Relaxin suppresses atrial fibrillation, reverses fibrosis and reduces inflammation in aged hearts.

Healthy aging results in cardiac structural and electrical remodeling that increase susceptibility to cardiovascular diseases. Relaxin has shown broad cardioprotective effects including anti-fibrotic, anti-arrhythmic and anti-inflammatory outcomes in multiple models. This paper focuses on the cardioprotective effects of Relaxin in a rat model of aging. Sustained atrial or ventricular fibrillation are readily induced in the hearts of aged but not young control animals. Treatment with Relaxin suppressed this arrhythmogenic response by increasing conduction velocity, decreasing fibrosis and promoting substantial cardiac remodeling. Relaxin treatment resulted in a significant increase in the levels of: Nav1.5, Cx43, ßcatenin and Wnt1 in rat hearts. In isolated cardiomyocytes, Relaxin increased Nav1.5 expression. These effects were mimicked by CHIR 99021, a pharmacological activator of canonical Wnt signaling, but blocked by the canonical Wnt inhibitor Dickkopf1. Relaxin prevented TGF-ß-dependent differentiation of cardiac fibroblasts into myofibroblasts while increasing the expression of Wnt1; the effects of Relaxin on cardiac fibroblast differentiation were blocked by Dickkopf1. RNASeq studies demonstrated reduced expression of pro-inflammatory cytokines and an increase in the expression of α- and ß-globin in Relaxin-treated aged males. Relaxin reduces arrhythmogenicity in the hearts of aged rats by reduction of fibrosis and increased conduction velocity. These changes are accompanied by substantial remodeling of the cardiac tissue and appear to be mediated by increased canonical Wnt signaling. Relaxin also exerts significant anti-inflammatory and anti-oxidant effects in the hearts of aged rodents. The mechanisms by which Relaxin increases the expression of Wnt ligands, promotes Wnt signaling and reprograms gene expression remain to be determined.

Physiological characteristics predictive of passing military physical employment standard tasks for ground close combat occupations in men and women.

Challenges for some women meeting the physical employment standards (PES) for ground close combat (GCC) roles stem from physical fitness and anthropometric characteristics. The purpose of this study was to identify the modifiable and nonmodifiable characteristics predictive of passing GCC-based PES tasks and determine the modifiable characteristics suitable to overcome nonmodifiable limitations. 107 adults (46 women) underwent multiday testing assessing regional and total lean mass (LM), percent body fat (BF%), aerobic capacity (V̇O2peak), strength, power, and PES performance. Predictors with p-value <0.200 were included in stepwise logistic regression analysis or binary logistic regression when outcomes among sexes were insufficient. Relative and absolute arm LM (OR: 4.617-8.522, p < 0.05), leg LM (OR: 2.463, p < 0.05), and upper body power (OR: 2.061, p < 0.05) predicted medicine ball chest throw success. Relative and absolute arm LM (OR: 3.734-11.694, p < 0.05), absolute trunk LM (OR: 2.576, p < 0.05), and leg LM (OR: 2.088, p < 0.05) predicted casualty drag success. Upper body power (OR: 3.910, p < 0.05), absolute trunk LM (OR: 2.387, p < 0.05), leg LM (OR: 2.290, p < 0.05), and total LM (OR: 1.830, p < 0.05) predicted maximum single lift success. Relative and absolute arm LM (OR: 3.488-7.377, p < 0.05), leg LM (OR: 1.965, p < 0.05), and upper body power (OR: 1.957, p < 0.05) predicted water can carry success. %BF (OR: 0.814, p = 0.007), V̇O2peak (OR: 1.160, p = 0.031), and lower body strength (OR: 1.059, p < 0.001) predicted repeated lift and carry success. V̇O2peak (OR: 1.540, p < 0.001) predicted 2-km ruck march success. Modifiable characteristics were the strongest predictors for GCC-based PES task success to warrant their improvement for enhancing PES performance for women.

Allostatic Load Is Associated with Overuse Musculoskeletal Injury during US Marine Corps Officer Candidates School.

