Sex-specific increases in myostatin and SMAD3 contribute to obesity-related insulin resistance in human skeletal muscle and primary human myotubes.

The purpose of the present study was to determine the effects of obesity and biological sex on myostatin expression in humans and to examine the direct effects of myostatin, SMAD2, and SMAD3 on insulin signaling in primary human skeletal muscle cells (HSkMCs). For cohort 1, 15 lean [body mass index (BMI): 22.1 ± 0.5 kg/m2; n = 8 males; n = 7 females] and 14 obese (BMI: 40.6 ± 1.4 kg/m2; n = 7 males; n = 7 females) individuals underwent skeletal muscle biopsies and an oral glucose tolerance test. For cohort 2, 14 young lean (BMI: 22.4 ± 1.9 kg/m2; n = 6 males; n = 8 females) and 14 obese (BMI: 39.3 ± 7.9 kg/m2; n = 6 males; n = 8 females) individuals underwent muscle biopsies for primary HSkMC experiments. Plasma mature myostatin (P = 0.041), skeletal muscle precursor myostatin (P = 0.048), and skeletal muscle SMAD3 (P = 0.029) were elevated in obese females compared to lean females, and plasma mature myostatin (r = 0.58, P = 0.029) and skeletal muscle SMAD3 (r = 0.56, P = 0.037) were associated with insulin resistance in females but not males. Twenty-four hours of myostatin treatment impaired insulin signaling in primary HSkMCs derived from females (P < 0.024) but not males. Overexpression of SMAD3, but not SMAD2, impaired insulin-stimulated AS160 phosphorylation in HSkMCs derived from lean females (-27%, P = 0.040), whereas silencing SMAD3 improved insulin-stimulated AS160 phosphorylation and insulin-stimulated glucose uptake (25%, P < 0.014) in HSkMCs derived from obese females. These results suggest for the first time that myostatin-induced impairments in skeletal muscle insulin signaling are sex specific and that increased body fat in females is associated with detrimental elevations in myostatin and SMAD3, which contribute to obesity-related insulin resistance.NEW & NOTEWORTHY Obesity is considered a main risk factor for the development of insulin resistance and type 2 diabetes. The present study utilizes in vivo and in vitro experiments in human skeletal muscle to demonstrate for the first time that females are inherently more susceptible to myostatin-induced insulin resistance, which is further enhanced with obesity due to increased myostatin and SMAD3 expression.

Estimating Compressive and Shear Forces at L5-S1: Exploring the Effects of Load Weight, Asymmetry, and Height Using Optical and Inertial Motion Capture Systems.

This study assesses the agreement of compressive and shear force estimates at the L5-S1 joint using inertial motion capture (IMC) within a musculoskeletal simulation model during manual lifting tasks, compared against a top-down optical motion capture (OMC)-based model. Thirty-six participants completed lifting and lowering tasks while wearing a modified Plug-in Gait marker set for the OMC and a full-body IMC set-up consisting of 17 sensors. The study focused on tasks with variable load weights, lifting heights, and trunk rotation angles. It was found that the IMC system consistently underestimated the compressive forces by an average of 34% (975.16 N) and the shear forces by 30% (291.77 N) compared with the OMC system. A critical observation was the discrepancy in joint angle measurements, particularly in trunk flexion, where the IMC-based model underestimated the angles by 10.92-11.19 degrees on average, with the extremes reaching up to 28 degrees. This underestimation was more pronounced in tasks involving greater flexion, notably impacting the force estimates. Additionally, this study highlights significant differences in the distance from the spine to the box during these tasks. On average, the IMC system showed an 8 cm shorter distance on the X axis and a 12-13 cm shorter distance on the Z axis during lifting and lowering, respectively, indicating a consistent underestimation of the segment length compared with the OMC system. These discrepancies in the joint angles and distances suggest potential limitations of the IMC system's sensor placement and model scaling. The load weight emerged as the most significant factor affecting force estimates, particularly at lower lifting heights, which involved more pronounced flexion movements. This study concludes that while the IMC system offers utility in ergonomic assessments, sensor placement and anthropometric modeling accuracy enhancements are imperative for more reliable force and kinematic estimations in occupational settings.

The Impact of Intracoronary Imaging on PCI Outcomes in Cases Utilising Rotational Atherectomy: An Analysis of 8,417 Rotational Atherectomy Cases from the British Cardiovascular Intervention Society Database.

