Impact of daily artificial gravity on autonomic cardiovascular control following 60-day head-down tilt bed rest.

Impaired cardiovascular autonomic control following space flight or immobilization may limit the ability to cope with additional hemodynamic stimuli. Head-down tilt bedrest is an established terrestrial analog for space flight and offers the opportunity to test potential countermeasures for autonomic cardiovascular deconditioning. Previous studies revealed a possible benefit of daily artificial gravity on cardiovascular autonomic control following head-down tilt bedrest, but there is a need for efficiency in a long-term study before an artificial gravity facility would be brought to space. We hypothesized that artificial gravity through short-arm centrifugation attenuates functional adaptions of autonomic function during head-down tilt bed rest. 24 healthy persons (8 women, 33.4 ± 9.3 years, 24.3 ± 2.1 kg/m2) participated in the 60-day head-down tilt bed rest (AGBRESA) study. They were assigned to three groups, 30 min/day continuous, or 6(5 min intermittent short-arm centrifugation, or a control group. We assessed autonomic cardiovascular control in the supine position and in 5 minutes 80° head-up tilt position before and immediately after bed rest. We computed heart rate variability (HRV) in the time (rmssd) and frequency domain, blood pressure variability, and baroreflex sensitivity (BRS). RR interval corrected rmssd was reduced supine (p = 0.0358) and during HUT (p = 0.0161). Heart rate variability in the high-frequency band (hf-RRI; p = 0.0004) and BRS (p < 0.0001) decreased, whereas blood pressure variability in the low-frequency band (lf-SBP, p = 0.0008) increased following bedrest in all groups. We did not detect significant interactions between bedrest and interventions. We conclude that up to daily 30 min of artificial gravity on a short-arm centrifuge with 1Gz at the center of mass do not suffice to prevent changes in autonomic cardiovascular control following 60-day of 6° head-down tilt bed rest. Clinical Trial Registration: https://drks.de/search/en/trial/DRKS00015677, identifier, DRKS00015677.

Effects of daily artificial gravity training on orthostatic tolerance following 60-day strict head-down tilt bedrest.

PURPOSE: Orthostatic intolerance commonly occurs following immobilization or space flight. We hypothesized that daily artificial gravity training through short-arm centrifugation could help to maintain orthostatic tolerance following head-down tilt bedrest, which is an established terrestrial model for weightlessness. METHODS: We studied 24 healthy persons (eight women; age 33.3 ± 9.0 years; BMI 24.3 ± 2.1 kg/m2) who participated in the 60-days head-down tilt bedrest (AGBRESA) study. They were assigned to 30 min/day continuous or 6 × 5 min intermittent short-arm centrifugation with 1Gz at the center of mass or a control group. We performed head-up tilt testing with incremental lower-body negative pressure until presyncope before and after bedrest. We recorded an electrocardiogram, beat-to-beat finger blood pressure, and brachial blood pressure and obtained blood samples from an antecubital venous catheter. Orthostatic tolerance was defined as time to presyncope. We related changes in orthostatic tolerance to changes in plasma volume determined by carbon dioxide rebreathing. RESULTS: Compared with baseline measurements, supine and upright heart rate increased in all three groups following head-down tilt bedrest. Compared with baseline measurements, time to presyncope decreased by 323 ± 235 s with continuous centrifugation, by 296 ± 508 s with intermittent centrifugation, and by 801 ± 354 s in the control group (p = 0.0249 between interventions). The change in orthostatic tolerance was not correlated with changes in plasma volume. CONCLUSIONS: Daily artificial gravity training on a short-arm centrifuge attenuated the reduction in orthostatic tolerance after 60 days of head-down tilt bedrest.

Restoration of marine ecosystems: Understanding possible futures for optimal outcomes.

