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Calcifying echinoid larvae respond to changes in seawater carbonate chemistry with reduced growth and developmental delay. To date, no information exists on how ocean acidification acts on pH homeostasis in echinoderm larvae. Understanding acid–base regulatory capacities is important because intracellular formation and maintenance of the calcium carbonate skeleton is dependent on pH homeostasis. Using H+-selective microelectrodes and the pH-sensitive fluorescent dye BCECF, we conducted in vivo measurements of extracellular and intracellular pH (pHe and pHi) in echinoderm larvae. We exposed pluteus larvae to a range of seawater CO2 conditions and demonstrated that the extracellular compartment surrounding the calcifying primary mesenchyme cells (PMCs) conforms to the surrounding seawater with respect to pH during exposure to elevated seawater pCO2. Using FITC dextran conjugates, we demonstrate that sea urchin larvae have a leaky integument. PMCs and spicules are therefore directly exposed to strong changes in pHe whenever seawater pH changes. However, measurements of pHi demonstrated that PMCs are able to fully compensate an induced intracellular acidosis. This was highly dependent on Na+ and HCO3, suggesting a bicarbonate buffer mechanism involving secondary active Na+-dependent membrane transport proteins. We suggest that, under ocean acidification, maintained pHi enables calcification to proceed despite decreased pHe. However, this probably causes enhanced costs. Increased costs for calcification or cellular homeostasis can be one of the main factors leading to modifications in energy partitioning, which then impacts growth and, ultimately, results in increased mortality of echinoid larvae during the pelagic life stage.  相似文献   
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Idiopathic pulmonary fibrosis is characterized by a progressive scarring and stiffening of the peripheral lung tissue that decreases lung function. Over the course of the disease, the lung microvasculature undergoes extensive remodeling. There is increased angiogenesis around fibrotic foci and an absence of microvessels within the foci. To elucidate how the anti-fibrotic drug nintedanib acts on vascular remodeling, we used an in vitro model of perfusable microvessels made with primary endothelial cells and primary lung fibroblasts in a microfluidic chip. The microvasculature model allowed us to study the impact of nintedanib on permeability, vascularized area, and cell–cell interactions. The anti-vasculogenic impact of nintedanib was visible at the minimal concentrations of 10 nM, showing a significant increase in vessel permeability. Furthermore, nintedanib decreased microvessel density, diameter, and influenced fibroblast organization around endothelial microvessels. These results show that nintedanib acts on the endothelial network formation and endothelial–perivascular interactions. Advanced in vitro microvasculature models may thus serve to pinpoint the mechanistic effect of anti-fibrotic drugs on the microvascular remodeling in 3D and refine findings from animal studies.  相似文献   
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Statement of problem

Polymeric material for 3-dimensional printing can be used to fabricate occlusal devices. However, information about fracture resistance and wear is scarce.

Purpose

The purpose of this in vitro study was to investigate the fracture resistance and 2-body wear of 3-dimensional–printed (3DP) (FotoDent splint; Dreve Dentamid GmbH), milled polymethylmethacrylate (CAM) (Temp Basic; Transpa 95H16, Zirkonzahn GmbH), and conventionally fabricated polymethylmethacrylate (CAST) (Castdon; Dreve Dentamid GmbH) occlusal devices.

Material and Methods

A total of 96 occlusal devices were prepared according to the 3 different manufacturing techniques 3DP, CAM, and CAST (n=32). For each manufacturing technique, specimens were further divided into initial fracture resistance tests (n=16) and artificial aging in the mastication simulator (50 N, 37°C) with 2-body wear followed by fracture resistance tests (n=16). The fracture resistance was determined using a universal testing machine (1 mm/min). The wear was measured after 20?000 and 120?000 mastication cycles with the replica technique, mapped with a laser scanner, and quantified in R software. Data were analyzed using a 2-way ANOVA followed by a 1-way ANOVA with Scheffé or Games-Howell post hoc tests, repeated measures ANOVA with corrected Greenhouse-Geisser P values, and the Levene, Mann-Whitney, and paired t tests (α=.05).

Results

CAM presented higher initial fracture resistance than 3DP or CAST (P<.001). After mastication simulation, CAM followed by 3DP showed higher fracture resistance than CAST (P<.001). Mastication simulation decreased the fracture resistance for CAM and CAST (P<.001) but not for 3DP (P=.78). Three-dimensional–printed occlusal devices showed the highest material volume loss, followed by CAM and the lowest in CAST (P<.001).

Conclusions

Three-dimensional–printed occlusal devices showed lower wear resistance and lower fracture resistance than those milled or conventionally fabricated. Therefore, only short-term application in the mouth is recommended. Further developments of occlusal device material for 3-dimensional printing are necessary.  相似文献   
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Cardiac involvement in systemic light chain amyloidosis (AL) is generally associated with a worse outcome, especially if other organs are also involved. We sought to determine whether concurrent cardiac and renal involvement were associated with a worse outcome than either organ alone. We identified 129 patients with AL, who received high‐dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto‐HCT) at our institution between 1997 and 2014. Ninety‐nine patients had either renal (group 1: n = 62, 62%), cardiac (group 2: n = 20, 20%), or both cardiac and renal (group 3: n = 17, 17%) involvement. The overall hematological response rate (CR+VGPR+PR) post‐auto‐HCT in groups 1, 2, and 3 was 69%, 74% and 82%, respectively (P = 0.62). Overall, organ response in groups 1, 2, and 3 was 39%, 42%, and 70%, respectively. The median PFS from auto‐HCT in groups 1, 2, and 3 was not reached (NR), 13.3 and 21 months, respectively (P = 0.02). The median OS in groups 1, 2, and 3 was 120, 46, and 60 months, respectively (P = 0.1). In conclusion, median PFS and OS in patients with concurrent cardiac and renal AL were comparable to patients with cardiac AL only, but worse than patients with renal AL.  相似文献   
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The reluctance of students in health professions to care for AIDS patients is partially based on the perceived risk of transmission of HIV from patient contact. We hypothesize that fear of contagion is due to lack of knowledge and deep‐rooted attitudes and emotions existing even in areas of low HIV seroprevalence. We tested this hypothesis on medical, nursing, and medical technology students. Using a questionnaire that yielded four scales, results showed only 58% of students were knowledgeable, 81% were fearful of contagion, 57% were homophobic, and 8% had death anxiety. Lack of knowledge was correlated with fear of contagion (p < .05), whereas homophobia was weakly associated (p = .08). We conclude that this perceived risk of infection is a result of lack of knowledge, disbelief of the facts, and the interplay of personal values and emotions. Alternative educational methods are needed to increase students’ knowledge and to encourage students to examine their personal feelings and attitudes.  相似文献   
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