Deciphering Redox State for a Metal-Rich World.

The Psyche mission's Oxidation-Reduction Working Group is focused on understanding, determining, and applying the redox state of (16) Psyche to understand the origin of a metal-rich world. The oxidation-reduction state of an asteroid, along with its temperature, parent body size, and composition, is a key parameter in determining the history of an asteroid. Determining the redox state from spacecraft data is most easily done by examining potential metal-oxide buffer pairs. The occurrence of Ni, Fe, C, Cr, P and Si, in that order, in the metal or sulfide phase of an asteroidal body indicates increasingly reduced conditions. Key observations by the Imager and Gamma-Ray and Neutron Spectrometer (GRNS) of Psyche can bracket the redox state using metal-oxide buffers. The presence of Fe,Ni metal can be confirmed by the ratios of Fe/O or Fe/Si and the concentration of Ni variability in metal across the asteroid can be determined by GRNS. The FeO concentration of silicates is complementary to the Ni concentration of metal and can be constrained using filters on the Imager. The presence of FeO in silicates from ground-based observations is one of the few measurements we already have of redox state, although available data permit a wide range of silicate compositions and mineralogies. The presence of C, P or Si concentrated in the metallic, Fe-rich portion of the asteroid, as measured by GRNS, or Ca-sulfide, determined by imaging, would indicate increasingly reducing conditions. Linkage to known types of meteorites, whether metal-rich chondrites, stony-irons or irons, expands the mineralogical, chemical and isotopic data not available from remote observations alone. Redox also controls both silicate and metal mineralogy, influencing differentiation, solidification, and subsolidus cooling, including the relative abundance of sulfur in the core and possible magnetic signatures. The redox state of Psyche, if a fully-differentiated metallic core, might constrain the location and timing of both the formation of Psyche and any oxidation it might have experienced.

Correlations Between Macular, Skin, and Serum Carotenoids.

Purpose: Ocular and systemic measurement and imaging of the macular carotenoids lutein and zeaxanthin have been employed extensively as potential biomarkers of AMD risk. In this study, we systematically compare dual wavelength retinal autofluorescence imaging (AFI) of macular pigment with skin resonance Raman spectroscopy (RRS) and serum carotenoid levels in a clinic-based population. Methods: Eighty-eight patients were recruited from retina and general ophthalmology practices from a tertiary referral center and excluded only if they did not have all three modalities tested, had a diagnosis of macular telangiectasia (MacTel) or Stargardt disease, or had poor AFI image quality. Skin, macular, and serum carotenoid levels were measured by RRS, AFI, and HPLC, respectively. Results: Skin RRS measurements and serum zeaxanthin concentrations correlated most strongly with AFI macular pigment volume under the curve (MPVUC) measurements up to 9° eccentricity relative to MPVUC or rotationally averaged macular pigment optical density (MPOD) measurements at smaller eccentricities. These measurements were reproducible and not significantly affected by cataracts. We also found that these techniques could readily identify subjects taking oral carotenoid-containing supplements. Conclusions: Larger macular pigment volume AFI and skin RRS measurements are noninvasive, objective, and reliable methods to assess ocular and systemic carotenoid levels. They are an attractive alternative to psychophysical and optical methods that measure MPOD at a limited number of eccentricities. Consequently, skin RRS and MPVUC at 9° are both reasonable biomarkers of macular carotenoid status that could be readily adapted to research and clinical settings.

Rates of visual acuity change in patients receiving hyperbaric oxygen in monoplace and multiplace chambers.

INTRODUCTION: Changes in visual acuity are a known side effect of hyperbaric oxygen (HBO2). We conducted a quality improvement initiative to better quantify visual change risk and to identify possible risk factors. METHODS: Vision was checked weekly in a clinical HBO2 population by Snellen eye chart. Visual acuity change was defined as Snellen test worsened to 20/40 or greater or by loss of 2 lines. RESULTS: Of 85 patients treated from January 2013 to February 2015 with 10 HBO2 sessions and ≥ 2 weeks of visual acuity testing, 53 (62%) were male. All were treated for UHMS-approved indications. A total of 34 patients (40%) had no change in visual acuity, 27 (32%) had a 1-line change, and 24 (28%) had at least a 2-line worsening in visual acuity. The number of sessions for those with at least a 2-line change was 36 ± 15 (15-60). A 2-line change occurred at similar rates for monoplace and multiplace patients (29% and 32%, respectively), but monoplace patients more frequently reached 20/40 or worse (32% vs. 18%). Seven of 11 patients with existing cataracts had ≥ 2 line change, as did six of 14 patients (43%) with a history of head/neck radiation. CONCLUSIONS: In this retrospective review of quality improvement data, 28% of patients had a 2-line change in visual acuity by Snellen exam after treat-ment with HBO2. Further study of possible risk factors, including chamber type, is warranted.

