A quality improvement strategy to reduce unintended extubation in the very low birth weight infant: A case report.

BACKGROUND: Unintended extubations remain a common complication across neonatal intensive care units, with very low birthweight infants being the most vulnerable of them all. Ongoing efforts across different institutions exist with the goal of reducing the rate of unintended extubations to keep a median rate of <2 events per 100 ventilator days as defined by the Vermont Oxford Network. Our objective was to reduce unintended extubations in the very low birthweight infant in a large delivery hospital to ≤2/100 ventilator days. METHODS: A collaborative group was formed between two academic health institutions targeting training and implementation of the Children's National unintended extubation system, focusing on endotracheal tube securement methods and surveillance protocols. RESULTS: The unintended extubation rate decreased from 3.23 to 0.64 per 100 ventilator days. Changes were implemented from 2018-2020 with a sustained reduction in the unintended extubation rate of 1.54 per 100 ventilator days. Most events occurred between 12 : 00 pm -4 : 00 pm and the commonest cause was spontaneous (25%) followed by dislodgment during repositioning (19%). CONCLUSION: Very low birth weight infants present a challenge to endotracheal tube maintenance due to their developmental and anatomical changes during their neonatal intensive care unit stay. Successful reduction of unintended extubations in the very low birthweight infant can be achieved by adaptation of successful protocols for older infants.

RNAseq reveals extensive metabolic disruptions in the sensitive SF-295 cell line treated with schweinfurthins.

The schweinfurthin family of natural compounds exhibit a unique and potent differential cytotoxicity against a number of cancer cell lines and may reduce tumor growth in vivo. In some cell lines, such as SF-295 glioma cells, schweinfurthins elicit cytotoxicity at nanomolar concentrations. However, other cell lines, like A549 lung cancer cells, are resistant to schweinfurthin treatment up to micromolar concentrations. At this time, the precise mechanism of action and target for these compounds is unknown. Here, we employ RNA sequencing of cells treated with 50 nM schweinfurthin analog TTI-3066 for 6 and 24 h to elucidate potential mechanisms and pathways which may contribute to schweinfurthin sensitivity and resistance. The data was analyzed via an interaction model to observe differential behaviors between sensitive SF-295 and resistant A549 cell lines. We show that metabolic and stress-response pathways were differentially regulated in the sensitive SF-295 cell line as compared with the resistant A549 cell line. In contrast, A549 cell had significant alterations in response genes involved in translation and protein metabolism. Overall, there was a significant interaction effect for translational proteins, RNA metabolism, protein metabolism, and metabolic genes. Members of the Hedgehog pathway were differentially regulated in the resistant A549 cell line at both early and late time points, suggesting a potential mechanism of resistance. Indeed, when cotreated with the Smoothened inhibitor cyclopamine, A549 cells became more sensitive to schweinfurthin treatment. This study therefore identifies a key interplay with the Hedgehog pathway that modulates sensitivity to the schweinfurthin class of compounds.

COVID-19 pandemic - Inequities and inequalities to exercise and their consequences on the physical and mental health of women with cardiovascular disease: recommendations on how to address the needs of women.

The coronavirus disease (COVID-19) pandemic disproportionately affects those with pre-existing conditions and has exacerbated gender inequalities. Cardiovascular disease (CVD) is the leading cause of death among Canadian women. Exercise improves physical and mental health and CVD management. Amid the pandemic, women are experiencing an increase in caregiving responsibilities, job insecurities, and domestic violence creating competing demands for prioritizing their health. Recommendations on how to meet the unique needs of Canadian women with CVD through exercise are provided. Novelty: Exercise recommendations amid the pandemic for women with CVD need to be flexible, feasible, and fun.

The effectiveness of eHealth interventions on physical activity and measures of obesity among working-age women: a systematic review and meta-analysis.