INTRODUCTION: Overuse musculoskeletal injuries (MSKIs) remain a significant medical challenge in military personnel undergoing military training courses; a further understanding of the biological process leading to overuse MSKI development and biological signatures for injury risk are warranted. The purpose of this study was to determine the association between overuse MSKI occurrence and physiological characteristics of allostatic load (AL) characterized as maladaptive biological responses to chronic stress measured by wearable devices in US Marine Corps officer candidates during a 10-week training course. METHODS: Devices recorded energy expenditure (EE), daytime heart rate (HR), sleeping HR, and sleep architecture (time and percent of deep, light, REM sleep, awake time, total sleep). Flux was calculated as the raw or absolute difference in the average value for that day or night and the day or night beforehand. Linear mixed-effect model analysis accounting for cardiorespiratory fitness assessed the association between overuse MSKI occurrence and device metrics (α = 0.05). RESULTS: Sixty-nine participants (23 females) were included. Twenty-one participants (eight females) sustained an overuse MSKI. Overuse MSKI occurrence in male participants was positively associated with daytime HR (ß = 5.316, p = 0.008), sleeping HR (ß = 2.708, p = 0.032), relative EE (ß = 8.968, p = 0.001), absolute flux in relative EE (ß = 2.994, p = 0.002), absolute EE (ß = 626.830, p = 0.001), and absolute flux in absolute EE (ß = 204.062, p = 0.004). Overuse MSKI occurrence in female participants was positively associated with relative EE (ß = 5.955, p = 0.026), deep sleep time (ß = 0.664, p < 0.001), %deep sleep (ß = 12.564, p < 0.001) and negatively associated with absolute flux in sleeping HR (ß = -0.660, p = 0.009). CONCLUSIONS: Overuse MSKI occurrences were associated with physiological characteristics of AL including chronically elevated HR and EE and greater time in restorative sleep stages, which may serve as biological signatures for overuse MSKI risk.

Circulating extracellular vesicle characteristics differ between men and women following 12 weeks of concurrent exercise training.

Concurrent resistance and endurance exercise training (CET) has well-studied benefits; however, inherent hormonal and genetic differences alter adaptive responses to exercise between sexes. Extracellular vesicles (EVs) are factors that contribute to adaptive signaling. Our purpose was to test if EV characteristics differ between men and women following CET. 18 young healthy participants underwent 12-weeks of CET. Prior to and following CET, subjects performed an acute bout of heavy resistance exercise (AHRET) consisting of 6 × 10 back squats at 75% 1RM. At rest and following AHRET, EVs were isolated from plasma and characteristics and miRNA contents were analyzed. AHRET elevated EV abundance in trained men only (+51%) and AHRET-induced changes were observed for muscle-derived EVs and microvesicles. There were considerable sex-specific effects of CET on EV miRNAs, highlighted by larger variation following the 12-week program in men compared to women at rest. Pathway analysis based on differentially expressed EV miRNAs predicted that AHRET and 12 weeks of CET in men positively regulates hypertrophy and growth pathways more so than in women. This report highlights sex-based differences in the EV response to resistance and concurrent exercise training and suggests that EVs may be important adaptive signaling factors altered by exercise training.

Definitive single-stage surgery for treating diabetic foot osteomyelitis: a protocolized pathway including antibiotic bone graft substitute use.

BACKGROUND: Diabetic foot ulcers (DFUs) are a challenging complication of diabetes mellitus, often leading to poor clinical outcomes and significant socioeconomic burdens. We evaluated the effectiveness of a definitive single-stage protocolized surgical management pathway, including the use of local antibiotic bone graft substitute, for the treatment of infected DFUs with associated osteomyelitis. METHODS: A retrospective cohort study was conducted. Medical records were extracted (from January 2017 to December 2020) to establish a database consisting of patients who underwent surgical intervention for the treatment of an infected DFU with osteomyelitis. Patients were divided into conventional (control) and protocolized (intervention) surgical groups depending on the treatment received. Clinical outcomes were assessed over a 12-month follow-up period. RESULTS: A total of 136 consecutive patients were included (conventional = 33, protocolized = 103). The protocolized group demonstrated a statistically significant reduction in the mean number of operations performed per patient (1.2 vs. 3.5) (P < 0.001) and a shorter accumulative hospital length of stay (12.6 vs. 25.1 days) (P < 0.001) compared to the conventional group. Major amputation rates were significantly lower in the protocolized group (2% vs. 18%) (P < 0.001). Within 12 months of surgical intervention, the protocolized group exhibited an ulcer healing rate of 89%, with a low rate of recurrence (3%). CONCLUSION: The protocolized surgical pathway, including local antibiotic bone graft substitute use, demonstrated superior outcomes compared to conventional management for the treatment of infected DFUs with osteomyelitis. Further research is needed to evaluate the cost-effectiveness and generalizability of this approach.

