The relationship between glenoid inclination and instability following primary reverse shoulder arthroplasty.

PURPOSE: Despite advances in implant design and surgical technique, instability remains the most common early complication and reason for early revision after reverse shoulder arthroplasty (RSA). The purpose of this study is to evaluate the glenoid implant inclination, as measured by the ß-angle, as an independent risk factor for instability after primary RSA. METHODS: A retrospective case-control study was conducted matching cases with instability after primary RSA using a single implant to controls without instability. Controls were matched to age, sex, body mass index, and baseplate type (1:3 ratio of cases to controls). The preoperative, postoperative, and the change in pre- to postoperative glenoid inclination (ß-angle) were compared between groups. RESULTS: Thirty-four cases (mean age, 66.2 years) were matched to 102 controls (mean age, 67.0 years). There was a wide range of postoperative (63° to 100°) and pre- to postoperative change (-16.5° to +30.5°) in ß-angles collectively. There was no significant difference in the postoperative ß-angle (mean, 80.8° vs. 82.7°, P = .19) or the change in ß-angle (mean, +1.7° vs. +3.4°, P = .35) between cases and controls, respectively. Regression analysis demonstrated no increased odds of instability with the postoperative ß-angle, odds ratio 0.965 (confidence interval [CI] = 0.916-1.02, P = .19). Likewise, for the preoperative to postoperative change in ß-angle, there was no significantly increased odds of instability, odds ratio 0.978 (CI = 0.934-1.03, P = .35). Finally, there was no difference in risk of instability in patients whose implant positioning resulted in a net superior increase in inclination, relative risk 0.85 (95% CI = 0.46-1.56, P = .28). CONCLUSIONS: Neither the final prosthetic glenoid inclination nor the change in glenoid inclination, as measured by the ß-angle, significantly influences the risk of prosthetic instability after primary RSA.

Deficiency of Dietary Fiber in Slc5a8-Null Mice Promotes Bacterial Dysbiosis and Alters Colonic Epithelial Transcriptome towards Proinflammatory Milieu.

Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the intestinal tract due to disruption of the symbiotic relationship between the host immune system and microbiota. Various factors alter the gut microbiota which lead to dysbiosis; in particular, diet and dietary fibers constitute important determinants. Dietary fiber protects against IBD; bacteria ferment these dietary fibers in colon and generate short-chain fatty acids (SCFAs), which mediate the anti-inflammatory actions of dietary fibers. SLC5A8 is a high-affinity transporter in the apical membrane of colonic epithelium which mediates the entry of SCFAs from the lumen into cells in Na+-coupled manner. Due to the unique transport kinetics, the function of the transporter becomes important only under conditions of low dietary fiber intake. Here, we have examined the impact of dietary fiber deficiency on luminal microbial composition and transcriptomic profile in colonic epithelium in wild-type (WT) and Slc5a8-null (KO) mice. We fed WT and KO mice with fiber-containing diet (FC-diet) or fiber-free diet (FF-diet) and analyzed the luminal bacterial composition by sequencing 16S rRNA gene in feces. Interestingly, results showed significant differences in the microbial community depending on dietary fiber content and on the presence or absence of Slc5a8. There were also marked differences in the transcriptomic profile of the colonic epithelium depending on the dietary fiber content and on the presence or absence of Slc5a8. We conclude that absence of fiber in diet in KO mice causes bacterial dysbiosis and alters gene expression in the colon that is conducive for inflammation.

Automatic registration of MRI-based joint models to high-speed biplanar radiographs for precise quantification of in vivo anterior cruciate ligament deformation during gait.

Understanding in vivo joint mechanics during dynamic activity is crucial for revealing mechanisms of injury and disease development. To this end, laboratories have utilized computed tomography (CT) to create 3-dimensional (3D) models of bone, which are then registered to high-speed biplanar radiographic data captured during movement in order to measure in vivo joint kinematics. In the present study, we describe a system for measuring dynamic joint mechanics using 3D surface models of the joint created from magnetic resonance imaging (MRI) registered to high-speed biplanar radiographs using a novel automatic registration algorithm. The use of MRI allows for modeling of both bony and soft tissue structures. Specifically, the attachment site footprints of the anterior cruciate ligament (ACL) on the femur and tibia can be modeled, allowing for measurement of dynamic ACL deformation. In the present study, we demonstrate the precision of this system by tracking the motion of a cadaveric porcine knee joint. We then utilize this system to quantify in vivo ACL deformation during gait in four healthy volunteers.

Sm-p80-based schistosomiasis vaccine: double-blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission-blocking efficacy.

