Adverse cardiovascular outcomes associated with proton pump inhibitor use after percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for gastroprotection in patients undergoing percutaneous coronary intervention (PCI), who are at increased risk of gastrointestinal bleeding due to antiplatelet therapy. However, emerging evidence suggests that PPIs may adversely impact cardiovascular outcomes. This systematic review and meta-analysis sought to assess the relationship between using PPIs and cardiovascular outcomes in patients following PCI. METHODS: We searched various databases up to March 15, 2024, for observational studies and randomized controlled trials (RCTs) assessing the cardiovascular effects of PPIs in PCI patients. Data were extracted on study characteristics, patient demographics, PPI use, and cardiovascular outcomes. The Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool 2 assessed study quality. Meta-analyses were conducted using a random-effects model using R software version 4.3. RESULTS: A total of 21 studies involving diverse populations and study designs were included. Observational studies suggested a moderate increase in risk for composite cardiovascular diseases (CVD), myocardial infarction (MI), and major adverse cardiac events (MACE) associated with PPI use, with pooled hazard ratios (HRs) of 1.20 (95% CI: 1.093-1.308) for CVD, 1.186 (95% CI: 1.069-1.303) for MI, and 1.155 (95% CI: 1.001-1.309) for MACE. However, RCTs showed no significant link between PPI therapy and negative cardiovascular events (Relative Risk: 1.016, 95% CI: 0.878-1.175). Substantial heterogeneity was observed among observational studies but not RCTs. CONCLUSION: The findings indicate that while observational studies suggest a potential risk of adverse cardiovascular events with post-PCI use of PPI, RCTs do not support this association. Further large-scale, high-quality studies are required to understand the cardiovascular implications of individual PPIs better and optimize patient management post-PCI. This analysis shows the complexity of PPI use in patients with coronary artery diseases and the necessity to balance gastroprotective benefits against potential cardiovascular risks.

Impact of age at first calving on fertility and production performance in Murrah buffalo.

The present study analyses the effect of age at first calving (AFC) on future fertility and productivity in Murrah buffaloes. The data of 314 buffalo heifers of animal farm section, ICAR-CIRB, Hisar were collected over a period of 9 years from 2010 to 2018. The buffalo heifers were categorized into six groups according to the AFC named as 30-35, 36-41, 42-47, 48-53, 54-59 and 60-65 months. The influence of AFC on standard lactation milk (SLMY), peak yield (PY), days in milk (DIM), calving to first service, service per conception, calving to conception interval (CCI) and calving interval till fifth lactation were studied. The study revealed poor productive traits in buffalo heifers calved at younger age (30-35 months) during first parity. The productive value positively corresponded with increase in AFC. During successive lactations, higher mean milk yield (SLMY and PY) was found in groups with 36-41, 42-47 and 48-53 months. The mean number of services per conception was lower in buffalo heifers with 36-41 and 42-47 months following first calving till fifth lactation. Similarly, the said groups had lower mean calving to first service, CCI and CI up to fifth lactation. The survival rate was higher in heifers with AFC 36-41, 42-47, 48-53 and 54-59 months than with AFC 30-35 and 60-65 months. The buffalo heifers with 36-41 and 42-47 months of AFC had higher survival rate and better productive and reproductive traits till fifth parity in the current study. The study concluded that a minimum ideal AFC of 36-41 months yielded the highest productive gain.

Characterization, phytochemical profiling, antioxidant, and cytotoxicity of underutilized medicinal plants and composite flour.

In this investigation, three medicinal plant powders and a composite flour developed from them were analyzed. FESEM/EDS illustrated irregularly shaped particles in the plant powders except for Withania, which had round to oval shape particles. XRD analysis displayed a semi-crystalline nature of powders, except for Asparagus, which showed amorphous behavior. Both methanol and ethanol plant extracts exhibited significantly higher antioxidants, total phenols, and cell viability. Amongst, optimized composite flour (OCF) methanolic extract demonstrated the highest total phenolic content (69.2 ± 0.11 µg GAE/ml), potent cell viability against A549 cells (3.35 ± 0.15% at 50 µg/ml), and strong free-radical scavenging activity (48.89 ± 0.67 at 200 µg/ml). GCMS and FTIR analyses of the methanolic extracts demonstrated the presence of essential phytoconstituents and functional groups. In silico studies of the phytocomponents, ethyl isoallocholate, 3-Deoxy-d-mannoic lactone, and 4,5-Diamino-2-hydroxypyrimidine suggested good binding affinity against BAX, P53, and EGFR proteins with no toxicity and a good drug score.

