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Aluminum metal matrix composites are potential materials for aerospace and automobile industrial applications due to their enhanced mechanical and tribological properties. Aluminum reinforced with silicon carbide particles has been developed with enhanced mechanical and tribological behavior, but it lacks wettability between matrix and reinforcement causing weak bonding, which reduces the degree of enhancement. The objectives of this study were to fabricate aluminum-based metal matrix composites with enhanced wettability at varying stirring speeds (350, 450, 550 rpm), stirring time (5, 10, 15 min), weight percentage of SiC (0, 5, 10 wt.%), and weight percentage of MoS 2 (0, 2, 4 wt.%). Nine samples were fabricated using stir casting based on Taguchi L9 orthogonal array. Hardness, tensile strength, and wear rate of the developed composite were investigated and analyzed as a single response characteristic using Taguchi's signal-to-noise ratio and as a multi-response characteristic using hybrid Taguchi-grey relational analysis (HTGRA). The results revealed that the addition of SiC in the composite produced better hardness, tensile strength, and wear rate. The addition of MoS 2 in the composite showed better hardness and tensile strength only up to 2 wt.% of MoS 2 , and in the case of wear rate, the addition of MoS 2 in the composite up to 4% showed better wear resistance. Al-SiC-MoS 2 hybrid composite shows better enhancement in hardness, tensile strength, and wear resistance than the Al-SiC composite.

Background: The prognostic implications of discordant grading in severe aortic stenosis (AS) are well known. However, the prevalence of different flow-gradient patterns and their prognostic implications in moderate AS are unknown., Objectives: The purpose of this study was to investigate the occurrence and prognostic implications of different flow-gradient patterns in patients with moderate AS., Methods: Patients with moderate AS (aortic valve area >1.0 and ≤1.5 cm 2 ) were identified and divided in 4 groups based on transvalvular mean gradient (MG), stroke volume index (SVi), and left ventricular ejection fraction (LVEF): concordant moderate AS (MG ≥20 mm Hg) and discordant moderate AS including 3 subgroups: normal-flow, low-gradient moderate AS (MG <20 mm Hg, SVi ≥35 mL/m 2 , and LVEF ≥50%); "paradoxical" low-flow, low-gradient moderate AS (MG <20 mm Hg, SVi <35 mL/m 2 , and LVEF ≥50%) and "classical" low-flow, low-gradient moderate AS (MG <20 mm Hg and LVEF <50%). The primary endpoint was all-cause mortality., Results: Of 1,974 patients (age 73 ± 10 years, 51% men) with moderate AS, 788 (40%) had discordant grading, and these patients showed significantly higher mortality rates than patients with concordant moderate AS (P < 0.001). On multivariable analysis, "paradoxical" low-flow, low-gradient (HR: 1.458; 95% CI: 1.072-1.983; P = 0.014) and "classical" low-flow, low-gradient (HR: 1.710; 95% CI: 1.270-2.303; P < 0.001) patterns but not the normal-flow, low-gradient moderate AS pattern were independently associated with all-cause mortality., Conclusions: Discordant grading is frequently (40%) observed in patients with moderate AS. Low-flow, low-gradient patterns account for an important proportion of the discordant cases and are associated with increased mortality. These findings underline the need for better phenotyping patients with discordant moderate AS., Competing Interests: Funding Support and Author Disclosures The Department of Cardiology of the Leiden University Medical Centre has received unrestricted research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, and Medtronic. Dr Stassen has received funding from the European Society of Cardiology (ESC Training Grant App000064741). Dr Butcher has received funding from the European Society of Cardiology (ESC Research Grant App000080404). Dr Pibarot has received funding from Edwards Lifesciences, Medtronic, Pi-Cardia, and Cardiac Phoenix for echocardiography core laboratory analyses and research studies in the field of transcatheter valve therapies, for which he received no personal compensation; and has received lecture fees from Edwards Lifesciences and Medtronic. Dr Delgado has received speaker fees from Abbott Vascular, Edwards Lifesciences, Merck Sharp and Dohme, and GE Healthcare. Dr Marsan has received speaker fees from Abbott Vascular and GE Healthcare. Dr Bax received speaker fees from Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Reduced left ventricular (LV) systolic function is associated with worse prognosis in patients with severe aortic stenosis (AS) treated with transcatheter aortic valve implantation (TAVI). We aimed to examine the changes in left ventricular ejection fraction (LVEF) after TAVI among patients with varying baseline LVEF. Moreover, variables associated with lack of LVEF improvement were identified and the association with long-term outcomes was investigated. A total of 560 patients (age 80 ± 7 years, 53% men) with severe AS who underwent transfemoral TAVI between 2007 and 2019 were selected. LVEF was assessed from transthoracic echocardiography at baseline (before TAVI) and at 6 and 12 months after TAVI. Patients were stratified according to baseline LVEF: (1) LVEF ≥50%, (2) LVEF 40% to 49%, and (3) LVEF <40%. The clinical end point was ≥5% LVEF improvement. The primary outcome was all-cause mortality. Patients with baseline LVEF<40% showed greater increase in LVEF than those with baseline LVEF 40% to 49% and LVEF ≥50% (from 33% ± 6% to 43% ± 10%, p <0.001; from 45% ± 3% to 52% ± 8%, p <0.001; and from 58% ± 5% to 59% ± 7%, p = 0.012, respectively, p for interaction <0.001). Coronary artery disease (odds ratio [OR] 1.80 [95% confidence interval (CI) 1.06 to 3.06], p = 0.031), myocardial infarction (OR 2.07 [95% CI 1.19 to 3.61], p = 0.010), and permanent pacemaker (OR: 1.93 [95% CI 1.25 to 3.00], p = 0.003) were independently associated with the lack of ≥5% LVEF improvement. During a median follow-up of 3.8 (interquartile range 2.6 to 5.2) years, 176 patients died (31%). Patients with ≥5% LVEF improvement had similar outcomes compared with those with <5% LVEF improvement (log-rank p = 0.89). In conclusion, patients with severe AS and baseline LVEF <40% had the greatest improvement in LVEF at 1-year follow-up after TAVI. Coronary artery disease, myocardial infarction, and permanent pacemaker were associated with lack of LVEF improvement. However, LVEF improvement at 12 months was not associated with long-term outcomes., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Titanium metal matrix composites/TMMCs are reinforced ceramic reinforcements that have been developed and used in the automotive, biological, implants, and aerospace fields. At high temperatures, TMMCs can provide up to 50% weight reduction compared to monolithic super alloys while maintaining comparable quality or state of strength. The objective of this research was the analysis and evaluation of the effect/influence of different sintering temperatures, reinforcement size dependence of mechanical properties, and fortification mechanisms on the particle size distribution of B 4 C, SiC, and ZrO 2 reinforced TMMCs that were produced and fabricated by powder metallurgy/PM. SEM, XRD, a Rockwell hardness tester, and the Archimedes principle were used in this analysis. The composites' hardness, approximation, tensile, yielding, and ultimate strength were all increased. As the composite was reinforced with low-density ceramics material and particles, its density decreased. The volume and void content in all the synthesized specimens is below 1%; this is the result of good sample densification, mechanical properties and uniform distribution of the reinforced particle samples; 5% B 4 C, 12.5% SiC, 7.5% ZrO 2 , 75% Ti develop higher mechanical properties, such as higher hardness, approximation tensile, yielding, and ultimate strength and low porosity.

