Blunting Effect Research Articles

The effects of chronic fatigue and chronic stress on alterations in immune cell responses to acute psychosocial stress

Fatigue is a common and debilitating symptom of a broad spectrum of diseases. Previous research has shown that individuals suffering from chronic forms of fatigue experience significantly more stress compared to healthy individuals, suggesting that stress is a potential pathophysiological factor in the onset and maintenance of chronic fatigue. Individually, chronic experiences of fatigue and stress have been associated with disruptions in adaptive immunity. However, how chronic fatigue and chronic stress together affect immune regulation is not fully understood. Here, we investigated the unique and combined contribution of chronic fatigue and chronic stress on immune cell redistribution in response to, and recovery from, acute psychosocial stress. Eighty women with high or low levels of chronic fatigue and varying levels of chronic stress were exposed to a psychosocial laboratory stressor. Blood samples were collected 10 min before and then at 10, 40, and 100 min after the end of stress. The main lymphocyte subpopulations (CD3+, CD3 + CD4+, CD3 + CD8+, CD16 + CD56+, and CD19 + cells) were enumerated via flow cytometry. Acute stress resulted in an increase in CD8 + and CD16+/CD56 + cells, a decline in CD4 + cells, and no effects on CD19 + B lymphocytes. Importantly, the magnitude of immune cell redistribution during stress reactivity (CD3+, CD4+, CD16+/CD56 + ) and recovery (CD3 + ) was contingent on fatigue and chronic stress levels of individuals. Notably, in contrast to low-fatigued individuals, who showed steeper changes in cell populations, increasing levels of chronic stress did not impact immune cell migration responses in high-fatigued individuals. Our findings demonstrate the compounded blunting effects of fatigue and chronic stress on adaptive immune functioning, highlighting a potential pathway for vulnerability and detrimental effects on long-term health.

Very high cycle fatigue behavior of TC4 titanium alloy: Faceting cracking mechanism and life prediction based on dislocation characterization

This research analyzes the very-high-cycle-fatigue behavior of TC4 titanium alloy through fatigue tests at R = −1, −0.3, and 0.1. The results show that the S-N curves are all bilinear and exhibit three failure modes as surface slip failure, surface cleavage failure and interior cleavage failure. Transmission electron microscopy analysis reveals the dislocation structure in interior cleavage failure and suggests that the deformation mechanism of faceting cracking involves both anti-phase boundary shearing and stacking fault shearing mechanisms. It concludes that interior failure results from cleavage fracture of α grains due to dislocation slip. Based on the stress intensity factor of the maximum defect, a slip-cleavage competitive failure model was developed by considering factors such as control volume, defect size, external loading, and grain content, with good predictive results. Additionally, on the basis of the failure mechanism and crack propagation rate model, considering the coupled effects of crack tip blunting, stress ratio, Vickers hardness, and material fracture toughness on crack propagation, the crack propagation life prediction model is constructed. The life prediction model is further modified to be more conservative and accurate in predicting life by consideration the maximum defect size, providing important theoretical support and practical guidance for engineering applications.

Enhanced strength–ductility synergy of SiC particles reinforced aluminum matrix composite via dual configuration design of reinforcement and matrix

To overcome the strength-ductility conflict in particle reinforced aluminum matrix composites (PRAMCs), a novel dual configuration strategy of microstructure was proposed in this work. The dual configuration including both heterogeneous grain structure and hybrid reinforcements was obtained by powder metallurgy, which was designed as submicron-sized SiC particles (SiCsm)/Al and micron-sized SiC particles (SiCm)/2024Al components. Representative alternating coarse grain (CG) bands containing SiCm and ultra fine grain (UFG) bands with dispersed SiCsm were revealed in microstructural characterizations. Compared to corresponding homogeneous composites with the same fraction particles, the dual configuration composite achieved simultaneous enhancement in strength and ductility and remained a comparable Young’s modulus of 98GPa, which represented 442 MPa in yield strength, 590 MPa in ultimate strength and 8.7 % in fracture elongation. The extra strength provided by hetero-deformation induced (HDI) strengthening is a potential dominant strengthening mechanism. The intrinsic toughening mechanisms primarily contribute to HDI strain hardening and enhanced dislocation accumulation capacity, while the extrinsic toughening mechanisms presumably attribute to more uniform microcrack distribution and blunting effect of CG zones on cracks. Our work provides a feasible route including ball milling and powder assembly to preparate high-modulus aluminum matrix composites for strength-ductility balance design.

