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1.
Sex steroids mediate discrete effects on HDL cholesterol efflux capacity and particle concentration in healthy men.
Rubinow, KB, Vaisar, T, Chao, JH, Heinecke, JW, Page, ST
Journal of clinical lipidology. 2018;(4):1072-1082
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Abstract
BACKGROUND Exogenous testosterone decreases serum concentrations of high-density lipoprotein cholesterol (HDL-C) in men, but whether this alters cardiovascular risk is uncertain. OBJECTIVE To investigate the effects of testosterone and estradiol on HDL particle concentration (HDL-Pima) and metrics of HDL function. METHODS We enrolled 53 healthy men, 19 to 55 years of age, in a double-blinded, placebo-controlled, randomized trial. Subjects were rendered medically castrate using the GnRH receptor antagonist acyline and administered either (1) placebo gel, (2) low-dose transdermal testosterone gel (1.62%, 1.25 g), (3) full replacement dose testosterone gel (1.62%, 5 g) or (4) full replacement dose testosterone gel together with an aromatase inhibitor for 4 weeks. At baseline and end of treatment, serum HDL total macrophage and ABCA1-specific cholesterol efflux capacity (CEC), HDL-Pima and size, and HDL protein composition were determined. RESULTS Significant differences in serum HDL-C were observed with treatment across groups (P = .01 in overall repeated measures ANOVA), with increases in HDL-C seen after both complete and partial testosterone deprivation. Medical castration increased total HDL-Pima (median [interquartile range] 19.1 [1.8] nmol/L at baseline vs 21.3 [3.1] nmol/L at week 4, P = .006). However, corresponding changes in total macrophage CEC and ABCA1-specific CEC were not observed. Change in serum 17β-estradiol concentration correlated with change in total macrophage CEC (β = 0.33 per 10 pg/mL change in serum 17β-estradiol, P = .03). CONCLUSIONS Testosterone deprivation in healthy men leads to a dissociation between changes in serum HDL-C and HDL CEC. Changes in serum HDL-C specifically due to testosterone exposure may not reflect changes in HDL function.
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Safety and Efficacy of Fludrocortisone in the Treatment of Cerebral Salt Wasting in Patients With Tuberculous Meningitis: A Randomized Clinical Trial.
Misra, UK, Kalita, J, Kumar, M
JAMA neurology. 2018;(11):1383-1391
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Abstract
IMPORTANCE Tuberculous meningitis is associated with high frequency of cerebral salt wasting. There is a paucity of objective information regarding the best method of treatment of this condition. OBJECTIVE To evaluate the efficacy and safety of fludrocortisone in the treatment of cerebral salt wasting in patients with tuberculous meningitis. DESIGN, SETTING, AND PARTICIPANTS This is a single-center, open-label, randomized clinical trial conducted from October 2015 to April 2017 in India. Patients were randomized in a 1:1 ratio to arms receiving saline only or saline plus fludrocortisone, in addition to a standard treatment of 4 antitubercular drugs, prednisolone, and aspirin. The 2 arms were matched for demographic, clinical, and magnetic resonance imaging findings. The patients were followed up for at least 6 months. INTERVENTIONS Patients were randomized to a 0.9% solution of intravenous saline with 5 to 12 g per day of oral salt supplementation, with or without the addition of 0.1 to 0.4 mg of fludrocortisone per day. MAIN OUTCOMES AND MEASURES The primary end point was the time needed to correct serum sodium levels; secondary end points were in-hospital deaths, disability at 3 months, disability at 6 months, occurence of stroke, and serious adverse reactions. RESULTS Ninety-three patients with suspected tuberculous meningitis were recruited; 12 did not meet the inclusion criteria, including 4 with alternate diagnoses. A total of 37 patients with cerebral salt wasting were eligible for the study. One refused to participate, and therefore 36 patients were included, with 18 randomized to each group. The median (range) age was 30 (20-46) years, and 19 were male (52.8%). Those receiving fludrocortisone regained normal serum sodium levels after 4 days, significantly earlier than those receiving saline only (15 days; P = .004). In an intention-to-treat analysis, hospital mortality, disability at 3 months, and disability at 6 months did not differ significantly, but fewer infarcts occurred in the deep border zone in the group receiving fludrocortisone (1 of 18 [6%]) vs those in the control arm (6 of 18 [33%]; P = .04). Fludrocortisone was associated with severe hypokalemia and hypertension in 2 patients each, and pulmonary edema occurred in 1 patient. These adverse reactions necessitated discontinuation of fludrocortisone in 2 patients. CONCLUSIONS AND RELEVANCE Fludrocortisone results in earlier normalization of serum sodium levels, but did not affect outcomes at 6 months. Fludrocortisone had to be withdrawn in 2 patients because of severe adverse effects. This study provides class II evidence on the role of fludrocortisone in treatment of hyponatremia associated with cerebral salt wasting in patients with tuberculous meningitis. TRIAL REGISTRATION Clinical Trials Registry of India (ctri.nic.in) Identifier: CTRI/2017/10/010255.
