Hand, foot and mouth disease (HFMD) caused by Human Enterovirus A71 (HEVA71) infection is typically a benign infection. However, in minority of cases, children can develop severe neuropathology that culminate in fatality. Approximately 36.9% of HEVA71-related hospitalizations develop neurological complications, of which 10.5% are fatal. Yet, the mechanism by which HEVA71 induces these neurological deficits remain unclear. Here, we show that HEVA71-infected astrocytes release CXCL1 which supports viral replication in neurons by activating the CXCR2 receptor-associated ERK1/2 signaling pathway. Elevated CXCL1 levels correlates with disease severity in a HEVA71-infected mice model. In humans infected with HEVA71, high CXCL1 levels are only present in patients presenting neurological complications. CXCL1 release is specifically triggered by VP4 synthesis in HEVA71-infected astrocytes, which then acts via its receptor CXCR2 to enhance viral replication in neurons. Perturbing CXCL1 signaling or VP4 myristylation strongly attenuates viral replication. Treatment with AZD5069, a CXCL1-specific competitor, improves survival and lessens disease severity in infected animals. Collectively, these results highlight the CXCL1-CXCR2 signaling pathway as a potential target against HFMD neuropathogenesis.
This study conducts a comprehensive analysis of forensic toxicology research trends, publication patterns, author's contributions, and collaboration. Utilizing the Scopus database, we scrutinized 3259 articles across 348 journals spanning from 1975 to 2023. Analysis employed diverse software tools such as VOSviewer, RStudio, MS Excel, and MS Access to dissect various publication aspects. We observed a notable surge in publications post-2007, indicating heightened research interest. Leading contributors included the United States, Germany, and Italy, with Logan B.K. emerging as the most prolific author. Forensic Science International stood out as the primary journal, publishing 888 articles and accruing significant citations. Keyword co-occurrences such as "forensic toxicology," "forensic science," and "toxicology" underscored core thematic areas in the field. Moreover, extensive research collaboration, especially among Western nations in Europe, was evident. This study underscores the imperative for enhanced collaboration between developing and developed nations to foster further advancements in forensic science. Strengthened partnerships can catalyze innovation, facilitate knowledge dissemination, and address emerging challenges, thereby propelling the field of forensic toxicology toward new frontiers of discovery and application.
In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.
In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.