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BACKGROUND: The etiology of atraumatic rotator cuff tears is not completely understood. Limited data suggest the role of genetic and familial predisposition in the etiology of rotator cuff tears. The purpose of this study was to assess whether there is an increased likelihood of rotator cuff tears in family members of patients with rotator cuff tears vs. those without tears. This would provide evidence for whether there is an association between familial predisposition and rotator cuff tearing. METHODS: Patients presenting to a shoulder clinic were recruited in this study. They provided information on personal medical history, shoulder symptoms, and family history of rotator cuff tears. The diagnosis of rotator cuff tears was based on imaging (magnetic resonance imaging or computed tomography arthrogram) confirmation of a structural defect in the rotator cuff. The association between family history of rotator cuff problems and the likelihood of an imaging-confirmed rotator cuff tear diagnosis was evaluated using multivariate logistic regression, adjusting for age, sex, race/ethnicity, cigarette smoking, hypertension, diabetes, and depression. RESULTS: In our cohort of 2335 patients, 52.6% (n = 1229) of patients had a rotator cuff tear. Among patients with tears, 17.9% (n = 0220) of patients reported a family history of rotator cuff issues vs. 11.1% (n = 123) in patients without tears. A family history of rotator cuff problems was significantly associated with the diagnosis of an imaging-confirmed rotator cuff tear (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.71, 2.95). Other confounding variables such as increasing age (OR 1.06, 95% CI 1.05, 1.07) and Hispanic race/ethnicity as compared to non-Hispanic white race/ethnicity (OR 1.48, 95% CI 1.07, 2.05) were significantly associated with rotator cuff tears. Sex, smoking, hypertension, diabetes, and depression were not significantly associated with rotator cuff tearing. CONCLUSION: Our study shows that individuals with rotator cuff tears were more than 2 times as likely to have a family member with a tear as compared to patients without tears. Increasing age and patients who identified as being of Hispanic ancestry were also significantly associated with higher odds of rotator cuff tears. LEVEL OF EVIDENCE: Level III; Retrospective Case-Control Design; Prognosis Study

A novel series of 4-(1-methyl-1H-indol-3-yl)-6-(methylthio) pyrimidine-5-carbonitriles (4a–i) was synthesized and evaluated for anticancer potential against cell lines for breast cancer. Compounds 4b, 4e, and 4h exhibited prominent cytotoxicity against human breast carcinoma MCF-7 cell line with GI50 of 2.0, 0.5, and 0.5 µM, respectively. Molecular docking study against EGFR tyrosine kinase could provide valuable insights into the plausible mechanism of action. The compounds could bind with significantly high binding affinity and their binding affinity scores could correlate well with the observed anticancer activity. Furthermore, compounds 4a, 4c, 4e, 4g, and 4i exhibited significant inflammatory activities as well which could expand the therapeutic domain of this novel series.

Epilepsy is a gathering of ongoing neurological problems described by intermittent, unconstrained, and unusual seizures. It is one of the most widely recognized neurological messes, influencing a huge number of individuals around the world. A biomarker is characterized as a dispassionately estimated normal for an ordinary or obsessive natural interaction. Recognizable proof and legitimate approval of biomarkers of epileptogenesis, the improvement of epilepsy, and ictogenesis, the affinity to create unconstrained seizures, may foresee the improvement of an epilepsy condition; recognize the presence and seriousness of tissue equipped for producing unconstrained seizures; measure movement after the condition is set up; furthermore, decide pharmacoresistant. Such biomarkers could be utilized to make creature models for more savvy screening of potential antiepileptogenic and antiseizure medications and gadgets and to lessen the expense of clinical preliminaries by enhancing the preliminary populace and going about as proxy markers to abbreviate the preliminary span. The destinations of the biomarker subgroup for the London Studio were to characterize approaches for distinguishing conceivable biomarkers for these reasons. Examination to recognize dependable biomarkers may likewise uncover basic instruments that could serve as helpful focuses for the improvement of new antiepileptogenic and antiseizure compounds.

