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The aim of this retrospective study was to assess blood loss during facial feminization surgeries and to evaluate blood transfusion requirements. Data from the medical records of all male-to-female transgender patients (transwomen) treated with gender affirming hormones and undergoing facial feminization surgeries were analysed. The total blood loss was calculated based on the haemoglobin balanced method. Twenty transwomen (average age of 25.9 years) were enrolled. Group 1 included 10 transwomen who underwent cranioplasty, genioplasty, and mandibular angles refining, group 2 included six transwomen who underwent cranioplasty and genioplasty, and group 3 included four transwomen who underwent mandibular angles refining and genioplasty. The median calculated blood loss for groups 1, 2, and 3 was 1159.7 ml, 828.5 ml, and 546.2 ml, respectively. The group differences in surgical time, intraoperative fluid amounts, and calculated blood loss volumes were significant. None of the patients required an intraoperative blood transfusion and the hormonal treatment had no effect on the amount of calculated blood loss. Hence, blood loss during facial feminization surgeries is well controlled and does not lead to life-threatening events, precluding the possibility of providing generalized recommendations for preoperative blood transfusion preparations.

Cardiometabolic disorders contribute to morbidity and mortality in people with severe mental illnesses (SMI), yet lifestyle-intervention efficacy in patients with SMI is unclear. Israel's unique mental-health rehabilitation hostels (MHRHs) provide housing to subjects with SMI. We tested how multi-component lifestyle intervention affects cardiometabolic risk-factors in at-risk SMI populations residing in MHRHs.In a prospective, cluster-randomized, controlled study, six MHRHs, paired by residents' functioning level, were randomized to lifestyle intervention (nutrition education, physical education), or usual care. Subjects recruited included those with ≥1 of: BMI 25 kg/mEighty residents were enrolled to intervention groups and 74 to control. Compared to baseline, intervention-arm participants experienced improvements in BMI (-0.83 kg/mLifestyle intervention significantly improved BMI, LDL and triglycerides compared to baseline in at-risk MHRHs residents with SMI, yet compared to usual care the differences did not reach statistical significance. The association between the number of dietitian's consultations and BMI improvement suggests that programs should highlight participants' adherence.

Post-SSRI sexual-dysfunction (PSSD) is an iatrogenic syndrome, the underlying neurobiological mechanisms of which are unclear. Symptom onset follows cessation of serotonergic antidepressants i.e. Selective Serotonin and Norepinephrine Reuptake Inhibitors (SSRI's, SNRI's), and Tricyclic antidepressants (TCA's). PSSD symptoms include genital anesthesia, erectile dysfunction and orgasmic/ejaculatory anhedonia, and should be differentiated from depression-related sexual-dysfunction. Recently, accumulated data of numerous case-reports suggest additional non-sexual symptoms including, anhedonia, apathy, and blunted affect. PSSD gained official recognition after the European medical agency concluded that PSSD is a medical condition that persists after discontinuation of SSRI's and SNRI's.To review possible underlying neurobiological mechanisms of this syndrome, update information on the pathophysiology, present a list of potential risk-factors and discuss potential management options for PSSD.Extensive literature review on the main symptom-patterns of this disorder was undertaken using PubMed. It includes introductory explications of relevant neurobiology with the objective of generating hypothesis.Precipitating factors for PSSD include previous exposure to certain drugs, genetic predisposition, psychological stress or chemical stressful reaction to antidepressants along pre-existing medical conditions affecting neuroplasticity. Different theories have been proposed to explain the pathophysiology of PSSD: epigenetic gene expression, dopamine-serotonin interactions, serotonin neurotoxicity and hormonal changes. The diagnosis of PSSD is achieved by excluding all other etiologies of sexual-dysfunction. Treatment is challenging, and many strategies have been suggested without definitive outcomes. We offer the contours of a future neurobiological research agenda, and propose several underlying mechanisms for the various symptoms of PSSD which could be the foundation for a future treatment algorithm.There is a need for well-designed neurobiological research in this domain, as well as in the prevalence, pathophysiology, and treatment of PSSD. Practitioners should be alert to the distinctive features of PSSD. Misdiagnosing this syndrome might lead to harmful treatments including reinstatement of medications which generated PSSD. Sexual Medicine Reviews. Peleg LC, Rabinovitch D, Lavie Y, et al. Post-SSRI Sexual Dysfunction (PSSD): Biological Plausibility, Symptoms, Diagnosis, and Presumed Risk Factors. Sex Med Rev 2022;10:91-98.

Anorexia nervosa (AN) is a severe psychiatric disease that is refractory to treatment. To date, there is no effective pharmacological therapy and existing psychotherapy treatment is only partially effective. In neuropsychological terms, AN is characterized by cognitive inflexibility and an overly detailed processing style. Creating artwork and drawing requires integrative thinking that encompasses the big picture.To describe preliminary observations of drawing treatment modality based on precise scientific drawing.The artwork method is based on the classic work by squares and on additional techniques from scientific drawing. The method was developed and implemented in a sheltered home for patients with eating disorders in Parma, Italy. Five patients, four women and one man, agreed to participate in a 10-session workshop as a part of multidisciplinary intervention. The ages of participants were 17-28 years and all had presented with AN for several years.Using the method of copying drawings on squares made it possible to identify features that were common to all the patients, such as focusing on the external form of the drawing rather than on the internal details, exerting strong pressure on the pencil without consideration of the need for future corrections, drawing distorted perceptions of curves, and the adding of significant volume.Precise scientific drawing could be a useful instrument in the understanding and correction of a patient's distorted world and self-perspective. More evidence could be provided by further studies with a larger sample and a control group.

BACKGROUND: The long-term outcome of COVID-19–associated collapsing glomerulopathy is unknown. METHODS: We retrospectively identified 76 native kidney biopsies from patients with history of COVID-19 between March 2020 and April 2021. Presenting and outcome data were obtained for all 23 patients with collapsing glomerulopathy and for seven patients with noncollapsing podocytopathies. We performed APOL1 genotyping by Sanger sequencing, immunostaining for spike and nucleocapsid proteins, and in situ hybridization for SARS-CoV-2. RESULTS: The 23 patients with COVID-19–associated collapsing glomerulopathy were median age 57 years (range, 35–72), included 16 men, and were predominantly (91%) Black. Severity of COVID-19 was mild or moderate in most (77%) patients. All but one patient presented with AKI, 17 had nephrotic-range proteinuria, and six had nephrotic syndrome. Fourteen (61%) patients required dialysis at presentation. Among 17 patients genotyped, 16 (94%) were high-risk APOL1. Among 22 (96%) patients with median follow-up at 155 days (range, 30–412), 11 (50%) received treatment for COVID-19, and eight (36%) received glucocorticoid therapy for podocytopathy. At follow-up, 19 (86%) patients were alive, and 15 (68%) were dialysis free, including seven of 14 who initially required dialysis. The dialysis-free patients included 64% (seven of 11) of those treated for COVID-19 and 75% (six of eight) of those treated with glucocorticoids for podocytopathy. Overall, 36% achieved partial remission of proteinuria, 32% had no remission, and 32% reached combined end points of ESKD or death. Viral infection of the kidney was not detected. CONCLUSIONS: Half of 14 patients with COVID-19–associated collapsing glomerulopathy requiring dialysis achieved dialysis independence, but the long-term prognosis of residual proteinuric CKD remains guarded, indicating a need for more effective therapy.

