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.

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.

Comparing outcomes of an 'early' versus 'late' diagnosis of cardiac sarcoidosis following a baseline presentation of high-grade atrioventricular block.

BACKGROUND: There is a paucity of evidence on impact of a delay in Cardiac Sarcoidosis (CS) diagnosis after high-grade atrioventricular-block (AVB) and this study aims to fill this void. METHODS: Consecutive CS patients (n = 77) with high grade AVB referred to one specialist hospital in London between February 2007 to February 2023 were retrospectively reviewed. The median time from AVB to diagnosing CS (112 days) was used to define the Early (n = 38) and Late (n = 39) cohorts. The primary endpoint was a composite of all-cause mortality, cardiac transplantation, ventricular arrhythmic events or heart failure hospitalisation. Secondary endpoints included difference in maintenance prednisolone dose, need for cardiac device upgrade and device complications. RESULTS: The mean age of the cohort was 54.4 (±10.6) years of whom 64 % were male and 81 % Caucasian. After a mean follow up of 54.9 (±45.3) months, the primary endpoint was reached by more patients from the Late cohort (16/39 vs. 6/38, p = 0.02; multivariable HR 6.9; 95 %CI 1.5-32.2, p = 0.01). Early Group were more likely to have received an Implantable Cardioverter Defibrillator or Cardiac Resynchronisation Therapy-defibrillator as index device after AVB (19/38 vs. 6/39; p < 0.01) and had fewer device upgrades (19/38 vs. 30/39, p = 0.01) and a trend towards fewer device complications (1 vs. 5, p = 0.20). The maintenance dose of prednisolone was significantly higher in Late Group [20.7(±9.7) mg vs. 15.3(±7.9) mg, p = 0.02]. CONCLUSION: A late diagnosis of CS was associated with more adverse events, a greater probability of needing a device upgrade and required higher maintenance steroid dose.

CHARACTERISTICS AND OUTCOMES OF HOSPITALISED PATIENTS WITH HEART FAILURE AND SARCOIDOSIS: A PROPENISTY-MATCHED ANALYSIS OF THE NATIONWIDE READMISSIONS DATABASE 2010-2019.

BACKGROUND: Sarcoidosis is associated with a poor prognosis. There is a lack of data examining the outcomes and readmission rates of sarcoidosis patients with heart failure (SwHF) and without heart failure (SwoHF). We aimed to compare the impact of non-ischemic heart failure on outcomes and readmissions in these two groups. METHODS: The US Nationwide Readmission Database was queried from 2010-2019 for SwHF and SwoHF patients identified using the International Classification of Diseases, Ninth and Tenth Editions. Those with ischemic heart disease were excluded, and both cohorts were propensity matched for age, gender, and Charlson Comorbidity Index (CCI). Clinical characteristics, length of stay, adjusted healthcare-associated costs, 90-day readmission and mortality were analyzed. RESULTS: We identified 97,961 hospitalized patients (median age 63 years, 37.9% male) with a diagnosis of sarcoidosis (35.9% SwHF vs. 64.1% SwoHF). On index admission, heart failure patients had higher prevalences of atrioventricular block (3.3% vs. 1.4%, p<0.0001), ventricular tachycardia (6.5% vs. 1.3%, p<0.0001), ventricular fibrillation (0.4% vs. 0.1%, p<0.0001) and atrial fibrillation (22.1% vs. 7.5%, p<0.0001). SwHF patients were more likely to be readmitted (hazard ratio 1.28, p<0.0001), had higher length of hospital stay (5 vs. 4 days, p<0.0001), adjusted healthcare-associated costs ($9,667.0 vs. $9,087.1, p<0.0001) and mortality rates on readmission (5.1% vs. 3.8%, p<0.0001). Predictors of mortality included heart failure, increasing age, male sex, higher CCI and liver disease. CONCLUSION: SwHF is associated with higher rates of arrhythmia at index admission, as well as greater hospital cost, readmission and mortality rates compared to those without heart failure.

Role of serial 18F-fludeoxyglucose positron emission tomography in determining the therapeutic efficacy of immunosuppression and clinical outcome in patients with cardiac sarcoidosis.

