Gestational undernourishment modifies the composition of skeletal muscle transverse tubule membranes and the mechanical properties of muscles in newborn rats.

BACKGROUND/AIMS: [corrected] Skeletal muscle (SM) constitutes more than 40% of the body weight in adulthood. Transports dietary glucose mainly through the insulin-dependent glucose transporter (Glut-4) located in the Transverse tubule membrane system (TT). The TT development ends shortly after birth. The TT membrane hosts the proteins involved in excitation-contraction coupling and glucose uptake. Glycaemic regulation through movement is a key function of fully developed skeletal muscle. In this study, we aimed to characterize the effect of gestational undernourishment (GUN) in rats GLUT-4 expression and on the protein/lipid content of the TT membranes. We also examined the effect of GUN on the mechanical properties of muscles as an indication of the metabolic condition of the SM at birth. METHODS: Isolated TT membrane from SM of GUN rats were used to study lipid/protein content and protein stability by differential scanning calorimetry. The effect of GUN on the SM mechanical properties was determined in isolated Extensor Digitorum Longus (EDL) muscle. RESULTS: We demonstrate that compared to control, GUN in the new-born produces; i) decreases body weight; ii) diminution in SM mass; iii) decreases the formation of TT membranes; iv) expresses TT membrane proteins with higher thermal stability. The TT membrane expression of GLUT-4 in GUN offspring was twice that of controls. The isolated EDL of GUN offspring was 20% stronger as measured by contractile force and more resistant to fatigue relative to controls. CONCLUSION: These results provide the first evidence of adaptive changes of the SM in new-borns exposed to severe gestational food restriction. The effects of GUN on muscle at birth are the first step toward detrimental SM metabolic function, contributing to the physiopathology of metabolic diseases in adulthood.

Auditory rehabilitation after temporal bone fracture with cochlear implants - a case control study.

OBJECTIVES: Temporal bone fracture can cause posttraumatic deafness. Sequelae like ossification or obliteration of the cochlea can impact the outcome of cochlear implantation. This study highlights the effect of localisation of the fracture to morphologic, electric and functional criteria. METHODS: The study group consists of patients suffering from hearing loss caused by temporal bone fracture (n = 61 ears). Patients were divided into otic capsule sparing (OCS) and otic capsule involving (OCI) fractures. The OCI group was additionally divided into subgroups with or without signs of ossification inside the cochlea. Postoperative imaging, hearing tests and electrode impedances were analysed. RESULTS: The results of postoperative hearing rehabilitation showed lower speech understanding scores for the OCI group, especially for the ossification group. OCI fractures with signs of ossification showed increased impedances. Patients in the OCI group suffered more frequently from facial nerve stimulation (FNS). FNS was most frequently observed within the ossification group. CONCLUSION: Cochlear implantation in patients with temporal bone fracture is adequate therapy for the treatment of fracture-induced deafness. In long-term observation, these patients show comparable results with regular cochlear implant (CI) patients. Implantation should be performed as soon as possible after hearing loss, before obstructing obliteration or ossification of the cochlea start.

Persistent Innate Immune Stimulation Results in IRF3-Mediated but Caspase-Independent Cytostasis.

Persistent virus infection continuously produces non-self nucleic acids that activate cell-intrinsic immune responses. However, the antiviral defense evolved as a transient, acute phase response and the effects of persistently ongoing stimulation onto cellular homeostasis are not well understood. To study the consequences of long-term innate immune activation, we expressed the NS5B polymerase of Hepatitis C virus (HCV), which in absence of viral genomes continuously produces immune-stimulatory RNAs. Surprisingly, within 3 weeks, NS5B expression declined and the innate immune response ceased. Proteomics and functional analyses indicated a reduced proliferation of those cells most strongly stimulated, which was independent of interferon signaling but required mitochondrial antiviral signaling protein (MAVS) and interferon regulatory factor 3 (IRF3). Depletion of MAVS or IRF3, or overexpression of the MAVS-inactivating HCV NS3/4A protease not only blocked interferon responses but also restored cell growth in NS5B expressing cells. However, pan-caspase inhibition could not rescue the NS5B-induced cytostasis. Our results underline an active counter selection of cells with prolonged innate immune activation, which likely constitutes a cellular strategy to prevent persistent virus infections.