Organ- and Cell-Selective Delivery of mRNA In Vivo Using Guanidinylated Serinol Charge-Altering Releasable Transporters.

Selective RNA delivery is required for the broad implementation of RNA clinical applications, including prophylactic and therapeutic vaccinations, immunotherapies for cancer, and genome editing. Current polyanion delivery relies heavily on cationic amines, while cationic guanidinium systems have received limited attention due in part to their strong polyanion association, which impedes intracellular polyanion release. Here, we disclose a general solution to this problem in which cationic guanidinium groups are used to form stable RNA complexes upon formulation but at physiological pH undergo a novel charge-neutralization process, resulting in RNA release. This new delivery system consists of guanidinylated serinol moieties incorporated into a charge-altering releasable transporter (GSer-CARTs). Significantly, systematic variations in structure and formulation resulted in GSer-CARTs that exhibit highly selective mRNA delivery to the lung (∼97%) and spleen (∼98%) without targeting ligands. Illustrative of their breadth and translational potential, GSer-CARTs deliver circRNA, providing the basis for a cancer vaccination strategy, which in a murine model resulted in antigen-specific immune responses and effective suppression of established tumors.

Cadmium toxicity: its' uptake and retaliation by plant defence system and ja signaling.

Cadmium (Cd+2) renders multifarious environmental stresses and highly toxic to nearly all living organisms including plants. Cd causes toxicity by unnecessary augmentation of ROS that targets essential molecules and fundamental processes in plants. In response, plants outfitted a repertory of mechanisms to offset Cd toxicity. The main elements of these are Cd chelation, sequestration into vacuoles, and adjustment of Cd uptake by transporters and escalation of antioxidative mechanism. Signal molecules like phytohormones and reactive oxygen species (ROS) activate the MAPK cascade, the activation of the antioxidant system andsynergistic crosstalk between different signal molecules in order to regulate plant responses to Cd toxicity. Transcription factors like WRKY, MYB, bHLH, bZIP, ERF, NAC etc., located downstream of MAPK, and are key factors in regulating Cd toxicity responses in plants. Apart from this, MAPK and Ca2+signaling also have a salient involvement in rectifying Cd stress in plants. This review highlighted the mechanism of Cd uptake, translocation, detoxification and the key role of defense system, MAPKs, Ca2+ signals and jasmonic acid in retaliating Cd toxicity via synchronous management of various other regulators and signaling components involved under stress condition.

Differential Expression of SRY-Related HMG-Box Transcription Factor 2, Oligodendrocyte Lineage Transcription Factor 2, and Zinc Finger E-Box Binding Homeobox 1 in Serum-Derived Extracellular Vesicles: Implications for Mithramycin Sensitivity and Targeted Therapy in High-Grade Glioma.

Glioblastoma multiforme (GBM) is the most aggressive type of glioma and is often resistant to traditional therapies. Evidence suggests that glioma stem cells (GSCs) contribute to this resistance. Mithramycin (Mit-A) targets GSCs and exhibits antitumor activity in GBM by affecting transcriptional targets such as SRY-related HMG-box transcription factor 2 (SOX2), oligodendrocyte lineage transcription factor 2 (OLIG2), and zinc finger E-box binding homeobox 1 (ZEB1). However, its clinical use has been limited by toxicity. This study explored the diagnostic potential of serum extracellular vesicles (EVs) to identify Mit-A responders. Serum EVs were isolated from 70 glioma patients, and targeted gene expression was analyzed using qRT-PCR. Using chemosensitivity assay, we identified 8 Mit-A responders and 17 nonresponders among 25 glioma patients. The M-score showed a significant correlation (p = 0.045) with isocitrate dehydrogenase 1 mutation but not other clinical variables. The genes SOX2 (p = 0.005), OLIG2 (p = 0.003), and ZEB1 (p = 0.0281) were found to be upregulated in the responder EVs. SOX2 had the highest diagnostic potential (AUC = 0.875), followed by OLIG2 (AUC = 0.772) and ZEB1 (AUC = 0.632).The combined gene panel showed significant diagnostic efficacy (AUC = 0.956) through logistic regression analysis. The gene panel was further validated in the serum EVs of 45 glioma patients. These findings highlight the potential of Mit-A as a targeted therapy for high-grade glioma based on differential gene expression in serum EVs. The gene panel could serve as a diagnostic tool to predict Mit-A sensitivity, offering a promising approach for personalized treatment strategies and emphasizing the role of GSCs in therapeutic resistance.

