Outcomes with physiologic His bundle pacing in patients with narrow QRS complex.

BACKGROUND: In patients with narrow QRS complex, both ventricular and biventricular pacing is associated with increased cardiac morbidity and mortality. This risk is not decreased by ventricular pacing avoidance algorithms, which cause nonphysiologic atrioventricular (AV) delays. OBJECTIVE: This study aimed to report outcomes in patients with narrow QRS complex when the paced complex is in normal range and physiologic AV delays are programmed. METHODS: In 196 patients with QRS duration of 92 ± 10 ms, permanent pacing was done at the site of the His bundle electrogram. The pacemakers were then programmed to maintain physiologic AV delays and to increase heart rates in response to exercise. Patients received usual care and were observed for 3 years. RESULTS: The paced complex exhibited a delta wave, and the ventricular activation time, QRS axis, and lead I voltage remained in normal range. Physiologic programming resulted in His bundle pacing burden of 92%. In patients with decreased ejection fraction, there was significant improvement in left ventricular function, left ventricular dilation, and mitral regurgitation (P < .003). In patients with normal ejection fraction, left ventricular function remained normal without new valvular abnormalities. The 3-year all-cause mortality was 10%, and there was no increase in heart failure admissions. CONCLUSION: In patients with narrow QRS complex, when paced QRS morphology is maintained in normal range and AV dyssynchrony is avoided, His bundle pacing is associated with low all-cause mortality and improvement in abnormal echocardiographic parameters. The paced QRS morphology and physiologic AV delays may be important factors to evaluate in future trials of conduction system pacing.

Normative isometric plantarflexion strength values for professional level, male rugby union athletes.

OBJECTIVES: The primary aim was to establish normative values of isometric plantarflexor muscle strength in professional male rugby union players and compare forwards with backs. The secondary aims were to examine how individual playing position or age influences isometric plantarflexor strength. DESIGN: Cross-sectional. SETTING: Testing at professional rugby clubs. PARTICIPANTS: 355 players (201 forwards and 154 backs) from 9 clubs in the English Premiership club competition. MAIN OUTCOME MEASURES: Maximal unilateral isometric plantarflexion strength was measured, using a Fysiometer C-Station, in a seated position with a flexed knee and in maximal available dorsiflexion. Values are reported normalised to body mass and specific to playing position. RESULTS: Mean combined limb isometric plantarflexion strength for the group was 193.1 kg (SD 32) or 1.86 xBW. (SD 0.31). Forwards were significantly weaker than backs (forwards = 1.75xBW (SD 0.26), backs = 2.00xBW (SD 0.28) (p=<0.0001)). Age category revealed no influence on plantarflexor strength. CONCLUSION: This study presents normative isometric plantarflexion strength values for professional male rugby union players. Forwards are typically relatively weaker than backs.

Fully automated CT-based adiposity assessment: comparison of the L1 and L3 vertebral levels for opportunistic prediction.

PURPOSE: The purpose of this study is to compare fully automated CT-based measures of adipose tissue at the L1 level versus the standard L3 level for predicting mortality, which would allow for use at both chest (L1) and abdominal (L3) CT. METHODS: This retrospective study of 9066 asymptomatic adults (mean age, 57.1 ± 7.8 [SD] years; 4020 men, 5046 women) undergoing unenhanced low-dose abdominal CT for colorectal cancer screening. A previously validated artificial intelligence (AI) tool was used to assess cross-sectional visceral and subcutaneous adipose tissue areas (SAT and VAT), as well as their ratio (VSR) at the L1 and L3 levels. Post-CT survival prediction was compared using area under the ROC curve (ROC AUC) and hazard ratios (HRs). RESULTS: Median clinical follow-up interval after CT was 8.8 years (interquartile range, 5.2-11.6 years), during which 5.9% died (532/9066). No significant difference (p > 0.05) for mortality was observed between L1 and L3 VAT and SAT at 10-year ROC AUC. However, L3 measures were significantly better for VSR at 10-year AUC (p < 0.001). HRs comparing worst-to-best quartiles for mortality at L1 vs. L3 were 2.12 (95% CI, 1.65-2.72) and 2.22 (1.74-2.83) for VAT; 1.20 (0.95-1.52) and 1.16 (0.92-1.46) for SAT; and 2.26 (1.7-2.93) and 3.05 (2.32-4.01) for VSR. In women, the corresponding HRs for VSR were 2.58 (1.80-3.69) (L1) and 4.49 (2.98-6.78) (L3). CONCLUSION: Automated CT-based measures of visceral fat (VAT and VSR) at L1 are predictive of survival, although overall measures of adiposity at L1 level are somewhat inferior to the standard L3-level measures. Utilizing predictive L1-level fat measures could expand opportunistic screening to chest CT imaging.

