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Alzheimer’s disease (AD) is one of the major reasons for 60-80% cases of senile dementia occurring as a result of the accumulation of plaques and tangles in the hippocampal and cortical neurons of the brain leading to neurodegeneration and cell death. The other pathological features of AD comprise abnormal microvasculature, network abnormalities, interneuronal dysfunction, increased β-amyloid production and reduced clearance, increased inflammatory response, elevated production of reactive oxygen species, impaired brain metabolism, hyperphosphorylation of tau, and disruption of acetylcholine signaling. Among all these pathologies, Mitochondrial Dysfunction (MD), regardless of it being an inciting insult or a consequence of the alterations, is related to all the associated AD pathologies. Observed altered mitochondrial morphology, distribution and movement, increased oxidative stress, dysregulation of enzymes involved in mitochondrial functioning, impaired brain metabolism, and impaired mitochondrial biogenesis in AD subjects suggest the involvement of mitochondrial malfunction in the progression of AD. Here, various pre-clinical and clinical evidence establishing MD as a key mediator in the progression of neurodegeneration in AD are reviewed and discussed with an aim to foster future MD based drug development research for the management of AD.

Monoamine oxidase (MAO) is an enzyme that catalyzes the deamination of monoamines and other proteins. MAO’s hyperactivation results in the massive generation of reactive oxygen species, which leads to a variety of neurological diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and depression-like disorders. Although synthetic MAO inhibitors are clinically available, they are associated with side effects such as hepatotoxicity, cheese reaction, hypertensive crisis, and so on, necessitating the investigation of alternative MAO inhibitors from a natural source with a safe profile. Herbal medications have a significant impact on the prevention of many diseases; additionally, they have fewer side effects and serve as a precursor for drug development. This review discusses the potential of herbal MAO inhibitors as well as their associated mechanism of action, with an aim to foster future research on herbal MAO inhibitors as a potential treatment for neurological diseases.

Non-destructive test (NDT) is used to find the physical properties of concrete without any destruction to the structure. There are various methods of NDT in order to calculate the strength of concrete members. Hemp is a type of agro-waste which can be used to make Hemp concrete by mixing cement, aggregates, Hemp, admixtures and water in desired proportion. The aim of the study was to correlate the Ultrasonic Pulse Velocity (UPV) with compressive strength, in order to determine equations between direct UPV with indirect UPV and to develop correlation between direct UPV with Compressive strength. In this study, 6 cubes of Hemp concrete of size 150 mm X 150 mm X 150 mm were casted and cured for 7–28 days, dried and tested for direct UPV, indirect UPV and compressive strength. Then these values are correlated with each other to determine the association in direct UPV, indirect UPV and Compressive strength. The most excellent fit curve for compressive strength and NDT values were obtained and equations were derived. These equations will be able to determine the concrete relative strength element (new or existing structural member) without destruction.

Background: Data are limited regarding the use of implantable cardioverter–defibrillators (ICDs) in diverse populations. This study explores cardiovascular (CV) outcomes and mortality from ICD randomized controlled trials (RCTs), by sex, race, and age. Methods: Five electronic databases (PubMed, Emcare, Embase, MEDLINE, and Cumulative Index to Nursing & Allied Health Literature CINAHL) were searched for dates from their inception to July 12, 2021, for RCTs of ICD therapy in adult patients. Data were analyzed for clinical outcomes, including all-cause or CV death, and heart failure hospitalization (HFH). Results: Among 5 RCTs (mean age: 63 years; 78% male; 76% White) with moderate overall risk of bias, clinical outcomes in patients with an ICD (n = 3260) vs a control group (n = 3685) were compared. No between-group sex differences were observed for all-cause death (odds ratio [OR] 0.86, P = 0.51), CV death (OR 0.98, P = 0.96), HFH (OR 0.95, P = 0.87), or HFH and all-cause death (OR 0.83, P = 0.51) in the ICD group, in a comparison of male vs female sex. All-cause death (OR 1.20, P = 0.67) did not differ for White vs Black patients receiving ICD therapy. Outcomes data for other non-White, non-Black race groups were often unreported. Most RCTs originated in North America, had male leadership, and were evenly sponsored by industry vs peer-reviewed funding. Conclusions: Outcomes data are sparse, by sex, race, and age, in current RCTs evaluating ICD therapy. Although ICD patient outcomes did not significantly differ by sex or race, improved data analyses and reporting are needed to determine the relationship between these sociocultural factors and clinical outcomes among distinct ICD patient cohorts. Résumé: Contexte: Les données sur l’utilisation des défibrillateurs cardioverteurs implantables (DCI) dans diverses populations sont limitées. Cette étude porte sur les résultats cardiovasculaires (CV) et les décès liés aux DCI qui ont été signalés dans le cadre d'essais contrôlés randomisés (ECR), en fonction du sexe, de la race et de l’âge. Méthodologie: Des recherches ont été effectuées dans cinq bases de données électroniques (PubMed, EmCare, Embase, Medline et CINAHL [Cumulative Index to Nursing & Allied Health Literature]) en ciblant une période allant de la date de leur création jusqu’au 12 juillet 2021 afin de recenser les ECR menés chez des patients adultes ayant reçu un DCI. Les données ont été analysées en fonction des résultats cliniques, notamment les décès toutes causes confondues ou d’origine CV et les hospitalisations pour insuffisance cardiaque (hIC). Résultats: Cinq ECR (âge moyen des patients : 63 ans; 78 % d’hommes; 76 % de race blanche) présentant globalement un risque de biais modéré ont permis de comparer les résultats cliniques obtenus chez les patients ayant reçu un DCI (n = 3 260) et ceux du groupe témoin (n = 3 685). Aucune différence intergroupe entre les sexes n’a été observée pour les décès toutes causes confondues (rapport de cotes [RC] : 0,86, p = 0,51), les décès d’origine CV (RC : 0,98, p = 0,96) et les hIC (RC : 0,95, p = 0,87), ou les hIC et les décès toutes causes confondues (RC : 0,83, p = 0,51) au sein du groupe de patients ayant reçu un DCI, dans une comparaison entre les sexes. Aucune différence entre les patients de race blanche et de race noire ayant reçu un DCI n’a été notée pour ce qui est des décès toutes causes confondues (RC : 1,20, p = 0,67). Souvent, les données sur les résultats obtenus au sein de groupes de patients de race autre que blanche ou noire n’étaient pas signalées. La plupart des ECR avaient été menés en Amérique du Nord, étaient dirigés par des hommes et commandités à parts égales par l’industrie et des organismes offrant du financement approuvé par les pairs. Conclusions: Les ECR portant sur l’utilisation des DCI fournissent actuellement peu de données sur les résultats en fonction du sexe, de la race et de l’âge. Les résultats obtenus chez les patients ayant reçu un DCI ne différaient pas significativement selon le sexe ou la race. Néanmoins, des analyses de données et des rapports plus détaillés sont nécessaires pour déterminer la relation entre ces facteurs socioculturels et les résultats cliniques au sein de cohortes distinctes de patients ayant reçu un DCI.

