Personal care workers' intention to stay in residential aged care: An integrative review.

AIM: To identify key factors that influence personal care workers' (PCW) intention to stay in residential aged care (RAC). BACKGROUND: PCWs are the 'backbone' of providing direct care in RAC settings. The well-being of older people hinges upon their dedication and commitment; thus, enhancing their intention to stay is a priority to reduce turnover and ensure continuity of care. METHODS: Six databases were searched for articles focusing on factors influencing PCWs' intention to stay in RAC. Studies were independently assessed for quality using the Joanna Briggs Institute Methodology for systematic review tools. Reporting of the results followed the PRISMA guidelines. FINDINGS: Eight articles published between 2010 and 2022 were included. The key issues were categorized as: (a) sociodemographic characteristics; (b) psychological factors; (c) workplace factors and (d) job satisfaction. Older age, being married and immigration status were positively associated with intention to stay. Work stress and burnout contributed towards demotivation, while a supportive and engaging organizational culture that recognized workers' contributions and provided appropriate remuneration and benefits, enhanced job satisfaction and retention. CONCLUSION: This review affirms the complexity of the decision-making process influencing workers' intention to stay. A comprehensive understanding of the interplay of these factors and the personal and sociocultural challenges faced by PCWs is essential to design strategies to provide support and enhance job satisfaction and retention. IMPLICATIONS FOR AGED CARE: This review showed that support from the organization is critical in improving PCWs' intention to stay in aged care. Given the interconnectedness of a range of key factors, decision-makers need to address modifiable factors holistically. Including PCWs in planning retention strategies could be the missing link in tailoring interventions towards workforce retention. IMPACT: Personal, psychological and workplace factors alone and in combination influence personal care workers' intention to stay in residential aged care (RAC). The interrelationships among the factors impacting PCWs' intention to stay are complex, wherein a change in one often influences other factors. Addressing the causes of psychological stress, improving workplace culture and understanding their interrelationships provide a foundation for co-designing strategies to promote intention to stay among PCWs in RAC. REPORTING METHOD: The authors have adhered to relevant EQUATOR guidelines PRISMA. NO PATIENT OR PUBLIC CONTRIBUTION: This integrative review is conducted with no involvement or contribution from patients or the public.

Machine-Learning Classification of Bacteria Using Two-Dimensional Tandem Mass Spectrometry.

Biothreat detection has continued to gain attention. Samples suspected to fall into any of the CDC's biothreat categories require identification by processes that require specialized expertise and facilities. Recent developments in analytical instrumentation and machine learning algorithms offer rapid and accurate classification of Gram-positive and Gram-negative bacterial species. This is achieved by analyzing the negative ions generated from bacterial cell extracts with a modified linear quadrupole ion-trap mass spectrometer fitted with two-dimensional tandem mass spectrometry capabilities (2D MS/MS). The 2D MS/MS data domain of a bacterial cell extract is recorded within five s using a five-scan average after sample preparation by a simple extraction. Bacteria were classified at the species level by their lipid profiles using the random forest, k-nearest neighbor, and multilayer perceptron machine learning models. 2D MS/MS data can also be treated as image data for use with image recognition algorithms such as convolutional neural networks. The classification accuracy of all models tested was greater than 99%. Adding to previously published work on the 2D MS/MS analysis of bacterial growth and the profiling of sporulating bacteria, this study demonstrates the utility and information-rich nature of 2D MS/MS in the identification of bacterial pathogens at the species level when coupled with machine learning.

Activation of TRPV1-Expressing Renal Sensory Nerves of Rats with N-Oleoyldopamine Attenuates High-Fat-Diet-Induced Impairment of Renal Function.