Cost-Effectiveness of 90-day Single-use Flexible Cystoscope Trial: Single Center Micro-Costing Analysis and User Satisfaction.

OBJECTIVE: To evaluate cost-effectiveness and user satisfaction of a single-use flexible cystoscope at a tertiary care center we conducted a 90-day trial. Single-use flexible cystoscope advancements have introduced alternative options to reusable scopes. However, there is a paucity of cost-effectiveness and provider satisfaction studies examining the implementation of a hospital-based transition to single-use cystoscopes. METHODS: Following institutional device-approval we initiated a 90-day trial period (November 1, 2020-January 29, 2021) where all flexible, transurethral, and percutaneous, urologic care was provided with a disposable AMBU aScope. We performed a micro-costing analysis examining payor per case cost of the reusable flexible cystoscope (including servicing and processing) to the disposable units. Provider surveys assessed visual quality, deflection, ease of working channel and overall satisfaction on a 10-point Likert scale. RESULTS: Over the 90-day period, we encountered 84 cases (78 operative, 5 inpatient, 1 emergency department) where flexible cystoscopy was required. One disposable flexible cystoscope was successfully used in 78 of 84 (93%) cases. Of the 6 failures, 2 were due to an inability to access a disposable scope/monitor. Per use cost of the reusable flexible cystoscope at our center was $272.41 versus $185.00 for the single use. Extrapolating our average case volume and conservative failure rate (3 single use failures/month, requiring reusable), transitioning to predominately single use scopes results in $39,142.84 annual cost savings. CONCLUSIONS: This single center 90-day trial of disposable flexible cystoscopy identified per-use costs to be less when a single-use flexible cystoscope was utilized at a high-volume tertiary care center.

COVID-19 Open-Data a global-scale spatially granular meta-dataset for coronavirus disease.

This paper introduces the COVID-19 Open Dataset (COD), available at goo.gle/covid-19-open-data . A static copy is of the dataset is also available at https://doi.org/10.6084/m9.figshare.c.5399355 . This is a very large "meta-dataset" of COVID-related data, containing epidemiological information, from 22,579 unique locations within 232 different countries and independent territories. For 62 of these countries we have state-level data, and for 23 of these countries we have county-level data. For 15 countries, COD includes cases and deaths stratified by age or sex. COD also contains information on hospitalizations, vaccinations, and other relevant factors such as mobility, non-pharmaceutical interventions and static demographic attributes. Each location is tagged with a unique identifier so that these different types of information can be easily combined. The data is automatically extracted from 121 different authoritative sources, using scalable open source software. This paper describes the format and construction of the dataset, and includes a preliminary statistical analysis of its content, revealing some interesting patterns.

Wnt5a Promotes AT1 and Represses AT2 Lineage-Specific Gene Expression in a Cell-Context-Dependent Manner.

