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Highlights: [•] We employed hydrogel nanoparticles to concentrate urinary hGH into the linear range of isoform differential immunoassays. [•] The pre-processing step allowed measurement of urine spiked with recombinant and pituitary hGH. [•] Nanoparticles pre-treatment was applied to urine from healthy volunteers administered with recombinant hGH. [•] The recombinant/pituitary hGH concentration ratios remained above the established WADA criterion for hGH misuse up to 24h after the last administration dose. [•] The use of nanoparticles appears to open the possibility of assessing rhGH misuse in urine. [ABSTRACT FROM AUTHOR]

Abstracts: The role of subcortical structures in language function is complex and dependent on language task, with studies increasingly showing subcortical involvement for the production of formulaic language, including recited speech. Individuals with Parkinson's disease (PD), with (n = 6) and without (n = 7) surgical treatment, deep brain stimulation (DBS), were compared to healthy adults (n = 14) to determine whether individuals with subcortical dysfunction produce more errors during a recitation speech task. Participants were asked to recite poems, prayers, and rhymes familiar to them in order to determine the effects of subcortical disease on recited speech ability. When compared with healthy controls, the DBS-OFF group produced significantly more error words, suggesting that deficits in recitation arise with severe states of subcortical dysfunction. Individuals with DBS in the ON or OFF conditions did not differ significantly during the recited speech task. Results support a model of language where large units of overlearned language are at least partially modulated by subcortical structures. [Copyright &y& Elsevier]

Abstract: Recent research into nonfluent forms of primary progressive aphasia and progressive apraxia of speech has highlighted the importance of speech rate as a diagnostic feature. We describe detailed investigation and comparison of speech rate (latencies and utterance length in single word/nonword production and speech rate in connected speech) on a range of experimental tasks in a man with progressive speech deterioration of 10 years duration from Pick's Disease. C.S. had a progressive nonfluent aphasia (PNFA) together with progressive apraxia of speech (pAOS) with an absence of significant interlectual, phonological or semantic impairment. C.S. showed increased latencies but reduced word length compared to matched controls on single word and nonword repetition and reading, an absence of a syllabic length effect in either single word/nonword tasks or connected speech tasks. Further investigation suggested that underlying his speech production impairments were problems with speech initiation, termination and inhibition. Most impairments worsened with progression over a 12-month period. Results provide support for the view that progressive apraxia of speech presents differently to apraxia of speech following stroke and, especially at advanced stages, involves deterioration in more central and supportive cognitive processes. [Copyright &y& Elsevier]

What is already known about this subject: Gastric upset is a common side effect of nilotinib therapy, and calcium carbonate is frequently used concomitantly, either as antacid or as calcium supplementation. With the increasing number of oral agents in cancer therapy, oral drug-drug interactions are becoming more relevant. Nilotinib has already been shown to be absorbed to a much lesser extent when co-administered with proton pump inhibitors. Because exposure to sub-therapeutic concentrations of anticancer drugs such as nilotinib may result in selection of resistant clones and ultimately relapse, we studied the effect of a calcium carbonate supplement (Tums Ultra 1000) on nilotinib pharmacokinetics. What this study adds: Calcium carbonate may be co-administered with nilotinib without significantly affecting the pharmacokinetics of nilotinib and potentially impacting efficacy. Purpose: Nilotinib is a second-generation oral tyrosine kinase inhibitor with superior efficacy compared with imatinib mesylate in the treatment for chronic phase chronic myelogenous leukemia. Calcium carbonate is commonly used as a source of calcium supplementation or as antacid to ameliorate the gastrointestinal side effects associated with nilotinib, which could have unknown effects on nilotinib absorption. The purpose of this study was to provide information on the effect of calcium carbonate on the PK of nilotinib in healthy volunteers. Methods: Healthy subjects were enrolled in a two-period, open-label, single-institution, randomized, cross-over, fixed-schedule study. In one period, each subject received 400 mg of nilotinib p.o. In the other period, 4,000 mg of calcium carbonate (4 X Tums Ultra 1000) was administered p.o. 15 min prior to the nilotinib dose. Plasma samples were collected at specified timepoints, concentrations of nilotinib were quantitated by LC-MS, and data were analyzed non-compartmentally. Results: Eleven subjects were evaluable. Calcium supplementation did not significantly affect nilotinib pharmacokinetic parameters including area under the plasma concentration versus time curve (18.4 μg/mL h alone vs. 16.9 μg/mL h with calcium carbonate, p = 0.83; 80 % power); maximum plasma concentration ( C) (0.670 μg/mL alone vs. 6.18 μg/mL with calcium carbonate, p = 0.97); or half-life (18.9 h alone vs. 17.2 h with calcium carbonate, p = 0.18). Conclusions: Our results indicate that the use of calcium carbonate does not significantly affect nilotinib pharmacokinetics. [ABSTRACT FROM AUTHOR]

Highlights: [•] An LC-MS/MS method for the determination of Nifekalant in human plasma. [•] The method is a simple, sensitive and rapid. [•] Successfully applied to a pharmacokinetic study in healthy volunteers. [Copyright &y& Elsevier]

Background and Aim Stress is believed to play a role in the pathogenesis of functional gastrointestinal disorders. The aim of the present study was to investigate the effect of acute auditory stress on gastric motor responses to a meal in healthy subjects. Methods A total of eight healthy volunteers (seven men and one woman; median age, 33.4 years [30-35 years]) who had no recurrent gastrointestinal symptoms participated in the prospective, randomized, crossover study. Gastric half-emptying time and meal-induced proximal gastric accommodation were measured using gastric scintigraphy under the auditory stress and control conditions in a randomized crossover design. Results The gastric half-emptying time under the stress condition was significantly longer than that under the control condition (130.8 ± 16.6 vs 105.0 ± 13.1 min; P = 0.005 by paired t-test). Under the stress and control conditions, the proximal gastric volume significantly increased after a meal ( P < 0.001 by repeated measures analysis of variance). The degree of the postprandial increase in proximal gastric volume did not significantly differ between both conditions ( P = 0.598 by tests of between-subjects effects using repeated measures analysis of variance). The severity scores of postprandial epigastric discomfort and fullness were significantly higher under the stress condition than under the control condition ( P = 0.001 and P = 0.039, respectively, by paired t-test). Conclusions Acute auditory stress delays gastric emptying and increases the severity of postprandial symptoms in the healthy subjects, suggesting the relevance of psychological stress to the pathophysiological mechanism of functional dyspepsia. [ABSTRACT FROM AUTHOR]

There are many factors that influence the pathogenesis of autoimmune disease of which host genetic factors play an important role. The aim of this study was to investigate the HLA Class I and II genes in a family with a high incidence of AID to establish whether they contribute to the development of these disease. Four of them had been diagnosed with SLE and one with AHA. The patients with SLE showed the presence of HLA-A*02 B*40 DRB1*04:07 DQB1*03:02 haplotype with a high statistical significance. This haplotype was not present in the healthy individuals and in the patient with AHA, although the DRB1*04:07 DQB1*03:02 haplotype (carried by both parents) was found in the AHA patients and one of the healthy individuals. We must consider how HLA Class I in linkage disequilibrium with HLA Class II may be involved in susceptibility or in the development of SLE. An extensive study in this population should be conducted to establish the true participation of the HLA Class I region. [ABSTRACT FROM AUTHOR]

