Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B

Background: We have previously reported that human recombinant granzyme B (grB) mediates apoptosis in membrane heat shock protein 70 (Hsp70)-positive tumor cells in a perforin-independent manner

Stronger diversity effects with increased environmental stress : a study of multitrophic interactions between oak, powdery mildew and ladybirds

Recent research has suggested that increasing neighbourhood tree species diversity may mitigate the impact of pests or pathogens by supporting the activities of their natural enemies and/or reducing the density of available hosts. In this study, we attempted to assess these mechanisms in a multitrophic study system of young oak (Quercus), oak powdery mildew (PM, caused by Erysiphe spp.) and a mycophagous ladybird (Psyllobora vigintiduo-punctata). We assessed ladybird mycophagy on oak PM in function of different neighbourhood tree species compositions. We also evaluated whether these species interactions were modulated by environmental conditions as suggested by the Stress Gradient Hypothesis. We adopted a complementary approach of a field experiment where we monitored oak saplings subjected to a reduced rainfall gradient in a young planted forest consisting of different tree species mixtures, as well as a lab experiment where we independently evaluated the effect of different watering treatments on PM infections and ladybird mycophagy. In the field experiment, we found effects of neighbourhood tree species richness on ladybird mycophagy becoming more positive as the target trees received less water. This effect was only found as weather conditions grew drier. In the lab experiment, we found a preference of ladybirds to graze on infected leaves from trees that received less water. We discuss potential mechanisms that might explain this preference, such as emissions of volatile leaf chemicals. Our results are in line with the expectations of the Natural Enemies Hypothesis and support the hypothesis that biodiversity effects become stronger with increased environmental stress

Web-based alcohol intervention:study of systematic attrition of heavy drinkers

Background: Web-based alcohol interventions are a promising way to reduce alcohol consumption because of their anonymity and the possibility of reaching a high numbers of individuals including heavy drinkers. However, Web-based interventions are often characterized by high rates of attrition. To date, very few studies have investigated whether individuals with higher alcohol consumption show higher attrition rates in Web-based alcohol interventions as compared with individuals with lower alcohol consumption. Objectives: The aim of this study was to examine the attrition rate and predictors of attrition in a Web-based intervention study on alcohol consumption. Methods: The analysis of the predictors of attrition rate was performed on data collected in a Web-based randomized control trial. Data collection took place at the University of Konstanz, Germany. A total of 898 people, which consisted of 46.8% males (420/898) and 53.2% females (478/898) with a mean age of 23.57 years (SD 5.19), initially volunteered to participate in a Web-based intervention study to reduce alcohol consumption. Out of the sample, 86.9% (781/898) were students. Participants were classified as non-completers (439/898, 48.9%) if they did not complete the Web-based intervention. Potential predictors of attrition were self-reported: alcohol consumption in the last seven days, per week, from Monday to Thursday, on weekends, excessive drinking behavior measured with the Alcohol Use Disorder Identification Test (AUDIT), and drinking motives measured by the Drinking Motive Questionnaire (DMQ-R SF). Results: Significant differences between completers and non-completers emerged regarding alcohol consumption in the last seven days (B=-.02, P=.05, 95% CI [0.97-1.00]), on weekends (B=-.05, P=.003, 95% CI [0.92-0.98]), the AUDIT (B=-.06, P=.007, 95% CI [0.90-0.98], and the status as a student (B=.72, P=.001, 95% CI [1.35-3.11]). Most importantly, non-completers had a significantly higher alcohol consumption compared with completers. Conclusions: Hazardous alcohol consumption appears to be a key factor of the dropout rate in a Web-based alcohol intervention study. Thus, it is important to develop strategies to keep participants who are at high risk in Web-based interventions

Aerobic Exercise during Pregnancy and Presence of Fetal-Maternal Heart Rate Synchronization

It has been shown that short-term direct interaction between maternal and fetal heart rates may take place and that this interaction is affected by the rate of maternal respiration. The aim of this study was to determine the effect of maternal aerobic exercise during pregnancy on the occurrence of fetal-maternal heart rate synchronization.In 40 pregnant women at the 36th week of gestation, 21 of whom exercised regularly, we acquired 18 min. RR interval time series obtained simultaneously in the mothers and their fetuses from magnetocardiographic recordings. The time series of the two groups were examined with respect to their heart rate variability, the maternal respiratory rate and the presence of synchronization epochs as determined on the basis of synchrograms. Surrogate data were used to assess whether the occurrence of synchronization was due to chance.In the original data, we found synchronization occurred less often in pregnancies in which the mothers had exercised regularly. These subjects also displayed higher combined fetal-maternal heart rate variability and lower maternal respiratory rates. Analysis of the surrogate data showed shorter epochs of synchronization and a lack of the phase coordination found between maternal and fetal beat timing in the original data.The results suggest that fetal-maternal heart rate coupling is present but generally weak. Maternal exercise has a damping effect on its occurrence, most likely due to an increase in beat-to-beat differences, higher vagal tone and slower breathing rates

Is there a role for CT coronary angiography in patients with symptomatic angina? Effect of coronary calcium score on identification of stenosis