Methyl jasmonate reduces cadmium toxicity by enhancing phenol and flavonoid metabolism and activating the antioxidant defense system in pigeon pea (Cajanus cajan).

Cadmium (Cd) is absorbed by plant roots from soil along with essential nutrients and affects plant growth and productivity. Methyl jasmonate (Me-JA) play important roles to mitigate Cd toxicity in plants. We have investigated the role of Me-JA to ameliorate Cd toxicity in Pigeon pea (Cajanus cajan). Plant root growth, biomass, cellular antioxidant defense system and expression of key regulatory genes in molecular and signaling process have been analyzed. Two Cajanus cajan varieties AL-882 and PAU-881 were grown at 25 °C, 16/8h light/dark conditions in three biological replicates at 5 mM Cd concentration, three concentration of Me-JA (0, 10 nM, 100 nM) and two concentrations in combination of Me-JA + Cd (10 nM Me-JA +5 mM Cd, 100 nM Me-JA +5 mM Cd). The seedlings were exposed to Cd stress consequently plants showed decrease in primary root growth (60.71%, in AL-882 and 8.33%, in PAU-881), shoot and root biomass and antioxidant enzymes activities. Me-JA treatment resulted in increased primary root growth (63.64%, in AL-882) and overall plant biomass. Oxidative stress generated due to Cd stress was counter balanced by Me-JA treatment. Me-JA reduced H2O2 free radicals formation and enhanced antioxidant enzyme activities and phenolic content in stressed seedlings. Me-JA treatment increased expression of CALM, IP3, CDPK2, MPKs (involved in calcium and kinase signaling pathways) and reduced expression of metal transporters (IRT1 and HMA3) genes. This reduction in metal transporters gene expression is a probable reason for low toxicity effect of Cd in root after Me-JA treatment which has potential implications in reducing the risk of Cd in the food chain.

Discovery of KRB-456, a KRAS G12D Switch-I/II Allosteric Pocket Binder That Inhibits the Growth of Pancreatic Cancer Patient-derived Tumors.

Currently, there are no clinically approved drugs that directly thwart mutant KRAS G12D, a major driver of human cancer. Here, we report on the discovery of a small molecule, KRB-456, that binds KRAS G12D and inhibits the growth of pancreatic cancer patient-derived tumors. Protein nuclear magnetic resonance studies revealed that KRB-456 binds the GDP-bound and GCP-bound conformation of KRAS G12D by forming interactions with a dynamic allosteric binding pocket within the switch-I/II region. Isothermal titration calorimetry demonstrated that KRB-456 binds potently to KRAS G12D with 1.5-, 2-, and 6-fold higher affinity than to KRAS G12V, KRAS wild-type, and KRAS G12C, respectively. KRB-456 potently inhibits the binding of KRAS G12D to the RAS-binding domain (RBD) of RAF1 as demonstrated by GST-RBD pulldown and AlphaScreen assays. Treatment of KRAS G12D-harboring human pancreatic cancer cells with KRB-456 suppresses the cellular levels of KRAS bound to GTP and inhibits the binding of KRAS to RAF1. Importantly, KRB-456 inhibits P-MEK, P-AKT, and P-S6 levels in vivo and inhibits the growth of subcutaneous and orthotopic xenografts derived from patients with pancreatic cancer whose tumors harbor KRAS G12D and KRAS G12V and who relapsed after chemotherapy and radiotherapy. These results warrant further development of KRB-456 for pancreatic cancer. SIGNIFICANCE: There are no clinically approved drugs directly abrogating mutant KRAS G12D. Here, we discovered a small molecule, KRB-456, that binds a dynamic allosteric binding pocket within the switch-I/II region of KRAS G12D. KRB-456 inhibits P-MEK, P-AKT, and P-S6 levels in vivo and inhibits the growth of subcutaneous and orthotopic xenografts derived from patients with pancreatic cancer. This discovery warrants further advanced preclinical and clinical studies in pancreatic cancer.

Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism.

The introduction of more effective and selective mRNA delivery systems is required for the advancement of many emerging biomedical technologies including the development of prophylactic and therapeutic vaccines, immunotherapies for cancer and strategies for genome editing. While polymers and oligomers have served as promising mRNA delivery systems, their efficacy in hard-to-transfect cells such as primary T lymphocytes is often limited as is their cell and organ tropism. To address these problems, considerable attention has been placed on structural screening of various lipid and cation components of mRNA delivery systems. Here, we disclose a class of charge-altering releasable transporters (CARTs) that differ from previous CARTs based on their beta-amido carbonate backbone (bAC) and side chain spacing. These bAC-CARTs exhibit enhanced mRNA transfection in primary T lymphocytes in vitro and enhanced protein expression in vivo with highly selective spleen tropism, supporting their broader therapeutic use as effective polyanionic delivery systems.

Tobacco Usage and Its Association With Mental Health Status of School-Going Adolescents Near Patna, Bihar: A Community-Based Cross-Sectional Study in Eastern India.

Background Of all the adolescents in India, 7.3% are suffering from some form of mental disorder. They frequently use tobacco to cope with these problems, but get stuck in a vicious cycle of deteriorating mental health. Our study aimed to determine the effect of tobacco on the mental health status of adolescents studying in the 9th to 12th standards in 10 high schools in urban and rural areas near Patna, Bihar. Methodology An analytical cross-sectional study was conducted among 360 school-going adolescents recruited using stratified random sampling. Selected adolescents were given the Indian Adolescent Health Questionnaire. The mental health status was calculated from the Strengths and Difficulties Questionnaire (SDQ) score. Information on sociodemographic characteristics and tobacco use was also obtained. Independent t-test, analysis of variance, and multiple linear regression analysis were used for predicting the significant factors. Significance was set at p-values <0.05. Results In this study, 40 (11.1%) adolescents had abnormal whereas 55 (15.3%) had borderline overall SDQ scores. The majority of those affected had peer problems (40%) and conduct problems (24.7%). All SDQ components of conduct (F = 2.94, p = 0.013), hyperactivity (F = 2.90, p = 0.014), emotional problems (F = 1.14, p = 0.001), and peer pressure (F = 3.06, p = 0.010), as well as the overall SDQ score (F = 5.74, p < 0.001), were significantly associated with increasing age. The adolescents attending rural schools (13.28 ± 5.22, p = 0.047) had significantly higher SDQ scores than those attending urban schools (12.08 ± 5.60). Hyperactivity scores were significantly higher in those studying in class 10 compared to other classes and in those attending rural rather than urban schools. Emotional problems score was significantly higher in 16-17-year-old students than in 14-15-year-old students, in females than in males, and in class 10 than in class 9 students. Only 24 (6.7%) adolescents had a history of tobacco consumption at least once which was significantly associated with the SDQ score (17.71 ± 5.69; t = 4.95, df = 358, p < 0.001). Around 79.4% of adolescents were exposed to passive smoking from close friends which deteriorated their overall mental health status (14.50 ± 5.99; F = 6.29, df = 2,357, p = 0.002). Those who had smoked for more than 10 days had significantly greater conduct problems and lesser pro-social behavior. Overall, 96.1% agreed that tobacco is harmful to health, and 76.1% had seen anti-smoking messages in the media. Female gender, increasing class and age, and history of smoking or chewing tobacco at least once also led to a significant increase in emotional problems. Age, area of the school, history of tobacco consumption, and exposure to cigarette smoke by either a close friend or male guardian had a significant impact on the conduct, hyperactivity, peer problems, and overall mental health status of school-going adolescents. Conclusions Predicting risk factors such as age, area of the school, and the history of tobacco consumption by self or by close friends is important for decision-making by school administration regarding counseling for mental health and preventing tobacco use.

