A Literature Review of Studies Evaluating Rotator Cuff Activation during Early Rehabilitation Exercises for Post-Op Rotator Cuff Repair

Despite the modern advancement of surgical repair equipment and techniques, many rotator cuff repairs do not clinically heal. Prescribed rehabilitative exercises must appropriately load the repaired muscle-tendon complex to promote healing and prevent capsular adhesions without damaging the repair. The clinician must possess an understanding of the anatomy and physiology of the healing rotator cuff, and understand the importance of the plane of movement, speed of the movement, position of the extremity, level of assistance, and type of resistance used. Electromyography (EMG) provides a useful means to determine muscle activation levels during specific exercises. Descriptions of specific exercises and EMG activation as they relate to the rotator cuff muscles are described. The specific performance of the exercises, the reliability of such EMG measures, and the descriptive figures are described. Practicing clinicians will benefit from the correct interpretation of the EMG data, and how it can be used in the exercise prescription when formulating a treatment plan

Comparative Effectiveness and Safety of Anti–Tumor Necrosis Factor Agents in Biologic-Naive Patients With Crohn’s Disease

Inhibitors of tumor necrosis factor (anti-TNF agents) are the most effective therapy for Crohn’s disease (CD). We evaluated the real-world comparative effectiveness and safety of different anti-TNF agents (infliximab, adalimumab, and certolizumab pegol) in biologic-naïve patients with CD in a retrospective, propensity-matched cohort study using a national administrative claims database (Optum Labs Data Warehouse)

Compositionally Graded Organic–Inorganic Nanocomposites for Enhanced Thermoelectric Performance

Thermoelectric generators (TEGs) operate in the presence of a temperature gradient, where the constituent thermoelectric (TE) material converts heat into electricity via the Seebeck effect. However, TE materials are characterised by a thermoelectric figure of merit (ZT) and/or power factor (PF), which often has a strong dependence on temperature. Thus, a single TE material spanning a given temperature range is unlikely to have an optimal ZT or PF across the entire range, leading to inefficient TEG performance. Here, we demonstrate compositionally graded organic-inorganic nanocomposites, where the composition of the TE nanocomposite is systematically tuned along the length of the TEG, in order to optimise the PF along the applied temperature gradient. The nanocomposite composition can be dynamically tuned by an aerosol-jet printing method with controlled in-situ mixing capability, thus enabling the realisation of such compositionally graded thermoelectric composites (CG-TECs). We show how CG-TECs can be realised by varying the loading weight percentage of Bi2Te3 nanoparticles or Sb2Te3 nanoflakes within an organic conducting matrix using bespoke solution-processable inks. The enhanced energy harvesting capability of these CG-TECs from low-grade waste heat (<100 °C) is demonstrated, highlighting the improvement in output power over single-component TEGs

Cyclic compression increases F508 DEL CFTR expression in ciliated human airway epithelium

The mechanisms by which transepithelial pressure changes observed during exercise and airway clearance can benefit lung health are challenging to study. Here, we have studied 117 mature, fully ciliated airway epithelial cell filters grown at air-liquid interface grown from 10 cystic fibrosis (CF) and 19 control subjects. These were exposed to cyclic increases in apical air pressure of 15 cmH2O for varying times. We measured the effect on proteins relevant to lung health, with a focus on the CF transmembrane regulator (CFTR). Immunofloures-cence and immunoblot data were concordant in demonstrating that air pressure increased F508Del CFTR expression and maturation. This effect was in part dependent on the presence of cilia, on Ca2+ influx, and on formation of nitrogen oxides. These data provide a mechanosensory mechanism by which changes in luminal air pressure, like those observed during exercise and airway clearance, can affect epithelial protein expression and benefit patients with diseases of the airways

Combination therapy with oral treprostinil for pulmonary arterial hypertension. A double-blind placebo-controlled clinical trial

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown. Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy. Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response. Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56–0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro–brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil–assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12–60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting. Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening. Clinical trial registered with www.clinicaltrials.gov (NCT01560624)

Rare variant analysis of 4241 pulmonary arterial hypertension cases from an international consortium implicates FBLN2, PDGFD, and rare de novo variants in PAH

Abstract: Background: Pulmonary arterial hypertension (PAH) is a lethal vasculopathy characterized by pathogenic remodeling of pulmonary arterioles leading to increased pulmonary pressures, right ventricular hypertrophy, and heart failure. PAH can be associated with other diseases (APAH: connective tissue diseases, congenital heart disease, and others) but often the etiology is idiopathic (IPAH). Mutations in bone morphogenetic protein receptor 2 (BMPR2) are the cause of most heritable cases but the vast majority of other cases are genetically undefined. Methods: To identify new risk genes, we utilized an international consortium of 4241 PAH cases with exome or genome sequencing data from the National Biological Sample and Data Repository for PAH, Columbia University Irving Medical Center, and the UK NIHR BioResource – Rare Diseases Study. The strength of this combined cohort is a doubling of the number of IPAH cases compared to either national cohort alone. We identified protein-coding variants and performed rare variant association analyses in unrelated participants of European ancestry, including 1647 IPAH cases and 18,819 controls. We also analyzed de novo variants in 124 pediatric trios enriched for IPAH and APAH-CHD. Results: Seven genes with rare deleterious variants were associated with IPAH with false discovery rate smaller than 0.1: three known genes (BMPR2, GDF2, and TBX4), two recently identified candidate genes (SOX17, KDR), and two new candidate genes (fibulin 2, FBLN2; platelet-derived growth factor D, PDGFD). The new genes were identified based solely on rare deleterious missense variants, a variant type that could not be adequately assessed in either cohort alone. The candidate genes exhibit expression patterns in lung and heart similar to that of known PAH risk genes, and most variants occur in conserved protein domains. For pediatric PAH, predicted deleterious de novo variants exhibited a significant burden compared to the background mutation rate (2.45×, p = 2.5e−5). At least eight novel pediatric candidate genes carrying de novo variants have plausible roles in lung/heart development. Conclusions: Rare variant analysis of a large international consortium identified two new candidate genes—FBLN2 and PDGFD. The new genes have known functions in vasculogenesis and remodeling. Trio analysis predicted that ~ 15% of pediatric IPAH may be explained by de novo variants