Central inhibition of HDAC6 re-sensitizes leptin signaling during obesity to induce profound weight loss.

Leptin resistance during excess weight gain significantly contributes to the recidivism of obesity to leptin-based pharmacological therapies. The mechanisms underlying the inhibition of leptin receptor (LepR) signaling during obesity are still elusive. Here, we report that histone deacetylase 6 (HDAC6) interacts with LepR, reducing the latter's activity, and that pharmacological inhibition of HDAC6 activity disrupts this interaction and augments leptin signaling.

Population Kinetics of 0.9% Saline Distribution in Hemorrhaged Awake and Isoflurane-anesthetized Volunteers.

Background: Population-based, pharmacokinetic modeling can be used to describe variability in fluid distribution and dilution between individuals and across populations. The authors hypothesized that dilution produced by crystalloid infusion after hemorrhage would be larger in anesthetized than in awake subjects and that population kinetic modeling would identify differences in covariates.

Methods: Twelve healthy volunteers, seven females and five males, mean age 28 ± 4.

WDR45 contributes to neurodegeneration through regulation of ER homeostasis and neuronal death.

Mutations in the macroautophagy/autophagy gene cause β-propeller protein-associated neurodegeneration (BPAN); however the molecular and cellular mechanism of the disease process is largely unknown. Here we generated constitutive knockout (KO) mice that displayed cognitive impairments, abnormal synaptic transmission and lesions in several brain regions. Immunohistochemistry analysis showed loss of neurons in prefrontal cortex and basal ganglion in aged mice, and increased apoptosis in prefrontal cortex, recapitulating a hallmark of neurodegeneration.

Protein Kinase C Lambda Mediates Acid-Sensing Ion Channel 1a-Dependent Cortical Synaptic Plasticity and Pain Hypersensitivity.

Chronic pain is a serious debilitating disease for which effective treatment is still lacking. Acid-sensing ion channel 1a (ASIC1a) has been implicated in nociceptive processing at both peripheral and spinal neurons. However, whether ASIC1a also contributes to pain perception at the supraspinal level remains elusive.

Can noninvasive hemoglobin measurement reduce the need for preoperative venipuncture in pediatric outpatient surgery?

Background: Noninvasive measurements of hemoglobin in the pediatric perioperative setting could be helpful to avoid venipunctures in children. The present study aims to evaluate this by using a noninvasive device for hemoglobin determination. We compared noninvasively obtained hemoglobin with laboratory hemoglobin concentrations in children during their preoperative assessment.

Closed-Loop- and Decision-Assist-Guided Fluid Therapy of Human Hemorrhage.

Objectives: We sought to evaluate the efficacy, efficiency, and physiologic consequences of automated, endpoint-directed resuscitation systems and compare them to formula-based bolus resuscitation.

Design: Experimental human hemorrhage and resuscitation.

Setting: Clinical research laboratory.

Intrathoracic Pressure Regulation Augments Stroke Volume and Ventricular Function in Human Hemorrhage.

Obtaining intravenous (i.v.) access for fluid administration is a critical step in treating hemorrhage.

The use of a noninvasive hemoglobin monitor for determining fluid distribution and elimination in pediatric patients undergoing minor surgery.

In pediatric fluid therapy it would be preferable to describe distribution and elimination a fluid bolus based on repetitive hemoglobin (Hb) according to kinetic principles. Pulse CO-Oximetry is a recent advancement in patient monitoring that allows for the continuous noninvasive measurement of Hb (SpHb). The aim of this study was to describe the distribution and elimination of hydroxyethylstarch (HES) 130/0.

Population volume kinetics predicts retention of 0.9% saline infused in awake and isoflurane-anesthetized volunteers.

Background: In previous work, extravascular expansion was observed to be enhanced by isoflurane anesthesia in sheep when a crystalloid bolus was administered. The aim of the current study was to further elaborate these investigations to humans and to explore the use of population kinetics in the analysis of fluid shifts.

Methods: Eleven healthy volunteers participated in two experiments each, either awake or isoflurane anesthetized, during which they received 25 ml/kg saline, 0.