The link between workforce health and safety and the health of the bottom line: tracking market performance of companies that nurture a "culture of health".

OBJECTIVE: To test the hypothesis that comprehensive efforts to reduce a workforce's health and safety risks can be associated with a company's stock market performance. METHODS: Stock market performance of Corporate Health Achievement Award winners was tracked under four different scenarios using simulation and past market performance. RESULTS: A portfolio of companies recognized as award winning for their approach to the health and safety of their workforce outperformed the market. Evidence seems to support that building cultures of health and safety provides a competitive advantage in the marketplace. This research may have also identified an association between companies that focus on health and safety and companies that manage other aspects of their business equally well. CONCLUSIONS: Companies that build a culture of health by focusing on the well-being and safety of their workforce yield greater value for their investors.

Adolescents' fMRI activation to a response inhibition task predicts future substance use.

BACKGROUND: Deficient behavioral regulation may be a risk factor for substance use disorders in adolescents. Abnormalities in brain regions critical to cognitive control have been linked to more intense and problematic future substance use (e.g., Durazzo, Gazdzinski, Mon, & Meyerhoff, 2010; Falk, Berkman, Whalen, & Lieberman, 2011; Paulus, Tapert, & Schuckit, 2005). The goal of this study was to examine the degree to which brain response to an inhibition task measured in mid-adolescence can predict substance use 18 months later. METHOD: Adolescents aged 16-19 (N=80) performed a go/no-go response inhibition task during fMRI at project baseline, and were followed 18 months later with a detailed interview on substance use and dependence symptoms. Participants were 39 high frequency users and 41 demographically similar low frequency users (458 versus 2 average lifetime drug use occasions at baseline, respectively). RESULTS: Across all subjects, no-go trials produced significant increases in neural response in the ventromedial prefrontal cortex and a region including the left angular and supramarginal gyri (p(FWE)<.01, cluster threshold ≥ 30 voxels). Less ventromedial prefrontal activation but more left angular gyrus activation predicted higher levels of substance use and dependence symptoms in the following 18 months, particularly for those who were high frequency users in mid-adolescence (p<.05). CONCLUSIONS: These findings are consistent with studies showing that impairments in cognitive control have strong associations with substance use. We found a predictive relationship between atypical activation patterns at baseline and substance use behavior 18 months later, particularly among adolescents with histories of previous heavy use.

Altered metabolism and mitochondrial genome in prostate cancer.

Mutations in mitochondrial DNA are frequent in cancer and the accompanying mitochondrial dysfunction and altered intermediary metabolism might contribute to, or signal, tumour pathogenesis. The metabolism of human prostate peripheral zone glandular epithelial cells is unique. Compared with many other soft tissues, these glandular epithelial cells accumulate high concentrations of zinc, which inhibits the activity of m-aconitase, an enzyme involved in citrate metabolism through Krebs cycle. This causes Krebs cycle truncation and accumulation of high concentrations of citrate to be secreted in prostatic fluid. The accumulation of zinc also inhibits terminal oxidation. Therefore, these cells exhibit inefficient energy production. In contrast, malignant transformation of the prostate is associated with an early metabolic switch, leading to decreased zinc accumulation and increased citrate oxidation. The efficient energy production in these transformed cells implies increased electron transport chain activity, increased oxygen consumption, and perhaps, excess reactive oxygen species (ROS) production compared with normal prostate epithelial cells. Because ROS have deleterious effects on DNA, proteins, and lipids, the altered intermediary metabolism may be linked with ROS production and accelerated mitochondrial DNA mutations in prostate cancer.

The incidence of hematuria in middle distance track running.

