Integrative Metabolomics Differentiate Coronary Artery Disease, Peripheral Artery Disease, and Venous Thromboembolism Risks.

BACKGROUND: Arterial and venous cardiovascular conditions, such as coronary artery disease (CAD), peripheral artery disease (PAD), and venous thromboembolism (VTE), are genetically correlated. Interrogating underlying mechanisms may shed light on disease mechanisms. In this study, we aimed to identify (1) epidemiological and (2) causal, genetic relationships between metabolites and CAD, PAD, and VTE. METHODS: We used metabolomic data from 95 402 individuals in the UK Biobank, excluding individuals with prevalent cardiovascular disease. Cox proportional-hazards models estimated the associations of 249 metabolites with incident disease. Bidirectional 2-sample Mendelian randomization (MR) estimated the causal effects between metabolites and outcomes using genome-wide association summary statistics for metabolites (n=118 466 from the UK Biobank), CAD (n=184 305 from CARDIoGRAMplusC4D 2015), PAD (n=243 060 from the Million Veterans Project), and VTE (n=650 119 from the Million Veterans Project). Multivariable MR was performed in subsequent analyses. RESULTS: We found that 196, 115, and 74 metabolites were associated (P<0.001) with CAD, PAD, and VTE, respectively. Further interrogation of these metabolites with MR revealed 94, 34, and 9 metabolites with potentially causal effects on CAD, PAD, and VTE, respectively. There were 21 metabolites common to CAD and PAD and 4 common to PAD and VTE. Many putatively causal metabolites included lipoprotein traits with heterogeneity across different sizes and lipid subfractions. Small VLDL (very-low-density lipoprotein) particles increased the risk for CAD while large VLDL particles decreased the risk for VTE. We identified opposing directions of CAD and PAD effects for cholesterol and triglyceride concentrations within HDLs (high-density lipoproteins). Subsequent sensitivity analyses including multivariable MR revealed several metabolites with robust, potentially causal effects of VLDL particles on CAD. CONCLUSIONS: While common vascular conditions are associated with overlapping metabolomic profiles, MR prioritized the role of specific lipoprotein species for potential pharmacological targets to maximize benefits in both arterial and venous beds.

Clonal haematopoiesis of indeterminate potential predicts incident cardiac arrhythmias.

BACKGROUND AND AIMS: Clonal haematopoiesis of indeterminate potential (CHIP), the age-related expansion of blood cells with preleukemic mutations, is associated with atherosclerotic cardiovascular disease and heart failure. This study aimed to test the association of CHIP with new-onset arrhythmias. METHODS: UK Biobank participants without prevalent arrhythmias were included. Co-primary study outcomes were supraventricular arrhythmias, bradyarrhythmias, and ventricular arrhythmias. Secondary outcomes were cardiac arrest, atrial fibrillation, and any arrhythmia. Associations of any CHIP [variant allele fraction (VAF) ≥ 2%], large CHIP (VAF ≥10%), and gene-specific CHIP subtypes with incident arrhythmias were evaluated using multivariable-adjusted Cox regression. Associations of CHIP with myocardial interstitial fibrosis [T1 measured using cardiac magnetic resonance (CMR)] were also tested. RESULTS: This study included 410 702 participants [CHIP: n = 13 892 (3.4%); large CHIP: n = 9191 (2.2%)]. Any and large CHIP were associated with multi-variable-adjusted hazard ratios of 1.11 [95% confidence interval (CI) 1.04-1.18; P = .001] and 1.13 (95% CI 1.05-1.22; P = .001) for supraventricular arrhythmias, 1.09 (95% CI 1.01-1.19; P = .031) and 1.13 (95% CI 1.03-1.25; P = .011) for bradyarrhythmias, and 1.16 (95% CI, 1.00-1.34; P = .049) and 1.22 (95% CI 1.03-1.45; P = .021) for ventricular arrhythmias, respectively. Associations were independent of coronary artery disease and heart failure. Associations were also heterogeneous across arrhythmia subtypes and strongest for cardiac arrest. Gene-specific analyses revealed an increased risk of arrhythmias across driver genes other than DNMT3A. Large CHIP was associated with 1.31-fold odds (95% CI 1.07-1.59; P = .009) of being in the top quintile of myocardial fibrosis by CMR. CONCLUSIONS: CHIP may represent a novel risk factor for incident arrhythmias, indicating a potential target for modulation towards arrhythmia prevention and treatment.

Associations between lipoprotein(a), oxidized phospholipids, and extracoronary vascular disease.