Effect of educational intervention on knowledge and attitude about the role of vitamins, minerals and nutraceuticals in COVID-19 and other disorders among medical and nursing undergraduates of a tertiary care teaching hospital.

PURPOSE: There must be a perfect balance between Food and Dietary supplements (DS) to ensure optimal well-being. The purpose of this study was to evaluate the impact of a webinar on the change in knowledge and attitude about the role of vitamins, minerals and DS among medical and nursing undergraduates so that they could bring about a positive change in popular practices, as well-informed Health Care Professionals (HCPs). MATERIALS AND METHODS: The study was a cross-sectional analytical study comprising 12 knowledge and 11 attitude questions administered to medical and nursing undergraduates with the help of semi-structured and pre-validated google form both before and after a webinar explaining the role of key nutrients and also the evidence and recommendations surrounding DS. Data were analyzed using STATA.12 to assess the impact of the webinar. RESULTS: There were 415 participants, with 265 medical and 150 nursing students. There was a significant improvement both in the knowledge (4.95 (±1.45), 7.76 (±1.69) and attitude scores (pre-webinar mean score 31.8 (±5.57) post-webinar mean score 27.7 (±4.90))of the participants after the webinar. An overall positive correlation before the webinar changed to a more significant negative correlation, indicating a positive impact of the webinar (0.0054-0.0701). CONCLUSION: The study suggests that continuing education informing various HCPs and undergraduate students about the absolute necessity of a diet rich in nutrients, vitamins, minerals, and probiotics is the need of the hour. Additionally, the efficacy and safety concerns, appropriate indications and dosages of various DS should be adequately stressed so that informed decisions can be made. Such training programs might have a far-reaching impact on the nutrition choices of the population at large.

Cross-sectional study to describe the severity, bio-chemical associations, and final outcomes of COVID-19-associated rhino-orbital-cerebral mucormycosis in a tertiary hospital of East India.

Purpose: The second wave of coronavirus disease 2019 (COVID-19) pandemic triggered a mucormycosis epidemic in India. Diabetes mellitus and dysregulated immune response were contributors, and rhino-orbital-cerebral mucormycosis (ROCM) was the most common presentation. It is however not known whether bio-chemical parameters at presentation correlate with stage of ROCM or final outcome in terms of vision or mortality. Methods: This retrospective, hospital-based study included all in-patients of mucormycosis with ophthalmic manifestations at presentation admitted during June 1, 2021 to August 31, 2021. It aimed to evaluate the association between severity of infection, serum levels of HbA1c, ferritin, interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer levels at presentation and outcome. Results: There were altogether 47 eligible cases having a mean age of 48.8 ± 10.9 years with a male:female ratio of 2.6:1; forty-two (89.4%) had pre-existing diabetes, and five (10.6%) had steroid-induced hyperglycemia. The mean HbA1c among diabetics was 9.7 ± 2.1. HbA1c and serum CRP showed an increase over subsequent stages, which was not statistically significant (P = 0.31). IL-6 values for all stages were similar (P = 0.97). Only serum ferritin levels showed a statistically significant increase over stages (P = 0.04). IL-6 was significantly lower (P = 0.03) in patients who survived, whereas CRP levels were significantly lower in patients who had final visual acuity (VA) better than only perception of light (P = 0.03). Conclusion: Uncontrolled diabetes mellitus is a significant association of ROCM. Serum ferritin levels at presentation best correlate with extent of the disease. CRP levels are best to prognosticate cases that will have sufficient VA to carry on activities of daily living, whereas IL-6 levels are best associated with survival.

Novel mutant KRAS addiction signature predicts response to the combination of ERBB and MEK inhibitors in lung and pancreatic cancers.

