Experimental and Computational Studies on RuII -Catalyzed C7-Allylation of Indolines with Allyl Bromide.

The selective C7-allylation of indolines with allyl bromide under ruthenium catalysis has been revealed here. Under established reaction conditions, C7-allylation of various indolines, including drug compounds, was accomplished with good selectivity and yields. Based on combined experimental and density functional theory (DFT) studies, the olefin insertion route was energetically favorable among four possible pathways. Experimental and DFT studies further revealed that the C-H activation is a reversible rate-limiting step.

Dating and friendships in adolescence: Variation across same-sex and other-sex romantic partners.

This research examined associations between dating and number of friends for rural adolescents with same-sex and other-sex dating partners using longitudinal sociometric data (N = 2826; 55% female, 87% White, mean age = 14 at baseline). In multilevel models assessing within-person change, boys gained female friends when they were in same-sex romantic relationships, compared to when they were single. In contrast, girls in same-sex relationships lost female friends and gained male friends. Adolescents in other-sex romantic relationships gained same-sex friends compared to when they were single. Results advance understanding of adolescent social and sexual development, suggesting that sexual minority adolescents find allies when dating but may struggle to maintain same-sex friendships.

Comparison of oral health-related quality of life and its association with the periodontal status among the adults: A questionnaire-based study.

Background: Oral health-related quality of life (OHRQoL) is used for evaluating needs of people, their health problems, their level of satisfaction, and various effects of any intervention which have been provided for recording of various nonclinical aspects of oral health. Aim: The objective of the study was to compare OHRQoL and its association with periodontal health among adult population. Materials and Methods: This prospective and cross-sectional study was conducted on 300 respondents who were diagnosed with periodontitis. 14-item containing Oral Health Impact Profile 14 (OHIP-14) questionnaire was used for study analysis. A single observer made clinical examinations. Mann-Whitney "U" and Kruskal-Wallis statistical tests were used for comparing the OHIP-14 scores. Statistically significance was set at P < 0.05. Results: Majority of study participants were of female gender (62.0%). A significant association was observed between loss of attachment and OHIP14 scores (P = 0.003). Conclusion: Poor periodontal health may affect the OHRQoL.

Résumé Contexte: La qualité de vie liée à la santé bucco-dentaire (OHRQoL) est utilisée pour évaluer les besoins des personnes, leurs problèmes de santé, leur niveau de satisfaction, et divers effets de toute intervention qui a été fournie pour l'enregistrement de divers aspects non cliniques de la santé bucco-dentaire. But: L'objectif de l'étude était de comparer la OHRQoL et son association avec la santé parodontale parmi la population adulte. Matériels et méthodes: ce Une étude prospective et transversale a été menée auprès de 300 répondants ayant reçu un diagnostic de parodontite. 14 articles contenant Orale Le questionnaire Health Impact Profile 14 (OHIP-14) a été utilisé pour l'analyse de l'étude. Un seul observateur a fait des examens cliniques. Man­Les tests statistiques Whitney " U " et Kruskal­Wallis ont été utilisés pour comparer les scores OHIP-14. La signification statistique a été fixée à P < 0,05. Résultats: La majorité des participants à l'étude étaient de sexe féminin (62,0 %). Une association significative a été observée entre la perte d'attachement et scores OHIP14 (P = 0,003). Conclusion: Une mauvaise santé parodontale peut affecter l'OHRQoL. Mots-clés: Adultes, Oral Health Impact Profile 14, qualité de vie liée à la santé buccodentaire, parodontite, questionnaire.

ACE2/ANG-(1-7)/Mas receptor axis activation prevents inflammation and improves cognitive functions in streptozotocin induced rat model of Alzheimer's disease-like phenotypes.