Objective: To investigate the prognostic impact of left ventricular (LV) diastolic dysfunction in patients with moderate aortic stenosis (AS) and preserved LV systolic function., Methods: Patients with a first diagnosis of moderate AS (aortic valve area >1.0 and ≤1.5 cm 2 ) and preserved LV systolic function (LV ejection fraction ≥50%) were identified. LV diastolic function was evaluated using echocardiographic criteria according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Clinical outcomes were defined as all-cause mortality and a composite of all-cause mortality and aortic valve replacement (AVR)., Results: Of 1247 patients (age 74±10 years, 47% men), 535 (43%) had LV diastolic dysfunction at baseline. Patients with LV diastolic dysfunction showed significantly higher mortality rates at 1-year, 3-year and 5-year follow-up (13%, 30% and 41%, respectively) when compared with patients with normal LV diastolic function (6%, 17% and 29%, respectively) (p<0.001). On multivariable analysis, LV diastolic dysfunction was independently associated with all-cause mortality (HR 1.368; 95% CI 1.085 to 1.725; p=0.008) and the composite endpoint of all-cause mortality and AVR (HR 1.241; 95% CI 1.035 to 1.488; p=0.020)., Conclusions: LV diastolic dysfunction is independently associated with all-cause mortality and the composite endpoint of all-cause mortality and AVR in patients with moderate AS and preserved LV systolic function. Assessment of LV diastolic function therefore contributes significantly to the risk stratification of patients with moderate AS. Future clinical trials are needed to investigate whether patients with moderate AS and LV diastolic dysfunction may benefit from earlier valve intervention., Competing Interests: Competing interests: The Department of Cardiology of the Leiden University Medical Centre received unrestricted research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare and Medtronic. JJB received speaker fees from Abbott Vascular. NAM received speaker fees from Abbott Vascular and GE Healthcare. VD received speaker fees from Abbott Vascular, Edwards Lifesciences, MSD and GE Healthcare. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

A sudden outbreak of a novel coronavirus SARS-CoV-2 in 2019 has now emerged as a pandemic threatening to efface the existence of mankind. In absence of any valid and appropriate vaccines to combat this newly evolved agent, there is need of novel resource molecules for treatment and prophylaxis. To this effect, flavonol morin which is found in fruits, vegetables and various medicinal herbs has been evaluated for its antiviral potential in the present study. PASS analysis of morin versus reference antiviral drugs baricitinib, remdesivir and hydroxychloroquine revealed that morin displayed no violations of Lipinski's rule of five and other druglikeness filters. Morin also displayed no tumorigenic, reproductive or irritant effects and exhibited good absorption and permeation through GI (clogP <5). In principal component analysis, morin appeared closest to baricitinib in 3D space. Morin displayed potent binding to spike glycoprotein, main protease 3CLPro and papain-like protease PLPro of SARS-CoV-2, SARS-CoV and MERS-CoV using molecular docking and significant binding to three viral-specific host proteins viz. human ACE2, importin-α and poly (ADP-ribose) polymerase (PARP)-1, further lending support to its antiviral efficacy. Additionally, morin displayed potent binding to pro-inflammatory cytokines IL-6, 8 and 10 also supporting its anti-inflammatory activity. MD simulation of morin with SARS-CoV-2 3CLPro and PLPro displayed strong stability at 300 K. Both complexes exhibited constant RMSDs of protein side chains and Cα atoms throughout the simulation run time. In conclusion, morin might hold considerable therapeutic potential for the treatment and management of not only COVID-19, but also SARS and MERS if studied further. Communicated by Ramaswamy H. Sarma.

Moderate aortic stenosis (AS) is associated with an increased risk for adverse events. Although reduced left ventricular (LV) global longitudinal strain (GLS) is associated with worse outcomes in patients with severe AS, its prognostic value in patients with moderate AS is unknown. The aim of this study was to investigate the prognostic implications of LV GLS in patients with moderate AS., Methods: LV GLS was evaluated using speckle-tracking echocardiography in patients with moderate AS (aortic valve area 1.0-1.5 cm 2 ) and reported as absolute (i.e., positive) values. Patients were divided into three groups: LV ejection fraction (LVEF) < 50% (group 1), LVEF ≥ 50% but LV GLS < 16% (group 2), and LVEF ≥ 50% and LV GLS ≥ 16% (group 3). The LV GLS value of 16% was based on spline curve analysis. The primary end point was all-cause mortality., Results: A total of 760 patients (mean age, 71 ± 12 years; 61% men) were analyzed. During a median follow-up period of 50 months (interquartile range, 26-94 months), 257 patients (34%) died. Patients with LVEF < 50% and LVEF ≥ 50% but LV GLS < 16% showed significantly higher mortality rates at 1-, 3-, and 5-year follow-up (82%, 71%, and 58%; and 92%, 77%, and 58%, respectively) compared with those with LVEF ≥ 50% and LV GLS ≥ 16% (96%, 91%, and 85%, respectively; P < .001). Long-term outcomes were not different between patients with LVEF < 50% and those with LVEF ≥ 50% but LV GLS < 16% (P = .592). LV GLS discriminated higher risk patients even among those with LVEF ≥ 60% (P < .001) or those who were asymptomatic (P < .001). On multivariable analysis, LVEF < 50% (hazard ratio, 2.384; 95% CI, 1.614-3.522; P < .001) and LVEF ≥ 50% but LV GLS < 16% (hazard ratio, 2.467; 95% CI, 1.802-3.378; P < .001) were independently associated with all-cause mortality., Conclusions: In patients with moderate AS, reduced LV GLS is associated with an increased risk for all-cause mortality, even if LVEF is still preserved., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Psoriatic arthritis (PsA) is a chronic inflammatory disease with clinical manifestations, including inflammatory arthritis and the presence of psoriasis (PsO). The present consensus statement evaluated the early diagnosis and treatment approaches in the management of psoriasis and psoriatic arthritis by rheumatologists and dermatologists. For PAN India representation, a panel of eight rheumatologists and five dermatologists from different institutes in India were constituted. These thirteen experts were divided into two groups (rheumatologists group and dermatologist group) who received a set of questionnaires each for diagnosis and treatment approaches in the management of psoriasis and psoriatic arthritis. Based on the responses received, a panel discussion took place, where the experts identified the early diagnostic criteria for PsA considering: Clinical signs and symptoms, and questionnaire-based PsA screening, which includes Psoriasis Epidemiology Screening Tool (PEST) for dermatologists and Classification Criteria for Psoriatic Arthritis (CASPAR) for rheumatologists. The experts also recommended shift from conventional disease-modifying anti-rheumatic drugs (DMARDs) to biologics like secukinumab, when there is extensive skin involvement and TNF inhibitors when there is extensive joint involvement. Overall, the objective of the consensus was to assist rheumatologists and dermatologists in the early diagnosis and management of patients of PsA and PsO in their clinical practice., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Dermatology.)

Background Coronavirus disease 2019 (COVID-19) presents clinically a variety of pathological and clinical organ dysfunctions, ranging in severity from asymptomatic to fatal. The care and monitoring of COVID-19 patients may benefit from the use of biochemical and hematological markers. Objective To observe the alteration of serum biochemical and hematological parameters in COVID-19 positive patients, attending a Tertiary Care Hospital. Method A descriptive cross-sectional study was conducted on all COVID-19 positive patients attending Nobel Medical College Teaching Hospital, Biratnagar, Nepal from 15th December 2021 to 15th February 2022. The test results of different serum biochemical and hematological parameters done for these patients were recorded in clinical laboratory services and obtained retrospectively for the analysis. The data were entered in MS excel and analyzed by SPSS version 20. Result Out of 1537 COVID-11699 declared positive patients, 712 (46.32%) were male and 825 (53.68%) female. Mean age of COVID positive patients was 40.03±20.08 years. The level of serum SGOT, SGPT, ALP and GGT was significantly elevated in 39.9%, 42.8%, 32.3% and 47.2% of COVID positive patients respectively. Blood Urea, creatinine, uric acid and sugar level were significantly elevated in 63%, 56.1%, 33.1% and 47.6% patients respectively. The serum level of LDH, D-dimer, CRP and procalcitonin (PCT) were significantly increased in 52.1%, 75.9%, 71.6% and 61.2% of patients respectively. The serum value of total cholesterol, triglyceride, HDL and LDL were significantly lowered in 52.2%, 43.8%, 70.1% and 60.3% of patients respectively. RBC concentration and level of hemoglobin was reduced in 56.6% and 53.6% of COVID positive patients respectively whereas total leukocyte count was elevated in 80.7% with increase in neutrophil in 87.9% and decrease in lymphocyte in 79.4%. Conclusion A portion of COVID-19 positive patients showed drastically altered test results for various serum biochemical and hematological markers, although many of them had normal findings.

