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Objective: To evaluate the antenatal profile of the mother and the immediate neonatal morbidity and mortality till discharge.Methods: The study was a retrospective analysis of 92 patients of preterm labour who delivered babies weighingResults: A total of 92 mothers in preterm labour at 26 to 34 weeks were admitted and subsequently delivered 70 VLBW babies (< 1500 gms) and 36 ELBW babies (< 1000 gms) including 8 pairs of twins and 3 triplets pregnancies. Majority of the patients (93.4%) were booked. Amongst the various high risk factors for preterm labour, anaemia during pregnancy (32.6%), bacterial vaginosis (26%), gestational hypertension (18.4%) and pervious history of preterm labour (18.4%) were common associations. Calcium channel blocker (Depin) tocolysis was effective in postponing labour from 48 hours to more than 2 weeks. The cesarean section rate was very high (67.3%) in our study. The commoner neonatal complications in both VLBW and ELBW babies were RDS, neonatal jaundice and sepsis. Features of IUGR were seen in both the groups (22.8% in VLBW and 22.2% in ELBW babies). The neonatal mortality rate till discharge was 15.7% in VLBW group and 33.3% in ELBW group. The morality rate was highest in 26 to 30 weeks gestation babies and in babies weighing < 800 gms.Conclusion: Antenatal profile of preterm labour in our series showed a number of high risk factors. The identification of common high risk factors is important for appropriate prenatal care. A better neonatal survival rate was possible due to timely intervention, appropriate management and NICU care facility available in our tertiary care centre. [ABSTRACT FROM AUTHOR]

The Kirsten rat sarcoma viral (KRAS) oncogene is the most frequently mutated isoform of RAS, associated with 85 % of RAS-driven cancers. KRAS functions as a signaling hub, participating in various cellular signaling pathways and regulating a wide range of important activities, including cell proliferation, differentiation, growth, metabolism, and migration. Despite being the most frequently altered oncogenic protein in solid tumors, over the past four decades, KRAS has historically been considered "undruggable" owing to a lack of pharmacologically targetable pockets within the mutant isoforms. However, improvements in drug design and development have culminated in the development of selective inhibitors for KRAS mutants. Recent developments have led to the successful targeting of the KRAS G12C mutant through covalent inhibitors that exploit the unique cysteine residue introduced by the mutation at 12th position. These inhibitors bind covalently to C12, locking KRAS in its inactive GDP-bound state and preventing downstream signaling. Some of these inhibitors have shown encouraging results in KRAS G12C mutant cancer patients but suffer from drug resistance, toxicity, and low therapeutic efficacy. Recently, there have been great advancements in the discovery of drugs that directly target the switch I (S-I), switch-II (S-II) and S-I/II interface sites of KRAS mutant proteins. These include KRAS G12C inhibitors like AMG510 (Sotorasib) and MRTX849 (Adagrasib), which have got FDA approval for non-small cell lung cancer harboring the KRAS G12C mutation. There is no approved drug for cancers harboring other KRAS mutations, although efforts have expanded to target other KRAS mutations and the Switch I/II interface, aiming to disrupt KRAS-driven oncogenic signaling. Structure-activity relationship (SAR) studies have been instrumental in optimizing the binding affinity, selectivity, and pharmacokinetic properties of these inhibitors, leading to the development of promising therapeutic agents like Sotorasib and Adagrasib. This review provides an overview of the KRAS pathway, KRAS binding sites, strategies for direct and indirect inhibition using small molecules, and SAR based on the co-crystal structures of inhibitors with KRAS mutants which is expected to offer new hope for patients with KRAS-driven cancers through the development of new KRAS-targeted drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Originating in South America, wheat blast disease has spread to both Asia and Africa and is considered a significant threat to food security. Bangladesh experienced the first outbreak of wheat blast outside of the Americas in 2016. Shortly thereafter, the blast-resistant variety BARI Gom 33 was released. Seeds of this variety are however not as widely available as required, although the disease threat remains. While varietal mixtures have been shown to mitigate some symptoms and yield losses associated with other fungal diseases in wheat, there is a complete research gap on this topic as it pertains to wheat blast. As such, we evaluated the potential of using BARI Gom 33 as a component of a variety mixture under high disease pressure in Bangladesh. During three cropping seasons, blast symptoms and yield were determined in a field experiment for the highly blast-susceptible variety BARI Gom 26, the moderately susceptible BARI Gom 30, the resistant BARI Gom 33, and seven mixture combinations of the three varieties using artificial inoculation to increase disease pressure. In addition to wheat blast, Bipolaris leaf blight (BpLB) symptoms were observed and evaluated. While yields of the susceptible varieties were severely affected by blast even after fungicide application, disease-inflicted yield loss without fungicide was only 15% for sole BARI Gom 33 and did not differ significantly from yield losses in BARI Gom 33 and BARI Gom 30 mixtures. Furthermore, in the mixture containing 67% BARI Gom 33 and 33% BARI Gom 30, blast incidence and severity were reduced by 25% and 16%, respectively, in comparison to weighted values in sole stands. Conversely, mixing varieties tended to increase the symptoms of BpLB. Under high wheat blast pressure, fungicide protection against blast was relatively weak, underscoring the importance of resistant varieties. Although variety mixtures did not increase yield, the yield advantage of BARI Gom 33 was maintained when its seeds were mixed with the less resistant BARI Gom 30. This study confirms recommendations that farmers should use BARI Gom 33 as a first line of defense against wheat blast in Bangladesh. Yet where farmers cannot access sufficient BARI Gom 33 seed for planting, our data suggest that agricultural extension services can recommend this variety with non-resistant cultivars as interim strategy without significant risk of yield loss., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Timothy J. Krupnik reports financial support was provided by 10.13039/100000200USAID, 10.13039/501100000974ACIAR, the 10.13039/100000865Bill and Melinda Gates Foundation, and 10.13039/501100015815CGIAR. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background Salpingectomy is a common surgical procedure in gynecology performed for various indications. Given its proximity to the ovaries and shared vascular supply, concerns have arisen regarding compromised ovarian reserve post-salpingectomy. Objective We aim to study the effect of two different energy sources (group 1: salpingectomy using bipolar electrocautery followed by division with scissors versus group 2: salpingectomy with ultrasonic shears) on residual ovarian reserve. The effect on ovarian reserve was assessed using serum levels of follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), antral follicle count (AFC), and ovarian size pre- and postoperatively. Materials and methods According to the inclusion criteria, 68 women were included in the study and randomized into the bipolar electrocautery group and the ultrasonic shear group. The final analysis included 34 women in the bipolar electrocautery group and 32 in the ultrasonic shear group. Preoperatively, the ovarian reserve of all women was assessed using FSH, AMH, AFC, and ovarian size. These parameters were then reassessed at three months postoperatively, and the percentage change was analyzed. Results The mean baseline serum AMH and serum FSH values in the bipolar electrocautery group were 3.9 ± 2.9 ng/ml and 6.6 ± 2.1 IU/L, respectively, comparable with the values in the ultrasonic shear group, where serum AMH was 3.2 ± 2.9 ng/ml and serum FSH was 7.3 ± 3.9 IU/L. AFC and ovarian size were comparable between the two groups preoperatively (bipolar electrocautery group AFC was 8 ± 2.2, ovarian size on the right side was 3.3 ± 0.7 cm and on the left was 3.2 ± 0.6 cm; ultrasonic shear group AFC was 5.7 ± 2.3, ovarian size on the right side was 3.4 ± 0.8 cm and on the left was 3.2 ± 0.8 cm). After three months of postoperative analysis, AFC showed a significant fall from the preoperative value in the bipolar electrocautery group compared to the ultrasonic shear group (AFC reduced from 8 ± 2.2 to 5.5 ± 2.3 vs. 8.6 ± 0.5 to 7.9 ± 2.3; p=0.002). The other parameters showed no statistically significant change. Conclusion Our study suggests that ultrasonic shear is safer than bipolar electrocautery for preserving ovarian reserve after salpingectomy. However, further research is needed to confirm these findings., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Zangmo et al.)

