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22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion in humans, with a heterogenous clinical presentation including medical, behavioural and psychiatric conditions. Previous neuroimaging studies examining the neuroanatomical underpinnings of 22q11.2DS show alterations in cortical volume (CV), cortical thickness (CT) and surface area (SA). The aim of this study was to identify (1) the spatially distributed networks of differences in CT and SA in 22q11.2DS compared to controls, (2) their unique and spatial overlap, as well as (3) their relative contribution to observed differences in CV. Structural MRI scans were obtained from 62 individuals with 22q11.2DS and 57 age-and-gender-matched controls (aged 6-31). Using FreeSurfer, we examined differences in vertex-wise estimates of CV, CT and SA at each vertex, and compared the frequencies of vertices with a unique or overlapping difference for each morphometric feature. Our findings indicate that CT and SA make both common and unique contributions to volumetric differences in 22q11.2DS, and in some areas, their strong opposite effects mask differences in CV. By identifying the neuroanatomic variability in 22q11.2DS, and the separate contributions of CT and SA, we can start exploring the shared and distinct mechanisms that mediate neuropsychiatric symptoms across disorders, e.g. 22q11.2DS-related ASD and/or psychosis/schizophrenia.
Assuntos
Espessura Cortical do Cérebro , Encéfalo/fisiopatologia , Síndrome de DiGeorge/fisiopatologia , Esquizofrenia/fisiopatologia , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Criança , Síndrome de DiGeorge/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico por imagem , Propriedades de Superfície , Adulto JovemRESUMO
BACKGROUND: Pelvic exenteration remains a viable and effective treatment option for the management of locally advanced or recurrent pelvic malignancy. The aim of this study was to present an early experience of robotic multivisceral resection of pelvic malignancy, and to compare this experience with similar series through a systematic review of the literature. METHODS: A retrospective study was performed on patients who had robotic-assisted multi-visceral resection for pelvic malignancy at a single Colorectal Surgical unit based between two tertiary academic hospitals. Primary outcomes observed included operation type, operation time, perioperative complications, and hospital length of stay. Secondary outcomes included R0 resection status, lymph node harvest, and rate of recurrence at clinical follow-up. RESULTS: Eight cases of robotic multivisceral resection were performed for primary locally advanced pelvic malignancy involving a rectal resection as part of their operative management. The median age of patients undergoing resection was 56 years (range 29-83 years). The male:female ratio was 6:2. The mean total operating time was 8.3 h (range 6-10 h). Perioperative blood transfusion requirements were minimal. Mean hospital length of stay was 15 days (range 7-26 days). No patients experienced any serious postoperative morbidity or mortality. All patients had clear margins on histological assessment and no patients have recurrence at 12-month follow-up. CONCLUSIONS: Robotic multivisceral resection for malignant disease of the pelvis is a safe and feasible minimally invasive approach in highly selected cases.
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Exenteração Pélvica , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Robótica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Objective: To describe the technical aspects and outcomes of robotic-assisted radical prostatectomy (RARP) following abandoned open radical prostatectomy (ORP). Patients and Methods: A retrospective review was performed of patients who underwent RARP following abandonment of ORP between 2016 and 2020. RARP was undertaken by two highly experienced robotic surgeons. Analysis of patient and operative characteristics, outcomes, and reasons for abandonment of ORP were described. Results: Six patients were included for analysis with a median age of 63.5 years [50.3-67.5]. The median body mass index (BMI) was 34.7 [27.8-36.2]. All patients had intermediate-risk prostate cancer. Small prostate and deep pelvis were given as reasons for abandoning ORP in five cases (83.3%), with four of these also attributing increased BMI as a factor. Extensive mesh from previous bilateral inguinal hernia repair was cited as the reason for abandonment in the remaining patient. One patient had commenced androgen deprivation therapy following abandoned ORP. Extensive retropubic adhesions were noted at the time of RARP in five of six patients, with intraoperative complication of small bladder lacerations encountered in the patient with prior mesh hernia repair. The median time from abandoned ORP to RARP was 128 days [40-216]. Median operating time was 160 minutes [139-190] and estimated blood loss was 225 mL [138-375]. Negative margins were obtained in four of six cases, with further salvage treatment being required in one case at a median follow-up duration of 10.5 months [6.5-25.3]. Conclusion: Abandonment of ORP is an uncommonly reported event, however, in this small case series, we demonstrate that, in the hands of experienced surgeons, RARP is a safe and technically feasible alternative in such cases. Increased BMI, small prostate size and pelvic anatomical constraints appear to be common catalysts for abandonment of open surgery in this cohort. Identifying these high-risk patients early and considering referral to robotic centers may be preferred.
