Effects of exercise on sleep among young women with Generalized Anxiety Disorder

Statement of the problemGeneralized Anxiety Disorder (GAD) and disturbed sleep are prevalent, debilitating, and frequently comorbid problems for which successful treatment remains limited. Exercise can promote sleep but whether it does among GAD patients is unknown.MethodsThirty sedentary women (18−37 y) with a primary DSM-IV diagnosis of GAD were randomized to six weeks of resistance (RET) or aerobic exercise training (AET), or waitlist (WL). RET and AET involved twice-weekly sessions of either lower-body weightlifting or leg cycling matched on multiple features of exercise. Outcomes included total sleep time (TST), lights out time, awakening out of bed time, time in bed (TIB), sleep onset latency (SOL), wakefulness after sleep onset, and sleep efficiency. Hedges' d effect sizes and 95% confidence intervals were calculated for each exercise condition compared to WL. Regression examined baseline associations between anxiety and sleep and associated change.ResultsTwenty-two of 26 participants reported poor baseline sleep (Pittsburgh Sleep Quality Index > 5). RET significantly decreased weekend TIB (d = −1.79; [−2.89,−0.70]) and SOL (d = −1.30; [−2.32,−0.28]), and significantly increased weekend sleep efficiency (d = 1.30; [0.29,2.32]). AET significantly reduced weekend TIB (d = −1.13; [−2.16,−0.11]) and SOL (d = −1.08; [−2.09,−0.06]). Reduced GAD clinical severity rating was significantly associated with improved weekend sleep efficiency among RET (t₆ = −3.48, p ≤ 0.013).ConclusionsShort-term exercise training improves sleep outcomes among GAD patients, especially for RET and weekend sleep. Findings suggest improved sleep may be associated with reduced clinical severity among GAD patients.     

Discovery of an Anion-Dependent Farnesyltransferase Inhibitor from a Phenotypic Screen

By employing a phenotypic screen, a set of compounds, exemplified by 1, were identified which potentiate the ability of histone deacetylase inhibitor vorinostat to reverse HIV latency. Proteome enrichment followed by quantitative mass spectrometric analysis employing a modified analogue of 1 as affinity bait identified farnesyl transferase (FTase) as the primary interacting protein in cell lysates. This ligand-FTase binding interaction was confirmed via X-ray crystallography and temperature dependent fluorescence studies, despite 1 lacking structural and binding similarity to known FTase inhibitors. Although multiple lines of evidence established the binding interaction, these ligands exhibited minimal inhibitory activity in a cell-free biochemical FTase inhibition assay. Subsequent modification of the biochemical assay by increasing anion concentration demonstrated FTase inhibitory activity in this novel class. We propose 1 binds together with the anion in the active site to inhibit farnesyl transferase. Implications for phenotypic screening deconvolution and HIV reactivation are discussed.     

Auditory brainstem,middle and late latency responses to short gaps in noise at different presentation rates

Objective: The effects of rate on auditory-evoked potentials (AEP) to short noise gaps (12?ms) recorded at high sampling rates using wide-band filters were investigated. Design: Auditory brainstem (ABR), middle latency (MLR), late latency (LLR) and steady-state (ASSR) responses were simultaneously recorded in adult subjects at four gap rates (0.5, 1, 5 and 40?Hz). Major components (V, Na, Pa, Nb, Pb, N1 and P2) were identified at each rate and analysed for latency/amplitude characteristics. Gap responses at 40?Hz were recovered from Quasi-ASSRs (QASSR) using the CLAD deconvolution method. Study Sample: Fourteen right ears of young normal hearing subjects were tested. Results: All major components were present in all subjects at 1?Hz. P1 (P50) appeared as a low-pass filtered component of Pa and Pb waves. At higher rates, N1 and P2 disappeared completely while major ABR-MLR components were identified. Peak latencies were mostly determined by noise onsets slightly delayed by offset responses. Conclusions: Major AEP components can be recorded to short gaps at 1?Hz using high sampling rates and wide-band filters. At higher rates, only ABR and MLRs can be recorded. Such simultaneous recordings may provide a complete assessment of temporal resolution and processing at different levels of auditory pathways.     

