Genetic Variants in Carbohydrate Digestive Enzyme and Transport Genes Associated with Risk of Irritable Bowel Syndrome.

Irritable Bowel Syndrome (IBS) is characterized by abdominal pain and alterations in bowel pattern, such as constipation (IBS-C), diarrhea (IBS-D), or mixed (IBS-M). Since malabsorption of ingested carbohydrates (CHO) can cause abdominal symptoms that closely mimic those of IBS, identifying genetic mutations in CHO digestive enzymes associated with IBS symptoms is critical to ascertain IBS pathophysiology. Through candidate gene association studies, we identify several common variants in TREH, SI, SLC5A1 and SLC2A5 that are associated with IBS symptoms. By investigating rare recessive Mendelian or oligogenic inheritance patterns, we identify case-exclusive rare deleterious variation in known disease genes (SI, LCT, ALDOB, and SLC5A1) as well as candidate disease genes (MGAM and SLC5A2), providing potential evidence of monogenic or oligogenic inheritance in a subset of IBS cases. Finally, our data highlight that moderate to severe IBS-associated gastrointestinal symptoms are often observed in IBS cases carrying one or more of deleterious rare variants.

Generalization of cognitive maps across space and time.

Prominent theories posit that associative memory structures, known as cognitive maps, support flexible generalization of knowledge across cognitive domains. Here, we evince a representational account of cognitive map flexibility by quantifying how spatial knowledge formed one day was used predictively in a temporal sequence task 24 hours later, biasing both behavior and neural response. Participants learned novel object locations in distinct virtual environments. After learning, hippocampus and ventromedial prefrontal cortex (vmPFC) represented a cognitive map, wherein neural patterns became more similar for same-environment objects and more discriminable for different-environment objects. Twenty-four hours later, participants rated their preference for objects from spatial learning; objects were presented in sequential triplets from either the same or different environments. We found that preference response times were slower when participants transitioned between same- and different-environment triplets. Furthermore, hippocampal spatial map coherence tracked behavioral slowing at the implicit sequence transitions. At transitions, predictive reinstatement of virtual environments decreased in anterior parahippocampal cortex. In the absence of such predictive reinstatement after sequence transitions, hippocampus and vmPFC responses increased, accompanied by hippocampal-vmPFC functional decoupling that predicted individuals' behavioral slowing after a transition. Collectively, these findings reveal how expectations derived from spatial experience generalize to support temporal prediction.

Decellularized vs Non-decellularized Allogeneic Pulmonary Artery Patches for Pulmonary Arterioplasty.

We studied pulmonary artery size, reinterventions, and panel reactive antibodies in patients with single-ventricle physiology who underwent a pulmonary arterioplasty with decellularized (DAPAP) and non-decellularized allogeneic pulmonary artery patches (non-DAPAP). Retrospective review identified 59 patients with single-ventricle physiology who underwent pulmonary arterioplasty from 2008 to 2017: 28 patients underwent arterioplasty with DAPAP and 31 patients with non-DAPAP. Demographic and operative variables were similar between groups. Among patients who underwent a Norwood procedure, a right ventricle to pulmonary artery shunt was more commonly used in the DAPAP group (12/20, 60%) and a modified Blalock-Taussig shunt was more commonly used in the non-DAPAP group (17/22, 77%). On multivariable analysis, the use of DAPAP was associated with higher pre-Fontan angiography Z-scores in right (estimate = 0.17, standard error = 0.04, P = 0.0005) and left pulmonary arteries (estimate = 0.12, standard error = 0.05, P = 0.01). No areas of calcification, discrete coarctation, or pulmonary dilation were noted in any of the pulmonary arteries. On multivariable analysis, the use of DAPAP was associated with higher freedom from pulmonary artery reinterventions (Hazard ratio = 0.36, 95% confidence interval = 0.13-0.9, P = 0.04). The median value for Class I panel reactive antibodies was 0% (IQR 0, 4) in the DAPAP and 23% (IQR 14, 36) in the non-DAPAP group. The median value for Class II panel reactive antibodies was 15% (IQR 0, 17) in the DAPAP and 21% (IQR 10, 22) in the non-DAPAP group. Pulmonary arterioplasty with DAPAP was associated with higher pre-Fontan pulmonary artery Z-scores and higher freedom from pulmonary artery reinterventions.