Search

Background: With increasingly aging societies, a comprehensive strategy for dementia research is important. The Organized Registration for the Assessment of dementia by the Nationwide General consortium toward Effective treatment (ORANGE) Registry is the first longitudinal multicenter prospective trial-ready cohort in Japan.Objective: To establish a large cohort for use in clinical trials and research in Japan.Methods: This registry, based on communities, hospitals, and nursing homes, covers three dementia stages (preclinical, mild cognitive impairment [MCI], and advanced dementia), and includes more than 30 hospitals. We analyzed enrollment and 1-year follow-up data for disease progression.Results: There were 1450 registered patients (649 men, 801 women; mean age, 77.92±6.70 years; mean Mini-Mental State Examination [MMSE] score, 25.19±2.76). The conversion rates from MCI to dementia and MCI to normal were 14.3% and 1.1%, respectively. High Clinical Dementia Rating score (odds ratio [OR] = 11.085, 95% confidence interval [CI]:1.619-75.913, p = 0.014), low MMSE score (OR = 0.835, 95% CI: 0.761-0.917, p < 0.001), high Geriatric Depression Scale score (OR = 1.093, 95% CI: 1.005-1.189, p = 0.038), and low body mass index (OR = 0.895, 95% CI: 0.829-0.967, p = 0.005) at enrollment were significant factors for conversion.Conclusion: The ORANGE MCI Registry is an established registry that facilitates creation of trial-ready cohorts to accelerate promotion of clinical trials with low reversion rates as it originates from a hospital. One-year follow-up analysis suggested assessing various factors for conversion risk. Further analyses will be possible in future with registry expansion. We will continue to refine this registry, including how it can be used more efficiently. [ABSTRACT FROM AUTHOR]

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]

Objectives: To provide updated evidence from randomized controlled trials (RCTs) on the efficacy of intradermal acupuncture for insomnia.Methods: A search of relevant literatures was performed on major medical databases, including the Cochrane Library, PubMed, EMBASE, CBM, CNKI, VIP, Wanfang Data and so on. Risk of bias evaluation, meta-analysis, sensitivity analysis and evidence rating of all extracted information were also conducted.Results: A total of 508 studies were initially identified. However, only 45 studies were deemed eligible for the present review. Meta-analyses were conducted in three comparisons separately: intradermal versus acupuncture, Effective rate (RR = 0.08, 95% CI -0.02 to 0.19), Global scales score (points) (SMD = -0.52, 95% CI: -0.81,-0.24, P = 0.02); intradermal acupuncture versus non acupuncture, Effective rate(RR = 1.22, 95% CI 1.04 to 1.42), Global scales score (points) (SMD = -0.81, 95% CI: -1.23,-0.38, P < 0.00001); control group versus control add intradermal acupuncture. Effective rate(RR = 1.27, 95% CI 1.13 to 1.42), Global scales score (points) (SMD = -1.15, 95% CI: -1.46,-0.84, P < 0.00001). Although these results suggested benefits of intradermal acupuncture, the overall quality of evidence rated was low.Conclusions: The summary estimates indicate that it improved the clinical effective rate and lowered PSQI or other scales score, when compared to sham acupuncture or placebo/conventional medications/herbs.Also,it significantly improved the clinical effective rate and lowered PSQI or other scales score, when the control groups add intradermal acupuncture. However, the quality of the evidence is varied from very low to low due to the potential risk of bias and inconsistency among included trials. The more larger sample size and much more rigorous designed RCTs are still further studied. [ABSTRACT FROM AUTHOR]

Background: This prerandomization analysis from the Australian HCL-Adult trial (registration number: ACTRN12617000520336) compared masked continuous glucose monitoring (CGM) metrics among adults using insulin pumps versus multiple daily injections (MDIs), who were all self-monitoring blood glucose (SMBG). Methods: Adults with type 1 diabetes, using an insulin pump or MDIs without real-time CGM (and entering a trial of closed-loop technology), were eligible. MDI users were given an insulin dosage calculator. All participants received diabetes and carbohydrate-counting education, then wore masked CGM sensors for 3 weeks. Ethics Approval: HREC-D 088/16 Results: Adults using MDIs (n = 61) versus pump (n = 59) did not differ by age, sex, diabetes duration, insulin total daily dose, or HbA1c at baseline. After education, median (interquartile range) CGM time in range (TIR) 70-180 mg/dL (3.9-10.0 mmol/L) was 54% (47, 62) for those using MDIs and 56% (48, 66) for those using pump (P = 0.40). All CGM metrics were equivalent for 24 h/day for MDI and pump users. Overnight, those using MDIs (vs. pump) spent more time with glucose <54 mg/dL (<3.0 mmol/L): 1.4% (0.1, 5.1) versus 0.5% (0.0, 2.0), respectively (P = 0.012). They also had more CGM hypoglycemia episodes (121 vs. 54, respectively; incidence rate ratio [95% confidence interval] 2.48 [1.51, 4.06]; P < 0.001). Conclusions: Adults with type 1 diabetes using pumps versus MDIs in conjunction with SMBG experienced less nocturnal hypoglycemia, measured by masked CGM, after equivalent diabetes and dietary education in conjunction with insulin dosage calculator provision to all. However, both groups had equivalent TIR. This observation may reflect advantages afforded by flexibility in basal insulin delivery provided by pumps. [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]