Physical inactivity and obesity are modifiable risk factors for cardiovascular disease, particularly in women. eHealth interventions may increase physical activity and improve obesity-related outcomes among women. The objective of this study was to review the evidence of the effectiveness of eHealth interventions to increase moderate-to-vigorous physical activity among working-age women. The secondary objective was to examine their effectiveness on improving obesity-related outcomes. A comprehensive search strategy was developed for eight electronic databases; through July 2016. All studies consisting of >80% women of working-age (18-65 years) in high income countries were included. Multiple unblinded reviewers determined study eligibility and extracted data. Risk of bias was evaluated using the Cochrane Risk of Bias Tool and data quality using the Grading of Recommendations Assessment, Development and Evaluation approach. Data were pooled using a random-effects model. Sixty studies were included in the review of which 20 were in the meta-analysis. The meta-analysis demonstrated eHealth interventions improved moderate-to-vigorous physical activity (standard mean difference = 1.13, 95% confidence interval: 0.58, 1.68, P < 0.0001); an increase of ~25 min week-1 . No changes were observed in obesity-related outcomes; waist circumference (P = 0.06), body mass (P = 0.05) and body mass index (P = 0.35). eHealth interventions are effective at increasing min week-1 of moderate-to-vigorous physical activity among working-age women from high income countries.

Correlates of sedentary behaviour in adults: a systematic review.

OBJECTIVE: The objective of this study was to systematically review evidence to identify intrapersonal, social environmental, physical environmental and policy correlates of sedentary behaviour (SB) among adults. METHODS: Six databases were searched to identify studies that reported on intrapersonal, social, physical environmental and/or policy correlates of SB across domains (i.e. occupational, leisure and transportation) in adults (mean ≥ 18 years old). Subgroup differences (sex, age, disease status, publication status and date, weekdays vs. weekend) were examined. Risk of bias was assessed, and a qualitative synthesis completed. PROSPERO: CRD42014009814 RESULTS: Searching identified 22,779 articles; 257 were used in the analysis. Most studies used self-reported SB and were cross-sectional. The most studied domain of SB and correlate was leisure and intrapersonal, respectively. Consistent evidence found positive relationships between full-time employment and higher transportation and lower leisure SB; higher income/socioeconomic status and greater transportation and occupation SB; living in more urban areas and greater sitting time and total SB; ownership of televisions and greater leisure SB; and, active workstations and lower occupational SB. CONCLUSIONS: The review identifies the need for longitudinal studies, as well as further research on factors in the physical, social and policy environments. The review also recognizes the need to standardize methodology for collecting, defining and reporting SB and correlates.

IVIg therapy increases delivery birthweight in babies born to women with elevated preconception proportion of peripheral blood (CD56+/CD3-) natural killer cells.

In this study, the authors investigated: (1) whether elevated preconception peripheral blood proportion of CD56+/CD3- lymphocytes (NK cells) was associated with low delivery birthweight in high risk women, and (2) whether intravenous immunoglobulin (IVIg) therapy could be used to improve the delivery outcome in these women. MATERIALS AND METHODS: Sixty-six women who had singleton deliveries were divided into four groups. Group 1: 16 women with elevated preconception NK cells (>12%) using IVIg, group 2: eight women with similar elevated preconception NK cells not using IVIg, group 3: 32 women with non-elevated preconception NK cells (≤12%) using IVIg, and group IV: ten women with similar non-elevated preconception NK cells not using IVIg. These groups were similar with regards to patient age, test results, and history. RESULTS: Mean gestational age (±cmaz, GSD) of babies at delivery wa± 39.3 ± 1.7± 37.4 ± 3.7± 38.5 ± 1.3, an± 38.7 ± 1.5 weeks, for groups 1, 2, 3 and 4, respectively. Mean birthweight of babies at delivery was± 3,267 373,±2,654 ± 627,±3,129 ± 527, and±3,202 ± 357 grams, respectively. Birthweight was significantly higher for1group I vs. group 2 (p = 0.006) but not for groups 1 vs. group 3. There was no significant difference between the groups for preeclampsia rate, C-section rate or preterm delivery rate. CONCLUSION: In women with elevated preconception peripheral NK cells, mean birthweight at delivery is low without IVIg therapy ±2,654 ± 627 grams) but significantly improved with IVIg therapy ±3,267 ± 373 grams). In high risk wom without preconception NK cell elevation, mean birthweight at delivery is not further-increased with IVIg therapy ±3,202 ± 357 grams with IVIg vs.±3,129 ± 527 grams without IVIg). IVIg may be a treatment option for women with preconception NK elevation at risk of a low birthweight baby. Preconception immune testing may be a tool for determining which patients will benefit from IVIg therapy. Larger repeat studies are needed for confirmation.

