Three-Dimensional Take-off Step Kinetics of Long Jumpers with and without a Transtibial Amputation

Purpose The loads applied on the musculo-skeletal system during the long jump take-off step are not well established for non-amputee athletes or athletes with a lower extremity amputation. Information on joint loading and potential injury mechanisms is important for improving training or rehabilitation protocols, prosthetic design and the general understanding of the long jump. Methods Three-dimensional take-off step kinematics and kinetics were used for inverse dynamic model calculations on three male athletes with and seven male athletes without a below the knee amputation (BKA). Athletes with BKA used their affected leg as their take-off leg. Results Despite equivalent long jump performance, ground reaction force application characteristics were widely different and calculated joint loads were significantly lower in athletes with BKA compared to non-amputee athletes during the take-off step. The take-off step of the long jump for athletes with BKA seems to be dominated by sagittal plane movements, while for non-amputee athletes it involves sagittal plane movement and compensatory joint work in the frontal plane. Conclusions Coaches and athletes should adapt training protocols to the unique musculo-skeletal loading patterns of long jumpers with or without a BKA. Specifically, non-amputee athletes should strengthen the muscles responsible for hip and knee extension, as well as for frontal plane stabilization, early in the season to avoid injuries. The presented data enables clinicians to identify potential causes of pain or injury more differentially in both groups of athletes and might stimulate future research in the field of robotics and prosthetic components. Furthermore, the altered joint mechanics of athletes with BKA versus non-amputees serves as an explanation for their previously described more effective take-off step. Corresponding author: Johannes Funken, MSc, German Sport University Cologne, Institute of Biomechanics and Orthopaedics, Am Sportpark Müngersdorf 6, 50933 Cologne, Germany. Email: j.funken@dshs-koeln.de. Phone: +49(0)22149827662 Funding was provided by the Japan Broadcasting Cooperation (NHK). JF was funded by a graduate fellowship of the German Sport University Cologne. HH was funded by JSPS KAKENHI Grant Number 26702027. AMG's contribution to this project was also partially supported by the BADER Consortium, a US Department of Defense Congressionally Directed Medical Research Programs cooperative agreement (W81XWH-11-2-0222). None of the authors had any conflict of interest associated with the study. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by the American College of Sports Medicine. Accepted for publication November 2018. © 2018 American College of Sports Medicine

from Sports Medicine via xlomafota13 on Inoreader https://ift.tt/2QofxvW
via IFTTT

Aerobic Exercise Improves Microvascular Function in Older Adults

Microvascular function is reduced with age, disease, and inactivity. Exercise is well known to improve vascular health and has the potential to improve microvascular function in aging and disease. Purpose The study aimed to assess changes in peripheral microvascular function in sedentary older adults following aerobic exercise training. Methods Twenty-three, sedentary older adults (67±5 yrs, BMI=29±5, mean±SD) successfully completed a randomized 12-week graded treadmill walking intervention. The exercise group (EX) performed 40 minutes of uphill walking 4 days a week at 70% heart rate reserve. The control group (CON) maintained a sedentary lifestyle for 12 weeks. MRI measured blood-oxygen-level dependent (BOLD) responses of the soleus were used to evaluate microvascular function; brief (1s) maximal plantar flexion contractions were performed. Separately, blood flow in the popliteal artery was measured by ultrasound following brief contraction. Phosphorus magnetic resonance spectroscopy of the calf was used to examine muscle oxidative capacity and whole body peak oxygen consumption (V[Combining Dot Above]O2peak) was used to confirm training induced cardiorespiratory adaptations. Results Peak post-contraction BOLD response increased by 33% in EX (PRE:3.3±1.0%, POST:4.4±1.4%) compared to CON (PRE:3.0±1.3%, POST:3.2±1.5%), p

from Sports Medicine via xlomafota13 on Inoreader https://ift.tt/2DOLgzI
via IFTTT

Morning vs Evening Aerobic Training Effects on Blood Pressure in Treated Hypertension

