Aristolochic acid I induces proximal tubule injury through ROS/HMGB1/mt DNA mediated activation of TLRs.

Aristolochic acids (AAs) are extracted from certain plants as folk remedies for centuries until their nephrotoxicity and carcinogenicity were recognized. Aristolochic acid I (AAI) is one of the main pathogenic compounds, and it has nephrotoxic, carcinogenic and mutagenic effects. Previous studies have shown that AAI acts mainly on proximal renal tubular epithelial cells; however, the mechanisms of AAI-induced proximal tubule cell damage are still not fully characterized. We exposed human kidney proximal tubule cells (PTCs; HK2 cell line) to AAI in vitro at different time/dose conditions and assessed cell proliferation, reactive oxygen species (ROS) generation, nitric oxide (NO) production, m-RNA/ protein expressions and mitochondrial dysfunction. AAI exposure decreased proliferation and increased apoptosis, ROS generation / NO production in PTCs significantly at 24 h. Gene/ protein expression studies demonstrated activation of innate immunity (TLRs 2, 3, 4 and 9, HMGB1), inflammatory (IL6, TNFA, IL1B, IL18, TGFB and NLRP3) and kidney injury (LCN2) markers. AAI also induced epithelial-mesenchymal transition (EMT) and mitochondrial dysfunction in HK2 cells. TLR9 knock-down and ROS inhibition were able to ameliorate the toxic effect of AAI. In conclusion, AAI treatment caused injury to PTCs through ROS-HMGB1/mitochondrial DNA (mt DNA)-mediated activation of TLRs and inflammatory response.

Antipsychotic-like profile of CIQ isomers in animal models of schizophrenia.

Earlier, we have shown the efficacy of racemic (±) CIQ, a positive allosteric modulator of GluN2C/2D receptor against MK-801 induced impairment of prepulse inhibition as well as working memory. The present study investigated the antipsychotic-like profile of different CIQ (±, +, -) isomers against schizophrenia-like symptoms in series of behavioural animal models like apomorphine climbing, social isolation behaviour and NMDA receptor antagonist MK-801 induced cognitive deficits. Further, we also tested CIQ (±, +, -) isomers in neurodevelopmental model against MK-801induced deficits using open field test, Y-maze test and novel object recognition test. CIQ (±, +, -) isomers decreased climbing behaviour, increased social interaction and improved the MK-801 induced deficits in working memory in Y-maze. Further, CIQ (±, +) but not CIQ (-) improved the recognition memory in novel object recognition test as well as reduced hyperlocomotion and stereotyped behaviour. We conclude that CIQ (±, +) but not CIQ (-) exhibit the significant antipsychotic-like profile.

Optimization and multivariate accelerated shelf life testing (MASLT) of a low glycemic whole jamun (Syzygium cumini L.) confection with tailored quality and functional attributes.

An optimization and multivariate accelerated shelf-life testing (MASLT) was demonstrated to develop a low glycemic (GI) whole jamun (Syzygium cumini L.) confection (WJC) with soft texture and fruity hedonics targeted for diabetic strata. The hydrocolloids viz., agar (1-3 g), pectin (1-3 g), and polydextrose (24-28 g) were optimized [mixture design (MD)] to obtain hydrocolloid mix (HM) with a soft texture. Next, whole jamun ingredients viz, jamun pulp (JP) (20-30 g), seed powder (JSP) (1-5 g), and HM (25-35 g) were optimized (MD + PCA) for satisfactory texture, total polyphenolic content (TPC), and fruity hedonics. The optimized WJC was assayed for GI and modelled by univariate kinetics and MASLT (10-45 °C/75% humidity/120 days). Using MASLT, the collated effects of quality attributes (anthocyanin content, TPC, moisture, hardness, and total color change) were extracted as principal components to estimate new stability parameters viz, multivariate rate constants (k m), acceleration factors ( α m T ), activation energy (E am), and cut-off criterion. The optimized WJC contains 2.3 g agar, 1.9 g pectin, 27.2 g polydextrose, 26.4 g JP, and 2 g JSP and had satisfactory hardness (1007 g), TPC (2.8 mg gallic acid equivalents/g), and low GI value (48.6). The zero-order kinetic fitting of univariate versus MASLT resulted in α ( 45 , 10 ) T , E a, and shelf life (10 °C) of 7.8 versus 6.2, 43.81 versus 39.22 kJ/mol and 175 versus 186 days, respectively. MASLT simplified the kinetic interpretations to a single variable by collating the useful information from critical quality parameters and predicted shelf life precisely than univariate kinetics.