Respiratory illnesses and its repercussions are becoming more prevalent worldwide. It is necessary to research both innovative treatment and preventative techniques. Millions of confirmed cases and fatalities from the COVID-19 epidemic occurred over the previous two years. According to the review research, cannabinoids are a class of medicines that should be considered for the treatment of respiratory conditions. Cannabinoids and inhibitors of endocannabinoid degradation have illustrated advantageous anti-inflammatory, asthma, pulmonary fibrosis, and pulmonary artery hypotension in numerous studies ( in vitro and in vivo ). It has been also noted that CB2 receptors on macrophages and T-helper cells may be particularly triggered to lower inflammation in COVID-19 patients. Since the majority of lung tissue contains cannabinoid receptors, cannabis can be an effective medical tool for treating COVID-19 as well as pulmonary infections. Notably, CB2 and CB1 receptors play a major role in immune system modulation and anti-inflammatory activities. In this review, we put forth the idea that cannabis might be helpful in treating pulmonary contagion brought on by viral integration, such as that caused by SARS-CoV-2, haemophilus influenza type b, Streptococcus pneumoniae , influenza virus, and respiratory syncytial virus. Also, a detailed overview of CB receptors, intricate mechanisms, is highlighted connecting link with COVID-19 viral structural modifications along with molecular basis of CB receptors in diminishing viral load in pulmonary disorders supported through evident literature studies. Further, futuristic evaluations on cannabis potency through novel formulation development focusing on in vivo/in vitro systems can produce promising results., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Incidence of Tuberculosis (TB) cases in India reported in 2019 is 193 per 1 lakh population [National Tuberculosis Elimination Plan (NTEP)]. In India, annual extra pulmonary TB burden is 20-25%, of which 4% of cases are of urogenital origin (Revised National TB Control Programme, 2019; World Health Organization, 2019). The Ministry of Health and Family Welfare has made a target of eliminating tuberculosis by 2025 under the NTEP by the process of identification, notification and treatment of cases. Tuberculosis being a leading cause of infertility in developing countries, employing best clinical practices and being "TB-minded" will also save the patient of enormous anxiety and uncertainity and also decrease the time gap between clinical presentation and diagnosis to optimize fertility outcome., Methodology: A prospective cohort study of cases presenting with unusual findings and ultimately being diagnosed as genital tuberculosis was conducted in the gynaecology OPD, AIIMS, New Delhi, from November 2020 to November 2021 (1 year). Patients were investigated judiciously, diagnosis made and followed up for their response to anti tuberculosis therapy (ATT)., Results: This data comprises of conglomerate of ten cases with unconventional exhibition of genital tuberculosis. 70% of the cases presented with pain lower abdomen not specifically related to menstrual cycle and often confused with IBD. Tubo ovarian mass (70%) mimicking as simple ovarian cyst, ovarian carcinoma or endometriosis was the most common clinical finding we came across., Competing Interests: Conflict of interest The authors have none to declare., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Tuberculosis is one of the most dreadful infectious diseases, afflicting global populations with anguish. With the emergence of multi-drug resistant strains of mycobacteria, the imperative for new anti-tuberculosis drugs has grown exponentially. Thus, the current study delves into evaluating the impact of Perovskia abrotanoides and its active metabolites-namely, rosmarinic acid and its derivatives-against strains of Mycobacterium tuberculosis (Mtb). Through the use of the CRI assay, the antimycobacterial potential of the high-altitude medicinal plant P. abrotanoides was gauged, while docking and molecular dynamics simulations unveiled plausible targets. Of these, the peak antimycobacterial effectiveness was observed in the P. abrotanoides ethyl acetate extract with 125 µg/mL as minimum inhibitory concentration against various strains of M. tuberculosis , encompassing H37Rv and strains resistant to multiple drugs. Following bioassay-guided fractionation and isolation, rosmarinic acid and rosmarinic acid methyl ester emerged as potent molecules against H37Rv and multidrug-resistant M. tuberculosis strains; minimum inhibitory concentration ranging from 15 to 32 µg/mL. Additionally, out of 22 targets explored, Mtb lipoamide dehydrogenase (PDB: 3II4) and Rv2623 (PDB: 3CIS) were forecasted as potential Mtb targets for rosmarinic acid and rosmarinic acid methyl ester, respectively, a supposition further affirmed by molecular simulations (100 ns). The stability of both complexes throughout the simulation was measured by protein backbone root-mean-square deviation, substantiating their roles as respective targets for antimycobacterial activities.Communicated by Ramaswamy H. Sarma.

Background We assessed the efficacy and safety of management of morbidly adherent placenta by the transfundal uterine incision approach. As a secondary outcome measure, we compared ultrasound and magnetic resonance imaging (MRI) for the diagnosis of adherent placenta. Methods We retrospectively analysed the records of 5 years of women with adherent placenta. Twenty-five women with an antenatal diagnosis of placenta increta and percreta operated by transfundal uterine incision were included. Blood loss, transfusion requirements, operative injuries, and maternal and neonatal intensive care unit (ICU) stay were compared among three different types of adherent placenta. Surgical and other outcome measures were also analysed. Results On antenatal screening with ultrasound, an accurate diagnosis could be achieved in all cases of increta and two-thirds of percreta. Antenatal diagnosis by MRI detected 93.3% of increta and all percreta cases. The mean (SD) gestation at delivery was 34 (4.9) weeks in accreta, 34.9 (2.7) weeks in increta and 31 (4.8) weeks in percreta patients. The mean blood loss encountered intraoperatively was 1012.5 (193.1) ml, 1566.67 (566.52) ml and 1591.67 (629.61) ml in accreta, increta and percreta patients, respectively. Inadvertent bladder injury occurred in 3 women who had placenta percreta invading the bladder. There was no long-term morbidity and no mortality. Conclusion Transfundal incision for delivery of baby is associated with the advantage of avoiding the placenta thereby minimizing blood loss.

