A novel approach to model cumulative stress:Area under the s-factor curve

OBJECTIVE: Using a large longitudinal sample of adults from the Midlife in the United States (MIDUS) study, the present study extended a recently developed hierarchical model to determine how best to model the accumulation of stressors, and to determine whether the rate of change in stressors or traditional composite scores of stressors are stronger predictors of health outcomes.METHOD: We used factor analysis to estimate a stress-factor score and then, to operationalize the accumulation of stressors we examined five approaches to aggregating information about repeated exposures to multiple stressors. The predictive validity of these approaches was then assessed in relation to different health outcomes.RESULTS: The prediction of chronic conditions, body mass index, difficulty with activities of daily living, executive function, and episodic memory later in life was strongest when the accumulation of stressors was modeled using total area under the curve (AUC) of estimated factor scores, compared to composite scores that have traditionally been used in studies of cumulative stress, as well as linear rates of change.CONCLUSIONS: Like endogenous, biological markers of stress reactivity, AUC for individual trajectories of self-reported stressors shows promise as a data reduction technique to model the accumulation of stressors in longitudinal studies. Overall, our results indicate that considering different quantitative models is critical to understanding the sequelae and predictive power of psychosocial stressors from midlife to late adulthood.</p

Neutral silicon vacancy centers in undoped diamond via surface control

Neutral silicon vacancy centers (SiV0) in diamond are promising candidates for quantum networks because of their long spin coherence times and stable, narrow optical transitions. However, stabilizing SiV0 requires high purity, boron doped diamond, which is not a readily available material. Here, we demonstrate an alternative approach via chemical control of the diamond surface. We use low-damage chemical processing and annealing in a hydrogen environment to realize reversible and highly stable charge state tuning in undoped diamond. The resulting SiV0 centers display optically detected magnetic resonance and bulk-like optical properties. Controlling the charge state tuning via surface termination offers a route for scalable technologies based on SiV0 centers, as well as charge state engineering of other defects

Live cell immunogold labelling of RNA polymerase II

Labeling nuclear proteins with electron dense probes in living cells has been a major challenge due to their inability to penetrate into nuclei. We developed a lipid-based approach for delivering antibodies coupled to 0.8 nm ultrasmall gold particles into the nucleus to label RNA polymerase II. Focussed Ion Beam slicing coupled to Scanning Electron Microscopy (FIB/SEM) enabled visualization of entire cells with probe localization accuracy in the 10 nm range

Promoting More Physical Activity and Less Sedentary Behaviour During the COVID-19 Situation – SportStudisMoveYou (SSMY): A Randomized Controlled Trial

Objective: To determine the effect of an innovative, online-based intervention, addressing the possible decline of physical activity (PA) and increase of sedentary behavior (SB) during COVID-19 stay at home restrictions in Switzerland. Methods: This study investigated the effect of a two-week, social cognitive theory based, online-video moderate to vigorous (MV)PA or SB intervention on MVPA and SB behaviour and intention via a 3 group by 2 time point parallel randomized controlled trial during the COVID-19 pandemic. Adults (≥18 yo) were recruited over the internet between April 10th and April 19th 2020 (n = 129; 75.2% female; mean age = 29.0 [SD 11.8] years). Both intervention groups received five videos targeting either SB for the SB group or MVPA for the MVPA group and were compared to an attention control group (fruit and vegetable consumption). It was hypothesized that MVPA time and intention would increase for the MVPA group and the SB group would outperform control on SB behaviour and intention indicators. Results: No significant interactions were found for the MVPA group (n = 41) versus control (n = 40). Only one significant interaction was measured for the SB group (n = 48; intention of active breaks F = (2,114) = 5.84, p = 0.004, ηp2 = 0.09). Although mostly non-significant and small effects, the MVPA group showed results pointing in the hypothesized direction on all PA indicators and the SB on all SB indicators, respectively. Conclusion: Considering this study’s limitations (e.g. small intervention dose), video-based online PA and SB interventions seem promising and feasible. This approach is appropriate for COVID-19 and other stay at home situations

Enhancing global vaccine pharmacovigilance: Proof-of-concept study on aseptic meningitis and immune thrombocytopenic purpura following measles-mumps containing vaccination

