In vivo microstructural heterogeneity of white matter and cognitive correlates in aging using tissue compositional analysis of diffusion magnetic resonance imaging.

BACKGROUND: Age-related cognitive decline is linked to changes in the brain, particularly the deterioration of white matter (WM) microstructure that accelerates after the age of 60. WM deterioration is associated with mild cognitive impairment and dementia, but the origin and role of white matter signal abnormalities (WMSA) seen in standard MRI remain debated due to their heterogeneity. This study explores the potential of single-shell 3-tissue constrained spherical deconvolution (SS3T-CSD), a novel technique that models diffusion data in terms of gray matter (TG ), white matter (Tw ), and cerebrospinal fluid (TC ), to differentiate WMSA from normal-appearing white matter and better understand the interplay between changes in WM microstructure and decline in cognition. METHODS: A total of 189 individuals from the GENIC cohort were included. MRI data, including T1-weighted and diffusion images, were obtained. Preprocessing steps were performed on the diffusion MRI data, followed by the SS3T-CSD. WMSA were segmented using FreeSurfer. Statistical analyses were conducted to assess the association between age, WMSA volume, 3-tissue signal fractions (Tw , TG , and TC ), and neuropsychological variables. RESULTS: Participants above 60 years old showed worse cognitive performance and processing speed compared to those below 60 (p < .001). Age was negatively associated with Tw in normal-appearing white matter (p < .001) and positively associated with TG in both WMSA (p < .01) and normal-appearing white matter (p < .001). Age was also significantly associated with WMSA volume (p < .001). Higher processing speed was associated with lower Tw and higher TG , in normal-appearing white matter (p < .01 and p < .001, respectively), as well as increased WMSA volume (p < .001). Similarly, lower MMSE scores correlated with lower Tw and higher TG in normal-appearing white matter (p < .05). High cholesterol and hypertension were associated with higher WMSA volume (p < .05). CONCLUSION: The microstructural heterogeneity within normal-appearing white matter and WMSA is associated with increasing age and cognitive variation, in cognitively unimpaired individuals. Furthermore, the 3-tissue signal fractions are more specific to potential white matter alterations than conventional MRI measures such as WMSA volume. These findings also support the view that the WMSA volumes may be more influenced by vascular risk factors than the 3-tissue metrics. Finally, the 3-tissue metrics were able to capture associations with cognitive tests and therefore capable of capturing subtle pathological changes in the brain in individuals who are still within the normal range of cognitive performance.

Recent Advances in Transition Metal-Based Catalysts for Ethylene Copolymerization with Polar Comonomer.

The synthesis of polar functionalized polyolefin (PFP) offers improvement in mixing properties, polymer surface, and rheological properties with the potential of upgraded polyolefins for modern and ingenious applications. The synthesis of PFP from metal-based catalyzed olefin (non-polar in nature) copolymerization with polar comonomers embodies energy-efficient, atom-efficient, and apparently an upfront methodology. Despite their outstanding success during conventional polymerization of olefin, 3rd and 4th group (early transition metal)-based catalysts, owing to their electrophilic nature, face challenges mainly due to Lewis basic sites of the polar monomers. On the contrary, late transition metal-based catalysts have also made progress, in recent years, for PFP synthesis. The recent past has also witnessed several advancements in the development of dominating palladium-based catalysts while their lower resistance towards ligand functional groups has limited the practical application of abundant and cheaper nickel-based catalysts. However, the relentless efforts of the scientific community, during the past half-decade, have indicated rigorous progress in the development of nickel-based catalysts for PFP synthesis. In this review, we have abridged the recent research trends in both early as well as late transition metal-based catalyst development. Furthermore, we have highlighted the role of transition metal-based catalysts in influencing the polymer properties.

Hybrid FSK-FDM Scheme for Data Rate Enhancement in Dual-Function Radar and Communication.

