Identifying trials run in India that are registered in other clinical trial registries: a cross-sectional study.

BACKGROUND: Clinical trials play a crucial role in biomedical research, and it is important to register them in public registries to ensure transparency and prevent research waste. In this study, we wished to determine what steps need to be taken to identify every clinical trial run in India that has been registered in any of the (non-Indian) World Health Organization-recognised primary registries. Of the 16 registries, we studied all except that of the European Union, which will be studied separately. METHODS: Two methodologies were employed for each registry, except for four that did not facilitate one or the other method. Methodology A involved downloading all the records in a registry and querying them. Methodology B involved conducting a search via the registry website. RESULTS: Only four registries provided consistent results with both methodologies. Seven registries had different results from the two methodologies. Of these, in four cases, in Methodology A one field indicated that the study ran in India, while another indicated otherwise. CONCLUSIONS: The above-mentioned ambiguities should be addressed by the concerned registries. Overall, this study reinforces the need for improved data accuracy and transparency in clinical trial registries and emphasizes the importance of resolving complications faced by users while navigating the registries. Ensuring accurate and comprehensive registration of clinical trials is essential for meta-research and the use of such data by a variety of stakeholders.

Retinal Penetrating Adeno-Associated Virus.

Purpose: The most common method of delivery of genes to the outer retina uses recombinant adeno-associated virus (AAV) injected into the subretinal space using a surgical procedure. In contrast, most drugs are delivered to the retina using an intravitreal approach in an office setting. The objective of the current study was to develop AAV vectors that can reach the outer retina via intravitreal injection. Methods: Recently, we described a molecular chaperone (Nuc1) that enhanced the penetration of small and large molecules, including AAV, into the retina. The Nuc1 amino acid sequence or a truncated version of Nuc1 (IKV) was genetically incorporated into an exposed loop of AAV2/9 VP1 protein. These novel recombinant AAV vectors expressing green fluorescent protein (GFP) or nuclear factor erythroid 2 p45-related factor 2 (Nrf2) were injected into the vitreous of C57Bl/6J or Nrf2 knockout mice, respectively. The amount of GFP expression or oxidative stress as measured by 8-Hydroxy-2'-deoxyguanosine staining in C57Bl/6J or Nrf2 knockout mice, respectively, was quantified. Results: Incorporation of Nuc1 into AAV2/9 did not lead to significant expression of GFP in the murine retina. However, incorporation of IKV into AAV2/9 led to robust expression of GFP in photoreceptors and retinal pigment epithelium (RPE) via the intravitreal and subretinal routes of delivery. Furthermore, expression of Nrf2 using an IKV vector led to a reduction in oxidative stress in the retina of C57Bl/6J and Nrf2 knockout mice. Conclusions: We have developed a novel AAV vector that enables delivery of transgenes to the outer retina of mice, including photoreceptors and RPE following intravitreal injection.

A dataset on consumers' knowledge, attitude, and practice: Investigating electric two-wheeler vehicle adoption in the Indian automobile sector.

This dataset encompasses on electric vehicle adoption among Indian consumers, conducted via a questionnaire survey at Two-Wheeler electric vehicle showrooms in Lucknow, India, between August and December 2023. A total of 1123 responses were collected, providing valuable insights into Electric Vehicle adoption behaviors across diverse segments of the Indian population. Utilizing established measures and statistical analyses, the dataset explores the relationships between knowledge, attitudes, practices, and demographic factors related to Electric Vehicle adoption. The questionnaire data were analyzed using SPSS (version 22).

Diagnostic Accuracy of Somatosensory Evoked Potential and Transcranial Motor Evoked Potential in Detection of Neurological Injury in Intradural Extramedullary Spinal Cord Tumor Surgeries: A Short-Term Follow-Up Prospective Interventional Study Experience from Tertiary Care Center of India.

