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Magnetic resonance spectroscopy (MRS) allows the analysis of biochemical processes non-invasively and in vivo. Still, its application in clinical diagnostics is rare. Routine MRS is limited to spatial, chemical and temporal resolutions of cubic centimetres, mM and minutes. In fact, the signal of many metabolites is strong enough for detection, but the resonances significantly overlap, exacerbating identification and quantification. Besides, the signals of water and lipids are much stronger and dominate the entire spectrum. To suppress the background and isolate selected signals, usually, relaxation times, J-coupling and chemical shifts are used. Here, we propose methods to isolate the signals of selected molecular groups within endogenous metabolites by using long-lived spin states (LLS). We exemplify the method by preparing the LLSs of coupled protons in the endogenous molecules N-acetyl-L-aspartic acid (NAA). First, we store polarization in long-lived, double spin states, followed by saturation pulses before the spin order is converted back to observable magnetization or double quantum filters to suppress background signals. We show that LLS and zero-quantum coherences can be used to selectively prepare and measure the signals of chosen metabolites or drugs in the presence of water, inhomogeneous field and highly concentrated fatty solutions. The strong suppression of unwanted signals achieved allowed us to measure pH as a function of chemical shift difference.

Magnetic resonance spectroscopy (MRS) allows the analysis of biochemical processes non-invasively and in vivo. Still, its application in clinical diagnostics is rare. Routine MRS is limited to spatial, chemical and temporal resolutions of cubic centimetres, mM and minutes. In fact, the signal of many metabolites is strong enough for detection, but the resonances significantly overlap, exacerbating identification and quantification. Besides, the signals of water and lipids are much stronger and dominate the entire spectrum. To suppress the background and isolate selected signals, usually, relaxation times, J-coupling and chemical shifts are used. Here, we propose methods to isolate the signals of selected molecular groups within endogenous metabolites by using long-lived spin states (LLS). We exemplify the method by preparing the LLSs of coupled protons in the endogenous molecules N-acetyl-L-aspartic acid (NAA). First, we store polarization in long-lived, double spin states, followed by saturation pulses before the spin order is converted back to observable magnetization or double quantum filters to suppress background signals. We show that LLS and zero-quantum coherences can be used to selectively prepare and measure the signals of chosen metabolites or drugs in the presence of water, inhomogeneous field and highly concentrated fatty solutions. The strong suppression of unwanted signals achieved allowed us to measure pH as a function of chemical shift difference.

Background The treatment of upper respiratory tract infections (URTIs) accounts for the majority of antibiotic prescriptions in primary care, although an antibiotic therapy is rarely indicated. Non-clinical factors, such as time pressure and the perceived patient expectations are considered to be reasons for prescribing antibiotics in cases where they are not indicated. The improper use of antibiotics, however, can promote resistance and cause serious side effects. The aim of the study was to clarify whether the antibiotic prescription rate for infections of the upper respiratory tract can be lowered by means of a short (2 x 2.25h) communication training based on the MAAS-Global-D for primary care physicians. Methods In total, 1554 primary care physicians were invited to participate in the study. The control group was formed from observational data. To estimate intervention effects we applied a combination of difference-in-difference (DiD) and statistical matching based on entropy balancing. We estimated a corresponding multi-level logistic regression model for the antibiotic prescribing decision of German primary care physicians for URTIs. Results Univariate estimates detected an 11-percentage-point reduction of prescriptions for the intervention group after the training. For the control group, a reduction of 4.7% was detected. The difference between both groups in the difference between the periods was -6.5% and statistically significant. The estimated effects were nearly identical to the effects estimated for the multi-level logistic regression model with applied matching. Furthermore, for the treatment of young women, the impact of the training on the reduction of antibiotic prescription was significantly stronger. Conclusions Our results suggest that communication skills, implemented through a short communication training with the MAAS-Global-D-training, lead to a more prudent prescribing behavior of antibiotics for URTIs. Thereby, the MAAS-Global-D-training could not only avoid unnecessary side effects but could also help reducing the emergence of drug resistant bacteria. As a consequence of our study we suggest that communication training based on the MAAS-Global-D should be applied in the postgraduate training scheme of primary care physicians.