Exploring the twin potential of nanostructured TiO2:SeO2 as a promising visible light photocatalyst and selective fluorosensing platform.

The present work describes the development of TiO2/SeO2 nanostructure as a potential candidate for visible light photocatalysis as well as selective fluorophore for the sensing of picric acid. The obtained nanostructure consists of uniform globular nanoparticles having approximate size of 170 nm and possess an optical band gap of 2.33 eV with absorption maxima at 473 nm. The photocatalyst was able to achieve 90.34% degradation efficiency for 2, 4-dichlorophenol (2,4-DCP) with rate constant of 0.0046 min-1 in the visible region. Further the nanostructure was able to serve as a selective fluorophore for sensing of Picric acid portraying more than 95% of fluorescence quenching when the concentration of PA is 10-4 M. Theoretical calculations indicate the interaction of organic pollutants with the nanostructure and reveal that both picric acid (- 66.21 kcal/mol) and 2,4-DCP (- 12.31 kcal/mol) possess more negative binding energy values demonstrating a strong interaction of both with the nanostructure, making it suitable for the degradation as well as sensing of organic pollutants. Thus this study explains the potential of prepared catalyst for waste water treatment.

Academic Neurosurgery in Nigeria- Past, Present, and Future: A Review.

Nigeria's neurosurgical field faces profound challenges, including a critically low neurosurgeon-to-patient ratio and significant migration of medical professionals to developed countries. High costs, low socioeconomic status, and the urban-centric location of neurosurgical centers impede access to care. Key barriers to service delivery include lack of manpower, insufficient emergency care, limited imaging modalities, inadequate operative equipment, and ineffective political and administrative policies. Neurotrauma is the primary reason for neurosurgical intervention but is poorly managed due to delayed access and insufficient guidelines. The neurosurgical education system is strained by limited training capacity and the absence of subspecializations, restricting specialized care. Research output is low, hindered by limited infrastructure, lack of databases, insufficient funding, and minimal international collaboration. To address these issues, it is critical to enhance the imaging capabilities, ensure the availability of operative equipment, and establish effective policies for task sharing and communication at different levels of care. Other approaches include expanding training capacity, particularly in rural areas, implementing a uniform match system for residency, addressing gender disparities, and utilizing dual practice to ensure adequate compensation for neurosurgeons. Furthermore, stakeholders should develop subspecialization programs in areas such as neurovascular, neuro-oncology, pediatric neurosurgery, and minimally invasive neurosurgery to expand service scope. To transform the neurosurgical research landscape, efforts should be made to establish electronic medical databases, foster international collaborations to ensure funding, and make research mandatory for accreditation renewal to ensure continuous academic contribution.

The emerging challenge of FLiRT variants: KP.1.1 and KP.2 in the global pandemic landscape.

The SARS-CoV-2 virus has undergone substantial evolution, leading to emergence of new FLiRT variants characterized by specific spike mutations-F to L at position 456 and R to T at position 346-enhancing their transmissibility and immune evasion capabilities. Particularly, KP.2 shows a significant increase in cases in the U.S., indicating a potential shift in the pandemic landscape due to its greater ability to evade vaccine-induced immunity and its higher effective reproduction number compared to JN.1. This evolving scenario underscores the need for continuous monitoring and adaptive response strategies to address the challenges posed by these new variants. This abstract examines the emergence of FLiRT variants KP.2 and KP1.1, descendants of the Omicron JN.1 variant, as they draw global attention amidst the ongoing COVID-19 pandemic.

Investigating the relationship of government revenue and expenditure on economic growth using a generalized method of moments: Does state-level panel ensure sustainable growth?