Why are adult women physically active? A systematic review of prospective cohort studies to identify intrapersonal, social environmental and physical environmental determinants.

OBJECTIVE: This study aims to systematically review available evidence from prospective cohort studies to identify intrapersonal, social environmental and physical environmental determinants of moderate-to-vigorous intensity physical activity (MVPA) among working-age women. METHODS: Six databases were searched to identify all prospective cohort studies that reported on intrapersonal (e.g. self-efficacy and socioeconomic status [SES]), social (e.g. crime, area SES and social support) and/or physical (e.g. weather, work and recreation) environmental determinants of MVPA in working-age (mean 18-65 years) women. A qualitative synthesis including harvest plots was completed. PROSPERO: CRD42014009750 RESULTS: Searching identified 17,387 potential articles; 97 were used in the analysis. The majority (n = 87 studies) reported on ≥1 intrapersonal determinant. Very few (n = 34) examined factors in the social or physical environments, and none looked at social policy. Positive and consistent influencers included higher self-efficacy (n = 18/23), self-rated health (n = 8/13) and intentions (n = 10/11) and perceived behavioural control (n = 5/7) to be physically active. Having children in the household was negatively related to MVPA (n = 9/15). CONCLUSIONS: Physical activity intervention studies should consider a woman's level of self-efficacy and perceived behavioural control to be physically active. Additional studies are needed on the impact of children in the household, having a spouse/partner and using group goal setting. More evidence is needed to evaluate the impact of environmental factors.

Exposure to a combination of heat and hyperoxia during cycling at submaximal intensity does not alter thermoregulatory responses.

In this study, we tested the hypothesis that breathing hyperoxic air (FinO2 = 0.40) while exercising in a hot environment exerts negative effects on the total tissue level of haemoglobin concentration (tHb); core (Tcore) and skin (Tskin) temperatures; muscle activity; heart rate; blood concentration of lactate; pH; partial pressure of oxygen (PaO2) and carbon dioxide; arterial oxygen saturation (SaO2); and perceptual responses. Ten well-trained male athletes cycled at submaximal intensity at 21°C or 33°C in randomized order: first for 20 min while breathing normal air (FinO2 = 0.21) and then 10 min with FinO2 = 0.40 (HOX). At both temperatures, SaO2 and PaO2, but not tHb, were increased by HOX. Tskin and perception of exertion and thermal discomfort were higher at 33°C than 21°C (p < 0.01), but independent of FinO2. Tcore and muscle activity were the same under all conditions (p > 0.07). Blood lactate and heart rate were higher at 33°C than 21°C. In conclusion, during 30 min of submaximal cycling at 21°C or 33°C, Tcore, Tskin and Tbody, tHb, muscle activity and ratings of perceived exertion and thermal discomfort were the same under normoxic and hyperoxic conditions. Accordingly, breathing hyperoxic air (FinO2 = 0.40) did not affect thermoregulation under these conditions.

Conduction-coupled Tesla transformer.

A proof-of-principle Tesla transformer circuit is introduced. The new transformer exhibits the high voltage-high power output signal of shock-excited transformers. The circuit, with specification of proper circuit element values, is capable of obtaining extreme oscillatory voltages. The primary and secondary portions of the circuit communicate solely by conduction. The destructive arcing between the primary and secondary inductors in electromagnetically coupled transformers is ubiquitous. Flashover is eliminated in the new transformer as the high-voltage inductors do not interpenetrate and so do not possess an annular volume of electric field. The inductors are remote from one another. The high voltage secondary inductor is isolated in space, except for a base feed conductor, and obtains earth by its self-capacitance to the surroundings. Governing equations, for the ideal case of no damping, are developed from first principles. Experimental, theoretical, and circuit simulator data are presented for the new transformer. Commercial high-temperature superconductors are discussed as a means to eliminate the counter-intuitive damping due to small primary inductances in both the electromagnetic-coupled and new conduction-coupled transformers.

