A Cross-Sectional Analysis of Whole Blood Long-Chain ω-3 Polyunsaturated Fatty Acids and Its Relationship with Dietary Intake, Body Composition, and Measures of Strength and Power in Collegiate Athletes.

ObjectiveLong-chain omega-3 polyunsaturated fatty acids (LC ω-3 PUFAs), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), have received widespread interest from the athletic community for their potential roles in physical performance and recovery. The purpose of this cross-sectional analysis was to evaluate the dietary intake and whole blood ω-3 PUFAs and their relationship with body composition, strength, and power in collegiate athletes.MethodThirty-six athletes completed a dual energy x-ray absorptiometry scan for body composition analysis (n = 35), ω-3 PUFAs food frequency questionnaire (n = 27), provided dried blood spot samples (n = 30) to quantify the Omega-3 Index (O3I) and total ω-3 PUFAs content, handgrip strength (n = 17), and countermovement jump (n = 26) testing.ResultsThe mean daily intake of LC ω-3 PUFAs and O3I was 140 mg and 4.6% ± 0.96, respectively, for all athletes. Dietary LC ω-3 PUFAs were positively correlated with the O3I (r = 0.635, p < .01), whole blood EPA (r = 0.778, p < .01), and DHA (r = 0.515, p < .01). Dietary LC ω-3 PUFA intake, whole blood EPA (%), and the EPA:AA ratio was positively associated with HGS (p < .05). Dietary or blood LC ω-3 PUFAs were not correlated with any other measures.Conclusions:Collegiate athletes consume low amounts of LC ω-3 PUFAs and have sub-optimal O3I status. Sports dietitians should encourage the intake of fatty fish and educate athletes about ω-3 PUFAs potential role on performance- and recovery-based outcomes.

MitoQ supplementation augments acute exercise-induced increases in muscle PGC1α mRNA and improves training-induced increases in peak power independent of mitochondrial content and function in untrained middle-aged men.

The role of mitochondrial ROS in signalling muscle adaptations to exercise training has not been explored in detail. We investigated the effect of supplementation with the mitochondria-targeted antioxidant MitoQ on a) the skeletal muscle mitochondrial and antioxidant gene transcriptional response to acute high-intensity exercise and b) skeletal muscle mitochondrial content and function following exercise training. In a randomised, double-blind, placebo-controlled, parallel design study, 23 untrained men (age: 44 ± 7 years, VO2peak: 39.6 ± 7.9 ml/kg/min) were randomised to receive either MitoQ (20 mg/d) or a placebo for 10 days before completing a bout of high-intensity interval exercise (cycle ergometer, 10 × 60 s at VO2peak workload with 75 s rest). Blood samples and vastus lateralis muscle biopsies were collected before exercise and immediately and 3 h after exercise. Participants then completed high-intensity interval training (HIIT; 3 sessions per week for 3 weeks) and another blood sample and muscle biopsy were collected. There was no effect of acute exercise or MitoQ on systemic (plasma protein carbonyls and reduced glutathione) or skeletal muscle (mtDNA damage and 4-HNE) oxidative stress biomarkers. Acute exercise-induced increases in skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) mRNA expression were augmented in the MitoQ group. Despite this, training-induced increases in skeletal muscle mitochondrial content were similar between groups. HIIT-induced increases in VO2peak and 20 km time trial performance were also similar between groups while training-induced increases in peak power achieved during the VO2peak test were augmented in the MitoQ group. These data suggest that training-induced increases in peak power are enhanced following MitoQ supplementation, which may be related to the augmentation of skeletal muscle PGC1α expression following acute exercise. However, these effects do not appear to be related to an effect of MitoQ supplementation on exercise-induced oxidative stress or training-induced mitochondrial biogenesis in skeletal muscle.

Mitochondria-targeted antioxidant supplementation does not affect muscle soreness or recovery of maximal voluntary isometric contraction force following muscle-damaging exercise in untrained men: a randomized clinical trial.