Introduction: Preclinical data implicate large conductance calcium-activated potassium (BKCa) channels in the pathogenesis of headache and migraine, but the exact role of these channels is still unknown. Here, we investigated whether opening of BKCa channels would cause headache and vascular effects in healthy volunteers.Methods: In a randomized, double-blind, placebo-controlled, cross-over study, 21 healthy volunteers aged 18-39 years were randomly allocated to receive an intravenous infusion of 0.05 mg/min BKCa channel opener MaxiPost and placebo on two different days. The primary endpoints were the difference in incidence of headache and the difference in area under the curve (AUC) for headache intensity scores (0-12 hours) and for middle cerebral artery blood flow velocity (VMCA) (0-2 hours) between MaxiPost and placebo. The secondary endpoints were the differences in area under the curve for superficial temporal artery and radial artery diameter (0-2 hours) between MaxiPost and placebo.Results: Twenty participants completed the study. Eighteen participants (90%) developed headache after MaxiPost compared with six (30%) after placebo (p = 0.0005); the difference of incidence is 60% (95% confidence interval 36-84%). The area under the curve for headache intensity (AUC0-12 hours, p = 0.0003), for mean VMCA (AUC0-2 hours, p = 0.0001), for superficial temporal artery diameter (AUC0-2 hours, p = 0.003), and for radial artery diameter (AUC0-2 hours, p = 0.03) were significantly larger after MaxiPost compared to placebo.Conclusion: MaxiPost caused headache and dilation in extra- and intracerebral arteries. Our findings suggest a possible role of BKCa channels in headache pathophysiology in humans. ClinicalTrials.gov, ID: NCT03887325. [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]

Objectives: To establish cutoff values for making recommendations for discharge to the home setting using standardized physical therapy assessments.Design: Retrospective study.Setting: Five ICUs at a large academic medical center.Patients: 1,203 ICU patients.Intervention: None.Measurements and Main Results: The Functional Status Score for the ICU and the ICU Mobility Scale were collected during the initial physical therapy assessment, at ICU discharge, and prior to hospital discharge. The Activity Measure for Post-Acute Care-Inpatient Mobility Short Form "6 clicks" was only collected during the initial physical therapy assessment. Receiver Operating Characteristic curves were used to determine a potential cutoff value for discharge home. The Receiver Operating Characteristic was adjusted for ICU and hospital length of stay along with mobility status prior to hospital admission. Cutoff values were then determined by using Youden's Index. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated based on these cut off values. The Functional Status Score for the ICU at ICU discharge was the best predictor of a discharge to the home setting in patients who had an ICU admission. The area under the curve for the Functional Status Score for the ICU at ICU discharge was 0.80. A Functional Status Score for the ICU score at ICU discharge of 19 or higher predicted discharge to home with a sensitivity of 82.9% and specificity of 73.6% CONCLUSIONS:: The Functional Status Score for the ICU at ICU discharge provided the best accuracy for making a timely recommendation for discharge home in patients who had an ICU admission. [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]

Objectives: Tailoring hypothermia duration to ischemia duration may improve outcome from out-of-hospital cardiac arrest. We investigated the association between the hypothermia/ischemia ratio and functional outcome in a secondary analysis of data from the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, or Placebo Study trial.Design: Cohort study of out-of-hospital cardiac arrest patients screened for Resuscitation Outcomes Consortium-Amiodarone, Lidocaine, or Placebo Study.Setting: Multicenter study across North America.Patients: Adult, nontraumatic, out-of-hospital cardiac arrest patients screened for Resuscitation Outcomes Consortium-Amiodarone, Lidocaine, or Placebo Study who survived to hospital admission and received targeted temperature management between May 2012 and October 2015.Interventions: Targeted temperature management in comatose survivors of out-of-hospital cardiac arrest. We defined hypothermia/ischemia ratio as total targeted temperature management time (initiation through rewarming) divided by calculated total ischemia time (approximate time of arrest [9-1-1 call or emergency medical services-witnessed] to return of spontaneous circulation).Measurements and Main Results: The primary outcome was hospital survival with good functional status (modified Rankin Score, 0-3) at hospital discharge. We fitted logistic regression models to estimate the association between hypothermia/ischemia ratio and the primary outcome, adjusting for demographics, arrest characteristics, and Resuscitation Outcomes Consortium enrolling site. A total of 3,429 patients were eligible for inclusion, of whom 36.2% were discharged with good functional outcome. Patients had a mean age of 62.0 years (SD, 15.8), with 69.7% male, and 58.0% receiving lay-rescuer cardiopulmonary resuscitation. Median time to return of spontaneous circulation was 21.1 minutes (interquartile range, 16.1-26.9), and median duration of targeted temperature management was 32.9 hours (interquartile range, 23.7-37.8). A total of 2,579 had complete data and were included in adjusted regression analyses. After adjustment for patient characteristics and Resuscitation Outcomes Consortium site, a greater hypothermia/ischemia ratio was associated with increased survival with good functional outcome (odds ratio, 2.01; 95% CI, 1.82-2.23). This relationship, however, appears to be primarily driven by time to return of spontaneous circulation in this patient cohort.Conclusions: Although a larger hypothermia/ischemia ratio was associated with good functional outcome after out-of-hospital cardiac arrest in this cohort, this association is primarily driven by duration of time to return of spontaneous circulation. Tailoring duration of targeted temperature management based on duration of time to return of spontaneous circulation or patient characteristics requires prospective study. [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]

