Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities.

Mellpaladines A-C (1-3) and dopargimine (4) are dopamine-derived guanidine alkaloids isolated from a specimen of Palauan Didemnidae tunicate as possible modulators of neuronal receptors. In this study, we isolated the dopargimine derivative 1-carboxydopargimine (5), three additional mellpaladines D-F (6-8), and serotodopalgimine (9), along with a dimer of serotonin, 5,5'-dihydroxy-4,4'-bistryptamine (10). The structures of these compounds were determined based on spectrometric and spectroscopic analyses. Compound 4 and its congeners dopargine (11), nordopargimine (15), and 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)ethan-1-amine (16) were synthetically prepared for biological evaluations. The biological activities of all isolated compounds were evaluated in comparison with those of 1-4 using a mouse behavioral assay upon intracerebroventricular injection, revealing key functional groups in the dopargimines and mellpaladines for in vivo behavioral toxicity. Interestingly, these alkaloids also emerged during a screen of our marine natural product library aimed at identifying antiviral activities against dengue virus, SARS-CoV-2, and vesicular stomatitis Indiana virus (VSV) pseudotyped with Ebola virus glycoprotein (VSV-ZGP).

Iron-engineered mesoporous biocarbon composite and its adsorption, activation, and regeneration approach for removal of paracetamol in water.

Three-dimensional multi-porous Iron Oxide/carbon (Fe2O3/C) composites derived from tamarind shell biomass were synthesized by a single-step co-pyrolysis technique and utilized for Paracetamol (PAC) dismissal in the combined adsorption, and advanced oxidation such as electrochemical regeneration techniques. The Fe2O3/C composites were prepared by different pyrolysis temperatures, and named as TS750 (without Fe2O3at 750 °C), MTS450 BCs (Low-450 °C), MTS600 BCs (Moderate-600 °C) and MTS750 BCs (high-750 °C), respectively. As-prepared Fe2O3/C composite was characterized by FE-SEM, XRD, BET, and XPS analysis. The specific surface area and the spatial interaction between the interlayers of Fe2O3 and C were significantly improved by increasing the pyrolysis temperatures from 450 to 750 °C, which improved the adsorption capacity of Fe2O3/C composites in terms of higher rate constants and chemisorption kinetics. The Pseudo-second-order kinetics model fitted in the adsorption test results of Fe2O3/C composites with the highest correlation co-efficiency. The Langmuir-isotherms model fitted in the adsorption test of the TS750 and MTS450 BCs. The Freundlich isotherms model is more fit with MTS600 and MTS750 BCs. Based on the isotherm results, the MTS750 BCs achieved 46.9 mg/g of maximum PAC adsorption capacity. The optimized MTS750 composites could be completely recovered by using an advanced electrochemical oxidation regeneration approach within 180 min. Also, with the adsorption and recovery process, the TOC removal rate improved to ∼79.4%. After the 6th cycle electrochemical oxidation process, the obtained results of the re-adsorption test showed the stabile adsorption activity of the sorbent material. The data outcomes herein propose that this type of combined adsorption and electrochemical approach will be useful in commercial water treatment plants.

Real-time 2-5A kinetics suggest that interferons ß and λ evade global arrest of translation by RNase L.

Cells of all mammals recognize double-stranded RNA (dsRNA) as a foreign material. In response, they release interferons (IFNs) and activate a ubiquitously expressed pseudokinase/endoribonuclease RNase L. RNase L executes regulated RNA decay and halts global translation. Here, we developed a biosensor for 2',5'-oligoadenylate (2-5A), the natural activator of RNase L. Using this biosensor, we found that 2-5A was acutely synthesized by cells in response to dsRNA sensing, which immediately triggered cellular RNA cleavage by RNase L and arrested host protein synthesis. However, translation-arrested cells still transcribed IFN-stimulated genes and secreted IFNs of types I and III (IFN-ß and IFN-λ). Our data suggest that IFNs escape from the action of RNase L on translation. We propose that the 2-5A/RNase L pathway serves to rapidly and accurately suppress basal protein synthesis, preserving privileged production of defense proteins of the innate immune system.

Rapid and sensitive analytical procedure for biomonitoring of organophosphate pesticide metabolites in human urine samples using a vortex-assisted salt-induced liquid-liquid microextraction technique coupled with ultra-high-performance liquid chromatography/tandem mass spectrometry.

