To Study the Efficacy and Safety of Diosmin with Tranexamic Acid and Mefenamic Acid Versus only Tranexamic Acid and Mefenamic Acid in Medical Management of Abnormal Uterine Bleeding: A Randomized Controlled Trial.

Background: Abnormal uterine bleeding (AUB) is a common problem in reproductive age group and perimenopausal age group being responsible for many outpatient visits. Traditional management of AUB consists of giving mefenamic acid, tranexamic acid, or their combination with progestogens or hormonal intrauterine deviced levonorgestrel intrauterine system (LNG-IUS) for severe or nonresponsive cases. The objective of the current study was to study the efficacy and safety of adding diosmin along with tranexamic acid and mefenamic acid in reducing menstrual blood loss in AUB patients. Materials and Methods: It was a prospective double-blind randomized controlled trial in which 900 mg of diosmin was given once daily along with 500 mg tranexamic acid and 250 mg mefenamic acid during menstruation (Group I-92 patients), or only tranexamic acid and mefenamic acid during menstruation (Group II-92 patients). Results: Mean age, parity, body mass index, and socioeconomic status were similar in the two groups. It was 35.68 years versus 36.78 years, 2.2 versus 2.3, 23.68 kg/m2 versus 24.62 kg/m2 respectively. Mean days of bleeding before this treatment were 6.8 versus 6.6 (P = 0.33) and were 3.5 versus 5.2 (P = 0.02) after treatment. There was a significant reduction in both groups as compared to before treatment (P = 0.021 in Group I, 0.027 in Group II) but the reduction was greater in Group I (P = 0.02). The amount of blood loss was 385 ml versus 390 ml (P = 0.7) before treatment which was significantly reduced in both groups to 68 ml versus 112 ml (P = 0.02 in Group I, 0.03 in Group II) with more decrease in Group I than in Group II (P = 0.01). Mean hemoglobin at beginning of the study was 8.4 versus 8.5 g/dl in Group I and Group II (P = 0.02) and significantly increased in both groups posttreatment to 10.9 and 9.8 g/dl in Group I and Group II (P = 0.012 in Group I, 0.011 in Group II) with increase being more in Group I than Group II (P = 0.03). Pictorial blood assessment chart score was 398 versus 406 (P = 0.35) before treatment and decreased significantly to 86.5 and 110.5 (P = 0.001 in Group I, 0.001 in Group II) with more decrease being in Group I than II (P = 0.01). There was significant decrease in dysmenorrhea with both treatments with no difference in the two groups. Various adverse effects such as nausea, vomiting, abdominal pain, diarrhea, constipation, and headache were equal in the two groups. Conclusion: Both the group's diosmin with tranexamic acid and mefenamic acid (Group I) and tranexamic acid and mefenamic acid (Group II) were efficacious in reducing menstrual blood loss, number of menstrual days and dysmenorrhea with effect being more by addition of diosmin. Adverse effects were equal in both the two groups.

Evaluation of cervical cancer screening during pregnancy in India: Human papillomavirus testing can change the paradigm.

Background The World Health Organization's call for elimination of cervical cancer envisages 70% screening coverage of women aged 35 and 45 years by an effective test. In India, this target seems unrealistic as awareness and access to cancer prevention services are poor. However, the institutional delivery rate is now >80%. We evaluated the acceptability and feasibility of human papillomavirus (HPV) testing and its role in screening during pregnancy. Methods This observational study recruited 275 pregnant women aged >25 years between 12 and 34 weeks of gestation for screening by cytology and HPV testing. Colposcopy was advised if either test was positive. Acceptability and feasibility were assessed by a questionnaire. Results Cytology and HPV reports were available for 269 subjects. The median age was 28 years and median parity was two. Only 98 (36.4%) had heard about carcinoma cervix. Awareness improved with education (p < 0.001). On cytology, only 4 (1.5%) were abnormal (atypical squamous cells of undetermined significance 3; low-grade squamous intraepithelial lesion 1). The prevalence of high-risk HPV infection was 8.2% (22/269). On colposcopy, all had the Swede score <5. No high-grade cervical intraepithelial neoplasia or carcinoma was detected. Pre-procedure, 183 (68.0%) subjects expressed apprehension, post-procedure 114 (42.4%) of them had realized that their apprehensions were unfounded. Women found screening to be more uncomfortable after 28 weeks of gestation (n=26/68; 38.2%; p<0.001). Physicians found the cervix more difficult to visualize after 20 weeks of gestation (p<0.001). Conclusions HPV screening at 16-20 weeks of pregnancy is acceptable, feasible, and can greatly improve screening coverage in resource-limited settings. Pregnancy is a good opportunity to improve awareness of the screening programmes.