Optimization of microwave roasting of peanuts and evaluation of its physicochemical and sensory attributes.

In this study, the microwave (MW) roasting (MWR) of peanuts (Arachis hypogaea L.) is attempted, optimized and compared with conventional drum roasting. A two factor/three level face centered composite design based MWR experiments was conducted at different roasting time (60, 180 and 300 s) and MW power levels (180, 540 and 900 W). The roasting quality was analyzed by physicochemical and sensory attributes of roasted peanuts and extracted oil viz., moisture loss, hardness, browning index (BI), induction period (IP) based on Rancimat, peroxide value (PV) and overall acceptability (OA), respectively. A roasting time and MW power dependent improvement in the desired quality of roasted peanuts and extracted oil was observed attributable to the formation of antioxidant Maillard reaction compounds. A second order polynomial model adequately described the roasting experimental data (p < 0.0001, R2 > 0.90) with an insignificant lack of fit (p > 0.05). Using response surface methodology, the MWR was optimized at roasting time of 201 s and MW power level of 900 W which yielded favorable values of quality attributes (moisture loss, 3.06%; hardness, 4528.34 g; BI, 58.89; IP, 8.12 h; PV, 8.80 milliequivalents O2/kg; OA, 6.40). Furthermore, the quality assessment of ground peanuts for selected time-power combinations (low, optimum and high roasts) was attempted using scanning electron microscopy, electronic nose and Fourier transform infrared spectroscopy which revealed better quality of optimized MWR peanuts.

Multivariate optimization of a synergistic blend of oleoresin sage (Salvia officinalis L.) and ascorbyl palmitate to stabilize sunflower oil.

The simultaneous optimization of a synergistic blend of oleoresin sage (SAG) and ascorbyl palmitate (AP) in sunflower oil (SO) was performed using central composite and rotatable design coupled with principal component analysis (PCA) and response surface methodology (RSM). The physicochemical parameters viz., peroxide value, anisidine value, free fatty acids, induction period, total polar matter, antioxidant capacity and conjugated diene value were considered as response variables. PCA reduced the original set of correlated responses to few uncorrelated principal components (PC). The PC1 (eigen value, 5.78; data variance explained, 82.53 %) was selected for optimization using RSM. The quadratic model adequately described the data (R (2) = 0. 91, p < 0.05) and lack of fit was insignificant (p > 0.05). The contour plot of PC 1 score indicated the optimal synergistic combination of 1289.19 and 218.06 ppm for SAG and AP, respectively. This combination of SAG and AP resulted in shelf life of 320 days at 25 °C estimated using linear shelf life prediction model. In conclusion, the versatility of PCA-RSM approach has resulted in an easy interpretation in multiple response optimizations. This approach can be considered as a useful guide to develop new oil blends stabilized with food additives from natural sources.

Role of SLMAP genetic variants in susceptibility of diabetes and diabetic retinopathy in Qatari population.

BACKGROUND: Overexpression of SLMAP gene has been associated with diabetes and endothelial dysfunction of macro- and micro-blood vessels. In this study our primary objective is to explore the role of SLMAP gene polymorphisms in the susceptibility of type 2 diabetes (T2DM) with or without diabetic retinopathy (DR) in the Qatari population. METHODS: A total of 342 Qatari subjects (non-diabetic controls and T2DM patients with or without DR) were genotyped for SLMAP gene polymorphisms (rs17058639 C > T; rs1043045 C > T and rs1057719 A > G) using Taqman SNP genotyping assay. RESULTS: SLMAP rs17058639 C > T polymorphism was associated with the presence of DR among Qataris with T2DM. One-way ANOVA and multiple logistic regression analysis showed SLMAP SNP rs17058639 C > T as an independent risk factor for DR development. SLMAP rs17058639 C > T polymorphism also had a predictive role for the severity of DR. Haplotype Crs17058639Trs1043045Ars1057719 was associated with the increased risk for DR among Qataris with T2DM. CONCLUSIONS: The data suggests the potential role of SLMAP SNPs as a risk factor for the susceptibility of DR among T2DM patients in the Qatari population.

MicroRNA Signature and Cardiovascular Dysfunction.

