Summary Tobacco smoking is a risk factor for several human diseases. Conversely, smoking also reduces the prevalence of Parkinson’s disease, whose hallmark is degeneration of substantia nigra dopaminergic neurons (DNs). We use C. elegans as a model to investigate whether tobacco-derived nicotine activates nicotinic acetylcholine receptors (nAChRs) to selectively protect DNs. Using this model, we demonstrate conserved functions of DN-expressed nAChRs. We find that DOP-2, a D3-receptor homolog; MCU-1, a mitochondrial calcium uniporter; PINK-1 (PTEN-induced kinase 1); and PDR-1 (Parkin) are required for nicotine-mediated protection of DNs. Together, our results support involvement of a calcium-modulated, mitochondrial stress-activated PINK1/Parkin-dependent pathway in nicotine-induced neuroprotection. This suggests that nicotine-selective protection of substantia nigra DNs is due to the confluence of two factors: first, their unique vulnerability to mitochondrial stress, which is mitigated by increased mitochondrial quality control due to PINK1 activation, and second, their specific expression of D3-receptors.

No abstract

Background As opioid prescription in Israel is increasing, there is a growing need for monitoring opioid use disorder and providing opioid agonist therapy. Our goal is to describe, sub-analyze, and identify obstacles in the treatment of opioid misuse in the Israeli medication assisted treatment centers. Methods Data on methadone, buprenorphine, and buprenorphine combined with naloxone for the indication of opioid addiction treatment for the period 2013–2020 were obtained from pharmaceutical companies that distribute them in Israel. Data on utilization of these drugs were also extracted from the database maintained by the Israel Ministry of Health's Pharmaceutical Administration Division. The data were converted to defined daily doses (DDD)/1000 inhabitants/day. Results The number of patients receiving medication assisted treatment increased by 10% since 2013, with a shift from buprenorphine alone to buprenorphine/naloxone in government-run centers. Methadone remains the most popular maintenance drug. Conclusions The change in opioid maintenance prescription does not match the significant increase in opioid consumption. Optimization of treatment can be achieved by the creation of a comprehensive database, cooperation between healthcare organizations and the government and further development of non-stigmatic and accessible services.

Summary Esophageal strictures in children may cause dysphagia, choking during feeds, and failure to thrive. They can be treated by balloon dilatations, either under endoscopic or fluoroscopic guidance; there is no literature comparing the methods. Retrospective review of the medical records of children (0–18 years) who were treated with balloon dilatations between 2010 and 2020. The primary outcome was the number of dilatation sessions required until clinical success after 3 months. Secondary outcomes were long-term success at 12 months, and complications of bleeding and perforation. Forty-six patients underwent 174 dilatation sessions. Success rates in the endoscopy and fluoroscopy groups were similar: 62% versus 67% (p = 0.454) at 3 months and 57% versus 67% (p = 0.721) at 12 months. Complication rate was lower in the endoscopy group (0% vs. 15%, p < 0.001). Both endoscopic and radiologic-guided balloon dilatations were shown to be equally effective, but endoscopic guidance had fewer complications.

Tobacco smoking is a risk factor for several human diseases. Conversely, smoking also reduces the prevalence of Parkinson's disease (PD), whose hallmark is degeneration of substantia nigra dopaminergic neurons (DNs). We use C. elegans as a model to investigate whether tobacco-derived nicotine activates nicotinic acetylcholine receptors (nAChRs) to selectively protect DNs. Using this model we demonstrate conserved functions of DNexpressed nAChRs. We find that DOP-2, a D3-receptor homolog, MCU-1, a mitochondrial calcium uniporter, and PINK-1, PTEN-induced kinase 1, are required for nicotine-mediated protection of DNs. Together, our results support involvement of calcium-dependent mitochondrial stress activation of PINK-1 in nicotine-dependent neuroprotection. This suggests that nicotine's selective protection of substantia nigra DNs is due to the confluence of two factors: first, their unique vulnerability to mitochondrial stress, which is mitigated by increased mitochondrial quality control due to PINK1 activation; and second, to their specific expression of D3 receptors.Epidemiological studies show that tobacco smoking reduces the prevalence of Parkinson's disease (PD) (Li et al., 2015). A hallmark of PD is degeneration of substantia nigra dopaminergic neurons (DNs). Effects of tobacco smoking on degeneration of these neurons may depend on tobacco-derived nicotine and on nicotinic acetylcholine receptors (nAChRs). Support for this hypothesis comes from several lines of evidence. These include: i)