Abstract
Background
There is a lack of international consensus regarding the prescription of high-intensity interval training (HIIT) for people with coronary artery disease (CAD) attending cardiac ...rehabilitation (CR).
Aims
To assess the clinical effectiveness and safety of low-volume HIIT compared with moderate-intensity steady-state (MISS) exercise training for people with CAD.
Methods and results
We conducted a multi-centre RCT, recruiting 382 patients from 6 outpatient CR centres. Participants were randomized to twice-weekly HIIT (n = 187) or MISS (n = 195) for 8 weeks. HIIT consisted of 10 × 1 min intervals of vigorous exercise (>85% maximum capacity) interspersed with 1 min periods of recovery. MISS was 20–40 min of moderate-intensity continuous exercise (60–80% maximum capacity). The primary outcome was the change in cardiorespiratory fitness peak oxygen uptake (VO2 peak) at 8 week follow-up. Secondary outcomes included cardiovascular disease risk markers, cardiac structure and function, adverse events, and health-related quality of life. At 8 weeks, VO2peak improved more with HIIT (2.37 mL.kg−1.min−1; SD, 3.11) compared with MISS (1.32 mL.kg−1.min−1; SD, 2.66). After adjusting for age, sex, and study site, the difference between arms was 1.04 mL.kg−1.min−1 (95% CI, 0.38 to 1.69; P = 0.002). Only one serious adverse event was possibly related to HIIT.
Conclusions
In stable CAD, low-volume HIIT improved cardiorespiratory fitness more than MISS by a clinically meaningful margin. Low-volume HIIT is a safe, well-tolerated, and clinically effective intervention that produces short-term improvement in cardiorespiratory fitness. It should be considered by all CR programmes as an adjunct or alternative to MISS.
Trial registration
ClinicalTrials.gov: NCT02784873. https://clinicaltrials.gov/ct2/show/NCT02784873.
Lay Summary
Cardiac rehabilitation exercise training can improve cardiorespiratory fitness and quality of life for people with coronary artery disease, but sometimes, it is not effective. The intensity of the exercise training may be important. We conducted a randomized controlled trial to test if moderate-intensity exercise or high-intensity exercise was better.High-intensity interval training was more effective than moderate-intensity exercise training for improving cardiorespiratory fitness in people with coronary artery disease attending cardiac rehabilitation.High-intensity interval training was safe and well tolerated.
Dose-related effects of smallpox vaccine Frey, Sharon E; Newman, Frances K; Cruz, John ...
New England journal of medicine/The New England journal of medicine,
04/2002, Letnik:
346, Številka:
17
Journal Article
Recenzirano
Odprti dostop
We conducted a double-blind, randomized trial of three dilutions of vaccinia virus vaccine in previously unimmunized adults in order to assess the clinical success rates, humoral responses, and ...virus-specific activity of cytotoxic T cells and interferon-gamma-producing T cells.
Sixty healthy adults were inoculated intradermally by bifurcated needle with undiluted vaccine (dose, 10(7.8) plaque-forming units pfu per milliliter), a 1:10 dilution (dose, 10(6.5) pfu per milliliter), or a 1:100 dilution (dose, 10(5.0) pfu per milliliter); there were 20 subjects in each group. The subjects were monitored with respect to vesicle formation (an indicator of successful vaccination), the viral titer at the time of peak lesion formation, antiviral antibodies, and cellular immune responses.
A vaccinia vesicle developed in 19 of the 20 subjects who received undiluted vaccine (95 percent), 14 of the 20 who received the 1:10 dilution (70 percent), and 3 of the 20 who received the 1:100 dilution (15 percent). One month after vaccination, 34 of 36 subjects with vesicles had antibody responses, as compared with only 1 of 24 subjects without clinical evidence of vaccinia virus replication. Vigorous cytotoxic T-cell and interferon-gamma responses occurred in 94 percent of subjects with vesicles, and a cytotoxic T-cell response occurred in only one subject without a vesicle.
The vaccinia virus vaccine (which was produced in 1982 or earlier) still has substantial potency when administered by a bifurcated needle to previously unvaccinated adults. Diluting the vaccine reduces the rate of successful vaccination. The development of vesicular skin lesions after vaccination correlates with the induction of the antibody and T-cell responses that are considered essential for clearing vaccinia virus infections.
