Discovery of BI-9508, a Brain-Penetrant GPR88-Receptor-Agonist Tool Compound for Mouse Studies.

Decreased activity and expression of the G-protein coupled receptor GPR88 is linked to many behavior-linked neurological disorders. Published preclinical GPR88 allosteric agonists all have pharmacokinetic properties that preclude their progression to the clinic, including high lipophilicity and poor brain penetration. Here, we describe our attempts to improve GPR88 agonists' drug-like properties and our analysis of the trade-offs required to successfully target GPR88's allosteric pocket.

A master regulator of opioid reward in the ventral prefrontal cortex.

In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping in mice to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone.

Development of Gerontological Learning Objectives to Enhance Nursing Educational Curricula.

Background: Many nursing schools are challenged to provide adequate gerontological education to students despite the enormous benefits to students' careers and society. This project developed student learning objectives to be used by nursing faculty to facilitate enriched gerontology courses and program curricula.

Method: The project team drafted a comprehensive list of nursing student learning objectives based on the 2020 Canadian Gerontological Nursing Association Standards of Practice and Competencies and included relevant supportive references.

Does Cardiac Contractility Modulation Therapy Reduce Atrial Fibrillation Burden?

Cardiac contractility modulation (CCM) is an implantable technology approved by the U.S. Food and Drug Administration and intended for heart failure patients without a cardiac resynchronization therapy indication.

Hedgehog-interacting protein acts in the habenula to regulate nicotine intake.

Hedgehog-interacting protein (HHIP) sequesters Hedgehog ligands to repress Smoothened (SMO)-mediated recruitment of the GLI family of transcription factors. Allelic variation in HHIP confers risk of chronic obstructive pulmonary disease and other smoking-related lung diseases, but underlying mechanisms are unclear. Using single-cell and cell-type-specific translational profiling, we show that HHIP expression is highly enriched in medial habenula (MHb) neurons, particularly MHb cholinergic neurons that regulate aversive behavioral responses to nicotine.

BABEL (Better tArgeting, Better outcomes for frail ELderly patients) advance care planning: a comprehensive approach to advance care planning in nursing homes: a cluster randomised trial.

Background: Nursing home (NH) residents should have the opportunity to consider, discuss and document their healthcare wishes. However, such advance care planning (ACP) is frequently suboptimal.

Objective: Assess a comprehensive, person-centred ACP approach.

Rat-bite Fever: A Rare Diagnosis for a Common Pediatric Presentation: Case Report.

Introduction: Fever and rash is a common pediatric presentation to the emergency department but can present a diagnostic challenge to the clinician. Here we report the successful identification and treatment of a rare zoonotic exanthem that was facilitated by a thorough history and physical exam.

Case Report: Rat-bite fever is a potentially fatal systemic illness characterized by relapsing fever, rash, and migratory polyarthralgias.

The Ca sensor proteins CML37 and CML42 antagonistically regulate plant stress responses by altering phytohormone signals.

Calmodulin-like-proteins (CML) belong to a family of calcium-sensing proteins that are unique for plants and involved in many different developmental and stress-related reactions. In defense against herbivory, some pathogens and drought, CML37 acts as a positive and CML42 as a negative regulator, respectively. We provide evidence that both CMLs act antagonistically in the regulation of induced defense responses.

A Rare Case Report of Lemierre Syndrome from the Anterior Jugular Vein.

Introduction: Lemierre syndrome is a rare, potentially fatal, septic thrombophlebitis of the internal jugular vein. Treatment includes intravenous antibiotics for Fusobacterium necrophorum, the most common pathogen, as well as consideration for anticoagulation therapy.

Case Report: A 27-year-old female presented with left-sided neck swelling and erythema.

La nécessité des approches interdisciplinaires et collaboratives pour évaluer l'impact de la COVID-19 sur les personnes âgées et le vieillissement: déclaration conjointe de l'ACG / CAG et de la RCV / CJA.

La pandémie de la COVID-19 et l'état d'urgence publique qui en a découlé ont eu des répercussions significatives sur les personnes âgées au Canada et à travers le monde. Il est impératif que le domaine de la gérontologie réponde efficacement à cette situation. Dans la présente déclaration, les membres du conseil d'administration de l'Association canadienne de gérontologie/Canadian Association on Gerontology (ACG/CAG) et ceux du comité de rédaction de La Revue canadienne du vieillissement/Canadian Journal on Aging (RCV/CJA) reconnaissent la contribution des membres de l'ACG/CAG et des lecteurs de la RCV/CJA.

Advanced Opacified Fiber-Reinforced Silica-Based Aerogel Composites for Superinsulation of Exhaust Tubing Systems in Semi-Stationary Motors.

Within this study, monolithic three-dimensional silica aerogel (SA) composite parts with super insulating properties are presented. A generic part based on fiber-reinforced (FR) silica aerogel for thermal insulation of the exhaust tubing system-to keep the exhaust gases as hot as possible to improve the efficiency of the catalyst system-was produced via a sol-gel-based molding process in combination with a supercritical drying using scCO. A thermal conductivity of 16 mW m K was measured via a heat flow meter technique.

Interdisciplinary and Collaborative Approaches Needed to Determine Impact of COVID-19 on Older Adults and Aging: CAG/ACG and / Joint Statement.

