Suspected Cutaneous Allergic Reactions with Ayurveda Medicine Punaranava Mandura: A Case Report.

INTRODUCTION: With the increasing use of traditional medicine, there is a need to be vigilant in identifying and reporting adverse reactions associated with them. Punarnava Mandura is a commonly used Ayurvedic medicine for the treatment of anemia. It is well tolerated by the patients. To our knowledge, allergic reactions to Punarnava Mandura have not been reported in the literature. We reported a case of adverse cutaneous reaction, which was probably associated with Purnarnava Mandura. CASE PRESENTATION: A 60-year-old female patient developed skin rashes over her neck region after taking Punarnava Mandura and other drugs for osteoarthritis. She recovered upon withdrawal of all the medicines and treatment with anti-allergic drugs. The patient re-initiated treatment for joint pain except for Punarnava Mandura and completed the course without a recurrence of the event making the Punarnava Mandura the culprit drug. CONCLUSION: Punarnava Mandura may cause allergic reactions, and clinicians should keep such adverse reactions in mind when using traditional medicine and report them to increase the scientific literature in this area.

Molecular detection of Listeria monocytogenes from different dairy and street food sources in North Karnataka, India.

BACKGROUND: Food-borne pathogen Listeria monocytogenes is abundantly present in nature and accountable for sporadic and epidemic cases of listeriosis in humans. The objective of this study was to screen common food sources for L. monocytogenes using biochemical and molecular methods to detect and characterise its toxin genes as well as for biofilm formation. METHODS: A total of 92 samples, comprising dairy and street food products, were randomly collected from various sources for this investigation. The collected samples were processed for biochemical and molecular methods to detect L. monocytogenes. Additionally, virulence factors associated genes, antibiogram profiles and biofilm formation related assays were determined. RESULTS: L. monocytogenes presence was confirmed using molecular detection methods targeting prs and lmo1030 genes, along with MALDI-TOF MS. Following 16 S rRNA sequencing, the identified Listeria species were further categorised into two groups. L. monocytogenes was detected in two (2.17%) food samples tested (L-23 and L-74). Multiplex PCR indicated the presence of seven virulence-related genes in L. monocytogenes isolates, i.e., inlA, inlB, prfA, iap, actA, plcB, and hlyA. In addition, 17 antibiotics were tested, whereby two isolates showed resistance to clindamycin and azithromycin, while one isolate (L-74) was also resistant to nalidixic acid, co-trimoxazole, ampicillin, norfloxacin, and cefotaxime. L-23 and L-74 isolates showed biofilm formation, especially at pH 8.6 and 37°C. CONCLUSIONS: Besides the demonstration of the presence of L. monocytogenes in some dairy and street food products, this study underscores the need to increase the standards of hygiene on the one hand and the importance of the surveillance of food-borne pathogens on the other.

Bifurcation analysis of autonomous and nonautonomous modified Leslie-Gower models.

In ecological systems, the predator-induced fear dampens the prey's birth rate; yet, it fails to extinguish their population, as they endure and survive even under significant fear-induced costs. In this study, we unveil a modified Leslie-Gower predator-prey model by incorporating the fear of predators, cooperative hunting, and predator-taxis sensitivity. We embark upon an exploration of the positivity and boundedness of solutions, unearthing ecologically viable equilibrium points and their stability conditions governed by the model parameters. Delving deeper, we unravel the scenario of transcritical, saddle-node, Hopf, Bogdanov-Takens, and generalized-Hopf bifurcations within the system's intricate dynamics. Additionally, we observe the bistable nature of the system under some parametric conditions. Further, the nonautonomous extension of our model introduces the intriguing interplay of seasonality in some crucial parameters. We establish a set of sufficient conditions that guarantee the permanence of the seasonally driven system. By conducting a numerical study on the seasonally forced model, we observe a myriad of phenomena manifesting the predator-prey dynamics. Notably, periodic solutions, higher periodic solutions, and bursting patterns emerge, alongside intriguing chaotic dynamics. Specifically, seasonal variations of the predator-taxis sensitivity and hunting cooperation can lead to the extinction of prey species and even the control of chaotic (higher periodic) solutions through the generation of a simple periodic solution. Remarkably, the seasonal forcing has the capacity to govern the chaotic behavior, leading to an exceptionally quasi-periodic arrangement in both prey and predator populations.