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BACKGROUND: Molecular phylogenetics are generally used to confirm hepatitis C virus (HCV) transmission events. In addition, the Laboratoire de santé publique du Québec (LSPQ) has been using molecular phylogenetics for surveillance of HCV genotyping since November 2001. OBJECTIVES: To describe the emergence of a specific lineage of HCV genotype 4d (G4d) and its characteristics using molecular phylogenetics as a surveillance tool for identifying HCV strain clustering. METHODS: The LSPQ prospectively applied Sanger sequencing and phylogenetic analysis to determine the HCV genotype on samples collected from November 2001 to December 2017. When a major G4d cluster was identified, demographic information, HIV-infection status and syphilis test results were analyzed. RESULTS: Phylogenetic analyses performed on approximately 22,000 cases identified 122 G4d cases. One major G4d cluster composed of 37 cases was singled out. Two cases were identified in 2010, 10 from 2011-2014 and 25 from 2015-2017. Cases in the cluster were concentrated in two urban health regions. Compared to the other G4d cases, cluster cases were all male (p<0.001) and more likely to be HIV-positive (adjusted risk ratio: 4.4; 95% confidence interval: 2.5-7.9). A positive syphilis test result was observed for 27 (73%) of the cluster cases. The sequences in this cluster and of four outlier cases were located on the same monophyletic lineage as G4d sequences reported in HIV-positive men who have sex with men (MSM) in Europe. CONCLUSION: Molecular phylogenetics enabled the identification and surveillance of ongoing transmission of a specific HCV G4d lineage in HIV-positive and HIV-negative men in Quebec and its cross-continental spread. This information can orient intervention strategies to avoid transmission of HCV in MSM.
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22q11.2 Deletion Syndrome (22q11.2DS) is a genetic condition associated with a high prevalence of neuropsychiatric conditions that include autism spectrum disorder (ASD). While evidence suggests that clinical phenotypes represent distinct neurodevelopmental outcomes, it remains unknown whether this translates to the level of neurobiology. To fractionate the 22q11.2DS phenotype on the level of neuroanatomy, we examined differences in vertex-wise estimates of cortical volume, surface area, and cortical thickness between 1) individuals with 22q11.2DS (n = 62) and neurotypical controls (n = 57) and 2) 22q11.2DS individuals with ASD symptomatology (n = 30) and those without (n = 25). We firstly observed significant differences in surface anatomy between 22q11.2DS individuals and controls for all 3 neuroanatomical features, predominantly in parietotemporal regions, cingulate and dorsolateral prefrontal cortices. We also established that 22q11.2DS individuals with ASD symptomatology were neuroanatomically distinct from 22q11.2DS individuals without ASD symptoms, particularly in brain regions that have previously been linked to ASD (e.g., dorsolateral prefrontal cortices and the entorhinal cortex). Our findings indicate that different clinical 22q11.2DS phenotypes, including those with ASD symptomatology, may represent different neurobiological subgroups. The spatially distributed patterns of neuroanatomical differences associated with ASD symptomatology in 22q11.2DS may thus provide useful information for patient stratification and the prediction of clinical outcomes.