The purpose of this study was to establish if middle distance track athletes experience hematuria during their competitive season interval workouts and, if so, what type of workout based on intensity and distance was most associated with hematuria. During a 4-week observational period, athletes (n = 10) underwent reagent strip urinalysis before and after their twice weekly interval sessions. Positive samples for hematuria were analyzed microscopically to accurately determine red blood cell (RBC) loss. Seventy-one individual interval workouts were observed, of which 32 cases of hematuria were reported. Nine cases of hematuria exhibited >100 RBC per High Power Field (Hpf). Furthermore, 90% of the athletes experienced post-workout hematuria at least once. The highest incidence of hematuria was observed after workouts run at 110% of VO(2peak) over short (600-1,500 m) to moderate (1,501-3,000 m) distances. All post-exercise cases of hematuria resolved within 2 hr of recovery.

The efficacy of SPORT as a dietary supplement on performance and recovery in trained athletes.

This study investigated the efficacy of SPORT (a popular dietary supplement) in improving performance and assisting recovery in 9 trained athletes. In a double-blind, crossover experiment, subjects ran at workloads of 60 and 80% of peak oxygen uptake (Peak VO2) for 5 min each with 5 min recovery after each bout and at 100% Peak VO2 until exhaustion. Two capsules of either SPORT or a gelatin placebo were administered 1 hr prior to exercise and immediately after each workload. Heart rate (HR) and blood lactate (BLa) were measured at 1 hr prior to exercise, immediately after the 100% exercise bout and at 5, 10, 20, and 45 min during recovery. No significant differences between treatments on HR and BLa measures at any of the 6 time periods, or on subjects' time to exhaustion were found. Under the conditions of this experimental design, SPORT had no beneficial effects on performance or recovery in trained athletes.

A decade of aerobic endurance training: histological evidence for fibre type transformation.

BACKGROUND: Researchers employing a variety of training methods have demonstrated a fast-to-slow fibre transformation in animal skeletal muscle. The observation as to whether this occurs in exercise trained humans is limited and equivocal. EXPERIMENTAL DESIGN: to examine this issue, skeletal muscle from seven subjects who had participated in a decade or more of high intensity aerobic training (DT) and six nontrained (NT) subjects was obtained by muscle biopsy from the vastus lateralis muscle (VL) and subjected to a modified myofibrillar ATPase technique to identify muscle fibre types. Muscle tissue was histochemically treated by exposure to an alkaline preincubation (pH 9.9), an acid preincubation (pH 4.3 or 4.6) and the formate-KCI preincubation buffer (pH 4.54), previously employed in animal studies. RESULTS: The formate-KCl preincubation medium identified all major fibre types at a single pH in human subjects. The percentage of type I fibres in DT was 70.9% vs 37.7% in NT (p<0.01), while the type IIa fibres in DT (25.3%) was much lower (p<0.01) than NT (51.8%). Surprisingly, type IIa fibres in the DT group displayed lesser oxidative staining intensity (p<0.01) than type IIa fibres from the NT group. Mean cross-sectional area of type I fibres for DT (6233.9+/-1421.7 microm2) was greater (p<0.05) than either type I (5746.8+/-1135.2 microm2) or II (5693.5+/-1214.6 microm2) from NT. CONCLUSIONS: The results revealed that endurance training may promote a transition from type II to type I muscle fibre types and occurs at the expense of the type II fibre population.

Comparison of fructose and glucose ingestion before and during endurance cycling to exhaustion.

BACKGROUND: Pre-exercise and exercise ingestion of fructose and glucose during cycling exercise were compared. EXPERIMENTAL DESIGN: Seventeen trained subjects ingested a placebo prior to and during a cycling test to exhaustion at 75% VO2max (control group = CG). One week later, subjects were matched on exercise time to exhaustion (ETE) and assigned to a fructose group (FG) or a glucose group (GG). Subjects then performed a second cycling test to exhaustion, ingesting fructose or glucose doses. For all groups (CG, FG and GG), blood was drawn before and at timed intervals during exercise to determine glucose, lactate and free fatty acid (FFA) levels. RESULTS: The ETE for CG was less than either FG (p<0.02) or GG (p<0.001) but FG and GG were similar. FG and GG did not show any differences in blood lactate or blood FFA during the ETE. However, CG FFA levels were higher than those of FG (p<0.02) prior to exercise. CONCLUSIONS: This study demonstrated that fructose and glucose are of equal value in prolonging ETE in endurance cycling Ingesting fructose before and during exercise apparently provided a more constant supply of glucose to be available to the working muscles. The more stable blood glucose levels with fructose ingestion may be beneficial in reducing perceived exhaustion, and thereby allowing for an enhancement in exercise performance.