Introduction: There is increasing evidence supporting the use of intracoronary imaging to optimize the outcomes of percutaneous coronary intervention (PCI). However, there are no studies examining the impact of imaging on PCI outcomes in cases utilising rotational atherectomy (RA-PCI). Our study examines the determinants and outcomes of using intracoronary imaging in RA-PCI cases including 12-month mortality. Methods: Using the British Cardiac Intervention Society database, data were analysed on all RA-PCI procedures in the UK between 2007 and 2014. Descriptive statistics and multivariate logistic regressions were used to examine baseline, procedural, and outcome associations with intravascular imaging. Results: Intracoronary imaging was used in 1,279 out of 8,417 RA-PCI cases (15.2%). Baseline covariates associated with significantly more imaging use were number of stents used, smoking history, previous CABG, pressure wire use, proximal LAD disease, laser use, glycoprotein inhibitor use, cutting balloons, number of restenosis attempted, off-site surgery, and unprotected left main stem (uLMS) PCI. Adjusted rates of in-hospital major adverse cardiac/cerebrovascular events (IH-MACCE), its individual components (death, peri-procedural MI, stroke, and major bleed), or 12-month mortality were not significantly altered by the use of imaging in RA-PCI. However, subgroup analysis demonstrated a signal towards reduction in 12-month mortality in uLMS RA-PCI cases utilising intracoronary imaging (OR 0.67, 95% CI 0.44-1.03). Conclusions: Intracoronary imaging use during RA-PCI is associated with higher risk of baseline and procedural characteristics. There were no differences observed in IH-MACCE or 12-month mortality with intracoronary imaging in RA-PCI.

The impaired healing hypothesis: a mechanism by which psychosocial stress and personal characteristics increase MSD risk?

While the effects of physical risk factors on MSD development have been a primary focus of musculoskeletal research, psychological stressors, and certain personal characteristics (e.g. ageing, sex, and obesity) are also associated with increased MSD risk. The psychological and personal characteristics listed above share a common characteristic: all are associated with disruption of the body's neuroendocrine and immune responses resulting in an impaired healing process. An impaired healing response may result in reduced fatigue life of musculoskeletal tissues due to a diminished ability to keep pace with accumulating damage (perhaps reparable under normal circumstances), and an increased vulnerability of damaged tissue to further trauma owing to the prolonged healing process. Research in engineered self-healing materials suggests that decreased healing kinetics in the presence of mechanical loading can substantially reduce the fatigue life of materials. A model of factors influencing damage accrual and healing will be presented. Practitioner summary: This article provides a potential reason why musculoskeletal disorder risk is affected by psychosocial stress, age, sex, and obesity. The reason is that these factors are all associated with a slower than normal healing response. This may lead to faster damage development in musculoskeletal tissues resulting in higher MSD risk.

Assessment of occupational dose reduction with the use of a floor mounted mobile lead radiation protection shield.

With the increasing number and complexity of interventional cardiology procedures, there is the potential for higher occupational radiation doses to the interventionists. In order to reduce the radiation exposure to interventionists, a number of different radiation protection measures can be implemented; the most common of which being personal protective equipment in the form of a lead-equivalent apron. However, significant development has been achieved with mobile lead equivalent radiation protection devices, which provide enhanced radiation protection without the requirement of being directly worn by staff. The RAMPART M1128 radiation protection shield is one of these devices. The dose reduction provided to staff within a Cardiac Catheterisation Laboratory was assessed via the use of electronic personal dosimeters with the Philips live dosimetry system DoseAware (Philips DoseAware). A 60% dose reduction to the primary operator can be achieved with the Rampart device. Further dose reductions are possible for other individuals in the range of 65%-84%. Additionally, dose rate measurements were taken in a simulated clinical set-up using a phantom, which showed that the device provided a 65% dose reduction at eye level and a 90% dose reduction at chest level for the primary operator position. This significant dose reduction means that there is the potential for at least the primary operator to wear a lead apron of reduced lead equivalence specification when the Rampart device is in use, without increasing their occupational exposure and potentially reducing musculoskeletal pain due to the reduced weight.

Combined use of rotational and excimer lASER coronary atherectomy (RASER) during complex coronary angioplasty-An analysis of cases (2006-2016) from the British Cardiovascular Intervention Society database.