Genome profiling of uropathogenic E. coli from strictly defined community-acquired UTI in paediatric patients: a multicentric study.

BACKGROUND: Urinary tract infection (UTI) in children is a common bacterial infection. The emergence of extended-spectrum beta-lactamases (ESBLs) poses a major challenge against the treatment of uropathogens. We aimed to characterize the E. coli isolates recovered from children with UTI for their resistance profile and circulating sequence types (ST). METHODS: Children (> 1.5-18 years of age) from different community health centres of India with symptoms of UTI were enrolled. Isolates causing significant bacteriuria were identified by Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) and tested for antimicrobial susceptibility by the automated system, VITEK-2 (Biomeriux, Durhum, US). Nineteen E. coli isolates (15 ESBL positive and 4 ESBL negative) were sequenced in Oxford Nanopore platform followed by core-genome phylogeny, accessory genome cluster analysis, identification of sequence types, mobile genetic elements, genetic antimicrobial resistance markers. The correlation between detection of antimicrobial resistance genes with phenotypic resistance profiles was also investigated. RESULTS: Eleven percent of children had significant bacteriuria [male:female-1:1, > 50% were 11-18 years of age group]. E. coli was predominant (86%) followed by K. pneumoniae (11%). Susceptibility of E. coli was highest against fosfomycin (100%) followed by carbapenems (90.7%) and nitrofurantoin (88.8%). ST131 (15.8%) and ST167 (10.5%) found as high-risk clones with the presence of plasmid [IncFIB (63.1%), IncFIA (52.6%)], and composite transposon [Tn2680 (46.6%)] in many isolates. Few isolates coharboured multiple beta-lactamases including blaNDM-5 (33.3%), blaOXA-1 (53.3%), blaCTX-M-15 (60%) and blaTEM-4 (60%). CONCLUSIONS: This study highlights horizontal transmission of resistance genes and plasmids in paediatric patients at community centers across the nation harbouring multidrug-resistant genes such as blaNDM-5 and blaCTX-M-15 associated with high-risk clones ST131 and ST167. The data is alarming and emphasizes the need for rapid identification of resistance markers to reduce the spread in community. To our knowledge, this is the first multicentric study targeting paediatric UTI patients from the community setting of India.

Negative Emotions, Triggers, and Coping Strategies Among Postpartum Indian Women During Second Wave of COVID-19 Pandemic: Lessons for the Subsequent Waves and Beyond.

Introduction: The study aimed to evaluate COVID-19 associated psychological distress among pregnant and postpartum women during the second wave of COVID-19 in India. Methods: A cross-sectional survey was done using a pre-validated tool involving 491 participants attending a tertiary-care hospital during the second wave of COVID-19 in India. Results: Three-fourths of participants experienced negative emotions such as fear and various features of depression. Participants (75%) reported COVID-related news on TV/Radio/Newspapers including social media as the major trigger for these negative emotions. Loss of social support mainly affected postpartum women (p < 0.001) and working women (p < 0.001). Inability to access healthcare services had negative associations with age (p < 0.001), education (p < 0.001), and socioeconomic class (p < 0.001). Various coping strategies being followed by participants included watching TV/Videos or reading books (93%), resorting to social media (77%), spending more time praying and meditating (86%), and engaging in hobbies (56%). Conclusion: During the second wave, the COVID-19 pandemic had a significantly high negative impact on the psychological and social well-being of pregnant and postpartum women. Hence, it is important to initiate appropriate preventive and corrective steps by the policymakers for any future waves of the pandemic.

Disrupted placental vitamin D metabolism and calcium signaling in gestational diabetes and pre-eclampsia patients.

INTRODUCTION: Gestational diabetes (GDM) and pre-eclampsia (PE) represents the unrecognized risk factors for reduced bone content in neonates. The present study is planned to explore the components of vitamin D metabolism and calcium transport in placenta of GDM and PE cases and its effect on the neonatal bone mass determination using bone densitometry system. METHODS: We have collected serum and placenta tissues from GDM (n = 20), PE (n = 20), and healthy pregnancies (n = 20). In the present study, we found mRNA expression of oxidative stress markers, vitamin D metabolic components and calcium channels, calcium channel binding proteins, plasma membrane calcium ATPase, ATP synthase and Ca2+ release genes; Ryanodine receptors genes were assessed by quantitative real-time PCR (qRT-PCR) in placental tissue of GDM, PE, and healthy pregnancies. RESULTS: We observed high level of oxidative stress in both GDM and PE placenta compared to normal pregnancies. CYP2R1 and VDR mRNA expression was significantly downregulated and upregulation of CYP27B1 and CYP24A1 in GDM and PE compared with healthy cases. Similarly, calcium transporters were downregulated in GDM and PE placental tissues. In addition, CYP24A1, VDR, CaBP28K, TRPV5 and PMCA3 mRNA expression were correlated with BMC of neonates. DISCUSSION: Oxidative stress is probably relevant to disrupted vitamin D homeostasis and calcium transport in the placenta of GDM and PE cases. The altered regulatory mechanism of CYP24A1 and VDR could indicates more pronounced serum 25(OH)D reduction. Additionally, reduced BMC in the neonates of these cases might be as consequences of modified CYP24A1, VDR, CaBP28K, TRPV5 and PMCA3 mRNA expression.

