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Abbreviations: CEB, colonic epithelial barrier; MetS, Metabolic Syndrome; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis. AbstractThere is compelling evidence implicating intestinal permeability in the pathogenesis of nonalcoholic steatohepatitis (NASH), but the underlying mechanisms remain poorly understood. Here we examined the role of bile acids (BA) in western diet (WD)-induced loss of colonic epithelial barrier (CEB) function in mice with a genetic impairment in intestinal epithelial barrier function, junctional adhesion molecule A knockout mice, F11r −/− . WD-fed knockout mice developed severe NASH, which was associated with increased BA concentration in the cecum and loss of CEB function. Analysis of cecal BA composition revealed selective increases in primary unconjugated BAs in the WD-fed mice, which correlated with increased abundance of microbial taxa linked to BA metabolism. In vitro permeability assays revealed that chenodeoxycholic acid (CDCA), which was elevated in the cecum of WD-fed mice, increased paracellular permeability, while the BA-binding resin sevelamer hydrochloride protected against CDCA-induced loss of barrier function. Sequestration of intestinal BAs by in vivo delivery of sevelamer to WD-fed knockout mice attenuated colonic mucosal inflammation and improved CEB. Sevelamer also reduced hepatic inflammation and fibrosis, and improved metabolic derangements associated with NASH. Collectively, these findings highlight a hitherto unappreciated role for BAs in WD-induced impairment of the intestinal epithelial barrier in NASH. K E Y W O R D S bile acids, intestinal permeability, microbiome, NAFLD, NASH, tight junction 7090 | GUPTA eT Al. | MATERIALS AND METHODS | MiceJunctional adhesion molecule A (JAM-A) knock out mice (F11r −/− ) were generated as previously described. 9 Mice were bred and maintained at Emory University and the University of Pittsburgh Divisions of Animal Resources. All animal studies were approved by the Institutional Animal Care and Use Committees. | BA feeding experimentC57BL/6 mice were fed CDCA (3mg/gm body weight, Millipore Sigma, St. Louis, MO) mixed with FITC-conjugated dextran (4 kDa) (0.6 mg/gm body weight, Millipore Sigma, St. Louis, MO) solution by oral gavage following a 6 hours fast. After 3 hours, blood was collected and fluorescence intensity was measured using Fluorescence Spectrophotometer (Synergy 2, BioTek, Winooski, VT) as described previously. 9

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Variations of the tendons of the first dorsal compartment of the wrist may be one of reasons of treatment failure and recurrence in De Quervain's tenosynovitis (DQT). The present cadaveric study was designed to look into the variations of the Extensor pollicis brevis (EPB) tendon in Indian population. Methods: Seventy-seven formaldehyde-fixed cadaveric upper limbs of Indian origins were dissected to observe the number of EPB tendons and its variations. Results: The EPB muscle was found to be absent in one hand (1.3%). The EPB muscle was found with single tendon, two tendons and three tendons in 73 limbs (94.8%), 2 limbs (2.6%) and one limb (1.3%) respectively. The muscle originated from the posterior surface of the radius and the adjacent interosseous membrane. The EPB muscle with single tendon was found to be inserted into the distal part of dorsal surface of the proximal phalanx of the thumb in 44 limbs (57.1%). In limbs with bitendinous EPB, the tendon slips were inserted into the base of proximal phalanx and into the base of distal phalanx of the thumb. An Osseo-fibrous septum separating EPB from Abductor Pollicis Longus (APL) was observed in 45 limbs (58%). Conclusion: EPB in first extensor compartment of Indians is usually monotendinous. It mostly inserts into the distal part of dorsal surface of proximal phalanx of thumb and into the base of distal phalanx. In majority of the wrists, one may find an osseofibrous ridge separating EPB from APL. These anatomical variations may be helpful to guide proper treatment in de Quervain's tenosynovitis.

Congenital accessory spleen or splenunculi is a small mass of splenic tissue that failed to fuse with the primary spleen during embryogenesis. The overall prevalence of splenunculus in 14.5% in the literature. Splenunculus is usually asymptomatic in most of the individuals and diagnosed incidentally during the abdominal imaging, laparotomy or necropsy. Rarely it might present as an acute abdomen in case of torsion or infract. Few cases of malignant changes in the accessory spleen are also reported. Surgeons need to be aware of such small masses of splenic tissue during splenectomy, if they are left unnoticed after total splenectomy, it may lead to the recurrence of hematological disorders. In the present case report, the authors described an isolated, solitary splenunculus in a 55 years old male cadaver found during dissection. KEY WORDS: Accessory spleen, Splenunculi, Splenectomy, Splenosis, Torsion.