Representation by Gender of Recognition Award Recipients from Gastroenterology and Hepatology Professional Societies.

Background: Recognition awards from professional medical societies play an important role in physicians' career advancement. Our aim was to evaluate the gender representation of award recipients from gastroenterology and hepatology societies. Methods: We analyzed the lists of award recipients from the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy and determined the gender of these award recipients. The primary outcome was the overall representation of women physician award recipients as compared with the representation of women in the specialty. Results: Between 1941 and 2019, there were 921 awards, of which 77 (8.4%) were given to women and 844 (91.6%) to men. There was a significant increase in the proportion of women recipients over time, from 0% in 1970-1984 to 22.0% in 2015-2019 (p for trend <0.0001). Compared with the concurrent representation of women in the specialty, women physician recipients were underrepresented from 1970 to 1981 and 1984 to 2015, equitably represented from 1981 to 1984, and overrepresented from 2015 to 2019. Of the total number of awards in each category, women received 13.8% of teaching/mentorship awards and 3.8% of the highest achievement awards (p = 0.002). The proportion of women recipients varied among the societies, from 6.8% to 14.5%. Conclusions: The representation of women physician recipients of gastroenterology and hepatology society recognition awards has generally been low until most recently, when it has surpassed the proportion of women in the specialty. Because award recognition is important to career development, professional societies should have transparent processes that aim to identify and reduce various forms of bias, including gender-related bias, in all phases of award recognition.

Oxidative stress disrupts purinergic neuromuscular transmission in the inflamed colon.

Colitis, induced by trinitrobenzene sulfonic acid (TNBS) in guinea pig, leads to decreased purinergic neuromuscular transmission resulting in a reduction in inhibitory junction potentials (IJPs) in colonic circular muscle. We explored possible mechanisms responsible for this inflammation-induced neurotransmitter plasticity. Previous studies have suggested that the deficit in inflamed tissue involves decreased ATP release. We therefore hypothesized that decreased purinergic transmission results from inflammation-induced free radical damage to mitochondria, leading to decreased purine synthesis and release. Stimulus-induced release of purines was measured using high-performance liquid chromatography, and quantities of all purines measured were significantly reduced in the inflamed colons as compared to controls. To test whether decreased mitochondrial function affects the IJP, colonic muscularis preparations were treated with the mitochondrial ATP synthase inhibitors oligomycin or dicyclohexylcarbodiimide, which resulted in a significant reduction of IJP amplitude. Induction of oxidative stress in vitro, by addition of H2O2 to the preparation, also significantly reduced IJP amplitude. Purinergic neuromuscular transmission was significantly restored in TNBS-inflamed guinea pigs, and in dextran sodium sulfate-inflamed mice, treated with a free radical scavenger. Furthermore, propulsive motility in the distal colons of guinea pigs with TNBS colitis was improved by in vivo treatment with the free radical scavenger. We conclude that oxidative stress contributes to the reduction in purinergic neuromuscular transmission measured in animal models of colitis, and that these changes can be prevented by treatment with a free radical scavenger, resulting in improved motility.

The roles of purinergic signaling during gastrointestinal inflammation.

Extracellular purines play important roles as neurotransmitters and paracrine mediators in the gastrointestinal (GI) tract. Inflammation of the GI tract causes marked changes in the release and extracellular catabolism of purines, and can modulate purinoceptor expression and/or signaling. The functional consequences of this include suppression of the purinergic component of inhibitory neuromuscular and neurovascular transmission, increased release of purines from immune and epithelial cells, loss of enteric neurons to damage through P2X(7) purinoceptors, and enhanced activation of pain fibres. The purinergic system represents an important target for drug therapies that may improve GI inflammation and its consequences.

Activation of neuronal P2X7 receptor-pannexin-1 mediates death of enteric neurons during colitis.

Inflammatory bowel diseases (IBDs) are chronic relapsing and remitting conditions associated with long-term gut dysfunction resulting from alterations to the enteric nervous system and a loss of enteric neurons. The mechanisms underlying inflammation-induced enteric neuron death are unknown. Here using in vivo models of experimental colitis we report that inflammation causes enteric neuron death by activating a neuronal signaling complex composed of P2X7 receptors (P2X7Rs), pannexin-1 (Panx1) channels, the Asc adaptor protein and caspases. Inhibition of P2X7R, Panx1, Asc or caspase activity prevented inflammation-induced neuron cell death. Preservation of enteric neurons by inhibiting Panx1 in vivo prevented the onset of inflammation-induced colonic motor dysfunction. Panx1 expression was reduced in Crohn's disease but not ulcerative colitis. We conclude that activation of neuronal Panx1 underlies neuron death and the subsequent development of abnormal gut motility in IBD. Targeting Panx1 represents a new neuroprotective strategy to ameliorate the progression of IBD-associated dysmotility.

Purinergic neuromuscular transmission is selectively attenuated in ulcerated regions of inflamed guinea pig distal colon.

This study was undertaken to investigate neuromuscular transmission in regions of the inflamed colon in which motility is disrupted. Propulsive motility was evaluated in segments of control guinea pigs and those treated 6 days previously with trinitrobenzene sulfonic acid. Intracellular recordings were then obtained from circular muscle cells to examine excitatory and inhibitory junction potentials (EJPs and IJPs). In inflamed preparations, propulsion of fecal pellets was temporarily halted or obstructed at sites of mucosal damage, whereas the propulsive motility was linear in control colons. The amplitudes of evoked and spontaneous IJPs were significantly reduced in ulcerated regions of inflamed preparations, but EJPs were comparable to controls. Pharmacological dissection of the IJP revealed that the purinergic component was reduced, while the nitrergic IJP was slightly increased. Furthermore, the reduction in the purinergic IJP in inflamed preparations persisted in the presence of hexamethonium, suggesting that the deficit involved the inhibitory motor neuron and/or smooth muscle. Nerve fibre density was not altered in the circular muscle, and pre-contracted rings of inflamed colon relaxed normally to ATP, suggesting that the deficit involves altered ATP release and/or degradation. The P2Y(1) receptor antagonist MRS2179 slowed propulsive motility indicating that decreased purinergic neuromuscular transmission could contribute to the inflammation-induced motor deficit. We conclude that purinergic inhibitory neuronal input to the circular muscle is selectively reduced in regions of the colon in experimental colitis where the mucosa is damaged, and this is likely to contribute to altered motility in colitis by diminishing downstream relaxation during the peristaltic reflex.

Multimodality treatment of trigeminal neuralgia.

Most trigeminal neuralgia (TN) studies focus on a single strategy, microvascular decompression (MVD) or percutaneous rhizotomy (PR). We use a multimodality approach to TN. We perform MVD on patients younger than 70 years and PR on older patients or those where MVD has failed. We performed a chart review of the procedures for TN over the past 3 years and used a questionnaire for long-term follow-up. The questionnaire asked patients to rate their pre- and postoperative pain, outcome, and medication changes. Seventy-four procedures (40 MVDs and 34 PRs) were performed on 67 patients. Twenty patients had undergone previous procedures. 93% of the patients had significant initial pain relief. Over a 1.2-year mean follow-up, 51% of the patients had complete pain relief while 27% had a substantial improvement. There were no deaths and 5 complications. Our results suggest that a multimodality approach to TN yields excellent results with minimal complications.