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PURPOSE: To design and build a new disease registry to track the natural history and outcomes of approved gene therapy in patients with inherited retinal diseases. METHODS: A core committee of six members was convened to oversee the construction of the Fight Inherited Retinal Blindness! module. A further 11 experts formed a steering committee, which discussed disease classification and variables to form minimum datasets using a consensus approach. RESULTS: The web-based Fight Inherited Retinal Blindness! registry records baseline demographic, clinical, and genetic data together with follow-up data. The Human Phenotype Ontology and Monarch Disease Ontology nomenclature were incorporated within the Fight Inherited Retinal Blindness! architecture to standardize nomenclature. The registry software assigns individual diagnoses to one of seven broad phenotypic groups, with minimum datasets dependent on the broad phenotypic group. In addition, minimum datasets were agreed on for patients undergoing approved gene therapy with voretigene neparvovec (Luxturna). New patient entries can be completed in 5 minutes, and follow-up data can be entered in 2 minutes. CONCLUSION: Fight Inherited Retinal Blindness! is an organized, web-based system that uses observational study methods to collect uniform data from patients with inherited retinal disease to track natural history and (uniquely) treatment outcomes. It is free to users who have control over their data.

Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]), in individuals of South Asian and African ancestry, respectively. Genotypes included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations. Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted. Functional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity. Nanopore sequencing confirmed the lower transcription of the TMEM216 c.-69G>T allele in blood-derived RNA from a heterozygous carrier, and reduced expression was further recapitulated by qPCR, using both leukocytes-derived RNA of c.-69G>T homozygotes and total RNA from genome-edited hTERT-RPE1 cells carrying homozygous TMEM216 c.-69G>A. In conclusion, these variants explain a significant proportion of unsolved cases, specifically in individuals of African ancestry, suggesting that reduced TMEM216 expression might lead to abnormal ciliogenesis and photoreceptor degeneration.

Accidents at work may force workers to face abrupt changes in their daily life: one of the most impactful accident cases consists of the worker remaining in a wheelchair. Return To Work (RTW) of wheelchair users in their working age is still challenging, encompassing the expertise of clinical and rehabilitation personnel and social workers to match the workers’ residual capabilities with job requirements. This work describes a novel and prototypical knowledge-based Decision Support System (DSS) that matches workers’ residual capabilities with job requirements, thus helping vocational therapists and clinical personnel in the RTW decision-making process for WUs. The DSS leverages expert knowledge in the form of ontologies to represent the International Classification of Functioning, Disability, and Health (ICF) and the Occupational Information Network (O*NET). These taxonomies enable both workers’ health conditions and job requirements formalization, which are processed to assess the suitability of a job depending on a worker’s condition. Consequently, the DSS suggests a list of jobs a wheelchair user can still perform, exploiting his/her residual abilities at their best. The manuscript describes the theoretical approach and technological foundations of such DSS, illustrating its development, its output metric, and application. The developed solution was tested with real wheelchair users’ health conditions provided by the Italian National Institute for Insurance against Accidents at Work. The feasibility of an approach based on objective data was thus demonstrated, providing a novel point of view in the critical process of decision-making during RTW.

Abstract Background Hypertensive disorders of pregnancy (HDPs) are common complications encountered in pregnancy that affect between 5% and 15% of pregnancies worldwide. Some studies have associated adherence to a diet with a high acid load with an increased risk of HDPs. This study investigates the association between Dietary Acid Load (DAL) and the incidence of preeclampsia, chronic hypertension (HTN), and gestational hypertension (GHTN). Methods Pregnant women aged 18 to 45 in the first trimester of pregnancy were selected and followed up until delivery. Diet was evaluated using a 168-question semi-quantitative food frequency questionnaire (FFQ). After calculating the DAL score, the inverse probability weight of the propensity scores, estimated from augmented generalized models, was used to obtain a causal risk ratio (RR) adjusted for potential confounders. Results Out of 1,856 women, 92 (4.95%) developed preeclampsia. The potential renal acid load (PRAL) score ranged from − 16.14 to 0.58, while the net endogenous acid production (NEAP) score ranged from 34.61 to 50.15. Multivariable analysis revealed a significant association between PRAL and preeclampsia in the first (aRR: 1.87, 95% CI: 1.01, 3.49, p = 0.048) and third (aRR: 2.01, 95% CI: 1.07, 3.81, p = 0.030) quartiles compared to the reference group (Q2). No significant linear association was found in continuous analyses. For chronic HTN, significant associations were observed in the first (aRR: 2.56, 95% CI: 1.21, 5.42, p = 0.014) and fourth (aRR: 4.79, 95% CI: 2.37, 9.71, p