Surgical Outcomes and Feasibility of Transvaginal Sacrospinous Ligament Fixation through Anterior Approach for Women with Pelvic Organ Prolapse.

Introduction: Supporting vaginal vault or apex is a central component of primary therapy and to prevent recurrence of prolapse. This study aims to review the surgical outcomes and feasibility of the anterior approach following both sacrospinous fixation (SSF) and sacrospinous hysteropexy (SSHP) in a single center over a specific period. And also to review its impact on quality of life. Materials and Methods: This was a retrospective study that included all women who underwent unilateral SSF or SSHP through anterior approach for pelvic organ prolapse (POP) from May 2021 to May 2023 after institutional ethical approval for the study. The anterior approach was undertaken in 47 patients which were included in final review. A retrospective case note review to assess urinary symptoms was undertaken at baseline and 3 months by urinary distress inventory 6 score. The main outcome measure was recurrence of prolapse, predominant compartment for prolapse, presenting complaints, concomitant surgeries performed, and associated urinary complaints. Results: The mean age was 56.17 ± 11.95 years and the average body mass index was 26.12 ± 3.11 kg/m2. Except for 4 cases of SSHP, remaining women were postmenopausal at the time of surgery. Ten women presented with urinary complaints as their chief complaint. On examination, POP Quantification evaluation, 35 cases have Ba as leading point, 10 have Ap as their leading point and in two cases C was the leading point. Conclusion: Anterior unilateral sacrospinous ligament fixation is a safe, effective strategy to treat POP and other concomitant surgery can also be well combined with it.

Antibiotic resistance of uropathogens among the community-dwelling pregnant and nonpregnant female: a step towards antibiotic stewardship.

BACKGROUND: Indiscriminate and widespread use of antibiotics has resulted in emergence of many antibiotic-resistant organisms. Antibiotic administration during pregnancy is mostly avoided, unless there is compelling medical condition. We hypothesized that the uropathogens isolated from pregnant women would be more susceptible to antibiotics compared to those isolated from nonpregnant women, thus will be helpful in formulating separate empiric guideline for pregnant women based on the resistance pattern. METHODS: This was a prospective cross-sectional study conducted over a period of 2 years in which females with the clinical diagnosis of either cystitis or asymptomatic bacteriuria during pregnancy were included from the community settings. Uropathogen species and their antimicrobial resistance pattern were compared between the pregnant and nonpregnant groups. After accounting for centre-to-centre variation and adjusting for age and socio-economic status, the adjusted odds ratio for antibiotic resistance was calculated and compared between pregnant and nonpregnant women using logistic regression analysis. RESULTS: A total of 1758 women (pregnant: 43.3%; nonpregnant: 56.6%) were screened in the study over a period of 2 years, out of which 9.3% (163/1758) were having significant bacteriuria. Escherichia coli and Klebsiella pneumoniae were the two commonest uropathogen in both the groups; their prevalence being 83.6% in pregnant women and 85.2% in nonpregnant women, respectively. Resistance against ampicillin, cefixime, cefoxitin, ceftazidime, ceftriaxone and amoxicillin-clavulanic acid were found significantly lower in the pregnant women compared to nonpregnant. After adjusting the age and socio-economic status accounting for centre-to-centre variation, the odds of resistance for cefixime, amoxicillin-clavulanic acid and co-trimoxazole were found lower and statistically significant among the pregnant women group. CONCLUSIONS: The antimicrobial resistance was significantly higher among the community-dwelling nonpregnant women compared to pregnant women in case of few antibiotics. The study highlighted the need of building local antibiogram that could help to initiate the empirical treatment and thus prevent emergence of antimicrobial resistance.

Role of Incontinence Severity Index in Evaluating Severity and Impact of Treatment Of Stress Urinary Incontinence.

