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Semion Kertzman,1,2 Michael Vainder,3 Baruch Spivak,1,2 Yosi Goclaw,1 Uri Markman,4 Abraham Weizman,2,5,6 Marina Kupchik1,2 1The Beer-Ya’akov/Ness Ziona Mental Health Center, Beer-Ya’akov, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Environics Analytics, Toronto, Canada; 4The Abarbanel Mental Health Center, Bat Yam, Israel; 5Research Unit, Geha Mental Health Center, Petach Tikva, Israel; 6Felsenstein Medical Research Center, Petach Tikva, IsraelCorrespondence: Semion Kertzman, Forensic Psychiatry Department, Beer-Yakov Mental Health Center, P.O. Box 1, Beer-Yakov, 70350, Israel, Tel +972-8-9776151, Fax +972-8-9776142, Email kertzman@animascan.comBackground: Over-reporting of posttraumatic stress disorder (PTSD) symptoms has been observed in some cases, following a motor vehicle accident (MVA). It has been suggested, however, that these are cases of underdiagnoses in primary care settings. The current study focused on people with PTSD in primary care settings who experienced an MVA and do not seek psychiatric help.Methods: In the over 3000 patient registry of a primary care clinic, 174 people who experienced an MVA (PE-MVA) were identified. The final sample included 45 PE-MVA, who were administered the Clinician-Administered Posttraumatic Stress Disorder Scale (CAPS-2), and completed the Injury Severity Scale (ISS) and the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) content scales.Results: PE-MVA with PTSD reported more psychopathology on both MMPI-2 and CAPS-2 than those without PTSD. Severity of injury, measured by the ISS, did not differ significantly between the two PE-MVA groups. The significant differences between the PE-MVA with PTSD and those without PTSD disappeared after adjusting for the covariates of bias scales [Infrequency (F) and Fake Bad (FBS)] in MMPI-2, but not in CAPS-2.Conclusion: The results suggest that in primary care settings, PE-MVA with PTSD who do not seek psychiatric help, over-report psychiatric and somatic symptoms. In a personal injury setting the F scale of the MMPI-2 showed less sensitivity to exaggerated somatic symptoms than the FBS scale. Bias scales of PE-MVA with PTSD are major contributors to the elevation of the MMPI-2 scores but not the CAPS-2 score.Keywords: posttraumatic stress disorder, PTSD, motor vehicle accidents, MVA, Minnesota multiphasic personality inventory-2, MMPI-2, clinician, administered posttraumatic stress disorder scale-2, CAPS-2, injury severity scale, ISS

Semion Kertzman,1,2 Amichai Fluhr,1 Michael Vainder,3 Abraham Weizman,2,4,5 Pinhas N Dannon1,2 1Department of Dual Disorders and Rehabilitation, Beer-Yaakov-Ness Ziona Mental Health Center, Ness Ziona, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Environics Analytics, Toronto, ON, Canada; 4Research Unit, Geha Mental Health Center, Petach Tichvah, Israel; 5Research Unit, Felsenstein Medical Research Center, Petach Tichvah, Israel Background: Research on the association between decision making and inhibition abilities has exhibited fundamental controversies. Some authors claim that inhibition abilities are an integral part of the decision-making process, whereas others suggest that the decision-making process does not operate in close association with inhibition abilities. Can gender explain variations in risky decisions via inhibition influences? Purpose: The purpose of the present study was to explore the associations between response inhibition, reflection inhibition, interference inhibition, and decision-making processes in men and women. Methods: To this end, 46 women and 46 men were assessed by the Go/NoGo task, a measure of response inhibition, by the Matching Familiar Figure Test, a measure of reflection inhibition; and by the Stroop task, a measure of interference inhibition. Results: No differences were detected in these measures between groups. The net score of the performance on the last section of the Iowa Gambling Task choices did not correlate with the inhibition measures in the two groups. We did not discover any significant main effects of gender on the association between these measures. Conclusion: These findings do not support the hypothesis that risky decisions are due to impaired inhibitory control. Further studies are needed to identify the cognitive mechanisms involved in the tendency to make risky decisions. Keywords: decision making, inhibition ability, gender differences, normal population