Drug use during pregnancy is a growing public health problem worldwide. This study determined the prevalence of illicit drug use among pregnant women in Kerman, Sought East Iran. This cross-sectional study was performed in 2020 on the 966 pregnant women referring to the Central Clinical Laboratory of Kerman for routine pregnancy tests. Urine sample of pregnant women was tested anonymously in two stages. At first, a qualitative screening test was done using the rapid immunoassay method. Then for positive specimens, thin layer chromatography was used to confirm the initial positive results. Data were analyzed using Chi-square test and multivariable logistic regression. The mean age of the participants was 27.3±6.6 years. Most of the respondents (93.8%) were urban dwellers. Also, 7.0% (95% CI: 5.4–8.7) of urine samples were positive for illicit drug. Opium was the most frequently used drug (83.8%). No urine sample was positive for marijuana and tramadol. The older the participants, the more likely they used drugs (odds ratio=1.05; CI 95%:1.01-1.09). Women with low socioeconomic status were nearly 2.2 times more likely to use illicit drugs. The prevalence of drug use is alarming among pregnant women in South eEast Iran. Considering this issue is necessary during prenatal care.

Introduction Annual screening for hydroxychloroquine (HCQ) retinopathy is recommended, and electroretinography (ERG) is considered a gold-standard test, but there are screening shortfalls and standard ERG is burdensome and has limited availability. Newer, portable ERG devices using skin-based electrodes may increase screening capacity but need validation. This study aims to determine initial device accuracies and feasibility of further research.Methods and analysis Prospective diagnostic device accuracy and feasibility study comparing novel ERG devices to standard screening tests. Three groups of 35 participants on HCQ, categorised by HCQ retinopathy (definite, possible and no retinopathy), and 35 healthy control participants, recruited by consecutive sampling, will have full field and multifocal ERG index tests, delivered using skin-contact electrodes by two devices—RETEval full-field and UTAS multifocal ERG, both manufactured by LKC Technologies (Gaithersburg, Maryland, USA), compared with spectral-domain optical coherence tomography and autofluorescence reference tests graded by two masked, independent retinal specialists. Eligible HCQ participants will either have diagnosed HCQ retinopathy or be eligible for screening per UK guidelines. Healthy control participants will have no prior HCQ exposure and be of similar age and sex to HCQ participants. Primary outcome is device-specific sensitivity and specificity. Secondary outcomes include the effect of dilation on device outputs, analysis of discriminatory waveforms, device acceptability and recruitment rate. Safety outcomes include adverse and serious adverse events and device events.Ethics and dissemination Cambridge East ethics committee gave a favourable opinion (24/EE/0011, 23/02/2024). Results will be published in a peer-reviewed ophthalmology journal.Trial registration number ClinicalTrials.gov NCT06035887.

Gallium‐based liquid metal alloys exhibit unconventional and intriguing properties as metallic solvents, demonstrating an exceptional potential to dissolve and reconfigure a vast array of elements within the liquid metal matrix. Leveraging on these distinctive characteristics of gallium‐based alloys, the synthesis of high‐entropy liquid metal alloys (HELMAs) in low dimensions is reported. The nanoscale HELMAs offer advantages including the solvation of multiple metallic elements at room temperature, while promoting their atomic dispersion at elevated concentrations. Entropy estimations for HELMAs surpass those of high‐temperature molten metals, leading to the realization of high‐entropy liquid metal systems at room temperature. Through a proof‐of‐concept hydrogen evolution reaction comparison, the potential of these HELMAs in enhancing the activities of nanocatalysts is demonstrated. In this case, atomic dispersion of Pt is shown in senary GaIn‐AuCuPtPd HELMA, contrasting with lower entropy systems in which Pt forms discernible clusters. These presented features can lead to catalytic systems with enhanced and tailored activities.

The identification of conservation priority areas for amphibians in Iran remains unexplored. Although protected areas play a vital role in biodiversity conservation, 40 percent of amphibians are at risk of extinction. The present study aimed to identify the priority areas for amphibian conservation and assess the effectiveness of the current protected conservation areas. 2192 species occurrence points for 23 amphibians, including 16 species of Anura and 7 species of Caudata, were curated. These occurrence points in addition to bioclimatic, anthropogenic, and geographical variables were used to model the species distribution. Then, the richness and rarity maps of amphibians were determined and hotspots identified based on the top 10 % area of the country with the highest richness and rarity values. Finally, Iran's protected areas were overlaid to evaluate the current coverage of hotspots and identify future conservation priorities. Although approximately 12 % of Iran is currently protected, the present study findings indicate that the current network of protected areas is ineffective for amphibian conservation; over 90 % of hotspots for amphibians lie outside the current national protected area network. The most important hotspots are located in the Caspian Hyrcanian Mixed Forest, the western margin of the North Zagros, and the Central Zagros Mountains Forest-Steppe ecoregions of the country. Among different types of protected areas that overlap with amphibian hotspots, protected areas and wildlife refuges respectively ranked the highest in quantity and size, while national parks ranked the lowest. In the current study, a baseline of top candidate areas for expanding protected areas where habitats can be managed to protect amphibians in Iran was provided. To further improve protected areas' coverage, priority conservation areas in the Zagros Mountains Forest-Steppe hotspots were recommended.

