Small Bowel Resection Increases Paracellular Gut Barrier Permeability via Alterations of Tight Junction Complexes Mediated by Intestinal TLR4.

Background: Short bowel syndrome resulting from small bowel resection (SBR) is associated with significant morbidity and mortality. Many adverse sequelae including steatohepatitis and bacterial overgrowth are thought to be related to increased bacterial translocation, suggesting alterations in gut permeability. We hypothesized that after intestinal resection, the intestinal barrier is altered via toll-like receptor 4 (TLR4) signaling at the intestinal level.

EGFR in enterocytes & endothelium and HIF1α in enterocytes are dispensable for massive small bowel resection induced angiogenesis.

Background: Short bowel syndrome (SBS) results from significant loss of small intestinal length. In response to this loss, adaptation occurs, with Epidermal Growth Factor Receptor (EGFR) being a key driver. Besides enhanced enterocyte proliferation, we have revealed that adaptation is associated with angiogenesis.

Adaptation of extracellular matrix to massive small bowel resection in mice.

Background: Extracellular matrix (ECM) affects cell behavior, and vice versa. How ECM changes after small bowel resection (SBR) to support adaptive cellular processes has not been described. Here we characterize changes in ECM following SBR and integrate this with concomitant transcriptional perturbations.

Patient-derived small intestinal myofibroblasts direct perfused, physiologically responsive capillary development in a microfluidic Gut-on-a-Chip Model.

The development and physiologic role of small intestine (SI) vasculature is poorly studied. This is partly due to a lack of targetable, organ-specific markers for in vivo studies of two critical tissue components: endothelium and stroma. This challenge is exacerbated by limitations of traditional cell culture techniques, which fail to recapitulate mechanobiologic stimuli known to affect vessel development.

Are surgeons behind the scientific eight ball: Delayed acquisition of the NIH K08 mentored career development award.

Background: Surgery residents complete their research training early in residency. Non-surgical trainees typically have research incorporated toward the last two years of their fellowship, conferring an advantage to apply for grants with recent research experience and preliminary data.

Methods: The NIH RePORTER database was queried for K08 awardees trained in medicine, pediatrics, and surgery from 2013 to 2017.

Single-Cell Analysis Reveals Regional Reprogramming During Adaptation to Massive Small Bowel Resection in Mice.

Background & Aims: The small intestine (SI) displays regionality in nutrient and immunological function. Following SI tissue loss (as occurs in short gut syndrome, or SGS), remaining SI must compensate, or "adapt"; the capacity of SI epithelium to reprogram its regional identity has not been described. Here, we apply single-cell resolution analyses to characterize molecular changes underpinning adaptation to SGS.

Lymphatic network remodeling after small bowel resection.

Background: Short gut syndrome (SGS) following massive small bowel resection (SBR) is a major cause of pediatric mortality and morbidity secondary to nutritional deficiencies and the sequelae of chronic total parenteral nutrition use, including liver steatosis. Despite the importance of lymphatic vasculature in fat absorption, lymphatic response after SBR has not been studied. We hypothesize that lymphatic vessel integrity is compromised in SGS, potentially contributing to the development of impaired lipid transport leading to liver steatosis and metabolic disease.

Assessing gender bias in qualitative evaluations of surgical residents.

Background: There are notable disparities in the training, recruitment, promotion, and evaluation of men and women in surgery. The qualitative assessment of surgical residents may be implicitly gender biased.

Methods: We used inductive analysis to identify themes in written evaluations of residents.

Tissue underlying the intestinal epithelium elicits proliferation of intestinal stem cells following cytotoxic damage.

The goals of this study were to document the proliferative response of intestinal stem cells (ISCs) during regeneration after damage from doxorubicin (DXR), and to characterize the signals responsible for ISC activation. To this end, jejuni from DXR-treated mice were harvested for histology, assessment of ISC numbers and proliferation by flow cytometry, crypt culture, and RNA analyses. Histology showed that crypt depth and width were increased 4 days after DXR.

Side population sorting separates subfractions of cycling and non-cycling intestinal stem cells.

We report here that side population (SP) sorting allows for the simultaneous isolation of two intestinal stem cell (ISC) subsets from wild-type (WT) mice which are phenotypically different and represent cycling and non-cycling pools of cells. Following 5-ethynyl-2'-deoxyuridine (EdU) injection, in the upper side population (USP) the percentage of EdU+ was 36% showing this fraction to be highly proliferative. In the lower side population (LSP), only 0.