Neurally mediated syncope (NMS) is associated with a sudden loss of consciousness. However, the diagnostic tools and measures for prognosis management are limited. To overcome these limitations, the ...differences in the binding energies of Giα-protein-coupled receptors to the Glu9 and Glu12 residues on the α2B-AR gene were elucidated through the analysis of α2B-AR gene polymorphism. The suppression of the activity of adenylate cyclase (AC), which is involved in vasoconstriction, may be related to the onset of NMS. The head-up tilt (HUT) test results indicated differences in systolic blood pressure (SBP) and AC activity between patients with vasodepressor (VT)-NMS and healthy volunteers. Patients with VT-NMS had increased AC activity and decreased SBP. Conversely, in healthy volunteers, no changes in AC activity or SBP were found. These findings suggest that a high SBP and elevated AC activity at rest are likely to cause syncope. A high incidence of cardiovascular events is found in patients with negative HUT test results, highlighting the importance of investigating the cause of syncope in cases where the HUT test results are negative. Overall, our results may provide a means of assessing the risk of NMS development within healthy populations and underscore the importance of subsequent treatments for NMS.
Dyskeratosis congenita (DC) is a rare inherited disease in which the telomere complex cannot be maintained. Shortened telomeres can cause a number of clinical conditions. We herein report a case of ...unrelated bone marrow transplantation due to aplastic anemia associated with DC. The patient died of uncontrollable refractory intestinal bleeding. Three cases of DC with life-threatening hemorrhaging after transplantation have been reported; however, the bleeding origin could not be determined. Our case is the only patient in which a gastrointestinal bleeding point, jejunal multiple angioectasia, was determined.
The optimal duration of dual antiplatelet therapy after currently available drug-eluting stent (DES) implantation to prevent stent thrombosis (ST) remains controversial. Delayed healing is frequently ...identified as a leading cause of ST in the early phase. However, a thorough pathological investigation into strut coverage after currently available DES implantation is lacking—a gap addressed in the current study.
From our autopsy registry of 199 stented lesions, 4,713 struts from 66 currently available DES-stented lesions with an implant duration ≤370 days were histologically evaluated. Endothelial coverage was defined as the presence of luminal endothelial cells overlying struts and an underlying smooth muscle cell layer. The stented lesions were classified into acute coronary syndrome (ACS) (n = 40) and chronic coronary syndrome (CCS) (n = 26) groups and were compared. Endothelial coverage predictors were identified through logistic analysis.
Although ACS and CCS lesions presented comparable clinical characteristics, including age, sex, and cause of death, the latter exhibited a significantly higher prevalence of chronic kidney disease and hemodialysis than the former (33.3% vs. 65.2%; p = 0.02, 7.7% vs. 30.4%; p = 0.02). The poststent implant median duration was significantly shorter in ACS lesions than in CCS lesions (13 IQR 5–26 days vs. 40 IQR 16–233 days; p < 0.01). The endothelial coverage percentage was 3.5% at 30 days and 27.7% at 90 days after currently available DES implantation. Multivariable logistic regression analysis implicated implant duration of ≤90 days odds ratio (OR), 0.009; 95% confidence interval (CI), 0.006–0.012; p < 0.01, superficial calcification (OR, 0.11; 95% CI, 0.07–0.17; p < 0.01), ACS culprit site (OR, 0.29; 95% CI, 0.09–0.94; p = 0.039), and circumferentially durable polymer-coated DES (OR, 0.32; 95% CI, 0.24–0.41; p < 0.01) as delayed endothelial coverage predictors.
Endothelial coverage was limited at 90 days after currently available DES implantation, and the ACS culprit site and circumferentially durable polymer-coated DES were identified as independent predictors of delayed endothelial coverage. Our findings suggest the importance of underlying plaque morphology and stent technology for vessel healing after such implantation.