INTRODUCTION: Combining rotational (RA) and excimer laser coronary atherectomy (ELCA)-RASER atherectomy-is technique utilized in the percutaneous management of calcific coronary disease. The evidence base examining its safety and utility is sparse and limited to small case-series. This study examines the patterns and outcomes of RASER atherectomy use in the largest cohort to date. METHODS: Using the British Cardiac Intervention Society database, data were analyzed on all PCI procedures in the UK between 2006 and 2016. Descriptive statistics and multivariate logistic regressions were used to examine baseline, procedural, and outcome associations with RASER. RESULTS: We identified 153 (0.02%) RASER atherectomy cases out of 686,358 PCI procedures. Baseline covariates associated with RASER use were age, BMI, diabetes, stable coronary disease, and previous CABG. Procedural co-variates associated with RASER were CTO-PCI, the use of more/longer stents, intravascular imaging, cutting balloons, and microcatheters. Adjusted rates of in-hospital major adverse cardiac/cerebrovascular events (MACCE) were not significantly different with RASER. However, there were higher odds of arterial complications (OR 3.23, 95% CI: 1.58-6.61), slow flow (OR 3.50, 95% CI: 1.29-9.55), and shock induction (OR 9.66, 95% CI: 3.44-27.06). CONCLUSIONS: RASER atherectomy use in complex PCI is associated with higher risk baseline and procedural characteristics. Although increased rates of shock induction, slow flow, and arterial complications were observed, RASER does not increase the likelihood of in-hospital MACCE, major bleeding, or death.

The impact of coronary perforation in percutaneous interventions involving the left main stem coronary artery in the United Kingdom 2007-2014: Insights from the British Cardiovascular Intervention Society database.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly utilized for treatment of coronary disease involving the unprotected left main stem (ULMS). However, no studies to date have examined the outcomes of such interventions when complicated by coronary perforation (CP). METHODS: Using the British Cardiovascular Intervention society (BCIS) database, data were analyzed on all ULMS-PCI procedures complicated by CP in England and Wales between 2007 and 2014. Multivariate logistic regressions were used to identify predictors of ULMS CP and to evaluate the association between this complication and outcomes. RESULTS: During 10,373 ULMS-PCI procedures, CP occurred more frequently than in non-ULMS-PCI (0.9 vs. 0.4%, p < .001) with a stable annual incidence. Covariates associated with CP included number of stents used, female gender, use of rotational atherectomy and chronic total occlusion (CTO) intervention. Adjusted odds of adverse outcomes for ULMS-PCI complicated by CP were higher for peri-procedural complications including cardiogenic shock, tamponade, side-branch loss, DC cardioversion, in-hospital major bleeding, transfusion requirement, and peri-procedural myocardial infarction. There were also significantly increased odds for in-hospital major adverse cardiac events (MACCE, OR 8.961, 95% CI [4.902-16.383]) and 30-day mortality (OR 5.301, 95% CI [2.741-10.251]). CONCLUSIONS: CP is an infrequent event during ULMS-PCI and is predicted by female gender, rotational atherectomy, CTO interventions or number of stents used. CP was associated with significantly higher odds of mortality and morbidity, but at rates similar to previously published all-comer PCI complicated by CP.

Vascular complications associated with intraaortic balloon pump supported percutaneous coronary intervention (PCI) and clinical outcomes from the British Cardiovascular Intervention Society National PCI Database.

INTRODUCTION: The impact of a vascular complication (VC) in the setting of intraaortic balloon pump (IABP) supported PCI on clinical outcomes is unclear. METHODS: Using data from the BCIS National PCI Database, multivariate logistic regression was used to identify independent predictors of a VC. Propensity scoring was used to quantify the association between a VC and outcomes. RESULTS: Between 2007 and 2014, 9,970 PCIs in England and Wales were supported by IABP (1.6% of total PCI), with 224 femoral VCs (2.3%). Annualized rates of a VC reduced as the use of radial access for PCI increased. The independent predictors of a VC included a procedural complication (odds ratio [OR] 2.9, p < .001), female sex (OR 2.3, p < .001), PCI for stable angina (OR 3.47, p = .028), and use of a glycoprotein inhibitor (OR 1.46 [1.1:2.5], p = .04), with a lower likelihood of a VC when radial access was used for PCI (OR 0.48, p = .008). A VC was associated with a higher likelihood of transfusion (OR 5.7 [3.5:9.2], p < .0001), acute kidney injury (OR 2.6 [1.2:6.1], p = .027), and periprocedural MI (OR 3.2 [1.5:6.7], p = .002) but not with adjusted mortality at discharge (OR 1.2 [0.8:1.7], p = .394) or 12-months (OR 1.1 [0.76:1.56], p = .639). In sensitivity analyses, there was a trend towards higher mortality in patients experiencing a VC who underwent PCI for stable angina (OR 4.1 [1.0:16.4], p value for interaction .069). Discussion and Conclusions Although in-hospital morbidity was observed to be adversely affected by occurrence of a VC during IABP-supported PCI, in-hospital and 1-year survival were similar between groups.

