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PURPOSE: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. METHODS: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. RESULTS: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. CONCLUSIONS: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.

Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.8% of patients were considered genetically explained by 460 different variants in 49 distinct genes of which 73 were novel variants, with some affecting splicing. The top five most frequent causative genes were ABCA4 (37.2%), PRPH2 (6.7%), CDHR1 (6.1%), PROM1 (4.3%) and RP1L1 (3.1%). Interestingly, variants with incomplete penetrance were revealed in almost one-third of patients considered solved (28.1%), and therefore, a proportion of patients may not be explained solely by the variants reported. This includes eight previously reported variants with incomplete penetrance in addition to CDHR1:c.783G>A and CNGB3:c.1208G>A. Notably, segregation analysis was not routinely performed for variant phasing-a limitation, which may also impact the overall diagnostic yield. The relatively high proportion of probands without any putative causal variant (60.2%) highlights the need to explore variants with incomplete penetrance, the potential modifiers of disease and the genetic overlap between iMDs and age-related macular degeneration. Our results provide valuable insights into the genetic landscape of iMDs and warrant future exploration to determine the involvement of other maculopathy genes.

Abstract Treatment for renal cell carcinoma (RCC) has improved dramatically over the last decade, shifting from high-dose cytokine therapy in combination with surgical resection of tumors to targeted therapy, immunotherapy, and combination therapies. However, curative treatment, particularly for advanced-stage disease, remains rare. Cell therapy as a “living drug” has achieved hematological malignancy cures with a high response rate, and significant research efforts have been made to facilitate its translation to solid tumors. Herein, we overview the cellular therapies for RCC focusing on allogeneic hematopoietic stem cell transplantation, T cell receptor gene-modified T cells, chimeric antigen receptor (CAR) T cells, CAR natural killer (NK) cells, lymphokine-activated killer (LAK) cells, γδ T cells, and dendritic cell vaccination. We have also included perspectives for using other recent approaches, such as CAR macrophages, dendritic cell-cytokine induced killer cells and regulatory CAR-T cells to shed light on preclinical development of cell therapy and advancing cell therapy into clinic to achieve cures for RCC.

Purpose: Indian government initiated several skill development policies and different types of vocational education and training (VET). Yet the participation in skill education is low because of poor labour market outcomes. This paper aims to calculate returns to skill education to understand the type of training that will have better labour market outcomes. Design/methodology/approach: In this paper nationally representative data from the periodic labour force survey (PLFS), collected by the national sample survey office for 2017-2018, are used to estimate the returns to formal and non-formal VET obtained (after different levels of general education) with the help of Heckman's two-stage method. Findings: Nearly 8% of the working-age population has received some form of VET (mostly non-formal), generating poor returns. For the overall population, formal on-job training (OJT) and full-time VET influence wage positively and significantly. Full-time VET obtained after secondary and below levels of education generates positive returns, whereas part-time VET is profitable only to those without formal education. At the graduate level, technical education obtained along with VET is associated with better wages. Originality/value: In India where a considerable proportion of the workforce is employed in the informal sector, different types of skill training like full-time, part-time and OJT influence labour market outcomes. This finding has policy implication for countries with large informal sector and calls for further research in such countries.

India's expectation of a demographic dividend owing to an increase in the working age population necessitated government measures aimed at skilling youth. Considerable emphasis was therefore placed on skill development policies and programmes, including revamping formal vocational education and training (VET) institutions that provide skills to students completing secondary schooling and opting vocational training. Although the number of VET institutions in India more than doubled in the last decade, their underutilisation calls for an analysis of underlying reasons. This paper analyses socio-economic factors influencing participation in VET using data from nationally representative survey on education. Findings of a multinomial logit analysis in the paper suggest that students in upper secondary VET institutions tend to belong to socially disadvantaged households, and that students in vocational courses are more likely to be male, urban, and from households whose principal occupation is blue-collar. Children from households belonging to higher socio-economic status and pursuing white-collar jobs are more likely to participate in general and professional education as compared to VET because of higher status assigned to the former in the society. These findings call for fine-tuning of current polices of promotion of VET in India.

PurposeThe purpose of this study was to compare the natural history of visual function change in cohorts of patients affected with retinal degeneration due to biallelic variants in Bardet-Biedl syndrome genes: BBS1 and BBS10.MethodsPatients were recruited from nine academic centers from six countries (Belgium, Canada, France, New Zealand, Switzerland, and the United States). Inclusion criteria were: (1) female or male patients with a clinical diagnosis of retinal dystrophy, (2) biallelic disease-causing variants in BBS1 or BBS10, and (3) measures of visual function for at least one visit. Retrospective data collected included genotypes, age, onset of symptoms, and best corrected visual acuity (VA). When possible, data on refractive error, fundus images and autofluorescence (FAF), optical coherence tomography (OCT), Goldmann kinetic perimetry (VF), electroretinography (ERG), and the systemic phenotype were collected.ResultsSixty-seven individuals had variants in BBS1 (n = 38; 20 female patients and 18 male patients); or BBS10 (n = 29; 14 female patients and 15 male patients). Missense variants were the most common type of variants for patients with BBS1, whereas frameshift variants were most common for BBS10. When ERGs were recordable, rod-cone dystrophy (RCD) was observed in 82% (23/28) of patients with BBS1 and 73% (8/11) of patients with BBS10; cone-rod dystrophy (CORD) was seen in 18% of patients with BBS1 only, and cone dystrophy (COD) was only seen in 3 patients with BBS10 (27%). ERGs were nondetectable earlier in patients with BBS10 than in patients with BBS1. Similarly, VA and VF declined more rapidly in patients with BBS10 compared to patients with BBS1.ConclusionsRetinal degeneration appears earlier and is more severe in BBS10 cases as compared to those with BBS1 variants. The course of change of visual function appears to relate to genetic subtypes of BBS.