The roles of lipoprotein(a) [Lp(a)] and related oxidized phospholipids (OxPLs) in the development and progression of coronary disease is known, but their influence on extracoronary vascular disease is not well-established. We sought to evaluate associations between Lp(a), OxPL apolipoprotein B (OxPL-apoB), and apolipoprotein(a) (OxPL-apo(a)) with angiographic extracoronary vascular disease and incident major adverse limb events (MALEs). Four hundred forty-six participants who underwent coronary and/or peripheral angiography were followed up for a median of 3.7 years. Lp(a) and OxPLs were measured before angiography. Elevated Lp(a) was defined as ≥150 nmol/L. Elevated OxPL-apoB and OxPL-apo(a) were defined as greater than or equal to the 75th percentile (OxPL-apoB ≥8.2 nmol/L and OxPL-apo(a) ≥35.8 nmol/L, respectively). Elevated Lp(a) had a stronger association with the presence of extracoronary vascular disease compared to OxPLs and was minimally improved with the addition of OxPLs in multivariable models. Compared to participants with normal Lp(a) and OxPL concentrations, participants with elevated Lp(a) levels were twice as likely to experience a MALE (odds ratio: 2.14, 95% confidence interval: 1.03, 4.44), and the strength of the association as well as the C statistic of 0.82 was largely unchanged with the addition of OxPL-apoB and OxPL-apo(a). Elevated Lp(a) and OxPLs are risk factors for progression and complications of extracoronary vascular disease. However, the addition of OxPLs to Lp(a) does not provide additional information about risk of extracoronary vascular disease. Therefore, Lp(a) alone captures the risk profile of Lp(a), OxPL-apoB, and OxPL-apo(a) in the development and progression of atherosclerotic plaque in peripheral arteries.

Impact of neoadjuvant pembrolizumab adherence on pathologic complete response in triple-negative breast cancer: a real-world analysis.

BACKGROUND: The addition of pembrolizumab (pembro) to neoadjuvant chemotherapy (NAC) is standard of care for the treatment of early triple-negative breast cancer (TNBC) after KEYNOTE-522 trial demonstrated improved pathologic complete response (pCR) rates with the combination. However, the optimal treatment strategy for TNBC remains uncertain as questions persist about which patients benefit from pembro and the best treatment schedule and regimen. We identified real-world clinical characteristics and treatment variables associated with response to NAC plus pembro. METHODS: Patients with early TNBC treated with NAC plus pembro between February 2020 and September 2023 were identified. Univariate and multivariate analysis was performed using logistic regression to identify factors associated with pCR. Cox proportional hazard prediction models were used to identify predictors of invasive disease-free survival and overall survival in this cohort. RESULTS: A pCR was achieved in 75 (63.6%) of 118 patients. Age at diagnosis (P = .04), Ki-67 (P = .004), duration from start of pembro to surgery (P = .006) and NAC to surgery (P = .01), number of cycles of pembro (P = .04) and NAC (P = .02), and completion of at least 8 cycles of pembro (P = .015) and NAC (P = .015) were each significantly associated with pCR in univariate analysis. In multivariate analysis, patients younger than 55 years at time of diagnosis (vs age > 55 years) and those completing at least 8 cycles of pembro remained predictive of pCR (OR's 2.50, 2.49, P = .035 and .037, respectively). CONCLUSIONS: In this real-world analysis of patients with TNBC treated with NAC plus pembro, younger age and the completion of at least 8 cycles of pembrolizumab were associated with pCR.

Role of Blood-Brain Barrier Dysfunction in Delirium following Non-cardiac Surgery in Older Adults.

OBJECTIVE: Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood-brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients. METHODS: Cognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before and after non-cardiac, non-neurologic surgery. Blood-brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio (CPAR). RESULTS: Of 207 patients (median age = 68 years, 45% female) with complete CPAR and delirium data, 26 (12.6%) developed postoperative delirium. Overall, CPAR increased from before to 24 hours after surgery (median change = 0.28, interquartile range [IQR] = -0.48 to 1.24, Wilcoxon p = 0.001). Preoperative to 24 hours postoperative change in CPAR was greater among patients who developed delirium versus those who did not (median [IQR] = 1.31 [0.004 to 2.34] vs 0.19 [-0.55 to 1.08], p = 0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24 hours postoperative change in CPAR was independently associated with delirium occurrence (per CPAR increase of 1, odds ratio = 1.30, 95% confidence interval [CI] = 1.03-1.63, p = 0.026) and increased hospital length of stay (incidence rate ratio = 1.15, 95% CI = 1.09-1.22, p < 0.001). INTERPRETATION: Postoperative increases in blood-brain barrier permeability are independently associated with increased delirium rates and postoperative hospital length of stay. Although these findings do not establish causality, studies are warranted to determine whether interventions to reduce postoperative blood-brain barrier dysfunction would reduce postoperative delirium rates and hospital length of stay. ANN NEUROL 2023;94:1024-1035.