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A Randomized Trial of a Novel Chewable Multivitamin and Mineral Supplement Following Roux-en-Y Gastric Bypass.
Perin, J, Prokopowicz, G, Furtado, M, Papas, K, Steele, KE
Obesity surgery. 2018;(8):2406-2420
Abstract
BACKGROUND Vitamin and mineral deficiencies are common following Roux-en-Y gastric bypass (RYGB) and can lead to significant morbidity, but little research on the efficacy of vitamin supplementation regimens exists. We compared the efficacy and tolerability of an investigational versus a standard multivitamin regimen in patients undergoing RYGB. METHODS Fifty-six patients, aged 18 to 65, were randomized to an investigational versus a standard multivitamin. Plasma levels of vitamins A, B-12, D, E-α, E-β/γ, thiamine, folate, iron, iron-binding capacity, iron saturation, prealbumin, and parathyroid hormone (PTH) were measured at 3 and 6 months postoperatively. Proteins induced by vitamin K absence (PIVKA), beta-carotene, coenzyme Q10, and mixed tocopherols were measured at 3 months postoperatively. Primary outcomes were differences in plasma levels at 3 and 6 months. Secondary outcomes were palatability, ease of use, and adherence. RESULTS Twenty-one patients were randomized to the standard regimen and 26 to the investigational multivitamin. Nine were lost to follow-up. At 3 months, plasma levels of PTH were lower (p = 0.042), and levels of vitamin D (p = 0.033), thiamine (p = 0.009), and beta-carotene (p = 0.033) were higher in the investigational multivitamin arm compared to those in the standard regimen arm. Patients receiving the investigational multivitamin reported higher taste satisfaction than those receiving the standard regimen (p = 0.035). CONCLUSION The investigational multivitamin appears to be more effective than a standard multivitamin in maintaining therapeutic levels of clinically relevant vitamins and minerals, and was more palatable. Additional studies should be conducted to confirm these findings and refine the optimal dosing regimen. TRIAL REGISTRATION www.clinicaltrials.gov under identifier NCT01475617.
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Acute effects of high-intensity interval, resistance or combined exercise protocols on testosterone - cortisol responses in inactive overweight individuals.
