Publications by authors named "Michael Stone"

537 Publications

Low-sound-level auditory processing in noise-exposed adults.

Hear Res 2021 Sep 9;409:108309. Epub 2021 Jul 9.

Manchester Centre for Audiology and Deafness, School of Health Sciences, University of Manchester, M13 9PL, UK.; Manchester University Hospitals NHS Foundation Trust, Manchester, M13 9WL, UK. Electronic address:

Early signs of noise-induced hearing damage are difficult to identify, as they are often confounded by factors such as age, audiometric thresholds, or even music experience. Much previous research has focused on deficits observed at high intensity levels. In contrast, the present study was designed to test the hypothesis that noise exposure causes a degradation in low-sound-level auditory processing in humans, as a consequence of dysfunction of the inner hair cell pathway. Frequency difference limens (FDLs) and amplitude modulation depth discrimination (MDD) were measured for five center frequencies (0.75, 1, 3, 4 and 6 kHz) at 15 and 25 dB sensation level (SL), as a function of noise exposure, age, audiometric hearing loss, and music experience. Forty participants, aged 33-75 years, with normal hearing up to 1 kHz and mild-to-moderate hearing loss above 2 kHz, were tested. Participants had varying degrees of self-reported noise exposure, and varied in music experience. FDL worsened as a function of age. Participants with music experience outperformed the non-experienced in both the FDL and MDD tasks. MDD thresholds were significantly better for high-noise-exposed, than for low-noise-exposed, participants at 25 dB SL, particularly at 6 kHz. No effects of age or hearing loss were observed in the MDD. It is possible that the association between MDD thresholds and noise exposure was not causal, but instead was mediated by other factors that were not measured in the study. The association is consistent, qualitatively, with a hypothesized loss of compression due to outer hair cell dysfunction.
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http://dx.doi.org/10.1016/j.heares.2021.108309DOI Listing
September 2021

Performance Comparisons of Youth Weightlifters as a Function of Age Group and Sex.

J Funct Morphol Kinesiol 2021 Jun 23;6(3). Epub 2021 Jun 23.

Center of Excellence for Sport Science and Coach Education, Department of Sport, Exercise, Recreation, and Kinesiology, East Tennessee State University, Johnson City, TN 37614, USA.

This study was designed to provide an overview of weightlifting performance as a function of age group and sex and evaluate the potential of countermovement jump height (CMJH) as a tool to gauge performance potential. Data from 130 youth athletes (female, = 65 & male, = 65) were used to examine progression of performance (Total and Sinclair total) and the relationship between CMJH and Sinclair total while considering interactions between CMJH and age and/or sex. ANOVAs with post hoc analyses revealed that both totals had a statistical first-order polynomial interaction effect between age group and sex and the difference between age groups of 12-13 and 14-15 years old was statistically greater for male than female. A linear model, developed to examine the relationship, revealed that CMJH and CMJH x sex x age rejected the null hypothesis. Our primary findings are that male youth weightlifters have a higher rate of performance progression, possibly owing to puberty, and CMJH may be a better gauging tool for older male youth weightlifters.
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http://dx.doi.org/10.3390/jfmk6030057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293357PMC
June 2021

Troubleshooting a Nonresponder: Guidance for the Strength and Conditioning Coach.

Sports (Basel) 2021 Jun 5;9(6). Epub 2021 Jun 5.

Center of Excellence for Sport Science and Coach Education, Department of Sport, Exercise, Recreation, & Kinesiology, East Tennessee State University, Johnson City, TN 37614, USA.

Ideally an athlete would continue to improve performance indefinitely over time, however improvement slows as the athlete approaches their genetic limits. Measuring performance is complex-performance may be temporarily depressed following aggressive training for multiple reasons, physiological and psychosocial. This reality may be vexing to the strength and conditioning coach, who, as a service provider, must answer to sport coaches about an athlete's progress. Recently an evaluation mechanism for strength and conditioning coaches was proposed, in part to help coaches establish their effectiveness within the organization. Without formal guidance and realistic expectations, if an athlete is not bigger, leaner, stronger, etc. as a result of training within a specified timeframe, blame is often placed upon the strength and conditioning coach. The purpose of this article is to explore possible causes of what may be perceived as athlete non-responses to training and to provide guidance for the coach on how to handle those issues within their domain. A process of investigation is recommended, along with resources to assist coaches as they consider a broad range of issues, including enhancing existing testing methods, improving athlete behaviors, and adjusting processes designed to bring about performance improvement.
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http://dx.doi.org/10.3390/sports9060083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227041PMC
June 2021

Periodization and Block Periodization in Sports: Emphasis on Strength-Power Training-A Provocative and Challenging Narrative.

J Strength Cond Res 2021 Aug;35(8):2351-2371

Department of Kinesiology and Health Science, Louisiana State University Shreveport, Shreveport, Louisiana.

Abstract: Stone, MH, Hornsby, WG, Haff, GG, Fry, AC, Suarez, DG, Liu, J, Gonzalez-Rave, JM, and Pierce, KC. Periodization and block periodization in sports: emphasis on strength-power training-a provocative and challenging narrative. J Strength Cond Res 35(8): 2351-2371, 2021-Periodization can be defined as a logical sequential, phasic method of manipulating fitness and recovery phases to increase the potential for achieving specific performance goals while minimizing the potential for nonfunctional over-reaching, overtraining, and injury. Periodization deals with the micromanagement of timelines and fitness phases and is cyclic in nature. On the other hand, programming deals with the micromanagement of the training process and deals with exercise selection, volume, intensity, etc. Evidence indicates that a periodized training process coupled with appropriate programming can produce superior athletic enhancement compared with nonperiodized process. There are 2 models of periodization, traditional and block. Traditional can take different forms (i.e., reverse). Block periodization has 2 subtypes, single goal or factor (individual sports) and multiple goals or factors (team sports). Both models have strengths and weaknesses but can be "tailored" through creative programming to produce excellent results for specific sports.
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http://dx.doi.org/10.1519/JSC.0000000000004050DOI Listing
August 2021

Training for Muscular Strength: Methods for Monitoring and Adjusting Training Intensity.

