Meta-Analysis of Adipose Tissue Derived Cell-Based Therapy for the Treatment of Knee Osteoarthritis.

Osteoarthritis (OA) is a degenerative disorder associated with cartilage loss and is a leading cause of disability around the world. In old age, the capacity of cartilage to regenerate is diminished. With an aging population, the burden of OA is set to rise. Currently, there is no definitive treatment for OA. However, cell-based therapies derived from adipose tissue are promising. A PRISMA systematic review was conducted employing four databases (MEDLINE, EMBASE, Cochrane, Web of Science) to identify all clinical studies that utilized adipose tissue derived mesenchymal stem cells (AMSCs) or stromal vascular fraction (SVF) for the treatment of knee OA. Eighteen studies were included, which met the inclusion criteria. Meta-analyses were conducted on fourteen of these studies, which all documented WOMAC scores after the administration of AMSCs. Pooled analysis revealed that cell-based treatments definitively improve WOMAC scores, post treatment. These improvements increased with time. The studies in this meta-analysis have established the safety and efficacy of both AMSC therapy and SVF therapy for knee OA in old adults and show that they reduce pain and improve knee function in symptomatic knee OA suggesting that they may be effective therapies to improve mobility in an aging population

Synovium-Derived Mesenchymal Stem Cell Transplantation in Cartilage Regeneration: A PRISMA Review of in vivo Studies.

Articular cartilage damaged through trauma or disease has a limited ability to repair. Untreated, focal lesions progress to generalized changes including osteoarthritis. Musculoskeletal disorders including osteoarthritis are the most significant contributor to disability globally. There is increasing interest in the use of mesenchymal stem cells (MSCs) for the treatment of focal chondral lesions. There is some evidence to suggest that the tissue type from which MSCs are harvested play a role in determining their ability to regenerate cartilage in vitro and in vivo. In humans, MSCs derived from synovial tissue may have superior chondrogenic potential. We carried out a systematic literature review on the effectiveness of synovium-derived MSCs (sMSCs) in cartilage regeneration in in vivo studies in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Twenty studies were included in our review; four examined the use of human sMSCs and 16 were conducted using sMSCs harvested from animals. Most studies reported successful cartilage repair with sMSC transplantation despite the variability of animals, cell harvesting techniques, methods of delivery, and outcome measures. We conclude that sMSC transplantation holds promise as a treatment option for focal cartilage defects. We believe that defining the cell population being used, establishing standardized methods for MSC delivery, and the use of objective outcome measures should enable future high quality studies such as randomized controlled clinical trials to provide the evidence needed to manage chondral lesions optimally

Infrapatellar fat pad adipose-derived stem cells co-cultured with articular chondrocytes from osteoarthritis patients exhibit increased chondrogenic gene expression.

AIM: The variable results in clinical trials of adipose tissue-derived stem cells (ASCs) for chondral defects may be due to the different ex vivo culture conditions of the ASCs which are implanted to treat the lesions. We sought to determine the optimal in vitro chondrocyte co-culture condition that promotes infrapatellar fat pad-derived (IFPD) ASC chondrogenic gene expression in a novel co-culture combination. METHODS: In our study, we utilized an in vitro autologous co-culture of IFPD ASCs and articular chondrocytes derived from Kellgren-Lawrence Grade III/IV osteoarthritic human knee joints at ASC-to-chondrocyte seeding log ratios of 1:1, 10:1, and 100:1. Gene expression following in vitro co-culture was quantified by RT-qPCR with a panel comprising COL1A1, COL2A1, COL10A1, L-SOX5, SOX6, SOX9, ACAN, HSPG2, and COMP for chondrogenic gene expression. RESULTS: The chondrogenic gene expression profiles from co-cultures were greater than would be expected from an expression profile modeled from chondrocyte and ASC-only monocultures. Additionally, chondrogenic gene expression decreased with increasing ASC-to-chondrocyte seeding ratios. CONCLUSIONS: These findings provide insight into the mechanisms underlying clinical ASC therapies and signifies that IFPD ASCs pre-conditioned by chondrocyte co-culture may have improved chondrogenic potential for cartilage repair. This model can help further understand IFPD ASCs in chondral and osteochondral repair and the chondrogenic pathways involved. Video Abstract

The association between alcohol consumption and osteoarthritis: a meta-analysis and meta-regression of observational studies.

