The value of medical shadowing for high school students: A three-dimensional view.

Medical shadowing helps provide clinical exposure to aspiring and current medical students, mainly at the college level. This paper makes a case for making medical shadowing opportunities more widely available for high school students. Through the who got such an opportunity, we demonstrate that high school students can gain valuable clinical knowledge and exposure to the ethics involved in patient care, inspiring them to explore further pathways that will help them make better-informed academic and career choices.

Shotgun metagenomic sequencing on skin microbiome indicates dysbiosis exists prior to the onset of atopic dermatitis.

Background: While the microbiome is increasingly seen as a targetable contributor to atopic dermatitis (AD), questions remain as to whether the dysbiosis is secondary to diseased skin or if it predates symptom onset. Previous work has evaluated how the skin microbiome changes with age and established the influence of factors like delivery mode and breastfeeding on global microbiome diversity. However, these studies were unable to identify taxa which predict subsequent AD.

Fecal sphingolipids predict parenteral nutrition-associated cholestasis in the neonatal intensive care unit.

Background: Parenteral nutrition-associated cholestasis (PNAC) in the neonatal intensive care unit (NICU) causes significant morbidity and associated healthcare costs. Laboratory detection of PNAC currently relies on elevated serum conjugated bilirubin levels in the aftermath of impaired bile flow. Here, we sought to identify fecal biomarkers, which when integrated with clinical data, would better predict risk for developing PNAC.

Prenatal and Peripartum Exposure to Antibiotics and Cesarean Section Delivery Are Associated with Differences in Diversity and Composition of the Infant Meconium Microbiome.

The meconium microbiome may provide insight into intrauterine and peripartum exposures and the very earliest intestinal pioneering microbes. Prenatal antibiotics have been associated with later obesity in children, which is thought to be driven by microbiome dependent mechanisms. However, there is little data regarding associations of prenatal or peripartum antibiotic exposure, with or without cesarean section (CS), with the features of the meconium microbiome.

Gram-negative Microbiota Blooms in Premature Twins Discordant for Parenteral Nutrition-associated Cholestasis.

Parenteral nutrition-associated cholestasis (PNAC) causes serious morbidity in the neonatal intensive care unit. Infection with gut-associated bacteria is associated with cholestasis, but the role of intestinal microbiota in PNAC is poorly understood. We examined the composition of stool microbiota from premature twins discordant for PNAC as a strategy to reduce confounding from variables associated with both microbiota and cholestasis.

Genomic and molecular characterization of preterm birth.

Preterm birth (PTB) complications are the leading cause of long-term morbidity and mortality in children. By using whole blood samples, we integrated whole-genome sequencing (WGS), RNA sequencing (RNA-seq), and DNA methylation data for 270 PTB and 521 control families. We analyzed this combined dataset to identify genomic variants associated with PTB and secondary analyses to identify variants associated with very early PTB (VEPTB) as well as other subcategories of disease that may contribute to PTB.

Comparison of Infant Gut and Skin Microbiota, Resistome and Virulome Between Neonatal Intensive Care Unit (NICU) Environments.

There is a growing move to provide care for premature infants in a single family, private room neonatal intensive care unit (NICU) in place of the traditional shared space, open bay NICU. The resultant effect on the developing neonatal microbiota is unknown. Stool and groin skin swabs were collected from infants in a shared-space NICU (old NICU) and a single-family room NICU (new NICU) on the same hospital campus.

Experience with genomic sequencing in pediatric patients with congenital cardiac defects in a large community hospital.

Background: Congenital cardiac defects, whether isolated or as part of a larger syndrome, are the most common type of human birth defect occurring on average in about 1% of live births depending on the malformation. As there is an expanding understanding of the underlying molecular mechanisms by which a cardiac defect may occur, there is a need to assess the current rates of diagnosis of cardiac defects by molecular sequencing in a clinical setting.

Methods And Results: In this report, we evaluated 34 neonatal and pediatric patients born with a cardiac defect and their parents using exomized preexisting whole genome sequencing (WGS) data to model clinically available exon-based tests.