Investigation of alpha amylase inhibitors from Bidens pilosa L. by in silico and in vitro studies.

Bidens pilosa L. has been traditionally used as an anti-diabetic herbal medicine; however, its mechanism of action remains elusive. In this study, the potential role of B. pilosa compounds on alpha-amylase inhibition and regulation of multiple pathways was investigated via computational and experimental studies. The phytocompounds were retrieved from plant databases and published literature. The druggability profile of these compounds was predicted using MolSoft. The probable targets of these phytocompounds were predicted using BindingDB (similarity index ≥ 0.7). Further, compound-gene set-pathway and functional enrichment analysis were performed using STRING and KEGG pathway databases. The network between compound-protein-pathway was constructed using Cytoscape. Molecular docking was performed using AutoDock Vina, executed through the POAP pipeline. The stability of the best docked complex was subjected to all-atom molecular dynamics (MD) simulation for 100 ns to investigate their structural stabilities and intermolecular interactions using GROMACS software. Finally, B. pilosa hydroalcoholic extract was subjected to LC-MS and tested for dose- and time-dependent alpha-amylase inhibitory activity. Out of 31 bioactive compounds, 13 were predicted to modulate the human pancreatic alpha-amylase (AMY2A) and 12 pathways associated with diabetes mellitus. PI3K-Akt signaling pathway (hsa04151) scored the lowest false discovery rate by triggering 15 genes. Further intermolecular interaction analysis of the docked complex revealed that Brassidin had the highest active site interaction and lowest binding energy compared to standard acarbose, and MD reveals the formation of a stable complex throughout 100 ns production run. LC-MS analysis revealed the presence of 13 compounds (targeting AMY2A) in B. pilosa hydroalcoholic extract, which showed potent AMY2A inhibition by in vitro studies that corroborate in silico findings for its anti-diabetic activity. Based on these findings, enriched fractions/pure compounds inhibitory activity that can be performed in future for drug discovery. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00187-9.

RAPIDIRON Trial follow-up study - the RAPIDIRON-KIDS Study: protocol of a prospective observational follow-up study.

BACKGROUND: Anemia is a worldwide problem with iron deficiency being the most common cause. When anemia occurs in pregnancy, it increases the risk of adverse maternal, fetal, and postnatal outcomes. It induces preterm births and low birth weight (LBW) deliveries, long-term neurodevelopmental sequelae, and an increased risk of earlier onset of postnatal iron deficiency. Anemia rates are among the highest in South Asia, and India's National Family Health Survey (NFHS-5) for 2019-2021 indicated that over half of pregnant women, and more than 65% of children, in the country are classified as anemic (Sciences IIfP, National Family Health Survey-5, 2019-21, India Fact Sheet). In 2021, the parent RAPIDIRON Trial (Derman et al., Trials 22:649, 2021) was initiated in two states in India, with the goal of assessing whether a dose of intravenous (IV) iron given to anemic women during early pregnancy results in a greater proportion of participants with normal hemoglobin concentrations in the third trimester and a lower proportion of participants with LBW deliveries compared to oral iron. As a follow-up to the RAPIDIRON Trial, the RAPIDIRON-KIDS Study will follow the offspring of previously randomized mothers to assess, neurobehavioral, hematological, and health outcomes. METHODS: This prospective observational cohort study will follow a subset of participants previously randomized as part of the RAPIDIRON Trial and their newborns. Study visits occur at birth, 6 weeks, 4 months, 12 months, 24 months, and 36 months and include blood sample collection with both maternal and infant participants and specific neurobehavioral assessments conducted with the infants (depending on the study visit). The primary outcomes of interest are (1) infant iron status as indicated by both hemoglobin and ferritin (a) at birth and (b) at 4 months of age and (2) the developmental quotient (DQ) for the cognitive domain of the Bayley Scales of Infant Development Version IV (BSID-IV) at 24 months of age. DISCUSSION: This RAPIDIRON-KIDS Study builds upon its parent RAPIDIRON Trial by following a subset of the previously randomized participants and their offspring through the first 3 years of life to assess neurodevelopmental and neurobehavioral (infants, children), hematological, and health outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05504863 , Registered on 17 August 2022. Clinical Trials Registry - India CTRI/2022/05/042933 . Registered on 31 May 2022.

