Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

A knowledge, attitudes, and practice survey among obstetrician-gynaecologists on intimate partner violence in Flanders, Belgium

BACKGROUND: Intimate partner violence (IPV) has consistently been found to afflict one in twenty pregnant women and is therefore considered a leading cause of physical injury, mental illness and adverse pregnancy outcome. A general antenatal screening policy has been advocated, though compliance with such guidelines tends to be low. We therefore attempted to identify potential barriers to IPV screening in a context where no guidelines have been instigated yet. METHODS: Questionnaire-based Knowledge, Attitude, and Practice survey among obstetrician-gynaecologists in Flanders, Belgium (n = 478). RESULTS: The response rate was 52.1% (249/478). Gynaecologists prove rather unfamiliar with IPV and therefore largely underestimate the extent of the problem. Merely 6.8% (17/249) of the respondents ever received or pursued any kind of education on IPV. Accordingly they do feel insufficiently skilled to deal with IPV, yet sufficiently capable of recognizing IPV among their patients. Survey participants largely refute the incentive of universal screening in favour of opportunistic screening and do not consider pregnancy as a window of opportunity for routine screening. They do consider screening for IPV as an issue of medical liability and therefore do not suffer from a lack of motivation to screen. In addition, obstetrician-gynaecologists do believe that screening for IPV may be an effective means to counteract abusive behaviours. Yet, their outcome expectancy is weighed down by their perceived lack of self-efficacy in dealing with IPV, by lack of familiarity with referral procedures and by their perceived lack of available referral services. Major external or patient-related barriers to IPV screening included a perceived lack of time and fear of offending or insulting patients. Overall, merely 8.4 % (21/245) of gynaecologists in this survey performed some kind of IPV questioning on a regular basis. Finally, physician education was found to be the strongest predictor of a positive attitude towards screening and of current screening practices. CONCLUSION: Endorsement of physician training on IPV is an important first step towards successful implementation of screening guidelines for IPV. Additional introduction of enabling and reinforcement strategies such as screening tools, patient leaflets, formal referral pathways, and physician feedback may further enhance compliance with screening recommendations and guidelines

Loss-of-Function Variants in HOPS Complex Genes VPS16 and VPS41 Cause Early Onset Dystonia Associated with Lysosomal Abnormalities.

OBJECTIVES: The majority of people with suspected genetic dystonia remain undiagnosed after maximal investigation, implying that a number of causative genes have not yet been recognized. We aimed to investigate this paucity of diagnoses. METHODS: We undertook weighted burden analysis of whole-exome sequencing (WES) data from 138 individuals with unresolved generalized dystonia of suspected genetic etiology, followed by additional case-finding from international databases, first for the gene implicated by the burden analysis (VPS16), and then for other functionally related genes. Electron microscopy was performed on patient-derived cells. RESULTS: Analysis revealed a significant burden for VPS16 (Fisher's exact test p value, 6.9 × 109 ). VPS16 encodes a subunit of the homotypic fusion and vacuole protein sorting (HOPS) complex, which plays a key role in autophagosome-lysosome fusion. A total of 18 individuals harboring heterozygous loss-of-function VPS16 variants, and one with a microdeletion, were identified. These individuals experienced early onset progressive dystonia with predominant cervical, bulbar, orofacial, and upper limb involvement. Some patients had a more complex phenotype with additional neuropsychiatric and/or developmental comorbidities. We also identified biallelic loss-of-function variants in VPS41, another HOPS-complex encoding gene, in an individual with infantile-onset generalized dystonia. Electron microscopy of patient-derived lymphocytes and fibroblasts from both patients with VPS16 and VPS41 showed vacuolar abnormalities suggestive of impaired lysosomal function. INTERPRETATION: Our study strongly supports a role for HOPS complex dysfunction in the pathogenesis of dystonia, although variants in different subunits display different phenotypic and inheritance characteristics. ANN NEUROL 2020;88:867-877

Ciguatera visvergiftiging; een overzicht

Het overzicht van ciguatera visvergiftiging bevat informatie over de ciguatera vergiftigingen en de veroorzakers (CTXs) en gambiertoxine-4b (GTX-4 B), van welke CTX-1 de belangrijkste component is aan het eind van de voedsel keten (roofvissen). Gegevens over chemische structuren, detectie methoden van ciguatoxinen (CTX), bronnen van CTX, marine organismen die worden geassocieerd met CTX, de toxiciteit van CTX in mens en dier, mogelijke preventieve maatregelen tegen ciguatera vergiftiging, rapportage van CTX-vergiftigingsgevallen, regulering en monitoring van CTX zijn beschreven. Tenslotte worden nog een aantal aanbevelingen gegeven voor een betere controle van het potentiele CTX-probleem in de toekomst.This review on ciguatera fish poisoning contains information on the ciguatera intoxication syndrome and the provoking ciguatoxins (CTXs) and gambiertoxin-4b (GTX-4B), of which CTX-1 is a major component at the end of food chain (the carnivore fish). Data on chemical structures and detection methods of ciguatoxin (CTX), sources for CTX, marine organisms associated with CTX, toxicity of CTX for animals and man, possible preventive measures for ciguatera intoxication, case reports of outbreaks of ciguatera intoxication and regulations and monitoring of CTX are included. Finally some recommendations are given for a better control of the putative CTX problem in the future

Ciguatera visvergiftiging; een overzicht

This review on ciguatera fish poisoning contains information on the ciguatera intoxication syndrome and the provoking ciguatoxins (CTXs) and gambiertoxin-4b (GTX-4B), of which CTX-1 is a major component at the end of food chain (the carnivore fish). Data on chemical structures and detection methods of ciguatoxin (CTX), sources for CTX, marine organisms associated with CTX, toxicity of CTX for animals and man, possible preventive measures for ciguatera intoxication, case reports of outbreaks of ciguatera intoxication and regulations and monitoring of CTX are included. Finally some recommendations are given for a better control of the putative CTX problem in the future.Het overzicht van ciguatera visvergiftiging bevat informatie over de ciguatera vergiftigingen en de veroorzakers (CTXs) en gambiertoxine-4b (GTX-4 B), van welke CTX-1 de belangrijkste component is aan het eind van de voedsel keten (roofvissen). Gegevens over chemische structuren, detectie methoden van ciguatoxinen (CTX), bronnen van CTX, marine organismen die worden geassocieerd met CTX, de toxiciteit van CTX in mens en dier, mogelijke preventieve maatregelen tegen ciguatera vergiftiging, rapportage van CTX-vergiftigingsgevallen, regulering en monitoring van CTX zijn beschreven. Tenslotte worden nog een aantal aanbevelingen gegeven voor een betere controle van het potentiele CTX-probleem in de toekomst