Probiotic Formulations: A Patent Landscaping Using the Text Mining Approach.

The outstanding research outcomes and registrations of myriads of probiotic strains have flooded the health market with various innovative probiotic-based products and their patents. The study of patented formulations of probiotics can give an overall insight into its existing application. A landscaping review of patents for probiotic-based preparations is presented in the current work. The patent search was performed over commercially available patent databased and analysis tool-PatSeer Pro®. Search strings containing words "Formulation" and "Composition" resulted in more than 3700 patents. Landscaping review of 400 + patents from the last 20 years (2000-2020) was performed using the Text-Mining approach. Text-Mining helped to identify 19 technological clusters which represent these patents. These clusters include the patents of probiotic preparations on animal feed, human food, cosmetics, antimicrobial, antidiabetic, arthritis, etc. A review of this massive number of patents unveiled many exciting preparations. Probiotic-based innovative products for depression, diabetes, Parkinson's, tumor, acne, and animal husbandry are reviewed comprehensively. The present work also unravels a few new-flanged products like probiotic layered condoms, products for acute alcoholism, and traditional Chinese medicine with probiotics. The patent landscape of probiotic-based preparations has presented a whole scenario of probiotic-based preparations. It has also revealed many unexplored areas where innovation can be excelled.

Provision of a DAPT Score to Cardiologists and Extension of Dual Antiplatelet Therapy Beyond 1 Year After ACS: Randomized Substudy of the Prospective Canadian ACS Reflective II Study.

BACKGROUND: Extension of dual antiplatelet therapy (DAPT) beyond 1 year after acute coronary syndrome is associated with a reduction in ischemic events but also increased bleeding. The DAPT score identifies individuals likely to derive overall benefit or harm from DAPT extension. We sought to evaluate the impact of providing the DAPT score to treating physicians on the decision to extend DAPT beyond 1 year after non-ST-segment elevation myocardial infarction. METHODS: Moderate to high-risk non-ST-segment elevation myocardial infarction patients were enrolled from July 2016 to May 2018 in 13 Canadian hospitals by 52 cardiologists. Participating cardiologists were randomly assigned 1:1 to receive their individual patients' DAPT scores before the 1-year follow-up visit vs not receiving their patients' DAPT scores. Rates of DAPT extension were compared among the randomized groups. RESULTS: At 1 year, 370 of the 585 (63.2%) patients discharged on DAPT were receiving DAPT. Among patients on DAPT at 1 year, the median (25th, 75th percentile) DAPT score was 2 (1,3). DAPT was extended beyond 1 year in 36.2% randomly assigned to provision of DAPT score vs 35.7% in the control group (P = 0.93). In the subgroup of patients with DAPT score ≥ 2, DAPT extension was 49.5% in the DAPT score provision arm vs 40.4% in the control arm (P = 0.22); among patients with DAPT score < 2, DAPT termination was 78.6% in the DAPT score provision arm vs 70.6% in the control arm (P = 0.26) (P value for interaction = 0.1). CONCLUSIONS: In this exploratory randomized trial, provision of the DAPT score to treating physicians had no impact on the duration of DAPT treatment beyond 1 year.

