Responses In Healthy Individuals Research Articles

Differential relations of locus of control to perceived social stress among help-seeking adolescents at low vs. high clinical risk of psychosis

Research suggests that perceived social stress influences illness presentation and course among youth in the clinical high-risk (CHR) phase of psychosis. Little is known, however, about the social cognitive factors associated with social stress perception in this population, particularly relative to youth with non-CHR psychopathology. Individuals with psychosis tend to endorse an external locus of control (LOC), which is associated with the stress response in healthy individuals. LOC may therefore be related to perceived social stress in youth at CHR. We examined the differential relations of self-reported LOC and perceived social stress, as measured by the Behavior Assessment System for Children, Second Edition, across 45 CHR and 65 help-seeking control (HSC) participants. Youth at CHR reported more social stress (F[1, 107]=6.28, p=0.01) and a more external LOC (F[1, 107]=4.98, p=0.03) than HSCs. Further, external LOC was more strongly associated with feelings of social stress in the CHR group relative to the HSC group (interaction: b=0.35, t[105]=2.32, p<0.05, f2=0.05). Group differences in social stress, however, were nonsignificant at internal levels of LOC (b=−2.0, t[105]=−0.72, p=0.48; f2=0.00). Results suggest that perceptions of uncontrollability over one's social environment may more often induce or exacerbate feelings of stress and tension in CHR youth relative to HSCs. A better understanding of the social cognition-stress relation may improve understanding of CHR phenomenology, etiology, and treatment.

A Quantitative Analysis of Complexity of Human Pathogen-Specific CD4 T Cell Responses in Healthy M. tuberculosis Infected South Africans.

We performed a quantitative analysis of the HLA restriction, antigen and epitope specificity of human pathogen specific responses in healthy individuals infected with M. tuberculosis (Mtb), in a South African cohort as a test case. The results estimate the breadth of T cell responses for the first time in the context of an infection and human population setting. We determined the epitope repertoire of eleven representative Mtb antigens and a large panel of previously defined Mtb epitopes. We estimated that our analytic methods detected 50–75% of the total response in a cohort of 63 individuals. As expected, responses were highly heterogeneous, with responses to a total of 125 epitopes detected. The 66 top epitopes provided 80% coverage of the responses identified in our study. Using a panel of 48 HLA class II-transfected antigen-presenting cells, we determined HLA class II restrictions for 278 epitope/donor recognition events (36% of the total). The majority of epitopes were restricted by multiple HLA alleles, and 380 different epitope/HLA combinations comprised less than 30% of the estimated Mtb-specific response. Our results underline the complexity of human T cell responses at a population level. Efforts to capture and characterize this broad and highly HLA promiscuous Mtb-specific T cell epitope repertoire will require significant peptide multiplexing efforts. We show that a comprehensive “megapool” of Mtb peptides captured a large fraction of the Mtb-specific T cells and can be used to characterize this response.

Comparative effects of acute hypoglycemia and hyperglycemia on pro-atherothrombotic biomarkers and endothelial function in non-diabetic humans

BackgroundThe comparative effects of acute moderate hyperglycemia and hypoglycemia on in vivo endothelial function together with pro-inflammatory and pro-atherothrombotic responses in healthy individuals have not been determined. MethodsTo investigate this question, 45 healthy subjects were compared during glucose clamp studies consisting of euinsulinemic hyperglycemia and hyperinsulinemic hyperglycemia (plasma glucose 11.1mmol/L, both with pancreatic clamps) and hyperinsulinemic euglycemia and hyperinsulinemic hypoglycemia (plasma glucose 5.1 and 2.9mmol/L, respectively). Two-dimensional Doppler ultrasound was used to determine brachial artery endothelial function. ResultsInsulin levels during euinsulinemia hyperglycemia were 194±23 and (850±49–988±114) pmol/L during all hyperinsulinemic protocols. Responses of VCAM-1, ICAM-1, E-selectin, P-selectin, PAI-1, and IL-6 were increased (p<0.05–0.0001) during euinsulinemic hyperglycemia or hypoglycemia as compared to hyperinsulinemic euglycemia or hyperinsulinemic hyperglycemia. PAI-1 was increased (p<0.04) during hypoglycemia as compared to euinsulinemic hyperglycemia, and TNF-α responses were also increased during hypoglycemia as compared to hyperinsulinemic euglycemia or hyperinsulinemic hyperglycemia (p<0.05). In vivo endothelial function was similarly blunted by acute moderate hyperglycemia or hypoglycemia. ConclusionIn summary, acute moderate hypoglycemia and euinsulinemic hyperglycemia can result in similar endothelial dysfunction and pro-atherothrombotic responses. Fibrinolytic balance was reduced by a greater extent by hypoglycemia as compared to moderate hyperglycemia. Acutely, hyperinsulinemia can prevent the acute pro-atherothrombotic and pro-inflammatory effects of moderate hyperglycemia but not hypoglycemia.