Relationship between core strength and key variables of performance in elite rink hockey players.

AIM: The aim of this study was to test the hypothesis that a significant relationship exists between the level of core strength-endurance and key variables of endurance, strength, power, speed, and agility performance in male elite rink hockey players. METHODS: Ten male elite rink hockey players of the German national team were tested for 1) time to exhaustion, maximum oxygen uptake, and running economy, 2) one repetition maximum bench press and half squat, 3) counter movement jump height, 4) 5 m, 10 m, and 20 m speed, and 5) 22 m agility. The rink hockey players were also tested for 6) ventral, lateral-left, lateral-right, and dorsal core strength-endurance using concentric-eccentric muscle tests. RESULTS: The level of total and ventral core strength-endurance was very largely correlated with maximum oxygen uptake (r=0.74 and r=0.71, both P<0.05). Additionally, there was a large correlation between the level of ventral core strength-endurance and time to exhaustion (r=0.66, P<0.05). No further significant relationships were observed (best r=0.60, P>0.05). CONCLUSION: The findings from this study suggest that the level of core strength-endurance is largely to very largely correlated with key variables of endurance performance, but not significantly with strength, power, speed, or agility indicators in male elite rink hockey players. These findings should be noted by coaches and scientists when testing physical fitness or planning strength and conditioning programs for male elite rink hockey players.

How accurate are Omron X-HJ-304-E and Yamax SW-700/701 pedometers at different speeds and various inclinations?

AIM: The purpose of this study was to investigate step count and energy expenditure accuracy of the piezoelectric Omron (Walking Style X-HJ-304-E) and spring-levered Yamax (Digi-Walker-SW-700/701) pedometers at different speeds and various inclinations. METHODS: Thirty subjects (15 females, aged: 24 ± 3 years) completed eleven 5-min trials at different treadmill speeds and inclinations (3.24 km∙h⁻¹ [inclination: 0, 9, 20%], 4.68 km∙h⁻¹ [0, 9, 20%], 6.48 km∙h⁻¹ [0, 9%], 9 km∙h⁻¹ [0%], 10.8 km∙h⁻¹ [0%], 12.6 km∙h⁻¹ [0%]). During each trial, an investigator recorded actual steps with a hand tally counter. Actual energy expenditure was measured using a portable indirect calorimeter. RESULTS: The Omron pedometer revealed high step count accuracy for all speeds and inclinations when worn on the hip or a backpack (Mean % of actual steps: 99.6%; Range: 95.8-101.3%). The Yamax pedometer revealed high step count accuracy (Mean % of actual steps: 99.8%; Range: 96.2-103.3%) when worn on the left hip at 6.48-12.6 km∙h⁻¹ (0%), 4.68 km∙h⁻¹ (9%, 20%), 6.48 km∙h⁻¹ (9%) and on the right hip at 10.8 km∙h⁻¹ (0%) and 6.48 km∙h⁻¹ (9%). The accuracy of the Omron and Yamax determined energy expenditure was poor (57.9-59.7%) when compared to indirect calorimetry. CONCLUSION: The Omron pedometer provides accurate step counts when worn on the hip and backpack at all tested speeds and inclinations. We therefore suggest an accurate application of this device for walking, hiking and running at moderate speeds. Both pedometers underestimated energy expenditure.

Determination of the intrinsic energy dependence of LiF:Mg,Ti thermoluminescent dosimeters for 125I and 103Pd brachytherapy sources relative to 60Co.