INTRODUCTION: La prolongation de la bithérapie antiplaquettaire au-delà d'un an après un syndrome coronarien aigu est associée à la réduction des accidents ischémiques, mais aussi à l'augmentation des hémorragies. Le score de bithérapie antiplaquettaire permet de déterminer les individus susceptibles d'obtenir des avantages globaux ou des inconvénients de la prolongation de la bithérapie antiplaquettaire. Nous avons cherché à évaluer les répercussions de l'obtention du score de bithérapie antiplaquettaire par les médecins traitants sur la décision quant à la prolongation de la bithérapie antiplaquettaire au-delà d'un an après l'infarctus du myocarde sans élévation du segment ST. MÉTHODES: De juillet 2016 à mai 2018, 52 cardiologues de 13 hôpitaux du Canada ont inscrit des patients exposés à un risque modéré à élevé d'infarctus du myocarde sans élévation du segment ST. Nous avons réparti de façon aléatoire selon un rapport 1:1 les cardiologues participants qui recevaient les scores de bithérapie antiplaquettaire individuels de leurs patients avant la consultation de suivi après un an vs ceux qui ne recevaient pas les scores de bithérapie antiplaquettaire de leurs patients. Nous avons comparé les taux de prolongation de la bithérapie antiplaquettaire des groupes répartis de façon aléatoire. RÉSULTATS: Après un an, 370 (63,2 %) patients sur 585 qui avaient eu à la sortie de l'hôpital une bithérapie antiplaquettaire recevaient la bithérapie antiplaquettaire. Parmi les patients qui prenaient la bithérapie antiplaquettaire après un an, le score médian de bithérapie antiplaquettaire (25e, 75e percentiles) était de 2 (1, 3). La bithérapie antiplaquettaire était prolongée au-delà d'un an chez 36,2 % des patients répartis de façon aléatoire qui avaient un score de bithérapie antiplaquettaire vs 35,7 % dans le groupe témoin (P = 0,93). Dans le sous-groupe de patients qui avaient un score de bithérapie antiplaquettaire ≥ 2, la prolongation de la bithérapie antiplaquettaire était de 49,5 % dans le bras qui avait un score de bithérapie antiplaquettaire vs 40,4 % dans le bras témoin (P = 0,22); parmi les patients qui avaient un score de bithérapie antiplaquettaire < 2, la cessation de la bithérapie antiplaquettaire était de 78,6 % dans le bras qui avait un score de bithérapie antiplaquettaire vs 70,6 % dans le bras témoin (P = 0,26) (valeur P pour l'interaction = 0,1). CONCLUSIONS: Dans cet essai exploratoire à répartition aléatoire, l'obtention du score de la bithérapie antiplaquettaire par les médecins traitants n'a pas engendré de répercussions sur la durée de la bithérapie antiplaquettaire au-delà d'un an.

A Library of Thiazolidin-4-one Derivatives as Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitors: An Attempt To Discover Novel Antidiabetic Agents.

Protein tyrosine phosphatase 1B (PTP1B) is an important target for the treatment of diabetes. A series of thiazolidin-4-one derivatives 8-22 was designed, synthesized and investigated as PTP1B inhibitors. The new molecules inhibited PTP1B with IC50 values in the micromolar range. 5-(Furan-2-ylmethylene)-2-(4-nitrophenylimino)thiazolidin-4-one (17) exhibited potency with a competitive type of enzyme inhibition. structure-activity relationship studies revealed various structural facets important for the potency of these analogues. The findings revealed a requirement for a nitro group-including hydrophobic heteroaryl ring for PTP1B inhibition. Molecular docking studies afforded good correlation with experimental results. H-bonding and π-π interactions were responsible for optimal binding and effective stabilization of virtual protein-ligand complexes. Furthermore, in-silico pharmacokinetic properties of test compounds predicted their drug-like characteristics for potential oral use as antidiabetic agents.Additionally, a binding site model demonstrating crucial pharmacophoric characteristics influencing potency and binding affinity of inhibitors has been proposed, which can be employed in the design of future potential PTP1B inhibitors.

Design, Synthesis and Pharmacological Evalution of 1,3,4-Oxadiazole Derivatives as Collapsin Response Mediator Protein 1 (CRMP 1) Inhibitors.