Psychological Factors and Conditioned Pain Modulation: A Meta-Analysis.

Conditioned pain modulation (CPM) responses may be affected by psychological factors such as anxiety, depression, and pain catastrophizing; however, most studies on CPM do not address these relations as their primary outcome. The aim of this meta-analysis was to analyze the findings regarding the associations between CPM responses and psychological factors in both pain-free individuals and pain patients. After a comprehensive PubMed search, 37 articles were found to be suitable for inclusion. Analyses used DerSimonian and Laird's random-effects model on Fisher's z-transforms of correlations; potential publication bias was tested using funnel plots and Egger's regression test for funnel plot asymmetry. Six meta-analyses were performed examining the correlations between anxiety, depression, and pain catastrophizing, and CPM responses in healthy individuals and pain patients. No significant correlations between CPM responses and any of the examined psychological factors were found. However, a secondary analysis, comparing modality-specific CPM responses and psychological factors in healthy individuals, revealed the following: (1) pressure-based CPM responses were correlated with anxiety (grand mean correlation in original units r=-0.1087; 95% confidence limits, -0.1752 to -0.0411); (2) heat-based CPM was correlated with depression (r=0.2443; 95% confidence limits, 0.0150 to 0.4492); and (3) electrical-based CPM was correlated with pain catastrophizing levels (r=-0.1501; 95% confidence limits, -0.2403 to -0.0574). Certain psychological factors seem to be associated with modality-specific CPM responses in healthy individuals. This potentially supports the notion that CPM paradigms evoked by different stimulation modalities represent different underlying mechanisms.

Effect of an Optimized Cracker on Glycemic and Insulinemic Responses in Healthy Individuals: a Double‐blind, Randomized, Cross‐over Trial

BackgroundConsumers are increasingly interested in snacks that supply energy over an extended period of time, potentially in the form of carbohydrates. Foods containing slowly released carbohydrates generally elicit attenuated postprandial blood glucose and insulin responses. A variety of ingredients and processing and formulation techniques were screened and applied to develop an optimized active cracker containing carbohydrates that were slowly digested in‐vitro, including a whole‐grain composite ingredient comprised of a hydrocolloid co‐processed with high‐amylose maize flour. The present study was undertaken to test the hypothesis that the active cracker, with a significantly lower ratio of rapidly available glucose to slowly available glucose in‐vitro, would elicit lower blood glucose and insulin responses than a control cracker in human subjects.MethodsHealthy men and women (n=25) were studied on 2 separate days using a randomized, double‐blind, cross‐over design. After 2 fasting finger‐prick blood samples were taken, subjects consumed 1 serving (56g) of the Active or Control Cracker and further blood samples were obtained over 4hr for serum glucose and insulin analysis. The 56g serving of Active (Control) Cracker, respectively, contained: protein, 3.9 (5.3)g; fat, 6.6 (6.5)g; carbohydrate, 42.4 (40.7)g; and fiber, 11.6 (1.7)g.ResultsCompared to the Control cracker, the Active cracker elicited a 36±3% lower glucose peak rise (1.59±0.09 vs 2.64±0.21 mmol/L, p&lt;0.00001) and a 35±7% lower insulin peak rise (17.4±2.3 vs 31.9±4.6 uU/mL, p=0.00005). The glucose and insulin AUCs from 0–2 hr after the Active cracker were 36±4% (85±7 vs 146±15 mmol×h/L, p&lt;0.05) and 39±10% 0.87±0.14 vs 1.79±0.33 mU×min/mL, p&lt;0.05), respectively, lower than those after the Control cracker. The glucose AUC from 2–4hr after the Active cracker was significantly higher than Control (22.1±5.1 vs 12.9±3.6 mmol×h/L, p&lt;0.05), whereas insulin AUC over 2–4hr was significantly less after the Active cracker compared to Control (0.15±0.05 vs 0.30±0.01 mU×min/mL, p&lt;0.05).ConclusionsThe results support the hypothesis that the carbohydrates in the Active cracker are digested and absorbed more slowly in‐vivo than those in the Control, as predicted by the in‐vitro glucose release profile.Support or Funding InformationFunded by PepsiCo and Ingredion, Inc.

