Percutaneous electrical nerve field stimulation for adolescents with irritable bowel syndrome: Cost-benefit and cost-minimization analysis.

Abdominal pain drives significant cost for adolescents with irritable bowel syndrome (IBS). We performed an economic analysis to estimate cost-savings for patients' families and healthcare insurance, and health outcomes, based on abdominal pain improvement with percutaneous electrical nerve field stimulation (PENFS) with IB-Stim® (Neuraxis). We constructed a Markov model with a 1-year time horizon comparing outcomes and costs with PENFS versus usual care without PENFS. Clinical outcomes were derived from a sham-controlled double-blind trial of PENFS for adolescents with IBS. Costs/work-productivity impact for parents were derived from appropriate observational cohorts. PENFS was associated with 18 added healthy days over 1 year of follow-up, increased annual parental wages of $5,802 due to fewer missed work days to care for the child, and $4744 in cost-savings to insurance. Percutaneous electrical field nerve stimulation for adolescents with IBS appears to yield significant cost-savings to patients' families and insurance.

Burden and Treatment of Chronic Upper GI Symptoms and Diagnoses: A Nationwide Study.

BACKGROUND & AIMS: Chronic gastrointestinal (GI) symptoms are a common reason for seeking medical care. We aim to determine the rates of ambulatory care use and to characterize demographics, work-up, and treatment (pharmacologic and nonpharmacologic) for patients with chronic upper GI symptoms and conditions in the United States. METHODS: Estimates of annual visits for the most common upper GI symptoms and diagnoses including gastroesophageal reflux disease, dyspepsia, nausea and vomiting, and gastroparesis were recorded from the 2007-2015 National Ambulatory Medical Care Surveys. Only chronic conditions, defined as >3 months, were included. We calculated the weighted proportion of ambulatory visits associated with pharmacologic, nonpharmacologic treatment (eg, diet, complementary and alternative medicine), or both. RESULTS: A total of 116,184,475 weighted ambulatory visits were identified between the years of 2007 and 2015 for adults (average of 12,909,386 annual visits) with chronic upper GI symptoms and diagnoses. Gastroesophageal reflux disease was the most common reason for an ambulatory visit (n = 11,200,193), followed by dyspepsia (n = 1,232,598), nausea and vomiting (n = 714,834), and gastroparesis (n = 140,312). Pharmacologic treatment was more common than nonpharmacologic treatment (44.7% vs 28.5%). A total of 37.6% of patients were not receiving treatment at the time of the visit. These treatment patterns did not significantly change over the time of our study. Upper endoscopies were the most ordered test, representing 7.5% of all investigated upper GI symptoms. CONCLUSIONS: Chronic upper GI symptoms and diagnoses account for a high number of annual health care visits, both in primary care and specialty care. Although there are several treatments, many of these patients are not on any treatments.

Accuracy of Serum Parathyroid Hormone Measured on the Early Morning of the First Postoperative Day in Predicting Clinically Significant Post-Total Thyroidectomy Hypocalcemia.

INTRODUCTION: Clinical hypocalcemia (CH) following total thyroidectomy (TT) is a potentially life-threatening condition if left untreated. This study aimed at evaluating the accuracy of parathyroid hormone (PTH) measured in the early morning of the first postoperative day (POD-1) in predicting CH, and determining the cutoff values of PTH that can predict the development of CH. METHODS: We performed a retrospective review of patients undergoing TT between February 2018 and July 2022. Serum PTH, calcium, and albumin levels were measured on morning (6-8 AM) of postoperative day one (POD-1), and serum calcium level was measured from POD-2 onwards. We performed ROC curve analysis to determine the accuracy of PTH in predicting postoperative CH, and cutoff values of PTH to predict CH. RESULTS: Ninety-one patients, 52 (57.1%) with benign and 39 (42.9%) with malignant goiter were included. The incidence of biochemical, and clinical hypocalcemia was 24.2% and 30.8%, respectively. In our study serum, PTH measured in the early morning of first postoperative day following TT was found to have good accuracy (AUC = .88) in predicting CH. A PTH value of ≥27.15 pg/mL was found to have a 96.4% sensitivity in ruling out CH, while a serum PTH value <10.65 pg/mL had a specificity of 95.2% in predicting CH. DISCUSSION: Patients with a serum PTH value of ≥27.15 pg/mL can be discharged without any supplements, those with PTH <10.65 pg/mL should be started on calcium and calcitriol supplements, while patients having PTH values between 10.65 and 27.15 pg/mL should be monitored for the development of signs and/or symptoms of hypocalcemia.

