Search

Background: Sorghum is the fifth most consumed cereal grain but limiting in the indispensable amino acid lysine. Complementing sorghum with lentils can improve the quality of sorghum-based diets. However, knowledge of lysine bioavailability in sorghum is lacking.Objectives: The study objectives were to determine the bioavailability of lysine in sorghum and to assess the effect of complementation of sorghum and lentils in a mixed-meal format.Methods: We studied 5 healthy young men (≤30 years; BMI <25 kg/m2) in a repeated-measure design using the indicator amino acid oxidation (IAAO) method, with L-[1-13C] phenylalanine as the indicator. Each subject participated in 8 determinations in random order. On the reference diet, subjects received 4 amounts of L-lysine (5, 8, 12, and 15 mg. kg-1 . d-1) from a crystalline amino acid mixture patterned after egg protein. On the test diet, they received 3 levels of lysine (8.2, 12.5, and 15.7 mg. kg-1 . d-1) from sorghum, and on the complementation diet they received 1 level of lysine from a mixed meal of sorghum and lentils. The bioavailability of lysine in sorghum was estimated by comparing the IAAO response to the test diet with the IAAO response to the reference diet using the slope-ratio method. Effectiveness of complementation was assessed by comparing the IAAO response to the mixed meal to the IAAO response to the test protein.Results: The bioavailability of lysine from sorghum was 94%. Upon complementation with lentils, there was a decline in the oxidation of L-[1-13C] phenylalanine by 19% (P < 0.0495), reflecting an improvement in available lysine in the mixed meal due to increased lysine intake.Conclusions: Although the bioavailability of lysine in sorghum is high, its lysine content is limiting. Complementation with lentils in a 1:1 ratio is recommended to achieve the lysine requirement for adult men consuming a sorghum-based diet. This trial was registered at clinicaltrials.gov as NCT03411005. [ABSTRACT FROM AUTHOR]

We detected Rift Valley fever virus (RVFV) IgM and IgG in human serum samples collected during 2018-2019 in northern KwaZulu-Natal Province, South Africa. Our results show recent RVFV circulation and likely RVFV endemicity in this tropical coastal plain region of South Africa in the absence of apparent clinical disease. [ABSTRACT FROM AUTHOR]

[Figure: see text]. [ABSTRACT FROM AUTHOR]

Background: Accurate measurement of dietary intake is vital for providing nutrition interventions and understanding the complex role of diet in health. Traditional dietary assessment methods are very resource intensive and burdensome to participants. Technology may help mitigate these limitations and improve dietary data capture.Objective: Our objective was to evaluate the accuracy of a novel mobile application (PIQNIQ) in capturing dietary intake by self-report. Our secondary objective was to assess whether food capture using PIQNIQ was comparable with an interviewer-assisted 24-h recall (24HR).Methods: This study was a single-center randomized clinical trial enrolling 132 adults aged 18 to 65 y from the general population. Under a provided-food protocol with 3 menus designed to include a variety of foods, participants were randomly assigned to 1 of 3 food capture methods: simultaneous entry using PIQNIQ, photo-assisted recall using PIQNIQ, and 24HR. Primary outcomes were energy and nutrient content (calories, total fat, carbohydrates, protein, added sugars, calcium, dietary fiber, folate, iron, magnesium, potassium, saturated fat, sodium, and vitamins A, C, D, and E) captured by the 3 methods.Results: The majority of nutrients reported were within 30% of consumed intake in all 3 food capture methods (n = 129 completers). Reported intake was highly (>30%) overestimated for added sugars in both PIQNIQ groups and underestimated for calcium in the photo-assisted recall group only (P < 0.001 for all). However, in general, both PIQNIQ methods had similar levels of accuracy and were comparable to the 24HR except in their overestimation (>30%) of added sugars and total fat (P < 0.001 for both).Conclusions: Our results suggest that intuitive, technology-based methods of dietary data capture are well suited to modern users and, with proper execution, can provide data that are comparable to data obtained with traditional methods. This trial was registered at clinicaltrials.gov as NCT03578458. [ABSTRACT FROM AUTHOR]

We report a zoonotic infection of a pig farmer in the Netherlands with a Eurasian avian-like swine influenza A(H1N1) virus that was also detected in the farmed pigs. Both viruses were antigenically and genetically characterized. Continued surveillance of swine influenza A viruses is needed for risk assessment in humans and swine. [ABSTRACT FROM AUTHOR]

Background: Descriptive and quantitative information on β-carotene whole-body kinetics in humans is limited.Objectives: Our objective was to advance the development of a physiologically based, working hypothesis compartmental model describing the metabolism of β-carotene and β-carotene-derived retinol.Methods: We used model-based compartmental analysis (Simulation, Analysis and Modeling software) to analyze previously published data on plasma kinetics of [2H8]β-carotene, [2H4]β-carotene-derived retinol, and [2H8]retinyl acetate-derived retinol in healthy, older US adults (3 female, 2 male; 50-68 y); subjects were studied for 56 d after consuming doses of 11 μmol [2H8]β-carotene and, 3 d later, 9 μmol [2H8]retinyl acetate in oil.Results: We developed a complex model for labeled β-carotene and β-carotene-derived retinol, as well as preformed vitamin A, using simulations to augment observed data during model calibration. The model predicts that mean (range) β-carotene absorption (bioavailability) was 9.5% (5.2-14%) and bioefficacy was 7.3% (3.6-14%). Of the absorbed β-carotene, 41% (25-58%) was packaged intact in chylomicrons and the balance was converted to retinol, with 58% (42-75%) transported as retinyl esters in chylomicrons and 0-2% by retinol-binding protein. Most (95%) chylomicron β-carotene was cleared by the liver. Later data revealed differences in the metabolism of retinyl acetate- versus β-carotene-derived retinol; data required that both β-carotene and derived retinol be recycled from extrahepatic tissues (e.g. adipose) in HDL. Of total bioconversion [73% (47-99%)], 82% occurred in the intestine, 17% in the liver, and 0.83% in other tissues.Conclusions: Our model advances knowledge about whole-body β-carotene metabolism in healthy adults, including the kinetics of transport in all lipoprotein species, and suggests hypotheses to be tested in future studies, such as the possibility that retinol derived from hepatic conversion over a long period of time might contribute to plasma retinol homeostasis and total body vitamin A stores. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) with preserved ejection fraction (HFpEF) constitutes half of all HF but lacks effective therapy. Understanding of its myocardial biology remains limited because of a paucity of heart tissue molecular analysis.Methods: We performed RNA sequencing on right ventricular septal endomyocardial biopsies prospectively obtained from patients meeting consensus criteria for HFpEF (n=41) contrasted with right ventricular septal tissue from patients with HF with reduced ejection fraction (HFrEF, n=30) and donor controls (n=24). Principal component analysis and hierarchical clustering tested for transcriptomic distinctiveness between groups, effect of comorbidities, and differential gene expression with pathway enrichment contrasted HF groups and donor controls. Within HFpEF, non-negative matrix factorization and weighted gene coexpression analysis identified molecular subgroups, and the resulting clusters were correlated with hemodynamic and clinical data.Results: Patients with HFpEF were more often women (59%), African American (68%), obese (median body mass index 41), and hypertensive (98%), with clinical HF characterized by 65% New York Heart Association Class III or IV, nearly all on a loop diuretic, and 70% with a HF hospitalization in the previous year. Principal component analysis separated HFpEF from HFrEF and donor controls with minimal overlap, and this persisted after adjusting for primary comorbidities: body mass index, sex, age, diabetes, and renal function. Hierarchical clustering confirmed group separation. Nearly half the significantly altered genes in HFpEF versus donor controls (1882 up, 2593 down) changed in the same direction in HFrEF; however, 5745 genes were uniquely altered between HF groups. Compared with controls, uniquely upregulated genes in HFpEF were enriched in mitochondrial adenosine triphosphate synthesis/electron transport, pathways downregulated in HFrEF. HFpEF-specific downregulated genes engaged endoplasmic reticulum stress, autophagy, and angiogenesis. Body mass index differences largely accounted for HFpEF upregulated genes, whereas neither this nor broader comorbidity adjustment altered pathways enriched in downregulated genes. Non-negative matrix factorization identified 3 HFpEF transcriptomic subgroups with distinctive pathways and clinical correlates, including a group closest to HFrEF with higher mortality, and a mostly female group with smaller hearts and proinflammatory signaling. These groupings remained after sex adjustment. Weighted gene coexpression analysis yielded analogous gene clusters and clinical groupings.Conclusions: HFpEF exhibits distinctive broad transcriptomic signatures and molecular subgroupings with particular clinical features and outcomes. The data reveal new signaling targets to consider for precision therapeutics. [ABSTRACT FROM AUTHOR]