Skeletal muscle adaptations to high-intensity, low-volume concurrent resistance and interval training in recreationally active men and women.

This study compared the structural and cellular skeletal muscle factors underpinning adaptations in maximal strength, power, aerobic capacity, and lean body mass to a 12-week concurrent resistance and interval training program in men and women. Recreationally active women and men completed three training sessions per week consisting of high-intensity, low-volume resistance training followed by interval training performed using a variety upper and lower body exercises representative of military occupational tasks. Pre- and post-training vastus lateralis muscle biopsies were analyzed for changes in muscle fiber type, cross-sectional area, capillarization, and mitochondrial biogenesis marker content. Changes in maximal strength, aerobic capacity, and lean body mass (LBM) were also assessed. Training elicited hypertrophy of type I (12.9%; p = 0.016) and type IIa (12.7%; p = 0.007) muscle fibers in men only. In both sexes, training decreased type IIx fiber expression (1.9%; p = 0.046) and increased total PGC-1α (29.7%, p < 0.001) and citrate synthase (11.0%; p < 0.014) content, but had no effect on COX IV content or muscle capillarization. In both sexes, training increased maximal strength and LBM but not aerobic capacity. The concurrent training program was effective at increasing strength and LBM but not at improving aerobic capacity or skeletal muscle adaptations underpinning aerobic performance.

Acute Resistance Exercise Modifies Extracellular Vesicle miRNAs Targeting Anabolic Gene Pathways: A Prospective Cohort Study.

BACKGROUND: Resistance training confers numerous health benefits that are mediated in part by circulating factors. Toward an enhanced molecular understanding, there is growing interest in a class of signaling biomarkers called extracellular vesicles (EV). EVs support physiological adaptations to exercise by transporting their cargo (e.g., microRNA (miRNA)) to target cells. Previous studies of changes in EV cargo have focused on aerobic exercise, with limited data examining the effects of resistance exercise. We examined the effect of acute resistance exercise on circulating EV miRNAs and their predicted target pathways. METHODS: Ten participants (5 men; age, 26.9 ± 5.5 yr; height, 173.4 ± 10.5 cm; body mass, 74.0 ± 11.1 kg; body fat, 25.7% ± 11.6%) completed an acute heavy resistance exercise test (AHRET) consisting of six sets of 10 repetitions of back squats using 75% one-repetition maximum. Pre-/post-AHRET, EVs were isolated from plasma using size exclusion chromatography, and RNA sequencing was performed. Differentially expressed miRNAs between pre- and post-AHRET EVs were analyzed using Ingenuity Pathway Analysis to predict target messenger RNAs and their target biological pathways. RESULTS: Overall, 34 miRNAs were altered by AHRET ( P < 0.05), targeting 4895 mRNAs, with enrichment of 175 canonical pathways ( P < 0.01), including 12 related to growth/metabolism (p53, IGF-I, STAT3, PPAR, JAK/STAT, growth hormone, WNT/ß-catenin, ERK/MAPK, AMPK, mTOR, and PI3K/AKT) and 8 to inflammation signaling (TGF-ß, IL-8, IL-7, IL-3, IL-6, IL-2, IL-17, IL-10). CONCLUSIONS: Acute resistance exercise alters EV miRNAs targeting pathways involved in growth, metabolism, and immune function. Circulating EVs may serve as significant adaptive signaling molecules influenced by exercise training.

The 31-Gene Expression Profile Test Outperforms AJCC in Stratifying Risk of Recurrence in Patients with Stage I Cutaneous Melanoma.