The purpose of this paper is to identify likely pathogenic non-coding variants in inherited retinal dystrophy (IRD) genes, using genome sequencing (GS). Patients with IRD were recruited to the study and underwent comprehensive ophthalmological evaluation and GS. The results of GS were investigated through virtual gene panel analysis, and plausible pathogenic variants and clinical phenotype evaluated by the multidisciplinary team (MDT) discussion. For unsolved patients in whom a specific gene was suspected to harbor a missed pathogenic variant, targeted re-analysis of non-coding regions was performed on GS data. Candidate variants were functionally tested by messenger RNA analysis, minigene or luciferase reporter assays. Previously unreported, likely pathogenic, non-coding variants in 7 genes (PRPF31, NDP, IFT140, CRB1, USH2A, BBS10 and GUCY2D), were identified in 11 patients. These were shown to lead to mis-splicing (PRPF31, IFT140, CRB1 and USH2A) or altered transcription levels (BBS10 and GUCY2D). MDT-led, phenotype-driven, non-coding variant re-analysis of GS is effective in identifying the missing causative alleles.

Background: Hepatitis is a major health issue. The aim of this study was to assess the knowledge, attitude and practices (KAP) of medical students regarding hepatitis B and C. Methods:A descriptive cross-sectional study conducted from March, 2018 to May, 2018. 310 medical students from Allama Iqbal Medical College participated. KAP towards Hepatitis B and C was assessed by using a pre-validated questionnaire. Association of gender and year of study was established with KAP of respondents. Also, associations of knowledge with attitude and practices were also established using Chi-square test taking ≤0.05 as standard p-value. SPSS version 21.0 was used. Results:269 (86.77%) out of 310 distributed questionnaires were received. 116 (43.1%) respondents fell in age group 16-20, 150 (55.8%) in 21-25 years while 3 respondents (1.1%) were 25 year and above. 146 (54.3%) respondents were females and 123 (45.7) respondents were male. There were 54 (20.1%) respondents from first year, 59 (21.9%) respondents from second year, 53 (19.7%) respondents from third year, 55 (20.4%) respondents from fourth year and 48 (17.8%) respondents from final year. 132 (90.4%) female respondents and 98 (79.7%) male respondents had good knowledge regarding hepatitis B and C. No significant relationship was established between gender of respondents with their attitude and practices. As for relationship of knowledge of respondents with their attitude and practices, no significant association could be established.Conclusion: Overall, the medical students have adequate knowledge, sensible attitude but unsatisfactory practices in regards to Hepatitis B and C.

PurposeAutosomal dominant cone rod dystrophy 7 (CORD7) was initially linked to the gene RIMS1 and reported in a 4-generation British family in 1998. The purpose of this study was to investigate the legitimacy of this association, and to correctly characterize the genetic cause of this condition.MethodsThe allele frequency of RIMS1 c.2459G>A, p.Arg820His, was investigated in the Genomes Aggregation Dataset (gnomAD) datasets and whole genome sequencing (WGS) was performed for 4 members of the CORD7 family with filtering of rare pathogenic variants in a virtual gene panel comprising all genes known to be associated with inherited retinal dystrophy (IRD). Cytogenetic analysis was performed to rule out interchromosomal translocation.ResultsRIMS1 p.Arg820His has a maximal carrier frequency of >1:5000 in Europeans. A previously well-characterized PROM1 variant: c.1118C>T, p.Arg373Cys, was detected in 9 affected members of the CORD7 family who underwent WGS or direct sequencing. One affected family member is now known to have macular dystrophy in the absence of RIMS1 p.Arg820His. Clinical analysis of affected family members and 27 individuals with retinopathy associated with the same - PROM1 - variant showed consistent phenotypes.ConclusionsThe case for pathogenicity of RIMS1 p.Arg820His is not strong based on its presence on 10 alleles in the gnomAD dataset and absence from additional CORD affected individuals. The finding of a known pathogenic variant in PROM1 correlates well with the phenotypic characteristics of the affected individuals, and is likely to account for the condition. Clear evidence of association between RIMS1 and a retinal dystrophy is yet to be described.