Neuroprotective effects induced by citicoline/coenzyme Q10 fixed combination in rat CTX-TNA2 astrocytes exposed to oxidative stress

The present study aimed to investigate the rationale and efficacy of testing endogenous substances widely used as dietary supplement such as citicoline, coenzyme Q10 (CoQ10) and a fixed combination of them in countering the oxidative stress and neurotoxicity occurring in neurological diseases. Rat CTX-TNA2 astrocytes, which have considerable antioxidant potential and could represent a key target for neurotherapies were selected as in vitro model to conduct the experiments. The efficacy of citicoline and coenzyme Q10 (1 nM-10 μM), with their fixed combination, were assayed in rat astrocytes either in basal condition or after challenging the cells with hydrogen peroxide in order to evaluate the biocompatibility of treatments. The gene expression of B-Cell Lymphoma protein 2 (BCL-2), BCL-2 Associated X (BAX), Superoxide dismutase 2 (SOD2), Cardiolipin Synthase 1 (CRLS1), interleukin-6 (IL-6), tumor necrosis factor α (TNFα), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) involved in neurodegenerative diseases and neuroinflammation were investigated in CTX-TNA2 cells. Furthermore, in the same condition, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was carried out to assess apoptosis in astrocytes. Neither citicoline, nor coenzyme Q10 significantly altered astrocytes cell viability; thus, suggesting the biocompatibility of single ingredients and fixed combination in the concentration range considered for the study. Moreover, each compound tested alone or in combination were effective in inhibiting the hydrogen peroxide-induced gene expression of BAX, and SOD2, in inducing the gene expression of BCL-2 and CRLS1 and in reducing apoptosis. The blunting effects induced by the abovementioned treatments on hydrogen-peroxide induced apoptosis was also confirmed by TUNEL assay that demonstrated the capability of citicoline, CoQ10, and their combination to reduce the ratio TUNEL positive nuclei/total nuclei, a reliable marker of apoptosis. Additionally, citicoline, CoQ10, and their association were effective in inhibiting the hydrogen peroxide-induced NFkB, TNFα, and IL-6 gene. In parallel, there was an inhibition of both TNFα and IL-6 gene expression in basal condition. The co-administration of citicoline/coenzyme Q10 was overall more effective than individual ingredients. The present findings support the beneficial and synergistic effects of citicoline and coenzyme Q10 in fixed combination in reducing oxidation, and in stimulating neuroprotection in rat CTX-TNA2 astrocytes.

Study of the Blunt Effect of 7.62 mm Sniper Bullet on Protected Targets

Study of the Blunt Effect of 7.62 mm Sniper Bullet on Protected Targets

Real-life hypoglycaemia partially blunts the inflammatory response to experimental hypoglycaemia in people with type 1 diabetes.

To determine whether recent repeated exposure to real-life hypoglycaemia affects the pro-inflammatory response during a hypoglycemia episode. This was a post hoc analysis of a hyperinsulinaemic normoglycaemic-hypoglycaemic clamp study, involving 40 participants with type 1 diabetes. Glucose levels 1 week before the clamp were monitored using a Freestyle Libre 1. Blood was drawn during normoglycaemia and hypoglycaemia, and 24 hours after resolution of hypoglycaemia for measurements of inflammatory responses and counterregulatory hormone levels. We determined the relationship between the frequency and duration of spontaneous hypoglycaemia, and time below range (TBR) and the inflammatory response to experimental hypoglycaemia. On average, participants experienced 0.79 (0.43, 1.14) hypoglycaemia episodes per day, with a duration of 78 (47, 110) minutes and TBR of 5.5% (2.8%, 8.5%). TBR and hypoglycaemia frequency were inversely associated with the increase in circulating granulocyte and lymphocyte counts during experimental hypoglycaemia (P < .05 for all). A protein network consisting of DNER, IF-R, uPA, Flt3L, FGF-5 and TWEAK was negatively associated with hypoglycaemia frequency (P < .05), but not with the adrenaline response. Neither other counterregulatory hormones, nor hypoglycaemia awareness status, was associated with any of the inflammatory parameters markers. Repeated exposure to spontaneous hypoglycaemia is associated with blunted effects of subsequent experimental hypoglycaemia on circulating immune cells and the number of inflammatory proteins.