Objectives: To prospectively determine the feasibility of preoperative supine breast MRI in breast cancer patients scheduled for oncoplastic breast-conserving surgery.Methods: In addition to a diagnostic prone breast MRI, a supplementary supine MRI was performed with the patient in the surgical position including skin markers. Tumours' locations were ink-marked on the skin according to findings obtained from supine MRI. Changes in tumours' largest diameter and locations between prone and supine MRI were measured and compared to histology. Nipple-to-tumour and tumour-to-chest wall distances were also measured. Tumours and suspicious areas were surgically removed according to skin ink-markings. The differences between MRI measurements with reference to histopathology were evaluated with the paired-sample t test.Results: Fourteen consecutive patients, 15 breasts and 27 lesions were analysed. Compared to histology, prone MRI overestimated tumour size by 47.1% (p = 0.01) and supine MRI by 14.5% (p = 0.259). In supine MRI, lesions' mean diameters and areas were smaller compared to prone MRI (- 20.9%, p = 0.009 and - 38.3%, p = 0.016, respectively). This difference in diameter was more pronounced in non-mass lesions (- 31.2%, p = 0.031) compared to mass lesions (- 9.2%, p = 0.009). Tumours' mean distance from chest wall diminished by 69.4% (p < 0.001) and from nipple by 18.2% (p < 0.001). Free microscopic margins were achieved in first operation in all patients.Conclusions: Supine MRI in the surgical position is feasible and useful in the precise localisation of prone MRI-detected lesions and provides a helpful tool to implement in surgery. Supine MRI more accurately determines tumours' size and location and might have an important role to diminish overestimations.Key Points: • Breath-hold supine breast MRI is feasible using commercially available coils and sequences. • Size and area of lesions on MRI were consistently smaller when measured from the supine position as compared to the prone position. • Supine breast MRI is useful in the precise preoperative localisation of prone MRI-detected lesions. •. [ABSTRACT FROM AUTHOR]

Background: A secular trend towards earlier puberty has been observed in girls, while a similar trend has been more uncertain in boys. We estimated current ages at pubertal development in both boys and girls.Methods: In this population-based cohort study, 14 759 of 22 439 invited boys and girls born from 2000 to 2003 in the Danish National Birth Cohort gave half-yearly self-reported information on puberty from the age of 11.5 years and throughout puberty. This late start of follow-up limits the estimation of age at onset of puberty but not later pubertal milestones. We estimated mean age at attaining the following pubertal milestones in years with 95% confidence intervals (CI): age at menarche, voice break, first ejaculation of semen and Tanner stages for pubic hair development and breast development or genital development. Further, the difference in mean age at menarche between mothers and daughters was estimated.Results: In boys, voice break occurred at 13.1 (95% CI 13.0, 13.1) years, first ejaculation of semen occurred at 13.4 (95% CI 13.3, 13.4) years, and Tanner Genital Stage 5 occurred at 15.6 (95% CI 15.5, 15.6) years. In girls, age at menarche occurred at 13.0 (95% CI 13.0, 13.1) years and Tanner Breast Stage 5 occurred at 15.8 (95% CI 15.7, 15.9) years. Daughters had menarche 3.6 (95% CI 3.1, 4.2) months earlier than their mothers had.Conclusion: These data indicate that age at menarche has declined and to some extent support a decline in age at attaining other markers of pubertal development among boys. [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]