RATIONALE: Organophosphate pesticides (OPPs) are the most commonly used insecticides around the world in various agricultural and domestic practices, and humans are frequently exposed to these hazardous insecticides that can lead to several chronic health effects. Therefore, a fast and sensitive analytical method is required for biomonitoring the markers of OPPs in humans for exposure estimation. In this study, a fast and sensitive analytical procedure was developed for the determination of the metabolites of OPPs in human urine samples. METHODS: Metabolites of OPPs were extracted from 2 mL of urine sample using a novel vortex-assisted salt-induced liquid-liquid microextraction (VA-SI-LLME) technique, and the preconcentrated metabolites were analyzed by ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS). Various factors affecting the efficiency of VA-SI-LLME were thoroughly investigated. RESULTS: The metabolites of OPPs exhibited very good linearity over the concentration range between 0.05 and 50 ng mL-1 with coefficient (r2 ) values ranging between 0.9986 and 0.9999. The method showed excellent sensitivity with detection limits ranging from 0.01 to 0.03 ng mL-1 and quantification limits from 0.03 to 0.05 ng mL-1 . The developed method was applied to the analysis of real samples and the recoveries ranged between 85.0 and 114.1% with related standard deviations <5%. CONCLUSIONS: The results showed the VA-SI-LLME/UHPLC/MS/MS method to be a simple, rapid, sensitive, and selective analytical procedure for the biomonitoring of the metabolites of OPPs in humans. This efficient and cost-effective analytical method could be a potential alternative method for the biomonitoring of the metabolites of pesticides in humans.

Acceptable errors with evaluation of 577 cervical pedicle screw placements.

PURPOSE: Cadaveric studies have discouraged the use of cervical pedicle screws (CPS) with high misplacement rates. However, the clinical results show minimal screw-related complications and have highlighted the advantages of using CPS. We introduce "acceptable errors classification" in the placement of cervical pedicle screws to bridge the gap between the high radiological perforation rates and low clinical complications. METHODS: Ninety-nine patients with average age of 49 years were operated between December 2011 and June 2017 using CPS. Sixty-one patients had trauma, 33 had CSM, 3 had tumors and 2 patients had fracture with ankylosing spondylitis. The screws were inserted using the medial cortical pedicle screw technique. Axial and sagittal CT reconstructed images along the axis of the inserted screws were evaluated for screw placements both in the medio-lateral and supero-inferior directions. RESULTS: A total of 577 pedicle screw placements (C3 to C7) were assessed in 99 patients using the conventional grading of screw perforations and acceptable errors classification in both medio-lateral and supero-inferior directions. There were 25.64% (148/577) screw perforations and 74.35% (429/577) screw placements within the pedicle using the conventional perforation grading system. The same set of screws, assessed using the "Acceptable errors classification", showed 529 screws (91.68%) having acceptable placements and 48 screws (8.31%) having unacceptable placements. CONCLUSION: The acceptable errors classification in placement of CPS seems to bridge the gap between the high radiological perforation rates and the low clinical complications. The present study reinforces studies reporting minimal clinical complications with high rates of screw misplacements. These slides can be retrieved under Electronic Supplementary Material.

Formulation and evaluation of ileo-colonic targeted matrix-mini-tablets of Naproxen for chronotherapeutic treatment of rheumatoid arthritis.

In this present research work, the aim was to develop ileo-colonic targeted matrix-mini-tablets-filled capsule system of Naproxen for chronotherapeutic treatment of Rheumatoid Arthritis. So Matrix-mini-tablets of Naproxen were prepared using microsomal enzyme dependent and pH-sensitive polymers by direct compression method which were further filled into an empty HPMC capsule. The compatibility was assessed using FT-IR and DSC studies for pure drug, polymers and their physical mixtures. The prepared batches were subjected to physicochemical studies, drug content estimation, in-vitro drug release and stability studies. When FTIR and DSC studies were performed, it was found that there was no interaction between Naproxen and polymers used. The physicochemical properties of all the prepared matrix-mini-tablets batches were found to be in limits. The drug content percentage in the optimized formulation F18 was found to be 99.24 ± 0.10%. Our optimized matrix-mini-tablets-filled-capsule formulation F18 releases Naproxen after a lag time of 2.45 ± 0.97 h and 27.30 ± 0.86%, 92.59 ± 0.47%, 99.38 ± 0.69% at the end of 5, 8, 12 h respectively. This formulation was also found to be stable as per the guidelines of International Conference on Harmonisation of Technical Requirements of Pharmaceuticals for Human Use. Thus, a novel ileo-colonic targeted delivery system of Naproxen was successfully developed by filling matrix-mini-tablets into an empty HPMC capsule shell for targeting early morning peak symptoms of rheumatoid arthritis.

