The conversion of photon energy into other energetic forms in molecules is accompanied by charge moving on ultrafast timescales. We directly observe the charge motion at a specific site in an ...electronically excited molecule using time-resolved x-ray photoelectron spectroscopy (TR-XPS). We extend the concept of static chemical shift from conventional XPS by the excited-state chemical shift (ESCS), which is connected to the charge in the framework of a potential model. This allows us to invert TR-XPS spectra to the dynamic charge at a specific atom. We demonstrate the power of TR-XPS by using sulphur 2p-core-electron-emission probing to study the UV-excited dynamics of 2-thiouracil. The method allows us to discover that a major part of the population relaxes to the molecular ground state within 220-250 fs. In addition, a 250-fs oscillation, visible in the kinetic energy of the TR-XPS, reveals a coherent exchange of population among electronic states.
Wild bee populations are declining due to human activities, such as land use change, which strongly affect the composition and diversity of available plants and food sources. The chemical composition ...of food (i.e., nutrition) in turn determines the health, resilience, and fitness of bees. For pollinators, however, the term 'health' is recent and is subject to debate, as is the interaction between nutrition and wild bee health. We define bee health as a multidimensional concept in a novel integrative framework linking bee biological traits (physiology, stoichiometry, and disease) and environmental factors (floral diversity and nutritional landscapes). Linking information on tolerated nutritional niches and health in different bee species will allow us to better predict their distribution and responses to environmental change, and thus support wild pollinator conservation.
The diversity, abundance, and health of wild bees is jeopardized primarily by land-use modifications, among other global change drivers.Defining and measuring health in wild bees requires an integrative approach across disciplines.We use elements from chemistry, stoichiometry, ecology, physiology, pathology, and genetics to (i) contribute to a more comprehensive definition of wild bee 'health', and (ii) define a framework linking bee health with floral resource/nutritional landscapes through assessing species-specific nutritional niches.We suggest a novel and holistic approach for capturing bee health through combining field and laboratory tools.Knowledge gained by applying this framework will serve as a blueprint for stakeholders engaged in pollinator conservation.
Protein energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes, especially in individuals receiving maintenance dialysis ...therapy. A multitude of factors can affect the nutritional and metabolic status of CKD patients requiring a combination of therapeutic maneuvers to prevent or reverse protein and energy depletion. These include optimizing dietary nutrient intake, appropriate treatment of metabolic disturbances such as metabolic acidosis, systemic inflammation, and hormonal deficiencies, and prescribing optimized dialytic regimens. In patients where oral dietary intake from regular meals cannot maintain adequate nutritional status, nutritional supplementation, administered orally, enterally, or parenterally, is shown to be effective in replenishing protein and energy stores. In clinical practice, the advantages of oral nutritional supplements include proven efficacy, safety, and compliance. Anabolic strategies such as anabolic steroids, growth hormone, and exercise, in combination with nutritional supplementation or alone, have been shown to improve protein stores and represent potential additional approaches for the treatment of PEW. Appetite stimulants, anti-inflammatory interventions, and newer anabolic agents are emerging as novel therapies. While numerous epidemiological data suggest that an improvement in biomarkers of nutritional status is associated with improved survival, there are no large randomized clinical trials that have tested the effectiveness of nutritional interventions on mortality and morbidity.
High prevalence rates of psychological distress in medical training and later professional life indicate a need for prevention. Different types of intervention were shown to have good effects, but ...little is known about the relative efficacy of different types of stress management interventions, and methodological limitations have been reported. In order to overcome some of these limitations, the present study aimed at evaluating the effect of a specifically developed mindfulness-based stress prevention training for medical students (MediMind) on measures of distress, coping and psychological morbidity.
We report on a prospective randomized controlled trial with three study conditions: experimental treatment (MediMind), standard treatment (Autogenic Training) and a control group without treatment. The sample consisted of medical or dental students in the second or eighth semester. They completed self-report questionnaires at baseline, after the training and at one year follow-up. Distress (Trier Inventory for the Assessment of Chronic Stress, TICS) was assessed as the primary outcome and coping (Brief COPE) as a co-primary outcome. Effects on the psychological morbidity (Brief Symptom Inventory, BSI) as a secondary outcome were expected one year after the trainings.
Initially, N = 183 students were randomly allocated to the study groups. At one year follow-up N = 80 could be included into the per-protocol analysis: MediMind (n =31), Autogenic Training (n = 32) and control group (n = 17). A selective drop-out for students who suffered more often from psychological symptoms was detected (p = .020). MANCOVA's on TICS and Brief COPE revealed no significant interaction effects. On the BSI, a significant overall interaction effect became apparent (p = .002, η2partial = .382), but post hoc analyses were not significant. Means of the Global Severity Index (BSI) indicated that MediMind may contribute to a decrease in psychological morbidity.
