Pattern of Facial Laceration at Tertiary Care Centre in Eastern Nepal: A Descriptive Cross-sectional Study.

INTRODUCTION: Facial lacerations are a source of concern as these can be life threatening at times due to extensive haemorrhage and also leave lifelong scars. The objective of this study was to find out the pattern of facial lacerations in the Nepalese population visiting a tertiary care centre in eastern Nepal. METHODS: A descriptive cross-sectional study was conducted among the maxillofacial trauma patients visiting the Emergency department and department of Dental Surgery at a tertiary care centre from 1 October 2022 to 30 September 2023. Ethical approval was taken from the Institutional Review Committee . All patients attending the Dental outpatient department and Emergency department for the management of facial laceration in the study period were included in the study. RESULTS: Out of 236 patients, there were 199 (84.32%) male and 37 (15.67%) female patients. The most common age group was of 21-30 years 88 (37.29%) and Road Traffic Accidents 183 (77.54%) was the main aetiology. Facial lacerations and maxillofacial fractures both were seen in 98 (41.53%) patients. There were a total of 358 facial laceration sites among 236 patients and chin region 76 (21.22%) was the most common followed by forehead region 54 (15.08%). CONCLUSIONS: Facial lacerations were mostly seen in males, younger adults and road traffic accidents were the main aetiology for these injuries. Facial lacerations showed predominant T-shaped distribution with chin being the most common site.

The Anticancer Drug Bleomycin Shows Potent Antifungal Activity by Altering Phospholipid Biosynthesis.

Invasive fungal infections are difficult to treat with limited drug options, mainly because fungi are eukaryotes and share many cellular mechanisms with the human host. Most current antifungal drugs are either fungistatic or highly toxic. Therefore, there is a critical need to identify important fungal specific drug targets for novel antifungal development. Numerous studies have shown the fungal phosphatidylserine (PS) biosynthetic pathway to be a potential target. It is synthesized from CDP-diacylglycerol and serine, and the fungal PS synthesis route is different from that in mammalian cells, in which preexisting phospholipids are utilized to produce PS in a base-exchange reaction. In this study, we utilized a Saccharomyces cerevisiae heterologous expression system to screen for inhibitors of Cryptococcus PS synthase Cho1, a fungi-specific enzyme essential for cell viability. We identified an anticancer compound, bleomycin, as a positive candidate that showed a phospholipid-dependent antifungal effect. Its inhibition on fungal growth can be restored by ethanolamine supplementation. Further exploration of the mechanism of action showed that bleomycin treatment damaged the mitochondrial membrane in yeast cells, leading to increased generation of reactive oxygen species (ROS), whereas supplementation with ethanolamine helped to rescue bleomycin-induced damage. Our results indicate that bleomycin does not specifically inhibit the PS synthase enzyme; however, it may affect phospholipid biosynthesis through disruption of mitochondrial function, namely, the synthesis of phosphatidylethanolamine (PE) and phosphatidylcholine (PC), which helps cells maintain membrane composition and functionality. IMPORTANCE Invasive fungal pathogens cause significant morbidity and mortality, with over 1.5 million deaths annually. Because fungi are eukaryotes that share much of their cellular machinery with the host, our armamentarium of antifungal drugs is highly limited, with only three classes of antifungal drugs available. Drug toxicity and emerging resistance have limited their use. Hence, targeting fungi-specific enzymes that are important for fungal survival, growth, or virulence poses a strategy for novel antifungal development. In this study, we developed a heterologous expression system to screen for chemical compounds with activity against Cryptococcus phosphatidylserine synthase, Cho1, a fungi-specific enzyme that is essential for viability in C. neoformans. We confirmed the feasibility of this screen method and identified a previously unexplored role of the anticancer compound bleomycin in disrupting mitochondrial function and inhibiting phospholipid synthesis.