Type 2 diabetes mellitus (T2DM) is considered a global epidemic, and is constantly on the rise. In Israel, the percentage of diabetics in the Arab population is twice that found in the Jewish population (12% and 6.2%, respectively). Findings suggest that low differentiation of self (DoS: emotional reactivity+ fusion with others, I-position, emotional cutoff) may raise vulnerability to certain physiological pathologies by increasing susceptibility to psychological distress. The major goal of this study was to test differences in DoS and emotional distress (anxiety and depressive symptoms) between diabetic and healthy participants. The second aim was to examine cultural differences within these metrics. Another purpose was to examine the relationship between DoS and emotional distress among healthy and diabetic participants. The sample included 261 participants, of whom 154 were healthy and 107 were diabetic. Diabetics reported more severe depressive symptoms, higher levels of anxiety and emotional cutoff and lower levels of I-position than healthy individuals. The groups did not differ in their levels of emotional reactivity + fusion with others. Arabs demonstrated higher levels of emotional cutoff, anxiety and depressive symptoms and lower levels of I-position than Jews. However, Arabs and Jews did not differ in their levels of emotional reactivity + fusion with others. Emotional reactivity + fusion with others contributed the most to diabetes among Arabs, while depressive symptoms contributed the most among Jews. Finally, among Jewish participants, age was positively correlated with emotional cutoff and depressive symptoms. Emotional cutoff was positively correlated with anxiety and depressive symptoms. Emotional reactivity + fusion with others was positively correlated with anxiety. Among Arab participants, age was positively correlated with emotional cutoff, anxiety and depressive symptoms. I-position was negatively correlated with all study variables. Emotional cutoff was positively correlated, anxiety and depressive symptoms. Emotional reactivity + fusion with others was positively correlated with anxiety and depressive symptoms.

Background Physical growth during childhood and adolescence is influenced by both genetic and environmental factors. Heritability, the proportion of phenotypic variance explained by genetic factors, has been demonstrated for stature and weight status. The aim of this study was to explore the heritability of body composition. Methods A real-life, observational study of the children and adolescents referred to the Endocrine Unit in a tertiary medical center. In January 2018, body composition by means of bioimpedance analysis (BIA) was implemented as part of the standard intake assessment of subjects referred for endocrine consultation. The clinic BIA database was searched for subjects with the term “observation of growth” as the sole reason for referral. BIA of 114 triads of healthy subjects aged 5–18 years and their parents were analyzed. The BIA report included the following data: fat mass, fat percentage, truncal fat percentage and muscle mass. Calculated variables included: appendicular skeletal muscle mass (ASMM = the sum of muscle mass of four limbs), muscle-to-fat ratio [MFR = ASMM (kg)/fat mass (kg)] and sarcopenic index [(SI = ASMM(kg)/height (meter)²]. Data collection from medical files included pubertal stage and home address for socioeconomic position grading. Results There were sex differences in body composition parameters in both the prepubertal and pubertal subjects. The boys among the prepubertal subjects had a lower fat percentage on average than girls (p = 0.020). Among the adolescents, boys on average had lower fat percentage (p = 0.011), higher sarcopenic index (p = 0.021), and higher muscle-to-fat ratio (p p = 0.050; boys-mothers: r = 0.435, p = 0.026; girls-fathers: r = 0.462, p = 0.012; girls-mothers: r = 0.365, p = 0.050) and adiposity indices (fat percentage, truncal fat percentage and muscle-to-fat ratio) of prepubertal boys and their mothers (r = 0.438, p = 0.025; r = 0.420, p = 0.033, and r = 0.478, p = 0.014, respectively). There were no associations between body composition parameters of adolescents and their parents. Socioeconomic position adversely affected fat percentage in adolescent girls and mothers. Conclusions Heritable body composition traits were demonstrated in childhood but not in adolescence, suggesting that environmental influence has a more telling effect during teenage years.

During Drosophila embryonic development, cell death eliminates 30% of the primordial germ cells (PGCs). Inhibiting apoptosis does not prevent PGC death, suggesting a divergence from the conventional apoptotic program. Here, we demonstrate that PGCs normally activate an intrinsic alternative cell death (ACD) pathway mediated by DNase II release from lysosomes, leading to nuclear translocation and subsequent DNA double-strand breaks (DSBs). DSBs activate the DNA damage-sensing enzyme, Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) and the ATR/Chk1 branch of the DNA damage response. PARP-1 and DNase II engage in a positive feedback amplification loop mediated by the release of PAR polymers from the nucleus and the nuclear accumulation of DNase II in an AIF- and CypA-dependent manner, ultimately resulting in PGC death. Given the anatomical and molecular similarities with an ACD pathway called parthanatos, these findings reveal a parthanatos-like cell death pathway active during Drosophila development., Caspase independent alternative cell death (ACD) pathways exist, but have been largely investigated under non-physiological conditions. Here, the authors show that Drosophila primordial germ cells normally elicit DNase II-dependent DNA damage, triggering a parthanatos-like ACD pathway.

Introduction: Extrapulmonary small-cell cancer (EPSCC) is a relatively rare malignancy. The management of EPSCC is usually extrapolated from small-cell lung cancer (SCLC). In spite of the morphological similarity of the 2 malignancies, there are many differences in clinical features, prognosis, and recommendations of treatment of these disorders. The data on the correlation of clinical-pathological characteristics of EPSCC and treatment results is scarce. Materials and Methods: This retrospective analysis of 41 consecutively treated patients diagnosed with EPSCC in 2015–2018 was performed in a tertiary medical center. The correlation between the clinical and pathological characteristics and the treatment outcome (response rate, disease-free interval, and overall medial survival) was done using the standard statistics, Kaplan-Meier method, and multivariate analyses. The stratification was done on the stage of the disease, Ki-67 proliferative index, the location of the tumor, and smoking. Results: Forty-one patients were included with a median age of 66.3 years. The most common primary site was the gastrointestinal tract (28, 68.3%) including the pancreas. The most common distant metastasis site was the liver (23, 56.1%). Only 2 patients (4.9%) had brain metastases. Unlike in SCLC, most patients did not have any history of smoking (23, 56.1%). Nineteen patients with metastatic disease received systemic treatment, mostly cisplatin-based chemotherapy, with a response rate of 57.9%. The results of treatment were significantly better in patients with disseminated EPSCC with Ki-67 Discussion: The results of our study show the unique entity of EPSCC. The rarity of brain metastases proves that prophylactic brain irradiation should not be recommended in practice. The provocative idea of prophylactic liver irradiation in limited-stage EPSCC of gastrointestinal origin can be evaluated in future studies. The predictive role of Ki-67 is important in metastatic EPSCC. There is probably no role of smoking in developing EPSCC.

BackgroundThe outbreak of a new Coronavirus disease (COVID-19) poses dramatic challenges to public health authorities worldwide. One measure put in place to contain the spread of the disease is self-quarantine of individuals who may have been exposed to the disease. While officials expect the public to comply with such regulation, studies suggest that a major obstacle to compliance for self-quarantine is concern over loss of income or employment due to the prolonged absence from work.MethodsA cohort study of the adult population of Israel was conducted in two time points during the COVID-19 outbreak, the last week of February and the third week of March 2020, in order to assess public attitudes. In particular, public compliance rates to self-quarantine with and without State-sponsored compensation for lost wages were assessed.ResultsThe results suggest that public attitudes changed as the threat increased, making people more compliant with regulations. In February 2020, compliance rate for self-quarantine dropped from 94% to less than 57% when monetary compensation for lost wages was removed; however, in March 2020 this drop became more moderate (from 96 to 71%). The multivariate logistic regression revealed that older, non-Jewish, worried over COVID-19, and trusting the Ministry of Health were more likely than their counterparts to comply with self-isolation, even when monetary compensation was not assumed.ConclusionsDespite the effects of threat on people’s obedience with regulations, this study demonstrates that providing people with assurances about their livelihood during absence from work remains an important component in compliance with public health regulations.

Feingold syndrome 1 (FGLDS1) is an autosomal dominant malformation syndrome, characterized by skeletal anomalies, microcephaly, facial dysmorphism, gastrointestinal atresias and learning disabilities. Mutations in the MYCN gene are known to be the cause of this syndrome. Congenital absence of the flexor pollicis longus (CAFPL) tendon is a rare hand anomaly. Most cases are sporadic and no genetic variants have been described associated with this abnormality. We describe here a pedigree combining familial CAFPL tendon as a feature of FGLDS1. Molecular analyses of whole exome sequence data in five affected family members spanning three generations of this family revealed a novel mutation in the MYCN gene (c.1171C>T; p.Arg391Cys). Variants in MYCN have not been published in association with isolated or syndromic CAFPL tendon, nor has this been described as a skeletal feature of Feingold syndrome. This report expands on the clinical and molecular spectrum of MYCN-related disorders and highlights the importance of MYCN protein in normal human thumb and foramen development.

