Superior Capsular Reconstruction using the Long Head of Biceps Tendon: A Biomechanical Assessment of Tenodesis Location and Angle of Fixation.

BACKGROUND: Massive irreparable rotator cuff tears (MIRCT) treated with superior capsular reconstruction (SCR) using the long head of the biceps tendon have shown satisfactory early results. Different techniques and positions for biceps tenodesis have been described. This study aimed to evaluate the effect of tenodesis location and glenohumeral fixation angle for graft tensioning on the biomechanics of a SCR using a single strand biceps technique. METHODS: Eight cadaveric shoulders were mounted to a custom biomechanical simulator which employed static tone loads to the deltoid and rotator cuff muscles. All cadavers were first tested in the intact condition, and then in the simulated MIRCT condition by sectioning the tendinous insertions of the supraspinatus and upper border of the infraspinatus. SCR using the long head of the biceps tendon was then evaluated. Three biceps tenodesis locations relative to the greater tuberosity (anterior, middle, and posterior) and two glenohumeral fixation angles (0° and 30°) for graft tensioning were tested. An optical tracking system was used to quantify superior-inferior (SI) and anterior-posterior (AP) humeral head translation relative to the glenoid, while the functional abduction force was quantified using a load sensor. All tests were conducted at 0°, 30° and 60° of glenohumeral abduction in a randomized fashion. RESULTS: When assessing isolated superior humeral head migration, all biceps tenodesis locations were effective at decreasing superior migration, with no tenodesis location significantly better than the other (P=0.213). However, biceps grafts tensioned at 30° of glenohumeral abduction were significantly better at reducing proximal humeral migration as compared to graft tensioning at 0° abduction (P=0.008). Posterior humeral head translation observed in the MIRCT condition was significantly reduced when tensioning the biceps tendon at 30° of glenohumeral abduction compared to 0° for all tenodesis locations (P≤0.043). Tenodesis location also significantly influenced posterior humeral head translation (P=0.001), with middle and posterior positions restoring near normal humeral head position when fixed at 30° glenohumeral abduction. All SCR techniques using the biceps tendon improved the functional abduction force relative to the MIRCT condition, although no statistically significant differences were observed relative to the intact condition (P≥0.448). DISCUSSION: SCR using the long head biceps tendon is biomechanically effective in reducing posterosuperior translation of the humeral head in the setting of a MIRCT. Graft tensioning and fixation at 30° of glenohumeral abduction combined with either a middle or posterior tenodesis location on the greater tuberosity most effectively restores near normal time-zero humeral head kinematics.

Stemless reverse shoulder arthroplasty neck shaft angle influences humeral component time-zero fixation and survivorship: a cadaveric biomechanical assessment.

Background: Stemless humeral components are being clinically investigated for reverse shoulder arthroplasty (RSA) procedures. There is, however, a paucity of basic science literature on the surgical parameters that influence the success of these procedures. Therefore, this cadaveric biomechanical study evaluated the neck shaft angle (NSA) of implantation on the survivability and performance of stemless RSA humeral components during cyclical loading. Methods: Twelve paired cadaveric humeri were implanted with stemless RSA humeral components at NSAs of 135° and 145°. Implant-bone motion at the periphery of the implant was measured with 3 optical machine vision USB3 cameras outfitted with c-mount premium lenses and quantified with ProAnalyst software. A custom 3-dimensional loading apparatus was used to cyclically apply 3 loading directions representative of physiological states at 5 progressively increasing loading magnitudes. Stemless 135° and 145° implants were compared based on the maximum implant-bone relative distraction detected, as well as the survivorship of the implants throughout the loading protocol. Results: Primary fixation and implant biomechanical survivorship were substantially better in the 145° NSA implants. The 135° NSA implants elicited significantly higher implant-bone distractions during cyclical loading (P = .001), and implant survivorship was considerably lower in the 135° NSA specimens when compared to the 145° NSA specimens (135° NSA: 0%, 145° NSA: 50%) (P < .001). Conclusion: NSA is a modifiable parameter that influences time-zero implant stability, as well as the early survivorship of the stemless RSA humeral components tested in this study. NSA resections of 145° appear to promote better stability than those utilizing 135° NSAs during early postoperative eccentric loads. Further studies are required to assess if other stemless reversed humeral implant designs have improved time-zero fixation at higher NSAs.