OBJECTIVE: The series of 2-(4-Phenylamino)-N-(5-((4-nitrophenoxy)methyl) -1,3,4-oxadiazol- 2-yl)aceta-mide (5a-5e) and substituted N-(5-(Phenoxymethyl)-1,3,4-oxadiazol-2-yl)-2- (phenylamino)acetamide (5f-5i) was designed, synthesized and investigated for Collapsin Response Mediator Protein 1 (CRMP 1) inhibitors as small lung cancer. DESIGN: Design of compounds was determined by literature review and molecular docking studies in iGEMDOCK 2.0. MATERIALS AND METHODS: Novel 1, 3, 4 Oxadiazole derivatives were synthesized and characterized by melting point, TLC, IR Spectroscopy, Mass spectroscopy and 1H NMR. In vitro biological evaluation was performed on NCI-H2066 cell line for different concentrations 10-1000µM by telomeric repeat amplification protocol assay. The assay of telomerase in cellular extracts was modified from the PCR-based Telomeric-Repeat Amplification Protocol (TRAP), using the oligonucleotides TS and CX. RESULTS: Novel substituted 2-(4-Phenylamino)-N-(5-((4-nitrophenoxy)methyl)-1,3,4-oxadiazol-2- yl) acetamide (5a-5e) and substituted N-(5-(Phenoxymethyl)-1,3,4-oxadiazol-2-yl)-2-(phenylamino) acetamide (5f-5i) were synthesized, and characterized using spectral and analytical data. All compounds have shown considerable % inhibition of Cell Growth with respect to Bevacizumab, but compound 5a and 5f were equipotent with respect to activity as compared to standard Bevacizumab. CONCLUSION: Amongst the hybrids, p-nitro substituted derivative (5a) and p-chloro substituted (5f) showed the highest activity against human lung cancer cell line NCI-H2066 by TRAP assay.

Association of body fat with stress levels and dietary intakes in Indian women.

A cross-sectional study of 605 women (aged 18-50 years) conducted from January 2013 to June 2014 in Gujarat, India assessed stress, dietary intakes and body fat percentage (PBF), and the inter-relationship of PBF with stress, dietary fat, and carbohydrates. The population was categorized according to PBF cutoffs for Asians. A generalized linear regression model adjusted for age was performed to assess the relationship of stress, fat, and carbohydrate intakes with PBF. PBF had a significant positive association with stress level (p = .02) and carbohydrate intake (p = .008); fat intake was not significantly associated (p = .8). Women with moderate PBF consumed significantly less carbohydrates (mean = 152.3 ± 13.3 gm/1000 kcal/day, p < .05) and had lower stress scores (mean = 9.7 ± 4.2, p < .05) than women with high PBF (mean carbohydrate intake = 156.2 ± 10.8 gm/1000 kcal/day; mean stress score = 10.9 ± 4.4) and very high PBF (mean carbohydrate intake = 156.8 ± 11.6 gm/1000 kcal/day; mean stress score = 11.2 ± 4.2). We conclude that PBF has a positive association with stress and dietary carbohydrate; women with higher stress and carbohydrate intake are more likely to accumulate higher body fat as compared to women with less stress and low carbohydrate intake.

Molecular Docking, In-Silico ADMET Study and Development of 1,6- Dihydropyrimidine Derivative as Protein Tyrosine Phosphatase Inhibitor: An Approach to Design and Develop Antidiabetic Agents.

BACKGROUND: 1,6-Dihydropyrimidine exerts notable pharmacological efficiency and emerged as integral backbones for treatment of type-II diabetes mellitus. To optimize the in vitro and In-silico study we carried out on substituted 1,6-Dihydropyrimidine. The objective of the present study is to evaluate the binding interaction of 1,6-Dihydropyrimidine compounds with Protein Tyrosine Phosphatase (PTP1B) enzyme and also check ADME/T properties of best scored compounds. METHODS: The In-silico study (docking) was carried out through target Protein Tyrosine Phosphatase (PTP1B) retrieved from protein data bank having PDB ID: 2QBS and the anti diabetic activity of the test compounds was tested against protein tyrosine phosphatase (PTP1B) enzyme by using Calbiochem ® PTP1B colorimetric assay kit. RESULTS AND CONCLUSION: The results of molecular Docking revealed that, with respect to their free binding energy 6A, 3K, 1B and 2K compounds have the lowest binding energy compared to positive control. In-silico ADME/T predictions revealed that all best scored compounds had good absorption as well as solubility characteristics through substrate binding sites. After conducting the in vitro studies it was observed that compounds having -3NO2, 3,4-OCH3, 4-NO2 and 4-Cl substitution on phenyl ring in the basic moiety shows good anti diabetic activity The present computational approach provided valuable information on the binding process of 1,6-Dihydropyrimidine compounds to the binding site of PTP-1B. These compounds may serve as potential lead compound for developing new 1,6- Dihyropyrimidine as a promising anti diabetic agent.