The worldwide increase in the prevalence of obesity and type 2 diabetes and the associated elevated risk of cardiovascular disease (CVD) has emphasized the need to seek new therapeutic targets to offset the negative impact on human health outcomes. In this regards, microRNAs (miRNAs), a class of small noncoding RNAs that mediate posttranscriptional gene silencing, have received considerable interest. miRNAs repress gene expression by their ability to pair with target sequences in the 3' untranslated region of the messenger RNA. miRNAs play a crucial role in the biogenesis and function of the cardiovascular system and are implicated as dynamic regulators of cardiac and vascular signaling and pathophysiology. Numerous miRNAs have been identified as novel biomarkers and potential therapeutic targets for CVD. In this review, we discuss the contribution of miRNAs to the regulation of CVD, their role in macrovascular/microvascular (dys)function, their potential as important biomarkers for the early detection of CVD, and, finally, as therapeutic targets.

Bilateral s-shaped kidneys: A rare congenital malformation.

A bilateral S-shaped kidney is a rare anomaly in which both the kidneys are in their normal position, in contrast to the commonly reported S-shaped fusion anomaly, in which the contralateral kidney crosses the midline to fuse with opposite kidney leaving the ipsilateral renal fossa empty. Here we present the diagnosis and management of a case of bilateral S-shaped renal anomaly with associated left pelviureteric junction obstruction and nonfunctioning kidney and right renal stones. Left kidney was managed by open nephrectomy and right kidney by PNL.

Role of novel and GWAS originated PLCE1 genetic variants in susceptibility and prognosis of esophageal cancer patients in northern Indian population.

Recent genome-wide association studies (GWAS) have identified variants in phospholipase C epsilon1 (PLCE1) as novel susceptibility markers for esophageal squamous cell carcinoma (ESCC) in Chinese population. Although few studies have replicated this findings in other populations, but results are contradictory. So, we aimed to replicate association of two previously reported non-synonymous polymorphisms (rs2274223A>G and rs3765524C>T) from haplotype block 10 and evaluated a novel variant (rs7922612C>T) from haplotype block 2 of PLCE1 with susceptibility and prognosis of ESCC in northern Indian population. The genotyping of PLCE1 variants were performed in 293 histopathologically confirmed incident ESCC cases (including 177 follow-up cases) and 314 age-, gender-, and ethnicity-matched controls using PCR RFLP. All statistical analyses were performed through SPSS version 15.0. Modeling and functional prediction of two non-synonymous variants were carried out using bioinformatics tools. PLCE1 polymorphisms were not associated with susceptibility to ESCC or its clinical phenotypes (tumor location/lymph node metastasis). No interaction with environmental risk factors was found. In silico analysis suggested negligible effect on structure of PLCE1 protein due to PLCE1 rs2274223 (H1927R) and rs3765524 (T1777I) polymorphisms. Survival analysis showed PLCE1 rs7922612CT + TT genotype conferred adverse outcome to ESCC patients. Our study for the first time suggests that GWAS originated PLCE1 variants do not have independent role in susceptibility of ESCC in northern Indian population; however, a novel haplo-tagging SNP rs7922612 may modify survival outcome of ESCC patients.

Urinary Tract Infections in Patients Undergoing Invasive Urodynamic Study: A Prospective Observational Study at a Tertiary Care Centre in Eastern India.

OBJECTIVE: The aim of the study was to find the estimate of the prevalence of urinary tract infections following invasive urodynamic studies (UDS) in a hospital setup and to identify the risk factors related to it. METHOD: A total of 100 patients were enrolled in this prospective observational study after standard preoperative work, which included both urine analysis and culture procedure. The study was carried out from April 2022 to April 2023 at the Department of Urology, Indira Gandhi Institute of Medical Sciences, India. Three days following the UDS test, all the patients underwent repeat urine analysis and culture, besides screening for any lower urinary tract symptoms, abdominal pain, and fever. RESULT: Among all, 14 patients (i.e., 6.1% of 85 individuals) had significant bacteriuria, and six patients (4.7%) developed symptoms of UTI. However, a strong association was observed between the maximal detrusor pressure during voiding (Pdet at Q max) and post-void residue (PVR), which were >20 mL before UDS, along with positive urine cultures after UDS, which was significant at <0.05. CONCLUSION: The study demonstrated that the risk of UTIs with this diagnostic technique is minimal and that prophylactic antibiotic medication is not necessary prior to UDS in all patients.

