgia/epidemiologia , Fibromialgia/fisiopatologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Transversais , Fadiga/epidemiologia , Medidas de Resultados Relatados pelo Paciente , Dor/epidemiologia , Qualidade de Vida , Idoso , Efeitos Psicossociais da Doença , Índice de Gravidade de Doença , Prevalência , Emprego , Avaliação da DeficiênciaRESUMO
OBJECTIVE: Pulmonary function is associated with the development of chronic liver disease. However, evidence of the association between pulmonary function and cirrhosis risk is still lacking. This study aimed to investigate the longitudinal associations of pulmonary function with the development of cirrhosis, and to explore whether genetic predisposition to cirrhosis could modify these associations. METHODS: Of 294,835 participants free of cirrhosis and had undergone spirometry at baseline from the UK Biobank were included. Cirrhosis diagnoses were ascertained through linked hospital records and death registries. Cox proportional hazard models were employed to investigate the longitudinal associations between pulmonary function, genetic predisposition, and cirrhosis risk. RESULTS: During a median follow-up of 12.0 years, 2598 incident cirrhosis cases were documented. Compared to individuals with normal spirometry findings, those with preserved ratio impaired spirometry (PRISm) findings (hazard ratio [HR] and 95% confidence interval [CI]: 1.32 [1.18, 1.48]) and airflow obstruction (HR [95%CI]: 1.19 [1.07, 1.31]) had a higher risk of developing cirrhosis after adjustments. These associations were consistent across all categories of genetic predisposition, with no observed modifying effect of genetic predisposition. In joint exposure analyses, the highest risk was observed in individuals with both a high genetic predisposition for cirrhosis and PRISm findings (HR [95% CI]: 1.74 [1.45, 2.08]). CONCLUSIONS: Our findings indicate that worse pulmonary function is a significant risk factor of cirrhosis, irrespective of genetic predisposition. Early identification and appropriate intervention for pulmonary function may lead to more effective healthcare resource utilization and reduce the burden associated with cirrhosis.
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Predisposição Genética para Doença , Cirrose Hepática , Espirometria , Humanos , Masculino , Feminino , Cirrose Hepática/genética , Cirrose Hepática/epidemiologia , Estudos Prospectivos , Pessoa de Meia-Idade , Reino Unido/epidemiologia , Fatores de Risco , Idoso , Adulto , Modelos de Riscos ProporcionaisRESUMO
Both hyper- and hypothermia are problematic in temperature based forensic time since death estimation. Hyperthermia may occur in infection, traumatic brain injury, and intoxication. Hypothermia is encountered predominantly in exposure. Sepsis may present itself clinically as hypothermic. Sepsis is not uncommon in the forensic setting and mostly occurs in the context of malpractice accusations. There is usually little overlap between sepsis and typical forensic time since death estimation scenarios of violent or otherwise suspicious deaths. In the presented case, hypothermia and time since death estimations did collide. An inmate was found dead in his jail cell. Wardens claimed they had visually approached him alive relatively shortly prior. Rectal temperature measurements, using two separate crime scene thermometers as well as temperature loggers, revealed low rectal temperature at relatively high ambient temperature. These findings suggested a much longer postmortem interval and consequently raised doubts about the stated timeline. The wardens' claims were however confirmed by camera recordings, which also allowed a reasonable estimate of the true time of death. The cause of death was confirmed as septic organ failure at autopsy, which explained low rectal temperature. The presence of WISCHNEWSKI-spots was noted. When the PRISM-method was applied to the temperature recordings, low rectal temperature at the time of death was detected successfully. However, adaptation of the underlying equation for lower "starting temperature" did not produce satisfactory results. It is concluded that even though hypothermia at the time of death may possibly be detected from temperature data, attempts at time since death estimation for cases of hypothermia by adaptation of the equation should be avoided.
