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1.
Nat Genet ; 55(3): 437-450, 2023 03.
Article in English | MEDLINE | ID: mdl-36849657

ABSTRACT

High-grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency and, while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multiomics approach to interrogate molecular diversity in end-stage disease, using multiple autopsy samples collected from 15 women with HR-deficient HGSC. Patients had polyclonal disease, and several resistance mechanisms were identified within most patients, including reversion mutations and HR restoration by other means. We also observed frequent whole-genome duplication and global changes in immune composition with evidence of immune escape. This analysis highlights diverse evolutionary changes within HGSC that evade therapy and ultimately overwhelm individual patients.


Subject(s)
Cystadenocarcinoma, Serous , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/genetics , Multiomics , Carcinoma, Ovarian Epithelial , Homologous Recombination/genetics , Cystadenocarcinoma, Serous/genetics
2.
Rev Sci Instrum ; 93(8): 085104, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-36050069

ABSTRACT

Calibration, commissioning, and design features of a new Mach 5 Ludwieg Tube wind tunnel at the University of Arizona are discussed. Mach number uniformity and free-stream noise levels are measured using a Pitot rake at a range of unit Reynolds numbers and at multiple spanwise and streamwise positions. The wind tunnel is shown to have a free-stream Mach number of 4.82 with maximum variance less than 0.8% (and less than 0.5% at most streamwise positions). The average free-stream acoustic noise level in the core (based on Pitot pressure) is shown to be less than 1.2% at an intermediate Reynolds number with some regions dropping locally below 1.0%. The core flow region is measured to be 282.4 mm (11.1 in.) in diameter at the nozzle exit.

3.
J Clin Oncol ; 40(18): 2036-2047, 2022 06 20.
Article in English | MEDLINE | ID: mdl-35263119

ABSTRACT

PURPOSE: Tubo-ovarian cancer (TOC) is a sentinel cancer for BRCA1 and BRCA2 pathogenic variants (PVs). Identification of a PV in the first member of a family at increased genetic risk (the proband) provides opportunities for cancer prevention in other at-risk family members. Although Australian testing rates are now high, PVs in patients with TOC whose diagnosis predated revised testing guidelines might have been missed. We assessed the feasibility of detecting PVs in this population to enable genetic risk reduction in relatives. PATIENTS AND METHODS: In this pilot study, deceased probands were ascertained from research cohort studies, identification by a relative, and gynecologic oncology clinics. DNA was extracted from archival tissue or stored blood for panel sequencing of 10 risk-associated genes. Testing of deceased probands ascertained through clinic records was performed with a consent waiver. RESULTS: We identified 85 PVs in 84 of 787 (11%) probands. Familial contacts of 39 of 60 (65%) deceased probands with an identified recipient (60 of 84; 71%) have received a written notification of results, with follow-up verbal contact made in 85% (33 of 39). A minority of families (n = 4) were already aware of the PV. For many (29 of 33; 88%), the genetic result provided new information and referral to a genetic service was accepted in most cases (66%; 19 of 29). Those who declined referral (4 of 29) were all male next of kin whose family member had died more than 10 years before. CONCLUSION: We overcame ethical and logistic challenges to demonstrate that retrospective genetic testing to identify PVs in previously untested deceased probands with TOC is feasible. Understanding reasons for a family member's decision to accept or decline a referral will be important for guiding future TRACEBACK projects.


Subject(s)
Breast Neoplasms , Ovarian Neoplasms , Australia , Breast Neoplasms/genetics , Carcinoma, Ovarian Epithelial/genetics , Family , Female , Genetic Predisposition to Disease , Genetic Testing/methods , Humans , Male , Ovarian Neoplasms/genetics , Ovarian Neoplasms/prevention & control , Pilot Projects , Retrospective Studies
4.
Int J Cardiol ; 341: 84-87, 2021 Oct 15.
Article in English | MEDLINE | ID: mdl-34416318

