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Cardiac ischemic reperfusion injury (IRI) is paradoxically instigated by reestablishing blood‐flow to ischemic myocardium typically from a myocardial infarction (MI). Although revascularization following MI remains the standard of care, effective strategies remain limited to prevent or attenuate IRI. We hypothesized that epicardial placement of human placental amnion/chorion (HPAC) grafts will protect against IRI. Using a clinically relevant model of IRI, swine were subjected to 45 min percutaneous ischemia followed with (MI + HPAC, n = 3) or without (MI only, n = 3) HPAC. Cardiac function was assessed by echocardiography, and regional punch biopsies were collected 14 days post‐operatively. A deep phenotyping approach was implemented by using histological interrogation and incorporating global proteomics and transcriptomics in nonischemic, ischemic, and border zone biopsies. Our results established HPAC limited the extent of cardiac injury by 50% (11.0 ± 2.0% vs. 22.0 ± 3.0%, p = 0.039) and preserved ejection fraction in HPAC‐treated swine (46.8 ± 2.7% vs. 35.8 ± 4.5%, p = 0.014). We present comprehensive transcriptome and proteome profiles of infarct (IZ), border (BZ), and remote (RZ) zone punch biopsies from swine myocardium during the proliferative cardiac repair phase 14 days post‐MI. Both HPAC‐treated and untreated tissues showed regional dynamic responses, whereas only HPAC‐treated IZ revealed active immune and extracellular matrix remodeling. Decreased endoplasmic reticulum (ER)‐dependent protein secretion and increased antiapoptotic and anti‐inflammatory responses were measured in HPAC‐treated biopsies. We provide quantitative evidence HPAC reduced cardiac injury from MI in a preclinical swine model, establishing a potential new therapeutic strategy for IRI. Minimizing the impact of MI remains a central clinical challenge. We present a new strategy to attenuate post‐MI cardiac injury using HPAC in a swine model of IRI. Placement of HPAC membrane on the heart following MI minimizes ischemic damage, preserves cardiac function, and promotes anti‐inflammatory signaling pathways.

Postmastectomy radiotherapy in patients with four or more positive axillary nodes reduces breast cancer mortality, but its role in patients with one to three involved nodes is controversial. We assessed the effects of postmastectomy radiotherapy on quality of life (QOL) in women with intermediate-risk breast cancer. SUPREMO is an open-label, international, parallel-group, randomised, controlled trial. Women aged 18 years or older with intermediate-risk breast cancer (defined as pT1–2N1; pT3N0; or pT2N0 if also grade III or with lymphovascular invasion) who had undergone mastectomy and, if node positive, axillary surgery, were randomly assigned (1:1) to receive chest wall radiotherapy (50 Gy in 25 fractions or a radiobiologically equivalent dose of 45 Gy in 20 fractions or 40 Gy in 15 fractions) or no radiotherapy. Randomisation was done with permuted blocks of varying block length, and stratified by centre, without masking of patients or investigators. The primary endpoint is 10-year overall survival. Here, we present 2-year results of QOL (a prespecified secondary endpoint). The QOL substudy, open to all UK patients, consists of questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23, Body Image Scale, Hospital Anxiety and Depression Scale [HADS], and EQ-5D-3L) completed before randomisation, and at 1, 2, 5, and 10 years. The prespecified primary outcomes within this QOL substudy were global QOL, fatigue, physical function, chest wall symptoms, shoulder and arm symptoms, body image, and anxiety and depression. Data were analysed by intention to treat, using repeated mixed-effects methods. This trial is registered with the ISRCTN registry, number ISRCTN61145589. Between Aug 4, 2006, and April 29, 2013, 1688 patients were enrolled internationally and randomly assigned to receive chest wall radiotherapy (n=853) or not (n=835). 989 (79%) of 1258 patients from 111 UK centres consented to participate in the QOL substudy (487 in the radiotherapy group and 502 in the no radiotherapy group), of whom 947 (96%) returned the baseline questionnaires and were included in the analysis (radiotherapy, n=471; no radiotherapy, n=476). At up to 2 years, chest wall symptoms were worse in the radiotherapy group than in the no radiotherapy group (mean score 14·1 [SD 15·8] in the radiotherapy group vs 11·6 [14·6] in the no radiotherapy group; effect estimate 2·17, 95% CI 0·40–3·94; p=0·016); however, there was an improvement in both groups between years 1 and 2 (visit effect −1·34, 95% CI −2·36 to −0·31; p=0·010). No differences were seen between treatment groups in arm and shoulder symptoms, body image, fatigue, overall QOL, physical function, or anxiety or depression scores. Postmastectomy radiotherapy led to more local (chest wall) symptoms up to 2 years postrandomisation compared with no radiotherapy, but the difference between groups was small. These data will inform shared decision making while we await survival (trial primary endpoint) results. Medical Research Council, European Organisation for Research and Treatment of Cancer, Cancer Australia, Dutch Cancer Society, Trustees of Hong Kong and Shanghai Banking Corporation.

