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The coronavirus disease 2019 (COVID-19) pandemic has necessitated the development of antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 3C-like protease (3CLpro) is a promising target for COVID-19 treatment. Here, we report a new class of covalent inhibitors of 3CLpro that possess chlorofluoroacetamide (CFA) as a cysteine-reactive warhead. Based on an aza-peptide scaffold, we synthesized a series of CFA derivatives in enantiopure form and evaluated their biochemical efficiency. The data revealed that 8a (YH-6) with the R configuration at the CFA unit strongly blocks SARS-CoV-2 replication in infected cells, and its potency is comparable to that of nirmatrelvir. X-ray structural analysis showed that YH-6 formed a covalent bond with Cys145 at the catalytic center of 3CLpro. The strong antiviral activity and favorable pharmacokinetic properties of YH-6 suggest its potential as a lead compound for the treatment of COVID-19.The interface of perovskite solar cells (PSCs) plays a significant role in influencing their performance, yet there is still scarce research focusing on their difficult-to-expose bottom interfaces. Herein, ethylammonium bromide (EABr) is introduced into the bottom interface and its passivation effects are studied directly. First, EABr can improve substrate wettability, which is beneficial for the perovskite-film deposition. By lifting off the perovskite film spontaneously from the substrate, it is found that EABr can significantly reduce the amount of unreacted PbI2 at the bottom interface. These PbI2 crystals have been recently identified as a major defect source and degradation site for perovskite film. Meanwhile, EABr also lifts the valence band maximum at the bottom side of perovskite from -5.38 to -5.09 eV, facilitating better hole transfer. Such a improvement is also verified by the study of charge carrier dynamics. Through introducing EABr, all photovoltaic parameters of the inverted PSCs are improved, and their power conversion efficiency (PCE) increases from 20.41% to 21.06%. The study highlights the importance of direct characterization of the bottom interface for a better passivation effect.

Sedative-hypnotic drugs (SHDs) used for insomnia are recommended for short-term use owing to concerns regarding abuse and dependence. Nevertheless, drug discontinuation is challenging owing to rebound insomnia that occurs when the SHD is ceased. Therefore, a strategy is required to reduce or discontinue SHDs, while minimizing rebound insomnia.

The present report discusses the cases of a 72-year-old man and 27-year-old man with insomnia. Both patients had been taking SHDs for more than 2 months.

Both patients were diagnosed with primary insomnia.

After 2 weeks of classical conditioning (CC) using Hwangryunhaedok-tang (HHT), both patients succeeded in tapering SHD; the Korean version of the insomnia severity index of patient 1 dropped from 14 to 5, and that of patient 2 dropped from 28 to 11. learn more In the final follow-up, the index dropped to 2 and 3, respectively.

The CC, a concept emerging in psychology, could be a new strategy for tapering drugs. In this case, SHDs, which had been taken for a long time, assist in tapering anticonvulsants or steroids as well as SHDs.

Female secondary school students are the primary recommended population for human papillomavirus (HPV) vaccines. However, vaccine hesitancy may affect uptake. In this study, we assessed the vaccine hesitancy levels among the guardians of female secondary school students in China.

We developed a questionnaire and conducted cross-sectional surveys among guardians of secondary school girls aged 12-19years in mainland China based on the Increasing Vaccination Model and the Precaution Adoption Process Model.

We collected 3,225 valid samples. Among the participating guardians, 53.9% were vaccine hesitant, although only 0.9% had refused HPV vaccines. Some individual characteristics of guardians (e.g. sex, education/income level) were associated with understanding HPV vaccines. Better knowledge of HPV vaccines and communication with reliable sources of information were associated with vaccine nonhesitancy. Practical barriers such as vaccine shortage and busy schedules prevented nonhesitant guardians from vaccinating their children.

A substantial proportion of the guardians surveyed were HPV vaccine hesitant. Promoting HPV knowledge and communication with reliable sources (e.g. clinical doctors) could help fight against vaccine hesitancy.

A substantial proportion of the guardians surveyed were HPV vaccine hesitant. Promoting HPV knowledge and communication with reliable sources (e.g. clinical doctors) could help fight against vaccine hesitancy.

To examine the association between state firearm legislation and youth/young adult handgun carrying in the United States and to identify policy priority areas for intervention.

We linked person-level gun carrying data from a nationally representative sample of U.S. youth and young adults with state-level gun policies over a 15-year period. Cross-classified mixed effects logistic regressions estimated the associations between state gun policies and handgun carrying and explored whether the associations varied by person-level demographic characteristics.