Effect of an Optimized Savory Cluster on Glycemic and Insulinemic Responses in Healthy Individuals: a Randomized, Cross‐over Study

Postprandial glycemia has been implicated in the development of chronic metabolic diseases such as obesity, type 2 diabetes mellitus and cardiovascular diseases. Foods with high contents of slowly digestible starch elicit lower glycemic responses have been proposed as better choices to help decrease postprandial glucose excursions and thus to improve glycemic control and health, For this reason, there is a growing interest in developing foods with slowly digestible starch, particularly for snacks. A low moisture, low temperature process was developed to produce a savory cluster snack (test‐cluster) containing nuts and grains and bound together with wheat starch and soluble fiber which is slowly digested in‐vitro. The objective of this study was to compare the glucose and insulin responses elicited by the test‐cluster to those of a control‐cluster made with ingredients commonly used in commercially available snacks or bars including oats, peanuts, puffed rice and corn syrup and an available‐carbohydrate matched portion of white‐bread in healthy subjects. Healthy men and women (n=25) were studied on 3 occasions using a randomized, cross‐over design. After 2 fasting finger‐prick blood samples, subjects consumed 1 serving (56g) of the test‐ or control‐cluster or 47g white‐bread and had blood glucose and serum insulin measured at intervals over the next 4 hr. Each serving of test‐cluster, control‐cluster and white‐bread, respectively, contained: 5, 5 and 4g protein; 12, 11 and 0.5g fat; 24, 33 and 24g available‐carbohydrate; and 10, 2 and 1g dietary fiber. The blood‐glucose peak‐rise and incremental area under the curve (AUC) after test‐cluster were significantly lower than those after both control‐cluster and white‐bread (mean±SEM; peak‐rise, 1.24±0.09 vs 2.27±0.13 and 2.27±0.16 mmol/L; AUC, 67±8 vs 117±10 and 114±9, respectively). The serum‐insulin peak‐rise and AUC after test‐cluster, 128±13 pmol/L and 6.10±0.73 nmol×min/L, were similar to those after white bread, 141±20 pmol/L and 6.47±1.11 nmol×min/L, but significantly less than those after the control‐cluster, 205±26 pmol/L and 9.60±1.31 nmol×min/L. It is concluded that a serving of test‐cluster elicits lower glucose and insulin responses than a serving of a similar control‐cluster. The results support the hypothesis that the carbohydrates in the test‐cluster are slowly digested and absorbed in‐vivo.Support or Funding InformationThis study is funded by PepsiCo, Inc.

Comparison of Two Administration Forms of a Highly Viscous Fibre Blend on Appetite and Glycemic Response in Healthy Individuals