A major outbreak of yellow fever (YF) occurred in Brazil during 2016-2018. Epizootics in New World nonhuman primates are sentinel events for YF virus circulation. However, genus-specific susceptibilities and suitability for YF surveillance remain poorly understood. We obtained and compared epidemiologic, histopathologic, immunohistochemical, and molecular results from 93 human and 1,752 primate cases submitted during the recent YF outbreak in Brazil (2017), with the support of the Brazilian National YF Surveillance Program. We detected heterogeneous YF-associated profiles among the various genera of primates we analyzed. Alouatta primates were the most reliable sentinel; Sapajus and Callicebus primates had higher viral loads but lower proportional mortality rates. Callithrix primates were the least sensitive, showing lower viral loads, lower proportional mortality rates, and no demonstrable YF virus antigen or extensive lesions in liver, despite detectable viral RNA. These differences in susceptibility, viral load, and mortality rates should be considered in strategic surveillance of epizootics and control measures for YF. [ABSTRACT FROM AUTHOR]

Background: Ventricular tachyarrhythmias and sudden cardiac death show a circadian pattern of occurrence in patients with heart failure. In the rodent ventricle, a significant portion of genes, including some ion channels, shows a circadian pattern of expression. However, genes that define electrophysiological properties in failing human heart ventricles have not been examined for a circadian expression pattern.Methods: Ventricular tissue samples were collected from patients at the time of cardiac transplantation. Two sets of samples (n=37 and 46, one set with a greater arrhythmic history) were selected to generate pseudo-time series according to their collection time. A third set (n=27) of samples was acquired from the nonfailing ventricles of brain-dead donors. The expression of 5 known circadian clock genes and 19 additional ion channel genes plausibly important to electrophysiological properties were analyzed by real-time polymerase chain reaction and then analyzed for the percentage of expression variation attributed to a 24-hour circadian pattern.Results: The 5 known circadian clock gene transcripts showed a strong circadian expression pattern. Compared with rodent hearts, the human circadian clock gene transcripts showed a similar temporal order of acrophases but with a ≈7.6 hours phase shift. Five of the ion channel genes also showed strong circadian expression. Comparable studies of circadian clock gene expression in samples recovered from nonheart failure brain-dead donors showed acrophase shifts, or weak or complete loss of circadian rhythmicity, suggesting alterations in circadian gene expression.Conclusions: Ventricular tissue from failing human hearts display a circadian pattern of circadian clock gene expression but phase-shifted relative to rodent hearts. At least 5 ion channels show a circadian expression pattern in the ventricles of failing human hearts, which may underlie a circadian pattern of ventricular tachyarrhythmia/sudden cardiac death. Nonfailing hearts from brain-dead donors show marked differences in circadian clock gene expression patterns, suggesting fundamental deviations from circadian expression. [ABSTRACT FROM AUTHOR]

Background: Pearl millet is the chief source of energy in the diet in some developing regions, but has a limited amount of indispensable amino acid lysine. Complementation with pulses like lentils can improve the protein quality of millet diets, but the knowledge of lysine bioavailability (BA) in millet and lentils is lacking.Objectives: The study objectives were to determine the BA of lysine in millet and lentils separately and to assess the effect of complementation of millet and lentils in a mixed meal format.Methods: We studied 9 healthy young men (≤30 y; BMI <25) in a repeated-measure design using the indicator amino acid oxidation (IAAO) method, with L-[1-13C] phenylalanine as the indicator. Each subject completed 7 or 8 experiments in random order. On the reference diet, subjects received 4 graded levels of L-lysine (5, 8, 12, and 15 mg·kg-1.d-1) from a crystalline amino acid mixture patterned after egg protein; on the test diets, they received 3 levels of lysine (10, 12, and 15 mg·kg-1.d-1) from either steamed millet or stewed lentils; and on the complementation diet, they received 1 level of lysine from a mixed meal of steamed millet and stewed lentils. The BA of lysine and the effect of complementation were assessed by comparing the IAAO responses to the test diets and the complementation diet with the IAAO response to L-lysine intakes in the reference protein, using the slope ratio method.Results: The BA of lysine was 97% from millet and 80% from lentils. Complementation of steamed millet with stewed lentils decreased the oxidation of L-[1-13C] phenylalanine by 27% (P < 0.05), signifying improved quality of the combined millet and lentil protein.Conclusions: Lysine has high BA but is still limiting in steamed pearl millet. Complementation with lentils in a 2:1 ratio is recommended to meet the lysine and protein requirements for adult men consuming a millet-based diet. This trial was registered at clinicaltrials.gov as NCT03674736 and NCT03339167. [ABSTRACT FROM AUTHOR]

Background: Better methods are needed for determining vitamin A absorption efficiency in humans to support development of dietary recommendations and to improve the accuracy of predictions of vitamin A status.Objectives: We developed and evaluated a method for estimating vitamin A absorption efficiency based on compartmental modeling of theoretical data on postprandial plasma retinyl ester (RE) kinetics.Methods: We generated data on plasma RE and retinol kinetics (30 min to 8 h or 56 d, respectively) after oral administration of labeled vitamin A for 12 theoretical adults with a range of values assigned for vitamin A absorption (55-90%); we modeled all data to obtain best-fit values for absorption and other parameters using Simulation, Analysis, and Modeling software. We then modeled RE data only (16 or 10 samples), with or without added random error, and compared assigned to predicted absorption values. We also compared assigned values to areas under RE response curves (RE AUCs).Results: We confirmed that a unique value for vitamin A absorption cannot be identified by modeling plasma retinol tracer kinetics. However, when RE data were modeled, predicted vitamin A absorptions were within 1% of assigned values using data without error and within 12% when 5% error was included. When the sample number was reduced, predictions were still within 13% for 10 of the 12 subjects and within 23% overall. Assigned values for absorption were not correlated with RE AUC (P = 0.21).Conclusions: We describe a feasible and accurate method for determining vitamin A absorption efficiency that is based on compartmental modeling of plasma RE kinetic data collected for 8 h after a test meal. This approach can be used in a clinical setting after fasting subjects consume a fat-containing breakfast meal with a known amount of vitamin A or a stable isotope label. [ABSTRACT FROM AUTHOR]

In a multicenter study, we determined a prevalence rate of 4% for azole-resistant Aspergillus fumigatus in Taiwan. Resistance emerged mainly from the environment (TR34/L98H, TR34/L98H/S297T/F495I, and TR46/Y121F/T289A mutations) but occasionally during azole treatment. A high mortality rate observed for azole-resistant aspergillosis necessitates diagnostic stewardship in healthcare and antifungal stewardship in the environment. [ABSTRACT FROM AUTHOR]

In a multicenter study, we determined a prevalence rate of 4% for azole-resistant Aspergillus fumigatus in Taiwan. Resistance emerged mainly from the environment (TR34/L98H, TR34/L98H/S297T/F495I, and TR46/Y121F/T289A mutations) but occasionally during azole treatment. A high mortality rate observed for azole-resistant aspergillosis necessitates diagnostic stewardship in healthcare and antifungal stewardship in the environment. [ABSTRACT FROM AUTHOR]

Emergency vaccination programs often are needed to control outbreaks of meningococcal disease caused by Neisseria meningitidis serogroup B (MenB) on college campuses. Such campaigns expend multiple campus and public health resources. We conducted a randomized, controlled, multicenter, observer-blinded trial comparing immunogenicity and tolerability of an accelerated vaccine schedule of 0 and 21 days to a longer interval of 0 and 60 days for 4-component MenB vaccine (MenB-4C) in students 17-25 years of age. At day 21 after the first MenB-4C dose, we observed protective human serum bactericidal titers >4 to MenB strains 5/99, H44/76, and NZ 98/254 in 98%-100% of participants. Geometric mean titers increased >22-fold over baseline. At day 180, >95% of participants sustained protective titers regardless of their vaccine schedule. The most common adverse event was injection site pain. An accelerated MenB-4C immunization schedule could be considered for rapid control of campus outbreaks. [ABSTRACT FROM AUTHOR]

