SARS-CoV-2 Omicron variant is highly sensitive to molnupiravir, nirmatrelvir, and the combination

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply. SARS-CoV-2 Delta and Omicron are globally relevant variants of...

Glucocorticoid hormones were discovered to have use as potent anti-inflammatory and immunosuppressive therapeutics in the 1940s and their continued use and development have successfully revolutionized the management of acute and chronic inflammatory diseases. However, long-term use of glucocorticoids is severely hampered by undesirable metabolic complications, including the development of type 2 diabetes mellitus. These effects occur due to glucocorticoid receptor activation within multiple tissues, which results in inter-organ crosstalk that increases hepatic glucose production and inhibits peripheral glucose uptake. Despite the high prevalence of glucocorticoid-induced hyperglycaemia associated with their routine clinical use, treatment protocols for optimal management of the metabolic adverse effects are lacking or underutilized. The type, dose and potency of the glucocorticoid administered dictates the choice of hypoglycaemic intervention (non-insulin or insulin therapy) that should be provided to patients. The longstanding quest to identify dissociated glucocorticoid receptor agonists to separate the hyperglycaemic complications of glucocorticoids from their therapeutically beneficial anti-inflammatory effects is ongoing, with selective glucocorticoid receptor modulators in clinical testing. Promising areas of preclinical research include new mechanisms to disrupt glucocorticoid signalling in a tissue-selective manner and the identification of novel targets that can selectively dissociate the effects of glucocorticoids. These research arms share the ultimate goal of achieving the anti-inflammatory actions of glucocorticoids without the metabolic consequences.

European Journal of Human Genetics (2022)Cite this article. Identifying appropriate outcomes for programs such as reproductive genetic carrier screening (RGCS) is important. Knowing which outcomes should be measured or evaluated is vital for assessing program success. Richardson et al. in this issue [1] review qualitative data on patient-reported outcomes in RGCS and provide valuable insights to inform the development of a core outcome set for RGCS.

Spinal cord stimulation (SCS) has been utilized for more than 50 years to treat refractory neuropathic pain. Currently, SCS systems with fully implantable pulse generators (IPGs) represent the standard. New wireless extracorporeal SCS (wSCS) devices without IPGs promise higher levels of comfort and convenience for patients. However, to date there are no studies on how charging and using this wSCS system affects patients and their therapy. This study is the first questionnaire-based survey on this topic focusing on patient experience. The trial was a single arm, open-label and mono-centric phase IV study. Standardized questionnaires were sent to all patients with a wSCS device in use at the time of trial. The primary endpoint was the convenience of the charging and wearing process scored on an ordinal scale from "very hard" (1) to "very easy" (5). Secondary endpoints included time needed for charging, the duration of stimulation per day and complication rates. Questionnaires of 6 out of 9 patients were returned and eligible for data analysis. The mean age of patients was 61.3"‰Â±"‰6.7 (±"‰SD) years. The duration of therapy was 20.3"‰Â±"‰15.9 months (mean"‰Â±"‰SD). The mean duration of daily stimulation was 17"‰Â±"‰5.9 h (mean"‰Â±"‰SD). n"‰="‰5 patients rated the overall convenience as "easy" (4) and n"‰="‰3 patients evaluated the effort of the charging process and wearing of the wSCS device as "low" (4). n"‰="‰5 patients considered the wearing and charging process as active participation in their therapy. n"‰="‰5 patients would choose an extracorporeal device again over a conventional SCS system. Early or late surgical complications did not occur in this patient collective. Overall, patients felt confident using extracorporeal wSCS devices without any complications. Effort to maintain therapy with this system was rated as low.