Prevalence of goitre and iodine deficiency among school children (6-12 years) in rural areas of North Karnataka, India: A cross-sectional survey, 2016-19.

Introduction: Iodine deficiency disorders (IDD) have remained an unresolved public health problem in India. In this survey, we have estimated the prevalence of IDD among 6-12 years of school children in rural areas of north Karnataka, India and estimated the prevalence of low iodine content (<15 ppm) in salt at the household level and urine iodine excretion in this population. Material and Methods: In this cross-sectional survey, we recruited 16,827 children between 6 and 12 years of age through multistage sampling from six districts. Goitre was examined clinically for all children. Household-level salt iodine estimation and urinary iodine estimation were carried out among a subset of the participants. Results: Overall prevalence of goitre was 17.1% (95% CI: 16.5, 17.7). Out of this, 76.7% (n = 2116) had Grade-1 goitre, and 23.7% (n = 656) had Grade-2 goitre. The prevalence of goitre was higher among females (17.9%, vs. male 16.4%, P < 0.05). The prevalence of low iodine content (<15 ppm) in salt was 48.5% (95%CI: 46.7, 50.3). The overall median iodine excretion in urine was 85 µg/L (IQR: 60-150 µg/L). In total, 37.2% (n = 601) had mild iodine deficiency, 5.2% (n = 84) had moderate deficiency, and 10.1% (n = 163) had severe deficiency. All parameters showed high inter- and intradistrict variations. Conclusion: North Karnataka has a high goitre prevalence. Low use of iodized salt can be a major reason for the high prevalence of the condition. Ensuring the availability of iodized salt in this region and periodic surveillance to measure the impact of the programme should be the priority in this region.

Unraveling snake venom phospholipase A2: an overview of its structure, pharmacology, and inhibitors.

Snake bite is a neglected disease that affects millions of people worldwide. WHO reported approximately 5 million people are bitten by various species of snakes each year, resulting in nearly 1 million deaths and an additional three times cases of permanent disability. Snakes utilize the venom mainly for immobilization and digestion of their prey. Snake venom is a composition of proteins and enzymes which is responsible for its diverse pharmacological action. Snake venom phospholipase A2 (SvPLA2) is an enzyme that is present in every snake species in different quantities and is known to produce remarkable functional diversity and pharmacological action like inflammation, necrosis, myonecrosis, hemorrhage, etc. Arachidonic acid, a precursor to eicosanoids, such as prostaglandins and leukotrienes, is released when SvPLA2 catalyzes the hydrolysis of the sn-2 positions of membrane glycerophospholipids, which is responsible for its actions. Polyvalent antivenom produced from horses or lambs is the standard treatment for snake envenomation, although it has many drawbacks. Traditional medical practitioners treat snake bites using plants and other remedies as a sustainable alternative. More than 500 plant species from more than 100 families reported having venom-neutralizing abilities. Plant-derived secondary metabolites have the ability to reduce the venom's adverse consequences. Numerous studies have documented the ability of plant chemicals to inhibit the enzymes found in snake venom. Research in recent years has shown that various small molecules, such as varespladib and methyl varespladib, effectively inhibit the PLA2 toxin. In the present article, we have overviewed the knowledge of snake venom phospholipase A2, its classification, and the mechanism involved in the pathophysiology of cytotoxicity, myonecrosis, anticoagulation, and inflammation clinical application and inhibitors of SvPLA2, along with the list of studies carried out to evaluate the potency of small molecules like varespladib and secondary metabolites from the traditional medicine for their anti-PLA2 effect.

Structural insights into modeling of hepatitis B virus reverse transcriptase and identification of its inhibitors from potential medicinal plants of Western Ghats: an in silico and in vitro study.