Unaccustomed exercise causes muscle damage resulting in loss of muscle function, which may be attributable to exercise-induced increases in skeletal muscle reactive oxygen species. This study examined the effect of mitochondria-targeted antioxidant supplementation on recovery of muscle function following exercise. Thirty-two untrained men received MitoQ (20 mg/day) or a placebo for 14 days before performing  300 maximal eccentric contractions of the knee extensor muscles of 1 leg. Muscle function was assessed using isokinetic dynamometry before, immediately after, and 24, 48, 72, and 168 hours after exercise. Muscle soreness was assessed using a visual analogue scale 24, 48, 72, and 168 hours after exercise. Blood samples were collected before, immediately after, and 2, 24, 48, 72, and 168 hours after exercise and urine samples were collected before and during the 48 hours after exercise. The reduction in maximal voluntary isometric contraction force and peak concentric torque following exercise was unaffected by MitoQ while recovery of peak eccentric torque was delayed in the MitoQ group. Exercise-induced increases in urine F2-isoprostanes were unaffected by MitoQ. MitoQ augmented exercise-induced increases in plasma creatine kinase levels, while plasma IL-6 was similar between groups. Muscle soreness was not affected by MitoQ. These results indicate that MitoQ does not attenuate post-exercise muscle soreness and may delay recovery of muscle function following eccentric exercise. Trial registration number: ACTRN12620001089921. Novelty: Post-exercise recovery of maximal voluntary isometric contraction force and peak concentric torque were unaffected by MitoQ. MitoQ delayed post-exercise recovery of peak eccentric torque. Post-exercise muscle soreness was unaffected by MitoQ.

Mitochondria-targeted antioxidant supplementation improves 8 km time trial performance in middle-aged trained male cyclists.

BACKGROUND: Exercise increases skeletal muscle reactive oxygen species (ROS) production, which may contribute to the onset of muscular fatigue and impair athletic performance. Mitochondria-targeted antioxidants such as MitoQ, which contains a ubiquinone moiety and is targeted to mitochondria through the addition of a lipophilic triphenylphosphonium cation, are becoming popular amongst active individuals as they are designed to accumulate within mitochondria and may provide targeted protection against exercise-induced oxidative stress. However, the effect of MitoQ supplementation on cycling performance is currently unknown. Here, we investigate whether MitoQ supplementation can improve cycling performance measured as time to complete an 8 km time trial. METHOD: In a randomized, double-blind, placebo-controlled crossover study, 19 middle-aged (age: 44 ± 4 years) recreationally trained (VO2peak: 58.5 ± 6.2 ml·kg- 1·min- 1, distance cycled per week during 6 months prior to study enrollment: 158.3 ± 58.4 km) male cyclists completed 45 min cycling at 70% VO2peak followed by an 8 km time trial after 28 days of supplementation with MitoQ (20 mg·day- 1) and a placebo. Free F2-isoprostanes were measured in plasma samples collected at rest, after 45 min cycling at 70% VO2peak and after completion of the time trial. Respiratory gases and measures of rating of perceived exertion (RPE) were also collected. RESULTS: Mean completion time for the time trial was 1.3% faster with MitoQ (12.91 ± 0.94 min) compared to placebo (13.09 ± 0.95 min, p = 0.04, 95% CI [0.05, 2.64], d = 0.2). There was no difference in RPE during the time trial between conditions (p = 0.82) despite there being a 4.4% increase in average power output during the time trial following MitoQ supplementation compared to placebo (placebo; 270 ± 51 W, MitoQ; 280 ± 53 W, p = 0.04, 95% CI [0.49, 8.22], d = 0.2). Plasma F2-isoprostanes were lower on completion of the time trial following MitoQ supplementation (35.89 ± 13.6 pg·ml- 1) compared to placebo (44.7 ± 16.9 pg·ml- 1 p = 0.03). CONCLUSION: These data suggest that MitoQ supplementation may be an effective nutritional strategy to attenuate exercise-induced increases in oxidative damage to lipids and improve cycling performance.