Excimer laser coronary atherectomy during complex PCI: An analysis of 1,471 laser cases from the British Cardiovascular Intervention Society database.

INTRODUCTION: Excimer laser coronary atherectomy (ELCA) is a recognized adjunctive therapy utilized in the percutaneous management of complex coronary lesions. Studies examining its safety and utility have been limited by small sample sizes. Our study examines the determinants and outcomes of ELCA. METHODS: Using the British Cardiac Intervention Society database, data were analyzed on all PCI procedures in the UK between 2006-2016. Descriptive statistics and multivariate logistic regressions were used to examine baseline, procedural and outcome associations with ELCA. RESULTS: We identified 1,471 (0.21%) ELCA cases out of 686,358 PCI procedures. Baseline covariates associated with ELCA use were age, BMI, number of lesions, CTO or restenosis attempted and history of prior MI, CABG or PCI. Procedural co-variates associated with ELCA were the use of glycoprotein inhibitors, intravascular imaging, rotational atherectomy, cutting balloons, microcatheters and intra-aortic balloon pumps. Adjusted rates of in-hospital major adverse cardiac/cerebrovascular events (MACCE) or its individual components (death, peri-procedural MI, stroke and major bleed) were not significantly altered by the use of ELCA. However, there were higher odds of dissection (OR 1.52, 95% CI 1.17-1.98), perforation (OR 2.18, 95% CI 1.44-3.30), slow flow (OR: 1.67, 95% CI 1.18-2.36), reintervention (OR: 2.12, 95% CI 1.14-3.93) and arterial complications (OR: 1.63, 95% CI 1.21-2.21). CONCLUSIONS: ELCA use during complex PCI is associated with higher risk baseline and procedural characteristics. Although increased rates of acute procedural complications were observed, ELCA does not increase likelihood of in-hospital MACCE or its individual components.

Single-dose intravenous ibuprofen for acute postoperative pain in adults.

BACKGROUND: Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, may reduce the incidence and severity of opioid-induced adverse events (AEs). OBJECTIVES: To assess the analgesic efficacy and adverse effects of single-dose intravenous (IV) ibuprofen, compared with placebo or an active comparator, for moderate-to-severe postoperative pain in adults. SEARCH METHODS: We searched the following databases without language restrictions: CENTRAL, MEDLINE, Embase and LILACS on 10 June 2021. We checked clinical trials registers and reference lists of retrieved articles for additional studies. SELECTION CRITERIA: We included randomized trials that compared a single postoperative dose of intravenous (IV) ibuprofen with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for review inclusion, assessed risk of bias, and extracted data. Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a 4- and 6-hour period. Our secondary outcomes were time to, and number of participants using rescue medication; withdrawals due to lack of efficacy, adverse events (AEs), and for any other cause; and number of participants reporting or experiencing any AE, serious AEs (SAEs), and specific NSAID-related or opioid-related AEs. We were not able to carry out any planned meta-analysis. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: Only one study met our inclusion criteria, involving 201 total participants, mostly female (mean age 42 years), undergoing primary, unilateral, distal, first metatarsal bunionectomy (with osteotomy and internal fixation). Ibuprofen 300 mg, placebo or acetaminophen 1000 mg was administered intravenously to participants reporting moderate pain intensity the day after surgery. Since we identified only one study for inclusion, we did not perform any quantitative analyses. The study was at low risk of bias for most domains. We downgraded the certainty of the evidence due to serious study limitations, indirectness and imprecision. Ibuprofen versus placebo Findings of the single study found that at both the 4-hour and 6-hour assessment period, the proportion of participants with at least 50% pain relief was 32% (24/76) for those assigned to ibuprofen and 22% (11/50) for those assigned to placebo. These findings produced a risk ratio (RR) of 1.44 (95% confidence interval (CI) 0.77 to 2.66 versus placebo for at least 50% of maximum pain relief over the 4-hour and 6-hour period (very low-certainty evidence). Median time to rescue medication was 101 minutes for ibuprofen and 71 minutes for placebo (1 study, 126 participants; very low-certainty evidence). The number of participants using rescue medication was not reported within the included study. During the study (1 study, 126 participants), 58/76 (76%) of participants assigned to ibuprofen and 39/50 (78%) assigned to placebo reported or experienced any adverse event (AE), (RR 0.98, 95% CI 0.81 to 1.19; low-certainty evidence). No serious AEs (SAEs) were experienced (1 study, 126 participants; very low-certainty evidence). Ibuprofen versus active comparators Ibuprofen (300 mg) was similar to the active comparator, IV acetaminophen (1000 mg) at 4 hours and 6 hours (1 study, 126 participants). For those assigned to active control (acetaminophen), the proportion of participants with at least 50% pain relief was 35% (26/75) at 4 hours and 31% (23/75) at 6 hours. At 4 hours, these findings produced a RR of 0.91 (95% CI 0.58 to 1.43; very low-certainty evidence) versus active comparator (acetaminophen). At 6 hours, these findings produced a RR of 1.03 (95% CI 0.64 to 1.66; very low-certainty evidence) versus active comparator (acetaminophen). Median time to rescue medication was 101 minutes for ibuprofen and 125 minutes for the active comparator, acetaminophen (1 study, 151 participants; very low-certainty evidence). The number of participants using rescue medication was not reported within the included study. During the study, 8/76 (76%) of participants assigned to ibuprofen and 45/75 (60%) assigned to active control (acetaminophen) reported or experienced any AE, (RR 1.27, 95% CI 1.02 to 1.59; very low-certainty evidence). No SAEs were experienced (1 study, 151 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: There is insufficient evidence to support or refute the suggestion that IV ibuprofen is effective and safe for acute postoperative pain in adults.