The current research project investigates the correlation between economic growth, government spending, and public revenue in seventeen Indian states spanning the years 1990 to 2020. An analysis of the relationship between key fiscal policy variables and economic growth was conducted utilising a panel data approach, the Generalised Method of Moments (GMM), and fully modified Ordinary Least Squares (FMOLS & DOLS) estimation. In our investigation, we assessed the impacts of non-tax revenue, development plan expenditure, tax revenue, and development non-plan expenditure on (i) the net state domestic product (NSDP) and (ii) the NSDP per capita. The findings indicate that the selected fiscal variables are significantly related. The results indicate that expeditious expansion of the fiscal sector is obligatory to stimulate economic growth in India and advance the actual development of the economies of these states.

Prevalence of human papillomavirus in head and neck cancer patients in India: a systematic review and meta-analysis.

BACKGROUND: Human papillomavirus (HPV) is increasingly recognized as a significant risk factor in the development of head and neck cancers (HNCs), with varying prevalence and impact. This study aims to systematically review and analyze the prevalence of HPV in HNCs in India, providing insights into regional variations. METHODS: A comprehensive literature search was carried out using PubMed, Embase, and Web of Science up to November 10, 2023. Inclusion criteria focused on original research reporting HPV-positive cases among HNC patients in India. We used Nested-Knowledge software, for screening, and data extraction. The modified Newcastle-Ottawa Scale was used for quality assessment of included studies. We pooled the prevalence of HPV among HNC patients and performed a random-effects model meta-analysis using R software (version 4.3). RESULTS: The search yielded 33 studies, encompassing 4654 HNC patients. The pooled prevalence of HPV infection was found to be 33% (95% CI: 25.8-42.6), with notable heterogeneity (I² = 95%). Analysis of subgroups according to geographical location indicated varying prevalence rates. Specifically, the prevalence was 47% (95% CI: 32.2-62.4) in the eastern regions and 19.8% (95% CI: 10.8-33.4) in the western regions. No evidence of publication bias was detected. CONCLUSION: The observed considerable regional disparities on the prevalence of HPV in HNC patients in India emphasizes the need for integrated HPV vaccination and screening programs in public health strategies. The findings underline the necessity for further research to explore regional variations and treatment responses in HPV-associated HNCs, considering the impact of factors such as tobacco use and the potential benefits of HPV vaccination.

Inequalities in cardiovascular disease among elderly Indians: A gender perspective analysis using LASI wave-I (2017-18).

BACKGROUND: While Cardiovascular disease (CVD) affects both men and women, emerging evidence suggests notable gender differentials in disease prevalence. This study aims to explore and analyse the gender differentials in CVD disease prevalence in India. METHODS: The present study utilizes data from first wave of the nationally representative survey "Longitudinal Ageing Study in India" (LASI, WAVE-I, 2017-18) with the eligible sample size of 31,464 individuals aged 60 years and above. Logistic regression analysis was used to understand risk of CVD by demographic characteristics. Factors contribution to gender differences in CVD prevalence was examined using a non-linear Fairlie decomposition. RESULTS: The prevalence of CVD was lower in men (31.06%) compared to women (38.85%). Women have a 33% higher likelihood of CVD compared to men (OR: 1.33; 95% CI: 1.25-1.42). Lack of education also confers a lower risk, more pronounced in women with no schooling (OR: 0.81; 95% CI: 0.7-0.94) compared to men (OR: 0.52; 95% CI: 0.47-0.58). Morbidity influences CVD presence more among women than men, with individuals suffering from three or more diseases having markedly increased odds (Men: OR: 3.89; 95% CI: 3.54-4.3, Women: OR: 6.97; 95% CI: 6.48-10.11). Smoking accounted increase in (20.52%) the gender gap while years of schooling dramatically lessened the gender gap (-46.30%). CONCLUSION: Result show gender differential in CVD prevalence and underlying risk factors, underscoring the need for gender-specific preventive strategies and interventions. Our findings highlight the importance of refined approach to cardiovascular health that considers the complex interplay of biological, social, and environmental determinants.

