Examining the Triple Burden of Malnutrition: Insights from a Community-Based Comprehensive Nutrition Survey among Indigenous Tribal Children (0-19 Years) in the Western Ghats Hills of India.

This article presents findings from a community-based cross-sectional study conducted in Attappadi, Kerala, India, aimed at assessing the prevalence of the triple burden of malnutrition among indigenous children aged 0-19 years. Historically, the indigenous population in Attappadi has faced significant developmental challenges, including high rates of malnutrition, infant mortality, and neonatal mortality. This study revealed alarming rates of undernutrition among children aged 0-59 months, with 40.9% experiencing stunting, 27.4% wasting, and 48.3% being underweight. Adolescent girls also suffered from undernutrition, with 21% classified as underweight and 43.3% experiencing stunting. Surprisingly, overweight or obesity was identified as a nutritional problem, affecting 1.4% of children aged 0-59 months, 4.2% of children aged 5-9 years, and 10.5% of adolescent girls. Additionally, a distressing proportion of young children aged 12-59 months (91.2%) were anaemic, with 50% diagnosed specifically with iron deficiency anaemia (IDA). Nearly all adolescent girls (96.6%) were reportedly suffering from anaemia. Deficiencies in vitamin B12, vitamin D, folate, and vitamin-A were prevalent among 35%, 20%, 16%, and 12% of children aged 12-59 months, respectively. The study underscores the urgent need for comprehensive interventions to address this triple burden of malnutrition. Recommendations include promoting culturally appropriate local food-based solutions, establishing participatory and community-led systems for health and nutrition information dissemination, and strengthening the nutrition surveillance system through village-level health and nutrition workers. By adopting a holistic approach, these interventions can help improve the nutritional status and well-being of the indigenous tribal children in Attappadi.

Separation, identification and characterization of stress degradation products of bortezomib using HPLC and LC-MS.

Bortezomib (BT) is a reversible inhibitor of proteasome which is used in the treatment of hematological cancers. To study the degradation behavior, BT was subjected to acidic, basic, neutral, photolytic, oxidative and thermal degradation conditions as per ICH guideline Q1A (R2). A gradient HPLC method has been developed for separating all the degradation products formed under various degradation conditions on Waters XBridge C18 column (150 mm × 4.6 mm × 3.5 µm) using the mobile phase composed of ammonium formate and acetonitrile. A total of six degradation products were formed in various stress conditions and these were separated identified, and characterized using high performance liquid chromatography in combination with electrospray ionization tandem mass spectrometric studies.

Demonstration of X-ray Thomson scattering as diagnostics for miscibility in warm dense matter.

The gas and ice giants in our solar system can be seen as a natural laboratory for the physics of highly compressed matter at temperatures up to thousands of kelvins. In turn, our understanding of their structure and evolution depends critically on our ability to model such matter. One key aspect is the miscibility of the elements in their interiors. Here, we demonstrate the feasibility of X-ray Thomson scattering to quantify the degree of species separation in a 1:1 carbon-hydrogen mixture at a pressure of ~150 GPa and a temperature of ~5000 K. Our measurements provide absolute values of the structure factor that encodes the microscopic arrangement of the particles. From these data, we find a lower limit of [Formula: see text]% of the carbon atoms forming isolated carbon clusters. In principle, this procedure can be employed for investigating the miscibility behaviour of any binary mixture at the high-pressure environment of planetary interiors, in particular, for non-crystalline samples where it is difficult to obtain conclusive results from X-ray diffraction. Moreover, this method will enable unprecedented measurements of mixing/demixing kinetics in dense plasma environments, e.g., induced by chemistry or hydrodynamic instabilities.

Objective evaluation of stubble emission of North India and quantifying its impact on air quality of Delhi.