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Temperatura Corporal , Hipotermia , Sepse , Humanos , Masculino , Mudanças Depois da Morte , AdultoRESUMO
Prism adaptation (PA) affects visuospatial attention such as spatial orienting in both the right and left hemifields; however, the systematic after-effects of PA on visuospatial attention remain unclear. Visuospatial attention can be affected by non-spatial attentional factors, and postural control difficulty, which delays the reaction time (RT) to external stimulation, may be one such factor. Therefore, we aimed to investigate the influence of postural control difficulty on changes in spatial orienting of attention after leftward PA. Seventeen healthy young adults underwent 15-min and 5-min PA procedures for a leftward visual shift (30 diopters). Participants underwent the Posner cueing test immediately before (pre-evaluation) and in between and after the PA procedures (post-evaluations) while standing barefoot on the floor (normal standing condition) and on a balance-disc (balance standing condition). In the pre-evaluation, RTs in the balance standing condition were significantly longer compared to those in the normal standing condition for targets appearing in both the right and left hemifields. Leftward PA improved the RT for targets appearing in the right, but no left, hemifield in the balance standing condition, such that RTs for targets in the right hemifield in the post-evaluation were not significantly different between the two standing conditions. However, leftward PA did not significantly change RTs for targets in both hemifields in the normal standing condition. Therefore, postural control difficulty may enhance sensitivity to the features of the visuospatial cognitive after-effects of leftward PA.
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Adaptação Fisiológica , Atenção , Orientação Espacial , Equilíbrio Postural , Tempo de Reação , Percepção Espacial , Humanos , Masculino , Adulto Jovem , Feminino , Equilíbrio Postural/fisiologia , Adulto , Atenção/fisiologia , Adaptação Fisiológica/fisiologia , Tempo de Reação/fisiologia , Percepção Espacial/fisiologia , Orientação Espacial/fisiologia , Percepção Visual/fisiologia , Desempenho Psicomotor/fisiologiaRESUMO
For the fields of implementation science and health equity, understanding and being responsive to local contexts is of utmost importance to better inform the development, implementation, and evaluation of healthcare and public health interventions to increase their uptake and sustainment. Contexts are multi-level and include political, historical, economic, and social factors that influence health, as well as organizational characteristics, reflecting the richness of members' views, resources, values, and needs. Poor alignment between solutions and those contextual characteristics could have an impact on inequities. The PRISM (Practical Robust Implementation and Sustainability Model) is a context-based implementation science framework that incorporates RE-AIM outcomes (Reach, Effectiveness, Adoption, Implementation, Maintenance) and offers guidance to researchers, practitioners, and their patient and community partners on how to conceptualize, assess, and address contextual domains with a focus on health equity. Drawing from systems thinking, participatory engagement, and health equity principles, this commentary expands on previous work to 1) offer a novel perspective on how to align an intervention's core functions and forms with the PRISM's contextual domains, and 2) foster an ongoing and iterative engagement process with diverse partners throughout the research and practice process using a co-creation approach. We recommend intervention-to-context alignment through iterative cycles. To that end, we present the RE-AIM Framework's 'outcomes cascade' to illustrate touch points of opportunity and gaps within and across each of the five RE-AIM outcomes to illustrate 'where things go wrong'. We present a case study to illustrate and offer recommendations for research and practice efforts to increase contextual responsiveness, and enhance alignment with context before, during, and after implementation efforts and to ensure equity is being addressed. We strive to make a conceptual contribution to advance the field of pragmatic research and implementation of evidence-based practices through the application of the contextually-based PRISM framework with a focus on health equity.
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Atenção à Saúde , Equidade em Saúde , Humanos , Ciência da Implementação , Saúde Pública , Planejamento SocialRESUMO
Our everyday life summons numerous novel sensorimotor experiences, to which our brain needs to adapt in order to function properly. However, tracking plasticity of naturalistic behavior and associated brain modulations is challenging. Here, we tackled this question implementing a prism adaptation-like training in virtual reality (VRPA) in combination with functional neuroimaging. Three groups of healthy participants (N = 45) underwent VRPA (with a shift either to the left/right side, or with no shift), and performed functional magnetic resonance imaging (fMRI) sessions before and after training. To capture modulations in free-flowing, task-free brain activity, the fMRI sessions included resting-state and free-viewing of naturalistic videos. We found significant decreases in spontaneous functional connectivity between attentional and default mode (DMN)/fronto-parietal networks, only for the adaptation groups, more pronouncedly in the hemisphere contralateral to the induced shift. In addition, VRPA was found to bias visual responses to naturalistic videos: Following rightward adaptation, we found upregulation of visual response in an area in the parieto-occipital sulcus (POS) only in the right hemisphere. Notably, the extent of POS upregulation correlated with the size of the VRPA-induced after-effect measured in behavioral tests. This study demonstrates that a brief VRPA exposure can change large-scale cortical connectivity and correspondingly bias visual responses to naturalistic sensory inputs.
