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1.
Am J Infect Control ; 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38657906

RESUMEN

BACKGROUND: Facial protective equipment (FPE) adherence is necessary for the health and safety of nursing professionals. This review was conducted to synthesize predisposing, enabling, and reinforcing factors that influence FPE adherence, and thus inform efforts to promote adherence. METHODS: Articles were collected using Cumulated Index to Nursing and Allied Health Literature and MEDLINE and screened for inclusion. Included articles were original studies focused on FPE adherence by nurses to prevent respiratory infection which contained occupation-specific data from at least 10 individuals and were published in English between January 2005 and February 2022. RESULTS: Thirty articles were included, 21 of which reported adherence rates. Adherence ranged from 33% to 100% for respiratory protection and 22% to 100% for eye protection. Predisposing demographic factors influencing adherence included tenure and occupation, while modifiable predisposing factors included knowledge and perception of FPE, infection transmission, and risk. Enabling factors included geography, care settings, and FPE availability. Reinforcing factors included organizational support for health and safety, clear policies, and training. CONCLUSIONS: The identified demographic factors suggest populations that may benefit from targeted interventions, while modifiable factors suggest opportunities to enhance education as well as operational processes and supports. Interventions that target these areas have the potential to promote adherence and thereby improve the occupational safety of nurses.

2.
Diagnostics (Basel) ; 14(7)2024 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-38611687

RESUMEN

BACKGROUND: Each year, millions of Americans develop truncal pressure ulcers (PUs) which can persist for months, years, or until the end of life. Despite the negative impact on quality of life and escalating costs associated with PUs, there is sparse evidence supporting validated and efficacious treatment options. As a result, treatment is based on opinion and extrapolation from other wound etiologies. The ideal reconstructive plan maximizes the patient's nutritional status, incorporates the basic tenets of wound bed preparation (debridement, offloading, proper moisture balance, reduction of bacterial burden), and employs diagnostics to guide therapeutic intervention. The use of combination therapies can potentially overcome several of the barriers to wound healing. Negative pressure wound therapy (NPWT), a commonly used modality in the management of PUs, facilitates healing by stimulating the formation of granulation tissue and promoting wound contraction; however, NPWT alone is not always effective. Clinical studies examining microbial bioburden in PUs determined that most ulcers contain bacteria at levels that impede wound healing (>104 CFU/g). OBJECTIVE: Thus, we hypothesized that adding an anti-microbial agent to decrease both planktonic and biofilm bacteria in the wound would increase the efficacy of NPWT. METHOD: In this prospective study, twenty patients with recalcitrant PUs that previously failed NPWT were treated with a biofilm-disrupting agent (Blast-X, Next Science, Jacksonville, FL, USA) in combination with NPWT. Fluorescence imaging was used to follow bacterial burden and guide therapy. RESULTS: In total, 45% of the PUs reduced in size over the course of the four-week study, with a resolution of bacterial fluorescence in the NPWT dressing and wound bed seen in an average of three weeks. CONCLUSION: The combination of an antibiofilm agent and NPWT reduced bacterial levels and improved wound healing in recalcitrant PUs.

3.
Workplace Health Saf ; : 21650799241232148, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38454778

RESUMEN

BACKGROUND: Workplace violence and harassment are commonplace for healthcare workers and most incidents are unreported. Normalization of these experiences, lack of confidence in reporting systems, and fear of the consequences of reporting contribute to the invisibility of these experiences. Challenges are exacerbated in homecare settings and for precarious workforces including Personal Support Workers (PSWs). We created, piloted, and evaluated an intervention to enhance safety culture and encourage reporting of workplace violence and harassment. METHODS: A multi-stakeholder steering committee designed an intervention combining policy changes, a pre-visit screening tool, education, and brief end-of-visit reporting. This was piloted with a PSW care team which provided >55,000 client visits during the 32-week intervention. Operational metrics characterized screening, education, and reporting uptake. Pre- and post-intervention surveys characterized PSWs' experiences with workplace violence and harassment, reporting experiences, training history and intervention feedback. FINDINGS: PSWs reported increased comfort discussing workplace violence and harassment, and increased confidence managing client-to-worker incidents. The screening went smoothly with most clients in private homes. Most PSWs (75%) engaged at least once with end-of-visit reporting and nearly half submitted reports regularly. During the pilot, 21% of PSWs reported incidents and 52% of reports shared client-specific strategies for managing these situations. APPLICATION TO PRACTICE: Changes in comfort and behavior with reporting indicated a shift toward a more open culture surrounding workplace violence and harassment. Tools created for this intervention and lessons for implementation are shared for consideration by occupational health practitioners throughout the homecare sector.