Objective Intraoperative neuromonitoring (IONM) is an acknowledged tool for real-time neuraxis assessment during surgery. Somatosensory evoked potential (SSEP) and transcranial motor evoked potential (MEP) are commonest deployed modalities of IONM. Role of SSEP and MEP in intradural extramedullary spinal cord tumor (IDEMSCT) surgery is not well established. The aim of this study was to evaluate sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of SSEP and transcranial MEP, in detection of intraoperative neurological injury in IDEMSCT patients as well as their postoperative limb-specific neurological improvement assessment at fixed intervals till 30 days. Materials and Methods Symptomatic patients with IDEMSCTs were selected according to the inclusion criteria of study protocol. On modified McCormick (mMC) scale, their sensory-motor deficit was assessed both preoperatively and postoperatively. Surgery was done under SSEP and MEP (transcranial) monitoring using appropriate anesthetic agents. Gross total/subtotal resection of tumor was achieved as per IONM warning alarms. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of SSEP and MEP were calculated considering postoperative neurological changes as "reference standard." Patients were followed up at postoperative day (POD) 0, 1, 7, and 30 for convalescence. Statistical Analysis With appropriate tests of significance, statistical analysis was carried out. Receiver-operating characteristic curve was used to find cutoff point of mMC for SSEP being recordable in patients with higher neurological deficit along with calculation of sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of SSEP and MEP for prediction of intraoperative neurological injury. Results Study included 32 patients. Baseline mean mMC value was 2.59. Under neuromonitoring, gross total resection of IDEMSCT was achieved in 87.5% patients. SSEP was recordable in subset of patients with mMC value less than or equal to 2 with diagnostic accuracy of 100%. MEP was recordable in all patients and it had 96.88% diagnostic accuracy. Statistically significant neurological improvement was noted at POD-7 and POD-30 follow-up. Conclusion SSEP and MEP individually carry high diagnostic accuracy in detection of intraoperative neurological injuries in patients undergoing IDEMSCT surgery. MEP continues to monitor the neuraxis, even in those subsets of patients where SSEP fails to record.

Cell-Penetrating Chaperone Nuc1 for Small- and Large-Molecule Delivery Into Retinal Cells and Tissues.

Purpose: There are currently no means available for the efficient delivery of recombinant proteins into retinal cells in vivo. Although cell-penetrating peptides have been somewhat effective in protein delivery to the retina, they generally require conjugation chemistry with the payload, negatively impacting function of the therapeutic protein. In this study, we developed a novel peptide (Nuc1) that acts as a chaperone for delivery of small and large molecules, including steroids, peptides, antibodies, recombinant proteins, and viruses (adeno-associated viruses [AAVs]) across biological membranes in vivo without the need for conjugation. Methods: Nuc1 peptide was designed based on sequences known to bind heparan sulfate proteoglycans and nucleolin found on the surface of retinal cells. Nuc1 was injected into the vitreous of mice with a variety of molecules and retinas examined for uptake and function of these molecules. Results: Nuc1 engages the process of macropynocytosis for cell entry. The delivery of functional recombinant X-linked inhibitor of apoptosis protein to photoreceptors via the intravitreal route of injection inhibited retinal apoptosis. Nuc1 was found to enhance the delivery of anti-VEGF antibodies delivered intravitreally or topically in models of age-related macular degeneration (AMD). Nuc1 enhanced delivery of decorin, facilitating significant inhibition of neovascularization and fibrosis in a model of AMD. Finally, Nuc1 was found to enhance penetration of retinal cells and tissues by AAV via both the subretinal and intravitreal routes of injection. Conclusions: Nuc1 shows promise as a novel approach for the delivery of recombinant proteins into retinal cells in vivo.

Asparagus officinalis Herb-Derived Carbon Quantum Dots: Luminescent Probe for Medical Diagnostics.