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Encéfalo , Córtex Cerebral , Humanos , Encéfalo/fisiologia , Córtex Cerebral/fisiologia , Mapeamento Encefálico , Imageamento por Ressonância Magnética/métodos , Adaptação Fisiológica/fisiologiaRESUMO
The complexity of micro-tidal inlets arises from the combined action of littoral drift and tidal range on their stability. Consequently, understanding and evaluating their stability poses a significant challenge. This study aims to shed some insight on the assessment of inlet stability by employing Delft 3D model. The stability of the inlet between the ocean and estuary relies on the balance between the longshore transport rate and the spring tidal prism. Disrupting this equilibrium results in the closure of the inlets. The movement of sediments in the surf zone is primarily driven by longshore velocity, which acts as the driving force for littoral drift, which is estimated using Delft 3D wave model. The longshore transport rate is estimated by employing empirical relationships and numerical codes based on the obtained driving force. Subsequently, the stability of the inlet is assessed based on these estimations. The spring tidal prism refers to the discharge of water flowing into the ocean from inlets and estuaries. Flow velocity is determined using Delft 3D flow model. The input data for nearshore circulation resulting from waves and currents is primarily collected through field measurements and data collected from Indian National Centre for Ocean Information Services (INCOIS). For the current study, Muttukadu (12°47'13â³N, 80°15'01â³E) inlet, Kovalam along the East Coast of the Indian Peninsula is investigated by assessing its seasonal variations. This study contributes to the management of marine biological ecology, the expansion of small-scale artisanal fishing, the promotion of water sports-related tourism, the advancement of fishing harbor development, and the execution of coastal engineering projects.
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Baías , Estuários , Água , Estações do Ano , Monitoramento Ambiental/métodosRESUMO
BACKGROUND: Preoperative prism adaptation (PPA) simulates postoperative status and possibly can predict postoperative undercorrection before surgery in esotropia. The present study aimed to assess the effect of 4-week PPA in preventing postoperative residual esotropia. METHODS: Seventy-five (75) esotropes who had undergone surgery at a single strabismus center were retrospectively enrolled. They included 25 basic, 31 acute comitant, 10 partially accommodative, and 9 recurrent esotropia patients. The preoperative deviation angle, which had been determined using the alternating prism and cover test, was fully corrected with press-on prisms 4 weeks before surgery. If there was an increase of 5 PD or more of esodeviation, the prisms were changed accordingly at 2 weeks. The deviation angle measured at 4 weeks was determined as the surgical target angle. Patients were then divided into increase (≥ 5 PD increase of angle during 4-week PPA) and non-increase groups. Success was defined as either esodeviation of 8 PD or under or exodeviation of 5 PD or under at distance at postoperative 6 months. RESULTS: The increase group included 44 patients (58.7%). The mean deviation angle before PPA was 27.4 PD, and after the 4-week PPA, there was an average increase of 9.4 PD. The success rate was 90.9% in the increase group and 96.8% in the non-increase group (p = 0.316). There were no intergroup differences in preoperative clinical characteristics, esotropia types, postoperative deviation angle or postoperative near stereopsis (p > 0.05). CONCLUSIONS: The results of this study indicated a beneficial effect of 4-week PPA in esotropia of various types, specifically by uncovering the hidden esodeviation in the increase group and simulating the postoperative alignment in both the increase and the non-increase groups.