Cognitive behavioral therapy for the treatment of chronic pelvic pain.

Chronic pelvic pain (CPP) in women is defined as noncyclical and persistent pain lasting more than six months perceived to be related to the pelvis. There are many etiologies that can cause CPP, including gynecologic, urologic, gastrointestinal, musculoskeletal, neurologic, and psychosocial. There is a strong association between psychological factors and CPP. It has been noted that almost half of women being treated for CPP report a history of sexual, physical, or emotional trauma. Women with CPP have been noted to have higher rates of psychological disorders in comparison to their peers. For men, the most common etiology for CPP is chronic prostatitis and there are also correlations with psychological disorders. There are many different treatment options for CPP: surgical, pharmacological, and non-pharmacological (alternative therapies). Cognitive-behavioral therapy may be another option when treating chronic pelvic pain syndrome and should be considered.

Folic Acid Supplementation in Patients with Elevated Homocysteine Levels.

INTRODUCTION: Folic acid is the most important dietary determinant of homocysteine (Hcy). Hcy serves as a critical intermediate in methylation reactions. It is created from methionine and either converted back to methionine or transformed into cysteine. This process is aided through several enzymes and three vitamins, folic acid, B12, and B6. Daily supplementation with 0.5-5.0 mg of folic acid typically lowers plasma Hcy levels by approximately 25%. Hyperhomocysteinemia is a known risk factor for coronary artery disease. In this regard, elevated levels of Hcy have been found in a majority of patients with vascular disease. METHODS: A literature review of folic acid supplementation for various disease states including cardiovascular disease was conducted. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. RESULTS: In this review, we discuss the biochemistry of folic acid, Hcy biosynthesis, Hcy and hydrogen sulfide bioavailability, pathogenesis of hyperhomocysteinemia and its role as a risk factor for disease, and treatment studies with folic acid supplementation in disease states. CONCLUSION: Folic acid supplementation should be recommended to any patient who has an elevated Hcy level, and this level should be measured and treated at an early age, since folic acid is easily obtained and may likely reduce vascular disease and other deleterious pathologic processes in high-risk populations.

Subcutaneous maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe and increases fetal but not cardiac growth.

KEY POINTS: Substrate restriction during critical developmental windows of gestation programmes offspring for a predisposition towards cardiovascular disease in adult life. This study aimed to determine the effect of maternal resveratrol (RSV) treatment in an animal model in which chronic fetal catheterisation is possible and the timing of organ maturation reflects that of the human. Maternal RSV treatment increased uterine artery blood flow, fetal oxygenation and fetal weight. RSV was not detectable in the fetal circulation, indicating that it may not cross the sheep placenta. This study highlights RSV as a possible intervention to restore fetal substrate supply in pregnancies affected by placental insufficiency. ABSTRACT: Suboptimal in utero environments with reduced substrate supply during critical developmental windows of gestation predispose offspring to non-communicable diseases such as cardiovascular disease (CVD). Improving fetal substrate supply in these pregnancies may ameliorate the predisposition these offspring have toward adult-onset CVD. This study aimed to determine the effect of maternal resveratrol (RSV) supplementation on uterine artery blood flow and the direct effects of RSV on the fetal heart in a chronically catheterised sheep model of human pregnancy. Maternal RSV treatment significantly increased uterine artery blood flow as measured by phase contrast magnetic resonance imaging, mean gestational fetal PaO2 and SaO2 as well as fetal weight. RSV was not detectable in the fetal circulation, and mRNA and protein expression of the histone/protein deacetylase SIRT1 did not differ between treatment groups. No effect of maternal RSV supplementation on AKT/mTOR or CAMKII signalling in the fetal left ventricle was observed. Maternal RSV supplementation is capable of increasing fetal oxygenation and growth in an animal model in which cardiac development parallels that of the human.