The present study was proposed to model full-length HBV-RT and investigate the intermolecular interactions of known inhibitor and libraries of phytocompounds to probe the potential natural leads by in silico and in vitro studies. Homology modeling of RT was performed by Phyre2 and Modeller and virtual screening of ligands implemented through POAP pipeline. Molecular dynamics (MD) simulation (100 ns) and MM-GBSA calculations were performed using Schrodinger Desmond and Prime, respectively. Phytocompounds probable host protein targets gene set pathway enrichment and network analysis were executed by KEGG database and Cytoscape software. Prioritized plant extracts/enriched fraction LC-MS analysis was performed and along with pure compound, RT inhibitory activity, time-dependent HBsAg and HBeAg secretion, and intracellular HBV DNA, and pgRNA by qRT-PCR was performed in HepG2.2.15 cell line. Among the screened chemical library of 268 phytocompounds from 18 medicinal plants, 15 molecules from Terminalia chebula (6), Bidens pilosa (5), and Centella asiatica (4)) were identified as potential inhibitors of YMDD and RT1 motif of HBV-RT. MD simulation demonstrated stable interactions of 15 phytocompounds with HBV-RT, of which 1,2,3,4,6-Pentagalloyl Glucose (PGG) was identified as lead molecule. Out of 15 compounds, 11 were predicted to modulate 39 proteins and 15 molecular pathways associated with HBV infection. TCN and TCW (500 µg/mL) showed potent RT inhibition, decreased intracellular HBV DNA, and pgRNA, and time-dependent inhibition of HBsAg and HBeAg levels compared to PGG and Tenofovir Disoproxil Fumarate. We propose that the identified lead molecules from T. chebula as promising and cost-effective moieties for the management of HBV infection.Communicated by Ramaswamy H. Sarma.

Three finger toxins of elapids: structure, function, clinical applications and its inhibitors.

The WHO lists snakebite as a "neglected tropical disease". In tropical and subtropical areas, envenoming is an important public health issue. This review article describes the structure, function, chemical composition, natural inhibitors, and clinical applications of Elapids' Three Finger Toxins (3FTX) using scientific research data. The primary venomous substance belonging to Elapidae is 3FTX, that targets nAChR. Three parallel ß-sheets combine to create 3FTX, which has four or five disulfide bonds. The three primary types of 3FTX are short-chain, long-chain, and nonconventional 3FTX. The functions of 3FTX depend on the specific toxin subtype and the target receptor or ion channel. The well-known effect of 3FTX is probably neurotoxicity because of the severe consequences of muscular paralysis and respiratory failure in snakebite victims. 3FTX have also been studied for their potential clinical applications. α-bungarotoxin has been used as a molecular probe to study the structure and function of nAChRs (Nicotinic Acetylcholine Receptors). Acid-sensing ion channel (ASIC) isoforms 1a and 1b are inhibited by Mambalgins, derived from Black mamba venom, which hinders their function and provide an analgesic effect. α- Cobra toxin is a neurotoxin purified from Chinese cobra (Naja atra) binds to nAChR at the neuronal junction and causes an analgesic effect for moderate to severe pain. Some of the plants and their compounds have been shown to inhibit the activity of 3FTX, and their mechanisms of action are discussed.

Correction: Effects of chronic exposure to arsenic on the fecal carriage of antibiotic-resistant Escherichia coli among people in rural Bangladesh.

[This corrects the article DOI: 10.1371/journal.ppat.1010952.].

The marijuana-schizophrenia multifaceted nexus: Connections and conundrums towards neurophysiology.

Delta-9-tetrahydrocannabinol, a component of marijuana, interacts with cannabinoid receptors in brain involved in memory, cognition, and emotional control. However, marijuana use and schizophrenia development is a complicated and contentious topic. As a result, more investigation is needed to understand this relationship. Through the functional enrichment analysis, we report the delta-9-tetrahydrocannabinol to manipulate the homeostatic biological process and molecular function of different macromolecules. Additionally, using molecular docking and subsequent processing for molecular simulations, we assessed the binding ability of delta-9-tetrahydrocannabinol with the estrogen-related protein, dopamine receptor 5, and hyaluronidase. It was found that delta-9-tetrahydrocannabinol may have an impact on the brain's endocannabinoid system and may trigger the schizophrenia progression in vulnerable people. Delta-9-tetrahydrocannabinol may interfere with the biological function of 18 proteins linked to schizophrenia and disrupt the synaptic transmission (dopamine, glutamine, and gamma-aminobutyric acid). It was discovered that it may affect lipid homeostasis, which is closely related to membrane integrity and synaptic plasticity. The negative control of cellular and metabolic processes, fatty acids binding /activity, and the manipulated endocannabinoid system (targeting cannabinoid receptors) were also concerned with delta-9-tetrahydrocannabinol. Hence, this may alter neurotransmitter signaling involved in memory, cognition, and emotional control, showing its direct impact on brain physiological processes. This may be one of the risk factors for schizophrenia development which is also closely tied to some other variables such as frequency, genetic vulnerability, dosage, and individual susceptibility.