Emergency vaccination programs often are needed to control outbreaks of meningococcal disease caused by Neisseria meningitidis serogroup B (MenB) on college campuses. Such campaigns expend multiple campus and public health resources. We conducted a randomized, controlled, multicenter, observer-blinded trial comparing immunogenicity and tolerability of an accelerated vaccine schedule of 0 and 21 days to a longer interval of 0 and 60 days for 4-component MenB vaccine (MenB-4C) in students 17-25 years of age. At day 21 after the first MenB-4C dose, we observed protective human serum bactericidal titers >4 to MenB strains 5/99, H44/76, and NZ 98/254 in 98%-100% of participants. Geometric mean titers increased >22-fold over baseline. At day 180, >95% of participants sustained protective titers regardless of their vaccine schedule. The most common adverse event was injection site pain. An accelerated MenB-4C immunization schedule could be considered for rapid control of campus outbreaks. [ABSTRACT FROM AUTHOR]

During October 2011-September 2014, we screened respiratory specimens for seasonal and avian influenza A(H5N1) virus infections among outpatients with influenza-like illness and inpatients with severe acute respiratory infection (SARI) in East Jakarta, an Indonesia district with high incidence of H5N1 virus infection among poultry. In total, 31% (1,875/6,008) of influenza-like illness case-patients and 15% (571/3,811) of SARI case-patients tested positive for influenza virus. Influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B virus infections were detected in all 3 years, and the epidemic season extended from November through May. Although 28% (2,810/10,135) of case-patients reported exposure to poultry, only 1 SARI case-patient with an H5N1 virus infection was detected. Therefore, targeted screening among case-patients with high-risk poultry exposures (e.g., a recent visit to a live bird market or close proximity to sick or dead poultry) may be a more efficient routine surveillance strategy for H5N1 virus in these types of settings. [ABSTRACT FROM AUTHOR]

Background: Height is an indicator of nutritional status; linear growth faltering has recognized consequences for cognitive, emotional, and chronic disease risk. Although height is routinely studied in developing countries, less attention is given to height in the United States.Objective: The objective of this study was to identify longitudinal associations between childhood and adolescent beverage intakes, nutrient adequacy, or energy intake and height in a birth cohort.Methods: Data for participants through ages 2-17 y (n = 717; 353 males, 364 females) recruited at birth for the longitudinal Iowa Fluoride Study (IFS) were used in the current cohort analyses. Beverage intakes (n = 708) were collected by beverage-frequency questionnaires at 3- to 6-mo intervals, whereas nutrient data (n = 652) were obtained from 3-d food diaries completed at 3- to 6-mo intervals through age 8.5 y and from Block Kids' food-frequency questionnaires at 2-y intervals after age 8.5 y. Nutrient adequacy ratios were calculated with the use of age- and sex-specific Estimated Average Requirements. Height was measured at clinic visits when the participants were approximately ages 5, 9, 11, 13, 15, and 17 y. Linear mixed models were used to identify longitudinal associations between dietary variables and height. A baseline model that adjusted for changing growth patterns during adolescence was established. Dietary and potential confounding variables were added to this baseline model.Results: Milk intake adjusted for mean adequacy ratio, energy intake, and baseline socioeconomic status was associated with height; for each additional 8 ounces (236 mL) of milk consumed per day throughout childhood and adolescence, height increased, on average, by 0.39 cm (95% CI: 0.18, 0.60 cm; P < 0.001).Conclusions: IFS participants' height increased by 0.39 cm for each additional 8 ounces (236 mL) of milk consumed throughout childhood and adolescence. The clinical implications of the mild linear growth faltering observed in healthy youth are unknown. This trial was registered at www.clinicaltrials.gov as 199112665. [ABSTRACT FROM AUTHOR]

Background: A meal rich in saturated fatty acids induces a postprandial metabolic challenge. The type of dietary protein may modulate postprandial metabolism.Objective: We studied the effect of dietary protein type on postprandial changes in the metabolome after a high-fat meal.Methods: In a 3-period, crossover, postprandial study, 10 healthy overweight men with an elevated waist circumference (>94 cm) ingested high-fat meals made up of cream fat (70% of energy), sucrose (15% energy), and protein (15% energy) from either casein (CAS), whey protein (WHE), or α-lactalbumin-enriched whey protein (LAC). Urine collected immediately before and 2, 4, and 6 h after the meal was analyzed for metabolomics, a secondary outcome of the clinical study. We used mixed-effect models, partial least-square regression, and pathway enrichment analysis.Results: At 4 and 6 h after the meal, the postprandial metabolome was found to be fully discriminated according to protein type. We identified 17 metabolites that significantly explained the effect of protein type on postprandial metabolomic changes (protein-time interaction). Among this signature, acylcarnitines and other acylated metabolites related to fatty acid or amino acid oxidation were the main discriminant features. The difference in metabolic profiles was mainly explained by urinary acylcarnitines and some other acylated products (protein type, Ps < 0.0001), with a dramatically greater increase (100- to 1000-fold) after WHE, and to a lesser extent after LAC, as compared with CAS. Pathway enrichment analysis confirmed that the type of protein had modified fatty acid oxidation (P < 0.05).Conclusion: Taken together, our results indicate that, in healthy overweight men, the type of protein in a high-fat meal interplays with fatty acid oxidation with a differential accumulation of incomplete oxidation products. A high-fat meal containing WHE, but not CAS, resulted in this outpacing of the tricarboxylic acid cycle. This study was registered at clinicaltrials.gov as NCT00931151. [ABSTRACT FROM AUTHOR]

Background: Poor fitness in middle age is a risk factor for heart failure, particularly heart failure with a preserved ejection fraction. The development of heart failure with a preserved ejection fraction is likely mediated through increased left ventricular (LV) stiffness, a consequence of sedentary aging. In a prospective, parallel group, randomized controlled trial, we examined the effect of 2 years of supervised high-intensity exercise training on LV stiffness.Methods: Sixty-one (48% male) healthy, sedentary, middle-aged participants (53±5 years) were randomly assigned to either 2 years of exercise training (n=34) or attention control (control; n=27). Right heart catheterization and 3-dimensional echocardiography were performed with preload manipulations to define LV end-diastolic pressure-volume relationships and Frank-Starling curves. LV stiffness was calculated by curve fit of the diastolic pressure-volume curve. Maximal oxygen uptake (Vo2max) was measured to quantify changes in fitness.Results: Fifty-three participants completed the study. Adherence to prescribed exercise sessions was 88±11%. Vo2max increased by 18% (exercise training: pre 29.0±4.8 to post 34.4±6.4; control: pre 29.5±5.3 to post 28.7±5.4, group×time P<0.001) and LV stiffness was reduced (right/downward shift in the end-diastolic pressure-volume relationships; preexercise training stiffness constant 0.072±0.037 to postexercise training 0.051±0.0268, P=0.0018), whereas there was no change in controls (group×time P<0.001; pre stiffness constant 0.0635±0.026 to post 0.062±0.031, P=0.83). Exercise increased LV end-diastolic volume (group×time P<0.001), whereas pulmonary capillary wedge pressure was unchanged, providing greater stroke volume for any given filling pressure (loading×group×time P=0.007).Conclusions: In previously sedentary healthy middle-aged adults, 2 years of exercise training improved maximal oxygen uptake and decreased cardiac stiffness. Regular exercise training may provide protection against the future risk of heart failure with a preserved ejection fraction by preventing the increase in cardiac stiffness attributable to sedentary aging.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02039154. [ABSTRACT FROM AUTHOR]