Oncologic Outcomes of Definitive Treatments for Low- and Intermediate-Risk Prostate Cancer After a Period of Active Surveillance.

BACKGROUND: To compare oncologic outcomes of different definitive treatment (DT) modalities in a cohort of patients with prostate cancer (PCa) after active surveillance (AS). METHODS: We identified 237 patients with National Comprehensive Cancer Network (NCCN) low- and intermediate-risk prostate cancer diagnosed from 1990 to 2012 who did not undergo immediate DT within 12 months of diagnosis (ie, AS patients as well as watchful waiting and those refusing DT). Charts were examined for clinical/pathologic data and type of DT: surgery (RP), radiation including brachytherapy (XRT), cryotherapy, and androgen deprivation therapy monotherapy (ADT). The impact of DT on oncologic outcomes of biochemical recurrence (BCR), metastasis, disease-specific (DSS), and overall survival (OS) was examined with the Cox proportional hazards model, along with the Kaplan-Meier method and log-rank test. RESULTS: After median time on AS of 63.4 months, 40% of patients underwent DT: 47% XRT, 28% RP, 14% ADT, and 11% cryotherapy. On multivariable analysis, the use of XRT predicted higher BCR (hazard ratio [HR] 6.1, P = .001) and worse overall mortality (HR 2.1, P = .03) compared with other treatments, controlling for age, Charlson Comorbidity Index (CCI), stage, Gleason score, and NCCN risk category. Median follow-up was 71.7 months. On Kaplan-Meier analysis, 10-year OS was superior for RP versus XRT among patients with prostatic specific antigen (PSA) velocity >2.0 ng/mL/y. CONCLUSIONS: Low- and intermediate-risk patients with PCa who progress to DT after AS may be inadequately treated with radiation therapy compared with other DT modalities, especially when pretreatment PSA velocity is > 2 ng/mL/y.

Maternal conjugated linoleic acid supplementation reverses high-fat diet-induced skeletal muscle atrophy and inflammation in adult male rat offspring.

A high-saturated-fat diet (HFD) during pregnancy and lactation leads to metabolic disorders in offspring concomitant with increased adiposity and a proinflammatory phenotype in later life. During the fetal period, the impact of maternal diet on skeletal muscle development is poorly described, despite this tissue exerting a major influence on life-long metabolic health. This study investigated the effect of a maternal HFD on skeletal muscle anabolic, catabolic, and inflammatory signaling in adult rat offspring. Furthermore, the actions of maternal-supplemented conjugated linoleic acid (CLA) on these measures of muscle phenotype were investigated. A purified control diet (CD; 10% kcal fat), a CD supplemented with CLA (CLA; 10% kcal fat, 1% total fat as CLA), a high-fat (HFD; 45% kcal fat from lard), or a HFD supplemented with CLA (HFCLA; 45% kcal fat from lard, 1% total fat as CLA) was fed ad libitum to female Sprague-Dawley rats for 10 days before mating and throughout gestation and lactation. Male offspring received a standard chow diet from weaning, and the gastrocnemius was collected for analysis at day 150. Offspring from HF and HFCLA mothers displayed lower muscular protein content accompanied by elevated monocyte chemotactic protein-1, IL-6, and IL-1ß concentrations. Phosphorylation of NF-κBp65 (Ser(536)) and expression of the catabolic E3 ligase muscle ring finger 1 (MuRF1) were increased in HF offspring, an effect reversed by maternal CLA supplementation. The present study demonstrates the importance of early life interventions to ameliorate the negative effects of poor maternal diet on offspring skeletal muscle development.

National assessment of margin status as a quality indicator after pancreatic cancer surgery.