Introduction The acute blood pressure (BP) decrease is greater after evening than morning exercise, suggesting that evening training may have a greater hypotensive effect. Objective To compare the hypotensive effect of aerobic training performed in the morning versus evening in treated hypertensives. Methods Fifty treated hypertensive men were randomly allocated to 3 groups: morning training (MT); evening training (ET); and control (C). Training groups cycled for 45min at moderate-intensity (progressing from the heart rate of the anaerobic threshold to 10% below the heart rate of the respiratory compensation point), while C stretched for 30 min. Interventions were conducted 3 times/week for 10 weeks. Clinic and ambulatory BP, hemodynamic, and autonomic mechanisms were evaluated before and after the interventions. Clinic assessments were performed in the morning (7-9a.m.) and evening (6-8p.m.). Between-within ANOVAs were used (P≤0.05). Results Only ET decreased clinic systolic BP differently from C and MT (morning assessment -5±6 mmHg and evening assessment -8±7 mmHg, P

from Sports Medicine via xlomafota13 on Inoreader https://ift.tt/2QoT1ml
via IFTTT

Analytical validity of a genotyping assay for use with personalized antihypertensive and chronic kidney disease therapy

Hypertension and chronic kidney disease are inextricably linked. Hypertension is a well-recognized contributor to chronic kidney disease progression and, in turn, renal disease potentiates hypertension. A generalized approach to drug selection and dosage has not proven effective in managing these conditions, in part, because patients with heterogeneous kidney disease and hypertension etiologies are frequently grouped according to functional or severity classifications. Genetic testing may serve as an important tool in the armamentarium of clinicians who embrace precision medicine. Increasing scientific evidence has supported the utilization of genomic information to select efficacious antihypertensive therapy and understand hereditary contributors to chronic kidney disease progression. Given the wide array of antihypertensive agents available and diversity of genetic renal disease predictors, a panel-based approach to genotyping may be an efficient and economic means of establishing an individualized blood pressure response profile for patients with various forms of chronic kidney disease and hypertension. In this manuscript, we discuss the validation process of a Clinical Laboratory Improvement Amendments-approved genetic test to relay information on 72 genetic variants associated with kidney disease progression and hypertension therapy. These genomic-based interventions, in addition to routine clinical data, may help inform physicians to provide personalized therapy. ✠Deceased. Correspondence to Michael T. Eadon, MD, 950 W Walnut St. E202, Indianapolis, IN 46202, USA Tel: +1 317 274 2502; fax: +1 317 274 8575; e-mail: meadon@iupui.edu Received May 29, 2018 Accepted October 11, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2P8lCIf
via IFTTT

CYP2D6 haplotypes with enhancer single-nucleotide polymorphism rs5758550 and rs16947 (*2 allele): implications for CYP2D6 genotyping panels

Introduction CYP2D6 metabolizes ∼25% of all clinically used drugs, with numerous genetic polymorphisms affecting enzyme activity and drug response. Clinical utility of current CYP2D6 genotyping is partially compromised the unresolved complex haplotype structure of the CYP2D6 locus. We have identified a distal enhancer single-nucleotide polymorphism rs5758550 that robustly increases CYP2D6 expression, whereas rs16947 (CYP2D6*2), previously considered inert, reduces correct mRNA splicing and expression, thereby affecting presumed activity of other alleles on the *2 haplotype. Objective This study aims to determine the structure and frequency of haplotypes containing either rs5758550 or rs16947, or both, together with other relevant CYP2D6 alleles, assigning predictive enzyme activity scores to each, and addressing ambiguities in estimating diplotypes in different populations. Methods The structure and frequency of haplotypes containing rs5758550 and/or rs16947 in different populations were determined by using phased genotype data from 'The 1000 Genomes Project'. The assigned haplotype–phenotype relationship was tested by associating assigned CYP2D6 activity score with CYP2D6 enzyme activity in a cohort of 122 human liver microsomes. Results Addition of enhancer single-nucleotide polymorphism rs5758550 and *2 to a CYP2D6 panel improves prediction of CYP2D6 activity. Moreover, the haplotype containing rs5758550 and rs16947 predict extensive CYP2D6 activity more accurately than CYP2D6*2A, a surrogate marker for extensive activity. Conclusion With further studies, the results support possible incorporation of rs5758550 and rs16947 into CYP2D6 biomarker panels for more accurate prediction of CYP2D6 metabolizer status. Correspondence to Danxin Wang, MD, PhD, Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, 1345 Center Drive MSB PG-05B, Gainesville, FL 32610, USA Tel: +1 352 273 7673; fax: +1 352 273 6121; e-mail: danxin.wang@cop.ufl.edu Received June 13, 2018 Accepted November 10, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2zyosRC
via IFTTT