The utilization of natural materials for the synthesis of highly fluorescent carbon quantum dots (CQDs) presents a sustainable approach to overcome the challenges associated with traditional chemical precursors. Here, we report the synthesis of novel S,N-self-doped CQDs (S,N@CQDs) derived from asparagus officinalis herb. These S,N@CQDs exhibit 16.7 % fluorescence quantum yield, demonstrating their potential in medical diagnostics. We demonstrate the efficacy of S,N@CQDs as luminescent probes for the detection of anti-pathogenic medications metronidazole (MTZ) and nitazoxanide (NTZ) over concentration ranges of 0.0-180.0 µM (with a limit of detection (LOD) of 0.064 µM) and 0.25-40.0 µM (LOD of 0.05 µM), respectively. The probes were successfully applied to determine MTZ and NTZ in medicinal samples, real samples, and spiked human plasma, with excellent recovery rates ranging from 99.82 % to 103.03 %. Additionally, S,N@CQDs demonstrate exceptional efficacy as diagnostic luminescent probes for hemoglobin (Hb) detection over a concentration range of 0-900 nM, with a minimal detectability of 9.24 nM, comparable to commercially available medical laboratory diagnostic tests. The eco-friendly synthesis and precise detection limits of S,N@CQDs meet necessary analytical requirements and hold promise for advancing diagnostic capabilities in clinical settings. This research signifies a significant step towards sustainable and efficient fluorescence-based medical diagnostics.

The intersection of frailty and metabolism.

On average, aging is associated with unfavorable changes in cellular metabolism, which are the processes involved in the storage and expenditure of energy. However, metabolic dysregulation may not occur to the same extent in all older individuals as people age at different rates. Those who are aging rapidly are at increased risk of adverse health outcomes and are said to be "frail." Here, we explore the links between frailty and metabolism, including metabolic contributors and consequences of frailty. We examine how metabolic diseases may modify the degree of frailty in old age and suggest that frailty may predispose toward metabolic disease. Metabolic interventions that can mitigate the degree of frailty in people are reviewed. New treatment strategies developed in animal models that are poised for translation to humans are also considered. We suggest that maintaining a youthful metabolism into older age may be protective against frailty.

Clinical diagnosis of viral hepatitis: Current status and future strategies.

Viral hepatitis (VH) is a significant public health issue with tremendous potential to aggravate into chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Recent decade has witnessed remarkable uprising in the drug development and effective treatment of VH. An upsurge is seen in identification of antiviral therapies with low rates of viral resistance, the improvement of Hepatitis B Virus (HBV) vaccination and the development of direct-acting antivirals for Hepatitis C Virus (HCV). But unfortunately, the "2030 worldwide eradication" objective of World Health Organization (WHO) is still unmet. It can be largely attributed to the deficit faced by the healthcare system concerning screening and diagnosis. A timely, accurate and comprehensive screening; encompassing maximum population coverage is essential to combat this disease. However, advancements in VH diagnostics remain inadequate and with a marginal use in routine practice. This paper deliberates upon the lacunae in traditional and prevailing diagnostic methodology of viral hepatitis, especially their inadequacy in meeting the unique situations prevailing low- and middle-income countries (LMIC).

Intracranial Interdural and Extradural Cerebellar Convexity Dermoid Cyst: A Case Report of Rare Tumor at the Rarest Location.

Intracranial dermoid cysts are rare dysembryonic tumors of benign nature. These are uncommon in adults. If present, they are usually located in the midline or along the lines of embryonic fusion. The posterior fossa region is an infrequent site. Extradural or interdural locations are even more rare. In this case report, the authors report a laterally located large posterior fossa right cerebellar convexity interdural and extradural dermoid cyst over the sigmoid sinus. It was managed by totally extradural maximum possible safe decompression with microneurosurgical technique. The authors share their experience of addressing this rare pathology at the rarest location with unusual imaging findings.

Recent Advances in Nanomechanical Measurements and Their Application for Pharmaceutical Crystals.

