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.

Mechanical performance of external fixators with wires for the treatment of bone fractures--Part I: Load-displacement behavior.

Using matrix algebra, a mathematical model is formulated for a particular type of external fixator with wires (system developed by Ilizarov) for the treatment of bone fractures. The mathematical model is used to give a linear estimate of the stiffness under lateral and axial loads in a representative number of practical conditions. Relative displacements of the bone ends at the fracture site are calculated not only in the common case of a gap, but also for various angles of inclined sliding contact; in this case, a realistic load is applied and nonlinear stiffening of the wires under transversal loads is iteratively taken into account.

Mechanical performance of external fixators with wires for the treatment of bone fractures--Part II: Wire tension and slippage.

The work shows correct procedures needed in order to gather reliable data from measurement of displacements versus axial load in a laboratory mounting of the Ilizarov external fixator. The mechanism of settling after load cycling is investigated. Detension under load is a major problem of wires. By means of vibration frequency measurements, tests on single wire allow determination of reduction in wire tension due to transverse loading: it is found that, almost independently from the amount of clamp tightening, the tension reaches a lower limit related only to the transverse load and not related to pretension. It is shown that, for higher clamp tightening torques, wire detension must be attributed to permanent plastic deformation of the wires; moreover, it is shown that the unavoidable errors in the spacing of the tensioned wires lead to marked decrease of their stiffness under transverse load.