Present guidelines discourage the use of CT coronary angiography (CTCA) in symptomatic angina patients. We examined the relation between coronary calcium score (CS) and the performance of CTCA in patients with stable and unstable angina in order to understand under which conditions CTCA might be a gate-keeper to conventional coronary angiography (CCA) in such patients. We included 360 patients between 50 and 70 years old with stable and unstable angina who were clinically referred for CCA irrespective of CS. Patients received CS and CCTA on 64-slice scanners in a multicenter cross-sectional trial. The institutional review board approved the study. Diagnostic performance of CTCA to detect or rule out significant coronary artery disease was calculated on a per patient level in pre-defined CS categories. The prevalence of significant coronary artery disease strongly increased with CS. Negative CTCA were associated with a negative likelihood ratio of <0.1 independent of CS. Positive CTCA was associated with a high positive likelihood ratio of 9.4 if CS was <10. However, for higher CS the positive likelihood ratio never exceeded 3.0 and for CS >400 it decreased to 1.3. In the 62 (17%) patients with CS <10, CTCA reliably identified the 42 (68%) of these patients without significant CAD, at no false negative CTCA scans. In symptomatic angina patients, a negative CTCA reliably excludes significant CAD but the additional value of CTCA decreases sharply with CS >10 and especially with CS >400. In patients with CS <10, CTCA provides excellent diagnostic performance

Quantifying Exocytosis by Combination of Membrane Capacitance Measurements and Total Internal Reflection Fluorescence Microscopy in Chromaffin Cells

Total internal reflection fluorescence microscopy (TIRF-Microscopy) allows the observation of individual secretory vesicles in real-time during exocytosis. In contrast to electrophysiological methods, such as membrane capacitance recording or carbon fiber amperometry, TIRF-Microscopy also enables the observation of vesicles as they reside close to the plasma membrane prior to fusion. However, TIRF-Microscopy is limited to the visualization of vesicles that are located near the membrane attached to the glass coverslip on which the cell grows. This has raised concerns as to whether exocytosis measured with TIRF-Microscopy is comparable to global secretion of the cell measured with membrane capacitance recording. Here we address this concern by combining TIRF-Microscopy and membrane capacitance recording to quantify exocytosis from adrenal chromaffin cells. We found that secretion measured with TIRF-Microscopy is representative of the overall secretion of the cells, thereby validating for the first time the TIRF method as a measure of secretion. Furthermore, the combination of these two techniques provides a new tool for investigating the molecular mechanism of synaptic transmission with combined electrophysiological and imaging techniques

Modified bathroom scale and balance assessment: a comparison with clinical tests

Frailty and detection of fall risk are major issues in preventive gerontology. A simple tool frequently used in daily life, a bathroom scale (balance quality tester: BQT), was modified to obtain information on the balance of 84 outpatients consulting at a geriatric clinic. The results computed from the BQT were compared to the values of three geriatric tests that are widely used either to detect a fall risk or frailty (timed get up and go: TUG; 10 m walking speed: WS; walking time: WT; one-leg stand: OS). The BQT calculates four parameters that are then scored and weighted, thus creating an overall indicator of balance quality. Raw data, partial scores and the global score were compared with the results of the three geriatric tests. The WT values had the highest correlation with BQT raw data (r = 0.55), while TUG (r = 0.53) and WS (r = 0.56) had the highest correlation with BQT partial scores. ROC curves for OS cut-off values (4 and 5 s) were produced, with the best results obtained for a 5 s cut-off, both with the partial scores combined using Fisher's combination (specificity 85 %: 0.48), and with the empirical score (specificity 85 %: 8). A BQT empirical score of less than seven can detect fall risk in a community dwelling population

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Psychometric evaluation of the Osteoporosis Patient Treatment Satisfaction Questionnaire (OPSAT-Q™), a novel measure to assess satisfaction with bisphosphonate treatment in postmenopausal women

BACKGROUND: The Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) is a new measure of patient satisfaction with bisphosphonate treatment for osteoporosis. The objective of this study was to evaluate the psychometric characteristics of the OPSAT-Q. METHODS: The OPSAT-Q contains 16 items in four subscales: Convenience, Confidence with Daily Activities, Side Effects, and Overall Satisfaction. All four subscale scores and an overall composite satisfaction score (CSS) can be computed. The OPSAT-Q, Osteoporosis Targeted Quality of Life (OPTQoL), and sociodemographic/clinical questionnaires, including 3 global items on convenience, functioning and side effects, were self-administered to women with osteoporosis or osteopenia recruited from four US clinics. Analyses included item and scale performance, internal consistency reliability, reproducibility, and construct validity. Reproducibility was measured using the intraclass correlation coefficient (ICC) via a follow-up questionnaire completed by participants 2 weeks post baseline. RESULTS: 104 women with a mean age of 65.1 years participated. The majority were Caucasian (64.4%), living with someone (74%), and not currently employed (58.7%). 73% had osteoporosis and 27% had osteopenia. 80% were taking weekly bisphosphonates and 18% were taking daily medication (2% missing data). On a scale of 0–100, individual patient subscale scores ranged from 17 to 100 and CSS scores ranged from 44 to 100. All scores showed acceptable internal consistency reliability (Cronbach's alpha > 0.70) (range 0.72 to 0.89). Reproducibility ranged from 0.62 (Daily Activities) to 0.79 (Side Effects) for the subscales; reproducibility for the CSS was 0.81. Significant correlations were found between the OPSAT-Q subscales and conceptually similar global measures (p < 0.001). CONCLUSION: The findings from this study confirm the validity and reliability of the OPSAT-Q and support the proposed composition of four subscales and a composite score. They also support the use of the OPSAT-Q to examine the impact of bisphosphonate dosing frequency on patient satisfaction