Antimicrobial resistance (AMR) to currently available antibiotics/drugs is a global threat. It is desirable to develop new drugs that work through a novel target(s) to avoid drug resistance. This review discusses the potential of the caseinolytic protease P (ClpP) peptidase complex as a novel target for finding novel antibiotics, emphasising the ClpP's structure and function. ClpP contributes to the survival of bacteria via its ability to destroy misfolded or aggregated proteins. In consequence, its inhibition may lead to microbial death. Drugs inhibiting ClpP activity are currently being tested, but no drug against this target has been approved yet. It was demonstrated that Nblocked dipeptides are essential for activating ClpP's proteolytic activity. Hence, compounds mimicking these dipeptides could act as inhibitors of the formation of an active ClpP complex. Drugs, including Bortezomib, Cisplatin, Cefmetazole, and Ixazomib, inhibit ClpP activation. However, they were not approved as drugs against the target because of their high toxicity, likely due to the presence of strong electrophiles in their warheads. The modifications of these warheads could be a good strategy to reduce the toxicity of these molecules. For instance, a boronate warhead was replaced by a chloromethyl ketone, and this new molecule was shown to exhibit selectivity for prokaryotic ClpP. A better understanding of the structure and function of the ClpP complex would benefit the search for compounds mimicking N-blocked dipeptides that would inhibit ClpP complex activity and cause bacterial death., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The cytochrome bcc-aa3 supercomplex, a key component in the electron transport chain pathway involved in bacterial energy production and homeostasis, is a clinically validated target for tuberculosis (TB), leading to Telacebec (Q203). Telacebec is a potent candidate drug under Phase II clinical development for the treatment of drug-sensitive and drug-resistant TB. Recently, the cryo-electron microscopy structure of this supercomplex from Mycobacterium tuberculosis (Mtb) complexed with Q203 was resolved at 6.9 Å resolution (PDB ID: 7E1W). To understand the binding site (Q P site) flexibility and Q203's stability at the Q P site of the Mtb cytochrome bcc complex, we conducted molecular dynamics (MD) simulation and free energy analysis on this complex in an explicit hydrated lipid bilayer environment for 500 ns. Through this study, the persistence of a range of direct and indirect interactions was observed over the course of the simulation. The significance of the interactions with His375, Tyr161, Ala178, Ala179, Ile183, His355, Leu356, and Thr313 is underlined. Electrostatic energy was the primary source of the net binding free energy, regardless of the important interacting residues. The overall binding free energy for Q203 was -112.84 ± 7.73 kcal/mol, of which the electrostatic and lipophilic energy contributions were -116.31 ± 1.14 and -21.32 ± 2.35 kcal/mol, respectively. Meanwhile, DFT calculations were utilized to elucidate Q203's molecular properties. Overall, this study deciphers key insights into the cytochrome bcc-aa3 supercomplex with Q203 on the ground of molecular mechanics and quantum mechanics that may facilitate structure-based drug design and optimization for the discovery of the next-generation antitubercular drug(s).Communicated by Ramaswamy H. Sarma.

Background It has been postulated that sodium bicarbonate can reduce postoperative pain by neutralizing the acidic peritoneal environment created by carbon dioxide. It also prevents phrenic nerve damage and peritoneal irritation. The present study is a randomized controlled trial aimed at studying the effects of sodium bicarbonate in reducing postoperative pain in laparoscopic gynecological surgeries. Materials and methods This was a single-center, prospective, two-arm, double-blinded randomized control trial in which intraperitoneal irrigation with sodium bicarbonate was compared with normal saline in operative laparoscopy. Group I (intervention group) consisted of 40 patients who received intraperitoneal sodium bicarbonate, and Group II (control group) consisted of 40 patients who received normal saline. All procedures were conducted under general anesthesia. Postoperative pain scores were compared between intervention and control groups.  Results The most common indication of laparoscopy was infertility. There was no difference in the duration of surgery between the two arms (p=0.27). The mean value of the visual analog scale (VAS) score at the shoulder tip was found to be significantly reduced in the intervention group at two hours (p=0.02), four hours (p=0.0009), and 12 hours (p=0.0002) after surgery. The mean VAS score at the abdomen and port sites was also found to be significantly reduced in the intervention group in the first 24 hours after surgery (p<0.05). With the increase in the time period from surgery, the mean VAS scores decreased in both intervention and control groups.  Conclusion Intraperitoneal irrigation with sodium bicarbonate is beneficial in reducing postoperative pain in operative laparoscopy. However, multicenter randomized trials with a greater number of participants will be helpful to confirm the findings., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Agarwal et al.)

Gradually increasing interest in laparoscopic surgeries has led to the advent of various lesser invasive techniques in the form of vaginal natural orifice transluminal endoscopic surgery (vNOTES) and laparoendoscopic single-site (LESS) surgery. Very few studies have analyzed the advantages and disadvantages of vNOTES over LESS surgeries in hysterectomy. After a comprehensive search, full texts of relevant manuscripts were obtained to assess eligibility for recruitment. A comprehensive meta-analysis was subsequently performed to compare the outcomes of vNOTES and LESS in hysterectomy, and forest plots were constructed. Four articles were rendered for review (three retrospective cohort studies and one randomized controlled trial). Three studies showed lesser postoperative pain in vNOTES compared to LESS. In one study, postoperative vaginal pain was higher in vNOTES due to additional suture between uterine artery and vaginal wall. The meta-analysis concluded that vNOTES could be better alternative to LESS hysterectomies. However, further large multicentric randomized trials are required for the standardization of the surgical method., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Gynecology and Minimally Invasive Therapy.)