Iron-enriched Aspergillus oryzae as an alternative to iron sulphate to limit iron accumulation, growth and motility of the enteric pathogen S. Typhimurium.

Excess unabsorbed iron in the gastrointestinal tract may select for enteric pathogens and increase the incidence and severity of infectious disease. Aspergillus oryzae (Ao) is a filamentous fungus that has the ability to accumulate and store large amounts of iron, and when used as a supplement or fortificant, has similar absorption to ferrous sulphate (FeSO4) in humans. The objective of this study was to determine the effect of iron-enriched Ao (Ao iron) compared with FeSO4 on iron accumulation, growth and motility of the Gram-negative enteric pathogen, S. Typhimurium. S. Typhimurium was cultured in media containing no added iron or 1 µM elemental iron as either Ao iron or FeSO4. S. Typhimurium cultured with FeSO4 accumulated more iron than those cultured with Ao iron. Genes regulated by the iron-activated transcriptional repressor, Fur, did not differ between control and Ao iron, but decreased in S. Typhimurium cultured with FeSO4 compared with both groups. Growth of S. Typhimurium was greater when cultured with FeSO4 compared with Ao iron and control. S. Typhimurium swam faster, had greater acceleration and travelled further when cultured with FeSO4 compared with Ao iron and control; swim speed, acceleration and distance travelled did not differ between Ao iron and control. These findings provide evidence that Ao iron reduces the virulence of a common enteric pathogen in vitro. Further research is required to determine whether iron-enriched Ao is a suitable iron supplement to improve iron delivery in areas with a high infection burden.

Coverage of Quality Maternal and Newborn Healthcare Services in India: Examining Dropouts, Disparity and Determinants.

Background: Abundant research studies has recorded availability, accessibility and quality of antenatal care and safe delivery in India but comparatively less information is known for postnatal care and furthermore limited attempts at capturing the whole spectrum of obstetric and newborn health services. Assessing discontinuity in maternal and child health service utilization provides us holistic information about existing health inequities and barriers in service provision. Objective: Current study evaluated the coverage of quality antenatal care (QANC), delivery care (QDC) and postnatal care (QPNC) in India as a part of a single continuum accounting for significant regional and sub-regional disparities. Methods: This study analyzed nationally representative data obtained from NFHS-4 (2015-16). Included in the data, were 190 898 Indian women who had a recent birth in last five years. Coverage of QANC, QDC and QPNC was examined at the national, state and district level. Bivariate association of key sociodemographic variables with coverage of services was assessed during chi-squared analysis. Multilevel logistic regression analysis examined correlates associated with coverage of services. The output was presented using odds ratios (OR) with 95% CI. Findings: About 23.5% women utilized QANC out of which 92.9% opted for QDC and 35.1% of newborns received QPNC. About 400 and 471 districts out of 640 had less than 30% coverage of QANC and QPNC, respectively. Women residing in rural regions of Bihar and Northeastern states were found with less than 10% coverage of QANC. Regression analysis shows that women with more than 12 years of education and belonging to richest households had increased odds of availing QANC (OR 1.95; 95%CI: 1.84-2.06) and QDC (OR: 2.86; 95%CI: 2.27-3.60), respectively. Conclusion: Focused interventions targeting the delivery of quality services especially ANC and PNC among newborns are imperative to achieve SDG-3 goals to achieve improvement in maternal and newborn health.

Iron deficient diets modify the gut microbiome and reduce the severity of enteric infection in a mouse model of S. Typhimurium-induced enterocolitis.

