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Parents' experience of a shared parent-child stay during the first week of hospitalization in a child psychiatry inpatient ward

Shilton, Tal; Shilton, Hany; Mosheva, Mariela; Amsalem, Doron; Negri, Ofir; Cohen, Tal; Hertz-Palmor, Nimrod; Waniel-Zaga, Ariela; Pesach, Itai M; Tuval-Mashiach, Rivka; Hasson-Ohayon, Ilanit; Gothelf, Doron
Hospitalization of children in an inpatient psychiatric ward is stressful for both the children and their parents, and separation from the parents during hospitalization is probably one major cause of this stress. We designated one room in a closed inpatient unit to enable a parent to stay with his/her child, including overnight, during the 1st week of hospitalization. We then examined the parents' experience of the shared parent-child stay. Thirty parents of 16 children aged 6-12 years admitted to our inpatient child psychiatry ward completed in-depth semi-structured interviews after that week's experience. The interviews covered the parents' experiences of the 1st week in the larger context of pre-hospitalization period, which also includes the decision to hospitalize the child. The contents of the interviews were analyzed by means of independent coders that identified the following major themes: (1) ambivalence and confusion of the parents as related to their decision to hospitalize their child in the time period just before admission; (2) gradual process of separation from the child during the joint stay at the ward; (3) building confidence and trust toward the staff. Themes 2 and 3 express benefits from the joint hospitalization that may have a strong positive impact on the child's and the parent's recovery. These themes warrant further evaluation of the proposed shared stay during hospitalization in future studies.
PMID: 37202584
ISSN: 1435-165x
CID: 5656822

CAR-engineered lymphocyte persistence is governed by a FAS ligand/FAS auto-regulatory circuit

Yi, Fei; Cohen, Tal; Zimmerman, Natalie; Dündar, Friederike; Zumbo, Paul; Eltilib, Razan; Brophy, Erica J; Arkin, Hannah; Feucht, Judith; Gormally, Michael V; Hackett, Christopher S; Kropp, Korbinian N; Etxeberria, Inaki; Chandran, Smita S; Park, Jae H; Hsu, Katharine C; Sadelain, Michel; Betel, Doron; Klebanoff, Christopher A
Chimeric antigen receptor (CAR)-engineered T and NK cells can cause durable remission of B-cell malignancies; however, limited persistence restrains the full potential of these therapies in many patients. The FAS ligand (FAS-L)/FAS pathway governs naturally-occurring lymphocyte homeostasis, yet knowledge of which cells express FAS-L in patients and whether these sources compromise CAR persistence remains incomplete. Here, we constructed a single-cell atlas of diverse cancer types to identify cellular subsets expressing FASLG, the gene encoding FAS-L. We discovered that FASLG is limited primarily to endogenous T cells, NK cells, and CAR-T cells while tumor and stromal cells express minimal FASLG. To establish whether CAR-T/NK cell survival is regulated through FAS-L, we performed competitive fitness assays using lymphocytes modified with or without a FAS dominant negative receptor (ΔFAS). Following adoptive transfer, ΔFAS-expressing CAR-T and CAR-NK cells became enriched across multiple tissues, a phenomenon that mechanistically was reverted through FASLG knockout. By contrast, FASLG was dispensable for CAR-mediated tumor killing. In multiple models, ΔFAS co-expression by CAR-T and CAR-NK enhanced antitumor efficacy compared with CAR cells alone. Together, these findings reveal that CAR-engineered lymphocyte persistence is governed by a FAS-L/FAS auto-regulatory circuit.
PMID: 38464085
CID: 5656872

The supine moving apprehension test-Reliability and validity among healthy individuals and patients with anterior shoulder instability

Rabin, Alon; Chechik, Ofir; Olds, Margie K; Uhl, Timothy L; Kazum, Efi; Deutsch, Adin; Citron, Eran; Cohen, Tal; Dolkart, Oleg; Bibas, Assaf; Maman, Eran
BACKGROUND/UNASSIGNED:Performance-based tests for patients with anterior shoulder dislocation are lacking. This study determined the reliability and validity of the supine moving apprehension test designed to assess the ability to control anterior instability loads. METHODS/UNASSIGNED:Thirty-six participants were recruited (18 healthy individuals, and 18 patients following anterior shoulder dislocation). Healthy participants performed the supine moving apprehension test on 2 separate occasions to determine test-retest reliability. Patients completed the supine moving apprehension test and the Western Ontario Shoulder Instability index before and 6 months after surgical stabilization of their shoulder. The presence of anterior apprehension was also documented post-operatively. RESULTS/UNASSIGNED: < 0.01). CONCLUSIONS/UNASSIGNED:The supine moving apprehension test is reliable and valid among patients with anterior shoulder dislocation and may serve to assess patients' ability to control shoulder anterior instability loads.
PMID: 38435037
ISSN: 1758-5732
CID: 5656862