Abstract: The study of healthy human volunteers ascending to high altitude provides a robust model of the complex physiological interplay that emulates human adaptation to hypoxaemia in clinical conditions. Nitric oxide (NO) metabolism may play an important role in both adaptation to high altitude and response to hypoxaemia during critical illness at sea level. Circulating nitrate and nitrite concentrations can be augmented by dietary supplementation and this is associated with improved exercise performance and mitochondrial efficiency. We hypothesised that the administration of a dietary substance (beetroot juice) rich in nitrate would improve oxygen efficiency during exercise at high altitude by enhancing tissue microcirculatory blood flow and oxygenation. Furthermore, nitrate supplementation would lead to measurable increases in NO bioactivity throughout the body. This methodological manuscript describes the design and conduct of the ‘Xtreme Alps’ expedition, a double-blind randomised controlled trial investigating the effects of dietary nitrate supplementation on acclimatisation to hypobaric hypoxia at high altitude in healthy human volunteers. The primary outcome measure was the change in oxygen efficiency during exercise at high altitude between participants allocated to receive nitrate supplementation and those receiving a placebo. A number of secondary measures were recorded, including exercise capacity, peripheral and microcirculatory blood flow and tissue oxygenation. Results from this study will further elucidate the role of NO in adaption to hypoxaemia and guide clinical trials in critically ill patients. Improved understanding of hypoxaemia in critical illness may provide new therapeutic avenues for interventions that will improve survival in critically ill patients. [Copyright &y& Elsevier]

Abstract: Audit studies represent an emerging method for examining disparities in access to care, like substance use treatment, whereby fake patients (i.e., actors) attempt to procure a service with one or more characteristics isolated across condition. This allows for manipulation of variables, like insurance status, that are normally fixed or impossible to standardize with precision when studying actual patients. This pilot study explored whether these methods were feasible for the examination of community-based substance use treatment access. Masked telephone calls (n =48) were made to providers (k =8) in a single city seeking an appointment. A male and female “patient” made calls in three insurance status conditions: no insurance, state-funded insurance, and private insurance. All other subject characteristics were held constant. Results showed an audit design to be a feasible method for examining disparities in access and demonstrated substantial barriers to voluntary treatment. Implications and future directions are discussed. [Copyright &y& Elsevier]

Background: DA-3031 is a newly developed pegylated filgrastim, a recombinant human granulocyte colony-stimulating factor, that is expected to have an extended duration of action compared with non-modified filgrastim. Objective: This study evaluated the tolerability, pharmacokinetics, and pharmacodynamics of DA-3031 in humans, and compared them with filgrastim. Methods: The study was conducted in 48 healthy male Korean subjects. Forty subjects received subcutaneous single doses of 1.8, 3.6, 6, or 18 mg of DA-3031 or placebo in a dose block-randomized, double-blind, dose-escalation design. The remaining eight subjects were given subcutaneous doses of 100 μg/m of filgrastim daily for 5 days. Serial blood samples were collected for pharmacokinetic and pharmacodynamic analyses up to 312 h after the administration of DA-3031 and up to 264 h following the first administration of filgrastim. Results: DA-3031 reached its peak plasma concentration at 6.0-48.0 h and was eliminated mono-exponentially. The pharmacokinetic parameters of DA-3031 increased with dose in a non-linear fashion. Absolute neutrophil count (ANC) levels increased with the dose of DA-3031, although the extent of the increase in ANC decreased at higher dose levels. DA-3031 resulted in similar ANC changes in the 3.6 to 6 mg dose range as 100 μg/m of filgrastim. The most frequent adverse event was back pain, which was observed after both DA-3031 and filgrastim administration. Conclusions: DA-3031 showed non-linear pharmacodynamic and pharmacokinetic profiles and an extended duration of action compared with non-modified filgrastim, without unexpected toxicities in healthy subjects. [ABSTRACT FROM AUTHOR]

Background: Canakinumab is a human anti-interleukin-1beta antibody approved for the treatment of cryopyrin associated periodic syndrome currently formulated as a lyophilized powder requiring reconstitution. A new formulation (solution for injection as pre-filled syringe) has been developed to avoid reconstitution. Objective: The objective of this study was to evaluate the bioequivalence of pre-filled syringe and reconstituted formulations following 150 mg administration in healthy subjects. Methods: This was an open-labeled, randomized, single dose, parallel-group study in 130 healthy subjects, followed for 120 days. Subjects received a single subcutaneous injection of 150 mg canakinumab after either reconstitution or in pre-filled syringe formulation, followed by pharmacokinetics/pharmacodynamics evaluations and safety assessments. The main outcome measure for the study was the pharmacokinetic bioequivalence of the two formulations, which was concluded if the 90 % confidence intervals for the ratios of AUC (area under the serum concentration-time curve from time zero to time of last measurable concentration) and C (maximum serum concentration) were entirely contained within the interval, 0.80-1.25. Results: The arithmetic mean values for the exposure parameters C and AUC were similar for the two formulations. The geometric mean ratio (pre-filled syringe vs. lyophilized form) of C and AUC were 0.99 and 1.01. The associated 90 % confidence intervals were 0.90 to 1.08 and 0.94 to 1.09, respectively. Most common adverse events were headache and nasopharyngitis. Neutropenia occurred in 2 cases (reported as serious adverse events). No deaths occurred. Conclusion: The 150 mg liquid pre-filled syringe and lyophilized formulations of canakinumab are bioequivalent. [ABSTRACT FROM AUTHOR]

Background and Objectives: Dyslipidaemia is a major cardiovascular risk factor associated with type 2 diabetes mellitus. Saroglitazar (ZYH1) is a novel peroxisome proliferator-activated receptor (PPAR) agonist with predominant PPARα and moderate PPARγ activity. It has been developed for the treatment of dyslipidaemia and has favourable effects on glycaemic parameters in type 2 diabetes mellitus. The objective of this phase 1 study was to evaluate the pharmacokinetics, safety and tolerability of saroglitazar in healthy human subjects. Methods: This was a randomized, double-blind, placebo-controlled, single-centre, phase I study in healthy human volunteers, and was performed in two parts; part I evaluated single ascending oral doses of saroglitazar (0.125, 0.25, 0.5, 1, 2, 4, 8, 16, 32, 64 and 128 mg) in healthy subjects, and part II measured the effects of food and sex on the pharmacokinetics of 1 mg saroglitazar, the human equivalent efficacy dose derived from pre-clinical studies. A total of 96 subjects were enrolled in the study, which included 88 healthy male subjects in part I and 16 healthy subjects (8 males from part I of the study and 8 females) in part II. Results: Saroglitazar was rapidly and well absorbed across all doses in the single-dose pharmacokinetic study, with a median time to the peak plasma concentration ( t) of less than 1 h (range 0.63-1 h) under fasting conditions across the doses studied. The maximum plasma concentration ranged from 3.98 to 7,461 ng/mL across the dose range. The area under the plasma concentration-time curve increased in a dose-related manner. The average terminal half-life of saroglitazar was 5.6 h. Saroglitazar was not eliminated via the renal route. There was no effect of sex on the pharmacokinetics of saroglitazar, except for the terminal half-life, which was significantly shorter in females than in males. Food had a small effect on the pharmacokinetics; however, it was not consistent in males and females. Single oral doses of saroglitazar up to 128 mg were well tolerated. No serious adverse events were reported. Adverse events were generally mild and moderate in nature. Saroglitazar did not show any clinically relevant findings in clinical laboratory investigations, physical examinations, vital signs and electrocardiograms. Conclusion: The highest dose of saroglitazar evaluated in this study was 128 mg, several times the estimated therapeutic doses (1-4 mg). The pharmacokinetics of saroglitazar support a once daily dosage schedule. Saroglitazar was found to be safe and well tolerated in this study. [ABSTRACT FROM AUTHOR]

