Injuries to articular cartilage and menisci can lead to cartilage degeneration that ultimately results in arthritis. Different forms of arthritis affect ~50 million people in the USA alone, and it is ...therefore crucial to identify methods that will halt or slow the progression to arthritis, starting with the initiating events of cartilage and meniscus defects. The surgical approaches in current use have a limited capacity for tissue regeneration and yield only short-term relief of symptoms. Tissue engineering approaches are emerging as alternatives to current surgical methods for cartilage and meniscus repair. Several cell-based and tissue-engineered products are currently in clinical trials for cartilage lesions and meniscal tears, opening new avenues for cartilage and meniscus regeneration. This Review provides a summary of surgical techniques, including tissue-engineered products, that are currently in clinical use, as well as a discussion of state-of-the-art tissue engineering strategies and technologies that are being developed for use in articular cartilage and meniscus repair and regeneration. The obstacles to clinical translation of these strategies are also included to inform the development of innovative tissue engineering approaches.
The clinical practice of platelet-rich plasma (PRP) therapy has grown significantly in recent years in multiple medical specialties. However, comparisons of PRP studies across medical fields remain ...challenging because of inconsistent reporting of protocols and characterization of the PRP being administered. The purpose of this systematic review was to determine the quantity of level I/II studies within each medical specialty and compare the level of study reporting across medical fields.
The Cochrane Database, PubMed, and EMBASE databases were queried for level I/II clinical studies on PRP injections across all medical specialties. From these studies, data including condition treated, PRP processing and characterization, delivery, control group, and assessed outcomes were collected.
A total of 132 studies met the inclusion and exclusion criteria and involved 28 different conditions across 8 specialties (cardiothoracic surgery, cosmetic, dermatology, musculoskeletal (MSK), neurology, oral maxillofacial surgery, ophthalmology, and plastic surgery). Studies on PRP for MSK injuries made up the majority of the studies (74%), with knee osteoarthritis and tendinopathy being most commonly studied. Of the 132 studies, only 44 (33%) characterized the composition of PRP used, and only 23 (17%) reported the leukocyte component. MSK studies were more likely to use patient-reported outcome measures to assess outcomes, while studies from other specialties were more likely to use clinician- or imaging-based objective outcomes. Overall, 61% of the studies found PRP to be favorable over control treatment, with no difference in favorable reporting between MSK and other medical specialties.
The majority of level I/II clinical studies investigating PRP therapy across all medical specialties have been conducted for MSK injuries with knee osteoarthritis and tendinopathy being the most commonly studied conditions. Inconsistent reporting of PRP composition exists among all studies in medicine. Rigorous reporting in human clinical studies across all medical specialties is crucial for evaluating the effects of PRP and moving towards disease-specific and individualized treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic high‐fat‐diet (HFD) consumption can lead to the development of brain insulin resistance, which then exerts deleterious effects on learning and memory. Activity‐regulated ...cytoskeleton‐associated protein (Arc) is a memory‐related protein, and its expression can be induced by insulin stimulation. In HFD‐fed animals, their basal Arc protein levels in cerebral cortex and hippocampus are reduced. However, the effects of HFD on novelty‐induced Arc protein expression that is important for cognitive function is still unknown. In the present study, after feeding HFD (60% kcal from fat) for 5 weeks, mice developed brain insulin resistance and had a significant reduction in the novelty‐induced but not the basal Arc protein levels in their hippocampi. Further experiments were performed in primary rat hippocampal neurons. The results show that, under the condition of neuronal insulin resistance, acute insulin stimulation induced less activation of the phosphatidylinositol 3‐kinase/protein kinase B/p70 ribosomal S6 kinase (PI3K/Akt/p70S6K) pathway, resulting in reduced induction of Arc protein expression. Accordingly, it is suggested that following HFD feeding, the reduction in novelty‐induced Arc protein expression in animal's hippocampus is probably related to a suppressed activation of the PI3K/Akt/p70S6K pathway due to the existence of brain insulin resistance.
Mice were fed with either a normal chow diet (NCD) or a high‐fat diet (HFD) for 5 weeks. In NCD‐fed mice, exposure to novelty‐induced significantly enhanced expression of Arc protein, whereas, in HFD‐fed mice, the basal Arc protein level was unchanged, but the novelty‐induced Arc protein expression was reduced. In addition, brain insulin resistance was found in HFD‐fed mice.