Adult Human Brain Tissue Cultures to Study NeuroHIV.

HIV-associated neurocognitive disorders (HAND) persist under antiretroviral therapy as a complex pathology that has been difficult to study in cellular and animal models. Therefore, we generated an ex vivo human brain slice model of HIV-1 infection from surgically resected adult brain tissue. Brain slice cultures processed for flow cytometry showed >90% viability of dissociated cells within the first three weeks in vitro, with parallel detection of astrocyte, myeloid, and neuronal populations. Neurons within brain slices showed stable dendritic spine density and mature spine morphologies in the first weeks in culture, and they generated detectable activity in multi-electrode arrays. We infected cultured brain slices using patient-matched CD4+ T-cells or monocyte-derived macrophages (MDMs) that were exposed to a GFP-expressing R5-tropic HIV-1 in vitro. Infected slice cultures expressed viral RNA and developed a spreading infection up to 9 days post-infection, which were significantly decreased by antiretrovirals. We also detected infected myeloid cells and astrocytes within slices and observed minimal effect on cellular viability over time. Overall, this human-centered model offers a promising resource to study the cellular mechanisms contributing to HAND (including antiretroviral toxicity, substance use, and aging), infection of resident brain cells, and new neuroprotective therapeutics.

An In-Vitro Comparison of Mixed Reality Navigation to Traditional Freehand and Patient Specific Instrumentation Techniques for Glenoid Guide Pin Insertion during Shoulder Arthroplasty.

BACKGROUND: Accurate insertion of the glenoid guide pin in shoulder arthroplasty (RSA) is important for obtaining optimized glenoid component position and orientation. The objective of this study was to evaluate and compare the accuracy of three glenoid guide pin insertion techniques: 1) traditional software planning using freehand guide pin insertion (freehand), 2) guide pin insertion utilizing patient-specific instrumentation (PSI), and 3) using a mixed reality navigation (MR-NAV) system. METHODS: Twenty (20) computer tomography (CT) scans were obtained from patients exhibiting glenoid erosion patterns according to the Walch and Favard classifications. Cases were planned using validated three-dimensional (3D) preoperative planning software. The CT data was then used to 3D print triplicate plastic models of each glenoid to evaluate the three guide pin insertion techniques. The first technique employed traditional software planning with freehand guide pin insertion. The second method used preoperatively planned PSI guides, while the third utilized a MR-NAV system, which provided real-time holographic guidance during guide pin insertion. Once all guide pins had been inserted into the models, an independent optical tracking system and custom digitization device was used to quantify the position and orientation of each guide pin relative to the glenoid. The outcomes for this study included the absolute mean error in guide pin inclination, version, and entry point relative to the preoperative plan. The absolute Total Global Error was also assessed, which was defined as the sum of the absolute guide pin orientation and position error relative to the preoperative plan. RESULTS: No statistically significant differences between MR-NAV and PSI were found for the inclination error (2±1° versus 2±1°; P=0.056), version error (1±1° versus 1±1°; P=1.000), and Total Global Error (5±1 [mm+deg] versus 5±1 [mm+deg], P=1.000), respectively. The freehand technique produced significantly greater error than MR-NAV and PSI for inclination (5±3°, P≤0.017), version (4±3°, P≤0.032) and Total Global Error (8±3 [mm+deg], P<0.001). No statistically significant differences in the entry point error were observed between all guide pin insertion methods (P≥0.058). DISCUSSION: These results demonstrate that the precision and accuracy of MR-NAV is comparable to PSI and superior to a freehand technique for glenoid guide pin insertion in-vitro. Further study is needed to compare the accuracy of these techniques intra-operatively, in addition to assessing a potential learning curve between surgeons of varying experience with the MR-NAV system.

The Kouvalchouk procedure vs. distal tibial allograft for treatment of posterior shoulder instability: the deltoid "hammock" effect exists.