Elasticity of whole blood clots measured via Volume Controlled Cavity Expansion

Varner, Hannah; Sugerman, Gabriella P; Rausch, Manuel K; Cohen, Tal
Measuring and understanding the mechanical properties of blood clots can provide insights into disease progression and the effectiveness of potential treatments. However, several limitations hinder the use of standard mechanical testing methods to measure the response of soft biological tissues, like blood clots. These tissues can be difficult to mount, and are inhomogeneous, irregular in shape, scarce, and valuable. To remedy this, we employ in this work Volume Controlled Cavity Expansion (VCCE), a technique that was recently developed, to measure local mechanical properties of soft materials in their natural environment. Through highly controlled volume expansion of a water bubble at the tip of an injection needle, paired with simultaneous measurement of the resisting pressure, we obtain a local signature of whole blood clot mechanical response. Comparing this data with predictive theoretical models, we find that a 1-term Ogden model is sufficient to capture the nonlinear elastic response observed in our experiments and produces shear modulus values that are comparable to values reported in the literature. Moreover, we find that bovine whole blood stored at 4 °C for greater than 2 days exhibits a statistically significant shift in the shear modulus from 2.53 ± 0.44 kPa on day 2 (N = 13) to 1.23 ± 0.18 kPa on day 3 (N = 14). In contrast to previously reported results, our samples did not exhibit viscoelastic rate sensitivity within strain rates ranging from 0.22 - 21.1 s-1. By surveying existing data on whole blood clots for comparison, we show that this technique provides highly repeatable and reliable results, hence we propose the more widespread adoption of VCCE as a path forward to building a better understanding of the mechanics of soft biological materials.
PMID: 37207527
ISSN: 1878-0180
CID: 5656832

Do patients with Peyronie's disease perceive penile curvature in adults and children differently than the general population?

Henry, Alexander J; Holler, Jordan T; Lui, Jason; Breyer, Benjamin N; Ziegelmann, Matthew; Cohen, Tal; Smith, Ryan P; Yeaman, Clinton; Winkelman, Andrew J; Villanueva, Carlos; Kern, Nora G
BACKGROUND:As perception of penile curvature varies widely, we sought to understand how adults perceive curvature and how these opinions compare with those of patients with curvature, specifically Peyronie's disease (PD). AIM:To investigate the perspectives of curvature correction from adults with and without PD, as well as differences within demographics. METHODS:A cross-sectional survey was administered to adult patients and nonpatient companions in general urology clinics at 3 institutions across the United States. Men, women, and nonbinary participants were recruited. Patients were grouped as having PD vs andrology conditions without PD vs general urology conditions plus companions. The survey consisted of unlabeled 2-dimensional images of penis models with varying degrees of curvature. Participants selected images that they would want surgically corrected for themselves and their children. Univariable and multivariable analyses were performed to identify demographic variables associated with willingness to correct. OUTCOMES:Our main outcome was to detect differences in threshold to correct curvature between those with and without PD. RESULTS:Participants were grouped as follows: PD (n = 141), andrology (n = 132), and general (n = 302) . Respectively, 12.8%, 18.9%, and 19.9% chose not to surgically correct any degree of curvature (P = .17). For those who chose surgical correction, the mean threshold for correction was 49.7°, 51.0°, and 51.0° (P = .48); for their children, the decision not to correct any degree of curvature was 21.3%, 25.4%, and 29.3% (P = .34), which was significantly higher than correction for themselves (P < .001). The mean threshold for their children's correction was 47.7°, 53.3°, and 49.4° for the PD, andrology, and general groups (P = .53), with thresholds no different vs themselves (P = .93). On multivariable analysis, no differences were seen in demographics within the PD and andrology groups. In the general group, participants aged 45 to 54 years and those who identified as LGBTQ (lesbian, gay, bisexual, transgender, queer) had a higher threshold for correction as compared with their counterparts when factoring other demographic variables (63.2° vs 48.8°, P = .001; 62.1° vs 50.4°, P = .05). CLINICAL IMPLICATIONS:With changing times and viewpoints, this study stresses the importance of shared decision making and balancing risks and benefits to correction of penile curvature. STRENGTHS AND LIMITATIONS:Strengths include the broad population surveyed. Limitations include the use of artificial models. CONCLUSION:No significant differences were seen in the decision to surgically correct curvature between participants with and without PD, with participants being less likely to choose surgical correction for their children.
PMID: 37279444
ISSN: 1743-6109
CID: 5656842