Working memory (WM) is a cognitive function important for guiding the on‐going or upcoming behavior. A memory‐related protein Arc (activity‐regulated cytoskeleton‐associated protein) is implicated in ...long‐term memory consolidation. Recent evidence further suggests the involvement of hippocampal Arc in spatial WM. The medial prefrontal cortex (mPFC) is a key brain region mediating WM. However, the role of mPFC Arc in WM is still uncertain. To investigate whether mPFC Arc protein is involved in WM performance, delayed non‐match to sample (DNMS) T‐maze task was performed in rats with or without blocking new synthesis of mPFC Arc. In DNMS task, a 10‐s or 30‐s delay between the sample run and the choice run was given to evaluate WM performance. To block new Arc protein synthesis during the DNMS task, Arc antisense oligodeoxynucleotides (ODNs) were injected to the bilateral mPFC. The results show that, in rats without surgery for cannula implantation and subsequent intracerebral injection of ODNs, WM was functioning well during the DNMS task with a delay of 10 s but not 30 s, which was accompanied with a significantly increased level of mPFC Arc protein, indicating a possible link between enhanced Arc protein expression and the performance of WM. After preventing the enhancement of mPFC Arc protein expression with Arc antisense ODNs, rat's WM performance was impaired. These findings support enhanced mPFC Arc protein expression playing a role during WM performance.
The coarse-mesh finite difference (CMFD) scheme is a very effective nonlinear diffusion acceleration method for neutron transport calculations. CMFD can become unstable and fail to converge when the ...computational cell optical thickness is relatively large in k-eigenvalue problems or diffusive fixed-source problems. Some variants and fixups have been developed to enhance the stability of CMFD, including the partial current-based CMFD (pCMFD), optimally diffusive CMFD (odCMFD), and linear prolongation-based CMFD (lpCMFD). Linearized Fourier analysis has proven to be a very reliable and accurate tool to investigate the convergence rate and stability of such coupled high-order transport/low-order diffusion iterative schemes. It is shown in this paper that the use of different transport solvers in Fourier analysis may have some potential implications on the development of stabilizing techniques, which is exemplified by the odCMFD scheme. A modification to the artificial diffusion coefficients of odCMFD is proposed to improve its stability. In addition, two explicit expressions are presented to calculate local optimal successive overrelaxation (SOR) factors for lpCMFD to further enhance its acceleration performance for fixed-source problems and k-eigenvalue problems, respectively.
This study explored the effect of a moderate (90 g/d) low-carbohydrate diet (LCD) in type 2 diabetes patients over 18 months.
Ninety-two poorly controlled type 2 diabetes patients aged 20-80 years ...with HbA1c ≥7.5% (58 mmol/mol) in the previous three months were randomly assigned to a 90 g/d LCD r traditional diabetic diet (TDD). The primary outcomes were glycaemic control status and change in medication effect score (MES). The secondary outcomes were lipid profiles, small, dense low-density lipoprotein (sdLDL), serum creatinine, microalbuminuria and carotid intima-media thickness (IMT).
A total of 85 (92.4%) patients completed 18 months of the trial. At the end of the study, the LCD and TDD group consumed 88.0±29.9 g and 151.1±29.8 g of carbohydrates, respectively (p < 0.05). The 18-month mean change from baseline was statistically significant for the HbA1c (-1.6±0.3 vs. -1.0±0.3%), 2-h glucose (-94.4±20.8 vs. -18.7±25.7 mg/dl), MES (-0.42±0.32 vs. -0.05±0.24), weight (-2.8±1.8 vs. -0.7±0.7 kg), waist circumference (-5.7±2.7 vs. -1.9±1.4 cm), hip circumference (-6.1±1.8 vs. -2.9±1.7 cm) and blood pressure (-8.3±4.6/-5.0±3 vs. 1.6±0.5/2.5±1.6 mmHg) between the LCD and TDD groups (p<0.05). The 18-month mean change from baseline was not significantly different in lipid profiles, sdLDL, serum creatinine, microalbuminuria, alanine aminotransferase (ALT) and carotid IMT between the groups.