Background and Aims: Cryoneurolysis, a neuroablative technique, is used in the event of failure of conservative treatment in chronic pain conditions. To date, no systematic review has been published to demonstrate its effectiveness in managing chronic non-cancer pain. Therefore, this review was done to ascertain the efficacy of cryoneurolysis and describe its role in chronic non-cancer pain management., Methods: We searched PubMed, Cochrane, Embase, Scopus, and Google Scholar databases for articles published between January 2011 and September 2021. Two independent reviewers extracted the data from the included studies. Assessment of risk of bias of included randomised controlled trials (RCTs) was done using RevMan 5.4.1 software and Newcastle-Ottawa scale was used for non-randomised studies., Results: Ten studies enroling a total of 425 patients were included in the qualitative analysis. Eight studies were assessed quantitatively. RCTs were found only for cervicogenic headache and knee osteoarthritis management. The rest of the included studies were prospective non-controlled and retrospective studies. A significant pain reduction was seen at seven-day [Standardised Mean Difference (SMD) 1.77 (1.07, 2.46)], P < 0.00001, I 2 = 79%), one-month (SMD 3.26 [2.60, 3.92], P < 0.00001, I 2 = 45%), three-month (SMD 2.58 [1.46, 3.70], P < 0.00001, I 2 = 93%), six-month (SMD 2.38 [0.97, 3.79], P = 0.001, I 2 = 86%) follow-ups. Improved disability and no serious complications were noted., Conclusion: Cryoneurolysis appeared to be effective in pain alleviation in refractory painful conditions for up to six months. It is safe and well-tolerated with an excellent safety profile but the quality of evidence is limited by substantial heterogeneity between trials. Therefore, more comparative clinical trials on a larger sample size are needed to provide more concrete evidence., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Anaesthesia.)

Most research on cancer patient survival uses registry-based (e.g., SEER) incidence and survival data that have limited socioeconomic status and health-risk information. In this study, we used the 1997-2015 National Health Interview Survey-National Death Index prospectively-linked pooled cohort database (n = 40,291 cancer patients) to examine disparities in patient survival by a broad range of social determinants, including race/ethnicity, nativity, educational attainment, income/poverty level, occupation, housing tenure, physical and mental health status, smoking, physical activity, body mass index, and alcohol consumption. We used Cox proportional hazards models to estimate mortality hazard ratios and cause-specific 1-year, 5-year, and 10-year survival rates for all-cancer and lung cancer. During 1997-2015, the 10-year age-adjusted (all-cause) survival rate for cancer patients with professional and managerial occupations was 89.66%, significantly higher than the survival rate of 83.17% for laborers or 83.66% for the unemployed. Cancer patients with renting house had significantly lower age-adjusted survival rates than those owning house (82.65% vs. 85.80%). The 10-year age-adjusted survival rates were significantly greater among cancer patients with regular physical activity than those without regular physical activity (90.18% vs. 83.24%). Age-adjusted survival rates were significantly reduced for cancer patients with lower income and education, poor health, and serious psychological distress, and among current and former smokers. The gap in survival narrowed with additional sociodemographic, health, or behavioral adjustment. Similarly large differentials were found in lung cancer survival. Marked disparities in all-cancer and lung cancer survival were found by a wide range of sociodemographic and health characteristics., Competing Interests: CONFLICTS OF INTEREST No potential conflicts of interest were disclosed., (Copyright © 2022 Korean Society of Cancer Prevention.)

Competing Interests: Hereby I/we certify that No financial support or benefits have been received by me or any co-author, by any member of my/our immediate family or any individual or entity with whom or with which I/we have a relationship from any commercial source which is related directly or indirectly to the scientific work which is reported on in the article.

Competing Interests: There are no conflicts of interest.

Background: Recent data showed poor long-term survival in patients with moderate AS. Although sex differences in left ventricular (LV) remodeling and outcome are well described in severe AS, it has not been evaluated in moderate AS., Methods: In this retrospective, multicenter study, patients with a first diagnosis of moderate AS diagnosed between 2001 and 2019 were identified. Clinical and echocardiographic parameters were recorded at baseline and compared between men and women. Patients were followed up for the primary endpoint of all-cause mortality with censoring at the time of aortic valve replacement., Results: A total of 1895 patients with moderate AS (age 73 ± 10 years, 52% male) were included. Women showed more concentric hypertrophy and had more pronounced LV diastolic dysfunction than men. During a median follow-up of 34 (13-60) months, 682 (36%) deaths occurred. Men showed significantly higher mortality rates at 3- and 5-year follow-up (30% and 48%, respectively) than women (26% and 39%, respectively) ( p = 0.011). On multivariable analysis, male sex remained independently associated with mortality (hazard ratio 1.209; 95% CI: 1.024-1.428; p = 0.025). LV remodeling (according to LV mass index) was associated with worse outcomes (hazard ratio 1.003; CI: 1.001-1.005; p = 0.006), but no association was observed between the interaction of LV mass index and sex with outcomes., Conclusions: LV remodeling patterns are different between men and women having moderate AS. Male sex is associated with worse outcomes in patients with medically treated moderate AS. Further studies investigating the management of moderate AS in a sex-specific manner are needed., Competing Interests: The Department of Cardiology, Heart Lung Center, Leiden University Medical Centre, received research grants from 10.13039/100011949Abbott Vascular, 10.13039/100004326Bayer, 10.13039/501100005035Biotronik, Bioventrix, 10.13039/100008497Boston Scientific, 10.13039/100006520Edwards Lifesciences, 10.13039/100006775GE Healthcare, Ionis, and 10.13039/100004374Medtronic. Jeroen J. Bax received speaker fees from Abbott Vascular. Nina Ajmone Marsan received speaker fees from Abbott Vascular and GE Healthcare. Victoria Delgado received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, Medtronic, MSD, and Novartis. The remaining authors have nothing to disclose., (© 2022 The Authors.)