Sports Med 2021 Oct 8;51(10):2051-2066. Epub 2021 Jun 8.

Center of Excellence for Sport Science and Coach Education, Department of Exercise and Sport Sciences, East Tennessee State University, Johnson City, TN, 37614, USA.

Linear loading, the two-for-two rule, percent of one repetition maximum (1RM), RM zones, rate of perceived exertion (RPE), repetitions in reserve, set-repetition best, autoregulatory progressive resistance exercise (APRE), and velocity-based training (VBT) are all methods of adjusting resistance training intensity. Each method has advantages and disadvantages that strength and conditioning practitioners should be aware of when measuring and monitoring strength characteristics. The linear loading and 2-for-2 methods may be beneficial for novice athletes; however, they may be limited in their capacity to provide athletes with variation and detrimental if used exclusively for long periods of time. The percent of 1RM and RM zone methods may provide athletes with more variation and greater potential for strength-power adaptations; however, they fail to account for daily changes in athlete's performance capabilities. An athlete's daily readiness can be addressed to various extents by both subjective (e.g., RPE, repetitions in reserve, set-repetition best, and APRE) and objective (e.g., VBT) load adjustment methods. Future resistance training monitoring may aim to include a combination of measures that quantify outcome (e.g., velocity, load, time, etc.) with process (e.g., variability, coordination, efficiency, etc.) relevant to the stage of learning or the task being performed. Load adjustment and monitoring methods should be used to supplement and guide the practitioner, quantify what the practitioner 'sees', and provide longitudinal data to assist in reviewing athlete development and providing baselines for the rate of expected development in resistance training when an athlete returns to sport from injury or large training load reductions.
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http://dx.doi.org/10.1007/s40279-021-01488-9DOI Listing
October 2021

Short-Term Periodized Programming May Improve Strength, Power, Jump Kinetics, and Sprint Efficiency in Soccer.

J Funct Morphol Kinesiol 2021 May 24;6(2). Epub 2021 May 24.

Department of Sport, Exercise, Recreation, and Kinesiology, East Tennessee State University, Johnson City, TN 37604, USA.

The purpose of this study was to examine if short-term periodized programming may improve strength, power, jump kinetics, and sprint efficiency in soccer. Seventeen players (19.6 ± 1.6 yrs; 73.8 ± 8.2 kg; 1.77 ± 0.6 m) were divided into two groups based on mean isometric midthigh pull peak force (IPF) (stronger and weaker) and squat jump (SJ) peak power (PP) (higher power and lower power). Eight weaker players were included in the lower power group, while six stronger players were included in the higher power group. Block periodization was adopted to design strength training consisting of 3-week strength endurance and 4-week maximum strength blocks. Performance data included SJ with polyvinyl chloride pipe (SJ0), 20 kgs bar (SJ20), and 40 kgs (SJ40) bar and 20 m sprint across three time points (baseline: T; post-block 1: T; post-block 2: T). Stronger group showed significant increases from T to T in SJ20 peak power (PP), net impulse, and allometrically-scaled PP ( = 0.005 to 0.01, ES = 0.32 to 0.49). Weaker group demonstrated moderate to large increases from T to T in SJ20, allometrically-scaled peak force (PF), PP, and allometrically-scaled PP ( = <0.001 to 0.04, ES = 1.41 to 1.74). Lower power group showed significant increases from T to T in SJ20 allometrically-scaled PF, net impulse, PP, and allometrically-scaled PP ( = <0.001 to 0.026, ES = 1.06 to 2.01). Weaker and less powerful soccer players can benefit from strength-focused training to improve loaded SJ kinetics associating with force production.
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http://dx.doi.org/10.3390/jfmk6020045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163170PMC
May 2021

Short-Term RCT of Increased Dietary Potassium from Potato or Potassium Gluconate: Effect on Blood Pressure, Microcirculation, and Potassium and Sodium Retention in Pre-Hypertensive-to-Hypertensive Adults.

Nutrients 2021 May 11;13(5). Epub 2021 May 11.

Nutrition Science, Purdue University, West Lafayette, IN 47907, USA.

Increased potassium intake has been linked to improvements in cardiovascular and other health outcomes. We assessed increasing potassium intake through food or supplements as part of a controlled diet on blood pressure (BP), microcirculation (endothelial function), and potassium and sodium retention in thirty pre-hypertensive-to-hypertensive men and women. Participants were randomly assigned to a sequence of four 17 day dietary potassium treatments: a basal diet (control) of 60 mmol/d and three phases of 85 mmol/d added as potatoes, French fries, or a potassium gluconate supplement. Blood pressure was measured by manual auscultation, cutaneous microvascular and endothelial function by thermal hyperemia, utilizing laser Doppler flowmetry, and mineral retention by metabolic balance. There were no significant differences among treatments for end-of-treatment BP, change in BP over time, or endothelial function using a mixed-model ANOVA. However, there was a greater change in systolic blood pressure (SBP) over time by feeding baked/boiled potatoes compared with control (-6.0 mmHg vs. -2.6 mmHg; = 0.011) using contrast analysis. Potassium retention was highest with supplements. Individuals with a higher cardiometabolic risk may benefit by increasing potassium intake. This trial was registered at ClinicalTrials.gov as NCT02697708.
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http://dx.doi.org/10.3390/nu13051610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151047PMC
May 2021

Cryo-EM structures tell a tale of two telomerases.

