Isometric training is used in the rehabilitation and physical preparation of athletes, special populations, and the general public. However, little consensus exists regarding training guidelines for ...a variety of desired outcomes. Understanding the adaptive response to specific loading parameters would be of benefit to practitioners. The objective of this systematic review, therefore, was to detail the medium‐ to long‐term adaptations of different types of isometric training on morphological, neurological, and performance variables. Exploration of the relevant subject matter was performed through MEDLINE, PubMed, SPORTDiscus, and CINAHL databases. English, full‐text, peer‐reviewed journal articles and unpublished doctoral dissertations investigating medium‐ to long‐term (≥3 weeks) adaptations to isometric training in humans were identified. These studies were evaluated further for methodological quality. Twenty‐six research outputs were reviewed. Isometric training at longer muscle lengths (0.86%‐1.69%/week, ES = 0.03‐0.09/week) produced greater muscular hypertrophy when compared to equal volumes of shorter muscle length training (0.08%‐0.83%/week, ES = −0.003 to 0.07/week). Ballistic intent resulted in greater neuromuscular activation (1.04%‐10.5%/week, ES = 0.02‐0.31/week vs 1.64%‐5.53%/week, ES = 0.03‐0.20/week) and rapid force production (1.2%‐13.4%/week, ES = 0.05‐0.61/week vs 1.01%‐8.13%/week, ES = 0.06‐0.22/week). Substantial improvements in muscular hypertrophy and maximal force production were reported regardless of training intensity. High‐intensity (≥70%) contractions are required for improving tendon structure and function. Additionally, long muscle length training results in greater transference to dynamic performance. Despite relatively few studies meeting the inclusion criteria, this review provides practitioners with insight into which isometric training variables (eg, joint angle, intensity, intent) to manipulate to achieve desired morphological and neuromuscular adaptations.
Mechanisms mediating androgen receptor (AR) reactivation in prostate cancer that progresses after castration (castration-resistant prostate cancer; CRPC) and subsequent treatment with abiraterone ...(CYP17A1 inhibitor that further suppresses androgen synthesis) remain unclear.
Prostate cancer xenografts were examined to identify mechanism of progression after castration and abiraterone.
AR reactivation in abiraterone-resistant VCaP xenografts was not associated with restoration of intratumoral androgens or alterations in AR coregulators. In contrast, mRNA encoding full-length AR (AR-FL) and a constitutively active splice variant (AR-V7) were increased compared with xenografts before castration, with an increase in AR-V7 relative to AR-FL. This shift toward AR-V7 was due to a feedback mechanism whereby the androgen-liganded AR stimulates expression of proteins that suppress generation of AR-V7 relative to AR-FL transcripts. However, despite the increases in AR-V7 mRNA, it remained a minor transcript (<1%) relative to AR-FL in resistant VCaP xenografts and CRPC clinical samples. AR-V7 protein expression was similarly low relative to AR-FL in castration-resistant VCaP xenografts and androgen-deprived VCaP cells, but the weak basal AR activity in these latter cells was further repressed by AR-V7 siRNA.
AR-V7 at these low levels is not adequate to restore AR activity, but its rapid induction after androgen deprivation allows tumors to retain basal AR activity that may be needed for survival until more potent mechanisms emerge to activate AR. Agents targeting AR splice variants may be most effective when used very early in conjunction with therapies targeting the AR ligand-binding domain.
•OpenMC is an open source Monte Carlo particle transport code.•Solid geometry and continuous-energy physics allow high-fidelity simulations.•Development has focused on high performance and modern I/O ...techniques.•OpenMC is capable of scaling up to hundreds of thousands of processors.•Other features include plotting, CMFD acceleration, and variance reduction.
This paper gives an overview of OpenMC, an open source Monte Carlo particle transport code recently developed at the Massachusetts Institute of Technology. OpenMC uses continuous-energy cross sections and a constructive solid geometry representation, enabling high-fidelity modeling of nuclear reactors and other systems. Modern, portable input/output file formats are used in OpenMC: XML for input, and HDF5 for output. High performance parallel algorithms in OpenMC have demonstrated near-linear scaling to over 100,000 processors on modern supercomputers. Other topics discussed in this paper include plotting, CMFD acceleration, variance reduction, eigenvalue calculations, and software development processes.
Abstract Over 118 million blood donations are collected globally each year. Recipients of blood products include those who experience major trauma or surgery, have acute blood loss and anemia, or ...impaired bone marrow function. Solid organ transplant recipients often require transfusion of blood products which places them at risk of transfusion‐associated adverse events including transfusion‐transmitted infection. National hemovigilance networks have documented low rates of transfusion‐transmitted infection in the general population. Incidence transfusion‐transmitted infection continues to occur in solid organ transplant patients and arises mainly from existing gaps in blood donor biovigilance processes. Emerging infectious diseases have highlighted existing gaps in the donor‐recipient pathway to administering safe blood products. This article reviews the current process and regulatory oversight of blood donor biovigilance, including donor screening and microbiological testing, highlights cases of transfusion‐transmitted infection documented in the literature, and addresses ways in which biovigilance may be improved, with a focus on the impact of solid organ transplantation.
