Volumetric MRI and MRS and early motor development of infants born preterm.

Purpose: To investigate the relationship between volumetric magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in infants born less than 30 weeks gestation and early motor development at 6 months adjusted age.

Methods: Twenty infants born preterm and 4 born at term (control) underwent MRI with volumetric analysis and MRS prior to neonatal intensive care unit discharge. Infants were assessed using the Bayley Scale of Infant Development at 6 months adjusted age.

Hospitalists at an academic medical center, part 2: guidelines and suggestions for the successful expansion of a voluntary pilot hospitalist program.

Previously, the authors discussed the successful introduction of a pilot hospitalist program at an academic medical center. Here they examine best practices for the expansion of such a program. Many studies have shown hospitalists to be associated with improvements in hospital quality indicators such as decreased length of stay, but the conditions necessary for the expansion of a hospitalist program have received considerably less attention.

Hospitalists at an academic medical center, part 1: impact of a voluntary pilot hospitalist program.

The use of hospitalists-physicians who limit their practice largely or exclusively to hospital inpatient care-has been a growing trend in the United States. The authors examine some pressures affecting an academic medical center and present the results of a hospitalist pilot project there. Based on the criteria of reduced patient length of hospital stay, hospital financial savings, physician satisfaction, and payer interest, the pilot hospitalist program was successful within 6 months.

Cx50 requires an intact PDZ-binding motif and ZO-1 for the formation of functional intercellular channels.

The three connexins expressed in the ocular lens each contain PDZ domain-binding motifs directing a physical association with the scaffolding protein ZO-1, but the significance of the interaction is unknown. We found that Cx50 with PDZ-binding motif mutations did not form gap junction plaques or induce cell-cell communication in HeLa cells, whereas the addition of a seven-amino acid PDZ-binding motif restored normal function to Cx50 lacking its entire C-terminal cytoplasmic domain. C-Terminal deletion had a similar although weaker effect on Cx46 but little if any effect on targeting and function of Cx43.

Electrical synapses formed by connexin36 regulate inhibition- and experience-dependent plasticity.

The mammalian brain constantly adapts to new experiences of the environment, and inhibitory circuits play a crucial role in this experience-dependent plasticity. A characteristic feature of inhibitory neurons is the establishment of electrical synapses, but the function of electrical coupling in plasticity is unclear. Here we show that elimination of electrical synapses formed by connexin36 altered inhibitory efficacy and caused frequency facilitation of inhibition consistent with a decreased GABA release in the inhibitory network.

Whey protein but not soy protein supplementation alters body weight and composition in free-living overweight and obese adults.

A double-blind, randomized clinical trial was conducted to determine the effect of consumption of supplemental whey protein (WP), soy protein (SP), and an isoenergetic amount of carbohydrate (CHO) on body weight and composition in free-living overweight and obese but otherwise healthy participants. Ninety overweight and obese participants were randomly assigned to 1 of 3 treatment groups for 23 wk: 1) WP; 2) SP (each providing ~56 g/d of protein and 1670 kJ/d); or 3) an isoenergetic amount of CHO. Supplements were consumed as a beverage twice daily.

Characterization of the impaired glucose homeostasis produced in C57BL/6 mice by chronic exposure to arsenic and high-fat diet.

Background: Type 2 diabetes is characterized by glucose intolerance and insulin resistance. Obesity is the leading cause of type 2 diabetes. Growing evidence suggests that chronic exposure to inorganic arsenic (iAs) also produces symptoms consistent with diabetes.

Clinical vignettes provide an understanding of antibiotic prescribing practices in neonatal intensive care units.

Objective: To use clinical vignettes to understand antimicrobial prescribing practices in neonatal intensive care units (NICUs).

Design: Vignette-based survey.

Setting: Four tertiary care NICUs.

NS4B self-interaction through conserved C-terminal elements is required for the establishment of functional hepatitis C virus replication complexes.

Hepatitis C virus (HCV) is an important human pathogen, persistently infecting more than 170 million individuals worldwide. Studies of the HCV life cycle have become possible with the development of cell culture systems supporting the replication of viral RNA and the production of infectious virus. However, the exact functions of individual proteins, especially of nonstructural protein 4B (NS4B), remain poorly understood.

Deletion of oligodendrocyte Cx32 and astrocyte Cx43 causes white matter vacuolation, astrocyte loss and early mortality.

