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Background: Thoracoabdominal periprocedural occlusion/reperfusion injury of the spinal cord (SCII/R) can lead to devastating paraplegia, underscoring the critical need for effective interventions. However, our knowledge of optimal medical strategies and their efficacy remains limited. Preclinical investigations have shown promise in harnessing adult stem cells, including pluripotent and multipotent stem cells such as mesenchymal stem cells (MSCs), to address SCII/R by enhancing neuro-inflammation, axonal growth, and myelination. Particularly, growth factors derived from adipose tissue-derived MSCs (ADSCs) have been proposed to facilitate recovery. Despite advancements, achieving complete recovery remains a formidable challenge. Therefore, gaining a more profound insight into the role of ADSCs in alleviating SCII/R-induced paraplegia, including optimizing the delivery systems for therapies, is imperative. Materials and methods: In this study, we assessed the impact of subpial allogeneic rat adipose tissue-derived MSCs (rADSCs) transplantation on paraplegia using a rat SCII/R model induced by ephemeral aortic occlusion, known as the Taira-Marsala model. rADSCs were isolated from adipose tissue of male Sprague-Dawley rats, cultured, characterized, and cryopreserved. One week following the induction of paraplegia, rADSCs (n = 6) or physiological saline (n = 6) were transplanted. Hind limb motor function was evaluated before treatment and at 3-, 7-, and 14-days post-treatment using the Basso-Beattie-Bresnahan scoring system. Results: The rADSC-treated group demonstrated a significant improvement in hind limb motor function compared to the saline-treated group (p

Spinal cord injury (SCI) has limited treatment options for regaining function. Adipose-derived stem cells (ADSCs) show promise owing to their ability to differentiate into multiple cell types, promote nerve cell survival, and modulate inflammation. This review explores ADSC therapy for SCI, focusing on its potential for improving function, preclinical and early clinical trial progress, challenges, and future directions.Preclinical studies have demonstrated ADSC transplantation's effectiveness in promoting functional recovery, reducing cavity formation, and enhancing nerve regrowth and myelin repair. To improve ADSC efficacy, strategies including genetic modification and combination with rehabilitation are being explored. Early clinical trials have shown safety and feasibility, with some suggesting motor and sensory function improvements.Challenges remain for clinical translation, including optimizing cell survival and delivery, determining dosing, addressing tumor formation risks, and establishing standardized protocols. Future research should focus on overcoming these challenges and exploring the potential for combining ADSC therapy with other treatments, including rehabilitation and medication.

Chronic wounds represent a significant global burden, afflicting millions with debilitating complications. Despite standard care, impaired healing persists due to factors like persistent inflammation and impaired tissue regeneration. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) offer an innovative regenerative medicine approach, delivering stem cell-derived therapeutic cargo in engineered nanoscale delivery systems. This review examines pioneering bioengineering strategies to engineer MSC-EVs into precision nanotherapeutics for chronic wounds. Emerging technologies like CRISPR gene editing, microfluidic manufacturing, and biomimetic delivery systems are highlighted for their potential to enhance MSC-EV targeting, optimize therapeutic cargo enrichment, and ensure consistent clinical-grade production. However, key hurdles remain, including batch variability, rigorous safety assessment for potential tumorigenicity, immunogenicity, and biodistribution profiling. Crucially, collaborative frameworks harmonizing regulatory science with bioengineering and patient advocacy hold the key to expediting global clinical translation. By overcoming these challenges, engineered MSC-EVs could catalyze a new era of off-the-shelf regenerative therapies, restoring hope and healing for millions afflicted by non-healing wounds.

Abstract Introduction Cenegermin is approved for treatment of neurotrophic keratopathy (NK) and has been studied in patients with stage 2 or 3 NK. This study evaluated the efficacy and safety of cenegermin in adults with stage 1 NK. Methods This was a phase IV, multicenter, prospective, open-label, uncontrolled trial. Adults with stage 1 NK (Mackie criteria) and decreased corneal sensitivity (≤ 4 cm) received 1 drop of cenegermin 20 mcg/ml in the affected eye(s) 6 times/day for 8 weeks with a 24-week follow-up. Results Of 37 patients, corneal epithelial healing was observed in 84.8% (95% confidence interval [CI] 68.1–94.9%; P

