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Atherosclerosis is a chronic inflammatory disease involving the accumulation of monocytes and macrophages in the vascular wall. Monocytes and macrophages play a central role in the initiation and progression of atherosclerotic lesion development. Oxidative stress, which occurs when reactive oxygen species (ROS) overwhelm cellular antioxidant systems, contributes to the pathophysiology of many chronic inflammatory diseases, including atherosclerosis. Major targets of ROS are reactive thiols on cysteine residues in proteins, which when oxidized can alter cellular processes, including signaling pathways, metabolic pathways, transcription, and translation. Protein-S-glutathionylation is the process of mixed disulfide formation between glutathione (GSH) and protein thiols. Until recently, protein-S-glutathionylation was associated with increased cellular oxidative stress, but S-glutathionylation of key protein targets has now emerged as a physiologically important redox signaling mechanism, which when dysregulated contributes to a variety of disease processes. In this review, we will explore the role of thiol oxidative stress and protein-S-glutathionylation in monocyte and macrophage dysfunction as a mechanistic link between oxidative stress associated with metabolic disorders and chronic inflammatory diseases, including atherosclerosis. [ABSTRACT FROM AUTHOR]

Abstract  Novel chemosensors based on 2-(2′-hydroxyphenyl)-4-phenylthiazole were synthesized and their anion sensing behaviors were investigated. Sensors 1 and 2 show fluoride ion selective behaviors related to their absorption and emission spectra amongst F−, CH3CO2 −, H2PO4 −, Cl−, Br−, I−, ClO4 −, NO3 −, and HSO4 − anions. Sensor 2 shows color change upon interaction with F−. Interactions of 1, 2 and 3 with F− cause a red-shift in UV–vis absorption and a large Stokes shift in fluorescence emission due to the inhibition of ESIPT induced by the deprotonation of phenolic proton by F−. [ABSTRACT FROM AUTHOR]

Expression of 21Sdi1 downstream of p53 is essential for induction of cellular senescence, although cancer cell senescence can also occur in the p53 null condition. We report herein that senescence-associated phosphorylated extracellular signal-regulated protein kinases 1 and 2 (SA-pErk1/2) enhanced p21Sdi1 transcription by phosphorylating Sp1 on Ser59 downstream of protein kinase C (PKC) α. Reactive oxygen species (ROS), which was increased in cellular senescence, significantly activated both PKCα and PKCβI. However, PKCα, but not PKCβI, regulated ROS generation and cell proliferation in senescent cells along with activation of cdk2, proven by siRNAs. PKCα-siRNA also reduced SA-pErk1/2 expression in old human diploid fibroblast cells, accompanied with changes of senescence phenotypes to young cell-like. Regulation of SA-pErk1/2 was also confirmed by using catalytically active PKCα and its DN-mutant construct. These findings strongly suggest a new pathway to regulate senescence phenotypes by ROS via Sp1 phosphorylation between PKCα and SA-pErk1/2: employing GST-Sp1 mutants and MEK inhibitor analyses, we found that SA-pErk1/2 regulated Sp1 phosphorylation on the Ser59 residue in vivo, but not threonine, in cellular senescence, which regulated transcription of p21Sdi1 expression. In summary, PKCα, which was activated in senescent cells by ROS strongly activated Erk1/2, and the SA-pErk1/2 in turn phosphorylated Sp1 on Ser59. Sp1-enhanced transcription of 21Sdi1 resulted in regulation of cellular senescence in primary human diploid fibroblast cells. [ABSTRACT FROM AUTHOR]

In this paper, we investigate comprehensive issues of modularized robot systems and present architecture for effective development of personal robots. The proposed architecture includes the interface and interaction methodology of the hardware modules and the software among the modules. Based on the architecture, we present a fully modularized personal robot dynamically reconfigurable personal robot I. Its hardware modules are easily added to or removed from the original system, and also the distributed software functions of the modules are rearrangeable accordingly. We focus on how to effectively build up the robot, and discuss the dynamically reconfigurable features of it for evaluating the proposed idea and approach. [ABSTRACT FROM AUTHOR]

