Cardiometabolic outcomes in offspring of women treated with metformin versus insulin for gestational diabetes: A Systematic Review and meta-analysis.

INTRODUCTION: Gestational diabetes mellitus (GDM) is commonly managed with either metformin or insulin, but their comparative effects on offspring cardiometabolic outcomes are not fully understood. OBJECTIVE: To investigate the impact of metformin and insulin, two distinct pharmacological interventions, on cardiometabolic outcomes in offspring of mothers with GDM. METHODOLOGY: Systematic literature review was performed for articles (randomized control trials) published from 1974 to May 2024 using a predefined search strategy. Studies were screened for title and abstract followed by full text. Quality assessment was done using a separate risk of bias tool in line with the PRISMA-2020 checklist. RESULTS: Among 5463 records, five studies (metformin = 409 children or insulin n = 434 children) were included. Offspring of metformin-treated mothers in the age range of 5-9 years had more fat-free mass (kg) by bioimpedance and abdominal (subcutaneous and visceral) fat volume (cm3) by MRI. Fasting plasma glucose and triglycerides were lower in the metformin-treated group for offspring aged 5-9 years. No significant differences were observed for other cardiometabolic outcomes. Limited data available for offsprings less than 5 years of age precluded meta-analysis for the available outcomes, except for body weight, and difference for this was also not significant. CONCLUSION: In short term no major differences has been seen in most of the cardiometabolic outcomes evaluated in the meta-analysis. Future trials with longer follow up are required and in different ethnicities. SYSTEMATIC REVIEW REGISTRATION: PROSPERO-CRD42023450990.

Redefining Cancer Care in India: Dr. Viswanathan Shanta's Lasting Contributions and Its Enduring Impact.

Dr. V. Shanta (1927-2021) made priceless contributions that significantly changed advanced cancer care in India. Trained at Madras Medical College and further trained in oncology internationally, she transformed the Cancer Institute in Chennai from a 12-bed facility into a leading cancer care institute of global repute. Dr. Shanta championed early cancer detection and sought to dismantle the stigma surrounding the disease, particularly in rural communities. Under her leadership, the institute introduced pioneering technologies and established India's first pediatric oncology institute. She was instrumental in creating comprehensive cancer registries that informed national health policies. Her dedication to holistic, patient-oriented care and her commitment to equitable healthcare earned her numerous accolades, including India's highest civilian awards such as the Padma Vibhushan and Padma Bhushan and Asia's premier prize the Ramon Magsaysay Award. Her work remains a cornerstone of oncology in India, continuing to inspire future generations of medical professionals.

Photoinduced [4+2] cycloaddition of dienes and quinonemethides.

A visible light-induced cycloaddition of 1,3-dienes and p-quinonemethides through EDA complexation is reported. The reaction does not require any external photocatalyst, oxidant or additive. The generality of the method is established through a broad substrate scope. This newly developed strategy presents an exciting prospect for the development of metal-free photocatalytic [4+2] cycloaddition reactions.

Analysis of sociodemographic profile of glaucoma patients with risk factors, subtypes, and disease severity in a tertiary eye care facility in Northern India.

PURPOSE: To study the different subtypes of glaucoma and to analyze the demographic and clinical profile of glaucoma patients along with associated risk factors in a multi-locational North Indian study. METHODS: Newly diagnosed and known glaucoma patients on treatment were enrolled in the study. Complete history was taken, and clinical evaluation was done by senior glaucoma experts. RESULTS: Five hundred and eighty-six patients (1121 eyes) were included with 383 males (65.4%) and 203 females (34.6%). Of these, 508 (86.7%) had primary glaucoma and 78 (13.3%) had secondary glaucoma. Also, 263 (44.9%) patients had primary open angle glaucoma (POAG) and 172 (29.4%) had primary angle closure glaucoma. Four hundred and fifty-one (77%) were graduates or postgraduates and 293 (50%) were dependents on family income. One hundred and forty-one (24%) had a positive family history. Secondary glaucoma patients had a lower average age (52.6 ± 16.8 years) and higher average intraocular pressure (IOP; 34.23 ± 13 mm) compared to primary glaucoma patients (26.6 ± 9.7 mm) (P < 0.0001). Thirty-three (47.8%) out of 78 secondary glaucoma patients had advanced disease. Seventy-four (12.6%) were first-time diagnosed and 18 had advanced disease. In addition, 161 eyes had one or more glaucoma surgeries done (128 trabeculectomy and 28 phacotrabeculectomy). Ninety-five (16.2%) patients were advised surgery at our centers (46 trab, 26 phacotrab, 15 phaco, five Ahmed glaucoma valve implantation, and three pars plana vitrectomy). Disease progression was noted in 62 patients reporting good compliance to medicines. CONCLUSION: POAG was the most common variant in this study. Secondary glaucoma patients were youngest in age and had the highest IOP. Trabeculectomy was the most performed surgery. A good literacy rate did not prevent late presentations.