Crop residue burning during post monsoon season in the neighboring provinces leads to frequent episodes of extreme pollution events, associated with premature morbidity and mortality. A synergistic use of multiple satellite measurements in conjunction with actual field incidences data at the ground led us to develop the realistic high-resolution emission inventory of the hazardous pollutant PM2.5 due to stubble burning. We quantify the share of biomass burning in deteriorating Delhi's air quality during 2018 using the SAFAR chemical transport model that has been validated with dense observational network of Delhi. The impact of biomass burning on Delhi's PM2.5 is found to vary on day-to day basis (peaking at 58%) as it is highly dependent on transportation pathway of air mass, controlled by meteorological parameters from source to target region. Comprehending the multi-scale nature of such events is crucial to plan air quality improvement strategies.

Isolation and evolutionary analysis of Australasian topotype of bluetongue virus serotype 4 from India.

Bluetongue (BT) is a Culicoides-borne disease caused by several serotypes of bluetongue virus (BTV). Similar to other insect-borne viral diseases, distribution of BT is limited to distribution of Culicoides species competent to transmit BTV. In the tropics, vector activity is almost year long, and hence, the disease is endemic, with the circulation of several serotypes of BTV, whereas in temperate areas, seasonal incursions of a limited number of serotypes of BTV from neighbouring tropical areas are observed. Although BTV is endemic in all the three major tropical regions (parts of Africa, America and Asia) of the world, the distribution of serotypes is not alike. Apart from serological diversity, geography-based diversity of BTV genome has been observed, and this is the basis for proposal of topotypes. However, evolution of these topotypes is not well understood. In this study, we report the isolation and characterization of several BTV-4 isolates from India. These isolates are distinct from BTV-4 isolates from other geographical regions. Analysis of available BTV seg-2 sequences indicated that the Australasian BTV-4 diverged from African viruses around 3,500 years ago, whereas the American viruses diverged relatively recently (1,684 CE). Unlike Australasia and America, BTV-4 strains of the Mediterranean area evolved through several independent incursions. We speculate that independent evolution of BTV in different geographical areas over long periods of time might have led to the diversity observed in the current virus population.

Biological evaluation of 3-hydroxybenzyl alcohol, an extrolite produced by Aspergillus nidulans strain KZR-132.

AIMS: The aim of the study was to purify and characterize a bioactive compound from Aspergillus nidulans strain KZR-132 and its biological evaluation. METHODS AND RESULTS: A bioactive extolite was purified from A. nidulans strain KZR-132, and its chemical structure was elucidated as 3-hydroxylbenzyl alcohol (3-HBA) based on 1 H and 13 C NMR, FT-IR and mass spectroscopic analysis. The antimicrobial efficacy of 3-HBA was established against Gram-positive, Gram-negative bacteria and different Candida strains. It also showed promising antibiofilm activity against various tested microbial strains. Reactive oxygen species induced by 3-HBA treatment on different Candida strains killed most of the cells and showed necrotic effect. It also exhibited dose-dependent antioxidant and anti-inflammatory activities. CONCLUSIONS: This bioactive extrolite produced by A. nidulans isolated from a niche habitat was demonstrated to possess significant biotechnological and pharmacological potential since it exhibited broad-spectrum antimicrobial and antibiofilm activities which are reported for the first time. SIGNIFICANCE AND IMPACT OF THE STUDY: The overall study demonstrates that 3-HBA produced by A. nidulansKZR-132 is a promising bioactive metabolite and possibly can function as a pharmacologically suitable broad-spectrum antimicrobial drug candidate against various dreaded human-related bacterial and fungal pathogens.

Mangiferin from Pueraria tuberosa reduces inflammation via inactivation of NLRP3 inflammasome.