KRAS mutations are prevalent in pancreatic and lung cancers, but not all mutant (mt) KRAS tumors are addicted to mt KRAS. Here, we discovered a 30-gene transcriptome signature "KDS30" that encodes a novel EGFR/ERBB2-driven signaling network and predicts mt KRAS, but not NRAS or HRAS, oncogene addiction. High KDS30 tumors from mt KRAS lung and pancreatic cancer patients are enriched in genes upregulated by EGFR, ERBB2, mt KRAS or MEK. EGFR/ERBB2 (neratinib) and MEK (cobimetinib) inhibitor combination inhibits tumor growth and prolongs mouse survival in high, but not low, KDS30 mt KRAS lung and pancreatic xenografts, and is synergistic only in high KDS30 mt KRAS patient-derived organoids. Furthermore, mt KRAS high KDS30 lung and pancreatic cancer patients live significantly shorter lives than those with low KDS30. Thus, KDS30 can identify lung and pancreatic cancer patients whose tumors are addicted to mt KRAS, and predicts EGFR/ERBB2 and MEK inhibitor combination response.

An Epidemiological Investigation to evaluate the link between hypovitaminosis D and COVID-19.

Background: The COVID-19 pandemic has become a global threat, with an inexplicable course of action and suboptimal response to the multitudes of therapies being tried. Vitamin D's pleiotropic effects (immunomodulatory, anti-inflammatory, and antiviral) have lately received considerable attention in the scientific community, and it has been shown to be helpful in the defense against viral respiratory infections. Aim: To find out the association between vitamin D and COVID-19. Methods: Overall, 360 (156 COVID-19 +ve and 204 COVID-19 -ve) subjects were investigated in this hospital-based case-control study. The study participants were taken from the COVID-19 wards and Flu clinic of a dedicated COVID hospital between August 1 and September 15, 2020. The demographics and clinical data including alcohol and smoking history along with serum vitamin D levels were recorded. Binary logistic regression analysis was performed to assess the association between age, gender, alcohol intake, smoking history, vitamin D status, and COVID-19. Results: There was no significant difference in the mean vitamin D levels between cases and controls. Bivariate analysis of predictors and COVID-19 revealed that predictors such as advanced age, BMI, alcohol intake, smoking habit, diabetes, hypertension, and vitamin D deficiency were significantly associated with COVID-19. Conclusions: This study showed that serum vitamin D status might be able to reduce the impact of COVID-19, although more studies are required to establish clear causality.

Interim Analysis of Impact of Adding Low Dose Pulmonary Radiotherapy to Moderate COVID-19 Pneumonia Patients: IMpaCt-RT Study.

Background: Treatment for coronavirus disease 2019 (COVID-19) pneumonia remains largely supportive till date and multiple clinical trials took place within the short span of time to evaluate the role of investigational therapies. The anti-inflammatory effect of low dose whole lung radiation in treating pneumonia has been documented earlier. This clinical trial analyzed the effect of low dose radiation therapy (LDRT) in a moderately affected COVID-19 pneumonia patient cohort and has evaluated its effect in stopping the conversion of moderate disease into severe disease. Methods: Patients with moderate COVID-19 pneumonia as characterized by the Ministry of Health and Family Welfare (MOHFW), Government of India, were randomized (1:1) to low dose whole lung radiation versus no radiation. All treatment of patients was concurrently being given as per institutional protocol. Patients were followed up with clinical and laboratory parameters monitored on Days 1, 3, 7, and 14. Computed tomography scan (CT scan) of thorax was performed on Days 1 and 7. Patients were evaluated for conversion of moderate into severe disease as per National Early Warning Score-2 (NEWS-2 score) as the primary end point. The secondary endpoints included changes in ratio between peripheral capillary oxygen saturation and fraction of inspired oxygen (SpO2/FiO2), biochemical markers, 25-point CT severity score, and radiation induced acute pulmonary toxicities. Findings: At the interim analysis, there were seven patients in the radiation arm and six in the control. A whole lung LDRT improved the outcome of SpO2/FiO2 at Day 3; however it did not convert into a statistically significant improvement for the NEWS-2 score. The serum levels of LDH, CRP, Ferritin and D-dimer were significantly reduced on 14 days in the LDRT arm in comparison to the baseline value but were not significant between the two groups. Interpretation: LDRT seems to have the potential to prevent moderate COVID-19 pneumonia from a deteriorating to severe category. However, further randomized clinical trial with an adequate number of such patients is warranted to establish the definitive role of LDRT in the management of COVID-19 pneumonia. Funding: An intramural research project bearing code: I-27/621, was sanctioned from the All India Institute of Medical Sciences, Patna, India. Clinical Trial Registration: Clinical Trials Registry-India (CTRI/2021/06/033912, 25th May 2021) ctri.nic.in/Clinicaltrials/login.php.