Cardiovascular impact of post-traumatic stress disorder: A systematic review and meta-analysis.

BACKGROUND: Post-traumatic stress disorder (PTSD) is increasingly recognized for its effects beyond mental health, with emerging evidence suggesting a significant association with cardiovascular diseases (CVD). This systematic review and meta-analysis aimed to synthesize available evidence on the association between PTSD and various cardiovascular outcomes. METHODS: We conducted a comprehensive literature search in databases until March 15, 2024. Studies were included if they were observational in design and assessed the association between PTSD and cardiovascular outcomes. Data were extracted on study characteristics, participant demographics, PTSD assessment, cardiovascular outcomes, and effect estimates. Meta-analyses were performed using random-effects models, and heterogeneity was assessed using the I² statistic. All statistical analyses were conducted using R software version 4.3. RESULTS: Twenty studies met the inclusion criteria, encompassing a total of over 335,000 participants. The pooled analyses demonstrated a statistically significant increased risk of any CVD (HR = 1.417, 95 % CI: 1.313-1.522), MI (HR = 1.415, 95 % CI: 1.331-1.500), and stroke (HR = 2.074, 95 % CI: 1.165-2.982) associated with PTSD. Substantial heterogeneity was observed across the studies for stroke and MACE, and evidence of publication bias was noted. CONCLUSION: This meta-analysis confirms a significant association between PTSD and an increased risk of several cardiovascular outcomes, indicating the importance of integrating cardiovascular risk management with psychiatric care for PTSD patients to mitigate the heightened risk of CVDs. Future research should focus on exploring the underlying mechanisms and potential interventions to manage both PTSD and its associated cardiovascular risks effectively.

Efficacy of stem cell therapy in patients with chronic liver disease: an umbrella review of systematic reviews.

BACKGROUND: Stem cell therapy offers promising benefits like modulating immune responses, reducing inflammation, and aiding liver regeneration. This umbrella review seeks to compile evidence from systematic reviews to assess the efficacy of stem cell therapy for improving liver function and survival rates in chronic liver disease patients. METHODS: We searched electronic databases up to February 15, 2024. The selection process focused on systematic reviews comparing stem cell therapy with standard care or a placebo. The primary outcomes evaluated were changes in liver enzymes, the MELD score, and survival rates. Nested Knowledge software was utilized for screening and data extraction. All statistical analyses were performed using R software, version 4.3. RESULTS: Our umbrella review included 28 systematic reviews. The meta-analysis showcased a notable improvement in survival rates with a pooled RR of 1.487 (95% CI: 1.281 to 1.727). In non-randomized studies, albumin levels exhibited an SMD of 0.786 (95% CI: 0.368 to 1.204), indicating positive therapeutic effects. For ALT, the meta-analysis revealed a decrease in levels with an SMD of -0.499 (95% CI: -0.834 to -0.164), and for AST, an overall SMD of -0.362 (95% CI: -0.659 to -0.066) was observed, suggesting hepatoprotective effects. No significant changes were observed in total bilirubin levels and MELD scores in RCTs. CONCLUSION: Stem cell therapy exhibits potential as a novel treatment for chronic liver diseases, as it has demonstrated improvements in survival rates and certain liver function markers. More high-quality RCTs are needed in the future to fully ascertain the efficacy of stem cell therapy in this patient population.

Buparvaquone Induces Ultrastructural and Physiological Alterations Leading to Mitochondrial Dysfunction and Caspase-Independent Apoptotic Cell Death in Leishmania donovani.