ObjectiveThe effect of viscous fibres on appetite and food intake have been equivocal, limited by the capacity of gel‐formation within the gastrointestinal tract. Differences in fibre administration form many determine the physiological effects of viscous fibres. Using a highly viscous fibre blend (VFB) of two complimentary fibres, konjac glucomannan and xanthan gum, we investigated the acute effects of pre‐hydrating VFB into a solid gel compared to the powdered form on appetite and glycemic response.MethodsEighteen (18) healthy participants completed the study (F: 11/M: 7; Age: 28.6 ± 3.2 years; BMI: 23.3 ± 0.7 kg/m2) and 15 provided blood samples. In an acute, randomized, double‐blinded, cross‐over design, participants consumed 1 of 5 test meals on 5 separate occasions with &gt; 2 day washout period. The test meals were: 50 g available carbohydrates in bread with 5 g VFB as a powder (50Pow), 5 g VFB as a pre‐hydrated gel (50Gel), or a fibre‐free control (50Con), and 25 g available carbohydrates in bread with 25 g available carbohydrates in the gel dessert with 5 g VFB pre‐hydrated into the gel (25Gel) or a fibre‐free control (25Con). All meals consisted of bread, margarine, and a gel dessert which totaled 50 g of available carbohydrates. A metabolically controlled lunch was consumed 180 min later. Satiety was recorded using visual analogue scales.ResultsThe incremental area under the curve (iAUC) after 120 min for blood glucose was lower after 50Pow (mean difference: −40 %, p &lt; 0.001) and 50Gel (mean difference: −23 %, p = 0.049) vs. 50Con. No differences were observed between 50Pow and 50Gel (p = 0.16). Additionally, 50Gel increased satiety after 120 min vs. 50Pow (MD: +26 %, p=0.035) and 50Con (mean difference: +28 %, p = 0.025). The iAUC after 120 min for blood glucose was lower in 25Gel vs. 25Con (mean difference: −28 %, p = 0.006), but no significant differences were observed in satiety.ConclusionsThese findings suggest that VFB may improve the postprandial glycemic response irrespective of administration mode, but consumption in a pre‐hydrated gel may confer additional benefits from improved satiety.Clinicaltrials.gov Identifier: NCT01657058

17D yellow fever vaccine elicits comparable long-term immune responses in healthy individuals and immune-compromised patients.

The 17D live attenuated yellow fever (YF) vaccine is contra-indicated in immune-compromised individuals and may elicit a suboptimal immunologic response. The aim of this study is to assess whether long-term immune responses against the YF vaccine are impaired in immune-compromised patients. Fifteen patients using different immunosuppressive drugs and 30 healthy individuals vaccinated 0-22 years ago were included. The serological response was measured using the plaque reduction neutralization test (PRNT). CD8(+) and CD4(+) T-cell responses were measured following proliferation and re-stimulation with YFV peptide pools. Phenotypic characteristics and cytokine responses of CD8(+) T-cells were determined using class I tetramers. The geometric mean titre of neutralizing antibodies was not different between the groups (p=0.77). The presence of YFV-specific CD4(+) and CD8(+) T-cell did not differ between patients and healthy individuals (15/15, 100.0% vs. 29/30, 96.7%, p=0.475). Time since vaccination correlated negatively with the number of YFV-specific CD8(+) T-cells (r=-0.66, p=0.0045). Percentages of early-differentiated memory cells increased (r=0.67, p=0.017) over time. These results imply that YF vaccination is effective despite certain immunosuppressive drug regimens. An early-differentiated memory-like phenotype persisted, which is associated with effective expansion upon re-encounter with antigen, suggesting a potent memory T-cell pool remains.

Exertion Does Not Affect the Optic Nerve Sheath Diameter in Healthy Participants

The purpose of this study was to determine if exertion influences the ONSD in healthy individuals. Healthy adults were eligible for inclusion. Activities were performed by each participant for 60 seconds and were as follows: sprinting, holding a 10-pound weight with both arms outstretched parallel to the floor, a Valsalva maneuver, a plank position, and positioning the head down thirty degrees with the participant in the supine position. Two-dimensional ultrasound images visualizing the optic nerve sheath (ONS) were recorded in three orientations and averaged to determine the mean ONSD 3 millimeters posterior to the retina. Baseline measurements ranged from 3.57 to 4.90 millimeters. Post-exertion measurements ranged from 3.60 to 4.93 millimeters. Based on a one sample paired t-test the difference between baseline and post-activity measurements were not significant. This study demonstrates that ONSD measurements by ultrasound do not change in healthy individuals in response to exertion.