Neuroanatomical studies using transneuronal virus tracers in macaque monkeys recently demonstrated that substantial interactions exist between basal ganglia and the cerebellum. To what extent these interactions are present in the human brain remains unclear; however, these connections are thought to provide an important framework for understanding cerebellar contributions to the manifestation of basal ganglia disorders, especially with respect to tremor genesis in movement disorders such as Parkinson's disease. Here, we tested the feasibility of assessing these connections in vivo and non-invasively in the human brain with diffusion magnetic resonance imaging and tractography. After developing a standardized protocol for manual segmentation of basal ganglia and cerebellar structures, masks for diffusion tractography were defined based on structural magnetic resonance images. We tested intra- and inter-observer stability and carried out tractography for dentato-pallidal and subthalamo-cerebellar projections. After robustly achieving connection probabilities per tract, the connectivity values and connectional fingerprints were calculated in a group of healthy volunteers. Probabilistic diffusion tractography was applicable to probe the inter-connection of the cerebellum and basal ganglia. Our data confirmed that dentato-thalamo-striato-pallidal and subthalamo-cerebellar connections also exist in the human brain at a level similar to those that were recently suggested by transneuronal tracing studies in non-human primates. Standardized segmentation protocols made these findings reproducible with high stability. We have demonstrated that diffusion tractography in humans in vivo is capable of revealing the structural bases of cerebellar networks with the basal ganglia. These findings support the role of the cerebellum as a satellite system of established cortico-basal ganglia networks in humans. [ABSTRACT FROM AUTHOR]

Highlights: [•] Report on first-in-human safety and immunogenicity testing of a genetically attenuated parasite (GAP) P. falciparum strain. [•] Five out of six volunteers remained peripheral blood smear negative after GAP-infected mosquitoe bite. [•] Severe attenuation and favorable immune responses following administration p52 − /p36 − GAP were observed. [•] Results suggest that further development of live-attenuated GAP strains using genetic engineering should be pursued. [Copyright &y& Elsevier]

Background: Previous studies have suggested that melatonin may produce antinociception through peripheral and central mechanisms. Based on the preliminary encouraging results of studies of the effects of melatonin on pain modulation, the important question has been raised of whether there is a dose relationship in humans of melatonin on pain modulation. Objective: The objective was to evaluate the analgesic dose response of the effects of melatonin on pressure and heat pain threshold and tolerance and the sedative effects. Methods: Sixty-one healthy subjects aged 19 to 47 y were randomized into one of four groups: placebo, 0.05 mg/kg sublingual melatonin, 0.15 mg/kg sublingual melatonin or 0.25 mg/kg sublingual melatonin. We determine the pressure pain threshold (PPT) and the pressure pain tolerance (PPTo). Quantitative sensory testing (QST) was used to measure the heat pain threshold (HPT) and the heat pain tolerance (HPTo). Sedation was assessed with a visual analogue scale and bispectral analysis. Results: Serum plasma melatonin levels were directly proportional to the melatonin doses given to each subject. We observed a significant effect associated with dose group. Post hoc analysis indicated significant differences between the placebo vs. the intermediate (0.15 mg/kg) and the highest (0.25 mg/kg) melatonin doses for all pain threshold and sedation level tests. A linear regression model indicated a significant association between the serum melatonin concentrations and changes in pain threshold and pain tolerance (R2 = 0.492 for HPT, R2 = 0.538 for PPT, R2 = 0.558 for HPTo and R2 = 0.584 for PPTo). Conclusions: The present data indicate that sublingual melatonin exerts well-defined dose-dependent antinociceptive activity. There is a correlation between the plasma melatonin drug concentration and acute changes in the pain threshold. These results provide additional support for the investigation of melatonin as an analgesic agent. : Brazilian Clinical Trials Registry (ReBec): (U1111-1123-5109). : IRB: Research Ethics Committee at the Hospital de Clínicas de Porto Alegre. [ABSTRACT FROM AUTHOR]

Abstract: This study is the first one investigating the correlation between the concentration of polycyclic aromatic hydrocarbon (PAHs) in blood and semen qualities for residents in the Pearl River Delta (PRD) region in China. Blood samples from 53 infertile volunteers were studied for measures of semen quality and 16 PAHs. Information on the study subjects' living habits (such as smoking, drinking and preference of consumption for food) and general information (age, body-mass-index (BMI) and educational background) were also collected. Statistical results showed that age and BMI were significantly and negatively related to semen motilities. The total concentrations of PAHs (∑16 PAHs) in the blood were 12,010, 7493, 9105 and 8647ng/g for factory workers, office workers, technicians and salespersons, respectively. In addition, ∑16 PAHs in the blood of smokers, drinkers and heavy-taste food consumers were 11,950, 11,266 and 12,141ng/g, which were higher than those observed in nonsmokers (10,457ng/g), nondrinkers (10,920ng/g) and light-taste food consumers (9202ng/g), individually. Furthermore, the Pearson correlation analysis results showed significant positive correlations between BMI and ∑16 PAHs in the blood. Statistically significant correlations were observed between semen motilities and ∑16 PAHs in the blood as well. Logistic regression results showed that for each 1ng/g increase in ∑16 PAHs in blood samples, the log odds of experiencing a pregnancy decrease by 0.039 on average. However, more evidences are needed to clarify the impact of PAHs in the blood to male infertility. [Copyright &y& Elsevier]

Background: Most of the glycan changes reported in cancers were based on the examinations of a small number of patients or particular proteins. The aim of this study was to determine the changes of the serum N-glycan profile comprehensively in a large number of pancreatic cancer patients and investigate its clinical utility. Methods: Glycan levels in the serum of 92 pancreatic cancer patients and 243 healthy volunteers (HLT) were examined by comprehensive quantitative high-throughput glycome analysis and were compared with clinical parameters. Results: Out of 66 glycans detected, 15 were differentially expressed in pancreatic cancer, and 10 out of the 15 glycans were significantly up-regulated in cases with distant metastasis. There was a clear increase in overall expression of serum glycans, especially highly-branched glycans with fucose moieties, in pancreatic cancer. Among these 15 glycans, a tri-antennary complex type glycan ( m/ z 3195) showed the highest area under the receiver operating characteristic curve (AUROC = 0.799) for the diagnosis of pancreatic cancer. The ratio of pairs of glycans on the same path of the biosynthesis pathway ( m/ z 3195/1914) was found to be significantly higher in pancreatic cancer than in HLT (median = 1.11 and 0.41, respectively; p < 0.0001, AUROC = 0.831). For this pair ratio, the hazard ratio for survival (2.60, 95 % CI = 1.44-4.79) was higher than that of any single glycan and 1-year survival of patients with a high and low ratio was 36.9 and 69.2 %, respectively, ( p = 0.001). Conclusions: Comprehensive glycome analysis can be used to know the presence of pancreatic cancer, distant metastasis, and patient prognosis, simultaneously. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: We aimed to investigate the expression of T cell immunoglobulin and mucin domain 3 (Tim-3) on peripheral blood cells in spontaneous intracerebral hemorrhage (ICH) patients and to analyze its clinical significance. Design and methods: Tim-3 expression on peripheral immunocytes from ICH patients and healthy volunteers was measured by flow cytometry. The correlation between Tim-3 expression and the clinical indices was estimated using linear regression. Results: Tim-3 expressions on peripheral CD3+ T cells and CD8+ T cells in ICH patients are significantly downregulated, while Tim-3 expressions on CD14+ monocytes and CD16+CD56+ NK cells are increased. Furthermore, Tim-3 expression on peripheral CD8+ T cells was negatively correlated with the inflammatory response, the disease severity and the outcome of ICH patients. However, there was no relationship between Tim-3 expression and blood glucose concentration. Conclusions: Altered expression of Tim-3 might play an important role in the pathogenesis of ICH, demonstrating that Tim-3 might be a novel candidate molecule for prognosis evaluation of ICH patients. [Copyright &y& Elsevier]