Enteric infections are widespread in infants and children living in low-resource settings. Iron availability in the gastrointestinal tract may modify the gut microbiome and impact the incidence and severity of enteropathy. This study was designed to determine the effect of an iron-deplete compared to an iron-rich environment in the lower intestine on the gut microbiome, and whether iron availability in the lower intestine affects the host immune response and severity of enteric infection in young mice. Weanling C57BL/6 female mice were fed an iron deficient (Fe-, <6 ppm iron) or an iron fortified (Fe+, 300 ppm iron) diet for 6 weeks. Mice were pretreated with streptomycin prior to oral inoculation of Salmonella enterica subspecies enterica serovar Typhimurium to induce enteric infection (Sal+) or saline control (Sal-). Cecal iron concentrations were 55-fold greater with Fe+Sal- compared to Fe-Sal-. Microbiome sequencing revealed shifts in gut microbiota with dietary iron and enteric infection. There was ∼30% more S. Typhimurium in the cecum of Fe+Sal+ compared to Fe-Sal+. Plasma hepcidin increased with dietary iron and enteric infection, but was greatest in Fe+Sal+. Plasma lipocalin-2 and spleen size relative to bodyweight were greater in Fe+Sal+ compared to Fe+Sal-, Fe-Sal- and Fe-Sal+, and Fe+Sal+ lost more bodyweight compared to Fe-Sal+. Unabsorbed iron in the lower intestine modifies the gut microbiome and promotes a more severe enteropathy. These findings could suggest the need for alternative iron supplementation strategies in areas where enteric infection are common.

The Role of Food in the Treatment of Bowel Disorders: Focus on Irritable Bowel Syndrome and Functional Constipation.

Irritable bowel syndrome (IBS) and functional constipation (FC) are among the most common disorders of gut-brain interaction, affecting millions of individuals worldwide. Most patients with disorders of gut-brain interaction perceive food as a trigger for their gastrointestinal symptoms, and specific dietary manipulations/advice have now been recognized as a cornerstone therapeutic option for IBS and FC. We discuss in detail the 2 most common dietary interventions used for the management of IBS-general dietary advice based on the National Institute for Health and Care Excellence guidelines and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). We summarize the literature around the possible mechanisms of FODMAP-mediated IBS pathophysiology, the current 3-step, top-down approach of administering a low FODMAP diet (LFD) (restriction phase, followed by reintroduction and personalization), the efficacy data of its restriction and personalization phases, and possible biomarkers for response to an LFD. We also summarize the limitations and challenges of an LFD along with the alternative approach to administering an LFD (e.g., bottom-up). Finally, we discuss the available efficacy data for fiber, other dietary interventions (e.g., Mediterranean diet, gluten-free diet, and holistic dietary interventions), and functional foods (e.g., kiwifruit, rhubarb, aloe, and prunes) in the management of IBS and FC.

Reduced NCOR2 expression accelerates androgen deprivation therapy failure in prostate cancer.

This study addresses the roles of nuclear receptor corepressor 2 (NCOR2) in prostate cancer (PC) progression in response to androgen deprivation therapy (ADT). Reduced NCOR2 expression significantly associates with shorter disease-free survival in patients with PC receiving adjuvant ADT. Utilizing the CWR22 xenograft model, we demonstrate that stably reduced NCOR2 expression accelerates disease recurrence following ADT, associates with gene expression patterns that include neuroendocrine features, and induces DNA hypermethylation. Stably reduced NCOR2 expression in isogenic LNCaP (androgen-sensitive) and LNCaP-C4-2 (androgen-independent) cells revealed that NCOR2 reduction phenocopies the impact of androgen treatment and induces global DNA hypermethylation patterns. NCOR2 genomic binding is greatest in LNCaP-C4-2 cells and most clearly associates with forkhead box (FOX) transcription factor FOXA1 binding. NCOR2 binding significantly associates with transcriptional regulation most when in active enhancer regions. These studies reveal robust roles for NCOR2 in regulating the PC transcriptome and epigenome and underscore recent mutational studies linking NCOR2 loss of function to PC disease progression.

Protective effect of standardised fruit extract of Garcinia cowa Roxb. ex Choisy against ethanol induced gastric mucosal lesions in Wistar rats.