Nat Struct Mol Biol 2021 06;28(6):457-459

Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, CA, USA.

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http://dx.doi.org/10.1038/s41594-021-00611-8DOI Listing
June 2021

Soman-induced toxicity, cholinesterase inhibition and neuropathology in adult male Göttingen minipigs.

Toxicol Rep 2021 19;8:896-907. Epub 2021 Apr 19.

U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States.

Animal models are essential for evaluating the toxicity of chemical warfare nerve agents (CWNAs) to extrapolate to human risk and are necessary to evaluate the efficacy of medical countermeasures. The Göttingen minipig is increasingly used for toxicological studies because it has anatomical and physiological characteristics that are similar to those of humans. Our objective was to determine whether the minipig would be a useful large animal model to evaluate the toxic effects of soman (GD). We determined the intramuscular (IM) median lethal dose (LD) of GD in adult male Göttingen minipigs using an up-and-down dosing method. In addition to lethality estimates, we characterized the observable signs of toxicity, blood and tissue cholinesterase (ChE) activity and brain pathology following GD exposure. The 24 h LD of GD was estimated to be 4.7 μg/kg, with 95 % confidence limits of 3.6 and 6.3 μg/kg. As anticipated, GD inhibited ChE activity in blood and several tissues. Neurohistopathological analysis showed neurodegeneration and neuroinflammation in survivors exposed to 4.7 μg/kg of GD, including in the primary visual cortex and various thalamic nuclei. These findings suggest that the minipig will be a useful large animal model for assessing drugs to mitigate neuropathological effects of exposure to CWNAs.
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http://dx.doi.org/10.1016/j.toxrep.2021.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095108PMC
April 2021

Lean Body Mass and Muscle Cross-Sectional Area Adaptations Among College Age Males with Different Strength Levels across 11 Weeks of Block Periodized Programmed Resistance Training.

Int J Environ Res Public Health 2021 04 29;18(9). Epub 2021 Apr 29.

Center of Excellence for Sport Science and Coach Education, Department of Sport, Exercise, Recreation and Kinesiology, East Tennessee State University, Johnson City, TN 37614, USA.

The block periodization training paradigm has been shown to produce enhanced gains in strength and power. The purpose of this study is to assess resistance training induced alterations in lean body mass and cross-sectional area using a block periodization training model among individuals (n = 15) of three differing strength levels (high, moderate and low) based on one repetition maximum back squat relative to body weight. A 3 × 5 mixed-design ANOVA was used to examine within-and between-subject changes in cross-sectional area (CSA), lean body mass (LBM), lean body mass adjusted (LBM) and total body water (TBW) over an 11-week resistance training program. LBM is total body water subtracted from lean body mass. The ANOVA revealed no statistically significant between-group differences in any independent variable ( > 0.05). Within-group effects showed statistically significant increases in cross-sectional area ( < 0.001), lean body mass ( < 0.001), lean body mass adjusted ( ˂ 0.001) and total body water ( < 0.001) from baseline to post intervention: CSA: 32.7 cm ± 8.6; 36.3 cm ± 7.2, LBM: 68.0 kg ± 9.5; 70.6 kg ± 9.4, LBM: 20.4 kg ± 3.1; 21.0 kg ± 3.3 and TBW: 49.8 kg ± 6.9; 51.7 kg ± 6.9. In conclusion, the results of this study suggest subjects experienced an increase in both lean body mass and total body water, regardless of strength level, over the course of the 11-week block periodized program. Gains in lean body mass and cross-sectional area may be due to edema at the early onset of training.
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http://dx.doi.org/10.3390/ijerph18094735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124523PMC
April 2021

A new SARS-CoV-2 lineage that shares mutations with known Variants of Concern is rejected by automated sequence repository quality control.

bioRxiv 2021 Apr 6. Epub 2021 Apr 6.

We report a SARS-CoV-2 lineage that shares N501Y, P681H, and other mutations with known variants of concern, such as B.1.1.7. This lineage, which we refer to as B.1.x (COG-UK sometimes references similar samples as B.1.324.1), is present in at least 20 states across the USA and in at least six countries. However, a large deletion causes the sequence to be automatically rejected from repositories, suggesting that the frequency of this new lineage is underestimated using public data. Recent dynamics based on 339 samples obtained in Santa Cruz County, CA, USA suggest that B.1.x may be increasing in frequency at a rate similar to that of B.1.1.7 in Southern California. At present the functional differences between this variant B.1.x and other circulating SARS-CoV-2 variants are unknown, and further studies on secondary attack rates, viral loads, immune evasion and/or disease severity are needed to determine if it poses a public health concern. Nonetheless, given what is known from well-studied circulating variants of concern, it seems unlikely that the lineage could pose larger concerns for human health than many already globally distributed lineages. Our work highlights a need for rapid turnaround time from sequence generation to submission and improved sequence quality control that removes submission bias. We identify promising paths toward this goal.
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http://dx.doi.org/10.1101/2021.04.05.438352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043452PMC
April 2021

Strength, Endocrine, and Body Composition Alterations across Four Blocks of Training in an Elite 400 m Sprinter.

J Funct Morphol Kinesiol 2021 Mar 9;6(1). Epub 2021 Mar 9.

Department of Sport, Exercise, Recreation, and Kinesiology, East Tennessee University, Johnson City, TN 36714, USA.