Introduction: Previous studies have suggested that oxidative stress may play an important role in the pathogenesis of alopecia areata (AA) but these reports are limited and conflicting. Objectives: The aim of this study was to investigate serum paraoxonase-1 (PON1) activity and oxidative status in subjects with AA. Materials and methods: Thirty-nine subjects with AA and 39 healthy controls were enrolled. Serum PON1 activity, total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI) were determined. Results: Serum TAC levels and PON1 activity were significantly lower in the subjects with AA than controls ( p = 0.038, p = 0.001, respectively), whereas TOS levels and OSI were significantly higher (both, p = 0.001) in the subjects with AA. Conclusions: Our results suggest that reduced PON1 activity may be related to increased oxidant and decreased antioxidant levels. These data indicated that oxidant/antioxidant imbalance may play a role in the etiopathogenesis of AA. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to investigate the relationship between body awareness, pain, emotional status, and quality of life among healthy people. Methods: In the study, 100 healthy volunteers aged 20-40 years were evaluated. A Visual Analog Scale (VAS) was used to describe pain intensity. To determine the emotional status of the subjects, the Beck Depression Inventory was used. The Body Awareness Questionnaire (BAQ) was used to evaluate body awareness status, and the SF-36 survey was used to evaluate quality of life. Results: The mean age of the participants was 36.88±10.45 years. The mean of pain intensity was 3.32±2.90. The mean of the scores of emotional status was 8.54±7.77, and the mean of the scores of the BAQ was 94.77±13.97. There was a negative correlation between VAS and BAQ. The BAQ scores showed a negative correlation with emotional status, but the correlation was not statistically significant, due to the fact that all participants had depressive symptoms at a minimal level (p=0.264). BAQ scores were showed a positive correlation with some subscales of SF-36 including energy level (p=0.001) and general health perceptions (p=0.023). Conclusion: This study has showed that the level of body awareness has positive effects on quality of life. Pain and emotional status has affected indirectly on body awareness due to body awareness is a matter that should be assessment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Repeated application of whole-body periodic acceleration (WBPA) upregulates endothelial nitric oxide synthase and improves brachial artery endothelial function (BAEF) as assessed by measurement of flow-mediated vasodilatation (FMD). However, the acute effect of a single application of WBPA on BAEF has not been fully characterized. In addition, although a novel semi-automatic vessel chasing system (UNEXEF18G) has now been developed in Japan, the direct comparison of UNEXEF18G with a conventional method for FMD measures has not been conducted even if UNEXEF18G has already been utilized in a relatively large scale study. METHODS: We have developed a novel semi-automatic vessel chasing system (UNEXEF18G) that can measure FMD on-line, identify time to peak vasodilatation (TPV), and determine the area under the vasodilatation curve (AUC). Thus, 45 min of WBPA was applied in 20 healthy volunteers (age, 34+13 years), and BAEF was measured by UNEXEF18G before and after WBPA. Also, UNEXEF18G measured FMD was compared with those of a conventional FMD measurement method at rest in order to validate a novel UNEXEF18G measured FMD. RESULTS: Single WBPA resulted in a significant increase in FMD (from 6.4 ± 3.4 to 10.7 ± 43%, p < 0.01), a significant decrease in TPV and a significant increase in AUC. In the validation study for UNEXEF18G, Bland and Altman analysis showed that UNEXEF18G measured FMD was almost identical to those of the conventional method at rest. CONCLUSION: These data suggest the usefulness of a new UNEXEF18G and that single application of WBPA results in acute improvement in BAEF in humans. [ABSTRACT FROM AUTHOR]

Objectives To assess the extent of dengue virus exposure in the population. Methods In this seroepidemiological study, 685 blood samples were collected (from April 2007 to July 2009) from two subject groups: (i) 344 samples from anonymous blood donors of the Hong Kong Red Cross and (ii) 341 samples from healthy volunteers recruited from a university, a community centre and a hospital. Demographic information and travel history were collected for the second subject group. All blood samples were subjected to the PanBio Dengue IgG Indirect ELISA. Results Anti-dengue virus IgG was detected in 1.6% of the blood samples. Individuals who visited countries in Southeast Asia in the past year were significantly associated with seropositivity ( P = 0.03, OR 5.38, CI 1.13-25.54). Conclusions The overall dengue seroprevalence was 1.6%, and visit to Southeast Asia was the only independent predictor for seropositivity. Although the current situation is not alarming, frequent travel, presence of mosquito vector and emergence of local cases suggest that the risk of dengue virus infection within the local community cannot be overlooked, and continuous vigilance is warranted. [ABSTRACT FROM AUTHOR]

Abstract: Complex regional pain syndrome (CRPS) is characterised by autonomic, sensory, and motor disturbances. The underlying mechanisms of the autonomic changes in CPRS are unknown. However, it has been postulated that sympathetic inhibition in the acute phase with locally reduced levels of noradrenaline is followed by an up-regulation of alpha-adrenoceptors in chronic CRPS leading to denervation supersensitivity to catecholamines. This exploratory study examined the effect of cutaneous sympathetic activation and inhibition on cutaneous noradrenaline release, vascular reactivity, and pain in CRPS patients and in healthy volunteers. Seven patients and nine controls completed whole-body cooling (sympathetic activation) and heating (sympathetic inhibition) induced by a whole-body thermal suit with simultaneous measurement of the skin temperature, skin blood flow, and release of dermal noradrenaline. CRPS pain and the perceived skin temperature were measured every 5min during thermal exposure, while noradrenaline was determined from cutaneous microdialysate collected every 20min throughout the study period. Cooling induced peripheral sympathetic activation in patients and controls with significant increases in dermal noradrenaline, vasoconstriction, and reduction in skin temperature. The main findings were that the noradrenaline response did not differ between patients and controls or between the CRPS hand and the contralateral unaffected hand, suggesting that the evoked noradrenaline release from the cutaneous sympathetic postganglionic fibres is preserved in chronic CRPS patients. [Copyright &y& Elsevier]

Background: Volunteering has been advocated by the United Nations, and American and European governments as a way to engage people in their local communities and improve social capital, with the potential for public health benefits such as improving wellbeing and decreasing health inequalities. Furthermore, the US Corporation for National and Community Service Strategic Plan for 2011-2015 focused on increasing the impact of national service on community needs, supporting volunteers' wellbeing, and prioritising recruitment and engagement of underrepresented populations. The aims of this review were to examine the effect of formal volunteering on volunteers' physical and mental health and survival, and to explore the influence of volunteering type and intensity on health outcomes. Methods: Experimental and cohort studies comparing the physical and mental health outcomes and mortality of a volunteering group to a non-volunteering group were identified from twelve electronic databases (Cochrane Library, Medline, Embase, PsychINFO, CINAHL, ERIC, HMIC, SSCI, ASSIA, Social Care Online, Social Policy and Practice) and citation tracking in January 2013. No language, country or date restrictions were applied. Data synthesis was based on vote counting and random effects meta-analysis of mortality risk ratios. Results: Forty papers were selected: five randomised controlled trials (RCTs, seven papers); four non-RCTs; and 17 cohort studies (29 papers). Cohort studies showed volunteering had favourable effects on depression, life satisfaction, wellbeing but not on physical health. These findings were not confirmed by experimental studies. Meta-analysis of five cohort studies found volunteers to be at lower risk of mortality (risk ratio: 0.78; 95% CI: 0.66, 0.90). There was insufficient evidence to demonstrate a consistent influence of volunteering type or intensity on outcomes. Conclusion: Observational evidence suggested that volunteering may benefit mental health and survival although the causal mechanisms remain unclear. Consequently, there was limited robustly designed research to guide the development of volunteering as a public health promotion intervention. Future studies should explicitly map intervention design to clear health outcomes as well as use pragmatic RCT methodology to test effects. [ABSTRACT FROM AUTHOR]

