Genetic diversity, morphological traits, quality traits and antioxidants potentiality of Coccinia grandis germplasm under rainfed semi-arid region.

The present study was conducted to evaluate the genetic variability for morphological and qualitative traits of Coccinia for development of trait specific lines at ICAR-Central Horticultural Experiment Station (CIAH-RS), Panchmahals (Godhra), Gujarat during 2020-2022. In this study, we evaluated 26 gynoecious accessions to assess the genetic divergence through principal component and cluster analysis. The experiment was carried out in a randomized complete block design with three replications under rainfed semi-arid conditions. High values of PCV and GCV were observed for variables such as NFFP (25.13 and 22.20), PL (23.14 and 20.69), FD (24.01 and 21.46), AFW (22.98 and 20.13), NFPY (26.38 and 24.40), FYP (37.57 and 31.29), FY (35.55 and 33.20), AsC (28.65 and 27.73), Ac (24.32 and 21.06), TSS (37.23 and 35.94), DPPHL (20.71 and 20.38), FRAPL (21.08 and 20.92), TPF(20.81 and 20.45) respectively. High heritability coupled with high genetic advance as per cent of mean was observed for vine length (VL), internodal length (IL), number of female flowers per plant (NFFP), fruit length (FL), peduncle length (PL), fruit diameter (FD), average fruit weight (AFW), number of fruit per plant per year (NFPY), fruit yield per plant (FYP), fruit yield (FY), ascorbic acid (AsC), acidity (Ac), total soluble solids (TSS), total phenols in leaves TPL), total flavonoids in leaves TFL, CUPRAC in leaves (CUPRACL), DPPH in leaves (DPPHL), FRAP in leaves (FRAPL), Total phenols in fruits (TPF), Total flavonoids in fruits (TFF), CUPRAC in fruits (CUPRACF) and DPPH in fruits (DPPHF). The FYP exhibited a significant positive correlation with variables like VL (0.6833), IL (0.2991), NFFP (0.8107), FD (0.5245), AFW (0.6766), NFPY (0.7659), ASC (0.4611), TSS (0.5004) and TPF (0.4281). The estimates of genetic parameters revealed scope for further improvement of fruit yield by selection. Of the eight principal components, PC-I through PC-VIII had eigen values greater than 1 and it accounts 85.02% of the total variation for 26 gynoecious accessions of Ivy gourd. The eigen values of PC-I comprised 5.775% of total variation followed by PC-II (4.250%), PC-III (3.175%), PC-IV (2.588%), PC-V (1.828%), PC-VI (1.447%), PC-VII (1.179%) and PC-VIII (1.013%).The cluster VI and cluster I having highest mean values for most of traits under study. Thus, genotypes from the distinct cluster like cluster VI and I for should be used for selection of parents and varietal improvement for further breeding programme in ivy gourd.

Deciphering Intermediate Nugent scores: Utility of Real-time PCR for Bacterial Vaginosis diagnosis.

PURPOSE: To optimize real-time PCR assays for diagnosis of Bacterial Vaginosis (BV) and determine cut-off loads by ROC analysis for Gardnerella vaginalis, Atopobium vaginae and Lactobacillus spp. as compared to Nugent scoring (Gold standard) in clinical samples. RESULTS: Out of 125 women, 34 were positive, 26 intermediate and 65 negative for BV by Nugent scoring. All three real-time PCR assays were found to be highly sensitive & specific and AUC suggested excellent diagnostic accuracy. An optimal cut-off was >9.45 × 103 copies/ ml, >3.34 × 103 copies/ ml & ≤ 18.63 × 103 copies/ ml for G. vaginalis, A. vaginae and Lactobacillus spp. respectively, in BV positives. Gram staining and qPCR were discordant only in patients with intermediate scores (n = 26) where qPCR identified 15 (57.69%) as positive and 11 (42.3%) as negative. CONCLUSION: PCR-based molecular BV diagnosis is more accurate and can be used for deciphering intermediate Nugent scores.

Anti-tubercular therapy (ATT) induced thrombocytopenia: A systematic review.