Accelerating declines in the extent, quality and functioning of the world's marine ecosystems have generated an upsurge in focus on practical solutions, with ecosystem restoration becoming an increasingly attractive mitigation strategy for systems as diverse as coral reefs, mangroves and tidal flats. While restoration is popular because it promises positive outcomes and a return to something approaching unimpacted condition and functioning, it involves substantial public and private investment, both for the initial restoration activity and for on-going maintenance of the restored asset. This investment often affords one big chance to get things right before irretrievable damage is done. As a result, precise, well considered and accountable decision-making is needed to determine the specific focus for restoration, the scale of restoration, the location for deploying restoration activities, and indeed whether or not restoration is necessary or even possible. We explore the environmental/ecological considerations and constraints governing optimal decisions about the nature, location and prioritisation of restoration activities in marine ecosystems, and in particular the constraints on achieving understanding of possible futures and the likelihood of achieving them. We conclude that action must be informed by a context-specific understanding of the historical situation, the current situation, the constraints on change, the range of potential outcome scenarios, and the potential futures envisioned.

Cardiac biomarkers for risk stratification of arrhythmic death in patients with heart failure and reduced ejection fraction.

Objectives. Patients with heart failure and reduced left ventricular ejection fraction (HFrEF) are prone to ventricular tachyarrhythmias. We tested whether biomarkers C-terminal Endothelin 1 (CT-ET1), midregional pro atrial natriuretic peptide (MR-proANP) and midregional pro adrenomedullin (MR-proADM) might improve risk stratification for arrhythmic death.Methods: This prospective observational study included 160 heart failure patients with ischaemic cardiomyopathy (ICM) or non-ischaemic, dilated cardiomyopathy (DCM) and 30 control patients without heart disease. Primary endpoint was arrhythmic death (ArD) or resuscitated cardiac arrest (resCA).Results: A total of 61 patients died during the median follow-up of 7.0 [5.2-8.4] years. An ArD or resCA was observed in 48 patients. Plasma levels of CT-ET1 (p = 0.002), MR-proANP (p < 0.001) and MR-proADM (p = 0.013) were significantly higher in ICM or DCM patients compared to controls. MR-proANP levels in ICM patients were associated with a significantly increased risk for ArD or resCA (hazard ratio (HR) = 1.42, [95%CI: 1.08-1.85], p = 0.011) in a multivariable Cox regression model. Plasma levels of CT-ET1 (HR = 1.07 [0.98-1.17], p = 0.113) and MR-proADM (HR = 1.80 [0.92-3.55], p = 0.087) were not associated with ArD or resCA in ICM patients. No significant association with ArD or resCA was found in DCM patients. Multivariable Cox regression showed that CT-ET1 (HR = 1.14 [1.07-1.22], p < 0.001), MR-proANP (HR = 1.64 [1.29-2.08], p < 0.001) and MR-pro ADM (HR = 2.06 [1.12-3.77], p = 0.020) were associated with a higher risk for overall mortality.Conclusion: Patients with HFrEF had elevated levels of CT-ET1, MR-proANP and MR-proADM. Plasma levels of MR-proANP are useful as predictor for arrhythmic death in patients with ICM.

Our Environmental Value Orientations Influence How We Respond to Climate Change.

People variably respond to global change in their beliefs, behaviors, and grief (associated with losses incurred). People that are less likely to believe in climate change, adopt pro-environmental behaviors, or report ecological grief are assumed to have different psycho-cultural orientations, and do not perceive changes in environmental condition or any impact upon themselves. We test these assumptions within the context of the Great Barrier Reef (GBR), a region currently experiencing significant climate change impacts in the form of coral reef bleaching and increasingly severe cyclones. We develop knowledge of environmental cultural services with the Environmental Schwartz Value Survey (ESVS) into four human value orientations that can explain individuals' environmental beliefs and behaviors: biospheric (i.e., concern for environment), altruistic (i.e., concern for others, and intrinsic values), egoistic (i.e., concern for personal resources) and hedonic values (i.e., concern for pleasure, comfort, esthetic, and spirituality). Using face-to-face quantitative survey techniques, where 1,934 residents were asked to agree or disagree with a range of statements on a scale of 1-10, we investigate people's (i) environmental values and value orientations, (ii) perceptions of environmental condition, and (iii) perceptions of impact on self. We show how they relate to the following climate change responses; (i) beliefs at a global and local scale, (ii) participation in pro-environmental behaviors, and (iii) levels of grief associated with ecological change, as measured by respective single survey questions. Results suggest that biospheric and altruistic values influenced all climate change responses. Egoistic values were only influential on grief responses. Perception of environmental change was important in influencing beliefs and grief, and perceptions of impact on self were only important in influencing beliefs. These results suggest that environmental managers could use people's environmental value orientations to more effectively influence climate change responses toward environmental stewardship and sustainability. Communications that target or encourage altruism (through understanding and empathy), biospherism (through information on climate change impacts on the environment), and egoism (through emphasizing the benefits, health and wellbeing derived from a natural resource in good condition), could work.