BACKGROUND: Surgical margin involvement is an important outcome after pancreatic cancer surgery; however, variation in pathologic review practices may limit its use as a quality indicator. Our objectives were to assess variation in hospital performance and the reliability of margin involvement after pancreatic cancer surgery. METHODS: From the National Cancer Data Base, patients who underwent pancreatic resection for stage I to III adenocarcinoma were identified. Risk-adjusted surgical margin involvement was evaluated using hierarchical regression methods, and variation in hospital performance and reliability was determined. RESULTS: From 1,002 hospitals, 14,889 patients underwent pancreatic resection for adenocarcinoma, and 3,573 (24.0 %) had an involved surgical margin (R1 22.8 %; R2 1.2 %). The strongest predictors associated with margin involvement were T stage [T3: odds ratio (OR) 2.08, 95 % confidence interval (CI) 1.68-2.59; T4: OR 7.26, 95 % CI 5.50-9.60; vs. T1] and tumor size (2-3.9 cm: OR 1.66, 95 % CI 1.39-1.98, ≥ 4 cm: OR 2.28, 95 % CI 1.90-2.74; vs. <2 cm). Factors associated with a decreased likelihood of margin involvement were the use of neoadjuvant therapy and hospital type (academic and National Cancer Institute-designated comprehensive cancer centers vs. community). At the hospital level, the mean risk-adjusted surgical margin involvement rate was 25.9 % and ranged 10.1 to 50.5 %. Twenty-one (2.1 %) hospitals had lower-than-expected and 17 (1.7 %) had higher-than-expected margin involvement. A minimum acceptable reliability of 0.4 was met after 13 cases and was achieved by 249 hospitals that performed 79 % of pancreatic resections assessed. CONCLUSIONS: Despite differences in pathologic evaluation practices, hospitals can be feasibly and reliably provided comparative data on surgical margin status after resection for pancreatic cancer.

Supportive care considerations during concurrent chemoradiotherapy for pancreatic adenocarcinoma: lessons learned from clinical experience.

Concurrent chemotherapy and radiotherapy (chemoradiotherapy) for the management of pancreatic adenocarcinoma in either adjuvant or locally regional advanced settings produces predictable acute toxicities that are proportional in severity to the intensity and type of systemic therapy and to the parameters of radiotherapy. In addition, relevant to the adjuvant setting, surgery for pancreatic cancer often produces physiologic alterations that may impact a patient's ability to tolerate chemoradiotherapy. Failures to anticipate, monitor, and proactively manage the effects of surgery and toxicities of chemoradiotherapy can result in the need for unplanned treatment interruptions and/or inability to complete all planned therapy. In this review, complications of pancreatic cancer itself and of pancreatic resection as well as toxicities of chemoradiotherapy are delineated, and approaches to their management before, during, and after chemoradiotherapy are presented. Planning for the treatment of side effects before the anticancer therapy begins facilitates therapy administration and improves patient tolerance.

Comparing phosphorus indices from twelve southern U.S. states against monitored phosphorus loads from six prior southern studies.

Forty-eight states in the United States use phosphorus (P) indices to meet the requirements of their Natural Resources Conservation Service (NRCS) Code 590 Standard, which provides national guidance for nutrient management of agricultural lands. The majority of states developed these indices without consultation or coordination with neighboring states to meet specific local conditions and policy needs. Using water quality and land treatment data from six previously published articles, we compared P loads with P-Index values and ratings using the 12 southern P indices. When total measured P loads were regressed with P-Index rating values, moderate to very strong relationships (0.50 to 0.97) existed for five indices (Arkansas, Florida, Georgia, North Carolina, and South Carolina) and all but one index was directionally correct. Regressions with dissolved P were also moderate to very strong ( of 0.55 to 0.95) for the same five state P indices (Arkansas, Florida, Georgia, North Carolina, and South Carolina); directionality of the Alabama Index was negative. When total measured P loads were transformed to current NRCS 590 Standard ratings (Low [<2.2 kg P ha], Moderate, [2.2-5.5 kg P ha], and High [>5.5 kg P ha]) and these ratings were then compared to the southern-Index ratings, many of the P indices correctly identified Low losses (77%), but most did not correctly identify Moderate or High loss situations (14 and 31%, respectively). This study demonstrates that while many of the P indices were directionally correct relative to the measured water quality data, there is a large variability among southern P indices that may result in different P management strategies being employed under similar conditions.