INTRODUCTION: Drug-induced thrombocytopenia is a known adverse event of several drugs. Antitubercular therapy (ATT) is rarely reported but important cause of thrombocytopenia. The present review aimed to understand the profile of thrombocytopenia caused by first-line ATT i.e. isoniazid, rifampicin, pyrazinamide, and ethambutol. MATERIALS AND METHODS: We screened case reports, case series, and letter-to-editor from databases, like Pubmed/MEDLINE, Ovid, and EMBASE from 1970 to 2021. The PRISMA guidelines were followed in the present systematic review. RESULTS: Categorical data were expressed as n (%) and quantitative data were expressed as median (IQR). After applying the inclusion/exclusion criteria, 17 case reports and 7 letters to the editor were selected for the present review. Rifampicin was most frequently associated with thrombocytopenia (65%). A median (IQR) drop to 20,000 (49,500) platelets/mm3 was observed. Anti-rifampicin associated antibodies and anti-dsDNA positivity were found in six studies. Except for two, all patients responded to symptomatic treatment. DISCUSSION: ATT-induced thrombocytopenia can be life-threatening and require hospitalization. Clinicians should be aware of the association of ATT with thrombocytopenia and should take appropriate measures for patient management. CONCLUSION: This review provides clinicians a comprehensive picture of adverse effects and their management in ATT induced thrombocytopenia.

Multi-omic cross-sectional cohort study of pre-malignant Barrett's esophagus reveals early structural variation and retrotransposon activity.

Barrett's esophagus is a pre-malignant lesion that can progress to esophageal adenocarcinoma. We perform a multi-omic analysis of pre-cancer samples from 146 patients with a range of outcomes, comprising 642 person years of follow-up. Whole genome sequencing reveals complex structural variants and LINE-1 retrotransposons, as well as known copy number changes, occurring even prior to dysplasia. The structural variant burden captures the most variance across the cohort and genomic profiles do not always match consensus clinical pathology dysplasia grades. Increasing structural variant burden is associated with: high levels of chromothripsis and breakage-fusion-bridge events; increased expression of genes related to cell cycle checkpoint, DNA repair and chromosomal instability; and epigenetic silencing of Wnt signalling and cell cycle genes. Timing analysis reveals molecular events triggering genomic instability with more clonal expansion in dysplastic samples. Overall genomic complexity occurs early in the Barrett's natural history and may inform the potential for cancer beyond the clinically discernible phenotype.

Effectiveness of two tobacco cessation methods among TB patients.

BACKGROUND: Tobacco and TB are the world´s two greatest public health problems. Exposure to tobacco has been shown to be associated with higher risk of acquiring TB and adverse outcomes such as relapse and TB mortality.OBJECTIVE: To assess and compare self-reported tobacco quit status and biochemically verified cotinine levels among TB patients at different time intervals among two study groups.METHODS: A cluster, randomised controlled trial was conducted on TB patients attending DOTS centres in Delhi, India, who reported using tobacco in any form. Participants were assigned into one of two treatment groups. Centres were randomly assigned to two intervention groups: 1) integrated intervention using behavioural counselling with nicotine replacement therapy (NRT) gum, and 2) intervention using behavioural counselling alone (50 each in intervention and control group). The subjects were followed at Week 1, Month 1, Month 3 and Month 6 for tobacco cessation.RESULTS: At the end of 6 months, patients who received the integrated intervention had significantly higher rate of success in quitting tobacco than those who received the conventional TB treatment alone (78.7% vs. 57.8%; P < 0.03).CONCLUSION: DOTS with tobacco use dependence treatment was successful in our study in helping TB patients to quit tobacco dependence and should therefore be offered to every tobacco user.

Impact of lifestyle modifications on snoring and mild sleep apnoea patients.

OBJECTIVE: Behavioural modification through increasing nutritional awareness, along with customised dietary changes and education about physical inactivity, for obese snorers and mildly sleep apnoeic patients would help improve their quality of life. METHODS: A one-year prospective interventional study enrolled snorers and/or mild obstructive sleep apnoea sufferers, with 36 patients each in the test group and control group. Nutritional information and tailor-made diet charts were given to the 36 test subjects. The severity of snoring and daytime sleepiness after 6 and 12 months was compared using the Epworth Sleepiness Scale and Thornton Snoring Scale as measures of quality of life. RESULTS: Subjective scores on both scales showed highly significant improvement (p ≤ 0.001) in the test group. No significant improvement was seen in the control group. CONCLUSION: Awareness of basic nutrition and customised diet plans help to achieve behavioural modification in the long term, resulting in a better quality of life.