The ultrasonic motor (USM) has many merits for use in a robot arm application. Therefore, the disk-type traveling wave B14 rotary ultrasonic motor (RUSM) is proposed in this paper for that application. Up to the present time, the analysis and design of the USM have been almost always performed using rough analytic methods or using commercial analysis tools. As a result, it was impossible to achieve an exact analysis and design of the USM. In order to address this problem, this paper proposes the analysis and design methodology of the B14 RUSM using a numerical method (3-D FEM) combined with an analytic method taking the contact mechanism into consideration in a linear operation. This methodology is applicable to many other kinds of USMs that use similar mechanisms. In addition, the mechanical system and the driving circuit of the B14 RUSM are designed and prototyped. Finally, the proposed analysis and design methodology is validated by comparing its outcomes with the experimental data. Also, the appropriateness of the suggested RUSM for the application of a robot arm was verified. [ABSTRACT FROM AUTHOR]

In warm forming of aluminum sheet materials, determination, realization, and maintenance of optimal temperature gradient is a key process parameter for increased formability. In this study, a two-phase procedure for efficient and accurate determination of proper temperature condition for warm forming of aluminum sheet metal blanks is presented using a hybrid 3D isothermal/non-isothermal finite element analysis (FEA) and design of experiments (DOE) approach. First, the relative trend, priority and overall temperature ranges of aluminum sheet metal blank regions are obtained using isothermal FE modeling and DOE techniques to reduce the analysis time significantly. In this phase, different temperature levels were assigned onto different regions of the deforming blank material (i.e., holding region, corner region, etc.). Heat transfer with the tooling and environment during the deformation process is ignored in order to achieve rapid predictions. Second, few additional non-isothermal FEAs, taking heat transfer into account, are conducted to validate and to refine the warm forming conditions based on the results from the isothermal FEA/DOE analysis. The proposed hybrid methodology offers rapid and relatively accurate design of warm forming process, especially for large parts that require 3D FE analysis. In addition, effects of forming speed (v), friction (μ), and blank holder pressure on formability are investigated. Increasing part formability is observed with decreasing punch speed and blank holder pressure while an optimal process window is found in case of varying friction coefficients. [ABSTRACT FROM AUTHOR]

In this study, thermomechanically coupled finite element analysis (FEA) was performed for forming aluminum rectangular cups at elevated temperatures. In order to identify the onset of a failure during FEA, applicability, accuracy, and repeatability of three different failure criteria (maximum load, minimum thickness, and thickness ratio) were investigated. The thickness ratio criterion was selected since it resulted in accurate prediction of necking-type failure when compared with experimental measurements obtained under a variety of warm forming conditions. Predicted part depth values from FEA at various die-punch temperature combinations and blank holder pressures conditions were also compared with experiments, and showed good agreement. Forming limit diagrams were established at three different warm forming temperature levels (250°C, 300°C, and 350°C). An increasing limiting strain was observed with increasing forming temperature both in FEA and experiments. In addition, strain distributions on the formed part obtained under different die-punch temperature combinations were also compared to further validate the accuracy of FEA. A high temperature gradient between die and punch (Tdie>Tpunch) was found to result in increased formability; i.e., high part depths. [ABSTRACT FROM AUTHOR]

Investigates the mechanism of senescence-associated cytoplasmic induction of p-Erk1/2 proteins in human fibroblasts. Dephosphorylation of proteins in vitro by protein phosphatases 1 and 2A and MAPK phosphatase 3; Mechanisms of phosphatase inactivation; Measurement of the reactive oxygen species generation by fluorescence-activated cell sorting analysis.