The ability to produce force rapidly has the potential to directly influence sprinting performance through changes in stride length and stride frequency. This ability is commonly referred to as the rate of force development (RFD). For this reason, many elite sprinters follow a combined program consisting of resistance training and sprint training. The purpose of this study was to investigate the strength, endocrine and body composition adaptations that occur during distinct phases of a block periodized training cycle in a 400 m Olympic level sprinter. The athlete is an elite level 400 m male sprinter (age 31 years, body mass: 74 kg, years of training: 15 and Personal Best (PB): 45.65 s). This athlete completed four distinct training phases of a block periodized training program (16 weeks) with five testing sessions consisting of testosterone:cortisol (T/C) profiles, body composition, vertical jump, and maximum strength testing. Large fluctuations in T/C were found following high volume training and the taper. Minor changes in body mass were observed with an abrupt decrease following the taper which coincided with a small increase in fat mass percentage. Jump height (5.7%), concentric impulse (9.4%), eccentric impulse (3.4%) and power ratio (18.7%) all increased substantially from T1 to T5. Relative strength increased 6.04% from T1 to T5. Lastly, our results demonstrate the effectiveness of a competitive taper in increasing physiological markers for performance as well as dynamic performance variables. Block periodization training was effective in raising the physical capabilities of an Olympic level 400 m runner which have been shown to directly transfer to sprinting performance.
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http://dx.doi.org/10.3390/jfmk6010025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006296PMC
March 2021

Exercise intensity influences plasma and sweat amino acid concentrations: a crossover trial.

J Sports Med Phys Fitness 2021 03 9. Epub 2021 Mar 9.

Department of Exercise and Nutritional Science, San Diego State University, San Diego, CA, USA -

Background: The purpose of this study was to explore the relationship between concentrations of amino acid (AA) and related metabolites in plasma and sweat obtained before and after exercise performed at different intensities and therefore different rates of sweat loss.

Methods: Ten subjects completed a maximally ramped exercise test and three 30-min submaximal (45/60/75% VO2max) exercise bouts. Blood samples were collected before/after the exercise bouts and sweat was collected from the forearm throughout. Samples were analyzed for concentrations of AA and related molecules.

Results: Sweat AA excretion rate was higher during the 60% bout compared to the 45% bout but was similar in comparison to the 75% indicating a plateau in rates of sweat AA losses as sweat rate increased. Plasma concentrations of AAs, urea, ammonia, and other non-proteinogenic AAs were not significantly different between exercise bouts performed at 45 and 60%. Exercise at 75% tended to reduce concentrations of sweat amino acids with significantly depressed concentrations of glycine, lysine, serine, threonine, histidine, arginine, tryptophan, aspartate and ornithine.

Conclusions: Overall, this research suggests that increasing exercise intensity increases AA metabolism as demonstrated by reduced plasma AA concentrations and increased excretion through sweat glands, which is mediated by a mechanism yet to be identified.
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http://dx.doi.org/10.23736/S0022-4707.21.12134-6DOI Listing
March 2021

Novel Genetically Modified Mouse Model to Assess Soman-Induced Toxicity and Medical Countermeasure Efficacy: Human Acetylcholinesterase Knock-in Serum Carboxylesterase Knockout Mice.

Int J Mol Sci 2021 Feb 14;22(4). Epub 2021 Feb 14.

Medical Toxicology Research Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.

The identification of improved medical countermeasures against exposure to chemical warfare nerve agents (CWNAs), a class of organophosphorus compounds, is dependent on the choice of animal model used in preclinical studies. CWNAs bind to acetylcholinesterase and prevent the catalysis of acetylcholine, causing a plethora of peripheral and central physiologic manifestations, including seizure. Rodents are widely used to elucidate the effects of CWNA-induced seizure, albeit with a caveat: they express carboxylesterase activity in plasma. Carboxylesterase, an enzyme involved in the detoxification of some organophosphorus compounds, plays a scavenging role and decreases CWNA availability, thus exerting a protective effect. Furthermore, species-specific amino acid differences in acetylcholinesterase confound studies that use oximes or other compounds to restore its function after inhibition by CWNA. The creation of a human acetylcholinesterase knock-in/serum carboxylesterase knockout (C57BL/6-Ces1cAChE/J; a.k.a KIKO) mouse may facilitate better modeling of CWNA toxicity in a small rodent species. The current studies characterize the effects of exposure to soman, a highly toxic CWNA, and evaluate the efficacy of anti-seizure drugs in this newly developed KIKO mouse model. Data demonstrate that a combination of midazolam and ketamine reduces seizure duration and severity, eliminates the development of spontaneous recurrent seizures, and protects certain brain regions from neuronal damage in a genetically modified model with human relevance to organophosphorus compound toxicity. This new animal model and the results of this study and future studies using it will enhance medical countermeasures development for both defense and homeland security purposes.
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http://dx.doi.org/10.3390/ijms22041893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918218PMC
February 2021

Short-Term Outcomes of Lower Trapezius Tendon Transfer With Achilles Allograft for Irreparable Posterosuperior Rotator Cuff Tears.

Arthrosc Sports Med Rehabil 2021 Feb 24;3(1):e23-e29. Epub 2020 Dec 24.

Rothman Orthopaedic Institute at Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A.

Purpose: To evaluate functional outcomes, return to work, and reoperations associated with lower trapezius tendon transfer (LTT) for irreparable rotator cuff tears.

Methods: This is a retrospective study performed by a single surgeon with minimum 1-year follow-up. LTT was performed using an open (n = 9; 60%) or arthroscopically assisted (n = 6, 40%) technique. Outcomes included failure rate, range of motion, satisfaction, return to work, and pre- and postoperative functional scores, as well as American Shoulder and Elbow Surgeons score, Single Assessment Numeric Evaluation, and the Simple Shoulder Test.