4.
Gerontol Geriatr Med ; 10: 23337214241237119, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38487275

RESUMEN

Grab bars facilitate bathing and reduce the risk of falls during bathing. Suction cup handholds and rim-mounted tub rails are an alternative to grab bars. The objective of this study was to determine whether older adults could install handholds and tub rails effectively to support bathing transfers. Participants installed rim-mounted tub rails and suction cup handholds in a simulated bathroom environment. Installation location and mechanical loading performance were evaluated. Participant perceptions during device installation and a bathing transfer were characterized. While 85% of suction cup handholds met loading requirements, more than half of participants installed the suction cup handhold in an unexpected location based on existing guidance documents. No rim-mounted tub rails were successfully installed. Participants were confident that the devices had been installed effectively. Suction cup handholds and rim mounted tub rails are easy to install, but clients may need additional guidance regarding where, and how to install them.

5.
J Wound Care ; 33(Sup3): S39-S43, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38457305

RESUMEN

DECLARATION OF INTEREST: TS is a consultant for Inotec AMD Ltd., UK. The authors have no other conflicts of interest to declare.


Asunto(s)
Diabetes Mellitus , Pie Diabético , Humanos , Pie Diabético/tratamiento farmacológico , Cicatrización de Heridas
6.
J Community Health Nurs ; 41(3): 175-188, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38391137

RESUMEN

PURPOSE: This study describes how an employer-based tuition-assistance program for homecare workers at one Canadian homecare organization enabled nursing career advancement and retention. DESIGN: A convergent parallel mixed-methods design. METHODS: We reviewed existing administrative data and concurrently conducted semi-structured interviews. Descriptive statistics were used on quantitative data and qualitative data was analyzed using thematic analysis. A joint data display was developed to integrate findings from both quantitative and qualitative data together. FINDINGS: Tuition assistance reduced financial barriers to career advancement; 83% of recipients remained with their employer for at least 1-year post-studies but only 29% experienced career advancement. Psychosocial supports, career navigation and coaching to ease the licensing and role transition processes were identified as opportunities to support learners. CONCLUSION: Employer-based tuition assistance programs are impactful in helping to develop skilled employees. Practical enhancements to further support career transitions may maximize retention to address urgent homecare staffing challenges. CLINICAL EVIDENCE: Employer-based tuition assistance can be a useful strategy to support nursing career growth and staff retention.


Asunto(s)
Servicios de Atención de Salud a Domicilio , Humanos , Femenino , Masculino , Adulto , Servicios de Atención de Salud a Domicilio/organización & administración , Persona de Mediana Edad , Canadá , Reorganización del Personal , Investigación Cualitativa , Movilidad Laboral , Entrevistas como Asunto
7.
J Wound Care ; 33(2): 84-89, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38329833

RESUMEN

OBJECTIVE: Excessive numbers of bacteria in hard-to-heal wounds impede wound healing. Numerous topical antiseptics have demonstrated effectiveness in benchtop studies; however, few clinical studies have demonstrated efficacy in the target population: patients with hard-to-heal wounds. This study addressed the clinical efficacy of a novel antibiofilm cleanser and gel in reducing bacterial load and improving wound outcomes. METHOD: Hard-to-heal wounds were photographed, measured and evaluated for bacterial load using fluorescence imaging weekly for four weeks. The target ulcers were randomised to be cleaned and treated with either a synergistic antibiofilm cleanser and antibiofilm gel with standard of care (AMC-AMG + SoC) or normal saline wash and an amorphous gel with standard of care (NSS-HG + SoC). RESULTS: A Chi-squared test of independence determined that the relationship between the treatment and the patient reaching 40% percentage area reduction (PAR) in four weeks was not significant (χ2(1, n=54)=0.73; p=0.39 at a significance level of 0.05); however, there was a strong trend favouring the antibiofilm cleanser and gel. A significant reduction (p<0.05) in bacterial load was observed in the antibiofilm group. CONCLUSION: This randomised controlled double-blind proof-of-concept study suggests that the performance of antibiofilm agents in vivo is comparable to that in vitro studies.