ABSTRACT

Studies assessing exercise ventilatory responses during real-life exercise in pulmonary arterial hypertension (PAH) which include patients with cyanotic congenital heart disease are scarce. We assessed the ventilatory response to stairclimbing in patients with idiopathic PAH (IPAH) and congenital heart disease-associated PAH with Eisenmenger (EIS) physiology compared to healthy controls. Fifteen adults with IPAH, six EIS and 15 age and body mass index (BMI) matched controls were prospectively recruited. Participants completed spirometry and a self-paced stair-climb (48 steps) with portable cardiopulmonary exercise testing (CPET) equipment in-situ. Borg dyspnoea scores were measured at rest and on stair-climb cessation. Both IPAH and EIS groups had amplified ventilatory responses compared to Controls. The rate of increase in minute ventilation (VE) was exaggerated in EIS driven by an early increase in tidal volume (Tv) and more gradual increase in respiratory rate (RR). Peak Tv, RR, Tv: forced vital capacity (FVC) ratio, VE/VCO2 slope and stairclimb duration were significantly higher in EIS and IPAH compared to controls despite similar baseline spirometry and change in oxygen uptake on exercise. A decline in end-tidal carbon dioxide (CO2) and arterial oxygen saturations in early exercise distinguished EIS and IPAH patients. Significant correlations were observed between peak exercise Borg score and stair-climb time (r = 0.73, p = 0.002), peak end-tidal CO2 (r = -0.73, p = 0.001), peak VE (r = 0.53, p = 0.008), peak RR (r = 0.42, p = 0.011) and VE/VCO2 slope (r = 0.54, p = 0.001). Patients with IPAH and EIS have exaggerated ventilatory responses to stair-climbing compared to the controls with more severe levels of dyspnoea perception in Eisenmenger syndrome for equivalent oxygen uptake and work.


Subject(s)
Eisenmenger Complex , Adult , Cyanosis , Eisenmenger Complex/diagnosis , Exercise , Exercise Test , Familial Primary Pulmonary Hypertension , Humans , Oxygen Consumption
5.
J Health Econ ; 77: 102423, 2021 05.
Article in English | MEDLINE | ID: mdl-33838593

ABSTRACT

Prices negotiated between payers and providers affect a health insurance contract's value via enrollees' cost-sharing and self-insured employers' costs. However, price variation across payers is difficult to observe. We measure negotiated prices for hospital-payer pairs in Massachusetts and characterize price variation. Between-payer price variation is similar in magnitude to between-hospital price variation. Administrative-services-only contracts, in which insurers do not bear risk, have higher prices. We model negotiation incentives and show that contractual form and demand responsiveness to negotiated prices are important determinants of negotiated prices.


Subject(s)
Insurance Carriers , Insurance, Health , Contracts , Cost Sharing , Humans , Negotiating
6.
Am J Obstet Gynecol ; 224(2): 195.e1-195.e17, 2021 02.
Article in English | MEDLINE | ID: mdl-32777264

ABSTRACT

BACKGROUND: Women with gynecologic cancer face socioeconomic disparities in care that affect survival outcomes. The Affordable Care Act offered states the option to expand Medicaid enrollment eligibility criteria as a means of improving timely and affordable access to care for the most vulnerable. The variable uptake of expansion by states created a natural experiment, allowing for quasi-experimental methods that offer more unbiased estimates of treatment effects from retrospective data than the traditional regression adjustment. OBJECTIVE: To use a quasi-experimental, difference-in-difference framework to create unbiased estimates of impact of Medicaid expansion on women with gynecologic cancer. STUDY DESIGN: We performed a quasi-experimental retrospective cohort study from the National Cancer Database files for women with invasive cancers of the uterus, ovary and fallopian tube, cervix, vagina, and vulva diagnosed from 2008 to 2016. Using a marker for state Medicaid expansion status, we created difference-in-difference models to assess the impact of Medicaid expansion on the outcomes of access to and timeliness of care. We excluded women aged <40 years owing to the suppression of the state Medicaid expansions status in the data and women aged ≥65 years owing to the universal Medicare coverage availability. Our primary outcome was the rate of uninsurance at diagnosis. Secondary outcomes included Medicaid coverage, early-stage diagnosis, treatment at an academic facility, and any treatment or surgery within 30 days of diagnosis. Models were run within multiple subgroups and on a propensity-matched cohort to assess the robustness of the treatment estimates. The assumption of parallel trends was assessed with event study time plots. RESULTS: Our sample included 335,063 women. Among this cohort, 121,449 were from nonexpansion states and 213,614 were from expansion states, with 79,886 posttreatment cases diagnosed after the expansion took full effect in expansion states. The groups had minor differences in demographics, and we found occasional preperiod event study coefficients diverging from the mean, but the outcome trends were generally similar between the expansion and nonexpansion states in the preperiod, satisfying the necessary assumption for the difference-in-difference analysis. In a basic difference-in-difference model, the Medicaid expansion in January 2014 was associated with significant increases in insurance at diagnosis, treatment at an academic facility, and treatment within 30 days of diagnosis (P<.001 for all). In an adjusted model including all states and accounting for variable expansion implementation time, there was a significant treatment effect of Medicaid expansion on the reduction in uninsurance at diagnosis (-2.00%; 95% confidence interval, -2.3 to -1.7; P<.001), increases in early-stage diagnosis (0.80%; 95% confidence interval, 0.2-1.4; P=.02), treatment at an academic facility (0.83%; 95% confidence interval, 0.1-1.5; P=.02), treatment within 30 days (1.62%; 95% confidence interval, 1.0-2.3; P<.001), and surgery within 30 days (1.54%; 95% confidence interval, 0.8-2.3; P<.001). In particular, large gains were estimated for women living in low-income zip codes, Hispanic women, and women with cervical cancer. Estimates from the subgroup and propensity-matched cohorts were generally consistent for all outcomes besides early-stage diagnosis and treatment within 30 days. CONCLUSION: Medicaid expansion was significantly associated with gains in the access and timeliness of treatment for nonelderly women with gynecologic cancer. The implementation of Medicaid expansion could greatly benefit women in nonexpansion states. Gynecologists and gynecologic oncologists should advocate for Medicaid expansion as a means of improving outcomes and reducing socioeconomic and racial disparities.