Results: Fifteen patients were included. LTT was performed using an open or arthroscopically assisted technique. Mean age was 52 (range 31-62 years), 13 (92.9%) were manual laborers, and 9 (60%) had a worker's compensation claim. Three patients (20%) underwent conversion to reverse shoulder arthroplasty. Of the remaining 12 patients, there were significant improvements in American Shoulder and Elbow Surgeons, Single Assessment Numeric Evaluation, and Simple Shoulder Test at 24.1 ± 9.6 (range 12-38.5) months. Active forward elevation, abduction, and external rotation were all significantly improved. Postoperative satisfaction ratings indicated 67% of the revision-free cohort was "very satisfied" and 33% was "somewhat satisfied" with their outcome. Seven (50%) returned to full duty, 4 (28.6%) returned to modified duty, and 3 (21.4%) were unable to return to work. Two patients (open techniques) underwent a superficial wound debridement for seroma and wound breakdown.

Conclusions: LTT results in successful clinical outcomes with a high rate of return to work in a challenging patient population. However, only 67% of patients rated themselves as "very satisfied," and 20% of patients were revised to reverse shoulder arthroplasty before 1 year. Limited preoperative active forward elevation (<90°) appears to predict poor functional results and risk for reoperation.

Level Of Evidence: Level IV, therapeutic case series.
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http://dx.doi.org/10.1016/j.asmr.2020.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879194PMC
February 2021

DNA Sequence Modulates the Efficiency of NEIL1-Catalyzed Excision of the Aflatoxin B-Induced Formamidopyrimidine Guanine Adduct.

Chem Res Toxicol 2021 03 17;34(3):901-911. Epub 2021 Feb 17.

Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, United States.

Dietary exposure to aflatoxins is a significant risk factor in the development of hepatocellular carcinomas. Following bioactivation by microsomal P450s, the reaction of aflatoxin B (AFB) with guanine (Gua) in DNA leads to the formation of stable, imidazole ring-opened 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxyaflatoxin B (AFB-FapyGua) adducts. In contrast to most base modifications that result in destabilization of the DNA duplex, the AFB-FapyGua adduct increases the thermal stability of DNA via 5'-interface intercalation and base-stacking interactions. Although it was anticipated that this stabilization might make these lesions difficult to repair relative to helix distorting modifications, prior studies have shown that both the nucleotide and base excision repair pathways participate in the removal of the AFB-FapyGua adduct. Specifically for base excision repair, we previously showed that the DNA glycosylase NEIL1 excises AFB-FapyGua and catalyzes strand scission in both synthetic oligodeoxynucleotides and liver DNA of exposed mice. Since it is anticipated that error-prone replication bypass of unrepaired AFB-FapyGua adducts contributes to cellular transformation and carcinogenesis, the structural and thermodynamic parameters that modulate the efficiencies of these repair pathways are of considerable interest. We hypothesized that the DNA sequence context in which the AFB-FapyGua adduct is formed might modulate duplex stability and consequently alter the efficiencies of NEIL1-initiated repair. To address this hypothesis, site-specific AFB-FapyGua adducts were synthesized in three sequence contexts, with the 5' neighbor nucleotide being varied. DNA structural stability analyses were conducted using UV absorbance- and NMR-based melting experiments. These data revealed differentials in thermal stabilities associated with the 5'-neighbor base pair. Single turnover kinetic analyses using the NEIL1 glycosylase demonstrated corresponding sequence-dependent differences in the repair of this adduct, such that there was an inverse correlation between the stabilization of the duplex and the efficiency of NEIL1-mediated catalysis.
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http://dx.doi.org/10.1021/acs.chemrestox.0c00517DOI Listing
March 2021

Principles of Locking Plate Fixation of Proximal Humerus Fractures.

J Am Acad Orthop Surg 2021 Jun;29(11):e523-e535

From the Department of Orthopaedic Surgery, University of Southern California, Los Angeles, CA (Omid), Midwest Orthopaedics at Rush, Chicago, IL (Trasolini), the Department of Orthopaedic Surgery, Cedars-Sinai Medical Center, Los Angeles, CA (Stone), and Rothman Orthopaedic Institute, Philadelphia, PA (Namdari).

Proximal humerus fractures are common, particularly in elderly patients and those with osteopenia or osteoporosis. Although nonsurgical management results in satisfactory outcomes for most patients, surgical treatment is indicated in select cases. Despite an increasing trend toward arthroplasty, open reduction and internal fixation of proximal humerus fractures can still provide excellent clinical outcomes. Proper technique for internal fixation of the proximal humerus requires an understanding of osseous and neurovascular anatomy. In particular, understanding reliable regions of biomechanically superior bone can help prevent failure of fixation. Biomechanical studies have shown that locked plating of proximal humerus fractures provides stable fixation. Cadaveric and finite element models underscore the importance of screw placement in the posteromedial metaphysis. When medial column support is challenging to obtain, or when bone quality is poor, augmentation with bone autograft, allograft, and/or synthetic composites can improve the biomechanics of internal fixation constructs. The purpose of this review is to outline the anatomic, biologic, and biomechanical principles of plate fixation for proximal humerus fractures to provide evidence-based recommendations for optimizing fixation and preventing fixation failure.
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http://dx.doi.org/10.5435/JAAOS-D-20-00558DOI Listing
June 2021

Emphasizing Task-Specific Hypertrophy to Enhance Sequential Strength and Power Performance.

J Funct Morphol Kinesiol 2020 Oct 27;5(4). Epub 2020 Oct 27.

Center of Excellence for Sport Science and Coach Education, Department of Sport, Exercise, Recreation, and Kinesiology, East Tennessee State University, Johnson City, TN 37604, USA.

