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The gene therapy approach for retinal disorders has been considered largely over the last decade owing to the favorable outcomes of the US Food and Drug Administration-approved commercial gene therapy, Luxturna. Technological advances in recent years, such as next-generation sequencing, research in molecular pathogenesis of retinal disorders, and precise correlations with their clinical phenotypes, have contributed to the progress of gene therapies for various diseases worldwide, and more recently in India as well. Thus, considerable research is being conducted for the right choice of vectors, transgene engineering, and accessible and cost-effective large-scale vector production. Many retinal disease-specific clinical trials are presently being conducted, thereby necessitating the collation of such information as a ready reference for the scientific and clinical community. In this article, we present an overview of existing gene therapy research, which is derived from an extensive search across PubMed, Google Scholar, and clinicaltrials.gov sources. This contributes to prime the understanding of basic aspects of this cutting-edge technology and information regarding current clinical trials across many different conditions. This information will provide a comprehensive evaluation of therapies in existing use/research for personalized treatment approaches in retinal disorders.

Introduction: Frozen Section (FS) is a diagnostic technique performed intraoperatively to obtain relevant information about the primary diagnosis, margin status, or sentinel lymph nodes, which helps guide the course of surgery. With the prevalent use of FS, it is imperative to recognise and scrutinise its diagnostic pitfalls and make efforts for rectification. Aim: To compare diagnostic results obtained on FS with final paraffin-embedded histopathology and calculate the Diagnostic Accuracy (DA) of FS. Materials and Methods: This cross-sectional study was conducted in the Department of Pathology at a tertiary care hospital, DVVPFs Medical College in Ahmednagar district, Maharashtra, India over a period of two years from January 1, 2020, to December 31, 2021. The diagnosis provided on specimens received for intraoperative FS was compared with the final histopathological diagnosis, considered as the gold standard for the same specimen. The results were categorised as concordant, discordant, and deferred cases. The diagnosis on FS and the final histopathological diagnosis, along with relevant clinical data, were entered into an excel sheet. Further, the DA of FS was calculated. All the discordant cases were analysed. Statistical analysis utilised simple percentage calculations from the excel sheet. Results: A total of 130 cases were analysed using FS, with the most common indication being sentinel lymph node analysis to detect metastatic deposits in 72 (55.4%) cases. Out of the total 130 cases, 119 (91.5%) were concordant, 10 (7.7%) were discordant, and 1 (0.8%) was deferred due to an insufficient specimen. Therefore, the overall DA rate was found to be 91.5% with an error rate of 8.5%. Upon analysis of the 10 discordant cases, the cause of inaccuracy was technical error in 7 (70%) cases and interpretation error in 3 (30%) cases. Conclusion: The DA obtained in the present study was somewhat lower than expected due to technical errors during FS sectioning, leading to artifacts, especially during lymph node processing. Analysis of the discordant cases unveiled this deficit. Therefore, such assessment studies should be performed periodically as they assist in highlighting the shortfalls and provide a plan to boost DA.

Very few studies exist on tele-health models of parent-mediated interventions delivered in low resource developing countries. The global COVID-19 pandemic catalysed a pilot of an online delivery of an evidence-based parent-mediated intervention (Project ImPACT) for children with Autism Spectrum Disorder in Mumbai, India. Context and culture-specific adaptations were made in program structure and a mixed-methods approach was adopted to evaluate acceptability, feasibility and preliminary efficacy of this model. Quantitative results (n = 12) showed excellent completion rates, with significant improvement in parent fidelity to intervention and child social-communication skills. Analysis of qualitative data from focus groups with parents on completion revealed that parents found the online mode convenient and acceptable, found the synchronous model of sessions especially beneficial and perceived improvements in their own parenting skills and children's developmental profiles. Though piloted in pandemic times, the results from the study have implications for future service delivery models across similar settings in other developing countries.