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Esotropia , Músculos Oculomotores , Procedimentos Cirúrgicos Oftalmológicos , Visão Binocular , Humanos , Esotropia/cirurgia , Esotropia/fisiopatologia , Esotropia/prevenção & controle , Masculino , Estudos Retrospectivos , Feminino , Músculos Oculomotores/cirurgia , Músculos Oculomotores/fisiopatologia , Pré-Escolar , Visão Binocular/fisiologia , Criança , Óculos , Acuidade Visual/fisiologia , Complicações Pós-Operatórias/prevenção & controle , Adolescente , Cuidados Pré-Operatórios/métodos , Adaptação Ocular/fisiologia , Período Pós-Operatório , AdultoRESUMO
BACKGROUND: Convergence insufficiency is a common issue in the field of binocular vision. Various treatment options have been suggested for managing this condition, but their efficacy in individuals with presbyopia remains unclear. The objective of this study is to compare the effectiveness of home-based vision therapy and prism prescription, in presbyopic patients with convergence insufficiency. METHODS/DESIGN: It is a randomized, prospective, double-blind clinical trial, with total of 150 participants randomly assigned to the three groups. The Control Group will receive a new near glasses as a conventional prescription, along with aimless and random eye movement exercises that do not have any convergence or accommodation effects. The Home Vision Therapy Group will receive new near glasses with accommodative and convergence eye exercises. The Prism Group will receive a near prismatic glasses prescribed using the Sheard's criterion. All treatments will be administered for a period of 2 months, and measurements of the modified convergence insufficiency symptoms survey (CISS), near point convergence, near phoria, and positive fusional vergence will be taken at baseline, one month later, and at the end of the treatment. DISCUSSION: We aim to identify which component - either the prism prescription or the home vision therapy - is more effective in improving binocular abilities and reducing patients' symptom scores. TRIAL REGISTRATION: ClinicalTrials.gov NCT05311917 with last update on 04/22/2023.
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Transtornos da Motilidade Ocular , Estrabismo , Humanos , Transtornos da Motilidade Ocular/terapia , Estudos Prospectivos , Estrabismo/terapia , Movimentos Oculares , Ortóptica/métodos , Visão Binocular , Acomodação Ocular , Convergência Ocular , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Early diagnosing Chronic Obstructive Pulmonary Disease (COPD) is relatively difficult. Therefore, the concepts of preserved ratio impaired spirometry (PRISm) and small airway disease (SAD) were proposed to achieve early diagnosis for COPD. Besides, the occurrence of COPD is positively related to age. However, the relationship among COPD, PRISm, and SAD still requires clarification. Thus, we estimated the proportions and risk factors of COPD and PRISm in the positive screening participants, and searched the methods of early diagnosing COPD via the SAD indicators. METHODS: A total of 53,641 residents aged more than 60 years old from Shaoxing City, Zhejiang Province, China, completed a series of screening projects. And 2327 of positive screening participants ultimately finished bronchodilator tests. The data were statistically analyzed to figure out the proportions and risk factors of COPD and PRISm, and the efficacy of early diagnosing COPD by the SAD indicators. RESULTS: Totally 2229 positive screening participants were included, the proportion of PRISm was 6.3% (141/2229), and of COPD was 78.2% (1743/2229). Statistical analyses showed that COPD patients were more likely to be smokers, males, and older. And COPD patients had higher questionnaire scores, meaning that they were more prone to have family history of respiratory diseases and more severe respiratory symptoms. Additionally, COPD patients had lower maximal mid-expiratory flow (MMEF) pred, forced expiratory flow (FEF) 75pred, and FEF50pred. And we found that male sex and presence of respiratory symptoms might lead to COPD and PRISm. Also, the methods of early diagnosing COPD through the SAD indicators might be acceptable. CONCLUSION: There is a close association between COPD and decreased small airway function (SAF) among the participants included. Age, smoking, male sex, worse SAF, and respiratory symptoms might cause the progressing from normal people to PRISm, then to COPD patients. Besides, the SAD indicators such as MMEFpred, FEF75pred, and FEF50pred were included in lung function tests and bronchodilator tests. Intriguingly, it was found that early diagnosing COPD via the SAD indicators might be feasible. In the future, early diagnosis for COPD requires further research.
