Site-specific RNA modification initiation of transcription reactions with mA and isomorphic emissive adenosine analogs.

The templated enzymatic incorporation of adenosine and its analogs, including mA, A and A into RNA transcripts, has been explored. Enforced transcription initiation with excess free nucleosides and the native triphosphates generates 5'-end modified transcripts, which can be 5'-phosphorylated and ligated to provide full length, singly modified RNA oligomers. To explore structural integrity, functionality and utility of the resulting non-canonical purine-containing RNA constructs, a MazF RNA hairpin substrate has been synthesized and analyzed for its susceptibility to this endonuclease.

Manufacturing DNA in yields higher-fidelity DNA than enzymatic synthesis.

Biotechnologies such as gene therapy have brought DNA vectors to the forefront of pharmaceuticals. The quality of starting material plays a pivotal role in determining final product quality. Here, we examined the fidelity of DNA replication using enzymatic methods () compared to plasmid DNA produced in .

Electrochemical potential enables dormant spores to integrate environmental signals.

The dormant state of bacterial spores is generally thought to be devoid of biological activity. We show that despite continued dormancy, spores can integrate environmental signals over time through a preexisting electrochemical potential. Specifically, we studied thousands of individual spores that remain dormant when exposed to transient nutrient pulses.

Increased Fear Generalization and Amygdala AMPA Receptor Proteins in Chronic Traumatic Brain Injury.

Cognitive impairments and emotional lability are common long-term consequences of traumatic brain injury (TBI). How TBI affects interactions between sensory, cognitive, and emotional systems may reveal mechanisms that underlie chronic mental health comorbidities. Previously, we reported changes in auditory-emotional network activity and enhanced fear learning early after TBI.

Switching from long-acting beta-agonist and inhaled corticosteroid to long-acting beta-agonist and long-acting muscarinic antagonist for chronic obstructive pulmonary disease: a case report of inhaled corticosteroid withdrawal.

Chronic obstructive pulmonary disease (COPD) is a medical condition characterised by persistent respiratory symptoms and airflow limitation. For the long-term management of COPD, inhaled therapies are the main approach to maintenance treatment. In order to improve treatment efficacy and tolerability for patients with COPD, recent clinical trials have focused on the withdrawal of inhaled corticosteroids (ICSs), the use of which has been associated with adverse outcomes, including pneumonia.

Sensory sensitivity as a link between concussive traumatic brain injury and PTSD.

Traumatic brain injury (TBI) is one of the most common injuries to military personnel, a population often exposed to stressful stimuli and emotional trauma. Changes in sensory processing after TBI might contribute to TBI-post traumatic stress disorder (PTSD) comorbidity. Combining an animal model of TBI with an animal model of emotional trauma, we reveal an interaction between auditory sensitivity after TBI and fear conditioning where 75 dB white noise alone evokes a phonophobia-like phenotype and when paired with footshocks, fear is robustly enhanced.

Cholinergic Signaling Alters Stress-Induced Sensitization of Hippocampal Contextual Learning.

Post-traumatic stress disorder (PTSD) has a profound contextual component, and has been demonstrated to alter future contextual learning. However, the mechanism by which a single traumatic event affects subsequent contextual experiences has not been isolated. Acetylcholine (ACh) is an important modulator of hippocampus-dependent learning such as contextual memory strength.

CPAP therapy for patients with sleep apnea and type 2 diabetes mellitus improves control of blood pressure.

Purpose: Obstructive sleep apnea (OSA) is highly associated with type 2 diabetes mellitus (DM), and treatment of OSA may have a positive impact on cardiometabolic profile. This study investigates the effects of continuous positive airway pressure (CPAP) treatment on glycemic control and cardiometabolic parameters in patients with diabetes.

Methods: Diabetic patients, who were newly diagnosed of OSA with an apnea hypopnea index (AHI) ≥15 and HbA1c ≥7%, were randomly assigned to either CPAP treatment or no treatment (control) for 3 months.