Background:  Lung protective ventilation during the intraoperative period is now well established. However, the additional role of positive end-expiratory pressure (PEEP) during the intraoperative period remains uncertain in major laparoscopic gynecological surgery. The authors hypothesized that compliance-based optimum PEEP titration reduces postoperative lung atelectasis and improves outcomes., Methods:  Patients undergoing major laparoscopic pelvic gynecological surgeries with healthy lungs were randomized to the fixed PEEP group (PEEP 5 cm H 2 O and recruitment maneuver {RM}) and optimum PEEP group (compliance-based PEEP and RM). Lung ultrasound and arterial blood gas analysis were performed at four time points. Modified lung ultrasound scoring was done, and the same was used as means of assessing lung aeration and the amount of lung atelectasis. Postoperative supplemental oxygen requirement and duration were also assessed and compared., Results: Lung ultrasound score (LUS) 30 minutes after extubation in fixed (Group F) and optimum (Group O) PEEP groups were median (interquartile range {IQR}) 3 (2-3) versus 1 (1-2), p=0.0001. Ventilatory parameters between Group F and Group O after lung recruitment were tidal volume (mean 357 mL {SD: 35} versus 362 mL {SD: 22}, p=0.46), PEEP (median, 5 cm H 2 O {IQR: 5-5} versus median 16 cm H 2 O {IQR: 14-18}), peak airway pressure (median 26 cm H 2 O {IQR: 24-28} versus median 30 cm H 2 O {IQR: 28-32} p<0.0001), plateau pressure (median 22 cm H 2 O {IQR: 20-24} versus median 26 cm H 2 O {IQR: 24-28} p<0.0001), static compliance (32.07±8.36 mL cm H 2 O-1 versus 39.58±8.99 mL cm H 2 O-1, p=0.0002). The number of patients requiring postoperative oxygen therapy to maintain SpO 2  >94% after extubation in postanesthesia care unit (PACU) was statistically significantly greater in group F (39/41 {95%} versus 30/41 {73%}, p=0.007). Median (IQR) duration of oxygenation therapy in the first 24 hours of the postoperative period between Group F and Group O differed with statistical significance, with the median (IQR) values being 25 (20-30) minutes versus 10 (0-15) minutes (p<0.0001)., Conclusions:  The modified lung ultrasound score significantly differed intraoperatively between the two groups, with lower scores in the optimum PEEP group. This has reflected improved postoperative outcomes in optimum PEEP group patients, with fewer patients requiring postoperative oxygen supplementation and reduced supplemental oxygen requirement duration., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, L et al.)

Objectives: The objective of this study was to assess the effect of local infiltration of anesthetic to the vaginal vault on postoperative pain after total laparoscopic hysterectomy., Materials and Methods: This was a single-center, randomized trial. Women assigned to laparoscopic hysterectomy were randomly divided into two groups. In the intervention group ( n = 30), the vaginal cuff was infiltrated with 10 ml of bupivacaine, whereas the control group ( n = 30) did not receive local anesthetic infiltration to vaginal vault. The primary outcome measure was to analyze the efficacy of bupivacaine infiltration in the study group by comparing the postoperative pain in both the groups at 1, 3, 6, 12, and 24 h using pain visual analog scale (VAS). The secondary outcome was to measure the need for rescue opioid analgesia., Results: Group I (intervention group) had lesser mean VAS score at 1 st , 3 rd , 6 th , 12 th , and 24 h compared to Group II (control group). There was an additional requirement of opioid analgesia for postoperative pain in Group II than in Group I, which was statistically significant ( P < 0.05)., Conclusion: Injection of local anesthetic into the vaginal cuff increased the number of women experiencing only minor pain after laparoscopic hysterectomy and decreased postoperative opioid usage and its side effects. Local anesthesia of the vaginal cuff is safe and feasible., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Gynecology and Minimally Invasive Therapy.)

The endocannabinoid system consists of several phytocannabinoids, cannabinoid receptors, and enzymes that aid in numerous steps necessary to manifest any pharmacological activity. It is well known that the endocannabinoid system inhibits the pathogenesis of the inflammatory and autoimmune disease rheumatoid arthritis (RA). To the best of our knowledge, no research has been done that explains the network-pharmacology-based anti-rheumatic processes by focusing on the endocannabinoid system. Therefore, the purpose of this study is to further our understanding of the signaling pathways, associated proteins, and genes underlying RA based on the abundant natural endocannabinoids. The knowledge on how the phytocannabinoids in Cannabis sativa affect the endocannabinoid system was gathered from the literature. SwissTarget prediction and BindingDB databases were used to anticipate the targets for the phytocannabinoids. The genes related to RA were retrieved from the DisGeNET and GeneCards databases. Protein-protein interactions (high confidence > 0.7) were carried out with the aid of the string web server and displayed using Cytoscape. The Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis was used to perform enrichment analyses on the endocannabinoid-RA common targets. ShinyGO 0.76 was used to predict the biological processes listed in the Gene Ontology (GO) classification system. The binding affinity between the ligand and the receptors was precisely understood using molecular docking, induced-fit docking, and a molecular dynamics simulation. The network pharmacology analyses predicted that processes like response to oxygen-containing compounds and peptodyl-amino acid modification are related to the potential mechanisms of treatment for RA. These biological actions are coordinated by cancer, neuroactive ligand-receptor interaction, lipids and atherosclerosis, the calcium signaling pathway, and the Rap1 signaling pathway. According to the results of molecular docking, in the context of RA, phytocannabinoids may bind to important target proteins such PIK3CA, AKT1, MAPK9, PRKCD, BRAF, IGF1R, and NOS3. This entire study predicted the phytocannabinoids' systemic biological characteristics. Future experimental research is needed, however, to confirm the results so far.

Malaria continues to be a significant public health problem threatened by the emergence and spread of resistance to artemisinin-based combination therapies and marked half a million deaths in 2016. A new imidazopyridine chemotype has been envisaged through scaffold-hopping approach combined with docking studies for putative-binding interactions with Plasmodium falciparum phosphatidylinositol-4-kinase (PfPI4K) target. The docking results steered to the synthesis of compound 1 [5-(3-(methylsulfonyl)phenyl)-3-(4-(methylsulfonyl)phenyl)-3H-imidazo[4,5-b]pyridine] followed by the in vitro screening for antiplasmodial activity and ADME-PK studies. Combined with potent antimalarial activity of compound 1 (Pf3D7 IC 50  = 29 nM) with meager in vitro intrinsic clearance, moderate plasma-protein binding, and acceptable permeability, compound 1 displayed sustained exposure and high oral bioavailability in mice and can thus have the potential as next generation PI4K inhibitor for in vivo studies., (© 2022 John Wiley & Sons Ltd.)

Background & Objectives: Female genital tuberculosis (FGTB) is an important variety of extrapulmonary TB causing significant morbidity, especially infertility, in developing countries like India. The aim of this study was to evaluate the laparoscopic findings of the FGTB., Methods: This was a cross-sectional study on 374 cases of diagnostic laparoscopy performed on FGTB cases with infertility. All patients underwent history taking and clinical examination and endometrial sampling/biopsy for acid-fast bacilli, microscopy, culture, PCR, GeneXpert (only last 167 cases) and histopathological evidence of epithelioid granuloma. Diagnostic laparoscopy was performed in all the cases to evaluate the findings of FGTB., Results: Mean age, parity, body mass index and duration of infertility were 27.5 yr, 0.29, 22.6 kg/m 2 and 3.78 years, respectively. Primary infertility was found in 81 per cent and secondary infertility in 18.18 per cent of cases. Endometrial biopsy was positive for AFB microscopy in 4.8 per cent, culture in 6.4 per cent and epithelioid granuloma in 15.5 per cent. Positive peritoneal biopsy granuloma was seen in 5.88 per cent, PCR in 314 (83.95%) and GeneXpert in 31 (18.56%, out of last 167 cases) cases. Definite findings of FGTB were seen in 164 (43.86%) cases with beaded tubes (12.29%), tubercles (32.88%) and caseous nodules (14.96%). Probable findings of FGTB were seen in 210 (56.14%) cases with pelvic adhesions (23.52%), perihepatic adhesions (47.86%), shaggy areas (11.7%), pelvic adhesions (11.71%), encysted ascites (10.42%) and frozen pelvis in 3.7 per cent of cases., Interpretation & Conclusions: The finding of this study suggests that laparoscopy is a useful modality to diagnose FGTB with a higher pickup rate of cases. Hence it should be included as a part of composite reference standard.

