Visualizing the DNA Damage Response in Purkinje Cells Using Cerebellar Organotypic Cultures.

Cerebellar Purkinje cells (PCs) exhibit a unique interplay of high metabolic rates, specific chromatin architecture, and extensive transcriptional activity, making them particularly vulnerable to DNA damage. This necessitates an efficient DNA damage response (DDR) to prevent cerebellar degeneration, often initiated by PC dysfunction or loss. A notable example is the genome instability syndrome, ataxia-telangiectasia (A-T), marked by progressive PC depletion and cerebellar deterioration.

Genotype-Specific Cortisol Reserve in a Cohort of Subjects With Nonclassic Congenital Adrenal Hyperplasia (NCCAH).

Context: Recent guidelines suggest that patients with nonclassic congenital adrenal hyperplasia (NCCAH) stop glucocorticoid therapy after achieving adult height. However, these guidelines do not differentiate between NCCAH genotype groups.

Objective: Compare ACTH-stimulated cortisol and 17-hydroxyprogesterone (17OHP) levels, and the rate of partial cortisol insufficiency in subjects with NCCAH carrying one mild and one severe (mild/severe) mutation vs subjects with biallelic mild (mild/mild) mutations.

A personalized approach to lymphoproliferations in patients with inborn errors of immunity.

Biopsies from patients with inborn error of immunity (IEI) may pose a diagnostic challenge due to the abnormal anatomy of their lymphoid organs and the tendency for the development of lymphoproliferations in various organs, some of which may lead to the wrong impression of malignant lymphoma which may prompt aggressive unnecessary treatment. In this article we will review typical histologic findings in various IEI's described in the literature and discuss the appropriate approach to the diagnosis of lymphoproliferations in these patients by presenting illustrative cases.

Upward perturbations trigger a stumbling effect.

Background: Vertical perturbations are one major cause of falling. Incidentally, while conducting a comprehensive study comparing effects of vertical versus horizontal perturbations, we commonly observed a stumbling-like response induced by upward perturbations. The present study describes and characterizes this stumbling effect.

Sexual needs and sexual function of patients with Parkinson's disease.

Background: Sexual dysfunction (SD) is a frequent non-motor symptom in Parkinson's disease (PD) that is rarely addressed, and sexual counseling is sporadic.

Objectives: To investigate PD patients' SD and sexual counseling motivation and to propose an interventional strategy for movement disorder specialists.

Methods: All consecutive PD patients who presented to a movement disorder unit between 2018 and 2019 completed anonymous questionnaires containing the Female Sexual Function Index, the International Index of Erectile Function, and a questionnaire on sexual needs and motivation to receive sexual counseling.

Association of Preoperative Clinical, Laboratory, Imaging, and Pathologic Data With Clinically Beneficial Pathology Among Routine Splenectomy Specimens.

Importance: Previous studies have shown that uniform pathologic review of all splenectomy surgical specimens reveals new clinically actionable diagnoses only in a minority of cases.

Objective: To examine whether the aggregate of clinical, laboratory, imaging, and pathologic preoperative data is associated with a clinically beneficial pathologic study for routine splenectomy surgical specimens.

Design, Setting, And Participants: This single-center retrospective cohort study included all patients who underwent splenectomy from January 1, 2013, through December 31, 2018, at a single center.

A predictive algorithm using clinical and laboratory parameters may assist in ruling out and in diagnosing MDS.

We present a noninvasive Web-based app to help exclude or diagnose myelodysplastic syndrome (MDS), a bone marrow (BM) disorder with cytopenias and leukemic risk, diagnosed by BM examination. A sample of 502 MDS patients from the European MDS (EUMDS) registry (n > 2600) was combined with 502 controls (all BM proven). Gradient-boosted models (GBMs) were used to predict/exclude MDS using demographic, clinical, and laboratory variables.

Predicting Breast Cancer by Applying Deep Learning to Linked Health Records and Mammograms.

Background Computational models on the basis of deep neural networks are increasingly used to analyze health care data. However, the efficacy of traditional computational models in radiology is a matter of debate. Purpose To evaluate the accuracy and efficiency of a combined machine and deep learning approach for early breast cancer detection applied to a linked set of digital mammography images and electronic health records.

Depletion of B cells rejuvenates the peripheral B-cell compartment but is insufficient to restore immune competence in aging.

Aging is associated with increasing prevalence and severity of infections caused by a decline in bone marrow (BM) lymphopoiesis and reduced B-cell repertoire diversity. The current study proposes a strategy to enhance immune responsiveness in aged mice and humans, through rejuvenation of the B lineage upon B-cell depletion. We used hCD20Tg mice to deplete peripheral B cells in old and young mice, analyzing B-cell subsets, repertoire and cellular functions in vitro, and immune responsiveness in vivo.

Dysphagia characteristics in Huntington's disease patients: insights from the Fiberoptic Endoscopic Evaluation of Swallowing and the Swallowing Disturbances Questionnaire.

Background: Huntington's disease (HD) is a neurodegenerative disease characterized by increasing dysphagia as the disease progresses. Specific characteristics of the HD dysphagia are not well defined.

Objective: To characterize the swallowing disturbances of HD patients, to evaluate the feasibility of Fiberoptic Endoscopic Evaluation of Swallowing (FEES) in assessing dysphagia in HD patients, and to discern the relation between FEES findings and patients' self-report on dysphagia symptoms and swallowing related quality of life (SWAL-QOL).

High-fat diet protects the blood-brain barrier in an Alzheimer's disease mouse model.

Type 2 diabetes (T2D) is associated with increased risk of Alzheimer's disease (AD). There is evidence for impaired blood-brain barrier (BBB) in both diseases, but its role in the interplay between them is not clear. Here, we investigated the effects of high-fat diet (HFD), a model for T2D, on the Tg2576 mouse model of AD, in regard to BBB function.