Mutations in more than 150 genes are responsible for inherited hearing loss, with thousands of different, severe causal alleles that vary among populations. The Israeli Jewish population includes communities of diverse geographic origins, revealing a wide range of deafness-associated variants and enabling clinical characterization of the associated phenotypes. Our goal was to identify the genetic causes of inherited hearing loss in this population, and to determine relationships among genotype, phenotype, and ethnicity. Genomic DNA samples from informative relatives of 88 multiplex families, all of self-identified Jewish ancestry, with either non-syndromic or syndromic hearing loss, were sequenced for known and candidate deafness genes using the HEar-Seq gene panel. The genetic causes of hearing loss were identified for 60% of the families. One gene was encountered for the first time in human hearing loss: ATOH1 (Atonal), a basic helix-loop-helix transcription factor responsible for autosomal dominant progressive hearing loss in a five-generation family. Our results demonstrate that genomic sequencing with a gene panel dedicated to hearing loss is effective for genetic diagnoses in a diverse population. Comprehensive sequencing enables well-informed genetic counseling and clinical management by medical geneticists, otolaryngologists, audiologists, and speech therapists and can be integrated into newborn screening for deafness.

Background Coronavirus disease 2019 (COVID-19) is thought to cause kidney injury by a variety of mechanisms. To date, pathologic analyses have been limited to patient reports and autopsy series. Methods We evaluated biopsy samples of native and allograft kidneys from patients with COVID-19 at a single center in New York City between March and June of 2020. We also used immunohistochemistry, in situ hybridization, and electron microscopy to examine this tissue for presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results The study group included 17 patients with COVID-19 (12 men, 12 black; median age of 54 years). Sixteen patients had comorbidities, including hypertension, obesity, diabetes, malignancy, or a kidney or heart allograft. Nine patients developed COVID-19 pneumonia. Fifteen patients (88%) presented with AKI; nine had nephrotic-range proteinuria. Among 14 patients with a native kidney biopsy, 5 were diagnosed with collapsing glomerulopathy, 1 was diagnosed with minimal change disease, 2 were diagnosed with membranous glomerulopathy, 1 was diagnosed with crescentic transformation of lupus nephritis, 1 was diagnosed with anti-GBM nephritis, and 4 were diagnosed with isolated acute tubular injury. The three allograft specimens showed grade 2A acute T cell-mediated rejection, cortical infarction, or acute tubular injury. Genotyping of three patients with collapsing glomerulopathy and the patient with minimal change disease revealed that all four patients had APOL1 high-risk gene variants. We found no definitive evidence of SARS-CoV-2 in kidney cells. Biopsy diagnosis informed treatment and prognosis in all patients. Conclusions Patients with COVID-19 develop a wide spectrum of glomerular and tubular diseases. Our findings provide evidence against direct viral infection of the kidneys as the major pathomechanism for COVID-19-related kidney injury and implicate cytokine-mediated effects and heightened adaptive immune responses.

Purpose: Pelvic fracture evaluation with abdominopelvic computed tomography (CT) and formal CT cystography for rule out of urine bladder injury have been commonly employed in pediatric trauma patients. The additional delayed imaging required to obtain optimal CT cystography is, however, associated with increased doses of ionizing radiation to pelvic organs and represent a significant risk in the pediatric population for future carcinogenic risk. We hypothesized that avoidance of routine CT cystography among pediatric pelvic fracture victims would not result in an appreciable rate of missed bladder injuries and would aid in mitigating the radiation exposure risk associated with these additional images. Methods: A retrospective cohort study involving blunt trauma pelvic fractures among pediatric trauma patients (age

Introduction Dental trauma and congenital anodontia are common causes of anodontia in the anterior maxilla. The proposed restorative treatment constitutes a challenge for many dentists, particularly if it is a question of a young patient who has not yet completed skeletal and dental development. Current treatments for anterior maxillary anodontia include: fixed or removable partial dentures; orthodontic closure of interdental spaces; and dental implants. Dental implants do not move with the dento-alveolar complex during the growth period of the maxilla. Therefore, many researchers maintain that implants should be postponed until after adolescence, in order to prevent complications, such as infra-occlusion, that would require the replacement of the abutment and crown-implant restoration, or even invasive treatments, such as the removal of the implant in the future. The objective of this literature review is to investigate the aetiology of the phenomenon, and outcome. Results Continuous tooth eruption is not affected by age, so considerable changes may occur due to eruption of adjacent teeth. In addition, both women and men are affected by this phenomenon and, usually, there is no significant difference in the amount of growth between the short face and the long face. Conclusion It can be concluded that continuous facial skeletal growth and teeth eruption are evident in the second and third decades. Where possible, it is advisable to delay placement of an anterior maxillary implant in the adolescent patient.

Sinonasal inverted papillomas occasionally undergo malignant transformation into squamous cell carcinoma, which can be associated with EGFR mutations. Since biopsy can potentially under-sample the tumor, CT and MRI can provide clues as to the presence of malignant transformation. In particular, this entity tends to appear different from benign inverted papilloma on imaging, including prominent bone erosions, necrosis, low diffusivity in the solid tumor components, and absence of the cerebriform pattern on MRI. The radiology findings, pathology features, and management of squamous cell carcinoma arising from inverted papilloma are described.

Early application of tourniquets has reduced injury death rates. At the end of 2013, the Israel Defense Forces Medical Corps completed a military-wide introduction of the Combat Application Tourniquet as the standard-issued tourniquet. The accompanying clinical practice guideline encouraged combat soldiers and medical teams towards a liberal use of tourniquets for extremity injuries, even when in doubt.This study aimed to assess the effects of the wide introduction of advanced tourniquets on the rate of tourniquet applications, the type of tourniquet applied, and the differences in hospitalisation outcomes following the introduction.The study population was composed of hospitalised military casualties with an extremity injury treated by military medical teams between 2006 and 2015. Prehospital data were extracted from the Israel Defense Forces Trauma Registry and matched to corresponding hospital data from the Israeli National Trauma Registry. Two periods were compared: 2006-2013 "pre-intervention period" and 2014-2015 "post-intervention period".A total of 1,578 casualties were recorded during the study period. Of these, 320 (20.3%) occurred between 2014-2015. Characteristics of casualties in the post-intervention period were similar to those in the pre-intervention period including the rate of traumatic amputations (2.5% vs 2.2%, p = 0.93) and Injury Severity Score of 16 or above (12.8% vs 14.9%, p = 0.40). The rate of tourniquet application was more than four-fold in the post-intervention period compared to the pre-intervention period (22.8% vs 5.5%, p 0.001). Nevertheless, rates of in-hospital amputations (1.6% vs 1.6%, p = 1.00) and death (0.9% vs 1.3%, p = 0.53) were similar in the two periods.Following the IDF military-wide introduction of advanced tourniquets, the tourniquet application rate rose sharply, the use of old tourniquets ceased over time, and in-hospital amputation rate did not increase. These findings suggest that the awareness for haemorrhage control using advanced tourniquets rose.

Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are common conditions following motor vehicle accidents (MVAs). Mild TBI and PTSD not only share similar features but may also coexist and interact. Nonetheless, research on psychotherapeutic interventions for PTSD in patients with a history of mTBI, particularly regarding pediatric populations, is limited. The present study compared the efficacy of the prolonged exposure treatment protocol for children and adolescents (PE-A) with PTSD and mTBI (n = 16) versus PTSD alone (n = 21); treatment commenced at least 3 months following an MVA. Emotional status and cognitive functioning were assessed pre- and postintervention using questionnaires and standardized neuropsychological tests. Participants from both groups benefitted from the intervention, as reflected in their emotional status via increased ratings of well-being and decreased ratings of PTSD, anxiety, depression, and postconcussive symptoms, η2 = .21-.50. Ratings of cognitive function also improved for cognitive flexibility, η2 = .30; executive function in everyday life, η2 = .27; and attention and inhibition, η2 = .16. Parental PTSD was the strongest predictor of improvement after intervention, sr2 = .35. Thus, it appears that PE-A is an effective intervention for children with MVA-related PTSD regardless of its comorbidity with mTBI.

Brain metastases are common in patients with advanced melanoma and constitute a major cause of morbidity and mortality. Between 40% and 60% of melanomas harbor BRAF mutations. Selective BRAF inhibitor therapy has yielded improvement in clinical outcome; however, genetic discordance between the primary lesion and the metastatic tumor has been shown to occur. Currently, the only way to characterize the genetic landscape of a brain metastasis is by tissue sampling, which carries risks and potential complications. The aim of this study was to investigate the use of radiomics analysis for non-invasive identification of BRAF mutation in patients with melanoma brain metastases, based on conventional magnetic resonance imaging (MRI) data. We applied a machine-learning method, based on MRI radiomics features for noninvasive characterization of the BRAF status of brain metastases from melanoma (BMM) and applied it to BMM patients from two tertiary neuro-oncological centers. All patients underwent surgical resection for BMM, and their BRAF mutation status was determined as part of their oncological work-up. Their routine preoperative MRI study was used for radiomics-based analysis in which 195 features were extracted and classified according to their BRAF status via a support vector machine. The BRAF status of 53 study patients, with 54 brain metastases (25 positive, 29 negative for BRAF mutation) was predicted with mean accuracy = 0.79 ± 0.13, mean precision = 0.77 ± 0.14, mean sensitivity = 0.72 ± 0.20, mean specificity = 0.83 ± 0.11 and with a 0.78 area under the receiver operating characteristic curve for positive BRAF mutation prediction. Radiomics-based noninvasive genetic characterization is feasible and should be further verified using large prospective cohorts.

Sex estimation of skeletal remains is of great importance in the fields of physical and forensic anthropology. Since skeletons are often incomplete, it is essential to estimate sex from as many skeletal remains as possible. The aim of this study was to establish new methods for estimating sex using the morphology of the sternum and the fifth to ninth ribs. We considered two conditions of skeletal preservation: All skeletal elements measured are available, or only a single element is available. Traditional or virtual measurements were carried out on three samples: (1) A skeletal sample from the Hamann-Todd Human osteological collection, Cleveland Museum of Natural History, USA (N = 413), was used to create prediction equations for sex estimation. (2) A recent, CT-based sample from Israel (N = 33) was used to cross-validate the accuracy of the prediction equations. (3) A skeletal sample from the Anthropological Collection at Tel Aviv University (N = 15) was used to test the validity of the virtual measurements. Reliability and validity analyses were carried out via intraclass correlation coefficient analysis. Prediction equations for sex were created using logistic regression. The measurements were found to be highly reliable and valid. Success rates for sex estimation were high (> 80%) and correspond well between the skeletal and recent samples, especially for the left sixth, left eigth, and left ninth ribs. To conclude, measurements of the sternum and ribs are valuable for estimating sex and can be carried out using either traditional or virtual tools. Of all the skeletal elements examined in this study, the sternum, left sixth, left eighth, and left ninth ribs were found to be the most reliable skeletal elements for estimating the sex of an individual.

The basal ganglia (BG) are a group of subcortical nuclei responsible for motor and executive function. Central to BG function are striatal cells expressing D1 (D1R) and D2 (D2R) dopamine receptors. D1R and D2R cells are considered functional antagonists that facilitate voluntary movements and inhibit competing motor patterns, respectively. However, whether they maintain a uniform function across the striatum and what influence they exert outside the BG is unclear. Here, we address these questions by combining optogenetic activation of D1R and D2R cells in the mouse ventrolateral caudoputamen with fMRI. Striatal D1R/D2R stimulation evokes distinct activity within the BG-thalamocortical network and differentially engages cerebellar and prefrontal regions. Computational modeling of effective connectivity confirms that changes in D1R/D2R output drive functional relationships between these regions. Our results suggest a complex functional organization of striatal D1R/D2R cells and hint toward an interconnected fronto-BG-cerebellar network modulated by striatal D1R and D2R cells., Cell Reports, 37 (13), ISSN:2666-3864, ISSN:2211-1247

Introduction The use of oral fosfomycin for urinary tract infections (UTIs) caused by non-Escherichia coli uropathogens is uncertain, including Klebsiella pneumoniae, the second most common uropathogen. Methods A multicompartment bladder infection in vitro model was used with standard media and synthetic human urine (SHU) to simulate urinary fosfomycin exposure after a single 3 g oral dose (fAUC0–72 16884 mg·h/L, t½ 5.5 h) against 15 K. pneumoniae isolates including ATCC 13883 (MIC 2 to >1024 mg/L) with a constant media inflow (20 mL/h) and 4-hourly voiding of each bladder. The impact of the media (CAMHB + G6P versus SHU) on fosfomycin MIC measurements, drug-free growth kinetics and regrowth after fosfomycin administration was assessed. A low and high starting inoculum (5.5 versus 7.5 log10 cfu/mL) was assessed in the bladder infection model. Results Compared with CAMHB, isolates in SHU had a slower growth rate doubling time (37.7 versus 24.1 min) and reduced growth capacity (9.0 ± 0.3 versus 9.4 ± 0.3 log10 cfu/mL), which was further restricted with increased inflow rate (40 mL/h) and more frequent voids (2-hourly). Regrowth was commonly observed in both media with emergence of fosfomycin resistance promoted by a high starting inoculum in CAMHB (MIC rise to ≥1024 mg/L in 13/14 isolates). Resistance was rarely detected in SHU, even with a high starting inoculum (MIC rise to ≥1024 mg/L in 2/14 isolates). Conclusions Simulated in an in vitro UTI model, the regrowth of K. pneumoniae urinary isolates was inadequately suppressed following oral fosfomycin therapy. Efficacy was further reduced by a high starting inoculum.

Cognitive, Affective and Behavioral Neuroscience, 15 (4), ISSN:1530-7026, ISSN:1531-135X

Objectives To compare the relative strengths of cognitive and emotional factors in explaining variance in adherence to recommendations for protective health behaviors against the coronavirus disease 2019 (COVID-19). Design A longitudinal (4-month) study with 422 participants who completed an online survey assessing cognitive factors: perceptions of the severity of the disease, vulnerability to it, and the effectiveness of the protective behavior recommendations against it. The emotional factors investigated were: trait health anxiety, worries, and anxiety related to COVID-19. Results Adherence and perceived behavior efficacy decreased over time, while perceived vulnerability and worries increased. Regression analyses showed a clear predictive advantage of beliefs about the efficacy of adherence to protective behaviors. Conclusions The findings support the "cognitive approach" to explaining pandemic-related behaviors, particularly the key role of perceived efficacy of behavior recommendations. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Introduction: Weight stigmatization is reflected in anti-fat attitudes and stereotypical perceptions of people who are overweight; it has been demonstrated to be prevalent in many segments of society across multiple countries. Studies examining the prevalence of weight stigmatization use different research tools, which can hinder inter-study comparisons. There is also evidence indicating weight stigmatization among registered physical therapists, although its magnitude differs between studies. Limited information exists regarding the attitudes and beliefs of physical therapy (PT) students toward individuals with obesity. Examining weight stigmatization among PT students is particularly important for developing appropriate educational interventions that may influence the professional lives of future physical therapists. Objective: This study aims to characterize and compare the stigmatizing attitudes and beliefs of PT students and certified physical therapists regarding people with obesity in Israel. Its secondary objective is to translate three weight stigmatization questionnaires into Hebrew and determine their psychometric properties. Methods: A cross-sectional, anonymous, and computerized self-report survey was completed by 285 certified physical therapists (average age 39.6 ± 10.1 years) and 115 PT students (average age 26.4 ± 4.9 years). The study used three validated weight stigma questionnaires employed in earlier studies to determine different aspects of weight stigmatization: the Fat Phobia Scale (short form; FPS), Anti-Fat Attitudes (AFA) questionnaire, and Beliefs about Obese People (BAOP). These questionnaires were translated into Hebrew and their psychometric properties ascertained. Results: Similar to the original English versions, the translated versions of the three questionnaires demonstrated good internal consistency (Cronbach’s α values of FPS = 0.77; AFA = 0.75; BOAP = 0.59). The three questionnaires showed a low correlation. No significant difference was noted in the FPS and AFA scores between groups, reflecting that both demonstrated average weight stigmatization (FBS in both groups: average score of 3.6 out of 5; AFA therapists: 3.3 ± 1.2, students: 3.0 ± 1.2 out of 9). However, significant between-group differences were observed for BOAP, which examines beliefs regarding individuals’ control over their weight (therapists: 16.4 ± 5.6, students: 18.0 ± 5.7 out of 48; p < 0.01). Conclusion: Student and certified physical therapists demonstrate average levels of weight stigmatization, as reflected in the FPS and AFA scores. Nevertheless, compared to certified physical therapists, physical therapist students believe more strongly that obesity cannot be controlled by the individual. The students’ beliefs could affect their clinical judgment and behavior as health care professionals in the future. Therefore, anti-fat attitudes and stereotypical perceptions should be addressed and remediated early using educational interventions during the study period.