Cognitive and Cerebrospinal Fluid Alzheimer's Disease-related Biomarker Trajectories in Older Surgical Patients and Matched Nonsurgical Controls.

BACKGROUND: Anesthesia and/or surgery accelerate Alzheimer's disease pathology and cause memory deficits in animal models, yet there is a lack of prospective data comparing cerebrospinal fluid (CSF) Alzheimer's disease-related biomarker and cognitive trajectories in older adults who underwent surgery versus those who have not. Thus, the objective here was to better understand whether anesthesia and/or surgery contribute to cognitive decline or an acceleration of Alzheimer's disease-related pathology in older adults. METHODS: The authors enrolled 140 patients 60 yr or older undergoing major nonneurologic surgery and 51 nonsurgical controls via strata-based matching on age, sex, and years of education. CSF amyloid ß (Aß) 42, tau, and p-tau-181p levels and cognitive function were measured before and after surgery, and at the same time intervals in controls. RESULTS: The groups were well matched on 25 of 31 baseline characteristics. There was no effect of group or interaction of group by time for baseline to 24-hr or 6-week postoperative changes in CSF Aß, tau, or p-tau levels, or tau/Aß or p-tau/Aß ratios (Bonferroni P > 0.05 for all) and no difference between groups in these CSF markers at 1 yr (P > 0.05 for all). Nonsurgical controls did not differ from surgical patients in baseline cognition (mean difference, 0.19 [95% CI, -0.06 to 0.43]; P = 0.132), yet had greater cognitive decline than the surgical patients 1 yr later (ß, -0.31 [95% CI, -0.45 to -0.17]; P < 0.001) even when controlling for baseline differences between groups. However, there was no difference between nonsurgical and surgical groups in 1-yr postoperative cognitive change in models that used imputation or inverse probability weighting for cognitive data to account for loss to follow up. CONCLUSIONS: During a 1-yr time period, as compared to matched nonsurgical controls, the study found no evidence that older patients who underwent anesthesia and noncardiac, nonneurologic surgery had accelerated CSF Alzheimer's disease-related biomarker (tau, p-tau, and Aß) changes or greater cognitive decline.

Preoperative electroencephalographic alpha-power changes with eyes opening are associated with postoperative attention impairment and inattention-related delirium severity.

BACKGROUND: In the eyes-closed, awake condition, EEG oscillatory power in the alpha band (7-13 Hz) dominates human spectral activity. With eyes open, however, EEG alpha power substantially decreases. Less alpha attenuation with eyes opening has been associated with inattention; thus, we analysed whether reduced preoperative alpha attenuation with eyes opening is associated with postoperative inattention, a delirium-defining feature. METHODS: Preoperative awake 32-channel EEG was recorded with eyes open and eyes closed in 71 non-neurological, noncardiac surgery patients aged ≥ 60 years. Inattention and other delirium features were assessed before surgery and twice daily after surgery until discharge. Eyes-opening EEG alpha-attenuation magnitude was analysed for associations with postoperative inattention, primarily, and with delirium severity, secondarily, using multivariate age- and Mini-Mental Status Examination (MMSE)-adjusted logistic and proportional-odds regression analyses. RESULTS: Preoperative alpha attenuation with eyes opening was inversely associated with postoperative inattention (odds ratio [OR] 0.73, 95% confidence interval [CI]: 0.57, 0.94; P=0.038). Sensitivity analyses showed an inverse relationship between alpha-attenuation magnitude and inattention chronicity, defined as 'never', 'newly', or 'chronically' inattentive (OR 0.76, 95% CI: 0.62, 0.93; P=0.019). In addition, preoperative alpha-attenuation magnitude was inversely associated with postoperative delirium severity (OR 0.79, 95% CI: 0.65, 0.95; P=0.040), predominantly as a result of the inattention feature. CONCLUSIONS: Preoperative awake, resting, EEG alpha attenuation with eyes opening might represent a neural biomarker for risk of postoperative attentional impairment. Further, eyes-opening alpha attenuation could provide insight into the neural mechanisms underlying postoperative inattention risk.

