The clinical course and treatment of black mamba (Dendroaspis polylepis) envenomations: a narrative review

CONTEXT: The black mamba (Dendroaspis polylepis) is, due to its extremely toxic venom, one of the most dangerous snake species in Sub-Saharan Africa. A D. polylepis bite is a medical emergency and requires adequate action to prevent severe complications. However, there are no comprehensive reviews available based on clinical cases, and no readily accessible guidelines for standardized treatment. Therefore, we aim to provide an overview regarding the currently available clinical literature on D. polylepis envenomations; in order to promote knowledge on symptomatology and treatment options. METHODS: We searched for cases reporting humans bitten by D. polylepis in PubMed, Embase, Scopus, and Sabinet. We searched the reference lists of all eligible articles for additional articles. After quality assessment, 29 cases were included in this review. We used descriptive analysis to create an overview of the collected parameters. DISCUSSION: Among the included case reports and case series, D. polylepis envenomations most frequently resulted in decreased respiratory function, sweating and paralysis. The onset of symptoms usually occurred within 60 minutes. Neurological symptoms occurred more often than symptoms of autonomic dysfunction. In the reported cases most patients (26/29) received antivenom and most survived (25/29). We recommend the reporting of additional structured case reports to improve future analyses on the clinical course of envenomations, in order to improve public health response to D. polylepis envenomations

TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila

Transportin-2 (TNPO2) mediates multiple pathways including non-classical nucleocytoplasmic shuttling of >60 cargoes, such as developmental and neuronal proteins. We identified 15 individuals carrying de novo coding variants in TNPO2 who presented with global developmental delay (GDD), dysmorphic features, ophthalmologic abnormalities, and neurological features. To assess the nature of these variants, functional studies were performed in Drosophila. We found that fly dTnpo (orthologous to TNPO2) is expressed in a subset of neurons. dTnpo is critical for neuronal maintenance and function as downregulating dTnpo in mature neurons using RNAi disrupts neuronal activity and survival. Altering the activity and expression of dTnpo using mutant alleles or RNAi causes developmental defects, including eye and wing deformities and lethality. These effects are dosage dependent as more severe phenotypes are associated with stronger dTnpo loss. Interestingly, similar phenotypes are observed with dTnpo upregulation and ectopic expression of TNPO2, showing that loss and gain of Transportin activity causes developmental defects. Further, proband-associated variants can cause more or less severe developmental abnormalities compared to wild-type TNPO2 when ectopically expressed. The impact of the variants tested seems to correlate with their position within the protein. Specifically, those that fall within the RAN binding domain cause more severe toxicity and those in the acidic loop are less toxic. Variants within the cargo binding domain show tissue-dependent effects. In summary, dTnpo is an essential gene in flies during development and in neurons. Further, proband-associated de novo variants within TNPO2 disrupt the function of the encoded protein. Hence, TNPO2 variants are causative for neurodevelopmental abnormalities

Advantage of preserving bi-orientation structure of isotactic polypropylene through die drawing

YesThe isotactic polypropylene (iPP) usually shows a unique parent-daughter lamellae structure in which the parent and daughter lamellae are against each other with a near perpendicular angle (80° or 100°). Inducing a high fraction of oriented cross-hatched structure in iPP during processing is desirable for designing the bi-oriented iPP products. We processed a commercial iPP via tensile-stretching and die-drawing to evaluate the structural evolution of oriented parent-daughter lamellae. It turned out that the die-drawing process had an advantage in attaining a high fraction of oriented cross-hatched structure of iPP, as compared to the free tensile stretching. Besides, the presence of α-nucleating agents affected the formation of oriented parent-daughter lamellae in the die-drawn samples whereas such influence diminished in the free stretched ones. It was found that the confined deformation inside the die led to the well-preserved oriented cross-hatched structure in the die-drawn iPP.This work was financially supported by the National Natural Science Foundation of China (Nos. 21704102, U1832186, and 51525305), Newton Advanced Fellowship of the Royal Society, United Kingdom (No. NA150222) and ExxonMobil Asia Pacific Research & Development Co., Ltd