N-Terminal Capping of the αO-Conotoxin Analogue GeX-2 Improves the Serum Stability and Selectivity toward the Human α9α10 Nicotinic Acetylcholine Receptor.

α9α10 nicotinic acetylcholine receptors (nAChRs) are a promising nonopioid analgesic target, with α9α10 nAChR antagonists showing efficacy against chemotherapy-induced hyperalgesia and allodynia. GeX-2, a potent analgesic conotoxin antagonist of α9α10 nAChRs, has limited serum stability. This study improved GeX-2 stability by capping its N-terminal with fatty acids or polyethylene glycol chains, which enhanced its serum stability but eliminated activity at G protein-coupled γ-aminobutyric acid type B (GABA) receptor-coupled Ca2.

Overexpression of forebrain PTP1B leads to synaptic and cognitive impairments in obesity.

Obesity has reached pandemic proportions and is a risk factor for neurodegenerative diseases, including Alzheimer's disease. Chronic inflammation is common in obese patients, but the mechanism between inflammation and cognitive impairment in obesity remains unclear. Accumulative evidence shows that protein-tyrosine phosphatase 1B (PTP1B), a neuroinflammatory and negative synaptic regulator, is involved in the pathogenesis of neurodegenerative processes.

Dual Antagonism of α9α10 nAChR and GABA Receptor-Coupled Ca2.2 Channels by an Analgesic αO-Conotoxin Analogue.

Pain severely affects the physical and mental health of patients. The need to develop nonopioid analgesic drugs to meet medical demands is urgent. In this study, we designed a truncated analogue of αO-conotoxin, named GeX-2, based on disulfide-bond deletion and sequence truncation.

Probiotic Clostridium butyricum ameliorates cognitive impairment in obesity via the microbiota-gut-brain axis.

Obesity is a risk factor for cognitive dysfunction and neurodegenerative disease, including Alzheimer's disease (AD). The gut microbiota-brain axis is altered in obesity and linked to cognitive impairment and neurodegenerative disorders. Here, we targeted obesity-induced cognitive impairment by testing the impact of the probiotic Clostridium butyricum, which has previously shown beneficial effects on gut homeostasis and brain function.

The role of ion channels in T cell function and disease.

T lymphocytes (T cells) are an important sub-group of cells in our immune system responsible for cell-mediated adaptive responses and maintaining immune homeostasis. Abnormalities in T cell function, lead the way to the persistence of infection, impaired immunosurveillance, lack of suppression of cancer growth, and autoimmune diseases. Ion channels play a critical role in the regulation of T cell signaling and cellular function and are often overlooked and understudied.

A previously unrecognized superfamily of macro-conotoxins includes an inhibitor of the sensory neuron calcium channel Cav2.3.

Animal venom peptides represent valuable compounds for biomedical exploration. The venoms of marine cone snails constitute a particularly rich source of peptide toxins, known as conotoxins. Here, we identify the sequence of an unusually large conotoxin, Mu8.

Effects of Resistance Training on Academic Outcomes in School-Aged Youth: A Systematic Review and Meta-Analysis.

Background: The primary aim of our systematic review and meta-analysis was to investigate the effect of resistance training on academic outcomes in school-aged youth.

Methods: We conducted a systematic search of six electronic databases (CINAHL Complete, PsycINFO, SCOPUS, Ovid MEDLINE, SPORTDiscus and EMBASE) with no date restrictions. Studies were eligible if they: (a) included school-aged youth (5-18 years), and (b) examined the effect of resistance training on academic outcomes (i.

DM506 (3-Methyl-1,2,3,4,5,6-hexahydroazepino[4,5-]indole fumarate), a Novel Derivative of Ibogamine, Inhibits α7 and α9α10 Nicotinic Acetylcholine Receptors by Different Allosteric Mechanisms.

The main objective of this study was to determine the pharmacological activity and molecular mechanism of action of DM506 (3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-]indole fumarate), a novel ibogamine derivative, at different nicotinic acetylcholine receptor (nAChR) subtypes. The functional results showed that DM506 neither activates nor potentiates but inhibits ACh-evoked currents at each rat nAChR subtype in a non-competitive manner. The receptor selectivity for DM506 inhibition follows the sequence: α9α10 (IC = 5.

Triplex qPCR assay for Campylobacter jejuni and Campylobacter coli monitoring in wastewater.