Experimental study on rooftop flow field of building based on the operation of vertical-axis wind turbines

Vertical-axis wind turbines (VAWTs) demonstrate good adaptability for harnessing wind energy on the building rooftops. However, knowledge gaps still exist in the understanding of the wind resources on the rooftop, the operation of VAWTs, and its effect on the wind field. To add new knowledge on this subject, the operation of wind turbines modeled by the NACA0018 airfoil on the rooftop of a building is experimentally studied via wind tunnel. The results indicate that flow above the rooftop of building shows an obvious speed reduction due to the blunt body effect of the turbines, and the turbulence intensities are dramatically enhanced. The different tip-speed ratios, wind directions, and installation locations of wind turbine have significant effect on flow field on the roof. Due to the flow characteristics above the rooftop, the power spectral density of the fluctuating wind speed exhibits high energy below the top position of the VAWT on the rooftop. Additionally, the wind profiles and probability distribution of the wake of VAWTs on the rooftop are analyzed and mathematically fitted for quantifying wind field characteristics rooftop turbines on the roof. For the VAWTs investigated in this study, the impacts of the operation of VAWTs on the wind field are non-negligible on the roof of building. The findings of this study will provide valuable insights for the optimal placement of VAWTs and utilization of wind energy on the rooftops.

Nosetip bluntness effects on a cone-cylinder-flare at mach 6

Nosetip bluntness effects on a cone-cylinder-flare at mach 6

Transabdominal motor evoked potential neuromonitoring of lumbosacral spine surgery

BACKGROUND CONTEXTTranscranial Motor Evoked Potentials (TcMEPs) can improve intraoperative detection of femoral plexus and nerve root injury during lumbosacral spine surgery. However, even under ideal conditions, TcMEPs are not completely free of false-positive alerts due to the immobilizing effect of general anesthetics, especially in the proximal musculature. The application of transcutaneous stimulation to activate ventral nerve roots directly at the level of the conus medularis (bypassing the brain and spinal cord) has emerged as a method to potentially monitor the motor component of the femoral plexus and lumbosacral nerves free from the blunting effects of general anesthesia. PURPOSETo evaluate the reliability and efficacy of transabdominal motor evoked potentials (TaMEPs) compared to TcMEPs during lumbosacral spine procedures. DESIGNWe present the findings of a single-center 12-month retrospective experience of all lumbosacral spine surgeries utilizing multimodality intraoperative neuromonitoring (IONM) consisting of TcMEPs, TaMEPs, somatosensory evoked potentials (SSEPs), electromyography (EMG), and electroencephalography. PATIENT SAMPLETwo hundred and twenty patients having one, or a combination of lumbosacral spine procedures, including anterior lumbar interbody fusion (ALIF), lateral lumbar interbody fusion (LLIF), posterior spinal fusion (PSF), and/or transforaminal lumbar interbody fusion (TLIF). OUTCOME MEASURESIntraoperative neuromonitoring data was correlated to immediate postoperative neurologic examinations and chart review. METHODSBaseline reliability, false positive rate, true positive rate, false negative rate, area under the curve at baseline and at alerts, and detection of preoperative deficits of TcMEPs and TaMEPs were compared and analyzed for statistical significance. The relationship between transcutaneous stimulation voltage level and patient BMI was also examined. RESULTSTaMEPs were significantly more reliable than TcMEPs in all muscles except abductor hallucis. Of the 27 false positive alerts, 24 were TcMEPs alone, and 3 were TaMEPs alone. Of the 19 true positives, none were detected by TcMEPs alone, 3 were detected by TaMEPs alone (TcMEPs were not present), and the remaining 16 true positives involved TaMEPs and TcMEPs. TaMEPs had a significantly larger area under the curve (AUC) at baseline than TcMEPs in all muscles except abductor hallucis. The percent decrease in TcMEP and TaMEP AUC during LLIF alerts was not significantly different. Both TcMEPs and TaMEPs reflected three preexisting motor deficits. Patient BMI and TaMEP stimulation intensity were found to be moderately positively correlated. CONCLUSIONSThese findings demonstrate the high reliability and predictability of TaMEPs and the potential added value when TaMEPs are incorporated into multimodality IONM during lumbosacral spine surgery.