BACKGROUND AND AIM: The fruit of Garcinia is a rich and valuable source of bioactive compounds and is traditionally used for treating wounds and ulcers. The present study was carried out to investigate the protective effect of chromatographically standardized fruit extract of Garcinia cowa (GCE) on ethanol-induced gastric lesions in rats and its possible mechanisms. METHODS: The effect of GCE (200 and 400 mg/kg body weight) was evaluated by determining various gastric ulcer parameters like gastric wall mucus, non-protein sulfhydryls (NP-SH) content, microvascular permeability, endogenous antioxidant enzyme, and gastric histopathological study. RESULTS AND CONCLUSIONS: Oral administration of GCE at doses of 200 and 400 mg/kg exhibited significant (p < .01) dose-dependent inhibition of ulcer index by 18.94-44.02%, respectively. Pre-treatment of rats with GCE (400 mg/kg) significantly restored the depleted gastric wall mucus level by 34.09% and NP-SH content by 33.35% induced by ethanol administration. In addition, GCE (400 mg/kg) showed a significant decrease in microvascular permeability of Evans Blue by 47.43%, rationalizing its protective effect. Furthermore, a significant increase in oxidative enzyme levels with reduction in malondialdehyde level and elevation of superoxide dismutase (SOD) activity was observed in the GCE treated group as compared to the ulcer control group. The histopathological assessment also confirmed the protective nature of GCE. HPTLC analysis showed the presence of 0.27%, 0.11% w/w gallic acid, and amentoflavone, respectively in GCE. The content of α-mangostin and xanthochymol in the G. cowa extract sample quantified by HPLC-PDA method was 0.72 and 8.46%, respectively. The results obtained indicate that the protective effect of GCE against gastric ulcers in rats through multiple actions confirmed by the reduction of oxidative stress and restoration of adhered gastric mucus, NP-SH content, and histological architecture.KEY MESSAGESEthanol is the most typical ulcerogenic agent and has been shown to extend the risk of ulcer in humans.Natural products are promising alternative medication for the development of new drugs to regulate gastrointestinal diseases.Garcinia cowa protects the gastric mucosa through multiple actions that include restoration of adhered gastric mucus and inhibition of lipid peroxidation.

Genes Relevant to Tissue Response to Cancer Therapy Display Diurnal Variation in mRNA Expression in Human Oral Mucosa.

BACKGROUND: To address a critical gap for application of cancer chronotherapy of when would be the best time(s) for treating an individual cancer patient, we conducted a pilot study to characterize diurnal variations of gene expression in oral mucosal tissue, which is vulnerable to damage from cancer therapies. METHODS: We conducted RNA-seq assay on individual oral mucosal samples collected from 11 healthy volunteers every 4 hours (6 time points). Using a cosine-based method, we estimated the individual and average values of peak-time and amplitude for each gene. Correlations between gene expression peak-times and age was examined, adjusting for individual's sleep timing. RESULTS: Among candidate gene pathways that are relevant to treatment response, 7 of 16 genes (PER3, CIART, TEF, PER1, PER2, CRY2, ARNTL) involved in circadian regulation and 1 of 118 genes (WEE1) involved in cell cycle regulation achieved p-value ≤ 0.1 and relative amplitude>0.1. The average peak times were approximately 10:15 for PER3, CIART and TEF, 10:45 for PER1, 13:00 for WEE1, PER2 and CRY2, and 19:30 for ARNTL. Ranges in peak times across individuals differed by gene (e.g., 8 hours for PER1; 16.7 hours for WEE1). Older people had later peak times for PER1 (r = 0.77, p = 0.03) and PER3 (r = 0.69, p-value = 0.06). CONCLUSION: In oral mucosa, expression of some genes relevant to treatment response displayed diurnal variation. These genes may be candidates for development of biomarkers for optimizing individual timing of cancer therapy using non-invasively collected oral mucosa.

Chemical profiling, in vitro antioxidant, membrane stabilizing and antimicrobial properties of wild growing Murraya paniculata from Amarkantak (M.P.).