Assuntos
Transtorno do Espectro Autista/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Síndrome de DiGeorge/diagnóstico por imagem , Adolescente , Adulto , Transtorno do Espectro Autista/etiologia , Transtorno do Espectro Autista/patologia , Transtorno do Espectro Autista/psicologia , Encéfalo/patologia , Estudos de Casos e Controles , Criança , Síndrome de DiGeorge/complicações , Síndrome de DiGeorge/patologia , Síndrome de DiGeorge/psicologia , Córtex Entorrinal/diagnóstico por imagem , Córtex Entorrinal/patologia , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/patologia , Humanos , Masculino , Tamanho do Órgão , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/patologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/patologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Adulto JovemRESUMO
The heterogeneity of prostate cancer has made imaging modalities of crucial importance in this disease. Accurate diagnosis and staging of the volume and extent of disease, especially in advanced and metastatic prostate cancer, can help to tailor the timing and modalities of treatment. While MRI has been effective in the detection of significant prostate cancer, its use in the identification and quantification of extraprostatic disease is limited. This gap is now being filled by PSMA PET. PSMA PET scans have now been shown to have a role in all stages in the prostate cancer journey. Emerging evidence has shown its promise in primary staging, restaging and theranostics. In this paper, we review the evidence for the use of PSMA PET in the various stages of prostate cancer, from initial diagnosis to advanced metastatic disease where other systemic treatments have failed.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico por imagem , Dipeptídeos/uso terapêutico , Isótopos de Gálio , Radioisótopos de Gálio , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Humanos , Lutécio , Masculino , Glicoproteínas de Membrana , Metástase Neoplásica , Compostos Organometálicos , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/radioterapia , Compostos Radiofarmacêuticos , Nanomedicina TeranósticaRESUMO
Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology.
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Transtorno do Espectro Autista/epidemiologia , Adolescente , Adulto , Fatores Etários , Transtorno do Espectro Autista/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Relações Interpessoais , Masculino , Fenótipo , Caracteres SexuaisRESUMO
Autism spectrum disorder (ASD) is a common, highly heritable, developmental disorder and later-born siblings of diagnosed children are at higher risk of developing ASD than the general population. Although the emergence of behavioural symptoms of ASD in toddlerhood is well characterized, far less is known about development during the first months of life of infants at familial risk. In a prospective longitudinal study of infants at familial risk followed to 36 months, we measured functional near-infrared spectroscopy (fNIRS) brain responses to social videos of people (i.e. peek-a-boo) compared to non-social images (vehicles) and human vocalizations compared to non-vocal sounds. At 4-6 months, infants who went on to develop ASD at 3 years (N = 5) evidenced-reduced activation to visual social stimuli relative to low-risk infants (N = 16) across inferior frontal (IFG) and posterior temporal (pSTS-TPJ) regions of the cortex. Furthermore, these infants also showed reduced activation to vocal sounds and enhanced activation to non-vocal sounds within left lateralized temporal (aMTG-STG/pSTS-TPJ) regions compared with low-risk infants and high-risk infants who did not develop ASD (N = 15). The degree of activation to both the visual and auditory stimuli correlated with parent-reported ASD symptomology in toddlerhood. These preliminary findings are consistent with later atypical social brain responses seen in children and adults with ASD, and highlight the need for further work interrogating atypical processing in early infancy and how it may relate to later social interaction and communication difficulties characteristic of ASD.
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Percepção Auditiva/fisiologia , Transtorno do Espectro Autista/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Percepção Social , Lobo Temporal/fisiopatologia , Percepção Visual/fisiologia , Transtorno do Espectro Autista/diagnóstico por imagem , Feminino , Neuroimagem Funcional , Predisposição Genética para Doença , Humanos , Lactente , Estudos Longitudinais , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Irmãos , Espectroscopia de Luz Próxima ao Infravermelho , Percepção da Fala/fisiologia , Lobo Temporal/diagnóstico por imagemRESUMO
Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the 'responsivity' of the E-I system to pharmacologic challenge; or whether E-I modulation alters abnormalities in functional connectivity of brain regions implicated in the disorder. Therefore, we used magnetic resonance spectroscopy ([1H]MRS) to measure prefrontal E-I flux in response to the glutamate and GABA acting drug riluzole in adult men with and without ASD. We compared the change in prefrontal 'Inhibitory Index'-the GABA fraction within the pool of glutamate plus GABA metabolites-post riluzole challenge; and the impact of riluzole on differences in resting-state functional connectivity. Despite no baseline differences in E-I balance, there was a significant group difference in response to pharmacologic challenge. Riluzole increased the prefrontal cortex inhibitory index in ASD but decreased it in controls. There was also a significant group difference in prefrontal functional connectivity at baseline, which was abolished by riluzole within the ASD group. Our results also show, for we believe the first time in ASD, that E-I flux can be 'shifted' with a pharmacologic challenge, but that responsivity is significantly different from controls. Further, our initial evidence suggests that abnormalities in functional connectivity can be 'normalised' by targeting E-I, even in adults.