The CYP17A1 inhibitor abiraterone markedly reduces androgen precursors and is thereby effective in castration-resistant prostate cancer (CRPC). However, abiraterone increases progesterone, which can ...activate certain mutant androgen receptors (AR) identified previously in flutamide-resistant tumors. Therefore, we sought to determine if CYP17A1 inhibitor treatment selects for progesterone-activated mutant ARs.
AR was examined by targeted sequencing in metastatic tumor biopsies from 18 patients with CRPC who were progressing on a CYP17A1 inhibitor (17 on abiraterone, 1 on ketoconazole), alone or in combination with dutasteride, and by whole-exome sequencing in residual tumor in one patient treated with neoadjuvant leuprolide plus abiraterone.
The progesterone-activated T878A-mutant AR was present at high allele frequency in 3 of the 18 CRPC cases. It was also present in one focus of resistant tumor in the neoadjuvant-treated patient, but not in a second clonally related resistant focus that instead had lost one copy of PTEN and both copies of CHD1. The T878A mutation appeared to be less common in the subset of patients with CRPC treated with abiraterone plus dutasteride, and transfection studies showed that dutasteride was a more potent direct antagonist of the T878A versus the wild-type AR.
These findings indicate that selection for tumor cells expressing progesterone-activated mutant ARs is a mechanism of resistance to CYP17A1 inhibition.
Mucosal-associated Invariant T (MAIT) cells are recognized for their antibacterial functions. The protective capacity of MAIT cells has been demonstrated in murine models of local infection, ...including in the lungs. Here we show that during systemic infection of mice with Francisella tularensis live vaccine strain results in evident MAIT cell expansion in the liver, lungs, kidney and spleen and peripheral blood. The responding MAIT cells manifest a polarised Th1-like MAIT-1 phenotype, including transcription factor and cytokine profile, and confer a critical role in controlling bacterial load. Post resolution of the primary infection, the expanded MAIT cells form stable memory-like MAIT-1 cell populations, suggesting a basis for vaccination. Indeed, a systemic vaccination with synthetic antigen 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil in combination with CpG adjuvant similarly boosts MAIT cells, and results in enhanced protection against both systemic and local infections with different bacteria. Our study highlights the potential utility of targeting MAIT cells to combat a range of bacterial pathogens.
American Indian/Alaska Native (AI/AN) populations have been disproportionately affected by chronic respiratory diseases for reasons incompletely understood. Past research into disease disparity using ...population-based surveys mostly focused on state-specific factors. The present study investigates the independent contributions of AI/AN racial status and other socioeconomic/demographic variables to chronic respiratory disease disparity in an 11-state region with historically high AI/AN representation. Using data from the Behavioral Risk Factor Surveillance System (BRFSS) spanning years 2011-2018, this work provides an updated assessment of disease disparity and potential determinants of respiratory health in AI/AN populations.
This cross-sectional study used data from the BRFSS survey, 2011-2018. The study population included AI/AN and non-Hispanic white individuals resident in 11 states with increased proportion of AI/AN individuals. The yearly number of respondents averaged 75,029 (62878-87,350) which included approximately 5% AI/AN respondents (4.5-6.3%). We compared the yearly adjusted prevalence for chronic respiratory disease, where disease status was defined by self-reported history of having asthma and/or chronic obstructive pulmonary disease (COPD). Multivariable logistic regression was performed to determine if being AI/AN was independently associated with chronic respiratory disease. Covariates included demographic (age, sex), socioeconomic (marital status, education level, annual household income), and behavioral (smoking, weight morbidity) variables.
The AI/AN population consistently displayed higher adjusted prevalence of chronic respiratory disease compared to the non-Hispanic white population. However, the AI/AN race/ethnicity characteristic was not independently associated with chronic respiratory disease (OR, 0.93; 95% CI, 0.79-1.10 in 2017). In contrast, indicators of low socioeconomic status such as annual household income of <$10,000 (OR, 2.02; 95% CI, 1.64-2.49 in 2017) and having less than high school education (OR, 1.37; 95% CI, 1.16-1.63 in 2017) were positively associated with disease. These trends persisted for all years analyzed.
This study highlighted that AI/AN socioeconomic burdens are key determinants of chronic respiratory disease, in addition to well-established risk factors such as smoking and weight morbidity. Disease disparity experienced by the AI/AN population is therefore likely a symptom of disproportionate socioeconomic challenges they face. Further promotion of public health and social service efforts may be able to improve AI/AN health and decrease this disease disparity.