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Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Broncodilatadores , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Espirometria , Fatores de Risco , China/epidemiologiaRESUMO
Although waste-to-energy (WtE) incineration projects have boosted the economic effectiveness of the waste management system, locals frequently view them with suspicion, opposition, or even outright rejection because of potential environmental and health risks. In this study, by incorporating two additional variables, namely, objective knowledge and benefit perceptions, the planned risk information seeking model (PRISM) was extended in the context of the WtE incineration project. A total of 1726 respondents were interviewed in person. Results from the structural equation modeling indicated that the extended PRISM achieved excellent fits, suggesting the generalizability of the model in these contexts. Objective knowledge and subjective knowledge have a positive and direct impact on perceived knowledge insufficiency. The impact of benefit and risk perceptions on worry is the opposite, with risk perceptions having a greater direct effect on worry. However, compared with risk perceptions, the direct effect that benefit perceptions have on perceived knowledge insufficiency is stronger. Additionally, perceived knowledge insufficiency partially or completely mediates the relationships between all antecedents, except perceived seeking control, and information-seeking intention. This study suggests that risk managers carefully consider how to establish powerful communication tactics to shape these antecedents when introducing a "not in my backyard" project to the local community.
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PURPOSE: To articulate proof of concept in relation to a complex pedagogical values intervention for a range of medical education's historically accumulated symptoms. METHODS: Using a discursive approach, symptoms that hinder development of medical education are set out. Such symptoms rest with the instrumentality of current pedagogical approaches, supressing potential. A 'cure' is articulated - that the dominant values complex of instrumentalism is raised in quality through embracing ethical, aesthetic, political, and transcendental (meaning) values. Key to this is the use of language in clinical encounters, where the productive metaphor count is repressed in instrumental-technical approaches but multiplied in embracing other values and qualities. This 'Values Prism' model shows instrumentalism passing through an expansive educational prism to create expansion in types and qualities. RESULTS AND CONCLUSIONS: Proof of concept is achieved. The Values Prism model can be adapted for any undergraduate medicine curriculum as a process model - a set of values that permeate the curriculum beyond the dominant instrumental. The enhanced and expanded curriculum acts in a translational capacity.
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Educação de Graduação em Medicina , Educação Médica , Humanos , Currículo , Estudantes , MetáforaRESUMO
BACKGROUND: Self-assessment and self-reflection of competencies are crucial skills for undergraduate students. This monocentric cross-sectional study aims to assess the self-perceived knowledge, skills and interests in conservative dentistry and periodontology of third-, fourth-, and fifth-year dental students by the Pictorial Representation of Illness and Self-measure (PRISM). METHODS: Seventy-five undergraduate dental students (n = 25 of each year) who studied between 2021 and 2022 at the Department of Cariology, Endodontology and Periodontology at the University of Leipzig, Germany, were included. All of them underwent a PRISM-based interview regarding their perceived knowledge, practical skills, and interests in conservative dentistry as well as its sub-disciplines. The distances in the PRISM task (in millimeters) were measured and compared between the groups. Spearman's Rho was used to reveal correlations between knowledge, skills, and interests in the cohort. RESULTS: Perceived theoretical knowledge and practical skills differed significantly between groups for the sub-disciplines periodontology, cariology, restorative dentistry and preventive dentistry (p < 0.05). However, students' interests did not significantly vary between groups (p > 0.05). In the field of conservative dentistry and its sub-disciplines, significant moderate to high positive correlations were found between knowledge and skills (p < 0.01), and weak to moderate positive correlations were found between interests and knowledge (p < 0.05). Regarding the relationship between perceived interests and skills, only restorative dentistry, endodontology and periodontology were significant and only moderate to weak correlations were found (p < 0.05). CONCLUSION: PRISM revealed differences in perceived knowledge and skills between third-, fourth-, and fifth-year dental students. Correlations were found between perceived knowledge and skills, as well as between interests and knowledge. PRISM may be a promising tool to support students and teachers in dental education.
