Responses In Human Subjects Research Articles

Norovirus-Specific Memory T Cell Responses in Adult Human Donors.

Norovirus (NoV) is a leading cause of acute gastroenteritis in people of all ages worldwide. NoV-specific serum antibodies which block the binding of NoV virus-like particles (VLPs) to the cell receptors have been thoroughly investigated. In contrast, only a few publications are available on the NoV capsid VP1 protein-specific T cell responses in humans naturally infected with the virus. Freshly isolated peripheral blood mononuclear cells of eight healthy adult human donors previously exposed to NoV were stimulated with purified VLPs derived from NoV GII.4-1999, GII.4-2012 (Sydney), and GI.3, and IFN-γ production was measured by an ELISPOT assay. In addition, 76 overlapping synthetic peptides spanning the entire 539-amino acid sequence of GII.4 VP1 were pooled into two-dimensional matrices and used to identify putative T cell epitopes. Seven of the eight subjects produced IFN-γ in response to the peptides and five subjects produced IFN-γ in response to the VLPs of the same origin. In general, stronger T cell responses were induced with the peptides in each donor compared to the VLPs. A CD8+ T cell epitope in the shell domain of the VP1 (134SPSQVTMFPHIIVDVRQL151) was identified in two subjects, both having human leukocyte antigen (HLA)-A∗02:01 allele. To our knowledge, this is the first report using synthetic peptides to study NoV-specific T cell responses in human subjects and identify T cell epitopes.

Utility of cooling overshoot for energy efficient thermal comfort in temporarily occupied space

Temporarily occupied space (TOS) is defined as an air-conditioned space in which most of occupants stay for less than a certain period (e.g., 40 min) such as post offices, supermarkets, bookstores and banks. After moving from a hot and humid outdoor environment to TOS in summer, thermal alliesthesia takes effect, which refers to ‘thermal pleasure sensation and overshoot generated by the restoration of thermal stress toward a neutral interior condition’. Because of the overshoot, occupants' acceptable temperature ranges in TOS are possibly elevated while they still feel thermally comfortable. To study the temperature ranges, a human subjective response study was performed in one climatic chamber used to simulate TOS in Tianjin. Real outdoor environments, instead of chamber simulated outdoor environments, were used for exploring this thermal transient process. Sixteen healthy university students, 8 males and 8 females, were exposed to an outdoor environment for 20 min before they stayed in the chamber for 40 min. Their votes on thermal sensation, comfort and preference were recorded for evaluation at different time points. The results show that the recommended design standard effective temperature (SET) range of TOS is between 24.5 °C and 26.5 °C. Meanwhile, thermal comfort for staffs who have long term exposure to TOS could be maintained by personal comfort systems such as desk fans or personalized ventilation.

Effect of White Grape Juice Compared to Apple Juice on Gastrointestinal Tolerance and Breath Hydrogen Response in Healthy Human Subjects

Participants will better understand the tools used to determine gastrointestinal tolerance, and explain how white grape juice and apple juice were tolerated in healthy adults.

Physical exercise alleviates ER stress in obese humans through reduction in the expression and release of GRP78 chaperone

