Continuous Positive Airway Pressure-Mandibular Advancement Device Combination Therapy for Moderate-to-Severe Obstructive Sleep Apnea: A Preliminary Study.

Objectives:  The purpose of this pilot study was to determine whether compliance to auto-adjusting positive airway pressure (APAP) improves with the addition of a mandibular advancement device (MAD). Secondary outcome measures included were APAP pressure, subjective daytime sleepiness, apnea-hypopnea index (AHI), and mask leaks.

Setting And Sample Population:  Participants included were diagnosed with moderate-to-severe obstructive sleep apnea (OSA) and became noncompliant to prescribed APAP.

Behavioral and psychological treatments for chronic insomnia disorder in adults: an American Academy of Sleep Medicine clinical practice guideline.

Introduction: This guideline establishes clinical practice recommendations for the use of behavioral and psychological treatments for chronic insomnia disorder in adults.

Methods: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine and sleep psychology to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The task force evaluated a summary of the relevant literature and the quality of evidence, the balance of clinically relevant benefits and harms, patient values and preferences, and resource use considerations that underpin the recommendations.

Behavioral and psychological treatments for chronic insomnia disorder in adults: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.

Introduction: The purpose of this systematic review is to provide supporting evidence for a clinical practice guideline on the use of behavioral and psychological treatments for chronic insomnia disorder in adult populations.

Methods: The American Academy of Sleep Medicine commissioned a task force of 9 experts in sleep medicine and sleep psychology. A systematic review was conducted to identify randomized controlled trials that addressed behavioral and psychological interventions for the treatment of chronic insomnia disorder in adults.

Impact of Obstructive Sleep Apnea on Neurocognitive Function and Impact of Continuous Positive Air Pressure.

There is evidence that obstructive sleep apnea (OSA) can negatively impact attention, memory, learning, executive function, and overall intellectual function in adults and children. Imaging techniques, including MRI, MR diffusion tensor imaging, MR spectroscopy, and fMRI, have provided additional insight into the anatomic and functional underpinnings of OSA-related cognitive impairment. Both animal and human studies have looked to elucidate the separate effects of oxygen desaturation and sleep fragmentation on independent aspects of cognition.

Investigation of 4-piperidinols as novel H3 antagonists.

Compounds containing a substituted 4-piperidinol core have been found to be potent antagonists of the human H(3) receptor. The compounds exhibited up to a 60-fold preference for inhibiting the human H(3) receptor over the mouse and showed a low binding affinity for the hERG channel.

3-Indolyl sultams as selective CRTh2 antagonists.

CRTh2 (DP(2)) is a prostaglandin D(2) receptor implicated in the recruitment of eosinophils and basophils within the asthmatic lung. Here we report the discovery of a novel series of 3-indolyl sultam antagonists with low nM affinity for CRTh2. These compounds proved to be selective over the other primary prostaglandin D(2) receptor (DP1) as well as the thromboxane A(2) receptor (TP).

GPRC6A null mice exhibit osteopenia, feminization and metabolic syndrome.

Background: GPRC6A is a widely expressed orphan G-protein coupled receptor that senses extracellular amino acids, osteocalcin and divalent cations in vitro. The physiological functions of GPRC6A are unknown.

Methods/principal Findings: In this study, we created and characterized the phenotype of GPRC6A(-/-) mice.

Sleep and older patients.

Sleep disturbances are common among older adults. The elderly population reports more symptoms associated with poor sleep initiation and maintenance and increased daytime napping. Sleep problems may be caused by various factors, including medication use, medical and psychiatric illnesses, and primary sleep disorders.

Sleep problems in primary care: a North Carolina Family Practice Research Network (NC-FP-RN) study.

Background: The prevalence and nature of sleep disorders in primary care has not been widely studied. As part of a survey conducted in 5 family practice offices in North Carolina, we screened adult patients for sleep syndromes and sought to ascertain which demographic status and health status were associated with these disorders.

Methods: We approached 2963 consecutive adults who presented for office visits to the 5 study practices.

Sleep medicine content of major medical textbooks continues to be underrepresented.

Objective: Sleep-related material in medical textbooks may be the only method by which physicians educate themselves about sleep. In the last decade significant progress in sleep research has been made, but how textbooks in relevant fields reflect it has not been examined. Our purpose was to review and compare (2005 with 1998) sleep content in representative medical textbooks.

Identification of novel and improved antimitotic agents derived from noscapine.

Analogues of the natural product noscapine were synthesized and their potential as antitumor agents evaluated. The discovery of a novel regioselective O-demethylation facilitated the synthesis of the potent aniline 6, which arrests mammalian cells in the G2/M phase of the cell cycle at 0.1 microM and also affects tubulin polymerization.

Identification of a novel extracellular cation-sensing G-protein-coupled receptor.

The C family G-protein-coupled receptors contain members that sense amino acid and extracellular cations, of which calcium-sensing receptor (CASR) is the prototypic extracellular calcium-sensing receptor. Some cells, such as osteoblasts in bone, retain responsiveness to extracellular calcium in CASR-deficient mice, consistent with the existence of another calcium-sensing receptor. We examined the calcium-sensing properties of GPRC6A, a newly identified member of this family.

Treatment of sleep disorders in elderly patients.

Sleep disorders are common among the elderly and are associated with diminished quality of life, increased risk for development of psychiatric disorders, inappropriate use of sleep aids, and decreased daytime functioning. The most common and important sleep disorders in the elderly include insomnia, obstructive sleep apnea syndrome, restless legs syndrome, rapid eye movement sleep behavior disorder, and the advanced sleep phase syndrome. In this article, we summarize the current treatment strategies for each of these sleep-related disorders.

Discovery of S-phase arresting agents derived from noscapine.

Analogues of the natural product noscapine were synthesized, and their potential as antitumor agents were examined. The discovery of a novel regio- and stereoselective O-demethylation led to the synthesis of several O-alkylated analogues that induced an unexpected S-phase arrest of mammalian cells. Compound 4a was the most potent analogue inhibiting cell proliferation at an EC(50) of 1.

Isosteric ramatroban analogs: selective and potent CRTH-2 antagonists.

The chemoattractant receptor-homologous molecule expressed on T(H)2 cells (CRTH-2), also found on eosinophils and basophils, is a prostaglandin D2 receptor involved in the recruitment of these cell types during an inflammatory response. In this report, we describe the synthesis and optimization of a ramatroban isostere that is a selective and potent antagonist of CRTH-2 which may be useful in the treatment of certain diseases.

High-throughput target discovery using cell-based genetics.

High-throughput target discovery requires robust disease models and the ability to rapidly survey the genome for function. In the post-genomics era, there has been a strong emphasis placed upon "gene-to-function" approaches that take advantage of the large amount of gene sequence information now available. Here, we advocate a return to "function-to-gene" approaches as a first step in target discovery (and validation), followed by hypothesis-driven research to validate new targets identified by their activity in cell-based disease models.