Steroidogenic enzyme histochemistry in the testis of Sprague Dawley rats following the administration the water extracts from Carica papaya seed.

Water extracts from pawpaw seed have been reported to reversibly decrease the testicular weight and to suppress spermatogenesis, and fertility of Wistar rats. The reversible changes become evident, 30 - 45 days after the withdrawal of the extract. The possible effect of this extract on the activities of steroidogenic enzymes of the testis has not been investigated. Water extract of papaya seeds was administered to male Sprague Dawley rats ad libitum for 84 days. Following the discontinuation of the extracts, ten rats each were sacrificed on days 0, 10, 20 and 30 after the withdrawal. Their testes were quickly dissected out and frozen. Cryostat sections, 10µm thick were cut. These sections were used for immunohistochemical stains for side chain cleavage enzyme and aromatase, and for histochemical stains for 17-ß Hydroxysteroid dehydrogenase, 3-ß Hydroxysteroid dehydrogenase. We conclude that the water extract of papaya seed suppresses the activities of steroidogenic enzymes in the testis of Sprague Dawley rats, and that this may contribute to reversible suppression of spermatogenesis, a property that gives a possible male contraceptive potential.

Expression of ZmLEC1 and ZmWRI1 increases seed oil production in maize.

Increasing seed oil production is a major goal for global agriculture to meet the strong demand for oil consumption by humans and for biodiesel production. Previous studies to increase oil synthesis in plants have focused mainly on manipulation of oil pathway genes. As an alternative to single-enzyme approaches, transcription factors provide an attractive solution for altering complex traits, with the caveat that transcription factors may face the challenge of undesirable pleiotropic effects. Here, we report that overexpression of maize (Zea mays) LEAFY COTYLEDON1 (ZmLEC1) increases seed oil by as much as 48% but reduces seed germination and leaf growth in maize. To uncouple oil increase from the undesirable agronomic traits, we identified a LEC1 downstream transcription factor, maize WRINKLED1 (ZmWRI1). Overexpression of ZmWRI1 results in an oil increase similar to overexpression of ZmLEC1 without affecting germination, seedling growth, or grain yield. These results emphasize the importance of field testing for developing a commercial high-oil product and highlight ZmWRI1 as a promising target for increasing oil production in crops.

Impact of ambient bright light on agitation in dementia.

OBJECTIVE: To evaluate the effect of ambient bright light therapy (BLT) on agitation among institutionalized persons with dementia. METHODS: High intensity, low glare ambient lighting was installed in activity and dining areas of a state psychiatric hospital unit in North Carolina and a dementia-specific residential care facility in Oregon. The study employed a cluster-unit crossover design involving four ambient lighting conditions: AM bright light, PM bright light, All Day bright light, and Standard light. Sixty-six older persons with dementia participated. Outcome measures included direct observation by research personnel and completion by staff caregivers of the 14-item, short form of the Cohen-Mansfield Agitation Inventory (CMAI). RESULTS: Analyses of observational data revealed that for participants with mild/moderate dementia, agitation was higher under AM light (p = 0.003), PM light (p < 0.001), and All Day light (p = 0.001) than Standard light. There was also a trend toward severely demented participants being more agitated during AM light than Standard light (p = 0.053). Analysis of CMAI data identified differing responses by site: the North Carolina site significantly increased agitation under AM light (p = 0.002) and PM light (p = 0.013) compared with All Day light while in Oregon, agitation was higher for All Day light compared to AM light (p = 0.030). In no comparison was agitation significantly lower under any therapeutic condition, in comparison to Standard lighting. CONCLUSIONS: Ambient bright light is not effective in reducing agitation in dementia and may exacerbate this behavioral symptom.

Acute toxicity of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) in male Sprague-Dawley rats: effects on hepatic oxidative stress, glutathione and metals status.