Background and objectivesPerturbation of the endoplasmic reticulum (ER) homeostasis has emerged as one of the prominent features of obesity and diabetes. This occurs when the adaptive unfolded protein response (UPR) fails to restore ER function in key metabolic tissues. We previously reported increased inflammation and impaired heat shock response (HSR) in obese human subjects that were restored by physical exercise. Here, we investigated the status of ER stress chaperone; glucose-regulated protein 78 (GRP78) and its downstream UPR pathways in human obese, and their modulation by a supervised 3-month physical exercise. MethodsSubcutaneous adipose tissue (SAT) and blood samples were collected from non-diabetic adult human lean (n=40) and obese (n=40, at baseline and after 3months of physical exercise). Transcriptomic profiling was used as a primary screen to identify differentially expressed genes and it was carried out on SAT samples using the UPR RT2 Profiler PCR Array. Conventional RT-PCR, immunohistochemistry, immunofluorescence, Western blot and ELISA were used to validate the transcriptomic data. Correlation analyses with the physical, clinical and biochemical outcomes were performed using Pearson's rank correlation coefficient. ResultsLevels of GRP78 and its three downstream UPR arms; activating transcription factor-6 (ATF6), inositol-requiring enzyme-1α (IRE1α) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) were increased in obese subjects. More interestingly, higher levels of circulating GRP78 protein were found in obese compared to lean subjects which correlated negatively with maximum oxygen uptake (VO2 Max) but positively with high-sensitivity C-reactive protein (hsCRP) and obesity indicators such as BMI, percentage body fat (PBF) and waist circumference. GRP78 increased secretion in obese was further confirmed in vitro using 3T3-L1 preadipocyte cells under ER stress. Finally, we showed that physical exercise significantly attenuated the expression and release of GRP78 with a concomitant reduction in the phosphorylation of IRE1α and eukaryotic initiation factor-2α (eIF2α). ConclusionOur results suggest that physical exercise alleviates ER stress in human obese through attenuation of GRP78 signaling network.

Biological effects of inhaled nitrogen dioxide in healthy human subjects

Several epidemiological studies indicate that inhaled nitrogen dioxide (NO2) at low concentrations have been statistically associated with adverse health effects. However, these results are not reflected by exposure studies in humans. The aim of the study was to assess the acute functional and cellular responses to different NO2 concentrations in healthy human subjects with various techniques. Twenty-five subjects were exposed for 3h to NO2 concentrations 0, 0.1, 0.5, and 1.5ppm in a randomized crossover study design during 4 consecutive weeks. In each subject, lung function, diffusion capacity and exhaled nitric oxide were measured and inflammation markers were assessed in blood, nasal secretions, induced sputum and exhaled breath condensate. From all lung function indices under consideration, only intrathoracic gas volume was borderline significantly increased after 0.5ppm (p=0.048) compared to 0.1ppm NO2. Regarding the cellular effect parameters, the macrophage concentration in induced sputum decreased with increasing NO2 concentration, although these changes were only borderline significant (p=0.05). These results do not suggest a considerable acute adverse response in human subjects after 3h of exposure to NO2 in the NO2 concentration range investigated in this study.

Acquisition of Conditioned Responses to a Novel Alcohol-Paired Cue in Social Drinkers.

This study examined the acquisition of conditioning between novel stimuli and single doses of alcohol in social drinkers. Environmental stimuli present during the consumption of alcohol or other drugs come to elicit conditioned responses that subsequently increase drug seeking. However, relatively few studies have examined the process of acquisition of these conditioned drug responses in human subjects. We used a procedure previously developed to study acquisition of conditioned responses to a methamphetamine-associated cue. In the present study we applied the paradigm to alcohol, pairing de novo neutral cues with alcohol in social drinkers (N = 36). We obtained measures of self-report, behavioral preference, emotional reactivity (assessed using facial electromyography), and attention to specific cues paired with administration of 0.6 g/kg 95% absolute alcohol or placebo. After conditioning, participants showed an increase in attention toward the alcohol-paired cue, and this increase was associated with ratings of liking the alcohol-containing beverage during the conditioning sessions. In contrast to our previous findings with methamphetamine, the alcohol-paired cue did not elicit changes in emotional reactivity (measured by facial electromyography) or behavioral preference. This study extends our previous findings with a stimulant drug to alcohol and highlights possible similarities and differences in conditioning with different classes of drugs. Conditioning with alcohol was less robust than with methamphetamine, but in both cases the conditioning that did occur was related to positive subjective drug response.