Velasco-Orjuela, GP, Domínguez-Sanchéz, MA, Hernández, E, Correa-Bautista, JE, Triana-Reina, HR, García-Hermoso, A, Peña-Ibagon, JC, Izquierdo, M, Cadore, EL, Hackney, AC, et al
Physiology & behavior. 2018;:401-409
Abstract
The purpose of this study was to compare the hormonal responses to one session of high-intensity interval training (HIIT, 4 × 4 min intervals at 85-95% maximum heart rate [HRmax], interspersed with 4 min of recovery at 75-85% HRmax), resistance training (RT at 50-70% of one repetition maximum 12-15 repetitions per set with 60s of recovery) or both (HIIT+RT) exercise protocol in a cohort of physical inactivity, overweight adults (age 18-30 years old). Randomized, parallel-group clinical trial among fifty-one men (23.6 ± 3.5 yr; 83.5 ± 7.8 kg; 28.0 ± 1.9 kg/m2), physical inactivity (i.e., <150 min of moderate-intensity exercise per week for >6 months), with abdominal obesity (waist circumference ≥90 cm) or body mass index ≥25 and ≤30 kg/m2 were randomized to the following 4 groups: high-intensity interval training (HIIT, n = 14), resistance training (RT, n = 12), combined high-intensity interval and resistance training (HIIT+RT, n = 13), or non-exercising control (CON, n = 12). Cortisol, total- and free-testosterone and total-testosterone/cortisol-ratio (T/C) assessments (all in serum) were determined before (pre) and 1-min post-exercise for each protocol session. Decreases in cortisol levels were -57.08 (95%CI, -75.58 to -38.58; P = 0.001; ɳ2 = 0.61) and - 37.65 (95%CI, -54.36 to -20.93; P = 0.001; ɳ2 = 0.51) in the HIIT and control group, respectively. Increases in T/C ratio were 0.022 (95%CI, 0.012 to 0.031; P = 0.001; ɳ2 = 0.49) and 0.015 (95%CI, 0.004 to 0.025; P = 0.007; ɳ2 = 0.29) in the HIIT and control group, respectively. In per-protocol analyses revealed a significant change in cortisol levels [interaction effect F(7.777), ɳ2 = 0.33] and T/C ratio [interaction effect F(5.298), ɳ2 = 0.25] between groups over time. Additionally, we showed that in both the intention-to-treat (ITT) and per protocol analyses, HIIT+RT did not change serum cortisol, total or free testosterone. The present data indicate a HIIT reduced cortisol and increased total-testosterone/cortisol-ratio levels significantly in physically inactive adults. Further study is required to determine the biological importance of these changes in hormonal responses in overweight men.
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[Preventive Counselling With the Use of Remote Technologies Provides Effective Control of Metabolic Risk Factors in Patients With High and Very High Cardiovascular Risk].
Pogosova, NV, Yufereva, YM, Yusubova, AI, Allenov, AM, Karpova, AV, Ausheva, AK, Pogozheva, AV, Eganyan, RA, Vygodin, VA
Kardiologiia. 2018;(10):34-44
Abstract
PURPOSE to assess the impact of preventive counseling with focus on diet modification on lipid and metabolic parameters in patients with high / very high cardiovascular (CV) risk who visited Health centers. MATERIALS AND METHODS This was a prospective randomized controlled study of patients aged 40 to 65 years with high/very high CV risk (≥5% according to the Systematic Coronary Risk Evaluation scale [SCORE]) and any 2 criteria for metabolic syndrome. Patients were 1:1 randomized into 2 groups. The intervention group (n=50) received comprehensive preventive counseling with focus on diet modification followed by remote preventive counseling by phone every two weeks for the first 3 months after enrollment (a total of 6 sessions). The control group (n=50) received usual care in Health centers which also included basic preventive counseling. RESULTS A total of 100 patients (women 82%, age 59.74±4.66 years) were randomized. At baseline 81% of patients had high and 19% - very high CV risk. The groups were well balanced according to demographic and clinical features. At 1 year of follow-up patients from the intervention group experienced significant improvement of metabolic parameters compared with controls: their diastolic blood pressure (BP) decreased by 5.62±7.7 mm Hg, total and low-density lipoprotein cholesterol (TC and LDL-C) - by 0.5±0.83 and 0.46±0.62 mmol/l, respectively. Both groups experienced statistically and clinically significant decreases in systolic BP (intervention, - 17.76±16.2 mm Hg, control, - 13.44±15.6 mm Hg; both groups p.
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High-Dose DHA Has More Profound Effects on LDL-Related Features Than High-Dose EPA: The ComparED Study.
