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Sleep Conference, Colon Cancer Prevention, Homocysteine, and Microdermabrasion

August 2016

By Life Extension

Sleep Conference

Alpha1-Blockers Improve Benign Prostatic Obstruction in Men with Lower Urinary Tract Symptoms: A Systematic Review and Meta-analysis of Urodynamic Studies.

CONTEXT: The urodynamic outcomes for alpha1-blockers (ABs) treatment in patients with lower urinary tract symptoms related to benign prostatic enlargement (LUTS/BPE) is a matter of debate. OBJECTIVE: To perform a systematic review and meta-analysis of studies evaluating the ABs urodynamic outcomes in patients with LUTS/BPE. The primary endpoint was variation in bladder outlet obstruction index (BOOI). Secondary endpoints were the maximum urinary flow rate (Qmax) and detrusor pressure at Qmax (PdetQmax). A meta-analysis of placebo-controlled randomized clinical trials (RCTs) was performed to compare ABs with placebo. EVIDENCE ACQUISITION: A systematic review of PubMed/Medline, ISI Web of Knowledge, and Scopus databases was performed in May 2015. Seventeen studies were selected for inclusion. EVIDENCE SYNTHESIS: The overall pooled data showed a mean BOOI change of -14.19 (p<0.0001), a mean PdetQmax change of -11. 39cm H2O (p<0.0001), and a mean Qmax improvement of 2.27ml/s (p<0.0001). Subgroup analysis showed a mean BOOI change of -14.88 (p=0.01) for alfuzosin, -19.41 (p=0.01) for doxazosin, -16.47 (p<0.0001) for naftopidil, -30.45 (p<0.0001) for silodosin, -14.27 (p=0.002) for tamsulosin, and -6.69 (p=0.005) for terazosin. Subanalysis of RCTs containing a placebo arm showed a significant improvement in BOOI in patients undergoing ABs treatment. Meta-regression revealed a significant positive association between the percentage of patients with obstruction at baseline and the improvement in BOOI after treatment with ABs. CONCLUSION: ABs improve BOOI in patients with LUTS/BPE mainly by reducing PdetQmax, and this effect is higher in patients presenting with urodynamic obstruction at baseline. The free Qmax variation underestimates the real effect of ABs on benign prostatic obstruction. PATIENT SUMMARY: Results of this meta-analysis suggest that alpha1-blockers objectively improve urinary voiding function in patients with benign prostatic obstruction.

Eur Urol . 2016 Jan 28.

Sleep-wake regulation and its impact on working memory performance: the role of adenosine.

The sleep-wake cycle is regulated by a fine-tuned interplay between sleep-homeostatic and circadian mechanisms. Compelling evidence suggests that adenosine plays an important role in mediating the increase of homeostatic sleep pressure during time spent awake and its decrease during sleep. Here, we summarize evidence that adenosinergic mechanisms regulate not only the dynamic of sleep pressure, but are also implicated in the interaction of homeostatic and circadian processes. We review how this interaction becomes evident at several levels, including electrophysiological data, neuroimaging studies and behavioral observations. Regarding complex human behavior, we particularly focus on sleep-wake regulatory influences on working memory performance and underlying brain activity, with a specific emphasis on the role of adenosine in this interplay. We conclude that a change in adenosinergic mechanisms, whether exogenous or endogenous, does not only impact on sleep-homeostatic processes, but also interferes with the circadian timing system.

Biology (Basel) . 2016 5(1).

The neurobiology, investigation, and treatment of chronic insomnia.