Activation of the renin-angiotensin system (RAS), by Angiotensin converting enzyme/Angiotensin II/Angiotensin receptor-1 (ACE/Ang II/AT1 R) axis elicits amyloid deposition and cognitive impairment. Furthermore, ACE2 induced release of Ang-(1-7) binds with the Mas receptor and autoinhibits ACE/Ang II/AT1 axis activation. Inhibition of ACE by perindopril has been reported to improve memory in preclinical settings. However, the functional significance and mechanism by which ACE2/Mas receptor regulate cognitive functions and amyloid pathology is not known. The present study is aimed to determine the role of ACE2/Ang-(1-7)/Mas receptor axis in STZ induced rat model of Alzheimer's disease (AD). We have used pharmacological, biochemical and behavioural approaches to identify the role of ACE2/Ang-(1-7)/Mas receptor axis activation on AD-like pathology in both in vitro and invivo models. STZ treatment enhances ROS formation, inflammation markers and NFκB/p65 levels which are associated with reduced ACE2/Mas receptor levels, acetylcholine activity and mitochondrial membrane potential in N2A cells. DIZE mediated ACE2/Ang-(1-7)/Mas receptor axis activation resulted in reduced ROS generation, astrogliosis, NFκB level and inflammatory molecules and improved mitochondrial functions along with Ca2+ influx in STZ treated N2A cells. Interestingly, DIZE induced activation of ACE2/Mas receptor significantly restored acetylcholine levels and reduced amyloid-beta and phospho-tau deposition in cortex and hippocampus that resulted in improved cognitive function in STZ induced rat model of AD-like phenotypes. Our data indicate that ACE2/Mas receptor activation is sufficient to prevented cognitive impairment and progression of amyloid pathology in STZ induced rat model of AD-like phenotypes. These findings suggest the potential role of ACE2/Ang-(1-7)/Mas axis in AD pathophysiology by regulating inflammation cognitive functions.

Activation of Angiotensin-converting Enzyme 2 Protects Against Lipopolysaccharide-induced Glial Activation by Modulating Angiotensin-converting Enzyme 2/Angiotensin (1-7)/Mas Receptor Axis.

Neuroinflammation is associated with activation of glial cells and pro-inflammatory arm of the central Renin Angiotensin System (RAS) namely, Angiotensin-Converting Enzyme/Angiotensin II/Angiotensin Type 1 Receptor (ACE/Ang II/AT1R) axis. Apart from this, another axis of RAS also exists, Angiotensin-Converting Enzyme 2/Angiotensin (1-7)/Mas Receptor (ACE2/Ang (1-7)/MasR), which counters ACE/Ang II/AT1R axis by showing anti-inflammatory properties. However, the role of ACE2/Ang (1-7)/MasR axis has not been explored in glial activation and neuroinflammation. Hence, the present study tries to unveil the role of ACE2/Ang (1-7)/MasR axis in lipopolysaccharide (LPS)-induced neuroinflammation using diminazene aceturate (DIZE), an ACE2 activator, in astroglial (C6) and microglial (BV2) cells as well as male SD rats. We found that ACE2 activation efficiently prevented LPS-induced changes by decreasing glial activation, inflammatory signaling, cell migration, ROS generation via upregulation of ACE2/Ang (1-7)/MasR signaling. In addition, activation of ACE2/Ang (1-7)/MasR axis by DIZE significantly suppressed the pro-inflammatory ACE/Ang II/AT1R axis by reducing Ang II level in neuroinflammatory conditions induced by LPS in both in vitro and in vivo. ACE2/Ang (1-7)/MasR axis activation further decreased mitochondrial depolarization and apoptosis, hence providing neuroprotection. Furthermore, to validate that the beneficial effect of the ACE2 activator was indeed through MasR, a selective MasR antagonist (A779) was used that significantly blocked the anti-inflammatory effect of ACE2 activation by DIZE. Hence, our study demonstrated that ACE2 activation imparted neuroprotection by enhancing ACE2/Ang (1-7)/MasR signaling which in turn decreased glial activation, neuroinflammation, and apoptosis and improved mitochondrial health.

Pten associates with important gene regulatory network to fine-tune Müller glia-mediated zebrafish retina regeneration.