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Transtorno do Espectro Autista/fisiopatologia , Encéfalo/fisiopatologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Córtex Pré-Frontal/fisiopatologia , Riluzol/farmacologia , Adulto , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Mapeamento Encefálico/métodos , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/metabolismo , Neuroimagem Funcional/métodos , Ácido Glutâmico/metabolismo , Ácido Glutâmico/fisiologia , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Vias Neurais/fisiopatologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Riluzol/administração & dosagem , Riluzol/metabolismo , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/fisiologiaRESUMO
Autism spectrum conditions (ASC) are more prevalent in males than females. The biological basis of this difference remains unclear. It has been postulated that one of the primary causes of ASC is a partial disconnection of the frontal lobe from higher-order association areas during development (that is, a frontal 'disconnection syndrome'). Therefore, in the current study we investigated whether frontal connectivity differs between males and females with ASC. We recruited 98 adults with a confirmed high-functioning ASC diagnosis (61 males: aged 18-41 years; 37 females: aged 18-37 years) and 115 neurotypical controls (61 males: aged 18-45 years; 54 females: aged 18-52 years). Current ASC symptoms were evaluated using the Autism Diagnostic Observation Schedule (ADOS). Diffusion tensor imaging was performed and fractional anisotropy (FA) maps were created. Mean FA values were determined for five frontal fiber bundles and two non-frontal fiber tracts. Between-group differences in mean tract FA, as well as sex-by-diagnosis interactions were assessed. Additional analyses including ADOS scores informed us on the influence of current ASC symptom severity on frontal connectivity. We found that males with ASC had higher scores of current symptom severity than females, and had significantly lower mean FA values for all but one tract compared to controls. No differences were found between females with or without ASC. Significant sex-by-diagnosis effects were limited to the frontal tracts. Taking current ASC symptom severity scores into account did not alter the findings, although the observed power for these analyses varied. We suggest these findings of frontal connectivity abnormalities in males with ASC, but not in females with ASC, have the potential to inform us on some of the sex differences reported in the behavioral phenotype of ASC.
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Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/patologia , Imagem de Tensor de Difusão , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) share abnormalities in hot executive functions such as reward-based decision-making, as measured in the temporal discounting task (TD). No studies, however, have directly compared these disorders to investigate common/distinct neural profiles underlying such abnormalities. We wanted to test whether reward-based decision-making is a shared transdiagnostic feature of both disorders with similar neurofunctional substrates or whether it is a shared phenotype with disorder-differential neurofunctional underpinnings. METHODS: Age and IQ-matched boys with ASD (N = 20), with OCD (N = 20) and 20 healthy controls, performed an individually-adjusted functional magnetic resonance imaging (fMRI) TD task. Brain activation and performance were compared between groups. RESULTS: Boys with ASD showed greater choice-impulsivity than OCD and control boys. Whole-brain between-group comparison revealed shared reductions in ASD and OCD relative to control boys for delayed-immediate choices in right ventromedial/lateral orbitofrontal cortex extending into medial/inferior prefrontal cortex, and in cerebellum, posterior cingulate and precuneus. For immediate-delayed choices, patients relative to controls showed reduced activation in anterior cingulate/ventromedial prefrontal cortex reaching into left caudate, which, at a trend level, was more decreased in ASD than OCD patients, and in bilateral temporal and inferior parietal regions. CONCLUSIONS: This first fMRI comparison between youth with ASD and with OCD, using a reward-based decision-making task, shows predominantly shared neurofunctional abnormalities during TD in key ventromedial, orbital- and inferior fronto-striatal, temporo-parietal and cerebellar regions of temporal foresight and reward processing, suggesting trans-diagnostic neurofunctional deficits.