Dietary omega-6 fatty acid replacement selectively impairs cardiac functional recovery after ischemia in female (but not male) rats.

A definitive understanding of the role of dietary lipids in determining cardioprotection (or cardiodetriment) has been elusive. Randomized trial findings have been variable and sex specificity of dietary interventions has not been determined. In this investigation the sex-selective cardiac functional effects of three diets enriched by omega-3 or omega-6 polyunsaturated fatty acids (PUFA) or enriched to an equivalent extent in saturated fatty acid components were examined in rats after an 8-wk treatment period. In females the myocardial membrane omega-6:omega-3 PUFA ratio was twofold higher than males in the omega-6 diet replacement group. In diets specified to be high in omega-3 PUFA or in saturated fat, this sex difference was not apparent. Isolated cardiomyocyte and heart Langendorff perfusion experiments were performed, and molecular measures of cell viability were assessed. Under basal conditions the contractile performance of omega-6 fed female cardiomyocytes and hearts was reduced compared with males. Omega-6 fed females exhibited impaired systolic resilience after ischemic insult. This response was associated with increased postischemia necrotic cell damage evaluated by coronary lactate dehydrogenase during reperfusion in omega-6 fed females. Cardiac and myocyte functional parameters were not different between omega-3 and saturated fat dietary groups and within these groups there were no discernible sex differences. Our data provide evidence at both the cardiac and cardiomyocyte levels that dietary saturated fatty acid intake replacement with an omega-6 (but not omega-3) enriched diet has selective adverse cardiac effect in females. This finding has potential relevance in relation to women, cardiac risk, and dietary management.

Performance of three large-volume infusion pumps with the monoplace hyperbaric chamber.

We evaluated the Zyno Medical Z-800F, CME Body Guard 323 Color Vision, and Baxter Flo-Gard 6201 infusion pumps for monoplace chamber conditions. We adjusted pump occlusion pressure allowing infusion to 3 atmospheres absolute (atm abs). Baxter and Zyno pumps were connected to the chamber pass-through with rigid small-bore tubing. The CME infusion set was connected directly to the pass-through. We infused saline to a collection manifold inside a monoplace chamber at 1-100 mL/ hour under pressures ranging from 0.85-3.0 atm abs. We averaged results from three to five separate tests for each condition. At baseline, pumps performed within ±10% of expected (our measurement capability). However, clinical engineering verified performance within manufacturer specifications (±5% at atmospheric pressure). During a carbon monoxide hyperbaric protocol (3 atm abs/2 atm abs), measured flow with the Baxter, CME and Zyno pumps was ±5% of setting at 10 mL/hour (95%, 103%, 95%, respectively); at 1 mL/hour, average flow were 91%, 83%, 83%, respectively. During timed testing (volume recorded before decompression), pump accuracy was ±10% at 10 and 100 mL/hour. Tubing compliance compromised performance at lower flow rates, magnified by increased pressure. These pumps have potential for monoplace chamber use, although not supported by the manufacturers or FDA-cleared. At low flow rates, tubing compliance affects delivered volumes.

Myocardial and cardiomyocyte stress resilience is enhanced in aromatase-deficient female mouse hearts through CaMKIIδ activation.