With an estimated failure rate of about 90%, immunotherapies that are intended for the treatment of solid tumors have caused an anomalous rise in the mortality rate over the past decades. It is apparent that resistance towards such therapies primarily occurs due to elevated levels of HIF-1 (Hypoxia-induced factor) in tumor cells, which are caused by disrupted microcirculation and diffusion mechanisms. With the advent of nanotechnology, several innovative advances were brought to the fore; and, one such promising direction is the use of perfluorocarbon nanoparticles in the management of solid tumors. Perfluorocarbon nanoparticles enhance the response of hypoxia-based agents (HBAs) within the tumor cells and have been found to augment the entry of HBAs into the tumor micro-environment. The heightened penetration of HBAs causes chronic hypoxia, thus aiding in the process of cell quiescence. In addition, this technology has also been applied in photodynamic therapy, where oxygen self-enriched photosensitizers loaded perfluorocarbon nanoparticles are employed. The resulting processes initiate a cascade, depleting tumour oxygen and turning it into a reactive oxygen species eventually to destroy the tumour cell. This review elaborates on the multiple applications of nanotechnology based perfluorocarbon formulations that are being currently employed in the treatment of tumour hypoxia.

The production of major field crops, namely, rice, wheat, and maize, is highly vulnerable to climatic factors and abiotic stresses. In the present era of climate change, abiotic factors emerged as limiting concerns for flourishing the growth and yield. Among the abiotic factors, temperature, soil moisture, salinity, elevated carbon dioxide levels and solar radiation are the prime concerns for affecting the productivity of major cereals. To combat with the situation, it is necessary to understand the adverse impacts of the abiotic factors on crops with special reference to major cereals. However, adaptation potions are much more important to ensure the agricultural sustainability of major cereals. The available literature reviewed suggested some adaptation options for major cereals to combat the ill effects of abiotic stresses which include the change in variety and crop, manipulation in sowing or transplanting time, adoption of proper nutrient and water management, water conservation measures, adoption of the appropriate crop establishment methods and suitable cropping system. Further, the review article has made some recommendations and future perspectives highlighting the scope of further research for a climate-resilient production of foods for the future considering the adverse effects of the climate change.

In this work, we demonstrate a simple sol-gel technique to prepare metal-ion(s)-doped ceria-zirconia solid solution for efficient catalytic methane activation. The cation-depicting formula units are Ce

Objectives: physically-demanding occupations may increase rotator cuff disease (RCD) risk and need for surgery. We linked a job-exposure matrix (JEM) to the UK Biobank cohort study to measure physical occupational exposures and estimate associations with RCD surgery.Methods: jobs and UK Standard Occupational Classification (SOC) codes were recorded during the UK Biobank verbal interview. Lifetime job histories were captured through a web-based survey. UK SOC codes were linked to a JEM based on the US O*NET database. O*NET-based scores [static strength, dynamic strength, general physical activities, handling/moving objects (range=1-7), time spent using hands, whole body vibration, and cramped/awkward positions (range=1-5)] were assigned to jobs. RCD surgeries were identified through linked national hospital inpatient records. Multivariable Cox regression was used to calculate hazard ratios (HR) as estimates of associations with RCD surgery. Among those with lifetime job histories, associations were estimated for duration of time with greatest exposure (top quartile of exposure).Results: of 277 808 people reporting jobs, 1997 (0.7%) had an inpatient RCD surgery. After adjusting for age, sex, race, education, area deprivation, and body mass index, all O*NET variables considered were associated with RCD surgery (HR per point increase range=1.10-1.45, all P10 years of work (eg, HR for 11-20 versus 0 years with static strength score ≥4 = 2.06, 95% confidence interval 1.39-3.04).Conclusions: workplace physical demands are an important risk factor for RCD surgery, particularly for workers with more than a decade of exposure.

This article presents a load flow analysis of an IEEE14 BUS system using the Newton-Raphson method, which simplifies the analysis of load balancing problems. The software used for the programming platform is MATLAB. This paper gives an overview of the electrical performance and power flows (real and reactive) under a steady state. There are various methods for load flow computations. The gauss-seidel method is more popular in smaller systems because of less computational time. In the case of larger systems computation time increases in this condition, the Newton-Raphson method is preferred. This project aims to develop a MATLAB program to calculate voltages and active and reactive power at each bus for IEEE 14 bus systems. The MATLAB program is executed with the input data and results are compared. Keywords: load flow studies, Newton-Raphson method, IEEE 14 bus system.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2), a novel member of the betacoronavirus family is a single-stranded RNA virus that has spread worldwide prompting the World Health Organization to declare a global pandemic. This creates an alarming situation and generates an urgent need to develop innovative therapeutic agents. In this context, an in silico molecular docking and molecular dynamics (MD) simulation study on the existing 58 antiviral and antimalarial compounds was performed on 3CLpro, PLpro and RdRp SARS-CoV-2 proteins. The antiviral compounds are best fitted in the binding pockets and interact more profoundly with the amino acid residues compared to antimalarial compounds. An HIV protease inhibitor, saquinavir showed a good dock score and binding free energy with varied binding interactions against 3CLpro and PLpro. While, adefovir, a nucleotide HBV DNA polymerase inhibitor exhibited good dock score and binding interactions against RdRp. Although, the antimalarial compounds showed relatively less dock score but were found to be crucial in displaying essential binding interactions with these proteins. The MD simulation runs for 100 ns on 3CLpro–saquinavir, PLpro–saquinavir and RdRp–adefovir complexes using Desmond revealed fairly stable nature of interactions. This study helped in understanding the key interactions of the vital functionalities that provide a concrete base to develop lead molecules effective against SARS-CoV-2. Communicated by Ramaswamy H. Sarma