Acceptability, feasibility, and likelihood of stakeholders implementing the novel BPaL regimen to treat extensively drug-resistant tuberculosis patients.

BACKGROUND: BPaL, a 6 month oral regimen composed of bedaquiline, pretomanid, and linezolid for treating extensively drug-resistant tuberculosis (XDR-TB) is a potential alternative for at least 20 months of individualized treatment regimens (ITR). The ITR has low tolerability, treatment adherence, and success rates, and hence to limit patient burden, loss to follow-up and the emergence of resistance it is essential to implement new DR-TB regimens. The objective of this study was to assess the acceptability, feasibility, and likelihood of implementing BPaL in Indonesia, Kyrgyzstan, and Nigeria. METHODS: We conducted a concurrent mixed-methods study among a cross-section of health care workers, programmatic and laboratory stakeholders between May 2018 and May 2019. We conducted semi-structured interviews and focus group discussions to assess perceptions on acceptability and feasibility of implementing BPaL. We determined the proportions of a recoded 3-point Likert scale (acceptable; neutral; unacceptable), as well as the overall likelihood of implementing BPaL (likely; neutral; unlikely) that participants graded per regimen, pre-defined aspect and country. We analysed the qualitative results using a deductive framework analysis. RESULTS: In total 188 stakeholders participated in this study: 63 from Kyrgyzstan, 51 from Indonesia, and 74 from Nigeria The majority were health care workers (110). Overall, 88% (146/166) of the stakeholders would likely implement BPaL once available. Overall acceptability for BPaL was high, especially patient friendliness was often rated as acceptable (93%, 124/133). In contrast, patient friendliness of the ITR was rated as acceptable by 45%. Stakeholders appreciated that BPaL would reduce workload and financial burden on the health care system. However, several stakeholders expressed concerns regarding BPaL safety (monitoring), long-term efficacy, and national regulatory requirements regarding introduction of the regimen. Stakeholders stressed the importance of addressing current health systems constraints as well, especially in treatment and safety monitoring systems. CONCLUSIONS: Acceptability and feasibility of the BPaL regimen is high among TB stakeholders in Indonesia, Kyrgyzstan, and Nigeria. The majority is willing to start using BPaL as the standard of care for eligible patients despite country-specific health system constraints.

Efficacy and safety of aspirin as an adjunctive therapy in tubercular meningitis: A systematic review and meta-analysis.

BACKGROUND: Tubercular meningitis (TBM) is associated with high mortality and stroke with chronic neurological sequelae even with best of care and antitubercular therapy. Studies have shown that aspirin as an adjunctive therapy might play some role in management of TBM. This systematic review and meta-analysis has been planned to evaluate the efficacy and safety of aspirin as an adjunctive therapy in TBM patients. METHODS: We conducted a systematic search of randomized controlled trials in patients with tubercular meningitis published till October 2019 in all major clinical journals. Study was registered with PROSPERO with registration number: CRD42019136689. Articles were tested for eligibility and assessed for quality and various bias. Data synthesis and analysis was done using Review manager 5.3. The primary end point for assessment of efficacy was mortality at three months. The secondary end point was stroke or composite outcome of stroke and mortality at three months. Adverse effects were also assessed as secondary safety end point. FINDINGS: Overall, three eligible randomized controlled trials with 365 participants were included that provided quantitative data for this meta-analysis. The analysis of primary and secondary end points was done using fixed effect model. There was not significant reduction in mortality [hazard ratio 0.78 (95% CI 0.45-1.35, p = 0.37)] and composite outcome of mortality and new onset stroke [hazard ratio 0.86 (95% CI 0.60-1.24, p = 0.43)] in aspirin group as compared to placebo. However, aspirin as compared to placebo significantly reduced new onset stroke [hazard ratio of 0.51 (95% CI 0.29-0.87, p = 0.01)]. INTERPRETATION: We did not find significant reduction in mortality and composite outcome (mortality and new onset stroke) with aspirin as compared to placebo but there was significant reduction in new onset stroke in aspirin group as compared to placebo with Number Needed to Treat (NNT) = 10, which might be of clinical importance since stroke is responsible for high mortality and morbidity in these subset of patients. However, a large well conducted randomized controlled trial is required to put more light on the available evidence.