The role of sex steroids in cardioprotection is contentious, with large clinical trials investigating hormone supplementation failing to deliver outcomes expected from observational studies. Mechanistic understanding of androgen/estrogen myocardial actions is lacking. Using a genetic model of aromatase tissue deficiency (ArKO) in female mice, the goal of this investigation was to evaluate the capacity of a shift in cardiac endogenous steroid conversion to influence ischemia-reperfusion resilience by optimizing cardiomyocyte Ca2+ handling responses. In isolated normoxic cardiomyocytes, basal Ca2+ transient amplitude and extent of shortening were greater in ArKO myocytes, with preservation of diastolic Ca2+ levels. Isolated ArKO cardiomyocytes exposed to a high Ca2+ load exhibited greater Ca2+ transient and contractile amplitudes, associated with a greater postrest spontaneous sarcoplasmic reticulum Ca2+ load-release. Microarray differential gene expression analysis of normoxic ventricular tissues from ArKO vs wild-type identified a significant influence of aromatase on genes involved in cardiac Ca2+ handling and signaling [including calmodulin dependent kinase II (CaMKII)-δ], myofilament structure and function, glucose uptake and signaling, and enzymes controlling phosphorylation-specific posttranslational modification status. CaMKII expression was not changed in ventricular tissues, although CaMKIIδ activation and phosphorylation of downstream targets was enhanced in ArKO hearts subjected to ischemia-reperfusion. Overall, this investigation shows that relative withdrawal of estrogen in favor of testosterone through genetically induced tissue aromatase deficiency in females modifies the gene expression profile to effect inotropic support via optimized Ca2+ handling in response to stress, with a modest impact on basal function. Consideration of aromatase inhibition, acutely or chronically, may have a role in cardioprotection, of particular relevance to women.

Performance of the Hospira Plum A+ (HB) hyperbaric infusion pump.

BACKGROUND: We evaluated the Hospira Plum A+ (HB) hyperbaric infusion pump under monoplace and multiplace hyperbaric conditions to test pump flow accuracy. METHODS: Pump flow accuracy was tested in monoplace and multiplace hyperbaric chambers at different rates, fluid viscosities, pressures and volumes. Output was recorded from the pump (programmed) and from graduated cylinders or syringes (actual). The lead acid battery life was recorded for multiplace trials. RESULTS: In monoplace trials to 3.0 atmospheres absolute (atm abs), the pump functioned within the published tolerance of 12.5% at 1 ml/hour (mean deviation +3.3%, range 0.0% to +5.0%) and at faster flow rates (mean deviation -0.4%, range -11.5% to +6.0%). A trial of packed red blood cells (deviation -3.3%) was also within acceptable limits. For all multiplace trials, the pump functioned well within the manufacturer's limits (mean deviation -0.1%, range -0.8% to +0.9%). At the maximum flow rate, the interval to the first battery alarm for two trials was shorter than the duration of a clinical hyperbaric session (first alarm at 82 and 94 minutes). When we examined delivery variances in the compression and decompression phases for monoplace chambers, at 1 ml/hour 25/39 trials (64%) had no measurable infusion volume during compression. Conversely, more than twice the programmed volume was infused during the 10-minute decompression interval (mean 0.40 ml, range 0.32 to 0.60 ml). The tubing compliance effect was also noted, to a lesser degree, in trials at 3 and 5 ml/hour. CONCLUSIONS: This infusion pump can be useful in hyperbaric medicine departments that treat patients who need intravenous infusions. Tubing compliance may affect fluid volumes delivered by the pump, especially when delivery rates are low. Careful monitoring of patients with low volume infusions during monoplace chamber compression and decompression is advised.

Decompression tables for inside chamber attendants working at altitude.