Cancer treatment has become a major challenge amidst the resistance and relapse caused by the various treatments available. The PROteolysis TAargeting Chimera (PROTAC) technology involves the degradation of target protein against the inhibition by small drug molecules. The PROTACs with high potency and activity have been frequently reported; however, no PROTAC acting against cancer has reached the clinical trials. The concept of PROTACs involves the reduction in the disease-causing protein by its degradation through the ubiquitin-proteasomal enzyme system. This concept has attracted a lot of attention from both industry and academia due to its potential in drug discovery (in the form of PROTACs), which can conquer the resistance associated with current treatments of cancer. Thus, it is the need of the hour to identify and synthesize more PROTACs for a viable treatment of cancer. This article reviews the design, activity and effects produced in cancer by some recently developed PROTACs.

Inequity in healthcare utilization is typically measured as the unequal distribution of services by observable non-need indicators, such as income, after controlling for observable need indicators. However, important sources of unequal healthcare utilization are often unobserved. The unobserved element may reflect need factors, such as imperfectly measured severity of illness, that would predict greater utilization across different healthcare channels, but also based on choice, such as patient preferences to use a particular healthcare channel over an alternative one, which may differ in its effect between channels. Accounting for unobserved sources of utilization may, therefore, help to understand contradictory inequalities between different healthcare channels, such as pro-poor inequalities for general practitioner use and pro-rich inequalities for specialist visits. This paper uses survey data from the Household Income and Labour Dynamics in Australia and panel data methods to investigate if seemingly contradictory inequalities between different healthcare channels are explained by latent individual-level heterogeneity. Results show that unobserved individual-level heterogeneity affects inequities across different healthcare channels, providing indications that the unobserved element may primarily represent unobserved need.

Every aspect of the tourist experience has been transformed and automated due to the recent development and application of advanced technology like Artificial Intelligence and robotic services. Tourism and hospitality have seen tremendous changes due to the transformation brought about by the growth of information and communication technologies (ICT). This article will review current research and literature on Artificial Intelligence (AI) and robotics use in hotels and hospitality. The study will majorly centre on three filed of AI and automation applications. First, it explores the present position and current application of artificial intelligence and automation like robotics research in daily modern contemporary society, showcasing their use in each sector of the tourism and hospitality sectors; secondly, it analysed the Artificial intelligence and robotics impact on employment and job opportunities, consumers, and as well as businesses and society at large. Lastly, it examines the possible future trends of AI and robots in the tourism and hospitality sector to see what advantages or dangers may be derived from their use.

Today in the era of information and technology the whole scenario has been changed. Women have a multidimensional attitude and enjoy special place in the society by reaching all kinds of heights by their spectacular physical and mental performance in almost all possible fields. Problems of different age group of women are still present and the most suffering age group is forty plus due to change in reproductive life by cessation of menstruation causing untoward physical and mental agonies called menopause. Every woman faces various physiological and psychological changes during this change as part of hormonal de arrangement. The presence of regular menstruation indicates the starting of reproductive life of women and menopause indicates the declining fertility rate of female. Rajonivritti word is made up of two different words viz., ‘Rajah and Nivritti Rajah denoted as Aartava (menstrual blood) Nivritti as Uprama (cessation). In Ayurveda this phenomenon taken in different way not as a serious health problem. As Sushruta mentioned that menopause deals with Jarapakvya avastha of the body. Sometimes such disturbances attain the stage of disease or syndrome called Menopausal Syndromes accompanied by various vasomotor, psychological, genital, locomoter and G.I.T related symptoms.

PURPOSE OF REVIEW Liver disease (CFLD) as a complication of cystic fibrosis is recognized as a more severe disease phenotype in both children and adults. We review recent advances in understanding the disease mechanism and consider the implications of new strategies for the diagnosis and management of cystic fibrosis in those with evidence of clinically significant liver disease. RECENT FINDINGS Evidence suggests that the prevalence of CFLD has not declined with the introduction of newborn screening. Furthermore, children with CFLD, who have been diagnosed with cystic fibrosis following newborn screening continue to have a much higher mortality rate compared with those with no liver disease. There is further data suggesting noncirrhotic obliterative portal venopathy as the predominant pathological mechanism in the majority of children and young adults receiving a liver transplantation. Little progress has been made in developing an accurate noninvasive test for early diagnosis or monitoring disease progression in CFLD. The benefit of new modulator therapies is not well understood in those with established CFLD, whereas the risk of hepatotoxicity as a complication of treatment must be carefully monitored. SUMMARY Better understanding of the pathophysiology of CFLD would allow a standardized approach to diagnosis, with the potential to improve outcomes for those with CFLD.

