Infinium MethylationEPIC BeadChip profiling further reveals that DNA methylation alterations observed in HGPS fibroblasts are similarly enriched in LADs and different from those occurring during healthy aging and Werner syndrome (WS), another premature aging disease. Moreover, HGPS patients can be stratified into two different subgroups according to their DNA methylation profiles. Finally, we show that the epigenetic deregulation of LADs is associated with HGPS-specific gene expression changes. Conclusions Taken together, our results strongly implicate epigenetic deregulation of LADs as an important and previously unrecognized feature of HGPS, which contributes to disease-specific gene expression. Therefore, they not only add a new layer to the study of epigenetic changes in the progeroid syndrome, but also advance our understanding of the disease's pathology at the cellular level.Background The palmaris longus muscle is considered one of the most anatomically variable muscles in the human body. Localized swelling of the forearm due to hypertrophy of the palmaris longus muscle is rare. Case presentation Here, we report a rare case of a 24-year-old Arab man who presented with a painful mass on his forearm with symptoms of median nerve compression. A full radiological assessment was performed, and he was treated conservatively. Conclusion This case confirmed that a hypertrophied palmaris longus muscle can be the cause of swelling on the forearm and should always be considered in the differential diagnosis. With this report, we aimed to increase awareness regarding the unusual variations of palmaris longus muscle and the importance of using radiological investigations to establish a diagnosis.Background Clinical trials and other studies commonly assess the effectiveness of an intervention through the use of responder-based endpoints. These classify patients based on whether they meet a number of criteria which often involve continuous variables categorised as being above or below a threshold. The proportion of patients who are responders is estimated and, where relevant, compared between groups. An alternative method called the augmented binary method keeps the definition of the endpoint the same but utilises information contained within the continuous component to increase the power considerably (equivalent to increasing the sample size by > 30%). In this article we summarise the method and investigate the variety of clinical conditions that use endpoints to which it could be applied. Methods We reviewed a database of core outcome sets (COSs) that covered physiological and mortality trial endpoints recommended for collection in clinical trials of different disorders. We identified responder-based endpoints where the augmented binary method would be useful for increasing power. Results Out of the 287 COSs reviewed, we identified 67 new clinical areas where endpoints were used that would be more efficiently analysed using the augmented binary method. Clinical areas that had particularly high numbers were rheumatology (11 clinical disorders identified), non-solid tumour oncology (10 identified), neurology (9 identified) and cardiovascular (8 identified). Conclusions The augmented binary method can potentially provide large benefits in a vast array of clinical areas. Further methodological development is needed to account for some types of endpoints.Background As an irreversible, intractable disease with vision loss, glaucoma leads to permanent and progressive damage of visual function. Lowering high intraocular pressure (HIOP) is the first choice for treating glaucoma; however, the control of HIOP is not enough to prevent progressive vison loss. Currently, the therapies to treat glaucoma with controlled IOP (GPCI) are unsatisfactory. Chinese medicine is effective for improving visual function in patients with GPCI. Bujing Yishi tablets (BJYSP) have been the standard preparation for treating GPCI in our hospital for decades. However, no rigorous randomized controlled clinical studies have investigated its effects and safety. Methods This study will be a 6-month, multicenter, stratified trial following a prospective, randomized, open-label, blinded endpoint (PROBE) protocol. A total of 216 eligible GPCI patients aged 18-75 years will be stratified according to the early, moderate, and advanced stages of glaucoma. After stratifying, the participants will bRegistered on 1 June 2018.Background Pseudomonas aeruginosa (PA) is one of the most common and serious causes of healthcare-associated bacteremia. The emergence and dissemination of multidrug-resistant (MDR) and extensively drug-resistant (XDR) PA strains pose a major clinical concern. ST235-PA is a high-risk clone which shows a high capacity to acquire antibiotic resistance. Here we describe the first autochthonous New Delhi metallo-β-lactamase (NDM)-producing Pseudomonas aeruginosa ST235 identified in Italy. Case presentation In October 2019, a patient residing in an elderly health care and rehabilitation facility, was hospitalized and died from sepsis caused by an XDR-PA. The strain belonged to the high-risk clone sequence type ST235. Whole genome sequencing (WGS) revealed the presence of genes encoding NDM-1 and multiple β-lactamases, many clinically significant multidrug efflux pump complexes and also the virulence gene ExoU, which is associated with a high cytotoxic phenotype. Conclusions Few strains of NDM-1-PA have been identified worldwide, all belonging to ST235. The combination of ST235 and ExoU is a predictor of highly unfavorable prognosis. The potential spread of these high-risk clones in healthcare settings is worrisome because treatment options are limited. Early identification of high-risk clones could help in outbreaks investigation and infections control.Background Emerging evidence from China suggests that coronavirus disease 2019 (COVID-19) is deadlier for infected men than women with a 2.8% fatality rate being reported in Chinese men versus 1.7% in women. Further, sex-disaggregated data for COVID-19 in several European countries show a similar number of cases between the sexes, but more severe outcomes in aged men. Case fatality is highest in men with pre-existing cardiovascular conditions.  https://www.selleckchem.com/products/LBH-589.html  The mechanisms accounting for the reduced case fatality rate in women are currently unclear but may offer potential to develop novel risk stratification tools and therapeutic options for women and men. Content The present review summarizes latest clinical and epidemiological evidence for gender and sex differences in COVID-19 from Europe and China. We discuss potential sex-specific mechanisms modulating the course of disease, such as hormone-regulated expression of genes encoding for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) entry receptors angiotensin converting enzyme (ACE) 2 receptor and TMPRSS2 as well as sex hormone-driven innate and adaptive immune responses and immunoaging.