Unlike mammals, zebrafish possess a remarkable ability to regenerate damaged retina after an acute injury. Retina regeneration in zebrafish involves the induction of Müller glia-derived progenitor cells (MGPCs) exhibiting stem cell-like characteristics, which are capable of restoring all retinal cell-types. The induction of MGPC through Müller glia-reprograming involves several cellular, genetic and biochemical events soon after a retinal injury. Despite the knowledge on the importance of Phosphatase and tensin homolog (Pten), which is a dual-specificity phosphatase and tumor suppressor in the maintaining of cellular homeostasis, its importance during retina regeneration remains unknown. Here, we explored the importance of Pten during zebrafish retina regeneration. The Pten gets downregulated upon retinal injury and is absent from the MGPCs, which is essential to trigger Akt-mediated cellular proliferation essential for retina regeneration. We found that the downregulation of Pten in the post-injury retina accelerates MGPCs formation, while its overexpression restricts the regenerative response. We observed that Pten regulates the proliferation of MGPCs not only through Akt pathway but also by Mmp9/Notch signaling. Mmp9-activity is essential to induce the proliferation of MGPCs in the absence of Pten. Lastly, we show that expression of Pten is fine-tuned through Mycb/histone deacetylase1 and Tgf-ß signaling. The present study emphasizes on the stringent regulation of Pten and its crucial involvement during the zebrafish retina regeneration.

Devising the Set-up of Essential Equipments for a 250 Bedded COVID-19 Healthcare Facility for Mumbai and Suburban Regions.

The article assists with understanding the need to change the current accessible clinical resources; as well as gauging and sorting out the devices needed to provide food the uncommon requirements of the COVID-19 patients without trading off the smooth working of the medical services office without taking a chance with the security of the medical care experts conveying it. A primary objective of this study is to provide interim guidance for planning the medical equipment for an isolation facility in a way that satisfies the needs of patients in an exact manner. Additionally, to assist healthcare facility to follow the accreditation standards and plan the modifications necessary to ensure the safety of patients and employees. The documents reviewed for this study mainly focus on providing interim guidance, specifications, and essential devices for setting up of quarantine facilities in a COVID-19 healthcare facility. This study assists with understanding the rules to keep up with the current accessible clinical supplies and intending to procure more and usage of them at which departments to cater the extraordinary necessities of the COVID-19 patients without bargaining the smooth working of the medical care office and not taking a chance with the wellbeing of the medical care experts conveying it.

Oral Mucormycosis: An Inevitable Complication of COVID-19.

Individuals who have shown recovery from coronavirus disease (COVID-19) are increasingly getting diagnosed with Mucormycosis or "Black fungus." It is a difficult condition to diagnose as it has symptoms that are common among a variety of diseases. Hence, it is important to identify the presenting signs and understand the underlying pathogenesis of COVID-19 associated Mucormycosis. The incidence of these mycotic infections has shown a substantial increase in current times owing to an increase in the prevalence of immunocompromised subjects, human immunodeficiency virus (HIV) infection, and acquired immunodeficiency syndrome (AIDS). Any suspected case of mucormycosis requires rapid diagnosis and management due to its rapid progression as well as the destructive course of infection. This article reviews the taxonomy, pathogenesis, and clinical signs along with laboratory investigations that may play a vital role in the timely diagnosis of this condition as it is mostly fatal.

Well-Defined Phosphine-Free Manganese(II)-Complex-Catalyzed Synthesis of Quinolines, Pyrroles, and Pyridines.

Herein, we report a simple, phosphine-free, and inexpensive catalytic system based on a manganese(II) complex for synthesizing different important N-heterocycles such as quinolines, pyrroles, and pyridines from amino alcohols and ketones. Several control experiments, kinetic studies, and DFT calculations were carried out to support the plausible reaction mechanism. We also detected two potential intermediates in the catalytic cycle using ESI-MS analysis. Based on these studies, a metal-ligand cooperative mechanism was proposed.

Angiotensin-Converting Enzyme 2 Activation Mitigates Behavioral Deficits and Neuroinflammatory Burden in 6-OHDA Induced Experimental Models of Parkinson's Disease.