Preclinical work suggests that GET 73 (N-[4-(trifluoromethyl)benzyl]-4-methoxybutyramide), a novel metabotropic glutamate receptor subtype 5 negative allosteric modulator, may represent a novel pharmacological treatment for alcohol use disorder. Two independent experiments evaluated the effect of acutely administered GET 73 (0, 30, and 100 mg/kg, intragastrically) on alcohol-induced hypolocomotion ( n=72) and sedation/hypnosis ( n=36) in rats. In healthy male volunteers ( n=14), an open-label, randomised, crossover study was conducted to compare adverse events and pharmacokinetic parameters, in two experiments in which 300 mg GET 73 was administered, with and without alcohol, once and thrice. In rats, when administered with alcohol-vehicle, 100 mg/kg, but not 30 mg/kg, GET 73 reduced spontaneous locomotor activity. When administered with alcohol, no dose of GET 73 altered either alcohol-induced hypolocomotion or sedation/hypnosis. In humans, both single and thrice 300 mg GET 73 administration were well tolerated, in the presence and absence of alcohol, with no differences in adverse events. There were no significant differences in relative bioavailability between administering 300 mg GET 73 in the presence or absence of alcohol. [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: 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]

Background: Tip-localized adhesive proteins of bacterial fimbriae from diverse pathogens confer protection in animal models, but efficacy in humans has not been reported. Enterotoxigenic Escherichia coli (ETEC) commonly elaborate colonization factors comprising a minor tip adhesin and major stalk-forming subunit. We assessed the efficacy of antiadhesin bovine colostral IgG (bIgG) antibodies against ETEC challenge in volunteers.Methods: Adults were randomly assigned (1:1:1) to take oral hyperimmune bIgG raised against CFA/I minor pilin subunit (CfaE) tip adhesin or colonization factor I (CFA/I) fimbraie (positive control) or placebo. Two days before challenge, volunteers began a thrice-daily, 7-day course of investigational product administered in sodium bicarbonate 15 minutes after each meal. On day 3, subjects drank 1 × 109 colony-forming units of colonization factor I (CFA/I)-ETEC strain H10407 with buffer. The primary efficacy endpoint was diarrhea within 120 hours of challenge.Results: After enrollment and randomization, 31 volunteers received product, underwent ETEC challenge, and were included in the per protocol efficacy analysis. Nine of 11 placebos developed diarrhea, 7 experiencing moderate to severe disease. Protective efficacy of 63% (P = .03) and 88% (P = .002) was observed in the antiadhesin bIgG and positive control groups, respectively.Conclusions: Oral administration of anti-CFA/I minor pilin subunit (CfaE) antibodies conferred significant protection against ETEC, providing the first clinical evidence that fimbrial tip adhesins function as protective antigens. [ABSTRACT FROM AUTHOR]

Purpose: To compare two intensity levels (standard vs. enhanced) of a nutrition and physical activity intervention vs. a control (usual programs) on nutrition knowledge, body mass index, fitness, academic performance, behavior, and medication use among elementary school students.Design: Quasi-experimental with three arms.Setting: Elementary schools, students' homes, and a supermarket.Subjects: A total of 1487 third-grade students.Intervention: The standard intervention (SI) provided daily physical activity in classrooms and a program on making healthful foods, using food labels. The enhanced intervention (EI) provided these plus additional components for students and their families.Measures: Body mass index (zBMI), food label literacy, physical fitness, academic performance, behavior, and medication use for asthma or attention-deficit hyperactivity disorder (ADHD).Analysis: Multivariable generalized linear model and logistic regression to assess change in outcome measures.Results: Both the SI and EI groups gained less weight than the control (p < .001), but zBMI did not differ between groups (p = 1.00). There were no apparent effects on physical fitness or academic performance. Both intervention groups improved significantly but similarly in food label literacy (p = .36). Asthma medication use was reduced significantly in the SI group, and nonsignificantly (p = .10) in the EI group. Use of ADHD medication remained unchanged (p = .34).Conclusion: The standard intervention may improve food label literacy and reduce asthma medication use in elementary school children, but an enhanced version provides no further benefit. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests a positive association of diet and obesity with depression. Researchers have examined several diet-mood hypotheses, including investigating the extent to which carbohydrates may impact mood. There is limited research on how glycemic load, a characteristic of carbohydrates, impacts mood in healthy adults. Eighty-two healthy weight and overweight/obese, but otherwise healthy, adults enrolled in a randomized, crossover controlled feeding study testing low-compared to high-glycemic load diets. All participants completed self-report mood and energy level questionnaires during each arm of the intervention. Diets were isocaloric and were matched by macronutrient content as a percent of total energy. Mood was assessed with the Profile of Mood States (POMS) subscales; tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment, total mood disturbance (TMD), and negative affect (NA) in addition to the Center for Epidemiological Studies - Depression (CES-D) scale at baseline and end of both 28-day feeding periods. Linear mixed models tested the intervention effect on mood, controlling for baseline POMS and CES-D scores, diet type, diet sequence, feeding period, sex, and percent body fat classification. The consumption of the high-glycemic load diet resulted in a 38% higher score for depressive symptoms on the CES-D (P = 0.002) compared to the low-glycemic load diet as well as 55% higher score for TMD (P = 0.05), and 26% higher score for fatigue/inertia (P = 0.04). In subgroup analyses, the overweight/obese participants had 40% higher scores on the CES-D scale compared to healthy weight participants (P = 0.05). In conclusion, a high-glycemic load diet was associated with higher depression symptoms, total mood disturbance, and fatigue compared to a low-glycemic load diet especially in overweight/obese, but otherwise healthy, adults. This trial was registered at clinicaltrials.gov: NCT00622661. [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: Accurate rotational alignment of the femoral component is of vital importance for successful total knee arthroplasty (TKA). Two anatomical references located on the anterior femur were recently introduced. To determine which is more reliable reference axis for the femoral component rotation in female patients receiving TKA, the trochlear anterior line was compared with the femoral anterior tangent line.Materials and Methods: Preoperative computed tomography in 76 patients receiving TKA for varus deformity was performed, and the images were reconstructed into three-dimensional models. The trochlear anterior line was defined as the line connecting the most anterior portion of the lateral and medial femoral condyles and the femoral anterior tangent line as the line parallel to distal anterior femoral surface. The two angles between these reference axes and the surgical transepicondylar axis (TEA) in three-dimensional images (trochlear anterior line/TEA, femoral anterior tangent line/TEA) were measured. The correlation between these two angles was computed. We investigated to see whether a significant difference in variance existed.Results: The trochlear anterior line was internally rotated by 6.1° ± 2.5° with respect to TEA, whereas the femoral anterior tangent line by 9.5° ± 3.8°. The trochlear anterior line was externally rotated by 3.4° ± 3.3° with respect to the femoral anterior tangent line. There was a significant correlation between the trochlear anterior line/TEA and the femoral anterior tangent line/TEA.Conclusions: The variance of the trochlear anterior line/TEA was significantly smaller than that of the femoral anterior tangent line/TEA demonstrating a more consistent distribution. When conventional reference axes such as the posterior condylar axis or the anteroposterior axis are unclear or differ, surgeons can rely on these alternative references. When trochlear anterior line and femoral anterior tangent line contradicts, the former might be more reliable for the rotational alignment of the femoral component in female patients.Level Of Evidence: Case series with no comparison group, Level IV. [ABSTRACT FROM AUTHOR]