Leishmaniasis is a neglected tropical disease (endemic in 99 countries) caused by parasitic protozoa of the genus Leishmania. As treatment options are limited, there is an unmet need for new drugs. The hydroxynaphthoquinone class of compounds demonstrates broad-spectrum activity against protozoan parasites. Buparvaquone (BPQ), a member of this class, is the only drug licensed for the treatment of theileriosis. BPQ has shown promising antileishmanial activity but its mode of action is largely unknown. The aim of this study was to evaluate the ultrastructural and physiological effects of BPQ for elucidating the mechanisms underlying the in vitro antiproliferative activity in Leishmania donovani. Transmission and scanning electron microscopy analyses of BPQ-treated parasites revealed ultrastructural effects characteristic of apoptosis-like cell death, which include alterations in the nucleus, mitochondrion, kinetoplast, flagella, and the flagellar pocket. Using flow cytometry, laser scanning confocal microscopy, and fluorometry, we found that BPQ induced caspase-independent apoptosis-like cell death by losing plasma membrane phospholipid asymmetry and cell cycle arrest at sub-G0/G1 phase. Depolarization of the mitochondrial membrane leads to the generation of oxidative stress and impaired ATP synthesis followed by disruption of intracellular calcium homeostasis. Collectively, these findings provide valuable mechanistic insights and demonstrate BPQ's potential for development as an antileishmanial agent.

Cooperative STAT3-NFkB signaling modulates mitochondrial dysfunction and metabolic profiling in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) continues to pose a significant health challenge and is often diagnosed at advanced stages. Metabolic reprogramming is a hallmark of many cancer types, including HCC and it involves alterations in various metabolic or nutrient-sensing pathways within liver cells to facilitate the rapid growth and progression of tumours. However, the role of STAT3-NFκB in metabolic reprogramming is still not clear. APPROACH AND RESULTS: Diethylnitrosamine (DEN) administered animals showed decreased body weight and elevated level of serum enzymes. Also, Transmission electron microscopy (TEM) analysis revealed ultrastructural alterations. Increased phosphorylated signal transducer and activator of transcription-3 (p-STAT3), phosphorylated nuclear factor kappa B (p-NFκß), dynamin related protein 1 (Drp-1) and alpha-fetoprotein (AFP) expression enhance the carcinogenicity as revealed in immunohistochemistry (IHC). The enzyme-linked immunosorbent assay (ELISA) concentration of IL-6 was found to be elevated in time dependent manner both in blood serum and liver tissue. Moreover, immunoblot analysis showed increased level of p-STAT3, p-NFκß and IL-6 stimulated the upregulation of mitophagy proteins such as Drp-1, Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK-1). Meanwhile, downregulation of Poly [ADP-ribose] polymerase 1 (PARP-1) and cleaved caspase 3 suppresses apoptosis and enhanced expression of AFP supports tumorigenesis. The mRNA level of STAT3 and Drp-1 was also found to be significantly increased. Furthermore, we performed high-field 800 MHz Nuclear Magnetic Resonance (NMR) based tissue and serum metabolomics analysis to identify metabolic signatures associated with the progression of liver cancer. The metabolomics findings revealed aberrant metabolic alterations in liver tissue and serum of 75th and 105th days of intervention groups in comparison to control, 15th and 45th days of intervention groups. Tissue metabolomics analysis revealed the accumulation of succinate in the liver tissue samples, whereas, serum metabolomics analysis revealed significantly decreased circulatory levels of ketone bodies (such as 3-hydroxybutyrate, acetate, acetone, etc.) and membrane metabolites suggesting activated ketolysis in advanced stages of liver cancer. CONCLUSION: STAT3-NFκß signaling axis has a significant role in mitochondrial dysfunction and metabolic alterations in the development of HCC.

Spatio-temporal epidemiology and associated indicators of COVID-19 (wave-I and II) in India.