One in three patients admitted to intensive care will sustain a pressure injury (PI) from a medical device. These injuries are painful and when on the face, head or neck they can result in permanent disfigurement. Preliminary evidence of the efficacy of hyper‐oxygenated fatty acids (HOFAs) to prevent facial pressure injuries from medical devices is promising; however, the feasibility of incorporating HOFAs into current standard care to prevent PI from a medical device of the face, head and neck has not been extensively explored. It is intended that the findings from this phase II feasibility study will inform the design of a larger phase III trial, by addressing two primary aims: (1) to assess the feasibility of incorporating HOFAs into standard care to prevent device‐related pressure ulcers of the skin associated with the face, head and neck assess the feasibility and (2) efficacy preliminary effectiveness of HOFA. This feasibility study is an investigator‐initiated mixed method study incorporating a multi‐centre randomised controlled trial of using HOFAs as an adjunct to standard pressure injury prevention and care, compared with standard care alone to prevent facial, head or neck from medical devices among adults admitted to intensive care. The primary outcome of interest is the incidence of facial, head or neck pressure injuries during the first 14 days in intensive care. Secondary outcomes include PI staging, medical device exposure and intensive care and hospital outcomes. The primary analysis will be undertaken using Cox's Proportional Hazards model, and due to the exploratory nature of this phase II trial, efficacy will be based on a one‐sided p‐value for superiority set at 0.10. Type I and Type II error rates are set at 20%; therefore, a total sample size of 196 study participants is planned. To explore the feasibility of incorporating HOFA into usual care and to design a larger phase III trial, we will aim to interview between 10 and 20 nurses across participating intensive care unit sites. Pressure injuries of the face, head or neck from medical devices, among adults admitted to intensive care, are considered preventable. This phase II study will investigate the feasibility and efficacy of HOFAs as an adjunct to standard care. Importantly, we aim to inform the development of a larger phase III trial.

There is growing evidence that stress and sleep deprivation are involved in development of type 2 diabetes (T2DM). The latter is one of the most challenging health problems in the UAE. Therefore, the present study aimed to investigate the effects of personalized intervention on glycemic and weight control in Emirati patients with T2DM. The intervention involved assessment and modification of stress levels and sleep patterns. This was a randomized controlled study conducted on 51 Emirati patients with T2DM (age 18-60 years, body-mass index (BMI) ≥25 kg/m ): those in the intervention group who completed the trial numbered 18 and those in the control group who completed the trial numbered 17. Heart-rate variability was used for real-life and long-term assessments of stress, sleep, and recovery. Body weight, BMI, HbA and lipid profile were included in the investigation. The National Clinical Trial identifier number is NCT03644134. Percentage change in body weight was significantly greater ( <0.05) in the intervention group (-3.2±2.9) than the control group (-0.02). Percentage change in the BMI of the intervention group was -4.50±5.9, while the control group exhibited less change in BMI (-0.0003±3.3, <0.05). In addition, a significant reduction in HbA was observed in the intervention group (-5.3±15.7) and an increase of 9.9±13.1 was observed in the control group ( <0.01). The findings of the present study show that personalized approaches that reduce stress levels, increase recovery levels, and promote healthy sleep habits play an important role in weight management and glycemic control in T2DM.

