Diasporic virginities: social representations of virginity and identity formation amongst British arab muslim women

This study compares how practising and non-practising British Arab Muslim women position themselves in relation to representations of virginity. Overall, in our qualitative study, we found that representations of culture and religion influenced social practices and social beliefs in different ways: non-practising Muslim women felt bound by culture to remain virgins, while practising Muslim women saw it as a religious obligation but were still governed by culture regarding the consequences of engaging in premarital sex. Interestingly, some practising Muslim participants used Mut’a (a form of temporary ‘marriage’) to justify premarital sex. This, however, did not diminish the importance of virginity in their understanding and identification as Arab women. In fact, this study found that virginity, for the British Arabs interviewed, embodied a sense of ‘Arabness’ in British society. Positioning themselves as virgins went beyond simply honour; it was a significant cultural symbol that secured their sense of cultural identity. In fact this cultural identity was often so powerful that it overrode their Islamic identities, prescribing their behaviour even if religion was seen as more ‘forgiving’

Pandemic intake questionnaire to improve quality, effectiveness, and efficiency of outpatient neurologic and developmental care at the Kennedy Krieger institute during the COVID-19 pandemic

BackgroundThe COVID-19 pandemic uniquely affects patients with neurologic and developmental disabilities at the Kennedy Krieger Institute. These patients are at increased risk of co-morbidities, increasing their risk of contracting COVID-19. Disruptions in their home and school routines, and restrictions accessing crucial healthcare services has had a significant impact.MethodsA Pandemic Intake questionnaire regarding COVID-19 related medical concerns of guardians of patients was distributed using Qualtrics. Data from May-December 2020 were merged with demographic information of patients from 10 clinics (Center for Autism and Related Disorders (CARD), Neurology, Epigenetics, Neurogenetics, Center for Development and Learning (CDL) Sickle Cell, Spinal Cord, Sturge-Weber syndrome (SWS), Tourette's, and Metabolism). A provider feedback survey was distributed to program directors to assess the effectiveness of this intervention.ResultsAnalysis included responses from 1643 guardians of pediatric patients (mean age 9.5 years, range 0–21.6 years). Guardians of patients in more medically complicated clinics reported perceived increased risk of COVID-19 (p < 0.001) and inability to obtain therapies (p < 0.001) and surgeries (p < 0.001). Guardian responses from CARD had increased reports of worsening behavior (p = 0.01). Providers increased availability of in-person and virtual therapies and visits and made referrals for additional care to address this. In a survey of medical providers, five out of six program directors who received the responses to this survey found this questionnaire helpful in caring for their patients.ConclusionThis quality improvement project successfully implemented a pre-visit questionnaire to quickly assess areas of impact of COVID-19 on patients with neurodevelopmental disorders. During the pandemic, results identified several major areas of impact, including patient populations at increased risk for behavioral changes, sleep and/or disruptions of medical care. Most program directors reported improved patient care as a result

Functional analysis of missense DARS2 variants in siblings with leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation

Biallelic pathogenic variants in the nuclear gene DARS2 (MIM# 610956), encoding the mitochondrial enzyme aspartyl-tRNA synthetase (MT-ASPRS) cause leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation (LBSL) (MIM# 611105), a neurometabolic disorder characterized by progressive ataxia, spasticity, developmental arrest or regression and characteristic brain MRI findings. Most patients exhibit a slowly progressive disease course with motor deterirartion that begins in childhood or adolescence, but can also occasionaly occur in adulthood. More severe LBSL presentations with atypical brain MRI findings have been recently described. Baker's yeast orthologue of DARS2, MSD1, is required for growth on oxidative carbon sources. A yeast with MSD1 knockout (msd1 Delta) demonstrated a complete lack of oxidative growth which could be rescued by wild-type MSD1 but not MSD1 with pathogenic variants. Here we reported two siblings who exhib-ited developmental regression and ataxia with different age of onset and phenotypic severity. Exome sequencing revealed 2 compound heterozygous missense variants in DARS2: c.473A>T (p.Glu158Val) and c.829G>A (p. Glu277Lys); this variant combination has not been previously reported. The msd1 Delta yeast transformed with plas-mids expressing p.Glu259Lys, equivalent to human p.Glu277Lys, showed complete loss of oxidative growth and oxygen consumption, while the strain carrying p.Gln137Val, equivalent to human p.Glu158Val, showed a signif-icant reduction of oxidative growth, but a residual ability to grow was retained. Structural analysis indicated that p.Glu158Val may interfere with protein binding of tRNAAsp, while p.Glu277Lys may impact both homodimerization and catalysis of MT-ASPRS. Our data illustrate the utility of yeast model and in silico analysis to determine pathogenicity of DARS2 variants, expand the genotypic spectrum and suggest intrafamilial variabil-ity in LBSL.(c) 2022 Elsevier Inc. All rights reserved

Neuronal ablation of mt-AspRS in mice induces immune pathway activation prior to severe and progressive cortical and behavioral disruption

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare, slowly progressive white matter disease caused by mutations in the mitochondrial aspartyl-tRNA synthetase (mt-AspRS, or DARS2). While patients show characteristic MRI T2 signal abnormalities throughout the cerebral white matter, brainstem, and spinal cord, the phenotypic spectrum is broad and a multitude of gene variants have been associated with the disease. Here, Dars2 disruption in CamKII alpha-expressing cortical and hippocampal neurons results in slowly progressive increases in behavioral activity at five months, and culminating by nine months as severe brain atrophy, behavioral dysfunction, reduced corpus callosum thickness, and microglial morphology indicative of neuroinflammation. Interestingly, RNAseq based gene expression studies performed prior to the presentation of this severe phenotype reveal the upregulation of several pathways involved in immune activation, cytokine production and signaling, and defense response regulation. RNA transcript analysis demonstrates that activation of immune and cell stress pathways are initiated in advance of a behavioral phenotype and cerebral deficits. An understanding of these pathways and their contribution to significant neuronal loss in CamKII-Dars2 deficient mice may aid in deciphering mechanisms of LBSL pathology

DataSheet2_Pandemic intake questionnaire to improve quality, effectiveness, and efficiency of outpatient neurologic and developmental care at the Kennedy Krieger institute during the COVID-19 pandemic.pdf

BackgroundThe COVID-19 pandemic uniquely affects patients with neurologic and developmental disabilities at the Kennedy Krieger Institute. These patients are at increased risk of co-morbidities, increasing their risk of contracting COVID-19. Disruptions in their home and school routines, and restrictions accessing crucial healthcare services has had a significant impact.MethodsA Pandemic Intake questionnaire regarding COVID-19 related medical concerns of guardians of patients was distributed using Qualtrics. Data from May-December 2020 were merged with demographic information of patients from 10 clinics (Center for Autism and Related Disorders (CARD), Neurology, Epigenetics, Neurogenetics, Center for Development and Learning (CDL) Sickle Cell, Spinal Cord, Sturge-Weber syndrome (SWS), Tourette's, and Metabolism). A provider feedback survey was distributed to program directors to assess the effectiveness of this intervention.ResultsAnalysis included responses from 1643 guardians of pediatric patients (mean age 9.5 years, range 0–21.6 years). Guardians of patients in more medically complicated clinics reported perceived increased risk of COVID-19 (p ConclusionThis quality improvement project successfully implemented a pre-visit questionnaire to quickly assess areas of impact of COVID-19 on patients with neurodevelopmental disorders. During the pandemic, results identified several major areas of impact, including patient populations at increased risk for behavioral changes, sleep and/or disruptions of medical care. Most program directors reported improved patient care as a result.</p

DataSheet1_Pandemic intake questionnaire to improve quality, effectiveness, and efficiency of outpatient neurologic and developmental care at the Kennedy Krieger institute during the COVID-19 pandemic.pdf

