Eighteen multiparous cows were used in a split-plot replicated Latin square with two 28-d periods to evaluate the effects of source of supplemental Cu, Zn, and Mn (sulfates or hydroxy) on apparent ...absorption of minerals when fed in either a forage- or by-product–based diet. The by-product diets were formulated to have greater concentrations of NDF and lesser concentrations of starch, and specific ingredients were chosen because they were good sources of soluble fiber and β-glucans, which bind trace minerals in nonruminants. We hypothesized that hydroxy trace minerals would interact less with digesta and have greater apparent absorption compared with sulfate minerals, and the difference in apparent absorption would be greater for the by-product diet compared with the forage-based diet. During the 56-d experiment, cows remained on the same fiber treatment but source of supplemental trace mineral was different for each 28-d period; thus, all cows were exposed to both mineral treatments. During each period cows were fed no supplemental Cu, Zn, or Mn for 16 d, followed by 12 d of feeding supplemental minerals from either sulfate or hydroxy sources. Supplemental minerals for each of the mineral sources fed provided approximately 10, 35, and 32 mg/kg of supplemental Cu, Zn, and Mn, respectively, for both fiber treatments. Total Cu, Zn, and Mn dietary concentrations, respectively, were approximately 19, 65, and 70 mg/kg for the forage diets and 21, 85, and 79 for the by-product diets. Treatment had no effect on dry matter intake (24.2 kg/d) or milk production (34.9 kg/d). Cows consuming the by-product diets had greater Zn (1,863 vs. 1,453 mg/d) and Mn (1,790 vs. 1,588 mg/d) intake compared with cows fed forage diets, but apparent Zn absorption was similar between treatments. Manganese apparent absorption was greater for the by-product diets compared with the forage diets (16 vs. 11%). A fiber by mineral interaction was observed for Cu apparent absorption, as cows fed hydroxy minerals with forage diets had greater apparent absorption compared with cows fed sulfate minerals; however, the opposite was observed with the by-product diets. Source of supplemental trace minerals and type of fiber in diets affected availability of Cu and Mn and should be considered in ration formulation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BACKGROUND: Cholesterol-lowering foods may be more effective when consumed as combinations rather than as single foods. OBJECTIVES: Our aims were to determine the effectiveness of consuming a ...combination of cholesterol-lowering foods (dietary portfolio) under real-world conditions and to compare these results with published data from the same participants who had undergone 4-wk metabolic studies to compare the same dietary portfolio with the effects of a statin. DESIGN: For 12 mo, 66 hyperlipidemic participants were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal), and almonds (23 g/1000 kcal). Fifty-five participants completed the 1-y study. The 1-y data were also compared with published results on 29 of the participants who had also undergone separate 1-mo metabolic trials of a diet and a statin. RESULTS: At 3 mo and 1 y, mean (±SE) LDL-cholesterol reductions appeared stable at 14.0 ± 1.6% (P < 0.001) and 12.8 ± 2.0% (P < 0.001), respectively (n = 66). These reductions were less than those observed after the 1-mo metabolic diet and statin trials. Nevertheless, 31.8% of the participants (n = 21 of 66) had LDL-cholesterol reductions of >20% at 1 y (x ± SE: -29.7 ± 1.6%). The LDL-cholesterol reductions in this group were not significantly different from those seen after their respective metabolically controlled portfolio or statin treatments. A correlation was found between total dietary adherence and LDL-cholesterol change (r = -0.42, P < 0.001). Only 2 of the 26 participants with <55% compliance achieved LDL-cholesterol reductions >20% at 1 y. CONCLUSIONS: More than 30% of motivated participants who ate the dietary portfolio of cholesterol-lowering foods under real-world conditions were able to lower LDL-cholesterol concentrations >20%, which was not significantly different from their response to a first-generation statin taken under metabolically controlled conditions.