Objective: There is growing evidence of involvement of inflammatory mechanisms in ADHD. Previous studies found significantly higher rates of ADHD among children with FMF. The present study examined the rate of exposure to FMF in children with a later (within a 5-year period) diagnosis of ADHD compared to non-ADHD children. Methods: A population-based case-control study of all children (<18 years) registered in Leumit Health Services during 01.01.2006 to 06.30.2021. All cases met ICD-9/10 criteria for ADHD. They were matched by age, sex, and socioeconomic status on a 1:2 rate to randomly selected non-ADHD controls. Results: Fifty-six (0.30%) children with ADHD (N = 18,756) were previously diagnosed with FMF compared to 65 of 37,512 controls (0.17%). A significant, independent association existed between a preceding FMF diagnosis and a later ADHD diagnosis [OR = 1.72 (95% CI 1.18-2.51); p = 0.003]. Conclusions: The mechanisms underlying the association w between FMF and later ADHD diagnosis merit further elucidation.

Objective: We examined the association between the number, magnitude, and frequency of febrile episodes during the 0 to 4 years of life and subsequent diagnosis of ADHD. Methods: This population-based case-control study in an Israeli HMO, Leumit Health Services (LHS), uses a database for all LHS members aged 5 to 18 years between 1/1/2002 and 1/30/2022. The number and magnitude of measured fever episodes during the 0 to 4 years were recorded in individuals with ADHD (N = 18,558) and individually matched non-ADHD controls in a 1:2 ratio (N = 37,116). Results: A significant, independent association was found between the number and magnitude of febrile episodes during the 0 to 4 years and the probability of a later diagnosis of ADHD. Children who never had a measured temperature >37.5°C had a significantly lower rate of ADHD (OR = 0.834, 95% CI [0.802, 0.866], p < 0.0001). Conclusions: Febrile episodes during 0 to 4 years are associated with a significantly increased rate of a later diagnosis of ADHD in a dose-response relationship.

Abstract Violence risk is a major challenge among acute psychiatric inpatients. The study aimed to predict violent behavior risk in an acute psychiatric ward using video recordings from the emergency department. 69 videos of the emergency department recording the first ten minutes following patients’ arrivals were included. Psychiatrists watched the videos, completed relevant Brief Psychiatric Rating Scale items and answered intuitive questions about each patient’s risk of violence. Demographic and clinical data were also collected. Motoric mannerisms as rated in the BPRS significantly differed between violent and non-violent patients (p

Abstract Radiation therapy (RT) remains a common treatment for cancer patients worldwide, despite the development of targeted biological compounds and immunotherapeutic drugs. The challenge in RT lies in delivering a lethal dose to the cancerous site while sparing the surrounding healthy tissues. Low linear energy transfer (low-LET) and high linear energy transfer (high-LET) radiations have distinct effects on cells. High-LET radiation, such as alpha particles, induces clustered DNA double-strand breaks (DSBs), potentially inducing cell death more effectively. However, due to limited range, alpha-particle therapies have been restricted. In human cancer, mutations in TP53 (encoding for the p53 tumor suppressor) are the most common genetic alteration. It was previously reported that cells carrying wild-type (WT) p53 exhibit accelerated senescence and significant rates of apoptosis in response to RT, whereas cells harboring mutant p53 (mutp53) do not. This study investigated the combination of the alpha-emitting atoms RT based on internal Radium-224 (224Ra) sources and systemic APR-246 (a p53 reactivating compound) to treat tumors with mutant p53. Cellular models of colorectal cancer (CRC) or pancreatic ductal adenocarcinoma (PDAC) harboring mutant p53, were exposed to alpha particles, and tumor xenografts with mutant p53 were treated using 224Ra source and APR-246. Effects on cell survival and tumor growth, were assessed. The spread of alpha emitters in tumors was also evaluated as well as the spatial distribution of apoptosis within the treated tumors. We show that mutant p53 cancer cells exhibit radio-sensitivity to alpha particles in vitro and to alpha-particles-based RT in vivo. APR-246 treatment enhanced sensitivity to alpha radiation, leading to reduced tumor growth and increased rates of tumor eradication. Combining alpha-particles-based RT with p53 restoration via APR-246 triggered cell death, resulting in improved therapeutic outcomes. Further preclinical and clinical studies are needed to provide a promising approach for improving treatment outcomes in patients with mutant p53 tumors.