New vaccines designed to prevent diseases endemic in low and middle-income countries (LMICs) are now being introduced without prior record of utilization in countries with robust pharmacovigilance systems. To address this deficit, our objective was to demonstrate feasibility of an international hospital-based network for the assessment of potential epidemiological associations between serious and rare adverse events and vaccines in any setting. This was done through a proof-of-concept evaluation of the risk of immune thrombocytopenic purpura (ITP) and aseptic meningitis (AM) following administration of the first dose of measles-mumps-containing vaccines using the self-controlled risk interval method in the primary analysis. The World Health Organization (WHO) selected 26 sentinel sites (49 hospitals) distributed in 16 countries of the six WHO regions. Incidence rate ratios (IRR) of 5.0 (95% CI: 2.5-9.7) for ITP following first dose of measles-containing vaccinations, and of 10.9 (95% CI: 4.2-27.8) for AM following mumps-containing vaccinations were found. The strain-specific analyses showed significantly elevated ITP risk for measles vaccines containing Schwarz (IRR: 20.7; 95% CI: 2.7-157.6), Edmonston-Zagreb (IRR: 11.1; 95% CI: 1.4-90.3), and Enders'Edmonston (IRR: 8.5; 95% CI: 1.9-38.1) strains. A significantly elevated AM risk for vaccines containing the Leningrad-Zagreb mumps strain (IRR: 10.8; 95% CI: 1.3-87.4) was also found. This proof-of-concept study has shown, for the first time, that an international hospital-based network for the investigation of rare vaccine adverse events, using common standardized procedures and with high participation of LMICs, is feasible, can produce reliable results, and has the potential to characterize differences in risk between vaccine strains. The completion of this network by adding large reference hospitals, particularly from tropical countries, and the systematic WHO-led implementation of this approach, should permit the rapid post-marketing evaluation of safety signals for serious and rare adverse events for new and existing vaccines in all settings, including LMICs

Potential health risks of complementary alternative medicines in cancer patients

Many cancer patients use complementary alternative medicines (CAMs) but may not be aware of the potential risks. There are no studies quantifying such risks, but there is some evidence of patient risk from case reports in the literature. A cross-sectional survey of patients attending the outpatient department at a specialist cancer centre was carried out to establish a pattern of herbal remedy or supplement use and to identify potential adverse side effects or drug interactions with conventional medicines. If potential risks were identified, a health warning was issued by a pharmacist. A total of 318 patients participated in the study. Of these, 164 (51.6%) took CAMs, and 133 different combinations were recorded. Of these, 10.4% only took herbal remedies, 42.1% only supplements and 47.6% a combination of both. In all, 18 (11.0%) reported supplements in higher than recommended doses. Health warnings were issued to 20 (12.2%) patients. Most warnings concerned echinacea in patients with lymphoma. Further warnings were issued for cod liver/fish oil, evening primrose oil, gingko, garlic, ginseng, kava kava and beta-carotene. In conclusion, medical practitioners need to be able to identify the potential risks of CAMs. Equally, patients should be encouraged to disclose their use. Also, more research is needed to quantify the actual health risks

Cell-Autonomous Requirement for Rx Function in the Mammalian Retina and Posterior Pituitary

Rx is a paired-like homeobox gene that is required for vertebrate eye formation. Mice lacking Rx function do not develop eyes or the posterior pituitary. To determine whether Rx is required cell autonomously in these tissues, we generated embryonic chimeras consisting of wild type and Rx−/− cells. We found that in the eye, Rx-deficient cells cannot participate in the formation of the neuroretina, retina pigment epithelium and the distal part of the optic stalk. In addition, in the ventral forebrain, Rx function is required cell autonomously for the formation of the posterior pituitary. Interestingly, Rx−/− and wild type cells segregate before the morphogenesis of these two tissues begins. Our observations suggest that Rx function is not only required for the morphogenesis of the retina and posterior pituitary, but also prior to morphogenesis, for the sorting out of cells to form distinct fields of retinal/pituitary cells

The lipid droplet coat protein perilipin 5 also localizes to muscle mitochondria

Perilipin 5 (PLIN5/OXPAT) is a lipid droplet (LD) coat protein mainly present in tissues with a high fat-oxidative capacity, suggesting a role for PLIN5 in facilitating fatty acid oxidation. Here, we investigated the role of PLIN5 in fat oxidation in skeletal muscle. In human skeletal muscle, we observed that PLIN5 (but not PLIN2) protein content correlated tightly with OXPHOS content and in rat muscle PLIN5 content correlated with mitochondrial respiration rates on a lipid-derived substrate. This prompted us to examine PLIN5 protein expression in skeletal muscle mitochondria by means of immunogold electron microscopy and Western blots in isolated mitochondria. These data show that PLIN5, in contrast to PLIN2, not only localizes to LD but also to mitochondria, possibly facilitating fatty acid oxidation. Unilateral overexpression of PLIN5 in rat anterior tibialis muscle augmented myocellular fat storage without increasing mitochondrial density as indicated by the lack of change in protein content of five components of the OXPHOS system. Mitochondria isolated from PLIN5 overexpressing muscles did not possess increased fatty acid respiration. Interestingly though, 14C-palmitate oxidation assays in muscle homogenates from PLIN5 overexpressing muscles revealed a 44.8% (P = 0.05) increase in complete fatty acid oxidation. Thus, in mitochondrial isolations devoid of LD, PLIN5 does not augment fat oxidation, while in homogenates containing PLIN5-coated LD, fat oxidation is higher upon PLIN5 overexpression. The presence of PLIN5 in mitochondria helps to understand why PLIN5, in contrast to PLIN2, is of specific importance in fat oxidative tissues. Our data suggests involvement of PLIN5 in directing fatty acids from the LD to mitochondrial fatty acid oxidation