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PurposeBiallelic loss-of-function variants in ST3GAL5 cause GM3 synthase deficiency (GM3SD) responsible for Amish infantile epilepsy syndrome. All Amish patients carry the homozygous p.(Arg288Ter) variant arising from a founder effect. To date only 10 patients from 4 non-Amish families have been reported. Thus, the phenotypical spectrum of GM3SD due to other variants and other genetic backgrounds is still poorly known.MethodsWe collected clinical and molecular data from 16 non-Amish patients with pathogenic ST3GAL5 variants resulting in GM3SD.ResultsWe identified 12 families originating from Reunion Island, Ivory Coast, Italy, and Algeria and carrying 6 ST3GAL5 variants, 5 of which were novel. Genealogical investigations and/or haplotype analyses showed that 3 of these variants were founder alleles. Glycosphingolipids quantification in patients’ plasma confirmed the pathogenicity of 4 novel variants. All patients (N = 16), aged 2 to 12 years, had severe to profound intellectual disability, 14 of 16 had a hyperkinetic movement disorder, 11 of 16 had epilepsy and 9 of 16 had microcephaly. Other main features were progressive skin pigmentation anomalies, optic atrophy or pale papillae, and hearing loss.ConclusionThe phenotype of non-Amish patients with GM3SD is similar to the Amish infantile epilepsy syndrome, which suggests that GM3SD is associated with a narrow and severe clinical spectrum.  相似文献   
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Background: Caregivers of stroke survivors often suffer depressive symptoms that interfere with their own health. Early recognition may lead to attenuation of symptoms and better health and well-being for caregivers.

Objective: We examined characteristics of caregivers and stroke survivors associated with caregivers’ depressive symptoms in the early poststroke period.

Methods: We conducted a prospective, longitudinal exploratory observational study with a convenience sample of 63 caregivers of older adult (≥ 65 years) stroke survivors recruited from urban acute-care settings. We enrolled caregivers by 2 weeks poststroke (T1) and revisited them 4 weeks later (T2). Depressive symptoms were measured using the Patient Health Questionnaire-9. A separate unadjusted linear mixed model was computed to explore significant associations between each caregiver or stroke-survivor characteristic and depressive symptoms.

Results: Caregivers, on average, reported mild depressive symptoms at T1 and T2. Each of the following characteristics was independently associated with caregiver depressive symptoms over the first 6 weeks poststroke: caregiver uncertainty (p < 0.001), perceived stress (p < 0.001) but not cortisol levels (p = 0.858 on waking, p = 0.231 evening), coping (p < 0.001), social support (p = 0.006), race (p = 0.022), income (p = 0.001), time spent on care (p = 0.039), and stroke-survivor race (p = 0.033) and functional status (p = 0.003). At T2, caregiver depressive symptoms were correlated with evening cortisol level (p = 0.001).

Conclusions: Caregiver and stroke-survivor characteristics may help identify caregivers at highest risk for early depressive symptoms and guide interventions aimed at their resolution.  相似文献   

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Although the research on specialty mental health probation (SMHP) is promising, there have been no randomized controlled trials (RCT) of the prototypical model advanced in the research literature and little focus on SMHP implementation. This study assesses the adoption of SMHP in two counties and examines its impact on mental health and criminal justice outcomes. Researchers conducted a RCT within a hybrid implementation-effectiveness study to examine intervention adoption as well as mental health treatment engagement and criminal justice outcomes for 100 individuals with serious mental illnesses on probation in one rural and one urban county in a southeastern state. Randomization produced equivalent treatment (n?=?47) and control (n?=?53) groups with no statistically significant differences between groups on demographic or background characteristics. Compared to standard probation officers, SMHP officers addressed the mental health needs of individuals with serious mental illness (i.e., adoption) at higher rates (p?<?0.001). Compared to individuals on standard caseloads, individuals on SMHP had a higher rate of mental health engagement (e.g., mental health assessment, attending treatment appointment; p?<?0.050); however, more individuals on SMHP caseloads had a new crime violation during follow-up compared with individuals on standard caseloads (p?<?0.01). In conclusions, results suggest successful adoption of the intervention and increased mental health engagement among those on SMHP caseloads. Results are consistent with the mixed findings on the impact of SMHP on improving criminal justice outcomes.

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The formation of the external genitalia is a highly complex developmental process, considering it involves a wide range of cell types and results in sexually dimorphic outcomes. Development is controlled by several secreted signalling factors produced in complex spatiotemporal patterns, including the hedgehog (HH), bone morphogenic protein (BMP), fibroblast growth factor (FGF) and WNT signalling families. Many of these factors act on or are influenced by the actions of the androgen receptor (AR) that is critical to masculinisation. This complexity of expression makes it difficult to conceptualise patterns of potential importance. Mapping expression during key stages of development is needed to develop a comprehensive model of how different cell types interact in formation of external genitalia, and the global regulatory networks at play. This is particularly true in light of the sensitivity of this process to environmental disruption during key stages of development. The goal of this review is to integrate all recent studies on gene expression in early penis development to create a comprehensive spatiotemporal map. This serves as a resource to aid in visualising potentially significant interactions involved in external genital development.  相似文献   
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Forensic Toxicology - The stability of NBOMes, potent new psychoactive substances, in whole blood was studied over 180&nbsp;days. We present a fully validated liquid chromatography–tandem...  相似文献   
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