In this paper, we present a hybrid frequency shift keying and frequency division multiplexing (i.e., FSK-FDM) approach for information embedding in dual-function radar and communication (DFRC) design to achieve an improved communication data rate. Since most of the existing works focus on merely two-bit transmission in each pulse repetition interval (PRI) using different amplitude modulation (AM)- and phased modulation (PM)-based techniques, this paper proposes a new technique that doubles the data rate by using a hybrid FSK-FDM technique. Note that the AM-based techniques are used when the communication receiver resides in the side lobe region of the radar. In contrast, the PM-based techniques perform better if the communication receiver is in the main lobe region. However, the proposed design facilitates the delivery of information bits to the communication receivers with an improved bit rate (BR) and bit error rate (BER) regardless of their locations in the radar's main lobe or side lobe regions. That is, the proposed scheme enables information encoding according to the transmitted waveforms and frequencies using FSK modulation. Next, the modulated symbols are added together to achieve a double data rate using the FDM technique. Finally, each transmitted composite symbol contains multiple FSK-modulated symbols, resulting in an increased data rate for the communication receiver. Numerous simulation results are presented to validate the effectiveness of the proposed technique.

Bone Marrow-Derived Mesenchymal Stem Cell Implants for the Treatment of Focal Chondral Defects of the Knee in Animal Models: A Systematic Review and Meta-Analysis.

Osteoarthritis remains an unfortunate long-term consequence of focal cartilage defects of the knee. Associated with functional loss and pain, it has necessitated the exploration of new therapies to regenerate cartilage before significant deterioration and subsequent joint replacement take place. Recent studies have investigated a multitude of mesenchymal stem cell (MSC) sources and polymer scaffold compositions. It is uncertain how different combinations affect the extent of integration of native and implant cartilage and the quality of new cartilage formed. Implants seeded with bone marrow-derived MSCs (BMSCs) have demonstrated promising results in restoring these defects, largely through in vitro and animal studies. A PRISMA systematic review and meta-analysis was conducted using five databases (PubMed, MEDLINE, EMBASE, Web of Science, and CINAHL) to identify studies using BMSC-seeded implants in animal models of focal cartilage defects of the knee. Quantitative results from the histological assessment of integration quality were extracted. Repair cartilage morphology and staining characteristics were also recorded. Meta-analysis demonstrated that high-quality integration was achieved, exceeding that of cell-free comparators and control groups. This was associated with repair tissue morphology and staining properties which resembled those of native cartilage. Subgroup analysis showed better integration outcomes for studies using poly-glycolic acid-based scaffolds. In conclusion, BMSC-seeded implants represent promising strategies for the advancement of focal cartilage defect repair. While a greater number of studies treating human patients is necessary to realize the full clinical potential of BMSC therapy, high-quality integration scores suggest that these implants could generate repair cartilage of substantial longevity.

The Effects of Chronological Age on the Chondrogenic Potential of Mesenchymal Stromal Cells: A Systematic Review.

Tissue engineering and cell therapy for regenerative medicine have great potential to treat chronic disorders. In musculoskeletal disorders, mesenchymal stromal cells (MSCs) have been identified as a relevant cell type in cell and regenerative strategies due to their multi-lineage potential, although this is likely to be a result of their trophic and immunomodulatory effects on other cells. This PRISMA systematic review aims to assess whether the age of the patient influences the chondrogenic potential of MSCs in regenerative therapy. We identified a total of 3027 studies after performing a search of four databases, including Cochrane, Web of Science, Medline, and PubMed. After applying inclusion and exclusion criteria, a total of 14 papers were identified that were reviewed, assessed, and reported. Cell surface characterization and proliferation, as well as the osteogenic, adipogenic, and chondrogenic differentiation, were investigated as part of the analysis of these studies. Most included studies suggest a clear link between aged donor MSCs and diminished clonogenic and proliferative potential. Our study reveals a heterogeneous and conflicting range of outcomes concerning the chondrogenic, osteogenic, and adipogenic potential of MSCs in relation to age. Further investigations on the in vitro effects of chronological age on the chondrogenic potential of MSCs should follow the outcomes of this systematic review, shedding more light on this complex relationship.

Alternating Direction Method of Multipliers-Based Constant Modulus Waveform Design for Dual-Function Radar-Communication Systems.

In this paper, we design constant modulus waveforms for dual-function radar-communication (DFRC) systems based on a multi-input multi-output (MIMO) configuration of sensors for a far-field scenario. At first, we formulate a non-convex optimization problem subject to waveform synthesis for minimizing the interference power while maintaining a constant modulus constraint. Next, we solve this non-convex problem, iteratively, using the alternating direction method of multipliers (ADMM) algorithm. Importantly, the designed waveforms approximate a desired beampattern in terms of a high-gain radar beam and a slightly high gain communication beam while maintaining a desired low sidelobe level. The designed waveforms ensure an improved detection probability and an improved bit error rate (BER) for radar and communications parts, respectively. Finally, we demonstrate the effectiveness of the proposed method through simulation results.