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Transtorno do Espectro Autista/fisiopatologia , Mapeamento Encefálico/métodos , Núcleo Caudado/fisiopatologia , Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Desvalorização pelo Atraso/fisiologia , Comportamento Impulsivo/fisiologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Recompensa , Adolescente , Transtorno do Espectro Autista/diagnóstico por imagem , Núcleo Caudado/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Criança , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologiaRESUMO
BACKGROUND: Many adults with autism spectrum disorder (ASD) remain undiagnosed. Specialist assessment clinics enable the detection of these cases, but such services are often overstretched. It has been proposed that unnecessary referrals to these services could be reduced by prioritizing individuals who score highly on the Autism-Spectrum Quotient (AQ), a self-report questionnaire measure of autistic traits. However, the ability of the AQ to predict who will go on to receive a diagnosis of ASD in adults is unclear. METHOD: We studied 476 adults, seen consecutively at a national ASD diagnostic referral service for suspected ASD. We tested AQ scores as predictors of ASD diagnosis made by expert clinicians according to International Classification of Diseases (ICD)-10 criteria, informed by the Autism Diagnostic Observation Schedule-Generic (ADOS-G) and Autism Diagnostic Interview-Revised (ADI-R) assessments. RESULTS: Of the participants, 73% received a clinical diagnosis of ASD. Self-report AQ scores did not significantly predict receipt of a diagnosis. While AQ scores provided high sensitivity of 0.77 [95% confidence interval (CI) 0.72-0.82] and positive predictive value of 0.76 (95% CI 0.70-0.80), the specificity of 0.29 (95% CI 0.20-0.38) and negative predictive value of 0.36 (95% CI 0.22-0.40) were low. Thus, 64% of those who scored below the AQ cut-off were 'false negatives' who did in fact have ASD. Co-morbidity data revealed that generalized anxiety disorder may 'mimic' ASD and inflate AQ scores, leading to false positives. CONCLUSIONS: The AQ's utility for screening referrals was limited in this sample. Recommendations supporting the AQ's role in the assessment of adult ASD, e.g. UK NICE guidelines, may need to be reconsidered.
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Transtorno do Espectro Autista/diagnóstico , Escalas de Graduação Psiquiátrica/normas , Autorrelato/normas , Inquéritos e Questionários/normas , Adulto , Transtorno do Espectro Autista/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, which is accompanied by differences in gray matter neuroanatomy and white matter connectivity. However, it is unknown whether these differences are linked or reflect independent aetiologies. Using a multimodal neuroimaging approach, we therefore examined 51 male adults with ASD and 48 neurotypical controls to investigate the relationship between gray matter local gyrification (lGI) and white matter diffusivity in associated fiber tracts. First, ASD individuals had a significant increase in gyrification around the left pre- and post-central gyrus. Second, white matter fiber tracts originating and/or terminating in the cluster of increased lGI had a significant increase in axial diffusivity. This increase in diffusivity was predominantly observed in tracts in close proximity to the cortical sheet. Last, we demonstrate that the increase in lGI was significantly correlated with increased diffusivity of short tracts. This relationship was not significantly modulated by a main effect of group (i.e., ASD), which was more closely associated with gray matter gyrification than white matter diffusivity. Our findings suggest that differences in gray matter neuroanatomy and white matter connectivity are closely linked, and may reflect common rather than distinct aetiological pathways.