Aims: Women with severe aortic stenosis (AS) have better long-term outcome after transcatheter aortic valve implantation (TAVI) but worse survival after surgical aortic valve replacement compared with men. Whether this is related to sex differences in left ventricular (LV) remodelling is unknown. The aim of this study was to examine the sex differences in LV remodelling with multidetector row computed tomography (MDCT) and outcome in patients with severe AS undergoing TAVI between 2007 and 2018., Methods and Results: A total of 289 patients (age 80 ± 6 years, 54% male) were included. LV volumes, mass, and function were analysed on pre-procedural MDCT scans. Women showed smaller LV volumes and mass compared with men. Patients were classified into four LV remodelling patterns: concentric hypertrophy (50%) was the most frequent pattern of LV remodelling followed by eccentric hypertrophy (33%), normal geometry (13%), and concentric remodelling (4%). Men showed more concentric remodelling compared with women (91% vs. 9%, respectively, P = 0.011). However, no differences were observed in the remaining LV remodelling patterns. During a median follow-up of 3.8 (IQR 2.2-5.1) years after TAVI, 87 (30%) patients died. Women demonstrated better outcome after TAVI compared with men (log-rank χ2 = 4.29, P = 0.038). No association was observed between the interaction of the LV remodelling patterns and sex with outcome., Conclusion: LV concentric hypertrophy and eccentric hypertrophy are similarly observed in men and women with severe AS but concentric remodelling was more common in men. Women demonstrated better outcome after TAVI when compared with men. The interaction between the LV remodelling patterns and sex was not associated with survival., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: The aim of this study is to investigate the independent determinants of survival in patients with moderate aortic stenosis (AS), stratified by severity of symptoms and left ventricular ejection fraction (LVEF)., Methods and Results: Patients with a first diagnosis of moderate AS (aortic valve area >1.0 and ≤1.5 cm2) were identified. Patients were stratified by New York Heart Association (NYHA) functional class (NYHA I, NYHA II, or NYHA III-IV) and LVEF (LVEF ≥60%, LVEF 50-59%, or LVEF <50%) at the time of moderate AS diagnosis. The primary endpoint was all-cause mortality, while the secondary endpoint included all-cause mortality and aortic valve replacement. Of 1961 patients with moderate AS (mean age 73 ± 10 years, 51% men), 1108 (57%) patients were in NYHA class I, while 527 (27%) and 326 (17%) patients had symptoms of NYHA class II and III-IV, respectively. Regarding LVEF, 1032 (53%) had LVEF ≥60%, 544 (28%) LVEF 50-59%, and 385 (20%) LVEF <50%. During a median follow-up of 50 (23-82) months, 868 (44%) patients died. On multivariable analysis, NYHA class II [hazard ratio (HR): 1.633; 95% confidence interval (CI): 1.431-1.864; P < 0.001], NYHA class III-IV (HR: 2.084; 95% CI: 1.797-2.417; P < 0.001), LVEF 50-59% (HR: 1.194; 95% CI: 1.013-1.406; P = 0.034), and LVEF <50% (HR: 1.694; 95% CI: 1.417-2.026; P < 0.001) were independently associated with increased mortality., Conclusion: Moderate AS is associated with poor long-term survival. Baseline symptom severity and LVEF are associated with worse outcomes in these patients. Patients with low-normal LVEF (<60%) and mild symptoms (NYHA II) already have an increased risk of adverse events., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Objective: The objective of the study is to evaluate the morphology of the symphyseal region of adult skeletal Class II and Class III malocclusion as compared with Skeletal Class I subjects., Materials and Methods: The symphyseal width and height were evaluated using data from 80 lateral cephalograms of the age range of 18 years to 25 years. Average growing Skeletal Class II ( n = 30) and Class III ( n = 20) subjects were used as a comparison group. Average growing normal occlusion samples ( n = 30) were used as controls., Results: Alveolar height was similar in all groups. The width of the symphyseal region including basal width, the width of the cervical region of the lower central incisor at the cementoenamel junction, and symphysis width were found to be similar in all groups. There is no significant difference in gonial angle in both Class II and III groups as compared to control. Articular angle showed no significant difference. Mandibular incisor dentoalveolar height (L1-AH) was found to be significantly higher in the Class II group ( P < 0.05)., Conclusions: There are no definite morphological differences in the symphyseal region between average grower Class I, Class II, and Class III skeletal malocclusions except mandibular incisor dentoalveolar height (L1-AH) and incisor mandibular plane angle which is higher whereas ramus length and body length which is lesser in Class II group as compared with controls. Width of the cervical region of the lower central incisor at the cementoenamel junction (Id-Id') and incisor mandibular plane angle was lower than control in Class III subjects., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 National Journal of Maxillofacial Surgery.)

Background: Sex-specific thresholds of computed tomography (CT)-derived aortic valve calcification (AVC) or AVC density (AVCd) to identify severe aortic stenosis (AS) have been established in populations that consisted mainly of Caucasians with a tricuspid aortic valve. The objective of this study was to evaluate the accuracy (i.e., sensitivity and specificity) of previously established thresholds to identify severe AS in patients with bicuspid aortic valve (BAV) and according to ethnicity: Caucasian vs. Asian., Methods: We built a multicenter registry of echocardiographic and CT data collected in BAV patients with at least mild AS and preserved left ventricular ejection fraction from 7 different centers. Anatomic severity of AS obtained by CT-derived AVC and AVCd was compared to hemodynamic severity of AS obtained by echocardiography., Results: Among 485 BAV patients (60% men, 73% Asians), the best thresholds of AVC and AVCd to identify severe AS in BAV patients were 2315 arbitrary units (AU) (sensitivity [Se]/specificity [Spe] = 82/78%) in men, 1103 AU (Se/Spe = 80/82%) in women, and 561 AU/cm 2 (Se/Spe = 86/91%) in men, and 301 AU/cm 2 (Se/Spe = 83/82%) in women, respectively. According to ethnicity, thresholds for severe AS in Caucasian patients were, respectively, in men and women: 2208 AU (Se/Spe = 83/83%) and 1230 AU (Se/Spe = 87/82%) for AVC and 474 AU/cm 2 (Se/Spe = 88/83%) and 358 AU/cm 2 (Se/Spe = 80/82%) for AVCd. In Asian patients, they were 2582 AU (Se/Spe = 76/78%) and 924 AU (Se/Spe = 84/80%) for AVC and 640 AU/cm 2 (Se/Spe = 82/89%) and 255 AU/cm 2 (Se/Spe = 86/80%) for AVCd., Conclusions: The optimal thresholds to identify hemodynamically severe AS in BAV patients are similar in Caucasians but appear to be higher in Asian men, compared with thresholds previously reported in tricuspid aortic valve patients. Nonetheless, the thresholds currently proposed in the guidelines have good accuracy and can be applied in BAV patients to confirm AS severity., Competing Interests: The department of Cardiology of the Leiden University Medical Center received unrestricted research grants from 10.13039/100011949Abbott Vascular, 10.13039/100004326Bayer, 10.13039/501100005035Biotronik, Bioventrix, 10.13039/100008497Boston Scientific, 10.13039/100006520Edwards Lifesciences, 10.13039/100006775GE Healthcare, and 10.13039/100004374Medtronic. Jeroen J. Bax received speaker fees from Abbott Vascular. Victoria Delgado received speaker fees from Abbott Vascular, MSD, Medtronic, Edwards Lifesciences, and GE Healthcare., (© 2022 The Author(s).)

Objective: The COVID-19 pandemic has resulted in health professionals facing unprecedented challenges and changes in practice. Responding to humanitarian crises involves saving lives and reducing suffering and as such, palliative care is an essential component of the response to COVID-19. This study aimed to explore health professionals' perspectives of the role of palliative care during the COVID-19 pandemic by analyzing their views and experiences expressed in articles and blogs located via Twitter., Method: Qualitative content analysis of 33 online articles and blogs written by health professionals from 1 February 2020 to 30 June 2020. Online articles and blogs were included if the URL was posted on Twitter. The consolidated criteria for reporting qualitative research (COREQ) guided data collection and reporting., Results: The health professionals whose viewpoints were analyzed were from Europe, North America, Oceania and Asia. The themes derived from content analysis were (a) the recognized value of palliative care during the pandemic, (b) positioning palliative care as every health professional's responsibility and (c) specialist palliative care supporting and guiding health professionals., Conclusions: This study utilizes a unique approach to exploring the perspectives of health professionals from several countries during a global pandemic. The study emphasizes the value of palliative care and identifies gaps in end-of-life care provision including resource allocation. This brings to light the urgent need to equip all health professionals with palliative care knowledge and skills, including discussing and planning care. Specialist palliative care teams are well placed to support health professionals to provide quality care.