While strength is indeed a skill, most discussions have primarily considered structural adaptations rather than ultrastructural augmentation to improve performance. Altering the structural component of the muscle is often the aim of hypertrophic training, yet not all hypertrophy is equal; such alterations are dependent upon how the muscle adapts to the training stimuli and overall training stress. When comparing bodybuilders to strength and power athletes such as powerlifters, weightlifters, and throwers, while muscle size may be similar, the ability to produce force and power is often inequivalent. Thus, performance differences go beyond structural changes and may be due to the muscle's ultrastructural constituents and training induced adaptations. Relative to potentiating strength and power performances, eliciting specific ultrastructural changes should be a variable of interest during hypertrophic training phases. By focusing on task-specific hypertrophy, it may be possible to achieve an optimal amount of hypertrophy while deemphasizing metabolic and aerobic components that are often associated with high-volume training. Therefore, the purpose of this article is to briefly address different types of hypertrophy and provide directions for practitioners who are aiming to achieve optimal rather than maximal hypertrophy, as it relates to altering ultrastructural muscular components, to potentiate strength and power performance.
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http://dx.doi.org/10.3390/jfmk5040076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739346PMC
October 2020

Addressing the Confusion within Periodization Research.

J Funct Morphol Kinesiol 2020 Aug 28;5(3). Epub 2020 Aug 28.

Center of Excellence for Sport Science and Coach Education, SERK, East Tennessee State University, Johnson City, TN 37614, USA.

In this editorial, we focus on recent problematic developments in sport science, and more specifically, problems related to periodization research. Primary areas discussed are (1) appreciation of history, (2) considerations for training studies, (3) the development of concepts, and (4) programming-driven training models.
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http://dx.doi.org/10.3390/jfmk5030068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739353PMC
August 2020

Alterations in Adiponectin, Leptin, Resistin, Testosterone, and Cortisol across Eleven Weeks of Training among Division One Collegiate Throwers: A Preliminary Study.

J Funct Morphol Kinesiol 2020 Jun 19;5(2). Epub 2020 Jun 19.

Center of Excellence for Sport Science and Coach Education, East Tennessee State University, Johnson City, TN 37614, USA.

Cytokine and hormone concentrations can be linked to the manipulation of training variables and to subsequent alterations in performance.

Subjects: Nine D-1 collegiate throwers and 4 control subjects participated in this preliminary and exploratory report.

Methods: Hormone (testosterone (T) and cortisol (C)) and adipokine (adiponectin, leptin, and resistin) measurements were taken at weeks 1, 7, and 11 for the throwers and weeks 1 and 11 for the control group. The throwers participated in an 11-week periodized resistance training and throws program during the fall preparatory period. Volume load was recorded throughout the study.

Results: Hormone values did not exhibit statistically significant changes across time; however, there were notable changes for C, the testosterone to cortisol ratio (T:C), and adiponectin.

Conclusions: T:C was increased as volume load decreased, and adiponectin increased in concert with decreases in C and increases in the T:C, possibly suggesting a lesser degree of obesity-related inflammation and a higher degree of "fitness" and preparedness.
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http://dx.doi.org/10.3390/jfmk5020044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739239PMC
June 2020

Associations of Body Composition, Maximum Strength, Power Characteristics with Sprinting, Jumping, and Intermittent Endurance Performance in Male Intercollegiate Soccer Players.

J Funct Morphol Kinesiol 2021 Jan 7;6(1). Epub 2021 Jan 7.

Center of Excellence for Sport Science and Coach Education, Department of Sport, Exercise, Recreation, and Kinesiology, East Tennessee State University, Johnson, TN 37604, USA.

The purpose of this study was to determine the relationships between body composition, strength, power characteristics, sprinting, jumping, and intermittent endurance performance in collegiate male players. Twenty-three players participated (19.7 ± 1.6 yrs; 71.8 ± 7.1 kg; 176.5 ± 5.1 cm). Measurements of interest in body composition included body fat percentage (BF%), lean body mass (LBM), and body mass (BM). Power characteristics were measured with an unloaded squat jump (SJ0) and loaded SJ at 20 kg (SJ20) and 40 kg (SJ40), and unloaded countermovement jump (CMJ0). Power assessments included peak power (PP) and PP allometrically scaled (PPa). Strength characteristics were assessed using isometric mid-thigh pull. Strength assessment included isometric peak force (IPF) and IPF allometrically scaled (IPFa). Performance measures included 10m and 20 m sprint time, CMJ0 jump-height, and Yo-Yo intermittent endurance test level 1 distance. Significant correlations ranging from moderate to very large were found for LBM and CMJ jump height (CM0 JH) ( = 0.01, = 0.50); BF% and sprint times at 10 m ( = 0.03, = 0.44) and 20 m ( = 0.02, = 0.50). PP and PPa from SJ0 and CMJ0 were significantly correlated to 10m sprint time ( < 0.05, = -0.45 to -0.53) and 20 m sprint time ( < 0.05, = -0.40 to -0.49). Our findings agree with previous literature in that body composition and power characteristics are directly related to soccer-related performance.
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http://dx.doi.org/10.3390/jfmk6010007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838787PMC
January 2021

Changes in Maximal Strength and Home Run Performance in NCAA Division I Baseball Players Across 3 Competitive Seasons: A Descriptive Study.

J Funct Morphol Kinesiol 2021 Jan 2;6(1). Epub 2021 Jan 2.

Department of Sport, Exercise, Recreation, and Kinesiology, East Tennessee University, Johnson City, TN 37604, USA.

The purpose of this longitudinal, descriptive study was to observe changes in maximal strength measured via isometric clean grip mid-thigh pull and home runs (total and home runs per game) across three years of training and three competitive seasons for four National Collegiate Athletic Association (NCAA) Division 1 baseball players. A one-way repeated measures analysis of variance (ANOVA) was performed, revealing significant univariate effects of time for peak force (PF) ( = 0.003) and peak force allometrically scaled (PFa) ( = 0.002). Increases in PF were noted from season 1 to season 2 ( = 0.031) and season 3 ( = 0.004), but season 2 was not significantly different than season 3 ( = 0.232). Additionally, increases in PFa were noted from season 1 to season 2 ( = 0.010) and season 3 ( < 0.001), but season 2 was not significantly different than season 3 ( = 0.052). Home runs per game rose from the 2009 (0.32) to 2010 season (1.35) and dropped during the 2011 season (1.07). A unique aspect of the study involves 2010 being the season in which ball-bat coefficient of restitution (BBCOR) bats were introduced to the NCAA competition.
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http://dx.doi.org/10.3390/jfmk6010004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838908PMC
January 2021

Prosthetic Bearing Surfaces in Anatomic and Reverse Total Shoulder Arthroplasty.