The Influence of Maturity Status on Drop Jump Kinetics in Male Youth.

ABSTRACT: Kumar, NTA, Radnor, JM, Oliver, JL, Lloyd, RS, CSCSD, Pedley, JS, Wong, MA, and Dobbs, IJ. The influence of maturity status on drop jump kinetics in male youth. J Strength Cond Res 38(1): 38-46, 2024-The aim of this study was to examine the effects of maturity status on drop jump (DJ) kinetics in young male athletes (categorized as early-pre-peak height velocity [PHV] [<-2.51 years], late-pre-PHV [-1.99 to -1.00 years], circa-PHV [-0.50 to 0.50 years], and post-PHV [>1.00 years]). All athletes performed a DJ from a 30-cm box onto force plates with performance variables (jump height, ground contact time, and reactive strength index) and absolute and relative kinetic variables during the braking and propulsive phases assessed. Subjects were categorized into GOOD (no impact-peak and spring-like), MODERATE (impact-peak and spring-like), or POOR (impact-peak and not spring-like) stretch-shortening cycle (SSC) function. The post-PHV group exhibited significantly greater values for most absolute kinetic variables compared with early-pre-PHV, late-pre-PHV, and circa-PHV (p < 0.05). The differences observed between consecutive maturity groups were similar in magnitude for most absolute variables (Cohen's d = 0.53-1.70). Post-PHV male athletes outperform their less mature counterparts during a DJ, and this may be attributed to the growth and maturity-related structural and motor control strategy changes that occur in children. Stretch-shortening cycle function in boys seems to improve with maturity status reflected by a greater number of post-PHV participants displaying GOOD SSC function (65.8%) and a greater number of early-pre-PHV participants displaying POOR SSC function (54.4%). However, a number of mature boys displayed POOR SSC function (17.8%), suggesting that the development of SSC function is not exclusively related to maturation.

Renal Pelvic Urothelial Carcinoma With Invasion Into Renal Medulla Can Be Redefined as pT2 to Improve Correlation With Survival.

According to the American Joint Cancer Committee, pT3 renal pelvic carcinoma is defined as tumor invading the renal parenchyma and/or peripelvic fat and is the largest pT category, with notable survival heterogeneity. Anatomical landmarks within the renal pelvis can be difficult to discern. Using glomeruli as a boundary to differentiate renal medulla invasion from renal cortex invasion, this study aimed to compare patient survival of pT3 renal pelvic urothelial carcinoma on the basis of the extent of renal parenchyma invasion and, thereafter, determine whether redefining pT2 and pT3 improves pT correlation with survival. Cases with primary renal pelvic urothelial carcinoma were identified through a review of pathology reports from nephroureterectomies completed at our institution from 2010 to 2019 (n = 145). Tumors were stratified by pT, pN, lymphovascular invasion, and invasion of the renal medulla versus invasion of the renal cortex and/or peripelvic fat. Overall survival between groups was compared using Kaplan-Meier survival models and Cox regression multivariate analysis. pT2 and pT3 tumors had similar 5-year overall survival, with multivariate analysis demonstrating an overlap between hazard ratios (HRs) for pT2 (HR, 2.20; 95% CI, 0.70-6.95) and pT3 (HR, 3.15; 95% CI, 1.63-6.09). pT3 tumors with peripelvic fat and/or renal cortex invasion had a 3.25-fold worse prognosis than pT3 tumors with renal medulla invasion alone. Furthermore, pT2 and pT3 tumors with only renal medulla invasion had similar overall survival, whereas pT3 tumors with peripelvic fat and/or renal cortex invasion had a worse prognosis (P = .00036). Reclassifying pT3 tumors with only renal medulla invasion as pT2 yielded greater separation between survival curves and HR. Thus, we recommend redefining pT2 renal pelvic carcinoma to include renal medulla invasion and restricting pT3 to peripelvic fat and/or renal cortex invasion to improve the prognostic accuracy of pT classification.

Perioperative changes in neurocognitive and Alzheimer's disease-related cerebrospinal fluid biomarkers in older patients randomised to isoflurane or propofol for anaesthetic maintenance.

