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1.
Med Educ ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597258

RESUMO

INTRODUCTION: Professional identity formation (PIF) is a central tenet of effective medical education. However, efforts to support, assess and study PIF are hindered by unclear definitions and conceptualisations of what it means to 'think, act, and feel like a physician'. Gaps in understanding PIF, and by extension, its support mechanisms, can predispose individuals towards disengaged or unprofessional conduct and institutions towards short-sighted or reactionary responses to systemic issues. METHODS: A Systematic Evidence-Based Approach-guided systematic scoping review of PIF theories was conducted related to medical students, trainees and practising doctors, published between 1 January 2000 and 31 December 2021 in PubMed, Embase, ERIC and Scopus databases. RESULTS: A total of 2441 abstracts were reviewed, 607 full-text articles evaluated and 204 articles included. The domains identified were understanding PIF through the lens of pivotal theories and characterising PIF by delineating the underlying factors that influence it and processes that define it. CONCLUSIONS: Based on regnant theories and frameworks related to self-concepts of identity and personhood, the relationships between key PIF influences, processes and outcomes were examined. A theory-backed integrated conceptual model was proposed to delineate the interconnected relationships among these, aiming to untangle some of the complexities inherent to PIF, to shed light on existing practices and to identify shortcomings in our understanding so as to develop mechanisms in support of its multifaceted, interlinked components.

2.
BMC Med Educ ; 24(1): 398, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600515

RESUMO

BACKGROUND: Reviewing experiences and recognizing the impact of personal and professional views and emotions upon conduct shapes a physician's professional and personal development, molding their professional identity formation (PIF). Poor appreciation on the role of reflection, shortages in trained tutors and inadequate 'protected time' for reflections in packed medical curricula has hindered its integration into medical education. Group reflection could be a viable alternative to individual reflections; however, this nascent practice requires further study. METHODS: A Systematic Evidence Based Approach guided Systematic Scoping Review (SSR in SEBA) was adopted to guide and structure a review of group reflections in medical education. Independent searches of articles published between 1st January 2000 and 30th June 2022 in bibliographic and grey literature databases were carried out. Included articles were analysed separately using thematic and content analysis, and combined into categories and themes. The themes/categories created were compared with the tabulated summaries of included articles to create domains that framed the synthesis of the discussion. RESULTS: 1141 abstracts were reviewed, 193 full-text articles were appraised and 66 articles were included and the domains identified were theories; indications; types; structure; and benefits and challenges of group reflections. CONCLUSIONS: Scaffolded by current approaches to individual reflections and theories and inculcated with nuanced adaptations from other medical practices, this SSR in SEBA suggests that structured group reflections may fill current gaps in training. However, design and assessment of the evidence-based structuring of group reflections proposed here must be the focus of future study.


Assuntos
Educação Médica , Humanos , Currículo , Emoções
3.
J Child Psychol Psychiatry ; 63(8): 855-870, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34762311

RESUMO

BACKGROUND: Identifying the brain bases for phenotypic heterogeneity in Autism Spectrum Disorder (ASD) will advance understanding of its pathogenesis and improve its clinical management. METHODS: We compared Diffusion Tensor Imaging (DTI) indices and connectome measures between 77 ASD and 88 Typically Developing (TD) control participants. We also assessed voxel-wise associations of DTI indices with measures of regional cerebral blood flow (rCBF) and N-acetylaspartate (NAA) to understand how tissue microstructure associates with cellular metabolism and neuronal density, respectively. RESULTS: Autism Spectrum Disorder participants had significantly lower fractional anisotropy (FA) and higher diffusivity values in deep white matter tracts, likely representing ether reduced myelination by oligodendrocytes or a reduced density of myelinated axons. Greater abnormalities in these measures and regions were associated with higher ASD symptom scores. Participant age, sex and IQ significantly moderated these group differences. Path analyses showed that reduced NAA levels accounted significantly for higher diffusivity and higher rCBF values in ASD compared with TD participants. CONCLUSIONS: Reduced neuronal density (reduced NAA) likely underlies abnormalities in DTI indices of white matter microstructure in ASD, which in turn are major determinants of elevated blood flow. Together, these findings suggest the presence of reduced axonal density and axonal pathology in ASD white matter. Greater pathology in turn accounts for more severe symptoms, lower intellectual ability, and reduced global efficiency for measures of white matter connectivity in ASD.


