Progression of myopathology in Kearns-Sayre syndrome

We report on the progression of myopathology by comparing two biopsies from a patient with a Kearns-Sayre-Syndrome. The first biopsy was taken in 1979 and showed 10% ragged-red fibers. Myopathic changes were slight including internal nuclei and fiber splitting in 10% of the fibers. Electron microscopy revealed typical mitochondrial abnormalities with regard to number and shape. In 1989 a second biopsy was performed for an extended analysis of mitochondrial DNA. This time less than 5% of all fibers were ragged-red. Severe myopathic changes could be detected which so far has rarely been reported in mitochondrial cytopathy

Effects of gestational age at birth on cognitive performance : a function of cognitive workload demands

Objective: Cognitive deficits have been inconsistently described for late or moderately preterm children but are consistently found in very preterm children. This study investigates the association between cognitive workload demands of tasks and cognitive performance in relation to gestational age at birth. Methods: Data were collected as part of a prospective geographically defined whole-population study of neonatal at-risk children in Southern Bavaria. At 8;5 years, n = 1326 children (gestation range: 23–41 weeks) were assessed with the K-ABC and a Mathematics Test. Results: Cognitive scores of preterm children decreased as cognitive workload demands of tasks increased. The relationship between gestation and task workload was curvilinear and more pronounced the higher the cognitive workload: GA2 (quadratic term) on low cognitive workload: R2 = .02, p<0.001; moderate cognitive workload: R2 = .09, p<0.001; and high cognitive workload tasks: R2 = .14, p<0.001. Specifically, disproportionally lower scores were found for very (<32 weeks gestation) and moderately (32–33 weeks gestation) preterm children the higher the cognitive workload of the tasks. Early biological factors such as gestation and neonatal complications explained more of the variance in high (12.5%) compared with moderate (8.1%) and low cognitive workload tasks (1.7%). Conclusions: The cognitive workload model may help to explain variations of findings on the relationship of gestational age with cognitive performance in the literature. The findings have implications for routine cognitive follow-up, educational intervention, and basic research into neuro-plasticity and brain reorganization after preterm birth

Which circulating antioxidant vitamins are confounded by socioeconomic deprivation? The MIDSPAN family study

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Antioxidant vitamins are often described as having “independent” associations with risk of cancer, cardiovascular disease (CVD) and mortality. We aimed to compare to what extent a range of antioxidant vitamins and carotenoids are associated with adulthood and childhood markers of socioeconomic deprivation and to adverse lifestyle factors.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and Findings:&lt;/b&gt; Socioeconomic and lifestyle measures were available in 1040 men and 1298 women from the MIDSPAN Family Study (30–59 years at baseline) together with circulating levels of vitamins A, C, E, and carotenoids (α-carotene, β-carotene, lutein and lycopene). Markers of socioeconomic deprivation in adulthood were consistently as strongly associated with lower vitamin C and carotenoid levels as markers of adverse lifestyle; the inverse association with overcrowding was particularly consistent (vitamin C and carotenoids range from 19.1% [95% CI 30.3–6.0] to 38.8% [49.9–25.3] lower among those in overcrowded residencies). These associations were consistent after adjusting for month, classical CVD risk factors, body mass index, physical activity, vitamin supplements, dietary fat and fibre intake. Similar, but weaker, associations were seen for childhood markers of deprivation. The association of vitamin A or E were strikingly different; several adult adverse lifestyle factors associated with higher levels of vitamin A and E, including high alcohol intake for vitamin A (9.5% [5.7–13.5]) and waist hip ratio for vitamin E (9.5% [4.8–14.4]), with the latter associations partially explained by classical risk factors, particularly cholesterol levels.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Plasma vitamin C and carotenoids have strong inverse associations with adulthood markers of social deprivation, whereas vitamin A and E appear positively related to specific adverse lifestyle factors. These findings should help researchers better contextualize blood antioxidant vitamin levels by illustrating the potential limitations associated with making causal inferences without consideration of social deprivation.&lt;/p&gt

Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog

Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

Background Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67), involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts

Better Together: Expanding Rural Partnerships to Support Families

Chronic shortages of health, social service, and mental health professionals in rural areas necessitate creative partnerships in support of families. Cooperative extension professionals in Family and Consumer Sciences and community health nurses are introduced as trusted professionals in rural communities who can bring critical skills to human services teams. Multidisciplinary prevention programs offer particularly good contexts for county extension educators and community health nurses to work in collaboration with social workers. The case of grandparents raising grandchildren illustrates the critical roles that can be filled by professionals in these two fields to extend the reach of family support programs