BACKGROUND: Patients with stage I cutaneous melanoma (CM) are considered at low risk for metastasis or melanoma specific death; however, because the majority of patients are diagnosed with stage I disease, they represent the largest number of melanoma deaths annually. The 31-gene expression profile (31-GEP) test has been prospectively validated to provide prognostic information independent of staging, classifying patients as low (Class 1A), intermediate (Class 1B/2A), or high (Class 2B) risk of poor outcomes. METHODS: Patients enrolled in previous studies of the 31-GEP were combined and evaluated for recurrence-free (RFS) and melanoma-specific survival (MSS) (n = 1261, "combined"). A second large, unselected real-world cohort (n = 5651) comprising clinically tested patients diagnosed 2013-2018 who were linked to outcomes data from the NCI Surveillance, Epidemiology, and End Results (SEER) Program registries was evaluated for MSS. RESULTS: Combined cohort Class 1A patients had significantly higher RFS than Class 1B/2A or Class 2B patients (97.3%, 88.6%, 77.3%, p < 0.001)-better risk stratification than AJCC8 stage IA (97.5%) versus IB (89.3%). The SEER cohort showed better MSS stratification by the 31-GEP (Class 1A = 98.0%, Class 1B/2A = 97.5%, Class 2B = 92.3%; p < 0.001) than by AJCC8 staging (stage IA = 97.6%, stage IB = 97.9%; p < 0.001). CONCLUSIONS: The 31-GEP test significantly improved patient risk stratification, independent of AJCC8 staging in patients with stage I CM. The 31-GEP provided greater separation between high- (Class 2B) and low-risk (Class 1A) groups than seen between AJCC stage IA and IB. These data support integrating the 31-GEP into clinical decision making for more risk-aligned management plans.

Effect of acute resistance exercise on bone turnover in young adults before and after concurrent resistance and interval training.

Weight-bearing physical activity can stimulate bone adaptation. This investigation explored the effect of an acute bout of resistance exercise before and after resistance+interval training on circulating biomarkers of bone metabolism and muscle-bone crosstalk. Healthy young male and female participants (n = 21 male, 28 ± 4 years; n = 17 female, 27 ± 5 years) performed a 6 × 10 squat test (75% 1RM) before and after a 12-week resistance+interval training program. Before and after completion of the training program, blood samples were collected at rest, immediately postexercise, and 2 h postexercise. Blood samples were analyzed for ßCTX, P1NP, sclerostin, osteocalcin, IGF-1, and irisin. Significant effects of acute exercise (main effect of time) were observed as increases in concentrations of IGF-1, irisin, osteocalcin, and P1NP from rest to postexercise. A sex*time interaction indicated a greater decline in ßCTX concentration from rest to 2 h postexercise and a greater increase in sclerostin concentration from rest to immediately postexercise in male compared with female participants. Sex differences (main effect of sex) were also observed for irisin and P1NP concentrations. In summary, changes in concentrations of biochemical markers of bone metabolism and muscle-bone crosstalk were observed in males and females after an acute bout of resistance exercise and following 12 weeks of resistance+interval training.

Anchoring on Hyperglycemia and Sepsis in the Presence of an Unforeseen Thyroid Storm.

Thyroid storm (TS) is a relatively rare but life-threatening complication of an overactive thyroid that can manifest in a myriad of ways due to its multisystem involvement. Due to its relatively high mortality rate, it is essential that TS is recognized and treated promptly. TS can occur due to trauma, drugs, and sepsis. Identifying TS as a diagnosis is challenging to pinpoint due to its similar presentation to more common pathologies like sepsis and diabetic ketoacidosis (DKA). Here, we present a case of a 31-year-old African-American woman with type 2 diabetes mellitus following sepsis secondary to Escherichia coli pyelonephritis and DKA. Despite standard sepsis treatment, which included appropriate intravenous fluids and antibiotics, the patient did not improve. Further workup, utilizing the Burch-Wartofsky score, helped identify TS as the underlying cause of the patient's hospitalization, despite no history of underlying thyroid disease. The inclusion of thyroid pathology as part of the differential diagnosis and workup of a patient with a sepsis-like presentation to avoid anchoring bias warrants further investigation.

The Integrated i31-GEP Test Outperforms the MSKCC Nomogram at Predicting SLN Status in Melanoma Patients.

