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One important challenge in treating avascular-degraded cartilage is the development of new drugs for both pain management and joint preservation. Considerable efforts have been invested in developing nanosystems using biomaterials, such as chitosan, a widely used natural polymer exhibiting numerous advantages, i.e., non-toxic, biocompatible and biodegradable. However, even if chitosan is generally recognized as safe, the safety and biocompatibility of such nanomaterials must be addressed because of potential for greater interactions between nanomaterials and biological systems. Here, we developed chitosan-based nanogels as drug-delivery platforms and established an initial biological risk assessment for osteocartilaginous applications. We investigated the influence of synthesis parameters on the physicochemical characteristics of the resulting nanogels and their potential impact on the biocompatibility on all types of human osteocartilaginous cells. Monodisperse nanogels were synthesized with sizes ranging from 268 to 382 nm according to the acidic solution used (i.e., either citric or acetic acid) with overall positive charge surface. Our results demonstrated that purified chitosan-based nanogels neither affected cell proliferation nor induced nitric oxide production in vitro. However, nanogels were moderately genotoxic in a dose-dependent manner but did not significantly induce acute embryotoxicity in zebrafish embryos, up to 100 µg∙mL−1. These encouraging results hold great promise for the intra-articular delivery of drugs or diagnostic agents for joint pathologies.

Purpose To explore the barriers to family resilience in caregivers of people who have schizophrenia. Design A qualitative descriptive approach was used. Methods Semistructured interviews were conducted with family caregivers of patients with schizophrenia registered at the psychiatry outpatient unit of a hospital center. Content analysis was performed on audio‐recorded and verbatim‐transcribed interviews. The consolidated criteria for reporting qualitative research (COREQ) checklist was applied to this study. Results A total of 31 family caregivers participated, the majority of whom were female (71%) with an average age of 57.5 years. Most participants lived with and cared for their relative (90.3%). The caregiver role was assumed mostly by mothers (54.8%) and fathers (22.6%). Barriers to family resilience in caregivers of people experiencing schizophrenia broadly fall under five categories: lack of knowledge about the disease, social stigma, expressed emotion, involvement in the relationship, and blame. Conclusions In view of the paucity of studies exploring and understanding the barriers to family resilience, this study presents itself as one of the first in this area. There are different barriers to family resilience. This research provides an overview and an understanding of key barriers to family resilience in caregivers of people experiencing schizophrenia. Clinical Relevance There is a need for nurses to help families to be resilient. By understanding the barriers to resilience, nurses are able to focus on these factors and help families to remove or reduce their influence.

SummaryAntiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing.BackgroundFracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing.MethodsNarrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT).ResultsFracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans.ConclusionOverall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fracture should be given prime consideration. It is imperative that new radiological and biological markers of fracture healing be identified. It is also important to synthesize clinical and basic science methodologies to assess fracture healing, so that a convergence of the two frameworks can be achieved.

Purpose The aims of this study were to determine the prevalence of metal hypersensitivity, and identify pre-operative factors which could predict susceptibility to hypersensitivity reactions among patients scheduled for primary total knee arthroplasty (TKA). The present study used a testing method consistent with the recognised biological response to metals. Methods A prospective cross-sectional analysis of 220 patients was conducted. All patients received a testing protocol using lymphocyte transformation test to evaluate reactivity to possible contents of orthopaedic implants. Test response is interpreted as stimulation index (SI) values. A comprehensive questionnaire was used to evaluate prior exposure. Patients were categorised according to SI values and the odds ratios (OR) were calculated as comparative effect measure for each predetermined prior exposure factor. Results The prevalence of metal sensitivity response was 28% ( n  = 61) among patients with susceptibility to at least one agent (SI = 2 to 4.9), and 3.2% ( n  = 7) among patients with true hypersensitivity (SI ≥ 5). The population-weighted prevalence, adjusted for sampling weights of symptomatic knee osteoarthritis, was SI ≥ 5 = 4.7% (95% CI 0.4–11.8%) and SI ≥ 2 = 35.2% (95% CI 24.8–48.6%). Stimulation index levels of response to materials were markedly varied with the highest being aluminium. Female sex, smoking history, cutaneous reaction to jewellery, occupational exposure, and dental procedures were among factors shown to increase the odds of having higher reactivity response to tested metals. Nevertheless, patients with well-functioning prior contralateral TKA did not appear at greater risk of having either sensitivity or susceptibility with odds ratio (OR) = 0.2 (95% CI 0.01–3.2), p: NS and OR = 0.6 (95% CI 0.3–1.2), p: NS, respectively. Prior positive patch test was neither predictor of susceptibility to hypersensitivity OR = 1.2 (95% CI 0.6–2.6) p: NS nor predictor of true hypersensitivity OR = 0.7 (95% CI 0.08–6.1), p: NS. Conclusion Among patients scheduled for primary TKA with no prior clinical features of metal allergy the prevalence of true hypersensitivity to at least one metal is just over 3%. Patients are likely to encounter a material to which they have pre-existing susceptibility to hypersensitivity. With certain prior exposure factors, there was increased susceptibility to metal hypersensitivity reaction evoking an acquired condition. Level of evidence: Level II, prospective cross-sectional study.