A pathway underlying the impact of CPAP adherence on intimate relationship with bed partner in men with obstructive sleep apnea.

Purpose: Our aim was to determine the pathway underlying the effects of continuous positive airway pressure (CPAP) adherence on intimate relationship with bed partner in men with obstructive sleep apnea (OSA). We hypothesized that CPAP with good adherence affected the intimate relationship with bed partner directly and indirectly, and it was mediated through daytime sleepiness and activity level in men with OSA.

Methods: Data were obtained from an education program for enhancing CPAP adherence.

Plasma EGFR Mutation Detection Associated With Survival Outcomes in Advanced-Stage Lung Cancer.

Unlabelled: We confirmed the performance of an array method for plasma epidermal growth factor receptor (EGFR) mutation detection and showed the association of plasma EGFR mutation with survival outcomes.

Background: Noninvasive detection of epidermal growth factor receptor (EGFR) mutation in plasma is feasible and could be adjunct for therapeutic monitoring especially when repeated biopsy of tumor tissue is challenging. The aims of this study were to establish the diagnostic performance of peptide nucleic acid-locked nucleic acid polymerase chain reaction followed by custom array for plasma EGFR mutation and to evaluate the association of detection with clinical characteristics and survival outcomes.

The efficacy of a brief motivational enhancement education program on CPAP adherence in OSA: a randomized controlled trial.

Background: Poor adherence to CPAP treatment in OSA adversely affects the effectiveness of this therapy. This randomized controlled trial (RCT) examined the efficacy of a brief motivational enhancement education program in improving adherence to CPAP treatment in subjects with OSA.

Methods: Subjects with newly diagnosed OSA were recruited into this RCT.

Linguistic and psychometric validation of the Chinese version of the self-efficacy measures for sleep apnea questionnaire.

Objectives: The self-efficacy measure for sleep apnea (SEMSA) questionnaire was shown to be an effective tool to assess adherence-related cognitions on continuous positive airway pressure (CPAP) therapy in obstructive sleep apnea (OSA) subjects. SEMSA helps to solicit fundamental information for formulating strategies to promote CPAP adherence for better treatment outcomes. The objective of our study was to perform a linguistic and psychometric evaluation of a Chinese version of the SEMSA (SEMSA-C).

Treatment outcomes in elderly with advanced-stage non-small cell lung cancer.

Purpose: Lung cancer remains the top cause of cancer morbidity and mortality in the world. Although the identification of epidermal growth factor receptor (EGFR) gene mutations could predict efficacy of tyrosine kinase inhibitor (TKI), testing for predictive biomarkers are not always possible due to tissue availability. The overall therapeutic decision remains a clinical one for a significant proportion of elderly patients with advanced stage lung cancer but no known EGFR mutation status.

Altered profile of circulating endothelial progenitor cells in obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) is independently associated with endothelial dysfunction, which may be perpetuated by alteration in endothelial repair capacity. Our study evaluates changes in endothelial progenitor cell (EPC) profile in relation to OSA and the role of advanced glycation end-products (AGE) in this relationship.

Methods: Consecutive Chinese adults undergoing sleep studies, who had no medical illnesses or regular medications, were enrolled.

Impact of nephrotic edema of the lower limbs on obstructive sleep apnea: gathering a unifying concept for the pathogenetic role of nocturnal rostral fluid shift.

Background: Nocturnal rostral fluid shift has been suggested to be a risk factor for obstructive sleep apnea (OSA) in healthy subjects after lower body positive pressurization. It remains unclear whether this may apply to subjects with nephrotic lower limb edema and, if so, whether disease remission may reverse the accompanying OSA.

Methods: Patients who presented with steroid-responsive primary nephrotic syndrome with lower limb edema as the predominant presenting clinical feature were recruited.

Increased serum levels of advanced glycation end-products is associated with severity of sleep disordered breathing but not insulin sensitivity in non-diabetic men with obstructive sleep apnoea.