Introduction: The environmentally acquired aerobic spore-forming (EAS-Fs) bacteria that are ubiquitous in nature (e.g., soil) are transient colonisers of the mammalian gastro-intestinal tract. Without regular exposure, their numbers quickly diminish. These species of bacteria have been suggested to be essential to the normal functioning of metabolic and immunogenic health. The modern Western lifestyle restricts exposure to these EAS-Fs, possibly explaining part of the pathogenesis of many Western diseases. To date, the only animal studies that address specific microbiome modelling are based around germ-free animals. We have designed a new animal model that specifically restricts exposure to environmental sources of bacteria. Methodology: A new protocol, termed Super Clean, which involves housing mice in autoclaved individually ventilated cages (IVCs), with autoclaved food/water and strict ascetic handling practice was first experimentally validated. The quantification of EAS-Fs was assessed by heat-treating faecal samples and measuring colony-forming units (CFUs). This was then compared to mice in standard conditions. Mice were housed in their respective groups from birth until 18 months. Stool samples were taken throughout the experiment to assess for abundance in transiently acquired environmental bacteria. Clinical, biochemical, histological, and gene expression markers were analysed for diabetes, hypercholesterolaemia, obesity, inflammatory bowel disease, and non-alcoholic fatty liver disease (the “diseases of the West”). Results: Our results show that stringent adherence to the Super Clean protocol produces a significantly decreased abundance of aerobic spore-forming Bacillota after 21 days. This microbiomic shift was correlated with significantly increased levels of obesity and impaired glucose metabolism. There was no evidence of colitis, liver disease or hypercholesterolaemia. Conclusions: This new murine model successfully isolates EAS-Fs and has potential utility for future research, allowing for an investigation into the clinical impact of living in relative hygienic conditions.

Introduction: Ageing tends to have a degenerative effect on the skin and emollient use may help maintain skin integrity in older people. In the hospital setting, skin conditions can sometimes be misinterpreted as minor and therefore regular emollient prescriptions are often incomplete or inaccurate.1 We undertook a quality improvement project to evaluate the prescribing of regular emollients in care of the elderly inpatients. Materials and methods: Baseline data were collected using electronic health records for patients in six care of the elderly wards at Northwick Park hospital. We undertook two Plan Do Study Act (PDSA) cycles to improve the accuracy and reduce the delay in regular emollient prescriptions on admission. Our interventions included posters clearly displayed in Accident and Emergency and on acute medical wards and discussions with pharmacists to alert admitting doctors when regular emollients were not prescribed appropriately over 3 months. Results and discussion: In the first PDSA cycle 156 patients were identified, out of which 46 were on regular emollients. The proportion of timely prescriptions was 26% with a mean delay of 11.5 days. In the second cycle 150 patients were identified, out of which 30 were on regular emollients. Following our interventions, the proportion of timely prescriptions rose to 30% and the mean delay time improved to 6.6 days. Conclusion: Our interventions resulted in increased timely prescriptions of regular emollients and reduced prescription delay time in care of the elderly inpatients. This project highlights the need to continue to raise awareness regarding the suboptimal emollient prescribing in elderly patients on admission and hence further cycles to sustain the improvements seen are planned.

Background Distal transradial access (dTRA) is an alternative to conventional forearm transradial access (fTRA) for coronary angiography (CAG). Differences in healing of the radial artery (RA) in the forearm have not been evaluated between these 2 access strategies. We sought to compare the mean difference in forearm RA intimal‐medial thickening (IMT) in patients randomized to dTRA versus fTRA. Methods and Results In this single‐center randomized clinical trial, 64 patients undergoing nonemergent CAG were randomized (1:1) to dTRA versus fTRA. Ultra–high‐resolution (55‐MHz) vascular ultrasound of the forearm and distal RA was performed pre‐CAG and at 90 days. The primary end point was the mean change in forearm RA IMT. Secondary end points included procedural characteristics, vascular injury, RA occlusion, and ipsilateral hand pain and function. Baseline demographics and clinical characteristics, mean forearm RA IMT, and procedural specifics were similar between the dTRA and fTRA cohorts. There was no difference in mean change in forearm RA IMT between the 2 cohorts (0.07 versus 0.07 mm; P=0.37). No RA occlusions or signs of major vascular injury were observed at 90 days. Ipsilateral hand pain and function (Borg pain scale score: 12 versus 11; P=0.24; Disabilities of the Arm, Shoulders, and Hand scale score: 6 versus 8; P=0.46) were comparable. Conclusions Following CAG, dTRA was associated with no differences in mean change of forearm RA IMT, hand pain, and function versus fTRA for CAG. Further investigation is warranted to elucidate mechanisms and predictors of RA healing and identify effective strategies to preserving RA integrity for repeated procedures. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04801901.

This article describes the arc of global measles and rubella elimination since 2000 from the perspective of the founding partners of the Measles Initiative. The Measles Initiative was formed in 2001 as a partnership among the American Red Cross, the Centers for Disease Control and Prevention, UNICEF, the United Nations Foundation, and the World Health Organization with the aim to reduce measles deaths in low-income countries. Recognizing rubella as the leading infectious disease cause of congenital abnormalities globally and achievement of measles and rubella elimination in the region of the Americas, the partnership was renamed the Measles and Rubella Initiative (MRI) in 2012. The goals of the MRI were at least a 95% reduction in global measles mortality and elimination of measles and rubella in at least five of the six WHO regions. In January 2023, the membership of the partnership was expanded to include the Bill and Melinda Gates Foundation (BMGF) and Gavi the Vaccine Alliance, and its name changed to the IA2030 Measles and Rubella Partnership. We describe the role the partnership has had in measles partner effectiveness and its impact on measles and rubella disease burden, including how the partnership has strategically adapted to the evolving immunization landscape. We conclude with lessons learned regarding the role global partnerships can play in furthering the impact of disease control programs within the current global immunization environment.