Comprehensive Surgical Audit of Live-Related Donor Nephrectomy: Procedural Parameters, Demographics, Health Assessments, Complications, and Postoperative Outcomes.

BACKGROUND AND OBJECTIVES: End-stage renal disease (ESRD) rates are on the rise globally, including in India. However, the affordability of dialysis treatment remains a significant challenge for many, with costs varying across different regions. Although cost-effective, kidney transplantation faces challenges like a surgeon shortage, lack of infrastructure, and lack of logistic support. The study examines Indian laparoscopic nephrectomy outcomes and their benefits for donor recovery. It covers kidney donor procedural details, demographics, preoperative health evaluations, complications, and one-month follow-up. METHODS: Ethical approval was obtained, and the study involved 102 cases at the Indira Gandhi Institute of Medical Science, Patna, Bihar, India, from 2019 to 2023. Detailed preoperative assessments, postoperative complications, and one-month follow-up analyses were conducted. Statistical analysis employed SPSS version 17 (IBM Corp., Armonk, NY). RESULTS: The results revealed an average surgery time of 152.3 min, blood loss of 205 ± 42 ml, and a hospital stay of 4.6 ± 2.2 days. The study found a female predominance (80.39%), with a mean donor age of 35.9 ± 5.2 years. Preoperative assessments showed robust patient health, with glomerular filtration rate (GFR) exceeding the expected threshold and normal urea levels, creatinine, electrolytes, liver enzymes, bilirubin, albumin, and total protein. Post-nephrectomy complications were reported, with females experiencing more difficulties than males. CONCLUSION: This study underscores the efficiency and safety of laparoscopic nephrectomy in the Indian context, providing valuable insights into donor demographics, preoperative health assessments, complications, and postoperative outcomes. The findings contribute to understanding laparoscopic nephrectomy outcomes and associated risk factors despite certain limitations.

Comparative Study of the Outcome of Buccal Mucosa Graft Urethroplasty and Preputial Flap Urethroplasty for Anterior Urethral Stricture: A Prospective Randomized Study.

BACKGROUND: Urethroplasty using a buccal mucosa graft (BMG) and a preputial skin flap (PSF) are two common techniques used for the treatment of anterior urethral stricture. The present study compared the efficacy of these two techniques on the basis of success rate, preservation of sexual function, and complications. MATERIALS AND METHODS: This prospective, randomized, interventional study was conducted on adult male patients diagnosed with non-obliterative anterior urethral strictures of length >2 cm from August 2021 to December 2022. Pre-operative and post-operative work-up done included assessment of the International Prostate Symptom Score (IPSS), Quality of Life (QOL), International Index of Erectile Function (IIEF) Score, Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EJD), Bother score, Urethral Stricture Surgery-Patient-Related Outcome Measure (USS-PROM), and peak urinary flow rate (Qmax) for each patient. Post-operative values for each score were compared with pre-operative values. RESULTS: Out of 31 patients, 16 underwent BMG urethroplasty, and 15 underwent PSF urethroplasty. The most common cause of stricture in both groups was idiopathic (35.5% and 53.3%). A statistically significant increase in IIEF score was observed in the BMG group in comparison to the PSF group (P<0.0001). The mean IPPS score in USS-PROM has shown a significant drop in BMG (19.6 vs. 17.3; P = 0.020). Hemoglobin drop was significantly higher in PSF than in BMG (2.6 vs. 1.9; P = 0.011). A higher incidence of surgical site infection was reported in the PSF group than in the BMG group (46.7% vs. 12.5%). The average operative time for surgery was higher in PSF than in BMG (154.8 min vs. 145.0 min), respectively. Each group had one patient with a recurrence. CONCLUSION: Both techniques are equally good for urethral reconstruction (UR); however, improvement of sexual function is more in favor of the BMG urethroplasty group.

Genetic polymorphisms in RNA binding proteins contribute to breast cancer survival.