Oranchuk, DJ, Storey, AG, Nelson, AR, Neville, JG, and Cronin, JB. Variability of multiangle isometric force-time characteristics in trained men. J Strength Cond Res 36(1): 284-288, 2022-Measurements ...of isometric force, rate of force development (RFD), and impulse are widely reported. However, little is known about the variability and reliability of these measurements at multiple angles, over repeated testing occasions in a homogenous, resistance-trained population. Thus, understanding the intersession variability of multiangle isometric force-time characteristics provides the purpose of this article. Three sessions of isometric knee extensions at 40°, 70°, and 100° of flexion were performed by 26 subjects across 51 limbs. All assessments were repeated on 3 occasions separated by 5-8 days. Variability was qualified by doubling the typical error of measurement (TEM), with thresholds of 0.2-0.6 (small), 0.6-1.2 (moderate), 1.2-2.0 (large), 2.0-4.0 (very large), and >4.0 (extremely large). In addition, variability was deemed large when the intraclass correlation coefficient (ICC) was <0.67 and coefficient of variation (CV) >10%; moderate when ICC >0.67 or CV <10% (but not both); and small when both ICC >0.67 and CV <10%. Small to moderate between-session variability (ICC = 0.68-0.95, CV = 5.2-18.7%, TEM = 0.24-0.49) was associated with isometric peak force, regardless of angle. Moderate to large variability was seen in early-stage (0-50 ms) RFD and impulse (ICC = 0.60-0.80, CV = 22.4-63.1%, TEM = 0.62-0.74). Impulse and RFD at 0-100 ms, 0-200 ms, and 100-200 ms were moderately variable (ICC = 0.71-0.89, CV = 11.8-42.1%, TEM = 0.38-0.60) at all joint angles. Isometric peak force and late-stage isometric RFD and impulse measurements were found to have low intersession variability regardless of joint angle. However, practitioners need to exercise caution when making inferences about early-stage RFD and impulse measures due to moderate-large variability.
Purpose
Eccentric quasi-isometric (EQI) contractions have been proposed as a novel training method for safely exposing the musculotendinous system to a large mechanical load/impulse, with few ...repetitions. However, understanding of this contraction type is rudimentary. We aimed to compare the acute effects of a single session of isotonic EQIs with isokinetic eccentric (ECC) contractions.
Methods
Fifteen well-trained men performed a session of impulse-equated EQI and ECC knee extensions, with each limb randomly allocated to one contraction type. Immediately PRE, POST, 24/48/72 h, and 7 days post-exercise, regional soreness, quadriceps swelling, architecture, and echo intensity were evaluated. Peak concentric and isometric torque, rate of torque development (RTD), and angle-specific impulse were evaluated at each time point.
Results
There were substantial differences in the number of contractions (ECC: 100.8 ± 54; EQI: 3.85 ± 1.1) and peak torque (mean: ECC: 215 ± 54 Nm; EQI: 179 ± 28.5 Nm). Both conditions elicited similar responses in 21/53 evaluated variables. EQIs resulted in greater vastus intermedius swelling (7.1–8.8%, ES = 0.20–0.29), whereas ECC resulted in greater soreness at the distal and middle vastus lateralis and distal rectus femoris (16.5–30.4%, ES = 0.32–0.54) and larger echogenicity increases at the distal rectus femoris and lateral vastus intermedius (11.9–15.1%, ES = 0.26––0.54). Furthermore, ECC led to larger reductions in concentric (8.3–19.7%, ES = 0.45–0.62) and isometric (6.3–32.3%, ES = 0.18–0.70) torque and RTD at medium-long muscle lengths.
Conclusion
A single session of EQIs resulted in less soreness and smaller reductions in peak torque and RTD versus impulse-equated ECC contractions, yet morphological shifts were largely similar. Long-term morphological, architectural, and neuromuscular adaptations to EQI training requires investigation.
Oranchuk, DJ, Storey, AG, Nelson, AR, and Cronin, JB. The scientific basis for eccentric quasi-isometric resistance training: A narrative review. J Strength Cond Res 33(10): 2846-2859, 2019-Eccentric ...quasi-isometric (EQI) resistance training involves holding a submaximal, yielding isometric contraction until fatigue causes muscle lengthening and then maximally resisting through a range of motion. Practitioners contend that EQI contractions are a powerful tool for the development of several physical qualities important to health and sports performance. In addition, several sports involve regular quasi-isometric contractions for optimal performance. Therefore, the primary objective of this review was to synthesize and critically analyze relevant biological, physiological, and biomechanical research and develop a rationale for the value of EQI training. In addition, this review offers potential practical applications and highlights future areas of research. Although there is a paucity of research investigating EQIs, the literature on responses to traditional contraction types is vast. Based on the relevant literature, EQIs may provide a practical means of increasing total volume, metabolite build-up, and hormonal signaling factors while safely enduring large quantities of mechanical tension with low levels of peak torque. Conversely, EQI contractions likely hold little neuromuscular specificity to high velocity or power movements. Therefore, EQI training seems to be effective for improving musculotendinous morphological and performance variables with low injury risk. Although speculative due to the limited specific literature, available evidence suggests a case for future experimentation.
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