Exosomal PTEN as a Predictive Marker of Aggressive Gliomas.

Background: Liquid biopsies have emerged as convenient alternative diagnostic methods to invasive biopsies, by evaluating disease-specific biomarkers and monitoring the disease risk noninvasively. Phosphatase and tensin homolog deleted in chromosome 10 (PTEN) is a potent tumor suppressor, and its deletion/mutations are common in gliomas. Objective: Evaluate the feasibility of non-invasive detection of PTEN and its downstream genes in serum exosomes of glioma patients. Materials and methods: PTEN, Yes-associated-protein 1 (YAP1), and lysyl oxidase (LOX) transcript expression were monitored through polymerase chain reaction (PCR) in serum exosomes and their paired tumor tissues. The impact of PTEN and its axis genes expression on the overall survival (OS) was monitored. Results: Out of the 106 glioma serum samples evaluated, PTEN was retained/lost in 65.4%/34.6% of the tumor samples while it was retained/lost in 67.1%/32.9% of their paired exosomal fractions. PTEN expression in both tissue and paired exosomal fractions was observed in 48.11% of the samples. Sanger sequencing detected three mutations (Chr10: 89720791(A>G), Chr10:89720749(C>T), and Chr10:89720850(A>G). Both PTEN-responsive downstream genes (YAP1) and LOX axis were upregulated in the PTEN-deficient samples. PTEN loss was associated with poor survival in the glioma patients (hazard ratio (HR) 0.68, confidence interval (CI): 0.35-1.31, P = 0.28). The OS of the exosomal PTEN cohort coincided with the tumor-tissue PTEN devoid group (HR 1.08, CI: 0.49-2.36, P = 0.85). While, old age yielded the worst prognosis; gender, location, and grade were not prognostic of OS in the multivariate analysis. Conclusions: PTEN and its responsive genes YAP1 and LOX can be detected in serum exosomes and can serve as essential tools for the non-invasive evaluation/identification of aggressive gliomas.

Comparison between dexmedetomidine and fentanyl bolus in attenuating the stress response to laryngoscopy and tracheal intubation: a randomized double-blind trial.

BACKGROUND AND OBJECTIVES: Laryngoscopy and tracheal intubation lead to a sympathoadrenal response. We compared the efficacy of dexmedetomidine with fentanyl bolus to attenuate this response. METHODS: One hundred patients admitted for routine surgical procedures under general anesthesia were enrolled in this double blind, randomized, controlled study. Patients were randomly assigned to two groups: Group F received injection of fentanyl 2 µg.kg-1 and Group D received injection of dexmedetomidine 0.5 µg.kg-1 diluted up to 5 mL by adding normal saline intravenously over 60 seconds. Five minutes thereafter, following induction with propofol and vecuronium, tracheal intubation was performed after 3 minutes of mask ventilation. Hemodynamic parameters were observed at an interval of 2 minutes before tracheal intubation and at an interval of 1 minute for 5 minutes after tracheal tube cuff inflation. Continuous variables are presented as mean with 95% confidence interval, and t-test was applied for comparing the difference of means between two groups after checking the normality condition. Chi-square test was applied to test the independence of attributes of categorical variables. Repeated measures two-way ANOVA was performed to compare the outcome variables between the two groups. RESULTS: The difference in heart rate and mean arterial pressure of patients in two groups after laryngoscopy and intubation was not statistically significant at any point of time. The hemodynamic changes did not require any intervention in the form of administration of rescue medication. CONCLUSIONS: Dexmedetomidine 0.5 µg.kg-1 is as effective as fentanyl 2 µg.kg-1 in attenuating the hemodynamic response accompanying laryngoscopy and tracheal intubation. CLINICAL TRIAL NUMBER & REGISTRY URL: CTRI/2017/09/009857 [ctri.nic.in].