Background: Cardiac resynchronization therapy (CRT) is beneficial in patients who have heart failure with reduced ejection fraction or arrhythmic events. However, most randomized controlled trials (RCTs) showing survival benefits primarily enrolled older white men. This study aims to evaluate CRT efficacy by sex, race, and age in RCTs. Methods: Five electronic databases (CINAHL, Embase, Emcare, Medline, and PubMed) were searched from inception to July 12, 2021 for RCTs with CRT in adult patients. Data were analyzed for clinical outcomes including all-cause or cardiovascular (CV) death, worsening heart failure (HF), and HF hospitalization (HFH) according to sex, race, and age. Results: Among six RCTs with up to moderate risk of bias, 54% (n = 3,630 of 6,682; mean age 64 years, 22% female, 8% black patients) had CRT device implantation. All-cause death (odds ratio [OR], 0.51; P = 0.053) was reduced in female versus male CRT patients, whereas CV death, HFH, or all-cause death with worsening HF or HFH did not differ significantly. No difference was seen in CRT patients for all-cause death and worsening HF (OR, 1.32; P = 0.46) among white vs black patients or for all-cause death and HFH (OR, 1.19; P = 0.55) among ≥ 65 versus < 65 years. Conclusions: Whereas all-cause death was lower in female CRT patients, other reported outcomes did not significantly differ by sex, race, or age. Only 6 studies partially reported outcomes. Thus, enhanced reporting and analyses are required to overcome such paucity of data to evaluate the impact of these factors on clinical outcomes in distinct patient cohorts with CRT indication. RÉsumÉ: Contexte: La thérapie de resynchronisation cardiaque (TRC) est salutaire chez les patients qui souffrent d’insuffisance cardiaque avec fraction d’éjection réduite ou qui subissent des épisodes arythmiques. Toutefois, la plupart des essais contrôlés randomisés (ECR) montrant des bienfaits en matière de survie ont été principalement menés chez des hommes blancs âgés. Cette étude vise à évaluer l’efficacité de la TRC en fonction du sexe, de la race et de l’âge des participants aux ECR. Méthodologie: Nous avons effectué des recherches dans cinq bases de données électroniques (CINAHL, Embase, Emcare, Medline et PubMed) en ciblant une période allant de la date de leur création jusqu’au 12 juillet 2021 afin de recenser les ECR menés chez des patients adultes ayant subi une TRC. Les données ont fait l’objet d’une analyse axée sur les résultats cliniques, notamment les décès toutes causes confondues ou d’origine cardiovasculaire (CV), l’aggravation de l’insuffisance cardiaque (IC) et les hospitalisations pour cause d’IC (HIC), en fonction du sexe, de la race et de l’âge des patients. Résultats: Dans six ECR présentant un risque de biais tout au plus modéré, 54 % des patients (n = 3 630 sur 6 682; âge moyen : 64 ans, 22 % de femmes, 8 % de patients noirs) étaient porteurs d’un dispositif de RC. Les décès toutes causes confondues (rapport de cotes [RC] : 0,51; p = 0,053) étaient moins nombreux chez les femmes que chez les hommes parmi les patients ayant subi une TRC. En revanche, aucune différence significative entre les deux sexes n’a été relevée en ce qui concerne les décès d’origine CV, les HIC ou les décès toutes causes confondues liés à l’aggravation de l’IC ou aux HIC. Au sein de la population ayant subi une TRC, aucune différence n’a été observée quant aux décès toutes causes confondues et à l’aggravation de l’IC (RC : 1,32; p = 0,46) chez les patients blancs par rapport aux patients noirs. Il y avait aussi absence de différence quant aux décès toutes causes confondues et aux HIC (RC : 1,19; p = 0,55) chez les patients âgés de 65 ans ou plus par rapport aux patients âgés de moins de 65 ans au sein de la même population. Conclusions: Les décès toutes causes confondues étaient moins nombreux chez les femmes qui avaient subi une TRC, mais les autres résultats rapportés ne différaient pas significativement selon le sexe, la race ou l’âge des patients. Seulement six études ont signalé partiellement les résultats. Des rapports et des analyses plus détaillés sont nécessaires pour remédier à la paucité des données et ainsi permettre d’évaluer l’effet des facteurs étudiés sur les résultats cliniques au sein de cohortes distinctes de patients chez qui la TRC est indiquée.

Temporary mechanical circulatory support (TMCS) provides short-term support to patients with or at risk of refractory cardiogenic shock. Although indications, contraindications, and compli...

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With recent advances in the pharmacological management of type 2 diabetes mellitus (T2DM), there is a growing need to understand which patients optimally benefit from these novel therapies. Various clinical clustering methodologies have emerged that utilise data-agnostic strategies to categorise patients that have similar clinical characteristics and outcomes; broadly, this characterisation is termed phenotyping. In patients with T2DM, we aimed to describe patient characteristics from phenotype studies, their cardiovascular risk profiles and the impact of antihyperglycemic treatment. Numerous phenotypic studies have been undertaken that have utilised a combination of clinical, biochemical, imaging and genetic variables. Each of these has produced phenotypes that display a spectrum of cardiovascular risk. Studies that aimed to describe pathophysiological phenotypes generally identified five phenotypes: autoimmune phenotype, insulin-related phenotypes (including permutations of insulin deficiency and resistance), obesity phenotype, ageing phenotype, and a sex-related phenotype. Studies examining risk profiles have demonstrated that across such phenotypes there is a spectrum of risk for diabetic complications. Few studies have examined treatment effects across these phenotypes, and thus provide little insights towards making phenotype-guided treatment decisions Clustering analyses in patients with T2DM have identified distinct phenotypes with unique risk profiles. Further studies are needed that harness the use of clinical, biochemical, imaging and genetic data to explore therapeutic heterogeneity and response to antihyperglycemic treatment across the spectrum of patient phenotypes.

Over the last decade multiple transcatheter mitral valve repair and replacement strategies have emerged, yet there is only one US Food and Drug Administration approved device, the MitraClip (Abbott Vascular, Inc., Santa Clara, California). Current guidelines support the use of the MitraClip in high or prohibitive surgical risk patients, but there are many patients that are not anatomically suited for the device. This review article discusses the approach to degenerative and functional mitral regurgitation in the high-prohibitive risk patient, how to choose transcatheter treatment options (both approved and investigational), and potential management for therapy failure.

Objective To detail clinical profile and outcome in children infected with SARS-CoV-2. Methods This retrospective study was undertaken at a tertiary care pediatric teaching hospital in Northern India. The data on clinical characteristics and outcome of children ( 10 y of age with malnutrition and comorbid illness. Supplementary Information The online version contains supplementary material available at 10.1007/s12098-021-03822-5.