Background: Stress urinary incontinence (SUI) is a common ailment in affecting quality of life. This study was performed to see role of incontinence severity index (ISI) in evaluating severity of SUI and to see the impact of treatment of SUI. Materials and Methods: A total of 40 women with the diagnosis of SUI on history and clinical examination were enrolled. ISI was calculated on all the women before treatment. All women were treated with either conservative treatment (pelvic floor exercises, life style modification, and duloxetine therapy) (4, 10%) or Burch's colposuspension (18, 45%) or tension-free obturator tape (18, 45%) as per clinical situation after discussion with patients. ISI was again calculated 6 months after treatment. Results: Mean age, parity, body mass index in the study were 41.60 years, 2.73, and 24.2 kg/m2, respectively. All 40 (100%) patients had SUI with the mean duration of symptoms being 4.04 years. A total of 11 (27.5%) had moderate SUI (ISI 3-6), while 24 (60%) had severe SUI (ISI 8-9), while 5 (12.5%) had very severe SUI (ISI 12). Range of pretreatment ISI was 3-12 with mean being 8.8 ± 3.2. Posttreatment ISI reduced significantly with range of 1-4 and mean of 1.3 ± 0.4 (P < 0.001). The reduction was significant for all the groups, but there was no significant difference in efficacy of three treatment groups. Statistical analysis was done using SPSS IBM Version 2-1-0 using Chi-square test, Fisher's Extract test, and ANOVA test as appropriate. Conclusion: ISI is a useful modality to evaluate the severity of SUI and to see the impact of treatment modalities on SUI.

Continuous Glucose Monitoring System Profile of Women with Gestational Diabetes Mellitus Missed Using Isolated Fasting Plasma Glucose-Based Strategies Alternative to WHO 2013 Criteria: A Cross-Sectional Study.

INTRODUCTION: The aim of the study was to evaluate the differences in the continuous glucose monitoring system (CGMS)-based glycemic parameters between women with normoglycemia and early gestational diabetes mellitus (GDM) identified on the basis of mild fasting plasma glucose elevation (FPG, 5.1-5.5 mmol/L) and/or post-load plasma glucose elevation (PLG, 1-h ≥ 10.0 mmol/L or 2-h ≥ 8.5 mmol/L). METHODS: This cross-sectional study included women with singleton pregnancy (8+0 to 19+6 weeks of gestation) and normoglycemia or GDM per World Health Organization (WHO) 2013 criteria. We evaluated the glycemic parameters of clinical interest using blinded CGMS evaluation and reported them per standard methodology proposed by Hernandez et al. RESULTS: A total of 87 women (GDM, n = 38) were enrolled at 28.6 ± 4.5 years. Among women with GDM, 10 (26.3%) had isolated mild FPG elevation (5.1-5.5 mmol/L), 10 (26.3%) had isolated PLG elevation (1-h ≥ 10.0 mmol/L or 2-h ≥ 8.5 mmol/L), and 7 (18.4%) had a combination of both. The remaining 11 (28.9%) had elevated FPG (≥ 5.6 mmol/L) with or without PLG elevation. Thus, when an isolated FPG cutoff ≥ 5.6 mmol/L is used to diagnose GDM, 27 (71.0%) women would be perceived as normoglycemic. Such women had significantly higher CGMS parameters of clinical interest, such as 24-h mean glucose, fasting glucose, 1-h and 2-h postprandial glucose (PPG), 1-h PPG excursion, and peak PPG. CONCLUSIONS: An isolated FPG threshold, especially the higher cutoff ≥ 5.6 mmol/L, can potentially miss a large proportion of women (nearly three-fourths) diagnosed with GDM per WHO 2013 criteria. Eventually, such women fare significantly differently from normoglycemic women in various CGMS parameters of clinical interest.

A Novel Rolling Circle Amplification-Based Detection of SARS-CoV-2 with Multi-Region Padlock Hybridization.

SARS-CoV-2 has remained a global health burden, primarily due to the continuous evolution of different mutant strains. These mutations present challenges to the detection of the virus, as the target genes of qPCR, the standard diagnostic method, may possess sequence alterations. In this study, we develop an isothermal one-step detection method using rolling circle amplification (RCA) for SARS-CoV-2. This novel strategy utilizes a multi-padlock (MP-RCA) approach to detect viral-RNA via a simplified procedure with the reliable detection of mutated strains over other procedures. We designed 40 padlock-based probes to target different sequences across the SARS-CoV-2 genome. We established an optimal one-step isothermal reaction protocol utilizing a fluorescent output detected via a plate reader to test a variety of padlock combinations. This method was tested on RNA samples collected from nasal swabs and validated via PCR. S-gene target failure (SGTF)-mutated strains of SARS-CoV-2 were included. We demonstrated that the sensitivity of our assay was linearly proportional to the number of padlock probes used. With the 40-padlock combination the MP-RCA assay was able to correctly detect 45 out 55 positive samples (81.8% efficiency). This included 10 samples with SGTF mutations which we were able to detect as positive with 100% efficiency. We found that the MP-RCA approach improves the sensitivity of the MP-RCA assay, and critically, allows for the detection of SARS-CoV-2 variants with SGTF. Our method offers the simplicity of the reaction and requires basic equipment compared to standard qPCR. This method provides an alternative approach to overcome the challenges of detecting SARS-CoV-2 and other rapidly mutating viruses.