Lung maturation is not limited to proper structural development but also includes differentiation and functionality of various highly specialized alveolar cell types. Alveolar type 1 (AT1s) cells occupy nearly 95% of the alveolar surface and are critical for establishing efficient gas exchange in the mature lung. AT1 cells arise from progenitors specified during the embryonic stage as well as alveolar epithelial progenitors expressing surfactant protein C (Sftpcpos cells) during postnatal and adult stages. Previously, we found that Wnt5a, a non-canonical Wnt ligand, is required for differentiation of AT1 cells during the saccular phase of lung development. To further investigate the role of Wnt5a in AT1 cell differentiation, we generated and characterized a conditional Wnt5a gain-of-function mouse model. Neonatal Wnt5a gain-of-function disrupted alveologenesis through inhibition of cell proliferation. In this setting Wnt5a downregulated ß-catenin-dependent canonical Wnt signaling, repressed AT2 (anti-AT2) and promoted AT1 (pro-AT1) lineage-specific gene expression. In addition, we identified 2 subpopulations of Sftpchigh and Sftpclow alveolar epithelial cells. In Sftpclow cells, Wnt5a exhibits pro-AT1 and anti-AT2 effects, concurrent with inhibition of canonical Wnt signaling. Interestingly, in the Sftpchigh subpopulation, although increasing AT1 lineage-specific gene expression, Wnt5a gain-of-function did not change AT2 gene expression, nor inhibit canonical Wnt signaling. Using primary epithelial cells isolated from human fetal lungs, we demonstrate that this property of Wnt5a is evolutionarily conserved. Wnt5a therefore serves as a selective regulator that ensures proper AT1/AT2 balance in the developing lung.

Implementation study of SARS-CoV-2 antigen lateral flow tests in men's professional (Premiership) rugby union sports squads in England during the COVID-19 pandemic.

This study evaluated the validity and utility of antigen-detection rapid diagnostic tests (Ag-RDTs) for SARS-CoV-2 in elite sports. The data on utility, ease of use and application for Ag-RDTs as a new testing format were positive from players and staff. This evaluation was limited by the low prevalence of SARS-CoV-2 circulating within the three squads. This study highlights the need for continued service evaluations for SARS-CoV-2 Ag-RDTs in elite sport settings.

Imaging Mutant Huntingtin Aggregates: Development of a Potential PET Ligand.

Mutant huntingtin (mHTT) protein carrying the elongated N-terminal polyglutamine (polyQ) tract misfolds and forms protein aggregates characteristic of Huntington's disease (HD) pathology. A high-affinity ligand specific for mHTT aggregates could serve as a positron emission tomography (PET) imaging biomarker for HD therapeutic development and disease progression. To identify such compounds with binding affinity for polyQ aggregates, we embarked on systematic structural activity studies; lead optimization of aggregate-binding affinity, unbound fractions in brain, permeability, and low efflux culminated in the discovery of compound 1, which exhibited target engagement in autoradiography (ARG) studies in brain slices from HD mouse models and postmortem human HD samples. PET imaging studies with 11C-labeled 1 in both HD mice and WT nonhuman primates (NHPs) demonstrated that the right-hand-side labeled ligand [11C]-1R (CHDI-180R) is a suitable PET tracer for imaging of mHTT aggregates. [11C]-1R is now being advanced to human trials as a first-in-class HD PET radiotracer.

WNT5a-ROR Signaling Is Essential for Alveologenesis.

WNT5a is a mainly "non-canonical" WNT ligand whose dysregulation is observed in lung diseases such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD) and asthma. Germline deletion of Wnt5a disrupts embryonic lung development. However, the temporal-specific function of WNT5a remains unknown. In this study, we generated a conditional loss-of-function mouse model (Wnt5aCAG) and examined the specific role of Wnt5a during the saccular and alveolar phases of lung development. The lack of Wnt5a in the saccular phase blocked distal airway expansion and attenuated differentiation of endothelial and alveolar epithelial type I (AT1) cells and myofibroblasts. Postnatal Wnt5a inactivation disrupted alveologenesis, producing a phenotype resembling human bronchopulmonary dysplasia (BPD). Mutant lungs showed hypoalveolization, but endothelial and epithelial differentiation was unaffected. The major impact of Wnt5a inactivation on alveologenesis was on myofibroblast differentiation and migration, with reduced expression of key regulatory genes. These findings were validated in vitro using isolated lung fibroblasts. Conditional inactivation of the WNT5a receptors Ror1 and Ror2 in alveolar myofibroblasts recapitulated the Wnt5aCAG phenotype, demonstrating that myofibroblast defects are the major cause of arrested alveologenesis in Wnt5aCAG lungs. Finally, we show that WNT5a is reduced in human BPD lung samples, indicating the clinical relevance and potential role for WNT5a in pathogenesis of BPD.