Aims: An echocardiographic staging system of severe aortic stenosis (AS) based on additional extra-valvular cardiac damage has been associated with prognosis after transcatheter aortic valve implantation (TAVI). Multidetector row computed tomography (MDCT) is key in the evaluation of AS patients undergoing TAVI and can potentially detect extra-valvular cardiac damage. This study aimed at evaluating the prognostic implications of an MDCT staging system of severe AS in patients undergoing TAVI., Methods and Results: A total of 405 patients (80 ± 7 years, 52% men) who underwent full-beat MDCT prior to TAVI were included. The extent of cardiac damage was assessed by MDCT and classified in five categories; Stage 0 (no cardiac damage), Stage 1 (left ventricular damage), Stage 2 (left atrium and mitral valve damage), Stage 3 (right atrial damage), and Stage 4 (right ventricular damage). Twenty-seven (7%) patients were stratified as Stage 0, 96 (24%) as Stage 1, 152 (38%) as Stage 2, 78 (19%) as Stage 3, and 52 (13%) as Stage 4. During a median follow-up of 3.7 (IQR 1.7-5.5) years, 150 (37%) died. On multivariable Cox regression analysis, cardiac damage Stage 3 (HR vs. Stage 0: 4.496, P = 0.039) and Stage 4 (HR vs. Stage 0: 5.565, P = 0.020) were independently associated with all-cause mortality., Conclusion: The MDCT-based staging system of cardiac damage in severe AS effectively identifies the patients who are at higher risk of death after TAVI., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Objectives: To evaluate any association between non-sustained ventricular tachycardia (NSVT) detected by intra-cardiac device and clinical outcomes in repaired adult congenital heart disease (ACHD) without tetralogy of Fallot (TOF)., Background: NSVT portends a higher risk of serious ventricular tachyarrhythmia in TOF. However its clinical significance when incidentally detected by implantable cardiac device is not well elucidated in non-TOF ACHD cohort., Methods: We performed a single center, retrospective, longitudinal follow-up study in repaired ACHD (≥18 years) patients without TOF who hosted a pacemaker or automatic implantable cardiac defibrillator (AICD). The cohort was divided based on presence/absence of device detected NSVT. The primary end-point was a composite of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), or sudden cardiac death (SCD)., Results: One hundred fifty eight patients (male 56.3%, median [IQR] age of 35 [28-43] years at last follow-up] with longitudinal post-implant follow-up duration of 8 (5-12) years were included. NSVT was detected in 52 (33%) patients. The primary composite end-point was more frequent in NSVT group [11.5% vs. 2.8%; p = .04]. Patients with NSVT were (i) older at the time of initial implant (age 25 vs. 18 years, p = .011) and more frequently demonstrated (ii) systemic ventricular dysfunction (44% vs. 26%; p = .015), as well as (iii) history of ventriculotomy (38% vs. 21%; p = .017)., Conclusions: In our repaired ACHD cohort, we noted a significant association between device-detected-NSVT and the primary composite end-point of sustained VT/VF or SCD. Systemic ventricular dysfunction and history of ventriculotomy were more frequent in the NSVT group and likely constituted the clinical milieu., (© 2021 Wiley Periodicals LLC.)

Hypo-attenuated leaflet thickening (HALT) of transcatheter aortic valves is detected on multidetector computed tomography (MDCT) and reflects leaflet thrombosis. Whether HALT affects left ventricular (LV) reverse remodeling, a favorable effect of LV afterload reduction after transcatheter aortic valve implantation (TAVI) is unknown. The aim of this study was to examine the association of HALT after TAVI with LV reverse remodeling. In this multicenter case-control study, patients with HALT on MDCT were identified, and patients without HALT were propensity matched for valve type and size, LV ejection fraction (LVEF), sex, age and time of scan. LV dimensions and function were assessed by transthoracic echocardiography before and 12 months after TAVI. Clinical outcomes (stroke or transient ischemic attack, heart failure hospitalization, new-onset atrial fibrillation, all-cause mortality) were recorded. 106 patients (age 81 ± 7 years, 55% male) with MDCT performed 37 days [IQR 32-52] after TAVI were analyzed (53 patients with HALT and 53 matched controls). Before TAVI, all echocardiographic parameters were similar between the groups. At 12 months follow-up, patients with and without HALT showed a significant reduction in LV end-diastolic volume, LV end-systolic volume and LV mass index (from 125 ± 37 to 105 ± 46 g/m 2 , p = 0.001 and from 127 ± 35 to 101 ± 27 g/m 2 , p < 0.001, respectively, p for interaction = 0.48). Moreover, LVEF improved significantly in both groups. In addition, clinical outcomes were not statistically different. Improvement in LVEF and LV reverse remodeling at 12 months after TAVI were not limited by HALT., (© 2021. The Author(s).)

Background: Facial nerve palsy often leads to functional and physiological impairment in patients and they often suffer from social stigma. The use of polydiaxone (PDO) threads has long been used to treat facial furrows and age-related sagging in the face. The basic principle of the thread lift procedure is placing cogged threads in the subcutaneous plane along a planned trajectory. The efficacy and ease of this procedure compared to a traditional face lift has made PDO threads a popular option in the past three decades., Methods: We treated 50 patients with a drooping face on one side following facial paralysis with thread lifting and botulinum injections to control contralateral hypertrophy and ipsilateral synkinesis. The Facial Grading System or the serial Sunnybrook Facial Grading System (SB scores) was used to assess at all the visits and serial photographs were recorded., Results: Following the threading procedure, all 50 patients displayed improved facial symmetry. There was significant improvement in the baseline SB scores compared to the scores over following year, with all the scores having significant p value less than 0.05., Conclusion: Based on our results, subdermal suspension with re-absorbable threads in conjunction with botulinum toxin constitutes an efficient and safe procedure for face lifting and rejuvenation of a drooping face as a result of long-lasting facial paralysis., Competing Interests: DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article., (Copyright © 2022. Matrix Medical Communications. All rights reserved.)

The pathological hallmarks of Alzheimer's disease (AD) are manifested as an increase in the level of oxidative stress and aggregation of the amyloid-β protein. In vitro , in vivo , and in silico experiments were designed and carried out with multifunctional cholinergic inhibitor, F24 (EJMC- 7a ) to explore its neuroprotective effects in AD models. The neuroprotection ability of F24 was tested in SH-SY5Y cells, a widely used neuronal cell line. The pretreatment and subsequent co-treatment of SH-SY5Y cells with different doses of F24 was effective in rescuing the cells from H 2 O 2 induced neurotoxicity. F24 treated cells were found to be effective in the reduction of cellular reactive oxygen species, DNA damage, and Aβ 1-42 induced neurotoxicity, which validated its neuroprotective effectiveness. F24 exhibited efficacy in an in vivo Drosophila model by rescuing eye phenotypes from degeneration caused by Aβ toxicity. Further, computational studies were carried out to monitor the interaction between F24 and Aβ 1-42 aggregates. The computational studies corroborated our in vitro and in vivo studies suggesting Aβ 1-42 aggregation modulation ability of F24. The brain entry ability of F24 was studied in the parallel artificial membrane permeability assay. Finally, F24 was tested at doses of 1 and 2.5 mg/kg in the Morris water maze AD model. The neuroprotective properties shown by F24 strongly suggest that multifunctional features of this molecule provide symptomatic relief and act as a disease-modifying agent in the treatment of AD. The results from our experiments strongly indicated that natural template-based F24 could serve as a lead molecule for further investigation to explore multifunctional therapeutic agents for AD management.