Assuntos
Transtorno do Espectro Autista , Substância Branca , Transtorno do Espectro Autista/metabolismo , Encéfalo/metabolismo , Imagem de Tensor de Difusão , Humanos , Imageamento por Ressonância Magnética , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
4.
BMC Palliat Care ; 21(1): 200, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36397067

RESUMO

BACKGROUND: Introduction to a multi-professional team who are working and caring for the dying, and facing complex moral and ethical dilemmas during Oncology and Palliative Medicine postings influence a medical student's professional identity formation (PIF). However, limited appreciation of PIF, inadequate assessments and insufficient support jeopardise this opportunity to shape how medical students think, feel and act as future physicians. To address this gap, a systematic scoping review (SSR) of PIF assessment methods is proposed. METHODS: A Systematic Evidence-based Approach (SEBA) guided SSR of assessments of PIF in medical schools published between 1st January 2000 and 31st December 2021 in PubMed, Embase, ERIC and Scopus databases was carried out. Included articles were concurrently content and thematically analysed using SEBA's Split Approach and the themes and categories identified were combined using SEBA's Jigsaw Perspective. The review hinged on the following questions: "what is known about the assessment of professional identity formation amongst medical students?", "what are the theories and principles guiding the assessment of professional identity formation amongst medical students?", "what factors influence PIF in medical students?", "what are the tools used to assess PIF in medical students?", and "what considerations impact the implementation of PIF assessment tools amongst medical students?". RESULTS: Two thousand four hundred thirty six abstracts were reviewed, 602 full-text articles were evaluated, and 88 articles were included. The 3 domains identified were 1) theories, 2) assessment, and 3) implementation in assessing PIF. Differing attention to the different aspects of the PIF process impairs evaluations, jeopardise timely and appropriate support of medical students and hinder effective implementation of PIF assessments. CONCLUSION: The Krishna-Pisupati model combines current theories and concepts of PIF to provide a more holistic perspective of the PIF process. Under the aegis of this model, Palliative Care and Oncology postings are envisaged as Communities of Practice influencing self-concepts of personhood and identity and shaping how medical students see their roles and responsibilities as future physicians. These insights allow the forwarding of nine recommendations to improve assessments of PIF and shape the design of a PIF-specific tool that can direct timely and personalized support of medical students.


Assuntos
Medicina Paliativa , Médicos , Estudantes de Medicina , Humanos , Identificação Social , Autoimagem
5.
J Public Health (Oxf) ; 41(2): 391-398, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29534234

RESUMO

BACKGROUND: The study evaluated the cost-effectiveness of hydrotherapy versus land-based therapy in patients with musculoskeletal disorders (MSDs) in Singapore. METHODS: A decision-analytic model was constructed to compare the cost-effectiveness of hydrotherapy to land-based therapy over 3 months from societal perspective. Target population comprised patients with low back pain (LBP), osteoarthritis (OA), rheumatoid arthritis (RA), total hip replacement (THR) and total knee replacement (TKR). Subgroup analyses were carried out to determine the cost-effectiveness of hydrotherapy in individual MSDs. Relative treatment effects were obtained through a systematic review of published data. RESULTS: Compared to land-based therapy, hydrotherapy was associated with an incremental cost-effectiveness ratio (ICER) of SGD 27 471 per quality-adjusted life-year (QALY) gained, which was below the willingness-to-pay threshold of SGD 70 000 per QALY (one gross domestic product per capita in Singapore in 2015). For the respective MSDs, hydrotherapy were dominant (more effective and less costly) in THR and TKR, cost-effective for LBP and RA, and not cost-effective for OA. Treatment adherence and cost of hydrotherapy were key drivers to the ICER values. CONCLUSIONS: Hydrotherapy was a cost-effective rehabilitation compared to land-based therapy for a population with MSDs in Singapore. However, the benefit of hydrotherapy was not observed in patients with OA.