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Metáfora , Estudantes de Odontologia , Humanos , Estudos Transversais , Educação em Odontologia , Alemanha , Competência ClínicaRESUMO
Prism adaptation training (PAT) as a treatment for visuospatial neglect (VSN) involves two components: recalibration and realignment. We conducted a randomized controlled trial with PAT protocols requiring different degrees of recalibration and realignment, by using a single or multi-step protocol and varying visibility of the pointing movement. Twenty-five VSN patients received an alertness treatment without prisms, followed by four PAT protocols, encompassing a multi- or single-step procedure with terminal exposure, a single-step procedure with concurrent exposure, and sham PAT, presented in random order. The primary outcome parameter was the mean response time (RT) to left-sided targets in an endogenous variant of the Posner task, and we also measured the sensorimotor aftereffect. The two protocols without visibility of most of the movement trajectory produced significant aftereffects. The single-step protocol without movement visibility resulted in shorter RTs to left-sided targets. Hence, aftereffects depended on the partial invisibility of the movement. Moreover, only allowing VSN patients to recalibrate several times and direct feedback from the pointing errors had a beneficial effect on non-motor leftward visuospatial attention. We provide preliminary evidence that maximizing the conscious experience of movement errors may be an important component for remediating VSN.Trial registration: German Clinical Trials Register identifier: DRKS00025938.
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Classical dynamins (DNMs) are GTPase proteins engaged in endocytosis, a fundamental process for cargo internalization from the plasma membrane. In mammals, three DNM genes are present with different expression patterns. DNM1 is expressed at high levels in neurons, where it takes place in the recycling of synaptic vesicles; DNM2 is ubiquitously expressed, while DNM3 is found in the brain and in the testis. Due to the conservation of genes in comparison to mammals, we took advantage of a zebrafish model for functional characterization of dnm1a, ortholog of mammalian DNM1. Our data strongly demonstrated that dnm1a has a nervous tissue-specific expression pattern and plays a role in the formation of both axon and synapse. This is the first in vivo study that collects evidence about the effects of dnm1a loss of function in zebrafish, thus providing a new excellent model to be used in different scientific fields.
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Tecido Nervoso , Peixe-Zebra , Animais , Masculino , Axônios , Neurônios/metabolismo , Sinapses/metabolismo , MamíferosRESUMO
Ataxia and impaired motor learning are both fundamental features in diseases affecting the cerebellum. However, it remains unclarified whether motor learning is impaired only when ataxia clearly manifests, nor it is known whether the progression of ataxia, the speed of which often varies among patients with the same disease, can be monitored by examining motor learning. We evaluated motor learning and ataxia at intervals of several months in 40 patients with degenerative conditions [i.e., multiple system atrophy (MSA), Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3), SCA6, and SCA31]. Motor learning was quantified as the adaptability index (AI) in the prism adaptation task and ataxia was scored using the Scale for the Assessment and Rating of Ataxia (SARA). We found that AI decreased most markedly in both MSA-C and MSA-P, moderately in MJD, and mildly in SCA6 and SCA31. Overall, the AI decrease occurred more rapidly than the SARA score increase. Interestingly, AIs remained normal in purely parkinsonian MSA-P patients (n = 4), but they dropped into the ataxia range when these patients started to show ataxia. The decrease in AI during follow-up (dAI/dt) was significant in patients with SARA scores < 10.5 compared with patients with SARA scores ≥ 10.5, indicating that AI is particularly useful for diagnosing the earlier phase of cerebellar degeneration. We conclude that AI is a useful marker for progressions of cerebellar diseases, and that evaluating the motor learning of patients can be particularly valuable for detecting cerebellar impairment, which is often masked by parkinsonisms and other signs.