Background International guidelines have recommended the long-acting formulation of nitrofurantoin as first-line treatment for uncomplicated urinary tract infections (UTIs) since 2010. Australian guidelines have only recently listed nitrofurantoin as a first-line agent, but the long-acting formulation is not available. In the setting of increasing multidrug-resistance, the unavailability of the long-acting formulation of nitrofurantoin in Australia, and anecdotal perception of confusion regarding dosing, we audited nitrofurantoin use. Methods We performed a retrospective audit of nitrofurantoin use at Alfred Health. All patients dispensed nitrofurantoin from January 2016 to June 2018, as identified from pharmacy dispensing records, were eligible. We used a standardised case report form to extract data from medical records, including dosing regimen and indication. Results We included 150 patients with 151 nitrofurantoin prescriptions in the analysis, of whom 74% [111/150] were female. Nitrofurantoin was most commonly dispensed for the treatment of UTIs (68% [103/151] versus 32% [48/151] for UTI prophylaxis). For the treatment of uncomplicated UTIs, the most frequently used dose was 100 mg twice daily for five days. In male patients, the 100 mg twice daily for seven days was the most popular regimen. The prophylactic dose of 50 mg once daily was used in women but rarely in men. We did not find evidence of dose adjustment for renal impairment. Conclusion While treatment duration was consistent with guidelines, the dosage and frequency used was often incorrect for the formulation and was not adjusted for renal function. Nitrofurantoin use is likely to increase, so clarification regarding optimal nitrofurantoin dosing regimens may be appropriate.

Agenesis of the corpus callosum (ACC) is a common prenatally-detected brain anomaly. Recently, an association between mutations in the DCC Netrin 1 receptor (DCC) gene and ACC, with or without mirror movements, has been demonstrated. In this manuscript, we present a family with a novel heterozygous frameshift mutation in DCC, review the available literature, and discuss the challenges involved in the genetic counseling for recently discovered disorders with paucity of medical information. We performed whole exome sequencing in a healthy nonconsanguineous couple that underwent two pregnancy terminations due to prenatal diagnosis of ACC. A heterozygous variant c.2774dupA (p.Asn925Lysfs*17) in the DCC gene was demonstrated in fetal and paternal DNA samples, as well as in a healthy 4-year-old offspring. When directly questioned, both father and child reported having mirror movements not affecting quality of life. Segregation analysis demonstrated the variant in three paternal siblings, two of them having mirror movements. Brain imaging revealed normal corpus callosum. Summary of literature data describing heterozygous loss-of-function variants in DCC (n = 61) revealed 63.9% penetrance for mirror movements, 9.8% for ACC, and 5% for both. No significant neurodevelopmental abnormalities were reported among the seven published patients with DCC loss-of-function variants and ACC. Prenatal diagnosis of ACC should prompt a specific anamnesis regarding any neurological disorder, as well as intentional physical examination of both parents aimed to detect mirror movements. In suspicious cases, detection of DCC pathogenic variants might markedly improve the predicted prognosis, alleviate the parental anxiety, and possibly prevent pregnancy termination.

The objective of this study is to shed light on the phenotype and inheritance pattern of rare 13q33-q34 microdeletions. Appropriate cases were retrieved using local databases of two largest Israeli centers performing CMA analysis. In addition, literature search in PubMed, DECIPHER and ClinVar databases was performed. Local database search yielded eight new patients with 13q33.1-q34 microdeletions (three of which had additional copy number variants). Combined with 15 cases detected by literature search, an additional 23 cases were reported in DECIPHER database, and 17 cases from ClinVar, so overall 60 patients with isolated 13q33.1-q34 microdeletions were described. Developmental delay and/or intellectual disability were noted in the vast majority of affected individuals (81.7% = 49/60). Of the 23 deletions involving the 13q34 cytoband only, in 3 cases, developmental delay and/or intellectual disability was not reported. Interestingly, in two of these cases (66.7%), the deletions did not involve the terminal CHAMP1 gene, as opposed to 3/20 (15%) of patients with 13q34 deletions and neurocognitive disability. Facial dysmorphism and microcephaly were reported in about half of the overall cases, convulsions were noted in one-fifth of the patients, while heart anomalies, short stature and hypotonia each involved about 10-30% of the cases. None of the 13q33-q34 deletions were inherited from a reported healthy parent. 13q33-q34 microdeletions are rare chromosomal aberrations, associated with high risk for neurodevelopmental disability. The rarity of this chromosomal aberration necessitates continuous reporting and collection of available evidence, to improve the ability to provide accurate genetic counseling, especially in the context of prenatal setting.

Autoreactivity to myeloperoxidase (MPO) causes anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with rapidly progressive glomerulonephritis. Here, we show that a Staphylococcus aureus peptide, homologous to an immunodominant MPO T-cell epitope (MPO409–428), can induce anti-MPO autoimmunity. The peptide (6PGD391–410) is part of a plasmid-encoded 6-phosphogluconate dehydrogenase found in some S. aureus strains. It induces anti-MPO T-cell autoimmunity and MPO-ANCA in mice, whereas related sequences do not. Mice immunized with 6PGD391–410, or with S. aureus containing a plasmid expressing 6PGD391–410, develop glomerulonephritis when MPO is deposited in glomeruli. The peptide induces anti-MPO autoreactivity in the context of three MHC class II allomorphs. Furthermore, we show that 6PGD391–410 is immunogenic in humans, as healthy human and AAV patient sera contain anti-6PGD and anti-6PGD391–410 antibodies. Therefore, our results support the idea that bacterial plasmids might have a function in autoimmune disease., Autoreactivity to myeloperoxidase (MPO) causes autoimmune vasculitis and severe glomerulonephritis. Here, Ooi et al. show that a Staphylococcus aureus plasmid encodes a peptide that is homologous to an immunodominant MPO epitope and induces anti-MPO autoimmunity and glomerulonephritis in mice.