Impact of a school-based nutrition educational intervention on knowledge related to iron deficiency anaemia in rural Karnataka, India: A mixed methods pre-post interventional study.

OBJECTIVE: To understand the extent to which adolescent awareness about anaemia and anaemia prevention can be changed by nutrition messages received at school. DESIGN: Mixed-methods pre-post intervention study. SETTING: Three government schools in Bagalkot, Belagavi and Raichur districts of Karnataka, India. POPULATION: Students of grade six and seven and teachers involved in implementing the intervention. METHODS: An educational intervention was co-developed by school teachers and nutrition experts using locally adapted resource materials that consisted of lectures, role play and practical demonstrations. Seven half-hour educational sessions were delivered by school teachers over 7 weeks to 455 students. Pre- and post-intervention tests measured changes in adolescents' knowledge about anaemia. Semi-structured in-depth interviews with teachers and focus groups with students explored their reactions to the intervention. MAIN OUTCOME MEASURES: Knowledge score related to anaemia. RESULTS: The percentage of children with correct scores increased by 7.3-49.0 percentage points for the tested questions after implementation of the intervention. The mean knowledge score increased by 3.67 ± 0.17 (p < 0.01). During interviews, teachers and students highlighted high acceptance of the intervention and materials, an increase in awareness, a positive attitude towards changing behaviour around diet, an increase in the demand for iron and folic acid supplements and improved sharing of messages learned with peers and families. Challenges expressed included need for further training, time limitations and hesitancy in teaching about menstruation and pregnancy. CONCLUSIONS: Educational interventions carried out for adolescents by teachers in schools are effective in improving awareness and attitude related to anaemia and its prevention.

Ethyl gallate isolated from phenol-enriched fraction of Caesalpinia mimosoides Lam. Promotes cutaneous wound healing: a scientific validation through bioassay-guided fractionation.

The tender shoots of Caesalpinia mimosoides Lam. are used ethnomedically by the traditional healers of Uttara Kannada district, Karnataka (India) for the treatment of wounds. The current study was aimed at exploring phenol-enriched fraction (PEF) of crude ethanol extract of tender shoots to isolate and characterize the most active bio-constituent through bioassay-guided fractionation procedure. The successive fractionation and sub-fractionation of PEF, followed by in vitro scratch wound, antimicrobial, and antioxidant activities, yielded a highly active natural antioxidant compound ethyl gallate (EG). In vitro wound healing potentiality of EG was evidenced by a significantly higher percentage of cell migration in L929 fibroblast cells (97.98 ± 0.46% at 3.81 µg/ml concentration) compared to a positive control group (98.44 ± 0.36%) at the 48th hour of incubation. A significantly higher rate of wound contraction (98.72 ± 0.41%), an elevated tensile strength of the incised wound (1,154.60 ± 1.42 g/mm2), and increased quantity of connective tissue elements were observed in the granulation tissues of the 1% EG ointment treated animal group on the 15th post-wounding day. The accelerated wound healing activity of 1% EG was also exhibited by histopathological examinations through Hematoxylin and Eosin, Masson's trichome, and Toluidine blue-stained sections. Significant up-regulation of enzymatic and non-enzymatic antioxidant contents (reduced glutathione, superoxide dismutase, and catalase) and down-regulation of oxidative stress marker (lipid peroxidation) clearly indicates the effective granular antioxidant activity of 1% EG in preventing oxidative damage to the skin tissues. Further, in vitro antimicrobial and antioxidant activities of EG supports the positive correlation with its enhanced wound-healing activity. Moreover, molecular docking and dynamics for 100 ns revealed the stable binding of EG with cyclooxygenase-2 (-6.2 kcal/mol) and matrix metalloproteinase-9 (-4.6 kcal/mol) and unstable binding with tumor necrosis factor-α (-7.2 kcal/mol), suggesting the potential applicability of EG in inflammation and wound treatment.

System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis.