Continuous glucose monitoring system profile of women diagnosed as gestational diabetes mellitus by International Association of Diabetes and Pregnancy Study Groups criteria and labeled as normoglycemic by alternate criteria in early pregnancy.

AIMS/INTRODUCTION: We aimed to evaluate and compare continuous glucose monitoring system (CGMS)-based glycemic parameters in women in early pregnancy (<20 weeks of gestation) who were classified as: (i) gestational diabetes mellitus (GDM) by the International Association of Diabetes and Pregnancy Study Groups (IADPSG), but normoglycemia by alternate (UK National Institute for Health and Care Excellence, Canadian Diabetes Association and Diabetes in Pregnancy Study group of India) criteria; and (ii) normoglycemia by both (IADPSG and alternate) criteria. MATERIAL AND METHODS: In this cross-sectional study, eligible women underwent standard 75-g oral glucose tolerance test, followed by the placement of a CGMS. Glycemia-related parameters were calculated using the standard approach for CGMS data in pregnancy. RESULTS: We enrolled 96 women at 14.0 ± 3.2 weeks of gestation. Of the women diagnosed as GDM by IADPSG criteria, 34.2%, 26.3% and 44.7% were classified as normoglycemic by UK National Institute for Health and Care Excellence, Canadian Diabetes Association and Diabetes in Pregnancy Study group of India criteria, respectively. Mean 1-h postprandial glucose and time above range were significantly higher in women who were GDM by IADPSG, but normoglycemia by Canadian Diabetes Association criteria, compared with women with normoglycemia using both criteria. Similarly, mean 1-h postprandial glucose, 2-h postprandial glucose, peak postprandial glucose, 1-h postprandial glucose excursion and time above range were significantly higher in women who were not identified as GDM by the UK National Institute for Health and Care Excellence criteria. Finally, women missed by the Diabetes in Pregnancy Study group of India criteria had significantly higher mean 1-h postprandial glucose, 2-h postprandial glucose, peak postprandial glucose, postprandial glucose excursion, 24-h glucose and time above range parameters. CONCLUSIONS: More than one-quarter of women diagnosed as GDM by IADPSG criteria are not identified by alternate criteria. Such women are significantly different from normoglycemic women in terms of several CGMS-based glycemic parameters of clinical significance.

Obstetrics outcome in pulmonary tuberculosis.

BACKGROUND: To evaluate the maternal and perinatal outcome in pulmonary tuberculosis cases as compared to low risk pregnancies in a tertiary referral hospital. METHODS: A total of 15 cases of pulmonary tuberculosis over a period of two years who delivered in our unit was studied in the retrospective study. The maternal and perinatal outcome in them was compared with 191 low risk pregnancies who delivered at the same time in the hospital after taking into account inclusion and exclusion criteria. RESULTS: The mean age and mean parity was 25.73 ± 2.85 and 28.75 ± 3.11, 2.1 and 1.9 in the 2 groups. Symptoms of pulmonary tuberculosis were cough (100%), chest pain (80%), expectoration (100%), hemoptysis (33.3%), fever (93.33%), anorexia (86.66%) and loss of weight (80%). Symptoms in study patients were significantly more common in study patients. The presence of associated medical problems was similar in the 2 groups. The prevalence of oligoamnios, gestational diabetes mellitus, antepartum hemorrhage and intrahepatic cholestasis was similar in the 2 groups. Prevalence of preterm labor was 53.33% in study group which was significantly higher than in controls (8.9%). Risk of premature rupture of membrane was also significantly higher in the study groups (53.33%) as compared to control groups (8.9%). Mean gestational age was also significantly lower (36.2 weeks) in study group as compared to 38.6 weeks in control group. The incidence of cesarean delivery was similar in the 2 groups (26.66% vs 28.79%). The mean birth weights was 2308.6 gm in the study group as compared to 2707.56 gm in control group. Fetal growth restrictions and Respiratory distress syndrome in babies was significantly higher in study group than in control group. Low APGAR score (<8) was also higher (33.3%) in study group as compared to control group (2.61%). CONCLUSION: Pulmonary tuberculosis during pregnancy is associated with increased perinatal morbidity, low birth weight, poor APGAR and increased respiratory distress rates.