Although polychlorinated biphenyl (PCBs) production, and new uses for PCBs, was halted in the 1970s in the United States, PCBs continue to be used in closed systems and persist in the environment, accumulating in fatty tissues. PCBs are efficacious inducers of drug metabolism and may increase oxidative events and alter many other biochemical and morphologic parameters within cells and tissues. The goal of the present study was to evaluate the effects of a single, very low dose of PCB 126 (3,3',4,4',5-pentachlorobiphenyl), a coplanar, dioxin-like PCB congener and aryl hydrocarbon receptor (AhR) agonist, on redox status, metals homeostasis, antioxidant enzymes, and cellular morphology. To examine these parameters, male Sprague-Dawley rats were fed a purified AIN-93 basal diet containing 0.2 ppm selenium for two weeks, then administered a single i.p. injection of corn oil (5 ml/kg body weight) or 1µmol PCB 126/kg body weight (326µg/kg body weight) in corn oil. Rats were maintained on the diet for an additional two weeks before being euthanized. This dose of PCB 126 did not alter feed intake or growth, but significantly increased liver weight (42%) and hepatic microsomal cytochrome P-450 (CYP1A) enzyme activities (10-40-fold increase). Hepatic zinc, selenium, and glutathione levels were significantly decreased 15%, 30%, and 20%, respectively, by PCB 126. These changes were accompanied by a 60% decrease in selenium-dependent glutathione peroxidase activity. In contrast, hepatic copper levels were increased 40% by PCB 126. PCB 126-induced pathology was characterized by hepatocellular hypertrophy and mild steatosis in the liver and a mild decrease in cortical T-cells in the thymus. This controlled study in rats fed a purified diet shows that even a single, very low dose of PCB 126 that did not alter feed intake or growth, significantly perturbed redox and metals homeostasis and antioxidant and enzyme levels in rodent liver.

Impact of a standard medication chart on prescribing errors: a before-and-after audit.

OBJECTIVES: (1) To develop and implement a standard medication chart, for recording prescribing (medication orders) and administration of medication in public hospitals in Queensland. (2) To assess the chart's impact on the frequency and type of prescribing errors, adverse drug reaction (ADR) documentation and safety of warfarin prescribing. (3) To use the chart to facilitate safe medication management training. DESIGN, SETTING AND PARTICIPANTS: The medication chart was developed through a process of incident analysis and work practice mapping by a multidisciplinary collaborative. Observational audits by nurse and pharmacist pairs, of all available prescriptions before and after introduction of the standard medication chart, were undertaken in five sites. RESULTS: Similar numbers of both patients (730 pre-implementation and 751 post-implementation; orders, 9772 before and 10 352 after) were observed. The prescribing error rate decreased from 20.0% of orders per patient before to 15.8% after (Mann-Whitney U test, p = 0.03). Previous ADRs were not documented for 19.5% of 185 patients before and 11.2% of 197 patients after (chi(2), p = 0.032). Prescribing errors involving selection of a drug to which a patient had had a previous ADR decreased from 11.3% of patients before to 4.6% after (chi(2), p = 0.021). International normalised ratios (INRs) >5 decreased from 1.9% of 14 405 INRs in the 12 months before to 1.45% of 15 090 INRs after (chi(2), p = 0.004). After minor modifications, the chart was introduced into all hospitals statewide, which enabled standardised medication training and safer rotation of staff. The chart also formed the basis for the National Inpatient Medication Chart. CONCLUSION: Introduction of a standard revised medication chart significantly reduced the frequency of prescribing errors, improved ADR documentation and decreased the potential risks associated with warfarin management. The standard chart has enabled uniform training in medicine management.

Zyflamend in men with high-grade prostatic intraepithelial neoplasia: results of a phase I clinical trial.