There is currently no drug available to treat mosquito-borne dengue. The C-terminal RNA-dependent RNA polymerase (RdRp) domain in the non-structural type 5 (NS5) protein of the dengue virus (DENV) is essential for viral RNA synthesis and replication, and therefore, it is an attractive target for the anti-dengue drug development. We report herein the discovery and validation of two novel non-nucleoside classes of small molecules as DENV RdRp inhibitors. Firstly, using the refined X-ray structure of the DENV NS5 RdRp domain (PDB-ID: 4V0R), we conducted docking, binding free-energy studies, and short-scale molecular dynamics simulation to investigate the binding sites of known small molecules that led to the optimized protein-ligand complex. Subsequently, protein structure-based screening of a commercial database (∼500,000 synthetic compounds), pre-filtered for the drug-likeness, led to the top-ranked 171 molecules, which was then subjected to structural diversity analysis and clustering. This process led to six structurally distinct and best-scored compounds that were procured from the commercial vendor, and then subjected to the in vitro testing in the MTT and dengue infection assays. It revealed two unique and structurally unique compounds, KKR-D-02 and KKR-D-03, exhibiting 84 and 81% reductions, respectively, in DENV copy number in repeated assays in comparison to the virus-infected cell controls. These active compounds represent novel scaffolds for further structure-based discovery of novel candidate molecules for the intervention of dengue.Communicated by Ramaswamy H. Sarma.

The extensive development in the strains of resistant bacteria is a potential hazard to public health worldwide. This necessitates the development of newer agents with the antibacterial property having new mechanisms of action. Mur enzymes catalyze the steps related to the biosynthesis of peptidoglycan, which constitutes a major part of the cell wall in bacteria. Peptidoglycan increases the stiffness of the cell wall, helping it to survive in unfavorable conditions. Therefore, the inhibition of Mur enzymes may lead to novel antibacterial agents that may help in controlling or overcoming bacterial resistance. Mur enzymes are classified into MurA, MurB, MurC, MurD, MurE, and MurF. Until-date, multiple inhibitors are reported for each class of the Mur enzymes. In this review, we have summarized the development of Mur enzyme inhibitors as antibacterial agents in the last few decades., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Copper T 380-A (CuT380A) intrauterine device (IUD) has been an effective method of emergency contraception (EC). Levonorgestrel intrauterine system (LNG-IUS) has not been approved by the Food and Drug Association for EC till now. There are few studies that provide data regarding the efficacy of LNG-IUS as EC. This systematic review tried to explore the efficacy of LNG-IUS in preventing accidental pregnancies up to five days of unprotected intercourse. A systematic review of the published studies on the use of LNG-IUS as EC was done. All randomized trials, prospective cohorts, retrospective cohorts. and case-control study designs pertaining to this topic were included in this review. Abstracts were retrieved and reviewed by two authors independently. Variables pertaining to socio-demographic parameters, EC use-related variables (reason for use, frequency, time elapsed since coitus), and those associated with sexual habits were selected and recorded. A total of six articles were rendered for the review. High school students and those attending college accounted for 36.8%-51.8% of the study population. Data on the reason for seeking EC showed noncompliance to routine contraception as the most common reason, followed by failure of withdrawal method, breach of barrier contraception, and unplanned intercourse. With a negligible failure rate, LNG-IUS seemed to be a good alternative to the existing copper EC. Considering the plethora of noncontraceptive benefits associated, LNG-IUS can be safely provided as an option of EC in the cafeteria approach within five days of unprotected intercourse., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Kumari et al.)

Background During the peak of the Omicron wave, elective laparoscopic surgeries were restricted; however, semi-emergency and emergency cases were managed despite the limited resources and manpower. We conducted this study to assess the types of gynaecological laparoscopic surgeries performed, the difficulties faced during the Omicron wave, and how we could implement the lessons learnt from the previous Delta wave for better management of gynaecological cases in the Omicron wave. Methodology We conducted a prospective cohort study over a period of three months involving 105 patients who underwent laparoscopic surgeries. Based on the decision regarding surgical incision time, the surgeries were sub-classified into immediate, urgent, and expedited. The surgical outcome and satisfaction rates among the patients were assessed through various parameters. Results Most of the women (81.9%) were pre-menopausal. Diabetes and chronic hypertension were the predominant medical co-morbidities. Three patients had a history of cardiac valve replacement which required switching warfarin to unfractionated heparin in the pre-operative period. Nearly three-fourthsof the study patients were doubly vaccinated against coronavirus disease 2019 (COVID-19) (77; 73.4%). A total of 14 (13.3%) patients had a history of COVID-19 infection in the past two weeks prior to the current admission. Immediate, urgent, and expedited surgeries comprised 11.4%, 22.8%, and 65.8% of total surgeries, respectively. On assessing the ease of pre-operative preparation according to the five-point Likert scale, immediate, urgent, and expedited surgeries were rated with a mean score of two, four, and five, respectively. The mean duration of surgery in the immediate and urgent groups was 37.6 and 44.2 minutes, respectively. The expedited group comprising mostly laparoscopic myomectomies and hysterectomies required an average duration of 92.6 minutes. The mean rating of patient satisfaction measured by the Likert scale was four, five, and five, respectively, in the three subgroups. Pre-operative patient preparation during the Omicron wave was faster, thereby decreasing the decision to incision interval compared to the Delta wave. Conclusions The lessons learnt from the previous Delta wave were used to modify the existing hospital policies in the Omicron wave. More number of vaccinated ground staff, less stringent intubation and extubation protocols during surgery, and lesser duration of post-operative stay helped modify our existing hospital policies for better patient care and satisfaction., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Sarkar et al.)