Mechanical behavior of pharmaceutical crystals directly impacts the formulation development and manufacturing of drug products. The understanding of crystal structure-mechanical behavior of pharmaceutical and molecular crystals has recently gained substantial attention among pharmaceutical and materials scientists with the advent of advanced nanomechanical testing instruments like nanoindentation. For the past few decades, instrumented nanoindentation was a popular technique for measuring the mechanical properties of thin films and small-length scale materials. More recently it is being implemented to investigate the mechanical properties of pharmaceutical crystals. Integration of correlative microscopy techniques and environmental control opened the door for advanced structure-property correlation under processing conditions. Preventing the degradation of active pharmaceutical ingredients from external factors such as humidity, temperature, or pressure is important during processing. This review deals with the recent developments in the synchronized nanomechanical measurements of pharmaceutical crystals toward the fast and effective development of high-quality pharmaceutical drug products. This review also summarizes some recent reports to intensify how one can design and control the nanomechanical properties of pharmaceutical solids. Measurement challenges and the scope for studying nanomechanical properties of pharmaceutical crystals using nanoindentation as a function of crystal structure and in turn to develop fundamental knowledge in the structure-property relationship with the implications for drug manufacturing and development are discussed in this review. This review further highlights recently developed capabilities in nanoindentation, for example, variable temperature nanoindentation testing, in situ imaging of the indented volume, and nanoindentation coupled Raman spectroscopy that can offer new quantitative details on nanomechanical behavior of crystals and will play a decisive role in the development of coherent theories for nanomechanical study of pharmaceutical crystal.

Survey data to evaluate consumer behaviour and consumption pattern of sustainable apparel: A study on consumer awareness level.

A consumer survey was conducted in Uttar Pradesh in five major cities Lucknow, Kanpur, Agra, Varanasi, and Meerut District, from 2022 to 2023 to understand consumer awareness and consumer behaviour towards Sustainable Apparel. The data were collected from 384 respondents via face-to-face interviews through field surveys in different colleges and universities. A paper-based questionnaire was analyzed using SPSS (version 22) using descriptive and, correlation, ANOVA, and regression statistical analysis.

Countrywide monitoring of absorbed dose rate in air due to outdoor natural gamma radiation in India.

The Indian Environmental Radiation Monitoring Network continuously monitors, throughout India, the absorbed dose rate in air due to outdoor natural gamma radiation, by using Geiger-Mueller detector-based standalone environmental radiation monitors. The network consists of 546 monitors spread across 91 monitoring locations distributed all over the country. In this paper, the countrywide long-term monitoring results are summarised. The measured mean dose rate of the monitoring locations followed a log-normal distribution and ranged from 50 to 535 nGy.h-1 with a median value of 91 nGy.h-1. Due to outdoor natural gamma radiation, the average annual effective dose was estimated to be 0.11 mSv.y-1.

Chronic testosterone deficiency increases late inward sodium current and promotes triggered activity in ventricular myocytes from aging male mice.