Background: The COVID-19 pandemic has had a substantial adverse impact on the health and well-being of populations in the United States (US) and globally. Although COVID-19 vaccine disparities among US adults aged ≥18 years are well documented, COVID-19 vaccination inequalities among US children are not well studied. Using the recent nationally representative data, we examine disparities in COVID-19 vaccination among US children aged 5-17 years by a wide range of social determinants and parental characteristics., Methods: Using the US Census Bureau's Household Pulse Survey from December 1, 2021 to April 11, 2022 (N=86,335), disparities in child vaccination rates by race/ethnicity, socioeconomic status, health insurance, parental vaccination status, parental COVID-19 diagnosis, and metropolitan area were modeled by multivariate logistic regression., Results: During December 2021-April 2022, an estimated 40.1 million or 57.2% of US children aged 5-17 received COVID-19 vaccination. Vaccination rates were lowest among children of parents aged 25-34 (34.9%) and highest among children of parents aged 45-54 (69.2%). Children of non-Hispanic Black parents, divorced/separated and single individuals, parents with lower education and household income levels, renters, not-employed parents, the uninsured, and parents without COVID-19 vaccination or with COVID-19 diagnoses had significantly lower rates of vaccination. Controlling for covariates, Asian and Hispanic children aged 5-17 had 134% and 47% higher odds of receiving vaccination than their non-Hispanic White counterparts. Children of parents with a high school education had 47% lower adjusted odds of receiving vaccination than children of parents with a master's degree or higher. Children with annual household income <$25,000 had 48% lower adjusted odds of vaccination than those with income ≥$200,000. Although vaccination rates were higher among children aged 12-17 than among children aged 5-11, sociodemographic patterns in vaccination rates were similar. Parental vaccination status was the strongest predictor of children's vaccination status. Vaccination rates for children aged 5-17 ranged from 49.6% in Atlanta, Georgia to 82.6% in San Francisco, California., Conclusion and Global Health Implications: Ethnic minorities, socioeconomically-disadvantaged children, uninsured children, and children of parents without COVID-19 vaccination or with COVID-19 diagnoses had significantly lower vaccination rates. Equitable vaccination coverage among children and adolescents is critical to reducing inequities in COVID-19 health outcomes in the US and globally., Competing Interests: Conflicts of Interest: The authors declare that they have no conflict of interest., (Copyright © 2022 Stokes et al.)

Background: Individuals with chronic heart failure experience high symptom burden, reduced quality of life and high health care utilisation. Although there is growing evidence that a palliative approach, provided concurrently with usual treatment improves outcomes, the method of integrating palliative care for individuals living with chronic heart failure across the care continuum remains elusive., Aim: To examine the key elements of integrated palliative care recommended for individuals living with chronic heart failure across the care continuum., Design: Scoping review., Data Sources: Databases searched were CINAHL, Ovid MEDLINE, Scopus and OpenGrey. Studies written in English and containing key strategic elements specific to chronic heart failure were included. Search terms relating to palliative care and chronic heart failure and the Joanna Briggs Institute methodology for scoping reviews was used., Results: Seventy-nine (79) articles were selected that described key elements to integrate palliative care for individuals with chronic heart failure. This review identifies four levels of key strategic elements: 1) clinical; 2) professional; 3) organisational and 4) system-level integration. Implementing strategies across these elements facilitates integrated palliative care for individuals with chronic heart failure., Conclusions: Inter-sectorial collaborations across systems and the intersection of health and social services are essential to delivering integrated, person-centred palliative care. Further research focussing on patient and family needs at a system-level is needed. Research with strong theoretical underpinnings utilising implementation science methods are required to achieve and sustain complex behaviour change to translate key elements., (Copyright © 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Patients with secondary mitral regurgitation (SMR) often have extramitral valve cardiac involvement, which can influence the prognosis. SMR can be defined according to groups of extramitral valve cardiac involvement. The prognostic implications of such groups in patients with moderate and severe SMR (significant SMR) are unknown. A total of 325 patients with significant SMR were classified according to the extent of cardiac involvement on echocardiography: left ventricular involvement (group 1), left atrial involvement (group 2), tricuspid valve and pulmonary artery vasculature involvement (group 3), or right ventricular involvement (group 4). The primary end point was all-cause mortality. The prevalence of each cardiac involvement group was 17% in group 1, 12% in group 2, 23% in group 3%, and 48% in group 4. Group 3 and group 4 were independently associated with all-cause mortality (hazard ratio 1.794, 95% confidence interval 1.067 to 3.015, p = 0.027 and hazard ratio 1.857, 95% confidence interval 1.145 to 3.012, p = 0.012, respectively). In conclusion, progressive extramitral valve cardiac involvement (group 3 and group 4) was independently associated with all-cause mortality in patients with significant SMR., Competing Interests: Disclosures The Department of Cardiology of the Leiden University Medical Center received research grants from Abbott Vascular, Bayer, Bioventrix, Biotronik, Boston Scientific, Edwards Lifesciences, GE Healthcare, and Medtronic. Victoria Delgado received speaker fees from Abbott Vascular, Edward Lifesciences, GE Healthcare, Merck Sharp & Dohme, and Medtronic. Nina Ajmone Marsan received speakers fees from Abbott Vascular and GE Healthcare. Jeroen J Bax received speaker fees from Abbott Vascular. The remaining authors have no conflicts of interest to declare., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Adolescents and young adults in the United States (US) have experienced a significant increase in drug overdose mortality rates in the last two decades. During the Coronavirus disease 2019 (COVID-19) pandemic, they experienced a lack of access to substance use disorder treatment, stay-home orders, school closure, social isolation, increased psychological distress, and financial strain. Few studies have examined the impact of the pandemic on monthly trends in drug-overdose mortality among youth by race/ethnicity. This study estimates differential changes in monthly drug overdose mortality among youth in the US by age, sex, and race/ethnicity., Methods: Monthly deaths from the final 2018-2020 national mortality data and the 2021 provisional mortality data were used, and monthly population estimates were obtained from the Census Bureau. We calculated age-specific monthly drug overdose deaths per one million population and used log-linear regression models to estimate monthly percent increases in mortality rates from January 2018 through October 2021., Results: Drug-overdose deaths among individuals aged 15-34 increased by 36.5% from 2019 (21,152 deaths) to 2020 (28,879 deaths). From February 2020 to May 2020, the drug-overdose mortality rate increased by 62% for males, 53% for females, 79% for Blacks, 62% for American Indians/Alaska Natives (AIANs), 57% for Hispanics, 56% for non-Hispanic Whites, and 47% for Asians. From January 2018 to October 2021, the average monthly drug-overdose mortality rate increased by 2.69% per month for Blacks, 2.54% for AIANs, 2.27% for Hispanics, 1.37% for Asians, and 0.81% for non-Hispanic Whites. Increases in drug-overdose mortality were more rapid among males than females and among youth aged 15-24 than youth aged 25-34., Conclusion and Global Health Implications: During the peak months in 2020 and 2021, the COVID-19 pandemic had a disproportionate impact by race/ethnicity on trends in drug overdose mortality among the youth. Drug overdose mortality rates increased faster among Blacks, Hispanics, AIANs, and Asians compared to non-Hispanic Whites., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to disclose., (Copyright © 2022 Stokes et al.)

Healthcare systems deal with disease prevention, early detection, diagnosis, investigation, and timely, affordable, and safe treatment. For the delivery of services in the health sector, communication is the key to linking the service provider and the patients. Mobile technology in the recent past has rendered various platforms of communications for the healthcare system. Thus, in health, mobile technology has greatly contributed to time management and cost reduction for healthcare at every level including hospital visits to individual appointments with doctors, hence the convenience. With advancements in mobile technologies and the growing number of mobile users, newer opportunities have opened up for the use of mobiles for patient care. Emerging information and communication technologies with the help of the Internet of Things (IoT) have been instrumental in integrating different domains of the health sector with mobile technology. Thus, the technology may have the potential to become powerful medical tools to support the health sector at all levels of care. In this review, the concept, applications, and advantages of mobile technology for health and the present pandemic have been discussed. It also discusses mobile health technology, as a support system for convenient and safer healthcare for public health, and the opportunities to improve its applications for unseen future health crises., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Background: Previous research has shown a significant association between psychological distress (PD) and all-cause mortality. However, there is a dearth of studies quantifying the contributions of sociodemographic and behavioral characteristics to group differences in mortality. In this study, we identify factors of mortality differences by PD., Methods: The Blinder-Oaxaca decomposition analysis was used to quantify the contributions of individual sociodemographic and behavioral characteristics to the observed mortality differences between United States (US) adults with no PD and those with serious psychological distress (SPD), using the pooled data from the 1997-2014 National Health Interview Survey prospectively linked to the 1997-2015 National Death Index (N = 263,825)., Results: Low educational level, low household income, and high proportions of current smokers, renters, former drinkers, and adults experiencing marital dissolution contributed to high all-cause mortality among adults with SPD. The relative percentage of all-cause mortality disparity explained by socioeconomic and demographic factors was 38.86%. Approximately 47% of the mortality disparity was attributed to both sociodemographic and behavioral risk factors. Lower educational level (21.13%) was the top contributor to higher all-cause mortality among adults with SPD, followed by smoking status (13.51%), poverty status (11.77%), housing tenure (5.11%), alcohol consumption (4.82%), marital status (3.61%), and nativity/immigrant status (1.95%). Age, sex, and body mass index alleviated all-cause mortality risk among adults with SPD., Conclusions and Global Health Implications: Improved education and higher income levels, and reduced smoking among US adults with SPD might eliminate around half of the all-cause mortality disparity by SPD. Such a policy strategy might lead to reductions in mental health disparities and adverse health impacts both in the US and globally., Competing Interests: Conflicts of Interests: The authors declare no competing interest., (Copyright © 2022 Ihekweazu, et al.)