Cardiovascular responses to facial cooling are age and fitness dependent.

PURPOSE: Aging of the cardiovascular system may be altered by differences in physical fitness. We investigated the cardiovascular responses to brief periods of facial cooling (5 degrees C) in 20 healthy men differing in age and aerobic fitness (VO2max). METHODS: Facial cooling was administered at rest in the supine position during 60-s quiet breathing to 6 fit young (FY; VO2max = 75.8 +/- 18 mL x kg(-1) x min(-1); 29 +/- 7 yr), 6 sedentary young (SY; VO2max = 36.0 +/- 2.2 mL x kg(-1) x min(-1); 27 +/- 3 yr), 6 fit old (FO; VO2max = 56.1 +/- 4.0 mL x kg(-1) x min(-1); 54 +/- 5 yr), and 6 sedentary old (SO; VO2max = 29.6 +/- 5.0 mL x kg(-1) x min(-1); 62 +/- 2 yr) volunteers. The following were measured before and after facial cooling: heart rate (HR), mean arterial blood pressure (MAP), pressure-rate product (PRP), and M-mode echocardiographically determined left ventricular internal dimensions, peak circumferential shortening (peak V(CF)), and ejection fraction (EF). RESULTS: Facial cooling produced a statistically significant bradycardia in all groups except for the SO whereas MAP was increased in the young groups but unchanged in the older groups. Pressure-rate product was significantly reduced in the FY, unchanged in the SY and FO, and significantly increased in the SO group. None of the groups showed a change in left ventricular dimensions, whereas only the SO group showed an increase in peak V(CF) (P < 0.05). CONCLUSIONS: These data suggest that endurance training and fitness level do not significantly alter cardiovascular responses to facial cooling in young men or physically fit older men. However, in older subjects, a sedentary lifestyle appears to be associated with an absent facial cooling reflex bradycardia, an increased PRP, and contractility (peak V(CF)).

Changes in rat muscle with compensatory overload occur in a sequential manner.

The present study was initiated to determine the time course of changes in the profile of selected skeletal muscle myofibril proteins during compensatory overload. Whole muscle isometric contractile properties were measured to assess the physiological consequences of the overload stimulus. Compensatory overload of plantaris muscle of rats was induced by surgical ablation of the synergistic soleus and gastrocnemius muscles. Myosin light chain (LC) and tropomyosin (TM) compositions of control (CP) and overloaded plantaris (OP) muscles were determined by electrophoresis and myofibrillar ATPase assays were performed to assess changes in contractile protein interactions. Within one week of overload decreases in the alpha:beta TM ratio and myofibrillar ATPase activity were observed. Following 30 days of overload, a transition in type II to type I fibres was associated with an increase in slow myosin LC1. Interestingly, after 77 days of overload, the TM subunit ratio returned to one resembling a fast twitch muscle. It is proposed that the early and transitory changes in the TM subunits of OP, as well as the rapid initial depression in maximum tetanic isometric force and myofibrillar ATPase activity may be explained as a result of muscle fibre degeneration-regeneration. We propose that alterations in protein expression induced by compensatory overload reflect both degenerative-regenerative change and increased neuromuscular activity.

The effect of exercise intensity on hematuria in healthy male runners.