Campylobacter spp. is one of the most frequent pathogens of bacterial gastroenteritis recorded worldwide. Campylobacter jejuni (C.

Automated Patch Clamp Screening of Amiloride and 5-,-Hexamethyleneamiloride Analogs Identifies 6-Iodoamiloride as a Potent Acid-Sensing Ion Channel Inhibitor.

Acid-sensing ion channels (ASICs) are transmembrane sensors of extracellular acidosis and potential drug targets in several disease indications, including neuropathic pain and cancer metastasis. The K-sparing diuretic amiloride is a moderate nonspecific inhibitor of ASICs and has been widely used as a probe for elucidating ASIC function. In this work, we screened a library of 6-substituted and 5,6-disubstituted amiloride analogs using a custom-developed automated patch clamp protocol and identified 6-iodoamiloride as a potent ASIC1 inhibitor.

Elucidating the Stoichiometries of Host-Pathogen Protein Interactions with Mass Photometry.

Mass photometry (MP) is a single molecule technique that enables the characterization of individual proteins. Here we show a detailed workflow using the Refeyn One to investigate molecular complexes, using the M53 protein, a plasminogen-binding group A streptococcal M-like protein (PAM), and human plasminogen as exemplar proteins. The methodology described herein confirmed a 1:1 binding stoichiometry for the M53-plasminogen complex.

The impact of montessori-based programmes on individuals with dementia living in residential aged care: A systematic review.

Objectives: This systematic review examined the effectiveness of Montessori-based programmes for individuals with dementia living in residential aged care.

Methods: Nine databases were searched between January 2010 to October 2021, including Scopus, CINAHL, MEDLINE, Web of Science, SocINDEX with Full Text, PubMed, PsycINFO, Cochrane library and Cochrane Registry. Publications were included if they used Montessori-based programmes as interventions for individuals with dementia living in residential aged care and were qualitative, quantitative, mixed-method, or pilot studies.

Calcium Imaging of Non-adherent Cells.

Live-cell imaging can reveal dynamic and multimodal cell signaling by monitoring calcium flux. Spatiotemporal changes in Ca concentrations instigate specific downstream processes and by categorizing these events, we can examine the language cells use to communicate both to themselves and with each other. Thus, calcium imaging is an understandably popular and versatile technique that relies on high-resolution optical data as measured by fluorescence intensity.

Incidence of postoperative delirium in older adults undergoing surgical procedures: A systematic literature review and meta-analysis.

Background: With the increase in life expectancy around the globe, the incidence of postoperative delirium (POD) among older people (≥65 years) is growing. Previous studies showed a wide variation in the incidence of POD, from 4% to 53%, with a lack of specific evidence about the incidence of POD by specific surgery type among older people. The aim of this systematic review and meta-analysis was to determine the incidence of POD by surgery type within populations 65 years and over.

A cross-sectional, observational study of nutritional status and eating behaviours in people living with dementia in acute care settings.

Aims And Objectives: To understand the nutritional status, observing eating difficulties during mealtimes for people living with dementia in acute care settings.

Background: Changed eating behaviours caused by declining cognitive function is common in people living with dementia which can lead to malnutrition. Malnutrition is associated with prolonged hospitalisation and increased mortality.

The Antinociceptive Activity of (E)-3-(thiophen-2-yl)- N -(p-tolyl)acrylamide in Mice Is Reduced by (E)-3-(furan-2-yl)- N -methyl- N -(p-tolyl)acrylamide Through Opposing Modulatory Mechanisms at the α7 Nicotinic Acetylcholine Receptor.

Background: The primary objective of this study was to characterize the pharmacological and behavioral activity of 2 novel compounds, DM497 [(E)-3-(thiophen-2-yl)- N -(p-tolyl)acrylamide] and DM490 [(E)-3-(furan-2-yl)- N -methyl- N -(p-tolyl)acrylamide], structural derivatives of PAM-2, a positive allosteric modulator of the α7 nicotinic acetylcholine receptor (nAChR).

Methods: A mouse model of oxaliplatin-induced neuropathic pain (2.4 mg/kg, 10 injections) was used to test the pain-relieving properties of DM497 and DM490.

Delirium education and post-anaesthetics care unit nurses' knowledge on recognising and managing delirium in older patients.

Background: Postoperative delirium (POD) is a major complication following a surgical procedure. There is evidence that improving knowledge about POD could enhance POD care and patient outcomes.

