Benzodiazepine and Z drug cessation in elderly patients: A qualitative study on the perception of healthcare providers and the place of advanced practice nurses.

Sedative-use disorder can occur in elderly individuals, but remains a taboo subject. France is the second top-consuming country of benzodiazepines (BZDs) and Z drugs in Europe, with 38% of women >80 years old using these drugs. Despite the recommendations of the French National Authority for Health (HAS) to general practitioners, deprescription remains rare. The aim of this study was to understand the perception of healthcare providers towards BZD or Z drug withdrawal within a psychogeriatric unit and to provide insights from advanced practice nurses (APRNs) on this topic. Eight healthcare providers from different professions in a psychogeriatric unit were interviewed. The interviews were recorded and transcribed verbatim, and the data were analysed following the interpretive phenomenological approach. The COREQ statement was used as a guide in the reporting of the study. Four themes were identified in the interview transcripts: (i) problems specific to the elderly; (ii) problems specific to BZD or Z drug consumption; (iii) present care; and (iv) envisioned practice. While the healthcare providers interviewed appeared to have knowledge on the adverse effects of BZDs, it appears difficult to taper the use of BZDs outside crisis periods of behaviour disorders in elderly patients. Caregivers recommend an evolution of practices, such as introducing BDZ and Z drug withdrawal programs that could involve the emerging profession of APRNs in general practice in France. APRNs could be a valuable resource to screen for BZD-related disorders and to manage withdrawal strategies in complex cases.

Poneratoxin, a neurotoxin from ant venom. Structure and expression in insect cells and construction of a bio-insecticide.

Poneratoxin is a small neuropeptide found in the venom of the ant Paraponera clavata. It is stored in the venom reservoir as an inactive 25-residue peptide. Here we describe both chemically synthesized poneratoxin and poneratoxin obtained by expression in insect cells. When expressed in insect cells, poneratoxin was observed attached to cell membranes. Both synthetic and recombinant ponerotoxins were soluble below pH 4.5. The structure of synthetic poneratoxin was characterized by circular dichroism and solved by nuclear magnetic resonance. In an environment imitating a lipid bilayer, at pH within the range of insect hemolymph, synthetic poneratoxin has a V shape, with two alpha-helices connected by a beta-turn. Insect larvae were paralyzed by injection of either of the purified toxins, with the recombinant one acting faster. The recombinant toxin-producing baculovirus reduced the average survival time of the insect host by 25 h compared with unmodified virus. Mass spectrometry analysis showed that the recombinant toxin has an N-terminal 21-residue extension, possibly improving its stability and/or stabilizing the membrane-bound state. The potential use of poneratoxin for the construction of biological insecticide is discussed.

In vitro radiation-induced effects on rat tracheal epithelial cells. I) Different radiosensitivity of cell inactivation after alpha and gamma irradiations.

In order to compare the radiotoxicity of alpha- and gamma-irradiations, primary cultures of tracheal epithelial cells from two rat strains, Sprague Dawley (SD) and Wistar Furth/Fisher F344 (WF/Fi) rats, were irradiated with 241Am alpha-particles or 60 Co gamma-rays. The survival ratio for each of the two rat strain cells appeared to be statistically different after high-LET irradiation. WF/Fi rat cells were 1.7-times more radiosensitive than SD rat cells, whereas no difference was observed following low-LET irradiation. A comparison of the cell survival yielded RBEs of 2.8 and 4.5 for SD and WF/Fi rat cells, respectively. As previously observed, with increasing LET of particles, the cell-survival curves approximate an exponential function of the dose. On the contrary, for low-LET, the survival curves showed a marked initial shoulder. This in vitro cellular model, using epithelial cells of the upper airway, provides a suitable system to estimate the mechanism involved in radiosensitivity after high-LET irradiation. The responses to radiation-induced lethal effects within a same type of cell were dependent on the irradiation parameters, but might be modulated by the individual sensitivity under genetic or epigenetic factor controls.

In vitro radiation-induced effects on rat tracheal epithelial cells. II) Different preneoplastic cell transformation after alpha and gamma irradiations.

In order to compare the cell transformation induced by alpha- and gamma-irradiation, primary cultures of tracheal epithelial cells from two rat strains, Sprague Dawley (SD) and Wistar Furth/Fisher F344 (WF/Fi) rats, were irradiated with 241Am alpha-particles or 60 Co gamma-rays. The relative transformation frequency (RTF) for WF/Fi primary cells was very close to the level of the spontaneous incidence and independent on the two irradiation types used. On the contrary, the RTF for the SD primary cells increased with a decrease of the LET radiation when the relative survival was higher than about 40%. Therefore, the RTF values reached 4-5 for alpha-particles and 10-12 for gamma-rays. The RTF can be related to the intrinsic radiosensitivity of the rat epithelial cells. However, the difference in the radiation-induced RTF for SD or WF/Fi primary cells seems to be due to the development, under genetic control, of the initial lesion to the neoplastic state.