INTRODUCTION: Hyperbaric oxygen (HBO2) multiplace chamber inside attendants (IAs) are at risk for decompression sickness (DCS). Standard decompression tables are formulated for sea-level use, not for use at altitude. METHODS: At Presbyterian/St. Luke's Medical Center (Denver, Colorado, 5,924 feet above sea level) and Intermountain Medical Center (Murray, Utah, 4,500 feet), the decompression obligation for IAs is managed with U.S. Navy Standard Air Tables corrected for altitude, Bühlmann Tables, and the Nobendem© calculator. IAs also breathe supplemental oxygen while compressed. Presbyterian/St. Luke's (0.83 atmospheres absolute/atm abs) uses gauge pressure, uncorrected for altitude, at 45 feet of sea water (fsw) (2.2 atm abs) for routine wound care HBO2 and 66 fsw (2.8 atm abs) for carbon monoxide/cyanide poisoning. Presbyterian/St. Luke's provides oxygen breathing for the IAs at 2.2 atm abs. At Intermountain (0.86 atm abs), HBO2 is provided at 2.0 atm abs for routine treatments and 3.0 atm abs for carbon monoxide poisoning. Intermountain IAs breathe intermittent 50% nitrogen/50% oxygen at 3.0 atm abs and 100% oxygen at 2.0 atm abs. The chamber profiles include a safety stop. RESULTS: From 1990-2013, Presbyterian/St. Luke's had 26,900 total IA exposures: 25,991 at 45 fsw (2.2 atm abs) and 646 at 66 fsw (2.8 atm abs); there have been four cases of IA DCS. From 2008-2013, Intermountain had 1,847 IA exposures: 1,832 at 2 atm abs and 15 at 3 atm abs, with one case of IA DCS. At both facilities, DCS incidents occurred soon after the chambers were placed into service. CONCLUSIONS: Based on these results, chamber inside attendant risk for DCS at increased altitude is low when the inside attendants breathe supplemental oxygen.

A blinded trial to investigate whether 'pressure-familiar' individuals can determine chamber pressure.

INTRODUCTION: We conducted a prospective study to determine whether divers or hyperbaric chamber attendants could discern chamber pressure--important to protecting blinding if they were to participate in blinded hyperbaric oxygen (HBO2) trials. METHODS: Experienced divers and chamber attendants were randomized by appointment group to one of four pressure changes. These pressure changes caused volume changes corresponding to starting compression from sea level or altitude, with final pressures of 1.5 atm abs (breathing 100% oxygen) or 1.2 atm abs (breathing air). Following the pressure excursions, participants estimated their depth in feet of sea water (fsw) and breathing gas. RESULTS: 42 volunteers participated: 10 females, 32 males, age 46 +/- 10 years (mean +/- 1 SD), dive experience 366 +/- 562 dives. Four were chamber attendants. When estimating the depth exposure, 19/42 (45%) selected I do not know. 3/23 (13%) were within 2 fsw of the actual depth (correlation between actual depth and estimate -0.0067) (p = 0.98). Two underestimated their depth. We found no indication of cluster randomization effect (p = 0.16). Participants could not discern breathing air or oxygen. CONCLUSIONS: The results suggest experienced divers cannot discriminate chamber pressures of 1.2 and 1.5 atm abs, and could be included in hyperbaric clinical trials using this dosing without compromising masking integrity.

Fructose modulates cardiomyocyte excitation-contraction coupling and Ca²âº handling in vitro.

BACKGROUND: High dietary fructose has structural and metabolic cardiac impact, but the potential for fructose to exert direct myocardial action is uncertain. Cardiomyocyte functional responsiveness to fructose, and capacity to transport fructose has not been previously demonstrated. OBJECTIVE: The aim of the present study was to seek evidence of fructose-induced modulation of cardiomyocyte excitation-contraction coupling in an acute, in vitro setting. METHODS AND RESULTS: The functional effects of fructose on isolated adult rat cardiomyocyte contractility and Ca²âº handling were evaluated under physiological conditions (37°C, 2 mM Ca²âº, HEPES buffer, 4 Hz stimulation) using video edge detection and microfluorimetry (Fura2) methods. Compared with control glucose (11 mM) superfusate, 2-deoxyglucose (2 DG, 11 mM) substitution prolonged both the contraction and relaxation phases of the twitch (by 16 and 36% respectively, p<0.05) and this effect was completely abrogated with fructose supplementation (11 mM). Similarly, fructose prevented the Ca²âº transient delay induced by exposure to 2 DG (time to peak Ca²âº transient: 2 DG: 29.0±2.1 ms vs. glucose: 23.6±1.1 ms vs. fructose +2 DG: 23.7±1.0 ms; p<0.05). The presence of the fructose transporter, GLUT5 (Slc2a5) was demonstrated in ventricular cardiomyocytes using real time RT-PCR and this was confirmed by conventional RT-PCR. CONCLUSION: This is the first demonstration of an acute influence of fructose on cardiomyocyte excitation-contraction coupling. The findings indicate cardiomyocyte capacity to transport and functionally utilize exogenously supplied fructose. This study provides the impetus for future research directed towards characterizing myocardial fructose metabolism and understanding how long term high fructose intake may contribute to modulating cardiac function.