CNS glia exhibit a variety of gap junctional interactions: between neighboring astrocytes, between neighboring oligodendrocytes, between astrocytes and oligodendrocytes, and as 'reflexive' structures between layers of myelin in oligodendrocytes. Together, these junctions are thought to form a network facilitating absorption and removal of extracellular K(+) released during neuronal activity. In mice, loss of the two major oligodendrocyte connexins causes severe demyelination and early mortality, while loss of the two major astrocyte connexins causes mild dysmyelination and sensorimotor impairment, suggesting that reflexive and/or oligo-oligo coupling may be more important for the maintenance of myelin than other forms.

In vitro interaction study of retinoic acid isomers with telmisartan and amlodipine by equilibrium dialysis method using UV spectroscopy.

The in vitro protein binding of retinoic acid isomers (isotretinoin and tretinoin) and the antihypertensive drugs (amlodipine and telmisartan) was studied by equilibrium dialysis method. In this study, free fraction of drugs and the % of binding of drugs in the mixture to bovine serum albumin (BSA) were calculated. The influence of retinoic acid isomers on the % of protein binding of telmisartan and amlodipine at physiological pH (7.

Increased odds of necrotizing enterocolitis after transfusion of red blood cells in premature infants.

Objectives: To determine if infants with very low birth weight who receive packed red blood cell (PRBC) transfusions have increased odds of developing necrotizing enterocolitis (NEC), to determine the rate of NEC after PRBC transfusion, and to characterize the blood transfused preceding the onset of NEC.

Study Design: A retrospective cohort design was used. The study population included infants with a birth weight of <1500 g who were from a single center.

Functional heterotypic interactions between astrocyte and oligodendrocyte connexins.

Human genetic diseases and mouse knockouts illustrate that the maintenance of central nervous system myelin requires connexin expression by both astrocytes and oligodendrocytes. Because these cell types express nonoverlapping sets of connexins, the intercellular channels formed between them must be asymmetric with regard to connexin content, defined as heterotypic. Here, we show that oligodendrocyte Cx47 can form heterotypic channels with astrocyte Cx43 or Cx30 but not Cx26, whereas oligodendrocyte Cx32 can functionally interact with astrocyte Cx30 or Cx26 but not Cx43.

In vitro identification and verification of inflammatory biomarkers in swine.

Currently there are no non-steroidal anti-inflammatory drugs (NSAIDs) approved for the control of inflammation in swine due to a lack of validated animal models and suitable biomarkers to assess drug efficacy. This study investigates the differential expression of genes altered in response to Escherichia coli lipopolysaccharide (LPS) induced inflammation which may serve as indicators of NSAID efficacy. Unstimulated whole blood from swine was mixed with tissue culture media, stimulated with LPS, and RNA extracted at the following time points 0h, 1h, 3h, 24h and 48h.

Mode of delivery and outcomes in very low-birth-weight infants in the vertex presentation.

We sought to determine the relationship between mode of delivery and neonatal outcomes in infants <1500 g in a vertex presentation. This was a retrospective cohort study of singleton, vertex-presenting infants weighing <1500 g in a level III neonatal intensive care unit between July 1993 and July 2006. Infants were divided into vaginal or cesarean delivery, and outcomes were compared with univariable and multivariable analysis.

Visual responses in the lateral geniculate evoked by Cx36-independent rod pathways.

Emerging evidence indicates rods can communicate with retinal ganglion cells (RGCs) via pathways that do not involve gap-junctions. Here we investigated the significance of such pathways for central visual responses, using mice lacking a key gap junction protein (Cx36(-/-)) and carrying a mutation that disrupts cone phototransduction (Gnat2(cpfl3)). Electrophysiological recordings spanning the lateral geniculate revealed rod-mediated ON and OFF visual responses in virtually every cell from all major anatomical sub-compartments of this nucleus.

Increased cesarean section rate over time (1994-2006) in Delaware is not associated with improved outcomes in very low birth weight infants.

Cesarean deliveries (C-section) have been increasing over time. The objectives of this study were to analyze cesarean section delivery rates over time, and determine whether there is an association between C-section, mortality, and severe intraventricular hemorrhage (IVH) in VLBW infants. We performed a retrospective cohort study of babies with birth weight < 1,500 grams, between 1994 and 2006, at Christiana Hospital (n = 2,040).

Thyroid function in term and late preterm infants with respiratory distress in relation to severity of illness.