Background Dental implants and bone augmentation are well-established procedures used for oral rehabilitation. There is an increasing interest in biological mediators used topically for prevention of bone resorption maybe enhancement of osseointegration of dental implants. The purpose of the manuscript is to describe preliminarily the effect of bisphosphonates on the ossification pattern of bone grafts in a rat model. Material and methods Twenty Wistar-derived male rats were divided into 2 groups study and control. Bone substitute was added to mandibular defects and was covered by a resorbable collagen membrane. In the study group, the membrane was soaked with bisphosphonates suspension. In the control group, the membrane was soaked with saline solution. Radiographic and histomorphometric evaluation were performed. Results Radiographically, it was found that bone density was significantly higher in the study group. Histomorphometric analysis revealed a trend of higher bone volume fraction along with reduced bone substitute volume fraction in the study group, and increased number of osteoclasts and blood vessels in the control group. Conclusions Within the limitations of our study it was found that there is a trend of increasing bone quantity and radiographic bone density by application of bisphosphonates.

The RASopathies are a group of genetic syndromes caused by upregulated RAS signaling. Noonan syndrome (NS), the most common entity among the RASopathies, is characterized mainly by short stature, cardiac anomalies and distinctive facial features. Mutations in multiple RAS-MAPK pathway-related genes have been associated with NS and related phenotypes. We describe two unrelated patients presenting with hypertrophic cardiomyopathy (HCM) and dysmorphic features suggestive of NS. One of them died in the neonatal period because of cardiac failure. Targeted sequencing revealed de novo MRAS variants, c.203C > T (p.Thr68Ile) and c.67G > C (p.Gly23Arg) as causative events. MRAS has only recently been related to NS based on the observation of two unrelated affected individuals with de novo variants involving the same codons here found mutated. Gly23 and Thr68 are highly conserved residues, and the corresponding codons are known hotspots for RASopathy-associated mutations in other RAS proteins. Functional analyses documented high level of activation of MRAS mutants due to impaired GTPase activity, which was associated with constitutive plasma membrane targeting, prolonged localization in non-raft microdomains, enhanced binding to PPP1CB and SHOC2 protein, and variably increased MAPK and PI3K-AKT activation. This report provides additional evidence that a narrow spectrum of activating mutations in MRAS represents another rare cause of NS, and that MRAS has to be counted among the RASopathy genes predisposing to HCM. Moreover, our findings further emphasize the relevance of the MRAS-SHOC2-PPP1CB axis in the control of MAPK signaling, and the contribution of both MAPK and PI3K-AKT pathways in MRAS functional upregulation.

We provide the results of the first interventional study of cytomegalovirus (CMV)-specific immune monitoring to direct the length of antiviral prophylaxis in lung transplantation (LTx).Patients (n = 118) at risk of CMV infection were randomized 1:2 to either 5 months or variable length valganciclovir prophylaxis (5-11 mo post-LTx), as determined by the QuantiFERON (QFN)-CMV assay. Patients with a negative QFN-CMV assay ( 0.2 IU/mL) received prolonged valganciclovir prophylaxis.The primary endpoint that was the incidence of CMV infection in the lung allograft within 18 months of LTx was significantly reduced in the QFN-CMV directed arm (37% versus 58%, P = 0.03). Secondary endpoints that included blood viremia, acute rejection, and chronic lung allograft dysfunction did not differ between the 2 arms. Of the 80/118 patients who ceased antiviral prophylaxis at 5 months, the incidence of viremia ( 600 copies/mL) within the blood was significantly reduced in patients with a positive QFN-CMV assay compared with those without protective immunity (13% versus 67%, P = 0.0003), as was the incidence of severe viremia ( 10 000 copies/mL) (3% versus 50%, P 0.001). Ceasing antiviral prophylaxis at 11 months in patients with a negative assay was associated with a 25% incidence of late CMV viremia.Cytomegalovirus immune monitoring allows an individualized approach to CMV prophylaxis and reduces late CMV infection within the lung allograft.

Rheumatoid Arthritis (RA) causes chronic inflammation of joints. The cytokines TNFα and IFNγ are central players in RA, however their source has not been fully elucidated. Natural Killer (NK) cells are best known for their role in elimination of viral-infected and transformed cells, and they secrete pro-inflammatory cytokines. NK cells are present in the synovial fluids (SFs) of RA patients and are considered to be important in bone destruction. However, the phenotype and function of NK cells in the SFs of patients with erosive deformative RA (DRA) versus non-deformative RA (NDRA) is poorly characterized. Here we characterize the NK cell populations present in the blood and SFs of DRA and NDRA patients. We demonstrate that a distinct population of activated synovial fluid NK (sfNK) cells constitutes a large proportion of immune cells found in the SFs of DRA patients. We discovered that although sfNK cells in both DRA and NDRA patients have similar phenotypes, they function differently. The DRA sfNK secrete more TNFα and IFNγ upon exposure to IL-2 and IL-15. Consequently, we suggest that sfNK cells may be a marker for more severely destructive RA disease.

The purpose of this study is to evaluate mandibular osteotomy procedures during orthognathic surgery, with an emphasis on the complications of the two leading procedures: intraoral vertical ramus osteotomy (IVRO) and sagittal split osteotomy (SSO). We conducted a retrospective cohort study by extracting the records of patients who underwent either IVRO or SSO procedures during orthognathic surgery in a single center between January 2010 and December 2019. A total of 144 patients were included (median age of 20.5 years, 52 males). The IVRO:SSO ratio was 118:26 procedures. When referring to all surgeries performed, IVRO procedures were associated with shorter hospitalization than the SSO procedures, while the overall durations of surgery and follow-up periods were comparable. In contrast, when referring only to bimaxillary procedures, the duration of the IVRO bimaxillary procedures was significantly shorter than the SSO bimaxillary procedures. There were 53 complications altogether. Postoperative complications consisting of skeletal relapse, temporomandibular joint dysfunction, sensory impairment, and surgical-site infection were significantly fewer in the IVRO group. Both types of osteotomies have acceptable rates of complications. IVRO appears to be a safer, simpler, though less acceptable procedure in terms of patient compliance.

Background: In recent years, there has been a shift in the clinical presentation and, hence, diagnostic definitions of eating disorders (EDs), reflected in a dramatic change in the diagnostic criteria of EDs in the DSM-5. The Eating Attitudes Test-26 (EAT-26) is currently considered an accepted instrument for community studies of EDs, although it features an inconsistent factorial structure in different cultures. Therefore, it is essential to investigate whether the EAT-26 can still be considered an adequate instrument for identifying the risk of developing EDs in different cultures. The aim of the present study was to examine the construct validity and internal consistency of the EAT-26. Method: The study used exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) among different cultural populations in Israel. Results: Findings indicated different factors in different ethnic groups, most of which do not correspond with the original EAT-26 three-factor structure. Results: The analysis yielded two main factors among Israeli Jews, four main factors among Israeli Muslim Arabs, and three main factors among Israeli Christian Arabs. Conclusion: These findings shed light on cultural factors affecting perceptions of the EAT-26 items. This calls for a reconsideration of the generalization of the original three-factor structure of the questionnaire in different cultures.

IntroductionVaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity and safety of messenger RNA (mRNA) vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited.MethodsA multicentre observational study evaluated the immunogenicity and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD (n=686) compared with the general population (n=121). Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2–6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/mL. Vaccination efficacy, safety, and disease activity were assessed within 6 weeks after the second vaccine dose.ResultsFollowing vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, pConclusionmRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity.

Introduction:Injury patterns are closely related to changes in behavior. Pandemics and measures undertaken against them may cause changes in behavior; therefore, changes in injury patterns during the coronavirus disease 2019 (COVID-19) outbreak can be expected when compared to the parallel period in previous years.Study Objective:The aim of this study was to compare injury-related hospitalization patterns during the overall national lockdown period with parallel periods of previous years.Methods:A retrospective study was completed of all patients hospitalized from March 15 through April 30, for years 2016-2020. Data were obtained from 21 hospitals included in the national trauma registry during the study years. Clinical, demographic, and circumstantial parameters were compared amongst the years of the study.Results:The overall volume of injured patients significantly decreased during the lockdown period of the COVID-19 outbreak, with the greatest decrease registered for road traffic collisions (RTCs). Patients’ sex and ethnic compositions did not change, but a smaller proportion of children were hospitalized during the outbreak. Many more injuries were sustained at home during the outbreak, with proportions of injuries in all other localities significantly decreased. Injuries sustained during the COVID-19 outbreak were more severe, specifically due to an increase in severe injuries in RTCs and falls. The proportion of intensive care unit (ICU) hospitalizations did not change, however more surgeries were performed; patients stayed less days in hospital.Conclusions:The lockdown period of the COVID-19 outbreak led to a significant decrease in number of patients hospitalized due to trauma as compared to parallel periods of previous years. Nevertheless, trauma remains a major health care concern even during periods of high-impact disease outbreaks, in particular due to increased proportion of severe injuries and surgeries.