Randomized clinical trials are a tool to generate high-quality evidence of efficacy and safety for new interventions. The statistical analysis plan (SAP) of a trial is generally pre-specified and documented prior to seeing outcome data, and it is encouraged that researchers follow the pre-specified analysis plan. The process of pre-specification of the primary analysis involves making assumptions about methods, models, and data that may not be supported by the final trial data. Sensitivity analysis examines the robustness of the result by conducting the analyses under a range of plausible assumptions about the methods, models, or data that differ from the assumptions used in the pre-specified primary analysis. If the results of the sensitivity analyses are consistent with the primary results, researchers can be confident that the assumptions made for the primary analysis have had little impact on the results, giving strength to the trial findings. Recent guidance documents for statistical principles have emphasized the importance of sensitivity analysis in clinical trials to ensure a robust assessment of the observed results [1].

The pharmaceutical company Pfizer has voluntary recalled a blood pressure medication for the second time in a month. Pfizer is recalling five lots of blood pressure medicine Accupril because of elevated levels of a nitrosamine, Nnitroso-quinapril, the company said in a news release posted Friday on the FDA website. Nitrosamines...

MILLIONS of Brits have been urged to take up a rapid test to see if they have bowel cancer. The Health Secretary has called on men over 60 to make sure they have the life-saving checkups. It couldn't be easier - with a home testing kit on offer, or use...

Walking at a brisk pace for just 75 minutes every week could cut your risk of depression, a new study finds. The World Health Organization recommends everyone should exercise for at least two-and-a-half hours every seven days. But researchers at Cambridge University, England, found adults who got half as much...

Tragic events like wars, famines, earthquakes, and accidents create fearful memories in our brain. These memories continue to haunt us even after the actual event has passed. Luckily, researchers from Tokyo University of Science (TUS) have recently been able to understand the hidden biochemical mechanisms involved in the selective suppression of fearful memories, which is called fear extinction. The researchers, who had previously demonstrated fear extinction in mice using the chemically synthesized compound "KNT-127," have now identified the underlying mechanism of this compound's action. Their findings have been published recently in Frontiers in Behavioral Neuroscience.

Christine Bronstein took at home colon cancer test after seeing blood in her stool. It was positive, but her doctor texted: "You don't have cancer :)"

To date, no study has reported the objective metabolic laboratory findings worldwide or the comorbidities for Ménière's disease (MD) using a population-based design in Asian populations. The aim of this study was to investigate the comorbidities and associated factors for MD using the Korean National Health Insurance Service database. This retrospective population-based study was conducted using a data from the National Sample Cohort database from 2009 to 2015. We only enrolled patients whose records showed a prescription for MD medicine and audiometry findings as well as an appropriate diagnostic code. We also included a matched cohort without MD who were enrolled randomly and matched for sex, age, year of diagnosis, income level, and residential area with the MD group with a ratio of 10:1. We evaluated comorbidities including autoimmune, allergic, metabolic diseases and cancer and the health screening data including general characteristics (height, weight, waist circumference, body mass index, and blood pressure), laboratory findings (fasting glucose, cholesterol, triglyceride, high-density lipoproteintryglyceride (HDL) cholesterol, low-density lipoproteintryglyceride cholesterol, hemoglobin, creatinine, aspartate aminotransferase and alanine aminotransferase, and gamma-glutamyltrans- peptidase (rGT)), and general health behaviors (smoking, alcohol, and exercise) of the MD group, and compared these characteristics with those of the MD-free control group. A total of 2,013 and 20,130 participants were included in the MD and MD-free control groups (1,640 and 15,458 for health screening data). We found the increase in incidence of allergic rhinitis and allergic asthma, decrease in systolic blood pressure, HDL cholesterol, and rGT, and less frequent alcohol consumption and less prevalent smoking in the MD group. No significant differences were observed between the groups in the incidence of autoimmune diseases, and cerebro- and cardiovascular disease as well as health screening data and objective laboratory findings. Inconsistence with published studies, the results of this study suggest that the autoimmunity and metabolic disorder, and skeletal growth might not be associated with the onset of MD. Another well-designed study for other races will be needed to the generalization of this study results.