Brain tissue microstructural and free-water composition 13 years after very preterm birth.

There have been many studies demonstrating children born very preterm exhibit brain white matter microstructural alterations, which have been related to neurodevelopmental difficulties. These prior studies have often been based on diffusion MRI modelling and analysis techniques, which commonly focussed on white matter microstructural properties in children born very preterm. However, there have been relatively fewer studies investigating the free-water content of the white matter, and also the microstructure and free-water content of the cortical grey matter, in children born very preterm. These biophysical properties of the brain change rapidly during fetal and neonatal brain development, and therefore such properties are likely also adversely affected by very preterm birth. In this study, we investigated the relationship of very preterm birth (<30 weeks' gestation) to both white matter and cortical grey matter microstructure and free-water content in childhood using advanced diffusion MRI analyses. A total of 130 very preterm participants and 45 full-term control participants underwent diffusion MRI at age 13 years. Diffusion tissue signal fractions derived by Single-Shell 3-Tissue Constrained Spherical Deconvolution were used to investigate brain tissue microstructural and free-water composition. The tissue microstructural and free-water composition metrics were analysed using a voxel-based analysis and cortical region-of-interest analysis approach. Very preterm 13-year-olds exhibited reduced white matter microstructural density and increased free-water content across widespread regions of the white matter compared with controls. Additionally, very preterm 13-year-olds exhibited reduced microstructural density and increased free-water content in specific temporal, frontal, occipital and cingulate cortical regions. These brain tissue composition alterations were strongly associated with cerebral white matter abnormalities identified in the neonatal period, and concurrent adverse cognitive and motor outcomes in very preterm children. The findings demonstrate brain microstructural and free-water alterations up to thirteen years from neonatal brain abnormalities in very preterm children that relate to adverse neurodevelopmental outcomes.

Neuroinflammation in the Cerebellum and Brainstem in Friedreich Ataxia: An [18F]-FEMPA PET Study.

BACKGROUND: Neuroinflammation is proposed to accompany, or even contribute to, neuropathology in Friedreich ataxia (FRDA), with implications for disease treatment and tracking. OBJECTIVES: To examine brain glial activation and systemic immune dysfunction in people with FRDA and quantify their relationship with symptom severity, duration, and onset age. METHODS: Fifteen individuals with FRDA and 13 healthy controls underwent brain positron emission tomography using the translocator protein (TSPO) radioligand [18 F]-FEMPA, a marker of glial activation, together with the quantification of blood plasma inflammatory cytokines. RESULTS: [18 F]-FEMPA binding was significantly increased in the dentate nuclei (d = 0.67), superior cerebellar peduncles (d = 0.74), and midbrain (d = 0.87), alongside increased plasma interleukin-6 (IL-6) (d = 0.73), in individuals with FRDA compared to controls. Increased [18 F]-FEMPA binding in the dentate nuclei, brainstem, and cerebellar anterior lobe correlated with earlier age of symptom onset (controlling for the genetic triplet repeat expansion length; all r part < -0.6), and in the pons and anterior lobe with shorter disease duration (r = -0.66; -0.73). CONCLUSIONS: Neuroinflammation is evident in brain regions implicated in FRDA neuropathology. Increased neuroimmune activity may be related to earlier disease onset and attenuate over the course of the illness. © 2021 International Parkinson and Movement Disorder Society.

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.

Research Trends in Carbon Chain Polymers and Their Derivatives: Highlighting the Decade-Long Research.

Polyolefins include low-density polyethylene (LDPE), high-density polyethylene (HDPE), linear low-density polyethylene (LLDPE), polypropylene (PP), and polybutylene (PB). Polyolefins offer unique characteristics such as chemical resistance, smooth surface, re-shapability, and are lighter than glass and metal-based materials. The global plastics industry produces polyolefin as their major product and these polyolefins are mostly used as commercial commodity plastics. Moreover, the characteristics of polyolefin can be further improved by forming their blends and/or composites and incorporating fillers. This review highlights the role of various fillers such as titanium dioixde-based, nitride-based, and carbon-based nanomaterials, in influencing polyolefin composites. Moreover, the contribution of layered double hydroxide in olefin polymerization, and the impact of filler properties such as filler content, filler type, filler phase stability, and synergistic effect between the fillers and polymers on nanocomposites are discussed.