Radiological evaluation of lacrimal apparatus injury after functional endoscopic sinus surgery.

OBJECTIVE: To determine the incidence of nasolacrimal duct injury after functional endoscopic sinus surgery radiologically, using computed tomography. METHODS: Fifty patients of either sex who underwent functional endoscopic sinus surgery were evaluated for nasolacrimal duct injury by computed tomography. Computed tomography was conducted pre-operatively, and post-operatively at the end of four weeks, and nasolacrimal duct injury was analysed. RESULTS: The prevalence of nasolacrimal duct injury dehiscence was 1.16 per cent, with a similar incidence of 1.16 per cent for nasolacrimal duct injury post-operatively. However, no cases of symptomatic nasolacrimal duct injury were recorded. CONCLUSION: Computed tomography scan is an effective, non-invasive method to evaluate nasolacrimal duct injury following functional endoscopic sinus surgery, in accordance with evidence-based medicine.

Nutritional intervention during maxillomandibular fixation of jaw fractures prevents weight loss and improves quality of life.

Maxillomandibular fixation (MMF) for the management of jaw fractures leads to compromised nutritional intake and consequent weight loss and poor quality of life (QoL). The present study aimed to evaluate the effectiveness of a home-based dietary plan to prevent weight loss, and its effect on the QoL of patients who underwent four weeks of MMF for the treatment of maxillofacial fractures. A total of 50 patients were randomised into nutritional intervention (Group1) and non-intervention groups (Group 2). Patients in Group1 were counselled by a dietitian and given a diet plan. Patients in Group 2 were advised to take a liquid diet of their own choice in the form of shakes, juices, and milk, along with protein supplements. Patients in Group1 lost significantly less weight than those in Group 2 (p=0.001) at week four of follow up. Group1 patients had significantly better oral health-related QoL in the 'physical pain' domain during the two weeks of MMF, and in the 'physical discomfort' and 'psychological disability' domains two weeks after the release of MMF. They had significantly better nutrition-related QoL in all the domains during the two weeks of MMF and, except for the 'physical' domain, also during the two weeks after its release. Individual home-based diet plans effectively helped the patients maintain their weight and improved QoL.

A mechanistic study of the tremor associated with epidural anaesthesia for intrapartum caesarean delivery.

BACKGROUND: It is not known if the tremor associated with an epidural top-up dose for intrapartum caesarean delivery is thermoregulatory shivering. A tremor is only shivering if it has the same frequency profile as cold stress-induced shivering. Thermoregulatory shivering is a response to a reduction in actual body temperature, whereas non-thermoregulatory shivering may be triggered by a reduction in sensed body temperature. This mechanistic study aimed to compare: 1. the frequency profiles of epidural top-up tremor and cold stress-induced shivering; and 2. body temperature (actual and sensed) before epidural top-up and at the onset of tremor. METHODS: Twenty obstetric patients received an epidural top-up for intrapartum caesarean delivery and 20 non-pregnant female volunteers underwent a cold stress. Tremor, surface electromyography, core temperature, skin temperature (seven sites) and temperature sensation votes (a bipolar visual analog score ranging from -50 to +50 mm) were recorded. RESULTS: The mean (SD) primary oscillation (9.9 (1.9) Hz) frequency of epidural top-up tremor did not differ from that of cold stress-induced shivering (9.0 (1.6) Hz; P=0.194), but the mean (SD) burst frequency was slower (6.1 (1.2) × 10-2 Hz vs 6.9 (0.7) × 10-2 Hz, respectively; P=0.046). Before the epidural top-up dose, the mean (SD) core temperature was 37.6 (0.6) °C. Between the epidural top-up dose and the onset of tremor the mean (SD) core temperature did not change (-0.1 (0.1) °C; P=0.126), the mean (SD) skin temperature increased (+0.4 (0.4) °C; P=0.002) and the mean (SD) temperature sensation votes decreased (-12 (16) mm; P=0.012). CONCLUSION: These results suggest that epidural top-up tremor is a form of non-thermoregulatory shivering triggered by a reduction in sensed body temperature.