Pharmacokinetics and pharmacodynamics of insulin glargine–insulin glulisine basal-bolus and twice-daily premixed analog insulin in type 1 diabetes mellitus patients during three standardized meals

AimsTo evaluate the pharmacokinetics and pharmacodynamics of basal insulin glargine with mealtime insulin glulisine or twice daily 75/25 premixed neutral protamine insulin lispro and insulin lispro in individuals with type 1 diabetes during three standardized meals over a 24 hour duration and compare to physiologic insulin and glucose responses in healthy non-diabetic individuals. MethodsTwelve healthy (4 male/8 female) and thirteen individuals with type 1 diabetes (8 male/5 female) were studied during three sequential standardized meals. Individuals with type 1 diabetes received either glargine and glulisine injected 5 minutes subcutaneously before each meal or premixed insulin lispro injected 5 minutes before breakfast and dinner in a randomized fashion separated by eight weeks. ResultsThe incremental systemic insulin AUC, maximal insulin concentration, and rate of rise of systemic insulin (0–30 minutes) during all three meal intervals were similar between glargine/glulisine and healthy controls. Incremental glucose AUC with glargine/glulisine was similar to controls at lunch and dinner. With premix 75/25 insulin, insulin AUC was lower and incremental glucose AUC was greater at lunch compared to the healthy and glargine/glulisine. Hypoglycemic events before lunch were greater with premix insulin group than with glargine/glulisine (p < 0.0001). ConclusionsGlargine/glulisine pharmacokinetics in type 1 diabetes can closely approximate physiologic insulin responses in healthy individuals during a day in which three standardized meals are consumed. Additionally, when glulisine is dosed only five minutes pre-meal, systemic insulin concentration rises as rapidly as prandial endogenous insulin levels. This present study compared glargine and glulisine administered in an approximate 50/50 proportion. Future studies of alternate meal times, meal content and differing premixed insulin preparations are indicated.

Practical guidelines for B-cell receptor repertoire sequencing analysis.

High-throughput sequencing of B-cell immunoglobulin repertoires is increasingly being applied to gain insights into the adaptive immune response in healthy individuals and in those with a wide range of diseases. Recent applications include the study of autoimmunity, infection, allergy, cancer and aging. As sequencing technologies continue to improve, these repertoire sequencing experiments are producing ever larger datasets, with tens- to hundreds-of-millions of sequences. These data require specialized bioinformatics pipelines to be analyzed effectively. Numerous methods and tools have been developed to handle different steps of the analysis, and integrated software suites have recently been made available. However, the field has yet to converge on a standard pipeline for data processing and analysis. Common file formats for data sharing are also lacking. Here we provide a set of practical guidelines for B-cell receptor repertoire sequencing analysis, starting from raw sequencing reads and proceeding through pre-processing, determination of population structure, and analysis of repertoire properties. These include methods for unique molecular identifiers and sequencing error correction, V(D)J assignment and detection of novel alleles, clonal assignment, lineage tree construction, somatic hypermutation modeling, selection analysis, and analysis of stereotyped or convergent responses. The guidelines presented here highlight the major steps involved in the analysis of B-cell repertoire sequencing data, along with recommendations on how to avoid common pitfalls.

Mulberry extract to modULate Blood glucosE Responses in noRmoglYcaemic adults (MULBERRY): study protocol for a randomised controlled trial.

BackgroundWorldwide sugar consumption has tripled during the last fifty years. High sugar intake is associated with weight gain and increased incidence of diabetes and has been linked with increased cardiovascular mortality. Reducing the health impact of dietary sugar and poor quality carbohydrate intake is a public health priority. IminoNorm®, a proprietary mulberry leaf extract (ME), may reduce blood glucose responses following dietary sugar and carbohydrate intake by reducing absorption of glucose from the gut. Previous research has shown that ME can reduce blood glucose and improve insulin responses in healthy subjects and also in subjects with raised fasting blood glucose levels. Mulberry leaf has an excellent safety profile. This pilot study will test a novel, safe, water soluble product in normoglycaemic adults in the UK to determine if it can reduce glucose absorption without increasing plasma insulin concentration.Methods/designThe trial will be a double-blind, individually randomised, four-arm single-dose crossover design to test the effect of three doses of ME in order to determine efficacy, dose response relationship and gastrointestinal side effects with respect to placebo. A total of 40 subjects will participate in this study and attend for four visits receiving each of the four interventions in random order.DiscussionWe aim to test the evidence that mulberry leaf extract can reduce blood glucose without a disproportionate increase in blood insulin responses in healthy individuals in a high-quality research study based in the UK. It is hoped that this will lead to further randomised controlled trials and an effective dietary supplement to lower blood glucose concentrations.Trial registrationISRCTN: ISRCTN14597438 (21 April 2015)