BACKGROUND: In 1993, Kouvalchouk described an acromial bone block with a pedicled deltoid flap for the treatment of posterior shoulder instability. This procedure provides a "double blocking" effect in that the acromial autograft restores posterior glenoid bone loss and the deltoid flap functions as a muscular "hammock" resembling the sling effect of the conjoint in the Latarjet procedure. The primary aim of this study was to compare the Kouvalchouk procedure to distal tibial allograft (DTA) reconstruction for the management of posterior shoulder instability with associated bone loss, while the secondary aim was to evaluate the deltoid hammock effect. METHODS: Ten upper extremity cadavers were evaluated using a validated shoulder testing apparatus in 0° and 60° of glenohumeral abduction in the scapular plane. Testing was first performed on the normal shoulder state and was followed by the creation of a 20% posterior glenoid defect. Subsequently, the Kouvalchouk and DTA procedures were conducted. Forces of 0N, 5N, 10N, and 15N were applied to the posterior deltoid tendinous insertion on the Kouvalchouk graft along the physiological muscle line-of-action to evaluate the 'hammock" effect of this procedure. Testing was additionally performed on the Kouvalchouk bone graft with the deltoid muscle sectioned from its bony attachment. For all test states, a posteriorly directed force was applied to the humeral head perpendicular to the direction of the glenoid bone defect, with the associated translation quantified using an optical tracking system. The outcome variable was posterior translation of the humeral head at an applied force magnitude of 30N. RESULTS: The Kouvalchouk procedure with the loaded deltoid flap (10N: P = .039 and 15N: P < .001) was significantly better at reducing posterior humeral head translation than the DTA. Overall, increased glenohumeral stability was observed with increased force applied to the posterior deltoid flap in the Kouvalchouk procedure. The 15 N Kouvalchouk was most effective at preventing posterior humeral translation, and the difference was statistically significant compared with the 20% glenoid defect (P = .003), detached Kouvalchouk (P < .001), and 0N Kouvalchouk (P < .001). The 15 N Kouvalchouk procedure restored posterior shoulder joint stability to near normal levels, such that it was not significantly different from the intact state (P = .203). CONCLUSIONS: The Kouvalchouk procedure with load applied to the deltoid was found to be biomechanically superior to the DTA for the management of posterior shoulder instability with associated bone loss. Additionally, the results confirmed the presence and effectiveness of the deltoid "hammock" effect.

Stabilizing effect of an elbow orthosis with an adjustable hinge axis after lateral collateral ligament injury: A biomechanical study.

Background: Current commercial elbow braces have a straight hinge that does not account for the native carrying angle of the elbow. The objective of this study was to determine the effectiveness of a custom-designed hinged elbow orthosis (HEO) with variable valgus angulations in stabilizing a lateral collateral ligament (LCL) deficient elbow. Methods: Eight cadaveric upper extremities were mounted in an elbow motion simulator in the abducted varus gravity-loaded position. The specimens were examined before and after simulated LCL injury and then with the addition of the custom-designed HEO with 0°, 10°, and 20° of valgus angulation. Kinematic data were recorded using an electromagnetic tracking system. Results: The LCL injured state with or without the brace resulted in significant increases in varus angulation of the elbow compared to the intact state in both pronation and supination (P < 0.05). There were no significant differences in varus-valgus angulation or ulnohumeral rotation between any of the brace angles and the LCL injured state with the forearm pronated and supinated. Discussion: The custom-designed HEO did not provide any additional stability to the LCL injured elbow. The varus arm position should be avoided during the rehabilitation of an LCL injured elbow even when an HEO is used.

Peripheral HMGB1 is linked to O3 pathology of disease-associated astrocytes and amyloid.

INTRODUCTION: Ozone (O3) is an air pollutant associated with Alzheimer's disease (AD) risk. The lung-brain axis is implicated in O3-associated glial and amyloid pathobiology; however, the role of disease-associated astrocytes (DAAs) in this process remains unknown. METHODS: The O3-induced astrocyte phenotype was characterized in 5xFAD mice by spatial transcriptomics and proteomics. Hmgb1fl/fl LysM-Cre+ mice were used to assess the role of peripheral myeloid cell high mobility group box 1 (HMGB1). RESULTS: O3 increased astrocyte and plaque numbers, impeded the astrocyte proteomic response to plaque deposition, augmented the DAA transcriptional fingerprint, increased astrocyte-microglia contact, and reduced bronchoalveolar lavage immune cell HMGB1 expression in 5xFAD mice. O3-exposed Hmgb1fl/fl LysM-Cre+ mice exhibited dysregulated DAA mRNA markers. DISCUSSION: Astrocytes and peripheral myeloid cells are critical lung-brain axis interactors. HMGB1 loss in peripheral myeloid cells regulates the O3-induced DAA phenotype. These findings demonstrate a mechanism and potential intervention target for air pollution-induced AD pathobiology. HIGHLIGHTS: Astrocytes are part of the lung-brain axis, regulating how air pollution affects plaque pathology. Ozone (O3) astrocyte effects are associated with increased plaques and modified by plaque localization. O3 uniquely disrupts the astrocyte transcriptomic and proteomic disease-associated astrocyte (DAA) phenotype in plaque associated astrocytes (PAA). O3 changes the PAA cell contact with microglia and cell-cell communication gene expression. Peripheral myeloid cell high mobility group box 1 regulates O3-induced transcriptomic changes in the DAA phenotype.