Abstract Background: Inhaled interferon-γ aerosol (aINF-γ) may be effective treatment for idiopathic pulmonary fibrosis (IPF). We evaluated safety and delivery of aIFN-γ (100 μg 3 times/week) in 10 IPF patients using the I-neb (Philips Respironics, Parsippany, NJ). Methods: IFN-γ activity in the aerosol was confirmed by viral inhibition. Ten patients with an average age of 68 diagnosed with IPF (American Thoracic Society/European Respiratory Society consensus guidelines) were enrolled. In vivo deposition was measured via a gamma camera. The nebulizer recorded patient adherence to therapy. Pulmonary function tests [PFTs, forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO)] and the 6-min walk test were measured at baseline, and every 12–14 weeks for 80 weeks. Bronchoalveolar lavage (BAL) of the middle lobe was performed at baseline and 28 weeks. BAL and plasma samples were analyzed for chemokines and cytokines, including INF-γ. Results: All 10 patients tolerated 80 weeks of inhaled IFN-γ well, with no systemic side effects. True adherence with aerosol treatment averaged 96.7±4.81% (±SEM). In vivo lung deposition averaged 65.4±4.8μg and oropharyngeal deposition 12.6±3.0 μg. BAL IFN-γ increased 60-fold and profibrotic cytokines (FGP-2, Flt-3 ligand, IL-5) were significantly decreased; IFN-γ plasma levels were unchanged. PFTs showed minimal change in FVC. Post hoc analysis indicated that the slope of decline in TLC and DLCO reversed after beginning therapy. The 6-min walk was unchanged. Conclusions: IFN-γ is safe in IPF and can be effectively delivered to lung parenchyma. PFTs remained stable throughout the trial. Reversal of pretherapy PFT decline may define an end-point for future clinical trials.

Background: To overcome the limitations of conventional jet nebulizers, vibrating mesh technology has been commercialized. The present paper is designed to address clinically relevant issues for routine aerosol therapy for a vibrating mesh nebulizer, the Omron NE U22 compared to traditional jet nebulizers. Methods: Inhaled mass (IM), aerodynamic particle distribution (MMAD) and run time were determined for radiolabeled albuterol (2.5 mg/3 mL). Omron NE U22 (Omron Healthcare Inc. Bannockburn, IL), Pari LC Plus (Pari Respiratory Equipment, Midlothian, VA), Sidestream, and modified Sidestream (Philips Respironics Parsippany, NJ) nebulizers were tested. The Omron was tested in two positions, tilted and horizontal. Finally robustness of the Omron NE U22 was determined by repeating treatment 60 times. All Omron experiments were performed using continuous operation. Results: IM between Omron and Pari were similar (20% of nebulizer charge) and greater than the Sidestream devices (10%). MMAD were similar for all devices but variability was much greater for Omron in the horizontal position. Run time in the tilted position was three times longer when compared in the horizontal position (p = 0.0159). IM and MMAD were unchanged after Omron robustness testing. Conclusion: Position was an important factor for the mesh device affecting run time and variability in particle distribution. Using a common commercial formulation and continuous operation, drug delivery was similar to an efficient jet nebulizer. The Omron mesh tolerated repeated use with our albuterol formulation.