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The African-American Study of Kidney Disease and Hypertension pilot study randomized 94 nondiabetic black men and women (mean age, 53 years; 75% male) with presumed hypertensive nephrosclerosis and a ...baseline glomerular filtration rate (GFR) of 25 to 70 mL/min/1.73 m2 (mean, 52.3 mL/min/1.73 m2) to blood pressure control at either a low mean arterial pressure (MAP) goal of < or = 92 mm Hg or a usual MAP goal of 102 to 107 mm Hg and an antihypertensive drug regimen that included either a calcium antagonist (amlodipine), a beta-blocker (atenolol), or an angiotensin-converting enzyme (ACE) inhibitor (enalapril). After 3 months of follow-up (n = 90), the mean GFR was similar (53.0 mL/min/1.73 m2 v 53.7 mL/min/1.73 m2) to the baseline levels in participants randomized to the low MAP group (n = 44), whereas the mean GFR increased by 3.9 mL/min/1.73 m2 (P = 0.02) in participants randomized to the usual MAP group (n = 46). During the same period of time, the mean GFR increased significantly in participants randomized to the calcium channel blocker regimen (n = 28) (5.7 mL/min/ 1.73 m2; P = 0.01) but not in participants randomized to the beta-blocker regimen (n = 31) (1.7 mL/min/1.73 m2; P = 0.10) or the ACE inhibitor regimen (n = 31) (1.1 mL/min/1.73 m2; P = 0.52). Changes in GFR at 3 months were significantly different among the three treatment groups (P = 0.04). We conclude that the magnitude of short-term effects of blood pressure control and antihypertensive drug regimens on GFR should be considered when estimating sample size for clinical trials designed to evaluate the effects of these interventions on long-term changes in GFR slope.
Objective: To study actual and perceived substance use in Canadian university students and to compare these rates with US peers. Participants: Students (N = 1,203) from a large Canadian university. ...Methods: Participants were surveyed using items from the National College Health (NCHA) Assessment of the American College Health Association questionnaire. Results: Alcohol was the most common substance used (65.8%), followed by marijuana (13.5%) and cigarettes (13.5%). Substance use and norms were significantly less than the NCHA US data. Overall, respondents generally perceived the typical Canadian student to have used all 3 substances. Perceived norms significantly predicted use, with students more likely to use alcohol, cigarettes, or marijuana if they perceived the typical student to use these substances. Conclusions: Similar to their US peers, Canadian university students have inaccurate perceptions of peer substance use. These misperceptions may have potentially negative influences on actual substance use and could be a target for intervention. Further research examining the cross-cultural differences for substance abuse is warranted.
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DOBA, FSPLJ, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood ...pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset.
We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK-based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053.
Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants' systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1): 3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for poor outcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2: 3 2–5; n=544, in the GTN group vs 3 2–5; n=558, in the sham group; 1·04 0·84–1·29; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group p=0·091), or serious adverse events (188 in the GTN group vs 170 in the sham group p=0·16) between treatment groups.
Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultra-acute prehospital setting.
British Heart Foundation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background and aim Compared to a DASH-type diet, an intensively applied dietary portfolio reduced diastolic blood pressure at 24 weeks as a secondary outcome in a previous study. Due to the ...importance of strategies to reduce blood pressure, we performed an exploratory analysis pooling data from intensively and routinely applied portfolio treatments from the same study to assess the effect over time on systolic, diastolic and mean arterial pressure (MAP), and the relation to sodium (Na+ ), potassium (K+ ), and portfolio components. Methods and results 241 participants with hyperlipidemia, from four academic centers across Canada were randomized and completed either a DASH-type diet (control n = 82) or a dietary portfolio that included, soy protein, viscous fibers and nuts (n = 159) for 24 weeks. Fasting measures and 7-day food records were obtained at weeks 0, 12 and 24, with 24-h urines at weeks 0 and 24. The dietary portfolio