Resting-state glutamatergic neurotransmission is related to the peak latency of the auditory mismatch negativity (MMN) for duration deviants: An (1)H-MRS-EEG study.

Mismatch negativity (MMN), an ERP elicited by a deviant stimulus in a train of standard stimuli, has been suggested to be associated to glutamatergic neurotransmission, mediated by glutamatergic NMDA receptors. In this study, we examined the relationship between interindividual variation of (1)H-MRS-measured glutamate+glutamine (Glx) in the superior temporal gyrus and MMN for duration and frequency deviants in 19 healthy young adults (9 male). We found a significant relationship between the peak latency of the duration-MMN peak and creatine-scaled Glx (p = .0003, η(2) = .43), with increased Glx level being associated to earlier peak of the duration-MMN (r = -.63). In contrast, the amplitude of the duration-MMN was not related to Glx. There was no significant relationship between Glx and the frequency-MMN. The present study is the first to demonstrate that interindividual variation in the glutamatergic neurotransmission affects the MMN response in healthy individuals.

Side by side treadmill walking reduces gait asymmetry induced by unilateral ankle weight

Asymmetric gait is a hallmark of many neurological and musculoskeletal conditions. This behavior is often the result of a decrease in the stability of interlimb coordination, and synchronization to external signals such as auditory cuing or another walking individual may be helpful for altering abnormal movement patterns. The purpose of this study was to investigate the interaction between interlimb coordination and unintentional, interpersonal synchronization of gait in healthy individuals in response to unilateral ankle loading. Fifty participants completed four trials while walking on a motorized treadmill: (1) by themselves, (2) with a partner on an adjacent treadmill, (3) by themselves with additional weight applied unilaterally to their right ankle, and (4) with both a partner and unilateral weight. As expected, the addition of unilateral weight increased asymmetry according to several spatiotemporal measures of gait, but the presence of a partner on an adjacent treadmill significantly reduced this effect. Further, the amount of unintentional, interpersonal synchronization among pairings was relatively unaffected by the addition of ankle weight to one of the partners. All pairings realized a beneficial effect on asymmetrical gait but this effect was greater for pairings that consistently synchronized unintentionally. These results suggest that side by side walking might be an effective approach for influencing bilateral coordination of gait and may hold insight for understanding gait asymmetry and interlimb movement variability.

Effective connectivity predicts future placebo analgesic response: A dynamic causal modeling study of pain processing in healthy controls

A better understanding of the neural mechanisms underlying pain processing and analgesia may aid in the development and personalization of effective treatments for chronic pain. Clarification of the neural predictors of individual variability in placebo analgesia (PA) could aid in this process. The present study examined whether the strength of effective connectivity (EC) among pain-related brain regions could predict future placebo analgesic response in healthy individuals. In Visit 1, fMRI data were collected from 24 healthy subjects (13 females, mean age=22.56, SD=2.94) while experiencing painful thermal stimuli. During Visit 2, subjects were conditioned to expect less pain via a surreptitiously lowered temperature applied at two of the four sites on their feet. They were subsequently scanned again using the Visit 1 (painful) temperature. Subjects used an electronic VAS to rate their pain following each stimulus. Differences in ratings at conditioned and unconditioned sites were used to measure placebo response (PA scores). Dynamic causal modeling was used to estimate the EC among a set of brain regions related to pain processing at Visit 1 (periaqueductal gray, thalamus, rostral anterior cingulate cortex, dorsolateral prefrontal cortex). Individual PA scores from Visit 2 were regressed on salient EC parameter estimates from Visit 1. Results indicate that both greater left hemisphere modulatory DLPFC➔PAG connectivity and right hemisphere, endogenous thalamus➔DLPFC connectivity were significantly predictive of future placebo response (R2=0.82). To our knowledge, this is the first study to identify the value of EC in understanding individual differences in PA, and may suggest the potential modifiability of endogenous pain modulation.