Background: Mood disorders (MD) are multifactorial disorders. Identifying new biomarkers for the early diagnosis of MD and predicting response to treatment is currently a significant research topic. Both eosinopenia and MD are associated with increased activity of the hypothalamic-pituitary-adrenal axis. The present study, therefore, used a clear definition of chronic idiopathic eosinopenia (CIE) to determine the rate of MD in a large cohort of individuals with CIE. Methods: This retrospective population-based, case-control study uses data of seven consecutive years from the database of Leumit Health Services (LHS) - a nationwide health maintenance organization in Israel. Results: Participants were 13928 LHS members with CIE and 27858 negative controls. The CIE group exhibited significantly higher rates of MD than the control group throughout the whole study period, except for atypical depressive disorder at baseline. Conclusions: CIE might be associated with a higher prevalence of MD. Further basic research should elucidate the pathophysiologic mechanisms linking CIE and MD.

Abstract Background Adaptive radiation therapy (ART) offers a dynamic approach to address structural and spatial changes that occur during radiotherapy (RT) for locally advanced head and neck cancers. The integration of daily ART with Cone-Beam CT (CBCT) imaging presents a solution to enhance the therapeutic ratio by addressing inter-fractional changes. Methods We evaluated the initial clinical experience of daily ART for patients with head and neck cancer using an online adaptive platform with intelligence-assisted workflows on daily CBCT. Treatment included auto-contour and structure deformation of Organs at Risk (OARs) and target structures, with adjustments by the treating physician. Two plans were generated: one based on the initial CT simulation with the edited structures (scheduled) and a re-optimized plan (adaptive). Both plans were evaluated and the superior one approved and delivered. Clinical and dosimetric outcomes were reviewed. Results Twenty two patients with head and neck cancers (7 Nasopharynx, 6 Oropharynx, 1 oral cavity, 8 larynx) stages I-IVA were treated with daily ART. 770 adaptive and scheduled radiotherapy plans were generated. 703 (91.3%) adaptive plans were chosen. Median time to deliver ART was 20 minutes (range: 18-23). Adaptive compared to scheduled plans demonstrated improved mean V95 values for the PTV70, PTV59.5, and PTV56 by 1.2%, 7.2%, and 6.0% respectively and a mean 1.4% lower maximum dose in PTV70. Fourteen of 17 OARs demonstrated improved dosimetry with adaptation, with select OARs reaching statistical significance. At a median follow up of 14.1 months, local control was 95.5%, two patients developed metastatic disease and four patients died. 9.1% of patients had acute grade 3 dysphagia and 13.6% had grade 2 chronic xerostomia. Discussion These findings provide real world evidence of the feasibility and dosimetric benefit of incorporating daily ART on CBCT in the treatment of head and neck cancer. Prospective study is needed to determine if these dosimetric improvements translate into improved outcomes.