Asunto(s)
Antiinfecciosos Locales , Antiinfecciosos , Úlcera Varicosa , Humanos , Antiinfecciosos/uso terapéutico , Antiinfecciosos Locales/uso terapéutico , Resultado del Tratamiento , Úlcera Varicosa/terapia , Cicatrización de Heridas , Método Doble Ciego
8.
J Virol ; 98(2): e0162323, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38193692

RESUMEN

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus responsible for adult T-cell leukemia/lymphoma, a severe and fatal CD4+ T-cell malignancy. Additionally, HTLV-1 can lead to a chronic progressive neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis. Unfortunately, the prognosis for HTLV-1-related diseases is generally poor, and effective treatment options are limited. In this study, we designed and synthesized a codon optimized HTLV-1 envelope (Env) mRNA encapsulated in a lipid nanoparticle (LNP) and evaluated its efficacy as a vaccine candidate in an established rabbit model of HTLV-1 infection and persistence. Immunization regimens included a prime/boost protocol using Env mRNA-LNP or control green fluorescent protein (GFP) mRNA-LNP. After immunization, rabbits were challenged by intravenous injection with irradiated HTLV-1 producing cells. Three rabbits were partially protected and three rabbits were completely protected against HTLV-1 challenge. These rabbits were then rechallenged 15 weeks later, and two rabbits maintained sterilizing immunity. In Env mRNA-LNP immunized rabbits, proviral load and viral gene expression were significantly lower. After viral challenge in the Env mRNA-LNP vaccinated rabbits, an increase in both CD4+/IFN-γ+ and CD8+/IFN-γ+ T-cells was detected when stimulating with overlapping Env peptides. Env mRNA-LNP elicited a detectable anti-Env antibody response after prime/boost vaccination in all animals and significantly higher levels of neutralizing antibody activity. Neutralizing antibody activity was correlated with a reduction in proviral load. These findings hold promise for the development of preventive strategies and therapeutic interventions against HTLV-1 infection and its associated diseases.IMPORTANCEmRNA vaccine technology has proven to be a viable approach for effectively triggering immune responses that protect against or limit viral infections and disease. In our study, we synthesized a codon optimized human T-cell leukemia virus type 1 (HTLV-1) envelope (Env) mRNA that can be delivered in a lipid nanoparticle (LNP) vaccine approach. The HTLV-1 Env mRNA-LNP produced protective immune responses against viral challenge in a preclinical rabbit model. HTLV-1 is primarily transmitted through direct cell-to-cell contact, and the protection offered by mRNA vaccines in our rabbit model could have significant implications for optimizing the development of other viral vaccine candidates. This is particularly important in addressing the challenge of enhancing protection against infections that rely on cell-to-cell transmission.


Asunto(s)
Virus Linfotrópico T Tipo 1 Humano , Vacunas Virales , Vacunas de ARNm , Animales , Humanos , Conejos , Anticuerpos Neutralizantes , Formación de Anticuerpos , Codón , Virus Linfotrópico T Tipo 1 Humano/fisiología , Leucemia de Células T , Vacunas de ARNm/inmunología , Enfermedades Neurodegenerativas , ARN Mensajero/genética , Vacunas Virales/inmunología
9.
Cardiol Young ; 34(2): 439-441, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38088365

RESUMEN

A 50-year-old woman who had atrial septal defect surgery at 11 months old underwent ascending aortic aneurysm resection and two attempts at closure of a residual atrial septal defect. Post-operatively, she had severe cyanosis. She was referred to our centre where a transesophageal echocardiogram and cardiac catheterisation showed an iatrogenic interatrial tunnel-type communication that was closed with an Amplatzer Vascular Plug.