BACKGROUND/AIM: Sentinel lymph node biopsy (SLNB) for patients with cutaneous melanoma is primarily a prognostic procedure that broadly identifies patients who may have disease progression and may warrant additional intervention. However, 88% of patients undergoing SLNB receive a negative result and of those, some will succumb to their disease. One clinical utility of the integrated 31-GEP test, which combines gene expression data with clinicopathologic factors to provide a personalized, precise risk of SLN positivity, is SLNB guidance. This study compared the i31-GEP for SLNB to a nomogram that predicts SLN positivity using only clinicopathologic factors. PATIENTS AND METHODS: Patients with T1-T2 tumors and known SLN status (N=465) were analyzed by the i31-GEP for SLNB and a nomogram developed at Memorial Sloan Kettering Cancer Center (MSKCC). A 5% risk threshold was used to conform with national guidelines. RESULTS: In patients with <5% predicted risk, SLN positivity was 2.7% (3/111) for i31-GEP versus 10.0% (11/110, p=0.026) for MSKCC. In each T-category, the i31-GEP maintained a false-negative rate below the 5% risk threshold in those predicted to have a <5% risk, while the MSKCC nomogram did not. CONCLUSION: Integrating the 31-GEP with traditional factors outperformed a nomogram that uses clinicopathologic factors alone to predict SLN status. Incorporating the i31-GEP into clinical practice could improve identification of patients for SLNB, resulting in better risk-aligned management.

Association of clinically-measured and dynamic ankle dorsiflexion assessed by markerless motion capture during the drop-jump task on landing biomechanics and risk of ankle injury in military personnel undergoing 10 weeks of physical training.

OBJECTIVES: Determine the influence of clinically-measured maximum dorsiflexion, dynamic peak dorsiflexion and percent of clinically-measured maximum dorsiflexion used during a drop-jump task on landing biomechanics and risk of ankle injury in military personnel. DESIGN: Prospective cohort study. METHODS: 672 participants (122 women) enrolled. The weightbearing lunge test assessed clinically-measured maximum dorsiflexion averaged across limbs (degrees). Markerless motion capture and force plates collected lower extremity kinematic and kinetic data during a drop-jump task. Percent of clinically-measured maximum dorsiflexion used during landing was calculated as dynamic peak dorsiflexion divided by clinically-measured value, multiplied by 100 (%). De-identified injury data was derived from military physical therapists. Simple linear regression analysis determined the association between dorsiflexion measures and landing biomechanics. Simple binary logistic regression analyses identified predictors of ankle injuries. Statistical significance was set at α = 0.05. RESULTS: Eighteen participants sustained a traumatic ankle injury from a landing. All measures of dorsiflexion were associated with movement patterns that countered the stiff-legged landing strategy with dynamic measures showing a higher predictive value. Protective factors against ankle injury included height (odds ratio: 0.818, p = 0.006) and weight (odds ratio: 0.824, p = 0.023) for women. Relative braking impulse was a risk factor for men (odds ratio: 1.890, p = 0.001). CONCLUSIONS: Greater clinically-measured and dynamic measures of dorsiflexion were associated with movement patterns that countered the stiff-legged landing strategy but neither measure of dorsiflexion predicted ankle injury risk. Resultant biomechanics and anthropometrics influenced ankle injury risk to warrant recognition for injury prevention initiatives.

31-Gene Expression Profile Testing in Cutaneous Melanoma and Survival Outcomes in a Population-Based Analysis: A SEER Collaboration.

PURPOSE: The DecisionDx-Melanoma 31-gene expression profile (31-GEP) test is validated to classify cutaneous malignant melanoma (CM) patient risk of recurrence, metastasis, or death as low (class 1A), intermediate (class 1B/2A), or high (class 2B). This study aimed to examine the effect of 31-GEP testing on survival outcomes and confirm the prognostic ability of the 31-GEP at the population level. METHODS: Patients with stage I-III CM with a clinical 31-GEP result between 2016 and 2018 were linked to data from 17 SEER registries (n = 4,687) following registries' operation procedures for linkages. Melanoma-specific survival (MSS) and overall survival (OS) differences by 31-GEP risk category were examined using Kaplan-Meier analysis and the log-rank test. Crude and adjusted hazard ratios (HRs) were calculated using Cox regression model to evaluate variables associated with survival. 31-GEP tested patients were propensity score-matched to a cohort of non-31-GEP tested patients from the SEER database. Robustness of the effect of 31-GEP testing was assessed using resampling. RESULTS: Patients with a 31-GEP class 1A result had higher 3-year MSS and OS than patients with a class 1B/2A or class 2B result (MSS: 99.7% v 97.1% v 89.6%, P < .001; OS: 96.6% v 90.2% v 79.4%, P < .001). A class 2B result was an independent predictor of MSS (HR, 7.00; 95% CI, 2.70 to 18.00) and OS (HR, 2.39; 95% CI, 1.54 to 3.70). 31-GEP testing was associated with a 29% lower MSS mortality (HR, 0.71; 95% CI, 0.53 to 0.94) and 17% lower overall mortality (HR, 0.83; 95% CI, 0.70 to 0.99) relative to untested patients. CONCLUSION: In a population-based, clinically tested melanoma cohort, the 31-GEP stratified patients by their risk of dying from melanoma.

