Long-Term Functional Outcomes and Quality of Life at Minimum 10-Year Follow-Up After Fixed-Bearing Unicompartmental Knee Arthroplasty and Total Knee Arthroplasty for Isolated Medial Compartment Osteoarthritis

BackgroundThe aim of this study is to compare the long-term functional outcome and quality of life between total knee arthroplasty (TKA) and fixed-bearing unicompartmental knee arthroplasty (UKA) for the treatment of isolated medial compartment osteoarthritis.MethodsBetween 2000 and 2008, a total of 218 patients underwent primary UKA at our tertiary hospital. A TKA group was matched through 1:1 propensity score matching and adjusted for age, gender, body mass index, preoperative knee flexion, and function scores. All patients had medial compartment osteoarthritis. The patients were assessed with the range of motion, Knee Society Knee Score and Knee Society Function Score, Oxford Knee Score, Short Form-36 physical component score (PCS) and mental component score preoperatively, at 6 months, 2 years, and 10 years. Patients’ satisfaction, expectation fulfillment, and minimal clinically important difference were analyzed.ResultsThere were no differences in baseline characteristics between groups after propensity score matching (P > .05). UKA had greater knee flexion at all time points. Although the Knee Society Function Score was superior in UKA by 5.5, 3, and 4.3 points at 6 months, 2 years, and 10 years, respectively (P < .001), these differences did not exceed the minimal clinically important difference (Knee Society Knee Score 6.1). There were no significant differences in the Oxford Knee Score and Short Form-36 physical component score/mental component score. At 10 years, similar proportions of UKA and TKA were satisfied (90.8% vs 89.9%, P = .44) and had expectation fulfillment (89.4% vs 88.5%, P = .46). Between 2 and 10 years, all function scores deteriorated significantly for both groups (P < .01).ConclusionUKA and TKA are excellent treatment modalities for isolated medial compartment osteoarthritis, with similar functional outcomes, quality of life, and satisfaction at 10 years.     

Change in Body Mass Index after Simultaneous Bilateral Total Knee Arthroplasty: Risk Factors and Its Influence on Functional Outcomes

BackgroundPrevious studies evaluating weight changes following total knee arthroplasty (TKA) were performed on heterogenous cohorts. However, no study has evaluated weight changes in a cohort of simultaneous-bilateral TKA (SB-TKA) patients. This study aimed to evaluate the prevalence of patients who lost or gained weight, determine if postoperative weight change influences functional outcome, and identify predictors of weight change after SB-TKA.MethodsProspectively collected registry data of 560 patients who underwent SB-TKA were reviewed. Patients were assessed preoperatively, at 6 months, and 2 years using the Knee Society Score, Oxford Knee Score, Short-Form 36, and range of motion. Change in body mass index (BMI) >5% was used to categorize patients into 3 groups: lost, maintained, or gained weight. Analysis of variance, Kruskal-Wallis test, and chi-squared test were used to compare functional outcomes between groups. Multivariable logistic regression evaluated predictors for postoperative weight changes.ResultsAt 2 years, 59% of patients maintained weight, 28% of patients gained weight, and 13% of patients lost weight. All groups experienced similar improvements in functional outcomes, rates of minimal clinically important difference attainment, and patient satisfaction (P > .05). Older patients were more likely to gain weight (P < .05). Patients with higher preoperative BMI were more likely to gain weight (P < .05) and less likely to lose weight (P < .05). Patients with greater preoperative comorbidities were less likely to lose weight (P < .05).ConclusionUp to 41% of patients experience significant weight changes after SB-TKA. Older patients with higher preoperative BMI were more likely to gain weight, while higher preoperative BMI with more comorbidities were less likely to lose weight following SB-TKA; however, postoperative weight changes do not appear to affect functional outcomes.Level of EvidenceIII, therapeutic study.     

Dendrite-specific remodeling of Drosophila sensory neurons requires matrix metalloproteases, ubiquitin-proteasome, and ecdysone signaling

During neuronal maturation, dendrites develop from immature neurites into mature arbors. In response to changes in the environment, dendrites from certain mature neurons can undergo large-scale morphologic remodeling. Here, we show a group of Drosophila peripheral sensory neurons, the class IV dendritic arborization (C4da) neurons, that completely degrade and regrow their elaborate dendrites. Larval dendrites of C4da neurons are first severed from the soma and subsequently degraded during metamorphosis. This process is controlled by both intracellular and extracellular mechanisms: The ecdysone pathway and ubiquitin-proteasome system (UPS) are cell-intrinsic signals that initiate dendrite breakage, and extracellular matrix metalloproteases are required to degrade the severed dendrites. Surprisingly, C4da neurons retain their axonal projections during concurrent dendrite degradation, despite activated ecdysone and UPS pathways. These results demonstrate that, in response to environmental changes, certain neurons have cell-intrinsic abilities to completely lose their dendrites but keep their axons and subsequently regrow their dendritic arbors.     

