Multidimensional sleep health is associated with mental well-being in Australian adults.

The few studies assessing the relationship between mental health and a multidimensional measure of sleep have been conducted in samples of almost exclusively women. In the present study, we therefore assessed associations of multidimensional sleep health with mental well-being in Australian adults. A cross-sectional, national online survey of sleep health was conducted in 2019 in 2,044 community dwelling adults aged 18-90 years.

Transient hypopharyngeal intrabolus pressurization patterns: Clinically relevant or normal variant?

Introduction: In oropharyngeal dysphagia, impaired pharyngoesophageal junction (PEJ) opening is reflected by an elevated hypopharyngeal intrabolus pressure (IBP), quantifiable using pharyngeal high-resolution manometry with impedance (P-HRM-I). Transient intrabolus pressurization (TP) phenomena are not sustained and last for only a brief period. We hypothesized that TP patterns reflect impaired coordination between timing of hypopharyngeal bolus arrival and PEJ relaxation.

Marine bioactives: from energy to nutrition.

Microalgae have been evaluated as promising resource for biodiesel production, but algal biofuel production is not yet commercially viable, which reflects the high energy costs linked with cultivation, harvesting, and dewatering of algae. As crude oil processing declines, microalgae biorefineries are being considered for producing bioactives such as enzymes, proteins, omega-3 oils, pigments, recombinant products, and vitamins, to offset the costs of biofuel production. We believe that producing algal bioactives through advanced manufacturing pathways, encompassing a biorefinery approach, would be effective, profitable, and economical.

Binding of SEP-363856 within TAAR1 and the 5HT receptor: implications for the design of novel antipsychotic drugs.

Current medications for schizophrenia typically modulate dopaminergic neurotransmission. While affecting positive symptoms, antipsychotic drugs have little clinical effect on negative symptoms and cognitive impairment. Moreover, newer 'atypical' antipsychotic drugs also have significant metabolic adverse-effects.

Effect of upper airway fat on tongue dilation during inspiration in awake people with obstructive sleep apnea.

Study Objectives: To investigate the effect of upper airway fat composition on tongue inspiratory movement and obstructive sleep apnea (OSA).

Methods: Participants without or with untreated OSA underwent a 3T magnetic resonance imaging (MRI) scan. Anatomical measurements were obtained from T2-weighted images.

Design of a Stable Cyclic Peptide Analgesic Derived from Sunflower Seeds that Targets the κ-Opioid Receptor for the Treatment of Chronic Abdominal Pain.

The rising opioid crisis has become a worldwide societal and public health burden, resulting from the abuse of prescription opioids. Targeting the κ-opioid receptor (KOR) in the periphery has emerged as a powerful approach to develop novel pain medications without central side effects. Inspired by the traditional use of sunflower () preparations for analgesic purposes, we developed novel stabilized KOR ligands (termed as helianorphins) by incorporating different dynorphin A sequence fragments into a cyclic sunflower peptide scaffold.

Breath-holding as a novel approach to risk stratification in COVID-19.

Background: Despite considerable progress, it remains unclear why some patients admitted for COVID-19 develop adverse outcomes while others recover spontaneously. Clues may lie with the predisposition to hypoxemia or unexpected absence of dyspnea ('silent hypoxemia') in some patients who later develop respiratory failure. Using a recently-validated breath-holding technique, we sought to test the hypothesis that gas exchange and ventilatory control deficits observed at admission are associated with subsequent adverse COVID-19 outcomes (composite primary outcome: non-invasive ventilatory support, intensive care admission, or death).

Olorinab (APD371), a peripherally acting, highly selective, full agonist of the cannabinoid receptor 2, reduces colitis-induced acute and chronic visceral hypersensitivity in rodents.

Abdominal pain is a key symptom of inflammatory bowel disease and irritable bowel syndrome, for which there are inadequate therapeutic options. We tested whether olorinab-a highly selective, full agonist of the cannabinoid receptor 2 (CB2)-reduced visceral hypersensitivity in models of colitis and chronic visceral hypersensitivity (CVH). In rodents, colitis was induced by intrarectal administration of nitrobenzene sulfonic acid derivatives.

A mouse model of endometriosis that displays vaginal, colon, cutaneous, and bladder sensory comorbidities.

Endometriosis is a painful inflammatory disorder affecting ~10% of women of reproductive age. Although chronic pelvic pain (CPP) remains the main symptom of endometriosis patients, adequate treatments for CPP are lacking. Animal models that recapitulate the features and symptoms experienced by women with endometriosis are essential for investigating the etiology of endometriosis, as well as developing new treatments.