Due to the high and selective dropout rates, the results cannot be generalized and further research is necessary. Since the participation rate of the trainings was high, a need for further prevention programs is indicated. The study gives important suggestions on further implementation and evaluation of stress prevention in medical schools.
This trial is recorded at German Clinical Trials Register under the number DRKS00005354 (08.11.2013).
Enterotoxigenic
(ETEC) contributes significantly to the substantial burden of infectious diarrhea among children living in low- and middle-income countries. In the absence of a vaccine for ETEC, ...children succumb to acute dehydration as well as nondiarrheal sequelae related to these infections, including malnutrition. The considerable diversity of ETEC genomes has complicated canonical vaccine development approaches defined by a subset of ETEC pathovar-specific antigens known as colonization factors (CFs). To identify additional conserved immunogens unique to this pathovar, we employed an "open-aperture" approach to capture all potential conserved ETEC surface antigens, in which we mined the genomic sequences of 89 ETEC isolates, bioinformatically selected potential surface-exposed pathovar-specific antigens conserved in more than 40% of the genomes (
= 118), and assembled the representative proteins onto microarrays, complemented with known or putative colonization factor subunit molecules (
= 52) and toxin subunits. These arrays were then used to interrogate samples from individuals with acute symptomatic ETEC infections. Surprisingly, in this approach, we found that immune responses were largely constrained to a small number of antigens, including individual colonization factor antigens and EtpA, an extracellular adhesin. In a Bangladeshi cohort of naturally infected children <2 years of age, both EtpA and a second antigen, EatA, elicited significant serologic responses that were associated with protection from symptomatic illness. In addition, children infected with ETEC isolates bearing either
or
genes were significantly more likely to develop symptomatic disease. These studies support a role for antigens not presently targeted by vaccines (noncanonical) in virulence and the development of adaptive immune responses during ETEC infections. These findings may inform vaccine design efforts to complement existing approaches.
The left atrial posterior wall (LAPW) is potentially an important area for the development and maintenance of atrial fibrillation. We assessed whether there are regional electrical differences ...throughout the murine left atrial myocardium that could underlie regional differences in arrhythmia susceptibility.
We used high-resolution optical mapping and sharp microelectrode recordings to quantify regional differences in electrical activation and repolarisation within the intact, superfused murine left atrium and quantified regional ion channel mRNA expression by Taqman Low Density Array. We also performed selected cellular electrophysiology experiments to validate regional differences in ion channel function.
Spontaneous ectopic activity was observed during sustained 1Hz pacing in 10/19 intact LA and this was abolished following resection of LAPW (0/19 resected LA, P<0.001). The source of the ectopic activity was the LAPW myocardium, distinct from the pulmonary vein sleeve and LAA, determined by optical mapping. Overall, LAPW action potentials (APs) were ca. 40% longer than the LAA and this region displayed more APD heterogeneity. mRNA expression of Kcna4, Kcnj3 and Kcnj5 was lower in the LAPW myocardium than in the LAA. Cardiomyocytes isolated from the LAPW had decreased Ito and a reduced IKACh current density at both positive and negative test potentials.
The murine LAPW myocardium has a different electrical phenotype and ion channel mRNA expression profile compared with other regions of the LA, and this is associated with increased ectopic activity. If similar regional electrical differences are present in the human LA, then the LAPW may be a potential future target for treatment of atrial fibrillation.
Coronary heart disease is caused by atherosclerotic narrowing of coronary arteries. It accounts for about two-thirds of heart failure cases, which are frequently secondary to myocardial infarction. ...Despite considerable progress in the understanding and management of heart failure, its incidence, prevalence and economic burden are steadily increasing. Therefore, efficient preventive and therapeutic measures are urgently needed. In order to investigate the mechanisms involved in the pathogenesis of coronary heart disease-related heart failure and to develop therapies, appropriate animal models are indispensable. According to the aetiology of this disorder, surgical models are based on various methods allowing for the narrowing or occlusion of coronary arteries. Depending on the duration and extent of the impairment of coronary blood flow and its consequences for cardiac tissue, these are classified as models of myocardial infarction, cardiac ischemia/reperfusion injury, or chronic cardiac ischemia. In addition, factors such as species, strain, and gender of the laboratory animals also significantly contribute to the pathophysiology of the induced disorder and, therefore, have to be taken into consideration thoroughly when an animal model is to be established.
In a proof-of-principle experiment, we demonstrate high-resolution resonant laser excitation in the soft x-ray region at 48.6 eV of the 2 (2)S(1/2) to 2 (2)P(1/2) transition of Li-like Fe23+ ions ...trapped in an electron beam ion trap by using ultrabrilliant light from Free Electron Laser in Hamburg (FLASH). High precision spectroscopic studies of highly charged ions at this and upcoming x-ray lasers with an expected accuracy gain up to a factor of a thousand, become possible with our technique, thus potentially yielding fundamental insights, e.g., into basic aspects of QED.