Systematic review and meta-analysis of the effect of protein and amino acid supplements in older adults with acute or chronic conditions.

The loss of lean body mass, muscle strength and physical function causes significant problems in older adults. Protein and amino acid supplements can preserve muscle strength but the effect on function is variable. We conducted a systematic literature review and meta-analysis to investigate the effect of protein and amino acid supplementation on fat-free mass, muscle strength and physical function in malnourished, frail, sarcopenic, dependent or elderly with acute or chronic conditions, with or without rehabilitation exercise.

The role of the vasopressin V1A receptor in oxytocin modulation of methamphetamine primed reinstatement.

The neuropeptide oxytocin has shown promise as an effective therapy in pre-clinical models of methamphetamine (METH) addiction. The nucleus accumbens core (NAcc) has been identified as an important site for oxytocin to inhibit METH behaviours, although previous findings suggest that the effects of oxytocin in the NAcc are mediated by receptors other than the oxytocin receptor (OTR). Oxytocin has high affinity for the vasopressin V1A receptor (V1AR) which has been implicated in numerous oxytocin-dependent social behaviours.

Abundance and richness of key Antarctic seafloor fauna correlates with modelled food availability.

Most seafloor communities at depths below the photosynthesis zone rely on food that sinks through the water column. However, the nature and strength of this pelagic-benthic coupling and its influence on the structure and diversity of seafloor communities is unclear, especially around Antarctica where ecological data are sparse. Here we show that the strength of pelagic-benthic coupling along the East Antarctic shelf depends on both physical processes and the types of benthic organisms considered.

The C2-formyl group in chlorophyll originates from molecular oxygen.

Chlorophylls (Chls) are the most important cofactors for capturing solar energy to drive photosynthetic reactions. Five spectral types of Chls have been identified to date, with Chl having the most red-shifted absorption maximum because of a C2-formyl group substitution of Chl However, the biochemical provenance of this formyl group is unknown. Here, we used a stable isotope labeling technique (O and H) to determine the origin of the C2-formyl group of Chl and to verify whether Chl is synthesized from Chl in the cyanobacterial species In the presence of either HO or O, the origin of oxygen atoms in the newly synthesized chlorophylls was investigated.

Reaction rates of glutathione and ascorbate with alkyl radicals are too slow for protection against protein peroxidation in vivo.

Reaction kinetics of amino acid and peptide alkyl radicals with GSH and ascorbate, the two most abundant endogenous antioxidants, were investigated by pulse radiolysis. Rate constants in the order of 10 Ms were found. Alkyl radicals react at almost diffusion controlled rates and irreversibly with oxygen to form peroxyl radicals, and competition with this reaction is the benchmark for efficient repair in vivo.

Neuroprotective role of Asiatic acid in aluminium chloride induced rat model of Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia, characterized by memory loss, cognitive impairment and personality disorders accompanied by diffuse structural abnormalities in the brain of elderly people. The current investigation explored the neuroprotective potential of asiatic acid (AA), a natural triterpene of on aluminium chloride (AlCl) induced rat model of AD. Oral administration of AlCl (100 mg/kg b.

Longitudinal co-variations between inflammatory cytokines, lung function and patient reported outcomes in patients with asthma.

Background: Asthma is a chronic inflammatory respiratory disorder associated with reduced lung function and poor quality of life. The condition is also associated with poor self-rated health, a major predictor of objective health trajectories. Of biological correlates to self-rated health, evidence suggests a role for inflammatory cytokines and related sickness behaviours.

Effect of anaesthetic and choice of neuromuscular blocker on vagal control of heart rate under laboratory animal experimental conditions.

Neuromuscular-blocking agents are commonly used in laboratory animal research settings. Due to actions of cholinergic receptors at locations other than the motor end-plate, these agents have a strong propensity to modulate autonomic outflow and may therefore not be desirable in studies examining autonomic function. This study aimed to compare the effect of two non-depolarizing neuromuscular-blocking agents, pancuronium and cisatracurium, on blood pressure, heart rate and non-invasive indices of autonomic function (heart rate variability, systolic blood pressure variability and baroreflex sensitivity) under two different types of anaesthesia in Lewis rats.

Synthesis and Pharmacological Profiling of the Metabolites of Synthetic Cannabinoid Drugs APICA, STS-135, ADB-PINACA, and 5F-ADB-PINACA.

Synthetic cannabinoids (SCs) containing a 1-pentyl-1-H substituted indole or indazole are abused around the world and are associated with an array of serious side effects. These compounds undergo extensive phase 1 metabolism after ingestion with little understanding whether these metabolites are contributing to the cannabimimetic activity of the drugs. This work presents the synthesis and pharmacological characterization of the major metabolites of two high concern SCs; APICA and ADB-PINACA.

Metastatic chromophobe renal cell carcinoma treated with targeted therapies: A Renal Cross Channel Group study.

Background: Treatment of non-clear cell renal cell carcinoma (RCC) remains controversial despite several recent prospective studies of targeted therapies (TT). Often Vascular Endothelial growth Factor (VEGF) and Mammalian Target of Rapamycin (mTOR) inhibitors are used, extrapolating the data from use of these agents in clear cell RCC.

Methods: We performed a retrospective data analysis within the Renal Cross Channel Group to determine metastatic chromophobe RCC (mChRCC) outcomes in the TT era.

Mechanisms and strategies to overcome resistance to molecularly targeted therapy for melanoma.