Aim: Hypovitaminosis A is a leading cause of preventable childhood blindness, especially in developing nations. Vitamin A is a fat‐soluble essential micronutrient that serves vital functions in the visual system and in regulating bone resorption. We report on a series of four children with mixed nutritional and compressive optic neuropathy and provide a review of the literature. Methods: A retrospective observational study of four males (ages 9–12), three with autism spectrum disorder who presented with loss of vision and multiple vitamin deficiencies including hypovitaminosis A. Results: Patients presented with unexplained visual loss or a change in visual behaviour. All patients had severely restricted diet comprising of predominantly carbohydrates. Two of the four cases demonstrated optic nerve pallor at initial presentation with marked optic atrophy developing in all patients over time. Electrophysiology available in two patients demonstrated optic nerve dysfunction with preserved retinal function. Extensive investigations revealed profound deficiency in multiple vitamins including vitamin A (<0.1–0.2 μmol/L, normal = 0.9–1.7 μmol/L). Three patients also had low vitamin B12 (90–111 pmol/L, normal = 170–800 pmol/L) with normal folate. All four cases had radiological evidence of skull base thickening indicative of low vitamin A. Genetic testing did not find any relevant pathogenic variants. Conclusions: Hypovitaminosis A is a crucial form of nutritional deprivation that results in significant visual loss with potential hyperostosis and optic nerve compression exacerbating nutritional optic neuropathy. Additional micronutrient deficiencies usually co‐exist and may contribute. Extra vigilance in vitamin replacement is required of clinicians with patients with autism who have restricted diets. [ABSTRACT FROM AUTHOR]

Background: The complexities of mitochondrial disease make epidemiological studies challenging, yet this information is important in understanding the healthcare burden and addressing service and educational needs. Existing studies are limited to quaternary centres or focus on a single genotype or phenotype and estimate disease prevalence at 12.5 per 100 000. New Zealand's (NZ) size and partially integrated national healthcare system make it amenable to a nationwide prevalence study. Aim: To estimate the prevalence of molecularly confirmed and suspected mitochondrial disease on 31 December 2015 in NZ. Methods: Cases were identified from subspecialists and laboratory databases and through interrogation of the Ministry of Health National Minimum Dataset with a focus on presentations between 2000 and 2015. Patient records were reviewed, and those with a diagnosis of 'mitochondrial disease' who were alive and residing in NZ on the prevalence date were included. These were divided into molecularly confirmed and clinically suspected cases. Official NZ estimated resident population data were used to calculate prevalence. Results: Seven hundred twenty‐three unique national health index numbers were identified. Five hundred five were excluded. The minimum combined prevalence for mitochondrial disease was 4.7 per 100 000 (95% confidence interval (CI): 4.1–5.4). The minimum prevalence for molecularly confirmed and suspected disease was 2.9 (95% CI 2.4–3.4) and 1.8 (95% CI 1.4–2.2) cases per 100 000 respectively. Conclusions: Within the limitations of this study, comparison to similar prevalence studies performed by specialist referral centres suggests mitochondrial disease is underdiagnosed in NZ. This highlights a need for improved education and referral pathways for mitochondrial disease in NZ. [ABSTRACT FROM AUTHOR]

"Teaching and Learning About Family Literacy and Family Literacy Programs" is a comprehensive book that explores family literacy practices and programs in the USA, UK, and Canada. The authors emphasize the importance of family literacy programs in promoting literacy development in individuals, families, and communities. They discuss the different goals of adult education in relation to family literacy programs and highlight the benefits for both children and parents. The book also addresses the need for digital literacy integration and the importance of cultural sensitivity in family literacy programs. The authors recommend further research and documentation on various aspects of family literacy, including the role of fathers, incarcerated individuals, same-sex families, and developing nations. [Extracted from the article]

With advances in gene‐based therapies for heritable retinal diseases, primary eye care clinicians should be informed on ocular genetics topics. This cross‐sectional survey evaluated knowledge, attitudes, and concerns regarding genetic testing and gene therapy for retinal diseases among optometrists in Australia and New Zealand. Survey data included practitioner background, attitudes and practices towards genetic testing for monogenic inherited retinal disease (IRDs) and age‐related macular degeneration, and knowledge of ocular genetics and gene therapy. Responses were received from 516 optometrists between 1 April and 31 December 2022. Key perceived barriers to accessing genetic testing were lack of clarity on referral pathways (81%), cost (65%), and lack of treatment options if a genetic cause is identified (50%). Almost all respondents (98%) believed that ophthalmologists should initiate genetic testing for IRDs and fewer understood the role of genetic counsellors and clinical geneticists. This study found that optometrists in Australia and New Zealand have a high level of interest in ocular genetics topics. However, knowledge gaps include referral pathways and awareness of genetic testing and gene therapy outcomes. Addressing perceived barriers to access and promoting sharing of knowledge between interdisciplinary networks can set the foundation for genetic education agendas in primary eye care. [ABSTRACT FROM AUTHOR]