Secondary crest myofibroblast PDGFRα controls the elastogenesis pathway via a secondary tier of signaling networks during alveologenesis.

Postnatal alveolar formation is the most important and the least understood phase of lung development. Alveolar pathologies are prominent in neonatal and adult lung diseases. The mechanisms of alveologenesis remain largely unknown. We inactivated Pdgfra postnatally in secondary crest myofibroblasts (SCMF), a subpopulation of lung mesenchymal cells. Lack of Pdgfra arrested alveologenesis akin to bronchopulmonary dysplasia (BPD), a neonatal chronic lung disease. The transcriptome of mutant SCMF revealed 1808 altered genes encoding transcription factors, signaling and extracellular matrix molecules. Elastin mRNA was reduced, and its distribution was abnormal. Absence of Pdgfra disrupted expression of elastogenic genes, including members of the Lox, Fbn and Fbln families. Expression of EGF family members increased when Tgfb1 was repressed in mouse. Similar, but not identical, results were found in human BPD lung samples. In vitro, blocking PDGF signaling decreased elastogenic gene expression associated with increased Egf and decreased Tgfb family mRNAs. The effect was reversible by inhibiting EGF or activating TGFß signaling. These observations demonstrate the previously unappreciated postnatal role of PDGFA/PDGFRα in controlling elastogenic gene expression via a secondary tier of signaling networks composed of EGF and TGFß.

Muscle Glycogen Utilization During an Australian Rules Football Game.

PURPOSE: To better understand the carbohydrate (CHO) requirement of Australian Football (AF) match play by quantifying muscle glycogen utilization during an in-season AF match. METHODS: After a 24-h CHO-loading protocol of 8 and 2 g/kg in the prematch meal, 2 elite male forward players had biopsies sampled from m. vastus lateralis before and after participation in a South Australian Football League game. Player A (87.2 kg) consumed water only during match play, whereas player B (87.6 kg) consumed 88 g CHO via CHO gels. External load was quantified using global positioning system technology. RESULTS: Player A completed more minutes on the ground (115 vs 98 min) and covered greater total distance (12.2 vs 11.2 km) than player B, although with similar high-speed running (837 vs 1070 m) and sprinting (135 vs 138 m). Muscle glycogen decreased by 66% in player A (pre: 656 mmol/kg dry weight [dw], post: 223 mmol/kg dw) and 24% in player B (pre: 544 mmol/kg dw, post: 416 mmol/kg dw). CONCLUSION: Prematch CHO loading elevated muscle glycogen concentrations (ie, >500 mmol/kg dw), the magnitude of which appears sufficient to meet the metabolic demands of elite AF match play. The glycogen cost of AF match play may be greater than in soccer and rugby, and CHO feeding may also spare muscle glycogen use. Further studies using larger sample sizes are now required to quantify the interindividual variability of glycogen cost of match play (including muscle and fiber-type-specific responses), as well examining potential metabolic and ergogenic effects of CHO feeding.

Human and server docking prediction for CAPRI round 30-35 using LZerD with combined scoring functions.