Adherence to antiretroviral medications and medical care in HIV-infected adults diagnosed with mental and substance abuse disorders.

This paper examines factors associated with adherence to antiretroviral medications (ARVs) in an HIV-infected population at high risk for non-adherence: individuals living with psychiatric and substance abuse disorders. Data were examined from baseline interviews of a multisite cohort intervention study of 1138 HIV-infected adults with both a psychiatric and substance abuse disorder (based on a structured psychiatric research interview using DSM-IV criteria). The baseline interview documented mental illness and substance use in the past year, mental illness and substance abuse severity, demographics, service utilization in the past three months, general health and HIV-related conditions, self-reported spirituality and self-reported ARV medication use. Among the participants, 62% were prescribed ARVs at baseline (n = 542) and 45% of those on ARVs reported skipping medications in the past three days. Reports of non-adherence were significantly associated with having a detectable viral load (p<.01). The factors associated with non-adherence were current drug and alcohol abuse, increased psychological distress, less attendance at medical appointments, non-adherence to psychiatric medications and lower self-reported spirituality. Increased psychological distress was significantly associated with non-adherence, independent of substance abuse (p<.05). The data suggest that both mental illness and substance use must be addressed in HIV-infected adults living with these co-morbid illnesses to improve adherence to ARVs.

Cell volume control in phospholemman (PLM) knockout mice: do cardiac myocytes demonstrate a regulatory volume decrease and is this influenced by deletion of PLM?

In addition to modulatory actions on Na+-K+-ATPase, phospholemman (PLM) has been proposed to play a role in cell volume regulation. Overexpression of PLM induces ionic conductances, with 'PLM channels' exhibiting selectivity for taurine. Osmotic challenge of host cells overexpressing PLM increases taurine efflux and augments the cellular regulatory volume decrease (RVD) response, though a link between PLM and cell volume regulation has not been studied in the heart. We recently reported a depressed cardiac contractile function in PLM knockout mice in vivo, which was exacerbated in crystalloid-perfused isolated hearts, indicating that these hearts were osmotically challenged. To address this, the present study investigated the role of PLM in osmoregulation in the heart. Isolated PLM wild-type and knockout hearts were perfused with a crystalloid buffer supplemented with mannitol in a bid to prevent perfusate-induced cell swelling and maintain function. Accordingly, and in contrast to wild-type control hearts, contractile function was improved in PLM knockout hearts with 30 mM mannitol. To investigate further, isolated PLM wild-type and knockout cardiomyocytes were subjected to increasing hyposmotic challenges. Initial validation studies showed the IonOptix video edge-detection system to be a simple and accurate 'real-time' method for tracking cell width as a marker of cell size. Myocytes swelled equally in both genotypes, indicating that PLM, when expressed at physiological levels in cardiomyocytes, is not essential to limit water accumulation in response to a hyposmotic challenge. Interestingly, freshly isolated adult cardiomyocytes consistently failed to mount RVDs in response to cell swelling, adding to conflicting reports in the literature. A proposed perturbation of the RVD response as a result of the cell isolation process was not restored, however, with short-term culture in either adult or neonatal cardiomyocytes.

Alcohol, drugs and Australian young people.

Experimentation with alcohol and other drugs is often seen as a normal part of adolescent development. The harm associated with substance misuse in young people include injury, violent behaviour, sexual risk taking, drink-driving, overdose, toxicity and death (1-4). Australian young people are drinking alcohol and using illicit substances at an earlier age than previous cohorts (5). hey are more likely to binge drink, have poly-substance use and are at risk of co-morbid mental health problems (1-3). The reasons young people use drugs are complex and varied. An effective response to illicit drug use by young people has to be holistic, as complex and varied as the needs it addresses. It must seek to prevent minimize and manage harm caused by drug use and must be provided to and involve young people in the context of their family, peer group, school and community. Reaching out to young people with drug and alcohol problems is everyone's responsibility. Australia has developed specific prevention and early intervention programs for young people at risk of substance abuse however, further research and development is still needed for effective prevention, early intervention and treatment programs.