Investigating the ductile to brittle transition phenomenon in binary Fe-Ni systems using molecular dynamics simulation

Ductile to brittle transition (DBT) phenomenon is commonly observed in BCC Fe-based systems, which significantly deteriorates their low temperature fracture toughness. Ni is known to be an effective alloying element to improve the low temperature toughness by reducing the ductile to brittle transition temperature (DBTT). The present article investigates the role of Ni in tailoring the DBT curve of BCC Fe by employing molecular dynamics (MD) simulation. Here, we performed mode-I loading of different pre-cracked systems (pure Fe, Fe-2 wt% Ni and Fe-4 wt% Ni alloys) over a temperature range of 1–800 K to construct their DBT curves. The DBT curves are subsequently correlated with the temperature sensitivity of fracture stress, which is estimated using the concept of critical strain energy release rate (GIC). The role of Ni in reducing the fracture stress sensitivity is responsible for decreasing the DBTT as well as the slope of the DBT region. The underlying mechanism is discussed in terms of the crack blunting effect of Ni which effectively increases the GIC and hence the fracture stress, particularly at the low temperature regimes. Besides, the significantly large strain rate imposed in MD simulation is mainly responsible for the higher DBTT values when compared with the experimental results. The present paper tackles this strain rate issue by using an appropriate strain rate sensitivity factor to rescale the simulated DBTT values down to the experimental ones, resulting in a good match between the simulated and experimental DBTT.

Effect of Leading-Edge Bluntness on Shockwave–Boundary-Layer Interaction in a Scramjet Intake

An experimental and numerical study was carried out to investigate the effect of leading edge bluntness on the flowfield characteristics of a Mach 6 scramjet inlet. The numerical study was performed using Ansys Fluent 18.0 software. A steady two-dimensional Reynolds-Averaged Navier–Stokes simulation was carried out using k-ε-Re-Normalisation Group model for a sharp edge and leading edge with bluntness of 0.5 and 1 mm (ramp and cowl tip). Significant changes in the flowfield characteristics and parameters were observed for a blunt leading edge compared to the sharp leading edge case. The experimental campaign was carried out in the Mach 6 S1 Hypersonic Ludwieg Tunnel to validate the numerical results, and a good match was observed up to the separation bubble, and deviation in the reattachment is observed. Furthermore, the unsteadiness associated with the shockwave–boundary-layer interaction region inside the isolator was studied for the sharp and blunt leading edge cases. It was observed that changing the leading edge bluntness modifies the flowfield oscillations, separation bubbles, shear layer oscillations, etc.

Transcriptomics identifies blunted immunomodulatory effects of vitamin D in people with multiple sclerosis

Vitamin D deficiency is a risk factor for developing multiple sclerosis (MS). However, the immune effects of vitamin D in people with MS are not well understood. We analyzed transcriptomic datasets generated by RNA sequencing of immune cell subsets (CD4+, CD8+ T cells, B cells, monocytes) from 33 healthy controls and 33 untreated MS cases. We utilized a traditional bioinformatic pipeline and weighted gene co-expression network analysis (WGCNA) to determine genes and pathways correlated with endogenous vitamin D. In controls, CD4+ and CD8+ T cells had 1079 and 1188 genes, respectively, whose expressions were correlated with plasma 25-hydroxyvitamin D level (P < 0.05). Functional enrichment analysis identified association with TNF-alpha and MAPK signaling. In CD4+ T cells of controls, vitamin D level was associated with expression levels of several genes proximal to multiple sclerosis risk loci (P = 0.01). Genes differentially associated with endogenous vitamin D by case–control status were enriched in TNF-alpha signaling via NF-κB. WGCNA suggested a blunted response to vitamin D in cases relative to controls. Collectively, our findings provide further evidence for the immune effects of vitamin D, and demonstrate a differential immune response to vitamin D in cases relative to controls, highlighting a possible mechanism contributing to MS pathophysiology.