The RNA-binding proteins TTP and HuR control expression of numerous genes associated with breast cancer pathogenesis by regulating mRNA stability. However, the role of genetic variation in TTP (ZFP36) and HuR (ELAVL1) genes is unknown in breast cancer prognosis. A total of 251 breast cancer patients (170 Caucasians and 81 African-Americans) were enrolled and followed up from 2001 to 2011 (or until death). Genotyping was performed for 10 SNPs in ZFP36 and 7 in ELAVL1 genes. On comparing both races with one another, significant differences were found for clinical and genetic variables. The influence of genetic polymorphisms on survival was analyzed by using Cox-regression, Kaplan-Meier analysis and the log-rank test. Univariate (Kaplan-Meier/Cox-regression) and multivariate (Cox-regression) analysis showed that the TTP gene polymorphism ZFP36*2 A > G was significantly associated with poor prognosis of Caucasian patients (HR = 2.03; 95% CI = 1.09-3.76; p = 0.025; log-rank p = 0.022). None of the haplotypes, but presence of more than six risk genotypes in Caucasian patients, was significantly associated with poor prognosis (HR=2.42; 95% CI = 1.17-4.99; p = 0.017; log-rank p = 0.007). The effect of ZFP36*2 A > G on gene expression was evaluated from patients' tissue samples. Both TTP mRNA and protein expression was significantly decreased in ZFP36*2 G allele carriers compared to A allele homozygotes. Conversely, upregulation of the TTP-target gene COX-2 was observed ZFP36*2 G allele carriers. Through its ability to attenuate TTP gene expression, the ZFP36*2 A > G gene polymorphism has appeared as a novel prognostic breast cancer marker in Caucasian patients.

Evaluation of common genetic variants in pre-microRNA in susceptibility and prognosis of esophageal cancer.

Genetic variants in micro-RNAs (miRNA) have been shown to affect progression, diagnosis, and prognosis of various malignancies; however, their role in esophageal squamous cell carcinoma (ESCC) susceptibility is controversial. Therefore, we aimed to determine role of common genetic variants in cancer related pre-miRNA in susceptibility and survival outcome of north Indian ESCC patients. We genotyped four common polymorphisms in pre-miRNA: mir-196a-2C>T, mir-146aG>C, mir-499T>C, and mir-423C>A in 289 incident ESCC cases (including 153 follow-up cases) and 309 controls using PCR/PCR RFLP-based methods. Binary logistic regression was applied for risk estimation, while Kaplan-Meier and Cox Regression tests were performed for survival analysis. We observed that none of the pre-miRNA genetic variants were associated with ESCC or its clinical phenotypes independently, however, combined risk genotypes of four pre-miRNA polymorphisms increased risk of ESCC in dose-response manner (Ptrend = 0.011). Specifically, patients with 2-4 risk genotypes of pre-miRNA polymorphisms had 1.4-fold higher risk of ESCC compared to patients with 0-1 risk genotypes (OR = 1.43, 95% CI = 1.02-1.09, P-value = 0.037). The risk was more pronounced in ESCC cases with upper-third esophageal tumors. Moreover, cumulative but not independent effect of risk genotypes of pre-miRNA polymorphisms was observed on survival outcome of ESCC patients. Cases with 2-4 risk genotypes had significantly lower median survival (11.60 vs. 30.2 months) and 2.3-fold greater hazard of death compared to patients with 0-1 risk genotypes. In conclusion, the four studied common pre-miRNA polymorphisms cumulatively affect susceptibility and survival of ESCC patients in north Indian population. © 2012 Wiley Periodicals, Inc.

PLCE1 rs2274223 A>G polymorphism and cancer risk: a meta-analysis.

Phospholipase C epsilon 1 gene (PLCE1) encodes a phospholipase enzyme which regulates various physiological processes (cell growth, differentiation, and apoptosis) and is supposed to play a critical role in carcinogenesis. Recently, a single nucleotide polymorphism (rs2274223 A>G) in PLCE1 was reported as a novel susceptibility locus for esophageal and gastric cancers by genome-wide association studies performed in Chinese population. However, individual association studies replicating this finding showed inconclusive results. Therefore, we performed a meta-analysis of eligible studies to derive precise estimation of the association of PLCE1 rs2274223 A>G polymorphism with cancer risk. We performed pooled analysis of 12 case­control studies including 7,622 cases and 9,555 controls. Odds ratios and 95 % confidence interval were calculated to assess strength of association in overall studies and in subgroup analysis stratified by ethnicity, cancer types, and source of controls. All statistical analyses were performed by MIX 2.0 software. We found that PLCE1 rs2274223 A>G polymorphism was significantly associated with increased risk of cancer in log additive/dominant model and at allele level (GG vs. AA: OR = 1.24, 95 % CI = 1.01­1.53, P = 0.039; AG vs. AA: OR = 1.24, 95 % CI = 1.16­1.32, P < 0.001; AG + GG vs. AA: OR = 1.22, 95 % CI = 1.12­1.34, P < 0.001; and G vs. A allele: OR = 1.15, 95 % CI = 1.05­1.25, P = 0.002). Further, stratified analysis showed elevated risk of only gastric and esophageal tumors. Sub-group analysis based on ethnicity suggests PLCE1 polymorphism conferred significant risk among Asian (Chinese) but not in Caucasian. In conclusion, PLCE1 rs2274223 polymorphism may be used as potential biomarker for cancer susceptibility particularly for esophageal/gastric cancer and for the Chinese population.