Stemless reverse humeral component neck-shaft angle has an influence on initial fixation.

BACKGROUND: Stemless anatomic humeral components are commonly used and are an accepted alternative to traditional stemmed implants in patients with good bone quality. Presently, little literature exists on the design and implantation parameters that influence primary time-zero fixation of stemless reverse humeral implants. Accordingly, this finite element analysis study assessed the surgical implantation variable of neck-shaft angle, and its effect on the primary time-zero fixation of reversed stemless humeral implants. METHODS: Eight computed tomography-derived humeral finite element models were used to examine a generic stemless humeral implant at varying neck-shaft angles of 130°, 135°, 140°, 145°, and 150°. Four loading scenarios (30° shoulder abduction with neutral forearm rotation, 30° shoulder abduction with forearm supination, a head-height lifting motion, and a single-handed steering motion) were employed. Implantation inclinations were compared based on the maximum bone-implant interface distraction detected after loading. RESULTS: The implant-bone distraction was greatest in the 130° neck-shaft angle implantation cases. All implant loading scenarios elicited significantly lower micromotion magnitudes when neck-shaft angle was increased (P = .0001). With every 5° increase in neck-shaft angle, there was an average 17% reduction in bone-implant distraction. CONCLUSIONS: The neck-shaft angle of implantation for a stemless reverse humeral component is a modifiable parameter that appears to influence time-zero implant stability. Lower, more varus, neck-shaft angles increase bone-implant distractions with simulated activities of daily living. It is therefore suggested that humeral head osteotomies at a higher neck-shaft angle may be beneficial to maximize stemless humeral component stability.

The effect of lateral collateral ligament repair tension on elbow stability: An in vitro biomechanical study.

BACKGROUND: The aim of this study was to determine the optimal repair tension of the lateral collateral ligament of the elbow by performing simulated active flexion with the arm in the varus gravity loaded position using an in vitro elbow simulator. METHODS: Eight cadaveric specimens were mounted in the varus gravity loaded orientation onto an elbow motion simulator. Four states were studied (intact, lateral collateral ligament injured, and 15 N and 20 N lateral collateral ligament repairs) with the forearm in supination and pronation. An electromagnetic tracking system was used to measure joint kinematics during active elbow flexion. FINDINGS: There was no difference in ulnohumeral rotation between the intact state and the 15 N repair (P = .150 for pronation; P = 1.0 for supination) or the 20 N repair (P = 1.0 for pronation; P = .568 for supination). For varus-valgus angulation, the 20 N repair was not statistically different from the intact state (P = .059 in pronation; P = 1.0 in supination). INTERPRETATION: Repair of the lateral collateral ligament following injury can restore joint kinematics with the arm in the varus position. A repair tension of 20 N was successful in restoring joint stability for simulated active motion with the forearm in pronation and supination. This study shows that when the lateral collateral ligament is repaired with adequate tension, avoidance of the varus position may not be as crucial during early motion.

Points of entry dynamics: understanding the cross-border threats for Ebola virus disease and COVID-19 in Ghana using a logic model approach.