Unraveling the effects of phason strain on the thermoelectric properties in Ag-In-Yb icosahedral quasicrystals

This study represents the experimental comparative analysis of the thermoelectric properties in an Ag-In-Yb phason-free icosahedral quasicrystal (iQC) and four phason-strained iQCs. The aim is to understand how phason strain affects these properties. The four phason-strained iQCs are 1/1 and 2/1 approximant crystals (1/1 AC and 2/1 AC), a sample grown by the Bridgman method with a high growth rate (phason QC-1), and a sample obtained by phonon–phason coupling (phason QC-2), the magnitude of phason strain decreasing in this order. Their compositions are similar to that of iQC, and in particular, the compositions of phason QC-1 and 2 are exactly the same as that of iQC, making them suitable for clarifying the correlation between physical properties and the magnitude of phason strain. Systematic changes were observed in the electrical resistivity, Seebeck coefficient, and electronic specific heat coefficient with increasing phason-strain magnitude, which can be interpreted as due to the effect of the phason-strain blunting the pseudogap at the Fermi level in the electronic density of states. In contrast, no appreciable dependence of phonon thermal conductivity on the phason-strain magnitude was observed; very low value and a plateau feature observed consistently for all the samples do not arise directly from the quasiperiodicity or high rotational symmetry but from complex structures with a large unit cell.

Simulated altitude is medicine: intermittent exposure to hypobaric hypoxia and cold accelerates injured skeletal muscle recovery.

Muscle injuries are the leading cause of sports casualties. Because of its high plasticity, skeletal muscle can respond to different stimuli to maintain and improve functionality. Intermittent hypobaric hypoxia (IHH) improves muscle oxygen delivery and utilization. Hypobaria coexists with cold in the biosphere, opening the possibility to consider the combined use of both environmental factors to achieve beneficial physiological adjustments. We studied the effects of IHH and cold exposure, separately and simultaneously, on muscle regeneration. Adult male rats were surgically injured in one gastrocnemius and randomly assigned to the following groups: (1) CTRL: passive recovery; (2) COLD: intermittently exposed to cold (4°C); (3) HYPO: submitted to IHH (4500m); (4) COHY: exposed to intermittent simultaneous cold and hypoxia. Animals were subjected to these interventions for 4h/day for 9 or 21days. COLD and COHY rats showed faster muscle regeneration than CTRL, evidenced after 9days at histological (dMHC-positive and centrally nucleated fibre reduction) and functional levels after 21days. HYPO rats showed a full recovery from injury (at histological and functional levels) after 9days, while COLD and COHY needed more time to induce a total functional recovery. IHH can be postulated as an anti-fibrotic treatment since it reduces collagen I deposition. The increase in the pSer473Akt/total Akt ratio observed after 9days in COLD, HYPO and COHY, together with the increase in the pThr172AMPKα/total AMPKα ratio observed in the gastrocnemius of HYPO, provides clues to the molecular mechanisms involved in the improved muscle regeneration. KEY POINTS: Only intermittent hypobaric exposure accelerated muscle recovery as early as 9days following injury at histological and functional levels. Injured muscles from animals treated with intermittent (4h/day) cold, hypobaric hypoxia or a simultaneous combination of both stimuli regenerated histological structure and recovered muscle function 21days after injury. The combination of cold and hypoxia showed a blunting effect as compared to hypoxia alone in the time course of the muscle recovery. The increased expression of the phosphorylated forms of Akt observed in all experimental groups could participate in the molecular cascade of events leading to a faster regeneration. The elevated levels of phosphorylated AMPKα in the HYPO group could play a key role in the modulation of the inflammatory response during the first steps of the muscle regeneration process.

Aerodynamic optimization of hypersonic blunted waveriders based on symbolic regression

The previous waverider optimization was mainly focused on the original configuration with sharp leading edge. In actual application, the leading edge must be blunted for hypersonic flight, which can change the aerodynamic performance significantly. Thus, the optimum waverider with sharp leading edge doesn't mean that it's still optimum after bluntness. To solve the problem, this paper first investigates the influence mechanism of leading edge bluntness on the aerodynamic performance of the waveriders in detail. And the novel methodology of symbolic regression is employed to establish an analytical pressure increment model for the original waverider caused by the bluntness effects. Then an efficient aerodynamic model for the blunted waverider is constructed by combining traditional approximate methods and the pressure increment model, which is further incorporated into the Genetic Algorithm optimization framework. Results show that the resulting blunted optimized waveriders have distinctly different shapes and better aerodynamic performance compared to previous optimization that considers only sharp leading edge. And as the bluntness radius or the design lift increases, the improvement of lift-to-drag ratio (L/D) turns larger. Finally, when the center of pressure is constrained during the optimization, the blunted optimized waverider exhibits both better trim characteristic and higher L/D.