Subjects diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN) at biopsy are at increased risk for developing prostate cancer (CaP). A prospective clinical trial was done to determine the safety and tolerability of a novel herbal amalgam, Zyflamend (New Chapter, Inc., Brattleboro, VT), with various dietary supplements in subjects with HGPIN. Men ages 40 to 75 years with HGPIN were eligible. Subjects were evaluated for 18 months. Every 3 months, standard blood chemistries and prostate-specific antigen (PSA) were monitored. Rebiopsy was done every 6 months. Tissue was evaluated for HGPIN or CaP and stained for cyclooxygenase-2, nuclear factor kappaB (NF-kappaB), interleukin-6, and thromboxane. Twenty-three subjects were evaluable. The median age was 64.1 years (range 46-75 years), and the mean (+/- SD) PSA level was 6.13 +/- 3.56 ng/mL. Side effects, when present, were mild and gastrointestinal in nature. There were no reported serious adverse events or toxicities. No significant changes in blood chemistries, testosterone, or cardiac function were noted. Forty-eight percent of subjects demonstrated a 25 to 50% decrease in PSA after 18 months. Of subjects who had the 18-month biopsy, 60% (9 of 15) had benign tissue, 26.7% (4 of 15) had HGPIN in one core, and 13.3% (2 of 15) had CaP at 18 months. A reduction in serum C-reactive protein was observed (95% confidence interval [CI] 0.7-1.7, p = .045). Immunoreactive staining demonstrated a reduction in NF-kappaB in the 18-month samples (95% CI 0.8-3.0, p = .017). Zyflamend alone and in combination with various dietary supplements is associated with minimal toxicity and no serious adverse events when administered orally for 18 months. Further studies are warranted to evaluate these agents in patients who are at risk for CaP.

A phenylalanine in DGAT is a key determinant of oil content and composition in maize.

Plant oil is an important renewable resource for biodiesel production and for dietary consumption by humans and livestock. Through genetic mapping of the oil trait in plants, studies have reported multiple quantitative trait loci (QTLs) with small effects, but the molecular basis of oil QTLs remains largely unknown. Here we show that a high-oil QTL (qHO6) affecting maize seed oil and oleic-acid contents encodes an acyl-CoA:diacylglycerol acyltransferase (DGAT1-2), which catalyzes the final step of oil synthesis. We further show that a phenylalanine insertion in DGAT1-2 at position 469 (F469) is responsible for the increased oil and oleic-acid contents. The DGAT1-2 allele with F469 is ancestral, whereas the allele without F469 is a more recent mutant selected by domestication or breeding. Ectopic expression of the high-oil DGAT1-2 allele increases oil and oleic-acid contents by up to 41% and 107%, respectively. This work provides insights into the molecular basis of natural variation of oil and oleic-acid contents in plants and highlights DGAT as a promising target for increasing oil and oleic-acid contents in other crops.

Transgenic maize plants expressing a fungal phytase gene.

Maize seeds are the major ingredient of commercial pig and poultry feed. Phosphorus in maize seeds exists predominantly in the form of phytate. Phytate phosphorus is not available to monogastric animals and phosphate supplementation is required for optimal animal growth. Undigested phytate in animal manure is considered a major source of phosphorus pollution to the environment from agricultural production. Microbial phytase produced by fermentation as a feed additive is widely used to manage the nutritional and environmental problems caused by phytate, but the approach is associated with production costs for the enzyme and requirement of special cares in feed processing and diet formulation. An alternative approach would be to produce plant seeds that contain high phytase activities. We have over-expressed Aspergillus niger phyA2 gene in maize seeds using a construct driven by the maize embryo-specific globulin-1 promoter. Low-copy-number transgenic lines with simple integration patterns were identified. Western-blot analysis showed that the maize-expressed phytase protein was smaller than that expressed in yeast, apparently due to different glycosylation. Phytase activity in transgenic maize seeds reached approximately 2,200 units per kg seed, about a 50-fold increase compared to non-transgenic maize seeds. The phytase expression was stable across four generations. The transgenic seeds germinated normally. Our results show that the phytase expression lines can be used for development of new maize hybrids to improve phosphorus availability and reduce the impact of animal production on the environment.