Hepatitis B infection caused by the hepatitis B virus is a life-threatening cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Researchers have produced multiple in vivo models for hepatitis B virus (HBV) and, currently, there are no specific laboratory animal models available to study HBV pathogenesis or immune response; nonetheless, their limitations prevent them from being used to study HBV pathogenesis, immune response, or therapeutic methods because HBV can only infect humans and chimpanzees. The current study is the first of its kind to identify a suitable chemically induced liver cirrhosis/HCC model that parallels HBV pathophysiology. Initially, data from the peer-reviewed literature and the GeneCards database were compiled to identify the genes that HBV and seven drugs (acetaminophen, isoniazid, alcohol, D-galactosamine, lipopolysaccharide, thioacetamide, and rifampicin) regulate. Functional enrichment analysis was performed in the STRING server. The network HBV/Chemical, genes, and pathways were constructed by Cytoscape 3.6.1. About 1546 genes were modulated by HBV, of which 25.2% and 17.6% of the genes were common for alcohol and lipopolysaccharide-induced hepatitis. In accordance with the enrichment analysis, HBV activates the signaling pathways for apoptosis, cell cycle, PI3K-Akt, TNF, JAK-STAT, MAPK, chemokines, NF-kappa B, and TGF-beta. In addition, alcohol and lipopolysaccharide significantly activated these pathways more than other chemicals, with higher gene counts and lower FDR scores. In conclusion, alcohol-induced hepatitis could be a suitable model to study chronic HBV infection and lipopolysaccharide-induced hepatitis for an acute inflammatory response to HBV.

Undernutrition among rural school-age children: a major public health challenge for an aspirational district in Karnataka, India.

Background: For school-age children, a healthy transition from childhood to adolescence and adulthood depends on proper nutrition. Globally, most nutritional surveys focus on preschool and adolescents, neglecting school-age children. Recent studies have shown the prevalence of thinness among adolescents to be 26.5% in Karnataka. Similarly, among children aged < 5 years in the Raichur district, the prevalence of stunting, wasting, and being underweight was 39.8, 23.2, and 40.7%, respectively. The present study aimed to bridge the data gap between < 5 years of children and adolescents through a nutritional survey of school-going children in Raichur, one of the aspirational districts of India. Materials and methods: A cross-sectional survey was conducted from January to March 2020 among rural school-age children (n = 2700) in 30 villages of the Raichur district of Karnataka, India. The school children were selected through a multi-stage cluster sampling technique. The WHO Anthro-plus software was used for calculating the age and sex-specific Z-scores for weight-for-age (WAZ), height-for-age (HAZ), and BMI-for-age (BAZ). Results: Of the 2,700 school-age children surveyed, the mean weight and height were 22.2 kg (+5.8) and 124.9 cm (+11.6), respectively. The prevalence of children having weight-for-age Z-scores < -2 SD (Underweight) was 45.3% (95% CI: 42.7%-47.8%). The magnitude of stunting and severe stunting was 19.5% (95% CI: 18.0%-21.0%) and 7.6% (95% CI: 6.6%-8.6%), respectively. The proportion of children with BMI for age Z-scores < -2SD (thinness) was 43% (95% CI: 41.1%-44.9%), with sub-district Sindhanur having a dual burden of malnutrition. Conclusion: Despite many flagship programs, the prevalence of undernutrition in school-age children remains a considerable public health problem in the aspirational district of Raichur, India. Furthermore, exploratory studies are recommended to identify the factors associated with undernutrition among school-age children and strategize evidence-based intervention.

Suspected cutaneous adverse drug reactions reported with traditional medicines: analysis of data for United Nations Asia region from WHO VigiBase.