Enhanced renal sympathetic nerve activity (RSNA) contributes to obesity-induced renal disease, while the role of afferent renal nerve activity (ARNA) is not fully understood. The present study tested the hypothesis that activating the transient receptor potential vanilloid 1 (TRPV1) channel in afferent renal nerves suppresses RSNA and prevents renal dysfunction and hypertension in obese rats. N-oleoyldopamine (OLDA, 1 ng/kg, daily) was administrated intrathecally (T8-L3) via an indwelled catheter to chronically activate, TRPV1-positive afferent renal nerves in rats fed a chow diet or high-fat diet (HFD) for 8 weeks. HFD intake significantly increased the body weight, impaired glucose and insulin tolerance, decreased creatinine clearance, and elevated systolic blood pressure in rats compared with the levels of the chow-fed rats (all p < 0.05). An intrathecal OLDA treatment for 8 weeks did not affect the fasting glucose level, glucose tolerance, and insulin tolerance in rats fed either chow or HFD. As expected, the chronic OLDA treatment significantly increased the levels of plasma calcitonin gene-related peptide and substance P and ARNA in the HFD-fed rats (all p < 0.05). Interestingly, the OLDA treatment decreased the urinary norepinephrine level and RSNA in rats fed HFD (both p < 0.05). Importantly, the OLDA treatment attenuated HFD-induced decreases in creatinine clearance and urinary Na+ excretion and increases in the plasma urea level, urinary albumin level, and systolic blood pressure at the end of an 8-week treatment (all p < 0.05). Taken together, the intrathecal administration of OLDA ameliorates the enhancement of RSNA, renal dysfunction, and hypertension in obese rats. These findings shed light on the roles of TRPV1-positive renal afferent nerves in obesity-related renal dysfunction and hypertension.

Ablation of TRPV1-positive nerves exacerbates salt-induced hypertension and tissue injury in rats after renal ischemia-reperfusion via infiltration of macrophages.

Background: High-salt intake after renal ischemia/reperfusion (I/R) injury leads to hypertension and further renal injury, but the mechanisms are largely unknown. This study tested the hypothesis that degeneration of transient receptor potential vanilloid 1 (TRPV1)-positive nerves exacerbates salt-induced hypertension and renal injury after I/R via enhancing renal macrophage infiltration.Methods: Large dose of capsaicin (CAP, 100 mg/kg, subcutaneously) was used to degenerate rat TRPV1-positive nerves. Then, rats were subjected to renal I/R injury and fed with a low-salt (0.4% NaCl) diet for 5 weeks after I/R, followed by a high-salt (4% NaCl) diet for 4 weeks during which macrophages were depleted using liposome-encapsulated clodronate (LC, 1.3 ml/kg/week, intravenously).Results: The protein level of TRPV1 in the kidney was downregulated by renal I/R injury and was further decreased by CAP treatment. LC treatment did not affect the protein levels of renal TRPV1. After renal I/R injury, high-salt diet significantly increased renal macrophage infiltration, inflammatory cytokines (tumor necrosis factor-alpha and interleukin 1 beta), systolic blood pressure, the urine/water intake ratio, plasma creatine and urea levels, urinary 8-isoprostane, and renal collagen deposition. Interestingly, CAP treatment further increased these parameters. These increases were abolished by depleting macrophages with LC treatment.Conclusions: These data suggest that degenerating TRPV1-positive nerves exacerbates salt-induced hypertension and tissue injury in rats after renal I/R injury via macrophages-mediated renal inflammation.

Compliance with preventative measures during the COVID-19 pandemic in the USA and Canada: Results from an online survey.

This study explored people's compliance with recommended preventative measures during early stages of the COVID-19 pandemic. An online survey was administered in June 2020 in the USA and Canada (N = 1,405). Regression analysis found that when controlling for other factors, age and political ideology were significant predictors of compliance with preventative measures. A content analysis of narrative answers of compliance/noncompliance found that the majority of individuals intended to comply with preventative measures, with primary reasons as social responsibility, self-protection, and protection of family members. Reasons identified for not complying were viewing preventative practices as unnecessary, getting mixed messages from various sources about effectiveness, distrust in government and inability to comply. This study informs social workers on intervention strategies on micro, mezzo and macro levels of practice.

Perspectives of residents and staff regarding food choice in residential aged care: A qualitative study.