Hypertension is reported to cause major brain disorders including Parkinson's disease (PD), apart from cardiovascular and chronic kidney disorders. Considering this, for the first time, we explored the effect of modulation of the ACE2/Ang (1-7)/MasR axis using diminazene aceturate (DIZE), an ACE2 activator, in 6-hydroxydopamine (6-OHDA) induced PD model. We found that DIZE treatment improved neuromuscular coordination and locomotor deficits in the 6-OHDA induced PD rat model. Further, the DIZE-mediated activation of ACE2 led to increased tyrosine hydroxylase (TH) and dopamine transporters (DAT) expression in the rat brain, indicating the protection of dopaminergic (DAergic) neurons from 6-OHDA induced neurotoxicity. Moreover, 6-OHDA induced activation of glial cells (astrocytes and microglia) and release of neuroinflammatory mediators were attenuated by DIZE treatment in both in vitro as well as in vivo models of PD. DIZE exerted its effect by activating ACE2 that produced Ang (1-7), a neuroprotective peptide. Ang (1-7) conferred its neuroprotective effect upon binding with the G-protein-coupled MAS receptor that led to the upregulation of cell survival proteins while downregulating apoptotic proteins. Importantly, these findings were further validated by using A-779, a MasR antagonist. The result showed that treatment with A-779 reversed the antioxidative and anti-inflammatory effects of DIZE by decreasing glial activation and neuroinflammatory markers. Although the role of ACE2 in PD pathology needs to be additionally confirmed using transgenic models in either ACE2 overexpressing or knockout mice, still, our study demonstrates that enhancing ACE2 activity could be a novel approach for ameliorating PD pathology.

Using Big Data Analytics to "Back Engineer" Protein Conformational Selection Mechanisms.

In the living cells, proteins bind small molecules (or "ligands") through a "conformational selection" mechanism, where a subset of protein structures are capable of binding the small molecules well while most other protein structures are not capable of such binding. The present work uses machine learning approaches to identify, in a very large amount of protein:ligand complexes, what protein properties are associated with their capacity to bind small molecules. In order to do so, we calculate 40 physicochemical properties on about 1.5 millions of protein conformations: ligand and protein conformations. This work describes a machine learning approach to identify the unique physico-chemical descriptors of a protein that maximize the prediction rate of potential protein molecular conformations for the test case proteins ADORA2A (Adenosine A2a Receptor), ADRB2 (Adrenoceptor Beta 2) and OPRK1 (Opioid Receptor Kappa 1). We find adequate machine learning techniques can increase by an order of magnitude the identification of "binding protein conformations" in an otherwise very large ensemble of protein conformations, compared to random selection of protein conformations. This opens the door to the systematic identification of such "binding conformations" for proteins and provides a big data approach to the conformational selection mechanism.

Reliability of cheiloscopy and dermatoglyphics in hypertension and diabetes. A comparative study.

Background: Both dermatoglyphic and cheiloscopic patterns are genetically determined. These patterns are known to be associated with type II diabetes or diabetes mellitus and hypertension which are also considered to have genetic influence due to their familial occurrence. Hence, the aim of this study was to compare reliability of both cheiloscopy and dermatoglyphics with hypertension and type II diabetes. Materials and Methods: This was a prospective study conducted on 300 study participants. Both cheiloscopic and dermatoglyphic patterns were recorded using validated techniques. Obtained patterns were analyzed and assessed for statistical analysis using the SPSS version 21.0 statistical software. The Chi-square test was used for analyzing the obtained data. Results: In the present study, no statistical correlation was obtained between either dermatoglyphic or cheiloscopic patterns and type II diabetes or hypertension. Conclusion: The present study showed that cheiloscopy or dermatoglyphics cannot be used as a predictive tool for assessing a subject's risk of developing type II diabetes or hypertension. These are contradictory findings, thus emphasizing more research in this area so that these noninvasive techniques can be used as predictive tools for developing essential hypertension or type II diabetes.

Résumé Contexte: Les modèles dermatoglyphiques et cheiloscopiques sont génétiquement déterminés. Ces modèles sont connus pour être associés au diabète de type II ou au diabète sucré et à l'hypertension qui sont également considérés comme ayant une influence génétique en raison de leur occurrence familiale.Par conséquent, le but de cette étude était de comparer la fiabilité de la cheiloscopie et des dermatoglyphes avec l'hypertension et le diabète de type II. Matériaux et méthodes: Il s'agissait d'une étude prospective menée auprès de 300 participants à l'étude.Les modèles cheiloscopiques et dermatoglyphiques ont été enregistrés utilisant des techniques validées.Les modèles obtenus ont été analysés et évalués pour analyse statistique à l'aide du logiciel statistique SPSS version 21.0.Le test Chi-square a été utilisé pour analyser les données obtenues. Résultats: Dans la présente étude, aucune corrélation statistique n'a été obtenue entre les modèles dermatoglyphiques ou cheiloscopiques et le diabète ou l'hypertension de type II. Conclusion: La présente étude a montré que la chéiloscopie ou les dermatoglyphes ne peuvent pas être utilisés comme outil prédictif pour évaluer le risque de développer le diabète ou l'hypertension de type II d'un sujet.Ce sont des résultats contradictoires, mettant ainsi l'accent sur plus de recherche dans ce domaine afin que ces techniques non invasives puissent être utilisées comme outils prédictifs pour développer l'hypertension essentielle ou le diabète de type II. Mots clés: Dermatoglyphes, hypertension, empreintes de lèvres, diabète de type II.