reduced systolic, diastolic and mean arterial blood pressure compared to the control by 2.1 mm Hg (95% CI, 4.2 to −0.1 mm Hg) (p = 0.056), 1.8 mm Hg (CI, 3.2 to 0.4 mm Hg) (p = 0.013) and 1.9 mm Hg (CI, 3.4 to 0.4 mm Hg) (p = 0.015), respectively. Blood pressure reductions were small at 12 weeks and only reached significance at 24 weeks. Nuts, soy and viscous fiber all related negatively to change in mean arterial pressure (ρ = −0.15 to −0.17, p ≤ 0.016) as did urinary potassium (ρ = −0.25, p = 0.001), while the Na+ /K+ ratio was positively associated (ρ = 0.20, p = 0.010). Conclusions Consumption of a cholesterol-lowering dietary portfolio also decreased blood pressure by comparison with a healthy DASH-type diet. Clinical Trial Reg. No. NCT00438425 , clinicaltrials.gov.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Genomic regulation of cardiomyocyte differentiation is central to heart development and function. This study uses genetic loss-of-function human-induced pluripotent stem cell-derived cardiomyocytes ...to evaluate the genomic regulatory basis of the non-DNA-binding homeodomain protein HOPX. We show that HOPX interacts with and controls cardiac genes and enhancer networks associated with diverse aspects of heart development. Using perturbation studies in vitro, we define how upstream cell growth and proliferation control HOPX transcription to regulate cardiac gene programs. We then use cell, organoid, and zebrafish regeneration models to demonstrate that HOPX-regulated gene programs control cardiomyocyte function in development and disease. Collectively, this study mechanistically links cell signaling pathways as upstream regulators of HOPX transcription to control gene programs underpinning cardiomyocyte identity and function.
An association between increasing anaesthetic depth and decreased postoperative survival has been shown in observational studies; however, evidence from randomised controlled trials is lacking. Our ...aim was to compare all-cause 1-year mortality in older patients having major surgery and randomly assigned to light or deep general anaesthesia.
In an international trial, we recruited patients from 73 centres in seven countries who were aged 60 years and older, with significant comorbidity, having surgery with expected duration of more than 2 h, and an anticipated hospital stay of at least 2 days. We randomly assigned patients who had increased risk of complications after major surgery to receive light general anaesthesia (bispectral index BIS target 50) or deep general anaesthesia (BIS target 35). Anaesthetists also nominated an appropriate range for mean arterial pressure for each patient during surgery. Patients were randomly assigned in permuted blocks by region immediately before surgery, with the patient and assessors masked to group allocation. The primary outcome was 1-year all-cause mortality. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000632897, and is closed to accrual.
Patients were enrolled between Dec 19, 2012, and Dec 12, 2017. Of the 18 026 patients screened as eligible, 6644 were enrolled, randomly assigned to treatment or control, and formed the intention-to-treat population (3316 in the BIS 50 group and 3328 in the BIS 35 group). The median BIS was 47·2 (IQR 43·7 to 50·5) in the BIS 50 group and 38·8 (36·3 to 42·4) in the BIS 35 group. Mean arterial pressure was 3·5 mm Hg (4%) higher (median 84·5 IQR 78·0 to 91·3 and 81·0 75·4 to 87·6, respectively) and volatile anaesthetic use was 0·26 minimum alveolar concentration (30%) lower (0·62 0·52 to 0·73 and 0·88 0·74 to 1·04, respectively) in the BIS 50 than the BIS 35 group. 1-year mortality was 6·5% (212 patients) in the BIS 50 group and 7·2% (238 patients) in the BIS 35 group (hazard ratio 0·88, 95% CI 0·73 to 1·07, absolute risk reduction 0·8%, 95% CI −0·5 to 2·0). Grade 3 adverse events occurred in 954 (29%) patients in the BIS 50 group and 909 (27%) patients in the BIS 35 group; and grade 4 adverse events in 265 (8%) and 259 (8%) patients, respectively. The most commonly reported adverse events were infections, vascular disorders, cardiac disorders, and neoplasms.
Among patients at increased risk of complications after major surgery, light general anaesthesia was not associated with lower 1-year mortality than deep general anaesthesia. Our trial defines a broad range of anaesthetic depth over which anaesthesia may be safely delivered when titrating volatile anaesthetic concentrations using a processed electroencephalographic monitor.