AIMS AND OBJECTIVES: To explore the experiences of food choice and meal service in residential aged care facilities and its impact on autonomy, self-determination and quality of life from the perspectives of both residents and staff. BACKGROUND: Globally, residential aged care is a principal provider of care for older people who can no longer live independently at home. Within this setting, lack of food choice has been identified as a significant factor impacting on residents' self-determination, sense of autonomy and quality of life. DESIGN: This study used an exploratory descriptive qualitative approach guided by self-determination theory. METHOD: A total of 14 participants (seven residents and seven staff members) from two Australian residential aged care facilities were recruited through purposive and snowball sampling with assistance from one independent contact nurse at each facility. In-depth, semi-structured interviews were conducted, digitally recorded and transcribed. The COREQ checklist was used in this qualitative study. RESULTS: Three main themes were identified from the interview data provided by residents and staff, which were as follows: (a) catering for the masses; (b) organisational barriers to providing choice; and (c) food impacts well-being. CONCLUSIONS: This study explored the experiences of food choice and service in residential aged care facilities, from the perspectives of both residents and staff. Results of interviews highlighted the importance of providing adequate food choice which has become an enduring issue that requires more attention and commitment to make a positive change for residents living in residential aged care facilities. RELEVANCE TO CLINICAL PRACTICE: Nurses and other staff working in residential aged care facilities need to be aware of the importance of providing adequate food choice, including for residents who require modified diets. As advocates for residents, nursing staff must address the persistent lack of food choice. However, this will require a radical change in organisational culture and strong leadership.

Knockout of TRPA1 exacerbates angiotensin II-induced kidney injury.

Macrophage-mediated inflammation plays a critical role in hypertensive kidney disease. Here, we investigated the role of transient receptor potential ankyrin 1 (TRPA1), a sensor of inflammation, in angiotensin II (ANG II)-induced renal injury. Subcutaneous infusion of ANG II (600 ng·min-1·kg-1) for 28 days was used to induce hypertension and renal injury in mice. The results showed that ANG II-induced hypertensive mice have decreased renal Trpa1 expression (P < 0.01), whereas ANG II receptor type 1a-deficient hypotensive mice have increased renal Trpa1 expression (P < 0.05) compared with their normotensive counterparts. ANG II induced similar elevations of systolic blood pressure in Trpa1-/- and wild-type (WT) mice but led to higher levels of blood urea nitrogen (P < 0.05), serum creatinine (P < 0.05), and renal fibrosis (P < 0.01) in Trpa1-/- mice than WT mice. Similarly, ANG II increased both CD68+/inducible nitric oxide synthase+ M1 and CD68+/arginase 1+ M2 macrophages in the kidneys of both Trpa1-/- and WT mice (all P < 0.01), with higher extents in Trpa1-/- mice (both P < 0.01). Compared with WT mice, Trpa1-/- mice had significantly increased expression levels of inflammatory cytokines and their receptors in the kidney. Cultured murine macrophages were stimulated with phorbol 12-myristate 13-acetate, which downregulated gene expression of TRPA1 (P < 0.01). A TRPA1 agonist, cinnamaldehyde, significantly inhibited phorbol 12-myristate 13-acetate-stimulated expression of IL-1ß and chemokine (C-C motif) ligand 2 in macrophages, which were attenuated by pretreatment with a TRPA1 antagonist, HC030031. Furthermore, activation of TRPA1 with cinnamaldehyde induced apoptosis of macrophages. These findings suggest that TRPA1 may play a protective role in ANG II-induced renal injury, likely through inhibiting macrophage-mediated inflammation.

Activation of TRPV1 Prevents Salt-Induced Kidney Damage and Hypertension After Renal Ischemia-Reperfusion Injury in Rats.