Corticosteroid-associated lupus pancreatitis: a case series and systematic review of the literature.

BACKGROUND: Acute pancreatitis is an uncommon complication that occurs in 0.85% to 4% of patients with systemic lupus erythematosus (SLE). In some patients, it occurs within days to weeks of starting medium-to-high dose corticosteroids. The authors have used the term 'corticosteroid-associated lupus pancreatitis' for these patients, and they report a case series and perform a systematic review of previously published reports. METHODS: For the purpose of this study, corticosteroid-associated lupus pancreatitis was defined as occurrence of acute pancreatitis in patients with SLE (fulfilling the 1997 ACR), within 3 weeks of starting therapy with medium-to-high dose corticosteroids - either newly initiated or escalated from a lower dose. All patients with SLE admitted in the last 2.5 years in a North Indian university hospital were reviewed, and those with pancreatitis who fulfilled the above criteria were included in the case series. For the systematic review, a PUBMED search using the keywords 'lupus' and 'pancreatitis' was performed, and reports in English were reviewed for an association with corticosteroids. RESULTS: Among 420 admissions of SLE patients, six patients (1.4%) fulfilled criteria for corticosteroid-associated lupus pancreatitis. All were female, with mean age and disease duration of 19.7 ± 3.3 and 3.8 ± 2.5 years respectively. All had active disease and developed acute pancreatitis within 48-72 hours of newly initiating medium-to-high dose corticosteroids (in three patients) or escalating them to medium-high dose (in three patients). After the development of pancreatitis, corticosteroids were continued in all except one patient. In addition, two patients received pulse methylprednisolone, two received pulse cyclophosphamide and one was started on azathioprine. Three patients died during hospitalization, all with severe pancreatitis. On systematic review, among 451 cases of lupus pancreatitis reported, 23 (5%) fulfilled criteria for 'corticosteroid-associated lupus pancreatitis'. A majority of them had pancreatitis within 3 days of starting treatment with medium-to-high dose corticosteroids. The mortality in these patients was 37.5%. CONCLUSION: In a small but substantial proportion of patients with lupus who develop pancreatitis, it occurs within days to weeks of starting medium-to-high dose corticosteroids. Many of these patients continue to receive corticosteroids, and some receive more aggressive immunosuppression. However, they have significant mortality, and further studies are required to identify appropriate treatment in this subgroup of patients.

Body temperature, cutaneous heat loss and skin blood flow during epidural anaesthesia for emergency caesarean section.

It is not clear how converting epidural analgesia for labour to epidural anaesthesia for emergency caesarean section affects either cutaneous vasomotor tone or mean body temperature. We hypothesised that topping up a labour epidural blocks active cutaneous vasodilation (cutaneous heat loss and skin blood flow decrease), and that as a result mean body temperature increases. Twenty women in established labour had body temperature, cutaneous heat loss and skin blood flow recorded before and after epidural top-up for emergency caesarean section. Changes over time were analysed with repeated measures ANOVA. Mean (SD) mean body temperature was 36.8 (0.5)°C at epidural top-up and 36.9 (0.6)°C at delivery. Between epidural top-up and delivery, the mean (SD) rate of increase in mean body temperature was 0.5 (0.5) °C.h-1 . Following epidural top-up, chest (p < 0.001) and forearm (p = 0.004) heat loss decreased, but head (p = 0.05), thigh (p = 0.79) and calf (p = 1.00) heat loss did not change. The mean (SD) decrease in heat loss was 15 (19) % (p < 0.001). Neither arm (p = 0.06) nor thigh (p = 0.10) skin blood flow changed following epidural top-up. Despite the lack of change in skin blood flow, the most plausible explanation for the reduction in heat loss and the increase in mean body temperature is blockade of active cutaneous vasodilation. It is possible that a similar mechanism is responsible for the hyperthermia associated with labour epidural analgesia.