Cervical cancer (CC) is a preventable disease using proven interventions, specifically prophylactic vaccination, pervasive disease screening, and treatment, but it is still the most frequently diagnosed cancer in women worldwide. Patients with advanced or metastatic CC have a very dismal prognosis and current therapeutic options are very limited. Therefore, understanding the mechanism of metastasis and discovering new therapeutic targets are crucial. New sequencing tools have given a full visualization of the human transcriptome's composition. Non-coding RNAs (NcRNAs) perform various functions in transcriptional, translational, and post-translational processes through their interactions with proteins, RNA, and even DNA. It has been suggested that ncRNAs act as key regulators of a variety of biological processes, with their expression being tightly controlled under physiological settings. In recent years, and notably in the past decade, significant effort has been made to examine the role of ncRNAs in a variety of human diseases, including cancer. Therefore, shedding light on the functions of ncRNA will aid in our better understanding of CC. In this review, we summarize the emerging roles of ncRNAs in progression, metastasis, therapeutics, chemo-resistance, human papillomavirus (HPV) regulation, metabolic reprogramming, diagnosis, and as a prognostic biomarker of CC. We also discussed the role of ncRNA in the tumor microenvironment and tumor immunology, including cancer stem cells (CSCs) in CC. We also address contemporary technologies such as antisense oligonucleotides, CRISPR-Cas9, and exosomes, as well as their potential applications in targeting ncRNAs to manage CC.

Tuberculosis (TB) is an infectious disease and the leading cause of death globally. The rapidly emerging cases of drug resistance among pathogenic mycobacteria have been a global threat urging the need of new drug discovery and development. However, considering the fact that the new drug discovery and development is commonly lengthy and costly processes, strategic use of the cutting-edge machine learning (ML) algorithms may be very supportive in reducing both the cost and time involved. Considering the urgency of new drugs for TB, herein, we have attempted to develop predictive ML algorithms-based models useful in the selection of novel potential small molecules for subsequent in vitro validation. For this purpose, we used the GlaxoSmithKline (GSK) TCAMS TB dataset comprising a total of 776 hits that were made publicly available to the wider scientific community through the ChEMBL Neglected Tropical Diseases (ChEMBL-NTD) database. After exploring the different ML classifiers, viz. decision trees (DT), support vector machine (SVM), random forest (RF), Bernoulli Naive Bayes (BNB), K-nearest neighbors (k-NN), and linear logistic regression (LLR), and ensemble learning models (bagging and Adaboost) for training the model using the GSK dataset, we concluded with three best models, viz. Adaboost decision tree (ABDT), RF classifier, and k-NN models that gave the top prediction results for both the training and test sets. However, during the prediction of the external set of known anti-tubercular compounds/drugs, it was realized that each of these models had some limitations. The ABDT model correctly predicted 22 molecules as actives, while both the RF and k-NN models predicted 18 molecules correctly as actives; a number of molecules were predicted as actives by two of these models, while the third model predicted these compounds as inactives. Therefore, we concluded that while deciding the anti-tubercular potential of a new molecule, one should rely on the use of consensus predictions using these three models; it may lessen the attrition rate during the in vitro validation. We believe that this study may assist the wider anti-tuberculosis research community by providing a platform for predicting small molecules with subsequent validation for drug discovery and development., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Wheat head blast is a dangerous fungal disease in South America and has recently spread to Bangladesh and Zambia, threatening wheat production in those regions. Host resistance as an economical and environment-friendly management strategy has been heavily relied on, and understanding the resistance loci in the wheat genome is very helpful to resistance breeding. In the current study, two recombinant inbred line (RIL) populations, Alondra/Milan (with 296 RILs) and Caninde#2/Milan-S (with 254 RILs and Milan-S being a susceptible variant of Milan), were used for mapping QTL associated with head blast resistance in field experiments. Phenotyping was conducted in Quirusillas and Okinawa, Bolivia, and in Jashore, Bangladesh, during the 2017-18 and 2018-19 cropping cycles. The DArTseq ® technology was employed to genotype the lines, along with four STS markers in the 2NS region. A QTL with consistent major effects was mapped on the 2NS/2AS translocation region in both populations, explaining phenotypic variation from 16.7 to 79.4% across experiments. Additional QTL were detected on chromosomes 2DL, 7AL, and 7DS in the Alondra/Milan population, and 2BS, 4AL, 5AS, 5DL, 7AS, and 7AL in the Caninde#2/Milan-S population, all showing phenotypic effects <10%. The results corroborated the important role of the 2NS/2AS translocation on WB resistance and identified a few novel QTL for possible deployment in wheat breeding. The low phenotypic effects of the non-2NS QTL warrantee further investigation for novel QTL with higher and more stable effects against WB, to alleviate the heavy reliance on 2NS-based resistance., (© 2021. The Author(s).)

Key Message: Genomic selection is a promising tool to select for spot blotch resistance and index-based selection can simultaneously select for spot blotch resistance, heading and plant height. A major biotic stress challenging bread wheat production in regions characterized by humid and warm weather is spot blotch caused by the fungus Bipolaris sorokiniana. Since genomic selection (GS) is a promising selection tool, we evaluated its potential for spot blotch in seven breeding panels comprising 6736 advanced lines from the International Maize and Wheat Improvement Center. Our results indicated moderately high mean genomic prediction accuracies of 0.53 and 0.40 within and across breeding panels, respectively which were on average 177.6% and 60.4% higher than the mean accuracies from fixed effects models using selected spot blotch loci. Genomic prediction was also evaluated in full-sibs and half-sibs panels and sibs were predicted with the highest mean accuracy (0.63) from a composite training population with random full-sibs and half-sibs. The mean accuracies when full-sibs were predicted from other full-sibs within families and when full-sibs panels were predicted from other half-sibs panels were 0.47 and 0.44, respectively. Comparison of GS with phenotypic selection (PS) of the top 10% of resistant lines suggested that GS could be an ideal tool to discard susceptible lines, as greater than 90% of the susceptible lines discarded by PS were also discarded by GS. We have also reported the evaluation of selection indices to simultaneously select non-late and non-tall genotypes with low spot blotch phenotypic values and genomic-estimated breeding values. Overall, this study demonstrates the potential of integrating GS and index-based selection for improving spot blotch resistance in bread wheat., (© 2022. The Author(s).)

