TRPV4-Expressing Tissue-Resident Macrophages Regulate the Function of Collecting Lymphatic Vessels via Thromboxane A2 Receptors in Lymphatic Muscle Cells.

Rationale: TRPV4 channels are critical regulators of blood vascular function and have been shown to be dysregulated in many disease conditions in association with inflammation and tissue fibrosis. These are key features in the pathophysiology of lymphatic system diseases, including lymphedema and lipedema; however, the role of TRPV4 channels in the lymphatic system remains largely unexplored. TRPV4 channels are calcium permeable, non-selective cation channels that are activated by diverse stimuli, including shear stress, stretch, temperature, and cell metabolites, which may regulate lymphatic contractile function.

Necessary Role of Ceramides in the Human Microvascular Endothelium During Health and Disease.

Background: Elevated plasma ceramides and microvascular dysfunction both independently predict adverse cardiac events. Despite the known detrimental effects of ceramide on the microvasculature, evidence suggests that activation of the shear-sensitive, ceramide-forming enzyme NSmase (neutral sphingomyelinase) elicits formation of vasoprotective nitric oxide (NO). Here, we explore a novel hypothesis that acute ceramide formation through NSmase is necessary for maintaining NO signaling within the human microvascular endothelium.

Necessary Role of Acute Ceramide Formation in The Human Microvascular Endothelium During Health and Disease.

Background: Elevated plasma ceramides independently predict adverse cardiac events and we have previously shown that exposure to exogenous ceramide induces microvascular endothelial dysfunction in arterioles from otherwise healthy adults (0-1 risk factors for heart disease). However, evidence also suggests that activation of the shear-sensitive, ceramide forming enzyme neutral sphingomyelinase (NSmase) enhances vasoprotective nitric oxide (NO) production. Here we explore a novel hypothesis that acute ceramide formation through NSmase is necessary for maintaining NO signaling within the human microvascular endothelium.

17β-Estradiol promotes sex-specific dysfunction in isolated human arterioles.

Despite data showing that estrogen is vasculoprotective in large conduit arteries, hormone therapy (HT) during menopause has not proven to mitigate cardiovascular disease (CVD) risk. Estrogen exposure through prolonged oral contraceptive use and gender-affirming therapy can also increase cis- and trans-females' risk for future CVD, respectively. The microvasculature is a unique vascular bed that when dysfunctional can independently predict future adverse cardiac events; however, studies on the influence of estrogen on human microvessels are limited.

S1P (Sphingosine-1-Phosphate)-Induced Vasodilation in Human Resistance Arterioles During Health and Disease.

Background: Preclinical studies suggest that S1P (sphingosine-1-phosphate) influences blood pressure regulation primarily through NO-induced vasodilation. Because microvascular tone significantly contributes to mean arterial pressure, the mechanism of S1P on human resistance arterioles was investigated. We hypothesized that S1P induces NO-mediated vasodilation in human arterioles from adults without coronary artery disease (non-coronary artery disease) through activation of 2 receptors, S1PR (S1P receptor 1) and S1PR (S1P receptor 3).

Blockade of endothelial Mas receptor restores the vasomotor response to phenylephrine in human resistance arterioles pretreated with captopril and exposed to propofol.

Background: Hypotension that is resistant to phenylephrine is a complication that occurs in anesthetized patients treated with angiotensin converting enzyme (ACE) inhibitors. We tested the hypothesis that Ang 1-7 and the endothelial Mas receptor contribute to vasodilation produced by propofol in the presence of captopril.

Methods: The internal diameters of human adipose resistance arterioles were measured before and after administration of phenylephrine (10 to 10 M) in the presence and absence of propofol (10 M; added 10 min before the phenylephrine) or the Mas receptor antagonist A779 (10 M; added 30 min before phenylephrine) in separate experimental groups.

Role of Adiponectin Receptor 1 in Promoting Nitric Oxide-Mediated Flow-Induced Dilation in the Human Microvasculature.

Chronic administration of exogenous adiponectin restores nitric oxide (NO) as the mediator of flow-induced dilation (FID) in arterioles collected from patients with coronary artery disease (CAD). Here we hypothesize that this effect as well as NO signaling during flow during health relies on activation of Adiponectin Receptor 1 (AdipoR1). We further posit that osmotin, a plant-derived protein and AdipoR1 activator, is capable of eliciting similar effects as adiponectin.

The anti-viral dynamin family member MxB participates in mitochondrial integrity.

The membrane deforming dynamin family members MxA and MxB are large GTPases that convey resistance to a variety of infectious viruses. During viral infection, Mx proteins are known to show markedly increased expression via an interferon-responsive promoter to associate with nuclear pores. In this study we report that MxB is an inner mitochondrial membrane GTPase that plays an important role in the morphology and function of this organelle.

Manipulation of the Sphingolipid Rheostat Influences the Mediator of Flow-Induced Dilation in the Human Microvasculature.

Background Elevated levels of ceramide, a sphingolipid known to cause a transition from nitric oxide (NO)- to hydrogen peroxide-dependent flow-induced dilation (FID) in human arterioles, correlate with adverse cardiac events. However, elevations of ceramide are associated with changed concentrations of other sphingolipid metabolites. The effects of sphingolipid metabolites generated through manipulation of this lipid pathway on microvascular function are unknown.

Taking the lead: Supporting staff in coping with grief and loss in dementia care.

Healthcare providers working with people living with dementia often experience a profound sense of grief when the person they support dies or moves to an alternative level of care. Unattended staff grief can impact healthcare leaders by reducing quality of care, increasing staff turnover and absenteeism, lowering morale, and creating a greater risk of long-term staff health problems. Organizational and self-care strategies can mitigate these challenges.

Know me - A new person-centered approach for dementia-friendly emergency department care.

A visit to an emergency department can be a disorientating experience for someone with dementia. Empowered caregivers can mitigate harm stemming from communication issues to support a successful emergency department visit. A qualitative study determined the feasibility of the structure, format, and content of eight hospital-readiness communication tools.

Vps4 stimulatory element of the cofactor Vta1 contacts the ATPase Vps4 α7 and α9 to stimulate ATP hydrolysis.

The endosomal sorting complexes required for transport (ESCRTs) function in a variety of membrane remodeling processes including multivesicular body sorting, abscission during cytokinesis, budding of enveloped viruses, and repair of the plasma membrane. Vps4 ATPase activity modulates ESCRT function and is itself modulated by its cofactor Vta1 and its substrate ESCRT-III. The carboxyl-terminal Vta1/SBP-1/Lip5 (VSL) domain of Vta1 binds to the Vps4 β-domain to promote Vps4 oligomerization-dependent ATP hydrolysis.

Resources for people with dementia: the Alzheimer Society and beyond.

Objective: To summarize services provided by the Alzheimer Society and discuss other supports and resources available for the management of people with dementia.

Sources Of Information: Ovid MEDLINE was searched using the terms dementia, Alzheimer disease, community health services utilization, and caregiver stress.

Main Message: Early diagnosis of dementia has been shown to be of benefit to patients and caregivers.

Personal perspectives of persons with Alzheimer's disease and their carers: a global survey.

Background: Alzheimer's disease (AD) impacts on persons with AD as well their families. This survey aimed to identify information/communication gaps, and quality of life and other issues, from both perspectives.

Methods: Persons with AD and their families or other carers from Europe, Brazil, and North America completed telephone interviews.