Background: Previous studies indicated the importance of the intrinsic left ventricular (LV) electric delay (QLV) for optimal benefit to cardiac resynchronization therapy. We investigated the use of QLV for achieving optimal acute hemodynamic response to cardiac resynchronization therapy with a quadripolar LV lead.Methods and Results: Forty-eight heart failure patients with a left bundle branch block were prospectively enrolled (31 men; age, 66±10 years; LV ejection fraction, 28±8%; QRS duration, 176±14 ms). Immediately after cardiac resynchronization therapy implantation, invasive LV pressure-volume loops were recorded during biventricular pacing with each separate electrode at 4 atrioventricular delays. Acute cardiac resynchronization therapy response, measured as change in stroke work (Δ%SW) compared with intrinsic conduction, was related to intrinsic interval between Q on the ECG and LV sensing delay (QLV), normalized for QRS duration (QLV/QRSd), and electrode position. QLV/QRSd was 84±9% and variation between the 4 electrodes 9±5%. Δ%SW was 89±64% and varied by 39±36% between the electrodes. In univariate analysis, an anterolateral or lateral electrode position and a high QLV/QRSd had a significant association with a large Δ%SW (all P <0.01). In a combined model, only QLV/QRSd remained significantly associated with Δ%SW (P<0.05). However, a direct relation between QLV/QRSd and Δ%SW was only seen in 24 patients, whereas 24 patients showed an inverse relation.Conclusions: The large variation in acute hemodynamic response indicates that the choice of the stimulated electrode on a quadripolar lead is important. Although QLV/QRSd was associated with acute hemodynamic response at group level, it cannot be used to select the optimal electrode in the individual patient. [ABSTRACT FROM AUTHOR]

Background: The mechanisms by which persistent atrial fibrillation (AF) terminates via localized ablation are not well understood. To address the hypothesis that sites where localized ablation terminates persistent AF have characteristics identifiable with activation mapping during AF, we systematically examined activation patterns acquired only in cases of unequivocal termination by ablation.Methods and Results: We recruited 57 patients with persistent AF undergoing ablation, in whom localized ablation terminated AF to sinus rhythm or organized tachycardia. For each site, we performed an offline analysis of unprocessed unipolar electrograms collected during AF from multipolar basket catheters using the maximum -dV/dt assignment to construct isochronal activation maps for multiple cycles. Additional computational modeling and phase analysis were used to study mechanisms of map variability. At all sites of AF termination, localized repetitive activation patterns were observed. Partial rotational circuits were observed in 26 of 57 (46%) cases, focal patterns in 19 of 57 (33%), and complete rotational activity in 12 of 57 (21%) cases. In computer simulations, incomplete segments of partial rotations coincided with areas of slow conduction characterized by complex, multicomponent electrograms, and variations in assigning activation times at such sites substantially altered mapped mechanisms.Conclusions: Local activation mapping at sites of termination of persistent AF showed repetitive patterns of rotational or focal activity. In computer simulations, complete rotational activation sequence was observed but was sensitive to assignment of activation timing particularly in segments of slow conduction. The observed phenomena of repetitive localized activation and the mechanism by which local ablation terminates putative AF drivers require further investigation. [ABSTRACT FROM AUTHOR]

Background: The VANISH trial (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease) compared the effectiveness of escalated antiarrhythmic drug therapy to catheter ablation in patients with prior myocardial infarction, an implanted defibrillator, and ventricular tachycardia (VT). The effectiveness of these interventions in patients on sotalol versus amiodarone was compared.Methods and Results: Analysis was conducted based on whether patients had recurrent VT, despite amiodarone (amio-refractory) or nonamiodarone drugs (sotalol-refractory). Outcomes included death, VT storm, appropriate implantable cardioverter defibrillator shock, and any ventricular arrhythmia. At baseline, 169 (65.2%) were amio-refractory, and 90 (34.7%) were sotalol-refractory (1 patient on procainamide rather than sotalol). Amio-refractory patients had more renal insufficiency (23.7% versus 10%; P=0.0008), worse New York Heart Association class (82.3% II/III versus 65.5%; P=0.0003), and lower ejection fraction (29±9.7% versus 35.2±11%; P<0.0001). Within the amio-refractory group, ablation resulted in reduction of any ventricular arrhythmia compared with escalated drug therapy (hazard ratio, 0.53; 95% confidence interval, 0.31-0.9), P=0.020). Sotalol-refractory patients had trends toward higher mortality and VT storm with ablation, with no effect on implantable cardioverter defibrillator shocks. Within the escalated drug therapy arm, amio-refractory patients had a higher rate of the composite outcome (hazard ratio, 1.94; 95% confidence interval, 1.14-3.29; P=0.0144) and a trend to higher mortality (hazard ratio, 2.40; 95% confidence interval, 0.93-6.22; P=0.07), whereas mortality was not different between amio- and sotalol-refractory patients within the ablation treatment group.Conclusions: Patients with amio-refractory VT have a higher rate of ventricular arrhythmia and mortality than those with sotalol-refractory VT and derive greater benefit of catheter ablation than for patients with sotalol-refractory VT who are switched to amiodarone.Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00905853. [ABSTRACT FROM AUTHOR]

Background: The optimal dosage of cryotherapy during cryoballoon ablation of pulmonary veins is still unclear. This trial tested the noninferiority of a novel, individualized, cryotherapy-dosing strategy for each vein.Methods and Results: This prospective, randomized, multicenter, noninferiority study included 140 patients with paroxysmal atrial fibrillation, which was refractory to antiarrhythmic drugs. Patients were randomly assigned to a conventional strategy of 180-second cryoballoon applications per vein with a bonus freeze (control group, n=70) or to a shorter-time application protocol, with 1 application that lasted the time required for electric block time to effect plus 60- and a 120-second freeze bonus (study group, n=70). Patients were followed with a long-term monitoring system of 30 days. At 1-year follow-up, no difference was observed in terms of free atrial fibrillation-recurrence rates: 79.4% in control versus 78.3% in study group (Δ=1.15%; 90% confidence interval, -10.33% to 12.63%; P=0.869). Time to effect was detected in 72.1% of veins. The control and study groups had similar mean number of applications per patient (9.6±2 versus 9.9±2.4; P=0.76). Compared with controls, the study group had a significantly shorter cryotherapy time (28.3±7 versus 19.4±4.3 minutes; P<0.001), left atrium time (104±25 versus 92±23 minutes; P<0.01), and total procedure time (135±35 versus 119±31 minutes; P<0.01). No differences were observed in complications or acute reconnections.Conclusions: The new time-to-effect-based cryotherapy dosage protocol led to shorter cryotherapy and procedure times, with equal safety, and similar acute and 1-year follow-up results, compared with the conventional approach.Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02789358. [ABSTRACT FROM AUTHOR]

Preventing emergence of new zoonotic viruses depends on understanding determinants for human risk. Nipah virus (NiV) is a lethal zoonotic pathogen that has spilled over from bats into human populations, with limited person-to-person transmission. We examined ecologic and human behavioral drivers of geographic variation for risk of NiV infection in Bangladesh. We visited 60 villages during 2011-2013 where cases of infection with NiV were identified and 147 control villages. We compared case villages with control villages for most likely drivers for risk of infection, including number of bats, persons, and date palm sap trees, and human date palm sap consumption behavior. Case villages were similar to control villages in many ways, including number of bats, persons, and date palm sap trees, but had a higher proportion of households in which someone drank sap. Reducing human consumption of sap could reduce virus transmission and risk for emergence of a more highly transmissible NiV strain. [ABSTRACT FROM AUTHOR]

Background: After sudden cardiac death with negative autopsy, clinical screening of relatives identifies a high proportion of inherited arrhythmia syndrome. However, the efficacy of this screening in families not selected by autopsy has never been assessed. We aim to investigate the value of clinical screening in relatives of all subjects who died suddenly before 45 years of age.Methods and Results: One hundred and three consecutive families who experienced unexplained sudden cardiac death before 45 years of age were included from May 2009 to December 2014 in a prospective multicenter registry. Clinical screening was provided to all relatives and performed in 64 families (230 relatives, 80 unexplained sudden cardiac death). Diagnosis was established in 16 families (25%), including Brugada syndrome (7), long QT syndromes (5), dilated cardiomyopathy (2), and hypertrophic cardiomyopathy (2). The diagnostic yield was mainly dependent on the number of screened relatives (3.8±3.4 screened relatives in diagnosed families versus 2.0±1.5; P<0.005) rising to 47% with at least 3 relatives. It additionally increased from 3 of 32 (9%) to 9 of 22 (41%) when both parents were screened (P=0.01). Diagnostic performance was also dependent on the exhaustiveness of screening (70% of complete screening in the diagnosed families versus 25%; P<0.0001) with 17 Brugada syndromes and 15 long QT syndromes diagnosed based on pharmacological tests.Conclusions: Even without autopsy, familial screening after sudden death in young patients is effective. Broad screening of relatives and systematic tests, including pharmacological challenges, greatly increases the likelihood of diagnosis in families. [ABSTRACT FROM AUTHOR]