Molecular Docking, Synthesis and Biological Evaluation of Sulphonylureas/ Guanidine Derivatives as Promising Antidiabetic Agent.

BACKGROUND: A series of novel sulphonylureas/guanidine derivatives was designed, synthesized, and evaluated for the treatment of diabetes mellitus. In this study, the designed compounds were docked with AKR1C1 complexes by using glide docking program and docking calculations were performed to predict the binding affinity of the designed compounds with the binding pocket of protein 4YVP and QikProp program was used to predict the ADME/T properties of the analogues. METHODS: All the targeted derivatives were synthesized and purified by recrystallization. Synthesized compounds were characterized by various physicochemical and various spectroscopic techniques like melting point, thin layer chromatography, infrared spectroscopy (KBr pellets), mass spectroscopy(m/z), 1H NMR (DMSO-d6), and 13C NMR. The synthesized compounds were further studied for biological evolution by alloxan (150 mg/dl, intraperitonial) induced diabetic rat model for in-vivo studies. RESULT: Among all the synthesized derivatives, 5c and 5d were most potent as per binding energy. Compound 5i have shown a better plasma glucose reduction compared to glibenclamide. Hence, it will be further used as a lead compound to develop a more such kind of agent. CONCLUSION: The docking study revealed that in all designed sulphonylureas/ guanidine series of compounds 5c and 5d were found to be most potent compounds as per the binding energy compared to glibenclamide. With the help of detailed study of in vivo biological activity, we observed that compound 5i gives better result compared to glibenclamide as standard.

Interrelationship between serum 25-hydroxyvitamin D3 concentration and lipid profiles in premenopausal Indian women.

CONTEXT: Vitamin D deficiency is prevalent worldwide, and observational studies have associated it with an atherogenic lipid profile. AIM: To determine the interrelationship between Vitamin D and lipid profile in apparently healthy premenopausal Indian women, considering confounding factors such as lifestyle that independently influence lipids. SETTING AND DESIGN: Cross-sectional study. SUBJECTS AND METHODS: One hundred and twenty healthy premenopausal women (20-45 year) were recruited from Gujarat, India. Data were collected on anthropometry, physical activity, sunlight exposure, and diet. Fasting blood samples were collected for the measurement of serum 25-hydroxyvitamin D3 (25[OH]D), parathyroid hormone, and lipid profile. STATISTICAL ANALYSIS: Pearson's correlation coefficient was used to derive correlation between serum 25[OH]D concentrations and serum lipids. RESULTS: Ninety-three percent women showed Vitamin D deficiency (serum 25[OH]D < 20 ng/ml). Serum 25(OH)D concentrations showed significant inverse correlation with total cholesterol (TC) (r = -0.202, P = 0.027), triglycerides (TG) (r = -0.284, P = 0.002), and low-density lipoprotein-cholesterol (LDL-C) (r = -0.184, P = 0.044) and positive correlation with high-density lipoprotein-cholesterol (HDL-C) (r = 0.250, P = 0.006). On dichotomizing the population according to median 25(OH)D concentration (11.1 ng/dl), no significant differences were observed between the groups for anthropometry, sunlight exposure, and lifestyle. Serum lipid profiles were significantly different, above median serum 25(OH)D concentration group showed favorable serum lipids (TC: 179.3 ± 30 vs. 191.8 ± 31.7 mg/dl; TG: 140 ± 39.1 vs. 165.5 ± 53.4 mg/dl; LDL-C: 100 ± 30.2 vs. 112 ± 32 mg/dl; HDL-C: 53 ± 14 vs. 47.6 ± 9.3 mg/dl)(P < 0.05). CONCLUSIONS: This study demonstrates that association of 25(OH)D concentrations with lipid profile even after considering lifestyle factors which independently influence lipids. Intervention trials would be required to prove this association to be causation.

Impact of occupation on stress and anxiety among Indian women.