PURPOSE: To determine the intrinsic energy dependence of LiF:Mg,Ti thermoluminescent dosimeters (TLD-100) for (125)I and (103)Pd brachytherapy sources relative to (60)Co. METHODS: LiF:Mg,Ti TLDs were irradiated with low-energy brachytherapy sources and with a (60)Co teletherapy source. The brachytherapy sources measured were the Best 2301 (125)I seed, the OncoSeed 6711 (125)I seed, and the Best 2335 (103)Pd seed. The TLD light output per measured air-kerma strength was determined for the brachytherapy source irradiations, and the TLD light output per air kerma was determined for the (60)Co irradiations. Monte Carlo (MC) simulations were used to calculate the dose-to-TLD rate per air-kerma strength for the brachytherapy source irradiations and the dose to TLD per air kerma for the (60)Co irradiations. The measured and MC-calculated results for all irradiations were used to determine the TLD intrinsic energy dependence for (125)I and (103)Pd relative to (60)Co. RESULTS: The relative TLD intrinsic energy dependences (relative to (60)Co) and associated uncertainties (k = 1) were determined to be 0.883 ± 1.3%, 0.870 ± 1.4%, and 0.871 ± 1.5% for the Best 2301 seed, OncoSeed 6711 seed, and Best 2335 seed, respectively. CONCLUSIONS: The intrinsic energy dependence of TLD-100 is dependent on photon energy, exhibiting changes of 13%-15% for (125)I and (103)Pd sources relative to (60)Co. TLD measurements of absolute dose around (125)I and (103)Pd brachytherapy sources should explicitly account for the relative TLD intrinsic energy dependence in order to improve dosimetric accuracy.

Acute hormonal responses before and after 2 weeks of HIT in well trained junior triathletes.

The aim was to compare the acute hormonal response to a single HIT session at the beginning and end of a HIT shock microcycle. 13 male junior triathletes (15.8±1.8 yrs.) performed 16 HIT sessions within a 2 week period. Venous blood samples were collected before and after the first and last HIT session. Significant increases in cortisol (first session +89.7%; last session +70.3%) and hGH (first session +435.1%; last session +314.6%) concentrations were observed after both training sessions (P<0.05). The acute responses of cortisol, hGH, T3, and fT3 were not different between the first and last HIT sessions (P=1.00). Although no acute changes in testosterone were detected after the training sessions, testosterone concentrations were significantly higher at all time points (62.6-80.1%) during the last compared to first training session (P≤0.001). Findings from the present study reveal that 16 sessions of HIT led to significant increases in baseline concentrations of serum testosterone. This might indicate a heightened anabolic state even in junior triathletes. Based on the hormonal data, we conclude that at the end of this 2 week microcycle no familiarization effect was evident and that the training stimulus produced by HIT was still great enough to "stress" the athletes and induce positive training adaptations.

Note: Tesla transformer damping.

Unexpected heavy damping in the two winding Tesla pulse transformer is shown to be due to small primary inductances. A small primary inductance is a necessary condition of operability, but is also a refractory inefficiency. A 30% performance loss is demonstrated using a typical "spiral strip" transformer. The loss is investigated by examining damping terms added to the transformer's governing equations. A significant alteration of the transformer's architecture is suggested to mitigate these losses. Experimental and simulated data comparing the 2 and 3 winding transformers are cited to support the suggestion.

Postexposure prevention of progressive vaccinia in SCID mice treated with vaccinia immune globulin.