J Am Acad Orthop Surg 2021 May;29(10):414-422

From the Department of Orthopaedic Surgery, Cedars-Sinai Medical Center, Los Angeles, CA (Stone and Noorzad), and the Department of Orthopaedic Surgery, Rothman Orthopaedic Institute-Thomas Jefferson University, Philadelphia, PA (Namdari and Abboud).

Total shoulder arthroplasty (TSA) and reverse TSA have provided an effective treatment for glenohumeral osteoarthritis; however, longevity of the procedure may be limited by osteolysis and polyethylene wear. In TSA, glenoid component failure occurs through several mechanisms, the most common being aseptic loosening and polyethylene wear. Newer bearing surfaces such as highly cross-linked ultra-high-molecular-weight polyethylene, vitamin E processing, ceramic heads, and pyrolytic carbon surfaces have shown improved wear characteristics in biomechanical and some early clinical studies. The purpose of this review is to provide a historical perspective and current state of the art of bearing surface technology in anatomic and reverse TSA.
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http://dx.doi.org/10.5435/JAAOS-D-20-00166DOI Listing
May 2021

Structure of a Stable Interstrand DNA Cross-Link Involving a β--Glycosyl Linkage Between an -dA Amino Group and an Abasic Site.

Biochemistry 2021 01 31;60(1):41-52. Epub 2020 Dec 31.

Department of Chemistry, Vanderbilt University Center for Structural Biology, and the Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37235, United States.

Abasic (AP) sites are one of the most common forms of DNA damage. The deoxyribose ring of AP sites undergoes anomerization between α and β configurations, via an electrophilic aldehyde intermediate. In sequences where an adenine residue is located on the opposing strand and offset 1 nt to the 3' side of the AP site, the nucleophilic -dA amino group can react with the AP aldehyde residue to form an interstrand cross-link (ICL). Here, we present an experimentally determined structure of the dA-AP ICL by NMR spectroscopy. The ICL was constructed in the oligodeoxynucleotide 5'-d(TATGTCTAAGTTCATCTA)-3':5'-d(TAGATGAACXTAGACATA)-3' (X=AP site), with the dA-AP ICL forming between A and X. The NMR spectra indicated an ordered structure for the cross-linked DNA duplex and afforded detailed spectroscopic resonance assignments. Structural refinement, using molecular dynamics calculations restrained by NOE data (rMD), revealed the structure of the ICL. In the dA-AP ICL, the 2'-deoxyribosyl ring of the AP site was ring-closed and in the β configuration. Juxtapositioning the -dA amino group and the aldehydic C1 of the AP site within bonding distance while simultaneously maintaining two flanking unpaired A and T bases stacked within the DNA is accomplished by the unwinding of the DNA at the ICL. The structural data is discussed in the context of recent studies describing the replication-dependent unhooking of the dA-AP ICL by the base excision repair glycosylase NEIL3.
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http://dx.doi.org/10.1021/acs.biochem.0c00596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952047PMC
January 2021

Dynamic Strength Index: Relationships with Common Performance Variables and Contextualization of Training Recommendations.

J Hum Kinet 2020 Aug 31;74:59-70. Epub 2020 Aug 31.

Department of Sport, Exercise, Recreation, and Kinesiology, East Tennessee State University, Johnson City, TN, USA.

The purposes of this study were to examine the relationships between dynamic strength index (DSI) and other strength-power performance characteristics and to contextualize DSI scores using case study comparisons. 88 male and 67 female NCAA division I collegiate athletes performed countermovement jumps (CMJ) and isometric mid-thigh pulls (IMTP) during a pre-season testing session as part of a long-term athlete monitoring program. Spearman's correlations were used to assess the relationships between DSI and CMJ peak force, height, modified reactive strength index, peak power and IMTP peak force and rate of force development (RFD). Very large relationships existed between DSI and IMTP peak force (r = -0.848 and -0.746), while small-moderate relationships existed between DSI and CMJ peak force (r = 0.297 and 0.313), height (r = 0.108 and 0.167), modified reactive strength index (r = 0.174 and 0.274), and IMTP RFD (r = -0.341 and -0.338) for men and women, respectively. Finally, relationships between DSI and CMJ peak power were trivial-small for male (r = 0.008) and female athletes (r = 0.191). Case study analyses revealed that despite similar DSI scores, each athlete's percentile rankings for each variable and CMJ force-time characteristics were unique, which may suggest different training emphases are needed. Based on the explained variance, an athlete's IMTP performance may have a larger influence on their DSI score compared to the CMJ. DSI scores should be contextualized using additional performance data to ensure each individual athlete receives the appropriate training stimulus during different training phases throughout the year.
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http://dx.doi.org/10.2478/hukin-2020-0014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706654PMC
August 2020

Cannabidiol reduces soman-induced lethality and seizure severity in female plasma carboxylesterase knockout mice treated with midazolam.

Neurotoxicology 2021 01 5;82:130-136. Epub 2020 Dec 5.