The Microbiome in Necrotizing Enterocolitis: A Case Report in Twins and Minireview.

Our case describes the serial microbiome changes in twins discordant for necrotizing enterocolitis (NEC), who shared similar intrauterine and early environmental exposures. The key findings were that the 2 neonates had distinctly different microbiome compositions from the first stool samples collected. Also, in the twin who developed NEC there was a decrease in bacterial diversity and an increase in Proteobacteria a week before developing any clinical symptoms, suggesting an early role of the intestinal microbiome in the development of NEC.

Diagnosis of D-Bifunctional Protein Deficiency through Whole-Genome Sequencing: Implications for Cost-Effective Care.

D-Bifunctional protein deficiency, caused by recessive mutations in HSD17B4, is a severe disorder of peroxisomal fatty acid oxidation. Nonspecific clinical features may contribute to diagnostic challenges. We describe a newborn female with infantile-onset seizures and nonspecific mild dysmorphisms who underwent extensive genetic workup that resulted in the detection of a novel homozygous mutation (c.

Neuropsychological Outcomes in Extremely Preterm Preschoolers Exposed to Tiered Low Oxygen Targets: An Observational Study.

An observational study of neuropsychological outcomes at preschool age of tiered lowered oxygen (O2) saturation targets in extremely preterm neonates. We studied 111 three-year-olds born <28 weeks' gestational age. Fifty-nine participants born in 2009-2010 during a time-limited quality improvement initiative each received three-tiered stratification of oxygen rates (83-93% until age 32 weeks, 85-95% until age 35 weeks, and 95% after age 35 weeks), the TieredO2 group.

Expanding the phenotypic spectrum in EP300-related Rubinstein-Taybi syndrome.

Rubinstein-Taybi syndrome (RSTS) can be caused by heterozygous mutations or deletions involving CREBBP or, less commonly, EP300. To date, only 15 patients with EP300 mutations have been clinically described. Frequently reported manifestations in these patients include characteristic facial and limb features, varying degrees of neurocognitive dysfunction, and maternal preeclampsia.

Diagnosis of an imprinted-gene syndrome by a novel bioinformatics analysis of whole-genome sequences from a family trio.

Whole-genome sequencing and whole-exome sequencing are becoming more widely applied in clinical medicine to help diagnose rare genetic diseases. Identification of the underlying causative mutations by genome-wide sequencing is greatly facilitated by concurrent analysis of multiple family members, most often the mother-father-proband trio, using bioinformatics pipelines that filter genetic variants by mode of inheritance. However, current pipelines are limited to Mendelian inheritance patterns and do not specifically address disorders caused by mutations in imprinted genes, such as forms of Angelman syndrome and Beckwith-Wiedemann syndrome.

Mutations in NOTCH1 cause Adams-Oliver syndrome.

Notch signaling determines and reinforces cell fate in bilaterally symmetric multicellular eukaryotes. Despite the involvement of Notch in many key developmental systems, human mutations in Notch signaling components have mainly been described in disorders with vascular and bone effects. Here, we report five heterozygous NOTCH1 variants in unrelated individuals with Adams-Oliver syndrome (AOS), a rare disease with major features of aplasia cutis of the scalp and terminal transverse limb defects.

Mesenchymal stromal cells expressing heme oxygenase-1 reverse pulmonary hypertension.

Pulmonary arterial hypertension (PAH) remains a serious disease, and although current treatments may prolong and improve quality of life, search for novel and effective therapies is warranted. Using genetically modified mouse lines, we tested the ability of bone marrow-derived stromal cells (mesenchymal stem cells [MSCs]) to treat chronic hypoxia-induced PAH. Recipient mice were exposed for 5 weeks to normobaric hypoxia (8%-10% O(2)), MSC preparations were delivered through jugular vein injection and their effect on PAH was assessed after two additional weeks in hypoxia.

Bone marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung disease.

Rationale: Neonatal chronic lung disease, known as bronchopulmonary dysplasia (BPD), remains a serious complication of prematurity despite advances in the treatment of extremely low birth weight infants.