Recent reports have demonstrated the role of phyto-constituents in modulating inflammatory responses. Mangiferin isolated from Mangifera indica is known to induce potent anti-oxidative, anti-diabetic and anti-inflammatory activity. However, the molecular mechanism of its anti-inflammatory activity is not properly understood. In this study we have isolated Mangiferin from the tubers of Pueraria tuberosa (PT-Mangiferin) and analysed the mechanism of its potent anti-inflammatory effects in LPS stimulated RAW 264.7 mouse macrophage cell line and in a carrageenan induced air pouch model. PT-Mangiferin was non-toxic to primary cells but showed significant toxicity and apoptotic effect on cancerous cells. It significantly reduced the production of pro-inflammatory mediators (COX-2, iNOS and TNF-α) in LPS stimulated RAW 264.7 cells. Further, it has also reduced the generation of ROS and inhibited LPS induced NF-kB translocation in these cells. Additionally, PT-Mangiferin significantly reduced inflammation in a mouse air pouch model by inhibiting the infiltration of monocytes and neutrophils and reducing the production of cytokines. These effects were mediated via inactivation of NLRP3 inflammasome complex and its downstream signalling molecules. Taken together these results suggest that PT-Mangiferin is potent anti-inflammatory compound that reduces inflammation and holds promise in development of herbal based anti-inflammatory therapeutics in future.

Incidence & prognosis of acute kidney injury in individuals of snakebite in a tertiary care hospital in India.

BACKGROUND & OBJECTIVES: The snakebites are considered to be an occupational hazard in agriculture workers and the snake handlers, resulting in a considerable morbidity, mortality and economical implications. This study was conducted to determine the incidence, clinical presentation, renal injury and clinical outcome in snakebite victims who developed acute kidney injury (AKI). METHODS: This hospital-based prospective, observational study was done on 100 cases who were admitted for the management of snakebite and found to develop AKI in a tertiary care hospital at Hyderabad, India. Renal function tests, complete blood picture, urine routine examination, ultrasound examination of abdomen and coagulation profile were done and the prognosis was assessed by noting recovery, mortality, morbidity and/or progress to chronic stage. RESULTS: A total of 100 patients with a mean age of 43.80±12.63 yr (range 18-70); 62 males and 38 females were studied. All had bites on lower limbs. A total of 86 patients arrived in the hospital within 24 h, and 14 arrived after 24 h. Oliguria was found in 60, bleeding tendencies in 64, haemodynamic instability noted - tachycardia in 86. Systolic blood pressure (BP) was <120 mm Hg in 68 and BP was not recordable in four patients. Twelve patients were in stage III kidney disease and needed haemodialysis. Of the 100 cases of snakebite-induced acute kidney failure, 86 recovered and six died. On follow up, after six months eight patients developed chronic kidney failure. INTERPRETATION & CONCLUSIONS: A cascade of events tends to occur in severe haemotoxic envenomation such as bleeding disorders, hypotension/circulatory shock, intravascular haemolysis, disseminated intravascular coagulation and acute respiratory disease syndrome (ARDS). The findings of this study showed that early hospitalization, quick antisnake venom administration and adequate supporting care provided promising results.

A diastereoselective synthesis of tetrahydro- and dihydro-pyrido[2,3-c]coumarin derivatives via a one-pot three-component Povarov reaction catalyzed by bismuth(III) chloride.

A diastereoselective synthesis of tetrahydro- and dihydro-pyrido[2,3-c]coumarin derivatives has been achieved via a one-pot three-component aza-Diels-Alder reaction of aromatic aldehydes, 3-aminocoumarin and dienophiles catalyzed by BiCl3. NOE studies proved that exo-isomers were obtained in all cases with high selectivity. The reaction proceeded at room temperature providing good yields of products as well as applicability on a wide range of substrates. Among all the synthesized derivatives, compounds 4i and 4k showed promising DPPH radical scavenging activity as compared to other tested derivatives.

Sequencing Analysis of NS3/4A, NS5A, and NS5B Genes from Patients Infected with Hepatitis C Virus Genotypes 5 and 6.