Background: Progesterone-primed ovarian stimulation (PPOS) protocol is based on the principle of preventing pre-mature luteinising hormone surge during ovarian stimulation using progesterone. Aims: In this study, we aimed to compare the cost-effectiveness of PPOS over GnRH antagonist cycles in oocyte donor cycles where freeze all is a norm. Settings and Design: It is a prospective cohort study with 130 participants. Materials and Methods: We included all women undergoing oocyte donation using PPOS protocol and antagonist protocol at our centre. Fifty-seven belonged to the PPOS group and were given medroxyprogesterone acetate (MPA) and 73 belonged to the GnRH antagonist group who received cetrorelix. The primary outcome was the number of mature oocyte retrieved at OPU and the cost involved per stimulation cycle. Statistical Analysis Used: For normally distributed observations, we used t-test, and for the variables of non-normal distribution, Mann–Whitney U-test was used. The significance was accepted for P < 0.05. Results: The baseline clinical characteristics of the donors were comparable with a mean age of 25.42 ± 2.90 years, body mass index of 24.00 ± 4.00 kg/m2 and antral follicle count of 18.63 ± 5.23. The duration of stimulation was similar in both the groups as well as the total gonadotropin dose required was not significantly different. The number of mature oocytes retrieved was same in both the groups (10.41 ± 4.04 with antagonist and 10.25 ± 3.23 with PPOS, P = 0.964). There were no reported cases of severe ovarian hyperstimulation syndrome (OHSS) in any of the groups. The incidence of mild-to-moderate OHSS in the antagonist group was 5.4% and in the PPOS group was 3.6%, and the difference was not significant (P = 0.69). The cost per mature oocyte (M2) was significantly higher in the antagonist protocol in comparison to the PPOS protocol (INR 9485.69 ± 5751.11 vs. Rs. 5945.86 ± 2848.59, respectively, P < 0.001). Conclusion: Our study identifies PPOS protocol using MPA to be more cost-effective and patient-friendly than conventional GnRH antagonist protocol in oocyte donor cycles.

There is rapidly emerging evidence from pre-clinical studies, patient samples and patient subpopulations that certain chemotherapeutics inadvertently produce prometastatic effects. Prior to this, we showed that doxorubicin and daunorubicin stiffen cells before causing cell death, predisposing the cells to clogging and extravasation, the latter being a step in metastasis. Here, we investigate which other anti-cancer drugs might have similar prometastatic effects by altering the biophysical properties of cells. We treated myelogenous (K562) leukemic cancer cells with the drugs nocodazole and hydroxyurea and then measured their mechanical properties using a microfluidic microcirculation mimetic (MMM) device, which mimics aspects of blood circulation and enables the measurement of cell mechanical properties via transit times through the device. We also quantified the morphological properties of cells to explore biophysical mechanisms underlying the MMM results. Results from MMM measurements show that nocodazole- and hydroxyurea-treated K562 cells exhibit significantly altered transit times. Nocodazole caused a significant (p < 0.01) increase in transit times, implying a stiffening of cells. This work shows the feasibility of using an MMM to explore possible biophysical mechanisms that might contribute to chemotherapy-induced metastasis. Our work also suggests cell mechanics as a therapeutic target for much needed antimetastatic strategies in general.

Unlike plants that have special gravity-sensing cells, such special cells in animals are yet to be discovered. However, microgravity, the condition of apparent weightlessness, causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. Decades of investigations show correlations between these organ and system-level dysfunctions with changes induced at the cellular level both by simulated microgravity as well as microgravity conditions in outer space. Changes in single bone, muscle and immune cells include morphological abnormalities, altered gene expression, protein expression, metabolic pathways and signaling pathways. These suggest that human cells mount some response to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear. Here, we addressed the question whether microgravity induces alterations to drug response in cancer cells. We used both adherent cancer cells (T98G) and cancer cells in suspension (K562) to confirm the known effects of simulated microgravity and then treated the K562 cells with common cancer drugs (hydroxyurea and paclitaxel) following 48 h of exposure to simulated microgravity via a NASA-developed rotary cell culture system. Through fluorescence-guided morphometry, we found that microgravity abolished a significant reduction (p < 0.01) in the nuclear-to-cytoplasm ratio of cancer cells treated with hydroxyurea. Our results call for more studies on the impact of microgravity on cellular drug response, in light of the growing need for space medicine, as space exploration grows.