This study aims to investigate the serum IL-21 levels in systemic lupus erythematosus (SLE) and its relations with clinical and laboratory features. Fifty-seven patients with SLE and 30 healthy volunteers were recruited in the current study. Serum IL-21 levels were detected by enzyme-linked immunosorbent assay. Statistical analyses were performed by SPSS 10.01. Results showed that IL-21 levels were significantly decreased in the serum of patients with SLE compared with controls ( P = 0.026). There was no significant difference regarding serum IL-21 level between SLE patients with nephritis and those without nephritis ( P = 0.066); no significant difference was found between less active SLE and more active SLE ( P = 0.588). The presence of anemia was associated with low serum IL-21 levels ( P = 0.030) in SLE patients. In summary, decreased serum level of IL-21 and its association with anemia indicate a possible role of IL-21 in human SLE. However, further studies are needed to confirm this preliminary results. [ABSTRACT FROM AUTHOR]

The aim is to assess metabolic disturbance in early rheumatoid arthritis patients and its relation to the clinical characteristics of patients. Forty recently diagnosed untreated rheumatoid arthritis (RA) patients with disease duration less than 1 year (group I) along with age- and sex-matched forty healthy volunteers who served as controls (group II) were studied. Disease activity score was used to assess disease activity. Blood pressure, BMI, glucose, insulin and complete lipid profile, visfatin, and adiponectin were measured. Insulin resistance (IR) was estimated by the homeostasis model assessment for insulin resistance (HOMA-IR). Beta-cell function was estimated by the homeostasis model assessment (HOMA-B). Also, rheumatoid factor, anticyclic citrullinated peptide antibodies were measured. Group I had significantly higher fasting insulin, HOMA-(IR, B), visfatin, lipid profile (except HDL), and lower adiponectin versus group II ( p = 0.000). There were significant positive correlations between visfatin and the following biochemical parameters: insulin, HOMA-IR, HOMA-B, cholesterol, triglycerides, LDL-C ( p = 0.05, 0.029, 0.005, 0.001, 0.002, 0.045, respectively). Also, the disease activity score was positively correlated with visfatin ( p = 0.003). Meanwhile, there were significant negative correlations between adiponectin and the following biochemical parameters: insulin, HOMA-IR, HOMA-B, cholesterol, triglycerides, LDL-C, visfatin ( p = 0.031, 0.023, 0.001, 0.000, 0.000, 0.016, 0.000, respectively). Also, the disease activity score was negatively correlated with adiponectin ( p = 0.001). The findings of the present study showed that recently diagnosed untreated RA patients are characterized by a severe metabolic disturbance state that is driven primarily by disease activity. [ABSTRACT FROM AUTHOR]

In 2003, we simultaneously quantified 27 metals by inductively coupled plasma–mass spectrometry (ICP–MS) in the whole blood, plasma and urine of 100 healthy volunteers. We again determined the metallic profile in whole blood and plasma during 2012. ICP–MS validated multielementary method was performed for metals in whole blood and plasma. Whole blood vanadium and chromium were quantified using ICP–MS collision cell technology. The aims of the study were to compare and assess any changes in this profile, particularly due to the environment. Healthy male/female staff volunteers (n = 106) with no professional exposure to metals, or medication containing lithium, strontium; or food supplements with trace elements and vitamins and with no metal prosthesis were included. Tobacco consumption and the number of dental amalgams were recorded. Our results demonstrated a blood lead level that had drastically decreased, i.e. reduced by half, during this period (12.5 versus 26.3 µg/L, P < 0.0001). Known differences were observed between males and females for copper and zinc; cadmium and lead were higher in smokers. Median plasmatic mercury, a specific test for dental amalgam exposure, did not significantly increase (0.38 versus 0.28 µg/L, P = 0.11). The ICP–MS metallic profile is a very practical concept that is useful for clinical, forensic and environmental toxicology, including industrial hygiene monitoring. [ABSTRACT FROM AUTHOR]

Highlights: [•] High-frequency TENS causes inhibition of LEPs and evoked pain perception. [•] This modulation reflects an objective inhibitory effect of TENS on pain pathways. [•] This modulation predominates within the segmental area of TENS application. [ABSTRACT FROM AUTHOR]

Rational and Objective: Dynamic contrast enhanced (DCE)-MRI has great potential to provide quantitative measure of inflammatory activity in rheumatoid arthritis. There is no current benchmark to establish the stability of signal in the joints of healthy subjects when imaged with DCE-MRI longitudinally, which is crucial so as to differentiate changes induced by treatment from the inherent variability of perfusion measures. The objective of this study was to test a pixel-by-pixel parametric map based approach for analysis of DCE-MRI (Dynamika) and to investigate the variability in signal characteristics over time in healthy controls using longitudinally acquired images. Materials and Methods: 10 healthy volunteers enrolled, dominant wrists were imaged with contrast enhanced 3T MRI at baseline, week 12, 24 and 52 and scored with RAMRIS, DCE-MRI was analysed using a novel quantification parametric map based approach. Radiographs were obtained at baseline and week 52 and scored using modified Sharp van der Heidje method. RAMRIS scores and dynamic MRI measures were correlated. Results: No erosions were seen on radiographs, whereas MRI showed erosion-like changes, low grade bone marrow oedema and low-moderate synovial enhancement. The DCE-MRI parameters were stable (baseline scores, variability) (mean±st.dev); in whole wrist analysis, MEmean (1.3±0.07, −0.08±0.1 at week 24) and IREmean (0.008±0.004, −0.002±0.005 at week 12 and 24). In the rough wrist ROI, MEmean (1.2±0.07, 0.04±0.02 at week 52) and IREmean (0.001±0.0008, 0.0006±0.0009 at week 52) and precise wrist ROI, MEmean (1.2±0.09, 0.04±0.04 at week 52) and IREmean (0.001±0.0008, 0.0008±0.001 at week 24 and 52). The Dynamic parameters obtained using fully automated analysis demonstrated strong, statistically significant correlations with RAMRIS synovitis scores. Conclusion: The study demonstrated that contrast enhancement does occur in healthy volunteers but the inherent variability of perfusion measures obtained with quantitative DCE-MRI method is low and stable, suggesting its suitability for longitudinal studies of inflammatory arthritis. These results also provide important information regarding potential cut-off levels for imaging remission goals in patients with RA using both RAMRIS and DCE-MRI extracted parametric parameters. [ABSTRACT FROM AUTHOR]

Abstract: A novel, fast, sensitive and robust method based on ultra-performance liquid chromatography coupled to atmospheric pressure electrospray ionization tandem mass spectrometry (UPLC–ESI-MS/MS) has been developed to separate two Tibolone stereoisomers i.e., 3α-Hydroxy Tibolone and 3β-Hydroxy Tibolone and to quantify 3α-Hydroxy Tibolone using p-toulenesulfonyl isocyanate (PTSI) as a derivatizing reagent in human plasma. 3α-Hydroxy Tibolone-13CD3 was used as an internal standard (IS). The analyte and IS were extracted from human plasma by liquid–liquid extraction using ethyl acetate. Extracted samples were analyzed by UPLC–ESI-MS/MS. Chromatography was performed using binary gradient on UPLC analytical column. A linear calibration curve over the range of 0.100–35.000ng/mL was obtained and lower limit of quantification (LLOQ) was 0.100ng/mL demonstrating acceptable accuracy and precision. This method was successfully applied to a pharmacokinetic study in order to compare a test Tibolone 2.5mg formulation vs. a reference 2.5mg Tibolone tablet formulation in 50 post-menopausal/surgical menopause female human volunteers under fasting conditions. It is concluded that test formulation of Tibolone is bioequivalent to reference formulation of Tibolone. [Copyright &y& Elsevier]