Utility of Gene Expression Profiling in Skin Cancer: A Comprehensive Review.

Understanding the metastatic potential of a skin cancer is essential to effective management. Gene expression profiling (GEP) is an innovative technology that has allowed for a better understanding of tumor biology in various skin cancers. Current methods focus on identifying and quantifying ribonucleic acid (RNA) transcripts in tissue samples. Using reverse transcriptase-polymerase chain reaction, specific RNA transcripts are reverted into deoxyribonucleic acid (DNA) for quantification. The addition of RNA-seq has further enhanced our knowledge of genomes not only by measuring known sequences, but also by identifying novel genes in various skin cancers. GEP requires only a small amount of RNA and has a high level of reproducibility. Using this technology, several GEPs for skin cancers have been developed to augment diagnosis and prognosis of skin cancer. This article reviews the process of gene expression profiling and the current GEPs that are available or under investigation for skin cancer. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7017.

Military tactical adaptive decision making during simulated military operational stress is influenced by personality, resilience, aerobic fitness, and neurocognitive function.

Laboratory-based studies designed to mimic combat or military field training have consistently demonstrated deleterious effects on warfighter's physical, cognitive, and emotional performance during simulated military operational stress (SMOS). Purpose: The present investigation sought to determine the impact of a 48-h simulated military operational stress (SMOS) on military tactical adaptive decision making, and the influence of select psychological, physical performance, cognitive, and physiological outcome measures on decision making performance. Methods: Male (n = 48, 26.2 ± 5.5 years, 177.7 ± 6.6 cm, 84.7 ± 14.1 kg.) subjects currently serving in the U.S. military were eligible to participate in this study. Eligible subjects completed a 96-h protocol that occurred over five consecutive days and four nights. Day 2 (D2) and day 3 (D3) consisted of 48-h of SMOS wherein sleep opportunity and caloric needs were reduced to 50%. Differences in SPEAR total block score from baseline to peak stress (D3 minus D1) were calculated to assess change in military tactical adaptive decision making and groups were stratified based on increase (high adaptors) or decrease (low adaptors) of the SPEAR change score. Results: Overall, military tactical decision-making declined 1.7% from D1 to D3 (p < 0.001). High adaptors reported significantly higher scores of aerobic capacity (p < 0.001), self-report resilience (p = 0.020), extroversion (p < 0.001), and conscientiousness (p < 0.001). at baseline compared to low adaptors, while low adaptors reported greater scores in Neuroticism (p < 0.001). Conclusion: The present findings suggest that service members whose adaptive decision making abilities improved throughout SMOS (i.e., high adaptors) demonstrated better baseline psychological/self-reported resilience and aerobic capacity. Further, changes in adaptive decision-making were distinct from those of lower order cognitive functions throughout SMOS exposure. With the transition of future military conflicts placing higher priority on enhancing and sustaining cognitive readiness and resiliency, data presented here demonstrates the importance of measuring and categorizing baseline measures inherent to military personnel, in order to change and train one's ability to suffer less of a decline during high stress conditions.

Predictive utility of commercial grade technologies for assessing musculoskeletal injury risk in US Marine Corps Officer candidates.

