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RNA viruses have developed specialized mechanisms to subvert host RNA-binding proteins (RBPs) favoring their own gene expression. The Leader (L) protein of foot-and-mouth disease virus, a member of the Picornaviridae family, is a papain-like cysteine protease that self-cleaves from the polyprotein. Early in infection, the L protease cleaves the translation initiation factors eIF4GI and eIF4GII, inducing the shutdown of cap-dependent translation. However, the cleavage sites on the viral polyprotein, eIF4GI, and eIF4GII differ in sequence, challenging the definition of a consensus site for L targets. Identification of Gemin5 and Daxx proteolytic products in infected cells unveiled a motif centered on the RKAR sequence. The RBP Gemin5 is a member of the survival of motor neurons complex, a ribosome interacting protein, and a translation downregulator. Likewise, the Fas-ligand Daxx is a multifunctional adaptor that plays key roles in transcription control, apoptosis, and innate immune antiviral response. Remarkably, the cleavage site on the RNA helicases MDA5 and LGP2, two relevant immune sensors of the retinoic acid-inducible gene-I (RIG-I)-like receptors family, resembles the L target site of Gemin5 and Daxx, and similar cleavage sites have been reported in ISG15 and TBK1, two proteins involved in type I interferon response and signaling pathway, respectively. In this review we dissect the features of the L cleavage sites in essential RBPs, eventually helping in the discovery of novel L targets. This article is categorized under RNA in Disease and Development > RNA in Disease Translation > Translation Regulation.

To assess the effects of fall prevention services initiated in the emergency department (ED) to support patients after discharge.

A systematic review and meta-analysis were conducted. Analysis of pooled data used random-effects modelling with results presented as a risk ratio (RR).

Eleven studies were identified (n=4,018). The proportion of older adults who fell did not differ between the intervention and control groups (RR 0.93; 95% CI, 0.82-1.06, I

68%, P=0.28). There was a significant (P=0.01) reduction in the monthly rate of falling (RR 0.69; 95% CI, 0.52-0.91, I

93%), fall-related injuries (RR 0.72; 95% CI, 0.59-0.88, I

0%, P=0.001), and hospital admissions (RR 0.76; 95% CI, 0.64-0.90, I

0%, P=0.002).

ED fall prevention services did not significantly reduce the proportion of older adults who had future falls. However, multifactorial intervention significantly reduced fall-related injuries and hospital admissions with low heterogeneity.

ED fall prevention services did not significantly reduce the proportion of older adults who had future falls. However, multifactorial intervention significantly reduced fall-related injuries and hospital admissions with low heterogeneity.This paper proposes a list of specifications (NanoTox metadata list) to be reported about nanotoxicity experiments (metadata) together with resultant data to add toxicological context to reported studies. In areas involving nanomaterials (NMs), existing metadata reporting standards include the reporting of experimental conditions and protocols (MIRIBEL) and material characteristics (MINChar and MIAN), as well as reporting focused on specific experiments (MINBE). NanoCRED is a similarly transparent and structured framework, however, it is developed to guide risk assessors in evaluating the reliability and relevance of NM ecotoxicity studies. There is no reporting standard which would include interpretation of the aims and outcomes of nanotoxicity studies beyond regulatory purposes. The proposed NanoTox metadata reporting checklist is elaborated to extend reporting toward describing nanotoxicological context and thus is a logical complement to technology/material-assay focused reporting checklists. It is further designed to allow for NM toxicity data and knowledge integration, reuse, and communication. Its ultimate goal is to adhere to the basic rules of toxicology when taking a stand on the toxicity of NMs and to limit speculations on safety. As nanotoxicology becomes more interdisciplinary with the advent of new tools and new materials to be tested, reporting standards will contribute to cross-disciplinary communication.

Diabetes and bone health are closely related. We examined the incidence and risk factors of hip fractures in Chinese patients with type 2 diabetes (T2D).

In this prospective cohort, we consecutively enrolled 22,325 adults with T2D above the age of 40years in the Hong Kong Diabetes Register between 1994 and 2015 with crude hip fracture incidence rate censored in 2017.

At baseline, the mean age of this cohort was 60.9±10.5years (mean duration of diabetes 6years, 52.4% male). During a mean±standard deviation (SD) follow-up period of 8.7±5.2years with 193,553 person-years, 603 patients were hospitalized due to hip fractures with an incidence (95% confidence interval, CI) of 315.1 (290.4-341.3) per 100,000 person-years. On multivariable analysis with competing death risk adjusted, the independent hazard ratios (95% CI) for hip fractures in T2D were 2.01 (1.61-2.51) for female sex, 1.08 (1.07-1.09) for age, 0.93 (0.90-0.95) for body mass index, 1.52 (1.25-1.85) for albuminuria and 1.12 (1.02-1.23) for low density lipoprotein-cholesterol. In men, the 30-day, 1-year and 5-year post-hip fracture mortality rate (95% CI) were 5.8 (2.4-9.1) %, 29.2 (22.3-35.5) % and 65.9 (57.3-72.8) % respectively. The corresponding rates in women were 3.4 (1.6-5.1) %, 18.6 (14.7-22.4) %, and 46.8 (40.9-52.1) %.

Southern Chinese patients with T2D have a high risk of hip fracture associated with suboptimal cardiometabolic-renal risk factors and a high post-fracture mortality rate. click here The effects of improving modifiable risk factors on bone health warrants further evaluation.

Southern Chinese patients with T2D have a high risk of hip fracture associated with suboptimal cardiometabolic-renal risk factors and a high post-fracture mortality rate. The effects of improving modifiable risk factors on bone health warrants further evaluation.Infectious complications after endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are rare but serious. Here, we report a very rare case of delayed onset of mediastinitis with tracheomediastinal fistula after EBUS-TBNA. Surgical debridement was performed, antibiotics were administered, and the postoperative course of the patient was good. Careful monitoring is needed to prevent the possible development of infectious complications after EBUS-TBNA.