International disaster volunteers are an important group of workers on the ground after a disaster who have not been the subject of much research. Utilizing survey data from volunteers with a non-governmental organization in Leogane, Haiti after the 12 January 2010 earthquake, this paper focuses on volunteers' characteristics, their health behaviors (i.e. protective and risky), and their interactions and relationships with their host community. The volunteer population was primarily made up of single young adults with a high level of education. They engaged in various protective health behaviors, with women more likely to use of bug repellent and sunscreen more frequently than men. The majority of volunteers believed that interactions with the host community were not significant to their work; however they believed that a strong relationship was important to the success of the relief effort. Disaster volunteer health behaviors and relationships with the host community should continue to be studied. [ABSTRACT FROM AUTHOR]

Background: Although two-dimensional speckle tracking (2DST) has been validated in animal and early clinical studies for quantitative evaluation of myocardial motion and contractility, there are only limited measurements in large healthy population to be used as reference data, which severely restricts its clinical application. This study aimed at determining the age-specific normal values of left ventricular (LV) longitudinal, circumferential and radial strain in healthy adults. Methods: We studied 228 healthy subjects (109 males, mean age 44±15years, range 18–78years). Their LV longitudinal, circumferential and radial strains were measured by 2DST at basal, middle and apical levels of parasternal short-axis and apical 2-, 4- and 3-chamber views. The effects of age, gender and echocardiographic machines (52 patients had measurements obtained by both GE and Philips machines) on these parameters were also evaluated. Results: The longitudinal and circumferential strains were −20.4±3.4% and −22.9±3.1%, respectively with higher values being observed at basal than apical segments. On the contrary, the radial strain which ranged 42.6±12.9% decreased towards apical segments. The longitudinal strain declined, the circumferential strain rose and the radial strain remained similar during aging. Adult females had slightly higher circumferential and longitudinal strains than males (23±3% vs −22±3%, −21±3% vs −20±3% respectively; both p<0.01). Strains measured by the 2 different echo machines had good correlations but Phillips-assessed strains (longitudinal and circumferential) were 10% higher than GE measurements. Inter- and intra-observer variabilities were acceptable. Conclusions: Strain measurements by 2DST echocardiography varies with age, gender and echocardiographic vendors in healthy adults. These findings are important to differentiate between health and disease and to assess the severity of disease. [ABSTRACT FROM AUTHOR]

Hippocampal learning is thought to induce metaplasticity, which can facilitate subsequent learning. Administered at single low doses, the N-methyl-D-aspartate-type glutamate receptor antagonist memantine predominantly blocks α7 nicotinic acetyl-choline receptors (α7 nAChRs). Placebo-controlled administration of a single lowdose ofmemantine in a pharmaco-fMRI experiment may thus help characterize the role of α7 nAChRs in hippocampal metaplasticity. We hypothesized that if α7 nAChRs contribute to learning-induced metaplasticity in the hippocampus, blockade of these receptors with low-dose memantine would selectively interfere with a facilitation of subsequent learning without impairing hippocampal learning per se. To specifically test this hypothesis, we devised a randomized controlled trial in which healthy volunteers were administered a 20-mg single oral dose of memantine or placebo and scanned on three subsequent runs of a hippocampal learning task. Our results indicate no discrepancies in behavioral learning between low-dose memantine- and placebo-treated participants in the first and second run of this task. In the third run, however, only the placebo-treated group showed facilitated behavioral learning, an effect paralleled by decreased neural responses in the hippocampal cornu ammonis region. Our findings suggest that blockade of α7 nAChRs selectively interfered with a learning-induced facilitation of subsequent learning while leaving unimpaired hippocampal learning per se. Taken together, our results provide support for a relevant contribution of α7 nAChRs to learning-associated metaplasticity in the hippocampus. [ABSTRACT FROM AUTHOR]

Abstract: Epidemiologic studies suggest that dietary vitamin E is an important candidate intervention for asthma. Our group has shown that daily consumption of vitamin E (γ-tocopherol, γT) has anti-inflammatory actions in both rodent and human phase I studies. The objective of this study was to test whether γT supplementation could mitigate a model of neutrophilic airway inflammation in rats and in healthy human volunteers. F344/N rats were randomized to oral gavage with γT versus placebo, followed by intranasal LPS (20μg) challenge. Bronchoalveolar lavage fluid and lung histology were used to assess airway neutrophil recruitment. In a phase IIa clinical study, 13 nonasthmatic subjects completed a double-blinded, placebo-controlled crossover study in which they consumed either a γT-enriched capsule or a sunflower oil placebo capsule. After 7 days of daily supplementation, they underwent an inhaled LPS challenge. Induced sputum was assessed for neutrophils 6 h after inhaled LPS. The effect of γT compared to placebo on airway neutrophils post-LPS was compared using a repeated-measures analysis of variance. In rats, oral γT supplementation significantly reduced tissue infiltration (p<0.05) and accumulation of airway neutrophils (p<0.05) that are elicited by intranasal LPS challenge compared to control rats. In human volunteers, γT treatment significantly decreased induced sputum neutrophils (p=0.03) compared to placebo. Oral supplementation with γT reduced airway neutrophil recruitment in both rat and human models of inhaled LPS challenge. These results suggest that γT is a potential therapeutic candidate for prevention or treatment of neutrophilic airway inflammation in diseased populations. [Copyright &y& Elsevier]

Abstract: The aim of this study was to develop a limited sampling strategy (LSS) to assess the bioequivalence of two formulations of pidotimod. A randomized, two-way, cross-over study was conducted in healthy Chinese volunteers to compare two formulations of pidotimod. A limited sampling model was established using regression models to estimate the pharmacokinetic parameters and assess the bioequivalence of pidotimod. The model was internally validated by the Jack-knife method and graphical methods. The traditional non-compartmental method was also used to analyze the data and compared with LSS method. The results indicate that following oral administration of a single 800mg dose, the plasma AUC0–12h and Cmax of pidotimod can be predicted accurately using only two to four plasma samples. The bioequivalence assessment based on the LSS models provided results very similar to that obtained using all the observed concentration–time data points and indicate that the two pidotimod formulations were bioequivalent. A LSS method for assessing the bioequivalence of pidotimod formulations was established and proved to be applicable and accurate. This LSS method could be considered appropriate for a pidotimod bioequivalence study, providing an inexpensive cost of sampling acquisition and analysis. And the methodology presented here may also be applicable to bioequivalence evaluation of other medications. [Copyright &y& Elsevier]

The main objective of this research is to explore which factors best predict the occurrence of burden on primary caregivers of children with cerebral palsy (CP). Understanding these factors enables the identification of those caregivers at risk of having their physical and psychological health adversely affected, and the implementation of intervention strategies to reduce the negative impact of caring on parents of children with chronic medical conditions. The study sample consisted of a total of 62 caregivers (89% women) aged between 30 and 54 years (Mean = 41.98, SD = 5.64). CP affected children were aged between 1 and 17 years (Mean = 7.69, SD = 4.18) and the average degree of disability (% reflected in the medical record assessed by the Ministry of health, social services and equality of Spain) was 77.098 (scale of 100) (SD = 14.62). A burden model was constructed based on multiple linear regressions. The model included the following variables: degree of disability, depression (assessed by Beck Depression Inventory-II) and self-efficacy (measured by the Revised Scale for Caregiving Self-Efficacy). The regression model explained 40.9% of the total variance. It was found that self-efficacy had a negative linear association with burden, while the degree of disability and depression showed a positive linear association. The most important predictors of caregiver burden were degree of disability, depression and self-efficacy. For this reason, we believe that it is necessary to develop interventions to reduce depression and enhance self-efficacy in parents of children with CP as one of the primary objectives for minimizing the burden on caregivers of disabled children. [ABSTRACT FROM AUTHOR]

