Excitation-contraction coupling in striated muscle requires proper communication of plasmalemmal voltage-activated Ca2+ channels and release on sarcoplasmic reticulum within junctional membrane complexes. Although previous studies revealed a loss complexes embryonic lethality germ-line junctophilin-2 (JPH2) knockout mice, it has remained unclear whether JPH2 plays an essential role complex formation the Ca(2+)-induced Ca(2+) process heart. Our recent work demonstrated loss-of-function...

Background— Junctophilin-2 (JPH2), a protein expressed in the junctional membrane complex, is necessary for proper intracellular calcium (Ca 2+ ) signaling cardiac myocytes. Downregulation of JPH2 expression model hypertrophy was recently associated with defective coupling between plasmalemmal L-type Ca channels and sarcoplasmic reticular ryanodine receptors. However, it remains unclear whether altered patients hypertrophic cardiomyopathy (HCM). In addition, effects downregulation on...

Junctophilins (JPHs) are members of a junctional membrane complex protein family important for the physical approximation plasmalemmal and sarcoplasmic/endoplasmic reticulum membranes. As such, JPHs facilitate signal transduction in excitable cells between voltage-gated calcium channels intracellular release channels. To determine molecular evolution JPH gene family, we performed phylogenetic analysis over 60 genes from 40 species compared conservation across different isoforms. We found...

We examined responses of volunteers with known medical disease to G forces in a centrifuge evaluate how potential commercial spaceflight participants (SFPs) might tolerate the despite significant history.Volunteers were recruited based upon suitability for each five categories (hypertension, cardiovascular disease, diabetes, lung back or neck problems) control group. Subjects underwent seven runs over 2 d. Day 1 consisted two +G(z) (peak = +3.5 G(z), Run 2) and +G(x), +6.0 G(x), 4). three...

INTRODUCTION: Ebullism is the pathophysiological process that occurs as a result of exposures to extremely low ambient pressures, traditionally below 47 mmHg (<0.9 psi, ∼63,000 ft/19,202 m equivalent). However, this field research has made minimal progress since 1940s–1960s, when physiology high altitude/space operations was being explored. This lack in part because it thought invariably lethal and also requires unique facilities simulate these environments. As result, no standardized...

Objective: To determine how routine inpatient provider-initiated HIV testing differs from traditional community-based client-initiated with respect to clinical characteristics of children identified and outcomes outpatient care. Design: Prospective observational cohort. Methods: Routine data were collected as HIV-infected by either modality in Lilongwe, Malawi, 2008. After 1 year care at the Baylor College Medicine Clinical Center Excellence, assessed. Results: Of 742 newly enrolling into...

Red Bull Stratos was a commercial program designed to bring test parachutist protected by full-pressure suit via stratospheric balloon with pressurized capsule 120,000 ft (36,576 m), from which he would freefall and subsequently parachute the ground. On March 15, 2012, successfully conducted preliminary manned flight jump, reaching final altitude of 71,581 (21,818 m). In light uniqueness operation medical threats faced, comprehensive plan needed ensure prompt efficient response any...

The Red Bull Stratos Project consisted of incremental high altitude parachute jumps [maximum 127,852 ft (38,969 m)] from a pressurized capsule suspended stratospheric helium-filled balloon. A physiological monitoring system was worn by the parachutist to provide operational medical and acceleration data record unique set in supersonic environment.Various parameters, including heart rate (HR), respiratory (RR), skin temperature, triaxial acceleration, were collected during ascent, float, free...

The Stratex Project is a high altitude balloon flight that culminated in freefall from 41,422 m (135,890 ft), breaking the record for highest to date. Crew recovery operations required an innovative approach due unique nature of event as well equipment involved. parachutist donned custom space suit similar NASA Extravehicular Mobility Unit (EMU), with life support system mounted front and parachute on back. This had metal structure around torso, which, conjunction assembly, created...

The development of manned sub-orbital commercial space vehicles is rapidly occurring and flight testing followed by operational flights will soon begin. experience suborbital spaceflight at the designated altitude (100 km/62.14 mi) very limited--two Mercury-Redstone flights, two X-15 one inadvertent Soyuz launch abort, three recent SpaceShipOne with only 15 min critical time each. All indications were that sequence acceleration-weightlessness-deceleration was well tolerated minimal...

