Glucose-6-phosphate dehydrogenase enzyme deficiency as a diagnostic factor of diabetes mellitus: An original study.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common genetic disorders affecting approximately 400 million people worldwide. Several recent studies have reported a relationship between G6PD deficiency and the incidence of diabetes. Objectives: The aim of the present study was to evaluate and compare levels of G6PD deficiency in diabetes mellitus patients. Materials and Methods: G6PD activity and fasting glucose levels were measured in blood samples of 49 diabetic patients and 21 healthy controls. Results: G6PD activity was decreased in patients with diabetes mellitus as compared to healthy controls and showed that overall G6PD deficiency was significantly associated with diabetes mellitus as compared to nondiabetics. Conclusion: The study concluded that G6PD deficiency is noted in diabetics than in nondiabetics and can be a biomarker of oxidative stress and poor glycemic control in diabetes mellitus.

An online glaucoma educational course for patients to facilitate remote learning and patient empowerment.

In both face-to-face and teleophthalmology glaucoma clinics, there are significant time constraints and limited resources available to educate the patient and their carers regarding the glaucoma condition. Glaucoma patients are often not satisfied with the content and amount of information they receive and have demonstrated a substantial lack of knowledge regarding their condition. Innovative educational tools that facilitate accessible digital remote patient education can be a powerful adjunct to empower patients in becoming healthcare partners.We describe the development of a free, comprehensive, multimodal online glaucoma patient education course for adults with glaucoma, their family and friends and carers, with the aim of providing a readable resource to aid remote learning and understanding of the condition.The working group for the development of the course comprised of consultants, medical practitioners and education specialists and expert patients. Given the specialised nature of ophthalmology and glaucoma, certain aspects can be difficult to conceptualise, and, therefore, clear and adequate explanations of concepts are provided in the course using diagrams, flow charts, medical illustrations, images, videos, written text, analogies and quizzes.The course is available in a short and long version to suit different learning needs which take approximately 2 hours and 10 hours to complete respectively. The contents list allows course takers to find sections relevant to them and it can be taken anywhere, as long as there is Internet access.We invite you to share this resource with your patients and their families, friends and carers.

Development of virtual ophthalmic surgical skills training.

BACKGROUND: This study aims to assess whether ophthalmic surgical skills can be taught successfully online to a diverse international and interprofessional student group. METHODS: Mixed methods study involving 20 students and 5 instructors. Each student completed a pre-session and post-session questionnaire to assess their perceptions regarding online instruction. Changes in questionnaire responses were analysed using Wilcoxon signed rank (SPSS 25). Semi-structured interviews were conducted to assess instructor perceptions towards virtual surgical skills teaching. Thematic analysis was undertaken using NVivo 12.0 software. RESULTS: There was a 100% completion rate of pre- and post-session questionnaires. Prior to the session, lack of instructor supervision and inability to provide constructive feedback were emergent themes from students. Pre-session concerns regarding online delivery: 40% of students thought their view of skills demonstration would be negatively impacted, 60% their level of supervision and 55% their interaction with instructors. Following the session 10%, 15% and 5% held this view respectively. All students were 'satisfied' or 'very satisfied' regarding the 'Surgeon's View' camera angle as well as the use of breakout rooms. 75% perceived an improvement in their confidence in instrument handling, 80% in cable knot tying and 70% in suture tying. Overall student rating for the virtual surgical skills session was 8.85 (±1.19) out of 10 (10 being most satisfied). CONCLUSIONS: We demonstrate that successful delivery of a virtual ophthalmic surgical skills course is feasible. We were able to widen accessibility and participation through virtual delivery, which has future implications for ophthalmic surgical teaching and its reach.

Role of poly(ADP-ribose) polymerase-1 in regulating human islet cell differentiation.

Poly(ADP-ribose) polymerase-1 (PARP1), a fundamental DNA repair enzyme, is known to regulate ß cell death, replication, and insulin secretion. PARP1 knockout (KO) mice are resistant to diabetes, while PARP1 overactivation contributes to ß cell death. Additionally, PARP1 inhibition (PARPi) improves diabetes complications in patients with type-2 diabetes. Despite these beneficial effects, the use of PARP1 modulating agents in diabetes treatment is largely neglected, primarily due to the poorly studied mechanistic action of PARP1 catalytic function in human ß cell development. In the present study, we evaluated PARP1 regulatory action in human ß cell differentiation using the human pancreatic progenitor cell line, PANC-1. We surveyed islet census and histology from PARP1 wild-type versus KO mice pancreas in a head-to-head comparison with PARP1 regulatory action for in-vitro ß cell differentiation following either PARP1 depletion or its pharmacological inhibition in PANC-1-differentiated islet cells. shRNA mediated PARP1 depleted (SiP) and shRNA control (U6) PANC-1 cells were differentiated into islet-like clusters using established protocols. We observed complete abrogation of new ß cell formation with absolute PARP1 depletion while its inhibition using the potent inhibitor, PJ34, promoted the endocrine ß cell differentiation and maturation. Immunohistochemistry and immunoblotting for key endocrine differentiation players along with ß cell maturation markers highlighted the potential regulatory action of PARP1 and augmented ß cell differentiation due to direct interaction of unmodified PARP1 protein elicited p38 MAPK phosphorylation and Neurogenin-3 (Ngn3) re-activation. In summary, our study suggests that PARP1 is required for the proper development and differentiation of human islets. Selective inhibition with PARPi can be an advantage in pushing more insulin-producing cells under pathological conditions and delivers a potential for pilot clinical testing for ß cell replacement cell therapies for diabetes.