The presence and biological significance of circulating glycated insulin has been evaluated by high-pressure liquid chromatography (HPLC), electrospray ionization mass spectrometry (ESI-MS), ...radioimmunoassay (RIA), receptor binding, and hyperinsulinemic-euglycemic clamp techniques. ESI-MS analysis of an HPLC-purified plasma pool from four male type 2 diabetic subjects (HbA(1c) 8.1 +/- 0.2%, plasma glucose 8.7 +/- 1.3 mmol/l means +/- SE) revealed two major insulin-like peaks with retention times of 14-16 min. After spectral averaging, the peak with retention time of 14.32 min exhibited a prominent triply charged (M+3H)(3+) species at 1,991.1 m/z, representing monoglycated insulin with an intact M(r) of 5,970.3 Da. The second peak (retention time 15.70 min) corresponded to native insulin (M(r) 5,807.6 Da), with the difference between the two peptides (162.7 Da) representing a single glucitol adduct (theoretical 164 Da). Measurement of glycated insulin in plasma of type 2 diabetic subjects by specific RIA gave circulating levels of 10.1 +/- 2.3 pmol/l, corresponding to approximately 9% total insulin. Biological activity of pure synthetic monoglycated insulin (insulin B-chain Phe(1)-glucitol adduct) was evaluated in seven overnight-fasted healthy nonobese male volunteers using two-step euglycemic-hyperinsulinemic clamps (2 h at 16.6 micro g x kg(-1) x min(-1), followed by 2 h at 83.0 micro g x kg(-1) x min(-1); corresponding to 0.4 and 2.0 mU x kg(-1) x min(-1)). At the lower dose, the exogenous glucose infusion rates required to maintain euglycemia during steady state were significantly lower with glycated insulin (P < 0.01) and approximately 70% more glycated insulin was required to induce a similar rate of insulin-mediated glucose uptake. Maximal responses at the higher rates of infusion were similar for glycated and control insulin. Inhibitory effects on endogenous glucose production, insulin secretion, and lipolysis, as indicated by measurements of C-peptide, nonesterified free fatty acids, and glycerol, were also similar. Receptor binding to CHO-T cells transfected with human insulin receptor and in vivo metabolic clearance revealed no differences between glycated and native insulin, suggesting that impaired biological activity is due to a postreceptor effect. The present demonstration of glycated insulin in human plasma and related impairment of physiological insulin-mediated glucose uptake suggests a role for glycated insulin in glucose toxicity and impaired insulin action in type 2 diabetes.
Concern exists regarding adverse metabolic effects of antihypertensive agents. In the United States, diuretics are recommended first-line but additional agents, usually angiotensin-converting enzyme ...(ACE) inhibitors, are often required to meet blood pressure targets. We have previously shown that the combination of low-dose diuretic with an ACE inhibitor has detrimental effects on insulin action compared with ACE inhibitor alone in hypertensive type 2 diabetic patients. Our aim was to establish whether similar effects occur in nondiabetic hypertensive patients using this combination. A randomized double-blind placebo-controlled crossover design was used. After a 6-week run-in, when regular antihypertensive medications were withdrawn and placebo substituted, patients received captopril 50 mg twice daily with either bendroflumethiazide 1.25 mg (CB) or placebo (CP) for 12 weeks with a 6-week wash-out between treatments. Insulin action was assessed by hyperinsulinemic euglycemic clamp after the 6-week run-in and at the end of each treatment period. There were no differences between treatments in fasting glucose or insulin concentrations. Glucose infusion rates required to maintain euglycemia were the same with each treatment (CP 22.1±2.2 vs CB 22.2±2.2 μmol/kg per minute). There was no difference in endogenous glucose production in the basal state (CP 8.9±0.5 vs CB 9.5±0.7 μmol/kg per minute; P=0.23) or during hyperinsulinemia (CP 2.2±0.6 vs CB 1.5±0.3 μmol/kg per minute; P=0.30). In contrast to the situation in type 2 diabetes mellitus, ACE inhibitor combined with low-dose thiazide diuretic does not adversely affect insulin action when compared with ACE inhibitor alone in nondiabetic hypertensive patients.
Time- and frequency-domain estimates of activation rate have been proposed to guide atrial fibrillation (AF) ablation in patients, but their electrophysiological correlates are unclear.
This study ...sought to examine the relative correlation of average electrical cycle length (CL) and dominant frequency (DF) during AF with reference optical mapping measures.
Eight sheep hearts were Langendorff-perfused and superfused with oxygenated Tyrode solution inside a tank representing the human thorax. Optical mapping (DI-4-ANEPPS) of 4 × 4 cm2 in the left atrium was performed at 0.5 mm/pixel and 600 fps. A 20-pole catheter was placed in the optical field of view to acquire 1.2-kHz unipolar recordings by the EnSite NavX System (ENS; St. Jude Medical, St. Paul, MN) optimized for CL and DF calculation. During AF, 5-second-long simultaneous optical and electrical signals were analyzed for CL and DF.
