Tobacco retail availability and smoking-A systematic review and meta-analysis.

Issues: Health policy makers worldwide have adopted evidence-based legislation, largely directed at consumers, to reduce tobacco-related harm. It is suggested that limiting supply by decreasing retail availability can also reduce cigarette smoking. To inform policy makers this systematic literature review assesses whether reducing availability is associated with smoking behaviours.

Co-Designed Cardiac Rehabilitation for the Secondary Prevention of Stroke (CARESS): A Pilot Program Evaluation.

Structured health system-based programs, such as cardiac rehabilitation, may reduce the risk of recurrent stroke. This study aimed to co-design and evaluate a structured program of rehabilitation, developed based on insights from focus groups involving stroke survivors and health professionals. Conducted in Tasmania, Australia in 2019, the 7-week program comprised one hour of group exercise and one hour of education each week.

A brainstem-hypothalamus neuronal circuit reduces feeding upon heat exposure.

Empirical evidence suggests that heat exposure reduces food intake. However, the neurocircuit architecture and the signalling mechanisms that form an associative interface between sensory and metabolic modalities remain unknown, despite primary thermoceptive neurons in the pontine parabrachial nucleus becoming well characterized. Tanycytes are a specialized cell type along the wall of the third ventricle that bidirectionally transport hormones and signalling molecules between the brain's parenchyma and ventricular system.

Novel synthetic procedures for C2 substituted imidazoquinolines as ligands for the α/β-interface of the GABAA-receptor.

Unlabelled: A series of substituted imidazoquinolines, a structurally related chemotype to pyrazoloquinolinones, a well-known class of GABA ligands, was prepared via two synthetic procedures and the efficiency of these procedures were compared. One method relies on classical heterocyclic synthesis, the other one aims at late-stage decoration of a truncated scaffold via direct C-H functionalization. A pharmacological evaluation disclosed that one of the synthesized derivatives showed interesting activity on a α1β3 containing receptor subtype.

Is sex a predictor for delayed cerebral ischaemia (DCI) and hydrocephalus after aneurysmal subarachnoid haemorrhage (aSAH)? A systematic review and meta-analysis.

Objectives: DCI and hydrocephalus are the most common complications that predict poor outcomes after aSAH. The relationship between sex, DCI and hydrocephalus are not well established; thus, we aimed to examine sex differences in DCI and hydrocephalus following aSAH in a systematic review and meta-analysis.

Methods: A systematic search was conducted using the PubMed, Scopus and Medline databases from inception to August 2022 to identify cohort, case control, case series and clinical studies reporting sex and DCI, acute and chronic shunt-dependent hydrocephalus (SDHC).

Sex differences in pressure and flow waveform physiology across the life course.

Cardiovascular disease (CVD) has long been deemed a disease of old men. However, in 2019 CVD accounted for 35% of all deaths in women and, therefore, remains the leading cause of death in both men and women. There is increasing evidence to show that risk factors, pathophysiology and health outcomes related to CVD differ in women compared with men, yet CVD in women remains understudied, underdiagnosed and undertreated.

Barriers and facilitators to more timely treatment of aneurysmal subarachnoid haemorrhage across two tertiary referral centres in Australia: A thematic analysis.

Background: Delays in treatment of aSAH appear to be common but the causes are not well understood. We explored facilitators and barriers to timely treatment of aSAH.

Methods: We used a multiple case study with cases of aSAH surviving> 1 day identified prospectively.

Tricyclic antipsychotics and antidepressants can inhibit α5-containing GABA receptors by two distinct mechanisms.

Background And Purpose: Many psychotherapeutic drugs, including clozapine, display polypharmacology and act on GABA receptors. Patients with schizophrenia show alterations in function, structure and molecular composition of the hippocampus, and a recent study demonstrated aberrant levels of hippocampal α5 subunit-containing GABA receptors. The purpose of this study is to investigate the effects of tricyclic compounds on α5 subunit-containing receptor subtypes.

Adherence to evidence-based processes of care reduces one-year mortality after aneurysmal subarachnoid hemorrhage (aSAH).

Background: There is limited research on the provision of evidence-based care and its association with outcomes after aneurysmal subarachnoid hemorrhage (aSAH).

Aims: We examined adherence to evidence-based care after aSAH and associations with survival and discharge destination. Also, factors associated with evidence-based care including age, sex, Charlson comorbidity index, severity scores, and delayed cerebral ischemia and infarction were examined for association with survival and discharge destination.

Time and predictors of time to treatment for aneurysmal subarachnoid haemorrhage (aSAH): a systematic review.

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is a serious form of stroke, for which rapid access to specialist neurocritical care is associated with better outcomes. Delays in the treatment of aSAH appear to be common and may contribute to poor outcomes. We have a limited understanding of the extent and causes of these delays, which hinders the development of interventions to reduce delays and improve outcomes.

Sex differences in aneurysmal subarachnoid haemorrhage (aSAH): aneurysm characteristics, neurological complications, and outcome.

Background: Women are over-represented in aSAH cohorts, but whether their outcomes differ to men remains unclear. We examined if sex differences in neurological complications and aneurysm characteristics contributed to aSAH outcomes.

Methods: In a retrospective cohort (2010-2016) of all aSAH cases across two hospital networks in Australia, information on severity, aneurysm characteristics and neurological complications (rebleed before/after treatment, postoperative stroke < 48 h, neurological infections, hydrocephalus, seizures, delayed cerebral ischemia [DCI], cerebral infarction) were extracted.

A novel de novo variant of GABRA1 causes increased sensitivity for GABA in vitro.

The GABRA1 gene encodes one of the most conserved and highly expressed subunits of the GABA receptor family. Variants in this gene are causatively implicated in different forms of epilepsy and also more severe epilepsy-related neurodevelopmental syndromes. Here we study functional consequences of a novel de novo missense GABRA1 variant, p.