Virulence gene mutations as a differentiator of clinical phenotypes: insights from community-acquired uropathogenic Escherichia coli.

Uropathogenic Escherichia coli (UPEC) remains an important cause of urinary tract infection during pregnancy. Multiple molecular virulence determinants and antibiotic resistant genes facilitate its pathogenesis and virulence phenotype. Hence it is hypothesized that there will be considerable variation in genes among the isolates from symptomatic as well as asymptomatic bacteriuria (ABU) during pregnancy. The aim of this study was to decipher the genetic variation among the two phenotypes. Six different UPEC isolates collected from urine specimens of consecutive pregnant females (five, symptomatic bacteriuria and one, ABU) were tested for their growth kinetics, and biofilm formation. A total of 87 virulence determinants and 56 antibiotic resistance genes were investigated using whole-genome sequencing, to identify putative drives of virulence phenotype. In this analysis, we identified eight different types of fully functional toxin antitoxin (TA) systems [HipAB, YefM-YoeB, YeeU-YeeV (CbtA), YhaV-PrlF, ChpBS, HigAB, YgiUT and HicAB] in the isolates from symptomatic bacteriuria; whereas partially functional TA system with mutations were observed in the asymptomatic one. Isolates of both the groups showed equivalent growth characteristics and biofilm-formation ability. Genes for an iron transport system (Efe UOB system, Fhu system except FhuA) were observed functional among all symptomatic and asymptomatic isolates, however functional mutations were observed in the latter group. Gene YidE was observed predominantly associated with the biofilm formation along with few other genes (BssR, BssS, YjgK, etc.). This study outlines putative critical relevance of specific variations in the genes for the TA system, biofilm formation, cell adhesion and colonization among UPEC isolates from symptomatic and asymptomatic bacteriuria among pregnant women. Further functional genomic study in the same cohort is warranted to establish the pathogenic role of these genes.

Prevalence and resistance pattern of uropathogens from community settings of different regions: an experience from India.

Introduction: Urinary tract infection (UTI) is one of the most common infections in clinical practice worldwide in both healthcare and community settings causing significant morbidity and mortality. It is one of the major conditions at the community level treated empirically and regarded as a potential cause of emergence of antimicrobial resistance (AMR). Limited information is available regarding community-acquired UTI (CA-UTI) from India. Methodology: This is a first of its kind, multicentric-cross-sectional study at the community level targeting patients attending the out-patient department (OPD) of the community health centre (CHC) from four geographical regions (North, South, West and East) of India. The study had been designed to determine the epidemiology, antibiogram profile and identification of extended-spectrum beta-lactamase (ESBL) producer and carbapenem resistant (CR) uropathogens. Samples were collected prospectively from UTI suspected patients coming at CHC and processed at the tertiary healthcare centres using a common standard operating procedure. Clinical history of all the patients exhibiting significant bacteriuria was collected and data was analysed. Result: Overall, 250 out of a total of 2459 (10.1 %) urine samples were positive for bacteria with significant bacteriuria (adult: paediatrics, 6.7 : 1). Females were predominantly affected (male: female, 1 : 2.9). History of recent episode of UTI was observed as the commonest risk factor followed by diabetes mellitus. Altogether, 86 % of total cases were caused by Escherichia coli (68 %) and Klebsiella pneumoniae (17.6 %) together. Among the commonly used oral antibiotics for the Gram-negative bacilli (GNB), the highest resistance was observed against beta-lactams, first- and second-generation cephalosporins, fluoroquinolones and co-trimoxazole. Overall, the prevalence of ESBL producer and CR isolates were 44.8, and 4.3 %, respectively. However, the ESBL production, CR and nitrofurantoin resistance among the uropathogenic E. coli (UPEC) isolates was 52.8, 5.1 and 14 %, respectively. No resistance was found against fosfomycin among the UPEC isolates. Conclusion: The current study highlights the increasing incidence of AMR among uropathogens at the community-settings of India. A significant percentage of ESBL producers among the isolated UPEC and K. pneumoniae were observed. The currently available evidence supports the clinical recommendation of fosfomycin and nitrofurantoin for empiric therapy in CA-UTI in India.

Knowledge, attitude, perceptions, and concerns of pregnant and lactating women regarding COVID-19 vaccination: A cross-sectional survey of 313 participants from a tertiary care centre of North India.