Chronic insomnia is defined by difficulties in falling asleep, maintaining sleep, and early morning awakening, and is coupled with daytime consequences such as fatigue, attention deficits, and mood instability. These symptoms persist over a period of at least 3 months (Diagnostic and Statistical Manual 5 criteria). Chronic insomnia can be a symptom of many medical, neurological, and mental disorders. As a disorder, it incurs substantial health-care and occupational costs, and poses substantial risks for the development of cardiovascular and mental disorders, including cognitive deficits. Family and twin studies confirm that chronic insomnia can have a genetic component (heritability coefficients between 42% and 57%), whereas the investigation of autonomous and central nervous system parameters has identified hyperarousal as a final common pathway of the pathophysiology, implicating an imbalance of sleep-wake regulation consisting of either overactivity of the arousal systems, hypoactivity of the sleep-inducing systems, or both. Insomnia treatments include benzodiazepines, benzodiazepine-receptor agonists, and cognitive behavioural therapy. Treatments currently under investigation include transcranial magnetic or electrical brain stimulation, and novel methods to deliver psychological interventions.

Lancet Neurol . 2015 May; 14(5): 547-558.

TNFalpha G308A polymorphism is associated with resilience to sleep deprivation-induced psychomotor vigilance performance impairment in healthy young adults.

Cytokines such as TNFalpha play an integral role in sleep/wake regulation and have recently been hypothesized to be involved in cognitive impairment due to sleep deprivation. We examined the effect of a guanine to adenine substitution at position 308 in the TNFalpha gene (TNFalpha G308A) on psychomotor vigilance performance impairment during total sleep deprivation. A total of 88 healthy women and men (ages 22-40) participated in one of five laboratory total sleep deprivation experiments. Performance on a psychomotor vigilance test (PVT) was measured every 2-3h. The TNFalpha 308A allele, which is less common than the 308G allele, was associated with greater resilience to psychomotor vigilance performance impairment during total sleep deprivation (regardless of time of day), and also provided a small performance benefit at baseline. The effect of genotype on resilience persisted when controlling for between-subjects differences in age, gender, race/ethnicity, and baseline sleep duration. The TNFalpha G308A polymorphism predicted less than 10% of the overall between-subjects variance in performance impairment during sleep deprivation. Nonetheless, the differential effect of the polymorphism at the peak of performance impairment was more than 50% of median performance impairment at that time, which is sizeable compared to the effects of other genotypes reported in the literature. Our findings provided evidence for a role of TNFalpha in the effects of sleep deprivation on psychomotor vigilance performance. Furthermore, the TNFalpha G308A polymorphism may have predictive potential in a biomarker panel for the assessment of resilience to psychomotor vigilance performance impairment due to sleep deprivation.

Brain Behav Immun . 2015 Jul; 47: 66-74.

Sleep, cognition, and normal aging: integrating a half century of multidisciplinary research.

Sleep is implicated in cognitive functioning in young adults. With increasing age, there are substantial changes to sleep quantity and quality, including changes to slow-wave sleep, spindle density, and sleep continuity/fragmentation. A provocative question for the field of cognitive aging is whether such changes in sleep physiology affect cognition (e.g., memory consolidation). We review nearly a half century of research across seven diverse correlational and experimental domains that historically have had little crosstalk. Broadly speaking, sleep and cognitive functions are often related in advancing age, though the prevalence of null effects in healthy older adults (including correlations in the unexpected, negative direction) indicates that age may be an effect modifier of these associations. We interpret the literature as suggesting that maintaining good sleep quality, at least in young adulthood and middle age, promotes better cognitive functioning and serves to protect against age-related cognitive declines.

Perspect Psychol Sci . 2015 Jan; 10(1): 97-137.

Phenotypic vulnerability of energy balance responses to sleep loss in healthy adults.

Short sleep duration is a risk factor for increased hunger and caloric intake, late-night eating, attenuated fat loss when dieting, and for weight gain and obesity. It is unknown whether altered energy-balance responses to sleep loss are stable (phenotypic) over time, and the extent to which individuals differ in vulnerability to such responses. Healthy adults experienced two laboratory exposures to sleep restriction separated by 60-2132 days. Caloric intake, meal timing and weight were objectively measured. Although there were substantial phenotypic differences among participants in weight gain, increased caloric intake, and late-night eating and fat intake, responses within participants showed stability across sleep restriction exposures. Weight change was consistent in both normal-weight and overweight adults. Weight change and increased caloric intake were more stable in men whereas late-night eating was consistent in both genders. This is the first evidence of phenotypic differential vulnerability and trait-like stability of energy balance responses to repeated sleep restriction, underscoring the need for biomarkers and countermeasures to predict and mitigate this vulnerability.