Exploration of Prominent Frequency Wave in EEG Signals from Brain Sensors Network

We investigated the signals regularity of electroencephalography (EEG) channels separately and determined the energy of selected frequency waves, such as, δ, θ, α, β, and γ. The goal of this research is to identify the prominent frequency band from selected frequencies. We recorded the EEG signal data of 30 controlled subjects with 18 EEG channels. These subjects are all males with an average age of 24 years. Emotional stimuli related to different emotions were presented to each of selected candidates. EEG data were extracted and further processed for artifact removal, filtering, epoch selection and averaging of the signals. We designed and tested our method for exploring the frequency waves of all EEG channels. We also employed the Hjorth parameters to measure the signal regularity in time and frequency domain. The detailed physiological response of human subjects is also presented in this paper. Our results showed that the energy level of delta wave is mostly high in all cases.

Robust decoding of selective auditory attention from MEG in a competing-speaker environment via state-space modeling

The underlying mechanism of how the human brain solves the cocktail party problem is largely unknown. Recent neuroimaging studies, however, suggest salient temporal correlations between the auditory neural response and the attended auditory object. Using magnetoencephalography (MEG) recordings of the neural responses of human subjects, we propose a decoding approach for tracking the attentional state while subjects are selectively listening to one of the two speech streams embedded in a competing-speaker environment. We develop a biophysically-inspired state-space model to account for the modulation of the neural response with respect to the attentional state of the listener. The constructed decoder is based on a maximum a posteriori (MAP) estimate of the state parameters via the Expectation Maximization (EM) algorithm. Using only the envelope of the two speech streams as covariates, the proposed decoder enables us to track the attentional state of the listener with a temporal resolution of the order of seconds, together with statistical confidence intervals. We evaluate the performance of the proposed model using numerical simulations and experimentally measured evoked MEG responses from the human brain. Our analysis reveals considerable performance gains provided by the state-space model in terms of temporal resolution, computational complexity and decoding accuracy.

Experimental study on skin temperature and thermal response of the foot-bather

Although warm footbath has been widely enjoyed in many Asian countries, little information is known about its effect on people’s thermal responses. This paper experimentally investigated the variations in objective and subjective thermal responses of foot bathers during summer and winter. The subjective thermal responses of foot bathers (12 males and 11 females) were collected by questionnaire, and their body skin temperatures were measured at seven locations. Due to blood circulation, the heat gained from immersed feet could affect other body parts, while the thermal effect of warm footbath varied in different body parts. The results indicate that the footbath could cause marked increases in the thermal sensation of feet, legs and overall body. Participants feel more comfortable at the early stage than other stages during footbath, even though the water temperature is constant. Higher water temperature is expected by the participants to remain footbath comfort. Additionally, noticeable differences in skin temperature and subjective human responses of the male and the female foot bathers were observed. This study demonstrates that the females’ foot is more sensitive to warm footbath than those of males. It can be concluded that warm footbath contributes to more satisfaction of thermal environment especially in winter and that males were likely to be more acceptable with footbath than females.

Apparent and Actual Trajectory Control Depend on the Behavioral Context in Upper Limb Motor Tasks.

A central problem in motor neuroscience is to understand how we select, plan, and control motor actions. An influential idea is that the motor system computes and implements a desired limb trajectory, an intermediary control process between the behavioral goal (reach a spatial goal) and motor commands to move the limb. The most compelling evidence for trajectory control is that corrective responses are directed back toward the unperturbed trajectory when the limb is disturbed during movement. However, the idea of trajectory control conflicts with optimal control theories that emphasize goal-directed motor corrections. Here we show that corrective responses in human subjects can deviate back toward the unperturbed trajectory, but these reversals were only present when there were explicit limits on movement time. Our second experiment asked whether trajectory control could be generated if the trajectory was made an explicit goal of the task. Participants countered unexpected loads while reaching to a static goal, tracking a moving target, or maintaining their hand within a visually constrained path to a static goal. Corrective responses were directed back toward the constrained path or to intercept the moving target. However, corrections back to the unperturbed path disappeared when reaching to the static target. Long-latency muscle responses paralleled changes in the behavioral goal in both sets of experiments, but goal-directed responses were delayed by 15-25 ms when tracking the moving goal. Our results show the motor system can behave like a trajectory controller but only if a "desired trajectory" is the goal of the task. Significance statement: One of the most influential ideas in motor control is that the motor system computes a "desired trajectory" when reaching to a spatial goal. Here we revisit the experimental paradigm from seminal papers supporting trajectory control to illustrate that corrective responses appear to return to the original trajectory of the limb, but only if there is an imposed timing constraint. We then provide direct evidence that the human motor system can behave like a trajectory controller, and return the limb to its original trajectory when a specified trajectory is the goal of the task. Our results show that the motor system is capable of a spectrum of corrective responses that depend on the behavioral goal of the motor task.