The excessive usage of antibiotics in humans and veterinary medicine has lead to the emergence of antibiotic resistance and now requires the use of novel antibiotics. There has been increased interest towards plants as source of drugs because of their pharmacological potency and long traditional usage. The aim of the current study was to evaluate bioactive components, antioxidant, and anti-inflammatory activities of the leaf extracts of Murraya paniculata, a plant traditionally used in Indian medicinal system. Evaluations were made for phytochemical analysis, antioxidant, membrane stabilizing, and antimicrobial activities. The methanol extract displayed the highest flavonoid and phenolic content, the acetone extract demonstrated considerable ABTS inhibitory activity (IC50value:555.18 ± 1.68 µg/mL) and the hexane extract exhibited highest H2O2 radical scavenging activity (IC50value: 509.84 ± 3.03 µg/mL). The aqueous extract displayed 19.4 ± 0.66% RBC hemolysis and 80.5 ± 0.66% protection caused by hypotonic solution at high concentration of the extract. The fractions of hexane extract revealed a higher zone of inhibition than crude extract. The major components found in the fractions were cyclohexane (40.11%) and 3-(6-Methoxy-3-methyl-2-benzofuranyl) Cyclohexanone (13.68%) as analyzed by GC-MS/MS technique. The current results validate the traditional use of the M. paniculata and warrant its potential in drug development programs in further investigations.

Structure of a ternary complex of lactoperoxidase with iodide and hydrogen peroxide at 1.77 Å resolution.

Lactoperoxidase (LPO) is a mammalian heme peroxidase which catalyzes the conversion of thiocyanate (SCN¯) and iodide (I-) by hydrogen peroxide (H2O2) into antimicrobial hypothiocyanite (OSCN¯) and hypoiodite (IO-). The prosthetic heme group is covalently attached to LPO through two ester linkages involving conserved glutamate and aspartate residues. On the proximal side, His351 is coordinated to heme iron while His 109 is located in the substrate binding site on the distal heme side. We report here the first structure of the ternary complex of LPO with iodide (I-) and H2O2 at 1.77 Å resolution. LPO was crystallized with ammonium iodide and the crystals were soaked in the reservoir solution containing H2O2. Structure determination showed the presence of an iodide ion and a H2O2 molecule in the substrate binding site. The iodide ion occupied the position which is stabilized by the interactions with heme moiety, His109, Arg255 and Glu258 while H2O2 was held between the heme iron and His109. The presence of I- in the distal heme cavity seems to screen the positive charge of Arg255 thus suppressing the proton transfer from H2O2 to His109. This prevents compound I formation and allows trapping of a stable enzyme-substrate (LPO-I--H2O2) ternary complex. This stable geometrical arrangement of H2O2 in the distal heme cavity of LPO is similar to that of H2O2 in the structure of the transient intermediate of the palm tree heme peroxidase. The biochemical studies showed that the catalytic activity of LPO decreased when the samples of LPO were preincubated with ammonium iodide.

Evaluation of ethnopharmacologically selected Vitex negundo L. for In vitro antimalarial activity and secondary metabolite profiling.

