Metabolic adaptation to the chronic loss of Ca signaling induced by KO of IP receptors or the mitochondrial Ca uniporter.

Calcium signaling is essential for regulating many biological processes. Endoplasmic reticulum inositol trisphosphate receptors (IPRs) and the mitochondrial Ca uniporter (MCU) are key proteins that regulate intracellular Ca concentration. Mitochondrial Ca accumulation activates Ca-sensitive dehydrogenases of the tricarboxylic acid (TCA) cycle that maintain the biosynthetic and bioenergetic needs of both normal and cancer cells.

Redox regulation of ER and mitochondrial Ca signaling in cell survival and death.

Physiological signaling by reactive oxygen species (ROS) and their pathophysiological role in cell death are well recognized. This review focuses on two ROS targets that are key to local Ca signaling at the ER/mitochondrial interface - notably, inositol trisphosphate receptors (IPRs) and the mitochondrial calcium uniporter (MCU). Both transport systems are central to molecular mechanisms in cell survival and death.

Redox regulation of type-I inositol trisphosphate receptors in intact mammalian cells.

A sensitization of inositol 1,4,5-trisphosphate receptor (IPR)-mediated Ca release is associated with oxidative stress in multiple cell types. These effects are thought to be mediated by alterations in the redox state of critical thiols in the IPR, but this has not been directly demonstrated in intact cells. Here, we utilized a combination of gel-shift assays with MPEG-maleimides and LC-MS/MS to monitor the redox state of recombinant IPR1 expressed in HEK293 cells.

Influence of Prehospital Function and Strength on Outcomes of Critically Ill Older Adults.

Objectives: To understand the influence of prehospital physical function and strength on clinical outcomes of critically ill older adults.

Design: Secondary analysis of prospective cohort study.

Setting: Health, Aging and Body Composition (Health ABC) Study.

Standardized Rehabilitation and Hospital Length of Stay Among Patients With Acute Respiratory Failure: A Randomized Clinical Trial.

Importance: Physical rehabilitation in the intensive care unit (ICU) may improve the outcomes of patients with acute respiratory failure.

Objective: To compare standardized rehabilitation therapy (SRT) to usual ICU care in acute respiratory failure.

Design, Setting, And Participants: Single-center, randomized clinical trial at Wake Forest Baptist Medical Center, North Carolina.

Cardiopulmonary resuscitation among mechanically ventilated patients.

Purpose: To evaluate the outcomes, including long-term survival, after cardiopulmonary resuscitation (CPR) in mechanically ventilated patients.

Methods: We analyzed Medicare data from 1994 to 2005 to identify beneficiaries who underwent in-hospital CPR. We then identified a subgroup receiving CPR one or more days after mechanical ventilation was initiated [defined by ICD-9 procedure code for intubation (96.

Variation in the rapid shallow breathing index associated with common measurement techniques and conditions.

Background: The rapid-shallow-breathing index (RSBI) is widely used to evaluate mechanically ventilated patients for weaning and extubation, but it is determined in different clinical centers in a variety of ways, under conditions that are not always comparable. We hypothesized that the value of RSBI may be significantly influenced by common variations in measurement conditions and technique.

Methods: Sixty patients eligible for a weaning evaluation after >or=72 hours of mechanical ventilation were studied over 15 months in a medical intensive care unit.

Peak pressures during manual ventilation.

Introduction: Manual (bag) ventilation sometimes achieves better oxygenation than does a mechanical ventilator. We speculated that clinicians might generate very high airway pressure during manual ventilation (much higher than the pressure delivered by a mechanical ventilator), and that the high airway pressure causes alveolar recruitment and thus improves oxygenation. Such high pressure might injure alveoli in some patients.

Ventilation of patients with acute lung injury and acute respiratory distress syndrome: has new evidence changed clinical practice?

Objectives: A recent randomized trial of mechanical ventilation in acute lung injury (ALI)/adult respiratory distress syndrome (ARDS) demonstrated a 22% relative reduction in mortality rate using 6 mL/kg predicted body weight tidal volume vs. 12 mL/kg predicted body weight tidal volume. We determined whether publication of these findings changed clinical practice.

Inpatient transfers to the intensive care unit: delays are associated with increased mortality and morbidity.

Objective: To examine if delayed transfer to the intensive care unit (ICU) after physiologic deterioration is associated with increased morbidity and mortality.

Design: Inception cohort.

Setting: Community hospital in Ogden, Utah.