Human perception of visual stimuli modulated by direction of linear polarization

This study explores both theoretically and experimentally the human perception of polarized light beyond that currently established. The radial analyser theory of Haidinger’s phenomenon (HP) is used to predict the effect of observing visual stimuli comprising patterned zones characterized by orthogonal planes of linear polarization (linear polarization direction fields, LPD-fields). Any pattern can be represented as an LPD-field including optotypes and geometric forms. Simulated percepts differ from the original patterns although edges are mostly preserved. In edge-rich images a cross of attenuating contrast spanning the field of view is predicted.The mathematical model is verified experimentally using a liquid crystal display (LCD)-based polarization modulator imaged through a tangential (azimuthal) analyser with properties complementary to a radial analyser. The LCD device is then used in vivo to elicit perceptual responses in human subjects. Normal humans are found to readily detect spatially and temporally modulated isoluminant spatially-isochromatic, highly polarized LPD stimuli. Most subjects match the stimuli to corresponding images of theoretically predicted percepts. In particular edge perception and the presence of the contrast cross was confirmed. Unlike HP, static patterned LPD stimuli are perceived without difficulty.The simplest manifestation of human polarization perception is HP which is the fundamental element of an open set of stimulus-dependent percepts. This study demonstrates that humans have the ability to perceive and identify visual pattern stimuli defined solely by polarization state modulation.

Evaluating a New Suite of Luminance-Based Design Metrics for Predicting Human Visual Comfort in Offices with Daylight

ABSTRACTA new suite of visual comfort metrics is proposed and evaluated for their ability to explain the variability in subjective human responses in a mock private office environment with daylight. Participants (n = 48) rated visual comfort and preference factors, including 1488 discreet appraisals, and these subjective results were correlated against more than 2000 unique luminance-based metrics that were captured using high dynamic range photography techniques. Importantly, luminance-based metrics were more capable than illuminance-based metrics for fitting the range of human subjective responses to data from visual preference questionnaire items. No metrics based upon the entire scene ranked in the top 20 squared correlation coefficients, nor did any based upon illuminance or irradiance data, nor did any of the studied glare indices, luminance ratios, or contrast ratios. The standard deviation of window luminance was the metric that best fit human subjective responses to visual preference on seven of 12 questionnaire items (with r2 = 0.43). Luminance metrics calculated using the horizontal 40° band (a scene-independent mask) and the window area (a scene-dependent mask) represented the majority of the top 20 squared correlation coefficients for almost all subjective visual preference questionnaire items. The strongest multiple regression model was for the semantic differential rating (too dim–too bright) of the window wall (adjR2 = 0.49) and was built upon three variables; standard deviation of window luminance, the 50th percentile luminance value from the lower view window, and mean luminance of the 40° horizontal band.

Human psychophysics and rodent spinal neurones exhibit peripheral and central mechanisms of inflammatory pain in the UVB and UVB heat rekindling models.