Background: Data on traditional medicine-induced cutaneous adverse drug reactions (ADRs) is very scarce. The current secondary analysis based on the WHO database (VigiBase) of individual case safety reports (ICSRs) focuses on the suspected cutaneous ADRs linked to traditional medicines (TMs). Methods: All the ICSRs reported between 1st January 2016 and 30th June 2021 from the UN Asia region in VigiBase where at least one TM was suspected to cause cutaneous ADRs were included in the study. Data regarding demographic details, suspected drug, adverse reaction as per MedDRA term, the seriousness of the reaction, de-challenge, re-challenge, and clinical outcome for suspected cutaneous ADRs associated with TM were obtained from VigiBase and analyzed for frequency of reported events and suspected medicines. Findings: Total 3,523 ICSRs with 5,761 ADRs related to "skin and subcutaneous tissue disorders" were included in the analysis. Amongst these, 6.8% of ICSRs were reported as serious. Pruritus (29.6%), rash (20.3%), urticaria (18.9%), and hyperhidrosis (3.3%) were commonly reported ADRs. Artemisia argyi H.Lév. and Vaniot. (14.9%), Ginkgo biloba L. (5.1%), Vitis vinifera L. (4%), Vitex agnus-castus L. (3.8%), Silybum marianum (L.), Gaertn (3.5%), and Viscus album L. (2.7%) were some commonly suspected TMs for cutaneous ADRs. There were 46 cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported with TMs during the study period. Death was reported in 5 ICSRs. Interpretation: TMs are linked with various cutaneous ADRS ranging from pruritus to toxic epidermal necrolysis which may have serious consequences. TMs listed as suspected offending agents in this analysis, should be kept in mind while dealing with suspected cutaneous ADRs. Clinicians should be more vigilant in detecting and reporting events associated with TMs.

Computational and experimental pharmacology to decode the efficacy of Theobroma cacao L. against doxorubicin-induced organ toxicity in EAC-mediated solid tumor-induced mice.

Background and objective: Doxorubicin is extensively utilized chemotherapeutic drug, and it causes damage to the heart, liver, and kidneys through oxidative stress. Theobroma cacao L (cocoa) is reported to possess protective effects against several chemical-induced organ damages and also acts as an anticancer agent. The study aimed to determine whether the administration of cocoa bean extract reduces doxorubicin-induced organ damage in mice with Ehrlich ascites carcinoma (EAC) without compromising doxorubicin efficacy. Methodology: Multiple in vitro methods such as cell proliferation, colony formation, chemo-sensitivity, and scratch assay were carried out on cancer as well as normal cell lines to document the effect of cocoa extract (COE) on cellular physiology, followed by in vivo mouse survival analysis, and the organ-protective effect of COE on DOX-treated animals with EAC-induced solid tumors was then investigated. In silico studies were conducted on cocoa compounds with lipoxygenase and xanthine oxidase to provide possible molecular explanations for the experimental observations. Results: In vitro studies revealed potent selective cytotoxicity of COE on cancer cells compared to normal. Interestingly, COE enhanced DOX potency when used in combination. The in vivo results revealed reduction in EAC and DOX-induced toxicities in mice treated with COE, which also improved the mouse survival time; percentage of lifespan; antioxidant defense system; renal, hepatic, and cardiac function biomarkers; and also oxidative stress markers. COE reduced DOX-induced histopathological alterations. Through molecular docking and MD simulations, we observed chlorogenic acid and 8'8 methylenebiscatechin, present in cocoa, to have the highest binding affinity with lipoxygenase and xanthine oxidase, which lends support to their potential in ameliorating oxidative stress. Conclusion: The COE reduced DOX-induced organ damage in the EAC-induced tumor model and exhibited powerful anticancer and antioxidant effects. Therefore, COE might be useful as an adjuvant nutritional supplement in cancer therapy.

A community-based study of dental fluorosis in rural children (6-12 years) from an aspirational district in Karnataka, India.

Objectives: The present study was planned to estimate the prevalence of dental fluorosis in 6-12 years of children and its association with various drinking water sources, water, and urine fluoride levels among the subset of children under the umbrella of a larger study to address iodine deficiency disorders and iron deficiency anemia in 17 villages of Manvi and Devadurga talukas of Raichur district of Karnataka. Methods: Analysis of subset of data and urine samples of children under the umbrella of a larger cross-sectional community-based study was conducted in 17 villages of Manvi and Devadurga taluks of Raichur district. House to house survey was carried out to collect data using a semi-structured questionnaire in ODK software. Demographic details, source of drinking water, clinical assessment of dental fluorosis, and height and weight measurements were performed by trained staff. Urine and water samples were collected for fluoride level estimation. The overall prevalence of dental fluorosis and its severity-wise prevalence were estimated. Association between dental fluorosis and age, gender, type of diet, source of drinking water, height for age, BMI for age, water fluoride level, and urine fluoride level were carried out using logistic regression analysis. Results: The prevalence of dental fluorosis was 46.0%. Mild, moderate, and severe dental fluorosis was found in 37.9, 7.8, and 0.3% of children. With the increasing age of participants, the odds of dental fluorosis were found to increase by 2-4 folds. The odds of having dental fluorosis were significantly increased with increasing water fluoride levels of 3 to 5 ppm [AOR = 3.147 (1.585-6.248); P = 0.001] in comparison with water fluoride levels of < 1 ppm. The similar trend was found with urine fluoride level > 4 ppm [AOR = 3.607 (1.861-6.990); P < 0.001]. As compared to river water, other sources of drinking water were significantly associated with higher odds of dental fluorosis. Conclusions: Prevalence of dental fluorosis was high in 6 to 12 years due to overexposure of fluoride from drinking water. High water and urine fluoride levels in children indicate the chronic exposure to fluoride and suggest that the population is at high risk of developing chronic fluorosis.