We assessed the anti-inflammatory activity of the TSPO ligand 2-Cl-MGV-1. Lipopolysaccharide (LPS) was used to induce inflammatory response in a murine RAW264.7 macrophage model (LPS: 100 ng/mL) and a mouse model (C57BL/6) of lung inflammation (LPS: 5 mg/kg). In the macrophage model, the presence of 2-Cl-MGV-1 (25 µM) caused the LPS-induced elevation in nitrite levels to decrease by 70% (p < 0.0001) and interleukin (IL)-6 by 50% (p < 0.05). In the mouse model, 2-Cl-MGV-1, administered 30 min before, or co-administered with, an LPS injection, significantly inhibited the elevation in serum IL-5 levels (both by 65%; p < 0.001 and p < 0.01, respectively). 2-Cl-MGV-1 administration to mice 30 min before LPS injection and 1 h thereafter significantly inhibited the elevation in IL-1β serum levels (both by 63%, p < 0.005). IL-6 elevation was inhibited by 73% (p < 0.005) when 2-Cl-MGV-1 was administered 30 min before LPS, by 60% (p < 0.05) when co-administered with LPS, and by 64% (p < 0.05) when administered 1 h after LPS. All cytokine assessments were conducted 6 h post LPS injection. Histological analyses showed decreased leukocyte adherence in the lung tissue of the ligand-treated mice. 2-Cl-MGV-1 administration 30 min prior to exposure to LPS inhibited inflammation-induced open field immobility. The beneficial effect of 2-Cl-MGV-1 suggests its potential as a therapeutic option for inflammatory diseases.

This review reports on the use of sensors in wheelchair sports to monitor and analyze performance during match and training time. With rapid advancements in electronics and related technologies, understanding performance metrics in wheelchair sports is essential. We reviewed nine studies using various sensor types, including electric motors, inertial measurement units, miniaturized data loggers with magnetic reed switches, and smartphones with inbuilt accelerometers and gyroscopes, operating at frequencies from 8 Hz to 1200 Hz. These studies measured parameters such as angular and translational velocities, distance, number of starts/pushes, and other performance indicators in sports such as basketball, rugby, tennis, and racing. Despite differences in sport types and methodologies, most studies found sensor-derived data effective for assessment of performance. Future developments and research in this field should focus on multi-sensor systems that could provide real-time match analysis and deeper insights into performance metrics. Overall, sensor technologies show significant potential for improving wheelchair sport performance diagnostics, contributing to better athlete training and future wheelchair design, and enhancing competitive outcomes. This review emphasizes the need for continued innovation and standardization in applying sensor technologies in wheelchair sports.

Clinical observations suggest that girls suspected to have ASD manage to perform better in social and emotional tasks than boys, leading to a camouflage effect which results in the under-diagnosis of girls with ASD. We used the Social Attribution Task (SAT) in order to assess the performance of 12 girls who were previously diagnosed with ASD, and additionally to compare their performance in SAT to that of 12 boys who were previously diagnosed with ASD. No significant differences were found between girls and boys in all the indices of SAT except for the Person index; girls performed better than the boys in the Person index. The lack of significant differences between the boys and the girls in five out of the six SAT indices suggests that girls with ASD do not have a better social understanding than boys. They outperformed the boys only when the instructions included a clue that triggered them to name human traits, as they are instructed to do in the Person index. Implications of the usefulness of the Social Attribution Task (SAT) for diagnosing ASD in girls are discussed.

In evaluating the effectiveness of COVID-19 control measures, we propose a standardized approach to assess the impact of COVID-19 management on flattening the curve by analyzing the case data of Victoria, Australia. Its capital, Melbourne, is considered the most lock-downed city in the world. We used the daily case data from Victoria and their first time derivative and compared the dates when the six lockdowns were imposed with the start and end of the effective period, i.e., the period between the maximum and minimum acceleration. Lockdowns 1, 2 (Level 4 restrictions), 3, and 4 were found to be implemented too late, as they were expected to come into effect at the end or after the effective phase, and they were therefore ineffective. It was determined that Lockdown 2 (Level 3 restrictions) did not initiate the effective phase, and it was therefore ineffective, too. Lockdown 5 was expected to take effect in the second half of the effective phase, but showed no changes in the acceleration curve, and it was therefore also ineffective. Lockdown 6, implemented well before the effective period, did not flatten the curve, and was thus also found to be ineffective. The mask mandate between Lockdown 2 (Level 3 and 4 restrictions) initiated the effective phase (likely along with Lockdown 2, Level 3 restrictions), and was therefore found to effectively flatten the curve. The temporal relationship between the assumed cause (control measure) and the observed effect (flattening of the curve) is thus a crucial parameter for assessing the effect of control measures.