THE EFFECT OF A SINGLE DOSE OF MAGNESIUM SULPHATE AS AN ADJUVANT TO EPIDURAL BUPIVACAINE FOR INFRAUMBILICAL SURGERIES: A PROSPECTIVE DOUBLE-BLIND, RANDOMIZED CONTROL TRIAL.

CONTEXT: Epidural anesthesia provides the advantage of segmental blockade and many adjuvants have been added to shorten the onset of action, improve the quality of analgesia and prolong the duration of analgesia. Magnesium sulphate(MgSO4) by virtue of its anti-iociceptive property has been administered by various routes. AIM: To assess the effect of MgSO4 on the duration of onset of action of injection bupivacaine for epidural anesthesia in infraumbilical surgeries. MATERIALS AND METHODS: A prospective, double-blind, randomized control study was conducted in 40 patients. Group M received 15 ml of bupivacaine 0.5% + 1 ml of 50 mg MgSO4 and Group C received 15 ml of bupivacaine 0.5% + 1 ml of normal saline via epidural route. Onset time of the sensory and motor blockade were the primary outcomes studied. Highest level of sensory block, time for two segment regression, hemodynamic parameters, side effects were the secondary parameters. RESULTS: There was a significant difference between the groups in the mean onset time of sensory blockade at T8, 12.85 ± 2.32 min in Group M and 16.75 ± 1.74 min in Group C. Median level of sensory blockade was comparable. Mean onset time of motor blockade was 13.85 ± 3.28 min in Group M and 23.25 ± 3.35 min in Group C which was clinically and statistically significant. Time for two segment regression of sensory blockade was 95.75 ± 11.84 min in Group M and 55.5 ± 8.57 min in Group C which was significant. Hemodynamic parameters and side effects were comparable. CONCLUSION: Magnesium sulphate as an adjuvant provides rapid onset of epidural anesthesia and prolongs the duration of analgesia with minimal side effects.

EFFECT OF DEXMEDETOMIDINE ON HEMODYNAMIC PARAMETERS DURING EXTUBATION. A PROSPECTIVE RANDOMIZED DOUBLE BLIND STUDY.

BACKGROUND: Extubation is known to produce significant hemodynamic disturbances. There is a need to avoid increase in heart rate and blood pressure in hypertensive and cardiac patients and in vascular, neuro and intraocular surgeries. AIMS: To study the ability of dexmedetomidine to attenuate the hemodynamic responses during extubation. MATERIALS AND METHODS: 80 patients of ASA Grade I-II aged 18-50 years received standard anesthesia. At the closure of skin incision, patients were randomly allocated to receive either dexmedetomidine 0.5 µg/kg (Group D) or saline placebo (Group C) intravenously over 10 minutes in a double-blind design. Heart rate (HR), systolic, diastolic and mean arterial pressures (SBP, DBP, MAP) were assessed before, during- and after extubation. Time to eye opening and extubation, sedation, complications such as coughing, laryngospasm, bronchospasm and desaturation were recorded. RESULTS: HR, SBP, DBP and MAP were comparable to basal values in group D at extubation and lower than baseline values post-extubation but significant increase was noted in group C (P <0.001). Time to extubation and eye opening were prolonged in Group D (P <0.001). Incidence of hypotension was more in group D (22%) but was transient. Incidence of coughing was lower in Group D than in group C (P <0.001). Patients in group D were more sedated for 30 minutes post extubation. CONCLUSION: Dexmedetomidine 0.5 µg/kg given before extubation attenuates hemodynamic reflexes during emergence from anesthesia without causing undue sedation, but prolongs time to extubation.

Role of different vehicles in carotenoids delivery and their influence on cell viability, cell cycle progression, and induction of apoptosis in HeLa cells.