Clinical studies suggest low testosterone levels are associated with cardiac arrhythmias, especially in later life. We investigated whether chronic exposure to low circulating testosterone promoted maladaptive electrical remodeling in ventricular myocytes from aging male mice and determined the role of late inward sodium current (INa,L) in this remodeling. C57BL/6 mice had a gonadectomy (GDX) or sham surgery (1 mo) and were aged to 22-28 mo. Ventricular myocytes were isolated; transmembrane voltage and currents were recorded (37°C). Action potential duration at 70 and 90% repolarization (APD70 and APD90) was prolonged in GDX compared with sham myocytes (APD90, 96.9 ± 3.2 vs. 55.4 ± 2.0 ms; P < 0.001). INa,L was also larger in GDX than sham (-2.4 ± 0.4 vs. -1.2 ± 0.2 pA/pF; P = 0.002). When cells were exposed to the INa,L antagonist ranolazine (10 µM), INa,L declined in GDX cells (-1.9 ± 0.5 vs. -0.4 ± 0.2 pA/pF; P < 0.001) and APD90 was reduced (96.3 ± 14.8 vs. 49.2 ± 9.4 ms; P = 0.001). GDX cells had more triggered activity (early/delayed afterdepolarizations, EADs/DADs) and spontaneous activity than sham. EADs were inhibited by ranolazine in GDX cells. The selective NaV1.8 blocker A-803467 (30 nM) also reduced INa,L, decreased APD and abolished triggered activity in GDX cells. Scn5a (NaV1.5) and Scn10a (NaV1.8) mRNA was increased in GDX ventricles, but only NaV1.8 protein abundance was increased in GDX compared with sham. In vivo studies showed QT prolongation and more arrhythmias in GDX mice. Thus, triggered activity in ventricular myocytes from aging male mice with long-term testosterone deficiency arises from APD prolongation mediated by larger NaV1.8- and NaV1.5-associated currents, which may explain the increase in arrhythmias.NEW & NOTEWORTHY Older men with low testosterone levels are at increased risk of developing cardiac arrhythmias. We found aged mice chronically exposed to low testosterone had more arrhythmias and ventricular myocytes had prolonged repolarization, abnormal electrical activity, larger late sodium currents, and increased expression of NaV1.8 sodium channels. Drugs that inhibit late sodium current or NaV1.8 channels abolished abnormal electrical activity and shortened repolarization. This suggests the late sodium current may be a novel target to treat arrhythmias in older testosterone-deficient men.

Leishmania donovani Attenuates Dendritic Cell Trafficking to Lymph Nodes by Inhibiting C-Type Lectin Receptor 2 Expression via Transforming Growth Factor-ß.

To initiate an antileishmanial adaptive immune response, dendritic cells (DCs) must carry Leishmania antigens from peripheral tissues to local draining lymph nodes. However, the migratory capacity of DCs is largely compromised during Leishmania donovani infection. The molecular mechanism underlying this defective DC migration is not yet fully understood. Here, we demonstrate that L. donovani infection impaired the lymph node homing ability of DCs by decreasing C-type lectin receptor 2 (CLEC-2) expression. L. donovani exerted this inhibitory effect by inducing transforming growth factor-ß (TGF-ß) secretion from DCs. Indeed, TGF-ß produced in this manner inhibited nuclear factor-κB (NF-κB)-mediated CLEC-2 expression on DCs by activating c-Src. Notably, suppression of c-Src expression significantly improved the arrival of DCs in draining lymph nodes by preventing L. donovani-induced CLEC-2 downregulation on DCs. These findings reveal a unique mechanism by which L. donovani inhibits DC migration to lymph nodes and suggest a key role for TGF-ß, c-Src, and CLEC-2 in regulating this process. IMPORTANCE Dendritic cells (DCs) play a key role in initiating T cell-mediated protective immunity against visceral leishmaniasis (VL), the second most lethal parasitic disease in the world. However, the T cell-inducing ability of DCs critically depends on the extent of DC migration to regional lymph nodes. Notably, the migration of DCs is reported to be impaired during VL. The cause of this impaired DC migration, however, remains ill-defined. Here, we provide the first evidence that L. donovani, the causative agent of VL, attenuates the lymph node homing capacity of DCs by decreasing C-type lectin receptor 2 (CLEC-2) expression on DCs. Additionally, we have demonstrated how L. donovani mediates this inhibitory effect. Overall, our work has revealed a unique mechanism underlying L. donovani-induced impairment of DC migration and suggests a potential strategy to improve antileishmanial T cell activity by increasing DC arrival in lymph nodes.

TIM-3 increases the abundance of type-2 dendritic cells during Leishmania donovani infection by enhancing IL-10 production via STAT3.