There is conflicting evidence for the association between alcohol consumption and common joint conditions such as Osteoarthritis (OA), which affects millions of people. We sought to determine the true association between alcohol intake and OA. We conducted a PRISMA systematic review and meta-analysis of observational studies that reported associations between alcohol consumption and OA. Pooled estimates of association were represented through odds ratios (ORs). Publication bias was assessed with Funnel and Galbraith plots, and risk of bias was assessed with the Newcastle Ottawa Scale. We included 29 studies and 25,192 subjects with OA and reported an OR between any alcohol consumption and OA of 0.79 (0.68-0.93), suggesting a protective effect. OR of weekly or more frequent use was 0.79 (0.65-0.97). When grouped by covariates, alcohol consumption was negatively associated with radiographic (0.83, 0.70-0.98), hand (0.80, 0.66-0.95) and knee OA (0.85, 0.72-0.99), North American ethnicity and female gender. Subgroup analysis of unadjusted data resulted in an OR of 0.70 (0.55-0.89) but this disappeared upon analysis of studies with data adjusted for any covariate (0.93, 0.78-1.10). Whilst our pooled analysis suggest that weekly or more frequent alcohol consumption was negatively associated with OA, this was not observed when adjusted for confounding factors. Reasons for this include selection bias and lack of longitudinal exposure and adjustment for confounding variables. Therefore, this meta-analysis provides evidence to dispel notions that alcohol use may be protective against OA

The Treatment of Cartilage Damage Using Human Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Systematic Review of in vivo Studies

Damage to joints through injury or disease can result in cartilage loss, which if left untreated can lead to inflammation and ultimately osteoarthritis. There is currently no cure for osteoarthritis and management focusses on symptom control. End-stage osteoarthritis can be debilitating and ultimately requires joint replacement in order to maintain function. Therefore, there is growing interest in innovative therapies for cartilage repair. In this systematic literature review, we sought to explore the in vivo evidence for the use of human Mesenchymal Stem Cell-derived Extracellular Vesicles (MSC-EVs) for treating cartilage damage. We conducted a systematic literature review in accordance with the PRISMA protocol on the evidence for the treatment of cartilage damage using human MSC-EVs. Studies examining in vivo models of cartilage damage were included. A risk of bias analysis of the studies was conducted using the SYRCLE tool. Ten case-control studies were identified in our review, including a total of 159 murine subjects. MSC-EVs were harvested from a variety of human tissues. Five studies induced osteoarthritis, including cartilage loss through surgical joint destabilization, two studies directly created osteochondral lesions and three studies used collagenase to cause cartilage loss. All studies in this review reported reduced cartilage loss following treatment with MSC-EVs, and without significant complications. We conclude that transplantation of MSC-derived EVs into damaged cartilage can effectively reduce cartilage loss in murine models of cartilage injury. Additional randomized studies in animal models that recapitulates human osteoarthritis will be necessary in order to establish findings that inform clinical safety in humans

Competitive Inoculation as an Effective Prophylaxis Against Recurrent Urinary Tract Infections: A Systematic Review

Urinary tract infection (UTI) is a common condition defined as the presence of bacteria within the urine above a certain threshold (usually >100,000 m/L). The lifetime risk in women is estimated to be 50%, of whom 25% will develop recurrence within 6 months. Unfortunately, the use of antibiotics to treat and manage recurrent UTI (rUTI) is a growing problem, due to the burden of growing antibiotic resistance on public health. As such, new approaches to manage rUTI are being investigated and developed. Competitive inoculation via instillation of Escherichia coli 83972 or HU2117 in the bladder is a new prophylactic non-antimicrobial therapy for rUTIs. It utilizes the principle of the protective nature of asymptomatic bacteriuria to prevent recurrence of symptomatic UTIs. However, the effectiveness and safety of this technique remains unclear. This systematic review examined the current outcomes data on competitive inoculation as an effective and safe treatment for rUTI prophylaxis. Based on a limited number of studies, current evidence suggests that competitive inoculation is an effective and safe prophylactic measure against UTIs in a select group of patients with incomplete bladder emptying. However, administration of the technology is both resource and time intensive, and there is strong data demonstrating low successful colonisation rates. Competitive inoculation is an alternative to antibiotics only to rUTI patients with incomplete bladder emptying. There is no evidence to suggest that the technology would be suitable for other subsets of rUTI patients. Further randomized controlled trials should be conducted to improve the evidence base before drawing conclusions for clinical practice, and ideas to improve colonisation rates and simplify the administration process should be explored