Subject(s)
Genital Neoplasms, Female/diagnosis , Genital Neoplasms, Female/therapy , Medicaid/statistics & numerical data , Medically Uninsured/statistics & numerical data , Time-to-Treatment/statistics & numerical data , Adult , Black or African American , Cohort Studies , Early Detection of Cancer , Educational Status , Ethnicity/statistics & numerical data , Female , Genital Neoplasms, Female/pathology , Health Policy , Hispanic or Latino , Humans , Medicaid/legislation & jurisprudence , Middle Aged , Neoplasm Staging , Non-Randomized Controlled Trials as Topic , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Patient Protection and Affordable Care Act/legislation & jurisprudence , Poverty , Propensity Score , Residence Characteristics , Retrospective Studies , United States , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/therapy , Uterine Neoplasms/diagnosis , Uterine Neoplasms/pathology , Uterine Neoplasms/therapy , Vaginal Neoplasms/diagnosis , Vaginal Neoplasms/pathology , Vaginal Neoplasms/therapy , Vulvar Neoplasms/diagnosis , Vulvar Neoplasms/pathology , Vulvar Neoplasms/therapy , White People
7.
Health Aff (Millwood) ; 38(2): 184-189, 2019 02.
Article in English | MEDLINE | ID: mdl-30715987

ABSTRACT

Evidence suggests that growth in providers' prices drives growth in health care spending on the privately insured. However, existing work has not systematically differentiated between the growth rate of hospital prices and that of physician prices. We analyzed growth in both types of prices for inpatient and hospital-based outpatient services using actual negotiated prices paid by insurers. We found that in the period 2007-14 hospital prices grew substantially faster than physician prices. For inpatient care, hospital prices grew 42 percent, while physician prices grew 18 percent. Similarly, for hospital-based outpatient care, hospital prices grew 25 percent, while physician prices grew 6 percent. A majority of the growth in payments for inpatient and hospital-based outpatient care was driven by growth in hospital prices, not physician prices. Our work suggests that efforts to reduce health care spending should be primarily focused on addressing growth in hospital rather than physician prices. Policy makers should consider a range of options to address hospital price growth, including antitrust enforcement, administered pricing, the use of reference pricing, and incentivizing referring physicians to make more cost-efficient referrals.


Subject(s)
Commerce , Economic Competition , Hospital Costs/statistics & numerical data , Physicians/economics , Adult , Commerce/economics , Commerce/statistics & numerical data , Female , Humans , Insurance Carriers/statistics & numerical data , Insurance Claim Review , Male , Middle Aged , Private Sector/statistics & numerical data , United States
8.
Health Aff (Millwood) ; 38(2): 230-236, 2019 02.
Article in English | MEDLINE | ID: mdl-30715989

ABSTRACT

We examined the growth in health spending on people with employer-sponsored private insurance in the period 2007-14. Our analysis relied on information from the Health Care Cost Institute data set, which includes insurance claims from Aetna, Humana, and UnitedHealthcare. In the study period private health spending per enrollee grew 16.9 percent, while growth in Medicare spending per fee-for-service beneficiary decreased 1.2 percent. There was substantial variation in private spending growth rates across hospital referral regions (HRRs): Spending in HRRs in the tenth percentile of private spending growth grew at 0.22 percent per year, while HRRs in the ninetieth percentile experienced 3.45 percent growth per year. The correlation between the growth in HRR-level private health spending and growth in fee-for-service Medicare spending in the study period was only 0.211. The low correlation across HRRs suggests that different factors may be driving the growth in spending on the two populations.