Multispecific Aspergillus T cells selected by CD137 or CD154 induce protective immune responses against the most relevant mold infections.

Aspergillus and Mucorales species cause severe infections in patients after hematopoietic stem cell transplantation (HSCT). Induction of antifungal CD4(+) T-helper type 1 (Th1) immunity is an appealing strategy to combat these infections. Immunotherapeutic approaches are so far limited because of a lack of antigens inducing protective T cells, their elaborate production, and the need of targeting a broad spectrum of pathogenic fungi. We examined the response to different Aspergillus fumigatus proteins in healthy individuals and patients after HSCT and compared rapid selection protocols for fungus-specific T cells based on CD137 or CD154 expression. The A. fumigatus proteins Crf1, Gel1, and Pmp20 induced strong Th1 responses in healthy individuals. T cells specific for these antigens expanded in patients with active invasive aspergillosis, indicating their contribution to infection control. Th1 cells specific for the 3 proteins can be selected with similar specificity within 24 hours, based on CD137 or CD154 expression. These cells recognize naturally processed A. fumigatus and the multispecific T-cell lines, directed against all 3 proteins, especially those selected by CD154, additionally cross-react to different Aspergillus and Mucorales species. These findings may form the basis for adoptive T-cell transfer for prophylaxis or treatment in patients with these devastating infections.

Age-related difference in postural control during recovery from posterior and anterior perturbations.

Decreased reactive postural responses in elderly adults may place them at increased risk for falls and related injuries. The first step in addressing the high rate of falls in the elderly population is to determine a baseline for postural response in healthy young and healthy elderly individuals. To determine these age-related differences in reactive postural responses during recovery from posterior and anterior perturbations, we used the tether-release method in conjunction with a motion analysis system to evaluate overall movement latencies, overall movement amplitude and velocity, and joint-specific amplitude and velocity in healthy young (n = 10, mean age=25 ± 5) and healthy elderly participants (n = 10, mean age = 67 ± 6). During posterior perturbations, healthy elderly participants had increased recovery time (P = 0.01) and ratio of center of mass to step length (P = 0.013) when compared with young participants. Elderly participants also had decreased step length (P = 0.006), peak COM velocity (P = 0.01), peak knee flexion angle (P = 0.002), and decreased hip (P = 0.005) and knee (P = 0.0005) average angular velocity when compared with young participants. We conclude that these movement deficiencies at the hip and knee limited the length of the recovery step. With this restricted step, elderly participants could not achieve adequate mechanical advantage to counteract the displacement of their COM using a single step. During anterior perturbations, elderly participants did not exhibit any significant differences compared to young participants in overall movement variables. This understanding of postural responses in healthy individuals is clinically relevant to the development of rehabilitation programs for individuals at high fall risk.

Induction of a robust T- and B-cell immune response in non- and low-responders to conventional vaccination against hepatitis B by using a third generation PreS/S vaccine