Chronic Obstructive Pulmonary Disease (COPD) is a highly prevalent condition characterized by inflammation and progressive obstruction of the airways. At present, there is no treatment that suppresses the chronic inflammation of the disease, and COPD patients often succumb to the condition. Excessive oxidative stress caused by smoke inhalation is a major driving force of the disease. The transcription factor NRF2 is a critical player in the battle against oxidative stress and its function is impaired in COPD. Increasing NRF2 activity may therefore be a viable therapeutic option for COPD treatment. We show that down regulation of KEAP1, a NRF2 inhibitor, protects primary human lung epithelial cells from cigarette-smoke-extract (CSE) induced cell death in an established in vitro model of radical stress. To identify new potential drug targets with a similar effect, we performed a siRNA screen of the ‘druggable’ genome using a NRF2 transcriptional reporter cell line. This screen identified multiple genes that when down regulated increased NRF2 transcriptional activity and provided a survival benefit in the in vitro model. Our results suggest that inhibiting components of the ubiquitin-proteasome system will have the strongest effects on NRF2 transcriptional activity by increasing NRF2 levels. We also find that down regulation of the small GTPase Rab28 or the Estrogen Receptor ESRRA provide a survival benefit. Rab28 knockdown increased NRF2 protein levels, indicating that Rab28 may regulate NRF2 proteolysis. Conversely ESRRA down regulation increased NRF2 transcriptional activity without affecting NRF2 levels, suggesting a proteasome-independent mechanism.

We investigated contemporary and historical influences on the pattern of genetic diversity of European roe deer (Capreolus capreolus). The study was conducted in northeastern Poland, a zone where vast areas of primeval forests are conserved and where the European roe deer was never driven to extinction. A total of 319 unique samples collected in three sampling areas were genotyped at 16 microsatellites and one fragment (610 bp) of mitochondrial DNA (mtDNA) control region. Genetic diversity was high, and a low degree of genetic differentiation among sampling areas was observed with both microsatellites and mtDNA. No evidence of genetic differentiation between roe deer inhabiting open fields and forested areas was found, indicating that the ability of the species to exploit these contrasting environments might be the result of its phenotypic plasticity. Half of the studied individuals carried an mtDNA haplotype that did not belong to C. capreolus, but to a related species that does not occur naturally in the area, the Siberian roe deer (C. pygargus). No differentiation between individuals with Siberian and European mtDNA haplotypes was detected at microsatellite loci. Introgression of mtDNA of Siberian roe deer into the genome of European roe deer has recently been detected in eastern Europe. Such introgression might be caused by human-mediated translocations of Siberian roe deer within the range of European roe deer or by natural hybridization between these species in the past.

Individuals can increase inclusive fitness benefits through a complex network of social interactions directed towards kin. Preferential relationships with relatives lead to the emergence of kin structures in the social system. Cohesive social groups of related individuals and female philopatry of wild boar create conditions for cooperation through kin selection and make the species a good biological model for studying kin structures. Yet, the role of kinship in shaping the social structure of wild boar populations is still poorly understood. In the present study, we investigated spatio-temporal patterns of associations and the social network structure of the wild boar Sus scrofa population in Białowieża National Park, Poland, which offered a unique opportunity to understand wild boar social interactions away from anthropogenic factors. We used a combination of telemetry data and genetic information to examine the impact of kinship on network cohesion and the strength of social bonds. Relatedness and spatial proximity between individuals were positively related to the strength of social bond. Consequently, the social network was spatially and genetically structured with well-defined and cohesive social units. However, spatial proximity between individuals could not entirely explain the association patterns and network structure. Genuine, kin-targeted, and temporarily stable relationships of females extended beyond spatial proximity between individuals while males interactions were short-lived and not shaped by relatedness. The findings of this study confirm the matrilineal nature of wild boar social structure and show how social preferences of individuals translate into an emergent socio-genetic population structure.