Background: In the northeastern United States, tick-borne diseases are a major public health concern. In controlled studies, a single springtime application of acaricide has been shown to kill 68%-100% of ticks. Although public health authorities recommend use of acaricides to control tick populations in yards, the effectiveness of these pesticides to prevent tick bites or human tick-borne diseases is unknown.Methods: We conducted a 2-year, randomized, double-blinded, placebo-controlled trial among 2727 households in 3 northeastern states. Households received a single springtime barrier application of bifenthrin or water according to recommended practices. Tick drags were conducted 3-4 weeks after treatment on 10% of properties. Information on human-tick encounters and tick-borne diseases was collected through monthly surveys; reports of illness were validated by medical record review.Results: Although the abundance of questing ticks was significantly lower (63%) on acaricide-treated properties, there was no difference between treatment groups in human-tick encounters, self-reported tick-borne diseases, or medical-record-validated tick-borne diseases.Conclusions: Used as recommended, acaricide barrier sprays do not significantly reduce the household risk of tick exposure or incidence of tick-borne disease. Measures for preventing tick-borne diseases should be evaluated against human outcomes to confirm effectiveness. [ABSTRACT FROM AUTHOR]

Studies of wine tasters and patients with self-induced vomiting have revealed that 30-50% of individuals at high risk do not develop erosive lesions. The aim was to investigate this apparent individual susceptibility to enamel erosion. Two enamel specimens were made from each of 3 premolars from 8 persons (donors). Six acrylic mouth appliances were worn by 6 volunteers (carriers). One specimen from each donor was mounted on each appliance. The carriers wore the appliances for 9 days. The appliances were immersed in 0.01 M HCl for 3 min twice per day to imitate a vomiting/reflux situation. The enamel specimens were analysed by a white-light interferometer to measure enamel loss (in micrometres). The enamel loss varied significantly both between the donor teeth (p = 0.009) and the carriers (p = 0.004). The lesion in the specimen with the largest amount of enamel loss was 4 times as deep as in the specimen with the lowest. In 1 carrier, all specimens displayed enamel loss above the mean, including the specimen from the donor with the most resistant enamel. The variation in susceptibility to erosion among individuals appears to be influenced both by the sustainability of the enamel and by factors in the oral environment. This could explain the variation in prevalence and severity of dental erosions among patients exposed to similar acidic challenges. The results suggest that for certain individuals, only minimal acidic challenges may be sufficient to cause damage to the teeth, while others may never develop dental erosions despite extensive exposure to acid. [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]