Prevalence and knowledge of hepatitis B infection in pregnant women in a primary health center of Patna district, Bihar.

INTRODUCTION: There is a risk of chronic hepatitis B virus (HBV)infection to the newborn through perinatal transmission from a hepatitis B surface antigen (HBsAg) positive mother that can later cause liver cirrhosis or hepatocellular carcinoma. This study was undertaken in a primary health center (PHC)in the Patna district to determine the prevalence of HBV among pregnant women and assess their knowledge across different characteristics. METHODOLOGY: A cross-sectional study was done among 275 pregnant women attending the PHC for the first time, using consecutive sampling. The study duration was 12 months. Socioeconomic, obstetric, risk history, and levels of knowledge about hepatitis B were collected followed by rapid diagnostic test (RDT)for serum HBsAg. Univariate analysis was used to compare the knowledge levels across different background characteristics. The significance was set at P < 0.05. RESULTS: Hepatitis B-positive pregnant women were 0.4%. Out of the 275 participants, only 43 had heard about hepatitis B. The mean knowledge score was 0.65 (±1.73) with 1.45% having adequate knowledge. The knowledge score was significant across education (P 0.040), category (P 0.022), hepatitis B immunization status (P 0.003), and risk factor (P 0.039). CONCLUSION: Knowledge was higher in the literate women belonging to the general category and higher social class, who received hepatitis B vaccination. However, the overall level of knowledge among the pregnant women was very poor, so they should be targeted for quality health education. Additionally, identifying the afflicted pregnant women through point-of-contact diagnosis will aid in community prevention of chronic hepatitis B.

The ligation of the intersphincteric fistula tract (LIFT) technique for simple and complex fistula-in-ano

Background: Fistula-in-ano is one of the most common clinical condition encountered in a surgical outpatient department. Many treatment modalities have been described with variable outcomes but gold standard surgical treatment is yet to be agreed upon. The aim of the present study is to evaluate the treatment outcomes of ligature of intersphincteric fistula tract (LIFT) technique in the treatment of simple and complex fistula-in-ano with the primary objective of recurrence rate and broad objective of other postoperative complications during the period of study and after long-term follow-up. Methods: It is a retrospective study of prospectively collected data from the patients who havebeen operated for fistula-in-ano using the LIFT technique at our institute from February 2018 to March 2020 and followed-up until September 2020. Results: A total of 56 patients with fistula-in-ano were treated with the LIFT procedure during the study period, of which 20 patients had simple fistula and 36 had complex fistula. A success rate of 83% was obtained with completely healed fistulas in 46 patients. No patient developed postoperative incontinence. Conclusion: Ligature of intersphincteric fistula tract is an effective treatmentmodality for fistula-in-ano with less procedure-related morbidity, but it is associated with a higher recurrence rate in simple fistula than in complex fistula. (AU)

Alleviating aluminum toxicity in plants: Implications of reactive oxygen species signaling and crosstalk with other signaling pathways.