A fluorescent probe designed for studying protein conformational change

The usefulness of fluorescence in studying protein motions derives from its sensitivity, kinetic resolution, and compatibility with both live cells and physiological assays. Recent advances in microscopy and membrane protein purification have permitted the observation of fluorescence changes that accompany the functional transitions of complex eukaryotic membrane proteins. These techniques rely on probes that can clearly report the environmental changes of specific residues, but most commonly available side-chain-reactive probes are not well suited for this purpose. Here, we introduce a red Cys-reactive probe, aminophenoxazone maleimide (APM), designed with improved chemical and spectral properties for reporting protein conformational change. APM is compact, uncharged, and has a short linker between probe and protein, all of which ensure that it can closely track the motions of the side chain to which it is attached. It undergoes large polarity-dependent changes in Stokes shift, as well as large bathochromic shifts in both excitation maximum (from 521 nm in toluene to 598 nm in water) and emission maximum (580 nm to 633 nm). These polarity-dependent spectral changes offer a potentially simple means of relating fluorescence to local structure and motion, although they are partially offset by some complicating factors in APM fluorescence. We find that, like a rhodamine maleimide, APM senses the conformational changes underlying voltage sensing in the Shaker potassium channel, and it is superior at a site that shows limited reactivity to the rhodamine. The spectral characteristics of APM can also report subtle differences between aqueous positions in purified preparations of the beta2 adrenergic receptor.     

Genghis Khan (Gek) as a putative effector for Drosophila Cdc42 and regulator of actin polymerization

The small GTPases Cdc42 and Rac regulate a variety of biological processes, including actin polymerization, cell proliferation, and JNK/mitogen-activated protein kinase activation, conceivably via distinct effectors. Whereas the effector for mitogen-activated protein kinase activation appears to be p65^PAK, the identity of effector(s) for actin polymerization remains unclear. We have found a putative effector for Drosophila Cdc42, Genghis Khan (Gek), which binds to Dcdc42 in a GTP-dependent and effector domain-dependent manner. Gek contains a predicted serine/threonine kinase catalytic domain that is 63% identical to human myotonic dystrophy protein kinase and has protein kinase activities. It also possesses a large coiled-coil domain, a putative phorbol ester binding domain, a pleckstrin homology domain, and a Cdc42 binding consensus sequence that is required for its binding to Dcdc42. To study the in vivo function of gek, we generated mutations in the Drosophila gek locus. Egg chambers homozygous for gek mutations exhibit abnormal accumulation of F-actin and are defective in producing fertilized eggs. These phenotypes can be rescued by a wild-type gek transgene. Our results suggest that this multidomain protein kinase is an effector for the regulation of actin polymerization by Cdc42.     

Evidence that the nucleotide exchange and hydrolysis cycle of G proteins causes acute desensitization of G-protein gated inward rectifier K+ channels

The G-protein gated inward rectifier K⁺ channel (GIRK) is activated in vivo by the Gβγ subunits liberated upon G_i-coupled receptor activation. We have recapitulated the acute desensitization of receptor-activated GIRK currents in heterologous systems and shown that it is a membrane-delimited process. Its kinetics depends on the guanine nucleotide species available and could be accounted for by the nucleotide exchange and hydrolysis cycle of G proteins. Indeed, acute desensitization is abolished by nonhydrolyzable GTP analogues. Whereas regulators of G-protein signaling (RGS) proteins by their GTPase-activating protein activities are regarded as negative regulators, a positive regulatory function of RGS4 is uncovered in our study; the opposing effects allow RGS4 to potentiate acute desensitization without compromising GIRK activation.     

Alpinia oxyphylla Miq extract ameliorates cardiac fibrosis associated with D‐galactose induced aging in rats

Cardiac fibrosis is a common pathophysiological process observed during chronic and stress‐induced acceleration of cardiac aging. Fibrosis is a necessary process during wound healing and tissue repair. However, its deposition in organs would proceed to scarring and organ damage. Here Alpinate Oxyphyllae Fructus (AOF), a Chinese medicine extract was used to protect aging heart from collagen accumulation. About 8 weeks old, male SD rats were randomly divided into (i) Control, (ii) D‐galactose induced aging (IA), (iii) IA + AOF 50 (AOF low, AL), (iv) IA + AOF 100 (AOF medium, AM), (v) IA + AOF 150 (AOF high, AH) mg/kg/day, AOF was administered orally. After 8 weeks rats were sacrificed and hearts were collected. Results showed collagen deposition and up‐regulation of matrix metalloproteinases‐MMP‐2 and ‐9 in D‐galactose‐induced aging rats. Furthermore, western blotting and immunostaining were also confirmed the upregulation of TGF‐β1 mediated fibrosis in aging induced rats. However, collagen deposition and fibrosis were significantly decreased by AOF treatments (AM and AH). AOF treatments salvaged the cardiac fibrosis. Hence, AOF might be a potential therapeutic agent in the prevention of cardiac fibrosis associated with aging. The protective effects of AOF might have promising results in anti‐aging treatments.