The objective of the present study was to determine the role of different vehicles in carotenoids delivery and their influence on cell viability, cell cycle progression and induction of apoptosis in HeLa cells. Cells (5 × 10(3)) were treated with different concentrations (25-100 µM) of ß-carotene (BC) or lutein (L) or astaxanthin (AST) dissolved in 0.5% of tetrahydrofuran (THF), dimethylsulfoxide (DMSO), and fetal bovine serum (FBS), respectively. The effect of delivery vehicle on carotenoids uptake, cytotoxicity, oxidative status, cell cycle distribution, and apoptosis was examined after 48 h of incubation. The results shown that, cell viability reduced significantly in a dose- and time-dependent manner irrespective of carotenoid delivered in vehicles. Cellular uptake of BC delivered in THF was higher by 49.1, 29.7% and L delivered through THF was higher by 41.7 and 37.5% than DMSO and FBS, respectively. While, AST delivered through DMSO was higher by 36.1 and 43.7% than the THF and FBS, respectively. In case of cells treated either with BC or L delivered through THF and AST in DMSO decreased the glutathione and increased the malondialdehyde levels. The net increase in the G 2/M phase percentage of cell cycle progression was observed in carotenoid-treated cells. The % induction of apoptosis by BC or L delivered with THF and AST in DMSO was higher than other treated groups. In conclusion, choice of suitable vehicle for specific carotenoids delivery is essential that in turn may influence on cell proliferation and cell-based assays.

(177)Lu-DOTATATE therapy in patients with neuroendocrine tumours: 5 years' experience from a tertiary cancer care centre in India.

PURPOSE: The choice of an appropriate treatment option in patients with inoperable or metastatic neuroendocrine tumours (NETs) is limited, and approximately 50 % of patients have advanced NET at diagnosis, and 65 % die within 5 years. Treatment with (177)Lu-DOTATATE ((177)Lu-[DOTA(0),Tyr(3)] octreotate) is a promising new option in the treatment of metastatic NETs. METHODS: Patients with metastatic NET who underwent (177)Lu-DOTATATE during the period 2009 to 2013 were included in this retrospective study. Follow-up imaging studies including a (68)Ga-DOTANOC PET/CT scan and a posttherapy (177)Lu-DOTATATE scan were compared with baseline imaging to determine response to treatment. Progression-free survival (PFS) was calculated using the Kaplan-Meier method and Cox regression analysis was also done. RESULTS: Ten patients (25 %) had a minimal response, 13 (32.5 %) had a partial response and 9 (22.5 %) had stable disease. Progressive disease was seen in 8 patients (20 %), including 6 patients who died during or after the treatment period. The estimated mean PFS in those who received one or two cycles of (177)Lu-DOTATATE was 8.3 months (95 % CI 6.2 to 10.3 months) compared to an estimated mean PFS of 45.6 months (95 % CI 40.9 to 50.2 months) in those who received more than two cycles of (177)Lu-DOTATATE (log-rank Mantel-Cox Χ (2) = 8.01, p = 0.005). CONCLUSION: Our study showed that treatment with (177)Lu-DOTATATE should be considered in the management of NETs, considering the limited success of alternative treatment modalities. Treatment response and PFS is determined primarily by the dose delivered and best results are obtained when more than two cycles of (177)Lu-DOTATATE are given, with careful monitoring for possible side effects.

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism among Gaddi tribe of Indian state of Himachal Pradesh.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been suggested to be positively associated with several disorders. Distribution of the mutant T-allele varies in ethnic and geographical populations of the world. AIM: The aim of the present study was to investigate the distribution of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in a transhumant (Gaddi) tribal population of Himachal Pradesh dwelling at high and middle altitude and exposed to strong ultraviolet radiation. METHOD AND RESULTS: A total of 486 samples (141 males and 345 females) were randomly enrolled from the individuals aged 25-75 years who were unrelated up to first cousin. Among Gaddis, genotype frequencies of CC, CT and TT were 67.90%, 27.78% and 4.32%, respectively. Among males and females distribution of genotype frequencies also followed a similar trend. The studied population was in Hardy-Weinberg equilibrium (χ(2 )= 2.213, df = 1, p = 0.136). Frequency of mutant T-allele in the Gaddi population was found to be 0.183, which might be due to European ancestry, endogamous nature and selection.

An oxidative amidation and heterocyclization approach for the synthesis of ß-carbolines and dihydroeudistomin Y.