Investigating the cardiac pathology of SCO2-mediated hypertrophic cardiomyopathy using patients induced pluripotent stem cell-derived cardiomyocytes.

Mutations in SCO2 are among the most common causes of COX deficiency, resulting in reduced mitochondrial oxidative ATP production capacity, often leading to hypertrophic cardiomyopathy (HCM). To date, none of the recent pertaining reports provide deep understanding of the SCO2 disease pathophysiology. To investigate the cardiac pathology of the disease, we were the first to generate induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) from SCO2-mutated patients.

Induced Pluripotent Stem Cell-Derived Cardiomyocytes Provide In Vivo Biological Pacemaker Function.

Background: Although multiple approaches have been used to create biological pacemakers in animal models, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have not been investigated for this purpose. We now report pacemaker function of iPSC-CMs in a canine model.

Methods And Results: Embryoid bodies were derived from human keratinocytes, their action potential characteristics determined, and their gene expression profiles and markers of differentiation identified.

Developmental changes in electrophysiological characteristics of human-induced pluripotent stem cell-derived cardiomyocytes.

Background: Previous studies proposed that throughout differentiation of human induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs), only 3 types of action potentials (APs) exist: nodal-, atrial-, and ventricular-like.

Objectives: To investigate whether there are precisely 3 phenotypes or a continuum exists among them, we tested 2 hypotheses: (1) During culture development a cardiac precursor cell is present that-depending on age-can evolve into the 3 phenotypes. (2) The predominant pattern is early prevalence of a nodal phenotype, transient appearance of an atrial phenotype, evolution to a ventricular phenotype, and persistence of transitional phenotypes.

Characterization of Onthophagus sellatus as the major intermediate host of the dog esophageal worm Spirocerca lupi in Israel.

Spirocerca lupi is a parasitic nematode of dogs, that causes significant morbidity and mortality. Its intermediate hosts in Israel have never been described. The aim of this study was therefore to identify the intermediate hosts of S.

B-cell depletion reactivates B lymphopoiesis in the BM and rejuvenates the B lineage in aging.

Aging is associated with a decline in B-lymphopoiesis in the bone marrow and accumulation of long-lived B cells in the periphery. These changes decrease the body's ability to mount protective antibody responses. We show here that age-related changes in the B lineage are mediated by the accumulating long-lived B cells.

Development of ALS-like disease in SOD-1 mice deficient of B lymphocytes.

Several recent studies proposed a role for innate immunity and inflammation in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, possible links, if any, between disease and adaptive immunity are poorly understood. The present study probed for the role of B cells in ALS disease using the G93A-SOD-1 transgenic mouse model.

"Brain Screen": A self-referral, screening program for strokes, falls and dementia risk factors.

Background: Falls, strokes and dementia can be predicted and their occurrence can be delayed or even prevented by treatment of risk factors. The value of screening self-referred adults is unknown.

Objectives: To assess whether a screening program of self-referred adults provides new and valuable medical information on risk factors for falls, stroke and dementia.

Low incidence of delirium in very old patients after surgery for hip fractures.

Objective: The authors sought to determine the incidence of delirium, its predisposing and precipitating factors, and its implications for rehabilitation outcomes and mortality in elderly patients.

Methods: This was a prospective cohort study, conducted in Gedera, Israel, from August 2001 to January 2002, with 137 consecutive patients over age 75, with hip fractures, who were admitted to the orthopedic section of the emergency department. They were evaluated at admission, 1 week after the surgery for hip fracture, and 1 month after surgery.

Treating depression in Alzheimer's disease: integration of differing guidelines.

Background: The developments in the understanding of Alzheimer's disease (AD) have led to genetic testing, expansion of research centers, and emergence of novel treatment modalities. However, behavioral symptoms and disturbances remain the leading cause of distress to families and patients. The management of these disturbances is not fully elucidated and not without controversies.

The serotonin antagonist mianserin for treatment of serotonin reuptake inhibitor-induced sexual dysfunction in women: an open-label add-on study.

The aim of this study was to determine if the serotonin antagonist mianserin improves antidepressant-induced sexual dysfunction in women. The work was prompted by an earlier study of men by our team of researchers. The study population included 16 women aged 20-65 years undergoing treatment at a psychiatric outpatient clinic, who presented with sexual dysfunction subsequent to intake of a serotonin reuptake inhibitor (SRI) for depression.

Clozapine in elderly psychiatric patients: tolerability, safety, and efficacy.

Psychotic disorders in the elderly are frequent, of multiple etiologies, and little researched. With the advent of "atypical" neuroleptics, their role in treating elderly psychiatric patients needs to be investigated. Clozapine is widely used; however, its use is common in the elderly whose psychosis is a feature of neurological morbidity (Parkinson's disease, dementia, etc.

[Combined tricyclic antidepressants and ritalin in elderly depressives].

Psychostimulants, including ritalin (methylphenidate), were used as antidepressives in the '50s but were then replaced by tricyclics and MAO inhibitors. Treatment of depression with psychostimulants is still controversial. Several anecdotal reports in the past decade approved the use of tricyclic antidepressants (TCA) together with methylphenidate in apathetic and withdrawal states in medically ill and in elderly patients.

["Saddam syndrome:" acute psychotic reactions during the Gulf War--renewal of concept of brief reactive psychosis].

6 patients came to our psychiatric emergency room during the first 2 weeks of the Gulf War presenting the clinical picture of acute delusional paranoid psychosis (4 women and 2 men between the ages of 30-77). 4 were without previously known psychopathology, while the other 2 were known to have had some nonpsychotic cognitive impairment. The first 4 recovered completely within a short time while the other 2 continued to have psychopathological symptoms.