The spatio-temporal distribution of COVID-19 across India's states and union territories is not uniform, and the reasons for the heterogeneous spread are unclear. Identifying the space-time trends and underlying indicators influencing COVID-19 epidemiology at micro-administrative units (districts) will help guide public health strategies. The district-wise daily COVID-19 data of cases and deaths from February 2020 to August 2021 (COVID-19 waves-I and II) for the entire country were downloaded and curated from public databases. The COVID-19 data normalized with the projected population (2020) and used for space-time trend analysis shows the states/districts in southern India are the worst hit. Coastal districts and districts adjoining large urban regions of Mumbai, Chennai, Bengaluru, Goa, and New Delhi experienced > 50,001 cases per million population. Negative binomial regression analysis with 21 independent variables (identified through multicollinearity analysis, with VIF < 10) covering demography, socio-economic status, environment, and health was carried out for wave-I, wave-II, and total (wave-I and wave-II) cases and deaths. It shows wealth index, derived from household amenities datasets, has a high positive risk ratio (RR) with COVID-19 cases (RR: 3.577; 95% CI: 2.062-6.205) and deaths (RR: 2.477; 95% CI: 1.361-4.506) across the districts. Furthermore, socio-economic factors such as literacy rate, health services, other workers' rate, alcohol use in men, tobacco use in women, overweight/obese women, and rainfall have a positive RR and are significantly associated with COVID-19 cases/deaths at the district level. These positively associated variables are highly interconnected in COVID-19 hotspot districts. Among these, the wealth index, literacy rate, and health services, the key indices of socio-economic development within a state, are some of the significant indicators associated with COVID-19 epidemiology in India. The identification of district-level space-time trends and indicators associated with COVID-19 would help policymakers devise strategies and guidelines during public health emergencies.

Recellularization of Acellular Xeno Kidney Scaffold: An In Vivo Method to Generate Bioartificial Kidney.

A significant hurdle for kidney tissue engineering is reproducing the complex three-dimensional structure of the kidney. In our study, a stepwise approach of generating a reproducible Xeno kidney scaffold from a goat kidney is described, which can be implanted and recellularized by host cells. We have proposed a combination of sodium dodecyl sulfate and Triton-X-100-based protocol to generate a reproducible Xeno kidney scaffold, which was then analyzed by histology, DNA quantification, SEM, and renal angiography. Further, a small portion from the cortico-medullar region of the acellular scaffold was implanted in the rat's kidney subcapsular pocket for a period of 1 month, to check the recruitment of host cells into the scaffold. Post implantation, the extracellular matrix of the scaffold was well preserved and it did not induce any damage or inflammation in the native kidney. Implantation of the Xeno scaffold resulted in apparent early vascularization which helped in the recruitment of the host cells, which was characterized by histology, immunohistochemistry, and scanning electron microscopy. Implanted Xeno scaffold showed AQP-1, Nephrin, α-SMA, and VEGF expression in proximal tubules and renal glomerulus. Importantly, Ki-67 and WTAP-expressing cells were also observed near proximal tubules suggesting a high level of proliferation in the scaffold. Thus, showing the potential of Xeno kidney development that can be recellularized by the host cell to engineer into a functional kidney.

Ethyl Isothiocyanate as a Novel Antifungal Agent Against Candida albicans.

In the recent years, occurrence of candidiasis has increased drastically which leads to significant mortality and morbidity mainly in immune compromised patients. Glucosinolate (GLS) derivatives are reported to have antifungal activities. Ethyl isothiocyanate (EITC) and its antifungal activity and mechanism of action is still unclear against Candida albicans. The present work was designed to get a mechanistic insight in to the anti-Candida efficacy of EITC through in vitro and in vivo studies. EITC inhibited C. albicans planktonic growth at 0.5 mg/ml and virulence factors like yeast to hyphal form morphogenesis (0.0312 mg/ml), adhesion to polystyrene surface (0.0312 mg/ml) and biofilm formation (developing biofilm at 2 mg/ml and mature biofilm at 0.5 mg/ml) effectively. EITC blocked ergosterol biosynthesis and arrested C. albicans cells at S-phase. EITC caused ROS-dependent cellular death and nuclear or DNA fragmentation. EITC at 0.0312 mg/ml concentration regulated the expression of genes involved in the signal transduction pathway and inhibited yeast to hyphal form morphogenesis by upregulating TUP1, MIG1, and NRG1 by 3.10, 5.84 and 2.64-fold, respectively and downregulating PDE2 and CEK1 genes by 15.38 and 2.10-fold, respectively. EITC has showed haemolytic activity at 0.5 mg/ml concentration. In vivo study in silk worm model showed that EITC has toxicity to C. albicans at 0.5 mg/ml concentration. Thus, from present study we conclude that EITC has antifungal activity and to reduce its MIC and toxicity, combination study with other antifungal drugs need to be done. EITC and its combinations might be used as alternative therapeutics for the prevention and treatment of C. albicans infections.