Impact of Medicaid expansion on women with gynecologic cancer: a difference-in-difference analysis.

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.

Betaine supplementation enhances anabolic endocrine and Akt signaling in response to acute bouts of exercise.

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.

Multiomic analysis of homologous recombination-deficient end-stage high-grade serous ovarian cancer.

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.

Calibration and performance characterization of a Mach 5 Ludwieg tube.

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.

TRACEBACK: Testing of Historical Tubo-Ovarian Cancer Patients for Hereditary Risk Genes as a Cancer Prevention Strategy in Family Members.

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.

Effect of 15 days of betaine ingestion on concentric and eccentric force outputs during isokinetic exercise.

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.

The effects of chronic betaine supplementation on exercise performance, skeletal muscle oxygen saturation and associated biochemical parameters in resistance trained men.

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.

How important is price variation between health insurers?

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.

Impact of cyanosis on ventilatory responses during stair climb exercise in Eisenmenger syndrome and idiopathic pulmonary arterial hypertension.

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.

THE PRICE AIN'T RIGHT? HOSPITAL PRICES AND HEALTH SPENDING ON THE PRIVATELY INSURED.

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).

Variation In Health Spending Growth For The Privately Insured From 2007 To 2014.

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.

Hospital Prices Grew Substantially Faster Than Physician Prices For Hospital-Based Care In 2007-14.

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.

Influence of betaine consumption on strenuous running and sprinting in a hot environment.

This investigation evaluated the effects of a nutritional supplement (the organic osmolyte betaine) in rehydration solutions, with and without carbohydrate and electrolytes. Ten male runners ((mean +/- SD) age, 20 +/- 2 years; weight, 70.6 +/- 6.8 kg; maximal aerobic power, 63.5 +/- 4.1 mL O2 x kg(-1) x min(-1)) dehydrated to -2.7% of body weight. They next rehydrated to -1.4% of body weight by consuming 1 L fluid during each of four experiments (double-blind, randomized, cross-over design): flavored, non-caloric water (W); W + 5 g x L(-1) betaine (W+B); 6% carbohydrate-electrolyte fluid (C); or C + 5 g x L(-1) betaine (C+B). Subjects then performed prolonged treadmill running (75 minutes at 65%Vo2max) plus a performance sprint to volitional exhaustion (3.1-3.8 minutes at 84%Vo2max) in an environmental chamber (31.1 degrees C, 88.0 degrees F). Only W versus W+B and C versus C+B statistical comparisons were germane to the research questions. Observations indicated that rehydration with fluids containing betaine resulted in significant differences (p < 0.05) of plasma volume, oxygen consumption, plasma lactate concentration, and thermal sensation. The present experiments did not support the use of betaine to improve sprint duration, but nonsignificant trends occurred when betaine trials were compared with non-betaine trials (mean C+B > C by 32 seconds, +16%; mean W+B > W by 38 seconds, +21%). We interpret the increases of both aerobic and anaerobic metabolism (C+B > C) to mean that further investigation of betaine as a nutritional supplement, using other types of exercise, is warranted.

The effects of chronic betaine supplementation on body composition and performance in collegiate females: a double-blind, randomized, placebo controlled trial.

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.

Caloric availability of polydextrose.

Polydextrose is a randomly bonded polysaccharide produced by the bulk melt polycondensation of glucose and sorbitol in vacuo. It has been used as a bulking and texturizing agent and soluble fiber ingredient in many food products worldwide for over two decades. Because of its atypical linkages between glucose moieties, polydextrose resists digestion by mammalian gastrointestinal enzymes. It is minimally absorbed in the small intestine and partially fermented in the large intestine producing volatile fatty acids, with approximately 50% of the ingested dose being excreted undigested. In this it is similar to many other poorly digested soluble fiber ingredients. Numerous energy balance and isotope-label disposition studies have been conducted in animals and man to investigate the caloric availability of polydextrose. The weight of available experimental evidence in the 14 studies described herein shows that polydextrose has a caloric value of approximately 1 kcal/g.

Genomic characterisation of Eµ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene.

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.

Family-led rehabilitation after stroke in India: the ATTEND trial, study protocol for a randomized controlled trial.

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.

Betaine in human nutrition.

Betaine is distributed widely in animals, plants, and microorganisms, and rich dietary sources include seafood, especially marine invertebrates ( approximately 1%); wheat germ or bran ( approximately 1%); and spinach ( approximately 0.7%). The principal physiologic role of betaine is as an osmolyte and methyl donor (transmethylation). As an osmolyte, betaine protects cells, proteins, and enzymes from environmental stress (eg, low water, high salinity, or extreme temperature). As a methyl donor, betaine participates in the methionine cycle-primarily in the human liver and kidneys. Inadequate dietary intake of methyl groups leads to hypomethylation in many important pathways, including 1) disturbed hepatic protein (methionine) metabolism as determined by elevated plasma homocysteine concentrations and decreased S-adenosylmethionine concentrations, and 2) inadequate hepatic fat metabolism, which leads to steatosis (fatty accumulation) and subsequent plasma dyslipidemia. This alteration in liver metabolism may contribute to various diseases, including coronary, cerebral, hepatic, and vascular diseases. Betaine has been shown to protect internal organs, improve vascular risk factors, and enhance performance. Databases of betaine content in food are being developed for correlation with population health studies. The growing body of evidence shows that betaine is an important nutrient for the prevention of chronic disease.

Increased endogenous cytokinin in the Arabidopsis amp1 mutant corresponds with de-etiolation responses.

The high-cytokinin Arabidopsis thaliana (L.) Heynh. mutant amp1 of has been further characterised. We extend our previous work on the cytokinin level in the amp1 mutant and show that it contains high levels of endogenous cytokinins in both light- and dark-grown plants, and that amp1 can be phenocopied in the dark by growing wild-type plants on exogenous cytokinin. Previously we showed that dark-grown amp1 plants display de-etiolated characteristics such as short unhooked hypocotyls, opened cotyledons and formation of leaves. We further show that amp1 mutants display de-etiolated plastid morphology and increased levels of transcripts of light-regulated genes, indicating that in this mutant light-mediated processes are partially induced in the dark. The amp1 mutant also shows a reduced level of expression of several light-regulated genes compared with the wild type when grown in light, and has an altered dark-adaptation response when compared with the wild type. These results demonstrate an association between high cytokinin levels and de-etiolation, and we infer that cytokinin itself or a cytokinin-mediated process is involved in regulation of etiolation. The map location, phenotypes and de-etiolation responses in the amp1 mutant are different from those of previously described de-etiolated mutants such as det1, det2, cop1 and cop9. We propose a model in which cytokinin acts as a component of the induction of photomorphogenic processes via a signal transduction pathway which is independent of light.

Effects of betaine on body composition, performance, and homocysteine thiolactone.

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.