Disruption of the microbiota-gut-brain axis is a defining characteristic of the α-Gal A (-/0) mouse model of Fabry disease.

Fabry disease (FD) is an X-linked metabolic disease caused by a deficiency in α-galactosidase A (α-Gal A) activity. This causes accumulation of glycosphingolipids, especially globotriaosylceramide (Gb3), in different cells and organs. Neuropathic pain and gastrointestinal (GI) symptoms, such as abdominal pain, nausea, diarrhea, constipation, and early satiety, are the most frequent symptoms reported by FD patients and severely affect their quality of life. It is generally accepted that Gb3 and lyso-Gb3 are involved in the symptoms; nevertheless, the origin of these symptoms is complex and multifactorial, and the exact mechanisms of pathogenesis are still poorly understood. Here, we used a murine model of FD, the male α-Gal A (-/0) mouse, to characterize functionality, behavior, and microbiota in an attempt to elucidate the microbiota-gut-brain axis at three different ages. We provided evidence of a diarrhea-like phenotype and visceral hypersensitivity in our FD model together with reduced locomotor activity and anxiety-like behavior. We also showed for the first time that symptomology was associated with early compositional and functional dysbiosis of the gut microbiota, paralleled by alterations in fecal short-chain fatty acid levels, which partly persisted with advancing age. Interestingly, most of the dysbiotic features suggested a disruption of gut homeostasis, possibly contributing to accelerated intestinal transit, visceral hypersensitivity, and impaired communication along the gut-brain axis.

Vibrational states of nano-confined water molecules in beryl investigated by first-principles calculations and optical experiments.

Using quantum mechanical calculations within density functional theory, we provide a comprehensive analysis of infrared-active excitation of water molecules confined in nanocages of a beryl crystal lattice. We calculate infrared-active modes including the translational, librational, and mixed-type resonances of regular and heavy water molecules. The results are compared to the experimental spectra measured for the two principal polarizations of the electric field: parallel and perpendicular to the crystallographic c-axis. Good agreement is achieved between calculated and measured isotopic shifts of the normal modes. We analyze the vibrational modes in connection with the structural characteristics and arrangements of water molecules within the beryl crystal. Specific atomic displacements are assigned to each experimentally detected vibrational mode resolving the properties of nano-confined water on scales not accessible by experiments. Our results elucidate the applicability and efficiency of a combined experimental and computational approach for describing and an in-depth understanding of nano-confined water, and pave the way for future studies of more complex systems.

A fresh look at IBS-opportunities for systems medicine approaches.

NeuroGUT is a EU-funded initial training network (ITN) of 14 research projects in neurogastroenterology that have employed an equal number of early-stage researchers. Neurogut trainees have-among other activities-attended an international conference on irritable bowel syndrome (IBS) in Bologna in 2016 and were asked to critically review and evaluate the current knowledge on IBS for their respective research activities, and to state what they were missing. Most appreciated were the topics brain imaging of gut activity, the role of the gut microbiota, the pharmacology of gut functions, the IBS-IBD interrelation, the new Rome IV criteria, the role of gas, and the placebo response in functional disorders. Missed were more detailed coverage of high-resolution manometry, functional brain imaging, advanced "systems medicine" approaches and bioinformatics technology, better sub-classification of IBS patients, and the development of disease biomarkers, extended at the molecular (genetic/epigenetic, proteonomic) level. They summarize that despite excellent specialized research, there is a gap open that should be filled with systems medicine. For this, it would be necessary that medical research learns even more from the data sciences and other basic disciplines, for example, information technology and system biology, and also welcomes a change in paradigm that enhances open sharing of data, information, and resources.

In-medium effects on phase space distributions of antikaons measured in proton-nucleus collisions.

Differential production cross sections of K+/- mesons have been measured in p + C and p + Au collisions at 1.6, 2.5, and 3.5 GeV proton beam energy. At beam energies close to the production threshold, the K- multiplicity is strongly enhanced with respect to proton-proton collisions. According to microscopic transport calculations, this enhancement is caused by two effects: the strangeness exchange reaction NY --> K- NN and an attractive in-medium K- N potential at saturation density.