Subject(s)
Health Expenditures/trends , Insurance Claim Review/statistics & numerical data , Insurance, Health , Private Sector , Adult , Aged , Fee-for-Service Plans/statistics & numerical data , Humans , Insurance, Health/statistics & numerical data , Insurance, Health/trends , Medicare/statistics & numerical data , Middle Aged , Private Sector/statistics & numerical data , Private Sector/trends , United States
9.
Q J Econ ; 134(1): 51-107, 2019 Feb.
Article in English | MEDLINE | ID: mdl-32981974

ABSTRACT

We use insurance claims data covering 28% of individuals with employer-sponsored health insurance in the United States to study the variation in health spending on the privately insured, examine the structure of insurer-hospital contracts, and analyze the variation in hospital prices across the nation. Health spending per privately insured beneficiary differs by a factor of three across geographic areas and has a very low correlation with Medicare spending. For the privately insured, half of the spending variation is driven by price variation across regions, and half is driven by quantity variation. Prices vary substantially across regions, across hospitals within regions, and even within hospitals. For example, even for a nearly homogeneous service such as lower-limb magnetic resonance imaging, about a fifth of the total case-level price variation occurs within a hospital in the cross section. Hospital market structure is strongly associated with price levels and contract structure. Prices at monopoly hospitals are 12% higher than those in markets with four or more rivals. Monopoly hospitals also have contracts that load more risk on insurers (e.g., they have more cases with prices set as a share of their charges). In concentrated insurer markets the opposite occurs-hospitals have lower prices and bear more financial risk. Examining the 366 mergers and acquisitions that occurred between 2007 and 2011, we find that prices increased by over 6% when the merging hospitals were geographically close (e.g., 5 miles or less apart), but not when the hospitals were geographically distant (e.g., over 25 miles apart).

10.
J Int Soc Sports Nutr ; 15(1): 37, 2018 Jul 31.
Article in English | MEDLINE | ID: mdl-30064450

ABSTRACT

BACKGROUND: Betaine supplementation has been shown to improve body composition and some metrics of muscular performance in young men; but, whether betaine enhances body composition or performance in female subjects is currently unknown. Therefore, the purpose of this study was to investigate the interaction between resistance training adaptation and chronic betaine supplementation in females. METHODS: Twenty-three young women (21.0 ± 1.4 years, 165.9 ± 6.4 cm, 68.6 ± 11.8 kg) without prior structured resistance training experience volunteered for this study. Body composition (BodPod), rectus femoris muscle thickness (B-mode Ultrasound), vertical jump, back squat 1RM and bench press 1RM were assessed pre- and post-training. Following 1 week of familiarization training, subjects were matched for body composition and squat strength, and randomly assigned to either a betaine (2.5 g/day; n = 11) or placebo (n = 12) group that completed 3 sets of 6-7 exercises per day performed to momentary muscular failure. Training was divided into two lower and one upper body training sessions per week performed on non-consecutive days for 8 weeks, and weekly volume load was used to analyze work capacity. RESULTS: Significant main effects of time were found for changes in lean mass (2.4 ± 1.8 kg), muscle thickness (0.13 ± 0.08 cm), vertical jump (1.8 ± 1.6 cm), squat 1RM (39.8 ± 14.0 kg), and bench press 1 RM (9.1 ± 7.3 kg); however, there were no significant interactions. A trend (p = .056) was found for greater weekly training volumes for betaine versus placebo. Significant interactions were found for changes in body fat percentage and fat mass: body fat percentage and fat mass decreased significantly more in betaine (- 3.3 ± 1.7%; - 2.0 ± 1.1 kg) compared to placebo (- 1.7 ± 1.6%; - 0.8 ± 1.3 kg), respectively. CONCLUSIONS: The results of this study indicated that betaine supplementation may enhance reductions in fat mass, but not absolute strength, that accompany a resistance training program in untrained collegiate females.