Youth and young adults in states with a greater number of gun policies were less likely to carry a handgun than youth and young adults in states with fewer gun policies. Regulations on gun purchasing, concealed carrying permitting, and domestic violence-related laws were particularly important in reducing youth/young adult gun-carrying behavior. In addition, these associations varied by gender and race/ethnicity.

State firearm legislation may be an effective mechanism to reduce youth and young adult gun carrying and ultimately mitigate gun-related mortality and morbidity.

State firearm legislation may be an effective mechanism to reduce youth and young adult gun carrying and ultimately mitigate gun-related mortality and morbidity.

This study aimed to understand 10- to 19-year-old adolescents' conceptions of mental health and well-being, and suggestions for appropriate interventions, in three low- and middle-income countries to inform the design of adolescent-responsive preventive and promotive mental health programming.

Ninety-one adolescents participated in focus group discussions in Belize, Kazakhstan, and South Africa. The discussions were recorded, transcribed, translated, and analyzed using thematic analysis.

Adolescents were active contributors to the discussions and provided important information and solutions for improving adolescents' mental health from interpersonal skills training to interventions in schools and communities. Adolescents identified a need for social emotional skills development, particularly regarding interpersonal relationships and navigating peer pressure and bullying. Furthermore, the discussions highlighted the need for programming to be tailored to the local context regarding language, contextual challenges faced by adolescents, and choice of program facilitators. Adolescents valued supportive interactions with adults in their lives and recommended that programs should include teacher/parent training on interacting with adolescents.

These findings highlight that adolescents are valuable partners in developing adolescent health interventions and show that social emotional skills are key components in such interventions. These programs should be culturally and locally appropriate and include components for teachers and parents.

These findings highlight that adolescents are valuable partners in developing adolescent health interventions and show that social emotional skills are key components in such interventions. These programs should be culturally and locally appropriate and include components for teachers and parents.

Do patients with adenomyosis present a dysregulated endometrial receptivity that can be reversed with personalized embryo transfer (PET) by transcriptomic-based progesterone adjustment, improving IVF outcomes?

A multicentre, retrospective, cohort study that transcriptomically analysed the endometrial receptivity of the endometrium in patients with adenomyosis (n = 81) and healthy women (n = 231). Subsequently, implantation, biochemical and clinical miscarriage, and live birth rates between adenomyosis patients with one previous implantation failure using donor oocytes who received (n = 59) or did not receive (n = 66) PET based on endometrial receptivity, were observed to evaluate if adjusted progesterone improves reproductive outcomes of adenomyosis patients.

Patients with adenomyosis significantly presented an altered endometrial receptivity (non-receptive) compared with healthy patients (53.1% versus 37.2%, P = 0.0179), elevating the risk of adenomyosis patients having a non-receptive endometrium 42.5ng progesterone before PET, using endometrial transcriptomic signatures, does not improve IVF outcomes in patients with adenomyosis. Other molecular mechanisms beyond progesterone regulation may be involved in implantation failure.Residency education in oral and maxillofacial surgery (OMS) exists in an environment of transformation unlike anything seen in the past. Changes in American society accelerated by the COVID-19 pandemic are impacting all of health-care education and demand a comprehensive response by OMS programs and in standards for education. The oral health in America report of the National Institutes of Health and actions of the American Council on Graduate Medical Education provides a new framework for structuring and adapting OMS programs. These include incorporating the Quadruple Aims and ACGME core competencies into OMS education. The evolution of clinical education is being adapted to changes in technology and the American higher education environment. A changing workforce and practice model combined with today's technology revolution are being incorporated into OMS residency education.Despite being one of the most reliable procedures in orthopedic surgery, complications can occur after total hip arthroplasty, and radiology plays an essential role in their evaluation. This article will review the various types of hip arthroplasty and their normal appearances on imaging, followed by mechanisms and imaging appearances of component wear and fracture.

Helicopter search and rescue (SAR) in Africa is conducted primarily by military organizations. Since 2002, the Western Cape of South Africa has had a dedicated contracted civilian helicopter emergency medical service (HEMS) conducting air ambulance, terrestrial, and aquatic rescue. To our knowledge, this is the first description of the operations of an African helicopter rescue service.

A 5-y retrospective review of the terrestrial and aquatic helicopter rescue activity of a civilian-operated HEMS in the Western Cape, South Africa, from January 1, 2012 through December 31, 2016, was conducted. Data were extracted from the organization's operational database, aviation documents, rescue reports, and patient care records. Patient demographics and activity at the time of rescue, temporal and geographical distribution, crewing compositions, patient injury, triage, clinical interventions, and rescue techniques were analyzed.

A total of 581 SAR missions were conducted, of which 451 were terrestrial and 130 were aquatic rescues.