Knee osteoarthritis pendulum therapy : in vivo evaluation and a randomised, single-blind feasibility clinical trial

Background. Exercise is recommended as the first-line management for knee osteoarthritis (KOA); however, it is difficult to determine which specific exercises are more effective. This study aimed to explore the potential mechanism and effectiveness of a leg-swinging exercise practiced in China, called ‘KOA pendulum therapy’ (KOAPT). Intraarticular hydrostatic and dynamic pressure (IHDP) are suggested to partially explain the signs and symptoms of KOA. As such this paper set out to explore this mechanism in vivo in minipigs and in human volunteers alongside a feasibility clinical trial. The objective of this study is 1) to analyze the effect of KOAPT on local mechanical and circulation environment of the knee in experimental animals and healthy volunteers; and 2) to test if it is feasible to run a large sample, randomized/single blind clinical trial. Methods. IHDP of the knee was measured in ten minipigs and ten volunteers (five healthy and five KOA patients). The effect of leg swinging on synovial blood flow and synovial fluid content depletion in minipigs were also measured. Fifty KOA patients were randomly divided into two groups for a feasibility clinical trial. One group performed KOAPT (targeting 1000 swings/leg/day), and the other performed walking exercise (targeting 4000 steps/day) for 12 weeks with 12 weeks of follow-up. Results. The results showed dynamic intra-articular pressure changes in the knee joint, increases in local blood flow, and depletion of synovial fluid contents during pendulum leg swinging in minipigs. The intra-articular pressure in healthy human knee joints was −11.32 ± 0.21 (cmH2O), whereas in KOA patients, it was −3.52 ± 0.34 (cmH2O). Measures were completed by 100% of participants in all groups with 95–98% adherence to training in both groups in the feasibility clinical trial. There were significant decreases in the Oxford knee score in both KOAPT and walking groups after intervention (p < 0.01), but no significant differences between the two groups. Conclusion. We conclude that KOAPT exhibited potential as an intervention to improve symptoms of KOA possibly through a mechanism of normalising mechanical pressure in the knee; however, optimisation of the method, longer-term intervention and a large sample randomized-single blind clinical trial with a minimal 524 cases are needed to demonstrate whether there is any superior benefit over other exercises

High drug-loaded microspheres enabled by controlled in-droplet precipitation promote functional recovery after spinal cord injury

High drug loading improves therapeutic efficacy and reduces side effects in drug delivery. Here, the authors use controlled diffusion of solvents to precipitate drug nanoparticles in polymer particles while the polymer is solidifying and demonstrate the particles for drug delivery in a spinal cord injury model. Drug delivery systems with high content of drug can minimize excipients administration, reduce side effects, improve therapeutic efficacy and/or promote patient compliance. However, engineering such systems is extremely challenging, as their loading capacity is inherently limited by the compatibility between drug molecules and carrier materials. To mitigate the drug-carrier compatibility limitation towards therapeutics encapsulation, we developed a sequential solidification strategy. In this strategy, the precisely controlled diffusion of solvents from droplets ensures the fast in-droplet precipitation of drug molecules prior to the solidification of polymer materials. After polymer solidification, a mass of drug nanoparticles is embedded in the polymer matrix, forming a nano-in-micro structured microsphere. All the obtained microspheres exhibit long-term storage stability, controlled release of drug molecules, and most importantly, high mass fraction of therapeutics (21.8-63.1 wt%). Benefiting from their high drug loading degree, the nano-in-micro structured acetalated dextran microspheres deliver a high dose of methylprednisolone (400 mu g) within the limited administration volume (10 mu L) by one single intrathecal injection. The amount of acetalated dextran used was 1/433 of that of low drug-loaded microspheres. Moreover, the controlled release of methylprednisolone from high drug-loaded microspheres contributes to improved therapeutic efficacy and reduced side effects than low drug-loaded microspheres and free drug in spinal cord injury therapy.Peer reviewe

A review of phase change heat transfer in shape-stabilized phase change materials (ss-PCMs) based on porous supports for thermal energy storage

Latent heat thermal energy storage (LHTES) uses phase change materials (PCMs) to store and release heat, and can effectively address the mismatch between energy supply and demand. However, it suffers from low thermal conductivity and the leakage problem. One of the solutions is integrating porous supports and PCMs to fabricate shape-stabilized phase change materials (ss-PCMs). The phase change heat transfer in porous ss-PCMs is of fundamental importance for determining thermal-fluidic behaviours and evaluating LHTES system performance. This paper reviews the recent experimental and numerical investigations on phase change heat transfer in porous ss-PCMs. Materials, methods, apparatuses and significant outcomes are included in the section of experimental studies and it is found that paraffin and metal foam are the most used PCM and porous support respectively in the current researches. Numerical advances are reviewed from the aspect of different simulation methods. Compared to representative elementary volume (REV)-scale simulation, the pore-scale simulation can provide extra flow and heat transfer characteristics in pores, exhibiting great potential for the simulation of mesoporous, microporous and hierarchical porous materials. Moreover, there exists a research gap between phase change heat transfer and material preparation. Finally, this review outlooks the future research topics of phase change heat transfer in porous ss-PCMs

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Recent Changes in the Occurrences and Damages of Floods and Droughts in the United States

In this study, we compile and analyse 136,920 records of flood and 50,967 records of drought from a survey-based database to investigate recent changes in annual occurrence and economical cost in the United States. Results show that an average of 6520 floods has occurred per year during 1996&ndash;2016, with annual mean economic losses up to 3986 million US dollars, while 2427 drought events/year are recorded causing an average loss of 1684 million US dollars per year. Importantly, we found there is no evident changing tendency in annual economic damages of floods and droughts, despite an upward trend in their annual occurrences. This could be partly explained by changes in regional vulnerabilities, as indirectly reflected by the ratio of damaging events to total number of events experienced and the average damage per event. Spatially, vulnerability to droughts has decreased in most of the country, while increased vulnerability to floods is observed in a number of states. Despite limitations from the records and incomplete characterization of vulnerability, this study has great implications for targeted mitigation and adaptation, through identifying the regions that are most vulnerable to floods and droughts respectively and highlighting the contrasting patterns in regional vulnerability to floods and droughts