We report the performance of protein-protein docking predictions by our group for recent rounds of the Critical Assessment of Prediction of Interactions (CAPRI), a community-wide assessment of state-of-the-art docking methods. Our prediction procedure uses a protein-protein docking program named LZerD developed in our group. LZerD represents a protein surface with 3D Zernike descriptors (3DZD), which are based on a mathematical series expansion of a 3D function. The appropriate soft representation of protein surface with 3DZD makes the method more tolerant to conformational change of proteins upon docking, which adds an advantage for unbound docking. Docking was guided by interface residue prediction performed with BindML and cons-PPISP as well as literature information when available. The generated docking models were ranked by a combination of scoring functions, including PRESCO, which evaluates the native-likeness of residues' spatial environments in structure models. First, we discuss the overall performance of our group in the CAPRI prediction rounds and investigate the reasons for unsuccessful cases. Then, we examine the performance of several knowledge-based scoring functions and their combinations for ranking docking models. It was found that the quality of a pool of docking models generated by LZerD, that is whether or not the pool includes near-native models, can be predicted by the correlation of multiple scores. Although the current analysis used docking models generated by LZerD, findings on scoring functions are expected to be universally applicable to other docking methods. Proteins 2017; 85:513-527. © 2016 Wiley Periodicals, Inc.

The efficacy of instrument assisted soft tissue mobilization: a systematic review.

BACKGROUND: Instrument assisted soft tissue mobilization (IASTM) is a popular treatment for myofascial restriction. IASTM uses specially designed instruments to provide a mobilizing effect to scar tissue and myofascial adhesions. Several IASTM tools and techniques are available such as the Graston® technique. Currently, there are no systematic reviews that have specifically appraised the effects of IASTM as a treatment or to enhance joint range of motion (ROM). PURPOSE: The purpose of this study was to systematically appraise the current evidence assessing the effects of IASTM as an intervention to treat a musculoskeletal pathology or to enhance joint ROM. METHODS: A search of the literature was conducted during the month of December 2015 which included the following databases: PubMed, PEDro, Science Direct, and the EBSCOhost collection. A direct search of known journals was also conducted to identify potential publications. The search terms included individual or a combination of the following: instrument; assisted; augmented; soft-tissue; mobilization; Graston®; and technique. RESULTS: A total of 7 randomized controlled trials were appraised. Five of the studies measured an IASTM intervention versus a control or alternate intervention group for a musculoskeletal pathology. The results of the studies were insignificant (p>.05) with both groups displaying equal outcomes. Two studies measured an IASTM intervention versus a control or alternate intervention group on the effects of joint ROM. The IASTM intervention produced significant (P<.05) short term gains up to 24 hours. CONCLUSION: The literature measuring the effects of IASTM is still emerging. The current research has indicated insignificant results which challenges the efficacy of IASTM as a treatment for common musculoskeletal pathology, which may be due to the methodological variability among studies. There appears to be some evidence supporting its ability to increase short term joint ROM.

CONTEXTE: La mobilisation des tissus mous assistée par instrument (MTMAI) est un traitement populaire pour la restriction des tissus myofasciaux. La MTMAI utilise des instruments spécialement conçus pour fournir un effet de mobilisation sur les tissus cicatriciels et les adhérences myofasciales. Plusieurs outils et techniques de MTMAI sont disponibles, comme la technique GrastonMD. Actuellement, il n'y a aucun examen systématique ayant notamment évalué les effets de la MTMAI comme traitement ou pour améliorer l'amplitude articulaire. OBJECTIF: Cette étude visait à évaluer systématiquement les données actuelles évaluant les effets de la MTMAI comme méthode d'intervention pour traiter une pathologie musculo-squelettique ou pour améliorer l'amplitude articulaire. MÉTHODOLOGIE: Une recherche des publications scientifiques a été réalisée au cours du mois de décembre 2015, incluant les bases de données suivantes : PubMed, PEDro, Science Direct, et la collection EBSCOhost. Une recherche directe a également été réalisée dans les revues connues pour relever les publications possibles. La recherche était basée sur les termes ou combinaisons de termes suivants : instrument; assistée; accrue; tissu mou; mobilisation; GrastonMD; technique. RÉSULTATS: Au total, sept essais contrôlés randomisés ont été évalués. Cinq des études mesuraient une intervention de MTMAI par rapport à un groupe de contrôle ou une intervention différente pour l'évaluation de la pathologie musculo-squelettique. Les résultats des études étaient négligeables (p > ,05) les deux groupes affichant des résultats égaux. Deux études mesuraient une intervention de MTMAI par rapport à un groupe de contrôle ou une intervention différente sur les effets de l'amplitude articulaire. L'intervention de MTMAI a produit des gains à court terme significatifs (P < ,05) allant jusqu'à 24 heures. CONCLUSION: Les publications scientifiques sur la mesure des effets de la MTMAI sont encore à leur début. La recherche actuelle a indiqué des résultats négligeables qui mettent en question l'efficacité de la MTMAI comme traitement de la pathologie musculo-squelettique courante, ce qui peut être dû à la variabilité de la méthodologie entre les études. Il semble y avoir des preuves soutenant sa capacité à augmenter l'amplitude articulaire à court terme.