Background Prescription information for many drugs entering the market lacks dosage guidance for hepatic impairment. Dedicated studies for assessing the fate of drugs in hepatic impairment commonly stratify patients using Child-Pugh score. Child-Pugh is a prognostic clinical score with limitations in reflecting the liver's metabolic capacity. Aims To demonstrate the need for better drug dosing approaches in hepatic impairment, summarise the current status, identify knowledge gaps related to drug kinetic parameters in hepatic impairment, propose solutions for predicting the liver disease impact on drug exposure and discuss barriers to dosing guidance in those patients. Methods Relevant reports on dosage adjustment in hepatic impairment were analysed concerning the prediction of the impairment impact on drug kinetics using physiologically-based pharmacokinetic (PBPK) modelling. Results PBPK models are suggested as a potential framework to understand drug clearance changes in hepatic impairment. Quantifying changes in abundance and activity of drug-metabolising enzymes and transporters, understanding the impact of shunting, and accounting for interindividual variations in drug absorption could help in extending the success of these models in hepatically-impaired populations. These variables might not correlate with Child-Pugh score as a whole. Therefore, new metabolic activity markers, imaging techniques and other scoring systems are proposed to either support or substitute Child-Pugh score. Conclusions Many physiological changes in hepatic impairment determining the fate of drugs do not necessarily correlate with Child-Pugh score. Quantifying these changes in individual patients is essential in future hepatic impairment studies. Further studies assessing Child-Pugh alternatives are recommended to allow better prediction of drug exposure.

The present study explored the association between daily ambient air pollution and daily emergency room (ER) visits due to acute respiratory symptoms in children of Delhi. The daily counts of ER visits (ERV) of children (≤15 years) having acute respiratory symptoms were obtained from two hospitals of Delhi for 21 months. Simultaneously, data on daily concentrations of particulate matter (PM10 and PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3) and weather variables were provided by the Delhi Pollution Control Committee. K-means clustering with time-series approach and multi-pollutant generalized additive models with Poisson link function was used to estimate the 0-6-day lagged change in daily ER visits with the change in multiple pollutants levels. Out of 1,32,029 children screened, 19,120 eligible children having acute respiratory symptoms for ≤2 weeks and residing in Delhi for the past 4 weeks were enrolled. There was a 29% and 21% increase in ERVs among children on high and moderate level pollution cluster days, respectively, compared to low pollution cluster days on the same day and previous 1-6 days of exposure to air pollutants. There was percentage increase (95% CI) 1.50% (0.76, 2.25) in ERVs for acute respiratory symptoms for 10 μg/m3 increase of NO2 on previous day 1, 46.78% (21.01, 78.05) for 10 μg/m3 of CO on previous day 3, and 13.15% (9.95, 16.45) for 10 μg/m3 of SO2 on same day of exposure. An increase in the daily ER visits of children for acute respiratory symptoms was observed after increase in daily ambient air pollution levels in Delhi.

Underground coal fires (UCFs) cause remarkable loss of energy resources and significant environmental pollution. Due to the limited capacity of oxygen transport, the inception and development of UCFs represent a very unique mode of coal–oxygen reactions. Therefore, a high-volatile flammable coal sample is thermally analyzed with the combined TGA–DSC approach under four oxygen concentrations (21%, 15%, 9% and 3%) and three heating rates (1 °C min−1, 2 °C min−1 and 5 °C min−1). It is found that the oxygen concentration does not significantly influence the early (low-temperature) stage of coal–oxygen reactions. With the decrease in oxygen concentration, the intensity of the exothermic reactions is reduced and the duration of reactions is extended. Based on the experimental results, the apparent activation energy is calculated. The variation of the apparent activation energy reflects the different reaction stages: volatiles burning and char oxidation, which is verified by the TGA–DSC results. Under the extreme condition of 3% oxygen concentration, a very distinct macroscopic thermochemical behavior is observed, and the limited oxygen supply controls the reaction rate throughout the entire process, which qualitatively explains the persistency of the burning phenomena in most UCFs.

The present study has been carried out in South-Western and Central agro climatic regions of Punjab state for studying the cost-returns and marketing pattern of dairy and fish farming based integrated model. It was observed from the study that the net returns from crop farming was ` Rs.65,852 per farm per year, whereas the net returns on per acre basis were found to be ` Rs.32,328 per acre per year. Further, the net returns from dairy farming were found to be ` Rs. 4,928 per farm per year and ` Rs.8,822 per acre per year. From fish farming, net returns were observed to be ` Rs. 2, 47, 396 per farm per annum and ` Rs.84,725 per acre per year. Total profitability of the crop-dairy-fish farming integrated model was observed to be `Rs. 4,58,176 per farm per annum, and net returns per acre from this model were ` Rs. 53,030 per year. Hence, it may be inferred that dairy and fish farming are more profitable as compared to crops and when adopted in an integrated manner along with crops, can enhance the overall profitability of the farm by efficient utilisation of farm waste products and by-products. At the same time, there is need of creating awareness among the farmers regarding the importance of dairy and fish farming based integrated models, so that they can adopt these types of models for enhancing their income levels.