Objectives We verified subnational (state/union territory (UT)/district) claims of achievements in reducing tuberculosis (TB) incidence in 2020 compared with 2015, in India.Design A community-based survey, analysis of programme data and anti-TB drug sales and utilisation data.Setting National TB Elimination Program and private TB treatment settings in 73 districts that had filed a claim to the Central TB Division of India for progress towards TB-free status.Participants Each district was divided into survey units (SU) and one village/ward was randomly selected from each SU. All household members in the selected village were interviewed. Sputum from participants with a history of anti-TB therapy (ATT), those currently experiencing chest symptoms or on ATT were tested using Xpert/Rif/TrueNat. The survey continued until 30 Mycobacterium tuberculosis cases were identified in a district.Outcome measures We calculated a direct estimate of TB incidence based on incident cases identified in the survey. We calculated an under-reporting factor by matching these cases within the TB notification system. The TB notification adjusted for this factor was the estimate by the indirect method. We also calculated TB incidence from drug sale data in the private sector and drug utilisation data in the public sector. We compared the three estimates of TB incidence in 2020 with TB incidence in 2015.Results The estimated direct incidence ranged from 19 (Purba Medinipur, West Bengal) to 1457 (Jaintia Hills, Meghalaya) per 100 000 population. Indirect estimates of incidence ranged between 19 (Diu, Dadra and Nagar Haveli) and 788 (Dumka, Jharkhand) per 100 000 population. The incidence using drug sale data ranged from 19 per 100 000 population in Diu, Dadra and Nagar Haveli to 651 per 100 000 population in Centenary, Maharashtra.Conclusion TB incidence in 1 state, 2 UTs and 35 districts had declined by at least 20% since 2015. Two districts in India were declared TB free in 2020.

The entire world seems to have responded to COVID-19 pandemic in a knee-jerk manner with a short mindset without building on the existing strengths of public health infrastructure. National governments cannot be blamed for this as we are dealing with a crisis that comes once in a lifetime. Realising this, the Organized Medicine Academic Guild (OMAG) an association of major health associations in this country has suggested measures for long-term solutions to COVID-19-like pandemics in the form of a policy paper by OMAG.

BackgroundEstimating the clinical demand for blood and components arising in a health facility is crucial to ensure timely availability of blood. This study aims to estimate disease-specific clinical demand, supply and utilization of whole blood and components in India.MethodsWe conducted a national level cross-sectional study in five randomly selected states from five regions of the country. We included 251 public and private facilities representing primary, secondary and tertiary care facilities. We collected annual disease-specific demand, supply and utilization of blood and components using a structured tool. We estimated the national demand by extrapolating the study data (demand and beds) to the total number of estimated beds in the country.FindingsAccording to the study, the total clinical demand of 251 health facilities with 51,562 beds was 474,627 whole blood units. Based on this, the clinical demand for India was estimated at 14·6 million whole blood units (95 CI: 14·59-14·62), an equivalent of 36·3 donations per 1,000 eligible populations, which will address whole blood and component requirement. The medicine specialty accounted for 6·0 million units (41·2%), followed by surgery 4·1 million (27·9%), obstetrics and gynecology 3·3 million (22·4%) and pediatrics 1·2 million (8·5%) units. The supply was 93% which is equivalent to 33·8 donations against the demand.ConclusionThe study indicated a demand and supply gap of 2.5 donations per 1,000 eligible persons which is around one million units. The gap emphasises the need for sustained and concerted efforts from all stakeholders and for increasing the awareness about repeat voluntary non-remunerated blood donation (VNRBD); optimizing the availability of blood components through efficient blood component separation units; promoting modern principles of patient blood management and strengthening capacities of human resources in the blood transfusion system in India.