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Transtorno do Espectro Autista/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adolescente , Adulto , Imagem de Tensor de Difusão , Humanos , Imageamento Tridimensional , Inteligência , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Tamanho do Órgão , Reconhecimento Automatizado de Padrão , Adulto JovemRESUMO
The aim of this paper was to examine the eligibility criteria, surveillance protocols and oncological outcomes of published active surveillance (AS) series. We also assessed the evidence for utility of novel tools for optimal risk stratification and surveillance of men suitable for AS. A non-systematic literature search of the Medline, Embase, and Scopus databases was performed in April 2015 using medical subject headings and free-text protocol. The search was conducted by applying free-text protocol with the following search terms: "active surveillance", "prostate cancer", "prostatic neoplasm", "watchful waiting", "low risk prostate cancer" and "very low risk prostate cancer". The definition of insignificant disease remains debatable as criteria for patient selection vary among studies. Tools for better selection of candidates and monitoring of the disease process have evolved since the conception of AS, including new biomarkers like phi, mpMRI and alternate biopsy strategies. AS is a sound strategy for reducing overtreatment of men with low-risk, and potentially selected men with intermediate-risk prostate cancer and shorter life expectancy, without compromising overall and cancer specific survival. More data are needed on the optimal integration of the new tools on AS paradigms and on the long-term health impact of AS in different populations.
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Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Conduta Expectante , Medicina Baseada em Evidências , Humanos , Masculino , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico por imagemRESUMO
BACKGROUND: Increasing evidence suggests that autism is associated with abnormal white-matter (WM) anatomy and impaired brain 'connectivity'. While myelin plays a critical role in synchronized brain communication, its aetiological role in autistic symptoms has only been indirectly addressed by WM volumetric, relaxometry and diffusion tensor imaging studies. A potentially more specific measure of myelin content, termed myelin water fraction (MWF), could provide improved sensitivity to myelin alteration in autism. METHOD: We performed a cross-sectional imaging study that compared 14 individuals with autism and 14 age- and IQ-matched controls. T 1 relaxation times (T 1), T 2 relaxation times (T 2) and MWF values were compared between autistic subjects, diagnosed using the Autism Diagnostic Interview - Revised (ADI-R), with current symptoms assessed using the Autism Diagnostic Observation Schedule (ADOS) and typical healthy controls. Correlations between T 1, T 2 and MWF values with clinical measures [ADI-R, ADOS, and the Autism Quotient (AQ)] were also assessed. RESULTS: Individuals with autism showed widespread WM T 1 and MWF differences compared to typical controls. Within autistic individuals, worse current social interaction skill as measured by the ADOS was related to reduced MWF although not T 1. No significant differences or correlations with symptoms were observed with respect to T 2. CONCLUSIONS: Autistic individuals have significantly lower global MWF and higher T 1, suggesting widespread alteration in tissue microstructure and biochemistry. Areas of difference, including thalamic projections, cerebellum and cingulum, have previously been implicated in the disorder; however, this is the first study to specifically indicate myelin alteration in these regions.
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Transtorno Autístico/patologia , Imageamento por Ressonância Magnética/métodos , Bainha de Mielina/patologia , Substância Branca/patologia , Adulto , Humanos , Masculino , Bainha de Mielina/química , Substância Branca/química , Adulto JovemRESUMO
Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition that is accompanied by an atypical development of brain maturation. So far, brain development has mainly been studied during early childhood in ASD, and using measures of total or lobular brain volume. However, cortical volumetric measures are a product of two distinct biological neuroanatomical features, cortical thickness, and surface area, which most likely also have different neurodevelopmental trajectories in ASD. Here, we therefore examined age-related differences in cortical thickness and surface area in a cross-sectional sample of 77 male individuals with ASD ranging from 7 to 25 years of age, and 77 male neurotypical controls matched for age and FSIQ. Surface-based measures were analyzed using a general linear model (GLM) including linear, quadratic, and cubic age terms, as well as their interactions with the main effect of group. When controlling for the effects of age, individuals with ASD had spatially distributed reductions in cortical thickness relative to controls, particularly in fronto-temporal regions, and also showed significantly reduced surface area in the prefrontal cortex and the anterior temporal lobe. We also observed significant group × age interactions for both measures. However, while cortical thickness was best predicted by a quadratic age term, the neurodevelopmental trajectory for measures of surface area was mostly linear. Our findings suggest that ASD is accompanied by age-related and region-specific reductions in cortical thickness and surface area during childhood and early adulthood. Thus, differences in the neurodevelopmental trajectory of maturation for both measures need to be taken into account when interpreting between-group differences overall.