The face of postural tachycardia syndrome - insights from a large cross-sectional online community-based survey.

BACKGROUND: Patients with postural tachycardia syndrome (POTS) experience chronic symptoms of orthostatic intolerance. There are minimal data detailing the demographics, clinical features and clinical course of this condition. This online, community-based survey highlights patients' experience with POTS. It consists of the largest sample of POTS patients reported to date. OBJECTIVES: To describe the demographics, past medical history, medications, treatments and diagnostic journey for patients living with POTS. METHODS: Postural tachycardia syndrome patients completed an online, community-based, cross-sectional survey. Participants were excluded if they had not received a diagnosis of POTS from a physician. The questions focused on the patient experience and journey, rather than physiological responses. RESULTS: The final analysis included 4835 participants. POTS predominantly affects white (93%) females (94%) of childbearing age, with approximately half developing symptoms in adolescence (mode 14 years). POTS is a chronic multisystem disorder involving a broad array of symptoms, with many patients diagnosed with comorbidities in addition to POTS. POTS patients often experience lengthy delays [median (interquartile range) 24 (6-72) months] and misdiagnosis, but the diagnostic delay is improving. POTS patients can present with a myriad of symptoms most commonly including lightheadedness (99%), tachycardia (97%), presyncope (94%), headache (94%) and difficulty concentrating (94%). CONCLUSIONS: These data provide important insights into the background, clinical features and diagnostic journey of patients suffering from POTS. These data should serve as an essential step for moving forward with future studies aimed at early and accurate diagnoses of these patients leading to appropriate treatments for their symptoms.

Nanoparticle-Based Mucosal Vaccines Targeting Tumor-Associated Antigens to Human Dendritic Cells.

The induction of effective T cell-mediated immune responses is the main objective of vaccination against cancer. T cell responses are initiated by dendritic cells (DCs) as the most potent antigen-presenting cells. Designing vaccines for efficient delivery of tumor antigens to these cells in immunogenic fashion is, therefore, a major task in tumor immunology. In this human-based in vitro study we investigated the suitability of different polymeric nanoparticles (NPs) for delivering the tumor-associated antigen Her2/neu to DCs for induction of T cell responses by mucosal vaccination. The natural polymer chitosan and novel functionalized PLGA-based polymers were used for NP production. All NPs were efficiently taken up by DCs. Her2/neu delivered by NPs was more efficiently processed and presented by DCs than the soluble protein and induced more vigorous CD4+ and CD8+ T cell proliferation, and cytotoxic T cells. Testing the suitability of this platform for mucosal vaccination, NPs were applied to the apical side of an intestinal epithelium model and found to be efficiently transported across the epithelial layer to become available to basolateral DCs. Thus, chitosan and PLGA-based NPs are efficient carriers for delivery of antigens to DCs for induction of T cell-based immunity, and suitable for mucosal vaccine formulations.

Similar appearance, different mechanisms: xerosis in HIV, atopic dermatitis and ageing.