Asunto(s)
Defectos del Tabique Interatrial , Femenino , Humanos , Persona de Mediana Edad , Cateterismo Cardíaco , Ecocardiografía Transesofágica , Defectos del Tabique Interatrial/cirugía , Enfermedad Iatrogénica , Resultado del Tratamiento
10.
JFMS Open Rep ; 9(2): 20551169231216859, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38146394

RESUMEN

Case summary: Ductal plate malformations (DPMs) are poorly documented in the veterinary literature, particularly those of the polycystic liver disease (PCLD) phenotype. A 13-year-old female spayed cat presented with progressive icterus, abdominal distension, weight loss and elevated liver enzymes. Initial empirical treatment consisting of amoxicillin/clavulanate, ursodiol and later prednisolone was attempted; however, clinical signs progressed. On abdominal ultrasound, numerous large hepatic cystic masses were noted, characterized by an anechoic center with a heterogeneous, hyperechoic wall. A post-mortem examination confirmed numerous hepatic cysts, the larger of which resulted in hemorrhage and subsequent hemoabdomen. Histologically, these cysts were determined to be of biliary origin, and a diagnosis of PCLD was assigned. Relevance and novel information: Herein, we present a detailed report of clinical, gross and histologic findings in a cat clinically affected by PCLD. This case demonstrates that cysts present in this congenital disease can ultimately lead to hepatobiliary malfunction and clinical decline via marked expansion of cysts, compression of the liver and hemoabdomen from cyst rupture. DPMs, specifically PCLD, should be considered in cats presenting with multifocal large hepatic cysts.

11.
Health Serv Insights ; 16: 11786329231211774, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38028118

RESUMEN

Background: Reducing hospital readmissions can improve individual health outcomes and lower system-level costs. This study aimed to understand the characteristics of home care Personal Support clients who experienced a hospital admission (ie, hospital hold) and to identify factors that predict hospital readmission within 30 days of resuming home care Personal Support services. Methods: We conducted a retrospective cohort study using client administrative data from a home healthcare provider organization (2018-2021). The sample included clients (⩾18 years) who received publicly funded Personal Support services and experienced a hospital hold. Descriptive statistics and a binary logistic regression model analyzed the relationship between demographics, hospital service utilization, home care service utilization, and contextual factors on the outcome of 30-day hospital readmission. Results: Approximately 17% (n = 662) of all clients with a hospital hold (n = 3992) were readmitted to hospital within 30 days. Compared with non-readmitted clients, those with greater home care Personal Support service intensity after the index hospital hold were less likely to experience a hospital 30-day readmission. In contrast, those with greater acuity, higher assessed care needs, more hospital holds overall, more extended hospital stays (⩾2 weeks), and lower social support had a higher likelihood of 30-day hospital readmission. Conclusion: The findings from this study provide a greater understanding of factors associated with home care clients' risk of hospital readmission within 30 days and can be used to inform targeted, evidence-based support to reduce home care clients' hospital readmissions.

12.
Health Serv Insights ; 16: 11786329231210692, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38028120

RESUMEN

Home care personal support service delivery decreased during the COVID-19 pandemic, and qualitative studies have suggested many potential contributors to these reductions. This paper provides insight into the source (client or provider) of reductions in home care service volumes early in the pandemic through analysis of a retrospective administrative dataset from a large provider organization. The percentage of authorized services not delivered was 17.2% in Wave 1, 12.6% in Wave 2 and 10.5% in Wave 3, nearing the pre-pandemic baseline of 8.9%. The dominant contribution to reduced home care service volumes was client-initiated holds and cancellations, collectively accounting for 99.3% of the service volume; missed care visits by the provider accounted for 0.7%. Worker availability also declined due to long-term absences (which increased 5-fold early in Wave 1 and remained 4× above baseline in Waves 2 and 3); short-term absences rose sharply for 6 early-pandemic weeks, then dropped below the pre-pandemic baseline. These data reveal that service volume reductions were primarily driven by client-initiated holds and cancellations; despite unprecedented decreases in Personal Support Worker availability, missed care did not increase, indicating that the decrease in demand was more substantial and occurred earlier than the decrease in worker availability.