BACKGROUND: Myocardial inflammation and perfusion defects detected by 18F-fludeoxyglucose (FDG) and Rubidium-82 positron emission tomography (PET) may be associated with ventricular arrhythmias (VAs) in cardiac sarcoidosis (CS). The role of serial quantitative PET in determining the effect of treatment on myocardial inflammation and clinical outcomes is yet to be defined. METHODS: Newly diagnosed CS patients with active myocardial inflammation (maximum standardised uptake value (SUVmax) ≥ 2.5) were treated with immunosuppression, then underwent repeat FDG-PET, Rubidium-82, and echocardiographic imaging 6-12 months later. Serial changes in SUVmax, SUVmean, inflammatory extent, perfusion defect (PD) extent, metabolism/perfusion mismatch extent, global cardiac metabolic activity, and left ventricular ejection fraction (LVEF) were assessed. The primary endpoint was a composite of all-cause mortality, serious VA and heart-failure (HF) hospitalisation. Event data were recorded from the date of the second FDG-PET. RESULTS: The study population consisted of 113 patients (66% male, age: 55 ± 11 years, LVEF: 54 ± 13%). SUVmax reduced from 4.5 (interquartile range: 3.3-7.1) to 2.7 (2.2-3.6). Overall, 94 (83%) patients saw serial reduction in SUVmax, with 42 (37%) demonstrating complete response (SUVmax <2.5). Following a median of 46 (25-57) months, 28 (25%) patients reached the endpoint (8 deaths, 17 VAs, and 3 HF hospitalisations). PD extent (Hazard ratio 1.03, 95% confidence interval: 1.01-1.05; p = 0.035) was a significant predictor of outcome following treatment, even after accounting for LVEF and change in SUVmean. The risk of adverse events was the greatest in those with a pre-treatment or post-treatment PD extent of >10%. CONCLUSION: In our cohort with active CS, following a treatment-induced reduction in myocardial inflammation, PD extent was the main predictor of adverse events.

Clinical Investigation of Large Volume Subcutaneous Delivery up to 25 mL for Lean and Non-Lean Subjects.

PURPOSE: To evaluate the clinical feasibility and tolerability of large volume subcutaneous delivery at different injection depths for lean and non-lean subjects. METHODS: A single-center, randomized, subject-blinded, crossover study in 62 healthy subjects was conducted to evaluate delivery of a 10-cP solution containing hyaluronic acid. Subjects were separated into lean and non-lean cohort by SC thickness. A syringe pump was used to study the effect of different volumes (5, 12, 25 mL) of a viscous placebo solution and needle lengths (6, 9 and 12 mm) delivered at 0.5 mL/min. RESULTS: Across all treatments, injection sites were observed to have negligible leakage, ~34 kPa of back pressure, and VAS of mild pain with higher pain from needle insertion than during injection. While mild to moderate erythema was the most frequently reported ISR and edema was most prominent for 25 mL injections, all ISRs were resolved within 4 hours post injection. Subjects were unbothered by ISRs across all treatments and rated them as low distress scores (average 1.0-1.5 out of 6). CONCLUSION: SC injection of 25 mL is feasible and tolerable using a low-pain formulation for abdomen injection irrespective of subcutaneous thickness and injection depths at a delivery rate of 0.5 mL/min.

Characterisation and management of expected and unexpected urgent findings from positron emission tomography with 18F-fluorodeoxyglucose integrated with computed tomography in cardiovascular disease.

BACKGROUND: Cardiac 18F-fluorodeoxyglucose (FDG)-PET-CT plays an important role in the assessment of cardiovascular diseases. Effective management of urgent scan findings facilitates optimal patient care. METHODS: We characterised the management of urgent, expected and unexpected findings in patients referred for cardiac [18F]fluorodeoxyglucose integrated with computed tomography (FDG-PET-CT) at the Royal Brompton Hospital (United Kingdom). Urgent findings are escalated by the reporting physicians/radiologists raising RadAlert notifications to the referring clinician. We characterised the indications and time to management (TTM) between the RadAlert and the resulting management. As controls, we characterised the TTM of 33 urgent findings identified before the RadAlert system was implemented. RESULTS: Of the 1497 consecutive FDG-PET-CT scans screened (April 2021 to February 2023), 93 RadAlerts were suitable for analysis (TTM 7 days [interquartile range: 2-14]). Expected urgent findings included active cardiac sarcoidosis (56%; TTM 8 days [5-18]), heart transplant rejection (12%; 6 ± 4 days), infective endocarditis (9%; 2 days [1-12]), cardiac device infections (5%; 1 day [0-2]), acute myocarditis (2%; 5 and 14 days) and epicardial mass (1%; 1 day). TTM did not differ significantly between indications (P = 0.06). RadAlert cases had significantly shorter TTM than controls without RadAlert, P = 0.001. After the RadAlerts, 81% of patients had clinical reviews, and 55% had escalation of medical/surgical therapies. Unexpected findings (total N = 45; median TTM 6 days [1-10]) included malignancies (N = 3), infections (N = 2), pneumothorax (N = 1), benign diagnosis (N = 30), unclear diagnosis (N = 5) and 4 findings disappeared on repeat imaging. CONCLUSIONS: Cardiac FDG-PET-CT identifies expected and unexpected findings in a range of cardiovascular diseases. Serious, unexpected findings are rare and can be effectively escalated by the RadAlert system.