Copyright of Brazilian Journal of Pulmonology / Jornal Brasileiro de Pneumologia is the property of Sociedade Brasileira de Pneumologia e Tisiologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Immune response rates following influenza vaccination are often lower in HIV-infected individuals. Low vitamin D levels were correlated with weak immune response in cancer patients and are known to be lower in HIV-infected patients. Methods: Diagnostic study to determine immune response against the H1N1v component after a single, intramuscular dose of the 2010/11 seasonal, trivalent influenza vaccine (TIV) in adult HIV-infected and healthy controls scheduled for influenza vaccination (ClinicalTrials.gov Identifier: NCT01017172). Influenza A/H1N1 antibody titers (AB) were determined before and 21 days after vaccination by hemagglutination inhibition assay. Results: Immune response was not different between HIV-infected patients (n = 36) and healthy controls (n = 42) who were previously naïve to the H1N1v component of the TIV. Comparing HIV-infected patients (n = 55) and healthy controls (n = 63) who had received 1 or 2 doses of an AS03 adjuvanted H1N1 vaccine in the previous winter season (2009/10), seroconversion rate and the geometric mean AB titer after TIV of the HIV-infected patients were more than twice as high compared to healthy controls. This difference was mainly driven by the 2-dose schedule for HIV patients in 2009/10. Vitamin D levels were lower in HIV patients but did not correlate with immune response. Conclusion: HIV-infected patients who had received 1 or 2 doses of an adjuvanted H1N1 vaccine in the previous year (2009/10) had a significant higher seroconversion rate following TIV as compared to healthy controls, indicating a stronger memory cell response due to the 2-dose schedule. [ABSTRACT FROM AUTHOR]

Highlights: [•] The tested OSR cultivars differed significantly in their dormancy potential. [•] The potential of oilseed rape seeds (OSR) to acquire dormancy was highly heritable. [•] Within cultivars a plant-to-plant variability of the ‘dormancy’ trait was observed. [•] Genotypic variability could be used to develop low-dormancy lines of current cultivars. [•] The trait ‘low-dormancy’ proved to be stable in the offspring under field conditions. [Copyright &y& Elsevier]

Summary: Aim of the study: To explore the effects of caffeine and bright light therapy on simulated nighttime driving in sleep-deprived healthy volunteers. Participants and methods: Twelve male healthy volunteers aged 20 to 50 years participated in a randomized cross-over study of simulated nighttime driving at a sleep laboratory, followed by recovery sleep with polysomnography at home. The volunteers received variable combinations of caffeine 200mg (C+), caffeine placebo (C–), bright light 10,000 lux (L+), and bright light placebo<50 lux (L–), in four sessions (C+L+, C+L–, C–L+, C–L–), in random order with a wash-out period of 7 days. Treatments were given at 1 a.m. and testing was performed at 1:30 a.m., 3 a.m., 4 a.m., and 6 a.m. Lane drifting was the primary outcome measure. Other measures were reaction times, self-rated fatigue, sleepiness and recovery sleep. Results: Without treatment, lane drifting increased throughout the night, and objective and subjective vigilance declined. Paired comparisons showed that lane drifting was significantly worse at 6 a.m. and at 4 a.m. than at 1:30 a.m. There was a global treatment effect on lane drifting. Lane drifting at 6 a.m. was significantly decreased with C+L+ compared to C–L–. Conclusions: Bright light therapy combined with caffeine administered at 1 a.m. decreased lane drifting by healthy volunteers during simulated nighttime driving. [Copyright &y& Elsevier]

Abstract: It has been suggested to use gait modifications in the retraining of patients with knee osteoarthritis (OA), in order to reduce the external knee adduction moment (KAdM). This study focused on the effect of walking speed, foot position and trunk sway, and on the 3D knee moments. Gait analyses of fourteen healthy volunteers were performed in a gait laboratory. Subjects walked at three different speeds in their normal gait pattern, as well as with toe-in and toe-out gait and with medio-lateral trunk sway at a self-selected speed. Fast walking speed increased the KAdM (17–30%) and flexion moment (32%). A slower walking speed did not decrease the KAdM. Toe-in mainly decreased the KAdM (45%) and the transverse moment (38%) during early stance. Toe-out decreased the KAdM during late stance (56%), but increased the KAdM during early stance and midstance (21–24%), due to decreased endorotation of the hip with knee flexion. Trunk sway decreased the KAdM during early stance and midstance (31–33%). Gait modifications mainly affected the KAdM, but changes in sagittal and transverse knee moments and kinematics were also observed. This indicates that, when estimating knee load, taking only the frontal plane kinetics into consideration may lead to erroneous simplifications. No conclusive beneficial effects were found in any of the gait modifications throughout the entire stance phase. [Copyright &y& Elsevier]

Serial focus group data shed light on the experiences of senior volunteers and nonprofit agency professional staff with the aim of maximizing the volunteer experience and contribution. Data were analyzed using a serial focus group approach to suggest pathways towards increasing mutual benefits. Themes from both volunteers and non-profit professionals included the need for better utilization of volunteers, the importance of communication and the advantage of defining roles at the beginning of the volunteer experience. Data from the groups also highlighted the need for planning on the part of the nonprofit staff and flexibility from the volunteers. Discussion and implications follow the report on the data. [ABSTRACT FROM AUTHOR]

Background Hyperoxaemia depresses the output of peripheral and central chemoreceptors. Patients treated with opioids often receive supplemental oxygen to avert possible decreases in oxygen saturation (). We examined the effect of a single dose of remifentanil in healthy volunteers inhaling room air vs air enriched with 50% oxygen. Methods Twenty healthy volunteers received i.v. 50 μg remifentanil (infused over 60 s) at anormoxic (N) or hyperoxic ( 0.5, H) background on separate occasions. Minute ventilation (Vi), respiratory rate (RR), end-tidal Pco2, and were collected on a breath-to-breath basis. The occurrence of apnoea was recorded. Results During normoxia, remifentanil decreased Vi from 7.4 (1.3) [mean (sd)] to 2.2 (1.2) litre min−1 (P<0.01), and during hyperoxia from 7.9 (1.0) to 1.2 (1.2) litre min−1 (P<0.01; H vs N: P<0.001). RR decreased from 13.1 (2.9) to 6.1 (2.8) bpm during N (P<0.01) and from 13.2 (3.0) to 3.6 (4.0) bpm during H (P<0.01; H vs N: P<0.01). During normoxia, decreased from 98.4 (1.5) to 88.6 (6.7)% (P<0.01), while during hyperoxia, changed from 99.7 (0.7) to 98.7 (1.0)% (P<0.001). Apnoea developed in two subjects during normoxia and 10 during hyperoxia. Conclusions Respiratory depression from remifentanil is more pronounced in hyperoxia than normoxia as determined from minute ventilation, end-tidal Pco2, and RR. During hyperoxia, respiratory depression may be masked when measuring as pulse oximetry remains in normal values during the first minutes of respiratory depression. [ABSTRACT FROM PUBLISHER]

Abstract: This paper reports the development and validation of an assay for ifenprodil based on liquid chromatography–tandem mass spectrometry (LC–MS/MS) and its application to a pharmacokinetic study involving single and multiple intravenous infusions to healthy Chinese volunteers. After sample preparation of plasma by liquid–liquid extraction with ethyl acetate, the analyte and internal standard, urapidil, were separated by reversed phase chromatography in a run time of 4min and detected by positive ion electrospray ionization followed by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 326.2→308.1 for ifenprodil and m/z 388.4→205.3 for IS. The assay was linear in the concentration range 0.2–50.0ng/mL with recovery >76.4%. In the pharmacokinetic study of single intravenous infusions of 5, 10 and 15mg ifenprodil, peak plasma concentrations and areas under the plasma concentration–time curve were both linearly related to dose. In the pharmacokinetic study of multiple once daily intravenous infusions of 10mg ifenprodil for 7 days, pharmacokinetic parameters were similar to those after the single dose showing that ifenprodil does not accumulate on repeated administration. [Copyright &y& Elsevier]