Generation of six multiple sclerosis patient-derived induced pluripotent stem cell lines.

Multiple sclerosis (MS) is considered a chronic autoimmune disease of the central nervous system that leads to gliosis, demyelination, axonal damage and neuronal death. The MS disease aetiology is unknown, though a polymorphism of the TNFRSF1A gene, rs1800693, is known to confer an increased risk for MS. Using retroviral delivery of reprogramming transgenes, we generated six MS patient-specific iPSC lines with two distinct genotypes, CC or TT, of the polymorphism rs1800693. iPSC lines had normal karyotype, expressed pluripotency genes and differentiated into the three germ layers. These lines offer a good tool to study MS pathomechanisms and for drug testing.

Vulvo-vaginal ano-gingival syndrome: Another variant of mucosal lichen planus.

Vulvo-vagino-gingival syndrome was described as a distinctive pattern of erosive plurimucosal lichen planus (LP), and it is a clinical triad of vulval, vaginal, and gingival LP. It can lead to sequelae such as vaginal and urethral stenosis which can have severe implications on the quality of life. We report a case of a 40-year-old female who developed urethral, vaginal, as well as anal stenosis as a result of long-term exclusive mucosal LP involving vulvo-vaginal and anal mucosa along with oral LP without any other cutaneous involvement. This case is being reported because of the rare association of anal LP with vulvo-vagino-gingival syndrome and its gross similarity to lichen sclerosus.

Response to interferon-beta treatment in multiple sclerosis patients: a genome-wide association study.

Up to 50% of multiple sclerosis (MS) patients do not respond to interferon-beta (IFN-ß) treatment and determination of response requires lengthy clinical follow-up of up to 2 years. Response predictive genetic markers would significantly improve disease management. We aimed to identify IFN-ß treatment response genetic marker(s) by performing a two-stage genome-wide association study (GWAS). The GWAS was carried out using data from 151 Australian MS patients from the ANZgene/WTCCC2 MS susceptibility GWAS (responder (R)=51, intermediate responders=24 and non-responders (NR)=76). Of the single-nucleotide polymorphisms (SNP) that were validated in an independent group of 479 IFN-ß-treated MS patients from Australia, Spain and Italy (R=273 and NR=206), eight showed evidence of association with treatment response. Among the replicated associations, the strongest was observed for FHIT (Fragile Histidine Triad; combined P-value 6.74 × 10-6) and followed by variants in GAPVD1 (GTPase activating protein and VPS9 domains 1; combined P-value 5.83 × 10-5) and near ZNF697 (combined P-value 8.15 × 10-5).

Comparison of short-axis out-of-plane versus long-axis in-plane ultrasound-guided radial arterial cannulation in adult patients: a randomized controlled trial.

BACKGROUND: The current available literature is not unanimous in reporting the utility of short-axis and long-axis techniques for radial artery cannulation in both adults and children. This study was designed to compare short-axis out-of-plane (SA-OOP) and long-axis in-plane (LA-IP) techniques in ultrasound-guided radial artery cannulation in adults. METHODS: In this prospective randomized controlled trial, 150 adult patients of American Society of Anesthesiologists physical status I-III aged between 18 and 70 years were included. All patients were randomized into two groups (group SA-OOP) and (group LA-IP) of 75 each undergoing ultrasound-guided radial artery cannulation. The primary outcome was successful cannulation in the first attempt. Secondary outcomes included antero-posterior arterial diameter, skin-to-artery distance, ultrasonic localization time, cannulation time, no of attempts to cannulate artery, cannula insertion failure, and vascular complications. RESULTS: First-attempt arterial cannulation was successful in 80 % of patients in the SA-OOP group as opposed to 82.6 % patients in the LA-IP group (p = 0.67). The time to cannulate the artery was similar between the two groups, but the time to localize artery was significantly higher in the long-axis technique (p < 0.001). CONCLUSIONS: The first-attempt cannulation success rate and cannulation time in adult patients are similar in ultrasound-guided radial artery cannulation with both short-axis as well as long-axis techniques. Trial registration Clinical Trial Registry of India (CTRI/2015/02/005552).