The synthesis, spectroscopic characterization, and potentiometric measurements of new 1,3,5-trisphenoxy-2,4,6-triethylbenzenes are described. The cation binding abilities of trisphenoxy-2,4,6-triethylbenzenes were strongly dependent on the substituents introduced on the phenoxy units: the receptors with electron-donating alkoxy groups (–OCH3 and –OCH2C6H5) provided similar potentiometric performance to that of nonactin in PVC-based, ion-selective membrane electrodes. The trisphenoxy-2,4,6-triethylbenzene receptors with ether groups on ortho and meta positions of phenoxy units exhibit almost identical cation recognition properties in the PVC membranes. It is postulated that the electron-donating nature of the alkoxy substituents increases the electron density in the phenoxy units, resulting in increased cation-π interactions. [ABSTRACT FROM AUTHOR]

Reports on the development of a synthetic ammonium-selective ionophores whose resulting potentiometric properties in solvent polymeric membranes are superior to nonacting, using a class of crown ethers containing heterocyclic units. Preparation of the electrodes and their potentiometric evaluation; Compounds prepared; Cation complex formation.

Investigates the limitation and applicability of the ductile fracture criteria on the prediction of ductile fracture in cold forging of aluminum alloys based on a work hypothesis and Cockroft and Latham. Advantages of the Cockroft and Latham criterion in prediction of crack initiation site; Difference of limiting damage factor values between simple upsetting and pin-shape forging.

Abstract Background In metaphyseo-diaphyseal (M-D) mismatched Dorr A femurs, it is difficult to achieve proper fixation with a type 1 stem. Proper interpretation of the geometry of the femur is integral at the preoperative stage in an M-D mismatched femur, but there has been a scarcity of studies on the radiologic indices. Therefore, we analyze the previous radiologic indices and suggest the novel ones for M-D mismatched femurs. Methods Our study was a retrospective review of preoperative radiographs of patients who underwent total hip arthroplasty with the smallest type 1 stem or with type 3 C stem at a single institution from July 2014 to March 2022. A Type 3 C stem was used when the smallest type 1 stem failed to achieve metaphyseal fixation. One hundred twenty-six patients were categorized into two main groups. Canal-flare index, canal-calcar ratio, modified morphological cortical index, and two novel indices (lesser trochanter-to-distal ratio-α and -β [LDR-α and -β]) were assessed on preoperative pelvic radiographs. Results Multivariate and ROC analysis demonstrated that high LDR-β (Exp[B]: 485.51, CI: 36.67-6427.97, p

Abstract Background Leg length discrepancy (LLD) is one of the troublesome complications of total hip arthroplasty (THA). Previously, several risk factors have been suggested, but they were subjected to their inherent limitations. By controlling confounding variables, we hypothesized that known risk factors be re-evaluated and novel ones be discovered. This study aimed to analyze the independent risk factors for LLD after primary THA in patients with non-traumatic osteonecrosis of the femoral head (ONFH). Methods We retrospectively reviewed patients with non-traumatic ONFH who underwent unilateral THA between 2014 and 2021. All patients were operated by one senior surgeon using a single implant. Demographic data, surgical parameters, and radiological findings (pre-operative LLD, Dorr classification, and femoral neck resection) were analyzed to identify the risk factors of ≥ 5 mm post-operative LLD based on radiological measurement and to calculate odds ratios by logistic regression analysis. Post hoc power analysis demonstrated that the number of analyzed patients was sufficient with 80% power. Results One hundred and eighty-six patients were analyzed, including 96 females, with a mean age of 58.8 years at the time of initial THA. The average post-operative LLD was 1.2 ± 2.9 mm in the control group and 9.7 ± 3.2 mm in the LLD group, respectively. The LLD group tended to have minimal pre-operative LLD than the control group (-3.2 ± 5.1 mm vs. -7.9 ± 5.8 mm p = 2.38 × 10− 8). No significant difference was found between the groups in age, gender, body mass index, femoral cortical index, and implant size. Conclusion Mild pre-operative LLD is associated with an increased risk of post-operative LLD after primary THA in patients with ONFH. Thus, surgeons should recognize pre-operative LLD to achieve an optimal outcome and must inform patients about the risk of developing LLD.

Abstract The biological process of aging is thought to result in part from accumulation of senescent cells in organs. However, the present study identified a subset of fibroblasts and smooth muscle cells which are the major constituents of organ stroma neither proliferative nor senescent in tissues of the elderly, which we termed “mid-old status” cells. Upregulation of pro-inflammatory genes (IL1B and SAA1) and downregulation of anti-inflammatory genes (SLIT2 and CXCL12) were detected in mid-old cells. In the stroma, SAA1 promotes development of the inflammatory microenvironment via upregulation of MMP9, which decreases the stability of epithelial cells present on the basement membrane, decreasing epithelial cell function. Remarkably, the microenvironmental change and the functional decline of mid-old cells could be reversed by a young cell-originated protein, SLIT2. Our data identify functional reversion of mid-old cells as a potential method to prevent or ameliorate aspects of aging-related tissue dysfunction.