Purpose: Analysis of outcomes of macular hole (MH) surgery using 12% C 3 F 8 , 16% C 2 F 6 , or 18% SF 6 as randomized gas tamponading agent., Methods: This is a prospective, randomized, interventional study of 159 eyes with idiopathic MH undergoing 23/25G pars-plana vitrectomy with internal limiting membrane peeling and gas tamponade. Eyes were stratified into two groups: Group I (MH < 800 µ) and group II (MH > 800 µ) according to MH apical diameter. Eyes in group I were randomized to receive either 18% SF 6 , 16% C 2 F 6, or 12% C 3 F 8 . Eyes in group II were randomized to either 16% C 2 F 6 or 12% C 3 F 8 . Clinical details, MH parameters on optical coherence tomography, surgical details and complications were analyzed. Outcome measures were type of hole closure (I/II), best corrected visual acuity, intraocular pressure, and cataract progression., Results: In Group I (n = 139), type 1 closure was achieved in 107 (77%) eyes. Type 1 closure rates in group I per gas tamponade were as follows: SF 6 (70%), C 2 F 6 (80%), C 3 F 8 (78%) (p = 0.503, chi-square test for independence). There was no statistical difference in MH closure rates between SF 6 and C 2 F 6 (p = 0.134), SF 6 and C 3 F 8 (p = 0.186), and C 2 F 6 and C 3 F 8 (p = 0.373). In Group II (n = 20), type 1 closure was achieved in 12 (60%) eyes. Type 1 closure rates in group II per gas tamponade were as follows: C 2 F 6 (75%), C 3 F 8 (50%) (p = 0.132, Two proportion Z test). Mean follow-up after surgery was 2.66 ± 2.74 months., Conclusion: Given the similar outcomes of using 18% SF 6 , 16% C 2 F 6, or 12% C 3 F 8 in idiopathic macular hole surgery, the advantage of using a shorter acting tamponade translates into earlier recovery and rehabilitation., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

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/m 2 , 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., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Mid-life Health.)

Wheat blast (WB) is a devastating fungal disease that has recently spread to Bangladesh and poses a threat to the wheat production in India, which is the second-largest wheat producing country in the world. In this study, 350 Indian wheat genotypes were evaluated for WB resistance in 12 field experiments in three different locations, namely Jashore in Bangladesh and Quirusillas and Okinawa in Bolivia. Single nucleotide polymorphisms (SNPs) across the genome were obtained using DArTseq ® technology, and 7554 filtered SNP markers were selected for a genome-wide association study (GWAS). All the three GWAS approaches used identified the 2NS translocation as the only major source of resistance, explaining up to 32% of the phenotypic variation. Additional marker-trait associations were located on chromosomes 2B, 3B, 4D, 5A and 7A, and the combined effect of three SNPs (2B&#95;180938790, 7A&#95;752501634 and 5A&#95;618682953) showed better resistance, indicating their additive effects on WB resistance. Among the 298 bread wheat genotypes, 89 (29.9%) carried the 2NS translocation, the majority of which (60 genotypes) were CIMMYT introductions, and 29 were from India. The 2NS carriers with a grand mean WB index of 6.6 showed higher blast resistance compared to the non-2NS genotypes with a mean index of 46.5. Of the 52 durum wheats, only one genotype, HI 8819, had the 2NS translocation and was the most resistant, with a grand mean WB index of 0.93. Our study suggests that the 2NS translocation is the only major resistance source in the Indian wheat panel analysed and emphasizes the urgent need to identify novel non-2NS resistance sources and genomic regions.

Inhibition of extracellular secreted enzyme autotaxin (ATX) represents an attractive strategy for the development of new therapeutics to treat various diseases and a few inhibitors entered in clinical trials. We herein describe structure-based design, synthesis, and biological investigations revealing a potent and orally bioavailable ATX inhibitor 1. During the molecular docking and scoring studies within the ATX enzyme (PDB-ID: 4ZGA), the S-enantiomer (Gscore = -13.168 kcal/mol) of the bound ligand PAT-494 scored better than its R-enantiomer (Gscore = -9.562 kcal/mol) which corroborated with the reported observation and analysis of the results suggested the scope of manipulation of the hydantoin substructure in PAT-494. Accordingly, the docking-based screening of a focused library of 10 compounds resulted in compound 1 as a better candidate for pharmacological studies. Compound 1 was synthesized from L-tryptophan and evaluated against ATX enzymatic activities with an IC 50 of 7.6 and 24.6 nM in biochemical and functional assays, respectively. Further, ADME-PK studies divulged compound 1 as non-cytotoxic (19.02% cell growth inhibition at 20 μM in human embryonic kidney cells), metabolically stable against human liver microsomes (CL int  = 15.6 μl/min/mg; T 1/2  = 113.2 min) with solubility of 4.82 μM and orally bioavailable, demonstrating its potential to be used for in vivo experiments., (© 2021 John Wiley & Sons Ltd.)

Objectives: Compare pain intensity at entry into the cervical os, during uterine distension and 15 min after the procedure, in patients undergoing diagnostic hysteroscopy with room temperature normal saline versus that with saline warmed to 38-40°C, using visual analog scale (VAS) score. Furthermore, compare the time taken and failed procedures between them., Materials and Methods: This was a randomized controlled, prospective study conducted at a Tertiary Care Center on 100 patients planned for diagnostic hysteroscopy with a 4 mm 30° hysteroscope using vaginoscopy technique. They were divided into two groups of 50 each, with control undergoing the procedure using normal saline at room temperature and the test with saline warmed to 38-40°C as distension medium. Primary outcomes were VAS at the point of entry into the internal os (T0), 1 min later (T1), and 15 min after the procedure (T15). Secondary outcomes were procedural acceptance, time taken, and failed procedures., Results: The mean VAS in the control group at T0, T1, T15 was 3.31 (1.461;‒0.870-0.245), 2.46 (1.398;‒0.539-0.498), 0.75 (0.911;‒0.379-0.338), respectively, as compared to the test group of 3.62 (1.282;‒0.870-0.245), 2.48 (1.148;‒0.540-0.498), 0.77 (0.911;‒0.379-0.379), respectively. About 73.5% of controls and 68.8% in the test group were willing to undergo the procedure again. About 93.9% of controls would recommend it further as against 93.8% among the test controls. The time taken and number of failed procedures showed no statistical difference., Conclusion: No significant difference was noted in terms of outcomes measured by warming the distension medium., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Gynecology and Minimally Invasive Therapy.)

Study Objective: To evaluate the hysteroscopic findings in female genital tuberculosis., Design: It was a prospective study of hysteroscopic findings performed on 348 cases of female genital tuberculosis (FGTB)., Setting: It was a prospective cross-sectional study in a tertiary referral centre., Patients: A total of 348 patients with infertility with FGTB on various tests., Intervention: A total of 348 patients of infertility found to have FGTB on various investigations were enrolled in the study. A detailed history was taken. Clinical examination, endometrial sampling and diagnostic laparoscopy were performed was also performed in selected cases. All patients underwent hysteroscopy as part of evaluation for infertility and tuberculosis (TB) findings., Measurements and Main Results: The mean age, parity, body mass index and duration of infertility was 28.2 years, 0.31,23.1kg/m 2 and 3.44 years respectively. Infertility was primary in 81.03% and secondary in 18.96% cases. Diagnosis of FGTB was made by endometrial aspirate findings of positive AFB on microscopy (4.02%), positive culture (4.88%), positive PCR (83.90%), epithelioid granuloma (14.65%), positive AFB on microscopy or culture of peritoneal cytology (1.14%) or epithelioid granuloma on peritoneal biopsy (1.72%), definitive findings of TB on laparoscopy (41.95%) or probable findings of TB on laparoscopy (58.05%). Various hysteroscopic findings observed were normal findings (28.16%), pale endometrial cavity (54.31%), features of active TB (7.47%), features of chronic TB (19.54%), features of TB sequelae like obstructed ostia (both ostia in 13.79%, one ostia 14.94%, periostial fibrosis; (bilateral 4.59%, unilateral 5.17%), endometrial glands atrophy (12.35%), small shrunken cavity (6.32%), distorted cavity (5.17%), various grades of intrauterine adhesions (29.88%). Hysteroscopy in FGTB was associated with increased difficulties and complications like failed procedures, difficult visualisation, false passage and uterine perforation., Conclusion: Hysteroscopy is useful modality to detect endometrial TB but is associated with increased difficulty and complications., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2021 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