Aims: Peak left atrial longitudinal strain (PALS) is a marker of the left atrial (LA) reservoir function. Novel feature tracking (FT) software allows assessment of LA strain from multidetector computed tomography (MDCT) data. This study aimed at evaluating the agreement between speckle tracking echocardiography (STE) and FT MDCT for the measurement of PALS in patients with sinus rhythm (SR) and with atrial fibrillation (AF)., Methods and Results: The current study included 318 patients (80 ± 7 years, 54% male) with dynamic MDCT data acquired prior to transcatheter aortic valve implantation. PALS was measured by transthoracic echocardiography using STE (PALSecho) and MDCT using dedicated FT software (PALSCT). In the overall population, the median values of PALSecho and PALSCT were 19.0 [interquartile range (IQR) 12.0-25.0] % and 15.3 (IQR 9.2-19.7) %, respectively. High correlation between PALSecho and PALSCT was observed (r = 0.789, P < 0.001) with a mean bias of -3.7%. The correlation between PALSecho and PALSCT was better among patients with SR (N = 258; r = 0.704, P < 0.001) as compared to patients with AF (N = 60; r = 0.622, P < 0.001)., Conclusion: PALSecho and PALSCT showed a good agreement in patients with severe aortic stenosis (AS) regardless of the cardiac rhythm. FT MDCT may be an important adjuvant modality for assessing LA reservoir function in patients with severe AS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Introduction: The coronavirus disease 2019 (COVID-19) pandemic is the largest public health challenge of the twenty-first century. While COVID-19 primarily affects the respiratory system, manifesting as interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also has implications for the cardiovascular system. Moreover, those admitted to hospital with severe COVID-19 are more likely to have cardiovascular comorbidities such as hypertension and diabetes mellitus. The underlying pathophysiology of why COVID-19 onset can further decline cardiac pathologies as well as trigger acute onset of new cardiac complications is not yet well understood., Areas Covered: In this review, the authors extensively review literature focused on the current understanding and approaches of managing patients who have underlying cardiovascular diseases and concomitant COVID-19 infection. Furthermore, the authors explore the possible cardiovascular implications of the suggested COVID-19 therapeutic agents that are used to treat this lethal disease., Expert Opinion: Current evidence is evolving around the many trialed pharmacotherapeutic considerations for the management of coronavirus disease 2019 (COVID-19) in patients with cardiovascular disease. While we await such data, clinicians should advocate for careful consideration of all concomitant medications for those presenting with COVID-19 on a patient-by-patient basis.

Background: Vocal cord palsy is one of the recognised complications of complex cardiac surgery in the paediatric population. While there is an abundance of literature highlighting the presence of this complication, there is a scarcity of research focusing on the pathophysiology, presentation, diagnosis, and treatment options available for children affected by vocal cord palsy., Materials and Methods: Electronic searches were conducted using the search terms: "Vocal Cord Palsy," "VCP," "Vocal Cord Injury," "Paediatric Heart Surgery," "Congenital Heart Surgery," "Pediatric Heart Surgery," "Vocal Fold Movement Impairment," "VFMI," "Vocal Fold Palsy," "PDA Ligation." The inclusion criteria were any articles discussing the outcomes of vocal cord palsy following paediatric cardiac surgery., Results: The two main populations affected by vocal cord palsy are children undergoing aortic arch surgery or those undergoing PDA ligation. There is paucity of prospective follow-up studies; it is therefore difficult to reliably assess the current approaches and the long-term implications of management options., Conclusion: Vocal cord palsy can be a devastating complication following cardiac surgery, which if left untreated, could potentially result in debilitation of quality of life and in severe circumstances could even lead to death. Currently, there is not enough high-quality evidence in the literature to aid recognition, diagnosis, and management leaving clinicians to extrapolate evidence from adult studies to make clinical judgements. Future research with a focus on the paediatric perspective is necessary in providing evidence for good standards of care.

Competing Interests: There are no conflicts of interest.

Aims: Left ventricular ejection fraction is the conventional measure used to guide heart failure management, regardless of underlying etiology. Left ventricular global longitudinal strain (LV-GLS) by speckle tracking echocardiography (STE) is a more sensitive measure of intrinsic myocardial function. We aim to establish LV-GLS as a marker of replacement myocardial fibrosis on cardiovascular magnetic resonance (CMR) and validate the prognostic value of LV-GLS thresholds associated with fibrosis. Methods and results: LV-GLS thresholds of replacement fibrosis were established in the derivation cohort: 151 patients (57 ± 10 years; 58% males) with hypertension who underwent STE to measure LV-GLS and CMR. Prognostic value of the thresholds was validated in a separate outcome cohort: 261 patients with moderate-severe aortic stenosis (AS; 71 ± 12 years; 58% males; NYHA functional class I-II) and preserved LVEF ≥50%. Primary outcome was a composite of cardiovascular mortality, heart failure hospitalization, and myocardial infarction. In the derivation cohort, LV-GLS demonstrated good discrimination (c-statistics 0.74 [0.66-0.83]; P < 0.001) and calibration (Hosmer-Lemeshow χ 2 = 6.37; P = 0.605) for replacement fibrosis. In the outcome cohort, 47 events occurred over 16 [3.3, 42.2] months. Patients with LV-GLS > -15.0% (corresponding to 95% specificity to rule-in myocardial fibrosis) had the worst outcomes compared to patients with LV-GLS < -21.0% (corresponding to 95% sensitivity to rule-out myocardial fibrosis) and those between -21.0 and -15.0% (log-rank P < 0.001). LV-GLS offered independent prognostic value over clinical variables, AS severity and echocardiographic LV mass and E/e'. Conclusion: LV-GLS thresholds associated with replacement myocardial fibrosis is a novel approach to risk-stratify patients with AS and preserved LVEF., Competing Interests: The department of Cardiology at Leiden University receives unrestricted research grants from Abbott Vascular, Bayer, Biotronik, BIoventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis and Medtronic. VD received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, MSD, Medtronic and Novartis. JJB received speaker fees from Abbott Vascular. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Le, Huang, Singh, Toh, Ewe, Tang, Loo, Bryant, Ang, Tay, Soo, Yip, Oon, Gong, Lunaria, Yong, Lee, Yeo, Chai, Goh, Ling, Ong, Richards, Delgado, Bax, Ding, Ling and Chin.)