Recent Advances in Bimetallic Catalysts for Hydrogen Production from Ammonia.

The emerging concept of the hydrogen economy is facing challenges associated with hydrogen storage and transport. The utilization of ammonia as an energy (hydrogen) carrier for the on-site generation of hydrogen via ammonia decomposition has gained attraction among the scientific community. Ruthenium-based catalysts are highly active but their high cost and less abundance are limitations for scale-up application. Therefore, combining ruthenium with cheaper transition metals such as nickel, cobalt, iron, molybdenum, etc., to generate metal-metal (bimetallic) surfaces suitable for ammonia decomposition has been investigated in recent years. Herein, the recent trends in developing bimetallic catalyst systems, the role of metal type, support materials, promoter, synthesis techniques, and the investigations of the reaction kinetics and mechanism for ammonia decomposition have been reviewed.

Morphology of cells undergoing epithelial mesenchymal transition in microinvasive and early invasive oral squamous cell carcinom a - a light microscopic study.

The present study focuses on identification of cancer attributes of epithelial mesenchymal transition (EMT) at the earliest possible stage (microinvasion) under a light microscope by using hematoxylin and eosin stains, making it feasible for researchers to investigate such cases with ease without the use of extensive setups. The present study is the first in the English literature to define EMT features in micro-invasive and early invasive oral squamous cell carcinoma (OSCC) under a light microscope. This is a retrospective study of histological sections of 43 cases of OSCC from the Department of Oral Pathology and Microbiology. The data collected were later statistically analyzed. A total of 11 micro-invasive and 32 early invasive OSCC cases were assessed for core features of EMT. The predominant feature defining EMT found was dense inflammatory infiltrate in both microinvasive (91%) and early invasive OSCC (88%) followed by cell individualization in 82% of microinvasive and 75% of early invasive OSCC, which was then followed by other features. Reporting EMT in histopathological reports on a daily basis can aid in early diagnosis of OSCC as well as understanding carcinogenesis in early stages. Thereby, inclusion of EMT targeting therapeutics in early stages of OSCC can significantly alter the prognosis of cancer.

The Use of Autologous Chondrocyte and Mesenchymal Stem Cell Implants for the Treatment of Focal Chondral Defects in Human Knee Joints-A Systematic Review and Meta-Analysis.

Focal chondral defects of the knee occur commonly in the young, active population due to trauma. Damage can insidiously spread and lead to osteoarthritis with significant functional and socioeconomic consequences. Implants consisting of autologous chondrocytes or mesenchymal stem cells (MSC) seeded onto scaffolds have been suggested as promising therapies to restore these defects. However, the degree of integration between the implant and native cartilage still requires optimization. A PRISMA systematic review and meta-analysis was conducted using five databases (PubMed, MEDLINE, EMBASE, Web of Science, CINAHL) to identify studies that used autologous chondrocyte implants (ACI) or MSC implant therapies to repair chondral defects of the tibiofemoral joint. Data on the integration of the implant-cartilage interface, as well as outcomes of clinical scoring systems, were extracted. Most eligible studies investigated the use of ACI only. Our meta-analysis showed that, across a total of 200 patients, 64% (95% CI (51%, 75%)) achieved complete integration with native cartilage. In addition, a pooled improvement in the mean MOCART integration score was observed during post-operative follow-up (standardized mean difference: 1.16; 95% CI (0.07, 2.24), p = 0.04). All studies showed an improvement in the clinical scores. The use of a collagen-based scaffold was associated with better integration and clinical outcomes. This review demonstrated that cell-seeded scaffolds can achieve good quality integration in most patients, which improves over time and is associated with clinical improvements. A greater number of studies comparing these techniques to traditional cartilage repair methods, with more inclusion of MSC-seeded scaffolds, should allow for a standardized approach to cartilage regeneration to develop.

Mendelian Randomization Studies of Lifestyle-Related Risk Factors for Osteoarthritis: A PRISMA Review and Meta-Analysis.