Human cytomegalovirus persists in myeloid progenitors and is passed to the myeloid progeny in a latent form

CD34+ progenitor cells can harbour latent human cytomegalovirus (HCMV); however, the mechanisms of HCMV latency remain unclear. We have investigated the effects of the haematopoietic lineage restriction on the establishment and spread of the latent HCMV to progeny cells. In vitro-infected and latently-infected haematopoietic progenitor cells derived from HCMV seropositive donors were studied. The presence of HCMV DNA in bone marrow progenitor (BMP) cells was determined by single colony polymerase chain reaction and fluorescent in situ hybridization (FISH). The presence of CMV DNA was found to be restricted to myeloid progenitors and the percentage of HCMV-infected cells was lower in naturally-infected cells than in in vitro-infected cells. Erythroid differentiation resulted in an abortive infection with persistence of the viral nucleic acids in red cell precursors. In BMP cells from HCMV seronegative donors, HCMV DNA was localized in the nucleus. Bone marrow progenitors in the presence of granulocyte-macrophage colony stimulating factor (GMCSF) maintained HCMV DNA for extended periods of time. No viral production could be detected throughout the culture but the comparison of the numbers of latently-infected cells prior to and after the culture suggests that proliferation of haematopoietic progenitor cells may lead to the expansion of latently-infected cells.     

Modafinil in the treatment of idiopathic hypersomnia without long sleep time—a randomized,double‐blind,placebo‐controlled study

In 2010 the European Medicines Agency withdrew the indication of modafinil for the treatment of obstructive sleep apnea, shift work sleep disorder and for idiopathic hypersomnia (IH). In uncontrolled studies, modafinil has been reported to be efficacious in the treatment of sleep disorders. We therefore performed a randomized, placebo‐controlled study with the aim of proving the efficacy of modafinil treatment in these patients. Drug‐free IH patients without long sleep according to ICSD2 criteria, age >18 years and disease duration >2 years were included. After a washout phase, patients at baseline received placebo or 100 mg modafinil in the morning and at noon over 3 weeks, followed by 1 week without medication. At each visit the Epworth Sleepiness Scale (ESS) and Clinical Global Impression (CGI) rating scale were performed. At baseline and on days 8 and 21 four Maintenance of Wakefulness Tests (MWTs)/day or per day were performed. Patients kept a sleep–wake diary throughout the study. Between 2009 and 2011 three sleep centres recruited 33 participants. Compared to placebo, modafinil decreased sleepiness significantly and improved mean sleep latency in the MWT non‐significantly. The CGI improved significantly from baseline to the last visit on treatment. The most frequent adverse events were headaches and gastrointestinal disorders; skin and psychiatric reactions were not reported. The number of reported naps and duration of daytime sleepiness decreased significantly. Total sleep time of nocturnal sleep was slightly reduced. The sleep diaries showed increases in feeling refreshed in the morning; the diurnal diaries showed significant improvement of performance and of exhaustion. Modafinil is an effective and safe medication in the treatment of IH. Adverse events are mild to moderate.     

Ultrasound-Guided Versus Landmark-Guided Local Corticosteroid Injection for Carpal Tunnel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective

To review the literature and assess the comparative effectiveness of ultrasound-guided versus landmark-guided local corticosteroid injections in patients with carpal tunnel syndrome (CTS).

Sleepiness, Troika of Consciousness Cycle, and the Epworth Sleepiness Scale

Excessive daytime sleepiness (EDS) is an important indicator when diagnosing sleep-disordered breathing and evaluating its treatment results. However, there appears to be some confusion as to what exactly is sleepiness; Dorlands Illustrated Medical Dictionary does not help. The medical literature was reviewed in order to assemble a schematic model that would suggest a definition of sleepiness and how it can be measured. The derived model is entitled the troika of consciousness cycle (TCC). It assumes that the presence of wakefulness, nonrapid eye movement sleep (NREMS), and rapid eye movement sleep (REMS) is determined by the interactions of four drives: two promoting wakefulness and one each for the two sleep states. The TCC illustrates that inadequate sleep results in sleep debt, but that sleepiness is determined solely by the nearness of the secondary wake drive line to the NREMS drive line. Contact of these lines indicates dozing, a change in consciousness state, an observable event. The probability of this event may be defined as objective sleepiness; this is what the Epworth sleepiness scale (ESS) attempts to measure. Studies indicate that the ESS can determine EDS with greater sensitivity and selectivity than either the multiple sleep latency test or the maintenance of wakefulness test.