AIM: The study aimed to assess the knowledge, attitude, perceptions, and concerns of pregnant and lactating women regarding COVID-19 vaccination. METHODS: A cross-sectional survey was conducted using a pre-validated questionnaire to assess the knowledge, attitude, perceptions, and concerns about COVID 19 vaccination among pregnant and lactating women. RESULTS: Most (90%) of the study participants(n =313) agreed that it was essential to get vaccinated for COVID-19 and were aware that pregnant (72.2%) or lactating women (65.2%) are eligible for vaccination. There was a significant positive association between willingness to pay for the vaccine and the socio-economic status (p<0.01). Women residing in rural areas wanted to wait to see the effect of the vaccine on other pregnant and lactating women (p<0.001). The major factors associated with vaccine hesitancy were unforeseen future effects of vaccines on the foetus (58.6%) and rapid development and approval of vaccine without including pregnant and lactating women in vaccine trials (53.6%). These factors were positively associated with socioeconomic status (p<0.05) and residence (p<0.01) CONCLUSION: The safety concerns regarding the COVID-19 vaccine is a major reason for vaccine hesitancy. The policymakers should advocate, investigate, and publicize relevant data on vaccine efficacy and safety among these women.

mRNA modifications in cardiovascular biology and disease: with a focus on m6A modification.

Among several known RNA modifications, N6-methyladenosine (m6A) is the most studied RNA epitranscriptomic modification and controls multiple cellular functions during development, differentiation, and disease. Current research advancements have made it possible to examine the regulatory mechanisms associated with RNA methylation and reveal its functional consequences in the pathobiology of many diseases, including heart failure. m6A methylation has been described both on coding (mRNA) and non-coding RNA species including rRNA, tRNA, small nuclear RNA and circular RNAs. The protein components which catalyze the m6A methylation are termed methyltransferase or 'm6A writers'. The family of proteins that recognize this methylation are termed 'm6A readers' and finally the enzymes involved in the removal of a methyl group from RNA are known as demethylases or 'm6A erasers'. At the cellular level, different components of methylation machinery are tightly regulated by many factors to maintain the m6A methylation dynamics. The m6A methylation process impacts different stages of mRNA metabolism and the biogenesis of long non-coding RNA and miRNA. Although, mRNA methylation was initially described in the 1970s, its regulatory roles in various diseases, including cardiovascular diseases are broadly unexplored. Recent investigations suggest the important role of m6A mRNA methylation in both hypertrophic and ischaemic heart diseases. In the present review, we evaluate the significance of m6A methylation in the cardiovascular system, in cardiac homeostasis and disease, all of which may help to improve therapeutic intervention for the treatment of heart failure. RNA methylation in cardiovascular diseases: altered m6A RNA (coding and non-coding RNA) methylation is identified during different cardiovascular diseases. Increased cardiac hypertrophy is observed following METTL3 overexpression. In contrast, reduced FTO level was seen in mice following myocardial infarction. Increased cardiac fibroblasts activation or increased atherosclerotic plaques were also co-related with m6A RNA methylation.

Role of Preoperative and Postoperative Pelvic Floor Distress Inventory-20 in Evaluation of Posthysterectomy Vault Prolapse.

BACKGROUND: Posthysterectomy vault prolapse is a common problem after vaginal or abdominal hysterectomy. The objective was to assess the role of Pelvic Floor Distress Inventory 20 (PFDI-20) in evaluation of vault prolapse. MATERIALS AND METHODS: Prospective study in 20 women with posthysterectomy vault prolapse of Stage 2 and above. The outcome measure was to calculate PFDI-20 score in all cases before surgical intervention and to recalculate it again in 6 months after different surgical procedures for vault prolapse and to statistically compare the PFDI-20 score in different types of surgery over 4 years period at a tertiary referral hospital for surgical treatment. Prolapse was classified using Pelvic Organ Prolapse Quantification and intraoperative findings. All women were operated for vault prolapse as per hospital protocol and stage of prolapse by either vaginal sacrospinous fixation or abdominal sacrocolpopexy. RESULTS: Mean age, parity, and body mass index were 54.8 years, 3.5, and 22.71 kg/m2 respectively. Preceding surgery was vaginal hysterectomy in 75% women and abdominal hysterectomy in 25% women. Complaints were bulge or mass feeling at perineum (100%), pressure in lower abdomen and perineum (55%), and constipation (60%). The type of prolapse was vault prolapse (100%), cystocele (100%), rectocele (100%), and enterocele (45%). The range of PFDI-20 was 88-152 with mean being 123.50 ± 22.71 before surgery while its range decreased significantly to 80-126 with mean being 106.40 ± 16.45 after surgery (P < 0.01). Mean postoperative PFDI-20 score was 107.40 in vaginal sacrospinous fixation group and was 105.30 in abdominal sacrocolpopexy group and was not statistically different (P = 0.18). CONCLUSION: PFDI-20 score can be used to see the adverse impact of vault prolapse on pelvic floor and to assess the beneficial effect of different types of surgeries on the score.