Direct-acting antivirals (DAAs) with activity against multiple genotypes of the hepatitis C virus (HCV) were recently developed and approved for standard-of-care treatment. However, sequencing assays to support HCV genotype 5 and 6 analysis are not widely available. Here, we describe the development of a sequencing assay for the NS3/4A, NS5A, and NS5B genes from HCV genotype 5 and 6 patient isolates. Genotype- and subtype-specific primers were designed to target NS3/4A, NS5A, and NS5B for cDNA synthesis and nested PCR amplification. Amplification was successfully performed for a panel of 32 plasma samples from HCV-infected genotype 5 and 6 patients with sequencing data obtained for all attempted samples. LiPA 2.0 (Versant HCV genotype 2.0) is a reverse hybridization line probe assay that is commonly used for genotyping HCV-infected patients enrolled in clinical studies. Using NS3/4A, NS5A, and NS5B consensus sequences, HCV subtypes were determined that were not available for the initial LiPA 2.0 result for genotype 6 samples. Samples amplified here included the following HCV subtypes: 5a, 6a, 6e, 6f, 6j, 6i, 6l, 6n, 6o, and 6p. The sequencing data generated allowed for the determination of the presence of variants at amino acid positions previously characterized as associated with resistance to DAAs. The simple and robust sequencing assay for genotypes 5 and 6 presented here may lead to a better understanding of HCV genetic diversity and prevalence of resistance-associated variants.

A Complete Profile on Blind-your-eye Mangrove Excoecaria Agallocha L. (Euphorbiaceae): Ethnobotany, Phytochemistry, and Pharmacological Aspects.

Traditional system of medicine consists of large number of plants with various medicinal and pharmacological importances. This article provides a comprehensive review of the complete profile of an important mangrove plant Excoecaria agallocha L. (Euphorbiaceae) and elaborately describing the ethnobotany, phytochemistry, and pharmacological properties. It is used traditionally in the treatment of various diseases such as epilepsy, ulcers, leprosy, rheumatism, and paralysis. The latex obtained from the bark is poisonous in nature and may cause temporary blindness, thus it is also known as the blind-your-eye mangrove plant. Many phytoconstituents were isolated from the plant, which were mainly diterpenoids, triterpenoids, flavonoids, sterols, and few other compounds. The plant also showed many pharmacological activities such as antioxidant, antimicrobial, anti-inflammatory, analgesic, antiulcer, anticancer, antireverse transcriptase, antihistamine-release, antifilarial, DNA damage protective, antidiabetic, and antitumor protecting activities. Hence, this review could help guide researchers anticipating to undertake further investigations in these directions.

Evaluation of the influence of ayurvedic formulation (Ayushman-15) on psychopathology, heart rate variability and stress hormonal level in major depression (Vishada).

INTRODUCTION: Ayurveda (Indian-complimentary and alternative medicine) is still most sought after in India and has promising potential in management of Vishada [major depressive disorder (MDD)]. But, systematic research is lacking. In this study we evaluated of influence of ayurvedic treatment (Panchakarma and Ayushman-15) on psychopathology, heart rate variability (HRV) and endocrinal parameters in patients with major depression. METHODS: 81 drug naive patients diagnosed as Vishada by ayurvedic physician and MDD according to DSM IV-TR were given ayurvedic Virechana module (therapeutic purgation) and were randomized into two groups. Patients in group A (n=41) received Ayushman-15A while group B (n=40) received Ayushman-15B for two months and Shirodhara (forehead-oil pouring therapy). Patients were assessed with Hamilton Depression Rating Scale (HDRS), Montgomery Asberg Depression Rating Scale (MADRS), Heart Rate Variability (HRV). Cortisol and adrenocorticotropic hormone (ACTH) were estimated at baseline and after ayurvedic therapy. HRV and endocrinal parameters were compared with age and gender matched healthy volunteers. RESULTS: HRV parameters showed significant sympathetic dominance in patients compared to healthy volunteers. Two months of ayurvedic treatment significantly decreased psychopathology, showed increase in vagal tone, decrease in sympathetic tone and reduced cortisol levels. However, there was no significant difference between groups receiving Ayushman A and B. CONCLUSION: This study provides evidence for antidepressant, cardiac (HRV) and beneficial neuroendocrine modulatory influence of Ayurveda therapy in patients of Vishada (MDD). Further studies are needed to confirm these findings. Greater insight into the neurobiology behind this therapy might provide valuable information about newer drug target.