Objective We previously reported the questionable result of reoperation using metal‐on‐polyethylene (MoP) bearing after the fracture of the ceramic component. After the report, we abandoned the use of MoP; instead, we used ceramic‐on‐ceramic (CoC) bearing. This report aimed to present the outcome of reoperation to CoC bearing after ceramic component failures along with the longer‐term outcome of the previously reported cohort with an MoP bearing. Results The mean follow‐up of the MoP cohort was extended from 4.3 years to 8.8 years. Metallosis had occurred in three of nine patients of the previous cohort, which all required re‐reoperations. Two hips from 11 patients with revision to CoC had re‐reoperations due to ceramic liner fracture and non‐union of the osteotomized fragment, respectively. No metallosis and wear occurred in the cohort revised with CoC articulation. Otherwise, there were no adverse changes in radiographs and no impairment in functions. Methods We conducted an extended prospective evaluation of a previous cohort consisting of six head fractures and three liner fractures. In this cohort, the patients underwent a bearing change to metal‐on‐polyethylene. Additionally, we retrospectively analyzed 11 cases of third‐generation ceramic bearing fractures, comprising nine head fractures and two liner fractures. These cases were subsequently treated with a bearing change to fourth‐generation CoC. We assessed clinical and radiological outcomes, including complication rates, in both groups. Conclusion We recommend the latest CoC as the bearing of choice in reoperation after the fracture of ceramic components. In the case of an MoP bearing after the ceramic component fracture, the risk of metallosis seemed high in the early postoperative period.

We report on the fabrication and electrical transport properties of gate-tunable superconducting quantum interference devices (SQUIDs), made from a semiconducting PbS nanowire contacted with PbIn superconducting electrodes. With a magnetic field applied perpendicular to the plane of the nanohybrid SQUID, periodic oscillations of the critical current due to the flux quantization in SQUID are observed up to T = 4.0 K. A nonsinusoidal current–phase relationship is obtained as a function of temperature and gate voltage, which is consistent with a short and diffusive junction model. [ABSTRACT FROM AUTHOR]

Maternal obesity and gestational diabetes are associated with childhood obesity and increased cardiovascular risk. In this review, we will discuss and summarize extensive clinical and experimental studies that metabolically imbalanced environment exposure in early life plays a critical role in influencing later susceptibility to chronic inflammatory diseases and metabolic syndrome. The effect of maternal obesity and metabolic disorders, including gestational diabetes cause Large-for-gestational-age (LGA) children to link future development of adverse health issues such as obesity, atherosclerosis, hypertension, and non-alcoholic fatty liver disease by immune reprogramming to adverse micro-environment. This review also addresses intrauterine environment-driven myeloid reprogramming by epigenetic regulations and the epigenetic markers as an underlying mechanism. This will facilitate future investigations regarding maternal-to-fetal immune regulation and the epigenetic mechanisms of obesity and cardiovascular diseases.