BACKGROUND: Animal studies have shown that isoflurane and propofol have differential effects on Alzheimer's disease (AD) pathology and memory, although it is unclear whether this occurs in humans. METHODS: This was a nested randomised controlled trial within a prospective cohort study; patients age ≥60 yr undergoing noncardiac/non-neurological surgery were randomised to isoflurane or propofol for anaesthetic maintenance. Cerebrospinal fluid (CSF) was collected via lumbar puncture before, 24 h, and 6 weeks after surgery. Cognitive testing was performed before and 6 weeks after surgery. Nonparametric methods and linear regression were used to evaluate CSF biomarkers and cognitive function, respectively. RESULTS: There were 107 subjects (54 randomised to isoflurane and 53 to propofol) who completed the 6-week follow-up and were included in the analysis. There was no significant effect of anaesthetic treatment group, time, or group-by-time interaction for CSF amyloid-beta (Aß), tau, or phospho-tau181p levels, or on the tau/Aß or p-tau181p/Aß ratios (all P>0.05 after Bonferroni correction). In multivariable-adjusted intention-to-treat analyses, there were no significant differences between the isoflurane and propofol groups in 6-week postoperative change in overall cognition (mean difference [95% confidence interval]: 0.01 [-0.12 to 0.13]; P=0.89) or individual cognitive domains (P>0.05 for each). Results remained consistent across as-treated and per-protocol analyses. CONCLUSIONS: Intraoperative anaesthetic maintenance with isoflurane vs propofol had no significant effect on postoperative cognition or CSF Alzheimer's disease-related biomarkers within 6 weeks after noncardiac, non-neurological surgery in older adults. CLINICAL TRIAL REGISTRATION: NCT01993836.

Selection into youth cricket academies: The influence of relative age and maturity status.

The aim of the study was to examine the birth quartile and maturity status distributions of male academy cricketers. Participants included 213 junior cricket players, aged between 9 and 18 years. Players were separated into birth quartiles and also grouped as early, average or late maturers. For the whole cohort, there was a medium effect bias towards players born in BQ1, but the number of early, average and late maturers was as expected. However, there were significantly more early maturers in the U10 and U11 groups than expected, and maturity distributions of the BQ groups showed that there was a small effect size bias towards early maturers in BQ4. Selection biases towards cricketers who are born earlier in the competitive year are consistent from U9 to U16, but more prevalent in the U12 and U14 age groups. There is a bias towards early maturers at U10 and U11, but this reduces as age increases. Practitioners working in academy pathways should be encouraged to assess the maturity status of players to assist in the retention and progression of players. Relative age effects should also be considered, and strategies may be required to identify players born later in the year.

Doxycycline sclerotherapy of cervical spine aneurysmal bone cysts: single-institution 13-year experience.

BACKGROUND: Aneurysmal bone cysts (ABCs) are benign, locally aggressive neoplasms that typically affect patients during their first two decades of life. Curettage with or without bone grafting or adjuvants is the current standard treatment; however, other surgical and medical treatments, such as sclerotherapy, have been reported. Treatment options for cervical spine ABCs are more limited because the proximity of ABCs to critical structures leads to greater risk of spontaneous or treatment-related adverse events, including death. OBJECTIVE: To retrospectively review all children and young adults with cervical spine ABCs treated with doxycycline sclerotherapy at one referral center to assess its viability as a standalone treatment. MATERIALS AND METHODS: We retrospectively reviewed the clinical notes and imaging of 16 patients treated with doxycycline sclerotherapy for pathologically proven cervical spine ABCs at our institution between May 2008 and March 2021. All patients underwent image-guided percutaneous doxycycline sclerotherapy to ablate the ABC and stimulate bone formation. We assessed clinical outcomes through chart review and described post-treatment imaging outcomes using modified Neer scoring. RESULTS: Of the 16 total children and young adults treated, 2 were lost to follow-up, leaving 14 patients with a median age of 14.5 years. Twelve of these 14 patients were successfully treated with doxycycline sclerotherapy for a success rate of 86%. One patient experienced one treatment-related complication (Society of Interventional Radiology [SIR] adverse event classification D), before ultimately being successfully treated. Doxycycline treatment failed in two patients, who then underwent surgical management. Post-treatment imaging of successfully treated cases had a mean modified Neer score of 1.3, whereas post-treatment imaging in failed cases had a mean score of 3.5. CONCLUSION: Doxycycline sclerotherapy is a viable standalone treatment for cervical spine ABCs because it is safe and effective while avoiding the morbidity associated with open surgical treatments.

Effects of a 4-Week Neuromuscular Training Program on Movement Competency During the Back-Squat Assessment in Pre- and Post-Peak Height Velocity Male Athletes.