Sci Rep . 2015 5: 14920.

Obstructive sleep apnoea syndrome and its management.

Obstructive sleep apnoea (OSA) is a common disorder characterized by repetitive episodes of nocturnal breathing cessation due to upper airway collapse. OSA causes severe symptoms, such as excessive daytime somnolence, and is associated with a significant cardiovascular morbidity and mortality. Different treatment options are now available for an effective management of this disease. After more than three decades from its first use, continuous positive airway pressure (CPAP) is still recognized as the gold standard treatment. Nasal CPAP (nCPAP) is highly effective in controlling symptoms, improving quality of life and reducing the clinical sequelae of sleep apnoea. Other positive airway pressure modalities are available for patients intolerant to CPAP or requiring high levels of positive pressure. Mandibular advancement devices, particularly if custom made, are effective in mild to moderate OSA and provide a viable alternative for patients intolerant to CPAP therapy. The role of surgery remains controversial. Uvulopalatopharyngoplasty is a well established procedure and can be considered when treatment with CPAP has failed, whereas maxillar-mandibular surgery can be suggested to patients with a craniofacial malformation. A number of minimally invasive procedures to treat snoring are currently under evaluation. Weight loss improves symptoms and morbidity in all patients with obesity and bariatric surgery is an option in severe obesity. A multidisciplinary approach is necessary for an accurate management of the disease.

Ther Adv Chronic Dis . 2015 Sep; 6(5): 273-285.

Feedback Blunting: Total Sleep Deprivation Impairs Decision Making that Requires Updating Based on Feedback.

STUDY OBJECTIVES: To better understand the sometimes catastrophic effects of sleep loss on naturalistic decision making, we investigated effects of sleep deprivation on decision making in a reversal learning paradigm requiring acquisition and updating of information based on outcome feedback. DESIGN: Subjects were randomized to a sleep deprivation or control condition, with performance testing at baseline, after 2 nights of total sleep deprivation (or rested control), and following 2 nights of recovery sleep. Subjects performed a decision task involving initial learning of go and no go response sets followed by unannounced reversal of contingencies, requiring use of outcome feedback for decisions. A working memory scanning task and psychomotor vigilance test were also administered. SETTING: Six consecutive days and nights in a controlled laboratory environment with continuous behavioral monitoring. SUBJECTS: Twenty-six subjects (22-40 y of age; 10 women). INTERVENTIONS: Thirteen subjects were randomized to a 62-h total sleep deprivation condition; the others were controls. MEASUREMENTS AND RESULTS: Unlike controls, sleep deprived subjects had difficulty with initial learning of go and no go stimuli sets and had profound impairment adapting to reversal. Skin conductance responses to outcome feedback were diminished, indicating blunted affective reactions to feedback accompanying sleep deprivation. Working memory scanning performance was not significantly affected by sleep deprivation. And although sleep deprived subjects showed expected attentional lapses, these could not account for impairments in reversal learning decision making. CONCLUSIONS: Sleep deprivation is particularly problematic for decision making involving uncertainty and unexpected change. Blunted reactions to feedback while sleep deprived underlie failures to adapt to uncertainty and changing contingencies. Thus, an error may register, but with diminished effect because of reduced affective valence of the feedback or because the feedback is not cognitively bound with the choice. This has important implications for understanding and managing sleep loss-induced cognitive impairment in emergency response, disaster management, military operations, and other dynamic real-world settings with uncertain outcomes and imperfect information

Sleep . 2015 May; 38(5): 745-754.