A moderate (90 g/d) LCD showed better glycaemic control with decreasing MES, lowering blood pressure, decreasing weight, waist and hip circumference without adverse effects on lipid profiles, sdLDL, serum creatinine, microalbuminuria, ALT and carotid IMT than TDD for type 2 diabetic patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Long-term exposure to excess 27-hydroxycholesterol (27-OHC) enhances histone deacetylase (HDAC) activity.•HDAC inhibitor improves 27-OHC-induced memory deficits.•HDAC inhibitor prevents ...27-OHC-induced decrease in amyloid-β clearance.•HDAC inhibitor prevents 27-OHC-induced decrease in PSD-95 levels.•The ability to retrieve spatial memory is much more vulnerable to 27-OHC exposure.
Hypercholesterolemia is a risk factor for Alzheimer’s disease (AD). Plasma cholesterol does not pass the blood–brain barrier whereas its metabolite 27-hydroxycholesterol (27-OHC) can enter the brain. High 27-OHC in the brain has been suggested to mediate hypercholesterolemia-induced impairments of learning and memory through promoting amyloid-β accumulation and facilitating synaptic disruption. In AD brains, the activity of histone deacetylase (HDAC) is elevated. Treating AD animals with HDAC inhibitors decreases amyloid-β levels and synaptic damages, which leads to memory improvement. Whether HDAC activity is involved in the actions of 27-OHC is still uncertain. In this study, 4 weekly injections of 27-OHC/vehicle were given to rats followed by 3 daily injections of HDAC inhibitor trichostatin (TSA)/vehicle. The results of Morris water maze test reveal that all rats have intact spatial learning ability during the 5-d training phase. However, the behavioral performance during the probe trial was impaired by 27-OHC treatment, which was improved by adding TSA treatments. Furthermore, 27-OHC treatments reduced the hippocampal levels of acetylated histone H3, acetylated α tubulin, insulin-degrading enzyme and postsynaptic protein PSD-95, indicating that 27-OHC treatments may induce enhanced HDAC activity, decreased amyloid-β clearance and synaptic disruption. All reduced levels returned to the basal levels by adding TSA treatments. These findings support our hypothesis that HDAC activity is enhanced following long-term exposure to excess 27-OHC.
•Prenatal DEHP exposure impairs spatial learning and memory in the late-adolescent male rats.•Down-regulations of BDNF, NMDA receptor, Arc, and synaptophysin are found in the DEHP-exposed male ...rats.•Exercise prevents the impairment of learning and memory in prenatally DEHP exposed male rats.•Exercise improves the hippocampal expressions of plasticity-related proteins in the DEHP-exposed male rats.
Regular exercise has been identified to facilitate neuroplasticity that maximize functional outcome after brain injuries. Brain-derived neurotrophic factor (BDNF) has emerged as a key facilitator of neuroplasticity after exercise. The activity-regulated cytoskeleton associated protein (Arc) is induced by BDNF and N-methyl-d-aspartic acid receptor (NMDAR), contributing to functional modification of neuroplasticity in the hippocampus. Meanwhile, early-life exposure to neuroendocrine disruptor di-(2-ethylhexyl)-phthalate (DEHP) is a risk factor for behavioral deficits, but the mechanisms responsible for DEHP-induced neurotoxicity are not well understood. The purpose of this study is to investigate whether hippocampal Arc expression is impaired by DEHP exposure and to examine the protective role of exercise in the prenatally DEHP-exposed male rats. Sprague Dawley dams were fed with vehicle or DEHP during gestation. The male offspring were trained to treadmill running for 5 weeks followed by examination of behavioral and biochemical outcomes. The results showed that DEHP-exposed rats exhibited impairment of spatial learning and memory as well as down-regulations of BDNF, NMDAR, Arc, and synaptophysin. Importantly, aerobic exercise during childhood-adolescence prevented the impairment of learning and memory by recovering the expressions of BDNF, NMDAR, Arc, and synaptophysin. These findings suggest that exercise may provide beneficial effects on ameliorating the impairment of neuroplasticity in the prenatally DEHP-exposed male rats at late adolescence.