Background: The influx of people across the national borders of Ghana has been of interest and concern in the public health and national security community in recent times due to the low capacity for the prevention and management of epidemics and other public health risks. Although the international health regulations (IHR) stipulate core public health capacities for designated border facilities such as international airports, seaports, and ground crossings, contextual factors that influence the attainment of effective public health measures and response capabilities remain understudied. Objective: This study aims to assess the relationship between contextual factors and COVID-19 procurement to help strengthen infrastructure resources for points of entry (PoE) public health surveillance functions, thereby eliminating gaps in the design, implementation, monitoring, and evaluation of pandemic-related interventions in Ghana. Methods: This study employed a mixed-methods design, where quantitative variables were examined for relationships and effect size interactions using multiple linear regression techniques and the wild bootstrap technique. Country-level data was sourced from multiple publicly available sources using the social-ecological framework, logic model, and IHR capacity monitoring framework. The qualitative portion included triangulation with an expert panel to determine areas of convergence and divergence. Results: The most general findings were that laboratory capacity and Kotoka International Airport testing center positively predicted COVID-19 procurement, and public health response and airline boarding rule negatively predicted COVID-19 procurement. Conclusion: Contextual understanding of the COVID-19 pandemic and Ebola epidemic is vital for strengthening PoE mitigation measures and preventing disease importation.

Mixed reality visualization in shoulder arthroplasty: is it better than traditional preoperative planning software?

BACKGROUND: Preoperative traditional software planning (TSP) is a method used to assist surgeons with implant selection and glenoid guide-pin insertion in shoulder arthroplasty. Mixed-Reality (MR) is a new technology that uses digital holograms of the preoperative plan and guide-pin trajectory projected into the operative field. The purpose of this study was to compare TSP to MR in a simulated surgical environment involving insertion of guide-pins into models of severely deformed glenoids. METHODS: Eight surgeons inserted guide-pins into eight randomized three-dimensional-printed severely eroded glenoid models in a simulated surgical environment using either TSP or MR. In total, 128 glenoid models were used and statistically compared. The outcomes compared between techniques included procedural time, difference in guide-pin start point, difference in version and inclination, and surgeon confidence via a confidence rating scale. RESULTS: When comparing traditional preoperative software planning to MR visualization as techniques to assist surgeons in glenoid guide pin insertion, there were no statistically significant differences in terms of mean procedure time (P=0.634), glenoid start-point (TSP = 2.2 ± 0.2 mm , MR = 2.1 ± 0.1 mm; P=0.760), guide-pin orientation (P=0.586), or confidence rating score (P=0.850). CONCLUSIONS: The results demonstrate that there were no significant differences between traditional preoperative software planning and MR visualization for guide-pin placement into models of eroded glenoids. A perceived benefit of MR is the real-time intraoperative visibility of the surgical plan and the patient's anatomy; however, this did not translate into decreased procedural time or improved guide-pin position. Level of evidence: Basic Science Study; Biomechanics.

The bidirectional lung brain-axis of amyloid-ß pathology: ozone dysregulates the peri-plaque microenvironment.

The mechanisms underlying how urban air pollution affects Alzheimer's disease (AD) are largely unknown. Ozone (O3) is a reactive gas component of air pollution linked to increased AD risk, but is confined to the respiratory tract after inhalation, implicating the peripheral immune response to air pollution in AD neuropathology. Here, we demonstrate that O3 exposure impaired the ability of microglia, the brain's parenchymal immune cells, to associate with and form a protective barrier around Aß plaques, leading to augmented dystrophic neurites and increased Aß plaque load. Spatial proteomic profiling analysis of peri-plaque proteins revealed a microenvironment-specific signature of dysregulated disease-associated microglia protein expression and increased pathogenic molecule levels with O3 exposure. Unexpectedly, 5xFAD mice exhibited an augmented pulmonary cell and humoral immune response to O3, supporting that ongoing neuropathology may regulate the peripheral O3 response. Circulating HMGB1 was one factor upregulated in only 5xFAD mice, and peripheral HMGB1 was separately shown to regulate brain Trem2 mRNA expression. These findings demonstrate a bidirectional lung-brain axis regulating the central and peripheral AD immune response and highlight this interaction as a potential novel therapeutic target in AD.