Effects of Nasal Respiratory Support on Laryngeal and Esophageal Reflexes in Preterm Lambs.

Significant cardiorespiratory events can be triggered in preterm infants as part of laryngeal chemoreflexes (LCRs) and esophageal reflexes (ERs). We previously showed that nasal continuous positive airway pressure (nCPAP) blunted the cardiorespiratory inhibition induced with LCRs. Therefore, we aimed to compare the effects of nCPAP and high-flow nasal cannulas (HFNC) on the cardiorespiratory events induced during LCRs and ERs. The hypothesis is that nCPAP but not HFNC decreases the cardiorespiratory inhibition observed during LCRs and ERs. Eleven preterm lambs were instrumented to record respiration, ECG, oxygenation, and states of alertness. LCRs and ERs were induced during non-rapid eye movement sleep in a random order under these conditions: nCPAP 6 cmH2O, HFNC 7 L/min, high-flow nasal cannulas 7 L/min at a tracheal pressure of 6 cmH2O, and no respiratory support. nCPAP 6 cmH2O decreased the cardiorespiratory inhibition induced with LCRs, but not with ERs in preterm lambs. This blunting effect was less marked with HFNC 7 L/min, even when the tracheal pressure was maintained at 6 cmH2O. nCPAP might be a treatment for cardiorespiratory events related to LCRs in newborns, either in the context of laryngopharyngeal refluxes or swallowing immaturity. Our preclinical results merit to be confirmed through clinical studies. Laryngeal chemoreflexes can be responsible for significant cardiorespiratory inhibition in newborns, especially preterm. Nasal continuous positive airway pressure at 6 cmH2O significantly decreased this cardiorespiratory inhibition. High-flow nasal cannulas at 7 L/min had a lesser effect than nasal continuous positive airway pressure. Esophageal stimulation was responsible for a smaller cardiorespiratory inhibition, which was not significantly modified by nasal continuous positive airway pressure or high-flow nasal cannulas. Nasal continuous positive airway pressure should be tested for its beneficial effect on cardiorespiratory events related to laryngeal chemoreflexes in preterm newborns.

Abstract 17400: Effects of Concurrent Extracellular Vesicle and Metformin Therapy in Porcine Model of Chronic Myocardial Ischemia and Metabolic Syndrome

Introduction: We previously demonstrated using a swine model of chronic myocardial ischemia (CMI) that extracellular vesicle (EV) therapy improves cardiac function, perfusion, and angiogenic signaling, but these benefits were blunted in the setting of metabolic syndrome (MS). Hypothesis: We hypothesized that concurrent treatment with metformin may augment the cardiac effects of EV therapy in a swine model of CMI and MS. Methods: Twenty-nine Yorkshire swine were fed a high fat diet for four weeks to induce MS, then underwent placement of an ameroid constrictor to the left circumflex artery to induce CMI. Two weeks later, pigs receiving either oral placebo or 500mg metformin (MET) BID underwent intramyocardial injection of either vehicle or mesenchymal stem cell-derived EVs. This resulted in four groups: placebo+vehicle (CON, n=6), placebo+EV (EV, n=8), MET+vehicle (MET, n=7), and MET+EV (METEV, n=8). Five weeks after injection, pigs underwent functional measurements and harvest of ischemic myocardium. Perfusion, capillary density, and protein expression were measured by microspheres, immunofluorescence, and immunoblotting respectively. Results: Cardiac function was improved in EV compared to CON (SV p=0.02, SW p=0.01, CO p=0.03), and in MET compared to CON (SV p=0.03, SW p=0.09, CO p=0.2), though there were no differences between MET and METEV groups (p&gt;0.5 for all). Contractility as measured by slope of PRSW relationship was improved with METEV compared to CON (p=0.04), with a trend towards improvement in MET compared to CON (p=0.21), but not with EV alone. During pacing, there was increased perfusion in MET (p=0.04) and METEV (p=0.04) groups compared to CON. At rest, there was increased perfusion in MET (p=0.05) group, with a trend towards increased perfusion in METEV group (p=0.29) compared to CON, without differences between MET and METEV (p&gt;0.5). Capillary density was unchanged in METEV compared to CON (p&gt;0.5). The MET and METEV groups had decreased expression of p-Akt (p=0.01, p=0.06) and p-ERK (p=0.09, p=0.03) compared to CON, without changes in p-eNOS (p&gt;0.5), and all without differences between MET and METEV (p&gt;0.5). Conclusions: In the setting of CMI and MS, the blunted effects of EVs are not augmented by concurrent metformin therapy.