This study histologically evaluated 66 stented lesions from the autopsy registry with currently available DES implanted for ≤370 days. The percentage of endothelial coverage after currently available DES implantation was 3.5% and 27.7% at 30 and 90 days, respectively. Implant duration of ≤90 days, superficial calcification, ACS culprit site, and circumferentially DP-DES were determined as independent predictors of delayed endothelial coverage. ACS: acute coronary syndrome; BP-DES: biodegradable polymer-coated drug-eluting stent; DES: drug-eluting stent; DP-DES: durable polymer-coated drug-eluting stent; NC: necrotic core Display omitted
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background:
A recent meta-analysis of randomized control trials demonstrated a significantly higher risk of major amputation in patients treated with drug-coated balloons (DCBs) compared with ...standard treatment, especially in high-dose paclitaxel-coated DCBs. Distal particulate embolization after DCB use was considered a potential cause of the higher incidence of major amputation. The current study aimed to histologically and biologically compare biologic drug effect and distal particulate embolization in 3 DCBs (a high-dose paclitaxel-coated DCB IN.PACT Admiral and 2 low-dose paclitaxel-coated DCBs Ranger and Lutonix).
Methods and Results:
The DCBs were inflated in the healthy descending aortas of 18 rabbits, followed by euthanasia 28 days after the procedure. The treated descending aorta and distal skeletal muscles were histopathologically evaluated, and paclitaxel concentrations were measured. The paclitaxel concentration of the treated lesion was highest for Ranger, followed by IN.PACT and Lutonix (Ranger vs IN.PACT vs Lutonix: 1089 745–2170 pmol/mg vs 638 160–2075 pmol/mg vs 25 10–304 pmol/mg, respectively; p<0.0001). In the histopathological evaluation, the angle of severe medial smooth muscle cell loss was largest for Ranger followed by IN.PACT and Lutonix (12.8 8.0–20.4 degree vs 1.4 1.2–5.2 degree vs 0.8 0.5–2.5 degree, respectively), with significant differences for Ranger vs IN.PACT (p=0.007) and Ranger vs Lutonix (p=0.002). However, paclitaxel concentrations of distal skeletal muscles were lowest for Lutonix, followed by Ranger and IN.PACT (12 1–58 pmol/mg vs 15 13–21 pmol/mg vs 42 19–108 pmol/mg, respectively, p<0.0001). The numbers of arteries with downstream DCB effects were highest for IN.PACT, followed by Ranger and Lutonix (Ranger vs IN.PACT vs Lutonix, 3 3–4 vs 4 3–7 vs 2 1–2, respectively), which was consistent with the measured tissue paclitaxel concentrations.
Conclusion:
These findings suggest that Ranger demonstrates the strongest paclitaxel effect, as well as the second-best effect regarding distal particulate embolization, making it a good treatment option for patients with peripheral artery disease among the 3 DCBs evaluated in the current study. Further clinical head-to-head comparisons with larger numbers of patients are needed to explore which DCB is the most effective and safe treatment option.Clinical Impact:
The findings of the current preclinical study suggests that Ranger demonstrates the strongest paclitaxel effect, as well as the second-best effect regarding distal particulate embolization making it a good treatment for patients with intermittent claudication and chronic limb-threatening ischemia.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Ace of hearts: Liquid droplets can be manipulated in a controlled fashion along trajectories of any desired shape (such as a heart, see picture) by using light to create a wavelength‐dependent ...interfacial tension gradient at a liquid/liquid interface. In this new phenomenon, the “chromocapillary effect”, an interfacial flow generates droplet motion in the direction opposite to the gradient.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Osteoporosis, a disease of low bone mass, is associated with decreased osteoblast numbers and increased levels of oxidative stress within osteoblasts. Since transcription factors of the FoxO family ...confer stress resistance, we investigated their potential impact on skeletal integrity. Here we employ cell-specific deletion and molecular analyses to show that, among the three FoxO proteins, only FoxO1 is required for proliferation and redox balance in osteoblasts and thereby controls bone formation. FoxO1 regulation of osteoblast proliferation occurs through its interaction with ATF4, a transcription factor regulating amino acid import, as well as through its regulation of a stress-dependent pathway influencing p53 signaling. Accordingly, decreasing oxidative stress levels or increasing protein intake normalizes bone formation and bone mass in mice lacking
FoxO1 specifically in osteoblasts. These results identify FoxO1 as a crucial regulator of osteoblast physiology and provide a direct mechanistic link between oxidative stress and the regulation of bone remodeling.