BACKGROUND/AIMS: High-salt intake after recovery from renal ischemia-reperfusion (I/R) injury leads to hypertension with severe renal damage. Transient receptor potential vanilloid type 1 (TRPV1) channels have been involved in the regulation of inflammation and oxidative stress following ischemic organ injury. We tested the hypothesis that activation of TRPV1 conveys preconditioning protection to the kidney subjected to I/R. METHODS: TRPV1 was activated or down-regulated by subcutaneous injection of a low (1mg/kg) or high (100mg/kg) dose of capsaicin, respectively, 3 hours before ischemia. Rats were fed a 0.4% NaCl diet for 5 weeks after I/R followed by a 4% NaCl diet for 4 more weeks in 4 groups: sham, I/R, I/R+high-dose capsaicin (HCap), and I/R+low-dose capsaicin (LCap). RESULTS: Renal TRPV1 expression was decreased in I/R rats (P< 0.05) and further reduced in I/R+HCap group (P< 0.05) but unchanged in I/R+LCap rats compared with the sham group. Blood pressure were elevated in I/R rats (P< 0.05) and further increased in I/R+HCap group (P< 0.05) but unchanged in I/R+LCap rats compared with sham. Renal function was impaired in I/R rats (P< 0.05) and further deteriorated in I/R+HCap group (P< 0.05) but unchanged in I/R+LCap group. Renal inflammatory responses, oxidative stress, and renal collagen deposition were augmented in I/R rats (all P< 0.05) and further intensified in I/R+HCap group (all P< 0.05) but unchanged in I/R+LCap group. CONCLUSION: Activation of TRPV1 plays an anti-inflammatory and anti-oxidative stress role in preventing renal tissue damage and salt-induced hypertension after I/R injury, indicating that TRPV1 conveys preconditioning protection that may have therapeutic implication.

Ageism among social work faculty: impact of personal factors and other "isms".

The purpose of this article was (a) to determine the extent to which ageist attitudes are evident among social work faculty and how educational factors may contribute to ageism, (b) to determine if terror management theory (in terms of aging anxiety) offers a further explanation for ageist attitudes beyond known correlates, and (c) to understand how intersecting prejudices (attitudes toward women, gay men, and lesbians) may be associated with ageist attitudes. Results indicated a low bias toward older adults, with two variables, psychological anxiety about aging and paid experience with older adults, accounting for 29.7% of the variance. Further, no association was found between ageism and sexism and sexual prejudice in the multivariate analyses. These results indicate promising advances for terror management theory in explaining ageism. Social work faculty's low bias and perceived need for gerontological content in curricula is an encouraging finding for gerontological social work education.

Predicting social work students' interest in gerontology: results from an international sample.

The need for social workers with a specialization in gerontology has become a global priority. The purpose of this study was to explore social work students' interest in gerontology. This cross-sectional survey was completed by 1,042 students from the United States, England, and Australia, and only 5.4% of the sample indicated an interest in gerontology. Results of the logistic regression found that personal aging beliefs and the frequency of time spent with an older adult were significant in explaining gerontological interest. The infusion of aging content may facilitate further advancement in the field, but additional strategies may also be needed.

Transient receptor potential vanilloid in blood pressure regulation.

PURPOSE OF REVIEW: The involvement of neurohormonal factors in the pathogenesis of hypertension has been extensively studied. However, the mechanisms underlying the role of the transient receptor potential vanilloid type 1 (TRPV1) channels in hypertension are still largely unknown. This review presents some of the most recent findings regarding the potential mechanisms of TRPV1 in mediating blood pressure, the pathophysiology of hypertension, and its related disorders. RECENT FINDINGS: TRPV1 may be activated by exogenous vanilloid or endo-vanilloid compounds and its function modulated by vasoactive mediators. TRPV1 also interacts with various physiological and pathophysiological systems involved in salt and water homeostasis and cardiovascular homeostasis. Impairment of TRPV1 signaling may contribute to the pathogenesis of diseases such as hypertension, heart failure, atherosclerosis, diabetes, obesity, myocardial ischemia, and stroke. SUMMARY: Accumulating evidence implicates TRPV1 as serving a key role in cardiovascular health by regulating cardiovascular function and protecting against cardiovascular injury. Given the large prevalence of hypertension and its related disorders, the possible involvement of TRPV1 makes it a potential target of therapy for cardiovascular disease. Future study of TRPV1 may enhance our understanding of several cardiovascular diseases and may unveil novel pharmacological strategies for treating hypertension.