Allaire, J, Vors, C, Tremblay, AJ, Marin, J, Charest, A, Tchernof, A, Couture, P, Lamarche, B
The Journal of clinical endocrinology and metabolism. 2018;(8):2909-2917
Abstract
CONTEXT Supplementation with high-dose docosahexaenoic acid (DHA) increases serum low-density lipoprotein (LDL) cholesterol (LDL-C) concentrations more than high-dose eicosapentaenoic acid (EPA). The mechanisms underlying this difference are unknown. OBJECTIVE To examine the phenotypic change in LDL and mechanisms responsible for the differential LDL-C response to EPA and DHA supplementation in men and women at risk of cardiovascular disease. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION In a double-blind, controlled, crossover study, 48 men and 106 women with abdominal obesity and subclinical inflammation were randomized to a sequence of three treatment phases: phase 1, 2.7 g/d of EPA; phase 2, 2.7 g/d of DHA; and phase 3, 3 g/d of corn oil. All supplements were provided as three 1-g capsules for a total of 3 g/d. The 10-week treatment phases were separated by a 9-week washout period. MAIN OUTCOME MEASURE In vivo kinetics of apolipoprotein (apo)B100-containing lipoproteins were assessed using primed-constant infusion of deuterated leucine at the end of each treatment in a subset of participants (n = 19). RESULTS Compared with EPA, DHA increased LDL-C concentrations (+3.3%; P = 0.038) and mean LDL particle size (+0.7 Å; P < 0.001) and reduced the proportion of small LDL (-3.2%; P < 0.01). Both EPA and DHA decreased proprotein convertase subtilisin/kexin type 9 concentrations similarly (-18.2% vs -25.0%; P < 0.0001 vs control). Compared with EPA, DHA supplementation increased both the LDL apoB100 fractional catabolic rate (+11.4%; P = 0.008) and the production rate (+9.4%; P = 0.03). CONCLUSIONS The results of the present study have shown that supplementation with high-dose DHA increases LDL turnover and contributes to larger LDL particles compared with EPA.
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Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination.
Campo, JJ, Le, TQ, Pablo, JV, Hung, C, Teng, AA, Tettelin, H, Tate, A, Hanage, WP, Alderson, MR, Liang, X, et al
eLife. 2018
Abstract
Pneumococcal whole cell vaccines (WCVs) could cost-effectively protect against a greater strain diversity than current capsule-based vaccines. Immunoglobulin G (IgG) responses to a WCV were characterised by applying longitudinally-sampled sera, available from 35 adult placebo-controlled phase I trial participants, to a panproteome microarray. Despite individuals maintaining distinctive antibody 'fingerprints', responses were consistent across vaccinated cohorts. Seventy-two functionally distinct proteins were associated with WCV-induced increases in IgG binding. These shared characteristics with naturally immunogenic proteins, being enriched for transporters and cell wall metabolism enzymes, likely unusually exposed on the unencapsulated WCV's surface. Vaccine-induced responses were specific to variants of the diverse PclA, PspC and ZmpB proteins, whereas PspA- and ZmpA-induced antibodies recognised a broader set of alleles. Temporal variation in IgG levels suggested a mixture of anamnestic and novel responses. These reproducible increases in IgG binding to a limited, but functionally diverse, set of conserved proteins indicate WCV could provide species-wide immunity. Clinical trial registration: The trial was registered with ClinicalTrials.gov with Identifier NCT01537185; the results are available from https://clinicaltrials.gov/ct2/show/results/NCT01537185.
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Reference intervals for reticulocyte hemoglobin content in healthy infants.
Löfving, A, Domellöf, M, Hellström-Westas, L, Andersson, O
Pediatric research. 2018;(5):657-661
Abstract
OBJECTIVES Iron deficiency anemia in childhood is a serious public health problem worldwide. Reticulocyte hemoglobin content (Ret-He) is a novel biomarker of iron deficiency adopted for adults but there is a lack of reference intervals for Ret-He in infants. The aim of this study was to provide data from healthy infants. METHODS Swedish infants (n = 456), born at term after normal pregnancies were included. Ret-He was measured at birth (umbilical cord sample), 48-72 h, 4 months, and 12 months. Reference intervals were calculated as ±2 standard deviations from the mean of Ret-He. RESULTS Reference intervals for newborn Ret-He were 27.4 to 36.0 pg/L (N = 376) in the cord sample, 28.1-37.7 pg/L (N = 253) at 48-72 h, 25.6-33.4 pg/L (N = 341) at four months and 24.9-34.1 pg/L (N = 288) at 12 months. Ret-He was significantly lower among iron-deficient infants, at 4 months mean difference (95% CI) -4.2 pg/L (-6.1 to -2.4) and at 12 months mean difference (95% CI) -3.4 pg/L (-5.0 to -1.8). CONCLUSIONS This longitudinal study presents Ret-He reference intervals based on non-anemic and non-iron-deficient infants and constitutes a step towards standardizing Ret-He as a pre-anemia biomarker of iron deficiency in children.