Observation of different azimuthal emission patterns of K+ and of K- mesons in heavy-ion collisions at 1-2 A GeV.

Azimuthal distributions of pi+, K+, and K- mesons have been measured in Au+Au reactions at 1.5A GeV and Ni+Ni reactions at 1.93 A GeV. In semicentral collisions at midrapidity, pi+ and K+ mesons are emitted preferentially perpendicular to the reaction plane in both collision systems. In contrast for K- mesons in Ni+Ni reactions, an in-plane elliptic flow was observed for the first time at these incident energies.

First evidence for different freeze-out conditions for kaons and antikaons observed in heavy-ion collisions.

Differential production cross sections of K- and K+ mesons have been measured in Ni+Ni and Au+Au collisions at a beam energy of 1.5 A GeV. The K(-)/K(+) ratio is found to be nearly constant as a function of the collision centrality and system size. The spectral slopes and the polar emission pattern differ for K- and K+ mesons. These observations indicate that K+ mesons decouple earlier from the fireball than K- mesons.

Coulomb dissociation of 8B and the low-energy cross section of the 7Be(p,gamma)8B solar fusion reaction.

An exclusive measurement of the Coulomb breakup of 8B into 7Be+p at 254A MeV allowed the study of the angular correlations of the breakup particles. These correlations demonstrate clearly that E1 multipolarity dominates and that E2 multipolarity can be neglected. By using a simple single-particle model for 8B and treating the breakup in first-order perturbation theory, we extract a zero-energy S factor of S17(0)=18.6+/-1.2+/-1.0 eV b, where the first error is experimental and the second one reflects the theoretical uncertainty in the extrapolation.

Evidence for a Soft Nuclear Equation-of-State from Kaon Production in Heavy-Ion Collisions.

The production of pions and kaons has been measured in 197Au+197Au collisions at beam energies from 0.6 to 1.5A GeV with the kaon spectrometer at SIS/GSI. The K+ meson multiplicity per nucleon is enhanced in Au+Au collisions by factors up to 6 relative to C+C reactions, whereas the corresponding pion ratio is reduced. The ratio of the K+ meson excitation functions for Au+Au and C+C collisions increases with decreasing beam energy. This behavior is expected for a soft nuclear equation-of-state.

[Coronary surgery in females]. / Koronarchirurgie bei Frauen.

In the last three years, of a total of 617 patients undergoing surgery for ischemic heart disease, 53 were women (8.6%). With one exception, all were in or shortly before the menopause. As compared with men, the women were found to have a preponderance of risk factors. The most unfavorable combination, that of hypertension and hypercholesterolemia, was present in one-third of the patients. Hospital mortality for isolated revascularization was higher in women at 4.9% than in men at 1.5%. The one-year survival rates, however, of 94.4% and 95%, respectively, did not differ between the two sexes. In women, the number of grafts per patient was 2.1 as compared with 2.9 in men. Complete revascularization was achieved less frequently in women than in men; similarly graft patency rate at one year of 66% in women was less than the 84% observed in men. The more marked coronary sclerosis as well as morphologic characteristics of coronary arteries in women construe a special challenge to the surgeon and prerequisite a high degree of technical skill.

[Chemoembolization of the hepatic artery combined with intraportal cytostatic infusion--a new concept in the regional chemotherapy of liver metastases]. / Chemoembolisation der A. hepatica kombiniert mit intraportaler Zytostatikum-Infusion--ein neues Konzept für die regionale Chemotherapie von Lebermetastasen.

At present international the regional cytostatic chemotherapy for hepatic metastases is used by the intraarterial way. Newest methods are the technically very pretentious intraarterial perfusion with venous hemofiltration and the chemo-embolization of the hepatic artery requiring meanwhile an adjuvant systemic chemotherapy because the chemo-embolization influences only the arterially supplied part of the metastases. By the combination of the transumbilical intraportal chemotherapy formerly developed in the Central Institute for Cancer Research Berlin-Buch with the intraarterial chemo-embolization it is possible to reduce considerably the technical expenditure and to increase the regional concentration of cytostatics simultaneous avoiding the load of the whole organism. The bases of this new method and the technical procedure are discussed.