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BACKGROUND AND AIMS: Telemonitoring is increasingly used in the management of IBD patients. We investigated the agreement between patients and physicians on scores of disease activity and burden. METHODS: Consecutive outpatients at one IBD clinic were recruited between February and December 2021. Enrolled patients completed a questionnaire for disease activity (Harvey-Bradshaw Index [HBI] for Crohn's disease or Simple Clinical Colitis Activity Index [SCCAI] for ulcerative colitis) and a test of disease burden (Pictorial Representation of Illness and Self Measure [PRISM]). They did the tests within 5 days of an outpatient visit, working independently on IBD Tool, a new web-based telemonitoring application. Concomitantly, the senior and junior physicians who examined them completed the same tests. The agreement was tested for every pair of scores. RESULTS: Five hundred and sixty patients (289 Crohn's disease; 271 ulcerative colitis) completed disease questionnaires on IBD Tool (in total, 742 times). By Spearman's correlation, the agreement was substantial both for HBI (rho 0.685-0.837) and SCCAI (rho 0.694-0.888) for comparisons between patients, junior and senior physicians. The agreement was moderate-to-substantial for PRISM (rho 0.406-0.725) for the same comparisons. The correlation between disease activity (HBI/SCCAI) and PRISM scores was substantial for senior (rho 0.757-0.788) or junior (rho 0.746-0.753) physicians and moderate for patients (rho 0.458-0.486). The median PRISM score difference was 2.3-1.6 points lower between patients and senior-junior physicians. CONCLUSION: Agreement between IBD patients and physicians was substantial for disease activity and moderate for disease impact. The inclusion of disease burden scoring in telemonitoring platforms provides important information for the management of IBD patients.Study highlightsWhat IS knownâ¢Continuous response to treatments and patient-reported outcomes became an essential goal for IBD patient management.â¢The use of tele-monitoring and eHealth technologies allows for regular disease assessments and for managing more efficiently IBD patients; disease questionnaires and tests are key to support eHealth tools.What is new hereâ¢Agreement between IBD patients and physicians was substantial for disease activity and moderate for disease burden, while agreement among junior and senior physicians was substantial for both.â¢PRISM performs as well for ulcerative colitis as for Crohn's patients.â¢The inclusion of disease burden tests might add to eHealth platforms valuable information, complemental to disease activity questionnaires.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Médicos , Humanos , Doença de Crohn/diagnóstico , Colite Ulcerativa/diagnóstico , Doenças Inflamatórias Intestinais/diagnóstico , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
Although prism adaptation has been studied extensively for over 100 years to better understand how the motor system adapts to sensory perturbations, very few studies have systematically studied how the combination of the hand used to adapt, and the direction of visual shift, might influence adaptation. Given that sensory inputs and motor outputs from the same side are processed (at least initially) in the same hemisphere, we wondered whether there might be differences in how people adapt when the hand used and the direction of visual shift were congruent (e.g., adapting to rightward shifting prisms with the right hand), compared to incongruent (e.g., adapting to rightward shifting prisms with the left hand). In Experiment 1 we re-analyzed a previously published dataset (Striemer, Enns, and Whitwell Striemer et al., Cortex 115:201-215, 2019a) in which healthy adults (n = 17) adapted to 17° leftward or rightward optically displacing prisms using their left or right hand (tested in separate sessions, counterbalanced). Our results revealed a "congruency effect" such that adaptation aftereffects were significantly larger for reaches performed without visual feedback (i.e., straight-ahead pointing) when the direction of prism shift and the hand used were congruent, compared to incongruent. We replicated this same congruency effect in Experiment 2 in a new group of participants (n = 25). We suggest that a better understanding of the cognitive and neural mechanisms underlying the congruency effect will allow researchers to build more precise models of visuomotor learning, and may lead to the development of more effective applications of prism adaptation for the treatment of attentional disorders following brain damage.
Assuntos
Lesões Encefálicas , Transtornos Cognitivos , Adulto , Humanos , Mãos , Extremidade Superior , Córtex CerebralRESUMO
Nanoscale particles described by Mie resonance in the UV-vis-NIR region are in high demand for optical applications. Controlling the shape and size of these particles is essential, as it results in the ability to control the wavelength of the Mie resonance peak. In this work, we study the extensive scattering properties of gadolinium niobate particles with complex bar- and cube-like shapes in the UV-vis-NIR region. We perform our experimental analysis by characterizing the morphology and extinction spectra, and our theoretical study by implementing a Mie scattering model for a distribution of spherical particles. We can accurately model the size distribution and extinction spectra of complex shaped particles and isolate the contribution of aggregates to the extinction spectra. We can separate the contributions of dipoles, quadrupoles, and octupoles to the Mie resonances for their respective electric and magnetic parts. Our results show that we can tune the broad Mie resonance peak in the extinction spectra by the nanoscale properties of our system. This behavior can aid in the design of lasing and luminescence-enhanced systems. These dielectric gadolinium niobate submicron particles are excellent candidates for light manipulation on the nanoscale.