Both the detrimental effect of prenatal exposure to di-(2-ethylhexyl)-phthalate (DEHP) and the beneficial effects of physical exercise on brain functions have been reported. The oxytocin pathway has ...been implicated in the onset of maternal behaviors. Epigenetic modification of the oxytocin receptor gene (OXTR) through DNA methylation has been associated with the pathogenesis of neuropsychiatric disorders. The purpose of this study was to investigate the effects of prenatal DEHP exposure on oxytocin-regulated maternal behaviors and to examine the protective effect of exercise. Pregnant rats (F0) were fed with vehicle or DEHP during gestation and the offspring females (F1) were assessed for their maternal behaviors by pup retrieval test at postpartum. The results showed that reduced pup retrieval activities without significant alteration of stress responses were observed in the prenatally DEHP-exposed females. Prenatal DEHP exposure decreased the expressions of oxytocin,
mRNA, and oxytocin receptor, and increased
methylation in the hypothalamus of postpartum female rats. There were no significant effects of exercise on behavioral, biochemical, and epigenetic measurements. These results suggest that prenatal DEHP exposure has a long-term adverse effect on maternal behaviors;
hyper-methylation may be a potential epigenetic mechanism for this alteration, which cannot be prevented by physical exercise during childhood.
This article was updated on December 4, 2018, because of previous errors. On pages 1949 and 1958, in the byline, the second author was incorrectly listed as “Dean X. Wang, MD,” which was then ...abbreviated to “D.X. Wang” in the ORCID iD list. The authorʼs name is now listed as “Dean Wang, MD” in the byline and abbreviated to “D. Wang” in the ORCID iD list. Additionally, on page 1958, in the ORCID iD list, the ORCID iD for Dr. Scott A. Rodeo was incorrectly listed as “0000-0003-2991-7173.” Dr. Rodeoʼs ORCID iD is now listed as “0000-0002-0745-9880.”An erratum has been publishedJ Bone Joint Surg Am. 2019 Jan 16;101(2):e9.
BACKGROUND:Fresh osteochondral allograft transplantation is an appealing option to address a failed cartilage repair surgical procedure, given the ability to treat large lesions and to address the subchondral osseous changes commonly seen in the revision setting. We hypothesized that osteochondral allograft transplantation after failed cartilage repair would result in low failure rates and improved function and that improved graft incorporation on postoperative magnetic resonance imaging (MRI) would correlate with a superior clinical outcome.
METHODS:A retrospective review of prospectively collected data was used to identify 43 patients treated with fresh osteochondral allograft transplantation after a previous cartilage repair surgical procedure and having a minimum follow-up of 2 years. Clinical outcomes were evaluated using the Short Form-36 (SF-36) score, International Knee Documentation Committee (IKDC) Subjective Knee Score, Marx Activity Scale, Knee Outcome Survey-Activities of Daily Living (KOS-ADL) Questionnaire, Cincinnati Sports Activity Score, and Cincinnati Overall Symptom Assessment. Postoperative MRI scans were obtained at a mean time of 19.7 months and were independently reviewed by a musculoskeletal radiologist using the Osteochondral Allograft MRI Scoring System (OCAMRISS).
RESULTS:At a mean 3.5-year follow-up after osteochondral allograft transplantation, significant improvements (p < 0.05) in SF-36 Physical Function, SF-36 Pain, KOS-ADL, IKDC Subjective Knee Score, and Cincinnati Overall Symptom Assessment were seen. Over 90% of grafts remained in situ at the time of the latest follow-up, although 17 knees (40%) underwent reoperation, the majority for arthroscopic debridement or manipulation for stiffness. Body mass index (BMI) of >30 kg/m was associated with worse clinical outcomes. The mean total OCAMRISS score demonstrated poorer allograft integration in patients with graft failure, but the total score did not meaningfully correlate with clinical outcome scores. However, better individual articular cartilage appearance and osseous integration subscores were associated with better clinical outcome scores.
CONCLUSIONS:Significant improvements in pain and function were seen following fresh osteochondral allograft transplantation after failed cartilage repair, with an overall graft survival rate of >90%. Patients with greater bone and cartilage incorporation on MRI had superior clinical outcomes, although persistent osseous edema was frequently seen. We concluded that osteochondral allograft transplantation is an effective salvage treatment after failed cartilage repair and recommend further evaluation of techniques to optimize graft integration.
LEVEL OF EVIDENCE:Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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