Background Resolvin D1 (RvD1), an important member of resolvins, exerts a wide spectrum of biological effects , including resolution of inflammation, tissue repair, and preservation of cell viability. The aim of the present study is to investigate the anti-arthritic potential and clarify the bone protective actions of RvD1 in vitro and in vivo. Methods RAW264.7 cells were treated with 50 ng/ml LPS for 72 h in the presence or absence of RvD1 (0–500 nM). Primary human monocytes were treated with M-CSF + RANKL for 14 days ± RvD1 (0–500 nM) with or without siRNA against RvD1 receptor FPR2. Expressions of inflammatory mediators, degrading enzymes, osteoclasts (OC) formation, and bone resorption were analyzed. The therapeutic effect of RvD1 (0–1000 ng) was carried out in murine collagen antibody-induced arthritis. Arthritis scoring, joint histology, and inflammatory and bone turnover markers were measured. Results RvD1 is not toxic and inhibits OC differentiation and activation. It decreases bone resorption, as assessed by the inhibition of TRAP and cathepsin K expression, hydroxyapatite matrix resorption, and bone loss. In addition, RvD1 reduces TNF-α, IL-1β, IFN-γ, PGE 2 , and RANK and concurrently enhances IL-10 in OC. Moreover, in arthritic mice, RvD1 alleviates clinical score, paw inflammation, and bone and joint destructions. Besides, RvD1 reduces inflammatory mediators and markedly decreases serum markers of bone and cartilage turnover. Conclusion Our results provide additional evidence that RvD1 plays a key role in preventing bone resorption and other pathophysiological changes associated with arthritis. The study highlights the clinical relevance of RvD1 as a potential compound for the treatment of inflammatory arthritis and related bone disorders.

Cu-containing hierarchical SAPO-34 catalysts were synthesized by the bottom-up method using different mesoporogen templates: CTAB encapsulated within ordered mesoporous silica nanoparticles (MSNs) and sucrose. A high fraction of the Cu centers exchanged in the hierarchical SAPO-34 architecture with high mesopore surface area and volume was achieved when CTAB was embedded within ordered mesoporous silica nanoparticles. Physicochemical characterization was performed by using structural and spectroscopic techniques to elucidate the properties of hierarchical SAPO-34 before and after Cu introduction. The speciation of the Cu sites, investigated by DR UV-Vis, and the results of the catalytic tests indicated that the synergy between the textural properties of the hierarchical SAPO-34 framework, the high Cu loading, and the coordination and localization of the Cu sites in the hierarchical architecture is the key point to obtaining good preliminary results in the NO selective catalytic reduction with hydrocarbons (HC-SCR).

Background The objective of this systematic review is to appraise evidence on the economic evaluations of advanced practice physiotherapy (APP) care compared to usual medical care. Methods Systematic searches were conducted up to September 2021 in selected electronic bibliographical databases. Economic evaluation studies on an APP model of care were included. Economic data such as health care costs, patient costs, productivity losses were extracted. Methodological quality of included studies was assessed with the Effective Public Health Practice Project tool and the Critical Appraisal Skills Programme checklist. Meta-analyses were performed and mean differences (MD) in costs per patient were calculated using random-effect inverse variance models. Certainty of the evidence was assessed with the GRADE Approach. Results Twelve studies ( n  = 14,649 participants) including four randomized controlled trials, seven analytical cohort studies and one economic modeling study were included. The clinical settings of APP models of care included primary, emergency and specialized secondary care such as orthopaedics, paediatrics and gynaecology. The majority of the included participants were adults with musculoskeletal disorders ( n  = 12,915). Based on low quality evidence, health system costs including salaries, diagnostic tests, medications, and follow-up visits were significantly lower with APP care than with usual medical care, at 2 to 12-month follow-up (MD: -139.08 €/patient; 95%CI: -265.93 to -12.23; n  = 7648). Based on low quality evidence, patient costs including travel and paid medication prescriptions, or treatments were significantly higher with APP care compared to usual medical care, at 2 to 6-month follow-up (MD: 29.24 €/patient; 95%CI: 0.53 to 57.95 n  = 1485). Based on very low quality evidence, no significant differences in productivity losses per patient were reported between both types of care (MD: 590 €/patient; 95%CI: -100 to 1280; n  = 819). Conclusions This is the first systematic review and meta-analysis on the economic evaluation of APP models of care. Low quality evidence suggests that APP care might result in lower health care costs, but higher patient costs compared to usual medical care. Costs differences may vary depending on various factors such as the cost methodology used and on the clinical setting. More evidence is needed to evaluate cost benefits of APP models of care.