Subject(s)
Adaptation, Physiological , Betaine/administration & dosage , Body Composition/drug effects , Dietary Supplements , Resistance Training , Double-Blind Method , Female , Humans , Muscle Strength/drug effects , Muscle, Skeletal/drug effects , Sports Nutritional Physiological Phenomena , Young Adult
11.
Nat Commun ; 8: 14581, 2017 03 06.
Article in English | MEDLINE | ID: mdl-28262675

ABSTRACT

The Eµ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising Eµ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identify frequent disruptive mutations in the PRC1-like component and BCL6-corepressor gene Bcor. Moreover, we find unexpected concomitant multigenic lesions involving Cdkn2a loss and other cancer genes including Nras, Kras and Bcor. These findings challenge the assumed two-hit model of Eµ-Myc lymphoma and demonstrate a functional in vivo role for Bcor in suppressing tumorigenesis.


Subject(s)
B-Lymphocytes/metabolism , Gene Expression Regulation, Neoplastic , Lymphoma, B-Cell/genetics , Mutation , Proto-Oncogene Proteins c-myc/genetics , Repressor Proteins/genetics , Alleles , Animals , B-Lymphocytes/immunology , B-Lymphocytes/pathology , CRISPR-Cas Systems , Cyclin-Dependent Kinase Inhibitor p16/genetics , Cyclin-Dependent Kinase Inhibitor p16/immunology , Disease Models, Animal , Gene Editing , Gene Frequency , Janus Kinase 2/genetics , Janus Kinase 2/immunology , Lymphoma, B-Cell/immunology , Lymphoma, B-Cell/pathology , Mice , Mice, Transgenic , Proto-Oncogene Proteins c-myc/immunology , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/immunology , Repressor Proteins/immunology , STAT5 Transcription Factor/genetics , STAT5 Transcription Factor/immunology , Transcriptome , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/immunology , Whole Genome Sequencing
12.
Trials ; 17: 13, 2016 Jan 07.
Article in English | MEDLINE | ID: mdl-26739268

ABSTRACT

BACKGROUND: Globally, most strokes occur in low- and middle-income countries, such as India, with many affected people having no or limited access to rehabilitation services. Western models of stroke rehabilitation are often unaffordable in many populations but evidence from systematic reviews of stroke unit care and early supported discharge rehabilitation trials suggest that some components might form the basis of affordable interventions in low-resource settings. We describe the background, history and design of the ATTEND trial, a complex intervention centred on family-led stroke rehabilitation in India. METHODS/DESIGN: The ATTEND trial aims to test the hypothesis that a family-led caregiver-delivered home-based rehabilitation intervention, designed for the Indian context, will reduce the composite poor outcome of death or dependency at 6 months after stroke, in a multicentre, individually randomized controlled trial with blinded outcome assessment, involving 1200 patients across 14 hospital sites in India. DISCUSSION: The ATTEND trial is testing the effectiveness of a low-cost rehabilitation intervention that could be widely generalizable to other low- and middle-income countries. TRIAL REGISTRATION: Clinical Trials Registry-India CTRI/2013/04/003557 . Australian New Zealand Clinical Trials Registry ACTRN12613000078752 . Universal Trial Number U1111-1138-6707.


Subject(s)
Clinical Protocols , Family , Stroke Rehabilitation , Caregivers , Humans , India , Outcome Assessment, Health Care , Prospective Studies , Sample Size
13.
J Int Soc Sports Nutr ; 10(1): 39, 2013 Aug 22.
Article in English | MEDLINE | ID: mdl-23967897