Does Unidirectional Polyglycolide Caprolactone Barbed Suture Have Improved Outcomes Over Non-barbed Suture When Applied for Intra-oral Incision Closure?

Purpose: The choice of wound closure material may influence the clinical outcomes of intra-oral incision closure. Studies evaluating the application of barbed suture in the oral cavity are scarce. Hence, the present study was carried out with the aim to monitor and compare the efficacy and ease of handling of monofilament polyglycolide caprolactone (PGCL) unidirectional barbed and non-barbed sutures used for intra-oral incision closure in patients undergoing transalveolar extraction of impacted mandibular third molar and mandible fracture open reduction internal fixation. Methods: A prospective randomized open label study was carried out among subjects requiring intra-oral incision closure following mandibular third molar extraction and isolated mandible fracture fixation. The difficulty index of the impacted third molars was evaluated pre-operatively. Subjects were randomized to receive either 3-0 monofilament PGCL unidirectional barbed or non-barbed sutures. Incision closure time and ease of suture handling were recorded intra-operatively. Post-operatively, patients were monitored for incision healing using the Hollander wound evaluation scale (HWES) and intensity of pain using visual analog scale (VAS) on post-operative days 1, 3 and 7. Data analysis involved descriptive statistics, Chi-square, unpaired t test and multivariate analysis using the IBM SPSS-PC software (v.25.0). Results: A total of 60 subjects completed the study protocol, who were randomized into two groups (n1 = n2 = 30), comparable in terms of age, gender and treatment (TAE = 51; ORIF = 9) received. The incision healing outcomes were significantly better (p = 0.016) with barbed suture using HWES on day 7. The mean closure time using barbed suture (142.50 ± 34.803 secs) was significantly (p = 0.001) shorter than that with non-barbed suture (204.56 ± 52.94 secs). The mean VAS for the barbed suture (0.97 ± 1.89) was less (p = 0.015, 95% CI) than the non-barbed suture (2.50 ± 2.91) on day 3. The suture handling ease was comparable between the two groups. Conclusion: Monofilament unidirectional PGCL barbed suture has merits over the non-barbed suture with regards to superior post-operative incision healing, reduced incision closure time (43%), lower post-operative pain and comparable ease of suture handling. Hence, knotless PGCL suture is a promising alternative for intra-oral surgical incision closure in oral and maxillofacial surgery.

Grossing to reporting of Wilms tumor with emphasis on proper sampling in treatment-naive and postchemotherapy specimens and their clinicopathological correlation with outcome.

Context: Emphasis on grossing to reporting for the assessment of histopathological parameters predicting outcomes in Wilms tumor. Aims: To analyze various clinicopathological parameters that effect outcomes in treatment naïve and post chemotherapy Wilms tumor specimens. Settings and Design: This was a retrospective observational study. Subjects and Methods: All patients diagnosed with Wilms tumor between 2012 and 2018 at our institute will be included with their clinical findings, laboratory reports, and radiological findings. The patients will be categorized into two groups based on treatment protocol (Society of Pediatric Oncology (SIOP) or the National Wilms Tumor Study Group/Children's Oncology Group (COG) guidelines) used. Details of Grossing and reporting protocols used for the in pre treatment and post treatment specimens will be analyzed. Follow-up till December 2020 will be analyzed. Statistical Analysis Used: Chi-square and Fisher's exact tests were used for statistical analysis. Results: A total of 36 patients with the diagnosis of Wilms tumor were included in the present study. The mean age of presentation was 3.9 ± 0.7 years, and males were more common than females. Most of them presented as abdominal mass and few with isolated hematuria. Twenty-six (72%) patients were treated under SIOP protocol with preoperative neoadjuvant chemotherapy. Ten patients underwent upfront surgery as per COG protocol. In SIOP group patients, the mean tumor size was 9.3cm. Forty percent (n = 10) we mixed histological type followed by blastemal type constituting (32%, n = 8). Regressive and epithelial histological types constituted 16% (n = 4) and 12% (n = 3), respectively. In the SIOP group 72% (n = 19) had no anaplasia and 28% (n = 7) had anaplasia. Fifty seven percent (n = 15) cases were Stage I, followed by 26.9% n = 7) and 11.5% (n = 3) being Stage II and Stage III, respectively. Ten patients underwent upfront surgery as per COG protocol. The mean tumor size among this group was 8 cm ranging from 7 cm to 11 cm. Eight (80%) cases had favorable histology and two cases showed focal anaplasia. Heterologous differentiation is seen in 3 (70%). Out of the 10 cases, one case was Stage I, six were Stage 2, one was Stage III, and two were clinical Stage IV. None of the cases showed either vessel or lymph node metastasis. All the patients received adjuvant chemotherapy postsurgery and were followed up till December 2020 for (at least 3 years). Of 25 patients in the SIOP group, 18 (72%) had complete remission with no radiological evidence of residual disease. Of the 10 patients in the COG group, 6 (70%) had complete remission. Conclusions: Histopathological evaluation of Wilms tumor is a critical aspect in the management of Wilms tumor, as tumor characteristics are different in the tumors treated under SIOP and COG protocols, which will ultimately affect the prognostic risk stratification. This necessitates the knowledge of the important grossing and reporting of these tumors under the two protocols.