Aluminum (Al) toxicity is a major limiting factor for plant growth and productivity in acidic soil. At pH lower than 5.0 (pH < 5.0), the soluble and toxic form of Al (Al3+ ions) enters root cells and inhibits root growth and uptake of water and nutrients. The organic acids malate, citrate, and oxalate are secreted by the roots and chelate Al3+ to form a non-toxic Al-OA complex, which decreases the entry of Al3+ into the root cells. When Al3+ enters, it leads to the production of reactive oxygen species (ROS) in cells, which are toxic and cause damage to biomolecules like lipids, carbohydrates, proteins, and nucleic acids. When ROS levels rise beyond the threshold, plants activate an antioxidant defense system that comprises of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione S-transferase (GST), ascorbic acid (ASA), phenolics and alkaloids etc., which protect plant cells from oxidative damage by scavenging and neutralizing ROS. Besides, ROS also play an important role in signal transduction and influence many molecular and cellular process like hormone signaling, gene expression, cell wall modification, cell cycle, programed cell death (PCD), and development. In the present review, the mechanisms of Al-induced ROS generation, ROS signaling, and crosstalk with other signaling pathways helping to combat Al toxicity have been summarized, which will help researchers to understand the intricacies of Al-induced plant response at cellular level and plan research for developing Al-toxicity tolerant crops for sustainable agriculture in acid soil-affected regions of the world.

A Comparative Study Between Ondansetron and Gabapentin for Prevention of Postoperative Nausea and Vomiting Following Maxillofacial Surgery.

BACKGROUND AND AIM: Gabapentin is an antiepileptic drug with antiemetic properties. We evaluated prophylactic oral gabapentin as compared with ondansetron for postoperative nausea and vomiting (PONV) in patients undergoing maxillo facial surgery. SETTINGS AND DESIGN: A double-blind, randomized study in a teaching hospital. MATERIALS AND METHODS: Seventy patients of ASA physical status I and II, scheduled to undergo maxillofacial surgery, were randomly assigned into two groups to receive 300 mg gabapentin or 8 mg ondansetron 1 h before surgery. Standard anaesthesia technique was used in all patients. Students' t test for difference of means between two groups was used for continuous variables. Chi square or Fisher's exact test was used for comparing proportion between two groups. Kaplan-Meier survival analysis was performed to compare the time to event observed between ondansetron and gabapentin groups. Log-rank test was performed to detect statistical significance of time to events between two groups. RESULTS: There was no significant difference in incidence of PONV between two groups within 2 h postoperatively. No incidence of PONV was observed in gabapentin group within 2-24 h as compared to ondansetron group in which PONV was observed in five cases. CONCLUSION: Gabapentin effectively suppresses PONV in maxillo facial surgery.

Pimozide Suppresses the Growth of Brain Tumors by Targeting STAT3-Mediated Autophagy.

Brain tumors are considered as one of the most aggressive and incurable forms of cancer. The majority of the patients with brain tumors have a median survival rate of 12%. Brain tumors are lethal despite the availability of advanced treatment options such as surgical removal, chemotherapy, and radiotherapy. In this study, we have evaluated the anti-cancer effects of pimozide, which is a neuroleptic drug used for the treatment of schizophrenia and chronic psychosis. Pimozide significantly reduced the proliferation of U-87MG, Daoy, GBM 28, and U-251MG brain cancer cell lines by inducing apoptosis with IC50 (Inhibitory concentration 50) ranging from 12 to 16 µM after 48 h of treatment. Our Western blotting analysis indicated that pimozide suppressed the phosphorylation of STAT3 at Tyr705 and Src at Tyr416, and it inhibited the expression of anti-apoptotic markers c-Myc, Mcl-1, and Bcl-2. Significant autophagy induction was observed with pimozide treatment. LC3B, Beclin-1, and ATG5 up-regulation along with autolysosome formation confirmed the induction of autophagy with pimozide treatment. Inhibiting autophagy using 3-methyladenine or LC3B siRNA significantly blocked the apoptosis-inducing effects of pimozide, suggesting that pimozide mediated its apoptotic effects by inducing autophagy. Oral administration of 25 mg/kg pimozide suppressed the intracranially implanted U-87MG tumor growth by 45% in athymic nude mice. The chronic administration of pimozide showed no general signs of toxicity, and the behavioral activity of the mice remained unchanged. Taken together, these results indicate that pimozide inhibits the growth of brain cancer by autophagy-mediated apoptosis.