A recently reported case of progressive vaccinia (PV) in an immunocompromised patient has refocused attention on this condition. Uniformly fatal prior to the licensure of vaccinia immune globulin (VIG) in 1978, PV was still fatal in about half of VIG-treated patients overall, with a greater mortality rate in infants and children. Additional therapies would be needed in the setting of a smallpox bioterror event, since mass vaccination following any variola virus release would inevitably result in exposure of immunocompromised people through vaccination or contact with vaccinees. Well-characterized animal models of disease can support the licensure of new products when human studies are not ethical or feasible, as in the case of PV. We chose vaccinia virus-scarified SCID mice to model PV. As in immunocompromised humans, vaccinia virus-scarified SCID animals develop enlarging primary lesions with minimal or no inflammation, eventual distal virus spread, and lethal outcomes if left untreated. Postexposure treatment with VIG slowed disease progression, caused local lesion regression, and resulted in the healthy survival of most of the mice for more than 120 days. Combination treatment with VIG and topical cidofovir also resulted in long-term disease-free survival of most of the animals, even when initiated 7 days postinfection. These results support the possibility that combination treatments may be effective in humans and support using this SCID model of PV to test new antibody therapies and combination therapies and to provide further insights into the pathogenesis and treatment of PV.

Estrogen and progesterone exposure is reduced in response to energy deficiency in women aged 25-40 years.

BACKGROUND: Alterations in circulating steroids are believed to be important mediators of the impact that diet and exercise have on breast cancer risk and changes in bone density. This study aimed to test the hypothesis that moderate exercise training combined with caloric restriction would produce significant menstrual disturbances and alterations in ovarian steroids in premenopausal women. METHODS: Sedentary premenopausal women (25-40 years; body mass index: 23.6 +/- 0.6 kg/m(2)) assigned to either a light conditioning (LC, n = 9) or an exercise combined with caloric restriction group (EX + CR, n = 24) were studied for one screening, one baseline and four intervention periods equivalent to the length of subjects' menstrual cycles. Exercise consisted of supervised training sessions, i.e. two LC or four EX + CR times per week, 30-60 min at a moderate intensity. The EX + CR group was prescribed a diet representing a caloric restriction of 20-35% below baseline energy requirements, whereas the LC group remained eucaloric. Ovarian steroid exposure was determined with daily urinary estrone-1- and pregnanediol glucuronides (E1G and PdG, respectively) and mid-cycle urinary LH measures. Fitness, body composition, and serum sex hormone binding globulin (SHBG) and serum estradiol (E2) were assessed repeatedly. RESULTS: The intervention produced significant increases in VO(2) max and decreases in both body weight (-3.7 +/- 0.5 kg; ranged from -8.8 to +1.8 kg) and percent body fat (-4.5 +/- 0.7%; ranged from -12 to +0.3%), which were attributable primarily to changes in the EX + CR subjects (time x group; P < 0.05). Serum E2 and urinary E1G and PdG concentrations declined significantly across the intervention period (time; P < 0.05), whereas SHBG increased transiently (time; P < 0.05) in the EX + CR subjects, with no significant changes observed in the LC group. The decrease in E1G area under the curve was significantly related to the daily energy deficit (R =0.61; P = 0.003), not the amount of weight lost. There was no significant impact of the intervention on menstrual cyclicity or the incidence of menstrual disturbances in either group. CONCLUSIONS: A moderate aerobic exercise training program combined with modest weight loss in accordance with recommended guidelines produces significant reductions in ovarian steroid exposure without disrupting menstrual cyclicity in premenopausal women aged 25-40 years. Exposure to a daily energy deficit is a stronger predictor of the decline in estrogen exposure than decreases in body weight.

Effects of sex composition by class and instructor's sex on physical self-efficacy of college men.

The relationship of sex composition of class and instructor's sex to Physical Self-efficacy has yielded conflicting results in several studies. This study examined the relationship of sex composition of class and instructor's sex to scores on Physical Self-efficacy, Perceived Physical Ability, and Physical Self-presentation Confidence of 80 male students enrolled in one of four sections of a strength training class. Analysis indicated no significant difference on Physical Self-efficacy between male students who were enrolled in all male classes or in coeducational classes; improvements in scores on Physical Self-efficacy were not specific to the sex composition of the class or sex of the instructor and no significant difference on Perceived Physical Ability and Physical Self-presentation Confidence between male students who joined an all male class or a coeducational class. Perceived Physical Ability improved from the pretest to the posttest in all classes; and no improvement in scores for Physical Self-presentation Confidence was found in all classes. In conclusion, the analysis showed sex composition of the class and sex of the instructor were not significantly related to scores for self-efficacy.