Mesodermal ALK5 controls lung myofibroblast versus lipofibroblast cell fate.

BACKGROUND: Epithelial-mesenchymal cross talk is centerpiece in the development of many branched organs, including the lungs. The embryonic lung mesoderm provides instructional information not only for lung architectural development, but also for patterning, commitment and differentiation of its many highly specialized cell types. The mesoderm also serves as a reservoir of progenitors for generation of differentiated mesenchymal cell types that include αSMA-expressing fibroblasts, lipofibroblasts, endothelial cells and others. Transforming Growth Factor ß (TGFß) is a key signaling pathway in epithelial-mesenchymal cross talk. Using a cre-loxP approach we have elucidated the role of the TGFß type I receptor tyrosine kinase, ALK5, in epithelial-mesenchymal cross talk during lung morphogenesis. RESULTS: Targeted early inactivation of Alk5 in mesodermal progenitors caused abnormal development and maturation of the lung that included reduced physical size of the sub-mesothelial mesoderm, an established source of specific mesodermal progenitors. Abrogation of mesodermal ALK5-mediated signaling also inhibited differentiation of cell populations in the epithelial and endothelial lineages. Importantly, Alk5 mutant lungs contained a reduced number of αSMA(pos) cells and correspondingly increased lipofibroblasts. Elucidation of the underlying mechanisms revealed that through direct and indirect modulation of target signaling pathways and transcription factors, including PDGFRα, PPARγ, PRRX1, and ZFP423, ALK5-mediated TGFß controls a process that regulates the commitment and differentiation of αSMA(pos) versus lipofibroblast cell populations during lung development. CONCLUSION: ALK5-mediated TGFß signaling controls an early pathway that regulates the commitment and differentiation of αSMA(pos) versus LIF cell lineages during lung development.

Postoperative Rehabilitation After Hip Resurfacing: A Systematic Review.

CONTEXT: Hip-resurfacing arthroplasty (HRA) has become a popular procedure in the treatment of hip-joint arthritis in individuals under the age of 65 y. Although the body of literature examining operative procedures has grown, there is a lack of consistent reporting of the effectiveness of an HRA postoperative rehabilitation program. To date, no systematic reviews have evaluated the available evidence on postoperative rehabilitation programs. OBJECTIVE: To evaluate the available evidence on postoperative rehabilitation programs after HRA. EVIDENCE ACQUISITION: A systematic review was conducted according to the PRISMA guidelines. A search of PubMed, CINAHL, SPORTDiscus, ProQuest, and Google Scholar was conducted in April 2014 using the following keywords alone and in combination: postoperative, postsurgical, rehabilitation, physical therapy, programs, hip resurfacing, arthroplasty, and metal-on-metal. The grading of studies was conducted using the PEDro and Oxford Centre for Evidence-Based Medicine scales. EVIDENCE SYNTHESIS: The authors identified 648 citations, 4 of which met the inclusion criteria. The qualifying studies yielded 1 randomized control trial, 2 case reports, and 1 case series, for a total of 90 patients. Patients were mostly male (n = 86), had a mean age of 48 ± 5.47 y, and had been physically active before HRA. Postoperative rehabilitation programs varied in length (range 8-24 wk) and consisted of at least 3 phases. The methodology to assess program effects varied, but all 4 studies did measure a combination of function, pain, and quality of life using written questionnaires, with follow-up ranging from 9 mo to 1 y. The most common questionnaire was the Harris Hip Score. CONCLUSION: This review found postoperative rehabilitation programs after HRA to be underinvestigated. Limited results indicate that postoperative rehabilitation programs may be effective in improving gait (stride length, velocity, and cadence), hip range of motion, and pain and function, as measured by questionnaires, but not hip strength.