Impairment experiences, identity and attitudes towards genetic screening : the views of people with Spinal Muscular Atrophy

Developments in genetics are rapidly changing the capacity and scope of screening practices. However, people with genetic conditions have been under-represented in the literature exploring their implications. This mixed methods study explores the attitudes of people with Spinal Muscular Atrophy (SMA) towards three different population-level genetic screening programmes for SMA: pre-conception, prenatal and newborn. Drawing on qualitative interviews (n= 15) and a survey (n=82), this study demonstrates that more severely affected individuals with early-onset symptoms (Type II SMA), are less likely to support screening and more likely to view SMA positively than those with milder, later onset and/or fluctuating symptoms (Types III/ IV SMA). Indeed, this clinically milder group were more likely to support all forms of screening and view SMA negatively. This paper highlights that screening is a complex issue for people with genetic conditions, and the nature of impairment experiences plays a critical role in shaping attitudes

Integrated Delivery of Health Services During Outreach Visits: A Literature Review of Program Experience Through a Routine Immunization Lens

Background. Outreach services are used systematically to deliver immunization and health services to individuals with insufficient access to health facilities in lower-income countries. Currently, the topic of integrated service delivery during immunization outreach lacks the attention paid to integration at fixed sites or during campaigns. This article explores integrated outreach and risks associated with service integration

Unusual multisystemic involvement and a novel BAG3 mutation revealed by NGS screening in a large cohort of myofibrillar myopathies

Background: Myofibrillar myopathies (MFM) are a group of phenotypically and genetically heterogeneous neuromuscular disorders, which are characterized by protein aggregations in muscle fibres and can be associated with multisystemic involvement. Methods: We screened a large cohort of 38 index patients with MFM for mutations in the nine thus far known causative genes using Sanger and next generation sequencing (NGS). We studied the clinical and histopathological characteristics in 38 index patients and five additional relatives (n = 43) and particularly focused on the associated multisystemic symptoms. Results: We identified 14 heterozygous mutations (diagnostic yield of 37%), among them the novel p.Pro209Gln mutation in the BAG3 gene, which was associated with onset in adulthood, a mild phenotype and an axonal sensorimotor polyneuropathy, in the absence of giant axons at the nerve biopsy. We revealed several novel clinical phenotypes and unusual multisystemic presentations with previously described mutations: hearing impairment with a FLNC mutation, dysphonia with a mutation in DES and the first patient with a FLNC mutation presenting respiratory insufficiency as the initial symptom. Moreover, we described for the first time respiratory insufficiency occurring in a patient with the p.Gly154Ser mutation in CRYAB. Interestingly, we detected a polyneuropathy in 28% of the MFM patients, including a BAG3 and a MYOT case, and hearing impairment in 13%, including one patient with a FLNC mutation and two with mutations in the DES gene. In four index patients with a mutation in one of the MFM genes, typical histological findings were only identified at the ultrastructural level (29%). Conclusions: We conclude that extraskeletal symptoms frequently occur in MFM, particularly cardiac and respiratory involvement, polyneuropathy and/or deafness. BAG3 mutations should be considered even in cases with a mild phenotype or an adult onset. We identified a genetic defect in one of the known genes in less than half of the MFM patients, indicating that more causative genes are still to be found. Next generation sequencing techniques should be helpful in achieving this aim

Improved parental dietary quality is associated with children’s dietary intake through the home environment

Background Improving access to supermarkets has been shown to improve some dietary outcomes, yet there is little evidence for such effects on children. Relatedly, there is a dearth of research assessing the impact of a structural change (i.e. supermarket in a former food desert) on the home environment and its relationship with children’s diet. Objective Assess the relative impact of the home environment on children’s diet after the introduction of a new supermarket in a food desert. Methods Among a randomly selected cohort of households living in a food desert, parental diet was assessed before and after the opening of a full-service supermarket. The home environment and children’s intake of fruits and vegetables was measured at one point – after the store’s opening. Structural equation models were used to estimate the pathways between changes in parental dietary quality at follow-up and children’s dietary intake through the home environment. ResultsParental dietary improvement after the supermarket opened was associated with having a better home environment (β = 0.45, p = 0.001) and with healthier children’s dietary intake (β = 0.46, p Conclusions Policy solutions designed to improve diet among low-resource communities should take into account the importance of the home environment