Assuntos
Terapia por Exercício/economia , Hidroterapia/economia , Doenças Musculoesqueléticas/economia , Artrite Reumatoide/economia , Artrite Reumatoide/terapia , Artroplastia de Quadril/reabilitação , Artroplastia do Joelho/reabilitação , Análise Custo-Benefício , Terapia por Exercício/métodos , Humanos , Hidroterapia/métodos , Dor Lombar/economia , Dor Lombar/terapia , Doenças Musculoesqueléticas/terapia , Osteoartrite/economia , Osteoartrite/terapia , Anos de Vida Ajustados por Qualidade de Vida , Singapura
7.
Hum Brain Mapp ; 37(2): 443-61, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26526072

RESUMO

Individuals with autism spectrum disorders (ASD) often have difficulty recognizing and interpreting facial expressions of emotion, which may impair their ability to navigate and communicate successfully in their social, interpersonal environments. Characterizing specific differences between individuals with ASD and their typically developing (TD) counterparts in the neural activity subserving their experience of emotional faces may provide distinct targets for ASD interventions. Thus we used functional magnetic resonance imaging (fMRI) and a parametric experimental design to identify brain regions in which neural activity correlated with ratings of arousal and valence for a broad range of emotional faces. Participants (51 ASD, 84 TD) were group-matched by age, sex, IQ, race, and socioeconomic status. Using task-related change in blood-oxygen-level-dependent (BOLD) fMRI signal as a measure, and covarying for age, sex, FSIQ, and ADOS scores, we detected significant differences across diagnostic groups in the neural activity subserving the dimension of arousal but not valence. BOLD-signal in TD participants correlated inversely with ratings of arousal in regions associated primarily with attentional functions, whereas BOLD-signal in ASD participants correlated positively with arousal ratings in regions commonly associated with impulse control and default-mode activity. Only minor differences were detected between groups in the BOLD signal correlates of valence ratings. Our findings provide unique insight into the emotional experiences of individuals with ASD. Although behavioral responses to face-stimuli were comparable across diagnostic groups, the corresponding neural activity for our ASD and TD groups differed dramatically. The near absence of group differences for valence correlates and the presence of strong group differences for arousal correlates suggest that individuals with ASD are not atypical in all aspects of emotion-processing. Studying these similarities and differences may help us to understand the origins of divergent interpersonal emotional experience in persons with ASD. Hum Brain Mapp 37:443-461, 2016. © 2015 Wiley Periodicals, Inc.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Encéfalo/fisiopatologia , Emoções/fisiologia , Reconhecimento Facial/fisiologia , Adolescente , Adulto , Nível de Alerta/fisiologia , Mapeamento Encefálico , Circulação Cerebrovascular/fisiologia , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Oxigênio/sangue , Estimulação Luminosa , Adulto Jovem
8.
Acad Med ; 99(3): 343, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38015999

RESUMO

THE WHAT: Professional Identity Formation (PIF) in medicine is the gradual transformation that occurs in the process of becoming a doctor, as professional values, beliefs, behaviors, relationships, roles, and responsibilities become integrated into an aggregate of existing identities. 1 Conceptually, this process may be considered as a trajectory of self-perceived identities that transpires between an individual's existing identity and an evolving, aspirational identity toward which the individual may strive. 2 This process is individualized, yet contextual, psychosocially grounded, and subject to lifelong deconstruction and reconstruction depending on how the person experiences, and thus responds to, events. 2. THE SO WHAT: Faced with key transitions, conflicts, or crises, a medical student or physician may experience dissonance between their personal values and beliefs and their professional roles and expectations.1 If left unsupported (see light blue lines in graph below), this can challenge their sense of belonging or meaning, lower self-esteem or self-efficacy, or breed distress, burnout, or attrition. When recognized and supported (see dark blue line below), defining experiences can enhance tolerance for ambiguity, enable meaning-making, foster socialization into communities of learning or practice, and deepen enculturation and commitment to the profession. 2. THE WHAT NOW: PIF is implicitly a fundamental goal of medical education, necessitating institutional support along the medical education continuum. 1-3.