Background: Hypotension during anaesthesia for hip fracture surgery is common. Recent data suggest that there is an association between the lowest intra-operative blood pressure and mortality, even when adjusted for co-morbidities. This is consistent with data derived from the wider surgical population, where magnitude and duration of hypotension are associated with mortality and peri-operative complications. However, there are no trial to data to support more aggressive blood pressure control.Methods/design: We are conducting a three-centre, randomised, double-blinded pilot study in three hospitals in the United Kingdom. The sample size will be 75 patients (25 from each centre). Randomisation will be done using computer-generated concealed tables. Both participants and investigators will be blinded to group allocation. Participants will be aged >70 years, cognitively intact (Abbreviated Mental Test Score 7 or greater), able to give informed consent and admitted directly through the emergency department with a fractured neck of the femur requiring operative repair. Patients randomised to tight blood pressure control or avoidance of intra-operative hypotension will receive active treatment as required to maintain both of the following: systolic arterial blood pressure >80% of baseline pre-operative value and mean arterial pressure >75 mmHg throughout. All participants will receive standard hospital care, including spinal or general anaesthesia, at the discretion of the clinical team. The primary outcome is a composite of the presence or absence of defined cardiovascular, renal and delirium morbidity within 7 days of surgery (myocardial injury, stroke, acute kidney injury, delirium). Secondary endpoints will include the defined individual morbidities, mortality, early mobility and discharge to usual residence.Discussion: This is a small-scale pilot study investigating the feasibility of a trial of tight intra-operative blood pressure control in a frail elderly patient group with known high morbidity and mortality. Positive findings will provide the basis for a larger-scale study.Trial Registration: ISRCTN Registry identifier: ISRCTN89812075 . Registered on 30 August 2016. [ABSTRACT FROM AUTHOR]

We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness. [ABSTRACT FROM AUTHOR]

Purpose: Comparing the effectiveness of dietary vitamin C and weight loss exercises interventions for weight loss on semen characteristics in normal obese man.Materials and Methods: A total number of 200 men were randomly allocated into two groups based on body mass index, exercise and vitamin C groups. Also, 50 men with normal spermogram were placed in a control group. In exercise group, a 6 months intensive exercise program was designed under a coach's supervision to reduce the body weight. In vitamin C group, 1,000 mg of vitamin C were given every other day as supplement.Results: Weight loss increased the volume of semen in participants with 25-30 (P = .02) and more than 30 body mass index (P = .001). The increased concentration of sperm per mL of semen in body mass index (BMI) 25-30 group (P = .01) and more than 30 (P = .003) BMI was significant. Improving sperm motility after two hours in participants with more than 30 (P = .01) BMI was significant. In vitamin C group, the improvement of sperm concentration in participants who had less than 25 (P = .01), between 25 and 30 (P = .01), more than 30 (P = .02) BMI was significant. Sperm motility improved in all three groups (P = .001, P = .02 and P = .003, respectively).Conclusion: Weight loss can significantly increase semen volume, its concentration, its mobility and percentage of normal morphology. Consuming vitamin C significantly improves sperm concentration and mobility, but the semen volume and the percentage of normal morphology will not change significantly. [ABSTRACT FROM AUTHOR]

Purpose: Urinary tract infections (UTIs) are widespread and affect a large portion of the human population. Cranberry juices and extracts have been used for UTI prevention due to their content of bioactive proanthocyanidins (PACs), particularly of the A type (PAC-A). Controversial clinical results obtained with cranberry are often due to a lack of precise determination and authentication of the PAC-A content. This study used Oximacro (Biosfered S.r.l., Turin, Italy), a cranberry extract with a high content of PAC-A, to prevent UTIs in female and male volunteers.Materials and Methods: The Oximacro PACs content was assayed using the Brunswick Laboratories 4-dimethylaminocinnamaldehyde (BL-DMAC) method, and the dimer and trimer PACs-A and PACs-B percentages were determined via high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS). A balanced group of female (ranging from 19 to over 51 years) and male volunteers (over 51 years) was divided into two groups. The experimental group received 1 capsule containing Oximacro (36 mg PACs-A) twice per day (morning and evening) for 7 days, and the placebo group was given the same number of capsules with no PACs.Results: Analysis of Oximacro revealed a high total PAC content (372.34 mg/g ± 2.3) and a high percentage of PAC-A dimers and trimers (86.72% ± 1.65). After 7 days of Oximacro administration, a significant difference was found between the placebo and Oximacro groups for both females (Mann-Whitney U-test = 875; P < .001; n = 60) and males (Mann-Whitney U-test = 24; P = .016; n = 10). When the female and male age ranges were analysed separately, the female age range 31-35 showed only slightly significant differences between the placebo and Oximacro groups (Mann-Whitney U-test = 20.5; P = .095; n = 10), whereas all other female age ranges showed highly significant differences between the placebo and Oximacro groups (Mann-Whitney U-test = 25; P = .008; n = 10). Furthermore, colony forming unit/mL counts from the urine cultures showed a significant difference (P < .001) between the experimental and the placebo groups (SD difference = 51688; df = 34, t = -10.27; Dunn-Sidak Adjusted P < .001, Bonferroni Adjusted P < .001).Conclusion: Careful determination of the total PAC content using the BL-DMAC method and the authentication of PACs-A with mass spectrometry in cranberry extracts are necessary to prepare effective doses for UTI prevention. A dose of 112 mg Oximacro containing 36 mg PACs-A was found to be effective in preventing UTIs when used twice per day for 7 days. [ABSTRACT FROM AUTHOR]

Background: Central sensitization is modulated by the endogenous opioid system and plays a major role in the development and maintenance of pain. Recent animal studies performed following resolution of inflammatory pain showed reinstatement of tactile hypersensitivity induced by administration of a mu-opioid-antagonist, suggesting latent sensitization is mediated by endogenous opioids. In a recent crossover study in healthy volunteers, following resolution of a first-degree burn, 4 out of 12 volunteers developed large secondary areas of hyperalgesia areas after a naloxone infusion, while no volunteer developed significant secondary hyperalgesia after the placebo infusion. In order to consistently demonstrate latent sensitization in humans, a pain model inducing deep tissue inflammation, as used in animal studies, might be necessary. The aim of the present study is to examine whether a high-dose target-controlled naloxone infusion can reinstate pain and hyperalgesia following recovery from open groin hernia repair and thus consistently demonstrate opioid-mediated latent sensitization in humans.Methods/design: Patients submitted to unilateral, primary, open groin hernia repair will be included in this randomized, placebo-controlled, double-blind, crossover study. The experimental days take place 6-8 weeks after surgery, time-points at which patients are expected to be almost pain- free. Prior to administration of naloxone or placebo, the primary outcome (a summated measure of pain: at rest, during transition from supine to standing position, and evoked by pressure algometry) and the secondary outcomes (secondary hyperalgesia/allodynia, pressure pain thresholds, assessed at the surgical site and at the mirror-site in the contralateral groin, and, opioid withdrawal symptoms) will be assessed. These assessments will be repeated at each step of the target-controlled infusion of placebo or naloxone at estimated median (95 % CI) plasma concentrations of 344 ng/ml (130;567), 1059 ng/ml (400;1752) and 3196 ng/ml (1205;5276).Discussion: We aim to demonstrate opioid-mediated latent sensitization in a post-surgical setting, using pain as a clinical relevant variable. Impairment of the protective endogenous opioid system may play an important role in the transition from acute to chronic pain. In order to sufficiently block the endogenous opioid system, a high-dose target-controlled naloxone-infusion is used, in accordance with recent findings in animal studies.Trial Registration Number: Eudract: 2015-000793-36 (Registration date: 16 February 2015) Clinicaltrials.gov: NCT01992146 (Registration date: 12 December 2014). [ABSTRACT FROM AUTHOR]