Copyright of Revista Brasileira de Nutrição e Esportiva is the property of Instituto Brasileiro de Pesquisa e Ensino em Fisiologia do Exercicio and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Allergic sensitisation has been ascribed to a dysregulated relationship between allergen-specific Th1, Th2 and regulatory T cells. We hypothesised that the relationship between these T cell subsets could be better defined using a short-term allergen stimulation system followed by direct analysis of CD154-positive T cells. Using peripheral blood samples from birch pollinosis patients and healthy non-atopic controls, we sought to explore the frequencies and phenotype of birch-stimulated CD154-positive T helper cells following ex vivo birch allergen stimulation. Results: Activated CD154-positive Th1, Th2 and Tr1-like cells, that co-expressed IFN?, IL-4 and IL-10 respectively, were identified in both birch-allergic and non-allergic participants. We observed a close correlation between Th1, Th2 and Tr1-like cell frequency in non-allergic volunteers, such that the three parameters increased together to maintain a low Th2: Th1 ratio. The relationship between Th1, Th2 and Tr1-like responses was dysregulated in birchallergic patients, with abrogation of the IL-10 response and a higher Th2: Th1 ratio. A close correlation was observed between Th2 cell frequency and the absolute concentration of birch-specific IgE within the birch-allergic group, and we confirmed previous reports of a more differentiated T cell phenotype in allergic subjects. Conclusions: The findings demonstrate an important balance between IFN?, IL-4 and IL-10 T cell responses to birch allergen in health, where Th2 responses to allergens were frequently observed, but apparently balanced by Th1 and regulatory responses. The detection of CD154 positive T cells after short-term antigen stimulation may be a useful method for the detection of T cell responses to allergens when cost, speed and convenience are priorities. [ABSTRACT FROM AUTHOR]

Background: Risperidone is a benzisoxazole derivate and is effective in the treatment of schizophrenia and other psychiatric illnesses in adults and children. Although there are a few reports in the literature regarding the pharmacokinetic characteristics of risperidone, insufficient data on its pharmacokinetic properties in a Chinese population are available. Objective: To meet the requirements for marketing a new generic product, this study was designed to compare the pharmacokinetic properties and bioequivalence of two 2 mg tablet formulations of risperidone: a newly developed generic formulation (test) and a branded formulation (reference) in healthy adult male Chinese volunteers. Methods: A single-dose, open-label, randomized-sequence, 2 × 2 crossover study was conducted in fasted healthy male Chinese volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive 1 tablet (2 mg each) of the test formulation (Risperidone tablet; Dr. Reddy's Laboratories Ltd., Hyderabad, India) or the reference formulation (Risperdal tablet; Xian-Janssen Pharmaceutical Ltd., Xi-an, China), followed by a 2-week washout period and subsequent administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Plasma samples were collected over 96 hours. Plasma concentrations of the parent drug, risperidone, and its active metabolite, 9-hydroxy-risperidone, were analyzed by a liquid chromatography-tandem mass spectrometry method. The formulations would be considered bioequivalent if the 90% confidence intervals (CIs) of the natural log-transformed values were within the predetermined 80-125% equivalence range for the maximum plasma drug concentration (C) and the area under the plasma concentration-time curve (AUC), in accordance with guidelines issued by the US Food and Drug Administration. Assessment of tolerability was based on recording of adverse events (AEs), monitoring of vital signs, electrocardiograms, and laboratory tests at baseline and at completion of the study. Results: A total of 24 healthy male Chinese volunteers (mean age 22.9 years [standard deviation (SD) 2.7, range 19.2-27.1]; weight 63.2 kg [SD 7.0, range 52.0-78.0]; and height 171.3 cm [SD 6.1, range 162.0-187.0]) were enrolled, and all completed the study. For the parent drug, risperidone, the 90% CIs of the relative values (test vs. reference) of the C, AUC from time zero to time t (AUC), and AUC from time zero to infinity (AUC) were 97.0-124.0%, 92.7-115.1%, and 92.8-114.2%, respectively. For the active metabolite, 9-hydroxy-risperidone, the values were 104.4-117.7%, 101.0-113.7%, and 100.4-113.4%, respectively. The two formulations met the predetermined criteria for bioequivalence. A total of 73 AEs were observed in 24 subjects during the study. The most common AE was sedation (48 events), followed by nasal reactions (14 events), postural hypotension (3 events), hypertriglyceridemia (2 events), dizziness (4 events), nausea (1 event), and anorexia (1 event). Their severity was as follows: 16 were mild, 57 were moderate, and none were severe. The majority of the AEs were considered to be related (48 events) or probably related (23 events) to the study medication. No clinically significant abnormalities on physical examination, vital sign measurements, or electrocardiographic recordings were reported. No serious AEs were reported. Conclusions: The data from this study in healthy adult male Chinese subjects suggest that the test formulation met the regulatory criteria for bioequivalence to the reference formulation, on the basis of the rate and extent of absorption. Both formulations were well tolerated. [ABSTRACT FROM AUTHOR]

This study investigated the effect of moderate consumption of horse meat on iron status, lipid profile and fatty acid composition of red blood cells in healthy male volunteers. Fifty-two subjects were randomly assigned to two groups of 26 subjects each: a test group consuming two portions of 175 g/week of horse meat, and a control group that abstained from eating horse meat during the 90 days trial. Before and after 90 days, blood samples were collected for analysis. Horse meat consumption significantly ( p ≤ 0.05) reduced serum levels of total and low-density lipoprotein cholesterol ( − 6.2% and − 9.1%, respectively) and transferrin ( − 4.6%). Total n − 3, long chain polyunsaturated fatty acids n − 3 and docosahexeanoic acid content in erythrocytes increased ( p ≤ 0.05) by about 7.8%, 8% and 11%, respectively. In conclusion, the regular consumption of horse meat may contribute to the dietary intake of n − 3 polyunsaturated fatty acids and may improve lipid profile and iron status in healthy subjects. [ABSTRACT FROM AUTHOR]

The aim of this randomised, double-blind, crossover study in normolipidaemic volunteers was to investigate the effect of consumption of an experimental cheese (from cows fed a grass and maize silage-based diet with 5% of linseed oil added) or a control cheese (without linseed oil) on both plasma lipids and fatty acid content of serum lipid fractions. A lower content of medium-chain saturated fatty acids as well as a higher content of stearic acid and polyunsaturated fatty acids were found in the experimental cheese; its consumption was successful in limiting the enhanced blood concentration of atherogenic fatty acids, without affecting fatty acid content of serum lipid fractions. These results indicate that dairy products could be considered as key foods for fat modifications with the objective of optimizing their nutritional quality. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate sucrase inhibition by D-xylose in humans. Sucrose was administered with D-xylose to 13 healthy volunteers (5 males and 8 females), and their blood glucose levels were examined. The mean ± standard error glycemic indices (GIs) of sucrose with 5% D-xylose (XF) and sucrose alone were 59.6 ± 4.0 and 77.6 ± 3.1, respectively. The mean glycemic index of sucrose with 5% D-xylose (XF) was 23% lower than that of sucrose alone. The mean glycemic index of sucrose with 5% D-xylose (XF) in obese individuals was significantly lower than that of sucrose with 5% D-xylose (XF) in normal-weight individuals. The glycemic index of sucrose with 5% D-xylose (XF) was reduced approximately 40% when compared with sucrose alone in obese individuals. However, the reduction in the glycemic index by D-xylose was relatively less in normal-weight individuals than in obese individuals. Additionally, there was a negative correlation between the glycemic index of sucrose with 5% D-xylose (XF) and body-fat percentage. Therefore, sucrose administered with an appropriate amount of D-xylose can contribute to the reduction of problems caused by excess sucrose consumption. [ABSTRACT FROM AUTHOR]