Xerosis is one of the most common dermatologic disorders occurring in the elderly and in patients with atopic dermatitis (AD) and human immunodeficiency virus (HIV) infection. Xerosis has been linked to an impaired skin barrier function of the stratum corneum. Using Raman microspectroscopy, we concentrated on deeper skin layers, viable epidermis and dermis of 47 volunteers and associated molecular alterations to the evolution of xerosis and the skin barrier, for example, lipid, water and antioxidant content. A decrease in lipids within the viable epidermis is found for elderly and HIV-patients. Lipid and water values of AD patients and their healthy reference group are similar. Decreases in lipids and simultaneous increases in water are found in the dermis for HIV and AD patients in comparison to their healthy reference groups. Excessive levels of epidermal carotenoids, mainly lycopene, in HIV-patients were found potentially leading to adverse effects such as premature skin ageing.

Timing and source of the maximum of the transthoracic impedance cardiogram (dZ/dt) in relation to the H-I-J complex of the longitudinal ballistocardiogram under gravity and microgravity conditions.

The transthoracic impedance cardiogram (ICG) and the acceleration ballistocardiogram (BCG) measured close to the center of mass of the human body are generated by changes of blood distribution. The transthoracic ICG is an integrated signal covering the whole thorax and spatial resolution is poor. Comparison between both signals can be used to elucidate the source of the ICG signal. We recorded the ECG, ICG, and BCG simultaneously in healthy subjects under resting and microgravity conditions during parabolic flights. The time interval between the R-peak of the ECG and the maximum of the ICG (R-dZ/dtmax) and the time interval between the R-peak of the ECG and the I-peak in the BCG (R-I) differed significantly (p<0.0001). The I-peak in the BCG always occurred earlier during systole than dZ/dtmax. The delay of dZ/dtmax ranged between 23 and 28 ms at rest and was lowest under microgravity conditions (12 ± 4 ms, p<0.02). Our results suggest that both signals have different sources. Combination of modern imaging techniques with classical non invasive approaches to detect changes of blood distribution may provide new insights into the complex interaction between blood flow and mechanocardiographic signals like the BCG.

Human baroreflex rhythms persist during handgrip and muscle ischaemia.

AIM: To determine whether physiological, rhythmic fluctuations of vagal baroreflex gain persist during exercise, post-exercise ischaemia and recovery. METHODS: We studied responses of six supine healthy men and one woman to a stereotyped protocol comprising rest, handgrip exercise at 40% maximum capacity to exhaustion, post-exercise forearm ischaemia and recovery. We measured electrocardiographic R-R intervals, photoplethysmographic finger arterial pressures and peroneal nerve muscle sympathetic activity. We derived vagal baroreflex gains from a sliding (25-s window moved by 2-s steps) systolic pressure-R-R interval transfer function at 0.04-0.15 Hz. RESULTS: Vagal baroreflex gain oscillated at low, nearly constant frequencies throughout the protocol (at approx. 0.06 Hz - a period of about 18 s); however, during exercise, most oscillations were at low-gain levels, and during ischaemia and recovery, most oscillations were at high-gain levels. CONCLUSIONS: Vagal baroreflex rhythms are not abolished by exercise, and they are not overwhelmed after exercise during ischaemia and recovery.

Watching the low-frequency motions in aqueous salt solutions: the terahertz vibrational signatures of hydrated ions.

The details of ion hydration still raise fundamental questions relevant to a large variety of problems in chemistry and biology. The concept of water "structure breaking" and "structure making" by ions in aqueous solutions has been invoked to explain the Hofmeister series introduced over 100 years ago, which still provides the basis for the interpretation of experimental observations, in particular the stabilization/destabilization of biomolecules. Recent studies, using state-of-the-art experiments and molecular dynamics simulations, either challenge or support some key points of the structure maker/breaker concept, specifically regarding long-ranged ordering/disordering effects. Here, we report a systematic terahertz absorption spectroscopy and molecular dynamics simulation study of a series of aqueous solutions of divalent salts, which adds a new piece to the puzzle. The picture that emerges from the concentration dependence and assignment of the observed absorption features is one of a limited range of ion effects that is confined to the first solvation shell.