XPC-PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair.

Cells employ global genome nucleotide excision repair (GGR) to eliminate a broad spectrum of DNA lesions, including those induced by UV light. The lesion-recognition factor XPC initiates repair of helix-destabilizing DNA lesions, but binds poorly to lesions such as CPDs that do not destabilize DNA. How difficult-to-repair lesions are detected in chromatin is unknown. Here, we identify the poly-(ADP-ribose) polymerases PARP1 and PARP2 as constitutive interactors of XPC. Their interaction results in the XPC-stimulated synthesis of poly-(ADP-ribose) (PAR) by PARP1 at UV lesions, which in turn enables the recruitment and activation of the PAR-regulated chromatin remodeler ALC1. PARP2, on the other hand, modulates the retention of ALC1 at DNA damage sites. Notably, ALC1 mediates chromatin expansion at UV-induced DNA lesions, leading to the timely clearing of CPD lesions. Thus, we reveal how chromatin containing difficult-to-repair DNA lesions is primed for repair, providing insight into mechanisms of chromatin plasticity during GGR.

Deubiquitinating enzymes and the proteasome regulate preferential sets of ubiquitin substrates.

The ubiquitin-proteasome axis has been extensively explored at a system-wide level, but the impact of deubiquitinating enzymes (DUBs) on the ubiquitinome remains largely unknown. Here, we compare the contributions of the proteasome and DUBs on the global ubiquitinome, using UbiSite technology, inhibitors and mass spectrometry. We uncover large dynamic ubiquitin signalling networks with substrates and sites preferentially regulated by DUBs or by the proteasome, highlighting the role of DUBs in degradation-independent ubiquitination. DUBs regulate substrates via at least 40,000 unique sites. Regulated networks of ubiquitin substrates are involved in autophagy, apoptosis, genome integrity, telomere integrity, cell cycle progression, mitochondrial function, vesicle transport, signal transduction, transcription, pre-mRNA splicing and many other cellular processes. Moreover, we show that ubiquitin conjugated to SUMO2/3 forms a strong proteasomal degradation signal. Interestingly, PARP1 is hyper-ubiquitinated in response to DUB inhibition, which increases its enzymatic activity. Our study uncovers key regulatory roles of DUBs and provides a resource of endogenous ubiquitination sites to aid the analysis of substrate specific ubiquitin signalling.

Corneal Endothelial Cell Density Loss after Glaucoma Surgery Alone or in Combination with Cataract Surgery: A Systematic Review and Meta-analysis.

TOPIC: Corneal endothelial cell density (ECD) loss after glaucoma surgery with or without cataract surgery. CLINICAL RELEVANCE: Corneal ECD loss may occur as the result of intraoperative surgical trauma in glaucoma surgery or postoperatively with chronic endothelial cell trauma or irritation. METHODS: Glaucoma filtration surgery or microinvasive glaucoma surgery (MIGS) in participants with ocular hypertension, primary and secondary open-angle glaucoma, normal-tension glaucoma, and angle-closure glaucoma were included. Electronic databases searched in December 2021 included MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the International Prospective Register of Systematic Reviews, Food and Drug Administration (FDA) Premarket Approval, and FDA 510(k). RESULTS: A total of 39 studies were included in quantitative synthesis. Twelve months after suprachoroidal MIGS, mean ECD loss was 282 cells/mm2 (95% confidence interval [CI], 220-345; P < 0.00001; chi-square = 0.06; I2 = 0%; 2 studies; very low certainty). Mean ECD loss after Schlemm's canal implantable devices was 338 cells/mm2 (95% CI, 185-491; P < 0.0001; chi-square = 0.08; I2 = 0%; 2 studies; low certainty) at 12 months. Mean ECD loss was 64 cells/mm2 (95% CI, 21-107; P = 0.004; chi-square = 4.55; I2 = 0%; 6 studies; low certainty) after Schlemm's canal procedures (without implantable devices) at 12 months. At 12 months, the mean ECD loss after trabeculectomy was 33 cells/mm2 (95% CI, -38 to 105, P = 0.36, chi-square = 1.17; I2 = 0%; moderate certainty). At 12 months, mean ECD loss was 121 cells/mm2 (95% CI, 53-189; P = 0.0005; chi-square = 3.00; I2 = 0%; 5 studies; low certainty) after Express (Alcon) implantation. When compared with the control fellow eye, aqueous shunt surgery reduced ECD by 5.75% (95% CI, -0.93 to 12.43; P = 0.09, chi-square = 1.32; I2 = 0%; low certainty) and 8.11% ECD loss (95% CI, 0.06-16.16 P = 0.05; chi-square = 1.93; I2 = 48%) at 12 and 24 months, respectively. CONCLUSIONS: Overall, there is low certainty evidence to suggest that glaucoma surgery involving long-term implants has a greater extent of ECD loss than glaucoma filtration surgeries without the use of implants. The results of this review support follow-up beyond 36 months to assess ECD loss and corneal decompensation after implantation of glaucoma drainage implants.