Purpose: Thermobalancing therapy, provided by Therapeutic Device, which contains a natural thermoelement, and is applied topically in the projection ofthe prostate,was aimed to improve blood circulation in the affected organ. We evaluated the effectiveness of new Therapeutic Device for the treatment of patients with benign prostatic hyperplasia (BPH).Materials and Methods: We performed a clinical non-randomized controlled trial before and after 6-month treatment. Therapeutic Device was administered to 124 patients with BPH as mono-therapy. The dynamic of the patients' condition was assessed by the International Prostate Symptom Score (IPSS), ultrasound measurement of prostate volume (PV) and uroflowmetry. The control-group comprised 124 men who did not receive any treatment. The IPSS score, maximum flow rate (Qmax), and PV were compared between the groups.Results: Baseline evaluation (pre-treatment) for both groups were comparable to each other with no clinically significant difference regarding age, IPSS score, Qmax and PV volume. Overall, thermobalancing therapy resulted in significant improvements from baseline to endpoint in IPSS (P = .001), IPSS storage and voiding subscores (both P = .001), and IPSS quality of life index (QoL) (P = .001) compared with control group. Moreover, comparison of parameters after 6 months treatment showed that thermobalancing therapy also improved the Qmax (P = .001), and PV (P = .001).Conclusion: Two years clinical trial demonstrated that thermobalancing therapy administered for 6 months provides a marked improvement in patients presenting with symptomatic BPH not only on lower urinary tract symptoms (LUTS) but also in QoL and Qmax. Thus urologists should be aware about thermobalancing therapy as a non-invasive physiotherapeutic treatment option for treatment of BPH. [ABSTRACT FROM AUTHOR]

Objective: To determine the feasibility of performing in vivo magnetic resonance elastography (MRE) for uterine leiomyoma.Design: Pilot study.Setting: Academic medical center.Patient(s): Six subjects planning surgical excision of uterine leiomyomas.Intervention(s): MRE before planned surgery.Main Outcome Measure(s): Achieving an appropriate phase signal-to-noise ratio (PSNR) in the leiomyoma to allow assessment of leiomyoma elasticity in kilopascals (kPa).Result(s): MRE was successful in all subjects for uteri ranging from 100 to >1,000 g. Subjects had body mass indexes ranging from 23.0 to 38.0 kg/m2. Appropriate PSNRs, ranging from 5.45 to 42.28, were achieved for leiomyomas in all subjects. Mean elasticity of uterine leiomyomas ranged from 3.95 to 6.68 kPa.Conclusion(s): MRE is a feasible technique for studying the in vivo mechanical properties of uterine leiomyomas and demonstrates significant heterogeneity in elasticity between lesions. Further work is necessary to optimize the technique and understand the clinical utility of this technique for women with uterine leiomyomas. [ABSTRACT FROM AUTHOR]

Objective:To investigate the effect of including seafood and fish oils, as part of an energy-restricted diet, on weight loss in young overweight adults.Design:Randomized controlled trial of energy-restricted diet varying in fish and fish oil content was followed for 8 weeks. Subjects were randomized to one of four groups: (1) control (sunflower oil capsules, no seafood); (2) lean fish (3 × 150 g portions of cod/week); (3) fatty fish (3 × 150 g portions of salmon/week); (4) fish oil (DHA/EPA capsules, no seafood). The macronutrient composition of the diets was similar between the groups and the capsule groups, were single-blinded.Subjects:A total of 324 men and women aged 20–40 years, BMI 27.5–32.5 kg/m2 from Iceland, Spain and Ireland.Measurements:Anthropometric data were collected at baseline, midpoint and endpoint. Confounding factors were accounted for, with linear models, for repeated measures with two-way interactions. The most important interactions for weight loss were (diet × energy intake), (gender × diet) and (gender × initial-weight).Results:An average man in the study (95 kg at baseline receiving 1600 kcal/day) was estimated to lose 3.55 kg (95% CI, 3.14–3.97) (1); 4.35 kg (95% CI, 3.94–4.75) (2); 4.50 kg (95% CI, 4.13–4.87) (3) and 4.96 kg (95% CI, 4.53–5.40) on diet (4) in 4 weeks, from baseline to midpoint. The weight-loss from midpoint to endpoint was 0.45 (0.41–0.49) times the observed weight loss from baseline to midpoint. The diets did not differ in their effect on weight loss in women. Changes in measures of body composition were in line with changes in body weight.Conclusion:In young, overweight men, the inclusion of either lean or fatty fish, or fish oil as part of an energy-restricted diet resulted in ∼1 kg more weight loss after 4 weeks, than did a similar diet without seafood or supplement of marine origin. The addition of seafood to a nutritionally balanced energy-restricted diet may boost weight loss.International Journal of Obesity (2007) 31, 1560–1566; doi:10.1038/sj.ijo.0803643; published online 15 May 2007 [ABSTRACT FROM AUTHOR]

Defining optimal nutrient requirements is critical for ensuring crew health during long-duration space exploration missions. Data pertaining to such nutrient requirements are extremely limited. The primary goal of this study was to better understand nutritional changes that occur during long-duration space flight. We examined body composition, bone metabolism, hematology, general blood chemistry, and blood levels of selected vitamins and minerals in 11 astronauts before and after long-duration (128-195 d) space flight aboard the International Space Station. Dietary intake and limited biochemical measures were assessed during flight. Crew members consumed a mean of 80% of their recommended energy intake, and on landing day their body weight was less (P = 0.051) than before flight. Hematocrit, serum iron, ferritin saturation, and transferrin were decreased and serum ferritin was increased after flight (P < 0.05). The finding that other acute-phase proteins were unchanged after flight suggests that the changes in iron metabolism are not likely to be solely a result of an inflammatory response. Urinary 8-hydroxy-2'-deoxyguanosine concentration was greater and RBC superoxide dismutase was less after flight (P < 0.05), indicating increased oxidative damage. Despite vitamin D supplement use during flight, serum 25-hydroxycholecalciferol was decreased after flight (P < 0.01). Bone resorption was increased after flight, as indicated by several markers. Bone formation, assessed by several markers, did not consistently rise 1 d after landing. These data provide evidence that bone loss, compromised vitamin D status, and oxidative damage are among critical nutritional concerns for long-duration space travelers. [ABSTRACT FROM AUTHOR]

Dietary lipids are hypothesized to be an important factor for carotenoid bioavailability. However, most carotenoid-rich fruits and vegetables are low in lipids. The objective of this study was to assess whether the addition of avocado fruit as a lipid source enhances carotenoid absorption in humans. Healthy subjects (n = 11/study) were recruited for 2 crossover, postprandial studies. The effect of avocado addition (150 g) to salsa on lycopene and beta-carotene absorption was examined in Study 1, and the absorption of lutein, alpha-carotene, and beta-carotene from salad in Study 2. Furthermore, the effects of avocado dose (75 vs. 150 g containing 12 vs. 24 g lipid, respectively) and of lipid source (avocado fruit vs. avocado oil) on carotenoid absorption were examined in Study 2. Intact carotenoids were quantified in the plasma triacylglycerol-rich lipoprotein (TRL) fraction during the 9.5 h after consumption of the test meal and expressed as baseline-corrected area under the concentration-vs.-time curve (AUC). The addition of avocado to salsa enhanced lycopene and beta-carotene absorption (P < 0.003), resulting in 4.4 and 2.6 times the mean AUC after intake of avocado-free salsa, respectively. In Study 2, supplementing 150 g avocado or 24 g avocado oil to salad similarly enhanced alpha-carotene, beta-carotene, and lutein absorption (P < 0.01), resulting in 7.2, 15.3, and 5.1 times the mean AUC after intake of avocado-free salad, respectively (150 g avocado). Neither the avocado dose nor the lipid source affected carotenoid absorption. In conclusion, adding avocado fruit can significantly enhance carotenoid absorption from salad and salsa, which is attributed primarily to the lipids present in avocado. [ABSTRACT FROM AUTHOR]