Motorized treadmills are commonly used in biomechanical and clinical studies of human walking. Whether treadmill walking induces identical motor responses to overground walking, however, is equivocal. The purpose of this study was to examine differences in the spatiotemporal gait parameters of the lower extremities and trunk during treadmill and overground walking using comparison of mean and variability values. Twenty healthy participants (age 23.8±1.2 years) walked for 6min on a treadmill and overground while wearing APDM 6 Opal inertial monitors. Stride length, stride time, stride velocity, cadence, stance phase percentage, and peak sagittal and frontal plane trunk velocities were measured. Mean values were calculated for each parameter as well as estimates of short- (SD1) and long-term variability (SD2) using Poincaré analyses. The mean, SD1, and SD2 values were compared between overground and treadmill walking conditions with paired t-tests (α=0.05) and with effect size estimates using Cohen's d statistic. Mean values for each of the gait parameters were statistically equivalent between treadmill and overground walking (p>0.05). The SD1 and SD2 values representing short- and long-term variability were considerably reduced (p<0.05) on the treadmill as compared to overground walking. This demonstrates the importance of consideration of gait variability when using treadmills for research or clinical purposes. Treadmill training may induce invariant gait patterns, posing difficulty in translating locomotor skills gained on a treadmill to overground walking conditions. [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]

Visual performance is impaired when the ocular blood flow decreases, indicating that ocular blood flow plays a role in maintaining visual performance during exercise. We examined the ocular blood flow response to incremental cycling exercise to test the hypothesis that ocular blood flow is relatively stable during dynamic exercise because of its autoregulatory nature. The blood flow in the inferior and superior temporal retinal arterioles (ITRA and STRA, respectively) and retinal and choroidal vessels (RCV), mean arterial pressure, and heart rate (HR) were measured at rest and during leg cycling in nine young and healthy subjects (26 ± 5 years, mean ± SD). Ocular blood flow was measured by laser speckle flowmetry. The exercise intensity was incremented by 30 W every 3 min until the subject was unable to maintain a position appropriate for measuring ocular blood flow. Blood flow data obtained during cycling exercise were categorized based on HR as follows: <100, 100-120, and >120 bpm. Blood flow in the RCV increased with the exercise intensity: by 16 ± 8, 32 ± 13, and 40 ± 19% from baseline, respectively. However, blood flow and vascular conductance in the ITRA and STRA did not change significantly with exercise. These findings demonstrate for the first time that ocular blood flow increases in the retina and choroid, but not in the arterioles, with increasing exercise intensity during dynamic exercise. [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]

The aim of this study was to quantify contributions of genetic and environmental factors to variation in timing of emergence of the primary teeth in a sample of monozygotic and dizygotic twins, using univariate model-fitting approaches. The sample comprised 94 pairs of monozygotic twins and 125 pairs of dizygous twins, all of European ancestry, aged from 2-6 years. Tooth emergence timing was based on parental report, with a subset of data validated by clinical assessment. Heritability estimates for tooth emergence timing were generally high, around 90%, however estimates for the lower right lateral incisor and the lower canines were around 50%. These findings confirm a strong genetic influence on observed variation in the timing of emergence of the human primary teeth. [ABSTRACT FROM AUTHOR]

This review focuses on the characteristics of heat-loss responses during exercise with respect to non-thermal factors. In addition, the effects of physical training on non-thermal heat-loss responses are discussed. When a subject is already sweating the sweating rate increases at the onset of dynamic exercise without changes in core temperature, while cutaneous vascular conductance (skin blood flow) is temporarily decreased. Although exercise per se does not affect the threshold for the onset of sweating, it is possible that an increase in exercise intensity induces a higher sensitivity of the sweating response. Exercise increases the threshold for cutaneous vasodilation, and at higher exercise intensities, the sensitivity of the skin-blood-flow response decreases. Facilitation of the sweating response with increased exercise intensity may be due to central command, peripheral reflexes in the exercising muscle, and mental stimuli, whereas the attenuation of skin-blood-flow responses with decreased cutaneous vasodilation is related to many non-thermal factors. Most non-thermal factors have negative effects on magnitude of cutaneous vasodilation; however, several of these factors have positive effects on the sweating response. Moreover, thermal and non-thermal factors interact in controlling heat-loss responses, with non-thermal factors having a greater impact until core temperature elevations become significant, after which core temperature primarily would control heat loss. Finally, as with thermally induced sweating responses, physical training seems to also affect sweating responses governed by non-thermal factors. [ABSTRACT FROM AUTHOR]