Effect of tacrolimus dispositional genetics on acute rejection in the first 2 weeks and estimated glomerular filtration rate in the first 3 months following kidney transplantation

Background CYP3A4/5 and P-glycoprotein (P-gp, ABCB1) affect tacrolimus (TAC) exposure in T cells and kidney cells. Genetic variability of these genes has been widely studied for effects on acute rejection and kidney function after transplantation, but findings remain contradictory. In addition, cytochrome P450 reductase (POR) is important for CYP3A4/5 activity, and the pregnane X receptor (NR1I2) regulates CYP3A4/5 and P-gp expression. However, the relationship between POR and NR1I2 genetics and acute rejection and kidney function has not been extensively investigated. Objective The aim of this study was to investigate the effect of ABCB1 (61A>G, 1199G>A, 1236C>T, 2677G>T, 3435C>T), CYP3A4*22, CYP3A5*3, NR1I2 (8055C>T, 63396C>T) and POR*28 genotypes/haplotypes on acute rejection and kidney function in the first 3 months after transplant. Participants and methods The study included 165 kidney transplant recipients, who received TAC, mycophenolate and prednisolone, and 129 donors. TAC dose was adjusted to target trough blood concentrations of 8–15 ng/ml by therapeutic drug monitoring. Recipient and donor genotype/haplotype differences in acute rejection incidence within the first 2 weeks after transplant were assessed by logistic regression, adjusting for induction therapy, human leucocyte antigen mismatches, kidney transplant number, peak panel-reactive antibodies and donor type. Recipient and donor genotype/haplotype differences in estimated glomerular filtration rate in the first 3 months after transplant were assessed by linear mixed effects analysis, adjusting for acute rejection, delayed graft function and donor type. Results No genetic factors significantly affected acute rejection or estimated glomerular filtration rate after correction for multiple comparisons (P>0.004). Conclusion Recipient and donor dispositional genetics had no significant effect on short-term clinical outcomes in kidney transplant patients receiving TAC therapeutic drug monitoring. Correspondence to Rong Hu, MSc, Discipline of Pharmacology, Level 3, Helen Mayo South Building, The University of Adelaide, SA 5005, Australia Tel: +61 883 136 035; e-mail: rong.hu@adelaide.edu.au Received August 29, 2018 Accepted November 4, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2P5uuy1
via IFTTT

Transcriptomic analysis of cells in response to EV71 infection and 2A pro as a trigger for apoptosis via TXNIP gene

Abstract

Background

Enterovirus 71 (EV71) is the main pathogen of hand-foot-mouth disease (HFMD) and sometimes causes several neurological complications. However, the underlying mechanism of the host response to the virus infection remains unclear.

Objective

To reveal the cell-specific transcriptional response of cultured RD cells following infection with EV71, and better understand the molecular mechanisms of virus-host interactions.

Methods

The RD cells were infected with or without EV71 for 24 h, and then transcriptome sequencing and qRT-PCR were performed to analyze the transcriptome difference of functional genes.

Results

More than 15000 genes were identified in transcriptome sequencing. In comparison with uninfected RD cells, 329 DEGs were identified in cells infected with EV71. GO and KEGG pathway enrichment analysis showed that most of the DEGs were related to DNA binding, transcriptional regulation, immune response and inflammatory response, apoptosis inducing factors and enriched in JAK-STAT and MAPK signaling pathways. TXNIP (thioredoxin-interacting protein) gene was further demonstrated to play an important role participating in cellular apoptosis induced by EV71, and the apoptosis and death mediated by TXNIP during EV71 infection was triggered by viral 2A protease (2Apro), not 3C protease (3Cpro).

Conclusion

Our study demonstrated that RD cells have a significant response to EV71 infection, including immune response and apoptosis. 2Apro might be a key inducer relative to the cellular apoptosis and death mediated by TXNIP during EV71 infection. These data would contribute to preferably understand the process at the molecular level and provide theoretical foundation for diagnosis and treatment of EV71-related diseases.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2Rhol3D
via IFTTT