The COVID-19 pandemic and subsequent state of public emergency have significantly affected older adults in Canada and worldwide. It is imperative that the gerontological response be efficient and effective. In this statement, the board members of the Canadian Association on Gerontology/L'Association canadienne de gérontologie (CAG/ACG) and the Canadian Journal on Aging/La revue canadienne du vieillissement (CJA/RCV) acknowledge the contributions of CAG/ACG members and CJA/RCV readers.

InterRAI Acute Care Instrument for Seniors in Canadian Hospitals: Findings of an Inter-Rater Reliability Pilot Study.

Background: Older adults are the biggest users of emergency departments and hospitals. However, healthcare professionals are often ill equipped to conduct comprehensive geriatric assessments causing missed opportunities for preventing adverse outcomes.

Purpose: To evaluate the inter-rater reliability of the interRAI Acute Care (AC) instrument for hospitalized older adults in two acute care hospitals in Ontario, Canada.

Chronic disease management models in nursing homes: a scoping review.

Objectives: Nursing home (NH) residents experience a high burden of chronic disease. Chronic disease management (CDM) can be a challenge, as the context of care provision and the way care is provided impact care delivery. This scoping review aimed to identify types of chronic diseases studied in intervention studies in NHs, influential contextual factors addressed by interventions and future CDM research considerations.

Effective Chronic Disease Interventions in Nursing Homes: A Scoping Review Based on the Knowledge-to-Action Framework.

: The purpose of this scoping review was two-fold: 1) to identify effective intervention studies addressing chronic disease for seniors living in nursing homes (e.x. chronic heart failure, diabetes, dementia, etc.

Habenular TCF7L2 links nicotine addiction to diabetes.

Diabetes is far more prevalent in smokers than non-smokers, but the underlying mechanisms of vulnerability are unknown. Here we show that the diabetes-associated gene Tcf7l2 is densely expressed in the medial habenula (mHb) region of the rodent brain, where it regulates the function of nicotinic acetylcholine receptors. Inhibition of TCF7L2 signalling in the mHb increases nicotine intake in mice and rats.

A Holistic Approach to Analyze Systemic Jasmonate Accumulation in Individual Leaves of Rosettes Upon Wounding.

Phytohormones, especially jasmonates, are known to be mediators of the plant responses to wounding and herbivore feeding. Their role in such stress responses has been largely studied locally in treated leaves. However, less is known about the induced systemic distribution of phytohormone signals upon these kinds of stresses.

Facile Preparation of Nanofibrillar Networks of "Ureido-Chitin" Containing Ureido and Amine as Chelating Functional Groups.

Aerogels of polysaccharides with chelating functions can be useful as supports in many applications because of their hosting properties. This work demonstrates a facile method for the preparation of aerogels of chitosan derivative "ureido-chitin", containing ureido functional groups. The nanofibrillar networks of "ureido-chitin" were produced by the nucleophilic addition of amine groups of chitosan with isocyanic acid prepared in situ.

Impact of the applied simulated and integrated learning approach on nursing assistants' knowledge and confidence caring for frail seniors in nursing homes.

Background: Increasing importance is being placed on optimizing the role of Nursing Aides (NAs) in improving quality of care for nursing home (NH) residents. One approach to do so is to have NAs participate in assessments embedded within the Minimum Data Set (MDS). This pilot study aimed to design and evaluate the program, a novel innovative training program for NAs employed in NHs to enhance their ability to assess residents within an inter-professional framework.

Herbivory-responsive calmodulin-like protein CML9 does not guide jasmonate-mediated defenses in Arabidopsis thaliana.

Calcium is an important second messenger in plants that is released into the cytosol early after recognition of various environmental stimuli. Decoding of such calcium signals by calcium sensors is the key for the plant to react appropriately to each stimulus. Several members of Calmodulin-like proteins (CMLs) act as calcium sensors and some are known to mediate both abiotic and biotic stress responses.

Evidence for GABA-Induced Systemic GABA Accumulation in upon Wounding.

The non-proteinogenic amino acid γ-aminobutyric acid (GABA) is present in all plant species analyzed so far. Its synthesis is stimulated by either acidic conditions occurring after tissue disruption or higher cytosolic calcium level. In mammals, GABA acts as inhibitory neurotransmitter but its function in plants is still not well understood.

Synthesis, metabolism and systemic transport of a fluorinated mimic of the endogenous jasmonate precursor OPC-8:0.

Jasmonates (JAs) are fatty acid derivatives that mediate many developmental processes and stress responses in plants. Synthetic jasmonate derivatives (commonly isotopically labeled), which mimic the action of the endogenous compounds are often employed as internal standards or probes to study metabolic processes. However, stable-isotope labeling of jasmonates does not allow the study of spatial and temporal distribution of these compounds in real time by positron emission tomography (PET).

Corticostriatal microRNAs in addiction.

Addiction is a chronically relapsing disorder characterized by compulsive drug use in spite of adverse consequences. Currently, there are very few effective treatments for addiction; in order to develop novel therapies, a clearer understanding of mechanisms underlying addiction is needed. Drugs of abuse induce lasting adaptations in corticostriatal and mesolimbic brain reward circuitry due to long-term alterations in gene expression.