Analysis of Pre-clerkship Medical Students' Perceptions and Performance During the COVID-19 Pandemic.

Purpose: Virtual instruction became the primary educational delivery method for pre-clerkship medical students during the COVID-19 pandemic. The aims of this study were to evaluate the effectiveness of a virtual and blended pre-clerkship curriculum and to assess its impact on students.

Methods: We surveyed 223 1st- and 2nd-year medical students (MS1s and MS2s) enrolled at the Paul L Foster School of Medicine.

Necrotizing enterocolitis induces T lymphocyte-mediated injury in the developing mammalian brain.

Necrotizing enterocolitis (NEC) causes acute intestinal necrosis in premature infants and is associated with severe neurological impairment. In NEC, Toll-like receptor 4 is activated in the intestinal epithelium, and NEC-associated brain injury is characterized by microglial activation and white matter loss through mechanisms that remain unclear. We now show that the brains of mice and humans with NEC contained CD4 T lymphocytes that were required for the development of brain injury.

The human milk oligosaccharides 2'-fucosyllactose and 6'-sialyllactose protect against the development of necrotizing enterocolitis by inhibiting toll-like receptor 4 signaling.

Background: Necrotizing enterocolitis (NEC) develops through exaggerated toll-like receptor 4 (TLR4) signaling in the intestinal epithelium. Breast milk is rich in non-digestible oligosaccharides and prevents NEC through unclear mechanisms. We now hypothesize that the human milk oligosaccharides 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL) can reduce NEC through inhibition of TLR4 signaling.

Cognitive impairments induced by necrotizing enterocolitis can be prevented by inhibiting microglial activation in mouse brain.

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease of the premature infant. One of the most important long-term complications observed in children who survive NEC early in life is the development of profound neurological impairments. However, the pathways leading to NEC-associated neurological impairments remain unknown, thus limiting the development of prevention strategies.

Early detection of necrotizing enterocolitis using broadband optical spectroscopy.

Purpose: The definitive diagnosis of necrotizing enterocolitis (NEC) is typically at an advanced stage, indicating the need for sensitive and noninvasive diagnostic modalities. Near infrared spectroscopy (NIRS) has been utilized to noninvasively measure intraabdominal tissue oxygenation and to diagnose NEC, but specificity is lacking, in part because sensors are limited to a narrow band of the electromagnetic spectrum. Here, we introduce the concept of broadband optical spectroscopy (BOS) as a noninvasive method to characterize NEC.

Myocardial oxidative stress correlates with left ventricular dysfunction on strain echocardiography in a rodent model of sepsis.

Background: Recognition of cardiomyopathy in sepsis can be challenging due to the limitations of conventional measures such as ejection fraction (EF) and fractional shortening (FS) in the context of variable preload and afterload conditions. This study correlates myocardial function using strain echocardiography (SE) with cardiomyocyte oxidative stress in a murine model of sepsis.

Methods: C57BL/6J mice were randomized into control (n = 10), sham (n = 25), and a cecal ligation and puncture (CLP) (n = 33) model of sepsis.

The human milk oligosaccharide 2'-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine.

Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2'-fucosyllactose (2'FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection.

Necrotizing enterocolitis: new insights into pathogenesis and mechanisms.

Necrotizing enterocolitis (NEC) is the most frequent and lethal disease of the gastrointestinal tract of preterm infants. At present, NEC is thought to develop in the premature host in the setting of bacterial colonization, often after administration of non-breast milk feeds, and disease onset is thought to be due in part to a baseline increased reactivity of the premature intestinal mucosa to microbial ligands as compared with the full-term intestinal mucosa. The increased reactivity leads to mucosal destruction and impaired mesenteric perfusion and partly reflects an increased expression of the bacterial receptor Toll-like receptor 4 (TLR4) in the premature gut, as well as other factors that predispose the intestine to a hyper-reactive state in response to colonizing microorganisms.

Retinoic Acid Improves Incidence and Severity of Necrotizing Enterocolitis by Lymphocyte Balance Restitution and Repopulation of LGR5+ Intestinal Stem Cells.

Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal disease of the premature infant. We have recently shown that NEC development occurs after an increase in proinflammatory CD4Th17 (Th17) cells and reduced anti-inflammatory forkhead box P3 regulatory T cells (Tregs) to the premature small intestine of mice and humans, which can be experimentally reversed in mice by administration of all-trans retinoic acid (ATRA). We have also shown that NEC is characterized by apoptosis of Lgr5-positive intestinal stem cells (ISCs-Lgr5 cells) within the crypts of Lieberkühn, which are subsequently essential for intestinal homeostasis.

Pulmonary Epithelial TLR4 Activation Leads to Lung Injury in Neonatal Necrotizing Enterocolitis.