Recently, commercial grade technologies have provided black box algorithms potentially relating to musculoskeletal injury (MSKI) risk and functional movement deficits, in which may add value to a high-performance model. Thus, the purpose of this manuscript was to evaluate composite and component scores from commercial grade technologies associations to MSKI risk in Marine Officer Candidates. 689 candidates (Male candidates = 566, Female candidates = 123) performed counter movement jumps on SPARTA™ force plates and functional movements (squats, jumps, lunges) in DARI™ markerless motion capture at the start of Officer Candidates School (OCS). De-identified MSKI data was acquired from internal OCS reports for those who presented to the Physical Therapy department for MSKI treatment during the 10 weeks of training. Logistic regression analyses were conducted to validate the utility of the composite scores and supervised machine learning algorithms were deployed to create a population specific model on the normalized component variables in SPARTA™ and DARI™. Common MSKI risk factors (cMSKI) such as older age, slower run times, and females were associated with greater MSKI risk. Composite scores were significantly associated with MSKI, although the area under the curve (AUC) demonstrated poor discrimination (AUC = .55-.57). When supervised machine learning algorithms were trained on the normalized component variables and cMSKI variables, the overall training models performed well, but when the training models were tested on the testing data the models classified MSKI "by chance" (testing AUC avg = .55-.57) across all models. Composite scores and component population specific models were poor predictors of MSKI in candidates. While cMSKI, SPARTA™, and DARI™ models performed similarly, this study does not dismiss the use of commercial technologies but questions the utility of a singular screening task to predict MSKI over 10 weeks. Further investigations should evaluate occupation specific screening, serial measurements, and/or load exposure for creating MSKI risk models.

The 31-gene expression profile test informs sentinel lymph node biopsy decisions in patients with cutaneous melanoma: results of a prospective, multicenter study.

BACKGROUND: The 31-gene expression profile test (Class 1A: low-risk; 1B/2A: intermediate-risk; 2B: high-risk) is validated to identify patients with cutaneous melanoma who can safely forego sentinel lymph node biopsy (SLNB). The objective of the current study is to quantify SLNB reduction by clinicians using 31-GEP. METHODS: Patients with T1-T2 tumors eligible for SLNB were seen by surgical oncologists (89.1%), dermatologists (7.8%), and medical oncologists (3.1%). After receiving 31-GEP results but before SLNB, clinicians were asked which clinical and pathological features influenced SLNB decisions (n = 191). The Exact binomial test was used to compare SLNB procedure rates to a contemporary study (78% SLNB baseline rate). Logistic regression modeling (odds ratio [OR], 95% CI) was used to identify features associated with SLNB procedure rates. RESULTS: One hundred clinical decisions (52.4%) were influenced by the 31-GEP to forego SLNB and 70% (70/100) were not performed. Of the 30 performed, 0% (0/30) were positive. The 31-GEP influenced sixty-three clinical decisions (33.0%) to perform SLNB, and 92.1% (58/63) were performed. There was a clinically meaningful 29.4% reduction of SLNBs performed in patients with a Class 1A result relative to the baseline rate of 78.0% (p < .01). In patients ≥55 or ≥65-year-old, SLNB reduction was 32.3% (p < .01), 28.3% (p < .01), respectively. Overall, 85.3% of decisions relating to SLNB were influenced by 31-GEP results. CONCLUSION: In this prospective, multicenter study, clinicians demonstrated clinically meaningful use of the 31-GEP test to forego or pursue SLNB in patients with T1-T2 tumors resulting in a significant, risk appropriate decrease in SLNBs.

Changes in eating pathology symptoms during initial military training in men and women and associations with BMI and injury risk.

Nutritional fitness, which comprises food choices, meal timing, and dietary intake behaviors, is an important component of military service member health and performance that has garnered recent attention. This study utilized generalized linear mixed effects modeling (GLMM) to investigate changes in eating pathology symptoms in men and women during initial military training (Marine Corps Officer Candidates School (OCS)). Associations among eating pathology, musculoskeletal injury risk and BMI were also assessed. This investigation includes data from the Eating Pathology Symptoms Inventory (EPSI) and BMI at the start of OCS (n = 598: Male n = 469, Female n = 129) and end of the 10-week program (n = 413: Male n = 329, Female n = 84), and injury surveillance throughout. At baseline, female candidates presented with greater body dissatisfaction, binge eating, purging, and restricting, but lower negative attitudes toward obesity compared to male candidates (p < 0.001). Eating symptoms changed during military training indicated by decreased body dissatisfaction in women (p = 0.003), decreased excessive exercise and negative attitudes toward obesity in men (p < 0.001), decreased cognitive restraint (p < 0.001), restricting (p < 0.001), purging (p = 0.013), and muscle building (p < 0.001) and increased binge eating (p < 0.001) in both sexes. Changes in restricting were significantly related to changes in BMI during training (p < 0.05). The likelihood of future injury was 108 % higher in female candidates than males and decreased by 5 % for each unit increase in excessive exercise. Eating attitudes and behaviors change during military training environments and are associated with military health and readiness outcomes including BMI and injury risk.