ETHANOPHARMACOLOGICAL RELEVANCE: Limited drugs, rise in drug resistance against frontline anti-malarial drugs, non-availability of efficacious vaccines and high cost of drug development hinders malaria intervention programs. Search for safe, effective and affordable plant based anti-malarial agents, thus becomes crucial and vital in the current scenario. The Vitex negundo L. is medicinal plant possessing a variety of pharmaceutically important compounds. The plant is used traditionally worldwide for the treatment of malaria including India and Malaysia by the indigenous tribes. In vitro studies have reported the anti-malarial use of the plant in traditional medicinal systems. AIM OF THE STUDY: The aim of the current study is to evaluate the traditionally used medicinal plants for in vitro anti-malarial activity against human malaria parasite Plasmodium falciparum and profiling secondary metabolite using spectroscopic and chromatographic methods. Chemical profiling of active secondary metabolites in the extracts was undertaken using LC-MS. MATERIALS AND METHODS: Based on the ethno-botanical data V. negundo L. was selected for in vitro anti-malarial activity against P. falciparum chloroquine-sensitive (3D7) and multidrug resistant (K1) strains using SYBR Green-I based fluorescence assay. Cytotoxicity of extracts was evaluated in VERO cell line using the MTT assay. Haemolysis assay was performed using human red blood cells. Secondary metabolites profiling was undertaken using chromatographic and spectroscopic analysis. Liquid chromatography analysis was performed using a C18, 150 X 2.1, 2.6 µm column with gradient mobile phase Solvent A: 95% (H2O: ACN), Solvent B: Acetonitrile, Solvent C: Methanol, Solvent D: 5 mM NH4 in 95:5 (H2O: ACN) at a constant flow rate of 0.250 ml/min. The LC-MS spectra were acquired in both positive and negative ion modes with electrospray ionization (ESI) source. RESULTS: The anti-malarial active extract of V. negundo L. leaf exhibited potent anti-malarial activity with IC50 values of 7.21 µg/ml and 7.43 µg/ml against 3D7 and K1 strains, respectively with no evidence of significant cytotoxicity against mammalian cell line (VERO) and no toxicity as observed in haemolysis assay. The HPLC-LC-MS analysis of the extract led to identification of 73 compounds. We report for the first time the presence of Sabinene hydrate acetate, 5-Hydroxyoxindole, 2(3,4-dimethoxyphenyl)-6, 7-dimethoxychromen-4-one, Cyclotetracosa-1, 13-diene and 5, 7-Dimethoxyflavanone in the anti-malarial active extract of V. negundo L. leaf. Agnuside, Behenic acid and Globulol are some of the novel compounds with no reports of anti-malarial activity so far and require further evaluation in pure form for the development of potent anti-malarial compounds. CONCLUSIONS: The result report and scientifically validate the traditional use of V. negundo L. for the treatment of malaria providing new avenues for anti-malarial drug development. Several novel and unknown compounds were identified that need to be further characterized for anti-malarial potential.

A computational approach for the screening of potential antiviral compounds against SARS-CoV-2 protease: Ionic liquid vs herbal and natural compounds.

The current scenario across the globe shows unprecedented healthcare and an economic crisis due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Recently, the World Health Organization (WHO) has declared a pandemic stage worldwide because of the high mortality and morbidity rate caused by novel infection disease. There have been several clinical trials and identification underway to find a treatment of this novel virus. For the treatment of severe infection involves the blocking of the replication of its CoV-2 protein. Hydroxychloroquine and remdesivir has been used on an emergency basis for its treatment. The uncontrolled infection and increasing death rate underline the emergence to develop the antiviral drug. In our study, the blind docking of various classes of compounds including control antiviral drugs (abacavir, acyclovir, quinoline, hydroxyquinoline), antimicrobial drugs (levofloxacin, amoxicillin, cloxacin, ofloxacin), natural compounds (lycorine, saikosaponins, myricetin, amentaflavone), herbal compounds (silymarin, palmatine, curcumin, eugenin) available in Indian Ayurveda was done. Besides, we have also performed the blind docking of various ionic liquids (ILs) such as pyrrolidinium, piperidinium, pyridinium, imidazolium based ILs against CoV-2 protease as they have recently emerged as a potential antimicrobial agent. Further, the pharmacokinetic properties and cytotoxicity of the compounds were determined computationally. The docking results showed successful binding to the active site or near a crucial site. The present computational approach was found helpful to predict the best possible inhibitor of protease and may result in an effective therapeutic agent against COVID-19.

Potassium-induced partial inhibition of lactoperoxidase: structure of the complex of lactoperoxidase with potassium ion at 2.20 Å resolution.

Lactoperoxidase, a heme-containing glycoprotein, catalyzes the oxidation of thiocyanate by hydrogen peroxide into hypothiocyanite which acts as an antibacterial agent. The prosthetic heme moiety is attached to the protein through two ester linkages via Glu258 and Asp108. In lactoperoxidase, the substrate-binding site is formed on the distal heme side. To study the effect of physiologically important potassium ion on the structure and function of lactoperoxidase, the fresh protein samples were isolated from yak (Bos grunniens) colostrum and purified to homogeneity. The biochemical studies with potassium fluoride showed a significant reduction in the catalytic activity. Lactoperoxidase was crystallized using 200 mM ammonium nitrate and 20% PEG-3350 at pH 6.0. The crystals of LPO were soaked in the solution of potassium fluoride and used for the X-ray intensity data collection. Structure determination at 2.20 Å resolution revealed the presence of a potassium ion in the distal heme cavity. Structure determination further revealed that the propionic chain attached to pyrrole ring C of the heme moiety, was disordered into two components each having an occupancy of 0.5. One component occupied a position similar to the normally observed position of propionic chain while the second component was found in the distal heme cavity. The potassium ion in the distal heme cavity formed five coordinate bonds with two oxygen atoms of propionic moiety, Nε2 atom of His109 and two oxygen atoms of water molecules. The presence of potassium ion in the distal heme cavity hampered the catalytic activity of lactoperoxidase.