The outcome of the disease visceral leishmaniasis (VL), caused by Leishmania donovani (LD), largely relies on the relative dominance of host-protective type-1 T helper (Th1) cell response versus disease-promoting type-2 T helper (Th2) cell response. The Th1 and Th2 responses, in turn, are believed to be elicited by type-1 conventional dendritic cells (cDC1) and type-2 conventional DCs (cDC2), respectively. However, it is still unknown which DC subtype (cDC1 or cDC2) predominates during chronic LD infection and the molecular mechanism governing such occurrence. Here we report that in chronically infected mice, the splenic cDC1-cDC2 balance shifted toward the cDC2 subtype and that the receptor T cell immunoglobulin and mucin protein-3 (TIM-3) expressed by DCs played a key role in mediating this effect. Transfer of TIM-3-silenced DCs in fact prevented the predominance of the cDC2 subtype in mice with chronic LD infection. We also found that LD actually upregulated TIM-3 expression on DCs by triggering a TIM-3-mediated signaling pathway STAT3 (signal transducer and activator of transcription 3)→interleukin (IL)-10→c-Src→transcription factors Ets1, Ets2, USF1, and USF2. Notably, TIM-3 promoted STAT3 activation via a non-receptor tyrosine kinase Btk. Adoptive transfer experiments further demonstrated a critical role for STAT3-driven TIM-3 upregulation on DCs in increasing cDC2 abundance in chronically infected mice, which ultimately aided disease pathogenesis by augmenting Th2 responses. These findings document a new immunoregulatory mechanism contributing to disease pathology during LD infection and define TIM-3 as a key mediator of this process.

The repertoire of mutational signatures in tobacco- and non-tobacco-induced oral cancer.

The use of tobacco products is one of the established contributors toward the development and spread of oral cancer. Additionally, recent research has indicated oral microbiome, infections with Human papilloma virus (HPV), Epstein-Barr virus (EBV), Candida as significant contributing factors to this disease along with lifestyle habits. Deregulation of cellular pathways envisaging metabolism, transcription, translation, and epigenetics caused by these risk factors either individually or in unison is manifold, resulting in the increased risk of oral cancer. Globally, this cancer continues to exist as one of the major causes of cancer-related mortalities; the numbers in the developing South Asian countries clearly indicate yearly escalation. This review encompasses the variety of genetic modifications, including adduct formation, mutation (duplication, deletion, and translocation), and epigenetic changes evident in oral squamous cell carcinoma (OSCC). In addition, it highlights the interference caused by tobacco products in Wnt signaling, PI3K/Akt/mTOR, JAK-STAT, and other important pathways. The information provided also ensures a comprehensive and critical revisit to non-tobacco-induced OSCC. Extensive literature survey and analysis has been conducted to generate the chromosome maps specifically highlighting OSCC-related mutations with the potential to act as spectacles for the early diagnosis and targeted treatment of this disease cancer.

Generation of map on natural environmental background absorbed dose rate in India.

A systematic mapping of natural absorbed dose rate was carried out to assess the existing exposure situation in India. The mammoth nationwide survey covered the entire terrestrial region of the country comprising of 45127 sampling grids (grid size 36 km2) with more than 100,000 data points. The data was processed using Geographic Information System. This study is based on established national and international approaches to provide linkage with conventional geochemical mapping of soil. Majority (93%) of the absorbed dose rate data was collected using handheld radiation survey meters and remaining were measured using environmental Thermo Luminescent Dosimeters. The mean absorbed dose rate of the entire country including several mineralized regions, was found to be 96 ± 21 nGy/h. The median, Geometric Mean and Geometric Standard Deviation values of absorbed dose rate were 94, 94 and 1.2 nGy/h, respectively. Among the High Background Radiation Areas of the country, absorbed dose rate varied from 700 to 9562 nGy/h in Karunagappally area of Kollam district, Kerala. The absorbed dose rate in the present nationwide study is comparable with the global database.