The crucial role of elasticity in regulating liquid-liquid phase separation in cells

Kothari, Mrityunjay; Cohen, Tal
Liquid-liquid phase separation has emerged as a fundamental mechanism underlying intracellular organization, with evidence for it being reported in numerous different systems. However, there is a growing concern regarding the lack of quantitative rigor in the techniques employed to study phase separation, and their ability to account for the complex nature of the cellular milieu, which affects key experimentally observable measures, such as the shape, size and transport dynamics of liquid droplets. Here, we bridge this gap by combining recent experimental data with theoretical predictions that capture the subtleties of nonlinear elasticity and fluid transport. We show that within a biologically accessible range of material parameters, phase separation is highly sensitive to elastic properties and can thus be used as a mechanical switch to rapidly transition between different states in cellular systems. Furthermore, we show that this active mechanically mediated mechanism can drive transport across cells at biologically relevant timescales and could play a crucial role in promoting spatial localization of condensates; whether cells exploit such mechanisms for transport of their constituents remains an open question.
PMID: 36565390
ISSN: 1617-7940
CID: 5656792

Torsion-induced stick-slip phenomena in the delamination of soft adhesives

Venkatadri, Tara K; Henzel, Thomas; Cohen, Tal
Soft adhesive contacts are ubiquitous in nature and are increasingly used in synthetic systems, such as flexible electronics and soft robots, due to their advantages over traditional joining techniques. While methods to study the failure of adhesives typically apply tensile loads to the adhesive joint, less is known about the performance of soft adhesives under shear and torsion, which may become important in engineering applications. A major challenge that has hindered the characterization of shear/torsion-induced delamination is imposed by the fact that, even after delamination, contact with the substrate is maintained, thus allowing for frictional sliding and re-adhesion. In this work, we address this gap by studying the controlled delamination of soft cylinders under combined compression and torsion. Our experimental observations expose the nucleation of delamination at an imperfection and its propagation along the circumference of the cylinder. The observed sequence of 'stick-slip' events and the sensitivity of the delamination process to material parameters are explained by a theoretical model that captures axisymmetric delamination patterns, along with the subsequent frictional sliding and re-adhesion. By opening up an avenue for improved characterization of adhesive failure, our experimental approach and theoretical framework can guide the design of adhesives in future applications.
PMID: 36919370
ISSN: 1744-6848
CID: 5656812

Human mitochondrial RNA modifications associate with tissue-specific changes in gene expression, and are affected by sunlight and UV exposure

Cohen, Tal; Medini, Hadar; Mordechai, Chen; Eran, Alal; Mishmar, Dan
RNA-DNA differences (RDD) have previously been identified in the human mitochondrial RNA (mt-RNA) transcripts, yet their functional impact is poorly understood. By analyzing 4928 RNA-seq samples from 23 body sites, we found that mtDNA gene expression negatively correlated with the levels of both m1A 947 16 S rRNA modification (mtDNA position 2617) and the m1A 1812 ND5 mRNA modification (mtDNA position 13,710) in 15 and 14 body sites, respectively. Such correlation was not evident in all tested brain tissues, thus suggesting a tissue-specific impact of these modifications on mtDNA gene expression. To assess the response of the tested modifications to environmental cues, we analyzed pairs of skin samples that were either exposed to the sun or not. We found that the correlations of mtDNA gene expression with both mt-RNA modifications were compromised upon sun exposure. As a first step to explore the underlying mechanism, we analyzed RNA-seq data from keratinocytes that were exposed to increasing doses of UV irradiation. Similar to sun exposure, we found a significant decrease in mtDNA gene expression upon increase in UV dosage. In contrast, there was a significant increase in the m1A 947 16 S rRNA modification levels upon elevation in UV dose. Finally, we identified candidate modulators of such responses. Taken together, our results indicate that mt-RNA modifications functionally correlate with mtDNA gene expression, and responds to environmental cues, hence supporting their physiological importance.
PMID: 35246665
ISSN: 1476-5438
CID: 5656742

Outcomes among patients admitted for non-ST-segment myocardial infarction in the pre-pandemic and pandemic COVID-19 era: Israel Nationwide study