A Cross-sectional Case-control Study of Depression in Incontinent Women.

BACKGROUND: Urinary incontinence (UI) presents in over 50% menopausal women affecting their quality of life leading to depression and hence needs addressal and treatment as very few of them seek medical help. AIMS: Our aim was to determine the prevalence of depression, and the correlation of severity of UI with depression in incontinent women versus continent controls. METHODOLOGY: A cross-sectional case-control study of previously diagnosed 100 incontinent women (Stress/Urgency/Mixed) was done over a period of 3 months. The severity of UI was assessed on Patient Incontinence Severity Assessment (a form of Likert scale) and depression was assessed on a validated Patient Health Questionnaire-9 scale. STATISTICAL ANALYSIS: The statistical analysis was performed using SPSS version 19.0. RESULTS: Most of our cases were 51-60 years, with Urge UI being the most predominant (88%). Hundred percent of our incontinent patients were depressed, with 48% and 45% being severely and moderately severely depressed, respectively. A highly significant correlation was found between the severity of incontinence, amount of leakage, leaking pattern, and depression. CONCLUSION: All of our incontinent patients were depressed, with the severity of depression increasing with the severity of incontinence.

Short and Long Term Follow up and Efficacy of Trans Obturator Tape for Management of Stress Urinary Incontinence.

BACKGROUND: Stress urinary incontinence (SUI) is involuntary leakage of urine on raised intra- abdominal pressure which adversely affects quality of life usually requiring surgical treatment. METHODS: This is a prospective study of efficacy, cure rates and complications of tension free transobturator tape (TOT) surgery on 85 women with SUI. Pre-operatively and 6 months post-operatively International consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) scores were calculated for all patients to know the severity of incontinence and efficacy of tape. RESULTS: Mean age, parity, body mass index and mean duration of symptoms were 45.78 years, 2.68, 26.38 kg/m2 and 3.85 years, respectively. SUI was demonstrated in all cases on cough stress test and Bonney's test. Mean operative time, blood loss, post-operative analgesic injections, post- operative stay and post- operative catheterisation were 23.28 min, 45.50 ml, 1.2 injections, 1.2 days and 1.2 days. Various complications noted were excessive bleeding (3.52%), urinary retention (7.05%), urinary urgency (8.23%), urinary tract infection (2.35%), surgical site infection (1.17%), groin pain (28.23%) and mesh exposure (3.52%). At 6 months follow-up, the complete cure rate was 83.52% , partial cure rate was 11.76% and failure rate was found to be 4.70% whereas it was 79.16%, 12.0% and 8.33% respectively at 3 years follow up. 2 patients (2.35%) required burch colposuspension and 12 patients (14.11%) required pelvic floor exercises and duloxetine therapy for their symptoms. Mean pre- operative ICIQ-SF score reduced post- operatively (17.8 ± 4.67 to 2.71 ± 1.42) (p value = 0.001). CONCLUSION: Study demonstrates short and long-term efficacy and safety of TOT for surgical management of SUI.

Autologous Fascial Slings for Surgical Management of Stress Urinary Incontinence: A Come Back.

Stress urinary incontinence (SUI) is a common type of urinary incontinence adversely affecting the quality of life of women. For mild SUI, life style changes, pelvic floor exercises and medical treatment with duloxetine may help. Most patients of moderate to severe SUI usually require surgical treatment. Various surgical treatment options include Kelly's plication, Burch colposuspension, bulking agents and sling surgeries. Although, suburethral fascial slings including the autologous rectus fascia slings were in vogue before 1990, they were overtaken by minimally invasive, faster and easier artificial midurethral slings (tension free vaginal tape and transobturator tape). However, observation of serious long-term and life changing complications of synthetic midurethral slings like mesh erosion, chronic pelvic pain and dyspareunia led to their adverse publicity and medico legal implications for the operating surgeons. This led US FDA (Food and Drug Administration) to issue a warning against their use. Currently, their use has significantly decreased in many countries, and they are no longer available in some countries. This has led to renaissance of use of natural autologous fascial sling, especially rectus fascia for surgical management of SUI. Although performing rectus fascia sling surgery is technically more challenging, takes longer, has more short-term morbidity like voiding dysfunction, their long-term success is high with very little risk of serious complications like mesh erosion, chronic pelvic pain and dyspareunia. However, multicentric trials and longer follow ups are needed before it's routine recommendation This review discusses the role of autologous fascial sling (especially rectus fascia) for the surgical management of SUI in the current time and the need of ongoing training of this procedure to gynecology residents and urogynecology fellows.