A novel synthetic methodology has been developed for the synthesis of dihydro-ß-carboline derivatives employing oxidative amidation-Bischler-Napieralski reaction conditions using tryptamine and 2,2-dibromo-1-phenylethanone as key starting materials. A number of dihydro-ß-carboline derivatives have been synthesized in moderate to good yields using this methodology. Attempts were made towards the conversion of these dihydro-ß-carbolines to naturally occurring eudistomin alkaloids.

In Vitro Synergistic Effect of Colistin with Fosfomycin Against Carbapenem-Resistant Klebsiella pneumoniae.

BACKGROUND: The dwindling antibiotic reserve owing to augmented drug-resistant bacteria is a major handicap for treating physicians. Klebsiella pneumoniae, a gram-negative encapsulated member of the Enterobacteriaceae family, is one such pathogenic bacteria. Carbapenemase-producing Klebsiella pneumoniae is globally recognized as one of the most critical bacterial threats to public health due to its extremely limited treatment options. Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections pose therapeutic challenges due to simultaneous resistance to various other groups of antibiotics. In this study, we have evaluated the synergistic effect of fosfomycinagainst CRKP isolates when used in combination with colistin by applying the Checkerboard method. METHODS: A laboratory-based prospective study was conducted in the Department of Microbiology, JSS Hospital, Mysuru, for a period of one year after obtaining ethical clearance. Klebsiella pneumoniae isolates obtained from clinical samples were screened for carbapenem resistance by the VITEK-2 compact system (bioMérieux, Marcy-l'Étoile, France). The minimum inhibitory concentration (MIC) of colistin and fosfomycin was individually ascertained by broth microdilution (BMD). Finally, the synergistic activity of the fosfomycin-colistin combination was determined by the BMD-based Checkerboard method. RESULTS: Among the 50 CRKP isolates, 36 (72%) isolates showed synergism, eight (16%) isolates showed indifference and six (12%) isolates showed partial synergism, while none of them showed additivity and antagonism by the Checkerboard method. These results are found to be statistically significant (chi-square value of 116.204 and p-value of < 0.00001). CONCLUSION: This study showed a promising in-vitro synergy between the drugs fosfomycin and colistin by Checkerboard BMD testing protocol. Colistin being a reserve antibiotic, monotherapy comes with the limitations of higher chances of resistance as well as toxicity, which can be overcome by combination therapy, thereby decreasing CRKP-associated mortality rates and delivering holistic patient benefit.

Investigation of inflammatory mechanisms induced by croton oil in mouse ear.

Croton oil is liquid at room temperature, with a pale-yellow color and spicy odor. It is commonly used in combination with phenol as a chemical peeling agent in dermatology, which reveals its caustic exfoliating effects. Topical use of croton oil at a high dose produces skin irritation, inflammation, swelling, pain, and even tumors. Therefore, croton oil has been widely used for inflammation, pain, and tumor related research, with different animal models having been established. However, mechanistic studies through which croton oil induces skin swelling, injury and activates tissue repair/regeneration are limited. The present study used croton oil to induce mouse ear edema and examined tissue responses 4 h after exposure. To this end, croton oil was applied to the ventral side of mouse ears, followed by tissue collection. Samples were analyzed by hematoxylin and eosin (H&E) staining, toluidine blue staining, and immunohistochemistry staining for myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9). Western blotting and ELISA were also carried out for MMP-9 together with unbiased proteomic analysis using mass-spectrometry. Results from our study demonstrated that as soon as 4 h of exposure to 2.5 % croton oil, the expression levels of MPO and MMP-9 in the dermis significantly increased compared to acetone-treated (vehicle) control ears, as did other inflammatory reactions such as swelling and neutrophil aggregation and infiltration. Subsequently, proteomic analysis confirmed that croton oil treatment resulted in significant upregulation of proteins such as myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9), and matrix metalloproteinase-8 (MMP-8) in the ear skin. Interestingly, mouse ears treated with acetone vehicle showed differential expression of 2,478 proteins relative to naïve tissues; among those differentially expressed in acetone-treated samples were members of the phosphatidylinositol-glycan biosynthesis class N, T and U proteins (PIGN, PIGT, and PIGU). Overall, this work confirms the presence of neutrophil-derived MPO and MMP-9 and extends the body of knowledge to show that MMP-8 is also present during croton oil-mediated skin inflammation in the mouse ear; moreover, we find that acetone vehicle is not inert and has effects on the skin that should be considered moving forward.

Prevalence of Amblyogenic Risk Factors Among School Children in India Using the Spot Vision Screener.

