My voyage in the enchanted world of sleep.

In this paper, I describe my 45-year career in sleep research. I started my undergraduate studies at Tel Aviv University, where I was first introduced to the enchanted world of sleep, continued to my graduate studies with Wilse B. Webb at the University of Florida, and then to post-doctoral training with Dan Kripke at the University of California at San Diego.

Near-total absence of REM sleep co-occurring with normal cognition: an update of the 1984 paper.

Background: REM sleep (REMS) is considered vital for supporting well-being and normal cognition. However, it remains unclear if and how decreases in REMS impair cognitive abilities. Rare case studies of patients with REMS abolishment due to pontine lesions remain sporadic, and formal evaluation of cognitive status is lacking.

Intermittent Hypoxia Affects the Spontaneous Differentiation In Vitro of Human Neutrophils into Long-Lived Giant Phagocytes.

Previously we identified, for the first time, a new small-size subset of neutrophil-derived giant phagocytes (Gϕ) which spontaneously develop in vitro without additional growth factors or cytokines. Gϕ are CD66b(+)/CD63(+)/MPO(+)/LC3B(+) and are characterized by extended lifespan, large phagolysosomes, active phagocytosis, and reactive oxygen species (ROS) production, and autophagy largely controls their formation. Hypoxia, and particularly hypoxia/reoxygenation, is a prominent feature of many pathological processes.

Clinical implications of sleep disordered breathing in acute myocardial infarction.

Background: Sleep disordered breathing (SDB), characterized by nightly intermittent hypoxia, is associated with multiple pathophysiologic alterations that may adversely affect patients with acute myocardial infarction (AMI). This prospective study investigated whether the metabolic perturbations associated with SDB are present when these patients develop AMI and if they affect clinical outcomes.

Methods: We prospectively enrolled 180 AMI patients.

Endothelial progenitor cells in acute myocardial infarction and sleep-disordered breathing.

Rationale: Mobilization and functions of endothelial progenitor cells (EPCs) are increased in patients with acute myocardial infarction (AMI). Yet, sleep-disordered breathing (SDB) is highly prevalent in patients with AMI.

Objectives: To compare EPC numbers and functions in patients with AMI with SDB (AMI-SDB) and without SDB (AMI-only) and to determine the effects of intermittent hypoxia (IH) in vitro on EPC proliferative and angiogenic properties.

Bax/Mcl-1 balance affects neutrophil survival in intermittent hypoxia and obstructive sleep apnea: effects of p38MAPK and ERK1/2 signaling.

Background: Prolonged neutrophil survival is evident in various cardiovascular and respiratory morbidities, in hypoxic conditions in-vitro and in patients with obstructive sleep apnea (OSA) characterized by nightly intermittent hypoxia (IH). This may lead to persistent inflammation, tissue injury and dysfunction. We therefore investigated by a translational approach the potential contribution of the intrinsic stress-induced mitochondrial pathway in extending neutrophil survival under IH conditions.

Screening for sleep disordered breathing among applicants for a professional driver's license.

Objectives: Individuals with sleep disordered breathing (SDB) are at high risk for falling asleep while driving. The aim of this study was to identify variables that would predict SDB among healthy young applicants for a professional driver's license.

Method: A total of 301 applicants for a driver's license completed self-administered questionnaires.

Obesity plays an independent worsening modifying effect on nocturnal hypoxia in obstructive sleep apnea.

Objective: Obesity's association with obstructive sleep apnea syndrome (OSAS) is well established. The aim of this study was to examine the impact of obesity on nocturnal hypoxia.

Methods: Twenty two thousand seven hundred and ninety three patients aged 21-80 years who underwent whole night polysomnography during 2000-2009 were included in the study.

Age- and gender-related characteristics of obstructive sleep apnea.

Purpose: The present study attempted to characterize the phenotype of men and women of different ages with a laboratory diagnosis of obstructive sleep apnea (OSA) using demographic, subjective complaints and medical history and to determine the best fitting apnea-hypopnea index (AHI) cutoff point for OSA diagnosis in each group.

Methods: Data collected from 23,806 patients examined by a whole-night polysomnography were retrospectively analyzed. First, descriptive analysis was used to determine the gender-specific relationship between AHI and age, then binary logistic regression was used to determine the best fitting gender- and age-specific AHIs and the predictors of OSA in each age and gender group.

Sleep profile and symptoms of sleep disorders in patients with stable mild to moderate chronic obstructive pulmonary disease.

Background: Sleep problems associated with chronic obstructive pulmonary disease may have an important impact on quality of life and health outcome measures in patients. The aim of this study was to prospectively assess differences in symptom profile and polysomnographic parameters in patients with stable mild to moderate COPD and age, gender, and body-mass-index matched controls without airflow obstruction.

Methods: The Sleep Disorders Questionnaire was administered to both patients and controls prior to clinical and polysomnographic evaluation.

Circadian pattern of life-threatening ventricular arrhythmia in patients with sleep-disordered breathing and implantable cardioverter-defibrillators.

Background: Sleep-disordered breathing (SDB) has been associated with various benign cardiac arrhythmias occurring during sleep.

Objective: The purpose of this study was to demonstrate that SDB contributes to the development of life-threatening ventricular arrhythmias in patients with an established arrhythmic substrate.

Methods: We prospectively studied the association between SDB and timing of life-threatening ventricular arrhythmic events in 45 patients with an implantable cardioverter-defibrillator (ICD).

Molecular pathways of spontaneous and TNF-{alpha}-mediated neutrophil apoptosis under intermittent hypoxia.

Apoptosis of polymorphonuclear cells (PMNs) is a fundamental mechanism to halt inflammation. It limits the lifespan of PMNs and thereby decreases tissue injury. In PMNs, unlike in other cells, hypoxia profoundly inhibits apoptosis.

Can an improvement in sleep positively impact on health?

Reports from a large number of studies document significant associations between sleep duration and various health problems such as cardiovascular events, risk of stroke, incident artery calcification, changes in inflammatory markers and many more. Furthermore, some sleep duration studies have shown that shorter sleep precedes some adverse health outcomes, although a causal relationship has yet to be demonstrated. Whilst clinical studies have shown that de-fragmenting (reducing awakenings and improving sleep continuity) sleep can reverse the harmful consequences of sleep apnea, and other studies have demonstrated that adjunctive treatment of insomnia improves depression, evidence that treatment of insomnia results in health benefit is more controversial.