Exploring hydrophobicity by THz absorption spectroscopy of solvated amino acids.

Although hydrophobicity is a commonly used concept, its microscopic nature, particularly in the context of hydration, is not well understood. Here, we present a study of hydrophobic and hydrophilic solutes using terahertz (THz) spectroscopy and molecular dynamics (MD) simulations. We measured the concentration dependent THz absorption (2.1-2.7 THz) of several amino acids and peptides in aqueous solution. Experimentally, we find a correlation between the change in THz absorption of solvating water and specific properties of the solute such as polarity and hydrophobicity. In addition, we studied the effect of hydrophobic and hydrophilic model particles on water dynamics by MD simulations. We are able to link the vibrational density of states (VDOS) in hydration water around the model particles to the experimentally observed change in THz absorption of solvated amino acids. We find a stronger increase in THz absorption and in the oxygen VDOS of solvating water molecules for the hydrophilic versus hydrophobic solutes. The simulations provide us with a microscopic insight into the change of the hydration dynamics as induced by hydrophobic and hydrophilic solutes. For hydrophobic and hydrophilic model particles a retardation of dynamical processes on the picosecond timescale is found, which is more pronounced for hydrophilic compared to hydrophobic solutes.

A novel pharmacological approach to determining parasympathetic heart rate reserve in human subjects.

Severe cardiac parasympathetic dysfunction can be diagnosed using bedside tests, such as a Valsalva maneuver. However, the tests that are in use are of limited value in detecting and quantifying an early impairment in cardiac parasympathetic function. We showed that α-2-adrenoreceptor stimulation with clonidine combined with pharmacological baroreceptor loading unmasks impaired parasympathetic heart rate reserve before overt changes in heart rate regulation occur. The methodology could be utilized to monitor the progression of autonomic nervous system disease in studies carried out to test neuroprotective strategies.

The effect of donepezil treatment on cardiovascular mortality.

The acetylcholinesterase inhibitor donepezil hydrochloride improves cognitive function in patients with Alzheimer's disease and vascular dementia. Given acetylcholine's important actions on the heart, we undertook a retrospective cohort investigation to assess whether donepezil usage affects cardiovascular mortality. In patients treated with donepezil, hazard ratios for total and cardiovascular mortality were 0.68 (P = 0.045, 95% confidence interval 0.46-0.99) and 0.54 (P = 0.042, 95% confidence interval 0.30-0.98), respectively. The apparent survival benefit in donepezil-treated patients should not be overinterpreted. Prospective clinical trials are warranted.

Interfacial Cu/ZnO contact by selective photodeposition of copper onto the surface of small ZnO nanoparticles in non-aqueous colloidal solution.

Nanoscale copper was selectively photodeposited onto the surface of hexadecylamine (HDA) stabilized (monodispersed not agglomerated) ZnO nanoparticles (NPs) of a diameter of 2-5 nm, which leads to HDA-stabilized Cu/ZnO NPs of varied Cu loading. The particles are soluble in non-polar organic solvents. The line broadening and the red shift of the surface plasmon band of Cu/ZnO NPs relative to HDA-stabilized Cu NPs, the profound decrease of the Cu/ZnO NPs visible photoluminescence at 525 nm, the increase of the UV emission intensity at 365 nm and the enhancement of the Raman scattering (RS) intensity in comparison to the parent ZnO NPs confirmed the interfacial contact between the Cu and ZnO phase.

Confocal Raman microspectroscopy as an analytical tool to assess the mitochondrial status in human spermatozoa.

Confocal Raman microspectroscopy was used to investigate human sperm cells. Raman mapping with a 532 nm excitation laser allowed to unambiguously characterize the nucleus, the neck, and, in particular, the mitochondria-rich middle piece of a human sperm cell. The effect of ultraviolet radiation on different organelles of the sperm was quantified by localized spectral Raman signatures obtained within milliseconds. Chemical changes within the sub-cellular structure of the sperm cells were recorded as a function of ultraviolet light exposure time, showing the proof-of-principle that Raman microspectroscopy can be a fast diagnostic method for detecting the mitochondrial and motility status of human spermatozoa.