Health Research Council of New Zealand; National Health and Medical Research Council, Australia; Research Grant Council of Hong Kong; National Institute for Health and Research, UK; and National Institutes of Health, USA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
CONTEXT To enhance the effectiveness of diet in lowering cholesterol, recommendations
of the Adult Treatment Panel III of the National Cholesterol Education Program
emphasize diets low in saturated ...fat together with plant sterols and viscous
fibers, and the American Heart Association supports the use of soy protein
and nuts. OBJECTIVE To determine whether a diet containing all of these recommended food
components leads to cholesterol reduction comparable with that of 3-hydroxy-3-methylglutaryl
coenzyme A reductase inhibitors (statins). DESIGN Randomized controlled trial conducted between October and December 2002. SETTING AND PARTICIPANTS Forty-six healthy, hyperlipidemic adults (25 men and 21 postmenopausal
women) with a mean (SE) age of 59 (1) years and body mass index of 27.6 (0.5),
recruited from a Canadian hospital-affiliated nutrition research center and
the community. INTERVENTIONS Participants were randomly assigned to undergo 1 of 3 interventions
on an outpatient basis for 1 month: a diet very low in saturated fat, based
on milled whole-wheat cereals and low-fat dairy foods (n = 16; control); the
same diet plus lovastatin, 20 mg/d (n = 14); or a diet high in plant sterols
(1.0 g/1000 kcal), soy protein (21.4 g/1000 kcal), viscous fibers (9.8 g/1000
kcal), and almonds (14 g/1000 kcal) (n = 16; dietary portfolio). MAIN OUTCOME MEASURES Lipid and C-reactive protein levels, obtained from fasting blood samples;
blood pressure; and body weight; measured at weeks 0, 2, and 4 and compared
among the 3 treatment groups. RESULTS The control, statin, and dietary portfolio groups had mean (SE) decreases
in low-density lipoprotein cholesterol of 8.0% (2.1%) (P = .002), 30.9% (3.6%) (P<.001), and 28.6%
(3.2%) (P<.001), respectively. Respective reductions
in C-reactive protein were 10.0% (8.6%) (P = .27),
33.3% (8.3%) (P = .002), and 28.2% (10.8%) (P = .02). The significant reductions in the statin and
dietary portfolio groups were all significantly different from changes in
the control group. There were no significant differences in efficacy between
the statin and dietary portfolio treatments. CONCLUSION In this study, diversifying cholesterol-lowering components in the same
dietary portfolio increased the effectiveness of diet as a treatment of hypercholesterolemia.
Exogenous ketone esters have demonstrated the capacity to increase oxygen availability during acute hypoxic exposure leading to the potential application of their use to mitigate performance declines ...at high altitudes. Voluntary hypoventilation (VH) with exercise reliably reduces oxygen availability and increases carbon dioxide retention without alterations to ambient pressure or gas content. Utilizing a double-blind randomized crossover design, fifteen recreational male distance runners performed submaximal exercise (4 × 5 min; 70% VO
2
Max) with VH. An exogenous ketone ester (KME; 573 mg⋅kg
–1
) or iso-caloric flavor matched placebo (PLA) was consumed prior to exercise. Metabolites, blood gases, expired air, heart rate, oxygen saturation, cognition, and perception metrics were collected throughout. KME rapidly elevated
R
-β-hydroxybutyrate and reduced blood glucose without altering lactate production. KME lowered pH, bicarbonate, and total carbon dioxide. VH with exercise significantly reduced blood (SpO
2
) and muscle (SmO
2
) oxygenation and increased cognitive mean reaction time and respiratory rate regardless of condition. KME administration significantly elevated respiratory exchange ratio (RER) at rest and throughout recovery from VH, compared to PLA. Blood carbon dioxide (PCO
2
) retention increased in the PLA condition while decreasing in the KME condition, leading to a significantly lower PCO
2
value immediately post VH exercise (IPE;
p
= 0.031) and at recovery (
p
= 0.001), independent of respiratory rate. The KME’s ability to rapidly alter metabolism, acid/base balance, CO
2
retention, and respiratory exchange rate independent of respiratory rate changes at rest, during, and/or following VH exercise protocol illustrates a rapid countermeasure to CO
2
retention in concert with systemic metabolic changes.
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