The purpose of the study was to examine the acute effect of a strength training session on brain-derived neurotrophic factor and insulin-like growth factor 1. Furthermore, the influence of a 10-week strength training program on brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) resting levels and memory performance was studied. Fifteen untrained subjects followed a strength training program for 10 weeks. Eight control subjects remained physically inactive. To study the influence of an acute strength training session, blood samples were taken before and after the sixth and 30th sessions. Training effects were evaluated by taking blood samples at rest before and following the training program. Short- and mid-term memories were assessed using the digit span and a recall of images test. BDNF, IGF-1 and its binding protein (IGFBP-3) were measured in serum samples. Data were analyzed (p < 0.05) using a mixed design ANOVA model, Duncan's multiple range post hoc tests, and Pearson's correlation. A single strength training session did not influence BDNF and IGF-1 concentrations. No effect of the strength training period on BDNF, IGF-1, and IGFBP-3 was found. No correlation was found between peripheral BDNF and IGF-1. Short-term memory improved in both the experimental and control groups, but no difference between groups was present. Mid-term memory did not improve following the 10 weeks of training. A period of strength training in sedentary subjects does not significantly change the growth factors or memory function compared to a control group. Also, BDNF and IGF-1 are not acutely influenced by a training session. Further research should focus on the beneficial role of physical exercise in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

We used unilateral plantar-flexor muscles fatigue to assess the capacity of the central nervous system to adapt quiet two-legged stance control to a unilateral ankle neuromuscular perturbation. Eighteen young healthy adults stood barefoot with their eyes closed and were asked to sway as little as possible. The Experimental group (n = 9) executed this postural task in two conditions, before (pre-test) and following the completion of a fatiguing exercise designed to induce a muscular fatigue in the plantar-flexor muscles of their dominant leg (post-test). For the Control group (n = 9), this fatiguing exercise was replaced with a standing rest period corresponding to the fatiguing exercise. Results of the Experimental group showed no significant difference between the weightbearing index measured in the pre-test condition and that observed in the post-test condition. Results further revealed that unilateral plantar-flexor muscles fatigue yielded different effects on the centre of foot pressure (CoP) displacements under the non-fatigued leg and under the fatigued leg: a wider surface area of the CoP displacements was observed under the non-fatigued than under the fatigued leg, and a higher mean speed of the CoP displacements was observed under the non-fatigued leg only in the post-test relative to the pre-test condition. These findings evidenced that the contribution of each leg to the control of quiet two-legged stance is modified as a result of muscle fatigue of unilateral plantar-flexor muscles. The greater contribution of the non-fatigued leg could be viewed as a fatigue-induced adaptive change in the control of quiet two-legged stance in response to an alteration of the unilateral ankle neuromuscular function induced by unilateral plantar-flexor muscles fatigue. [ABSTRACT FROM AUTHOR]

Aims: Open herniotomy with or without hernioscopy has been performed in our unit for a decade. Since 2005 the laparoscopic repair was also introduced. The aims of this study were: (1) to compare detection rates for direct visualization of the contralateral deep inguinal ring via the known sac using a 70 degrees scope and via umbilical 30 degrees laparoscopy and (2) to compare operative timings, metachronous and recurrence rates for the three different management pathways for inguinal hernia.Methods: A retrospective case note review was carried out over a 29 month period since the introduction of the laparoscopic hernia repair. All patients with inguinal hernia were identified from the work load of six surgeons encompassing the three methods of hernia management. Case notes were retrieved and the data analyzed using SPSS v.17.Results: A total of 308 patients had 326 hernias performed. Follow-up ranged from 3 months to 1 year (median 8 months). The male-female ratio was 4:1. Of the patients, 12% were neonates; 299 children presented with unilateral hernia. Of those, 164 (55%) children had open herniotomy without contralateral inspection, and 5 (3%) had metachronous hernia; 77 (26%) children had an open herniotomy with 70 degrees hernioscopy; 2 (3%) children, who were considered to have closed contralateral deep inguinal ring during hernioscopy, had metachronous hernia, and 58 (19%) children had a laparoscopic hernia repair and none of them had metachronous hernia. Detection of contralateral patent deep inguinal ring for 70 degrees hernioscopy and 30 degrees laparoscopy was 10 (13%) and 16 (28%), respectively (P = 0.0465). Operative timing was significantly longer for laparoscopic repair (P < or = 0.0001). During the study period there were 11 recurrences; 9 (5%) in the open only group and 2 (3%) in the laparoscopic group.Conclusions: The results of the laparoscopic inguinal hernia repair are important for discussion as operative methods differ from that of herniotomy. The detection rate of contralateral patent deep inguinal ring appears to be higher for direct visualization via umbilical 30 degrees laparoscopy versus 70 degrees scope via the hernia sac. Whilst laparoscopy offers potential advantage of improved visualization, longer term prospective data collection is needed to compare these methods of operative hernia management. [ABSTRACT FROM AUTHOR]

