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The COVID-19 pandemic posed a threat to global society. Delta and Omicron are concerning variants due to the risk of increasing human-to-human transmissibility and immune evasion. This study aims to evaluate the binding ability of these variants toward the angiotensin-converting enzyme 2 receptor and antibodies using a computational approach. The receptor-binding domain (RBD) of the two variants was created by CHARMM-GUI and then docked to the hACE2 receptor and two antibodies (REGN10933 and REGN10987). These complexes were also subjected to molecular dynamics simulation within 100 ns. As a result, the two variants, Omicron and Delta, exhibited stronger interaction with the hACE2 receptor than the wild type. The mutations in the RBD region also facilitated the virus's escape from antibody neutralization.

Achillea alpina L. (Alpine yarrow) is a noteworthy herb in the genus Achillea with many uses in vegetables and traditionally used to treat stomach disorders. In our continuous research on the chemical constituents and biological activities of medicinal plants, ten previously undescribed terpenoids including eight eudesmane-type sesquiterpenes (1-8), one nor-eudesmane-type sesquiterpene (9), one cyclo-geraniol derivative (10), and twenty-one known compounds were isolated and structurally elucidated from the aerial parts of A. alpina. Structures and absolute configurations of the undescribed terpenoids were identified using comprehensive spectroscopic analysis (NMR, HRESI-MS, and CD data) and computational methods (ECD and NMR calculation). Enzyme inhibitory assays showed that the isolated sesquiterpene (19), triterpene (22), and sterol (26) were protein tyrosine phosphatase 1B (PTP1B) inhibitors with IC 50 values ranging from 14.87 to 23.09 μM in comparison with positive control - ursolic acid, showing IC 50 value of 5.93 ± 0.16 μM. Further enzyme kinetics and molecular docking studies were performed to provide valuable insights into their mechanism of action., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Smoking has long been recognized as a risk factor for impaired wound and bone healing, particularly in the context of ankle and foot surgery. Despite numerous studies exploring the association between smoking and complications following ankle replacement, there remains significant inconsistency in their findings. Therefore, this meta-analysis study aims to elucidate whether smoking increases the rate of complications after total ankle arthroplasty (TAA), providing valuable insights for clinical management., Methods: A comprehensive systematic search was conducted in the PubMed, Embase, and Wiley databases to identify relevant English studies on the influence of smoking on postoperative complications following ankle replacement without any restrictions on publication dates. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Random-effect models were used to calculate odds ratios (OR) and 95 % confidence intervals (CI). This study adhered to PRISMA guidelines for transparent reporting and was registered with PROSPERO., Results: The analysis incorporated data from 12 retrospective cohort studies, totaling 17331 subjects, 2580 of whom were smokers and 791 complications following TAA. The findings revealed a statistically significant disparity in wound-related complications (OR: 2.26; 95 % CI: 1.13-4.50; P = .02), particularly evident in current smokers with an OR of 3.30 (95 % CI: 2.12-5.14; P < .00001). However, we lacked sufficient evidence to substantiate an association between smoking and complications related to the prosthesis (OR: 1.09; 95 % CI: 0.77-1.53; P = .64) or systemic complications (OR: 1.18; 95 % CI: 0.10-14.13; P = .90) following TAA., Conclusions: Smoking, especially current smoking, is associated with increased wound complication risk post-operation for total ankle arthroplasty. Despite a lack of definitive evidence on the optimal timeframe for smoking cessation before surgery, discontinuing smoking appears to be a prudent measure to mitigate these complications., Competing Interests: Competing interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. ICMJE forms for all authors are available online., (Copyright © 2024 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Purpose: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA., Materials and Methods: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process., Results: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit., Conclusions: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines., Competing Interests: The authors have nothing to disclose., (Copyright © 2025 Korean Society for Sexual Medicine and Andrology.)

Objective: National estimates and trends in insomnia symptoms in Canada are outdated. Updates are needed to inform the development of targeted prevention and intervention strategies. This study aimed to examine the prevalence and trends in nighttime insomnia symptoms among Canadians aged 12 years and older between 2007 and 2021., Methods: The Canadian Community Health Survey (CCHS), a nationally representative, repeated cross-sectional survey was used. Nighttime insomnia symptoms were self-reported and defined as trouble going to sleep or staying asleep most or all of the time., Results: This study included data from 197,469 participants. Nighttime insomnia symptoms in Canadians have remained relatively stable from 2007 to 2021, with higher prevalence in adults (18-20 %), particularly women (19-24 %), and those with a medium level of education defined as secondary school graduation (16-21 %). However, nighttime insomnia symptoms became 1.24-fold more prevalent from 2007 to 2021 among women aged 18-64 years (19.3 % vs. 24.0 %) and 1.33-fold more prevalent among those with a medium level of education (15.9 % vs. 21.2 %). Nighttime insomnia symptoms were roughly two times more prevalent in individuals with poorer self-perceived general health, mental health, and life satisfaction compared to those with better self-perception. The prevalence of nighttime insomnia symptoms among those with poor general health increased 1.18-fold from 23.8 % in 2007 to 28.1 % in 2021., Conclusions: Over this 14-year period, nighttime insomnia symptoms have remained consistently high in Canada, but have increasingly affected certain subgroups. Targeted efforts are needed to address this issue in the most affected segments of the population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Charles M. Morin has received research grants from Eisai, Idorsia, and Lallemand Health; has served on advisory boards for Idorsia and Haleon; and received royalties from Mapi Research Trust. Thien Thanh Dang-Vu has received research grants from Jazz Pharmaceuticals and Paladin Labs, and has served on advisory boards for Eisai and Idorsia. Judith R. Davidson has advised, and owns shares in, HALEO. The other authors have declared no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This systematic review and meta-analysis evaluates the efficacy in improving sleep quality and safety of hypnotics in individuals aged 65 years or older compared to those under 65 years., Methods: MEDLINE, EMBASE, Web of Science, and EBM Reviews were searched for randomized clinical trials comparing hypnotics to the placebo in adults with chronic insomnia between Jan 2000 and Dec 2022. The efficacy outcome included all participant self-assessments sleep quality questionnaires. The safety outcome included acceptability and tolerance. Standardized mean differences (SMD) was estimated using a random effect model., Results: We included 17 and 53 clinical trials with 3688 and 14,720 participants in the ≥65 years and <65 years group respectively. The SMD for the sleep quality outcome was -0.36 [Confidence interval (CI) 95 %: 0.45;-0.26] in the ≥65 years group compared to -0.51 [95%CI: 0.61; -0.41] in the <65 years group (p = 0.02). Differences in efficacy were observed between pharmacological classes. The overall SMD for the tolerance outcome was - 0.25 [95%CI: 0.34; -0.16] favoring the placebo group (p < 0.001). In the ≥65 years group the SMD was -0.07 [95%CI: 0.21; 0.08] compared to -0.31 [95%CI: 0.41; -0.21] in the <65 years group (p = 0.01). There were no differences for acceptability., Conclusion: We found that some hypnotics classes could be less effective in older individuals. We encourage authors to include details on multimorbidity and polypharmacy in their publications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thien Thanh Dang-Vu reports a relationship with Eisai Inc that includes: consulting or advisory. Thien Thanh Dang-Vu reports a relationship with Idorsia Pharmaceuticals Ltd that includes: consulting or advisory. Thien Thanh Dang-Vu reports a relationship with Paladin Labs Inc that includes: funding grants. Thien Thanh Dang-Vu reports a relationship with Jazz Pharmaceuticals Inc that includes: funding grants. Philippe Desmarais reports a relationship with Eisai Inc that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)