The purpose of this study were: (1) to establish the prevalence of exercise-induced hematuria in a group of otherwise healthy male runners (n = 70), and (2) to investigate the role of exercise intensity in those runners who exhibited exercise-related hematuria (n = 10) by evaluating the effect of running and cycling at high and low intensities. The identified and recruited subjects participated in four different exercise protocols: (1) a 60-min treadmill run (RUN) at 90% of anaerobic threshold (Th(ae)), (2) a 60-min leg cycle ergometer ride (BIKE) at 90% of Th(ae), (3) a 3x400-m sprint (SPRINT), each followed by 4 min of rest or light walking, and (4) 3x60-Wingate leg cycle ergometry tests, each followed by 4 min of rest or light cycling. The study employed a 3x4 (time by protocol) within-subjects design and dependent variables were measured before exercise, 4 min after, and 1 h after exercise, and included measurements of hematuria, proteinuria, urinary pH, serum haptoglobin concentration, serum creatine phosphokinase activity, plasma lactate concentration, and hemoglobin. The 400-m sprint at maximal effort significantly increased both hematuria and proteinuria (P<0.01). Post-exercise hematuria for the SPRINT protocol was significantly different than that for the BIKE (P<0.01) and RUN (P<0.01) protocols. Due to the significant increase in hematuria and proteinuria following the SPRINT protocol, it was concluded that exercise-related changes in renal function were associated with weight-bearing exercise intensity rather than non-weight-bearing exercise duration.

Self-regulation of mood: strategies for changing a bad mood, raising energy, and reducing tension.

Four studies evaluated the success of behaviors and strategies used to self-regulate bad moods, raise energy, and reduce tension. Study 1 (N = 102) used an open-ended questionnaire to identify behavioral categories. Studies 2 and 4 surveyed a representative sample (N = 308) with a fixed-response questionnaire to quantify behaviors, general strategies, and individual differences. Study 3 used psychotherapist (N = 26) judgments of the likely success of the strategies. Therapist and self-rating converged on success of strategies and gender differences. These studies clarify and confirm previous research findings, particularly gender differences in controlling depression. Exercise appears to be the most effective mood-regulating behavior, and the best general strategy to change a bad mood is a combination of relaxation, stress management, cognitive, and exercise techniques. Results support a 2-dimensional biopsychological model of mood.

Comparison of effects of two interval-training programmes on lactate and ventilatory thresholds.

Twenty-one women subjects were matched in terms of their Vo2max and assigned to one of two groups: (1) training at 30 s; or (2) 2 min with a 1:1 work: relief ratio (1:1 WR) before participating in a 7-week training programme which began at an intensity of 85% Vo2max and increased 5% every two weeks (90% and 95% Vo2max). The subjects trained to exhaustion four times per week. Maximal oxygen consumption (Vo2max), lactate threshold (Tlac) and ventilatory threshold (Tvent) were determined before and after the training programme. After training, there were significant increases (P < 0.05) in Vo2max (5% and 6%), Tlac (19.4% and 22.4%), and Tvent (19.5% and 18.5%). There were no significant group differences on any dependent measure but this research adds support to previous training studies in that a strong correlation (P < 0.05) between Tlac and Tvent is maintained from before to after the test. It was concluded that both formats of high intensity aerobic interval-training produce similar changes in Vo2max, Tlac and Tvent and that these changes appear to be independent of the length of the work interval.

Acute and chronic response of skeletal muscle to resistance exercise.