An outlook on chlorogenic acids-occurrence, chemistry, technology, and biological activities.

Phenolics are widespread dietary antioxidants. Among these, chlorogenic acids (CGAs) received considerable attention for their wide distribution and part of human diet with potential biological effects. CGAs (71 compounds), being esters of derivatives of cinnamic acids with quinic acid are widely distributed in plant materials. Coffee is among the highest found in plants, ranging from 4 to 14%. Besides, these are reported in plant foods such as apples, pears, carrot, tomato, sweet potato, Phyllostachys edulis, oilseeds, Prunus domestica L, cherries, and eggplant. The traditional Chinese medicinal plants such as flowers and buds of Lonicera japonica Thunb and the leaves of Eucommia ulmodies contained CGAs as bioactive compound. These play an important role in the formation of roasted coffee flavor and have a marked influence on coffee cup quality. CGAs are considered as main precursors of coffee flavor and pigments. Recent technological advancements in the separation and purification of CGAs such as molecular-imprinted polymer technique; microwave-assisted extraction; pH gradient counter current chromatography has also been described. The consumption of coffee correlated to several health benefits such as reducing the risk of human chronic diseases such as inflammation, diabetes, and cardiovascular disease owing to its antioxidant potential.

Modification of risk, but not survival of esophageal cancer patients by esophageal cancer-related gene 1 Arg290Gln polymorphism: a case-control study and meta-analysis.

BACKGROUND AND AIM: Esophageal cancer-related gene 1 (ECRG1) is a novel tumor suppressor gene known to affect matrix remodeling, cell growth, and differentiation. Previous studies in high incidence geographical regions of esophageal cancer (EC) have shown association of ECRG1 Arg290Gln polymorphism with risk of esophageal squamous cell carcinoma (ESCC); however, role of this variant in low incidence region is missing. So, we aimed to evaluate association of ECRG1 Arg290Gln with susceptibility and prognosis of EC patients in low-risk north Indian population. METHODS: The genotyping of ECRG1 Arg290Gln polymorphism was done in 310 incident EC cases (including 179 follow up cases) and 310 healthy controls through polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis applied were binary logistic regression for risk estimation and Kaplan-Meier/log-rank test for survival analysis. Meta-analysis of published studies, exploring role of ECRG1 polymorphism in ESCC risk, was carried out using MIX 2.0 software. RESULTS: ECRG1 Arg290Gln polymorphism significantly conferred 1.8-fold increased risk of EC in dominant model (odds ratio = 1.78, 95% confidence interval = 1.27-2.49, P = 0.001). Stratification based on clinical phenotypes showed pronounced risk in cases with ESCC histopathology and middle/lower third tumor locations. No significant interaction with environmental risk factors was observed. Meta-analysis also showed significant association of ECRG1 Arg290Gln polymorphism with risk of ESCC. Kaplan-Meier and Cox regression tests suggested that ECRG1 polymorphism did not modulate survival outcome of ESCC patients. CONCLUSIONS: ECRG1 Arg290Gln polymorphism significantly affects the susceptibility but not the prognosis of ESCC patients in low-risk north Indian population.

The spectrum and etiologies of lower urinary tract symptoms in postmenopausal women.