Translational research is key to bridging the gaps between preclinical findings and the patients, and a translational model of inflammatory pain will ideally induce both peripheral and central sensitisation, more effectively mimicking clinical pathophysiology in some chronic inflammatory conditions. We conducted a parallel investigation of two models of inflammatory pain, using ultraviolet B (UVB) irradiation alone and UVB irradiation with heat rekindling. We used rodent electrophysiology and human quantitative sensory testing to characterise nociceptive processing in the peripheral and central nervous systems in both models. In both species, UVB irradiation produces peripheral sensitisation measured as augmented evoked activity of rat dorsal horn neurones and increased perceptual responses of human subjects to mechanical and thermal stimuli. In both species, UVB with heat rekindling produces central sensitisation. UVB irradiation alone and UVB with heat rekindling are translational models of inflammation that produce peripheral and central sensitisation, respectively. The predictive value of laboratory models for human pain processing is crucial for improving translational research. The discrepancy between peripheral and central mechanisms of pain is an important consideration for drug targets, and here we describe two models of inflammatory pain that involve ultraviolet B (UVB) irradiation, which can employ peripheral and central sensitisation to produce mechanical and thermal hyperalgesia in rats and humans. We use electrophysiology in rats to measure the mechanically- and thermally-evoked activity of rat spinal neurones and quantitative sensory testing to assess human psychophysical responses to mechanical and thermal stimulation in a model of UVB irradiation and in a model of UVB irradiation with heat rekindling. Our results demonstrate peripheral sensitisation in both species driven by UVB irradiation, with a clear mechanical and thermal hypersensitivity of rat dorsal horn neurones and enhanced perceptual responses of human subjects to both mechanical and thermal stimulation. Additional heat rekindling produces markers of central sensitisation in both species, including enhanced receptive field sizes. Importantly, we also showed a correlation in the evoked activity of rat spinal neurones to human thermal pain thresholds. The parallel results in rats and humans validate the translational use of both models and the potential for such models for preclinical assessment of prospective analgesics in inflammatory pain states.

Delta Inulin Adjuvant Enhances Plasmablast Generation, Expression of Activation-Induced Cytidine Deaminase and B-Cell Affinity Maturation in Human Subjects Receiving Seasonal Influenza Vaccine.

There is a major need for new adjuvants to improve the efficacy of seasonal and pandemic influenza vaccines. Advax is a novel polysaccharide adjuvant based on delta inulin that has been shown to enhance the immunogenicity of influenza vaccine in animal models and human clinical trials. To better understand the mechanism for this enhancement, we sought to assess its effect on the plasmablast response in human subjects. This pilot study utilised cryopreserved 7 day post-vaccination (7dpv) peripheral blood mononuclear cell samples obtained from a subset of 25 adult subjects from the FLU006-12 trial who had been immunized intramuscularly with a standard dose of 2012 trivalent inactivated influenza vaccine (TIV) alone (n=9 subjects) or combined with 5mg (n=8) or 10mg (n=8) of Advax adjuvant. Subjects receiving Advax adjuvant had increased 7dpv plasmablasts, which in turn exhibited a 2-3 fold higher rate of non-silent mutations in the B-cell receptor CDR3 region associated with higher expression of activation-induced cytidine deaminase (AID), the major enzyme controlling BCR affinity maturation. Together, these data suggest that Advax adjuvant enhances influenza immunity in immunized subjects via multiple mechanisms including increased plasmablast generation, AID expression and CDR3 mutagenesis resulting in enhanced BCR affinity maturation and increased production of high avidity antibody. How Advax adjuvant achieves these beneficial effects on plasmablasts remains the subject of ongoing investigation.Trial RegistrationAustralia New Zealand Clinical Trials Register ACTRN12612000709842 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362709

Head boundary conditions in pedestrian crashes with passenger cars: six-degrees-of-freedom post-mortem human subject responses

In pedestrian–vehicle crashes, head injuries cause death and long-term disability. Thus, understanding the head kinematics is vital. Head rotation data are scarce, and the influence of individual anthropometry, upper body and arm kinematics on head kinematics is poorly understood. This paper investigates the influence of anthropometry, upper body and arm kinematics on head linear and angular kinematics, providing novel six-degrees-of-freedom data from pedestrian–vehicle-crash experiments. Five similarly positioned subjects were struck by a mid-size sedan at 40 km/h. Three-dimensional translation and three-dimensional rotation of the head, spine and shoulders were compared. Head kinematics differed considerably among the subjects. Variations in anthropometry changed pelvic sliding towards the windshield. Arm responses altered head impact velocity and head rotation. The results have implications for future experiments, evaluation of human models and the design of pedestrian safety systems. Head injury risk can be moderated by reducing head rotation before head impact, and by reducing pelvic sliding.