Comparative efficacy of cognitive behavior therapy and interpersonal therapy in the treatment of depression: A randomized controlled study.

Background: Depressive disorders are one of the most common psychiatric disorders that occur in people of all ages. Aim: To assess the efficacy of cognitive behavior therapy (CBT) and interpersonal therapy (IPT) in cases of depression. Materials and Methods: The sample for the study comprised 52 diagnosed cases of major depressive disorder (MDD) based on the 10th revision of the International Classification of Diseases (ICD-10) criteria in the age range of 21 to 50 years. They were randomized with the help of the app and assigned to CBT and IPT groups. Two patients had dropped out of the CBT group. Hence, finally, 50 cases were taken for study. A total of 12 therapy sessions were given. All patients were given standard treatment as prescribed. Results: Findings of paired samples t-test to assess the within-group differences in both the groups (CBT and IPT) as well as gains score statistics or difference score statistics (pre-test minus post-test) were applied to compare group differences. Results of paired samples 't' test suggest that there was a statistically significant difference in the scores of both the groups from pre-test to post-test. IPT group had shown significantly better outcomes as quantified by the percentage of patients scoring less on the outcome variable of the Beck Depression Inventory (BDI), Montgomery-Asberg Depression Rating Scale (MADRS), Hopelessness Scale, and General Health Questionnaire (GHQ). Conclusion: Both CBT and IPT are efficacious in the treatment of MDD. IPT yielded better results on MADRS as compared to CBT on parameters of outcome in the present study. The findings indicate that interventions were effective in reducing the symptoms of depression.

Optimization of a Novel DEL Hit That Binds in the Cbl-b SH2 Domain and Blocks Substrate Binding.

We were attracted to the therapeutic potential of inhibiting Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b), a RING E3 ligase that plays a critical role in regulating the activation of T cells. However, given that only protein-protein interactions were involved, it was unclear whether inhibition by a small molecule would be a viable approach. After screening an ∼6 billion member DNA-encoded library (DEL) using activated Cbl-b, we identified compound 1 as a hit for which the cis-isomer (2) was confirmed by biochemical and surface plasmon resonance (SPR) assays. Our hit optimization effort was greatly accelerated when we obtained a cocrystal structure of 2 with Cbl-b, which demonstrated induced binding at the substrate binding site, namely, the Src homology-2 (SH2) domain. This was quite noteworthy given that there are few reports of small molecule inhibitors that bind to SH2 domains and block protein-protein interactions. Structure- and property-guided optimization led to compound 27, which demonstrated measurable cell activity, albeit only at high concentrations.

Thinking Before the Journey of First 1000 Days of Life.

For any nation the health of its citizens especially that of the reproductive age women is critical and of paramount importance as they are the ones who usher in the new generation. Now that India is undergoing triple burden of malnutrition, if the pregnant woman is underweight, overweight, obese or diabetic both the mother and the baby are at a high risk of developing complications not only during pregnancy but also postpartum. Hence, having a good nutritional status is so important even before the woman conceives.

Lyme Borreliosis, a public health concern in India: Findings of Borrelia burgdorferi serosurvey from two states.

Background: Lyme borreliosis is a public health concern in India. The prevalence of the disease is still undetermined with major entomological and epidemiological gaps. The present study was conducted to determine the seropositivity of Borrelia burgdorferi in Sikkim and Arunachal Pradesh, India. Methods: A cross-sectional serosurvey was conducted in Sikkim and Arunachal Pradesh. Data collection tools were developed and standardized for the collection of clinico-socio-demographic data. Sample size for each site was calculated using the formula for the estimation of a single proportion. Qualitative detection of IgG antibodies in serum samples was done using NovaLisa™ Lyme Borrelia IgG ELISA kit. Results: A total of 793 participants were enrolled, 484 (61%) from Arunachal Pradesh and 309 (39%) from Sikkim. Out of 793 participants, 21 (2.7%), 22 (2.8%), 6 (0.8%), 29 (3.7%), 44 (5.5%), and 16 (2.1%) gave history of tick bite, rash, erythema migrans, migratory muscle pain, migratory joint pain, and numbness, respectively, in the past one year. The adjusted seroprevalence (for sensitivity and specificity of kit) for the study is 3.7 (2.4-5.2). No signs or symptoms were found to be associated with IgG ELISA positivity. The state-wise distribution of seropositivity for Arunachal Pradesh and Sikkim was 4.1 (95% CI: 2.5-6.3) and 2.3 (95% CI: 0.9-4.6), respectively. Conclusion: This study establishes the state of Sikkim as a new endemic area in India of Lyme disease besides its already reported endemicity in Arunachal Pradesh. No association was conclusively established between symptoms of Lyme and IgG seropositivity emphasizing the need for detailed history taking and clinical suspicion in endemic areas.