ABSTRACT

BACKGROUND: This study investigated the effects of long term betaine supplementation on body composition, performance, and homocysteine thiolactone (HCTL) in experienced strength trained men. METHODS: Twenty-three subjects were matched for training experience (4.8 ± 2.3 years) and body fat percentage (BF%: 16.9 ± 8.0%), randomly assigned to either a placebo (PL; n = 12) or betaine group (BET; n = 11; 2.5 g/day), and completed a 6 week periodized training program consisting of 3 two-week micro-cycles. Bench press and back squat training volumes were recorded and changes in training volume were assessed at each micro-cycle. Fasting urine was collected at baseline (BL), weeks 2, 4 and 6, and assayed for HCTL. Subjects were tested prior to and following 6 weeks of treatment. Arm and thigh cross sectional area (CSA) was estimated via girth and skin fold measurements. Body density was estimated via skin fold calipers and used to estimate BF%, fat mass (FM), and lean body mass (LBM). Performance was assessed via vertical jump (VJ), bench press 1 RM (BP), and back squat 1 RM (BS). RESULTS: Arm CSA increased significantly (p < .05) in BET but not PL. No differences existed between group and time for changes in thigh CSA. Back squat training volume increased significantly (p < .05) for both groups throughout training. Bench press training volume was significantly (p < .05) improved for BET compared to PL at microcycles one and three. Body composition (BF%, FM, LBM) improved significantly (p < .05) in BET but not PL. No differences were found in performance variables (BP, BS, VJ) between groups, except there was a trend (p = .07) for increased VJ power in BET versus PL. A significant interaction (p < .05) existed for HCTL, with increases from BL to week 2 in PL, but not BET. Additionally, HCTL remained elevated at week 4 in PL, but not BET. CONCLUSION: Six-weeks of betaine supplementation improved body composition, arm size, bench press work capacity, attenuated the rise in urinary HCTL, and tended to improve power (p = .07) but not strength.

14.
Eur J Appl Physiol ; 113(3): 793-802, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22976217

ABSTRACT

Our aim was to examine the effect of betaine supplementation on selected circulating hormonal measures and Akt muscle signaling proteins after an acute exercise session. Twelve trained men (age 19.7 ± 1.23 years) underwent 2 weeks of supplementation with either betaine (B) (1.25 g BID) or placebo (P). Following a 2-week washout period, subjects underwent supplementation with the other treatment (B or P). Before and after each 2-week period, subjects performed an acute exercise session (AES). Circulating GH, IGF-1, cortisol, and insulin were measured. Vastus lateralis samples were analyzed for signaling proteins (Akt, p70 S6k, AMPK). B (vs. P) supplementation approached a significant increase in GH (mean ± SD (Area under the curve, AUC), B: 40.72 ± 6.14, P: 38.28 ± 5.54, p = 0.060) and significantly increased IGF-1 (mean ± SD (AUC), B: 106.19 ± 13.45, P: 95.10 ± 14.23, p = 0.010), but significantly decreased cortisol (mean ± SD (AUC), B: 1,079.18 ± 110.02, P: 1,228.53 ± 130.32, p = 0.007). There was no difference in insulin (AUC). B increased resting Total muscle Akt (p = 0.003). B potentiated phosphorylation (relative to P) of Akt (Ser(473)) and p70 S6 k (Thr(389)) (p = 0.016 and p = 0.005, respectively). Phosphorylation of AMPK (Thr(172)) decreased during both treatments (both p = 0.001). Betaine (vs. placebo) supplementation enhanced both the anabolic endocrine profile and the corresponding anabolic signaling environment, suggesting increased protein synthesis.


Subject(s)
Betaine/administration & dosage , Dietary Supplements , Endocrine System/drug effects , Exercise/physiology , Gastrointestinal Agents/administration & dosage , Metabolism/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Adolescent , Adult , Cross-Over Studies , Double-Blind Method , Endocrine System/metabolism , Humans , Male , Physical Exertion/drug effects , Physical Exertion/physiology , Placebos , Signal Transduction/drug effects , Time Factors , Young Adult
15.
J Int Soc Sports Nutr ; 9(1): 12, 2012 Apr 03.
Article in English | MEDLINE | ID: mdl-22471891

ABSTRACT

PURPOSE: To examine the effect of betaine supplementation on cycling sprint performance. METHODS: Sixteen recreationally active subjects (7 females and 9 males) completed three sprint tests, each consisting of four 12 sec efforts against a resistance equal to 5.5% of body weight; efforts were separated by 2.5 min of cycling at zero resistance. Test one established baseline; test two and three were preceded by seven days of daily consumption of 591 ml of a carbohydrate-electrolyte beverage as a placebo or a carbohydrate-electrolyte beverage containing 0.42% betaine (approximately 2.5 grams of betaine a day); half the beverage was consumed in the morning and the other half in the afternoon. We used a double blind random order cross-over design; there was a 3 wk washout between trials two and three. Average and maximum peak and mean power were analyzed with one-way repeated measures ANOVA and, where indicated, a Student Newman-Keuls. RESULTS: Compared to baseline, betaine ingestion increased average peak power (6.4%; p < 0.001), maximum peak power (5.7%; p < 0.001), average mean power (5.4%; p = 0.004), and maximum mean power (4.4%; p = 0.004) for all subjects combined. Compared to placebo, betaine ingestion significantly increased average peak power (3.4%; p = 0.026), maximum peak power max (3.8%; p = 0.007), average mean power (3.3%; p = 0.034), and maximum mean power (3.5%; p = 0.011) for all subjects combined. There were no differences between the placebo and baseline trials. CONCLUSIONS: One week of betaine ingestion improved cycling sprint power in recreationally active males and females.