Objectives: Given the reported protective actions of bone marrow stromal cells (BMSCs; mesenchymal stem cells) in models of lung and cardiovascular injury, we tested their therapeutic potential in a murine model of BPD.

Methods: Neonatal mice exposed to hyperoxia (75% O(2)) were injected intravenously on Day 4 with either BMSCs or BMSC-conditioned media (CM) and assessed on Day 14 for lung morphometry, vascular changes associated with pulmonary hypertension, and lung cytokine profile.

Hepatic arterial flow becomes the primary supply of sinusoids following partial portal vein ligation in rats.

Background And Aim: Partial portal vein ligation (PPVL) is a commonly used procedure to induce prehepatic portal hypertension in animal models. The aim of this study was to test the hypothesis that the hepatic arterial flow becomes the primary source feeding the sinusoids in the liver after PPVL.

Methods: Sprague-Dawley rats underwent either sham operation or partial portal vein ligation (PPVL).

Pharmacological strategies in the prevention and management of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a disease of complex and multifactorial etiology and a major cause of morbidity in premature infants. Contributing factors include infection, exposure to toxic oxygen levels, and ventilator-induced lung injury, resulting in arrested lung development and impaired lung function. Several preventive and therapeutic strategies have been employed and include lung protective ventilator strategies, pharmacological and nutritional interventions.

Functional link between ETB receptors and eNOS maintain tissue oxygenation in the normal liver.

Objective: Endothelins and their receptors play a crucial role in regulating liver microcirculation in pathophysiological conditions. The authors investigated the functional significance of the coupling of ET(B) receptors and eNOS in maintaining regional perfusion and tissue oxygenation in the normal liver.

Methods: The effect of endothelin-1 or the ET(B) agonist IRL1620 on oxygen consumption was determined in isolated perfused liver and isolated hepatocytes.

Remote trauma sensitizes hepatic microcirculation to endothelin via caveolin inhibition of eNOS activity.

This study addresses the microvascular mechanisms by which a remote, mild stress such as blunt trauma sensitizes the liver to injury. Rats received closed femur fracture (FFx), and 24 h later livers were isolated and perfused at a similar starting flow rate for assessment of vascular response to endothelin-1 (ET-1). Sinusoidal volumetric flow (QS), red blood cell velocity (VRBC), and sinusoidal diameter (Ds) were determined by intravital microscopy.

Role of thromboxane A2 in early BDL-induced portal hypertension.

Although the mechanisms of cirrhosis-induced portal hypertension have been studied extensively, the role of thromboxane A(2) (TXA(2)) in the development of portal hypertension has never been explicitly explored. In the present study, we sought to determine the role of TXA(2) in bile duct ligation (BDL)-induced portal hypertension in Sprague-Dawley rats. After 1 wk of BDL or sham operation, the liver was isolated and perfused with Krebs-Henseleit bicarbonate buffer at a constant flow rate.

Potentiated hepatic microcirculatory response to endothelin-1 during polymicrobial sepsis.

We conducted this study to elucidate the role of endothelins (ET-1) in mediating the hepatic microcirculatory dysfunction observed in response to sepsis. Following 24 h of cecal ligation and puncture (CLP), we performed intravital microscopy both in vivo and on isolated perfused livers. Portal resistance increased in response to ET-1 in both sham and septic rats, with no significant difference between the two in either in vivo or in isolated livers.

Hepatic vascular response to elevated intraperitoneal pressure in the rat.

The rat is increasingly being used to study the physiological response to elevated intra-abdominal pressure (IAP) during laparoscopic surgery. Although decreased portal venous flow associated with the elevated IAP has been reported in large animals, little information is available in rats. Furthermore, the relative blood flow changes in the hepatic artery and portal vein have not been reported.

Endothelin 1 impairs oxygen delivery in livers from LPS-primed animals.

Endothelin 1 (ET-1) is a potent vasoactive peptide that acts at sinusoidal and extrasinusoidal sites in the liver. Sensitivity to ET-1 increases in LPS-primed animals and is associated with impaired liver microcirculation in these animals. We hypothesized that LPS priming leads to an exacerbation in the impaired oxygen delivery in response to intraportal infusion of ET-1.