High-mobility group box 1 (HMGB1) is a protein that binds to DNA and participates in various cellular processes, including DNA repair, transcription, and inflammation. It is also associated with cancer progression and therapeutic resistance. Despite its known role in promoting tumor growth and immune evasion in the tumor microenvironment, the contribution of HMGB1 to the development of Kaposi’s sarcoma (KS) is not well understood. We investigated the effect of HMGB1 on KS pathogenesis using immortalized human endothelial cells infected with Kaposi’s sarcoma-associated human herpes virus (KSHV). Our results showed that a higher amount of HMGB1 was detected in the supernatant of KSHV-infected cells compared to that of mock-infected cells, indicating that KSHV infection induced the secretion of HMGB1 in human endothelial cells. By generating HMGB1 knockout clones from immortalized human endothelial cells using CRISPR/Cas9, we elucidated the role of HMGB1 in KSHV-infected endothelial cells. Our findings indicate that the absence of HMGB1 did not induce lytic replication in KSHV-infected cells, but the cell viability of KSHV-infected cells was decreased in both 2D and 3D cultures. Through the antibody array for cytokines and growth factors, CXCL5, PDGF-AA, G-CSF, Emmprin, IL-17A, and VEGF were found to be suppressed in HMGB1 KO KSHV-infected cells compared to the KSHV-infected wild-type control. Mechanistically, phosphorylation of p38 would be associated with transcriptional regulation of CXCL5, PDGF-A and VEGF. These observations suggest that HMGB1 may play a critical role in KS pathogenesis by regulating cytokine and growth factor secretion and emphasize its potential as a therapeutic target for KS by modulating the tumor microenvironment.

Endothelial cell dysfunction and inflammatory responses play critical roles in the development of atherosclerosis. Recent data on the processes underlying atherogenesis indicate the substantial role of endotoxins (lipopolysaccharides; LPS) of the intestinal microflora in the initiation and progression of atherosclerosis. Mitogen-activated protein (MAP) kinase phosphatase-3 (MKP-3) is a cytoplasmic dual-specificity protein phosphatase that specifically binds to and inactivates MAP kinases in mammalian cells, but its biological function in endothelial cell dysfunction and inflammatory responses remains largely unknown. The aim of the present study was to investigate the role of MKP-3 in endotoxin-induced endothelial inflammation by western blotting, quantitative polymerase chain reaction, and immunofluorescence. The results of our study demonstrated that MKP-3 overexpression markedly inhibited the adhesion of human monocytic THP-1 cells to human umbilical vein endothelial cells (HUVECs) by downregulating the expression of vascular cell adhesion protein 1 (VCAM-1) and pro-inflammatory cytokines. In contrast, MKP-3-encoding gene knockdown by small interfering RNA (siRNA) exacerbated LPS-induced endothelial dysfunction. Additionally, we found that MKP-3 overexpression inhibited LPS-induced p38 MAPK phosphorylation and decreased the nuclear translocation of nuclear factor kappa B (NF-κB) after LPS treatment, suggesting its implication in the LPS/Toll-like receptor 4 (TLR4)/p38/NF-κB pathway. Overall, these observations suggest that MKP-3 plays a protective role in endothelial dysfunction and may be a therapeutic target.

Free-piston Stirling coolers (FPSCs), where the spring is connected to a piston instead of a crankshaft to eliminate the complicated mechanism, have a simple structure, and exhibit high thermal efficiency and reliability. The present study conducted a numerical analysis of the cooling performance of the FPSC system for various design factors such as the wire mesh number and porosity of the regenerator and displacer clearance. The system analysis model using the commercial SAGE software was established for heat exchangers with wire meshes. Also, this study investigated the effect of the cooling temperature at the acceptor wall on the cooling performance under the optimal condition. It was found that as the wire mesh number and porosity of the regenerator increased, the cooling capacity of the FPSC decreased. The friction loss decreased, but the leakage loss increased with the increase in displacer clearance thickness.

This study numerically investigated the cooling characteristics of a free-piston Stirling cooler (FPSC), which is considered as an alternative cooling system. In particular, the effect of the heat transfer area of the regenerator on the cooling performance and pressure loss of the FPSC was estimated. Commercial code ANSYS Fluent (v.17.2) was used for numerical analysis. A thermal non-equilibrium model was adopted to consider the effect of the heat transfer area of the wire mesh type regenerator. Furthermore, the dynamic mesh method was used to simulate the behavior of the dynamic components. As the heat transfer area of the regenerator increased, the cold end temperature that reached the quasi-steady state decreased. However, simultaneously, the pressure drop of the regenerator increased, which increased the input PV power required to drive the FPSC and decreased efficiency.

