Challenges and Opportunities in the Elective Management of Diverticulitis: Perspectives From a National Sample of Colorectal Surgeons.

Background: Diverticulitis is a complex, heterogeneous disease process that affects a diverse population of patients. In the elective management of this disease, treatment guidelines have shifted toward patient-centered, individualized decision-making. It is not known what challenges surgeons face as they approach these nuanced treatment decisions in practice.

Fibroblast activation in response to TGFβ1 is modulated by co-culture with endothelial cells in a vascular organ-on-chip platform.

Tissue fibrosis is a major healthcare burden that affects various organs in the body for which no effective treatments exist. An underlying, emerging theme across organs and tissue types at early stages of fibrosis is the activation of pericytes and/or fibroblasts in the perivascular space. In hepatic tissue, it is well known that liver sinusoidal endothelial cells (EC) help maintain the quiescence of stellate cells, but whether this phenomenon holds true for other endothelial and perivascular cell types is not well studied.

Proteomic Profiling of Fallopian Tube-Derived Extracellular Vesicles Using a Microfluidic Tissue-on-Chip System.

The human fallopian tube epithelium (hFTE) is the site of fertilization, early embryo development, and the origin of most high-grade serous ovarian cancers (HGSOCs). Little is known about the content and functions of hFTE-derived small extracellular vesicles (sEVs) due to the limitations of biomaterials and proper culture methods. We have established a microfluidic platform to culture hFTE for EV collection with adequate yield for mass spectrometry-based proteomic profiling, and reported 295 common hFTE sEV proteins for the first time.

Increased Local Testosterone Levels Alter Human Fallopian Tube mRNA Profile and Signaling.

Fallopian tube epithelium (FTE) plays a critical role in reproduction and can be the site where High Grade Serous Ovarian Carcinoma (HGSOC) originates. Tumorigenic oviductal cells, which are the murine equivalent of human fallopian tube secretory epithelial cells (FTSEC), enhance testosterone secretion by the ovary when co-cultured with the ovary, suggesting that testosterone is part of the signaling axis between the ovary and FTSEC. Furthermore, testosterone promotes proliferation of oviductal cells.

Aldosterone: Renal Action and Physiological Effects.

Aldosterone exerts profound effects on renal and cardiovascular physiology. In the kidney, aldosterone acts to preserve electrolyte and acid-base balance in response to changes in dietary sodium (Na ) or potassium (K ) intake. These physiological actions, principally through activation of mineralocorticoid receptors (MRs), have important effects particularly in patients with renal and cardiovascular disease as demonstrated by multiple clinical trials.

Surgical Trainee Perspectives on the Opioid Crisis: The Influence of Explicit and Hidden Curricula.

Objective: In order to effectively create and implement an educational program to improve opioid prescribing practices, it is important to first consider the unique perspectives of residents on the frontlines of the opioid epidemic. We sought to better understand resident perspectives on opioid prescribing, current practices in pain management, and opioid education as a needs assessment for designing future educational interventions.

Design: This is a qualitative study using focus groups of surgical residents at 4 different institutions.

A high-throughput, 28-day, microfluidic model of gingival tissue inflammation and recovery.

Nearly half of American adults suffer from gum disease, including mild inflammation of gingival tissue, known as gingivitis. Currently, advances in therapeutic treatments are hampered by a lack of mechanistic understanding of disease progression in physiologically relevant vascularized tissues. To address this, we present a high-throughput microfluidic organ-on-chip model of human gingival tissue containing keratinocytes, fibroblast and endothelial cells.

The Influence of Rural Healthcare Systems and Communities on Surgery and Recovery: A Qualitative Study.

Introduction: Successful recovery after surgery is complex and highly individual. Rural patients encounter greater barriers to successful surgical recovery than urban patients due to varying healthcare and community factors. Although studies have previously examined the recovery process, rural patients' experiences with recovery have not been well-studied.

Versican secreted by the ovary links ovulation and migration in fallopian tube derived serous cancer.