The carbon capture and storage (CCS) process has become one of the main technologies used for mitigating greenhouse gas emissions. The success of CCS projects relies on accurate subsurface reservoir petrophysical characterization, enabling efficient storage and captured CO 2 containment. In digital rock physics, X-ray microtomography ( μ -CT) is applied to characterize reservoir rocks, allowing a more assertive analysis of physical properties such as porosity and permeability, enabling better simulations of porous media flow. Estimating petrophysical properties through numeric simulations usually requires high-resolution images, which are expensive and time-inefficient to obtain with μ -CT. To address this, we propose using two deep learning models: a super-resolution model to enhance the quality of low-resolution images and a surrogate model that acts as a substitute for numerical simulations to estimate the petrophysical property of interest. A correction process inspired by generative adversarial network (GAN) adversarial training is applied. In this approach, the super-resolution model acts as a generator, creating high-resolution images, and the surrogate network acts as a discriminator. By adjusting the generator, images that correct the errors in the surrogate’s estimations are produced. The proposed method was applied to the DeePore dataset. The results shows the proposed approach improved permeability estimation overall.

Background The physiological balance between bone resorption and bone formation is now known to be mediated by a cascade of events parallel to the classic osteoblast-osteoclast interaction. Thus, osteoimmunology now encompasses the role played by other cell types, such as cytokines, lymphocytes and chemokines, in immunological responses and how they help modulate bone metabolism. All these factors have an impact on the RANK/RANKL/OPG pathway, which is the major pathway for the maturation and resorption activity of osteoclast precursor cells, responsible for osteoporosis development. Recently, immunoporosis has emerged as a new research area in osteoimmunology dedicated to the immune system’s role in osteoporosis. Methods The first part of this review presents theoretical concepts on the factors involved in the skeletal system and osteoimmunology. Secondly, existing treatments and novel therapeutic approaches to treat osteoporosis are summarized. These were selected from to the most recent studies published on PubMed containing the term osteoporosis . All data relate to the results of in vitro and in vivo studies on the osteoimmunological system of humans, mice and rats. Findings Treatments for osteoporosis can be classified into two categories. They either target osteoclastogenesis inhibition (denosumab, bisphosphonates), or they aim to restore the number and function of osteoblasts (romozumab, abaloparatide). Even novel therapies, such as resolvins, gene therapy, and mesenchymal stem cell transplantation, fall within this classification system. Conclusion This review presents alternative pathways in the pathophysiology of osteoporosis, along with some recent therapeutic breakthroughs to restore bone homeostasis.

Background Dirofilaria immitis is a life-threatening nematode spreading globally. Arsenical treatment is currently recommended for removal of adult worms. However, arsenical treatment is not available in some countries, and there are dogs that cannot tolerate the rapid kill of adult worms; therefore, alternative adulticide slow-kill treatments are needed. Criticisms against the use of these alternative protocols include the potential for allowing disease to progress and for the development of ML-resistant worms. Methods The efficacy of a protocol that includes semi-annual doses (i.e. every 6 months) of commercially available extended-release injectable moxidectin suspension (ProHeart ® SR-12) with 30-day oral administration of doxycycline was studied in 20 dogs with naturally occurring D. immitis infections. Each dog received treatment with ProHeart ® SR-12 (0.5 mg moxidectin/kg) by subcutaneous injection and oral doxycycline (10 mg/kg/bid × 30 days) every 6 months until two consecutive negative antigen test results were obtained. Pulmonary and cardiac evaluations were performed by radiographic and echocardiographic parameters. Physical examinations, complete blood counts, clinical chemistry profiles, microfilariae and antigen tests were performed periodically. Results At enrollment, all dogs were positive for D. immitis antigen and 18 were microfilaremic. On day 30, microfilaremia counts decreased, and all dogs became amicrofilaremic by day 150. On day 180, 11 dogs were antigen-negative, and 7 more became negative by day 360. The two remaining antigen-positive dogs converted to negative by day 540 or 810. All antigen tests performed 180 days after the first negative test were negative. There was no decline in cardiac performance of the dogs throughout the study. Overall, pulmonary clinical conditions, presence of worms by echocardiography, and enlargement of caudal and main pulmonary arteries improved after treatment. Physical examinations, complete blood count results, and clinical chemistry profiles were within normal reference values. Respiratory conditions were improved, no damage to the heart was observed, and the treatment protocol was well tolerated by the animals. Conclusions This alternative adulticide treatment was efficacious and well tolerated in naturally infected dogs. The injectable formulation provides the advantage of having veterinarians able to administer, monitor, and assess the efficacy and condition of the dog throughout the treatment and post-treatment periods.