Asher, Elad; Fardman, Alexander; Shmueli, Hezzy; Orvin, Katia; Oren, Daniel; Kofman, Natalia; Mohsen, Jameel; Moady, Gassan; Taha, Louay; Rubinshtein, Ronen; Azriel, Osherov; Efraim, Roi; Saleem, Dabbah; Taieb, Philippe; Ben-Assa, Eyal; Cohen, Tal; Klempfner, Robert; Orlev, Amir; Beigel, Roy; Segev, Amit; Matetzky, Shlomi
BACKGROUND:Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic in 2019, several countries have reported a substantial drop in the number of patients admitted with non-ST-segment myocardial infarction (NSTEMI). OBJECTIVE:We aimed to evaluate the changes in admissions, in-hospital management and outcomes of patients with NSTEMI in the COVID-19 era in a nationwide survey. METHOD/METHODS:A prospective, multicenter, observational, nationwide study involving 13 medical centers across Israel aimed to evaluate consecutive patients with NSTEMI admitted to intensive cardiac care units over an 8-week period during the COVID-19 outbreak and to compare them with NSTEMI patients admitted at the same period 2 years earlier (control period). RESULTS:There were 624 (43%) NSTEMI patients, of whom 349 (56%) were hospitalized during the COVID-19 era and 275 (44%) during the control period. There were no significant differences in age, gender and other baseline characteristics between the two study periods. During the COVID-19 era, more patients arrived at the hospital via an emergency medical system compared with the control period (P = 0.05). Time from symptom onset to hospital admission was longer in the COVID-19 era as compared with the control period [11.5 h (interquartile range, IQR, 2.5-46.7) vs. 2.9 h (IQR 1.7-6.8), respectively, P < 0.001]. Nevertheless, the time from hospital admission to reperfusion was similar in both groups. The rate of coronary angiography was also similar in both groups. The in-hospital mortality rate was similar in both the COVID-19 era and the control period groups (2.3% vs. 4.7%, respectively, P = 0.149) as was the 30-day mortality rate (3.7% vs. 5.1%, respectively, P = 0.238). CONCLUSION/CONCLUSIONS:In contrast to previous reports, admission rates of NSTEMI were similar in this nationwide survey during the COVID-19 era. With longer time from symptoms to admission, but with the same time from hospital admission to reperfusion therapy and with similar in-hospital and 30-day mortality rates. Even in times of crisis, adherence of medical systems to clinical practice guidelines ensures the preservation of good clinical outcomes.
PMID: 36271838
ISSN: 1464-3677
CID: 5656782

An analysis of factors that influence patient preference of third-line therapy for overactive bladder

Kapur, Anjali; Harandi, Arshia Aalami; Cohen, Tal; Ruan, Heng; Dabrowski, Colin; Anderson, Rebecca; Hwang, Kuemin; Lee, Edwin; Weissbart, Steven; Kim, Jason
OBJECTIVE:Patients with overactive bladder (OAB) refractory to first- and second-line therapy may pursue third-line therapies, including intradetrusor onabotulinum toxin-A (BTX), peripheral tibial nerve stimulation (PTNS), and sacral neuromodulation (SNM). The factors that influence patient preference for each treatment modality have not yet been explored. This study sought to investigate the specific parameters that patients consider in choosing a third-line therapy for OAB. METHODS:Patients refractory to first- and second-line therapies for OAB were identified in our outpatient clinic and asked to watch an educational video providing information on the risks and benefits of each third-line treatment option. They were then given a questionnaire to rank their preference of therapy and select reasons for why they found each therapy favorable and unfavorable. Patients under age 18 years, non-English speakers, those with a developmental disability, and those with a diagnosis of neurogenic bladder were excluded. RESULTS:Of the 98 patients included in the study, 40 participants (40.8%) chose intradetrusor BTX injections, 34 (34.7%) chose PTNS, and 16 (16.3%) chose SNM as their first choice. Seven patients (7.1%) chose none of the offered therapies, and one patient (1.0%) chose all three therapies with equal preference. BTX was found most attractive for its long efficacy (47%); its least attractive feature was the potential need for self-catheterization due to urinary retention (54%). PTNS was found most attractive for being a nonsurgical option (32%) and having no reported significant complications (39%); its least attractive feature was need for frequent office visits (61%). SNM was found most attractive for its potential for long-term relief without frequent office visits (53%); its least attractive feature was need for an implanted device (33%). Patients opting for SNM had higher scores on Urinary Distress Inventory-6 and Incontinence Impact Questionnaire-7 questionnaires when compared to patients opting for BTX injections or PTNS (p &lt; 0.05). 47.4% of patients eventually pursued a third-line therapy. Of those, there was a 67.6% concordance rate between the therapy patients ranked first and the therapy they eventually underwent. CONCLUSIONS:Patients with more severe OAB symptoms opt for more invasive and less time-consuming therapy with the potential for long-term relief, namely SNM. Despite thorough counseling, many patients do not progress to advanced OAB therapies. Understanding factors that influence patients' affinity toward a specific type of treatment can aid with individualized counseling on third-line OAB therapies.
PMID: 36104866
ISSN: 1520-6777
CID: 5656772