Anthelmintic efficacy of Phlogacanthus thyrsiflorus leaf extract on juvenile and adult worms of Hymenolepis diminuta (Cestoda).

The leaves of Phlogacanthus thyrsiflorus are used as an anthelmintic remedy by the tribal communities of upper Assam in India. The present study was carried out to validate the anthelmintic credentials of this plant. Mature and larval Hymenolepis diminuta worms were exposed to varying concentration of methanolic leaf extract of plant and parasites were observed for paralysis and mortality. At the end of the experiment, worms were collected and processed for scanning electron microscopy (SEM) study to observe the effect of extract on tegument of parasite. The in vivo study was carried out in H. diminuta-rat model with 200, 400 and 800 mg/kg concentrations of extract. The in vivo anthelmintic efficacy was assessed by reductions in egg per gram (EPG) and worm counts after necropsy of animals. In vitro studies revealed the earliest mortality of larval worms in 1.05 ± 0.04 h by 30 mg/ml concentration and of adult worms in 2.05 ± 0.08 h. SEM study revealed extensive damage to the suckers, body tegument and microtriches of worms treated with 30 mg/ml concentration of extract. In in-vivo studies, 800 mg/kg dose of extract showed highest efficacy, with 59% and 54.25% reduction in EPG counts and worm count against juvenile worms, and 63.16% and 66.75% reduction in EPG counts and worm counts, respectively against adult worms. Although the effects were comparatively less than the reference drug, nevertheless this study reveals that P. thyrsiflorus possess anthelmintic efficacy and justify its use in traditional medicine against intestinal-worm infections.

A Superparaelectric State in Relaxor Ferroelectric (Sr,Bi)TiO3-Bi(Mg,Ti)O3-Modified BaTiO3 Ceramics to Achieve High Energy Storage Performance.

Dielectric ceramic capacitors are highly regarded for their rapid charge-discharge, high power density, and cyclability in various advanced applications. However, their relatively low energy storage density has prompted intensive research aiming at developing materials with a higher energy density. To enhance energy storage properties, research has focused on modifying ferroelectric materials to induce relaxor ferroelectricity. The present study aims to induce a superparaelectric (SPE) state in relaxor ferroelectrics near room temperature by altering BaTiO3 ferroelectric ceramics using the (Sr,Bi)TiO3-Bi(Mg0.5Ti0.5)O3 system ((1-x)BT-x(SBT-BMT)). X-ray diffraction and Raman spectroscopy analysis demonstrated a shift in the crystal structure from tetragonal to cubic with an increasing x content. Notably, the compositions (except x = 0.1) satisfied the criteria for the SPE state manifestation near room temperature. The x = 0.2 specimen displayed characteristics at the boundary between the relaxor ferroelectric and SPE phases, while x ≥ 0.3 specimens exhibited increased SPE state fractions. Despite reduced maximum polarization, x ≥ 0.3 specimens showcased impressive energy storage capabilities, attributed to the enhanced SPE state, especially for x = 0.3, with impressive characteristics: a recoverable energy density (Wrec) of ~1.12 J/cm3 and efficiency (η) of ~94% at 170 kV/cm applied field. The good stability after the charge-discharge cycles reinforces the significance of the SPE phase in augmenting energy storage in relaxor ferroelectric materials, suggesting potential applications in high-energy density storage devices.

Epidemiology, Molecular Pathogenesis, Immuno-Pathogenesis, Immune Escape Mechanisms and Vaccine Evaluation for HPV-Associated Carcinogenesis.

Human papillomavirus (HPV) is implicated in over 90% of cervical cancer cases, with factors like regional variability, HPV genotype, the population studied, HPV vaccination status, and anatomical sample collection location influencing the prevalence and pathology of HPV-induced cancer. HPV-16 and -18 are mainly responsible for the progression of several cancers, including cervix, anus, vagina, penis, vulva, and oropharynx. The oncogenic ability of HPV is not only sufficient for the progression of malignancy, but also for other tumor-generating steps required for the production of invasive cancer, such as coinfection with other viruses, lifestyle factors such as high parity, smoking, tobacco chewing, use of contraceptives for a long time, and immune responses such as stimulation of chronic stromal inflammation and immune deviation in the tumor microenvironment. Viral evasion from immunosurveillance also supports viral persistence, and virus-like particle-based prophylactic vaccines have been licensed, which are effective against high-risk HPV types. In addition, vaccination awareness programs and preventive strategies could help reduce the rate and incidence of HPV infection. In this review, we emphasize HPV infection and its role in cancer progression, molecular and immunopathogenesis, host immune response, immune evasion by HPV, vaccination, and preventive schemes battling HPV infection and HPV-related cancers.