Polyunsaturated fatty acids (PUFAs) have important functions in biological systems. The beneficial effects of dietary PUFAs against inflammatory diseases, cardiovascular diseases, and metabolic disorders have been shown. Studies using cancer cells have presented the anti-tumorigenic effects of docosahexaenoic acid (DHA), an n-3 PUFA, while arachidonic acid (AA), an n-6 PUFA, has been shown to elicit both pro- and anti-tumorigenic effects. In the current study, the anti-tumorigenic effects of AA were evaluated in HT-29 human colon cancer cells. Upon adding AA in the media, more than 90% of HT-29 cells died, while the MCF7 cells showed good proliferation. AA inhibited the expression of SREBP-1 and its target genes that encode enzymes involved in fatty acid synthesis. As HT-29 cells contained lower basal levels of fatty acid synthase, a target gene of SREBP-1, than that in MCF7 cells, the inhibitory effects of AA on the fatty acid synthase levels in HT-29 cells were much stronger than those in MCF-7 cells. When oleic acid (OA), a monounsaturated fatty acid that can be synthesized endogenously, was added along with AA, the HT-29 cells were able to proliferate. These results suggested that HT-29 cells could not synthesize enough fatty acids for cell division in the presence of AA because of the suppression of lipogenesis. HT-29 cells may incorporate more AA into their membrane phospholipids to proliferate, which resulted in ER stress, thereby inducing apoptosis. AA could be used as an anti-tumorigenic agent against cancer cells in which the basal fatty acid synthase levels are low.

Multiple host proteins affect the gene expression of Kaposi's sarcomaassociated herpesvirus (KSHV) during latent and lytic replication. High-mobility group box 1 (HMGB1) serves as a highly conserved chromosomal protein inside the cell and a prototypical damage-associated molecular pattern molecule outside the cell. HMGB1 has been shown to play a pathogenic role in viral infectious diseases and to regulate the lytic replication of KSHV. However, its functional effects on the KSHV life cycle in KSHV-infected cells have not been fully elucidated. Here, we explored the role of intracellular and extracellular HMGB1 in KSHV virion production by employing CRISPR/Cas9-mediated HMGB1 knockout in the KSHV-producing iSLK BAC16 cell line. Intracellular HMGB1 formed complexes with various proteins, and the abundance of HMGB1-interacting proteins changed during latent and lytic replication. Moreover, extracellular HMGB1 was found to enhance lytic replication by phosphorylating JNK. Of note, the expression of viral genes was attenuated during lytic replication in HMGB1 knockout iSLK BAC16 cells, with significantly decreased production of infectious virions compared to that of wild-type cells. Collectively, our results demonstrate that HMGB1 is an important cellular cofactor that affects the generation of infectious KSHV progeny during lytic replication. [ABSTRACT FROM AUTHOR]

Platycodin D (PD) is a major active component of the roots of Platycodon grandiflorum (Jacq.) A.DC. and possesses multiple biological and pharmacological properties, including anti-cancer activity. The aim of this study was to characterize PD-induced cytoplasmic vacuolation in human cancer cells and investigate the underlying mechanisms. PD-induced cancer cell death was associated with cytoplasmic pinocytic and autophagic vacuolation. Cellular energy levels were decreased by this compound, leading to the activation of AMP-activated protein kinase (AMPK). Additionally, compound C, an inhibitor of AMPK, completely prevented PD-induced vacuolation. These results suggest that PD induces cancer cell death, associated with excessive vacuolation through AMPK activation when cellular energy levels are low. Therefore, our findings provide a mechanistic rationale for a novel combinatorial approach using PD to treat cancer.

Abstract Cellular senescence can either support or inhibit cancer progression. Here, it is shown that intratumoral infiltration of CD8+ T cells is negatively associated with the proportion of senescent tumor cells in colorectal cancer (CRC). Gene expression analysis reveals increased expression of C‐X‐C motif chemokine ligand 12 (CXCL12) and colony stimulating factor 1 (CSF1) in senescent tumor cells. Senescent tumor cells inhibit CD8+ T cell infiltration by secreting a high concentration of CXCL12, which induces a loss of CXCR4 in T cells that result in impaired directional migration. CSF1 from senescent tumor cells enhance monocyte differentiation into M2 macrophages, which inhibit CD8+ T cell activation. Neutralization of CXCL12/CSF1 increases the effect of anti‐PD1 antibody in allograft tumors. Furthermore, inhibition of CXCL12 from senescent tumor cells enhances T cell infiltration and results in reducing the number and size of tumors in azoxymethane (AOM)/dextran sulfate sodium (DSS)‐induced CRC. These findings suggest senescent tumor cells generate a cytokine barrier protecting nonsenescent tumor cells from immune attack and provide a new target for overcoming the immunotherapy resistance of CRC.