High grade serous ovarian cancers (HGSOC) predominantly arise in the fallopian tube epithelium (FTE) and colonize the ovary first, before further metastasis to the peritoneum. Ovarian cancer risk is directly related to the number of ovulations, suggesting that the ovary may secrete specific factors that act as chemoattractants for fallopian tube derived tumor cells during ovulation. We found that 3D ovarian organ culture produced a secreted factor that enhanced the migration of FTE non-tumorigenic cells as well as cells harboring specific pathway modifications commonly found in high grade serous cancers.

Socioeconomic disadvantage is associated with greater mortality after high-risk emergency general surgery.

Background: Socioeconomic disadvantage is associated with worse outcomes after elective surgery, but the effect on emergency general surgery (EGS) remains unclear. We examined the association of socioeconomic disadvantage and outcomes after EGS procedures and investigated whether admission to hospitals with comprehensive clinical and social resources mitigated this effect.

Methods: Adults undergoing 1 of the 10 most burdensome high- and low-risk EGS procedures were identified in six 2014 State Inpatient Databases.

Use of post-discharge opioid consumption patterns as a tool for evaluating opioid prescribing guidelines.

Background: Leftover pills from postoperative opioid prescriptions place patients and members of their communities at risk for opioid misuse. We aimed to better understand patients' post-discharge opioid consumption patterns to inform new methods of postoperative opioid prescribing.

Methods: We assessed post-discharge opioid consumption of general surgery patients and assessed the adequacy of discharge opioid prescriptions.

A high-throughput microfluidic bilayer co-culture platform to study endothelial-pericyte interactions.

Microphysiological organ-on-chip models offer the potential to improve the prediction of drug safety and efficacy through recapitulation of human physiological responses. The importance of including multiple cell types within tissue models has been well documented. However, the study of cell interactions in vitro can be limited by complexity of the tissue model and throughput of current culture systems.

Benign Colonic Strictures.

A 46-year-old man with no significant medical or surgical history presented to the emergency department with a 1-week history of worsening constipation, abdominal distension, nausea, and nonbloody, nonbilious emesis. Workup included a CT scan that was notable for a 5.3 × 3.

Correction: A high-throughput microfluidic microphysiological system (PREDICT-96) to recapitulate hepatocyte function in dynamic, re-circulating flow conditions.

Correction for 'A high-throughput microfluidic microphysiological system (PREDICT-96) to recapitulate hepatocyte function in dynamic, re-circulating flow conditions' by Kelly Tan et al., Lab Chip, 2019, 19, 1556-1566, DOI: .

Knockout of the circadian clock protein PER1 results in sex-dependent alterations of ET-1 production in mice in response to a high-salt diet plus mineralocorticoid treatment.

Previously, we showed that global knockout (KO) of the circadian clock transcription factor PER1 in male, but not female, mice fed a high-salt diet plus mineralocorticoid treatment (HS/DOCP) resulted in nondipping hypertension and decreased night/day ratio of sodium (Na) excretion. Additionally, we have shown that the endothelin-1 (ET-1) gene is targeted by both PER1 and aldosterone. We hypothesized that ET-1 would exhibit a sex-specific response to HS/DOCP treatment in PER1 KO.

, A Novel Long Non-coding RNA Regulating Endothelin-1 in Human Proximal Tubule Cells.

Endothelin-1 (ET-1) is a peptide hormone that functions as a vasoconstrictor in the vasculature, whereas in the collecting duct of the kidney it exerts blood pressure-lowering effects via natriuretic actions. Aberrant ET-1 signaling is associated with several pathological states including hypertension and chronic kidney disease. ET-1 expression is regulated largely through transcriptional control of the gene that encodes ET-1, .

A thermoplastic microfluidic microphysiological system to recapitulate hepatic function and multicellular interactions.

Hepatic in vitro platforms ranging from multi-well cultures to bioreactors and microscale systems have been developed as tools to recapitulate cellular function and responses to aid in drug screening and disease model development. Recent developments in microfabrication techniques and cellular materials enabled fabrication of next-generation, advanced microphysiological systems (MPSs) that aim to capture the cellular complexity and dynamic nature of the organ presenting highly controlled extracellular cues to cells in a physiologically relevant context. Historically, MPSs have heavily relied on elastomeric materials in their manufacture, with unfavorable material characteristics (such as lack of structural rigidity) limiting their use in high-throughput systems.