The coronavirus disease (COVID-19) pandemic is a global health crisis that negatively impacts the health infrastructure by diverting resources to manage this infection. The long-term impact on the health of patients due to a lack of appropriate medical care to avoid COVID-19 infection is already visible in the mortality rates of the general population. The presence of the severe acute respiratory syndrome coronavirus 2 in the female genital tract is not clear. Bubbles produced during hysteroscopy tend to cool down to the temperature of the distension medium and then dissolve. Hence, aerosols are not produced during hysteroscopy, which is usually performed in an office setting. If anesthesia is required, conscious sedation or regional anesthesia should preferably be used to reduce aerosol production. Hence, hysteroscopy is not an aerosol-generating procedure and the risk of COVID-19 infection is low; therefore, hysteroscopy should not be ruled out in emergencies.

The orphan class A G-protein coupled receptor 3 (GPR3) is highly expressed in brain and linked with various neuronal functions, and therefore, expected to play a vital role in the progression of Alzheimer's disease. In view of the lack of its experimental structure, we describe herein the three-dimensional structure and conformational dynamics of GPR3 complexed with the inverse agonist AF64394. The GPR3 model was predicted using the Iterative Threading ASSEmbly Refinement (I-TASSER) method. The Induced Fit Docking predicted two unique poses, Pose 1 and Pose 2, for AF64394, and then, molecular dynamics (MD) simulations followed by binding free-energy calculation revealed the Pose 1 as a very stable pose with the least fluctuation during the MD simulation while the Pose 2 underwent a significant fluctuation. The [1,2,4]triazolo[1,5-a]pyrimidine core was engaged in multiple hydrogen bonds (H-bonds), such as a water-mediated H-bond between the triazole nitrogen and T31, two direct H-bonds between the protonated triazole-ring nitrogen and V186 and T279, a direct H-bond between the secondary amine and V187. The phenyl substituent of AF64394 exhibited aromatic π-π stacking interactions with F97, F101, W43 and Y280. AF64394 showed a direct interaction with E28 and polar interactions with H96, T31 and T279. Throughout the MD simulation, the toggle switch residues, F120 and W260, remained in close contact, indicating that the GPR3 conformation represented an inactive state. The 4-(3-chloro-5-isopropoxyphenethyl) group resided near to the toggle switch residues. The insights gained here are expected to be useful in the structure-based design of new ligands targeting GPR3 modulation. Communicated by Ramaswamy H. Sarma.

Wheat blast (WB) disease, since its first identification in Bangladesh in 2016, is now an established serious threat to wheat production in South Asia. There is a need for sound knowledge about resistance sources and associated genomic regions to assist breeding programs. Hence, a panel of genotypes from India and Bangladesh was evaluated for wheat blast resistance and a genome-wide association study (GWAS) was performed. Disease evaluation was done during five crop seasons-at precision phenotyping platform (PPPs) for wheat blast disease at Jashore (2018-19), Quirusillas (2018-19 and 2019-20) and Okinawa (2019 and 2020). Single nucleotide polymorphisms (SNP) across the genome were obtained using DArTseq genotyping-by-sequencing platform, and in total 5713 filtered markers were used. GWAS revealed 40 significant markers associated with WB resistance, of which 33 (82.5%) were in the 2NS/2AS chromosome segment and one each on seven chromosomes (3B, 3D, 4A, 5A, 5D, 6A and 6B). The 2NS markers contributed significantly in most of the environments, explaining an average of 33.4% of the phenotypic variation. Overall, 22.4% of the germplasm carried 2NS/2AS segment. So far, 2NS translocation is the only effective WB resistance source being used in the breeding programs of South Asia. Nevertheless, the identification of non-2NS/2AS genomic regions for WB resistance provides a hope to broaden and diversify resistance for this disease in years to come.

Recent studies suggest that of the molecules postulated to function as inhibitors of the NADPH oxidase family of enzymes iodonium analogs known to broadly interfere with flavin dehydrogenase function demonstrate mechanistic validity as NADPH oxidase poisons. In recent work, we have produced a series of novel iodonium compounds as putative inhibitors of these oxidases. To evaluate the potential utility of two novel molecules with favorable chemical properties, NSC 740104 and NSC 751140, we compared effects of these compounds to the two standard inhibitors of this class, diphenyleneiodonium and di-2-thienyliodonium, with respect to antiproliferative, cell cycle, and gene expression effects in human colon cancer cells that require the function of NADPH oxidase 1. Both new agents blocked NADPH oxidase-related reactive oxygen production, inhibited tumor cell proliferation, produced a G1/S block in cell cycle progression, and inhibited NADPH oxidase 1 expression at the mRNA and protein levels at low nM concentrations in a fashion similar to or better than the parent molecules. These studies suggest that NSC 740104 and NSC 751140 should be developed further as mechanistic tools to better understand the role of NADPH oxidase inhibition as an approach to the development of novel therapeutic agents for colon cancer.

The ubiquitous antimicrobial peptides (AMPs), with a broad range of antimicrobial activities, represent a great promise for combating the multi-drug resistant infections. In this study, using a large and diverse set of AMPs (2638) and non-AMPs (3700), we have explored a variety of machine learning classifiers to build in silico models for AMP prediction, including Random Forest (RF), k-Nearest Neighbors (k-NN), Support Vector Machine (SVM), Decision Tree (DT), Naive Bayes (NB), Quadratic Discriminant Analysis (QDA), and ensemble learning. Among the various models generated, the RF classifier-based model top-performed in both the internal [Accuracy: 91.40%, Precision: 89.37%, Sensitivity: 90.05%, and Specificity: 92.36%] and external validations [Accuracy: 89.43%, Precision: 88.92%, Sensitivity: 85.21%, and Specificity: 92.43%]. In addition, the RF classifier-based model correctly predicted the known AMPs and non-AMPs; those kept aside as an additional external validation set. The performance assessment revealed three features viz. ChargeD2001, PAAC12 (pseudo amino acid composition), and polarity T13 that are likely to play vital roles in the antimicrobial activity of AMPs. The developed RF-based classification model may further be useful in the design and prediction of the novel potential AMPs., (© 2021. International Federation for Medical and Biological Engineering.)