Induction of PERV antigen in porcine peripheral blood mononuclear cells by human herpesvirus 1.

Xenotransplantation represents one of alternative candidates for allotransplantation due to the chronic shortage of suitable human tissues; however, many obstacles remain. Expression and release of endogenous retroviral antigens by porcine cells after transplantation may evoke adverse immune responses in human subjects. Here, we examined whether human herpesvirus 1 (HHV-1) could induce the production of porcine endogenous retrovirus (PERV) antigens in porcine peripheral blood mononuclear cells (PBMCs). Porcine PBMCs were infected with HHV-1 and examined for the production of PERV Gag protein and HHV-1 using antigen-capture ELISA and quantitative real-time polymerase chain reaction (PCR), respectively. HHV-1 infection resulted in a 1.7- to 33.2-fold induction of PERV Gag relative to mock infection controls, compared to a 2.9- to 12.9-fold induction following treatment with PMA. Expression of PERV Gag was detected in porcine PBMCs and PK-15 cells after HHV-1 infection by double immunofluorescence staining of PERV Gag and HHV-1 antigen. The viability of HHV-1-infected porcine PBMCs was significantly lower than that of mock-infected cells. The HHV-1 level in the culture supernatant increased 5.2-fold relative to controls 24-h post-infection, indicative of active replication within these cells; decreased levels of HHV-1 were detected 72-h post-infection. These results suggest that HHV-1 may be capable of infecting transplanted porcine cells, resulting in strong direct induction of PERV antigen.

Strengthened tumor antigen immune recognition by inclusion of a recombinant Eimeria antigen in therapeutic cancer vaccination.

The need for novel, effective adjuvants that are capable of eliciting stronger cellular and humoral adaptive immune responses to antigenic targets is well understood in the vaccine development field. Unfortunately, many adjuvants investigated thus far are either too toxic for human application or too weak to induce a substantial response against difficult antigens, such as tumor-associated antigens (TAAs). In spite of this trend, clinical investigations of recombinant Eimeria antigen (rEA) have revealed this protein to be a non-toxic immunogenic agent with the ability to trigger a Th1-predominant response in both murine and human subjects. Our past studies have shown that the injection of a rEA-encoding adenovirus (rAd5-rEA) alongside an HIV antigen-encoding adenovirus greatly improves the adaptive immune response against this pathogen-derived transgene. In this report, we investigated whether rAd5-rEA could promote and/or alter cytotoxic memory responses toward carcinoembryonic antigen (CEA), a colorectal cancer-related TAA. We found that the addition of rAd5-rEA to an Ad-based CEA vaccine induced a dose-dependent increase in several anti-CEA T and B cell responses. Moreover, inclusion of rAd5-rEA increased the number of CEA-derived antigenic epitopes that elicited significant cell-mediated and IgG-mediated recognition. These enhanced anti-CEA immune responses also translated into superior CEA-targeted cell killing, as evaluated by an in vivo cytotoxic T lymphocyte assay. Overall, these results suggest that co-administration of rAd5-rEA with a tumor antigen vaccine can substantially boost and broaden the TAA-specific adaptive memory response, thereby validating the potential of rAd5-rEA to be a beneficial adjuvant during therapeutic cancer vaccination.