ABSTRACT: Dobbs, IJ, Oliver, JL, Wong, MA, Moore, IS, Myer, GD, and Lloyd, RS. Effects of a 4-week neuromuscular training program on movement competency during the back-squat assessment in pre- and post-peak height velocity male athletes. J Strength Cond Res 35(10): 2698-2705, 2021-The back-squat assessment (BSA) is a novel movement screen to detect functional deficits; however, its sensitivity to detect meaningful changes in movement competency after exposure to short-term neuromuscular training remains unclear. Twenty-six pre- and 22 post-peak height velocity (PHV) males were divided into experimental (EXP) and control groups (CON) and performed the BSA before and after a twice weekly, 4-week neuromuscular training intervention. Intra-rater reliability was determined by rating both EXP group's baseline BSA on 3 separate sessions. Intraclass correlation coefficient (ICC) revealed very strong agreement for BSA total score in pre-PHV (ICC ≥ 0.81) and post-PHV (ICC ≥ 0.97) groups across all sessions, but systematic bias was evident in the pre-PHV group for sessions 1-2. Analysis of kappa values for BSA individual criteria showed greater variability for pre-PHV (K ≥ 0.31) than post-PHV (K ≥ 0.62) across sessions. At baseline, there were no differences in total score between the EXP and CON cohorts (p > 0.05). There were significant within-group improvements in total score for the EXP pre-PHV (5.0 to 3.0, effect size [ES] = 0.68) and post-PHV (2.0 to 1.0, ES = 0.82) cohorts, with no changes in total score for either CON groups (p > 0.05). Hip position was the criterion with the greatest improvement for both the EXP pre-PHV (12.0 to 7.0) and post-PHV (7.0 to 0.0) groups. The BSA seems to be a reliable screening tool for measuring movement competency in youth male athletes and was sensitive to adaptations in movement competency after neuromuscular training.

Movement competency and measures of isometric and dynamic strength and power in boys of different maturity status.

An understanding of how movement competency, strength, and power interact with natural growth and maturation is required in order to determine meaningful changes with developing athletes. Isometric and dynamic testing in youth athletes provides insight into the natural development of the force-velocity (F-V) spectrum. Two-hundred and six young male athletes, aged 9-17 years of age, were grouped according to stage of maturation based on their maturity offset which was determined as number of years from peak height velocity (PHV). All participants performed the back-squat assessment (BSA), isometric mid-thigh pull (IMTP), countermovement jump (CMJ), and squat jump (SJ) tests. Absolute and scaled force-time variables were collected from the IMTP, CMJ, and SJ. No significant differences were observed between maturational groups for squat movement competency (P > .05). One-way ANOVA with Bonferroni post-hoc analysis revealed that increasing maturity led to significant, moderate to large increases in allometrically scaled peak force (PFallo ) for all tests (P < .05). Multiple stepwise linear regression models revealed IMTP PFallo significantly predicted 34.8% and 41.3% of variance in SJ and CMJ jump height, respectively (P < .05). Natural growth and maturation induces positive adaptations to movement competency as well as isometric and dynamic strength and power. Trends from the IMTP, SJ, and CMJ tests indicate the largest differences in strength, and power may occur around the adolescent growth spurt despite the large variation in rates of change within the circa-PHV group.

Effects of a 12-Week Training Program on Isometric and Dynamic Force-Time Characteristics in Pre- and Post-Peak Height Velocity Male Athletes.

Dobbs, IJ, Oliver, JL, Wong, MA, Moore, IS, and Lloyd, RS. Effects of a 12-week training program on isometric and dynamic force-time characteristics in pre- and post-peak height velocity male athletes. J Strength Cond Res 34(3): 653-662, 2020-Literature shows that training children and adolescents can enhance strength and power irrespective of their stage of development; however, the development of the kinetic variables that underpin strength and power performance are typically unreported in youth training studies. Twenty-four pre- and 14 post-peak height velocity (PHV) male athletes were divided into maturity-specific experimental (EXP) and control groups (CON), with the EXP groups completing a twice-weekly, 12-week training program. Force-time characteristics during the isometric midthigh pull (IMTP), countermovement jump, and squat jump tests were quantified at both baseline and after the completion of the 12-week program. Alpha level was set at p < 0.05. No changes in total score for back-squat assessment were observed in any group (p > 0.05). Analysis of IMTP data revealed that only the post-PHV EXP group significantly increased absolute isometric peak force (PFabs) and peak rate of force development within the IMTP after training. Both EXP groups displayed significant increases in isometric PF at time epochs 0-90, 0-150, 0-200, and 0-250 ms. Data from the dynamic tests indicated that the pre-PHV EXP cohort improved concentric qualities as reflected by increased squat jump height and countermovement jump concentric power. There were no significant changes for any variables across all tests within either CON group (p > 0.05). Maturity-related differences in response to short-term training affects the kinetic variables associated with strength and power performance, but not movement competency in young male athletes.

