Muscle strength but not balance improves after arthroscopic biodegradable polyurethane meniscus scaffold application.

Purpose: This study aimed to assess the impact of biodegradable polyurethane meniscus scaffold implantation (BPMSI) on muscle strength and balance in comparison with the healthy contralateral knee in patients with irreparable medial meniscus defect. Methods: This observational and prospective case-cohort study was conducted with patients who had irreparable meniscal defects and underwent arthroscopic meniscus scaffold implantation. Surgeries were carried out on the medial meniscus of 16 right and 4 left knees. Visual analog scale (VAS) was used to assess the degree of pain relief. Knee Injury and Osteoarthritis Outcome Score (KOOS) and Lysholm (LYS) score were used to evaluate the functional improvement at weeks 12, 24 and 36. Concentric and eccentric quadriceps and hamstring peak torque (PT) as well as the peak torque-to-body weight (PTB) ratio, anterior-posterior, mediolateral and overall stability indexes were assessed at the same time points. Results: Twenty male patients with a mean age and body mass index of 32.2 ± 8.8 years and 26.2 ± 4.2 kg/m2, respectively, were included in the study. The amount of pain decreased from 7.6 ± 1.5% to 2.9 ± 1.5% at postoperative week 36. Range of motion, Lysholm score and KOOS increased from 87.0ο ± 9.5ο to 115.0ο ± 15.1ο, 30.8 ± 4.3 to 81.5 ± 5.3 and 37.4 ± 5.3 to 74.1 ± 7.2, respectively. Concentric quadriceps and hamstring peak torque values and peak torque/body weight ratios were improved in the knees that received a meniscus scaffold implant. Anterior/posterior, medial/lateral, and overall stability indexes with or without biofeedback exhibited a slight improvement, which was not statistically significant. Conclusion: BPMSI led to decreased pain and improved function at postoperative week 36. Although muscle strength almost returned to normal, balance parameters did not recover within 36 weeks after the procedure

Dysfunctional survival-signaling and stress-intolerance in aged murine and human myocardium

Changes in cytoprotective signaling may influence cardiac aging, and underpin sensitization to ischemic insult and desensitization to 'anti-ischemic' therapies. We tested whether age-dependent shifts in ischemia-reperfusion (I-R) tolerance in murine and human myocardium are associated with reduced efficacies and coupling of membrane, cytoplasmic and mitochondrial survival-signaling. Hormesis (exemplified in ischemic preconditioning; IPC) and expression of proteins influencing signaling/stress-resistance were also assessed in mice. Mouse hearts (18 vs. 2-4mo) and human atrial tissue (75±2 vs. 55±2yrs) exhibited profound age-dependent reductions in I-R tolerance. In mice aging negated cardioprotection via IPC, G-protein coupled receptor (GPCR) agonism (opioid, A and A adenosine receptors) and distal protein kinase c (PKC) activation (4nM phorbol 12-myristate 13-acetate; PMA). In contrast, p38-mitogen activated protein kinase (p38-MAPK) activation (1μM anisomycin), mitochondrial ATP-sensitive K channel (mK) opening (50μM diazoxide) and permeability transition pore (mPTP) inhibition (0.2μM cyclosporin A) retained protective efficacies in older hearts (though failed to eliminate I-R tolerance differences). A similar pattern of change in protective efficacies was observed in human tissue. Murine hearts exhibited molecular changes consistent with altered membrane control (reduced caveolin-3, cholesterol and caveolae), kinase signaling (reduced p70 ribosomal s6 kinase; p70s6K) and stress-resistance (increased G-protein receptor kinase 2, GRK2; glycogen synthase kinase 3β, GSK3β; and cytosolic cytochrome c). In summary, myocardial I-R tolerance declines with age in association with dysfunctional hormesis and transduction of survival signals from GPCRs/PKC to mitochondrial effectors. Differential changes in proteins governing caveolar and mitochondrial function may contribute to signal dysfunction and stress-intolerance

Chronic beta(1)-adrenoceptor blockade impairs ischaemic tolerance and preconditioning in murine myocardium

beta-adrenoceptor antagonists are commonly used in ischaemic heart disease (IHD) patients, yet may impair signalling and efficacy of 'cardioprotective' interventions. We assessed effects of chronic beta(1)-adrenoceptor antagonism on myocardial resistance to ischaemia-reperfusion (IR) injury and the ability of cardioprotective interventions [classic ischaemic preconditioning (IPC); novel sustained ligand-activated preconditioning (SLP)] to reduce IR injury in murine hearts

Novel platform technology for modular mucosal vaccine that protects against streptococcus

The upper respiratory tract (URT) is the major entry site for human pathogens and strategies to activate this network could lead to new vaccines capable of preventing infection with many pathogens. Group A streptococcus (GAS) infections, causing rheumatic fever, rheumatic heart disease, and invasive disease, are responsible for substantial morbidity and mortality. We describe an innovative vaccine strategy to induce mucosal antibodies of significant magnitude against peptide antigens of GAS using a novel biocompatible liposomal platform technology. The approach is to encapsulate free diphtheria toxoid (DT), a standard vaccine antigen, within liposomes as a source of helper T-cell stimulation while lipidated peptide targets for B-cells are separately displayed on the liposome surface. As DT is not physically conjugated to the peptide, it is possible to develop modular epitopic constructs that simultaneously activate IgA-producing B-cells of different and complementary specificity and function that together neutralize distinct virulence factors. An inflammatory cellular immune response is also induced. The immune response provides profound protection against streptococcal infection in the URT. The study describes a new vaccine platform for humoral and cellular immunity applicable to the development of vaccines against multiple mucosal pathogens