Emergence of two distinct variants of SARS-CoV-2 and an explosive second wave of COVID-19: the experience of a tertiary care hospital in Pune, India.

The emergence of novel variants of SARS-CoV-2 in several countries has been associated with increased transmissibility or reduced neutralization potential of antibodies against the Wuhan virus (wild type). From August 2021 onwards, India experienced a progressive decline in the number of active SARS-CoV-2 infections, indicative of a downward trend in the explosive second wave. This prospective study was conducted quarterly for one year (May 2020 to June 2021) at a tertiary care hospital in the city of Pune in western India. Receptor-binding domain (RBD, n = 319) and full genome (n = 20) sequences from viral-RNA-positive nasopharyngeal swabs of COVID-19 patients representing the first and second waves were used for analysis. No Brazilian, South African, or California variants were detected in this study. Until December 2020, only the wild-type strain was prevalent. Concurrent with the upsurge of the second wave in March 2021, 73% (33/45) of RBD sequences harboured L452R/E484Q mutations characteristic of the Kappa variant. In April 2021, co-circulation of Kappa (37%) and Delta (L452R/T478K, 59%) variants was recorded. During May and June 2021, the Delta variant became the predominant circulating variant, and this coincided with a significant decline in the number of COVID-19 cases. Of the 20 full genome sequences, six isolates each exhibited signature mutations of the Kappa and Delta variant. With several states witnessing a reduction in the number of COVID-19 cases, continuous monitoring of newer mutations and assessment of their effect on virus transmissibility and their impact on vaccinated or previously exposed individuals is necessary.

Correlation of density of microvessels and myofibroblasts with the aggressiveness of central giant cell granulomas of jaws: A preliminary study.

Objectives: Central giant cell granuloma (CGCG) is a fairly common lesion involving the jaw bones. CGCG can show relatively innocuous biological behaviour or it may show clinicoradiological features suggestive of aggressive biological behaviour. To date, there are no histological parameters which can be used to predict the behaviour of these lesions. This study was conducted to assess the utility of parameters of angiogenesis, i.e., total vascular area (TVA), mean vascular area (MVA) and microvessel density (MVD), and density of myofibroblasts in aggressive and non-aggressive CGCGs. Materials and Methods: The study was undertaken as a retrospective study. A total of 20 previously diagnosed cases (10 non-aggressive and 10 aggressive) of CGCGs were included in the study. The sections were subjected to immunohistochemistry using the markers CD34 and α-SMA. For the assessment of vascular parameters, image J software was used. The density of myofibroblasts was determined in each case ranging from score-1 to 4, using the criteria given by Sridhara et al. The correlation between mean values of vascular parameters and density of myofibroblasts with aggressiveness of CGCG was assessed using Mann-Whitney U test. Results: The result of Mann-Whitney U test suggested that the differences between the values of TVA (P < 0.001), MVA (P < 0.003) and density of myofibroblasts, i.e., SMA mean (P < 0.001) and SMA score (P < 0.001), in two groups are statistically significant. The formula for the assessment of aggressiveness was obtained using discriminant analysis. Conclusions: Angiogenesis and density of myofibroblasts significantly differ in aggressive and non-aggressive cases of CGCGs. The aggressiveness of CGCG case can be predicted using the obtained formula by entering the values of vascular parameters and myofibroblasts.

Glaucoma Health Coaching: A Survey of Eye Drop Instillation Education.