Assuntos
Educação Médica , Médicos , Humanos , Identificação Social , Autoimagem , Socialização
9.
Dev Med Child Neurol ; 54(3): 208-13, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22269006

RESUMO

AIM: The aim of this article is to review neuroimaging studies of autism spectrum disorders (ASD) that examine declarative, socio-emotional, and procedural learning and memory systems. METHOD: We conducted a search of PubMed from 1996 to 2010 using the terms 'autism,''learning,''memory,' and 'neuroimaging.' We limited our review to studies correlating learning and memory function with neuroimaging features of the brain. RESULTS: The early literature supports the following preliminary hypotheses: (1) abnormalities of hippocampal subregions may contribute to autistic deficits in episodic and relational memory; (2) disturbances to an amygdala-based network (which may include the fusiform gyrus, superior temporal cortex, and mirror neuron system) may contribute to autistic deficits in socio-emotional learning and memory; and (3) abnormalities of the striatum may contribute to developmental dyspraxia in individuals with ASD. INTERPRETATION: Characterizing the disturbances to learning and memory systems in ASD can inform our understanding of the neural bases of autistic behaviors and the phenotypic heterogeneity of ASD.


Assuntos
Encéfalo/patologia , Deficiências da Aprendizagem/diagnóstico , Transtornos da Memória/diagnóstico , Neuroimagem , Mapeamento Encefálico , Criança , Transtornos Globais do Desenvolvimento Infantil/complicações , Humanos , Deficiências da Aprendizagem/etiologia , Transtornos da Memória/etiologia , PubMed/estatística & dados numéricos
10.
Med Sci Educ ; 32(3): 697-702, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35493983

RESUMO

COVID-19 pandemic has transformed much of the medical curriculum delivery from in person to online. Given that interpersonal interaction facilitates team cohesion and professional identity formation, prolonged online learning with minimal social interaction might impact these competencies in medical education. To mitigate the impact of prolonged social isolation, we conducted synchronous team-based learning (TBL) classes, where half the class is physically present and the other is connected via an online platform, termed hybrid TBL. We present practical tips in implementing hybrid TBL for educators teaching in large-sized classes, should conditions exist where not all students can attend in person.

11.
Biol Psychiatry ; 87(2): 174-184, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31427037

RESUMO

BACKGROUND: Despite rising prevalence of autism spectrum disorder (ASD), its brain bases remain uncertain. Abnormal levels of N-acetyl compounds, glutamate+glutamine, creatine+phosphocreatine, or choline compounds measured by proton magnetic resonance spectroscopy suggest that neuron or glial density, mitochondrial energetic metabolism, and/or inflammation contribute to ASD neuropathology. The neuroanatomic distribution of these metabolites could help evaluate leading theories of ASD. However, most prior magnetic resonance spectroscopy studies had small samples (all <60, most <20), interrogated only a small fraction of the brain, and avoided assessing effects of age, sex, and IQ. METHODS: We acquired near-whole-brain magnetic resonance spectroscopy of N-acetyl compounds, glutamate+glutamine, creatine+phosphocreatine, and choline compounds in 78 children and adults with ASD and 96 typically developing children and adults, rigorously evaluating effects of diagnosis and severity on metabolites, as moderated by age, sex, and IQ. RESULTS: Effects of ASD and its severity included reduced levels of multiple metabolites in white matter and the perisylvian cortex and elevated levels in the posterior cingulate, consistent with white matter and social-brain theories of ASD. Regionally, both slower and faster decreases of metabolites with age were observed in ASD versus TD. Male-female metabolite differences were widely smaller in ASD than typically developing children and adults. ASD-specific decreases in metabolites with decreasing IQ occurred in several brain areas. CONCLUSIONS: Results support multifocal abnormal neuron or glial density, mitochondrial energetics, or neuroinflammation in ASD, alongside widespread starkly atypical moderating effects of age, sex, and IQ. These findings help parse the neurometabolic signature for ASD by phenotypic heterogeneity.


