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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.

Background Armed conflict can lead to increased stress, anxiety, and other psychological conditions. Benzodiazepines (BZDs), Z-drugs, and selective serotonin reuptake inhibitors (SSRIs) are used for stress-related conditions and sleep disturbances. This study aimed to identify the demographic and geographic predictors of BZD, Z-drug, and SSRI use during the first year of the 2023 Israel- Hamas war in Israel, while comparing these patterns to pre-war utilization trends. Methods Using data of 557,830 adults from the Meuhedet health maintenance organization, we compared the use of BZDs, Z-drugs, and SSRIs before and during the war, and between individuals residing near and away from combat areas. The analysis included two years of pre-war purchasing records and the first year of the war. Results During the year before the war, 78,307 individuals were identified as SSRI and/or BZD users, while 479,523 were non-users. Women predominated among medication users, who were generally older and had higher rates of psychiatric diagnoses compared to non-users. Previous use of SSRIs and BZDs was associated with a higher likelihood of wartime use (OR = 333.20, CI 320.74-346.21for SSRIs, OR = 140.44, CI 135.49–145.60 for BZDs). Women were also more likely to use these medications (OR = 1.30, CI 1.27–1.33 for SSRIs, and OR = 1.20, CI 1.18–1.25 for BZDs). Individuals living near combat areas were more likely to use BZDs (OR = 1.33, CI 1.25–1.42) and SSRIs (1.17, CI 1.09–1.27). The general population had a higher OR for the study medications compared to Arabs and Orthodox Jews. Conclusions Prior use was the strongest factor predicting wartime BZD and SSRI use. Female sex, non-Orthodox Jewish identity, and residing near combat areas were also associated with increased use. These findings emphasize the need for proactive mental health interventions for at-risk groups during times of armed conflicts.

This study will explore the significance of the Holocaust for the grandchildren of Holocaust survivors (third generation). Semi-structured, extensive interviews were conducted with 17 members of the third generation who varied in age, gender, and the number of surviving grandparents. These interviews allowed the explorations of some of the mental representations of the Holocaust for these grandchildren, and allowed them to reveal the ways that this past trauma, which happened in the grandparents' generation, is still present in their lives today. In studying these issues, the interviews were first analyzed by using the language measures of the Multiple Code Theory, which revealed that participants related differently to different parts of the interviews, depending on their emotional processing of the material. For example, participants were more able to immerse themselves in the stories about their grandparents and their families, but were more defended in talking about intrapsychic material (dreams, fantasies etc.). The use of the language measures was valuable in pointing out significant moments in the interviews, and hence turned out to be an important tool in narrative analysis. Moreover, theme dictionaries were developed for the purposes of this study in order to reveal the central themes that surfaced in the interviews. Some of these themes were dynamic between loss and survival, and conflicting attitudes towards the family heritage. Findings demonstrated the existence of the transmission of the Holocaust trauma among the generations, and how this impacts the lifestyle of participants.

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 DN-expressed 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. Competing Interest Statement The authors have declared no competing interest.

This study evaluates the efficacy of annuloplasty repair as a standalone procedure for treating bileaflet mitral valve prolapse with mitral regurgitation (MR). Various flexible ring bands for MR of different severities were compared to assess their biomechanical impact and treatment outcomes. Computational beating heart models, based on the Living Heart Human Model, were utilized to simulate annuloplasty repairs. Repairs using bands of varying lengths were modeled on moderate and severe MR cases, considering bileaflet mitral valve prolapse. Key parameters, including regurgitant orifice area (ROA), prolapse severity, coaptation length, leaflet position, and deformation, were computed to compare conditions before and after implantation. Annuloplasty repairs effectively reduced the ROA in both moderate and severe MR cases, achieving complete sealing in selective instances. Additionally, annuloplasty repair corrected bileaflet prolapse, with prolapse severity decreasing as the annular size increased. Successful coaptation was indicated by the expansion of each leaflet’s contact area distribution and percentage in contact with the opposing leaflet. The risk of systolic anterior motion, that may obstruct the left ventricular outflow tract, was minimized, as the anterior leaflet was directed towards the posterior position. In conclusion, annuloplasty repair alone can effectively treat MR when an appropriate band length is selected. It facilitates a significant reduction in ROA, correction of bileaflet prolapse, and improvement in leaflet coaptation. These findings have important clinical implications, potentially offering a less complex surgical treatment avenue and reducing complications in the management of MR.