Background: The hormone ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR) are expressed in myocardium. GHSR binding activates signalling pathways coupled to cardiomyocyte survival and contractility. These properties have made the ghrelin-GHSR axis a candidate for a biomarker of cardiac function. The dynamics of ghrelin-GHSR are altered significantly in late stages of heart failure (HF) and cardiomyopathy, when left ventricular (LV) function is failing. We examined the relationship of GHSR with ghrelin in cardiac tissue from patients with valvular disease with no detectable changes in LV function. Methods: Biopsy samples from the left ventricle and left atrium were obtained from 25 patients with valvular disease (of whom 13 also had coronary artery disease) and preserved LV ejection fraction, and compared to control samples obtained via autopsy. Using quantitative confocal fluorescence microscopy, levels of GHSR were determined using [Dpr3(n-octanoyl),Lys19(sulfo-Cy5)]ghrelin(1-19), and immunofluorescence determined ghrelin, the heart failure marker natriuretic peptide type-B (BNP), and contractility marker sarcoplasmic reticulum ATPase pump (SERCA2a). Results: A positive correlation between GHSR and ghrelin was apparent in only diseased tissue. Ghrelin and BNP significantly correlated in the left ventricle and strongly colocalized to the same intracellular compartment in diseased and control tissue. GHSR, ghrelin, and BNP all strongly and significantly correlated with SERCA2a in the left ventricle of diseased tissue only. Conclusions: Our results suggest that the dynamics of the myocardial ghrelin-GHSR axis is altered in cardiovascular disease in the absence of measurable changes in heart function, and might accompany a regional shift in endocrine programming. Résumé: Contexte: L’hormone ghréline et son récepteur, le récepteur sécrétagogue de l’hormone de croissance (GHSR, de l’anglais growth hormone secretagogue receptor), sont exprimés dans le myocarde. La liaison au récepteur GHSR active les voies de signalisation associées à la survie et à la contractilité des cardiomyocytes. Ces propriétés font de l’axe ghréline-récepteur GHSR un bon candidat biomarqueur de la fonction cardiaque. En effet, la dynamique de cet axe est considérablement altérée aux stades avancés de l’insuffisance cardiaque et de la cardiomyopathie, lorsque la fonction ventriculaire gauche décline. Nous avons donc étudié la relation entre le récepteur GHSR et la ghréline dans le tissu cardiaque de patients présentant une valvulopathie sans changements détectables dans la fonction ventriculaire gauche. Méthodologie: Des échantillons de tissus du ventricule et de l’oreillette gauches ont été prélevés par biopsie chez 25 patients présentant une valvulopathie (dont 13 avaient aussi une coronaropathie) et une fraction d’éjection ventriculaire gauche préservée, puis comparés avec des échantillons témoins prélevés à l’autopsie. Les taux du récepteur GHSR ont été mesurés par microscopie en fluorescence confocale quantitative à l’aide de [Dpr3(n-octanoyl),Lys19(sulfo-Cy5)] ghréline(1-19); les taux de ghréline, de peptide natriurétique de type B (BNP, un marqueur de l’insuffisance cardiaque), et de pompe ATPase du réticulum sarcoplasmique (SERCA2a; un marqueur de la contractilité) ont quant à eux été mesurés par immunofluorescence. Résultats: Nous avons noté une corrélation positive entre le récepteur GHSR et la ghréline uniquement dans les tissus lésés. Il existe une corrélation significative entre les taux de ghréline et de BNP dans le ventricule gauche, les deux substances étant fortement localisées dans le même compartiment intracellulaire, tant dans les tissus malades que dans les tissus témoins. Le récepteur GHSR, la ghréline et le BNP sont tous fortement et significativement corrélés avec la SERCA2a SERCA2a dans le tissu ventriculaire gauche malade seulement. Conclusions: Nos résultats semblent indiquer que la dynamique de l’axe ghréline-récepteur GHSR dans le myocarde est altérée en cas de maladie cardiovasculaire même en l’absence de changements mesurables de la fonction cardiaque, et que cette altération pourrait être attribuable à une modification régionale de la programmation endocrinienne.

The multicenter prospective Lipid Rich Plaque (LRP) registry showed that nonculprit (NC) lipid-rich plaques identified by near-infrared spectroscopy (maxLCBI4mm >400) with an intravascular ultrasound plaque burden (PB) >70% and/or minimum lumen area (MLA) 400) was 31.9% in both groups. Finally, there was no difference in NC-MACE at 2 years’ follow-up, although within each group (stable versus acute coronary syndrome), the NC-MACE rate associated with maxLCBI4mm >400 was significantly higher than maxLCBI4mm ≤400 (stable 13.8% vs 6.5%; acute patients 11.6% vs 6.3%, respectively). In conclusion, in patient groups that present with stable angina pectoris or silent ischemia versus acute coronary syndrome, the NC lipidic content was similar, as was NC-MACE, through 2 years of follow-up.

Development of cost effective early warning systems is of paramount importance for real time monitoring of natural hazards such as Landslides, Floods, Earthquake etc. The present research work discusses about the design and development of cost effective early warning system for monitoring shallow debri landslides. The warning system consist of field unit and remote network interface. The field system includes the rainfall, temperature, humidity, soil temperature, soil moisture and Tiltmeter as primary sensors for monitoring the landslide movements with an independent power supply of 50 W solar panel. The datasets that are received are stored in the local data logger with the help of microsd card. Real time monitoring of the datasets and analysis was made possible by storing the datasets in remote Database Management System. These datasets are transmitted via the Global System for Mobile communication module installed at the field unit. In order to convey the alerts during emergency time a simple visual message has been adopted for the current model. Level I, Level II and Level III, Level I being the threshold values are within the desired limit and actions are not necessary and Level III denotes threshold values have exceeded the set limit and warning are issued to local stake holders. A pilot study of the Early Warning System has been installed on site for quality checks of the sensor & data and the results were monitored. The model developed not only can address the early warning signs of mass movement but also can be calibrated to predict flood in major streams based on rainfall intensity.

A 50-year-old male diabetic, hypertensive and chronic smoker presented with complex aortic, splanchnic aneurysms with impending rupture of iliac artery aneurysm, underwent coiling of celiac artery, internal iliac artery, and fenestrated/chimney endovascular aortic repair. One month later, the patient landed in an emergency due to bleeding complications of common hepatic artery and gastroduodenal artery aneurysms, which were managed successfully using endovascular techniques. The mayhem of progressive nature of the disease in the patient continued as he had left lower limb ischemia due to occlusion of the iliac artery and iliac limb of the aortic graft device as he continued to smoke. All of the above sequences of events occurred over a period of 5 years. He also developed a giant aneurysm of left anterior descending of 6.8 cm diameter, which had to be repaired by open surgical technique. The patient has been followed up for 6 years since his first presentation, and he was managed successfully from all the catastrophe of events using endovascular techniques. Giant coronary artery aneurysm with previous aneurysms at multiple sites is quite unusual and rare. Currently, there is no consensus regarding the clinical characteristics, diagnostic method, and the treatment of these cases.

The Government of India has developed a National Strategic Plan for tuberculosis (TB) elimination by 2025, five years ahead of the global target set by the World Health Organization (WHO). For achieving these targets there has been a paradigm shift in the diagnostic and treatment strategies of TB at all ages. This update summarizes the specific changes in pediatric TB management in light of the guidelines developed by National Tuberculosis Elimination Program and Indian of Academy of Pediatrics.