Introduction The use of telemedicine in oncology practice is rapidly expanding and is considered safe and cost effective. However, the implications of telemedicine on patient‐physician interaction, patient satisfaction, and absence of the personal touch have not been studied to date. Following the spread of COVID‐19, telemedicine services were rapidly incorporated at the Oncology Division of Tel Aviv Medical Center. We aimed to evaluate patients' perspectives and preferences regarding telemedicine and to assess whether this virtual communication platform affects the patient‐physician relationship. Methods Between March 2020 and May 2020, adult cancer patients who conducted at least one successful telemedicine meeting were interviewed by trained medical personnel. The interview was based on validated patient satisfaction questionnaires and focused on patient‐physician interaction in relation to the last in‐patient visit. Results Of 236 patients, 172 (74%) patients agreed to participate. The study population comprised mainly patients with gastrointestinal malignancies (n = 79, 46%) with a median age of 63 years (range 21–88). The majority of patients were male (n = 93, 54%). Eighty‐nine (51.7%) patients were receiving active oncologic treatment, and 58 (33.7%) were under routine surveillance following completion of active therapy. Almost all had a sense of secured privacy (n = 171, 96%), the majority of patients affirmed that their concerns were met (n = 166, 93%) and perceived that eye contact with the treating physician was perceived (n = 156, 87%). Only a minority felt that the absence of physical clinic visits harmed their treatment (n = 36, 20%). Most patients (n = 146, 84.9%) wished to continue telemedicine services. A multivariate analysis revealed that higher satisfaction and visits for routine surveillance were both predictors of willingness to continue future telemedicine meetings over physical encounters (odds ratio [OR] = 2.41, p = .01; OR = 3.34, p = .03, respectively). Conclusion Telemedicine is perceived as safe and effective, and patients did not feel that it compromised medical care or the patient‐physician relationship. Integration of telemedicine is ideal for patients under surveillance after completion of active oncologic treatment. Physician communication skills workshops are warranted with implementing this platform. Implications for Practice During the COVID‐19 pandemic, telemedicine was rapidly implemented worldwide to facilitate continuity of quality care and treatment. Despite many potential setbacks, telemedicine has become a useful and safe tool for oncology practitioners to care for their patients. The use of telemedicine regarding patients' perspectives, emotions, and patient‐physician communication in daily oncology practice has not been studied to date. This study demonstrated telemedicine is perceived as safe and effective and does not compromise medical care or the patient‐physician relationship. Its use is ideal for surveillance after completion of active oncologic treatment. Physician communication skills workshops are warranted with implementing this platform., The use of telemedicine in oncology practice is rapidly expanding; however, the implications for patient‐physician interaction and patient satisfaction have not been well studied. This article evaluates patients' perspectives and preferences regarding telemedicine and whether a virtual communication platform affects the patient‐physician relationship.

Background Gynecologic oncologists should be aware of the option of conception through IVF/PGT-M for families with high BRCA related morbidity or mortality. Our objective was to investigate the cost-effectiveness of preimplantation genetic testing for selection and transfer of BRCA negative embryo in BRCA mutation carriers compared to natural conception. Methods Cost-effectiveness of two strategies, conception through IVF/PGT-M and BRCA negative embryo transfer versus natural conception with a 50% chance of BRCA positive newborn for BRCA mutation carriers was compared using a Markovian process decision analysis model. Costs of the two strategies were compared using quality adjusted life years (QALYs’). All costs were discounted at 3%. Incremental cost effectiveness ratio (ICER) compared to willingness to pay threshold was used for cost-effectiveness analysis. Results IVF/ PGT-M is cost-effective with an ICER of 150,219 new Israeli Shekels, per QALY gained (equivalent to 44,480 USD), at a 3% discount rate. Conclusions IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is cost effective and may be offered for selected couples with high BRCA mutation related morbidity or mortality. Our results could impact decisions regarding conception among BRCA positive couples and health care providers.

The widespread use of immune checkpoint inhibitors (ICI) has become a mainstay of care for a variety of malignancies. However, these therapies portend a range of adverse effects, including a potentially fatal form of cardiotoxicity which to date has not been elucidated. We aimed to evaluate the baseline characteristics of ICI-mediated cardiotoxicity. We performed a retrospective study evaluating patients treated with ICI who performed at least 2 echocardiography examinations, before and after the initiation of ICI. Cardiotoxicity was defined as Cancer Therapeutics-related Cardiac Dysfunction (CTRCD) development, with an absolute left ventricular ejection fraction reduction of >10%, to a value

BackgroundEthnic disparities have been associated with injury and mortality. The impact of ethnicity on head and neck injury (HNI), traumatic brain injury (TBI), in-hospital mortality and resource utilization following a motorcycle crash (MCC) is undetermined. This study explored the influence of ethnicity in these aspects and the effect of helmet use on HNI and TBI following a MCC.MethodsThe National Trauma Registry provided hospitalization data on motorcycle riders and passengers between 2008 and 2017. Ethnicity was classified as Jews or Arabs, the two major ethnic groups in Israel. Univariate followed by multivariable logistic models were applied to examine ethnic disparities. Mediation effect was tested by structural equation modeling.ResultsAmong 6073 MCC casualties, Arabs had increased odds of HNI (OR = 1.37,95% CI = 1.12–1.65) and TBI (OR = 1.51,95%CI = 1.12–1.99), and a six-fold decreased odds of helmet use (OR = 0.16,95%CI = 0.12–0.22). The HNI and TBI associations with ethnicity were mediated by helmet use. Arabs had significantly higher odds for admission to intensive care unit (OR = 1.36,95%CI = 1.00–1.83), and lower odds for ambulance evacuation (OR = 0.73,95%CI = 0.61–0.89) and discharge to rehabilitation (OR = 0.55,95%CI = 0.39–0.7). In-hospital mortality was not associated with ethnicity.ConclusionsHelmet non-use is an important etiologic factor associated with motorcycle-related HNI and TBI among Arabs. While in Israel, ethnic equality exists in in-hospital health care, disparities in ambulance and rehabilitation utilization was found. Intervention programs should target the Arab population and focus on helmet compliance.

Introduction A large proportion of patients with COVID-19 develop acute kidney injury (AKI). While the most severe of these cases require renal replacement therapy (RRT), little is known about their clinical course. Methods We describe the clinical characteristics of COVID-19 patients in the ICU with AKI requiring RRT at an academic medical center in New York City and followed patients for outcomes of death and renal recovery using time-to-event analyses. Results Our cohort of 115 patients represented 23% of all ICU admissions at our center, with a peak prevalence of 29%. Patients were followed for a median of 29 days (2542 total patient-RRT-days; median 54 days for survivors). Mechanical ventilation and vasopressor use were common (99% and 84%, respectively), and the median Sequential Organ Function Assessment (SOFA) score was 14. By the end of follow-up 51% died, 41% recovered kidney function (84% of survivors), and 8% still needed RRT (survival probability at 60 days: 0.46 [95% CI: 0.36–0.56])). In an adjusted Cox model, coronary artery disease and chronic obstructive pulmonary disease were associated with increased mortality (HRs: 3.99 [95% CI 1.46–10.90] and 3.10 [95% CI 1.25–7.66]) as were angiotensin-converting-enzyme inhibitors (HR 2.33 [95% CI 1.21–4.47]) and a SOFA score >15 (HR 3.46 [95% CI 1.65–7.25). Conclusions and relevance Our analysis demonstrates the high prevalence of AKI requiring RRT among critically ill patients with COVID-19 and is associated with a high mortality, however, the rate of renal recovery is high among survivors and should inform shared-decision making.

