Supplementary data are available at Bioinformatics online.

Background The fragile X premutation provides a unique opportunity for the study of genetic and brain mechanisms of behavior and cognition in the context of neurodevelopment and neurodegeneration. Although the neurodegenerative phenotype, fragile X-associated tremor/ataxia syndrome (FXTAS), is well described, evidence of a causal link between the premutation and psychiatric disorder earlier in life, clear delineation of a behavioral/cognitive phenotype, and characterization of the physiological basis of observed symptoms have been elusive. Methods We completed functional magnetic resonance imaging (fMRI) targeting the amygdala with an emotion-matching task and concurrent infra-red eyetracking, FMR1 molecular genetic testing, and neuropsychological assessment in 23 men with the premutation (mean age = 32.9 years) and 25 male controls (mean age = 30.1). Results Premutation carriers had significantly smaller left and right amygdala volume and reduced right amygdala activation during the task relative to controls. Although both elevated FMR1 mRNA and reduced FMR1 protein (FMRP) were associated with the reduced activation, multiple regression analysis suggested that reduced FMRP is the primary factor. Premutation carriers also had higher ratings of autism spectrum symptoms than controls that were associated with the reduced amygdala response. Conclusions Although prior studies have emphasized a toxic gain-of-function effect of elevated mRNA associated with the premutation, the current results point to the role of reduced FMRP in alterations of brain activity and behavior.

Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti-CDI antibiotics, respectively. Ninety-four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT-related adverse events (AE) occurred in 22.3% of cases, mainly comprising self-limiting conditions including nausea, abdominal pain, and FMT-related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT-related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus-seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non-CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.