Objective: A common form of validation study compares alternative methods for collecting data. The Bland-Altman plot pairs observations across methods and plots their mean values vs. their difference. This method provides only limited information, however, when the range of observed values is small relative to the number of observations. This brief report shows how adding a simple bar chart to a Bland-Altman plot adds essential additional information.Study Design and Setting: The methodological approach is illustrated using data from a randomized controlled clinical trial of patients in a U.S. county health system.Results: When the number of unique values is small, a Bland-Altman plot alone may provide inadequate information. Adding a bar chart yields new and essential information about agreement, bias, and heteroscedasticity.Conclusion: Studies validating one data-collection method against another can be performed successfully even when the number of unique values is small. [ABSTRACT FROM AUTHOR]

We compared two methods to determine IL-6 at rest and following exercise. On two occasions, plasma IL-6 was determined in 10 men and 13 women before and immediately following 90 min of cycling at 65% V(O)(2max) using a cytometric bead array (CBA) and an ELISA. The CBA detected IL-6 in 63% of pre-exercise samples and 84% of post-exercise samples; the ELISA detected IL-6 in all samples. In samples with detectable IL-6, resting values were comparable between the CBA and ELISA (2.3 +/- 1.0 and 2.4 +/- 1.2 pg/mL, respectively; p = 0.99); the IL-6 response to exercise was underestimated (p = 0.0003) by the CBA by ~45%, compared with the ELISA. CBA- and ELISA-determined IL-6 values were moderately correlated (r = 0.66, p < 0.0001), but exhibited poor agreement (mean bias +/- 1SD = -1.4 +/- 2.1 pg/mL). The CBA provided concordant IL-6 concentrations at rest, when detected, but underestimated exercise-induced increases in IL-6 versus the ELISA method. [ABSTRACT FROM AUTHOR]

Four elderly women (78 +/- 4.3 years) were resistance trained (RT) for one year and needle biopsies of the vastus lateralis muscle were taken pre- and post-RT. A training intensity of 60% one-repetition maximum (1RM) was adopted for the entire duration of the study. Following RT, significant gain in isometric force of the quadriceps muscles was observed and MHC isoform distribution of vastus lateralis muscle showed a very significant shift from MHC-1 and MHC-2X towards MHC-2A, i.e. a bi-directional shift. A large population (n = 310) of individual skinned muscle fibres were dissected from biopsy samples and used for determination of cross-sectional area (CSA), specific force (Po/CSA) and unloaded shortening velocity (Vo) at 12 degrees C and maximum activation. Fibres were classified on the basis of their MHC isoform content determined by SDS-PAGE in three pure fibre types (1, 2A and 2X) and two hybrid fibre types (1-2A and 2AX). Whereas the CSA of individual muscle fibres did not change, Po/CSA was significantly higher in both type 1 and type 2A fibres post training. Vo of type 1 fibres was significantly higher post-training, whereas no change in Vo was observed in type 2A fibres. The number of pure type 2X fibres was very low especially post-training and did not enable a statistically significant comparison. The data suggest that in elderly women moderate and prolonged RT: (1) can determine similar adaptations in MHC distribution of skeletal muscle to those expected in young subjects; (2) can improve function of muscle fibres. [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]

Unloaded inactivity induces atrophy and functional deconditioning of skeletal muscle, especially in the lower extremities. Information is scarce, however, regarding the effect of unloaded inactivity on muscle size and function about the hip. Regional bone loss has been demonstrated in hips and knees of elderly orthopaedic patients, as quantified by computerized tomography (CT). This method remains to be validated in healthy individuals rendered inactive, including real or simulated weightlessness. In this study, ten healthy males were subjected to 5 weeks of experimental bedrest and five matched individuals served as ambulatory controls. Maximum voluntary isometric hip and knee extension force were measured using the strain gauge technique. Cross-sectional area (CSA) of hip, thigh and calf muscles, and radiological density (RD) of the proximal tibial bone were measured using CT. Bedrest decreased ( P < 0.05) average (SD) muscle strength by 20 (8)% in knee extension, and by 22 (12)% in hip extension. Bedrest induced atrophy ( P < 0.05) of extensor muscles in the gluteal region, thigh and calf, ranging from 2 to 12%. Atrophy was more pronounced in the knee extensors [9 (4)%] and ankle plantar flexors [12 (3)%] than in the gluteal extensor muscles [2 (2)%]. Bone density of the proximal tibia decreased ( P < 0.05) by 3 (2)% during bedrest. Control subjects did not show any temporal changes in muscle or bone indices ( P > 0.05), when examined at similar time intervals. The present findings of a substantial loss in hip extensor strength and a smaller, yet significant atrophy of these muscles, demonstrate that hip muscle deconditioning accompanies losses in thigh and calf muscle mass after bedrest. This suggests that comprehensive quantitative studies on impaired locomotor function after inactivity should include all joints of the lower extremity. Our results also demonstrate that a decreased RD, indicating bone mineral loss, can be shown already after 5 weeks of unloaded bedrest, using a standard CT technique. [ABSTRACT FROM AUTHOR]