Role of health literacy and primary health-care access in self-care management of hypertension.

Background: Globally, hypertension is the leading risk factor for men and women and the largest contributor to premature deaths and diseases in India. Health literacy (HL) and health-care access are important determinants for self-care management of hypertension. Objectives: The purpose of this study was to estimate the prevalence of HL, health-care access, and their importance in the self-care management of hypertension. Methods: A community-based cross-sectional study was conducted among 104 known hypertensive patients for 2 months from May to June 2022. Data were collected by face-to-face interviews using a pretested, preformed, and validated questionnaire, and tabulated and analyzed using Microsoft Excel and SPSS version 20 software. Results: Most of the participants (80, 76.9%) have low levels of HL. However, more than half of the (62, 59.6%) participants were satisfied with their access to primary health care. The age of the participants ranged from 38 to 80 years, and half of them (54, 51.9%) were middle-aged adults. The majority (66, 63.5%) of the patients belonged to lower-middle socioeconomic status, and 15.4% (16) were living alone. We found poor HL, and primary health-care access is statistically significantly associated with poor self-care management. Conclusion: Our findings confirm that HL and access to primary health care are crucial factors in the self-care management of hypertension in hypertensive patients.

Anthelmintic evaluation of three ayurvedic formulations: a transmission electron microscopy study in Raillietina sp. (Cestoda).

Ayurveda is one of the ancient traditional medicine systems in India. However, several Ayurvedic medicines lack scientific evidence about their efficacy. This study reports the in vitro anthelmintic effects of three common Ayurvedic formulations, Krimimudgar Ras, Kriminol, and Birangasav on a poultry cestode Raillietina sp., using transmission electron microscopy (TEM). Adult cestodes were exposed to different concentrations of Ayurvedic formulations and the paralyzed parasites from the highest concentration (50 mg/mL) of Ayurvedic formulations, the reference anthelmintic praziquantel (PZQ) together with control were picked up and processed for TEM. The TEM studies of control cestode parasites revealed a normal arrangement of microthrix layer, basal lamina, longitudinal muscle layer, and a normal nucleus and mitochondria. Importantly, the cestodes that were exposed to 50 mg/mL concentration of Krimimudgar Ras revealed the most prominent ultrastructural alterations in the body of parasites in the form of a disrupted microthrix layer, basal lamina, muscle layer and mitochondria. The nucleus also appeared dense and irregular in shape with scattered chromatin and disrupted nuclear membrane. Kriminol-treated worms revealed considerably less damage, whereas Birangasav-treated worms revealed destructive effects in microthrix layer, nucleus and mitochondria. Through the findings of the present study, it can be concluded that of the three common Ayurvedic formulations studied, Krimimudgar Ras causes maximum degree of internal alterations in cestode parasites and thus may be considered as a good anthelmintic agent.

Implementation research: Road map from research to practice.

The challenge today is to make sure that the evidence available gets implemented for betterment of human wellbeing. The research which is closely associated with implementation, challenges and outcome of evidence in real life scenario is Implementation research (IR). The current prespective explains why there is a focus on IR by all icluding researchers, practitioners and policy makers. The approaches and study designs commonly used in the IR have been described. The IR is multi-disciplinary, multilevel and contextual in nature. The outcomes in IR are proximal. The article further describes the ethical issue and the way forward for IR. We need to do capacity building of practitioners, researchers and policymakers in IR.

Expression of miR-145 and miR-18b in Peripheral Blood Samples of Head and Neck Cancer Patients.

Head and neck squamous cell carcinomas (HNSCC) is one of the most prevalent type of cancer known in Indian population. Studies are needed to identify the early biomarkers for HNSCC. MicroRNAs (miRNAs) are non-coding RNA molecules, expression of which can be used as biomarker for early diagnosis of HNSCC. For miRNA profiling total RNA, which also contained small RNAs were isolated from ten HNSCC tissue samples and adjacent control. Purity and concentration of eluted RNA was assessed using the NanoDrop1000® spectrophotometer, Reverse Transcription reaction was carried out with megaplex RT primers of pool A and pool B and the expression of selected miRNAs (miR-143/145 and miR-18a/b) was measured using TaqMan primers specific for mature miRNAs. Our study showed dramatic downregulation in expression of two miRNAs, miR-18b and miR-145 in blood samples of HNSCC patients, which are inhibitor of tumorigenesis and can be targeted as biomarker of HNSCC pathogenesis therefore developing avenues for miRNA role in prognosis and therapeutics. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-023-01119-2.