The formation of nitrogen-containing functional groups on carbon nanotube surfaces: a quantitative XPS and TPD study.

Nitrogen-containing functional groups were generated on the surface of partially oxidized multi-walled carbon nanotubes (CNTs) via post-treatment in ammonia. The treatment temperature was varied in order to tune the amount and type of nitrogen- and oxygen-containing functional groups, which were studied using high-resolution X-ray photoelectron spectroscopy (XPS) and temperature-programmed desorption (TPD). The surface defects on CNTs due to the incorporation of nitrogen were investigated by Raman spectroscopy. Deconvoluted XP N1s spectra were used for the quantification of different nitrogen-containing functional groups, and TPD studies were performed in inert and ammonia atmosphere to investigate the surface reactions occurring on the oxidized CNT surfaces quantitatively. Nitrile, lactam, imide and amine-type functional groups were formed in the presence of ammonia below 300 degrees C. When the OCNTs were treated in the medium temperature range between 300 degrees C to 500 degrees C, mainly pyridine-type nitrogen groups were generated, whereas pyridinic, pyrrolic and quaternary-type nitrogen groups were the dominating species present on the CNT surface when treated above 500 degrees C. It was found that about 38% of the oxygen functional groups react with ammonia below 500 degrees C.

Rattling in the cage: ions as probes of sub-picosecond water network dynamics.

We present terahertz (THz) measurements of salt solutions that shed new light on the controversy over whether salts act as kosmotropes (structure makers) or chaotropes (structure breakers), which enhance or reduce the solvent order, respectively. We have carried out precise measurements of the concentration-dependent THz absorption coefficient of 15 solvated alkali halide salts around 85 cm(-1) (2.5 THz). In addition, we recorded overview spectra between 30 and 300 cm(-1) using a THz Fourier transform spectrometer for six alkali halides. For all solutions we found a linear increase of THz absorption compared to pure water (THz excess) with increasing solute concentration. These results suggest that the ions may be treated as simple defects in an H-bond network. They therefore cannot be characterized as either kosmotropes or chaotropes. Below 200 cm(-1), the observed THz excess of all salts can be described by a linear superposition of the water absorption and an additional absorption that is attributed to a rattling motion of the ions within the water network. By providing a comprehensive set of data for different salt solutions, we find that the solutions can all be very well described by a model that includes damped harmonic oscillations of the anions and cations within the water network. We find this model predicts the main features of THz spectra for a variety of salt solutions. The assumption of the existence of these ion rattling motions on sub-picosecond time scales is supported by THz Fourier transform spectroscopy of six alkali halides. Above 200 cm(-1) the excess is interpreted in terms of a change in the wing of the water network librational mode. Accompanying molecular dynamics simulations using the TIP3P water model support our conclusion and show that the fast sub-picosecond motions of the ions and their surroundings are almost decoupled. These findings provide a complete description of the solute-induced changes in the THz solvation dynamics for the investigated salts. Our results show that THz spectroscopy is a powerful experimental tool to establish a new view on the contributions of anions and cations to the structuring of water.

Water solvation properties: an experimental and theoretical investigation of salt solutions at finite dilution.

Our combined analysis of first-principle simulations and experiments conducted on salt solutions at finite dilution shows that the high frequency range of the infrared spectrum of an aqueous solution of NaCl displays a shift toward higher frequencies of the stretching band with respect to pure water. We ascribe this effect to a lowering of the molecular dipole moments due to a decrease in the dipole moments of molecules belonging to the first and second solvation shells with respect to bulk water. An analysis of the dipole orientation correlations proves that the screening of solutes is dominated by short-range effects. These jointly experimental and theoretical results are corroborated by the good agreement between calculated and measured dielectric constants of our target solution.