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Effects of a new intervention based on the Health at Every Size approach for the management of obesity: The "Health and Wellness in Obesity" study.
Dimitrov Ulian, M, Pinto, AJ, de Morais Sato, P, B Benatti, F, Lopes de Campos-Ferraz, P, Coelho, D, Roble, OJ, Sabatini, F, Perez, I, Aburad, L, et al
PloS one. 2018;(7):e0198401
Abstract
Health at Every Size® (HAES®) is a weight-neutral approach focused on promoting healthy behaviors in people with different body sizes. This study examined multiple physiological, attitudinal, nutritional, and behavioral effects of a newly developed, intensive, interdisciplinary HAES®-based intervention in obese women. This was a prospective, seven-month, randomized (2:1), controlled, mixed-method clinical trial. The intervention group (I-HAES®; n = 39) took part in an intensified HAES®-based intervention comprising a physical activity program, nutrition counseling sessions, and philosophical workshops. The control group (CTRL; n = 19) underwent a traditional HAES®-based intervention. Before and after the interventions, participants were assessed for physiological, psychological, and behavioral parameters (quantitative data) and took part in focus groups (qualitative data). Body weight, body mass index, and waist and hip circumferences did not significantly differ within or between groups (P > 0.05). I-HAES® showed increased peak oxygen uptake and improved performance in the timed-stand test (P = 0.004 and P = 0.004, between-group comparisons). No significant within- or between-group differences were observed for objectively measured physical activity levels, even though the majority of the I-HAES® participants indicated that they were engaged in or had plans to include physical activity in their routines. I-HAES® resulted in improvements in eating attitudes and practices. The I-HAES® group showed significantly improved all Body Attitude Questionnaire subscale and all Figure Rating Scale scores (P ≤ 0.05 for all parameters, within-group comparisons), whereas the CTRL group showed slight or no changes. Both groups had significant improvements in health-related quality of life parameters, although the I-HAES® group had superior gains in the "physical health," "psychological health," and "overall perception of quality of life and health" (P = 0.05, 0.03, and 0.02, respectively, between-group comparisons) domains. Finally, most of the quantitative improvements were explained by qualitative data. Our results show that this new intensified HAES®-based intervention improved participants' eating attitudes and practices, perception of body image, physical capacity, and health-related quality of life despite the lack of changes in body weight and physical activity levels, showing that our novel approach was superior to a traditional HAES®-based program.
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Enacting rituals to improve self-control.
Tian, AD, Schroeder, J, Häubl, G, Risen, JL, Norton, MI, Gino, F
Journal of personality and social psychology. 2018;(6):851-876
Abstract
Rituals are predefined sequences of actions characterized by rigidity and repetition. We propose that enacting ritualized actions can enhance subjective feelings of self-discipline, such that rituals can be harnessed to improve behavioral self-control. We test this hypothesis in 6 experiments. A field experiment showed that engaging in a pre-eating ritual over a 5-day period helped participants reduce calorie intake (Experiment 1). Pairing a ritual with healthy eating behavior increased the likelihood of choosing healthy food in a subsequent decision (Experiment 2), and enacting a ritual before a food choice (i.e., without being integrated into the consumption process) promoted the choice of healthy food over unhealthy food (Experiments 3a and 3b). The positive effect of rituals on self-control held even when a set of ritualized gestures were not explicitly labeled as a ritual, and in other domains of behavioral self-control (i.e., prosocial decision-making; Experiments 4 and 5). Furthermore, Experiments 3a, 3b, 4, and 5 provided evidence for the psychological process underlying the effectiveness of rituals: heightened feelings of self-discipline. Finally, Experiment 5 showed that the absence of a self-control conflict eliminated the effect of rituals on behavior, demonstrating that rituals affect behavioral self-control specifically because they alter responses to self-control conflicts. We conclude by briefly describing the results of a number of additional experiments examining rituals in other self-control domains. Our body of evidence suggests that rituals can have beneficial consequences for self-control. (PsycINFO Database Record