13.
Clin Nutr ; 42(11): 2241-2248, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37806076

RESUMEN

BACKGROUND & AIMS: Catheter-related bloodstream infection (CRBSI) is the most common, potentially life-threatening complication of long-term parenteral nutrition (PN). We prospectively assessed the incidence and risk factors for CRBSI in children receiving long-term home PN (HPN) for intestinal failure (IF) in a single IF rehabilitation center. METHODS: Data regarding episodes and potential risk factors for CRBSI in children on HPN were prospectively recorded. RESULTS: Forty-one of 75 children were diagnosed with CRBSI. The overall CRBSI rate was 1.61 per 1000 catheter days. The indications for HPN were gastrointestinal motility disorders in 35%, short bowel syndrome (SBS) in 28% graft versus host disease (GvHD) post bone marrow transplant in 17%, congenital enteropathy in 15%, and severe neurodevelopmental impairment in 5%. Gastrointestinal motility disorders had significantly higher CRBSI rate compared to other groups (p < 0.0005; 2.74 in motility group vs 1.54 in GvHD group vs 0.52 in congenital enteropathies vs 0.36 in SBS group vs 0.67 in severe neurodevelopmental delay). Multivariate analysis revealed that enterocutaneous distal stoma (ileostomy or colostomy) (HR 3.35 [95% CI, 1.63-6.86]; p < 0.001), age <2 years (HR 0.28 [95% CI, 0.15-0.53]; p < 0.0001), male sex (HR 2.28 [95% CI, 1.51-3.43]; p < 0.0001), non-use of taurolidine citrate lock (HR 2.70 [95% CI, 1.72-4.11]; p < 0.0001) and gastrointestinal motility disorder (HR 3.02 [95% CI, 1.81-4.91]; p < 0.001) were independent risk factors for developing CRBSI. CONCLUSIONS: Extra care in managing PN connections and disconnections should be taken in children with an underlying gastrointestinal motility disorder, distal enterocutaneous stoma, male sex and those aged <2 years since they are at a significantly higher risk of CRBSI. Early introduction of taurolidine lock should be considered.


Asunto(s)
Infecciones Relacionadas con Catéteres , Catéteres Venosos Centrales , Enfermedad Injerto contra Huésped , Enfermedades Intestinales , Insuficiencia Intestinal , Nutrición Parenteral en el Domicilio , Sepsis , Humanos , Masculino , Niño , Infecciones Relacionadas con Catéteres/epidemiología , Infecciones Relacionadas con Catéteres/etiología , Estudios Prospectivos , Estudios Retrospectivos , Catéteres , Enfermedades Intestinales/complicaciones , Enfermedades Intestinales/terapia , Nutrición Parenteral en el Domicilio/efectos adversos , Factores de Riesgo , Sepsis/complicaciones , Catéteres Venosos Centrales/efectos adversos
14.
Life (Basel) ; 13(10)2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37895365

RESUMEN

Chronic wound management is a global challenge. Millions of patients suffer from nonhealing ulcers and health systems are overwhelmed by the growing demand for treatment. Despite the prevalence of chronic wounds, the emergence of wound centers and specialized physicians is a recent phenomenon. Likewise, clinical research in wound healing is in its infancy. To date, many of the products in wound care have little or no clinical evidence. The field needs standardized clinical trial design, endpoints recognized by clinicians and payers, and improved overall clinical evidence. Wound healing is impeded by the presence of bacterial biofilms, which exist in most chronic wounds. It is not surprising that biofilm disruption is the focus of wound management and essential to the healing process. Multiple laboratory and preclinical studies demonstrate promising efficacy of several antimicrobials in treating biofilms; however, the field lacks in vivo clinical studies. In addition, a standardized trial design to evaluate efficacy of antimicrobials in chronic wounds does not exist. The advent of new diagnostic technologies, such as fluorescence imaging, has led to clinical trial designs that are reliable, easier to conduct, and cost efficient. The protocol presented here describes a randomized controlled double-blind trial designed to evaluate antiseptics in chronic wounds.