Memory B cells specific for SARS-CoV-2 spike and nucleocapsid proteins persist in peripheral blood after recovery from COVID-19., Lasting immunity following SARS-CoV-2 infection is questioned because serum antibodies decline in convalescence. However, functional immunity is mediated by long-lived memory T and B (Bmem) cells. Therefore, we generated fluorescently-labeled tetramers of the spike receptor binding domain (RBD) and nucleocapsid protein (NCP) to determine the longevity and immunophenotype of SARS-CoV-2-specific Bmem cells in COVID-19 patients. A total of 36 blood samples were obtained from 25 COVID-19 patients between 4 and 242 days post-symptom onset including 11 paired samples. While serum IgG to RBD and NCP was identified in all patients, antibody levels began declining at 20 days post-symptom onset. RBD- and NCP-specific Bmem cells predominantly expressed IgM+ or IgG1+ and continued to rise until 150 days. RBD-specific IgG+ Bmem were predominantly CD27+, and numbers significantly correlated with circulating follicular helper T cell numbers. Thus, the SARS-CoV-2 antibody response contracts in convalescence with persistence of RBD- and NCP-specific Bmem cells. Flow cytometric detection of SARS-CoV-2-specific Bmem cells enables detection of long-term immune memory following infection or vaccination for COVID-19.

Background Patient’s with Barrett’s esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). Neutrophil to lymphocyte ratio (NLR) was found to be a predictor of poor prognosis in patients with EAC; however, its performance in premalignant esophageal lesions is vague. We aimed to evaluate the utility of NLR as a predictor of histologic progression in patients with BE. Methods A prospective cohort of patients with proven BE in a tertiary referral center was retrospectively analyzed. All biopsies were reviewed by an expert gastrointestinal pathologist. The discriminatory capacity of NLR was evaluated by area under the receiver operating characteristic (AUC) curve analysis and Cox regression analysis. Results 324 patients (mean age 62.3 years, 241 [74.4 %] males) were included in the final analysis. Overall, 13 patients demonstrated histologic progression to neoplasia over a mean follow-up of 3.7 years (progression risk 1.0 % per year). The AUC of NLR for progression to high grade dysplasia (HGD) or EAC was 0.88 (95 % confidence interval [CI] 0.83 – 0.96), and baseline NLR was associated with a 3-fold increase of progression to HGD and EAC during follow-up (hazard ratio [HR] 3.2, 95 %CI 1.5 – 5.8; P Conclusion NLR predicted histologic progression in patients with BE. Patients with NDBE and NLR above 2.4 can be considered for specific surveillance programs with shorter intervals between sessions.

Background End-of-life decisions are highly complex socio-normative and ethical phenomena. The goal of this study was to provide an assessment of public opinions in Israel concerning aspects of end-of-life decisions. Methods An online cross sectional study was performed in February 2020. The primary tool including items pertaining to death assistance and truth telling to patients. A sample of 515 participants representative of the adult Israeli population was obtained. Results The majority of participants (71%) supports telling the entire truth to patients even in harsh conditions. Support for truth telling decreases with affiliation to religion, with as little as 40% support among ultra-orthodox. People with vocational education are the least supportive of truth telling. Concerning doctor assisted death, almost half (49%) of the sample were supportive. Opposition is positively associated with religiosity, with 90% of ultra-orthodox and 58% of religious participants opposing doctor-assisted death, compared to only 18% among seculars. Non-Jews were 3.35 times (95%CI: 1.90, 5.91) more likely to oppose doctor assisted death than Jews (p Conclusions Israelis are overwhelmingly supportive of truth telling to patients. In contrast, Israeli public opinions on doctor assisted death are divided. For both attitudes, religiousness plays a crucial role as a catalyst for conservatism and opposition to change. Almost a half of the public is also supportive of an autonomist approach that would allow patients to decide on ending their own lives.

OBJECTIVE To explore the body composition of pediatric patients referred for endocrine evaluation. METHODS This real-life observational study conducted between January 2018 and January 2020 included 10 001 clinic visits of 3500 children and adolescents; first visits of 5 to 18-year-old patients were included. Anthropometric data, blood pressure levels, pubertal status, and bioelectrical impedance analysis (BIA, Tanita MC-780 MA) were extracted from medical files. Excluded from the analysis were patients participating in other studies. RESULTS A total of 1001 patients (48% boys, mean age 11.3 ± 3.4 years, 33.5% prepubertal) were included. Mean anthropometric z-scores were normal and similar for boys and girls. Sex differences in body composition were as follows: boys had lower fat percentage, lower truncal fat percentage, higher appendicular skeletal muscle mass, and a higher muscle-to-fat ratio (MFR) than girls (P < .001 for all). MFR correlated with body mass index-standard deviation scores (BMI-SDS) in overweight/obese patients (r = -0.558, P < .001), although not in underweight patients. Systolic blood pressure (SBP) correlated with BMI-SDS in overweight/obese patients (r = 0.262, P < .001), although not in underweight patients. Diastolic blood pressure (DBP) did not correlate with BMI-SDS in either group of extreme weight status. MFR correlated with SBP and DBP in overweight/obese patients (r = -0.230, P < .001 and r = -0.141, P = .018, respectively) as well as in underweight patients (r = 0.331, P < .001 and r = 0.264, P = .005, respectively). CONCLUSIONS Our findings support BIA for a more refined characterization of patients referred for endocrine evaluation than BMI-SDS. MFR may be a better surrogate marker of blood pressure levels than BMI-SDS in both underweight and overweight/obese pediatric patients.

Learning to fear danger is essential for survival. However, overactive, relapsing fear behavior in the absence of danger is a hallmark of disabling anxiety disorders that affect millions of people. Its suppression is thus of great interest, but the necessary brain components remain incompletely identified. We studied fear suppression through a procedure in which, after acquiring fear of aversive events (fear learning), subjects were exposed to fear-eliciting cues without aversive events (safety learning), leading to suppression of fear behavior (fear extinction). Here we show that inappropriate, learning-resistant fear behavior results from disruption of brain components not previously implicated in this disorder: hypothalamic melanin-concentrating hormone–expressing neurons (MNs). Using real-time recordings of MNs across fear learning and extinction, we provide evidence that fear-inducing aversive events elevate MN activity. We find that optogenetic disruption of this MN activity profoundly impairs safety learning, abnormally slowing down fear extinction and exacerbating fear relapse. Importantly, we demonstrate that the MN disruption impairs neither fear learning nor related sensory responses, indicating that MNs differentially control safety and fear learning. Thus, we identify a neural substrate for inhibition of excessive fear behavior., Proceedings of the National Academy of Sciences of the United States of America, 117 (36), ISSN:0027-8424, ISSN:1091-6490

In multicultural Israel, the prevalence of eating disorders (EDs), a common chronic disorder among Western adolescents (especially females), has risen for Arab adolescents, who belong to an Eastern collectivist society. The study examines family and psychological factors that may increase the risk of EDs among Muslim Arab adolescents. We expected social anxiety and depressive symptoms to mediate the association between parenting styles and risk of EDs, with possible gender differences in the mediation model. Participants were 613 Muslim adolescents (394 females and 219 males); mean age = 15.4 ± 1.6; range = 12-19. The analyses revealed that the severity of depressive symptoms and especially social anxiety mediate the relationship between authoritarian parenting style and risk of EDs. Females reported higher levels of risk of EDs, social anxiety, depression and authoritative parenting style than males; no differences appeared for authoritarian or permissive parenting styles. The research sheds new light on risk factors for EDs and the likelihood of authoritarian parenting style and social anxiety being involved in the aetiology of EDs among Arab adolescents. The outcomes meaningfully add to understanding of specific psychological processes that may be associated with the risk of EDs in this population.