Points of entry dynamics: understanding the cross-border threats for Ebola virus disease and COVID-19 in Ghana using a logic model approach

Background. The influx of people across the national borders of Ghana has been of interest and concern in the public health and national security community in recent times due to the low capacity for the prevention and management of epidemics and other public health risks. Although the International Health Regulations (IHR) stipulate core public health capacities for designated border facilities such as international airports, seaports, and ground crossings, contextual factors that influence the attainment of effective public health measures and response capabilities remain understudied. Objective. To assess the relationship between contextual factors and COVID-19 procurement to help strengthen infrastructure resources for points of entry (PoE) public health surveillance functions, thereby eliminating gaps in the design, implementation, monitoring, and evaluation of pandemicrelated interventions in Ghana. Materials and Methods. This study employed a mixed-methods design, where quantitative variables were examined for relationships and effect size interactions using multiple linear regression techniques and the wild bootstrap technique. Country-level data was sourced from multiple publicly available sources using the social-ecological framework, logic model, and IHR capacity monitoring framework. The qualitative portion included triangulation with an expert panel to determine areas of convergence and divergence. Results. The most general findings were that laboratory capacity and KIA testing center positively predicted COVID-19 procurement, and public health response and airline boarding rule negatively predicted COVID-19 procurement. Conclusion. Contextual understanding of the COVID-19 pandemic and Ebola epidemic is vital for strengthening PoE mitigation measures and preventing disease importation.

Flyway-scale GPS tracking reveals migratory routes and key stopover and non-breeding locations of lesser yellowlegs.

Many populations of long-distance migrant shorebirds are declining rapidly. Since the 1970s, the lesser yellowlegs (Tringa flavipes) has experienced a pronounced reduction in abundance of ~63%. The potential causes of the species' decline are complex and interrelated. Understanding the timing of migration, seasonal routes, and important stopover and non-breeding locations used by this species will aid in directing conservation planning to address potential threats. During 2018-2022, we tracked 118 adult lesser yellowlegs using GPS satellite tags deployed on birds from five breeding and two migratory stopover locations spanning the boreal forest of North America from Alaska to Eastern Canada. Our objectives were to identify migratory routes, quantify migratory connectivity, and describe key stopover and non-breeding locations. We also evaluated predictors of southbound migratory departure date and migration distance. Individuals tagged in Alaska and Central Canada followed similar southbound migratory routes, stopping to refuel in the Prairie Pothole Region of North America, whereas birds tagged in Eastern Canada completed multi-day transoceanic flights covering distances of >4000 km across the Atlantic between North and South America. Upon reaching their non-breeding locations, lesser yellowlegs populations overlapped, resulting in weak migratory connectivity. Sex and population origin were significantly associated with the timing of migratory departure from breeding locations, and body mass at the time of GPS-tag deployment was the best predictor of southbound migratory distance. Our findings suggest that lesser yellowlegs travel long distances and traverse numerous political boundaries each year, and breeding location likely has the greatest influence on migratory routes and therefore the threats birds experience during migration. Further, the species' dependence on wetlands in agricultural landscapes during migration and the non-breeding period may make them vulnerable to threats related to agricultural practices, such as pesticide exposure.

Contextual factors in premature non-communicable disease mortality in selected African countries within the sustainable development goals framework: the implication of voice and accountability.

Sustainable Development Goal number 3, target 4 (SDG 3.4), seeks a 30% reduction in premature Non-Communicable Diseases (NCDs) mortality from 2015 levels by 2030. Africa United Nations (UN) Member States continue to experience increasing NCD mortality significantly, with the highest proportion of diabetes mortality among the working-age group. Past efforts to address this burden have been centered primarily on individual risk modifications evident by the NCDs Cluster Program at the World Health Organization (WHO) Africa Regional Office. To achieve a progressive reduction, a comprehensive premature NCD reduction approach which includes a consideration of contexts within which premature NCD, such diabetes mortality arises is necessary. The aim was to examine the relationship between contextual factors and diabetes-related deaths as premature NCD mortality and to enable an improved contextualized evidence-based approach to premature NCD mortality reduction. Country-level data was retrieved for post SDG initiative years (2016-2019) from multiple publicly available data sources for 32 selected Africa UN Member States in the International Diabetes Federation (IDF) East and West Africa Region. Multiple linear regression was employed to examine the relationship between diabetes-related deaths in individuals 20-79 years and contextual factors identified within the SDG framework. Weighted data analysis showed that voice and accountability as a contextual factor explained approximately 47% variability in diabetes-related deaths across the selected Africa UN Member Sates in IDF East and West Region (n=32). Civil society engagement is vital to develop effective premature NCD mortality reduction policies, and strategies and stakeholders' accountabilities are necessary to ensure adherence to obligations.