The identification of driver mutations in melanoma has changed the field of cancer treatment. BRAF and NRAS mutations are predominant in melanoma and lead to overactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways. Selective inhibitors targeting key effectors of the MAPK pathway have revolutionized the treatment of patients with advanced metastatic BRAF-mutant melanoma.

Anxiety disorders.

Anxiety disorders constitute the largest group of mental disorders in most western societies and are a leading cause of disability. The essential features of anxiety disorders are excessive and enduring fear, anxiety or avoidance of perceived threats, and can also include panic attacks. Although the neurobiology of individual anxiety disorders is largely unknown, some generalizations have been identified for most disorders, such as alterations in the limbic system, dysfunction of the hypothalamic-pituitary-adrenal axis and genetic factors.

Alterations in erythrocyte fatty acid composition in preclinical Alzheimer's disease.

Brain and blood fatty acids (FA) are altered in Alzheimer's disease and cognitively impaired individuals, however, FA alterations in the preclinical phase, prior to cognitive impairment have not been investigated previously. The current study therefore evaluated erythrocyte FA in cognitively normal elderly participants aged 65-90 years via trans-methylation followed by gas chromatography. The neocortical beta-amyloid load (NAL) measured via positron emission tomography (PET) using ligand F-Florbetaben, was employed to categorise participants as low NAL (standard uptake value ratio; SUVR < 1.

Patient-specific blood pressure correction technique for arterial stiffness: evaluation in a cohort on anti-angiogenic medication.

Arterial pulse wave velocity (PWV) depends on blood pressure (BP). Correction of PWV for BP is commonly performed using a statistical approach, requiring a patient cohort. We recently developed a mechanistic, model-predictive approach to assess BP-independent changes in carotid PWV (cPWV) at the level of the individual.

Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma.

Background: Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options.

Methods: In this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine. The coprimary end points were overall survival and progression-free survival, which were assessed among all patients and among patients who had a tumor PD-1 ligand (PD-L1) combined positive score (the percentage of PD-L1-expressing tumor and infiltrating immune cells relative to the total number of tumor cells) of 10% or more.

Socioeconomic and geographic disparities in access to pharmacotherapy for alcohol dependence.

A higher rate of alcohol-attributable morbidity and mortality exists in remote and socioeconomically disadvantaged regions of Australia. This study aimed to explore the dispensing pattern of pharmacotherapy for alcohol dependence across these groups. A retrospective cohort study of patients (aged 15-84) dispensed acamprosate or naltrexone (July 2009-June 2013) was conducted.

Enantiodivergence in the Biosynthesis of Bromotyrosine Alkaloids from Sponges?

The isolation of bromotyrosine alkaloids, some of which are enantiomers of previously isolated compounds, has highlighted a possible enantiodivergence in their biosynthesis. Two new (1, 2) and six known bromotyrosine alkaloids (4-9), and the enantiomer (10) of a known compound, have been isolated from a Western Australian marine sponge, Pseudoceratina cf. verrucosa.

Cerebellar Metastases From Prostate Cancer on 68Ga-PSMA PET/CT.

Ga prostate-specific membrane antigen PET/CT is increasingly used to evaluate extent of disease in prostate carcinoma. Parenchymal brain metastases originating from prostate cancer have highly variable imaging appearance. We present a 77-year-old man with cerebellar metastasis from prostate cancer showing focal uptake on prostate-specific membrane antigen PET/CT.

Chronic Treatment with the IDO1 Inhibitor 1-Methyl-D-Tryptophan Minimizes the Behavioural and Biochemical Abnormalities Induced by Unpredictable Chronic Mild Stress in Mice - Comparison with Fluoxetine.

We demonstrated that confronting mice to the Unpredictable Chronic Mild Stress (UCMS) procedure-a validated model of stress-induced depression-results in behavioural alterations and biochemical changes in the kynurenine pathway (KP), suspected to modify the glutamatergic neurotransmission through the imbalance between downstream metabolites such as 3-hydroxykynurenine, quinolinic and kynurenic acids. We showed that daily treatment with the IDO1 inhibitor 1-methyl-D-tryptophan partially rescues UCMS-induced KP alterations as does the antidepressant fluoxetine. More importantly we demonstrated that 1-methyl-D-tryptophan was able to alleviate most of the behavioural changes resulting from UCMS exposure.

Interaction of homocysteine, glutathione and 8-hydroxy-2'-deoxyguanosine in metabolic syndrome progression.

Purpose: The role of homocysteine (Hcy) and associated oxidative stress processes in the metabolic syndrome (MetS) continuum has not been explored extensively. Changes in Hcy and associated oxidative stress in relation to the number of metabolic syndrome factors present are explored in this study.

Method: Participants (n=266) attending a rural diabetes screening clinic had their medical history recorded as well as body mass index, Hcy, glucose, cholesterol, glutathione (GSH), and 8-hydroxy-2-deoxyguanosine (8-OHdG) measured.

Targeting Alzheimer's Disease Neuro-Metabolic Dysfunction with a Small Molecule Nuclear Receptor Agonist (T3D-959) Reverses Disease Pathologies.

Background: Alzheimer's disease (AD) could be regarded as a brain form of diabetes since insulin resistance and deficiency develop early and progress with severity of neurodegeneration. Preserving insulin's actions in the brain restores function and reduces neurodegeneration. T3D-959 is a dual nuclear receptor agonist currently in a Phase 2a trial in mild-to-moderate AD patients (ClinicalTrials.

Quantitative proteomics in Giardia duodenalis-Achievements and challenges.

Giardia duodenalis (syn. G. lamblia and G.