THE EFFECTS OF SELF-MYOFASCIAL RELEASE USING A FOAM ROLL OR ROLLER MASSAGER ON JOINT RANGE OF MOTION, MUSCLE RECOVERY, AND PERFORMANCE: A SYSTEMATIC REVIEW.

BACKGROUND: Self-myofascial release (SMR) is a popular intervention used to enhance a client's myofascial mobility. Common tools include the foam roll and roller massager. Often these tools are used as part of a comprehensive program and are often recommended to the client to purchase and use at home. Currently, there are no systematic reviews that have appraised the effects of these tools on joint range of motion, muscle recovery, and performance. PURPOSE: The purpose of this review was to critically appraise the current evidence and answer the following questions: (1) Does self-myofascial release with a foam roll or roller-massager improve joint range of motion (ROM) without effecting muscle performance? (2) After an intense bout of exercise, does self-myofascial release with a foam roller or roller-massager enhance post exercise muscle recovery and reduce delayed onset of muscle soreness (DOMS)? (3) Does self-myofascial release with a foam roll or roller-massager prior to activity affect muscle performance? METHODS: A search strategy was conducted, prior to April 2015, which included electronic databases and known journals. Included studies met the following criteria: 1) Peer reviewed, english language publications 2) Investigations that measured the effects of SMR using a foam roll or roller massager on joint ROM, acute muscle soreness, DOMS, and muscle performance 3) Investigations that compared an intervention program using a foam roll or roller massager to a control group 4) Investigations that compared two intervention programs using a foam roll or roller massager. The quality of manuscripts was assessed using the PEDro scale. RESULTS: A total of 14 articles met the inclusion criteria. SMR with a foam roll or roller massager appears to have short-term effects on increasing joint ROM without negatively affecting muscle performance and may help attenuate decrements in muscle performance and DOMS after intense exercise. Short bouts of SMR prior to exercise do not appear to effect muscle performance. CONCLUSION: The current literature measuring the effects of SMR is still emerging. The results of this analysis suggests that foam rolling and roller massage may be effective interventions for enhancing joint ROM and pre and post exercise muscle performance. However, due to the heterogeneity of methods among studies, there currently is no consensus on the optimal SMR program. LEVEL OF EVIDENCE: 2c.

Avascular necrosis of the femoral head.

The patient was a 51-year-old man who was evaluated by a physical therapist for a chief complaint of right hip pain. The patient was treated with a single bout of nonthrust hip joint mobilizations, but due to the patient's atypical response and long-term use of oral corticosteroid medications, he was referred to his primary care physician. Radiographs and subsequent magnetic resonance imaging revealed findings that were characteristic of avascular necrosis.

Dihydrotestosterone potentiates EGF-induced ERK activation by inducing SRC in fetal lung fibroblasts.