PRCIS: Health coaching is an effective strategy in supporting glaucoma patients to become champions of their own health. A personalized program should be implemented at the point of diagnosis. PURPOSE: Glaucoma is the leading cause of irreversible blindness worldwide. Its mainstay of treatment is intraocular pressure-lowering eye drops. Yet, many patients do not receive education regarding their condition, the importance of their eye drops, and how to instil them. The purpose of this audit was to assess what proportion of glaucoma patients had received any education regarding eye drop usage and whether a health coaching intervention would be beneficial. MATERIALS AND METHODS: This prospective audit was conducted during World Glaucoma Week at Moorfields Eye Hospital. Patients diagnosed with glaucoma were given a 6-part questionnaire. Subsequently, they received a coaching session with a pharmacy team member, focusing on eye drop instillation. Patient feedback was recorded. RESULTS: The sample size was 262. Overall, 92% of patients who had received teaching found it useful. Approximately half the patients had never been shown how to use eye drops before. In all, 79% of those who had never received a demonstration thought that further coaching would be helpful. When experiencing difficulties with eye drop instillation; 29% of patients felt comfortable asking a relative; 26% would not ask for help, and 16% would consult their glaucoma doctor. Almost 30% of patients had poked themselves in the eye at least once, during self-administration. CONCLUSIONS: Experienced and inexperienced patients found glaucoma health coaching beneficial. Health coaching empowers patients with long-term conditions to be champions of their own health condition, and it is important for patients to receive this training from the onset of their treatment.

Corneal endothelial cell density loss following glaucoma surgery alone or in combination with cataract surgery: a systematic review protocol.

OBJECTIVE: We aim to systematically assess and compare corneal endothelial cell density (ECD) loss in patients with glaucoma following glaucoma surgery and cataract surgery. INTRODUCTION: Corneal ECD loss may occur due to intraoperative surgical trauma in glaucoma surgery or postoperatively with chronic endothelial cell trauma or irritation. Corneal oedema and decompensation after aqueous shunt glaucoma surgery has been reported but the long-term ECD loss is still unknown. INCLUSION CRITERIA: Trabeculectomy, glaucoma filtration surgery or microinvasive glaucoma surgery in adults with ocular hypertension, primary and secondary open angle glaucoma, normal tension glaucoma and angle-closure glaucoma. Participants with pre-existing corneal disease will be excluded. Glaucoma laser treatments and peripheral iridotomy will be excluded. The outcomes include preoperative and postoperative corneal ECD, percentage change of corneal ECD and adverse events. METHODS: We will conduct an electronic database search for randomised controlled trials, prospective non-randomised studies, observational studies in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov and The International Prospective Register of Systematic Reviews (PROSPERO). Eligibility criteria will include quantitative articles published after and including the year 2000, written in English and containing data on ECD loss. Two independent reviewers will screen titles and abstracts and extract data from full texts, reporting outcomes according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data extraction of key characteristics will be completed using customised forms. Methodological quality will be assessed using the Joanna Briggs Institute critical appraisal forms. ETHICS AND DISSEMINATION: Ethics approval is not required for this review, as it will only include published data. Findings will be published in a peer-reviewed journal and disseminated across ophthalmic networks. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020192303.

Predictors of ophthalmology career success (POCS) study.

OBJECTIVE: Ophthalmology is the busiest outpatient specialty with demand predicted to rise over 40% in the next 20 years. A significant increase in the number of trainee ophthalmologists is required to fill currently vacant consultant posts and meet the UK's workforce demands by 2038. Our aim was to understand what determines success in ophthalmology training, in order to inform future ophthalmologists, refine recruitment and facilitate workforce planning. METHODS AND ANALYSIS: This was a retrospective longitudinal cohort study using routinely collected data available from UK Medical Education Database (UKMED) (https://www.ukmed.ac.uk/). Data were analysed on 1350 candidates who had applied for ophthalmology specialty training (OST) between 2012 and 2018, as well as 495 candidates who had attempted Fellow of the Royal College of Ophthalmologists (FRCOphth) Part 1 between 2013 and 2018. Participants who had not obtained their primary medical qualification from the UK medical schools were excluded. Primary outcome measures included gaining a place on the OST programme and passing the FRCOphth Part 1 examination on first attempt. RESULTS: Higher education performance measure decile scores at medical school are strongly predictive in securing an OST post and passing the part 1 examination first time (p<0.001). Candidates who attempt FRCOphth Part 1 prior to their ST1 application are more likely to get a place on OST on first attempt. Socioeconomic factors, gender and ethnicity do not influence success in OST entry. Male trainees are more likely to pass FRCOphth Part 1 on their first attempt. CONCLUSION: This study is the first quantitative assessment of the factors that determine success in OST recruitment and ophthalmology postgraduate examinations in the UK. Similar studies should be undertaken in all other medical and surgical specialties to understand what factors predict success.