Assuntos
Transtorno do Espectro Autista , Adulto , Encéfalo/diagnóstico por imagem , Criança , Colina , Feminino , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino
12.
MedEdPublish (2016) ; 9: 135, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-38073806

RESUMO

This article was migrated. The article was marked as recommended. Due to the increasing number of COVID-19 cases globally, and the need for critical containment, Duke-NUS Medical School, Singapore, moved all of its preclinical classes online, keeping with national and university guidelines. The sudden move from face-to-face to online learning posed several challenges to the school's team-based learning (TBL) pedagogy. In TBL, student engagement is key to promote peer-to-peer learning. The educational faculty found that it was challenging to ensure student engagement through an online platform. Additionally, online TBL is heavily dependent on the use of technology. Technological and internet connectivity issues were potential obstacles to the learning process. This manuscript proposes practical tips for a facilitator of an online TBL class to engage learners in this new format. To overcome technical complications, a dedicated centralized administrative team managed the logistics of hosting TBL online. Working synergistically, the facilitator, and the administrative team were instrumental in recreating the learning environment of a face-to-face TBL in an online platform.

13.
Biol Psychiatry ; 85(7): 584-595, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30711191

RESUMO

BACKGROUND: Our aim was to assess resting cerebral blood flow (rCBF) in children and adults with autism spectrum disorder (ASD). METHODS: We acquired pulsed arterial spin labeling magnetic resonance imaging data in 44 generally high-functioning participants with ASD simplex and 66 typically developing control subjects with comparable mean full-scale IQs. We compared rCBF values voxelwise across diagnostic groups and assessed correlations with symptom scores. We also assessed the moderating influences of participant age, sex, and IQ on our findings and the correlations of rCBF with N-acetylaspartate metabolite levels. RESULTS: We detected significantly higher rCBF values throughout frontal white matter and subcortical gray matter in participants with ASD. rCBF correlated positively with socialization deficits in participants with ASD in regions where hyperperfusion was greatest. rCBF declined with increasing IQ in the typically developing group, a correlation that was absent in participants with ASD, whose rCBF values were elevated across all IQ levels. rCBF in the ASD group correlated inversely with N-acetylaspartate metabolite levels throughout the frontal white matter, with greater rCBF accompanying lower and increasingly abnormal N-acetylaspartate levels relative to those of typically developing control subjects. CONCLUSIONS: These findings taken together suggest the presence of altered metabolism, likely of mitochondrial origin, and dysfunctional maintenance processes that support axonal functioning in ASD. These disturbances in turn likely reduce neural efficiency for cognitive and social functioning and trigger compensatory responses from supporting glial cells, which subsequently increase rCBF to affected white matter. These findings, if confirmed, suggest cellular and molecular targets for novel therapeutics that address axonal pathology and bolster glial compensatory responses in ASD.


Assuntos
Ácido Aspártico/análogos & derivados , Transtorno do Espectro Autista , Circulação Cerebrovascular/fisiologia , Lobo Frontal , Substância Cinzenta , Substância Branca , Adolescente , Adulto , Ácido Aspártico/metabolismo , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/fisiopatologia , Criança , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/metabolismo , Lobo Frontal/fisiopatologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/metabolismo , Substância Cinzenta/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Marcadores de Spin , Substância Branca/diagnóstico por imagem , Substância Branca/metabolismo , Substância Branca/fisiopatologia , Adulto Jovem
14.
Pediatr Neurol ; 37(5): 382-4, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17950430

RESUMO

Rhizomelic chondrodysplasia punctata is a rare genetic disorder of peroxisomal metabolism that is characterized clinically by shortening of the proximal limbs, cataracts, a characteristic facial appearance, failure to thrive, and psychomotor retardation. This report describes a newborn with a severe phenotype whose neuroimaging showed pachygyria-polymicrogyria, severe spinal stenosis causing compression of the cervical cord and brainstem, and tethering of the spinal cord. Imaging of the brain and spinal cord in patients with this disorder may aid prognosis and guide management decisions.