In evaluating potential indicators of biotin status, we quantitated the expression of biotin-related genes in leukocytes from human blood of normal subjects before and after inducing marginal biotin deficiency. Biotin deficiency was induced experimentally by feeding an egg-white diet for 28 d. Gene expression was quantitated for the following biotin-related proteins: methylcrotonyl-CoA carboxylase chains A (MCCA) and B (MCCB); propionyl-CoA carboxylase chains A (PCCA) and B (PCCB); pyruvate carboxylase (PC); acetyl-CoA carboxylase isoforms A (ACCA) and B (ACCB); holocarboxylase synthetase (HCS); biotinidase; and 2 potential biotin transporters: sodium-dependent multivitamin transporter (SMVT) and solute carrier family 19 member 3 (SLC19A3). For 7 subjects who successfully completed the study, the abundance of the specific mRNAs was determined by quantitative real-time RT-PCR at d 0 and 28. At d 28, SLC19A3 expression had decreased to 33% of d 0 (P < 0.02 by two-tailed, paired t test). Expression of MCCA, PCCA, PC, ACCA, ACCB, HCS, biotinidase, and SMVT decreased to approximately 80% of d 0 (P < 0.05). Expression of the MCCB and PCCB chains that do not carry the biotin-binding motif did not change significantly; we speculate that expression of the biotin-binding chains of biotin-dependent carboxylases is more responsive to biotin status changes. These data provide evidence that expression of SLC19A3 is a relatively sensitive indicator of marginal biotin deficiency. [ABSTRACT FROM AUTHOR]

Population-based studies report differences in folate status indicators among Mexican American (MA), African American (AA) and Caucasian (CA) women. It is unclear, however, whether these differences are due to variations in dietary folate intake. The present study was designed to investigate the influence of ethnicity/race on folate status parameters in MA, AA, and CA women (18-45 y; n = 14 in each group) under conditions of strictly controlled folate intake. In addition, the adequacy of the 1998 folate U.S. recommended dietary allowance (RDA), 400 micro g/d as dietary folate equivalents (DFE), for non-Caucasian women was assessed. Subjects (n = 42) with the methylenetetrahydrofolate reductase 677 CC genotype consumed a low-folate diet (135 micro g DFE/d) for 7 wk followed by repletion with 400 (7 MA, 7 AA, 7 CA) or 800 micro g DFE/d (7 MA, 7 AA, 7 CA) for 7 wk. AA women had lower (P

A hallmark of mucoid otitis media (MOM, i.e., chronic otitis media with mucoid effusion) is mucus accumulation in the middle ear cavity, a condition that impairs transduction of sounds in the ear and causes hearing loss. The mucin identities of mucus and the underlying mechanism for the production of mucins in MOM are poorly understood. In this study, we demonstrated that the MUC5B and MUC4 were major mucins in MOM that formed distinct treelike polymers (mucus strands). The MUC5B and MUC4 mRNAs in the middle ear mucosa with MOM were up regulated 5-fold and 6-fold, compared with the controls. This upregulation was accompanied by the extensive proliferation of the MUC5B- and MUC4-producing cells in the middle ear epithelium. Further study indicated that the mucin hyperproduction was significantly linked to CD4+ and CD8+ T cells and/or CD68+ monocyte macrophages. It suggests that MUC5B and MUC4 expression may be regulated by the products of these cells. [ABSTRACT FROM AUTHOR]

Flavonoids and related polyphenolics with antioxidant and anti-inflammatory activities may play a role in the prevention of cardiovascular disease by decreasing oxidative stress and inflammation. We wished to determine the effects of cocoa extract supplementation on markers of oxidative stress and inflammation. Healthy subjects (n = 25) were studied at baseline, after cocoa supplementation (36.9 g of dark chocolate bar and 30.95 g of cocoa powder drink) for 6 wk and after a 6-wk washout period. Fasting blood and early morning urine were collected at the three time points. Two indices of flavonoid intake, total phenols and oxygen radical absorbance capacity of plasma, were measured after an overnight fast. Neither was affected by supplementation. Measures of oxidative stress included copper-catalyzed LDL oxidation kinetics and urinary F(2) isoprostanes. LDL oxidizability was lower after chocolate supplementation as evidenced by a longer lag time (P < 0.05) of conjugated diene formation (101.0 +/- 20.7 min) compared with baseline (91.3 +/- 18.0 min) and washout (96.4 +/- 7.5 min) phases. There was no effect of chocolate on urinary F(2) isoprostane levels or on markers of inflammation including the whole-blood cytokines, interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha, high sensitivity C-reactive protein and P-selectin. In conclusion, cocoa products supplementation in humans affects LDL oxidizability, but not urinary F(2) isoprostanes or markers of inflammation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine a cut-off value of the molar ratio of retinol-binding protein to transthyretin (RBP:TTR) to indicate marginal vitamin A (VA) deficiency. Plasma RBP and TTR were measured by radial immunodiffusion in two groups of patients, i.e., surgical patients with known hepatic VA stores, and a cohort of children residing in a malaria-endemic area of Papua New Guinea who had received placebo or 210 micro mol of VA every 3 mo for 9 mo. A RBP:TTR ratio < or =0.36 selectively detected five of seven patients (71% sensitivity) with hepatic VA stores < or =69.9 nmol/g of tissue (i.e., < or =20 micro g/g), indicative of marginal VA deficiency. Using this cut-off value, 28% (n = 245) of children from Papua New Guinea had marginal VA deficiency before supplementation. After 7 mo, a low ratio persisted in 29% (n = 92) of placebo-treated children but in only 11% (n = 83) of those receiving VA supplements (chi(2), P < 0.01). At the end of the study, 13 mo after initiation or 4 mo after the last dose of VA, the percentage of children with a low ratio was still lower (chi(2), P < 0.02) in the VA group, 42.5% (n = 113) than in the placebo group, 58.6% (n = 118). These results demonstrate that a cut-off value < or =0.36 is indicative of marginal VA deficiency and can be used as an indirect method of VA assessment. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (ARMD) is inversely associated with the accumulation of lutein + zeaxanthin in the macula, but higher lutein intakes are inconsistently related to reduced risk of ARMD in epidemiologic studies. Resolution of efficacy awaits clinical trials designed with knowledge of lutein supplement pharmacokinetics. Lutein bioavailability was determined for lutein diester and unesterified lutein formulations as they might be incorporated into dietary supplements. Healthy subjects (n = 18) consumed a single dose of each formulation (either 0.5 or 0.67 micro mol lutein/kg body, 10 and 8 subjects, respectively) in random order, and the appearance of free lutein + zeaxanthin was measured in serum from 0 to 408 h. Areas under the serum concentration x time curves (AUC), as a measure of bioavailability, were independent of gender, body mass index and lutein dose. The lutein diester formulation was 61.6% more bioavailable than the unesterified lutein formulation with higher mean AUC, maximum serum concentration and ascending slope (P < 0.05). The AUC was greater in 14 of 18 subjects when they consumed the lutein diester formulation. Comparison with data from previous studies suggested that dissolution was a greater limitation to bioavailability than lutein ester hydrolysis because an oil-solubilized unesterified lutein preparation, given at 0.5 micro mol/kg body, resulted in greater mean peak concentrations and AUC compared with either the unesterified or lutein diester formulations used in our study. In conclusion, the lutein diester formulation poses no impediment to lutein bioavailability at the doses tested, but formulation dissolution is an important factor in lutein bioavailability and should be evaluated before a supplement and dose are selected for use in clinical trials. [ABSTRACT FROM AUTHOR]

Oral exposure to dietary fat (through modified sham feeding, which entails mastication and expectoration of foods) augments the postprandial triacylglycerol (TAG) concentration, in part, though augmented lipid absorption. This study was designed to characterize early events in this process. At 2200 h, 25 healthy adults (13 men, 12 women) consumed 80 g of almonds (high oleic acid content) and fasted until approximately 0700 h. After placement of a catheter in a hand vein and 4 blood draws at 10-min intervals, 50 1-g safflower oil (high linoleic acid content) capsules were consumed. After another blood draw, modified sham feeding was initiated with a cracker only or cracker with cream cheese in random order with 1 wk between trials. Oral exposures occurred at 5-min intervals for 60 min then at 15-min intervals from min 60 to 120. Additional blood draws occurred at 2, 4, 6, 8, 10, 12, 14, 30, 60, 120, 240, 360 and 480 min. Oral stimulation, especially by fat, prompted the rapid (mean approximately 23 min) release of lipid stored from the previous meal (almonds) in all participants. This resulted in multimodal postprandial triacylglycerol (TAG) peaks generally occurring at 0-30 min, 60-120 min and 240-480 min after loading and initiation of oral stimulation. TAG magnitudes during these times were correlated (r = 0.40-0.89, P < 0.001-P = 0.053). It is proposed that the sensory-enhanced release of lipid from the residual pool initiates an early TAG rise, which augments the peak attributable to absorption of meal lipid; this in turn supplements a later peak associated with release of endogenously synthesized TAG because lipid from all three sources competed for a common clearance mechanism. If substantiated, additional understanding of the behavioral factors (e.g., eating patterns) that initiate this cascade will be warranted. [ABSTRACT FROM AUTHOR]