Carbon-based catalyst for environmental bioremediation and sustainability: Updates and perspectives on techno-economics and life cycle assessment.

Global rise in the generation of waste has caused an enormous environmental concern and waste management problem. The untreated carbon rich waste serves as a breeding ground for pathogens and thus strategies for production of carbon rich biochar from waste by employing different thermochemical routes namely hydrothermal carbonization, hydrothermal liquefaction and pyrolysis has been of interest by researchers globally. Biochar has been globally produced due to its diverse applications from environmental bioremediation to energy storage. Also, several factors affect the production of biochar including feedstock/biomass type, moisture content, heating rate, and temperature. Recently the application of biochar has increased tremendously owing to the cost effectiveness and eco-friendly nature. Thus this communication summarized and highlights the preferred feedstock for optimized biochar yield along with the factor influencing the production. This review provides a close view on biochar activation approaches and synthesis techniques. The application of biochar in environmental remediation, composting, as a catalyst, and in energy storage has been reviewed. These informative findings were supported with an overview of lifecycle and techno-economical assessments in the production of these carbon based catalysts. Integrated closed loop approaches towards biochar generation with lesser/zero landfill waste for safeguarding the environment has also been discussed. Lastly the research gaps were identified and the future perspectives have been elucidated.

Big Data analytics for improved prediction of ligand binding and conformational selection.

This research introduces new machine learning and deep learning approaches, collectively referred to as Big Data analytics techniques that are unique to address the protein conformational selection mechanism for protein:ligands complexes. The novel Big Data analytics techniques presented in this work enables efficient data processing of a large number of protein:ligand complexes, and provides better identification of specific protein properties that are responsible for a high probability of correct prediction of protein:ligand binding. The GPCR proteins ADORA2A (Adenosine A2a Receptor), ADRB2 (Adrenoceptor Beta 2), OPRD1 (Opioid receptor Delta 1) and OPRK1 (Opioid Receptor Kappa 1) are examined in this study using Big Data analytics techniques, which can efficiently process a huge ensemble of protein conformations, and significantly enhance the prediction of binding protein conformation (i.e., the protein conformations that will be selected by the ligands for binding) about 10-38 times better than its random selection counterpart for protein conformation selection. In addition to providing a Big Data approach to the conformational selection mechanism, this also opens the door to the systematic identification of such "binding conformations" for proteins. The physico-chemical features that are useful in predicting the "binding conformations" are largely, but not entirely, shared among the test proteins, indicating that the biophysical properties that drive the conformation selection mechanism may, to an extent, be protein-specific for the protein properties used in this work.

Evolution in mitigation approaches for petroleum oil-polluted environment: recent advances and future directions.

Increasing petroleum consumption and a rise in incidental oil spillages have become global concerns owing to their aquatic and terrestrial toxicity. Various physicochemical and biological treatment strategies have been studied to tackle them and their impact on environment. One of such approaches in this regard is the use of microbial processes due to their being "green" and also apparent low cost and high effectiveness. This review presents the advancement in the physical and biological remediation methods and their progressive efficacy if employed in combination of hybrid modes. The use of biosurfactants and/or biochar along with microbes seems to be a more effective bioremediation approach as compared to their individual effects. The lacuna in research at community or molecular level has been overcome by the recent introduction of "-omics" technology in hydrocarbon degradation. Thus, the review further focuses on presenting the state-of-art information on the advancement of petroleum bioremediation strategies and identifies the research gaps for achieving total mitigation of petroleum oil.

Trends in mitigation of industrial waste: Global health hazards, environmental implications and waste derived economy for environmental sustainability.