US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, United States. Electronic address:

Cannabidiol, approved for treatment of pediatric refractory epilepsy, has anti-seizure effects in various animal seizure models. Chemical warfare nerve agents, including soman, are organophosphorus chemicals that can induce seizure and death if untreated or if treatment is delayed. Our objective was to evaluate whether cannabidiol would ameliorate soman-induced toxicity using a mouse model that similar to humans lacks plasma carboxylesterase. In the present study, adult female plasma carboxylesterase knockout (Es1-/-) mice were pre-treated with cannabidiol (20-150 mg/kg) or vehicle 1 h prior to exposure to a seizure-inducing dose of soman and evaluated for survival and seizure activity. The muscarinic antagonist atropine sulfate and the oxime HI-6 were administered at 1 min after exposure, and the benzodiazepine midazolam was administered at 30 min after seizure onset. Cannabidiol (150 mg/kg) pre-treatment led to a robust increase in survival rate and attenuated body weight loss in soman-exposed mice treated with medical countermeasures, compared to mice pre-treated with vehicle. In addition, mice pretreated with cannabidiol (150 mg/kg) had a modest reduction in seizure severity after midazolam treatment compared to vehicle-pretreated. These findings of improved outcome with cannabidiol administration in a severe seizure model of soman exposure provide additional pre-clinical support for the benefits of cannabidiol against exposure to seizure-inducing chemical agents and suggest cannabidiol may augment the anti-seizure effects of midazolam.
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http://dx.doi.org/10.1016/j.neuro.2020.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856212PMC
January 2021

Efficient Detection of Cortical Auditory Evoked Potentials in Adults Using Bootstrapped Methods.

Ear Hear 2020 11 30;42(3):574-583. Epub 2020 Nov 30.

Institute of Sound and Vibration Research, Faculty of Engineering and the Environment, University of Southampton, United Kingdom.

Background: Statistical detection methods are useful tools for assisting clinicians with cortical auditory evoked potential (CAEP) detection, and can help improve the overall efficiency and reliability of the test. However, many of these detection methods rely on parametric distributions when evaluating test significance, and thus make various assumptions regarding the electroencephalogram (EEG) data. When these assumptions are violated, reduced test sensitivities and/or increased or decreased false-positive rates can be expected. As an alternative to the parametric approach, test significance can be evaluated using a bootstrap, which does not require some of the aforementioned assumptions. Bootstrapping also permits a large amount of freedom when choosing or designing the statistical test for response detection, as the distributions underlying the test statistic no longer need to be known prior to the test.

Objectives: To improve the reliability and efficiency of CAEP-related applications by improving the specificity and sensitivity of objective CAEP detection methods.

Design: The methods included in the assessment were Hotelling's T2 test, the Fmp, four modified q-sample statistics, and various template-based detection methods (calculated between the ensemble coherent average and some predefined template), including the correlation coefficient, covariance, and dynamic time-warping (DTW). The assessment was carried out using both simulations and a CAEP threshold series collected from 23 adults with normal hearing.

Results: The most sensitive method was DTW, evaluated using the bootstrap, with maximum increases in test sensitivity (relative to the conventional Hotelling's T2 test) of up to 30%. An important factor underlying the performance of DTW is that the template adopted for the analysis correlates well with the subjects' CAEP.

Conclusion: When subjects' CAEP morphology is approximately known before the test, then the DTW algorithm provides a highly sensitive method for CAEP detection.
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http://dx.doi.org/10.1097/AUD.0000000000000959DOI Listing
November 2020

The Effect of Training Status on Adaptations to 11 Weeks of Block Periodization Training.

Sports (Basel) 2020 Oct 31;8(11). Epub 2020 Oct 31.

Center of Excellence for Sport Science and Coach Education, Department of Sport, Exercise, Recreation and Kinesiology, East Tennessee State University, Johnson City, TN 37614, USA.

Some controversy exists as to the most efficacious method of training to achieve enhanced levels of sport performance. Controversy concerning the efficacy of periodization and especially block periodization (BP) likely stems from the use of poorly or untrained subjects versus trained who may differ in their responses to a stimulus. The purpose of this study was to investigate the effect of training status on performance outcomes resulting from 11 weeks of BP training. Fifteen males were recruited for this study and placed into strong (age = 24.3 ± 1.9 years., body mass (BM) = 87.7 ± 8.7 kg, squat: body mass = 1.96 ± 0.16), moderate (age = 25.3 ± 2.7 years., body mass = 100.2 ± 15.5 kg, squat: body mass = 1.46 ± 0.14), or weak (age = 23.2 ± 3.9 yrs., body mass = 83.5 ± 17.1 kg, squat: body mass = 1.17 ± 0.07) groups based on relative strength. Testing was completed at baseline, and after each block which consisted of 1 repetition maximum (1RM) squat, 0 kg static jump (SJ), 0 kg countermovement jump (CMJ), 20 kg SJ, and 20 kg CMJ. Absolute and relative strength were strongly correlated with rates of improvement for absolute strength, relative strength, 0 kg, and 20 kg vertical jumps. All subjects substantially improved back squat ( < 0.001), relative back squat ( < 0.001) with large-very large effect sizes between groups for percent change favoring the weak group over the moderate and strong group for all performance variables. All subjects showed statistically significant improvements in 0 kg SJ ( < 0.001), 0 kg CMJ ( < 0.001), 20 kg SJ ( = 0.002), and 20 kg CMJ ( < 0.001). Statistically significant between group differences were noted for both 20 kg SJ ( = 0.01) and 20 kg CMJ ( = 0.043) with the strong group statistically greater jump heights than the weak group. The results of this study indicate BP training is effective in improving strength and explosive ability. Additionally, training status may substantially alter the response to a resistance training program.
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http://dx.doi.org/10.3390/sports8110145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693826PMC
October 2020

In Response.

Anesth Analg 2020 11;131(5):e236-e237

Unit of Anaesthesia, Intensive Care and Pain Management, Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy,

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http://dx.doi.org/10.1213/ANE.0000000000005143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7389741PMC
November 2020
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