Double Tubular Contractile Structure of the Type VI Secretion System Displays Striking Flexibility and Elasticity.

Antimicrobial treatment can induce many bacterial pathogens to enter a cell wall-deficient state that contributes to persistent infections. The effect of this physiological state on the assembly of transenvelope-anchored organelles is not well understood. The type VI secretion system (T6SS) is a widespread molecular weapon for interspecies interactions and virulence, comprising a long double tubular structure and a transenvelope/baseplate complex. Here, we report that cell wall-deficient spheroplasts assembled highly flexible and elastic T6SS structures forming U, O, or S shapes. Upon contacting the inner membrane, the T6SS tubes did not contract but rather continued to grow along the membrane. Such deformation likely results from continual addition of sheath/tube subunits at the distal end. Induction of TagA repressed curved sheath formation. Curved sheaths could also contract and deliver T6SS substrates and were readily disassembled by the ClpV ATPase after contraction. Our data highlight the dramatic effect of cell wall deficiency on the shape of the T6SS structures and reveal the elastic nature of this double tubular contractile injection nanomachine.IMPORTANCE The cell wall is a physical scaffold that all transenvelope complexes have to cross for assembly. However, the cell wall-deficient state has been described as a common condition found in both Gram-negative and Gram-positive pathogens during persistent infections. Loss of cell wall is known to have pleiotropic physiological effects, but how membrane-anchored large cellular organelles adapt to this unique state is less completely understood. Our study examined the assembly of the T6SS in cell wall-deficient spheroplast cells. We report the elastic nature of contractile T6SS tubules under such conditions, providing key insights for understanding how large intracellular structures such as the T6SS accommodate the multifaceted changes in cell wall-deficient cells.

Identification of divergent type VI secretion effectors using a conserved chaperone domain.

The type VI secretion system (T6SS) is a lethal weapon used by many bacteria to kill eukaryotic predators or prokaryotic competitors. Killing by the T6SS results from repetitive delivery of toxic effectors. Despite their importance in dictating bacterial fitness, systematic prediction of T6SS effectors remains challenging due to high effector diversity and the absence of a conserved signature sequence. Here, we report a class of T6SS effector chaperone (TEC) proteins that are required for effector delivery through binding to VgrG and effector proteins. The TEC proteins share a highly conserved domain (DUF4123) and are genetically encoded upstream of their cognate effector genes. Using the conserved TEC domain sequence, we identified a large family of TEC genes coupled to putative T6SS effectors in Gram-negative bacteria. We validated this approach by verifying a predicted effector TseC in Aeromonas hydrophila. We show that TseC is a T6SS-secreted antibacterial effector and that the downstream gene tsiC encodes the cognate immunity protein. Further, we demonstrate that TseC secretion requires its cognate TEC protein and an associated VgrG protein. Distinct from previous effector-dependent bioinformatic analyses, our approach using the conserved TEC domain will facilitate the discovery and functional characterization of new T6SS effectors in Gram-negative bacteria.

Validity and Reliability of Surface Electromyography Measurements from a Wearable Athlete Performance System.

The Athos ® wearable system integrates surface electromyography (sEMG ) electrodes into the construction of compression athletic apparel. The Athos system reduces the complexity and increases the portability of collecting EMG data and provides processed data to the end user. The objective of the study was to determine the reliability and validity of Athos as compared with a research grade sEMG system. Twelve healthy subjects performed 7 trials on separate days (1 baseline trial and 6 repeated trials). In each trial subjects wore the wearable sEMG system and had a research grade sEMG system's electrodes placed just distal on the same muscle, as close as possible to the wearable system's electrodes. The muscles tested were the vastus lateralis (VL), vastus medialis (VM), and biceps femoris (BF). All testing was done on an isokinetic dynamometer. Baseline testing involved performing isometric 1 repetition maximum tests for the knee extensors and flexors and three repetitions of concentric-concentric knee flexion and extension at MVC for each testing speed: 60, 180, and 300 deg/sec. Repeated trials 2-7 each comprised 9 sets where each set included three repetitions of concentric-concentric knee flexion-extension. Each repeated trial (2-7) comprised one set at each speed and percent MVC (50%, 75%, 100%) combination. The wearable system and research grade sEMG data were processed using the same methods and aligned in time. The amplitude metrics calculated from the sEMG for each repetition were the peak amplitude, sum of the linear envelope, and 95th percentile. Validity results comprise two main findings. First, there is not a significant effect of system (Athos or research grade system) on the repetition amplitude metrics (95%, peak, or sum). Second, the relationship between torque and sEMG is not significantly different between Athos and the research grade system. For reliability testing, the variation across trials and averaged across speeds was 0.8%, 7.3%, and 0.2% higher for Athos from BF, VL and VM, respectively. Also, using the standard deviation of the MVC normalized repetition amplitude, the research grade system showed 10.7% variability while Athos showed 12%. The wearable technology (Athos) provides sEMG measures that are consistent with controlled, research grade technologies and data collection procedures.