For the European Society for Blood and Marrow Transplantation (EBMT) For over two decades, the EBMT has updated recommendations on indications for haematopoietic cell transplantation (HCT) practice based on clinical and scientific developments in the field. This is the eighth special EBMT report on the indications for HCT for haematological diseases, solid tumours and immune disorders. Our aim is to provide general guidance on HCT indications according to prevailing clinical practice in EBMT countries and centres. In order to inform patient decisions, these recommendations must be considered in conjunction with the risk of the disease, risk of HCT procedure and non-transplant strategies, including evolving cellular therapies. HCT techniques are constantly evolving and we make no specific recommendations, but encourage harmonisation of practice, where possible, to ensure experience across indications can be meaningfully aggregated via registry outputs. We also recommend working according to JACIE accreditation standards to maintain quality in clinical and laboratory components of practice, including benchmarking of survival outcomes. Since the last edition, the COVID-19 pandemic has affected clinical decision making and activity across indications. Although the full impact of the pandemic is yet to be determined, we recommend that decision making across indications is delivered with ongoing reference to EBMT and national COVID-19 guidance, in accordance with current local conditions.

In the original version of this Article Huiting Yu and Zhou Liang were omitted as equally contributing authors. The original Article has been corrected. These authors contributed equally: Huiting Yu and Liang Zhou. Vital Statistical Department, Institute of Health Information, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, 200336,...

To investigate the use of intravitreal ziv-aflibercept (IVZ) in Ghanaian patients with diabetic macular edema (DME). A retrospective study of patients with DME, who had been treated with IVZ (1.25"‰mg/0.05"‰ml), as part of routine clinical practice, on pro re nata basis between 2016 and 2018 who had a minimum follow-up of 6 months was retrieved and analyzed. The primary outcome measure was change in best-corrected visual acuity (BCVA) at 6 months. Secondary outcome measures are change in BCVA at 12 months and at the last follow-up visit, adverse events and change in central macular thickness (CMT).

Correction to: Nature Communications https://doi.org/10.1038/s41467-019-10246-5, published online 24 May 2019. The original version of the Supplementary Information associated with this Article included an error in the Supplementary Data 2 file, in which the sequences of "circE7_WT" and "circE7_noATG" were inadvertently switched. The HTML has been updated to include a corrected version of Supplementary Data 2.

Correction to: Scientific Reports https://doi.org/10.1038/s41598-022-09232-7, published online 30 March 2022. The original version of this Article contained an error in the spelling of the authors Renata Auricchio, Ilaria Calabrese, Martina Galatola, Donatella Cielo, Fortunata Carbone, Marianna Mancuso, Giuseppe Matarese, Riccardo Troncone, Salvatore Auricchio & Luigi Greco which were incorrectly given as Auricchio Renata, Calabrese Ilaria, Galatola Martina, Cielo Donatella, Carbone Fortunata, Mancuso Marianna, Matarese Giuseppe, Troncone Riccardo, Auricchio Salvatore & Greco Luigi. The original article has been corrected.

Following the publication of the original article [1], it was noted that due to a typesetting error some elements in Fig. 5j were missing in the website version. The figure in the pdf version is correct. The correct figure has been corrected in the website version. These authors contributed equally:...

The Kilimanjaro Diabetic Programme used the Intervention Mapping framework to develop a theory- and evidence-based diabetic retinopathy screening programme. A Working Committee of health care workers and stakeholders ensured community engagement and empowerment of the target audience. Objectives. To deliver a culturally appropriate, sustainable, community supported health intervention, promoting eye...

Scripps Research, Department of Molecular Medicine, 10550 North Torrey Pines Rd, La Jolla, CA, 92037, USA. Frédéric Anglès, Chao Wang & William E. Balch. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

The development of time-resolved, multiscale and multi-modal X-ray imaging techniques at advanced light sources raises challenges on the data processing end - but image processing methods from other research areas will help. Next-generation beamlines in fourth-generation synchrotrons and X-ray free electron laser (XFEL) facilities will push the temporal and spatial...