► FoxO1 is required for normal osteoblast proliferation and bone formation ► FoxO1 interacts with ATF4 to promote amino acid import in osteoblasts ► Normal protein synthesis allows FoxO1 to maintain redox balance in osteoblasts ► These events downregulate p19/p16/p53 signaling and promote osteoblast proliferation
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose
The WULCA group, active since 2007 on Water Use in LCA, commenced the development of consensus-based indicators in January 2014. This activity is planned to last 2 years and covers human ...health, ecosystem quality, and a stress-based indicator. This latter encompasses potential deprivation of both ecosystem and human, hence aiming to represent potential impacts more comprehensively than any other available LCA-oriented method assessing the “water scarcity footprint” (ISO 2014).
Methods
A series of three expert workshops, including non-LCA experts from hydrology, eco-hydrology, and water supply science, was organized specifically on the topic of this generic midpoint indicator. They were held in Zurich on 10th September, in San Francisco on 5th October and in Tsukuba on 27th October 2014. In total 49 experts attended. The specific objectives of the workshops were twofold. First, it was to present the identified options of the stress-based indicator narrowed down by the active members of WULCA during the first 8 months of the project and to receive comments on the relevance, usefulness, acceptability, and focus of the selected indicator. Second, the workshop covered different challenges in the modeling of the indicator and presented the experts with background information and specific questions. This paper summarizes the discussions and outcome of these workshops. Where no agreement was reached, the working group of active members is considering all inputs received and continues the work.
Results and discussion
The discussion covered first the question to be answered by such indicator, resulting on an agreement on the evaluation of the potential to deprive other users of water, independently of who the user is (i.e., human or ecosystems). Special attention was given to the special case of arid areas as well as the definition of environmental water requirements. Specific modeling challenges were then addressed: definition and quantification of human and ecosystem water demand, consideration of green water and terrestrial ecosystems, sources of data, distinction of groundwater and surface water, and temporal and geographical resolution.
Conclusions
The input, decisions, and points of discussion were compiled and brought back within the group of active members. The group is using the recommendations and works further on the harmonization of the points of disagreement. It is expected that a selection of indicators representing different ways to address the most important issues will be produced and tested in spring 2015. The analysis of the result should lead to a provisional recommendation by summer 2015.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The design of dynamically self-assembled systems is of high interest in science and technology. Here, we report a unique cascade in the self-ordering of droplets accompanied by a dewetting ...transition. The dynamic self-emergent droplets are observed when a thin liquid layer of an immiscible fluorocarbon oil (perfluorooctyl bromide, PFOB) is placed on a water surface. Due to the gradual evaporation of PFOB, a circular PFOB-free domain appears as a result of a local dewetting transition. A circular pearling structure is generated at the rim with the growth of the dewetting hole. As the next stage, linear arrays of droplets are generated in a radial manner from the centre of the hole. These one-dimensional arrangements then evolve into two-dimensional hexagonal arrays of microdroplets through collective rhythmical shrinking/expanding motions. The emergence of such dynamic patterns is discussed in terms of the nonlinear kinetics of the dewetting transition under thermodynamically dissipative conditions.
Under non-equilibrium conditions, liquid droplets dynamically couple with their milieu through the continuous flux of matter and energy, forming active systems capable of self-organizing functions ...reminiscent of those of living organisms. Among the various dynamic behaviors demonstrated by cells, the pairing of heterogeneous cell units is necessary to enable collective activity and cell fusion (to reprogram somatic cells). Furthermore, the cyclic occurrence of eruptive events such as necroptosis or explosive cell lysis is necessary to maintain cell functions. However, unlike the self-propulsion behavior of cells, cyclic cellular behavior involving pairing and eruption has not been successfully modeled using artificial systems. Here, we show that a simple droplet system based on quasi-immiscible hydrophobic oils (perfluorodecalin and decane) deposited on water, mimics such complex cellular dynamics. Perfluorodecalin and decane droplet duos form autonomously moving Janus or coaxial structures, depending on their volumes. Notably, the system with a coaxial structure demonstrates cyclic behavior, alternating between autonomous motion and eruption. Despite their complexity, the dynamic behaviors of the system are consistently explained in terms of the spreading properties of perfluorodecalin/decane duplex interfacial films.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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