Majority of industries, in order to meet the technological development and consumer demands generate waste. The untreated waste spreads out toxic and harmful substances in the environment which serves as a breeding ground for pathogenic microorganisms thus causing severe health hazards. The three industrial sectors namely food, agriculture, and oil industry are among the primary organic waste producers that affect urban health and economic growth. Conventional treatment generates a significant amount of greenhouse gases which further contributes to global warming. Thus, the use of microbes for utilization of this waste, liberating CO2 offers an indispensable tool. The simultaneous production of value-added products such as bioplastics, biofuels, and biosurfactants increases the economics of the process and contributes to environmental sustainability. This review comprehensively summarized the composition of organic waste generated from the food, agriculture, and oil industry. The linkages between global health hazards of industrial waste and environmental implications have been uncovered. Stare-of-the-art information on their subsequent utilization as a substrate to produce value-added products through bio-routes has been elaborated. The research gaps, economical perspective(s), and future research directions have been identified and discussed to strengthen environmental sustainability.

Role of Hematological and Immunological Parameters in COVID-19 Patients.

BACKGROUND: The ongoing pandemic of coronavirus disease 2019 (COVID-19) which was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to efforts from the medical and scientific community in understanding the biological basis of COVID-19 pathophysiological mechanisms. Thus, analysis of various hematological and immunological parameters may be helpful for COVID-19 infection evaluation for risks involved and effectiveness in management. AIM: The aim of this study was to analyze the role of various hematological and immunological parameters in patients infected with SARS-CoV-2. MATERIALS AND METHODS: This retrospective analysis was performed on 300 patients who tested positive for SARS-CoV-2 by quantitative reverse transcription-polymerase chain reaction analysis. All participants of the study were divided into - (a) Group I: patients with mild symptoms and normal chest radiographic findings; (b) patients with moderate disease presenting with fever and cough along with other respiratory symptoms, and (c) patients suffering from severe disease. Data collection was done from all patients at the time of hospital admission for hematological and immunological parameters - (a) total leukocyte count, (b) lymphocyte count, (c) lymphocytic subset count, (d) lactate dehydrogenase (LDH) levels, (e) D-dimer, (f) C-reactive protein (CRP), and (g) ferritin levels. SPSS 22.0 software was used for determining P values by independent t-test and Chi-square test. RESULTS: The median age was 65 years (interquartile range -57-71 years). While comparing white blood cell and lymphocyte counts, extremely significant P values were obtained. D-dimers and ferritin levels demonstrated extremely significant P values while both LDH and CRPs showed statistical significance. Correlation of lymphocytic subsets showed extreme significance in total lymphocyte counts in mild-to-moderate as compared to severely infected patients while both CD4+ and CD8+ counts demonstrated statistical significance in mild-moderate infected cases. Statistical significance was noted in D-dimer, CRP, and LDH levels also. CONCLUSION: Assessment of hematological and immunological parameters can be used to plan the management of COVID-19 patients.

Durvalumab-associated vasculitis presenting as 'the blue toe syndrome'.

Durvalumab is a selective, high-affinity human immunoglobulin monoclonal antibody in a class called check point inhibitors, that blocks PD-L1 on tumour cells. Despite clinical success in increasing progression-free survival rates in patients with stage III non-small-cell lung cancer, durvalumab has been associated with immune-related side effects such as pneumonitis and colitis. We present a case of an 84-year-old woman with acral vasculitis presenting as blue toe syndrome, associated with prolonged use of durvalumab. After 1 year of fortnightly durvalumab therapy postchemoradiation therapy, the patient came in with a left blue big toe, and later developed bilateral livedo racemosa. The diagnosis of durvalumab-associated vasculitis was made and treatment with prednisolone was started with clinical improvement.

Corona Virus (COVID-19) and its Impact on Health Care Workers.

Pandemics always come up with various life-threatening issues. COVID-19 outbreak came up with the same issues along with certain other problems involving public, administrative and healthcare sector concerns. It resembled the SARS outbreak but posed such challenges against the world that are uneasy to handle. The disease which started from Wuhan, China has now affected almost every country in a ruthless manner. Healthcare workers are working day and night just to protect the citizens despite being at high-risk exposure and they are being aimed by the virus due to shortage of Personal Protection Equipment kits. Not only this, but they are being brutally harassed by the patients themselves. Social, economic, psychiatric and many other factors are responsible for deteriorating the health of these frontline healthcare workers who are now being allegedly regarded as "Healthcare Warriors".