We seek to define the mechanisms leading to the development of lung disease in the setting of neonatal necrotizing enterocolitis (NEC), a life-threatening gastrointestinal disease of premature infants characterized by the sudden onset of intestinal necrosis. NEC development in mice requires activation of the LPS receptor TLR4 on the intestinal epithelium, through its effects on modulating epithelial injury and repair. Although NEC-associated lung injury is more severe than the lung injury that occurs in premature infants without NEC, the mechanisms leading to its development remain unknown.

Generation of an artificial intestine for the management of short bowel syndrome.

Purpose Of Review: This article discusses the current state of the art in artificial intestine generation in the treatment of short bowel syndrome.

Recent Findings: Short bowel syndrome defines the condition in which patients lack sufficient intestinal length to allow for adequate absorption of nutrition and fluids, and thus need parenteral support. Advances toward the development of an artificial intestine have improved dramatically since the first attempts in the 1980s, and the last decade has seen significant advances in understanding the intestinal stem cell niche, the growth of complex primary intestinal stem cells in culture, and fabrication of the biomaterials that can support the growth and differentiation of these stem cells.

Toll-like receptor 4-mediated lymphocyte influx induces neonatal necrotizing enterocolitis.

The nature and role of the intestinal leukocytes in necrotizing enterocolitis (NEC), a severe disease affecting premature infants, remain unknown. We now show that the intestine in mouse and human NEC is rich in lymphocytes that are required for NEC development, as recombination activating gene 1–deficient (Rag1–/–) mice were protected from NEC and transfer of intestinal lymphocytes from NEC mice into naive mice induced intestinal inflammation. The intestinal expression of the lipopolysaccharide receptor TLR4, which is higher in the premature compared with full-term human and mouse intestine, is required for lymphocyte influx through TLR4-mediated upregulation of CCR9/CCL25 signaling.

Endoscopic revision of gastric bypass: Holy Grail or Epic fail?

Background: Approximately 20-30 % of patients who undergo Roux-en-Y gastric bypass (RYGB) will not meet the goals of weight loss surgery. Revisional surgery is associated with higher morbidity compared to initial operative management, and results in terms of weight loss have been inconsistent. Endoscopic plication has been seen as a less invasive option, with encouraging initial results.

Laparo-endoscopic transgastric resection of gastric submucosal tumors.

Background: Laparoscopic and endoluminal surgical techniques have evolved and allowed improvements in the methods for treating benign and malignant gastrointestinal diseases. To date, only case reports have been reported on the application of a laparo-endoscopic approach for resecting gastric submucosal tumors (SMT). In this study, we aimed to evaluate the efficacy, safety, and oncologic outcomes of a laparo-endoscopic transgastric approach to resect tumors that would traditionally require either a laparoscopic or open surgical approach.

Sustained expression of lipocalin-2 during polymicrobial sepsis.

Sepsis is a major healthcare problem and a leading cause of death worldwide. There is no dependable diagnosis, and treatment for this condition remains mainly supportive. The etiology of sepsis is related to an overwhelming inflammatory response.

Itraconazole, a commonly used antifungal, inhibits Fcγ receptor-mediated phagocytosis: alteration of Fcγ receptor glycosylation and gene expression.

Itraconazole (ICZ) is commonly used for the treatment of fungal infections, particularly in immunocompromised patients. In addition, ICZ has been recently found to have antiangiogenic effects and is currently being tested as a new chemotherapeutic agent in several cancer clinical trials. We have previously shown that ICZ impaired complex N-linked glycosylation processing, leading to the accumulation of high-mannose glycoproteins on the surface of macrophages (Møs).

Deletion of scavenger receptor A gene in mice resulted in protection from septic shock and modulation of TLR4 signaling in isolated peritoneal macrophages.

Scavenger receptor A (Sra), also known as macrophage scavenger receptor 1 (Msr1), is a surface glycoprotein preferentially present in macrophages that plays a primary role in innate immunity. Previous studies have shown that Sra is a modifier gene for the response to bacterial LPS in mice at the level of IL-10 production, in particular. In the present study, we found that Sra(-/-) mice are more resistant to septic shock induced by cecal ligation and puncture than wild-type C57BL/6 J (B6) mice.

Acute acalculous cholecystitis-like phenotype in scavenger receptor A knock-out mice.

Background: Sepsis is a major health problem in the United States that affects more than three-quarters of a million people every year. Previous studies have shown that scavenger receptor A (Sra), also known as macrophage scavenger receptor 1 (Msr1), is a modifier of interleukin 10 (IL-10) expression after injection of bacterial lipopolysaccharide (LPS). Therefore, we investigated the response to sepsis in Sra knock out mice.