Isolated pleural effusion is a rare manifestation of filariasis that mimics tuberculosis, especially in endemic regions. We describe a case of lymphocytic and exudative pleural effusion showing microfilaria on pleural fluid cytology. A retrospective review of all cases of filarial pleural effusion reported after 2000 was conducted to evaluate the association between filariasis and pleural effusion as well as to screen the features that can help in accurate detection of these patients. The analysis suggested a causal association between the parasite and the development of pleural effusion with a high sensitivity of pleural fluid cytology for diagnosis.

Bull fertility is considered an indispensable trait, as far as farm economics is concerned since it is the successful conception in a cow that provides calf crop, along with the ensuing lactation. This ensures sustainability of a dairy farm. Traditionally, bull fertility did not receive much attention by the farm managers and breeding animals were solely evaluated based on phenotypic predictors, namely, sire conception rate and seminal parameters in bull. With the advent of the molecular era in animal breeding, attempts were made to unravel the genetic complexity of bull fertility by the identification of genetic markers related to the trait. Marker-Assisted Selection (MAS) is a methodology that aims at utilizing the genetic information at markers and selecting improved populations for important traits. Traditionally, MAS was pursued using a candidate gene approach for identifying markers related to genes that are already known to have a physiological function related to the trait but this approach had certain shortcomings like stringent criteria for significance testing. Now, with the availability of genome-wide data, the number of markers identified and variance explained in relation to bull fertility has gone up. So, this presents a unique opportunity to revisit MAS by selection based on the information of a large number of genome-wide markers and thus, improving the accuracy of selection.

The performances of parabolic dish collector systems depend on the losses encountered during converting solar energy into thermal energy. It encompasses optical losses from the reflector and heat losses through the solar receiver. The geometry and surface properties of the receiver were seen considerably influencing the system performance. Thermally conductive copper fins (conical shaped, tip/cone angle 30°) have been fixed inside the cavity surface for three different pitch values e.g. 12.5 mm, 22 mm and 44 mm. During brazing operation, a selective Copper Oxide (CuO) surface was formed inside of the cavity, on account of heating. The system collection efficiency values obtained using finned cavities were compared with that of smooth (conventional) one. Performance improvement of about 23.56% and 31.35% (on average) over a smooth cavity was noticed after providing conical protrusions on the radiative surface of the modified cavity receiver, with medium and higher heat boundary conditions. The percentage contributions of heat losses by conduction, convection, and radiation modes, from the examined cavities, were obtained as 1.4–3.2%, 70–75%, and 22–28% of the total losses, respectively, in case of medium irradiation concentration. The energy concentration was seen influencing these contributions of heat losses from the receivers. Mathematical analysis is also presented for comparing one of the experimental test situations outcomes.

Background/Purpose: The Lipid Rich Plaque (LRP) study demonstrated the association between coronary plaque lipid content and outcomes. In this LRP substudy, we assessed the impact of optimal medical therapy (OMT) on the occurrence of non-culprit major adverse cardiac events (NC-MACE). Advanced intracoronary imaging modalities are able to identify patients with vulnerable coronary lesion morphology associated with future events.Methods/Materials: A total of 1270 patients who underwent cardiac catheterization for suspected coronary artery disease (CAD) with evaluable maxLCBI4mm in non-culprit vessels and known medical therapy after discharge were followed for 2 years. OMT was defined as the use of a statin and dual antiplatelet therapy (DAPT).Results: Among the 1270 patients included in this substudy, 1110 (87.7%) had PCI for an index event, and 1014 (80%) patients received OMT. Estimated cumulative incidence functions of NC-MACE did not differ significantly between patients treated with or without OMT (log-rank p-value = 0.876). In patients labeled high risk (maxLCBI4mm > 400), cumulative incidence function also did not differ between patients treated with vs without OMT (log-rank p-value = 0.19).Conclusions: In the current LRP analysis, we could not identify a beneficial effect of OMT in the reduction of NC-MACE rate, even in patients with high-risk plaques during 24-month follow-up.

Right ventricular (RV) failure remains a major complication after surgical implantation of a left ventricular assist device (LVAD). While the use of a percutaneous RV assist device has been described as a short‐term bridge to recovery in end‐stage heart failure patients with early post‐operative RV failure after index LVAD implant, management of refractory late RV failure remains challenging in these patients. We report the first successful case of extended Impella RP use as a safe and effective bridge to orthotopic heart transplant in an LVAD patient with refractory, haemodynamically significant late RV failure. The Impella RP provided support for 37 days. Haemodynamically intolerant arrhythmia precluded use of inotropic support. No adverse complications related to percutaneous Impella RP support were seen. We also review potential considerations for mechanical circulatory support strategies in this setting: central RV assist device cannulation requires sternotomy incision that can impact subsequent cardiac surgeries, while percutaneous Protek Duo insertion requires adequate vessel size and patency. With an LVAD in situ, veno‐arterial extracorporeal membrane oxygenation was not considered for isolated RV support in this case. The patient is currently over 6 months post‐orthotopic heart transplant.

Novel coronavirus (COVID-19) is a highly contagious virus that originated from China and has become a major threat in the current time Presently, finding an effective treatment strategy for COVID-19 is in infancy Worldwide, numerous clinical trials employing different treatment strategies (antiviral drugs and vaccines) are in progress to develop an effective therapeutic regimen against COVID-19 Literature related to the epidemiology, mortality, pathogenicity, treatment strategies and clinical data was studied and database was collected using various search engines such as j-gate, google scholar, scihub, pubmed, sciencedirect etc The present review systematically summarises the published information about epidemiology, various stages of pandemic, mortality, pathogenicity, modes of transmission, clinical characteristics, methods of prevention, ongoing treatment strategies and drugs under clinical trials associated with COVID-19 with a hope to avoid possible threatening of the lives of millions of human beings and provide directions for future studies © 2020 The Authors