INTRODUCTION: Amblyopia is a common cause of preventable visual impairment in children, affecting 1% to 6% globally. This study assesses amblyopia prevalence and risk factors among school children in rural Telangana, India, using the Spot Vision Screener (Welch Allyn, Inc., Skaneateles Falls, New York, USA), a portable, noninvasive device recommended for automated vision screening. METHODS: A cross-sectional study was conducted on 714 schoolchildren aged 5-10 years. Screening was performed using the Spot Vision Screener, evaluating refractive errors, ocular alignment, and other amblyopia risk factors. Children identified with potential amblyogenic factors were referred for comprehensive ophthalmological evaluation to confirm diagnosis. RESULTS: Out of 714 children screened, 84 were referred by the Spot Vision Screener for further evaluation. Subsequent examination by ophthalmologists confirmed amblyopia in 65 children, resulting in a prevalence of 9.10%. Myopic refractive error was the most prevalent (69.23%), followed by astigmatism (21.53%) and hypermetropia (9.23%) among amblyopia cases. CONCLUSION: The Spot Vision Screener proved to be a reliable tool for identifying amblyopia risk factors in school children, facilitating early detection and referral for appropriate management. This study underscores the importance of implementing effective vision screening programs in rural settings to mitigate preventable childhood blindness.

Effect of Yoga on Endothelial Function: A Systematic Review and Meta-Analysis.

Introduction: Endothelial dysfunction is the initial step in the pathogenesis of atherosclerosis; and it plays a central role in the development of cardiovascular diseases and many types of human diseases (diabetes, kidney failure, cancer, and viral infections). Strategies that are effective in protecting vascular endothelial function and retard or reversing endothelial dysfunction in the early stage appear to be potential in the prevention of vascular, cardiac, and many human diseases. Several studies have been carried out on the effects of yoga on endothelial function, but the results of these studies have not been synthesized. This study aimed at conducting a systematic review and meta-analysis to determine the effectiveness of yoga on endothelial function. Methods: A systematic review and meta-analysis of studies that assessed the effect of yoga practice on vascular endothelial function was done as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, Scopus, Google Scholar, and Cochrane controlled register of trials (CENTRAL) were searched from inception to August 2022. The search strategy was constructed around yoga-based techniques and endothelial function. All the yoga-based interventional studies on endothelial function or dysfunction were included in this review. A narrative synthesis and descriptive analysis were done due to the diverse methodology of selected studies. We carried out a formal meta-analysis of controlled trials that assessed the effect of yoga on flow-mediated dilatation (FMD), a measure of endothelial function. Results: A total of 18 studies were included for review involving 1043 participants. Yoga training showed improved endothelial function in 12 studies, whereas 6 studies did not find any statistically robust effect. Meta-analysis (n = 395 participants, 6-studies, 7 comparisons) showed an increase in brachial FMD by yoga practice (mean difference = -1.23%; 95% confidence interval -2.23 to -0.23; p = 0.02). The heterogeneity between the studies was 43% (Tau2 = 0.70, χ2 = 10.49). The risk of bias was low to moderate in these studies. No adverse effects were reported. Conclusions: Yoga practice improved endothelial function. Yoga could be a safe and potential integrative medicine to improve endothelial function. However, as the statistical heterogeneity, that is, variation in the FMD among the studies was moderate, large clinical trials are necessary for its clinical recommendations.

The development of a dexamethasone challenge model for evaluating feed additives in sheep.

OBJECTIVE: To develop an accessible ruminant immune challenge model for rapid in vivo assessments of feed additives. ANIMALS: 60 hair-breed ram lambs. METHODS: Sheep were randomly assigned to 1 of 4 treatments: treatment 1, not immunosuppressed, control fed (n = 12); treatment 2, immunosuppressed, supplemented with a yeast and botanical extract (n = 18); treatment 3, immunosuppressed, supplemented with a blend of natural aluminosilicates and yeast components (n = 18); and treatment 4, immunosuppressed, control fed (n = 12). Twice-daily injections of dexamethasone (Dex; 0.1 mg/kg bodyweight, SC) were used to induce immunosuppression throughout the study (from September 25, 2020, to November 2, 2020). All sheep were immunized with keyhole limpet hemocyanin (KLH) on days 0 and 14 and injected with heat-aggregated KLH, ID, to induce a skin induration on day 15. Measurements included body weight (BW), average daily gain (ADG), CBC, and skin induration diameter. RESULTS: Dex treatment resulted in reduced BW and ADG that was not mitigated by either feed additive. Dex reduced lymphocyte percentage, RBC count, hemoglobin, hematocrit, and skin induration diameter and increased concentrations of granulocytes and granulocyte percentage. Effects on hematocrit, hemoglobin, RBC, and skin induration diameter were mitigated with the addition of feed additives. CLINICAL RELEVANCE: The described model is a tool to evaluate the ability of feed additives to mitigate the immunosuppressive effects of Dex.