Inpatient care of mentally ill people in prison: results of a year's programme of semistructured inspections.

OBJECTIVE: To investigate the facilities for inpatient care of mentally disordered people in prison. DESIGN: Semistructured inspections conducted by doctor and nurse. Expected standards were based on healthcare quality standards published by the Prison Service or the NHS. SETTING: 13 prisons with inpatient beds in England and Wales subject to the prison inspectorate's routine inspection programme during 1997-8. MAIN OUTCOMES MEASURES: Appraisals of quality of care against published standards. RESULTS: The 13 prisons had 348 beds, 20% of all beds in prisons. Inpatient units had between 3 and 75 beds. No doctor in charge of inpatients had completed specialist psychiatric training. 24% of nursing staff had mental health training; 32% were non-nursing trained healthcare officers. Only one prison had occupational therapy input; two had input from a clinical psychologist. Most patients were unlocked for about 3.5 hours a day and none for more than nine hours a day. Four prisons provided statistics on the use of seclusion. The average length of an episode of seclusion was 50 hours. CONCLUSION: The quality of services for mentally ill prisoners fell far below the standards in the NHS. Patients' lives were unacceptably restricted and therapy limited. The present policy dividing inpatient care of mentally disordered prisoners between the prison service and the NHS needs reconsideration.

Regulatory mechanisms of poly(ADP-ribose) polymerase.

Here, we describe the latest developments on the mechanistic characterization of poly(ADP-ribose) polymerase (PARP) [EC 2.4.2.30], a DNA-dependent enzyme that catalyzes the synthesis of protein-bound ADP-ribose polymers in eucaryotic chromatin. A detailed kinetic analysis of the automodification reaction of PARP in the presence of nicked dsDNA indicates that protein-poly(ADP-ribosyl)ation probably occurs via a sequential mechanism since enzyme-bound ADP-ribose chains are not reaction intermediates. The multiple enzymatic activities catalyzed by PARP (initiation, elongation, branching and self-modification) are the subject of a very complex regulatory mechanism that may involve allosterism. For instance, while the NAD+ concentration determines the average ADP-ribose polymer size (polymerization reaction), the frequency of DNA strand breaks determines the total number of ADP-ribose chains synthesized (initiation reaction). A general discussion of some of the mechanisms that regulate these multiple catalytic activities of PARP is presented below.

Changes in serum lipids and apolipoproteins after exercise in men with high cholesterol: influence of intensity.

The purpose of this study was to characterize the short-term changes in blood lipid and apolipoprotein concentrations in healthy hypercholesterolemic men after high-intensity [80% maximal O2 uptake (VO2max); n = 20] or moderate-intensity (50% VO2max; n = 19) cycle ergometer exercise balanced for caloric expenditure (350 kcal). The men's age, height, weight, %fat, and VO2max were 46 +/- 2 yr, 173 +/- 7 cm, 82.7 +/- 2.2 kg, 28 +/- 1%, and 31.1 +/- 1.0 ml O2.kg-1.min-1, respectively. Blood samples were drawn before exercise, immediately after exercise, then 24 and 48 h later, and concentrations of all variables were adjusted for changes in plasma volume. Significant changes (P < 0.0016) were as follows: total and low-density lipoprotein cholesterol fell by 4% immediately after exercise and then rose by 5-8% by 48 h. Triglycerides were 18 and 15% lower at 24 and 48 h, respectively. HDL-cholesterol, high-density lipoprotein3-cholesterol, and apolipoprotein B rose 8-9% by 24 h and remained elevated. High-density lipoprotein2-cholesterol rose by 27% by 48 h after exercise, but this change was not significant. Apolipoprotein A-I did not change with exercise. The response patterns were not affected by exercise intensity. These data show that a single session of exercise performed by untrained hypercholesterolemic men alters blood lipid and apolipoprotein concentrations. Furthermore, the postexercise response patterns are not influenced by exercise intensity, as long as caloric expenditure is held constant.