Role of the transient receptor potential vanilloid type 1 channel in renal inflammation induced by lipopolysaccharide in mice.

To determine the role of the transient receptor potential vanilloid type 1 (TRPV1) channel in the regulation of renal inflammation, lipopolysaccharide (LPS, 3 mg/kg) was intraperitoneally injected into wild-type (WT) and TRPV1-null mutant (TRPV1(-/-)) mice. The kidney and serum were collected 6 or 24 h after LPS injection for morphological analysis and proinflammatory cytokine assay. LPS injection led to a similar degree of transient hypotension and bradycardia in WT and TRPV1(-/-) mice determined by a telemetry system. LPS administration caused parenchymal red blood cell congestion and fading of intact glomerular structure in TRPV1(-/-) compared with WT mice. Serum creatinine levels were higher 24 h after LPS injection in TRPV1(-/-) than in WT mice. Neutrophil and macrophage infiltration in the kidneys was greater 6 h for the former and 24 h for both after LPS injection in TRPV1(-/-) than in WT mice. Serum cytokine levels including tumor necrosis factor (TNF)-α, IL-1ß, and IL-6 were higher 6 h after LPS injection in TRPV1(-/-) compared with WT mice. Likewise, renal chemokine levels including keratinocyte-derived chemokines and macrophage inflammatory protein were higher 6 h after LPS injection in TRPV1(-/-) than in WT mice. Renal VCAM-1 and ICAM-1 expression was further elevated 6 h for the former and 24 h for the latter after LPS injection in TRPV1(-/-) than in WT mice. Renal nuclear factor-κB (NF-κB) activity was further increased 6 h after LPS injection in TRPV1(-/-) compared with WT mice. Pharmacological blockade TRPV1 in WT mice showed aggravated renal and serum inflammatory responses resembling that of TRPV1(-/-) mice. Thus TRPV1 gene ablation exacerbates LPS-induced renal tissue and function injury, including aggravated renal neutrophil and macrophage infiltration, chemokine and adhesion molecule levels, and glomerular hypercellularity accompanying with further increased serum creatinine and cytokine levels. These results indicate that TRPV1 is activated during LPS challenge, which may constitute a protect mechanism against LPS-induced renal injury via reducing renal inflammatory responses.

Cellular biophysical dynamics and ion channel activities detected by AFM-based nanorobotic manipulator in insulinoma ß-cells.

Distinct biochemical, electrochemical and electromechanical coupling processes of pancreatic ß-cells may well underlie different response patterns of insulin release from glucose and capsaicin stimulation. Intracellular Ca(2+) levels increased rapidly and dose-dependently upon glucose stimulation, accompanied with about threefold rapid increases in cellular stiffness. Subsequently, cellular stiffness diminished rapidly and settled at a value about twofold of the baseline. Capsaicin caused a similar transient increase in intracellular Ca(2+) changes. However, cellular stiffness increased gradually to about twofold until leveling off. The current study characterizes for the first time the biophysical properties underlying glucose-induced biphasic responses of insulin secretion, distinctive from the slow and single-phased stiffness response to capsaicin despite similar changes in intracellular Ca(2+) levels. The integrated AFM nanorobotics and optical investigation enables the fine dissection of mechano-property from ion channel activities in response to specific and non-specific agonist stimulation, providing novel biomechanical markers for the insulin secretion process. FROM THE CLINICAL EDITOR: This study characterizes the biophysical properties underlying glucose-induced biphasic responses of insulin secretion. Integrated AFM nanorobotics and optical investigations provided novel biomechanical markers for the insulin secretion process.

Social work faculty interest in aging: impact of education, knowledge, comfort, and experience.