Commensal Urinary Lactobacilli Inhibit Major Uropathogens In Vitro With Heterogeneity at Species and Strain Level.

The human urinary microbiome is thought to affect the development and progression of urinary tract infections (UTI), particularly recurrent UTIs in aging populations of women. To understand the possible interactions of urinary pathogens with commensal bacteria inhabiting the aging bladder, we conducted an initial functional assessment of a representative set of urinary lactobacilli that dominate this niche in postmenopausal women. We created a repository of urinary bladder bacteria isolated via Enhanced Quantitative Urinary Culture (EQUC) from healthy postmenopausal women, as well as those with a culture-proven recurrent UTI (rUTI) diagnosis. This repository contains lactobacilli strains from eight different species. As many other lactobacilli are known to inhibit human pathogens, we hypothesized that some urinary lactobacilli will have similar abilities to inhibit the growth of typical uropathogens and thus, provide a link between the urinary microbiome and the predisposition to the rUTI. Therefore, we screened the urinary lactobacilli in our repository for their ability to inhibit model uropathogens in vitro. We observed that many urinary isolates strongly inhibit model strains of gram-negative Escherichia coli and Klebsiella pneumoniae but demonstrate less inhibition of gram-positive Enterococcus faecalis. The observed inhibition affected model strains of uropathogens as well as clinical and multidrug-resistant isolates of those species. Our preliminary analysis of inhibition modes suggests a combination of pH-dependent and cell-dependent inhibition. Overall, inhibition strongly varies among species and strains of urinary lactobacilli. While the strength of the inhibition is not predictive of health outcomes in this limited repository, there is a high level of species and strain diversity that warrants future detailed investigations.

Discovery of Heteroaryl Urea Isosteres for Formyl Peptide Receptor 2 Agonists.

Formyl peptide receptor 2 (FPR2) agonists have shown efficacy in inflammatory-driven animal disease models and have the potential to treat a range of diseases. Many reported synthetic agonists contain a phenylurea, which appears to be necessary for activity in the reported chemotypes. We set out to find isosteres for the phenylurea and focused our efforts on heteroaryl rings. The wide range of potencies with heterocyclic isosteres demonstrates how electronic effects of the heteroatom placement impact molecular recognition. Herein, we report our discovery of benzimidazole and aminophenyloxadiazole FPR2 agonists with low nanomolar activity.

Draft Genome Sequence of a Lactobacillus gasseri Strain Isolated from the Catheterized Urine of a Healthy Postmenopausal Woman.

Urinary microbiome composition has been found to associate with health status and to change with age. Lactobacillus gasseri is one of the most frequently found lactic acid bacteria in the vaginal and urinary tracts of women. Here, we report a draft genome sequence of a urinary L. gasseri strain isolated from a healthy postmenopausal woman.

The biomechanical effectiveness of tendon transfers to restore rotation after reverse shoulder arthroplasty: latissimus versus lower trapezius.

BACKGROUND: The purpose of this biomechanical simulator study was primarily to compare latissimus dorsi to lower trapezius tendon transfers for active external rotation and the pectoralis major transfer for internal rotation after reverse shoulder arthroplasty. Secondarily, the role of humeral component lateralization on transfer function was assessed. METHODS: Eight rotator cuff deficient cadavers underwent reverse shoulder arthroplasty with an adjustable lateralization humeral component. Latissimus dorsi and lower trapezius transfers were compared for active external rotation restoration and pectoralis major transfer for internal rotation restoration. Internal rotation/external rotation torques were measured for each lateralization at varying abduction and internal rotation/external rotation ranges-of-motion. RESULTS: The lower trapezius transfer generated, on average, 1.6 ± 0.2 nm more torque than the latissimus dorsi transfer (p < 0.001). The internal rotation/external rotation torques of all tendon transfers decreased as abduction increased (p < 0.01). At 0° elevation, reverse shoulder arthroplasty humeral component lateralization had a significant positive effect on tendon transfer torque at 60° internal rotation and external rotation (p < 0.01). DISCUSSION: Both the lower trapezius and the latissimus dorsi tendon transfers were effective in restoring active external rotation after reverse shoulder arthroplasty; however, the lower trapezius generated significantly more torque. Additionally, the pectoralis major transfer was effective in restoring active internal rotation. All tendon transfers were optimized with greater humeral component lateralization.