The ClpP activator ONC-212 (TR-31) inhibits BCL2 and B-cell receptor signaling in CLL.

Despite advances in therapy, a significant proportion of patients with chronic lymphocytic leukemia (CLL) relapse with drug resistant disease. Novel treatment approaches are required, particularly for high risk disease. The imipridones represent a new class of cancer therapy that has been investigated in pre-clinical and clinical trials against a range of different cancers.

Extrapolation of Survival Curves Using Standard Parametric Models and Flexible Parametric Spline Models: Comparisons in Large Registry Cohorts with Advanced Cancer.

Background: It is often important to extrapolate survival estimates beyond the limited follow-up times of clinical trials. Extrapolated survival estimates can be highly sensitive to model choice; thus, appropriate model selection is crucial. Flexible parametric spline models have been suggested as an alternative to standard parametric models; however, their ability to extrapolate is not well understood.

SRRM4 Expands the Repertoire of Circular RNAs by Regulating Microexon Inclusion.

High-throughput RNA sequencing (RNA-seq) and dedicated bioinformatics pipelines have synergized to identify an expansive repertoire of unique circular RNAs (circRNAs), exceeding 100,000 variants. While the vast majority of these circRNAs comprise canonical exonic and intronic sequences, microexons (MEs)-which occur in 30% of functional mRNA transcripts-have been entirely overlooked. CircRNAs which contain these known MEs (ME-circRNAs) could be identified with commonly utilized circRNA prediction pipelines, CIRCexplorer2 and CIRI2, but were not previously recognized as ME-circRNAs.

Experimentally Induced Bladder Permeability Evokes Bladder Afferent Hypersensitivity in the Absence of Inflammation.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic urological condition characterised by urinary urgency, frequency and pelvic pain, that significantly impacts the quality of life for ∼5% of women. Bladder sensation is coordinated by primary afferent sensory neurons that innervate the bladder wall, translating bladder stretch into signals that travel to the brain via the spinal cord. Whilst the pathophysiology of IC/BPS remains unknown, an increase in the permeability of the bladder urothelium has been proposed as an initiating cause.

Identification of a Quorum Sensing-Dependent Communication Pathway Mediating Bacteria-Gut-Brain Cross Talk.

Despite recently established contributions of the intestinal microbiome to human health and disease, our understanding of bacteria-host communication pathways with regard to the gut-brain axis remains limited. Here we provide evidence that intestinal neurons are able to "sense" bacteria independently of the host immune system. Using supernatants from cultures of the opportunistic pathogen (.

Arginine-259 of UGT2B7 Confers UDP-Sugar Selectivity.

Enzymes of the human UDP-glycosyltransferase (UGT) superfamily typically catalyze the covalent addition of the sugar moiety from a UDP-sugar cofactor to relatively low-molecular weight lipophilic compounds. Although UDP-glucuronic acid (UDP-GlcUA) is most commonly employed as the cofactor by UGT1 and UGT2 family enzymes, UGT2B7 and several other enzymes can use both UDP-GlcUA and UDP-glucose (UDP-Glc), leading to the formation of glucuronide and glucoside conjugates. An investigation of UGT2B7-catalyzed morphine glycosidation indicated that glucuronidation is the principal route of metabolism because the binding affinity of UDP-GlcUA is higher than that of UDP-Glc.

CPAP combined with oral appliance therapy reduces CPAP requirements and pharyngeal pressure swings in obstructive sleep apnea.

Oral appliance (OA) therapy is the leading alternative to continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA). It is well tolerated compared with CPAP. However, ≥50% of patients using OA therapy have incomplete resolution of their OSA.

Zolpidem increases sleep efficiency and the respiratory arousal threshold without changing sleep apnoea severity and pharyngeal muscle activity.

Key Points: A decreased respiratory arousal threshold is one of the main contributors to obstructive sleep apnoea (OSA) pathogenesis. Several recent studies have sought to find a drug capable of increasing the respiratory arousal threshold without impairing pharyngeal muscle activity to reduce OSA severity, with variable success. Here we show that zolpidem increases the respiratory arousal threshold by ∼15%, an effect size which was insufficient to systematically decrease OSA severity as measured by the apnoea-hypopnoea index.

Pharmacological modulation of voltage-gated sodium (NaV) channels alters nociception arising from the female reproductive tract.

Dyspareunia, also known as vaginal hyperalgesia, is a prevalent and debilitating symptom of gynaecological disorders such as endometriosis and vulvodynia. Despite this, the sensory pathways transmitting nociceptive information from female reproductive organs remain poorly characterised. As such, the development of specific treatments for pain associated with dyspareunia is currently lacking.