16.
J Strength Cond Res ; 25(12): 3461-71, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22080324

ABSTRACT

Trepanowski, JF, Farney, TM, McCarthy, CG, Schilling, BK, Craig, SA, and Bloomer, RJ. The effects of chronic betaine supplementation on exercise performance, skeletal muscle oxygen saturation, and associated biochemical parameters in resistance trained men. J Strength Cond Res 25(12): 3461-3471, 2011-We examined the effects of chronic betaine supplementation on exercise performance and associated parameters in resistance trained men. Men were randomly assigned in a double-blind manner using a crossover design to consume betaine (2.5 g of betaine mixed in 500 ml of Gatorade®) or a placebo (500 ml of Gatorade®) for 14 days, with a 21-day washout period. Before and after each treatment period, tests of lower- and upper-body muscular power and isometric force were conducted, including a test of upper-body muscular endurance (10 sets of bench press exercise to failure). Muscle tissue oxygen saturation (StO2) during the bench press protocol was measured via near infrared spectroscopy. Blood samples were collected before and after the exercise test protocol for analysis of lactate, nitrate/nitrite (NOx), and malondialdehyde (MDA). When analyzed using a repeated measures analysis of variance, no significant differences were noted between conditions for exercise performance variables (p > 0.05). However, an increase in total repetitions (p = 0.01) and total volume load (p = 0.02) in the 10-set bench press protocol was noted with betaine supplementation (paired t-tests), with values increasing approximately 6.5% from preintervention to postintervention. Although not of statistical significance (p = 0.14), postexercise blood lactate increased to a lesser extent with betaine supplementation (210%) compared with placebo administration (270%). NOx was lower postintervention as compared with preintervention (p = 0.06), and MDA was relatively unchanged. The decrease in StO2 during the bench press protocol was greater with betaine vs. placebo (p = 0.01), possibly suggesting enhanced muscle oxygen consumption. These findings indicate that betaine supplementation results in a moderate increase in total repetitions and volume load in the bench press exercise, without favorably impacting other performance measures.


Subject(s)
Athletic Performance/physiology , Betaine/pharmacology , Muscle, Skeletal/metabolism , Oxygen/metabolism , Resistance Training , Cross-Over Studies , Dietary Supplements , Double-Blind Method , Humans , Isometric Contraction/drug effects , Lactic Acid/blood , Male , Malondialdehyde/blood , Muscle Strength/drug effects , Muscle, Skeletal/drug effects , Nitrates/blood , Nitrites/blood , Oxygen Consumption/drug effects , Physical Endurance/drug effects , Random Allocation
17.
J Strength Cond Res ; 25(8): 2235-41, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21747291

ABSTRACT

The purpose of this study was to examine the efficacy of 15 days of betaine supplementation on peak concentric (CON) and eccentric (ECC) force during isokinetic exercise in active college-aged men. Eleven men volunteered for this study (21.7 ± 5.1 years; height: 178.5 ± 6.4 cm; body mass: 79.8 ± 10.3 kg). Subjects were randomly assigned to either a supplement (BET) or placebo (PL) group. Supplementation occurred for 15 days. Subjects reported to the Human Performance Laboratory on 5 occasions during this period, separated by 72 hours, for a testing and exercise session on an isokinetic chest press device. After each exercise protocol, subjects rated their fatigue and muscle soreness on a 15-cm visual analog scale. Subjects then consumed no daily BET for 4 weeks but maintained familiarity with the exercise device once per week. After the washout period, subjects resumed the BET protocol using the opposite drink and repeated the same 15-day protocol. No differences were noted in maximum CON force output between pre (335.9 ± 78.3 and 321.6 ± 63.6 N) and post (330.3 ± 74.8 and 330.2 ± 71.6 N) workouts in both BET and PL, respectively. In addition, no differences were noted in maximum ECC force output between pre (352.0 ± 90.6 and 324.4 ± 85.2 N) and post (353.2 ± 98.2 and 366.9 ± 128.5 N) workouts in BET and PL, respectively. No differences in subjective measures of soreness and fatigue were seen, but a significant reduction in Δ fatigue was observed in BET compared to PL. In conclusion, 15 days of betaine supplementation did not increase peak CON or ECC force outputs during an isokinetic chest press but did appear to reduce subjective measures of fatigue to the exercise protocol.