During pacing, DF measurements had fewer false results than CL (6.6% to 2.5% vs. 21.5% to 4.4% depending on filtering, P <.001). During AF in regions showing periodic waves on both sides of the catheter optical 1,000/CL versus DF correlation showed 95% confidence identity and was better than unipolar measurements in the ENS (adjusted R(2): 0.58879 vs. 0.12902; P < 10(-6)). DFs of unipolar signals correlated better than CLs with DFs of optical signals. Similarly, bipolar DF correlation with optical DF was not different from identity (P >.157), but the bipolar CL showed smaller identity with the optical CL (P <.0004).
DF values of unipolar and bipolar signals correlate with those of optical signals better than CL values for the respective signals.
A wide range of chemical and physical parameters has been observed over the course of a severe Europe-wide air pollution episode in August 2003. Detailed surface observations made at the rural ...perimeter edge of London, UK, indicated significantly elevated levels of primary volatile organic compounds (VOCs), ozone (>110
ppbV), other photochemical by-products such as PAN, HCHO, and oxygenates but not NO
x
. Reactive tracers in combination with Doppler wind radar and back trajectories have been used to establish that initial morning rises in O
3 during the episode were caused by entrainment of air from aloft, polluted on regional scales from mainland Europe. Total VOC reactivity to OH approximately doubled during this episode, with similar distribution between functional groups, but showing a temperature dependent contribution from biogenic isoprene (maximum 1.2
ppbv). Under episodic conditions total peroxy radicals in excess of 60
pptv were observed in late afternoon with strong correlation to a later and higher peak in ozone. Episodic alkyl peroxy radicals were calculated to be substantially influenced by peroxy acetyl, via the thermal dissociation of PAN at high temperatures.
Over the past decade, new and emerging technologies in air pollution instrumentation have made it possible to involve students and citizen scientists in air pollution monitoring. Similarly, advances ...in data communication and transmission have made it increasingly easy to share and graphically display data. Two educational programs, the Global Ozone (GO3) Project and AQTreks, have used these advances to get air pollution monitors into the hands of thousands of students around the world and to automate data sharing. The pilot project for AQTreks, GO3 Treks, is also discussed. These educational projects began in 2009 with the GO3 Project, a stationary ground-level ozone monitoring project. In the GO3 Project, students and teachers at more than 100 schools from around the world installed ozone and weather monitoring stations at their schools with automatic uploading of their data every 15 min, resulting in more than 12 million ozone measurements along with associated weather data. Over the years, new technologies became available for students to expand their measurements from stationary to mobile platforms. Since 2016, the AQTreks educational program has been developed concurrently with the Personal Air Monitor (PAM), a mobile sensor suite paired with a smartphone app. Complementing the technology are online curricula and other resources for students and citizens to learn about air pollution and climate change. In these projects, a focus on data quality and the careful selection of monitoring technologies have resulted in scientific use of the student-collected data, including their incorporation in several research campaigns that have furthered understanding of ground-level ozone formation. This approach has demonstrated the utility of these types of educational programs both in terms of furthering scientific research and educating the next generation about air quality issues.
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•Through our programs we enable students and the public to measure air pollution.•Our air monitoring projects engaged 20,000 students at schools worldwide.•Our sensor package enables student-designed mobile Treks and active learning.•Seeing and sharing their data on the web make the data come alive for students.•Student measurements can be of sufficient quality to be useful to scientists.
Hantavirus pulmonary syndrome (HPS) is a rare but acute fulminant disease caused by Sin Nombre virus (SNV). To understand the role of the viral load in the pathogenesis of HPS, the load of virus in ...the blood of patients with HPS was measured. A quantitative reverse transcription-polymerase chain reaction assay was developed for SNV, because SNV is difficult to grow in cell culture. Thirty-eight samples from 26 patients with HPS were analyzed. Twenty of the 26 initial samples were positive for viral RNA (7 of 9 samples were obtained from patients with fatal cases, and 13 of 17 were obtained from survivors). Mean viral RNA copy numbers were 106.1±1.4/mL in positive cases (106.7±1.4/mL in fatal cases, 105.8±1.3/mL in survivors) and were correlated with peak hematocrit (P < .05) and with the lowest platelet count (P = .05). In 8 survivors who had serial samples obtained, viral RNA copy numbers decreased promptly after resolution of fever.
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