No abstract

Diabetic patients suffer from gastrointestinal disorders associated with dysmotility, enteric neuropathy and dysbiosis of gut microbiota, however gender differences are not fully known. Previous studies show that high-fat diet (HFD) causes type two diabetes (T2D) in male mice after 4-8 weeks, but only does so in female mice after 16 weeks. This study sought to determine whether sex influences the development of intestinal dysmotility, enteric neuropathy and dysbiosis in mice fed HFD. We fed 8-week old C57BL6 male and female mice a standard chow diet (SCD) or a 72% Kcal HFD for 8 weeks. We analyzed the associations between sex and intestinal dysmotility, neuropathy and dysbiosis using motility assays, immunohistochemistry and next generation sequencing. HFD ingestion caused obesity, glucose intolerance and insulin resistance in male but not female mice. However, HFD ingestion slowed intestinal propulsive motility in both male and female mice. This was associated with decreased inhibitory neuromuscular transmission, loss of myenteric inhibitory motor neurons, and axonal swelling and loss of cytoskeletal filaments. HFD induced dysbiosis and changed the abundance of specific bacteria, especially Allobaculum, Bifidobacterium and Lactobacillus, which correlated with dysmotility and neuropathy. Female mice had higher immunoreactivity and numbers of myenteric inhibitory motor neurons, matching larger amplitudes of inhibitory junction potentials.

We studied the effect of long-term correction of vitamin E deficiency on neurologic function in 14 children with chronic cholestasis. Vitamin E repletion was achieved in all, either by large oral doses (up to 120 IU per kilogram of body weight per day) or by intramuscular administration of dl-alpha-tocopherol (0.8 to 2.0 IU per kilogram per day). With early institution of therapy, neurologic function remained normal in two asymptomatic children below the age of three years after 15 and 18 months of therapy. Neurologic function became normal in three symptomatic children below age three after 18 to 32 months of therapy. Restitution of neurologic function was more limited in nine symptomatic children 5 to 17 1/2 years old after 18 to 48 months of therapy. We conclude that vitamin E repletion therapy should be initiated at an early age in children with chronic cholestasis complicated by vitamin E deficiency, to prevent irreversible neurologic injury.

PTSD-related nightmares, sleep disturbances, and overall illness severity showed a significant response to treatment with prazosin. With careful dose titration, prazosin was well tolerated and had no significant sustained effect on blood pressure.

Treatment failure rates between PICC and oral antibiotics did not differ. Children with complicated pneumonia should preferentially receive oral antibiotics at discharge when effective oral options are available.