Risk factors for osteoarthritis (OA) often exert effects over protracted time-courses. Mendelian randomization (MR) studies therefore have an advantage over conventional observational studies when studying the causal effect of long-term lifestyle-related risk factors on OA. However, given the heterogeneous design of existing MR studies on OA, the reported causal estimates of these effects remain inconsistent, thus obscuring the true extent of the biological effects of OA lifestyle-risk factors. We conducted a PRISMA systematic review and specifically included MR studies that investigated the causal effect between lifestyle-related risk factors and OA, where causal estimates for various lifestyle factors were pooled for meta-analysis. Quality of studies was assessed according to STROBE-MR guidelines. A total of 1576 studies were evaluated and 23 were included. Overall, the studies included were of high quality and had a low risk of bias. Our meta-analysis demonstrates the positive causal effect of BMI (ORIVW-random effects 1.49 [1.23-1.80]) and negative causal effects of serum calcium (ORIVW-random effects 0.69 [0.57-0.83]) and LDL levels (ORIVW-random effects 0.93 [0.90-0.96]) on OA. Despite the heterogeneous designs and estimates of causal effects provided by various MR studies, our meta-analysis suggests that lifestyle-related risk factors in the form of BMI, serum calcium, and LDL have true biological effects on the development of OA.

Evaluating the Effect of Hypoxia on Human Adult Mesenchymal Stromal Cell Chondrogenesis In Vitro: A Systematic Review.

Human adult mesenchymal stromal cells (MSCs) from a variety of sources may be used to repair defects in articular cartilage by inducing them into chondrogenic differentiation. The conditions in which optimal chondrogenic differentiation takes place are an area of interest in the field of tissue engineering. Chondrocytes exist in vivo in a normally hypoxic environment and thus it has been suggested that exposing MSCs to hypoxia may also contribute to a beneficial effect on their differentiation. There are two main stages in which MSCs can be exposed to hypoxia, the expansion phase when cells are cultured, and the differentiation phase when cells are induced with a chondrogenic medium. This systematic review sought to explore the effect of hypoxia at these two stages on human adult MSC chondrogenesis in vitro. A literature search was performed on PubMed, EMBASE, Medline via Ovid, and Cochrane, and 24 studies were ultimately included. The majority of these studies showed that hypoxia during the expansion phase or the differentiation phase enhances at least some markers of chondrogenic differentiation in adult MSCs. These results were not always demonstrated at the protein level and there were also conflicting reports. Studies evaluating continuous exposure to hypoxia during the expansion and differentiation phases also had mixed results. These inconsistent results can be explained by the heterogeneity of studies, including factors such as different sources of MSCs used, donor variability, level of hypoxia used in each study, time exposed to hypoxia, and differences in culture methodology.

Early migration of biliary stent leading to free intra-peritoneal duodenal perforation - A case report.

Intestinal perforation from a plastic biliary stent is a known but rare complication of endoscopic biliary stent placement. Intra-peritoneal perforation is less common but carries more morbidity and mortality. Only a few cases of early stent migration and perforation have been reported. We present the case of a duodenal perforation caused by early migration of plastic biliary stent that resulted in intra-peritoneal biliary peritonitis.

Laparoscopic cholecystectomy in a type Va Mirizzi syndrome patient.

Mirizzi syndrome is a rare syndrome, caused by the compression of gall stones which may result in CBD obstruction or fistula formation. It may sometimes present without any prior symptoms. It has been classified into five types by Csendes. Usually open surgical approach is recommended for the condition, especially for Types III-V. We present the case of a patient who presented with right hypochondrial pain and was intra-operatively discovered to have type Va Mirrizi syndrome and was managed successfully laparoscopically.

Investigating the microstructural properties of normal-appearing white matter (NAWM) preceding conversion to white matter hyperintensities (WMHs) in stroke survivors.