15.
J Wound Care ; 32(11): 748-757, 2023 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-37907360

RESUMEN

OBJECTIVE: To improve wound-related quality of life (QoL) in clients with hard-to-heal wounds in their lower limbs and to increase referrals to multidisciplinary teams in the management of care for these clients. METHOD: This was a quality improvement project with a two-group pretest-posttest interventional evaluation design. We implemented a package of interventions including the WounDS app, education related to wound care, and client engagement through a QoL self-assessment. Wound-related QoL was measured using the Cardiff Wound Impact Schedule and referrals to the multidisciplinary team were tracked through chart audits. We explored nurses' experiences with the interventions through semi-structured interviews. RESULTS: Clients' average ratings for 'wellbeing', 'physical symptoms and daily living', and 'overall QoL' improved by 27%, 38% and 54%, respectively. The number of referrals increased by 78% post intervention. Nurses described the interventions as effective strategies that motivated them to implement a holistic approach to care. CONCLUSION: The project was successful in creating a culture shift to practice holistic wound care. This package of interventions (WounDS app, education and client self-assessment of QoL) led to improvements in the QoL of clients with hard-to-heal wounds. Further studies are needed to generalise the findings. Strategies for sustainability include forming a champion group and providing the education and decision supports based on nurses' educational needs assessment.


Asunto(s)
Enfermeras y Enfermeros , Calidad de Vida , Humanos , Cicatrización de Heridas
16.
iScience ; 26(9): 107576, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37664640

RESUMEN

Heritability in the immune tumor microenvironment (iTME) has been widely observed yet remains largely uncharacterized. Here, we developed a machine learning approach to map iTME modifiers within loci from genome-wide association studies (GWASs) for breast cancer (BrCa) incidence. A random forest model was trained on a positive set of immune-oncology (I-O) targets, and then used to assign I-O target probability scores to 1,362 candidate genes in linkage disequilibrium with 155 BrCa GWAS loci. Cluster analysis of the most probable candidates revealed two subfamilies of genes related to effector functions and adaptive immune responses, suggesting that iTME modifiers impact multiple aspects of anticancer immunity. Two of the top ranking BrCa candidates, LSP1 and TLR1, were orthogonally validated as iTME modifiers using BrCa patient biopsies and comparative mapping studies, respectively. Collectively, these data demonstrate a robust and flexible framework for functionally fine-mapping GWAS risk loci to identify translatable therapeutic targets.

17.
bioRxiv ; 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37745481

RESUMEN

Genome editing technologies that install diverse edits can widely enable genetic studies and new therapeutics. Here we develop click editing, a genome writing platform that couples the advantageous properties of DNA-dependent DNA polymerases with RNA-programmable nickases (e.g. CRISPR-Cas) to permit the installation of a range of edits including substitutions, insertions, and deletions. Click editors (CEs) leverage the "click"-like bioconjugation ability of HUH endonucleases (HUHes) with single stranded DNA substrates to covalently tether "click DNA" (clkDNA) templates encoding user-specifiable edits at targeted genomic loci. Through iterative optimization of the modular components of CEs (DNA polymerase and HUHe orthologs, architectural modifications, etc.) and their clkDNAs (template configurations, repair evading substitutions, etc.), we demonstrate the ability to install precise genome edits with minimal indels and no unwanted byproduct insertions. Since clkDNAs can be ordered as simple DNA oligonucleotides for cents per base, it is possible to screen many different clkDNA parameters rapidly and inexpensively to maximize edit efficiency. Together, click editing is a precise and highly versatile platform for modifying genomes with a simple workflow and broad utility across diverse biological applications.

