Functional Analysis of Retinitis Pigmentosa 2 (RP2) Protein Reveals Variable Pathogenic Potential of Disease-Associated Missense Variants

Genetic mutations are frequently associated with diverse phenotypic consequences, which limits the interpretation of the consequence of a variation in patients. Mutations in the retinitis pigmentosa 2 (RP2) gene are associated with X-linked RP, which is a phenotypically heterogenic form of retinal degeneration. The purpose of this study was to assess the functional consequence of disease-associated mutations in the RP2 gene using an in vivo assay. Morpholino-mediated depletion of rp2 in zebrafish resulted in perturbations in photoreceptor development and microphthalmia (small eye). Ultrastructural and immunofluorescence analyses revealed defective photoreceptor outer segment development and lack of expression of photoreceptor-specific proteins. The retinopathy phenotype could be rescued by expressing the wild-type human RP2 protein. Notably, the tested RP2 mutants exhibited variable degrees of rescue of rod versus cone photoreceptor development as well as microphthalmia. Our results suggest that RP2 plays a key role in photoreceptor development and maintenance in zebrafish and that the clinical heterogeneity associated with RP2 mutations may, in part, result from its potentially distinct functional relevance in rod versus cone photoreceptors

Space Charge at Nanoscale: Probing Injection and Dynamic Phenomena Under Dark/Light Configurations by Using KPFM and C-AFM

International audienc

Type-specific dendritic integration in mouse retinal ganglion cells

Neural computation relies on the integration of synaptic inputs across a neuron’s dendritic arbour. However, it is far from understood how different cell types tune this process to establish cell-type specific computations. Here, using two-photon imaging of dendritic Ca2+ signals, electrical recordings of somatic voltage and biophysical modelling, we demonstrate that four morphologically distinct types of mouse retinal ganglion cells with overlapping excitatory synaptic input (transient Off alpha, transient Off mini, sustained Off, and F-mini Off) exhibit type-specific dendritic integration profiles: in contrast to the other types, dendrites of transient Off alpha cells were spatially independent, with little receptive field overlap. The temporal correlation of dendritic signals varied also extensively, with the highest and lowest correlation in transient Off mini and transient Off alpha cells, respectively. We show that differences between cell types can likely be explained by differences in backpropagation efficiency, arising from the specific combinations of dendritic morphology and ion channel densities

Factors associated with hospital service satisfaction in a sample of Arab subjects with schizophrenia

<p>Abstract</p> <p>Background</p> <p>Assessment of patients' satisfaction with health care services could help to identify the strengths and weaknesses of the system and provide guidance for further development. The study's objectives were to: (i) assess the pattern of satisfaction with hospital care for a sample of people with schizophrenia in Kuwait, using the Verona Service Satisfaction Scale (VSSS-EU); ii) compare the pattern of satisfaction with those of similar studies; and iii) assess the association of VSSS seven domains with a number of variables representing met and unmet needs for care, family caregiver burden, severity of psychopathology, level of psychosocial functioning, socio-demographic characteristics, psychological well-being and objective quality of life.</p> <p>Methods</p> <p>Consecutive outpatients in stable condition and their family caregivers were interviewed with the VSSS-EU and measures of needs for care, caregiver burden, quality of life and psychopathology.</p> <p>Results</p> <p>There were 130 patients (66.1%m, mean age 36.8). While over two-thirds expressed satisfaction with the domains of "overall satisfaction", "professionals' skills", "access", "efficacy", and "relatives' involvement", only about one-third were satisfied with the domains of "information" and "types of intervention". The later two domains were the areas in which European patients had better satisfaction than our patients, while our patients expressed better satisfaction than the Europeans in the domain of "relatives' involvement". In multiple regression analyses, self-esteem, positive and negative affect were the most important correlates of the domains of service satisfaction, while clinical severity, caregiver burden and health unmet needs for care played relatively minor roles.</p> <p>Conclusion</p> <p>The noted differences and similarities with the international data, as well as the predictive power of self-esteem and affective state, support the impression that patients' attitudes towards psychiatric care involve a complex relationship between clinical, personal and socio-cultural characteristics; and that many of the factors that impact on satisfaction with service relate to individual psychological characteristics. The weaknesses in the system, highlighted by the pattern of responses of the participants, indicate possible gaps in the provision of comprehensive psychiatric care in the country and obviate the need for public mental health education and development of services to enhance the quality of care.</p

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.814.4 million) incident T2D cases, representing 70.3% (68.871.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.027.1%)), excess refined rice and wheat intake (24.6% (22.327.2%)) and excess processed meat intake (20.3% (18.323.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.487.7%)) and Latin America and the Caribbean (81.8% (80.183.4%)); and lowest proportional burdens were in South Asia (55.4% (52.160.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally. (c) 2023, The Author(s)

Children's and adolescents' rising animal-source food intakes in 1990-2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the worlds child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 1519 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes. (c) 2023, The Author(s)