Identification of novel phenyl butenonyl C-glycosides with ureidyl and sulfonamidyl moieties as antimalarial agents.

A new series of C-linked phenyl butenonyl glycosides bearing ureidyl(thioureidyl) and sulfonamidyl moieties in the phenyl rings were designed, synthesized, and evaluated for their in vitro antimalarial activities against Plasmodium falciparum 3D7 (CQ sensitive) and K1 (CQ resistant) strains. Among all the compounds screened the C-linked phenyl butenonyl glycosides bearing sulfonamidyl moiety (5a) and ureidyl moiety in the phenyl ring (7d and 8c) showed promising antimalarial activities against both 3D7 and K1 strains with IC50 values in micromolar range and low cytotoxicity offering new HITS for further exploration.

Synthesis and anticancer activity of γ-(triazolyl ethylidene)butenolides and polyfunctional pyrrolinones.

A series of novel γ-(triazolyl ethylidene)butenolides (4-23) were prepared from commercially available l-ascorbic acid in good yields. These butenolides on reaction with ethanolic ammonia/amines led to formation of respective 5-hydroxy pyrrolinones (24-33). The two of these pyrrolinones on dehydration with p-toluenesulfonic acid, were transformed into γ-(triazolyl ethylidene)pyrrolinones (34, 35). Among all the newly synthesized hybrid molecules tested for anticancer activity in vitro, compounds 24, 25, 26, 27, 28, 30 and 32 showed significant activity against MCF-7, MDA-MB-231, PC-3 or U-937 cells. In particular compound 25 (IC50 = 11.3 µM) exhibited most potent activity against breast cancer cells and preliminary studies revealed that potency of this compound is due to ROS generation, subsequent activation of p38, leading to apoptosis and inhibition of cancer cells.

SRA- and SET-domain-containing proteins link RNA polymerase V occupancy to DNA methylation.

RNA-directed DNA methylation in Arabidopsis thaliana depends on the upstream synthesis of 24-nucleotide small interfering RNAs (siRNAs) by RNA POLYMERASE IV (Pol IV) and downstream synthesis of non-coding transcripts by Pol V. Pol V transcripts are thought to interact with siRNAs which then recruit DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2) to methylate DNA. The SU(VAR)3-9 homologues SUVH2 and SUVH9 act in this downstream step but the mechanism of their action is unknown. Here we show that genome-wide Pol V association with chromatin redundantly requires SUVH2 and SUVH9. Although SUVH2 and SUVH9 resemble histone methyltransferases, a crystal structure reveals that SUVH9 lacks a peptide-substrate binding cleft and lacks a properly formed S-adenosyl methionine (SAM)-binding pocket necessary for normal catalysis, consistent with a lack of methyltransferase activity for these proteins. SUVH2 and SUVH9 both contain SRA (SET- and RING-ASSOCIATED) domains capable of binding methylated DNA, suggesting that they function to recruit Pol V through DNA methylation. Consistent with this model, mutation of DNA METHYLTRANSFERASE 1 (MET1) causes loss of DNA methylation, a nearly complete loss of Pol V at its normal locations, and redistribution of Pol V to sites that become hypermethylated. Furthermore, tethering SUVH9 [corrected] with a zinc finger to an unmethylated site is sufficient to recruit Pol V and establish DNA methylation and gene silencing. These results indicate that Pol V is recruited to DNA methylation through the methyl-DNA binding SUVH2 and SUVH9 proteins, and our mechanistic findings suggest a means for selectively targeting regions of plant genomes for epigenetic silencing.