EMG and Joint Angle-Based Machine Learning to Predict Future Joint Angles at the Knee.

Electromyography (EMG) is commonly used to measure electrical activity of the skeletal muscles. As exoskeleton technology advances, these signals may be used to predict human intent for control purposes. This study used an artificial neural network trained and tested with knee flexion angles and knee muscle EMG signals to predict knee flexion angles during gait at 50, 100, 150, and 200 ms into the future. The hypothesis of this study was that the algorithm's prediction accuracy would only be affected by time into the future, not subject, gender or side, and that as time into the future increased, the prediction accuracy would decrease. A secondary hypothesis was that as the number of algorithm training trials increased, the prediction accuracy of the artificial neural network (ANN) would increase. The results of this study indicate that only time into the future affected the accuracy of knee flexion angle prediction (p < 0.001), whereby greater time resulted in reduced accuracy (0.68 to 4.62 degrees root mean square error (RMSE) from 50 to 200 ms). Additionally, increased number of training trials resulted in increased angle prediction accuracy.

Development and validation of a cumulative exposure shoulder risk assessment tool based on fatigue failure theory.

OBJECTIVE: To present a new risk assessment tool for shoulder intensive occupational tasks based on fatigue failure theory. METHODS: The tool estimates cumulative damage (CD) based on shoulder moments and loading cycles using an S-N curve derived from in vitro tendon fatigue failure tests. If multiple shoulder tasks are performed, the CD for each is summed. In the validation, 293 workers were evaluated for five separate shoulder outcomes. Logistic regression was used to assess the log CD against five shoulder outcomes adjusted for covariates including age, sex, body mass index (BMI), and plant site. RESULTS: Both crude and adjusted logistic regression results demonstrated strong dose-response associations between the log CD measure and all five shoulder outcomes (continuous ORs ranged from 2.12 to 5.20). CONCLUSIONS: The CD measure of The Shoulder Tool demonstrated dose-response relationships with multiple health outcomes. This provides further support that MSDs may be the result of a fatigue failure process. PRACTITIONER SUMMARY: This study presents a new, easy-to-use risk assessment tool for occupational tasks involving stressful shoulder exertions. The tool is based on fatigue failure theory. The tool was tested against an existing epidemiology study and demonstrated strong relationships to multiple shoulder outcomes. ABBREVIATIONS: MSD: musculoskeletal disorder; NORA: national occupational research agenda; RULA: rapid upper limb assessment; REBA: rapid entire body assessment; S-N: stress-number of cycles; EDL: extensor digitorum longus; DPC: damage per cycle; CD: cumulative damage; UTS: ultimate tensile strength; FTOV: first time office visit; 3DSSPP: 3-dimensional static strength prediction program; AS: visual analogue scale; BMI: body mass index; CI: confidence interval; Nm: newton-metre; LiFFT: lifting fatigue failure tool; DUET: distal upper extremity tool; OMNI-RES: OMNI resistance exercise scale.

Complex high-risk and indicated percutaneous coronary intervention for stable angina: Does operator volume influence patient outcome?