Assuntos
Condrodisplasia Punctata Rizomélica/patologia , Imageamento por Ressonância Magnética , Humanos , Recém-Nascido , Masculino , Malformações do Desenvolvimento Cortical , Medula Espinal/patologia
15.
Brain Behav ; 7(2): e00596, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28239517

RESUMO

INTRODUCTION: Our flexible and adaptive interactions with the environment are guided by our individual representation of the physical world, estimated through sensation and evaluation of available information against prior knowledge. When linking sensory evidence with higher-level expectations for action, the central nervous system (CNS) in typically developing (TD) individuals relies in part on distributed and interacting cortical regions to communicate neuronal signals flexibly across the brain. Increasing evidence suggests that the balance between levels of signal and noise during information processing may be disrupted in individuals with Autism Spectrum Disorders (ASD). METHODS: Participants with and without ASD performed a visuospatial interference task while undergoing functional Magnetic Resonance Imaging (fMRI). We empirically estimated parameters characterizing participants' latencies and their subtle fluctuations (noise accumulation) over the 16-min scan. We modeled hemodynamic activation and used seed-based analyses of neural coupling to study dysfunction in interference-specific connectivity in a subset of ASD participants who were nonparametrically matched to TD participants on age, male-to-female ratio, and magnitude of movement during the scan. RESULTS: Stochastic patterns of response fluctuations reveal significantly higher noise-to-signal levels and a more random and noisy structure in ASD versus TD participants, and in particular ASD adults who have the greatest clinical autistic deficits. While individuals with ASD show an overall weaker modulation of interference-specific functional connectivity relative to TD individuals, in particular between the seeds of Anterior Cingulate Cortex (ACC) and Inferior Parietal Sulcus (IPS) and the rest of the brain, we found that in ASD, higher uncertainty during the task is linked to increased interference-specific coupling between bilateral anterior insula and prefrontal cortex. CONCLUSIONS: Subtle and informative differences in the structure of experiencing information exist between ASD and TD individuals. Our findings reveal in ASD an atypical capacity to apply previously perceived information in a manner optimal for adaptive functioning, plausibly revealing suboptimal message-passing across the CNS.


Assuntos
Atenção/fisiologia , Transtorno do Espectro Autista/fisiopatologia , Encéfalo/fisiopatologia , Neuroimagem Funcional/métodos , Desempenho Psicomotor/fisiologia , Percepção Espacial/fisiologia , Percepção Visual/fisiologia , Adolescente , Adulto , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Ann Clin Transl Neurol ; 4(7): 491-505, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28695149

RESUMO

OBJECTIVE: No drug is yet approved to treat the core symptoms of autism spectrum disorder (ASD). Low-dose suramin was effective in the maternal immune activation and Fragile X mouse models of ASD. The Suramin Autism Treatment-1 (SAT-1) trial was a double-blind, placebo-controlled, translational pilot study to examine the safety and activity of low-dose suramin in children with ASD. METHODS: Ten male subjects with ASD, ages 5-14 years, were matched by age, IQ, and autism severity into five pairs, then randomized to receive a single, intravenous infusion of suramin (20 mg/kg) or saline. The primary outcomes were ADOS-2 comparison scores and Expressive One-Word Picture Vocabulary Test (EOWPVT). Secondary outcomes were the aberrant behavior checklist, autism treatment evaluation checklist, repetitive behavior questionnaire, and clinical global impression questionnaire. RESULTS: Blood levels of suramin were 12 ± 1.5 µmol/L (mean ± SD) at 2 days and 1.5 ± 0.5 µmol/L after 6 weeks. The terminal half-life was 14.7 ± 0.7 days. A self-limited, asymptomatic rash was seen, but there were no serious adverse events. ADOS-2 comparison scores improved by -1.6 ± 0.55 points (n = 5; 95% CI = -2.3 to -0.9; Cohen's d = 2.9; P = 0.0028) in the suramin group and did not change in the placebo group. EOWPVT scores did not change. Secondary outcomes also showed improvements in language, social interaction, and decreased restricted or repetitive behaviors. INTERPRETATION: The safety and activity of low-dose suramin showed promise as a novel approach to treatment of ASD in this small study.