Background: Patients with diabetes mellitus are known to have increased serum levels of advanced glycation end-products (AGEs), and this is also associated with insulin resistance. This study aimed to investigate the relationship between serum AGEs and insulin sensitivity in non-diabetic subjects with obstructive sleep apnoea (OSA).

Methods: Adult males with no known comorbidities were recruited from the sleep clinic of a university teaching hospital.

Obesity, obstructive sleep apnoea and metabolic syndrome.

OSA is increasingly recognized as a major health problem in developed countries. Obesity is the most common risk factor in OSA and hence, the prevalence of OSA is undoubtedly rising given the epidemic of obesity. Recent data also suggest that OSA is highly associated with the metabolic syndrome, and it is postulated that OSA contributes to cardiometabolic dysfunction, and subsequently vasculopathy.

The efficacy of oral appliances in the treatment of severe obstructive sleep apnea.

Objectives: The purpose of this study is to evaluate the efficacy of oral appliance (OA) treatment for subjects with severe obstructive sleep apnea (OSA) and to determine the dental parameters associated with treatment outcomes.

Study Design: This study uses a prospective longitudinal design.

Methods: Consecutive Chinese subjects with severe OSA who refused continuous positive airway pressure treatment were recruited.

Advantages of video trigger in problem-based learning.

Background: Traditionally, paper cases are used as 'triggers' to stimulate learning in problem-based learning (PBL). However, video may be a better medium because it preserves the original language, encourages the active extraction of information, avoids depersonalization of patients and allows direct observation of clinical consultations. In short, it exposes the students to the complexity of actual clinical problems.

Prevalence and recognition of obstructive sleep apnea in Chinese patients with type 2 diabetes mellitus.

Background: Obstructive sleep apnea (OSA) is associated with disorders of glucose metabolism. Previous studies revealed a high prevalence of OSA among subjects with type 2 diabetes mellitus (DM). The aims of this study were to determine the prevalence of OSA and associated clinical factors in Chinese patients with DM.

Obstructive sleep apnea and the metabolic syndrome.

Obstructive sleep apnea (OSA) and the metabolic syndrome have a strong association with each other owing to their common feature of obesity, but an association independent of obesity has been demonstrated in several studies. There is also evidence, of varying strengths, from epidemiologic and clinical studies, for the independent association between OSA and individual core components of the metabolic syndrome, including hypertension, insulin resistance and dyslipidemia. To date, the data are strongest for hypertension, while data for adverse glucose or lipid metabolism are more controversial.

Sleep & the metabolic syndrome.

Sleep is an essential part of our daily living, and sleep disturbances may intervene with the biological and physiological processes in human body leading to the development of metabolic dysfunction. Short sleep duration and poor sleep quality have adverse effects on metabolism and hormonal processes, contributing to increased cardiovascular risk. Obstructive sleep apnoea is a chronic condition characterized by repetitive upper airway collapse during sleep, causing intermittent hypoxaemia, recurrent arousals and sleep fragmentation.

Obstructive sleep apnoea: definitions, epidemiology & natural history.

Obstructive sleep apnoea (OSA) is increasingly being recognized as an important health issue in the last two to three decades. It is characterized by frequent episodes of upper airway collapse during sleep, causing recurrent arousals, intermittent hypoxaemia, sleep fragmentation and poor sleep quality. There is accumulating evidence that OSA is being considered as an independent risk factor for hypertension, glucose intolerance / diabetes mellitus, cardiovascular diseases and stroke, leading to increased cardiometabolic morbidity and mortality.

Determinants of daytime blood pressure in relation to obstructive sleep apnea in men.

This study investigated the roles of different potential pathophysiological mechanisms in the determination of blood pressure in relation to obstructive sleep apnea. The study was designed as a cross-sectional study. Consecutive healthy male subjects who were to undergo polysomnography were recruited.