BACKGROUND: Complex high-risk and indicated revascularization using percutaneous coronary intervention (CHIP-PCI) is an emerging concept that is poorly studied. OBJECTIVE: To define temporal changes in CHIP-PCI volumes, and the relationship between operator CHIP-PCI volume and patient outcomes. METHODS AND RESULTS: Data were analyzed on all CHIP-PCI procedures undertaken for stable angina in England and Wales between 2007 and 2014. Operator volume data was available for 2012-14. CHIP-PCI was defined by patient characteristics (age ≥80years, left ventricular (LV) ejection fraction <30%, previous CABG, or chronic renal failure) and/or by procedural characteristics (left main PCI, chronic total occlusion PCI, LV support, use of rotational atherectomy or laser atherectomy). CHIP-PCI as a percentage of total PCI increased from 28.1% in 2007 to 36.2% in 2014 (P < .001). Between 2012 and 2014, a total of 30,268 CHIP-PCI cases were performed. Total operator volume varied from 1 to 580 cases with median total operator volume of 29 cases. Higher operator volumes were associated with a greater degree of patient comorbidity and increasing procedural complexity. After adjustment for baseline difference, in-hospital major bleeding (P < .001 for trend), access site complications (P < .001) and coronary perforation (P = .002) were associated with increasing operator CHIP-PCI volumes. However, the frequency of in-hospital death (P = .394) and 12-month mortality (P = .638) were similar across the volume quartiles. Higher volumes quartiles were associated with a greater likelihood of same day discharge (P < .001). CONCLUSIONS: CHIP-PCI cases are an increasingly large population in contemporary PCI practice. Higher operator volumes were not associated with improved 12-month survival. CONDENSED ABSTRACT: Data were analyzed on all complex high-risk and indicated revascularization using percutaneous coronary intervention (CHIP-PCI) procedures in England and Wales between 2007 and 2014. CHIP-PCI as a percentage of total PCI increased from 28.1% in 2007 to 36.2% in 2014 (P < .001). Median total operator volume was 29 cases with higher volumes associated with more patient comorbidity and increasing procedural complexity. In-hospital major bleeding (P < .001 for trend), access site complications (P < .001) and coronary perforation (P = .002) all associated with increasing operator CHIP-PCI volumes. However, trends for in-hospital death (P = .394), and 12-month mortality (P = .638) were similar across the volume quartiles.

The value of avian gross pathology in identifying endocrine disrupting properties.

The European Chemical Agency and European Food Safety Authority recommend that gross pathology findings, from avian reproduction studies, be used to support assessment of potential endocrine disrupting properties of active pesticidal and biocidal substances. In open literature, little information is available on the utility of gross pathology data for informing endocrine evaluations. Here the gross pathology data from historical control groups of 51 northern bobwhite and 51 mallard reproduction tests is analyzed to evaluate the utility of such information. Incidence of gross morphology findings in untreated birds may aid the interpretation of some gross abnormalities, potentially indicative of an endocrine interaction (e.g. reproductive condition). Statistical analysis of the historical control data indicates that gross pathology is not likely to be useful for detecting endocrine effects as abnormalities with relatively high increases in prevalence (more than 20-30%, depending on prevalence in controls) are reliably interpreted as a treatment response. Gross pathology changes are only indicative and not diagnostic of endocrine interactions making it difficult to distinguish gross pathology abnormalities, due to endocrine-mediated effects, from systemic toxicity. This work demonstrates the utility of using historical control analyses to establish the value and properties of selected endpoints for regulatory applications.

Forced treadmill running reduces systemic inflammation yet worsens upper limb discomfort in a rat model of work-related musculoskeletal disorders.