Calcific aortic valve disease (CAVD) is characterized by stiffened aortic valve leaflets. Bicuspid aortic valve (BAV) is the most common congenital heart disease. Transcatheter aortic valve replacement (TAVR) is a treatment approach for CAVD where a stent with mounted bioprosthetic valve is deployed on the stenotic valve. Performing TAVR in calcified BAV patients may be associated with post-procedural complications due to the BAV asymmetrical structure. This study aims to develop refined computational models simulating the deployments of Evolut R and PRO TAVR devices in a representative calcified BAV. The paravalvular leakage (PVL) was also calculated by computational fluid dynamics simulations. Computed tomography scan of severely stenotic BAV patient was acquired. The 3D calcium deposits were generated and embedded inside a parametric model of the BAV. Deployments of the Evolut R and PRO inside the calcified BAV were simulated in five bioprosthesis leaflet orientations. The hypothesis of asymmetric and elliptic stent deployment was confirmed. Positioning the bioprosthesis commissures aligned with the native commissures yielded the lowest PVL (15.7 vs. 29.5 mL/beat). The Evolut PRO reduced the PVL in half compared with the Evolut R (15.7 vs. 28.7 mL/beat). The proposed biomechanical computational model could optimize future TAVR treatment in BAV patients.

Central-place foragers, such as social insects or nesting birds, repeatedly use the same routes from and to their nests when foraging for food. Such species forage more efficiently after accumulating experience. We examined, here, a relatively neglected aspect of such an improvement with experience—the avoidance of pitfall traps. Similar pits are built by antlions, which co-occur with the ants, but they also resemble other natural obstacles. We used the desert ant Cataglyphis niger, common in sandy habitats, and allowed it to forage for three successive runs for a food reward. Ant workers discovered food more slowly and in smaller numbers when pits were in their path. Pit presence also led to longer tracks by ants and slower movement. However, with experience, the ants fell into such pits less often and reached the food more quickly. To understand how past conditions affect current behavior, we investigated whether removing or adding pits led to a different result to that with a constant number of pits. Workers adjusted their behavior immediately when conditions changed. The only carryover effect was the longer tracks crossed by workers after pit removal, possibly resulting from the mismatch between the past and current conditions. Finally, the workers were more likely to fall into pits that were closer to the nest than those that were further away. This is a good example of the advantage that ambush predators can derive from ambushing their prey in specific locations.

Introduction Transient stress urinary incontinence (SUI) after holmium laser enucleation of prostate (HoLEP) is commonly linked to intraoperative injury of the external urethral sphincter (EUS). We assessed the reliability of the post-HoLEP endoscopic appearance of the membranous urethra mucosa (MUM) in predicting post-HoLEP continence. Methods Forty HoLEPs were prospectively recorded by an artificial intelligence video platform capable of segmenting clips by surgical steps. The final clip was assessed for postoperative MUM integrity by 2 experts in HoLEP and 2 residents, all blinded to the clinical outcome. Their findings were scored as no injury, anterior injury, and lateral injury, and the results underwent statistical analyses. Results The referent rating was 72% for no injury, 23% for anterior injury, and 5% for lateral injury. The overall inter-observer agreement was K = 0.26, the inter-experts’ agreement was K = 0.12, and the inter-residents’ agreement was K = 0.38, reflecting low inter-observer reliability. The postoperative rate of SUI, defined as any drop on a pad, was 30% at 1 month and 12.5% at 3 months. There was no association between the MUM injury graded and SUI according to any of the evaluators (univariate analysis OR 0.83, 95%CI 0.17–3.89). A multivariate analysis controlling for age, prostate size, resectoscope size (22 vs. 26 FR), surgery time, and use of final fulguration showed no significantly independent predictor of post-HoLEP-related incontinence. Conclusion The post-HoLEP endoscopic appearance of the MUM is apparently not a reliable marker of EUS injury. Further studies are needed to better understand the mechanism underlying post-HoLEP SUI.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. It is mostly sporadic, with the C9orf72 repeat expansion being the most common genetic cause. While the prevalence of C9orf72 -ALS in patients from different populations has been studied, data regarding the yield of C9orf72 compared to an ALS gene panel testing is limited. We aimed to explore the application of C9orf72 versus a gene panel in the general Israeli population. A total of 140 ALS patients attended our Neurogenetics Clinic throughout 2018–2023. Disease onset was between ages 60 and 69 years for most patients (34%); however, a quarter had an early-onset disease (< 50 years). Overall, 119 patients (85%) were genetically evaluated: 116 (97%) were tested for the C9orf72 repeat expansion and 64 (54%) underwent gene panel testing. The C9orf72 repeat expansion had a prevalence of 21% among Ashkenazi Jewish patients compared to 5.7% in non-Ashkenazi patients, while the gene panel had a higher yield in non-Ashkenazi patients with 14% disease-causing variants compared to 5.7% in Ashkenazi Jews. Among early-onset ALS patients, panel testing was positive in 12% compared to 2.9% for C9orf72 . We suggest a testing strategy for the Israeli ALS patients: C9orf72 should be the first-tier test in Ashkenazi Jewish patients, while a gene panel should be considered as the first step in non-Ashkenazi and early-onset patients. Tiered testing has important implications for patient management, including prognosis, ongoing clinical trials, and prevention in future generations. Similar studies should be implemented worldwide to uncover the diverse ALS genetic architecture and facilitate tailored care.