Background Long-term outcome after subarachnoid hemorrhage, beyond the first few months, is difficult to predict, but has critical relevance to patients, their families, and carers. Objective To assess the performance of the Subarachnoid Hemorrhage International Trialists (SAHIT) prediction models, which were initially designed to predict short-term (90 d) outcome, as predictors of long-term (2 yr) functional outcome after aneurysmal subarachnoid hemorrhage (aSAH). Methods We included 1545 patients with angiographically-proven aSAH from the Genetic and Observational Subarachnoid Haemorrhage (GOSH) study recruited at 22 hospitals between 2011 and 2014. We collected data on age, WNFS grade on admission, history of hypertension, Fisher grade, aneurysm size and location, as well as treatment modality. Functional outcome was measured by the Glasgow Outcome Scale (GOS) with GOS 1 to 3 corresponding to unfavorable and 4 to 5 to favorable functional outcome, according to the SAHIT models. The SAHIT models were assessed for long-term outcome prediction by estimating measures of calibration (calibration slope) and discrimination (area under the receiver-operating characteristic curve [AUC]) in relation to poor clinical outcome. Results Follow-up was standardized to 2 yr using imputation methods. All 3 SAHIT models demonstrated acceptable predictive performance for long-term functional outcome. The estimated AUC was 0.71 (95% CI: 0.65-0.76), 0.73 (95% CI: 0.68-0.77), and 0.74 (95% CI: 0.69-0.79) for the core, neuroimaging, and full models, respectively; the calibration slopes were 0.86, 0.84, and 0.89, indicating good calibration. Conclusion The SAHIT prediction models, incorporating simple factors available on hospital admission, show good predictive performance for long-term functional outcome after aSAH.

Ball-Screw is a mechanical actuator that transforms the rotational motion of the motor into a linear motion of drive. The ball-screw is commonly used in industrial precision machines and due to this very reason it had been a common topic of research for many scholars, as precision in motion renders to precision in work directly. In this paper, some of the work done by different research scholars on different parametric aspects of ball screw had been discussed alongside optimization of ball screw diameter. The aspects which had been reviewed are elastic deformation & stiffness in ball screw, feed velocity and preloading, preload control in ball screw and various other aspects of preloading such as loss detection. Furthermore, the Finite elemental method had been applied to find the suitable diameter of the ball screw to render minimum deflection and stress value possible with the chosen material.

Cardiac amyloidosis results in an infiltrative restrictive cardiomyopathy, with a number of characteristic features: biventricular hypertrophy, abnormal myocardial global longitudinal strain with relative apical sparing, biatrial dilation, and small pericardial effusion along with conduction abnormalities. Amyloid deposits leading to hemodynamically significant valvular heart disease are very rare. We describe a rare case of concomitant moderately severe tricuspid and mitral valve stenosis because of ongoing amyloid deposition in a patient with progressive multiple myeloma and fat pad biopsy‐proven light chain amyloidosis. Worsening infiltrative cardiomyopathy and valvulopathy despite evidence‐based chemotherapy and heart failure pharmacotherapy led to end‐stage disease and death. Valvular involvement in cardiac amyloidosis requires early recognition of the underlying disease condition to guide directed medical therapy and prevent its progression. In this instance, valvuloplasty or valve replacement is not a viable option.

We explore the global evidence of major health crisis potential impacts and the factors influencing the mental health outcomes among the population during the outbreak of COVID-19. Preparation measures for a COVID-19 focus on rapid quarantine of social isolation and economic concerns have risen metal health considerations that become an integrated part of the pandemic outbreak. This outbreak of novel Coronavirus disease (COVID-19) pandemic is swayed an overall 213 countries, areas or territories, with over 2,921,439 confirmed cases and 203,289 confirmed deaths reported till 26 April 2020. This created a lot of strain and fear; fear of falling ill and dying of being infected leading to heightened levels of insurmountable psychological pressure. This scrutiny attempt to assess the widespread outbreaks of COVID-19 on mental health professionals, healthcare workers and general population in association with adverse mental health sequelae like generalized anxiety disorder (GAD), depressive symptoms, insomnia, panic attacks, post-traumatic stress disorder, OCD, suicidal behavior, delirium, psychosis, harmful alcohol consumption, and drug use. There is a need for more evocative exploration to intensify awareness to address the potential psychological and behavioral risks that will remain elevated as long as the COVID-19 pandemic continues in the community. In conclusion, incessant surveillance of the subsyndromal mental health problems for outbreaks should be part of galvanized global action during the quarantine.

PurposeChimeric antibody Miltuximab®, a human IgG1 engineered from the parent antibody MIL-38, is in clinical development for solid tumour therapy. Miltuximab® targets glypican-1 (GPC-1), a cell surface protein involved in tumour growth, which is overexpressed in solid tumours, including prostate cancer (PCa). This study investigated the potential of89Zr-labelled Miltuximab® as an imaging agent, and177Lu-labelled Miltuximab® as a targeted beta therapy, in a mouse xenograft model of human prostate cancer.MethodsMale BALB/c nude mice were inoculated subcutaneously with GPC-1-positive DU-145 PCa cells. In imaging and biodistribution studies, mice bearing palpable tumours received (a) 2.62 MBq [89Zr]Zr-DFO-Miltuximab® followed by PET-CT imaging, or (b) 6 MBq [177Lu]Lu-DOTA-Miltuximab® by Cerenkov imaging, and ex vivo assessment of biodistribution. In an initial tumour efficacy study, mice bearing DU-145 tumours were administered intravenously with 6 MBq [177Lu]Lu-DOTA-Miltuximab® or control DOTA-Miltuximab® then euthanised after 27 days. In a subsequent survival efficacy study, tumour-bearing mice were given 3 or 10 MBq of [177Lu]Lu-DOTA-Miltuximab®, or control, and followed up to 120 days.ResultsAntibody accumulation in DU-145 xenografts was detected by PET-CT imaging using [89Zr]Zr-DFO-Miltuximab® and confirmed by Cerenkov luminescence imaging post injection of [177Lu]Lu-DOTA-Miltuximab®. Antibody accumulation was higher (% IA/g) in tumours than other organs across multiple time points. A single injection with 6 MBq of [177Lu]Lu-DOTA-Miltuximab® significantly inhibited tumour growth as compared with DOTA-Miltuximab® (control). In the survival study, mice treated with 10 MBq [177Lu]Lu-DOTA-Miltuximab® had significantly prolonged survival (mean 85 days) versus control (45 days), an effect associated with increased cancer cell apoptosis. Tissue histopathology assessment showed no abnormalities associated with [177Lu]Lu-DOTA-Miltuximab®, in line with other observations of tolerability, including body weight stability.ConclusionThese findings demonstrate the potential utility of Miltuximab® as a PET imaging agent ([89Zr]Zr-DFO-Miltuximab®) and a beta therapy ([177Lu]Lu-DOTA-Miltuximab®) in patients with PCa or other GPC-1 expressing tumours.