Alzheimer disease (AD) is the most common cause of dementia and the sixth leading cause of death in the United States. Today, more than 6 million Americans are living with AD and that number is expected to increase to 13.8 million by 2060. The progressive debilitating nature of this illness and the absence of disease-modifying treatments contributes to a substantial economic and societal burden on the healthcare system. In 2022, the estimated healthcare costs associated with AD treatment were $321 billion, with costs projected to exceed $1 trillion by 2050. These cost-of-care projections are based on direct healthcare costs and are likely underestimated because indirect costs associated with AD treatment are usually not included. Indirect costs such as loss in productivity, diminished quality of life, and an increasing dependence on informal unpaid care provided by family caregivers augments the economic and societal burden of this disease. As drug development continues to evolve, the emergence of disease-modifying therapy may help to offset the burden associated with AD-related dementia. Managed care organizations are uniquely positioned to mitigate costs and positively impact outcomes through the promotion of disease awareness, early diagnosis, and treatment and disease management programs focused on multidisciplinary care coordination and caregiver support.

Microvascular leakage due to endothelial barrier dysfunction is a prominent feature of T helper 2 (Th2) cytokine mediated allergic inflammation. Interleukin-4 (IL-4) is a potent Th2 cytokine, known to impair the barrier function of endothelial cells. However, the effectors mediating IL-4 induced cytoskeleton remodeling and consequent endothelial barrier dysfunction remain poorly defined. Here we have used whole genome transcriptome profiling and gene ontology analyses to identify the genes and processes regulated by IL-4 signaling in human coronary artery endothelial cells (HCAEC). The study revealed Wnt5A as an effector that can mediate actin cytoskeleton remodeling in IL-4 activated HCAEC through the regulation of LIM kinase (LIMK) and Cofilin (CFL). Following IL-4 treatment, LIMK and CFL were phosphorylated, thereby indicating the possibility of actin stress fiber formation. Imaging of actin showed the formation of stress fibers in IL-4 treated live HCAEC. Stress fiber formation was notably decreased in the presence of Wnt inhibitory factor 1 (WIF1). Non-invasive impedance measurements demonstrated that IL-4 increased the permeability and impaired the barrier function of HCAEC monolayers. Silencing Wnt5A significantly reduced permeability and improved the barrier function of HCAEC monolayers upon IL-4 treatment. Our study identifies Wnt5A as a novel marker of IL-4 activated vascular endothelium and demonstrates a critical role for Wnt5A in mediating IL-4 induced endothelial barrier dysfunction. Wnt5A could be a potential therapeutic target for reducing microvascular leakage and edema formation in Th2 driven inflammatory diseases.

Background Advanced nursing practice involves an expanded nursing scope, characterised by autonomy, expert knowledge, and complex decision-making to address diverse healthcare needs. Although roles such as nurse practitioner and clinical nurse specialist are established in New Zealand, there remains ambiguity in role definitions and a lack of exploration into the perspectives of registered nurses, particularly those pursuing postgraduate education. Aim This study seeks to explore focused perspectives of postgraduate nursing students on advanced nursing practice in New Zealand. Design A focused ethnography study. Setting Interviews were conducted online via videoconferencing. Participants The study involved fifteen registered nurses enrolled in postgraduate nursing programmes in New Zealand, who met the inclusion criteria, including providing direct patient care. Methods Semi-structured interviews were guided by a literature review. Data were transcribed verbatim and analysed thematically using an inductive, data-driven approach. Reflective notes and independent coding by two researchers ensured rigour. Results Two main themes emerged: (1) Defining advanced nursing practice, where participants associated advanced nursing practice with postgraduate education, autonomy, specialised care, advanced technology, and assessment skills. They emphasised the role of coaching and policy implementation. (2) Perspectives on advanced nursing practice roles in New Zealand, where participants voiced concerns about role ambiguity, limited career opportunities, and lack of clarity beyond nurse practitioner and clinical nurse specialist roles. They also noted insufficient emphasis on research within advanced nursing practice roles, despite the importance of evidence-based practice. Conclusions Postgraduate nursing students in New Zealand perceive advanced nursing practice as a vital field that requires advanced education and specialized skills. However, role ambiguity and limited research engagement hinder its development. Addressing structural challenges, enhancing role clarity, and incorporating research-oriented pathways, such as the doctor of nursing practice, could strengthen the impact of advanced nursing practice on healthcare delivery and policy. Clinical trial number Not applicable.