17.
J Child Neurol ; 20(5): 457-60, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15968936

RESUMO

Psychiatric disorders pose a significant burden to the quality of life of individuals with tuberous sclerosis complex and their caregivers. The relationship between the location and distribution of brain abnormalities in tuberous sclerosis complex and specific neuropsychiatric disorders is largely unknown. We present the first case in the literature of a child with tuberous sclerosis complex and anorexia nervosa and discuss the relevance of electroencephalography, magnetic resonance imaging, and neuropsychologic testing. To understand psychiatric disturbances in tuberous sclerosis complex, we must consider each of the following factors: cerebral pathology, seizure history, cognitive impairment, psychosocial stressors, and medications.


Assuntos
Anorexia Nervosa/etiologia , Esclerose Tuberosa/psicologia , Adolescente , Humanos , Masculino , Esclerose Tuberosa/patologia , Esclerose Tuberosa/fisiopatologia
18.
J Child Neurol ; 20(10): 837-41, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16417883

RESUMO

The objectives of this study were (1) to test the utility of tuber count and tuber location as biomarkers of disease severity in patients with tuberous sclerosis complex and (2) to examine the relationship between gene mutation, tuber count, and tuber location. We found that an increased tuber count per lobe and in total was associated with an increased risk of infantile spasms (P < .01). Increased tuber count in the occipital lobe was associated with an increased risk of pervasive developmental disorder (P = .0074). The mean tuber count per lobe and in total was higher in those with poorly controlled seizures and those with off-track development; however, these differences were not statistically significant (P > .01). The TSC2 gene mutation was associated with a significant increase in the tuber count per lobe and in total (P < .01). In summary, increased tuber count is strongly associated with infantile spasms and a TSC2 gene mutation. Seizure control and developmental delay do not show the strong association with tuber count suggested by the earlier literature.


Assuntos
Biomarcadores/análise , Espasmos Infantis/etiologia , Esclerose Tuberosa/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Lobo Frontal/patologia , Lateralidade Funcional , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Espasmos Infantis/patologia , Lobo Temporal/patologia , Esclerose Tuberosa/complicações , Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa , Proteínas Supressoras de Tumor/genética
20.
JAMA Psychiatry ; 71(6): 665-71, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24718932

RESUMO

IMPORTANCE: Impaired mitochondrial function impacts many biological processes that depend heavily on energy and metabolism and can lead to a wide range of neurodevelopmental disorders, including autism spectrum disorder (ASD). Although evidence that mitochondrial dysfunction is a biological subtype of ASD has grown in recent years, no study, to our knowledge, has demonstrated evidence of mitochondrial dysfunction in brain tissue in vivo in a large, well-defined sample of individuals with ASD. OBJECTIVES: To assess brain lactate in individuals with ASD and typically developing controls using high-resolution, multiplanar spectroscopic imaging; to map the distribution of lactate in the brains of individuals with ASD; and to assess correlations of elevated brain lactate with age, autism subtype, and intellectual ability. DESIGN, SETTING, AND PARTICIPANTS: Case-control study at Columbia University Medical Center and New York State Psychiatric Institute involving 75 children and adults with ASD and 96 age- and sex-matched, typically developing controls. MAIN OUTCOMES AND MEASURES: Lactate doublets (present or absent) on brain magnetic resonance spectroscopic imaging. RESULTS: Lactate doublets were present at a significantly higher rate in participants with ASD (13%) than controls (1%) (P = .001). In the ASD group, the presence of lactate doublets correlated significantly with age (P = .004) and was detected more often in adults (20%) than in children (6%), though it did not correlate with sex, ASD subtype, intellectual ability, or the Autism Diagnostic Observation Schedule total score or subscores. In those with ASD, lactate was detected most frequently within the cingulate gyrus but it was also present in the subcortical gray matter nuclei, corpus callosum, superior temporal gyrus, and pre- and postcentral gyri. CONCLUSIONS AND RELEVANCE: In vivo brain findings provide evidence for a possible neurobiological subtype of mitochondrial dysfunction in ASD.


Assuntos
Encéfalo/metabolismo , Transtornos Globais do Desenvolvimento Infantil/complicações , Transtornos Globais do Desenvolvimento Infantil/metabolismo , Ácido Láctico/metabolismo , Doenças Mitocondriais/complicações , Doenças Mitocondriais/metabolismo , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Neuroimagem Funcional , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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