Virtual reality for acute pain in outpatient hysteroscopy: a randomised controlled trial

Objective: To evaluate the effectiveness of virtual reality as a distraction technique in the management of acute pain and anxiety during outpatient hysteroscopy. Design: Parallel group, prospective randomised controlled trial. Setting: UK University Hospital. Methods: Forty consenting, eligible women were randomised to virtual reality intervention (immersive video content as a distraction method) or standard care during outpatient hysteroscopy from August to October 2018. Main outcome measures: Pain and anxiety outcomes were measured as a numeric rating score (scale 0–10). Results: Compared with standard care, women with virtual reality intervention experienced less average pain (score 6.0 versus 3.7, mean difference 2.3, 95% CI 0.61–3.99, P = 0.009) and anxiety (score 5.45 versus 3.3, mean difference 2.15, 95% CI 0.38–3.92, P = 0.02). Conclusion: Virtual reality was effective in reducing pain and anxiety during outpatient hysteroscopy in a mixed‐methods randomised control trial. Its wide potential role in ambulatory gynaecological procedures needs further evaluation. Tweetable abstract: Virtual reality can be used as a part of a multimodal strategy to reduce acute pain and anxiety in patients undergoing outpatient hysteroscopy

Single-Channel Properties in Endoplasmic Reticulum Membrane of Recombinant Type 3 Inositol Trisphosphate Receptor

The inositol 1,4,5-trisphosphate receptor (InsP3R) is an intracellular Ca2+-release channel localized in endoplasmic reticulum (ER) with a central role in complex Ca2+ signaling in most cell types. A family of InsP3Rs encoded by several genes has been identified with different primary sequences, subcellular locations, variable ratios of expression, and heteromultimer formation. This diversity suggests that cells require distinct InsP3Rs, but the functional correlates of this diversity are largely unknown. Lacking are single-channel recordings of the recombinant type 3 receptor (InsP3R-3), a widely expressed isoform also implicated in plasma membrane Ca2+ influx and apoptosis. Here, we describe functional expression and single-channel recording of recombinant rat InsP3R-3 in its native membrane environment. The approach we describe suggests a novel strategy for expression and recording of recombinant ER-localized ion channels in the ER membrane. Ion permeation and channel gating properties of the rat InsP3R-3 are strikingly similar to those of Xenopus type 1 InsP3R in the same membrane. Using two different two-electrode voltage clamp protocols to examine calcium store-operated calcium influx, no difference in the magnitude of calcium influx was observed in oocytes injected with rat InsP3R-3 cRNA compared with control oocytes. Our results suggest that if cellular expression of multiple InsP3R isoforms is a mechanism to modify the temporal and spatial features of [Ca2+]i signals, then it must be achieved by isoform-specific regulation or localization of various types of InsP3Rs that have relatively similar Ca2+ permeation properties

A Review of Supercapacitors: Materials Design, Modification, and Applications

This is the final version. Available on open access from MDPI via the DOI in this recordSupercapacitors (SCs) have received much interest due to their enhanced electrochemical performance, superior cycling life, excellent specific power, and fast charging–discharging rate. The energy density of SCs is comparable to batteries; however, their power density and cyclability are higher by several orders of magnitude relative to batteries, making them a flexible and compromis-ing energy storage alternative, provided a proper design and efficient materials are used. This review emphasizes various types of SCs, such as electrochemical double-layer capacitors, hybrid su-percapacitors, and pseudo-supercapacitors. Furthermore, various synthesis strategies, including sol-gel, electro-polymerization, hydrothermal, co-precipitation, chemical vapor deposition, direct coating, vacuum filtration, de-alloying, microwave auxiliary, in situ polymerization, electro-spin-ning, silar, carbonization, dipping, and drying methods, are discussed. Furthermore, various func-tionalizations of SC electrode materials are summarized. In addition to their potential applications, brief insights into the recent advances and associated problems are provided, along with conclu-sions. This review is a noteworthy addition because of its simplicity and conciseness with regard to SCs, which can be helpful for researchers who are not directly involved in electrochemical energy storage.Saudi Aramco Chair ProgrammeEngineering and Physical Sciences Research Council (EPSRC