Precolumn o-phthalaldehyde-N-acetyl-L-cysteine derivatization followed by RP-HPLC separation and fluorescence detection of sitagliptin enantiomers in rat plasma.

An indirect reversed-phase high-performance liquid chromatographic separation and fluorescence detection of sitagliptin enantiomers in rat plasma was developed and validated. Deproteinized rat plasma containing racemic sitagliptin was derivatized with o-phthalaldehyde and N-acetyl-L-cysteine under alkaline conditions, converted to diastereomers, and separated on a Lichrospher 100 RP-18e column using 20 mM phosphate buffer and methanol (45:55 v/v) as a mobile phase under isocratic mode of elution at a flow rate of 1.0 mL/min. Fluorescence detection was performed at 330 and 450 nm as excitation and emission wavelengths, respectively. The method was linear in the range of 50-5000 ng/ mL for both enantiomers. The intra- and interday accuracy and precision were within the predefined limits of ≤15% at all concentrations. The method was successfully applied to a pharmacokinetic study of sitagliptin after 5 mg/kg oral administration to Wistar rats. Robustness of the method was evaluated using design of experiments.

LC-MS/MS determination of pramipexole on rat dried blood spots: a pharmacokinetic study.

A simple and selective liquid chromatography-tandem mass spectrometric method for determination of pramipexole on rat dried blood spots was developed and validated. Chromatographic separation was achieved on a Synergy polar-RP column using 10mM ammonium acetate and methanol (50:50, v/v) as mobile phase in an isocratic mode of elution at a flow rate of 1.0mL/min. LC-MS was performed in a positive ion electro spray ionization mode and the MS/MS ion transitions 212.10→153.03 for PRX and 198.10→153.03 for internal standard (2-amino-4,5,6,7-tetrahydro-6-ethyl-amino-benzthiazole) were monitored. The developed method exhibited a linear dynamic range over 100-5000pg/mL for PRX on dried blood spots. The overall extraction recovery of PRX from DBS was 96.7%. The intra- and inter-day accuracy and precision were within the pre-defined limits of ≤15% at all concentrations. Influence of hematocrit and spot volume on dried blood spot was also evaluated and found to be well within the acceptable limits. The method was successfully applied to pharmacokinetic studies of PRX in rats.

Fluorimetric quantification of brimonidine tartrate in eye drops.

A simple and sensitive spectrofluorimetric method has been developed for the estimation of brimonidine tartrate in pure and eye drops. Linearity was obeyed in the range of 0.2-3.0 ΅g/ml in dimethyl formamide as solvent at an emission wavelength (λem) of 530 nm after excitation wavelength (λex) of 389 nm with good correlation coefficient of 0.998. The limit of detection and limit of quantification for this method were 22.0 and 72.0 ng/ml, respectively. The developed method was statistically validated as per International Conference on Harmonisation guidelines. The percentage relative standard deviation values were found to be less than 2 for accuracy and precision studies. The results obtained were in good agreement with the labelled amounts of the marketed formulations. The proposed method was effectively applied to routine quality control analysis of brimonidine tartrate in their eye drops.

Identification of 1-[4-Benzyloxyphenyl)-but-3-enyl]-1H-azoles as New Class of Antitubercular and Antimicrobial Agents.

A series of 1-[(4-benzyloxyphenyl)-but-3-enyl]-1H-azoles has been identified as potent antitubercular agents against Mycobacterium tuberculosis. Synthesis of compounds involved acid catalyzed ring-opening of cyclopropyl ring of phenyl cyclopropyl methanols followed by nucleophilic attack of the azoles on the carbocation intermediates. Several of the compounds 26, 34, and 36 exhibited significant antitubercular activities with MIC value as low as 1.56, 1.56, and 0.61 µg/mL, respectively, comparable to many standard drugs. These compounds were also screened against other strains of bacteria and fungi, and few of them showed good antifungal activity against A. fumigatus, responsible for lung infection.