Schistosomiasis is of public health importance to an estimated one billion people in 79 countries. A vaccine is urgently needed. Here, we report the results of four independent, double-blind studies of an Sm-p80-based vaccine in baboons. The vaccine exhibited potent prophylactic efficacy against transmission of Schistosoma mansoni infection and was associated with significantly less egg-induced pathology, compared with unvaccinated control animals. Specifically, the vaccine resulted in a 93.45% reduction of pathology-producing female worms and significantly resolved the major clinical manifestations of hepatic/intestinal schistosomiasis by reducing the tissue egg-load by 89.95%. A 35-fold decrease in fecal egg excretion in vaccinated animals, combined with an 81.51% reduction in hatching of eggs into the snail-infective stage (miracidia), demonstrates the parasite transmission-blocking potential of the vaccine. Substantially higher Sm-p80 expression in female worms and Sm-p80-specific antibodies in vaccinated baboons appear to play an important role in vaccine-mediated protection. Preliminary analyses of RNA sequencing revealed distinct molecular signatures of vaccine-induced effects in baboon immune effector cells. This study provides comprehensive evidence for the effectiveness of an Sm-p80-based vaccine for schistosomiasis.

Sm-p80-based vaccine trial in baboons: efficacy when mimicking natural conditions of chronic disease, praziquantel therapy, immunization, and Schistosoma mansoni re-encounter.

Sm-p80-based vaccine efficacy for Schistosoma mansoni was evaluated in a baboon model of infection and disease. The study was designed to replicate a human vaccine implementation scenario for endemic regions in which vaccine would be administered following drug treatment of infected individuals. In our study, the Sm-p80-based vaccine reduced principal pathology producing hepatic egg burdens by 38.0% and egg load in small and large intestines by 72.2% and 49.4%, respectively, in baboons. Notably, hatching rates of eggs recovered from liver and small and large intestine of vaccinated animals were significantly reduced, by 60.4%, 48.6%, and 82.3%, respectively. Observed reduction in egg maturation/hatching rates was supported by immunofluorescence and confocal microscopy showing unique differences in Sm-p80 expression in worms of both sexes and matured eggs. Vaccinated baboons had a 64.5% reduction in urine schistosome circulating anodic antigen, a parameter that reflects worm numbers/health status in infected hosts. Preliminary analyses of RNA sequencing revealed unique genes and canonical pathways associated with establishment of chronic disease, praziquantel-mediated parasite killing, and Sm-p80-mediated protection in vaccinated baboons. Overall, our study demonstrated efficacy of the Sm-p80 vaccine and provides insight into some of the epistatic interactions associated with protection.

In Vivo Tibial Cartilage Strains in Regions of Cartilage-to-Cartilage Contact and Cartilage-to-Meniscus Contact in Response to Walking.

BACKGROUND: There are currently limited human in vivo data characterizing the role of the meniscus in load distribution within the tibiofemoral joint. Purpose/Hypothesis: The purpose was to compare the strains experienced in regions of articular cartilage covered by the meniscus to regions of cartilage not covered by the meniscus. It was hypothesized that in response to walking, tibial cartilage covered by the meniscus would experience lower strains than uncovered tibial cartilage. STUDY DESIGN: Descriptive laboratory study. METHODS: Magnetic resonance imaging (MRI) of the knees of 8 healthy volunteers was performed before and after walking on a treadmill. Using MRI-generated 3-dimensional models of the tibia, cartilage, and menisci, cartilage thickness was measured in 4 different regions based on meniscal coverage and compartment: covered medial, uncovered medial, covered lateral, and uncovered lateral. Strain was defined as the normalized change in cartilage thickness before and after activity. RESULTS: Within each compartment, covered cartilage before activity was significantly thinner than uncovered cartilage before activity ( P < .001). After 20 minutes of walking, all 4 regions experienced significant cartilage thickness decreases ( P < .01). The covered medial region experienced significantly less strain than the uncovered medial region ( P = .04). No difference in strain was detected between the covered and uncovered regions in the lateral compartment ( P = .40). CONCLUSION: In response to walking, cartilage that is covered by the meniscus experiences lower strains than uncovered cartilage in the medial compartment. These findings provide important baseline information on the relationship between in vivo tibial compressive strain responses and meniscal coverage, which is critical to understanding normal meniscal function.

Effect of normal gait on in vivo tibiofemoral cartilage strains.

Altered cartilage loading is believed to be associated with osteoarthritis development. However, there are limited data regarding the influence of normal gait, an essential daily loading activity, on cartilage strains. In this study, 8 healthy subjects with no history of knee surgery or injury underwent magnetic resonance imaging of a single knee prior to and following a 20-min walking activity at approximately 1.1m/s. Bone and cartilage surfaces were segmented from these images and compiled into 3-dimensional models of the tibia, femur, and associated cartilage. Thickness changes were measured across a grid of evenly spaced points spanning the models of the articular surfaces. Averaged compartmental strains and local strains were then calculated. Overall compartmental strains after the walking activity were found to be significantly different from zero in all four tibiofemoral compartments, with tibial cartilage strain being significantly larger than femoral cartilage strain. These results provide baseline data regarding the normal tibiofemoral cartilage strain response to gait. Additionally, the technique employed in this study has potential to be used as a "stress test" to understand how factors including age, weight, and injury influence tibiofemoral cartilage strain response, essential information in the development of potential treatment strategies for the prevention of osteoarthritis.