BACKGROUND: Back pain is a leading reason for seeking care in the United States (US), and is a major cause of morbidity. OBJECTIVE: To analyze demographic, patient, and visit characteristics of adult ambulatory spine clinic visits in the United States from 2009–2016. METHODS: Data from the National Ambulatory Medical Care Survey from 2009–2016 were used and were sample weighted. RESULTS: Most patients presenting for ambulatory spine care were 45–64 years (45%), were most commonly female (56.8%), and private insurance (45%) and Medicare (26%) were most common payors. The percentage of visits for spine care done at a primary care setting was 50.1% in 2009–2010 and 48.3% in 2014–2015. Approximately 15.5% were seen in orthopedic surgery clinics in 2009–2010 and 7.3% in 2015–2016. MRI was utilized in 11.7% in 2009–2010 and 11.0% in 2015–2016. Physical therapy was prescribed in 13.2% and narcotic analgesic medications were prescribed in 36.2% of patients in 2015–2016. CONCLUSIONS: MRI was used more frequently than guidelines recommended, and physical therapy was less frequently utilized despite evidence. A relatively high use of opiates in treatment of back pain was reported and is concerning. Although back pain represents a substantial public health burden in the United States, the delivery of care is not evidence-based.

Tackling the problem of emissions is at the forefront of scientific research today. While industrial engines designed to operate in stable regimes produce emissions, attempts to operate them at 'greener' conditions often fail due to a dangerous phenomenon known as thermoacoustic instability. Hazardous high amplitude periodic oscillations during thermoacoustic instability lead to the failure of these engines in power plants, aircraft, and rockets. To prevent this catastrophe in the first place, identifying the onset of thermoacoustic instability is required. However, detecting the onset is a major obstacle preventing further progress due to spatiotemporal variability in the reacting field. Here, we show how to overcome this obstacle by discovering a critical condition in certain zones of the combustor, which indicates the onset of thermoacoustic instability. In particular, we reveal the critical value of the local heat release rate that allows us to distinguish stable operating regimes from hazardous operations. We refer to these zones as seeds of the phase transition because they show the earliest manifestation of the impending instability. The increase in correlations in the heat release rate between these zones indicates the transition from a chaotic state to a periodic state. Remarkably, we found that observations at the seeds of the phase transition enable us to predict when the onset occurs, well before the emergence of dangerous large-amplitude periodic acoustic pressure oscillations. Our results contribute to the operation of combustors in more environment-friendly conditions. The presented approach is applicable to other systems exhibiting such phase transitions. Indian Institute of Technology Madrashttps://doi.org/10.13039/501100003845 Federal Ministry for the Environment, Nature Conservation and Nuclear Safety and the International Climate Initiative Germany Department of Science and Technology India Russian Foundation for Basic Researchhttps://doi.org/10.13039/501100002261