Structure of Yak Lactoperoxidase at 1.55 Å Resolution.

Lactoperoxidase (LPO) is a heme containing oxido-reductase enzyme. It is secreted from mammary, salivary, lachrymal and mucosal glands. It catalyses the conversion of thiocyanate into hypothiocyanate and halides into hypohalides. LPO belongs to the superfamily of mammalian heme peroxidases which also includes myeloperoxidase (MPO), eosinophil peroxidase (EPO) and thyroid peroxidase (TPO). The heme prosthetic group is covalently linked in LPO through two ester bonds involving conserved residues Glu258 and Asp108. It was isolated from colostrum of yak (Bos grunniens), purified to homogeneity and crystallized using ammonium iodide as a precipitating agent. The crystals belonged to monoclinic space group P21 with cell dimensions of a = 53.91 Å, b = 78.98 Å, c = 67.82 Å and ß = 92.96°. The structure was determined at 1.55 Å resolution. This is the first structure of LPO from yak. Also, this is the highest resolution structure of LPO determined so far from any source. The structure determination revealed that three segments (Ser1-Cys15), (Thr117-Asn138) and (Cys167-Leu175) were disordered and formed one surface of LPO structure. In the substrate binding site, the iodide ions were observed in three subsites which are formed by (1) heme moiety and residues, Gln105, Asp108, His109, Phe113, Arg255, Glu258, Phe380 and Phe381, (2) residues, Asn230, Lys232, Pro236, Cys248, Phe254, Phe381 and Pro424 and (3) residues, Ser198, Leu199 and Arg202. The structure determination also revealed that the side chain of Phe254 was disordered. It was observed to adopt two conformations in the structures of LPO.

Characterization, biological evaluation and molecular docking of mulberry fruit pectin.

Contemplating the exemplary benefits of pectin on human health, we precisely characterized and evaluated the antibacterial and anticancer activities from purified Mulberry Fruit Pectins (MFP). Here, we tested BR-2 and S-13 varieties of mulberry fruit pectins against six bacterial strains and two human cancer cell lines (HT-29 and Hep G-2), using MIC and an in vitro cell-based assay respectively. The BR-2 mulberry fruit pectin performs superior to S-13 by inhibiting strong bacterial growth (MIC = 500-1000 µg/mL) against tested bacterial strains and cytotoxic activities at the lowest concentration (10 µg/ml) against the Hep G-2 cell line. However, both tested drugs failed to exhibit cytotoxicity on the human colon cancer cell line (HT-29). Based on molecular interaction through docking, pectin binds effectively with the receptors (1e3g, 3t0c, 5czz, 6j7l, 6v40, 5ibs, 5zsy, and 6ggb) and proven to be a promising antimicrobial and anti-cancer agents. The pursuit of unexploited drugs from mulberry fruit pectin will potentially combat against bacterial and cancer diseases. Finally, future perspectives of MFP for the treatment of many chronic diseases will help immensely due to their therapeutic properties.

Public health interventions to improve maternal nutrition during pregnancy: a nationally representative study of iron and folic acid consumption and food supplements in India.