Using advanced diffusion MRI, we aimed to assess the microstructural properties of normal-appearing white matter (NAWM) preceding conversion to white matter hyperintensities (WMHs) using 3-tissue diffusion signal compositions in ischemic stroke. Data were obtained from the Cognition and Neocortical Volume After Stroke (CANVAS) study. Diffusion-weighted MR and high-resolution structural brain images were acquired 3- (baseline) and 12-months (follow-up) post-stroke. WMHs were automatically segmented and longitudinal assessment at 12-months was used to retrospectively delineate NAWM voxels at baseline converting to WMHs. NAWM voxels converting to WMHs were further dichotomized into either: "growing" WMHs if NAWM adhered to existing WMH voxels, or "isolated de-novo" WMHs if NAWM was unconnected to WMH voxels identified at baseline. Microstructural properties were assessed using 3-tissue diffusion signal compositions consisting of white matter-like (WM-like: TW), gray matter-like (GM-like: TG), and cerebrospinal fluid-like (CSF-like: TC) signal fractions. Our findings showed that NAWM converting to WMHs already exhibited similar changes in tissue compositions at baseline to WMHs with lower TW and increased TC (fluid-like, i.e. free-water) and TG compared to persistent NAWM. We also found that microstructural properties of persistent NAWM were related to overall WMH burden with greater free-water content in patients with high WMH load. These findings suggest that NAWM preceding conversion to WMHs are accompanied by greater fluid-like properties indicating increased tissue water content. Increased GM-like properties may indicate a more isotropic microstructure of tissue reflecting a degree of hindered diffusion in NAWM regions vulnerable to WMH development. These results support the usefulness of microstructural compositions as a sensitive marker of NAWM vulnerability to WMH pathogenesis.

Obesity does not adversely impact the outcome of unicompartmental knee arthroplasty for osteoarthritis: a meta-analysis of 80,798 subjects.

BACKGROUND: Patients with end-stage single compartment osteoarthritis benefit from the less invasive unicompartmental knee arthroplasty (UKA). With increasing financial restraints, some healthcare services have set specific BMI cut-offs when determining patient eligibility for knee arthroplasty due to perceived obesity-related complications. The aim of this systematic review is to determine the effect obesity has on outcomes following UKA, and thus elucidate whether obesity should be a contraindication for UKA. METHODS: A PRISMA systematic review was conducted using five databases (MEDLINE, EMBASE, Cochrane, PubMed and Web of Science) to identify all clinical studies that examined the effect of obesity on outcomes following UKA. Quantitative meta-analysis was carried out using RevMan 5.3 software. Quality assessment was carried out using the Critical Appraisal Skills Programme (CASP) checklist. RESULTS: Thirty studies, including a total of 80 798 patients were analysed. The mean follow- up duration was 5.42 years. Subgroup meta-analyses showed no statistically significant difference following UKA between patients cohorts with and without obesity in overall complication rates (95% CI, P = 0.52), infection rates (95% CI, P = 0.81), and revision surgeries (95% CI, P = 0.06). When further analysing complications, no differences were identified in minor (95% CI, P = 0.23) and major complications (95% CI, P = 0.68), or venous thromboembolism rates (95% CI, P = 0.06). When further analysing revision surgeries, no differences were identified for revisions specifically for infection (95% CI, P = 0.71) or aseptic loosening (95% CI, P = 0.75). CONCLUSIONS: This meta-analysis shows that obesity does not result in poorer post-operative outcomes following UKA and should not be considered a contraindication for UKA. Future studies, including long-term follow-up RCTs and registry-level analyses, should examine factors associated with obesity and consider stratifying obesity to better delineate any potential differences in outcomes.

Mesenchymal stem cell therapy in hypertrophic and keloid scars.

Scars are the normal outcome of wound repair and involve a co-ordinated inflammatory and fibrotic process. When a scar does not resolve, uncontrolled chronic inflammation can persist and elicits excessive scarring that leads to a range of abnormal phenotypes such as hypertrophic and keloid scars. These pathologies result in significant impairment of quality of life over a long period of time. Existing treatment options are generally unsatisfactory, and there is mounting interest in innovative cell-based therapies. Despite the interest in mesenchymal stem cells (MSCs), there is yet to be a human clinical trial that investigates the potential of MSCs in treating abnormal scarring. A synthesis of existing evidence of animal studies may therefore provide insight into the barriers to human application. The aim of this PRISMA systematic review was to evaluate the effectiveness of MSC transplantation in the treatment of hypertrophic and keloid scars in in vivo models. A total of 11 case-control studies were identified that treated a total of 156 subjects with MSCs or MSC-conditioned media. Ten studies assessed hypertrophic scars, and one looked at keloid scars. All studies evaluated scars in terms of macroscopic and histological appearances and most incorporated immunohistochemistry. The included studies all found improvements in the above outcomes with MSC or MSC-conditioned media without complications. The studies reviewed support a role for MSC therapy in treating scars that needs further exploration. The transferability of these findings to humans is limited by factors such as the reliability and validity of the disease model, the need to identify the optimal MSC cell source, and the outcome measures employed.