Abstract The StratEx program used a self-contained space suit and balloon system to loft pilot Alan Eustace record-breaking altitude skydive from 135,897 feet (41,422 m). After releasing the stabilized freefall, safely landed using parachute based on modified tandem rig. A custom spacesuit provided life support similar NASA’s (National Aeronautics Space Administration; Washington, DC USA) Extravehicular Mobility Unit. It also tracking, communications, connection system. recovery team,...

Red Bull Stratos was a commercial program that brought test parachutist, protected by full-pressure suit, in stratospheric balloon with pressurized capsule to over 127,582 ft (38,969 m), from which he free fell and subsequently parachuted the ground. Given major risks parachutist included ebullism, negative Gz (toe-to-head) acceleration exposure an uncontrolled flat spin, trauma, comprehensive plan developed recover under nominal conditions respond any medical contingencies might have...

Astronauts training for extravehicular activity (EVA) operations can spend many hours submerged underwater in a pressurized suit, called an mobility unit (EMU), exposed to pressures exceeding 2 atmospheres absolute (ATA). To minimize the risk of decompression sickness (DCS) 46% nitrox mixture is used. This limits nitrogen partial pressure, decreasing DCS. The trade-off with using increased potential oxygen toxicity, which lead severe neurologic symptoms including seizures. Suited runs,...

BACKGROUND: NASA has been making efforts to assess the carbon dioxide (CO 2 ) washout capability of spacesuits using a standard CO sampling protocol. This study established methodology for determining partial pressure inspired (P I co in pressurized spacesuit. We applied characterize P extravehicular mobility unit (EMU). METHODS: suggested an automated and mathematical algorithm find end-tidal end inspiration. provided objective standardized guidelines identify acceptable breath traces,...

Introduction: Pulmonary fluid shifts can occur while scuba diving. Such shifts, generally thought to be rare, may result in a life-threatening phenomenon known as immersion pulmonary edema (IPE). This study aims better classify the normal physiology of diving using ultrasound (US) determine if these routinely during commercial work at NASA Neutral Buoyancy Laboratory (NBL). Methods: Chest US was performed on divers prospectively pre- and post-dive evaluate presence B-lines total 12...

Introduction: Pulmonary fluid shifts can occur while scuba diving. Such shifts, generally thought to be rare, may result in a life-threatening phenomenon known as immersion pulmonary edema (IPE). This study aims better classify the normal physiology of diving using ultrasound (US) determine if these routinely during commercial work at NASA Neutral Buoyancy Laboratory (NBL). Methods: Chest US was performed on divers prospectively pre- and post-dive evaluate presence B-lines total 12...

Background: Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young people. Recently, a patient with HCM paroxysmal atrial fibrillation (AF) and sinoatrial block was found to have missense mutation, E169K, junctophilin 2 (JPH2) protein. Loss JPH2 has been shown affect intracellular Ca2+ release heart. To date, no study evaluated effect E169K mutation on handling arrhythmogenesis. Hypothesis: The promotes sarcoplasmic reticulum leak causing abnormal...

Spacewalks or extravehicular activities (EVA) in microgravity are mentally and physically demanding. Current EVAs predominantly focused on upper body tasks engineered surfaces; however, the introduction of gravity means that crew members during future Lunar will be required to perform generate full workloads. To date, only 12 people have walked surface Moon, resulting limited knowledge suited thermal regulation under Lunar-relevant physical address this gap, a study is underway focus...

Background. Na + /Ca 2+ exchanger (NCX) is essential in tuning intracellular Ca and the development of heart failure (HF). We reported that loss Junctophilin 2 (JPH2) adult mouse hearts leads to reduced NCX activity addition hyperactive RyR2s more arrhythmogenic waves. has been found co-localize with RyR2 recently. However, what physiological significance junctional whether following JPH2 knockdown contributes arrhythmogenesis still unknown. Hypothesis. Dysfunction Junctional response alters...