Background: The main purposes of this study were to assess the levels of parenting stress in the mothers of children with congenital hand or foot differences and to evaluate the effects of this stress on the preferred roles of mothers in surgical decision-making for their children. Methods: This study included 89 mothers of children with polydactyly of the hand, polydactyly of the foot, a hypoplastic thumb, or macrodactyly. The parenting stress level was assessed using the Parenting Stress Index–Short Form (PSI-SF). Additionally, the mothers were requested to indicate their preferred and retrospectively perceived levels of involvement in surgical decision-making for their children using the Control Preferences Scale, which is comprised of five levels ranging from fully active to fully passive. Results: The average PSI-SF scores were 73.9, and 15 mothers (17%) had a clinically significant level of stress (PSI-SF ≥ 90). In the mothers of children with polydactyly of the foot, the PSI score was associated with the preferred role in surgical decision-making. Conclusion: The assessment of parenting stress levels in the mothers of children with congenital hand or foot differences can play an important role in the screening of candidates who require psychiatric treatment or support. An evaluation of the PSI in mothers of children with congenital hand or foot differences may aid physicians to modify their style of decision-making based on the preferred role of the mother. Level of evidence: Level IV Therapeutic study.

This study investigates the transient behavior of an electro-thermal drilling probe (ETDP) during a close-contact melting process within a glacier. In particular, the present work analyzes the effect of the tip temperature on the formation of molten thin liquid films and the subsequent rate of penetration (ROP) through numerical simulation. We used the commercial code of ANSYS Fluent (v.17.2) to solve the Reynolds-averaged Navier–Stokes equation, together with an energy equation considering the solidification and melting model. The ROP of the drilling probe is determined based on the energy balance between the heating power and melting rate of ice. As the results, the ETDP penetrates the ice through a close-contact melting process. The molten liquid layer with less than 1 mm of thickness forms near the heated probe tip. In addition, the ROP increases with the heated temperature of the probe tip.

Aims: Dietary supplementation with ursolic acid (UA) prevents monocyte dysfunction in diabetic mice and protects mice against atherosclerosis and loss of renal function. The goal of this study was to determine the molecular mechanism by which UA prevents monocyte dysfunction induced by metabolic stress. Methods and results: Metabolic stress sensitizes or “primes” human THP-1 monocytes and murine peritoneal macrophages to the chemoattractant MCP-1, converting these cells into a hyper-chemotactic phenotype. UA protected THP-1 monocytes and peritoneal macrophages against metabolic priming and prevented their hyper-reactivity to MCP-1. UA blocked the metabolic stress-induced increase in global protein-S-glutathionylation, a measure of cellular thiol oxidative stress, and normalized actin-S-glutathionylation. UA also restored MAPK phosphatase-1 (MKP1) protein expression and phosphatase activity, decreased by metabolic priming, and normalized p38 MAPK activation. Neither metabolic stress nor UA supplementation altered mRNA or protein levels of glutaredoxin-1, the principal enzyme responsible for the reduction of mixed disulfides between glutathione and protein thiols in these cells. However, the induction of Nox4 by metabolic stress, required for metabolic priming, was inhibited by UA in both THP-1 monocytes and peritoneal macrophages. Conclusion: UA protects THP-1 monocytes against dysfunction by suppressing metabolic stress-induced Nox4 expression, thereby preventing the Nox4-dependent dysregulation of redox-sensitive processes, including actin turnover and MAPK-signaling, two key processes that control monocyte migration and adhesion. This study provides a novel mechanism for the anti-inflammatory and athero- and renoprotective properties of UA and suggests that dysfunctional blood monocytes may be primary targets of UA and related compounds.