Hydrogen sulfide (H2S) is reported to have a neuroprotective activity; however, the role of H2S in neuroinflammation-induced neuronal damage is ambiguous. Here, we aimed to evaluate the underlying mechanisms for the neuroprotective effect of NaHS, a known H2S donor, against lipopolysaccharide (LPS)-induced memory impairment (MI). All the treatments were administered for 28 days, and LPS (0.25 mg/kg i.p.) was co-administered intermittently for 7 days from days 15 to 21. Morris water maze (MWM) and Y-maze tests were performed to evaluate MI. Neurodegeneration was histopathologically examined, and the brain homogenates were characterized for reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor (TNF)-α, interleukin (IL)-6, caspase-3, c-Jun, and acetylcholinesterase (AChE) by biochemical analysis. H2S administration significantly improved spatial and working memory in MWM and Y-maze tasks, respectively. Exogenous H2S significantly reversed LPS-induced oxidative stress as evidenced by improved GSH, MDA, and SOD levels. H2S pretreatment significantly attenuated LPS-induced apoptosis and inflammation by decreasing c-Jun and caspase-3 levels and inhibiting TNF-α and IL-6, respectively. The decrease in these markers was supported by H&E and Nissl staining, which confirmed the anti-necrotic activity of H2S. However, there was no significant improvement in LPS-induced increase in AChE activity. These results indicate that chronic systemic inflammation leads to neurodegeneration and MI and H2S exerts its neuroprotective effect due to its anti-oxidative, anti-inflammatory, and anti-apoptotic potential via modulation of JNK and extrinsic apoptosis pathways.

BACKGROUND While evidence indicates that familial predisposition influences the risk of developing degenerative rotator cuff disease (RCD), knowledge of specific genetic markers is limited. We conducted a genome-wide association study of RCD surgery using the UK Biobank, a prospective cohort of 500,000 people (40 to 69 years of age at enrollment) with genotype data. METHODS Cases with surgery for degenerative RCD were identified using linked hospital records. The cases were defined as an International Classification of Diseases, Tenth Revision (ICD-10) code of M75.1 determined by a trauma/orthopaedic specialist and surgery consistent with RCD treatment. Cases were excluded if a diagnosis of traumatic injury had been made during the same hospital visit. For each case, up to 5 controls matched by age, sex, and follow-up time were chosen from the UK Biobank. Analyses were limited to European-ancestry individuals who were not third-degree or closer relations. We used logistic regression to test for genetic association of 674,405 typed and >10 million imputed markers, after adjusting for age, sex, population principal components, and follow-up. RESULTS We identified 2,917 RCD surgery cases and 14,158 matched controls. We observed 1 genome-wide significant signal (p < 5 × 10-8) for a novel locus tagged by rs2237352 in the CREB5 gene on chromosome 7 (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.11 to 1.24). The single-nucleotide polymorphism (SNP) rs2237352 was imputed with a high degree of confidence (info score = 0.9847) and is common, with a minor allele frequency of 47%. After expanding the control sample to include additional unmatched non-cases, rs2237352 and another SNP in the CREB5 gene, rs12700903, were genome-wide significant. We did not detect genome-wide significant signals at loci associated with RCD in previous studies. CONCLUSIONS We identified a novel association between a variant in the CREB5 gene and RCD surgery. Validation of this finding in studies with imaging data to confirm diagnoses will be an important next step. CLINICAL RELEVANCE Identification of genetic RCD susceptibility markers can guide understanding of biological processes in rotator cuff degeneration and help inform disease risk in the clinical setting. LEVEL OF EVIDENCE Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Present study is specially designed for the recent advances in biosensors to detect and quantify urea concentration. Urea (carbamide) is an organic compound made up of the carbonyl (C=O) functional group with two -NH2 groups having chemical formula CO (NH2 )2 . In nature, urea is found everywhere as the result of various processes, and in the human body, urea is an end product of nitrogen metabolism. An excessive concentration of urea in the human body is responsible for different critical diseases such as indigestion, acidity, ulcers, cancer, malfunctioning of kidneys, renal failure, urinary tract obstruction, dehydration, shock, burns, gastrointestinal bleeding, and so on. Moreover, below the normal level may cause hepatic failure, nephritic syndrome, cachexia, and so on. As well as in various fields such as fishery, dairy, food preservation, agriculture, and so on, urea is normally found and its detection is necessary. In urea biosensors, enzyme urease (Urs) is used as a bioreceptor element and retains its long last activity is the critical issue in front of the researcher. During recent decades, different nanoparticles (zinc oxide, nickel oxide, iron oxide, titanium dioxide, tin(IV) oxide, etc.), conducting polymer (polyaniline, polypyrrole, etc.), conducting polymer-nanoparticles composites, carbon materials (carbon nanotubes, graphene oxide, reduced graphene oxide graphene), and so on are used in urea biosensors. The main emphasis of the present study is to provide cumulative and comprehensive information about the sensing parameters of urea biosensors based on the materials used for enzyme immobilization. Besides this special task, this review provides a fruitful discussion on the basics of biosensors briefly for new and upcoming researchers. Thus, the present study may act as a gift for a large audience that come from different fields and are working in biosensors research.