Purpose: Since the start of the coronavirus disease 2019 (COVID-19) pandemic in March 2020, ∼40% of U.S. adults have experienced delayed medical care. Rates of uninsurance, delayed care, and utilization of mental health services during the course of the pandemic have not been analyzed in detail. We examined monthly trends and disparities in access to care by household income levels in the United States. Methods: Using Census Bureau's nationally representative pooled 2020 Household Pulse Survey from April to December, 2020 ( N =778,819), logistic regression models were used to analyze trends and inequalities in various access to care measures. Results: During the COVID-19 pandemic, the odds of being uninsured, having a delayed medical care due to pandemic, delayed care of something other than COVID-19, or delayed mental health care were, respectively, 5.54, 1.50, 1.85, and 2.18 times higher for adults with income <$25,000, compared to those with incomes ≥$200,000, controlling for age, sex, race/ethnicity, education, marital status, housing tenure, region of residence, and survey month. Income inequities in mental health care widened over the course of the pandemic, while the probability of delayed mental health care increased for all income groups. Although the odds of taking prescription medication for mental health were higher for low-income adults, the odds of receiving mental health services were generally lower for lower income adults, controlling for all covariates. Conclusion: In light of our findings on persistent health care inequities during the pandemic, increased policy efforts are needed to improve access to care in low-income populations as an equitable COVID-19 recovery response., Competing Interests: No competing financial interests exist., (© Hyunjung Lee and Gopal K. Singh 2021; Published by Mary Ann Liebert, Inc.)

Background: Weight loss during chemotherapy and its impact on the cancer outcomes have been invariably reported in the literature. We also did a post-hoc analysis of a randomized phase III trial to see the same., Materials and Methods: The database of a recently published randomized study comparing cisplatin-radiation with nimotuzumab cisplatin-radiation was used for this analysis. Week-wise weight loss during the course of treatment was noted. The impact of severe weight loss (grade 2-3) on progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) was studied using the Kaplan Meier method. Binary logistic regression analysis was used to see the effect of various factors., Results: Out of a total of 536 patients, weight loss was captured in 524. Out of these 524 patients, any degree of weight loss was seen in 293 (55.91%) patients. Grade 1 weight loss was noted in 192 (36.6%) patients, grade 2 in 96 (18.3%) and grade 3 in 5 (1%) patients. The 2-year PFS was 53% and 57.1% in severe and non-severe weight loss groups respectively (p-value = 0.36). The 2-year LRC was 60% in patients with severe weight loss, while it was 63.5% in those with non-severe weight loss (p-value = 0.47). The 2-year OS was 59.3% versus 62.2% in severe and non-severe weight loss cohorts respectively (p-value = 0.21). None of the factors was found to be associated with severe weight loss., Conclusion: Severe weight loss was uncommon in our patients. Weight loss during treatment was not associated with poor survival outcomes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Research has shown worsening physical and mental health outcomes during the COVID-19 pandemic. Trends in general and mental health inequalities during the pandemic in the US have not been analyzed in detail., Methods: Using Census Bureau's nationally representative pooled Household Pulse Survey (HPS) from April 2020 to May 2021 (N = 1,144,405), we examined monthly trends and disparities in health status by race/ethnicity and socioeconomic status (SES). Logistic regression models and disparity indices were used to analyze trends and inequalities., Results: During the pandemic, the adjusted odds of fair and/or poor health were, respectively, 33%, 157%, 398%, 22% higher for non-Hispanic others, adults with

Setting: Nobel Medical College and Teaching Hospital, Biratnagar, Nepal., Objective: To determine the pattern of antimicrobial resistance and hospital exit outcomes in neonates with suspected sepsis in a tertiary neonatal intensive care unit (NICU)., Design: This hospital-based cohort study was conducted to follow patients from January to December 2019. All identified cases of suspected sepsis were enlisted from hospital records., Results: Sepsis was suspected in 177 (88%) of the 200 cases admitted in the NICU; 52 (29%) were culture-positive. Pseudomonas was the predominant organism isolated ( n = 40; 78%), followed by coagulase negative staphylococcus ( n = 12, 23%). Nine (17%) of the 52 isolates were resistant to the Access and Watch group of antibiotics, including some resistance to Reserve group drugs such as imipenem and linezolid. Most treated cases ( n = 170, 96%) improved, although 7 (4%) left against medical advice., Conclusion: Most of the pathogens were resistant to WHO Access and Watch antibiotics and occasional resistance was observed to Reserve group drugs. Most sepsis was caused by Gram-negative bacilli. Improving turnaround times for antibiotic sensitivity testing using point-of-care testing, and a greater yield of culture-positive results are needed to enhance the management of neonatal sepsis., (© 2021 The Union.)

Purpose: Living alone, an indicator of social isolation, has been increasing in the United States; 28% of households in 2019 were one-person households, compared with 13% in 1960. The working-age population is particularly vulnerable to adverse social conditions such as low social support. Although previous research has shown that social isolation and loneliness lead to poorer health and decreased longevity, few studies have focused on the working-age population and heart disease mortality in the United States using longitudinal data. Methods: This study examines social isolation as a risk factor for all-cause and heart disease mortality among U.S. adults aged 18-64 years using the pooled 1998-2014 data from the National Health Interview Survey (NHIS) linked to National Death Index (NDI) ( n =388,973). Cox proportional hazards regression was used to model survival time as a function of social isolation, measured by "living alone," and sociodemographic, behavioral, and health characteristics. Results: In Cox regression models with 17 years of mortality follow-up, the age-adjusted all-cause mortality risk was 45% higher (hazard ratio [HR]=1.45; 95% confidence interval [CI]=1.40-1.50) and the heart disease mortality risk was 83% higher (HR=1.83; 95% CI=1.67-2.00) among adults aged 18-64 years living alone at the baseline, compared with adults living with others. In the full model, the relative risk associated with social isolation was 16% higher (HR=1.16; 95% CI=1.11-1.20) for all-cause mortality and 33% higher (HR=1.33; 95% CI=1.21-1.47) for heart disease mortality after controlling for sociodemographic, behavioral-risk, and health status characteristics. Conclusion: In this national study, adults experiencing social isolation had statistically significantly higher relative risks of all-cause and heart disease mortality in the United States than adults living with others., Competing Interests: No competing financial interests exist., (© Hyunjung Lee and Gopal K. Singh 2021; Published by Mary Ann Liebert, Inc.)

In our earlier paper, we described ferulic acid (FA) template based novel series of multifunctional cholinesterase (ChE) inhibitors for the management of AD. This report has further extended the structure-activity relationship (SAR) studies of this series of molecules in a calibrated manner to improve upon the ChEs inhibition and antioxidant property to identify the novel potent multifunctional molecules. To investigate the effect of replacement of phenylpiperazine ring with benzylpiperazine, increase in the linker length between FA and substituted phenyl ring, and replacement of indole moiety with tryptamine on this molecular template, three series of novel molecules were developed. All synthesized compounds were tested for their acetyl and butyryl cholinestrases (AChE and BChE) inhibitory properties. Enzyme inhibition and PAS binding studies identified compound 13b as a lead molecule with potent inhibitor property towards AChE/BChE (AChE IC 50  = 0.96 ± 0.14 µM, BChE IC 50  = 1.23 ± 0.23 µM) compared to earlier identified lead molecule EJMC-G (AChE IC 50  = 5.74 ± 0.13 μM, BChE IC 50  = 14.05 ± 0.10 μM, respectively). Molecular docking and dynamics studies revealed that 13b fits well into the active sites of AChE and BChE, forming stable and strong interactions with key residues Trp86, Ser125, Glu202, Trp 286, Phe295, Tyr 337 in AChE, and with Trp 82, Gly115, Tyr128, and Ser287 in BChE. The compound, 13b was found to be three times more potent antioxidant in a DPPH assay (IC 50  = 20.25 ± 0.26 µM) over the earlier identified EJMC-B (IC 50  = 61.98 ± 0.30 µM) and it also was able to chelate iron. Co-treatment of 13b with H 2 O 2 , significantly attenuated and reversed H 2 O 2 -induced toxicity in the SH-SY5Y cells. The parallel artificial membrane permeability assay-blood brain barrier (PAMPA-BBB) revealed that 13b could cross BBB efficiently. Finally, the in-vivo efficacy of 13b at dose of 10 mg/kg in scopolamine AD model has been demonstrated. The present study strongly suggests that the naturally inspired multifunctional molecule 13b may behave as a potential novel therapeutic agent for AD management., (Copyright © 2021 Elsevier Ltd. All rights reserved.)