Background: Although the prevalence of lower urinary tract symptoms (LUTS) is high in the female population, it is even higher in postmenopausal females. The frequency, severity, and etiology of LUTS vary among populations and individuals. This study aimed to define the characteristics of LUTS in postmenopausal women and their underlying etiologies. Material and methods: Overall, 74 postmenopausal patients presenting with LUTS in the urological outpatient department were included in the study. A detailed evaluation of LUTS and their underlying etiologies was performed. Patients were divided into 2 groups based on age (<65 and ≥65 years), and the variation in different factors was compared across the groups. Variables were compared using the t test and 1-way analysis of variance. Results: Nocturia was the most common symptom (89.2%) followed by frequency (83.8%). Among voiding LUTS, the most common was a weak stream (63.5%). Frequency, nocturia, urgency, urge urinary incontinence (UI), stress UI, and nocturnal enuresis were more common in patients older than 65 years. Urgency and urge UI were recognized to be the most bothersome symptoms by 37% of the study population followed by straining (32%). The mean storage scores, incontinence scores, and quality of life (QoL) scores for patients younger than 65 years and 65 years or older were 6.9 and 8.5 (p < 0.01), 1.8 and 4.1 (p ≤ 0.01), 4.9 and 6.1, respectively. The most common diagnosis was bladder outlet obstruction due to urethral/meatal stenosis (40.5%) followed by an overactive bladder (32.4%), urinary tract infection (10.8%), cystocele (8.1%), urethral prolapse (4.1%), and urethral caruncle (4.1%). Conclusions: Storage LUTS were the most common and increased in both frequency and severity with age. The QoL was also more severely affected in older postmenopausal women. Bladder outlet obstruction due to meatal with or without distal urethral stenosis was the most common underlying cause of LUTS followed by an overactive bladder. Overactive bladder had the most severe impact on patients' QoL among all the etiologies.

Role of p53 and p73 genes polymorphisms in susceptibility to esophageal cancer: a case control study in a northern Indian population.

Genetic variants in p53 and in its homologue p73 may modulate Esophageal Cancer (EC) risk because they are supposed to influence cell cycle progression, apoptosis and DNA repair. Therefore, we aimed to evaluate the association of p53 intron3 16 bp duplication and p73 G4C14-to-A4T14 polymorphisms with susceptibility to EC in a northern Indian population in 255 EC patients and 255 age and sex matched healthy controls. We found that p53 intron3 16 bp duplication polymorphism was not associated with EC and its clinical characteristics. However, p73 G4C14-to-A4T14 polymorphism was associated with significant higher risk of EC (OR = 1.74, 95% CI = 1.16-2.60, P = 0.007) in an allele dose-dependent manner (P(trend) = 0.0047). Stratification of subjects on the basis of clinical characteristics showed that p73 AT genotype carriers were at significant increased risk of developing esophageal squamous cell carcinoma (OR = 1.78, 95% CI = 1.18-2.67, P = 0.006) at middle third tumor location (OR = 1.87, 95% CI = 1.18-2.97, P = 0.007) with lymph node metastasis (OR = 1.77, 95% CI = 1.04-3.02, P = 0.035). No interaction with environmental risk factors was observed with any of the studied polymorphisms. In summary, p73 G4C14-to-A4T14 polymorphism but not the p53 intron3 16 bp duplication polymorphism is associated with EC and its clinical characteristics in northern Indian population.

The Promising Role of Microbiome Therapy on Biomarkers of Inflammation and Oxidative Stress in Type 2 Diabetes: A Systematic and Narrative Review.

Background: One in 10 adults suffer from type 2 diabetes (T2D). The role of the gut microbiome, its homeostasis, and dysbiosis has been investigated with success in the pathogenesis as well as treatment of T2D. There is an increasing volume of literature reporting interventions of pro-, pre-, and synbiotics on T2D patients. Methods: Studies investigating the effect of pro-, pre-, and synbiotics on biomarkers of inflammation and oxidative stress in T2D populations were extracted from databases such as PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to January 2022. Results: From an initial screening of 5,984 hits, 47 clinical studies were included. Both statistically significant and non-significant results have been compiled, analyzed, and discussed. We have found various promising pro-, pre-, and synbiotic formulations. Of these, multistrain/multispecies probiotics are found to be more effective than monostrain interventions. Additionally, our findings show resistant dextrin to be the most promising prebiotic, followed closely by inulin and oligosaccharides. Finally, we report that synbiotics have shown excellent effect on markers of oxidative stress and antioxidant enzymes. We further discuss the role of metabolites in the resulting effects in biomarkers and ultimately pathogenesis of T2D, bring attention toward the ability of such nutraceuticals to have significant role in COVID-19 therapy, and finally discuss few ongoing clinical trials and prospects. Conclusion: Current literature of pro-, pre- and synbiotic administration for T2D therapy is promising and shows many significant results with respect to most markers of inflammation and oxidative stress.