Anti-Cholera toxin activity of selected polyphenols from Careya arborea, Punica granatum, and Psidium guajava.

Introduction: Careya arborea, Punica granatum, and Psidium guajava are traditionally used to treat diarrheal diseases in India and were reported to show anti-Cholera toxin activity from our earlier studies. As polyphenols are reported to neutralize Cholera toxin (CT), the present study investigated the inhibitory activity of selected polyphenols from these plants against CTB binding to GM1 receptor using in silico, in vitro, and in vivo approaches. Methods: Molecular modelling approach was used to investigate the intermolecular interactions of selected 20 polyphenolic compounds from three plants with CT using DOCK6. Based on intermolecular interactions, two phenolic acids, Ellagic acid (EA) and Chlorogenic acid (CHL); two flavonoids, Rutin (RTN) and Phloridzin (PHD) were selected along with their respective standards, Gallic acid (GA) and Quercetrin (QRTN). The stability of docked complexes was corroborated using molecular dynamics simulation. Furthermore, in vitro inhibitory activity of six compounds against CT was assessed using GM1 ELISA and cAMP assay. EA and CHL that showed prominent activity against CT in in vitro assays were investigated for their neutralizing activity against CT-induced fluid accumulation and histopathological changes in adult mouse. Results and discussion: The molecular modelling study revealed significant structural stability of the CT-EA, CT-CHL, and CT-PHD complexes compared to their respective controls. All the selected six compounds significantly reduced CT-induced cAMP levels, whereas EA, CHL, and PHD exhibited > 50% binding inhibition of CT to GM1. The EA and CHL that showed prominent neutralization activity against CT from in vitro studies, also significantly decreased CT-induced fluid accumulation and histopathological changes in adult mouse. Our study identified bioactive compounds from these three plants against CT-induced diarrhea.

Attention for and awareness of anemia in adolescents in Karnataka, India: A qualitative study.

Between 1990 and 2016 the number of adolescents with anemia world-wide increased by 20% to almost one in four. Iron deficiency in adolescence results in compromised growth, decreased cognitive function, and depressed immune function, and can increase the risk of negative outcomes in pregnancy, especially in the case of young adolescents. In India, despite several decades of governmental investment in anemia prevention and treatment, more than half of women of reproductive age are anemic, with rates even higher in the adolescent population. Although awareness of adolescence as a nutrition-sensitive developmental stage is increasing, there is a lack of qualitative research on the perspectives of adolescents and families on anemia and related services. In this study, we explored the issues influencing adolescents' awareness of anemia in three rural areas of Karnataka. Sixty-four in-depth interviews and six focus group discussions were conducted with adolescents (those who had never been pregnant, pregnant adolescents, and young mothers), community members, and nutrition-related service providers in the health and education sectors. An inductive analytical approach was used. We found that adolescent girls, particularly those who have not experienced pregnancy or motherhood, had very low awareness of anemia. State programs including school-based distribution of iron and folic acid supplements and nutrition talks were not seen to be resulting in knowledge and acceptance of the importance of preventing anemia. Pregnancy represents a turning point in which adolescents are systematically tested for anemia as part of routine antenatal care, increasing their awareness of, and access to, treatment for the condition. At the same time, pregnancy represents to family and community a period to insist on a nutritious diet. For progress in anemia reduction to be made, improved age-appropriate measures specific for adolescence are required. Improving school-based nutrition outreach is an important opportunity to reach adolescents.