18.
J Endocrinol ; 259(2)2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37725394

RESUMEN

Type 2 diabetes mellitus (T2DM), a condition characterised by insulin resistance (IR) and skeletal muscle mitochondrial abnormalities, is a leading cause of death in developed societies. Much work has postulated that improving pathways linked to mitochondrial health, including autophagy, may be a potential avenue to prevent or treat T2DM. Given the recent data indicating a role for tripartite motif-containing 28 (TRIM28) in autophagy and mitochondrial pathways, we investigated whether muscle-specific deletion of TRIM28 might impact on obesity, glucose tolerance, and IR in mice. We studied two different muscle-specific (MCK-cre and ACTA1-cre-ERT2) TRIM28 knockout models, which were phenotyped during and after being fed a chow or high-fat diet (HFD). Whilst muscle-specific deletion of TRIM28 in both models demonstrated alterations in markers of mitochondrial activity and autophagy in skeletal muscle, we did not observe major impacts on the majority of metabolic measures in these mice. Specifically, we demonstrate that deletion of TRIM28 in skeletal muscle of mice during (MCK-cre) or post-development (ACTA1-cre-ERT2) does not prevent HFD-induced obesity or glucose intolerance. These findings are consistent with those reported previously in relation to autophagy and mitochondria in other cell types, and thus warrant further study into the biological role TRIM28 has in relation to mitochondrial function.


Asunto(s)
Diabetes Mellitus Tipo 2 , Intolerancia a la Glucosa , Resistencia a la Insulina , Ratones , Animales , Diabetes Mellitus Tipo 2/metabolismo , Resistencia a la Insulina/genética , Músculo Esquelético/metabolismo , Intolerancia a la Glucosa/metabolismo , Obesidad/metabolismo , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BL , Mitocondrias Musculares/metabolismo , Proteína 28 que Contiene Motivos Tripartito/metabolismo
19.
Can J Aging ; : 1-6, 2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-37721030

RESUMEN

Most older adults prefer to age in place, which for many will require home and community care (HCC) support. Unfortunately, HCC capacity is insufficient to meet demand due in part to low wages, particularly for personal support workers (PSWs) who provide the majority of paid care. Using Ontario as a case study, this paper estimates the cost and capacity impacts of implementing wage parity between PSWs employed in HCC and institutional long-term care (ILTC). Specifically, we consider the cost of increased HCC PSW wages versus expected savings from avoiding unnecessary ILTC placement for those accommodated by HCC capacity growth. The expected increase in HCC PSW retention would create HCC capacity for approximately 160,000 people, reduce annual health system costs by approximately $7 billion, and provide an 88 per cent return on investment. Updating wage structures to reduce turnover and enable HCC capacity growth is a cost-efficient option for expanding health system capacity.

20.
Mol Cell Proteomics ; 22(11): 100649, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37730182

RESUMEN

Metastatic uveal melanoma (UM) patients typically survive only 2 to 3 years because effective therapy does not yet exist. Here, to facilitate the discovery of therapeutic targets in UM, we have identified protein kinase signaling mechanisms elicited by the drivers in 90% of UM tumors: mutant constitutively active G protein α-subunits encoded by GNAQ (Gq) or GNA11 (G11). We used the highly specific Gq/11 inhibitor FR900359 (FR) to elucidate signaling networks that drive proliferation, metabolic reprogramming, and dedifferentiation of UM cells. We determined the effects of FR on the proteome and phosphoproteome of UM cells as indicated by bioinformatic analyses with CausalPath and site-specific gene set enrichment analysis. We found that inhibition of oncogenic Gq/11 caused deactivation of PKC, Erk, and the cyclin-dependent kinases CDK1 and CDK2 that drive proliferation. Inhibition of oncogenic Gq/11 in UM cells with low metastatic risk relieved inhibitory phosphorylation of polycomb-repressive complex subunits that regulate melanocytic redifferentiation. Site-specific gene set enrichment analysis, unsupervised analysis, and functional studies indicated that mTORC1 and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 drive metabolic reprogramming in UM cells. Together, these results identified protein kinase signaling networks driven by oncogenic Gq/11 that regulate critical aspects of UM cell biology and provide targets for therapeutic investigation.


Asunto(s)
Subunidades alfa de la Proteína de Unión al GTP Gq-G11 , Neoplasias de la Úvea , Humanos , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/farmacología , Proliferación Celular , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/metabolismo , Neoplasias de la Úvea/patología , Proteína Quinasa C/metabolismo , Biología Computacional , Mutación
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