Model nematodes as a practical innovation to promote high throughput screening of natural products for anthelmintics discovery in South Asia: Current challenges, proposed practical and conceptual solutions.

With the increasing prevalence of anthelmintic resistance in animals recorded globally, and the threat of resistance in human helminths, the need for novel anthelmintic drugs is greater than ever. Most research aimed at discovering novel anthelmintic leads relies on high throughput screening (HTS) of large libraries of synthetic small molecules in industrial and academic settings in developed countries, even though it is the tropical countries that are most plagued by helminth infections. Tropical countries, however, have the advantage of possessing a rich flora that may yield natural products (NP) with promising anthelmintic activity. Focusing on South Asia, which produces one of the world's highest research outputs in NP and NP-based anthelmintic discovery, we find that limited basic research and funding, a lack of awareness of the utility of model organisms, poor industry-academia partnerships and lack of technological innovations greatly limit anthelmintics research in the region. Here we propose that utilizing model organisms including the free-living nematode Caenorhabditis elegans, that can potentially allow rapid target identification of novel anthelmintics, and Oscheius tipulae, a closely related, free-living nematode which is found abundantly in soil in hotter temperatures, could be a much-needed innovation that can enable cost-effective and efficient HTS of NPs for discovering compounds with anthelmintic/antiparasitic potential in South Asia and other tropical regions that historically have devoted limited funding for such research. Additionally, increased collaborations at the national, regional and international level between parasitologists and pharmacologists/ethnobotanists, setting up government-industry-academia partnerships to fund academic research, creating a centralized, regional collection of plant extracts or purified NPs as a dereplication strategy and HTS library, and holding regional C. elegans/O. tipulae-based anthelmintics workshops and conferences to share knowledge and resources regarding model organisms may collectively promote and foster a NP-based anthelmintics landscape in South Asia and beyond.

Discovery of Selective Tertiary Amide Inhibitors of Cyclin-Dependent Kinase 2 (CDK2).

Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and are frequently altered in cancer cells, thereby leading to uncontrolled proliferation. In this context, CDK2 has emerged as an appealing target for anticancer drug development. Herein, we describe the discovery of a series of selective small molecule inhibitors of CDK2 beginning with historical compounds from our ERK2 program (e.g., compound 6). Structure-based drug design led to the potent and selective tool compound 32, where excellent selectivity against ERK2 and CDK4 was achieved by filling the lipophilic DFG-1 pocket and targeting interactions with CDK2-specific lower hinge binding residues, respectively. Compound 32 demonstrated 112% tumor growth inhibition in mice bearing OVCAR3 tumors with 50 mg/kg bis in die (BID) oral dosing.

Occurrence of neuropathic pain and its characteristics in patients with traumatic spinal cord injury.

OBJECTIVES: Assess the occurrence of neuropathic pain in spinal cord injured persons (SCIP) and define the relationship between neuropathic pain with demographic and clinical characteristics in SCIPs. METHODS: This Analytical cross-sectional study was conducted on 104 SCIPs treated at our tertiary care hospital. Initial clinical evaluation was done according to the American Spinal Injury Association (ASIA) impairment scale. A clinical evaluation was done. All subjects were screened with the Leeds Assessment of Neuropathic Symptoms, Signs (LANSS) and DN4 questionnaire for neuropathic pain. The Visual Analogue Scale (VAS) was used to measure the severity of neuropathic pain. Later two groups were created based on the presence and absence of neuropathic pain. RESULTS: The mean age was 35.04 ± 13 years. Fifty-eight patients (55.8%) had a complete injury (ASIA grade A), 41 (39.4%) patients had an incomplete kind of injury (ASIA grade B-D) and 5(4.8%) patients had no deficits (ASIA grade E). Neuropathic pain was present in 77(74.0%) and absent in 27(26.0%) patients. Seventy-one patients (92.2%) experience neuropathic pain in the first year after traumatic SCI. Medicines were a common pain-relieving factor 64(83.1%). CONCLUSION: 74% of patients complained of neuropathic pain, indicating a significant complication. A comprehensive evaluation and treatment are necessary to address it while including variables like the completeness of injury, duration and timing.