The goal of this study was to investigate the effect of the dietary fat composition on LDL peak particle diameter. Therefore, we measured LDL size by gradient gel electrophoresis in 56 (30 men, 26 women) healthy participants in a controlled dietary study. First, all participants received a baseline diet rich in saturated fat for 2 wk; they were then randomly assigned to one of three dietary treatments, which contained refined olive oil [rich in monounsaturated fatty acids (MUFA), n = 18], rapeseed oil [rich in MUFA and (n-3)-polyunsaturated fatty acids (PUFA), n = 18], or sunflower oil [rich in (n-6)-PUFA, n = 20] as the principal source of fat for 4 wk. Repeated-measures ANOVA revealed a small, but significant reduction in LDL size during the oil diet phase (-0.36 nm, P = 0.012), which did not differ significantly among the three groups (P = 0.384). Furthermore, affiliation with one of the three diet groups did not contribute significantly to the observed variation in LDL size (P = 0.690). In conclusion, our data indicate that dietary unsaturated fat similarly reduces LDL size relative to saturated fat. However, the small magnitude of this reduction also suggests that the composition of dietary fat is not a major factor affecting LDL size. [ABSTRACT FROM AUTHOR]

Epidemiologic and clinical studies have shown that nut consumption is associated with favorable plasma lipid profiles and reduced cardiovascular risk. These effects may result from their high monounsaturated fat (MUFA) content but nuts contain constituents other than fatty acids that might be cardioprotective. We conducted a study to compare the effects of whole-almond vs. almond oil consumption on plasma lipids and LDL oxidation in healthy men and women. Using a randomized crossover trial design, 22 normolipemic men and women replaced half of their habitual fat (approximately 14% of approximately 29% energy) with either whole almonds (WA) or almond oil (AO) for 6-wk periods. Compliance was ascertained by monitoring dietary intake via biweekly 5-d food records, return of empty almond product packages and weekly meetings with a registered dietitian. Fat replacement with either WA and AO resulted in a 54% increase in percentage of energy as MUFA with declines in both saturated fat and cholesterol intake and no significant changes in total energy, total or polyunsaturated fat intake. The effects of WA and AO on plasma lipids did not differ compared with baseline; plasma triglyceride, total and LDL cholesterol significantly decreased, 14, 4 and 6% respectively, whereas HDL cholesterol increased 6%. Neither treatment affected in vitro LDL oxidizability. We conclude that WA and AO do not differ in their beneficial effects on the plasma lipid variables measured and that this suggests that the favorable effect of almonds is mediated by components in the oil fraction of these nuts. [ABSTRACT FROM AUTHOR]

Soybean isoflavones have been proposed to be anticarcinogenic, but their effective doses have not been established. To study their bioavailability, seven women consumed 3.4, 6.9, or 10.3 mumol isoflavones/kg body wt in soymilk in each of three meals of a liquid diet on one of three feeding days that were separated by 2-wk washout periods. Subjects were randomly assigned to doses in a cross-over design. Plasma, urine and fecal isoflavones were measured by reverse phase HPLC. In two subjects, fecal isoflavone recovery was 10-20 times that in the other five subjects. Average 48-h urinary recoveries of ingested daidzein and genistein were 16 +/- 4 and 10 +/- 4%, respectively, at all three doses among the five subjects excreting only small amounts of isoflavones in feces, whereas urinary recoveries of daidzein and genistein in the two subjects who excreted large amounts of fecal isoflavones were 32 +/- 5 and 37 +/- 6%, respectively. Urinary isoflavone excretion was nearly zero in all subjects at 48 h after dosing. Average plasma concentration of genistein at 24 h after the breakfast isoflavone dose in subjects excreting large amounts of fecal isoflavones was significantly greater by 2.5-fold than in subjects who excreted small amounts of fecal isoflavones (P < 0.05). In vitro anaerobic incubation of isoflavones with human feces showed that intestinal half-life of daidzein and genistein may be as little as 7.5 and 3.3 h, respectively. These data suggest that human isoflavone bioavailability depends upon the relative ability of gut microflora to degrade these compounds. [ABSTRACT FROM AUTHOR]

We evaluated the ability of a biological marker (nitrogen excretion expressed as protein) to accurately reflect the protein intake of 12 healthy subjects consuming a low protein diet (0.6 g protein/kg standard body wt). In this crossover study, protein intake was confirmed by chemically analyzing a duplicate of the constant diet each subject consumed for 3 d and by calculating protein content of self-selected diets recorded during two additional 3-d periods. Diet analysis matched excretion (difference 0.03 +/- 0.04 g protein/kg standard body wt, means +/- SEM). Self-selected intake manually calculated by subjects using educational materials matched the prescription [0.60 (0.42, 0.86) g protein/kg standard body wt, median (range)], but underestimated excretion by 0.18 +/- 0.02 g protein/kg standard body wt (means +/- SEM). Self-selected intake recalculated by the authors using a computerized database was only +0.05 (-0.08, +0.44) g protein/kg standard body wt higher than subjects' calculations, suggesting that discrepancies between databases and/or subject calculation errors only partially accounted for how greatly self-selected intake underestimated excretion. In a secondary analysis of self-selected intake, the three dietitian subjects consumed more energy and excreted less protein than nondietitians (137 +/- 4.9 vs. 94 +/- 3.5 kJ/standard body wt; 0.72 +/- 0.02 vs. 0.83 +/- 0.02 g protein/kg standard body wt), suggesting that adequate energy intake and/or additional training might improve agreement between intake and excretion. Thus, discrepancies between protein excretion and reported intake may reflect factors other than willful noncompliance. [ABSTRACT FROM AUTHOR]

Background: Clinical practice guidelines recommend routine kidney function and serum potassium testing within 30 days of initiating ACE (angiotensin-converting enzyme) inhibitor or angiotensin II receptor blocker therapy. However, evidence is lacking about whether follow-up testing reduces therapy-related adverse outcomes.Methods and Results: We conducted 2 population-based retrospective cohort studies in Kaiser Permanente Northern California and Ontario, Canada. Patients with outpatient serum creatinine and potassium tests in the 30 days after starting ACE inhibitor or angiotensin II receptor blocker therapy were matched 1:1 to patients without follow-up tests. We evaluated the association of follow-up testing with 30-day all-cause mortality and hospitalization with acute kidney injury or hyperkalemia using Cox regression. We also developed and externally validated a risk score to identify patients at risk of having abnormally high serum creatinine and potassium values in follow-up. We identified 75 251 matched pairs initiating ACE inhibitor or angiotensin II receptor blocker therapy between January 1, 2007, and December 31, 2017, in Kaiser Permanente Northern California. Follow-up testing was not significantly associated with 30-day all-cause mortality in Kaiser Permanente Northern California (hazard ratio, 0.75 [95% CI, 0.54-1.06]) and was associated with higher mortality in 84 905 matched pairs in Ontario (hazard ratio, 1.32 [95% CI, 1.07-1.62]). In Kaiser Permanente Northern California, follow-up testing was significantly associated with higher rates of hospitalization with acute kidney injury (hazard ratio, 1.66 [95% CI, 1.10-2.22]) and hyperkalemia (hazard ratio, 3.36 [95% CI, 1.08-10.41]), as was observed in Ontario. The risk score for abnormal potassium provided good discrimination (area under the curve [AUC], 0.75) and excellent calibration of predicted risks, while the risk score for abnormal serum creatinine provided moderate discrimination (AUC, 0.62) but excellent calibration.Conclusions: Routine laboratory monitoring after ACE inhibitor or angiotensin II receptor blocker initiation was not associated with a lower risk of 30-day mortality. We identified patient subgroups in which targeted testing may be effective in identifying therapy-related changes in serum potassium or kidney function. [ABSTRACT FROM AUTHOR]