GABA Receptor Ligands Often Interact with Binding Sites in the Transmembrane Domain and in the Extracellular Domain-Can the Promiscuity Code Be Cracked?

Many allosteric binding sites that modulate gamma aminobutyric acid (GABA) effects have been described in heteropentameric GABA type A (GABA) receptors, among them sites for benzodiazepines, pyrazoloquinolinones and etomidate. Diazepam not only binds at the high affinity extracellular "canonical" site, but also at sites in the transmembrane domain. Many ligands of the benzodiazepine binding site interact also with homologous sites in the extracellular domain, among them the pyrazoloquinolinones that exert modulation at extracellular α+/β- sites.

Life-long impairment of glucose homeostasis upon prenatal exposure to psychostimulants.

Maternal drug abuse during pregnancy is a rapidly escalating societal problem. Psychostimulants, including amphetamine, cocaine, and methamphetamine, are amongst the illicit drugs most commonly consumed by pregnant women. Neuropharmacology concepts posit that psychostimulants affect monoamine signaling in the nervous system by their affinities to neurotransmitter reuptake and vesicular transporters to heighten neurotransmitter availability extracellularly.

Sex differences in risk factors for aneurysmal subarachnoid haemorrhage: Systematic review and meta-analysis.

Background: Aneurysmal subarachnoid haemorrhage (aSAH) disproportionally affects women. We conducted a systematic review and meta-analysis to explore sex differences in aSAH risk factors.

Methods: Case-control/cohort studies were searched to November 2017 with sex-specific risk factors for aSAH.

Variations on a scaffold - Novel GABA receptor modulators.

Allosteric ligands of GABA receptors exist in many different chemotypes owing to their great usefulness as therapeutics, with benzodiazepines being among the best known examples. Many allosteric binding sites have been described, among them a site at the extracellular interface between the alpha principal face and the beta complementary face (α+/β-). Pyrazoloquinolinones have been shown to bind at α+/β-binding sites of GABA receptors, exerting chiefly positive allosteric modulation at this location.

Urban-rural differences in the care and outcomes of acute stroke patients: Systematic review.

Objective: To describe literature pertaining to urban-rural differences in both the quality of care and outcomes of acute stroke patients.

Methods: We systematically searched CINAHL, PubMed, ProQuest Dissertations & Theses, and Scopus for published and unpublished literature until 9th December 2017. Studies were included if they compared the acute care provided to, or outcomes of, patients hospitalised for stroke in urban versus rural settings.

Prevention of Congenital Syphilis Through Antenatal Screenings in Lusaka, Zambia: A Systematic Review.

Congenital syphilis is one of the preventable diseases caused by the gram-negative bacteria Treponema pallidum; yet, it imposes a serious global health and economic burden, with more than half of the cases resulting in serious adverse outcomes, including infant mortality. Mother-to-child transmission (MTCT) of syphilis is estimated at 3.6 million adjusted life years (DALYs) and around $309 million in medical costs.

A Public Health Analysis on Gaps in Disease Monitoring and Opportunities for Improved Care for the Management of Hepatitis B and C.

Hepatitis B and Hepatitis C have been major disease-causing agents among humans since they were discovered in the 1960s. Both cause jaundice-like symptoms initially but their prognosis and treatment are somehow different and depend upon many demographic details, such as the age and susceptibility of the patients and any other comorbid conditions. They clinically present primarily with hepatitis and can have many adverse effects or even be life-threatening at times, if not treated properly.

Molecular tools for GABA receptors: High affinity ligands for β1-containing subtypes.

γ-Aminobutyric acid type A (GABA) receptors are pentameric GABA-gated chloride channels that are, in mammalians, drawn from a repertoire of 19 different genes, namely α1-6, β1-3, γ1-3, δ, ε, θ, π and ρ1-3. The existence of this wide variety of subunits as well as their diverse assembly into different subunit compositions result in miscellaneous receptor subtypes. In combination with the large number of known and putative allosteric binding sites, this leads to a highly complex pharmacology.

Pharmacological and antihyperalgesic properties of the novel α2/3 preferring GABA receptor ligand MP-III-024.

γ-Aminobutyric acid type A (GABA) receptors are located in spinal nociceptive circuits where they modulate the transmission of pain sensory signals from the periphery to higher centers. Benzodiazepine-type drugs bind to GABA receptors containing α1, α2, α3, and α5 subunits (α1GABA, α2GABA, α3GABA and α5GABA receptors, respectively) through which they inhibit the transmission of these signals. In the present study we describe the novel benzodiazepine site positive allosteric modulator modulator methyl 8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxylate (MP-III-024).

A variant in a cis-regulatory element enhances claudin-14 expression and is associated with pediatric-onset hypercalciuria and kidney stones.

The greatest risk factor for kidney stones is hypercalciuria, the etiology of which is largely unknown. A recent genome-wide association study (GWAS) linked hypercalciuria and kidney stones to a claudin-14 (CLDN14) risk haplotype. However, the underlying molecular mechanism was not delineated.

Synthesis and Characterization of a Novel γ-Aminobutyric Acid Type A (GABA) Receptor Ligand That Combines Outstanding Metabolic Stability, Pharmacokinetics, and Anxiolytic Efficacy.

1,4-Benzodiazepines are used in the treatment of anxiety disorders but have limited long-term use due to adverse effects. HZ-166 (2) has been shown to have anxiolytic-like effects with reduced sedative/ataxic liabilities. A 1,3-oxazole KRM-II-81 (9) was discovered from a series of six bioisosteres with significantly improved pharmacokinetic and pharmacodynamic properties as compared to 2.