Female C57BL/6J mice lacking the circadian clock protein PER1 are protected from nondipping hypertension.

The circadian clock is integral to the maintenance of daily rhythms of many physiological outputs, including blood pressure. Our laboratory has previously demonstrated the importance of the clock protein period 1 (PER1) in blood pressure regulation in male mice. Briefly, a high-salt diet (HS; 4% NaCl) plus injection with the long-acting mineralocorticoid deoxycorticosterone pivalate (DOCP) resulted in nondipping hypertension [<10% difference between night and day blood pressure (BP) in Per1-knockout (KO) mice but not in wild-type (WT) mice].

Repair of Enlarging Left Ventricular Pseudoaneurysm Two Months After Coronary Artery Bypass Grafting.

Enlarging left ventricular pseudoaneurysms are a rare complication (especially after surgical revascularization) and require tailored surgical decision making and techniques for repair. We present a challenging patient with a rapidly enlarging left ventricular pseudoaneurysm 4 weeks after coronary bypass. The repair was approached through a left thoracotomy using circulatory arrest with selective antegrade cerebral perfusion.

Renal Na-handling defect associated with PER1-dependent nondipping hypertension in male mice.

Many physiological functions have a circadian rhythm, including blood pressure (BP). BP is highest during the active phase, whereas during the rest period, BP dips 10-20%. Patients that do not experience this dip at night are termed "nondippers.

Aldosterone alters the chromatin structure of the murine endothelin-1 gene.

Unlabelled: Aldosterone increases sodium reabsorption in the renal collecting duct and systemic blood pressure. Paradoxically, aldosterone also induces transcription of the endothelin-1 (Edn1) gene to increase protein (ET-1) levels, which inhibits sodium reabsorption.

Aims: Here we investigated changes in the chromatin structure of the Edn1 gene of collecting duct cell lines in response to aldosterone treatment.

Permanent Pacemaker Implantation Early After Cardiac Surgery: A Descriptive Study of Pacemaker Utility After One Year of Follow-Up.

Background: Complete heart block (CHB) is a common complication of cardiac surgery, which may resolve spontaneously. The optimal number of days to wait for resolution of CHB prior to proceeding with a permanent pacemaker (PPM) and the long-term utility of PPMs placed in this setting remain uncertain.

Methods And Results: This was a retrospective cohort study, which included members of Kaiser Permanente Northern California who had cardiac surgery, a PPM placed within 30 days after surgery, and one year of follow-up time.

Effect of mineralocorticoid treatment in mice with collecting duct-specific knockout of endothelin-1.

Aldosterone increases blood pressure (BP) by stimulating sodium (Na) reabsorption within the distal nephron and collecting duct (CD). Aldosterone also stimulates endothelin-1 (ET-1) production that acts within the CD to inhibit Na reabsorption via a negative feedback mechanism. We tested the hypothesis that this renal aldosterone-endothelin feedback system regulates electrolyte balance and BP by comparing the effect of a high-salt (NaCl) diet and mineralocorticoid stimulation in control and CD-specific ET-1 knockout (CD ET-1 KO) mice.

Expansion of Simian Immunodeficiency Virus (SIV)-Specific CD8 T Cell Lines from SIV-Naive Mauritian Cynomolgus Macaques for Adoptive Transfer.

Unlabelled: CD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). However, the specific qualities and characteristics of an effective CD8 T cell response remain unclear. Although targeting breadth, cross-reactivity, polyfunctionality, avidity, and specificity are correlated with HIV control, further investigation is needed to determine the precise contributions of these various attributes to CD8 T cell efficacy.

Whole genome sequencing of SIV-infected macaques identifies candidate loci that may contribute to host control of virus replication.

Background: A small percentage of human immunodeficiency virus (HIV)-infected people and simian immunodeficiency virus (SIV)-infected macaques control virus replication without antiretroviral treatment. The major determinant of this control is host expression of certain major histocompatibility complex alleles. However, this association is incompletely penetrant, suggesting that additional loci modify the major histocompatibility complex's protective effect.