Lung maturation is regulated by interactions between mesenchymal and epithelial cells, and is delayed by androgens. Fibroblast-Type II cell communications are dependent on extracellular signal-regulated kinases (ERK) 1/2 activation by the ErbB receptor ligands epidermal growth factor (EGF), transforming growth factor (TGF)-α, and neuregulin (Nrg). In other tissues, dihydrotestosterone (DHT) has been shown to activate SRC by a novel nontranscriptional mechanism, which phosphorylates EGF receptors to potentiate EGF-induced ERK1/2 activation. This study sought to determine if DHT potentiates EGFR signaling by a nontranscriptional mechanism. Embryonic day (E)17 fetal lung cells were isolated from dams treated with or without DHT since E12. Cells were exposed to 30 ng/ml DHT for periods of 30 minutes to 3 days before being stimulated with 100 ng/ml EGF, TGF-α, or Nrg for up to 30 minutes. Lysates were immunoblotted for ErbB and SRC pathway signaling intermediates. DHT increased ERK1/2 activation by EGF, TGF-α, and Nrg in fibroblasts and Type II cells. Characterization in fibroblasts showed that potentiation of the EGF pathway was significant after 60 minutes of DHT exposure and persisted in the presence of the translational inhibitor cycloheximide. SRC and EGF receptor phosphorylation was increased by DHT, as was EGF-induced SHC1 phosphorylation and subsequent association with GRB2. Finally, SRC silencing, SRC inhibition with PP2, and overexpression of a dominant-negative SRC each prevented DHT from increasing EGF-induced ERK1/2 phosphorylation. These results suggest that DHT activates SRC to potentiate the signaling pathway leading from the EGF receptor to ERK activation in primary fetal lung fibroblasts.

Left bundle branch block with acute thrombotic occlusion is associated with increased myocardial jeopardy score and poor clinical outcomes in primary percutaneous coronary intervention activations.

OBJECTIVE: To assess the utility of left bundle branch block (LBBB) as an activation criterion for primary percutaneous coronary intervention (PPCI). DESIGN: Retrospective observational cohort study. SETTING: Single UK heart attack centre. PATIENTS: Consecutive patients referred for PPCI September 2008-December 2011 (n=2192). INTERVENTIONS: Demographic and outcome data were obtained by review of case notes, angiograms and interrogation of local/national databases. MAIN OUTCOME MEASURES: Angiographic culprit lesion assessment defined appropriate and inappropriate activations. Patients outcomes were assessed by Major adverse cardiac events (MACE), defined as a composite of mortality and unplanned revascularisation at 1-year. RESULTS: LBBB-activation occurred in 120 patients (5.5%), of whom 21 (17.5%) had acute coronary occlusion angiographically, and were adjudicated appropriately. Compared with appropriate activations for ST segment elevation, appropriate LBBB-activations were older (71.0 ± 9.6 vs 64.2 ± 12.4 years, p=0.01) and more likely to be in cardiogenic shock (19.0% vs 4.3%, p<0.01). Extent of disease quantified by the SYNTAX score did not differ (median 21.5, IQR 11.0-27.0 vs 19, 11.0-25.5, p=0.66), but amount of myocardium at-risk was higher in appropriate LBBB-activations (culprit jeopardy score median 4, IQR 2-6 vs 2, 2-4, p=0.02). Final diagnoses for LBBB-activations were acute coronary syndrome (39.2%), non-acute coronary syndrome cardiac chest pain (33.3%) and non-cardiac chest pain (27.5%). In appropriate LBBB-activations 1-year mortality and MACE were higher (23.8% vs 6.6%, p=0.002 and 28.6% vs 10.5%, p=0.007, respectively). CONCLUSIONS: Our data suggests that despite its poor specificity for identifying acute coronary occlusion, LBBB should at the present time remain an activation criterion for PPCI and such patients should continue to be transferred to heart attack centres for assessment and treatment.

Discovery of AMG 369, a Thiazolo[5,4-b]pyridine Agonist of S1P1 and S1P5.

The optimization of a series of thiazolopyridine S1P1 agonists with limited activity at the S1P3 receptor is reported. These efforts resulted in the discovery of 1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo-[5,4-b]pyridin-2-yl)benzyl)azetidine-3-carboxylic acid (5d, AMG 369), a potent dual S1P1/S1P5 agonist with limited activity at S1P3 and no activity at S1P2/S1P4. Dosed orally at 0.1 mg/kg, 5d is shown to reduce blood lymphocyte counts 24 h postdose and delay the onset and reduce the severity of experimental autoimmune encephalomyelitis in rat.