IntroductionChloral hydrate (CH), a medication dating back to 1832, is tranquilizer and sleep promoter still used today. It remains an option for short-term insomnia therapy and sedation before medical procedures, despite its controversial safety profile.MethodsThis study investigated the potential benefits of chloral hydrate addition for increasing sleep duration and reducing agitation and violence in inpatients with treatment-resistant schizophrenia (TRS). A retrospective, observational case series design was utilized, analyzing data from fourteen patients diagnosed with TRS disorders.ResultsCH addition increased the rate of full night sleep and decreased the rates of agitation and verbal and physical violence events. Notably, no adverse events including falls were reported during CH addition.DiscussionCH shows some short-term benefits in improving sleep disorders and reducing violent and agitated behavior in patients with TRS. Our study has limitations due to its small sample size, retrospective design and lack of a control group. A large-scale, double-blind, randomized trial is needed to further explore the efficacy and safety of CH in psychiatric populations with TRS accompanied by agitation, violence and disturbed sleep.

The prevalence of autism spectrum disorder (ASD) is increasing worldwide. Youngsters with ASD demonstrate higher rates of intellectual disabilities (IDs), comorbid psychopathology and psychiatric hospitalizations, compared to children in the general population. This study characterizes the demographics and clinical parameters of adolescent psychiatric inpatients with ASD compared to inpatients without ASD, all hospitalized during the study period. Additionally, within the ASD group, those with ID were compared to those without. The rate of males among participants with ASD was significantly higher than among those without ASD, and the duration of hospitalization was longer. In contrast, the rate of cigarette smoking, major depressive disorder and suicidal thoughts among those with ASD was lower. One-third of those with ASD had moderate to severe ID, about 10% had comorbid epilepsy, and about half of them demonstrated aggressive behavior. Most ASD patients showed significant improvement upon discharge, although the extent of improvement was more prominent among ASD patients with no ID. Our findings, consistent with previous research, indicate that hospitalization is beneficial to youths with ASD, both those with and those without ID. Further studies that include long-term follow-up are needed.

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10-6). Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.

Abstract Background The 22q11.2 deletion syndrome (22q11.2DS) is caused by hemizygous microdeletions on chromosome 22q11.2 with highly variable physical and neuropsychiatric manifestations. We explored the genotype-phenotype relationship in a relatively large 22q11.2DS cohort treated and monitored in our clinic using comprehensive clinical evaluation and detailed molecular characterization of the deletion. Methods Molecular analyses in 142 subjects with 22q11.2DS features were performed by FISH and MLPA methods. Participants underwent clinical assessment of physical symptoms and structured psychiatric and cognitive evaluation. Results Deletions were found in 110 individuals including one with an atypical nested distal deletion which was missed by the FISH test. Most subjects (88.2%) carried the 3Mb typically deleted region and 11.8% carried 4 types of deletions differing in size and location. No statistically significant genotype-phenotype correlations were found between deletion type and clinical data although some differences in hypocalcemia and cardiovascular anomalies were noted. Analysis of the patient with the distal nested deletion suggested a redundancy of genes causing the physical and neuropsychiatric phenotype in 22q11.2DS and indicating that the psychiatric and cognitive trajectories may be governed by different genes. Conclusions MLPA is a useful and affordable molecular method combining accurate diagnosis and detailed deletion characterization. Variations in deletion type and clinical manifestations impede the detection of significant differences in samples of moderate size, but analysis of individuals with unique deletions may provide insight into the underlying biological mechanisms. Future genotype-phenotype studies should involve large multicenter collaborations employing uniform clinical standards and high-resolution molecular methods.