Skeletal muscle tissue is sensitive to the acute and chronic stresses associated with resistance training. These responses are influenced by the structure of resistance activity (i.e. frequency, load and recovery) as well as the training history of the individuals involved. There are histochemical and biochemical data which suggest that resistance training alters the expression of myosin heavy chains (MHCs). Specifically, chronic exposure to bodybuilding and power lifting type activity produces shifts towards the MHC I and IIb isoforms, respectively. However, it is not yet clear which training parameters trigger these differential expressions of MHC isoforms. Interestingly, many programmes undertaken by athletes appear to cause a shift towards the MHC I isoform. Increments in the cross-sectional area of muscle after resistance training can be primarily attributed to fibre hypertrophy. However, there may be an upper limit to this hypertrophy. Furthermore, significant fibre hypertrophy appears to follow the sequence of fast twitch fibre hypertrophy preceding slow twitch fibre hypertrophy. Whilst some indirect measures of fibre number in living humans suggest that there is no interindividual variation, postmortem evidence suggests that there is. There are also animal data arising from investigations using resistance training protocols which suggest that chronic exercise can increase fibre number. Furthermore, satellite cell activity has been linked to myotube formation in the human. However, other animal models (i.e. compensatory hypertrophy) do not support the notion of fibre hyperplasia. Even if hyperplasia does occur, its effect on the cross-sectional area of muscle appears to be small. Phosphagen and glycogen metabolism, whilst important during resistance activity appear not to normally limit the performance of resistance activity. Phosphagen and related enzyme adaptations are affected by the type, structure and duration of resistance training. Whilst endogenous glycogen reserves may be increased with prolonged training, typical isotonic training for less than 6 months does not seem to increase glycolytic enzyme activity. Lipid metabolism may be of some significance in bodybuilding type activity. Thus, not surprisingly, oxidative enzyme adaptations appear to be affected by the structure and perhaps the modality of resistance training. The dilution of mitochondrial volume and endogenous lipid densities appears mainly because of fibre hypertrophy.

LINE-1: a human transposable element.

Among the 10(5) LINE-1 sequences (L1Hs) in the human genome are one or more 6-kb segments that are active retrotransposons. Expression of these retrotransposons appears to be favored in cells of germ line origin, as well as in some other tumor cells of epithelial origin. In such cells, the product of the first L1Hs open reading frame (ORF), a protein called p40, is detectable; p40 has no apparent similarity to gag proteins, but contains a leucine zipper region which may be responsible for the occurrence of p40 multimers. Transcription of L1Hs initiates at residue 1 although the transcriptional regulatory regions are downstream in the first 670 bp of the 5' untranslated region; deletion of a YY1-binding site in the first 20 bp reduces transcription by fivefold. Translation of the second ORF, which encodes reverse transcriptase, is independent of the translation of the frame encoding p40.

Undermethylation of specific LINE-1 sequences in human cells producing a LINE-1-encoded protein.

Nucleotide sequences near the 5' ends of some long interspersed elements-1 (LINE-1) from Homo sapiens (L1Hs) are undermethylated in cell lines which produce a L1Hs-encoded protein. In contrast, these sequences are methylated in cell lines with little or no detectable L1Hs expression. The fact that the 5' end of L1Hs is differentially methylated in cells exhibiting different levels of L1Hs expression suggests that the methylation state of this region plays a role in L1Hs expression.

Binding of the ubiquitous nuclear transcription factor YY1 to a cis regulatory sequence in the human LINE-1 transposable element.

The first step of the currently favored model for the mechanism of transposition of the human LINE-1 element involves the synthesis of full length LINE-1 mRNA. Previous work demonstrated that the 5'-terminal 100 base pairs of the human LINE-1 element (L1Hs) has an important role in regulating it's expression. Here we report further deletion analysis revealing the presence of a cis regulatory element overlapping the region between base pairs +12 and +18. Oligonucleotides containing this sequence form a specific complex with a nuclear protein extracted from NTera2D1 and Jurkat cells, and with recombinant YY1 produced in E. coli. The complex is competed by YY1 binding sites found in other genes, and is ablated by anti-YY1 serum. These results suggest that YY1 is involved in the regulation of L1Hs transcription and therefore transposition.

Anticonvulsant activities of some arylsemicarbazones displaying potent oral activity in the maximal electroshock screen in rats accompanied by high protection indices.

Various semicarbazones derived from aryl aldehydes, phenylalkyl aldehydes, and phenylalkyl ketones as well as some related compounds were evaluated for anticonvulsant activity. Most of the compounds displayed anticonvulsant activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens accompanied by neurotoxicity when given to mice by the intraperitoneal route. However quantitative data revealed protection indices (TD50/ED50) of less than 4 in general. Oral administration of the compounds to rats led to excellent potency in the MES screen accompanied by high protection indices while virtually no activity in the scPTZ test was displayed. These observations support the theory that one large hydrophobic group (in this case the aryl ring) and two electron donor atoms (present in the semicarbazono group) are requirements for protection in the MES screen. In general, the semicarbazones had rapid onsets of action, and one of the ways in which these compounds displayed their anticonvulsant activity is likely to be interaction with chloride channels. Empirical and semiempirical conformational calculations indicated that certain molecular fragments and hydrophobicity of these molecules affect bioactivity.