Non-responsiveness to conventional hepatitis B vaccines in individuals at high risk of exposure to hepatitis B virus (HBV) is an important public health problem and of particular relevance in health care providers. Yeast-derived conventional HBsAg vaccines fail to induce protective antibody titers in up to 10% of immune competent vaccinees. Therefore, a third generation HBV vaccine, Sci-B-Vac™, was developed which contains in addition to the small S antigen the PreS1 and PreS2 antigens. This vaccine proved to induce a highly potent cellular and humoral immune response in healthy individuals as well as protective antibody levels in non- and low-responders to conventional HBV vaccines. The aim of the study was to examine whether Sci-B-Vac™ triggers cellular and humoral immunity in individuals who failed immunization with conventional vaccines. We immunized 21 volunteers (15 non- and 6 low-responders) according to the standard vaccination schedule (0, 4 and 24 weeks), determined the cellular immunity by proliferation assay and interferon (IFN)-γ ELISpot and measured the anti-HBs antibody titers prior to each vaccination and four weeks after the third vaccine dose. Following three vaccinations, PreS/S-specific T-cell proliferation was detected in 8 out of 15 non-responders and 5 out of 6 low-responders. Specific IFN-γ responses were measured in 2 out of 15 non-responders and 4 out of 6 low-responders. All but one (20/21) study participants developed anti-HBs titers ≥10IU/l after three vaccinations. Anti-HBs ≥100IU/L were detected in 12 out of 15 non-responders and in 6 out of 6 low-responders. Anti-HBs ≥10IU/l and <100IU/l were found in 2 non-responders. These results indicate that Sci-B-Vac™ induces cellular immunity as well as protective anti-HBs antibody titers in non- and low-responders. In conclusion, these results confirm that Sci-B-Vac™ should be administered to non-responders to conventional HBV vaccines and patients with impaired immune function.

Voxel-based morphometry and arterial spin labeling fMRI reveal neuropathic and neuroplastic features of brain processing of itch in end-stage renal disease

Pruritus of end-stage renal disease (ESRD) is a multifactorial symptom of complex etiology not yet fully understood. In this study we have investigated the cerebral perfusion patterns at rest in ESRD patients on hemodialysis, compared with those in healthy volunteers. We have also studied the brain responses evoked by experimental itch induction in ESRD, after stimulating the two distinct histamine and cowhage itch pathways, and compared them with the responses evoked in healthy volunteers. To identify potential structural alterations in ESRD patients compared with a group of age-matched healthy volunteers, we calculated the density of gray matter for the entire brain using a voxel-based morphometric analysis. Our results indicated that gray matter density was significantly reduced in ESRD patients in the frontal, parietal, temporal, and occipital cortices, as well as in the S1, precuneus, and insula, whereas the brain stem, hippocampus, amygdala, midcingulate cortex, and nucleus accumbens displayed an increased gray matter density. Functionally, we found a significantly higher brain perfusion at baseline associated with ESRD pruritus in the anterior cingulate, insula, claustrum, hippocampus, and nucleus accumbens. The brain responses evoked by cowhage itch, which are mediated by protease-activated receptors (PAR2), displayed significant differences compared with responses in healthy individuals and were correlated with perceived itch intensity in a dual, complex manner. The inverse correlations in particular suggested that a negative feedback mechanism modulated itch intensity, when elicited in a preexistent chronic itch background.

Effect of increased physical activity on fructose-induced glycemic response in healthy individuals

The purpose of the current study was to determine whether increased physical activity (PA) altered glycemic control while ingesting an energy-balanced high-fructose diet. Twenty-two normal-weight men and women (age: 21.2±0.6 years; body mass index: 22.6 ±0.6 kg/m(2)) participated in a randomized, cross-over design study in which they ingested an additional 75 g of fructose for 14 days while either maintaining low PA (FR+inactive) (<4500 steps/day) or high PA (FR+active) (>12,000 steps/day). Before and following the 2-week loading period, a fructose-rich meal challenge was administered and blood was sampled at baseline and for 6 h after the meal and analyzed for glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), c-peptide, glucose and insulin concentrations. Plasma insulin, glucose, c-peptide, GIP and GLP-1 concentrations significantly increased in response to the test meal on all test visits (P<0.05). C-peptide incremental area under the curve (AUC) decreased by 10,208 ±120 pmol/l × min for 6 h from pre to post Fr+active intervention (P=0.02) leading to a decrease in plasma insulin total AUC (pre: 58,470.2±6261.0 pmol/l; post: 49,444.3±3883.0 pmol/l; P=0.04) resulting in a decrease Δpeak[Insulin] (P=0.009). Following the FR+active intervention, GIP total AUC significantly decreased (P=0.005) yet only males had a lower total GLP-1 AUC after both interventions (P=0.049). There were no sex differences in GIP levels. Increased PA attenuates the deleterious effects on glycemic control caused by a high-fructose diet. These changes in glycemic control with PA are associated with decreases in insulin and GIP concentrations.