As the need for gerontological social workers increases, it is important to assess faculty interest in strengthening and bolstering this area in the classroom and curriculum. This study sought to compare training and experience of social work faculty that identified aging as a teaching or research interest with faculty who did not, and to identify predictors of aging interest among faculty. A national sample of social work faculty members was recruited, and a total of 609 individuals participated in the study. The findings reveal that faculty with an interest in aging differed from nonaging faculty in the areas of knowledge of older adults, personal and paid experience, and graduate and continuing education. In addition, predictors of interest in aging included taking a graduate course, continuing education units, having paid and volunteer experience, level of knowledge of older adults, and comfort level of covering content on aging in the classroom. The connection between social work faculty and student interest in aging are discussed as implications for further social work research and education.

Family visits and depression among residential aged care residents: An integrative review.

BACKGROUND: Depression in older people living in residential aged care is a serious and highly prevalent health issue, with loneliness and social isolation being major contributors. The COVID-19 pandemic underscored the harm visiting restrictions have on the mental wellbeing of older people in residential aged care. However, there is a need to systematically review the relationship between family visits and depression in this population. OBJECTIVE: This literature review seeks to explore the association between family visits and depression among those living in residential aged care. METHODS: An integrative review was conducted in March 2022, based on a search of seven databases from inception to 2022. Papers were included if the studies were situated in a residential aged care facility and explored the impact of in-person family visits on depression of residents. Those that examined impact of family visits on community-dwelling older people and papers examining virtual family visits were excluded. The quality of the included papers was assessed using appropriate critical appraisal tools. Guided by the aim of this study, the included papers were narratively synthesised and presented thematically (PROSPERO ID CRD42022325895). RESULTS: Ten papers, published between 1991 and 2022, were included in the final synthesis. Multiple categorisations of frequency of visits and different scales were used to assess depression. Depression among residents in aged care facilities varied from 20 % to 58.7 % with 40 % of studies showing a positive association between the frequency of family visits and lower rate of depression. Three themes influencing the association between family visits and depression in residential aged care were identified. These were: (i) intersection of culture, filial values, and depression; (ii) resident-related factors including whether admission was voluntary and presence of functional impairment; and (iii) non-resident-related factors such as social activities for residents and staff involvement. CONCLUSION: Family visits ameliorated loneliness and depression among residents in aged care however, other factors such as culture, comorbidities and functional impairment, opportunities for socialisation and the social involvement of facility staff also influenced depression. Whilst the low number of studies reviewed limited comparison and generalisation of results, the review highlighted the broader and crucial role of healthcare staff in facilitating socialisation and promoting mental wellbeing of residents especially those who are not visited by families. TWEETABLE ABSTRACT: Family visits ameliorate depression in institutionalised older people but may not be the "silver bullet" as depression is multifactorial.

IL-22RA2 Is a SMAD7 Target Mediating the Alleviation of Dermatitis and Psoriatic Phenotypes in Mice.

Long-term management of inflammatory skin diseases is challenging because of side effects from repeated use of systemic treatments or topical corticosteroids. This study sought to identify the mechanisms and developmental therapeutics for these diseases using genetic models and pharmacological approaches. We found that mice overexpressing SMAD7 in keratinocytes but not mice overexpressing the N-terminal domain of SMAD7 (i.e., N-SMAD7) were resistant to imiquimod-induced T helper 1/17- and T helper 2-type inflammation. We generated a Tat-PYC-SMAD7 (truncated SMAD7 protein encompassing C-terminal SMAD7 and PY motif fused with cell-penetrating Tat peptide). Topically applied Tat-PYC-SMAD7 to inflamed skin entered cells upon contact and attenuated imiquimod-, 2,4-dinitrofluorobenzene-, and tape-stripping-induced inflammation. RNA-sequencing analyses of mouse skin exposed to these insults showed that in addition to inhibiting TGFß/NF-κB, SMAD7 blunted IL-22/signal transducer and activator of transcription 3 activation and associated pathogenesis, which is due to SMAD7 transcriptionally upregulating IL-22 antagonist IL-22RA2. Mechanistically, SMAD7 facilitated nuclear translocation and DNA binding of C/EBPß to IL22RA2 promoter for IL22RA2 transactivation. Consistent with the observations in mice mentioned earlier, transcript levels of IL22RA2 were increased in human atopic dermatitis and psoriasis lesions with clinical remission. Our study identified the anti-inflammation functional domain of SMAD7 and suggests the mechanism and feasibility for developing SMAD7-based biologics as a topical therapy for skin inflammatory disorders.