Racial disparities among patients with cardiac sarcoidosis and arrhythmias in the United States: A propensity matched-analysis from the national inpatient sample database 2016-2020.

BACKGROUND: Cardiac sarcoidosis (CS) is frequently associated with conduction abnormalities and arrhythmias. In this study, we aim to evaluate racial disparities in the frequency of arrhythmias, and associated co-morbidities, among patients with CS. METHODS: White and African American (AA) patients diagnosed with CS were identified and compared from the 2016-2020 National Inpatient Sample (NIS) database whilst adjusting for confounders via logistic regression models. RESULTS: A total of 7,935 patients with CS were included in the study. The propensity-matched sample comprised of 5,570 patients, of whom 2,785 were White and 2,785 were AA. AA patients had a longer mean length of hospital stay (LOS) (7.84 vs. 6.94, p<0.01), a higher mean Charlson Comorbidity Index (CCI) score (3.10 vs. 2.84, p<0.01), and significantly higher incidences of cardiogenic shock [(9.2% vs 6.3%, p<0.01), aOR 1.45 (95% CI 1.17-1.78), p<0.01] and acute kidney injury (AKI) [(34.3% vs. 26.9%, p<0.01), aOR 1.41 (95% CI 1.24-1.61), p<0.01]. From an arrhythmia perspective, AA CS patients were shown to have a lower frequency of: (1) ventricular tachycardia (32.5% vs. 37.9%, p<0.01), (2) ventricular fibrillation (5.4% vs.7.2%, p<0.01), (3) first-degree AV block (1.8% vs. 4.1%, p<0.01), (4) complete AV block (6.3% vs. 14.2%, p<0.01), and (5) atrial fibrillation (31.8% vs. 34.8%, p=0.016) when compared to Whites with CS. Mortality remained higher for AAs (3.8% vs. 2.7%, p=0.024). CONCLUSION: Our study demonstrates a higher incidence of cardiac arrhythmias among White patients but a higher incidence of cardiogenic shock, AKI, mean LOS, and mortality among AA patients with cardiac sarcoidosis.

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.

Sarcoidosis Associated Pulmonary Hypertension.

In patients with sarcoidosis, the development of pulmonary hypertension is associated with significant morbidity and mortality. The global prevalence of sarcoidosis-associated pulmonary hypertension (SAPH) reportedly ranges between 2.9% and 20% of sarcoidosis patients. Multiple factors may contribute to the development of SAPH, including advanced parenchymal lung disease, severe systolic and/or diastolic left ventricular dysfunction, veno-occlusive or thromboembolic disease, as well as extrinsic factors such as pulmonary vascular compression from enlarged lymph nodes, anemia, and liver disease. Early diagnosis of SAPH is important but rarely achieved primarily due to insufficiently accurate screening strategies, which rely entirely on non-invasive tests and clinical assessment. The definitive diagnosis of SAPH requires right heart catheterization (RHC), with transthoracic echocardiography as the recommended gatekeeper to RHC according to current guidelines. A 6-min walk test (6MWT) had the greatest prognostic value in SAPH patients based on recent registry outcomes, while advanced lung disease determined using a reduced DLCO (<35% predicted) was associated with reduced transplant-free survival in pre-capillary SAPH. Clinical management involves the identification and treatment of the underlying mechanism. Pulmonary vasodilators are useful in several scenarios, especially when a pulmonary vascular phenotype predominates. End-stage SAPH may warrant consideration for lung transplantation, which remains a high-risk option. Multi-centered randomized controlled trials are required to develop existing therapies further and improve the prognosis of SAPH patients.

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.