Background Repeated failure to rescue the damaged retinal ganglion cells (RGCs) by various drugs has warranted the need to screen common herbal compounds available in the form of various eye formulations for their efficacy. Objective We aimed to investigate the neuroprotective effect of pretreatment with aqueous extract of A. cepa in Ischemia/Reperfusion (I/R) induced retinal injury. Methods Ischemia was induced for 2 h by pterygopalatine artery (PPA) ligation in C57BL/6J mice, followed by reperfusion. The neuroprotective role of oral pretreatment with aqueous extract of A. cepa (300 mg/kg) was analyzed with respect to control and injury only group at 7, 14, and 28 day after the surgery for expression of different genes in the retina by Real-Time PCR. Results Molecular analysis at different time points showed increased expression of BCl-2, GDNF, GFAP, and Brn3b in the retina at 14 and 28 day after A. cepa treatment in comparison to the injury alone group. However, at shorter time point (7th day), the expression of these genes was pronounced in the injury only group in comparison to the injury and pretreated group. Conclusion Pretreatment with aqueous extract of A. cepa may protect from the neuronal damage in I/R-induced retinal injury in mice by altering the expression of neurotrophic factor.

ObjectiveAfter aneurysmal subarachnoid haemorrhage (aSAH), extracellular haemoglobin (Hb) in the subarachnoid space is bound by haptoglobin, neutralising Hb toxicity and helping its clearance. Two exons in the HP gene (encoding haptoglobin) exhibit copy number variation (CNV), giving rise to HP1 and HP2 alleles, which influence haptoglobin expression level and possibly haptoglobin function. We hypothesised that the HP CNV associates with long-term outcome beyond the first year after aSAH.MethodsThe HP CNV was typed using quantitative PCR in 1299 aSAH survivors in the Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study, a retrospective multicentre cohort study with a median follow-up of 18 months. To investigate mediation of the HP CNV effect by haptoglobin expression level, as opposed to functional differences, we used rs2000999, a single nucleotide polymorphism associated with haptoglobin expression independent of the HP CNV. Outcome was assessed using modified Rankin and Glasgow Outcome Scores. SAH volume was dichotomised on the Fisher grade. Haemoglobin-haptoglobin complexes were measured in cerebrospinal fluid (CSF) of 44 patients with aSAH and related to the HP CNV.ResultsThe HP2 allele associated with a favourable long-term outcome after high-volume but not low-volume aSAH (multivariable logistic regression). However rs2000999 did not predict outcome. The HP2 allele associated with lower CSF haemoglobin-haptoglobin complex levels. The CSF Hb concentration after high-volume and low-volume aSAH was, respectively, higher and lower than the Hb-binding capacity of CSF haptoglobin.ConclusionThe HP2 allele carries a favourable long-term prognosis after high-volume aSAH. Haptoglobin and the Hb clearance pathway are therapeutic targets after aSAH.

Aim: The study was aimed to evaluate the role of two-dimensional (2D) perfusion angiography (PA) as a predictor in wound healing outcomes in patients of critical limb ischemia. Subject and Methods: It was a pilot study conducted over a period of 16 months after taking informed consent and institutional ethical clearance. The study included 40 patients of which 8 were lost to follow-up, hence the prospective data of 32 patients was collected and analyzed. Patients were subjected to endovascular intervention and 2D perfusion software was applied to the digital subtraction angiography images and its parameters were assessed. Transcutaneous oxygen tension (TcPO2) was measured pre- and postintervention and patients were closely followed up for the time taken for wound healing. Results: The median age was 62 years ranging from 30 to 85 years. Most common comorbidity was diabetes (21/32 patients). The mean Ankle–Brachial Index in the study was 0.55 and mean TcPO2 at admission was 26.5 mm of Hg. Most common involved angiosome was percutaneous transluminal angioplasty angiosome. Fifteen patients underwent direct, 9 indirect, and remaining 8 patients underwent revascularization in both territories. The mean percent improvement in TcPO2 was higher in indirect when compared to direct revascularization but it was not statistically significant. The time taken in wound healing was significantly higher in diabetics when compared to nondiabetics with P = 0.03. Most reliable parameter in 2D PA was area under the curve (AUC) which correlated with increase in volume of tissue perfusion. Patients with >100% improvement in AUC showed significantly better wound healing rates when compared to patients with

The review study considers the three-dimensional printing for anatomical simulations and their potential surgical applications. Three-dimensional (3D) printing has entirely transform the current era with its state-of-art usefulness and applications. The functional usability of three-dimensional printed models has been mentioned for orthopaedic, neurosurgery, heart valve surgery, and malignant tissues. Surgical planning of congenital anomalies has also pondered. By 3D printed models, surgical anatomical teaching methods have been explained. The key significance of 3D printed models during treatment of benign and cancerous tumors have been pointed with the conception of bone grinding. In final section, the complications and merits of 3D printed models in surgery have been postulated along with the ethical concerns associated with 3D printed models.

The cultural heritage has its importance due to the information communicated by the heritage to the future generations. It is difficult to preserve cultural heritage over the centuries because of their volatile nature. In this paper, the preservation aids are considered for sculptures. The sculpture also includes the type of monument. The challenges are face deterioration during logistic and handling. Hence, it destroys the information carried by sculpture. In addition, the knowledge about materials used for construction of these sculptures help in maintenance of these sculpture. It helps in reconstructing the shape and color, which have been damaged earlier. The common techniques reported in the literature for broken structure and material estimation are optical coherence tomography (OCT), X-ray, THz scanning and Raman spectroscopy. These techniques used for retrieving material information are not portable and are costlier. Thus, the need is established in this paper for the device offering 3D scanning along with the material details of each scanned pixel. This paper aims at material estimation of old age sculptures from 11th century CE and 13th century CE housed at Government Museum and Art Gallery, Chandigarh, India using radio frequency technique. The device captures the 3D scanning of the sculptures to maintain its heritage for a longer time. Further, the device needs to be portable and affordable so that it can be provided to various stakeholders of culture heritage preserve.