Subject(s)
Betaine/administration & dosage , Muscle Strength/drug effects , Muscle, Skeletal/drug effects , Resistance Training , Adolescent , Adult , Humans , Male , Muscle Fatigue/drug effects , Muscle Fatigue/physiology , Muscle Strength/physiology , Muscle, Skeletal/physiology , Young Adult
18.
Food Nutr Res ; 542010 Nov 01.
Article in English | MEDLINE | ID: mdl-21052531

ABSTRACT

A definition for dietary fiber was adopted in June 2009 by the Codex Alimentarius Commission based on the recommendation for endorsement of the Codex Committee on Nutrition and Foods for Special Dietary Uses (CCNFSDU) in November 2008. The definition listed three categories of carbohydrate polymers that are not hydrolyzed by the endogenous enzymes in the small intestine of humans. However, the definition left the inclusion of carbohydrates with degrees of polymerization (DP) in the range of 3 and 9 to the discretion of national authorities and left the 'physiological effect(s) of benefit to health' as undefined. The ILSI Europe and ILSI North America's committees on dietary carbohydrates organized a forum at the Ninth Vahouny Fiber Symposium in 2010 to discuss these implementation issues with the objective of building scientific consensus on how to resolve them. The results of this session are encouraging and indicated that the scientific community agrees on maintaining a worldwide consensus regarding the inclusion of non-digestible carbohydrates with ≥DP3 as dietary fiber and on a core, non-exhaustive list of beneficial physiological effects that dietary fibers have. These results are consistent with previous worldwide agreements.

19.
J Int Soc Sports Nutr ; 7: 27, 2010 Jul 19.
Article in English | MEDLINE | ID: mdl-20642826

ABSTRACT

BACKGROUND: We investigated the ergogenic effects of betaine (B) supplementation on strength and power performance. METHODS: Twelve men (mean +/- SD age, 21 +/- 3 yr; mass, 79.1 +/- 10.7 kg) with a minimum of 3 months resistance training completed two 14-day experimental trials separated by a 14-day washout period, in a balanced, randomized, double-blind, repeated measures, crossover design. Prior to and following 14 days of twice daily B or placebo (P) supplementation, subjects completed two consecutive days (D1 and D2) of a standardized high intensity strength/power resistance exercise challenge (REC). Performance included bench, squat, and jump tests. RESULTS: Following 14-days of B supplementation, D1 and D2 bench throw power (1779 +/- 90 and 1788 +/- 34 W, respectively) and isometric bench press force (2922 +/- 297 and 2503 +/- 28 N, respectively) were increased (p < 0.05) during REC compared to pre-supplementation values (1534 +/- 30 and 1498 +/- 29 W, respectively; 2345 +/- 64 and 2423 +/- 84 N, respectively) and corresponding P values (1374 +/- 128 and 1523 +/- 39 W; 2175 +/- 92 and 2128 +/- 56 N, respectively). Compared to pre-supplementation, vertical jump power and isometric squat force increased (p < 0.05) on D1 and D2 following B supplementation. However, there were no differences in jump squat power or the number of bench press or squat repetitions. CONCLUSION: B supplementation increased power, force and maintenance of these measures in selected performance measures, and these were more apparent in the smaller upper-body muscle groups.

20.
J Int Soc Sports Nutr ; 7(1): 3, 2010 Jan 22.
Article in English | MEDLINE | ID: mdl-20205750

ABSTRACT

BACKGROUND: This study was developed to establish whether betaine was present in the sweat of females and to determine any correlations with other sweat components. METHODS: Sweat patches were placed on eight trained adolescent Highland dancers (age = 13.6 +/- 2.3 yr), who then participated in a dance class for 2 hours. Patches were removed, and the sweat recovered via centrifugation. The sweat was subsequently analyzed for betaine, choline, sodium, potassium, chloride, lactate, glucose, urea and ammonia. RESULTS: Betaine was present in the sweat of all subjects (232 +/- 84 mumol.L-1), which is higher than typically found in plasma. The concentration of several sweat components were correlated, in particular betaine with most other measured components. CONCLUSION: Betaine, an osmoprotectant and methyl donor, is a component of sweat that may be lost from the body in significant amounts.

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