Effects of dietary salt levels on monocytic cells and immune responses in healthy human subjects: a longitudinal study

Increasing evidence indicated that excess salt consumption can impose risks on human health and a reduction in daily salt intake from the current average of approximately 12 g/d to 5-6 g/d was suggested by public health authorities. The studies on mice have revealed that sodium chloride plays a role in the modulation of the immune system and a high-salt diet can promote tissue inflammation and autoimmune disease. However, translational evidence of dietary salt on human immunity is scarce. We used an experimental approach of fixing salt intake of healthy human subjects at 12, 9, and 6 g/d for months and examined the relationship between salt-intake levels and changes in the immune system. Blood samples were taken from the end point of each salt intake period. Immune phenotype changes were monitored through peripheral leukocyte phenotype analysis. We assessed immune function changes through the characterization of cytokine profiles in response to mitogen stimulation. The results showed that subjects on the high-salt diet of 12 g/d displayed a significantly higher number of immune cell monocytes compared with the same subjects on a lower-salt diet, and correlation test revealed a strong positive association between salt-intake levels and monocyte numbers. The decrease in salt intake was accompanied by reduced production of proinflammatory cytokines interleukin (IL)-6 and IL-23, along with enhanced producing ability of anti-inflammatory cytokine IL-10. These results suggest that in healthy humans high-salt diet has a potential to bring about excessive immune response, which can be damaging to immune homeostasis, and a reduction in habitual dietary salt intake may induce potentially beneficial immune alterations.

A mixed diet supplemented with L-arabinose does not alter glycaemic or insulinaemic responses in healthy human subjects.

In addition to a yet-to-be published study showing arabinose to have an inhibiting effect on maltase, in vitro studies have shown L-arabinose to exert an inhibiting effect on small-intestinal sucrase and maltase and the consumption of a sucrose-rich drink containing L-arabinose to exert positive effects on postprandial blood glucose, insulin and C-peptide responses in humans. However, the effects of adding L-arabinose to mixed meals on the indices of glucose control are unknown. The purpose of the present study was to investigate whether the positive effects of L-arabinose added to a sugar drink could be reproduced in subjects consuming a mixed meal containing sucrose and/or starch from wheat flour. A total of seventeen healthy men participated in study 1, a randomised, double-blind, cross-over trial. In this study, the subjects consumed two different breakfast meals containing sucrose and starch from wheat flour (meal A) or starch from wheat flour (meal B) supplemented with 0, 5 and 10 % L-arabinose by weight after a 12 h fast. A total of six healthy men participated in study 2, a randomised, double-blind, cross-over trial. In this study, the subjects also consumed meal B served in two different textures and a liquid meal with maltose supplemented with 0 and 20% L-arabinose. In addition, 1·5 g of paracetamol was chosen as an indirect marker to assess gastric emptying. Postprandial plasma glucose, insulin and C-peptide concentrations were measured regularly for 3 h. The results of the present study showed that the peak plasma concentration, time to reach peak plasma concentration or AUC values of glucose, insulin and C-peptide were not altered after consumption of the test meals. Overall, it was not possible to reproduce the beneficial effects of L-arabinose added to sucrose drinks when L-arabinose was mixed in a solid or semi-solid mixed meal.

Does Acupuncture Reduce Stress Over Time? A Clinical Heart Rate Variability Study in Hypertensive Patients.

Background: Heart rate variability (HRV), a noninvasive autonomic measure, has been applied to acupuncture interventions in controlled academic settings comparing points used, types of stimulation, or the HRV parameters measured. There is evidence that acupuncture decreases the stress response in both human and animal subjects, and can increase HRV in the short term (minutes to hours). Objectives: The goal of this study was to explore an array of HRV parameters during acupuncture sessions and over the course of treatment (weeks to months) in a series of patients being treated for hypertension. Materials and Methods: This was a retrospective, uncontrolled case study of patients presenting to a private acupuncture clinic. Patients received manual body acupuncture prescribed by the tenets of Traditional Chinese Medicine (TCM) and by published protocols for hypertension treatment. Heart rate was monitored during and after needle placement. The tracings were then analyzed with the Vivosense HRV analysis system. The main outcome measures were were patients' blood pressure measurements and low-frequency-to-high-frequency (LF/HF) ratio of HRV. Results: Patients tended to have an increase in their HRV during treatment, after needling, and, in some instances, an increase in HRV over weeks to months. Conclusions: Some patients' HRV increased over weeks to months during the course of acupuncture treatment for hypertension as evidenced by a decrease in their LF/HF ratio. This would indicate a relative decrease in their physiologic stress.