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Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/patologia , Transtornos Globais do Desenvolvimento Infantil/patologia , Adolescente , Adulto , Envelhecimento , Criança , Estudos Transversais , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Testes Neuropsicológicos , Tamanho do Órgão , Adulto JovemRESUMO
OBJECTIVE: Prostate cancer and its treatment can result in numerous physical and psychological morbidities for the patient as well as his partner. This qualitative study aimed to explore the experiences of intimate spouses or partners of men diagnosed and/or treated for prostate cancer to better understand the personal impact of prostate cancer on the partner. METHODS: Twenty-seven partners participated in this study. Six focus groups were convened, and one in-depth interview was undertaken to explore the practical impact of prostate cancer on the intimate spouse/partner. All discussions were audio-recorded and transcribed and then coded using a thematic approach. RESULTS: Six themes emerged: (a) The influence of the man's response to prostate cancer on the partner, (b) The need to be involved in treatment and medical decision making, (c) Supporting a man who is experiencing a loss of masculinity, (d) Degree of congruence between each partner's coping responses, (e) Constrained communication, and (f) Changed roles and increased practical management. CONCLUSIONS: It is clear that prostate cancer impacts substantially on many areas of partner well-being. An effective intervention provided to this population seems warranted and may lead to improvements in partner well-being, assist the couple in lessening the impact of prostate cancer and its treatment on their relationship, and assist in the man's recovery.
Assuntos
Adaptação Psicológica , Comunicação , Tomada de Decisões , Neoplasias da Próstata , Cônjuges , Adulto , Idoso , Feminino , Grupos Focais , Humanos , Masculino , Masculinidade , Pessoa de Meia-Idade , Pesquisa QualitativaRESUMO
There is increasing evidence that abnormalities in glutamate signalling may contribute to the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectroscopy ([1H]MRS) can be used to measure glutamate, and also its metabolite glutamine, in vivo. However, few studies have investigated glutamate in the brain of adults with ADHD naive to stimulant medication. Therefore, we used [1H]MRS to measure the combined signal of glutamate and glutamine (Glu+Gln; abbreviated as Glx) along with other neurometabolites such as creatine (Cr), N-acetylaspartate (NAA) and choline. Data were acquired from three brain regions, including two implicated in ADHD-the basal ganglia (caudate/striatum) and the dorsolateral prefrontal cortex (DLPFC)-and one 'control' region-the medial parietal cortex. We compared 40 adults with ADHD, of whom 24 were naive for ADHD medication, whereas 16 were currently on stimulants, against 20 age, sex and IQ-matched healthy controls. We found that compared with controls, adult ADHD participants had a significantly lower concentration of Glx, Cr and NAA in the basal ganglia and Cr in the DLPFC, after correction for multiple comparisons. There were no differences between stimulant-treated and treatment-naive ADHD participants. In people with untreated ADHD, lower basal ganglia Glx was significantly associated with more severe symptoms of inattention. There were no significant differences in the parietal 'control' region. We suggest that subcortical glutamate and glutamine have a modulatory role in ADHD adults; and that differences in glutamate-glutamine levels are not explained by use of stimulant medication.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Gânglios da Base/metabolismo , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Córtex Pré-Frontal/metabolismo , Adulto , HumanosRESUMO
OBJECTIVE: To investigate potential abnormalities in subcortical brain structures in conversion disorder (CD) compared with controls using a region of interest (ROI) approach. METHODS: Fourteen patients with motor CD were compared with 31 healthy controls using high-resolution MRI scans with an ROI approach focusing on the basal ganglia, thalamus and amygdala. Brain volumes were measured using Freesurfer, a validated segmentation algorithm. RESULTS: Significantly smaller left thalamic volumes were found in patients compared with controls when corrected for intracranial volume. These reductions did not vary with handedness, laterality, duration or severity of symptoms. CONCLUSIONS: These differences may reflect a primary disease process in this area or be secondary effects of the disorder, for example, resulting from limb disuse. Larger, longitudinal structural imaging studies will be required to confirm the findings and explore whether they are primary or secondary to CD.