Aim: The study aimed to evaluate whether the amount of delirium education among registered nurses working in post-anaesthetics care units (PACU) impacts on their self-reported confidence and competence in recognising and managing delirium as well as prior knowledge on factors that influence the risk of delirium onset for older people.

The Metabolizable Energy and Lipid Bioaccessibility of Tree Nuts and Peanuts: A Systematic Review with Narrative Synthesis of Human and In Vitro Studies.

Nuts are an energy-dense food, yet regular consumption is not associated with weight gain. A proportion of the fats found within nuts remains encapsulated within cell walls and cannot be digested. Metabolizable energy (ME) can be explored by measuring fecal fat excretion in human studies and fat release among in vitro studies.

Effects of sewer biofilms on the degradability of carbapenems in wastewater using laboratory scale bioreactors.

Carbapenems are last-resort antibiotics used to treat bacterial infections unsuccessfully treated by most common categories of antibiotics in humans. Most of their dosage is secreted unchanged as waste, thereby making its way into the urban water system. There are two major knowledge gaps addressed in this study to gain a better understanding of the effects of their residual concentrations on the environment and environmental microbiome: development of a UHPLC-MS/MS method of detection and quantification from raw domestic wastewater via direct injection and study of their stability in sewer environment during the transportation from domestic sewers to wastewater treatment plants.

Advances in Xanthan Gum-Based Systems for the Delivery of Therapeutic Agents.

In the last three decades, polymers have contributed significantly to the improvement of drug delivery technologies by enabling the controlled and sustained release of therapeutic agents, versatility in designing different delivery systems, and feasibility of encapsulation of both hydrophobic and hydrophilic molecules. Both natural and synthetic polymers have been explored for the delivery of various therapeutic agents. However, due to the disadvantages of synthetic polymers, such as lack of intrinsic biocompatibility and bioactivity, hydrophobicity, and expensive and complex procedure of synthesis, there is a move toward the use of naturally occurring polymers.

Characterisation of Elevenin-Vc1 from the Venom of : A Structural Analogue of α-Conotoxins.

Elevenins are peptides found in a range of organisms, including arthropods, annelids, nematodes, and molluscs. They consist of 17 to 19 amino acid residues with a single conserved disulfide bond. The subject of this study, elevenin-Vc1, was first identified in the venom of the cone snail ( , , 11-18).

Dimethyl itaconate ameliorates cognitive impairment induced by a high-fat diet via the gut-brain axis in mice.

Background: Gut homeostasis, including intestinal immunity and microbiome, is essential for cognitive function via the gut-brain axis. This axis is altered in high-fat diet (HFD)-induced cognitive impairment and is closely associated with neurodegenerative diseases. Dimethyl itaconate (DI) is an itaconate derivative and has recently attracted extensive interest due to its anti-inflammatory effect.

In-sewer decay and partitioning of Campylobacter jejuni and Campylobacter coli and implications for their wastewater surveillance.

Campylobacter jejuni and coli are two main pathogenic species inducing diarrhoeal diseases in humans, which are responsible for the loss of 33 million lives each year. Current Campylobacter infections are mainly monitored by clinical surveillance which is often limited to individuals seeking treatment, resulting in under-reporting of disease prevalence and untimely indicators of community outbreaks. Wastewater-based epidemiology (WBE) has been developed and employed for the wastewater surveillance of pathogenic viruses and bacteria.

Butyrate ameliorates quinolinic acid-induced cognitive decline in obesity models.

Obesity is a risk factor for neurodegenerative disease associated with cognitive dysfunction, including Alzheimer's disease. Low-grade inflammation is common in obesity, but the mechanism between inflammation and cognitive impairment in obesity is unclear. Accumulative evidence shows that quinolinic acid (QA), a neuroinflammatory neurotoxin, is involved in the pathogenesis of neurodegenerative processes.

Nicotinic acetylcholine receptors: Key targets for attenuating neurodegenerative diseases.

Nicotinic acetylcholine receptors (nAChRs) are master regulators of immune functions via the cholinergic anti-inflammatory pathway and are expressed in microglia, the brain's resident immune cells. There is an extensive dialogue between the neurons and the glial cells around them from which microglia are tasked with monitoring, nurturing, and defending their microenvironment. Dysregulation of any of these processes can have devastating and long-lasting consequences involving microglia-mediated neuroinflammation associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, amongst others.