HLA class II SNP interactions and the association with type 1 diabetes mellitus in Bengali speaking patients of Eastern India.

BACKGROUND: Several studies have demonstrated a fundamental role for the HLA in the susceptibility of, or protection to, type 1 diabetes mellitus (T1DM). However, this has not been adequately studied in Asian Indian populations. To assess the frequency of HLA class II (DPA1, DPB1, DQA1, DQB1 and DRB1) associated to susceptibility or protection toT1DM in a Bengali population of India with diabetes. RESULTS: Single nucleotide polymorphism study. The HLA genotyping was performed by a polymerase chain reaction followed by their HLA-DP, DQ, and DRB1 genotypes and haplotypes by sequencing method. The results are studied by Plink software. The χ2 tests were used for the inferential statistics. To our knowledge, this study is the first of a kind which has attempted to check the HLA association with T1DM by SNPs analysis. The study recruited 151 patients with T1DM and same number of ethno-linguistic, sex matched non-diabetic controls. The present study found a significant SNP rs7990 of HLA-DQA1 (p = 0.009) negative correlation, again indicating that risk from HLA is considerably more with T1DM. CONCLUSIONS: This study demonstrates that the HLA class-II alleles play a major role in genetic basis of T1DM.

Menarcheal age of type 1 diabetic Bengali Indian females.

BACKGROUND: It has been observed that menstrual characteristics are generally influenced by lifestyle, socio-cultural and biological factors. AIM: The present study examines: (a) variation in menstrual characteristics between Type1 Diabetic females of rural and urban adolescents, i.e. the resident status; and (b) whether these characteristics can be predicted from various socio-economic, stress variables related to place of residence. SUBJECTS AND METHODS: The sample of the present study constituted 103T1DM females from West Bengal, a State of India. These girls belong to a Bengali-speaking ethnic group. Data on socio-economic variables and menstrual characteristics were collected using pretested questionnaires. RESULTS: Menstrual irregularity was common in our study participants, with age of menarche, but was not associated with current BMI, physical activity or insulin dose. CONCLUSIONS: Our study displays that age at menarche is delayed in young women with T1DM compared to the concurrent overall mean age at menarche in the West Bengal population.

Evaluation of anti-epileptic property of Marsilea quadrifolia Linn. in maximal electroshock and pentylenetetrazole-induced rat models of epilepsy.

OBJECTIVE: To study the anti-epileptic effects of methanolic extract of Marsilea quadrifolia Linn. (MQ) in maximal electroshock (MES) and pentylenetetrazole (PTZ) induced rat models of epilepsy. METHOD: A total of 84 adult male Wistar rats were used. An acute oral toxicity study was conducted on 36 rats and the remaining were used for other experiments. Each model had 24 rats which were allotted into four groups (n = 6). Group I (Control) received 1% carboxymethyl cellulose solution, Group II (Positive control) received phenytoin 300 mg kg(-1) b.w. in the MES model; sodium valproate 200 mg kg(-1) b.w. in the PTZ model, Group III (MQ) received 400 mg kg(-1) b.w. MQ extract and Group IV (MQ) received 600 mg kg(-1) b.w. MQ extract. Hind limb extension (HLE) time and recovery time were noted in the MES model. Latency for myoclonic jerk, seizures and EEG was recorded in the PTZ model. RESULTS: When compared to control, the phenytoin received group did not show HLE. In MQ pre-treated groups only 50% of rats showed HLE. Sodium valproate and various doses of MQ significantly increased the latency for onset of clonus and seizures. PTZ-induced EEG alterations were significantly attenuated by MQ administration and this was comparable to that of the sodium valproate effect. CONCLUSION: Marsilea quadrifolia Linn. showed significant anti-epileptic efficacy against various epilepsy models.