OBJECTIVE: Despite a reduction in maternal mortality in recent years, a high rate of anaemia and other nutrient inadequacies during pregnancy pose a serious threat to mothers and their children in the Global South. Using the framework of the WHO-Commission on Social Determinants of Health, this study examines the socioeconomic, programmatic and contextual factors associated with the consumption of iron and folic acid (IFA) tablets/syrup for at least 100 d (IFA100) and receiving supplementary food (SF) by pregnant women in India. DESIGN: We analysed a nationally representative cross-sectional survey of over 190 898 ever-married women aged 15-49 years who were interviewed as part of the National Family Health Survey (NFHS) conducted during 2015-16, who had at least one live birth preceding 5 years of the survey. SETTING: All twenty-nine states and seven union territories of India. PARTICIPANTS: Ever-married women aged 15-49 years. RESULTS: Less than one-third of women were found to be consuming IFA100, and a little over half received SF during their last pregnancy. The consumption of IFA100 was likely to improve with women's education, household wealth, early and more prenatal visits, and in a community with high pregnancy registration. Higher parity, early and more prenatal visits, contact with community health workers during pregnancy, belonging to a poor household and living in an aggregated poor community and rural area positively determine whether a woman might receive SF during pregnancy. CONCLUSIONS: Continuous monitoring and evaluation of provisioning IFA and SF in targeted groups and communities is a key to expanding the coverage and reducing the burden of undernutrition during pregnancy.

A potent enzybiotic against methicillin-resistant Staphylococcus aureus.

Staphylococcus aureus is one of the most dreadful infectious agents, responsible for high mortality and morbidity in both humans and animals. The increased prevalence of multidrug-resistant (MDR) Staphylococcus aureus strains has limited the number of available treatment options, which calls for the development of alternative and effective modalities against MDR S. aureus. Endolysins are bacteriophage-derived antibacterials, which attack essential conserved elements of peptidoglycan that are vital for bacterial survival, making them promising alternatives or complements to existing antibiotics for tackling such infections. For developing endolysin lysin-methicillin-resistant-5 (LysMR-5) as an effective antimicrobial agent, we evaluated its physical and chemical characteristics, and its intrinsic antibacterial activity against staphylococcal strains, including methicillin-resistant Staphylococcus aureus (MRSA). In this study, we cloned, expressed, and purified LysMR-5 from S. aureus phage MR-5. In silico analysis revealed that LysMR-5 harbors two catalytic and one cell wall-binding domain. Biochemical characterization and LC-MS analysis showed that both catalytic domains were active and had no dependence on divalent ions for their action, Zn2+ exerted a negative effect. The optimal lytic activity of the endolysin was at 37 °C/pH 7.0 and in the presence of ≥ 300 mM concentration of NaCl. Circular dichroism (CD) demonstrated a loss in secondary structure with an increase in temperature confirming the thermosensitive nature of endolysin. Antibacterial assays revealed that LysMR-5 was active against diverse clinical isolates of staphylococci. It showed high lytic efficacy against S. aureus ATCC 43300, as an endolysin concentration as low as 15 µg/ml was sufficient to achieve maximum lytic activity within 30 min and it was further confirmed by scanning electron microscopy. Our results indicate that rapid and strong bactericidal activity of LysMR-5 makes it a valuable candidate for eradicating multidrug-resistant S. aureus.

Comparative in vitro cytotoxicity and binding investigation of artemisinin and its biogenetic precursors with ctDNA.

Artemisinin (ART) and its biogenetic precursors artemisinic acid (AA) and dihydroartemisinic acid (DHAA) are important traditional medicinal herb compounds with tumor growth inhibition properties. Herein, we have studied the cytotoxicity of ART, AA, and DHAA on different cancer cell lines (H1299, A431, and HCT 116) and investigated in detail their binding mechanisms with ctDNA by using spectroscopy, cyclic voltammetry, and computational methods. The UV absorbance, cyclic voltammetry, DNA helix melting, competition binding, and circular dichroism studies suggested that the complex formation of ART-ctDNA and AA-ctDNA occurs through groove binding. However, in the case of DHAA-ctDNA interaction, electrostatic interaction plays a major role. The thermodynamic parameters, viz., ΔG 0, ΔH 0, and ΔS 0 were calculated, which showed the involvement of hydrogen bonds and van der Waals interactions for drug-ctDNA interaction. FTIR and molecular docking results suggested that ART, AA, and DHAA were bound to the A-T rich region in the minor groove of ctDNA.