Significant toxicity following an increase in poisonings with designer benzodiazepines in the Netherlands between 2010 and 2020

BACKGROUND: Designer benzodiazepines (DBs) are an emerging class of new psychoactive substances. While structurally derived from pharmaceutical benzodiazepines, their toxicological profile is less clear. We investigated time trends in the rate of DB poisonings and their clinical toxicity. METHODS: A retrospective observational study was performed on the incidence rate of DB poisonings, relative to all recreational drug poisonings reported to the Dutch Poisons Information Center (DPIC) from 2010 to 2020. Time-trend analysis was performed using Poisson regression. A prospective cohort study was performed on toxicity of DBs, including the Poisoning Severity Score, from January 2016-June 2019. Data was collected through telephone interviews. RESULTS: Between 2010 and 2020, the DPIC was consulted on 142 DB exposures. The incidence rate of DB exposures increased from 0.1% to 4.3%, with a year effect estimate of 1.35 (95% CI [1.14;1.54]). Twenty different DBs were reported, mostly etizolam (33%), clonazolam (17%), and flunitrazolam (8%). During consultation (often shortly after exposure), poisoning was graded moderate-severe in 29% of cases (n = 146). In the prospective cohort sample with follow-up (n = 22), 86% of cases (n = 19) showed a moderate-severe poisoning. The severity of poisoning did not differ between mono- and mixed intoxications. Frequently reported symptoms in the prospective cohort sample included drowsiness (86%), confusion (59%), and agitation (55%). Coma was observed in seven cases (32%) and respiratory depression requiring mechanical ventilation in five cases (23%). CONCLUSION: The rate of DB poisonings reported to the DPIC strongly increased from 2010 to 2020, indicating increased (ab)use of DBs. Most DB exposures resulted in moderate-severe toxicity with neurological effects

A hybrid-integrated diode laser in the visible spectral range

Generating visible light with wide tunability and high coherence based on photonic integrated circuits is of high interest for applications in biophotonics, precision metrology and quantum technology. Here we present the first demonstration of a hybrid-integrated diode laser in the visible spectral range. Using an AlGaInP optical amplifier coupled to a low-loss Si3N4 feedback circuit based on microring resonators, we obtain a spectral coverage of 10.8 nm around 684.4 nm wavelength with up to 4.8 mW output power. The measured intrinsic linewidth is 2.3$\pm$0.2 kHz.Comment: 8 pages, 6 figure

Vincristine, doxorubicin and dexamethasone (VAD) administered as rapid intravenous infusion for first-line treatment in untreated multiple myeloma

We examined the feasibility of achieving a rapid response in patients with previously untreated multiple myeloma by administering vincristine 0.4 mR and doxorubicin 9 mg/m2 as a rapid intravenous infusion for 4 d together with intermittent high-dose dexamethasone 40 mg (VAD) for remission induction treatment in patients who were scheduled to receive high-dose therapy. 139 patients (86 male, 53 female; median age 53 years, range 32-65 years; Durie and Salmon stage IIA: 42, IIB: one, IIIA: 89, IIIB: seven) were included in a prospective multicentre study in which VAD was administered as remission induction treatment and was followed by intensified treatment. The response was evaluated according to the criteria of the Eastern Cooperative Oncology Group (ECOG). The results of treatment were evaluable in 134 patients. Five patients died before evaluation. 86 patients (62%) achieved a partial response (PR) and seven patients (5%) achieved a complete response (CR), which equates to a response rate of 67%. The main side-effect was mild neurotoxicity, which was observed in 18% of the patients. Fever or infections were reported in 27% of the patients. VAD administered as an outpatient regimen, based on rapid intravenous infusion, is an effective induction regimen for untreated myeloma with a 67% response rate and acceptable toxicity

Taxonomy based on science is necessary for global conservation

Peer reviewe

Dermaseptins, Multifunctional Antimicrobial Peptides: A Review of Their Pharmacology, Effectivity, Mechanism of Action, and Possible Future Directions

International audienceDermaseptins are a group of α-helical shaped polycationic peptides isolated from the Hylid frogs, with antimicrobial effects against bacteria, parasites, protozoa, viruses in vitro. Besides, anti-tumor effects have been demonstrated. However, few animal experiments and no clinical trials have been conducted thus far. This review summarizes the current knowledge on the pharmacology, ethno pharmacology, effectivity against infectious pathogens and tumors cells and the mechanism of action of the Dermaseptins. Future research should focus on further clarification of the mechanisms of action, the effectivity of Dermaseptins against several cancer cell lines and their applicability in humans

Reverse logistics: A review of case studies

This paper gives an overview of scientific literature that describes and discusses cases of reverse logistics activities in practice. Over sixty case studies are considered. Based on these studies we are able to indicate critical factors for the practice of reverse logistics. In addition we compare practice with theoretical models and point out research opportunities in the field

A characterisation of logistics networks for product recovery

Recovery of used products is receiving much attention recently due to growing environmental concern. Efficient implementation requires appropriate logistics structures to be set up for the arising goods flow from users to producers. We investigate the design of such logistics networks. As a basis for our analysis we review recent case studies on logistics network design for product recovery in different industries. We identify general characteristics of product recovery networks and compare them with traditional logistics structures. Moreover, we derive a classification scheme for different types of recovery networks

A characterisation of logistics networks for product recovery

Recovery of used products is receiving much attention recently due to growing environmental concern. Efficient implementation requires appropriate logistics structures to be set up for the arising goods flow from users to producers. We investigate the design of such logistics networks. As a basis for our analysis we review recent case studies on logistics network design for product recovery in different industries. We identify general characteristics of product recovery networks and compare them with traditional logistics structures. Moreover, we derive a classification scheme for different types of recovery networks.Reverse logistics Distribution Location Case studies