The objectives of this study were to: (1) assess the prevalence of anxiety and stress in Indian women; and (2) evaluate the relationship of occupation to the prevalence of anxiety and stress. A cross-sectional study was performed from January 2013 to June 2014, on women (aged 18-50 years) randomly selected from different occupations in Gujarat, India. Anxiety was evaluated using Spielberg's State and Trait Anxiety Inventory scale and stress was assessed using the International Stress Management Association questionnaire. Serum cortisol concentration was measured in a sub-sample. The association of occupation with stress and anxiety was analyzed by a generalized linear model adjusted for age. Among all participants, 26% were the most prone and 66% were somewhat more prone to stress; 35% of women showed high anxiety levels. Homemakers had 1.2 times higher anxiety and 1.3 times higher stress than working women (p < .05). Prevalence of stress (37%, p < .001) and anxiety (40%, p = .068) were also higher in homemakers compared to working women and students. Serum cortisol levels did not differ significantly (p > .05) by occupation. This study revealed high prevalence rates of stress and anxiety in Indian women. Involvement in activities outside the home may help women to reduce stress.

Risk stratification and stroke prevention therapy care gaps in Canadian atrial fibrillation patients (from the Co-ordinated National Network to Engage Physicians in the Care and Treatment of Patients With Atrial Fibrillation chart audit).

The objectives of this national chart audit (January to June 2013) of 6,346 patients with atrial fibrillation (AF; ≥18 years without a significant heart valve disorder) from 647 primary care physicians were to (1) describe the frequency of stroke and bleed risk assessments in patients with nonvalvular AF by primary care physicians, including the accuracy of these assessments relative to established predictive indexes; (2) outline contemporary methods of anticoagulation used; and (3) report the time in the therapeutic range among patients prescribed warfarin. An annual stroke risk assessment was not undertaken in 15% and estimated without a formal risk tool in 33%; agreement with CHADS2 score estimation was seen in 87% of patients. Major bleeding risk assessment was not undertaken in 25% and estimated without a formal risk tool in 47%; agreement with HAS-BLED score estimation was observed in 64% with physician overestimation in 26% of patients. Antithrombotic therapy included warfarin (58%), dabigatran (22%), rivaroxaban (14%), and apixaban (<1%). Among warfarin-treated patients, the median international normalized ratio was 2.4 and time in therapeutic range (TTR) was 73%; however, the TTR was <50% in 845 (25%), 50% to 69% in 674 (20%), and ≥70% in 1,827 (55%) patients. In conclusion, we describe a contemporary real-world elderly population with AF at important risk for stroke. There is apparent overestimation of bleeding risk in many patients. Warfarin was the dominant stroke prevention treatment; however, the suggested TTR target was achieved in only 55% of these patients.

Glibenclamide reduces hippocampal injury and preserves rapid spatial learning in a model of traumatic brain injury.

Cognitive disturbances after traumatic brain injury (TBI) are frequent, even when neuroimaging shows no overt hemorrhagic or other abnormality. Sulfonylurea receptor 1 (SUR1) plays a key role in various forms of CNS injury, but its role in hippocampal dysfunction after mild to moderate TBI is unknown. To assess the hypothesis that postinjury SUR1 upregulation in the hippocampus is associated with a later disturbance in learning, we studied a rat model of cortical impact TBI calibrated to avoid primary and secondary hemorrhage in the underlying hippocampus. The transcription factor, specificity protein 1, which regulates expression of SUR1 and caspase-3, was activated in the hippocampus 15 minutes after injury. Upregulation of SUR1 protein and of Abcc8 (which encodes SUR1) messenger RNA was evident by 6 hours. To assess the role of SUR1, injured rats were administered vehicle or a low dose of the specific sulfonylurea inhibitor glibenclamide for 1 week. At 2 weeks, the increase in activated caspase-3 in the hilus of glibenclamide-treated rats was half of that in vehicle-treated rats. Testing for rapid learning in a Morris water maze at 4 weeks showed significantly better performance in glibenclamide-treated rats; performance inversely correlated with Fluoro-Jade staining for degenerated neurons in the hilus. We conclude that glibenclamide may have long-term protective effects on the hippocampus after mild-to-moderate TBI.