Determination of Vertical Jump as a Measure of Neuromuscular Readiness and Fatigue.

Watkins, CM, Barillas, SR, Wong, MA, Archer, DC, Dobbs, IJ, Lockie, RG, Coburn, JW, Tran, TT, and Brown, LE. Determination of vertical jump as a measure of neuromuscular readiness and fatigue. J Strength Cond Res 31(12): 3305-3310, 2017-Coaches closely monitor training loads and periodize sessions throughout the season to create optimal adaptations at the proper time. However, only monitoring training loads ignores the innate physiological stress each athlete feels individually. Vertical jump (VJ) is widely used as a measure of lower-body power, and has been used in postmatch studies to demonstrate fatigue levels. However, no pretraining monitoring by VJ performance has been previously studied. Therefore, the purpose of this study was to determine the sensitivity of VJ as a measure of readiness and fatigue on a daily sessional basis. Ten healthy resistance-trained males (mass = 91.60 ± 13.24 kg; height = 179.70 ± 9.23 cm; age = 25.40 ± 1.51 years) and 7 females (mass = 65.36 ± 12.29 kg; height = 162.36 ± 5.75 cm; age = 25.00 ± 2.71 years) volunteered to participate. Vertical jump and BRUNEL Mood Assessment (BAM) were measured 4 times: pre-workout 1, post-workout 1, pre-workout 2, and post-workout 2. Workout intensity was identical for both workouts, consisting of 4 sets of 5 repetitions for hang cleans, and 4 sets of 6 repetitions for push presses at 85% 1 repetition maximum (1RM), followed by 4 sets to failure of back squats (BSs), Romanian deadlift, and leg press at 80% 1RM. The major finding was that VJ height decrement (-8.05 ± 9.65 cm) at pre-workout 2 was correlated (r = 0.648) with BS volume decrement (-27.56 ± 24.56%) between workouts. This is important for coaches to proactively understand the current fatigue levels of their athletes and their readiness to resistance training.

Acute Effects of Eccentric Overload on Concentric Front Squat Performance.

Munger, CN, Archer, DC, Leyva, WD, Wong, MA, Coburn, JW, Costa, PB, and Brown, LE. Acute effects of eccentric overload on concentric front squat performance. J Strength Cond Res 31(5): 1192-1197, 2017-Eccentric overload is used to enhance performance. The purpose of this study was to investigate the acute effects of eccentric overload on concentric front squat performance. Twenty resistance-trained men (age = 23.80 ± 1.82 years, height = 176.95 ± 5.21 cm, mass = 83.49 ± 10.43 kg, 1 repetition maximum [1RM] front squat = 131.02 ± 21.32 kg) volunteered. A dynamic warm-up and warm-up sets of front squat were performed. Eccentric hooks were added to the barbell. They descended for 3 seconds, until eccentric hooks released, and performed the concentric phase as fast as possible. There were 3 randomly ordered conditions with the concentric phase always at 90% 1RM and the eccentric phase at 105, 110, and 120% of 1RM. Two repetitions were performed for each condition. A repeated measures analysis of variance was used to determine differences. For peak velocity, there were main effects for time and condition (p < 0.05), where post (1.01 ± 0.10 m·s) was greater than pre (0.96 ± 0.11 m·s) and 120% (1.03 ± 1.11 m·s) was greater than 105% (0.99 ± 0.13 m·s). For peak power, there was a main effect for condition where 120% (2,225.00 ± 432.37 W) was greater than 105% (2,021.84 ± 563.53 W). For peak ground reaction force, there were main effects for time and condition, where post was greater than pre and 120% was greater than 105%. For the rate of force development, there was no interaction or main effects. Eccentric overload enhanced concentric velocity and power; therefore, it can be used by strength coaches and athletes during the power phase of a training program. It can also be used to prescribe supramaximal loads and could be a tool to supplement the clean exercise because the front squat is a precursor.