Knockout of Trpa1 accelerates age-related cardiac fibrosis and dysfunction.

Age-related cardiac fibrosis contributes to the development of heart failure with preserved ejection fraction which lacks ideal treatment. Transient receptor potential ankyrin 1 (TRPA1) is an oxidative stress sensor and could attenuate age-related pathologies in invertebrates. The present study aimed to test whether TRPA1 plays a role in age-related cardiac remodeling and dysfunction. The cardiac function and pathology of 12-week-old (young) and 52-week-old (older) Trpa1-/- mice and wild-type (WT) littermates were evaluated by echocardiography and histologic analyses. The expression levels of 84 fibrosis-related genes in the heart were measured by quantitative polymerase chain reaction array. Young Trpa1-/- and WT mice had similar left ventricular wall thickness, volume, and systolic and diastolic function. Older Trpa1-/- mice had significantly increased left ventricular internal diameter and volume and impaired systolic (lower left ventricular ejection fraction) and diastolic (higher E/A ratio and isovolumetric relaxation time) functions compared with older WT mice (P<0.05 or P<0.01). Importantly, older Trpa1-/- mice had enhanced cardiac fibrosis than older WT mice (P<0.05) while the two strains had similar degree of cardiac hypertrophy. Among the 84 fibrosis-related genes, Acta2, Inhbe, Ifng, and Ccl11 were significantly upregulated, while Timp3, Stat6, and Ilk were significantly downregulated in the heart of older Trpa1-/- mice compared with older WT mice. Taken together, we found that knocking out Trpa1 accelerated age-related myocardial fibrosis, ventricular dilation, and cardiac dysfunction. These findings suggest that TRPA1 may become a therapeutic target for preventing and/or treating cardiac fibrosis and heart failure with preserved ejection fraction in the elderly.

Activation of TRPV1 improves natriuresis and salt sensitivity in high-fat diet fed mice.

Western diet (WD) intake increases morbidity of obesity and salt-sensitive hypertension albeit mechanisms are largely unknown. We investigated the role of transient receptor potential vanilloid 1 (TRPV1) in WD intake-induced hypertension. TRPV1-/- and wild-type (WT) mice were fed a normal (CON) or Western diet (WD) for 16-18 weeks. Mean arterial pressure (MAP) after normal sodium glucose (NSG) loading with or without L-NAME (a NO synthase inhibitor) or N-oleoyldopamine (OLDA, a TRPV1agonist) was not different between the two strains on CON.WT or TRPV1-/- mice fed WD had increased MAP after NSG, with a greater magnitude in TRPV1-/- mice. OLDA decreased while L-NAME increased MAP in WT-WD but not in TRPV1-/--WD mice. The urinary nitrates plus nitrites excretion (UNOx), an indicator of renal NO production, was increased in both strains on CON after NSG. TRPV1 ablation with WD intake abolished NSG-induced increment in UNOx. OLDA further increased while L-NAME prevented NSG-induced increment in UNOx in WT-WD mice. Urinary sodium excretion was increased in both strains on CON and in WT-WD mice but not in TRPV1-/--WD mice after NSG. OLDA further increased while L-NAME prevented NSG-induced increases in sodium excretion in WT-WD but not in TRPV1-/--WD mice. Thus, TRPV1 ablation increases salt sensitivity during WD intake possibly via impaired renal NO production and sodium excretion. Activation of TRPV1 enhances renal NO production and sodium excretion, resulting in prevention of increased salt sensitivity during WD intake.