Effect of intron A from human cytomegalovirus (Towne) immediate-early gene on heterologous expression in mammalian cells.

A 2.4 kb fragment of hCMV (Towne strain), containing the 5' end of the major immediate-early gene, has been cloned, sequenced, and used to construct a series of mammalian cell expression plasmids. The effects of regulatory regions present on this fragment were assessed using human glycoproteins as reporter molecules. We compared secreted levels of Factor VIII, t-PA, and HIV-1 envelope glycoproteins in cells transfected with plasmids in which intron A of the immediate-early gene was present or absent. Secretion of several glycoproteins was significantly higher when cells were transfected with intron A-containing plasmids. Mutation of three basepairs in the strong nuclear factor 1 (NF1) binding site in intron A led to reduced transient expression levels, but not to the level observed in the absence of intron A. Reduced expression from NF1 mutant plasmids was roughly correlated with reduced binding in vitro of NF1 proteins to a synthetic oligonucleotide containing the mutation. The evidence indicates that sequences in intron A positively regulate expression from the hCMV immediate-early enhancer/promoter in transformed monkey kidney cells.

Acute and chronic responses of skeletal muscle to endurance and sprint exercise. A review.

Skeletal muscle adapts to the stress of endurance and sprint exercise and training. There are 2 main types of skeletal muscle fibre--slow twitch (ST) and fast twitch (FTa, FTb, FTc). Exercise may produce transitions between FT and ST fibres. Sprint training has decreased the proportion of ST fibres and significantly increased the proportion of FTa fibres, while endurance training may convert FTb to FTa fibres, and increase the proportion of ST fibres (i.e. FTb----FTa----FTc----ST). However, the high proportion of ST fibres documented for elite endurance athletes may be simply the result of natural selection. ST fibres function predominantly during submaximal exercise, whereas FT fibres are recruited as exercise intensity approaches VO2max and/or glycogen stores are depleted. Long distance runners have greater ST and FT fibre areas than untrained controls. However, doubt remains as to whether the ST or FT fibre area is greatest in endurance athletes. Increases in FT fibre area seem to occur during the first 2 months of training whereas ST fibre areas appear to increase after 2 to 6 months of training. Sprint training leads to the preferential use of FT fibres and male, but not female sprinters have larger FT fibres than untrained controls. Mitochondrial proteins and oxidative enzymes, as opposed to VO2max, are important determinants of the duration of endurance exercise. Endurance training increases intramuscular glycogen stores in both FT and ST fibres and produces a 'glycogen-sparing' effect which is characterised by an increased free fatty acid (FFA) metabolism. The activity of glycogen synthase is also increased by endurance training. Sprint training increases glycogen concentrations similarly in all fibre types, reduces the rate of glycogen utilisation at submaximal workloads and allows supramaximal workloads to be maintained for longer periods of time. During endurance exercise the pattern of glycogen depletion varies between muscle fibre types and between muscle groups. Glycogen stores in ST fibres are utilised initially, followed by stores in FTa then FTb fibres. Sprint activities are associated with a much greater rate of glycogen depletion. However, it is unlikely that glycogen depletion causes fatigue during sprinting. Sprint work is associated with a preferential depletion of glycogen from FTb then FTa and ST fibres. Endurance training appears to increase triglyceride stores adjacent to mitochondria and ST fibres have greater triglyceride stores than FT fibres. Endurance exercise is associated with a preferential use of triglycerides from ST fibres and endogenous triglycerides may account for over 50% of the total lipid oxidised during exercise.(ABSTRACT TRUNCATED AT 400 WORDS)