Background: Transient hypothyroxinemia is common in extremely premature infants, but has not been extensively investigated in ill term and late preterm infants. We hypothesized that free thyroxine (T(4)) levels in term and late preterm infants with respiratory distress would be inversely related to severity of illness

Methods: Eligible infants included those had > or =35 weeks of gestation requiring mechanical ventilation or nasal continuous positive airway pressure. Thyroid function (thyroid-stimulating hormone, T(4), free T(4) [fT(4)], and free triiodothyronine) and cortisol levels were collected at four specified intervals (birth, day 2, day 3, and day 5 of life).

Gap junctions.

Gap junctions are aggregates of intercellular channels that permit direct cell-cell transfer of ions and small molecules. Initially described as low-resistance ion pathways joining excitable cells (nerve and muscle), gap junctions are found joining virtually all cells in solid tissues. Their long evolutionary history has permitted adaptation of gap-junctional intercellular communication to a variety of functions, with multiple regulatory mechanisms.

Connexin36 is required for gap junctional coupling of most ganglion cell subtypes in the mouse retina.

Converging evidence indicates that electrical synaptic transmission via gap junctions plays a crucial role in signal processing in the retina. In particular, amacrine and ganglion cells express numerous gap junctions, resulting in extensive electrical networks in the proximal retina. Both connexin36 (Cx36) and connexin45 (Cx45) subunits are widely distributed in the inner plexiform layer (IPL) and therefore are likely contribute to gap junctions formed by a number of ganglion cell subtypes.

Metabolism of arsenic in human liver: the role of membrane transporters.

Metabolism of inorganic arsenic (iAs) is one of the key factors determining the character of adverse effects associated with exposure to iAs. Results of previous studies indicate that liver plays a primary role in iAs metabolism. This paper reviews these results and presents new data that link the capacity of human hepatocytes to metabolize iAs to the expression of specific membrane transporters.

Direct rod input to cone BCs and direct cone input to rod BCs challenge the traditional view of mammalian BC circuitry.

Bipolar cells are the central neurons of the retina that transmit visual signals from rod and cone photoreceptors to third-order neurons in the inner retina and the brain. A dogma set forth by early anatomical studies is that bipolar cells in mammalian retinas receive segregated rod/cone synaptic inputs (either from rods or from cones), and here, we present evidence that challenges this traditional view. By analyzing light-evoked cation currents from morphologically identified depolarizing bipolar cells (DBCs) in the wild-type and three pathway-specific knockout mice (rod transducin knockout [Tralpha(-/-)], connexin36 knockout [Cx36(-/-)], and transcription factor beta4 knockout [Bhlhb4(-/-)]), we show that a subpopulation of rod DBCs (DBC(R2)s) receives substantial input directly from cones and a subpopulation of cone DBCs (DBC(C1)s) receives substantial input directly from rods.

Antibiotic use in neonatal intensive care units and adherence with Centers for Disease Control and Prevention 12 Step Campaign to Prevent Antimicrobial Resistance.

Background: The Centers for Disease Control and Prevention (CDC) 12-Step Campaign to Prevent Antimicrobial Resistance was launched to educate clinicians about antimicrobial resistance and provide strategies to improve clinical practice, including antimicrobial utilization.

Methods: A multicenter retrospective observational study of antibiotic use was performed in 4 tertiary care NICUs to assess adherence to the guidelines defined by the CDC 12-Step Campaign using predetermined criteria. Fifty infants per NICU were identified who received intravenous antibiotics at greater than 72 hours of age.

Claudin-16 and claudin-19 interaction is required for their assembly into tight junctions and for renal reabsorption of magnesium.

Claudins are tight junction integral membrane proteins that are key regulators of the paracellular pathway. Defects in claudin-16 (CLDN16) and CLDN19 function result in the inherited human renal disorder familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). Previous studies showed that siRNA knockdown of CLDN16 in mice results in a mouse model for FHHNC.

Genetic dissection of rod and cone pathways in the dark-adapted mouse retina.

A monumental task of the mammalian retina is to encode an enormous range (>10(9)-fold) of light intensities experienced by the animal in natural environments. Retinal neurons carry out this task by dividing labor into many parallel rod and cone synaptic pathways. Here we study the operational plan of various rod- and cone-mediated pathways by analyzing electroretinograms (ERGs), primarily b-wave responses, in dark-adapted wildtype, connexin36 knockout, depolarizing rod-bipolar cell (DBCR) knockout, and rod transducin alpha-subunit knockout mice [WT, Cx36(-/-), Bhlhb4(-/-), and Tralpha(-/-)].