BACKGROUND: Musculoskeletal disorders can result from prolonged repetitive and/or forceful movements. Performance of an upper extremity high repetition high force task increases serum pro-inflammatory cytokines and upper extremity sensorimotor declines in a rat model of work-related musculoskeletal disorders. Since one of the most efficacious treatments for musculoskeletal pain is exercise, this study investigated the effectiveness of treadmill running in preventing these responses. METHODS: Twenty-nine young adult female Sprague-Dawley rats were used. Nineteen were trained for 5 weeks to pull a lever bar at high force (15 min/day). Thirteen went on to perform a high repetition high force reaching and lever-pulling task for 10 weeks (10-wk HRHF; 2 h/day, 3 days/wk). From this group, five were randomly selected to undergo forced treadmill running exercise (TM) during the last 6 weeks of task performance (10-wk HRHF+TM, 1 h/day, 5 days/wk). Results were compared to 10 control rats and 6 rats that underwent 6 weeks of treadmill running following training only (TR-then-TM). Voluntary task and reflexive sensorimotor behavioral outcomes were assessed. Serum was assayed for inflammatory cytokines and corticosterone, reach limb median nerves for CD68+ macrophages and extraneural thickening, and reach limb flexor digitorum muscles and tendons for pathological changes. RESULTS: 10-wk HRHF rats had higher serum levels of IL-1α, IL-1ß and TNFα, than control rats. In the 10-wk HRHF+TM group, IL-1ß and TNFα were lower, whereas IL-10 and corticosterone were higher, compared to 10-wk HRHF only rats. Unexpectedly, several voluntary task performance outcomes (grasp force, reach success, and participation) worsened in rats that underwent treadmill running, compared to untreated 10-wk HRHF rats. Examination of forelimb tissues revealed lower cellularity within the flexor digitorum epitendon but higher numbers of CD68+ macrophages within and extraneural fibrosis around median nerves in 10-wk HRHF+TM than 10-wk HRHF rats. CONCLUSIONS: Treadmill running was associated with lower systemic inflammation and moderate tendinosis, yet higher median nerve inflammation/fibrosis and worse task performance and sensorimotor behaviors. Continued loading of the injured tissues in addition to stress-related factors associated with forced running/exercise likely contributed to our findings.

Job rotation and work-related musculoskeletal disorders: a fatigue-failure perspective.

Job rotation is an organisational strategy that can be used, in part, to reduce occupational exposure to physical risk factors associated with work-related musculoskeletal disorders (MSDs). Recent studies, however, suggest that job rotation schedules may increase the overall risk of injury to workers included in the rotation scheme. We describe a novel optimisation framework evaluating the effectiveness of a job rotation scheme using the fatigue failure model of MSD development and a case study with real injury data. Results suggest that the effect of job rotation is highly-dependent on the composition of the job pool, and inclusion of jobs with higher risk results in a drastic decrease in the effectiveness of rotation for reducing overall worker risk. The study highlights that in cases when high-risk jobs are present, job redesign of those high risk tasks should be the primary focus of intervention efforts rather than job rotation. Practitioner summary: Job rotation is often used in industry as a method to 'balance' physical demands experienced by workers to reduce musculoskeletal disorder (MSD) risk. This article examines the efficacy of reducing MSDs through job rotation using numerical simulation of job rotation strategies and utilising the fatigue failure model of MSD development.

Early language measures associated with later psychosis features in 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome (22q11DS) is associated with impaired cognitive functions and increased risk for schizophrenia spectrum disorders. Speech and language deficits are prominent, with evidence of decline anteceding emergence of psychosis. There is paucity of data examining language function in children with 22q11DS with follow-up assessment of psychosis spectrum (PS) symptoms. We examined the association between early language measures, obtained clinically, and PS status, obtained on average 10.1 years later, in 166 youths with 22q11DS, with repeated language testing in 48. Participants were administered the Preschool Language Scale (receptive/expressive), and/or, for school aged children, the Clinical Evaluation of Language Fundamentals (receptive/expressive), and age appropriate IQ tests. The structured interview for prodromal syndromes (SIPS) assessed PS symptoms. We found that performance on all preschool measures showed age associated decline, and males performed more poorly on core composite (receptive/expressive) and receptive language measures. For language assessment later in childhood, poorer performance was consistently associated with subsequent PS status. Furthermore, steeper age-related decline was seen in the PS group across language measures and marginally for full-scale IQ. These findings suggest that while preschool language testing is useful in characterizing performance decline in individuals with 22q11DS, it does not robustly differentiate those with subsequent PS from those without. However, language testing in the school age population can help identify individuals with 22q11DS who are at risk for psychosis. Such data are needed for elucidating a lifespan trajectory for affected individuals and may help understand pathways to psychosis applicable to the general population.

Regression Models for the Erector Spinae Muscle Mass (ESMM) Cross-Sectional Area: Asymptomatic Populations.