BackgroundThe COVID-19 pandemic uniquely affects patients with neurologic and developmental disabilities at the Kennedy Krieger Institute. These patients are at increased risk of co-morbidities, increasing their risk of contracting COVID-19. Disruptions in their home and school routines, and restrictions accessing crucial healthcare services has had a significant impact.MethodsA Pandemic Intake questionnaire regarding COVID-19 related medical concerns of guardians of patients was distributed using Qualtrics. Data from May-December 2020 were merged with demographic information of patients from 10 clinics (Center for Autism and Related Disorders (CARD), Neurology, Epigenetics, Neurogenetics, Center for Development and Learning (CDL) Sickle Cell, Spinal Cord, Sturge-Weber syndrome (SWS), Tourette's, and Metabolism). A provider feedback survey was distributed to program directors to assess the effectiveness of this intervention.ResultsAnalysis included responses from 1643 guardians of pediatric patients (mean age 9.5 years, range 0–21.6 years). Guardians of patients in more medically complicated clinics reported perceived increased risk of COVID-19 (p ConclusionThis quality improvement project successfully implemented a pre-visit questionnaire to quickly assess areas of impact of COVID-19 on patients with neurodevelopmental disorders. During the pandemic, results identified several major areas of impact, including patient populations at increased risk for behavioral changes, sleep and/or disruptions of medical care. Most program directors reported improved patient care as a result.</p

Genomic and phenotypic characterization of 404 individuals with neurodevelopmental disorders caused by CTNNB1 variants

Purpose: Germline loss-of-function variants in CTNNB1 cause neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV; OMIM 615075) and are the most frequent, recurrent monogenic cause of cerebral palsy (CP). We investigated the range of clinical phenotypes owing to disruptions of CTNNB1 to determine the association between NEDSDV and CP. Methods: Genetic information from 404 individuals with collectively 392 pathogenic CTNNB1 variants were ascertained for the study. From these, detailed phenotypes for 52 previously unpublished individuals were collected and combined with 68 previously published individuals with comparable clinical information. The functional effects of selected CTNNB1 missense variants were assessed using TOPFlash assay. Results: The phenotypes associated with pathogenic CTNNB1 variants were similar. A diagnosis of CP was not significantly associated with any set of traits that defined a specific phenotypic subgroup, indicating that CP is not additional to NEDSDV. Two CTNNB1 missense variants were dominant negative regulators of WNT signaling, highlighting the utility of the TOPFlash assay to functionally assess variants. Conclusion: NEDSDV is a clinically homogeneous disorder irrespective of initial clinical diagnoses, including CP, or entry points for genetic testing.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Genomic and phenotypic characterization of 404 individuals with neurodevelopmental disorders caused by CTNNB1 variants

PURPOSE: Germline loss-of-function variants in CTNNB1 cause neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV; OMIM 615075) and are the most frequent, recurrent monogenic cause of cerebral palsy (CP). We investigated the range of clinical phenotypes owing to disruptions of CTNNB1 to determine the association between NEDSDV and CP. METHODS: Genetic information from 404 individuals with collectively 392 pathogenic CTNNB1 variants were ascertained for the study. From these, detailed phenotypes for 52 previously unpublished individuals were collected and combined with 68 previously published individuals with comparable clinical information. The functional effects of selected CTNNB1 missense variants were assessed using TOPFlash assay. RESULTS: The phenotypes associated with pathogenic CTNNB1 variants were similar. A diagnosis of CP was not significantly associated with any set of traits that defined a specific phenotypic subgroup, indicating that CP is not additional to NEDSDV. Two CTNNB1 missense variants were dominant negative regulators of WNT signaling, highlighting the utility of the TOPFlash assay to functionally assess variants. CONCLUSION: NEDSDV is a clinically homogeneous disorder irrespective of initial clinical diagnoses, including CP, or entry points for genetic testing