A pill as a quick solution: association between painkiller intake, empathy, and prosocial behavior

Previous research has demonstrated a link between the administration of analgesic drugs and the reduction of empathy levels in humans. This apparent blunting effect of pain medication has been explained through shared neural mechanisms for the first-hand and the empathic experience of pain (simulation theory). Considering that analgesics are among the most consumed drugs in the world and the ability to empathize with others is fundamental to human social interactions, the aim of the present study was to investigate whether the typical day-to-day analgesic consumption rate in Austria and Germany is associated with a reduction in empathy and prosocial behavior. We therefore collected self-reports of analgesic consumption behavior as well as empathy for pain and prosocial behavior measures in an online survey (n = 940). Analyses revealed no significant association between the analgesic intake frequency and measures of empathy or prosocial behavior. However, liberal intake of analgesics (i.e. mind-set of “a pill is a quick solution”) was linked to lower empathic concern and helping behavior, which may hint towards a negative effect in people who take pain medication for non-pain related issues or episodes of low pain. Nevertheless, further research is needed to investigate the effects of analgesic drugs in high frequency users.

Effects of Nose Bluntness on Hypersonic Transition over Ogive-Cylinder Forebodies

Ogive cylinders are representative designs of hypersonic forebodies and harbor several flow complexities. This work evaluates the effects of nose bluntness of ogive-cylinder forebodies on their laminar, transitional, and turbulent boundary layers (BLs). Laminar simulations indicate that the thickness of BL and entropy layer (EL) increases with nose bluntness, with the latter displaying a stronger sensitivity to nose radius due to the increased strength and curvature of the leading-edge shock system. Linear perturbation analysis identifies the presence of the second mode, the first mode, and EL modes with increasing bluntness. While the former two are prevalent over a significant streamwise extent, EL modes are limited to the upstream region, well within the swallowing length. Using direct numerical simulations, it is found that transition over the sharpest nose design occurs through the modal fundamental resonance route, driven by second-mode instabilities. Due to weakened BL modes, the blunter geometries undergo transition further downstream in the low-amplitude freestream perturbation environment tested in this study. The transition mechanism in the blunter geometries is intermittent in nature and appears to be driven by turbulent spots generated from streamwise vortices reminiscent of Klebanoff modes.

Effects of Small Leading-Edge Bluntness on High-Speed Boundary-Layer Instabilities on Flat Plates

A numerical investigation of the effect of small leading-edge bluntness on the linear stability regime in high-speed boundary layers for flat plates was carried out using linear stability theory. While it is known that increasing leading-edge bluntness leads to stabilization of the linear instability, it is not completely understood when leading-edge bluntness effects become relevant; in other words, for which leading-edge radii the primary instability regime is affected for flat plates at higher Mach numbers. For the so-called “sharp” geometries, it is assumed that the influence of the nose radius on stability and transition is negligible. For cones, it is generally accepted that nose radii resulting in Reynolds numbers (based on nose radius) smaller than 1000 can be considered sharp. However, no clear guidelines supported by numerical or experimental data exist to conclusively determine what constitutes a sharp leading edge for a flat plate. In this work, bluntness effects are assessed by considering the influence of the leading-edge radius on the linear stability characteristics for high-speed flat-plate boundary layers. It was found from linear stability calculations that surprisingly small leading-edge radii have significant effects on the critical Reynolds number and spatial amplification rates, thus resulting in substantially reduced maximum -factors.