Understanding low back muscle morphology is critical to understanding spinal loading and the underlying injury mechanisms, which help in characterizing risk and, therefore, minimize low back pain injuries. Individualized erector spinae muscle mass (ESMM) cross-sectional area (CSA) allows biomechanics practitioners to calculate individualized force generating capacities and spinal loadings for given tasks. The objective is to perform morphological analyses and then provide regression models to estimate the ESMM CSA of an individual with his/her subject characteristics. Thirty-five subjects (13 females and 22 males) without low back pain (LBP) history were included in this magnetic resonance imaging (MRI) study. Axial-oblique scans of low back region were used to measure the ESMM CSA. Subject demographics and anthropometrics were obtained and regressed over the ESMM CSA. Best-subset regression analyses were performed. Lean body mass (LBM) and the ankle, wrist, and head indexes were the most frequent predictive variables. Regression models with easy-to-measure variables showed smaller predictive power and increased estimation error compared to other regression models. Practitioners should consider this trade-off between model accuracy and complexity. An individual's ESMM CSA could be estimated by his/her individual characteristics, which enables biomechanical practitioners to estimate individualized low back force capacity and spinal loading.

Temporal changes in radial access use, associates and outcomes in patients undergoing PCI using rotational atherectomy between 2007 and 2014: results from the British Cardiovascular Intervention Society national database.

AIMS: Access site choice for cases requiring rotational atherectomy (PCI-ROTA) is poorly defined. Using the British Cardiovascular Intervention Society PCI database, temporal changes and contemporary associates/outcomes of access site choice for PCI-ROTA were studied. METHODS AND RESULTS: Data were analysed from 11,444 PCI-ROTA procedures performed in England and Wales between 2007 and 2014. Multivariate logistic regression was used to identify predictors of access site choice and its association with outcomes. RESULTS: For PCI-ROTA, radial access increased from 19.6% in 2007 to 58.6% in 2014. Adoption of radial access was slower in females, those with prior CABG, and in patients with chronic occlusive (CTO) or left main disease. In 2013/14, the strongest predictors of femoral artery use were age (OR 1.02, [1.005-1.036], P = .008), CTO intervention (OR 1.95, [1.209-3.314], P = .006), and history of previous CABG (OR 1.68, [1.124-2.515], P = .010). Radial access was associated with reductions in overall length of stay, and increased rates of same-day discharge. Procedural success rates were similar although femoral access use was associated with increased access site complications (2.4 vs. 0.1%, P < .001). After adjustment for baseline differences, arterial complications (OR 15.6, P < .001), transfusion (OR 12.5, P = .023) and major bleeding OR 6.0, P < .001) remained more common with FA use. Adjusted mortality and MACE rates were similar in both groups. CONCLUSIONS: In contemporary practice, radial access for PCI-ROTA results in similar procedural success when compared to femoral access but is associated with shorter length of stay, and lower rates of vascular complication, major bleeding and transfusion.

Twelve-month outcomes of patients unsuitable for prolonged DAPT presenting with an acute coronary syndrome and treated with polymer-free biolimus A9 drug-coated stents.

INTRODUCTION: Prolonged dual anti-platelet therapy (DAPT) is undesirable in certain patients. The biolimus-A9 drug-coated stent (BA9-DCS) has a rapid drug-elution profile allowing shortened DAPT. METHODS: The demographics, procedural data, and clinical outcomes for 505 patients presenting with an ACS to three UK centres and treated with a BA9-DCS stent (PCI-DCS) were collected, and compared to a consecutive ACS cohort of unselected patients treated in the same period with drug-eluting stents (PCI-DES). RESULTS: PCI-DCS patients were older, more often female with hypertension, chronic kidney disease, severe LV dysfunction, and peripheral vascular disease more frequent than the PCI-DES cohort. PCI-DCS patients had a much higher Mehran bleed risk score (21.5 ± 7.7 vs. 15.9 ± 7.7, P < 0.0001). Baseline disease burden was greater in the PCI-DCS cohort with more left main and three vessel disease. During PCI, more stents (1.91 ± 1.1 vs. 1.57 ± 0.94, P < 0.0001), total stent length (38.2 ± 20.8 vs. 31.4 ± 20.3, P < 0.0001) and longer stents (38.2 ± 20.8 vs. 31.4 ± 20.3 mm, P < 0.0001) were used in the PCI-DCS cohort with rotational atherectomy also used more frequently. Physician-recommended DAPT duration was 2.9 ± 3.9 months for PCI-DCS patients and 11.3 ± 2.4 months for PCI-DES patients (P < 0.0001). At 12-month follow-up, definite stent thrombosis (0.6% vs. 1.1%) and TLR (3.2% vs. 2.7%) rates were similar between the two groups. After adjustment for baseline differences, there were no statistically significant differences in death and combined MACE rates at 12 months. CONCLUSIONS: The outcomes of patients treated with polymer-free BA9 drug-coated stent who present with an ACS and who were deemed unsuitable for prolonged DAPT are encouraging. Further studies are warranted.