Oxide dispersion strengthened (ODS) ferritic alloys are structural materials used in nuclear fusion reactors, which exhibit enhanced mechanical properties, as well as corrosion and irradiation ...resistance. In the present work, ODS ferritic alloys with composition Fe-14Cr-1.5W-0.4Ti-(0, 0.4, 0.8) Y2O3 (in wt.%) were prepared employing high energy milling (HEM) followed by Spark Plasma Sintering (SPS). The particle size distribution (PSD) of the milled powders was characterized by laser diffraction. These powders and the sintered materials produced were characterized using X-ray diffraction (XRD), and scanning electron microscopy (SEM). The sintered materials were also characterized by dilatometry, diametral compression, Vickers microhardness, and corrosion rate tests. The largest Young’s modulus, microhardness, and dimensional shrinkage/expansion were obtained for the 0.8 wt.% Y2O3 alloy. However, this alloy was the least ductile. Furthermore, the 0.8 wt.% Y2O3 alloy was the one with the least dimensional change. According to the potentiodynamic polarization studies, it was found that the protective layer of Cr2O3 formed on the surface of the three alloys studied was less effective for the yttria-free alloy, since in this case the rupture of such protective layer occurred earlier than for the case of the yttria-containing alloys. Based on these results, it is suggested that the 0.8 wt.% Y2O3 alloy having fine microstructure could constitute a potential alternative as a structural material for Gen IV-type reactors.
Intrauterine growth restriction (IUGR) is an obstetric complication characterised by placental insufficiency and secondary cardiovascular remodelling that can lead to cardiomyopathy in adulthood. ...Despite its aetiology and potential therapeutics are poorly understood, bioenergetic deficits have been demonstrated in adverse foetal and cardiac development. We aimed to evaluate the role of mitochondria in human pregnancies with IUGR. In a single‐site, cross‐sectional and observational study, we included placenta and maternal peripheral and neonatal cord blood mononuclear cells (PBMC and CBMC) from 14 IUGR and 22 control pregnancies. The following mitochondrial measurements were assessed: enzymatic activities of mitochondrial respiratory chain (MRC) complexes I, II, IV, I + III and II + III, oxygen consumption (cell and complex I‐stimulated respiration), mitochondrial content (citrate synthase CS activity and mitochondrial DNA copy number), total ATP levels and lipid peroxidation. Sirtuin3 expression was evaluated as a potential regulator of bioenergetic imbalance. Intrauterine growth restriction placental tissue showed a significant decrease of MRC CI enzymatic activity (P < 0.05) and CI‐stimulated oxygen consumption (P < 0.05) accompanied by a significant increase of Sirtuin3/β‐actin protein levels (P < 0.05). Maternal PBMC and neonatal CBMC from IUGR patients presented a not significant decrease in oxygen consumption (cell and CI‐stimulated respiration) and MRC enzymatic activities (CII and CIV). Moreover, CS activity was significantly reduced in IUGR new‐borns (P < 0.05). Total ATP levels and lipid peroxidation were preserved in all the studied tissues. Altered mitochondrial function of IUGR is especially present at placental and neonatal level, conveying potential targets to modulate obstetric outcome through dietary interventions aimed to regulate Sirtuin3 function.
Hepatitis E virus (HEV) is an emerging zoonotic pathogen with pigs and wild boar serving as reservoirs for human infection through direct contact with infected animals or the consumption of raw or ...undercooked pork products. The liver is considered the main target site of HEV replication in swine and an important organ in the pathogenesis of the disease. The aim of this study was to characterize the target liver cells for HEV entry in naturally infected wild boar and to evaluate the type and severity of the pathological changes in order to reach a better understanding of the hepatic pathogenic mechanisms involved in hepatitis E. In total, 58 livers from hunted wild boar were histopathologically evaluated. The presence of specific HEV antibodies in serum was determined by indirect ELISA. Immunohistochemistry was used for the detection of HEV antigen and Real time RT-PCR to detect HEV RNA in liver and serum. HEV seroprevalence in these animals was of 5.197% (CI95%: 1.77-14.14). By Real time RT-PCR, HEV was detected in the liver tissue of four wild boar (6.8%; CI95%: 2.7-16.4) and only one animal was also positive in serum (1.7%; CI95%: 0.3-9.1). The non-viremic animals naturally infected with HEV presented evidence of liver infection, mainly in Kupffer cells and liver sinusoidal endothelial cells, without apparent associated hepatitis lesions. This study supports the hypothesis that low viral titers may persist in the liver of non-viremic individuals, giving thus the possibility of consumption of contaminated liver of animals diagnosed as HEV-negative in serum. Further immunopathogenic studies are necessary to elucidate the mechanisms responsible for this process and to evaluate the protocols of HEV diagnosis in animals destined for human consumption.
Identifying pig farms infected with hepatitis E virus (HEV) is a key aspect to implement surveillance programmes for this emerging zoonotic agent. Detection of HEV in blood has several drawbacks, ...including animal handling, economic costs and animal stress. The objective of this study was to evaluate the effectiveness of a non-invasive screening approach for determining the HEV status of pig farms under different management systems.
Forty stool samples randomly collected from the pen floor of 17 intensive pig farms and the yard of nine extensive ones were tested for HEV RNA. The invasive method used to confirm the HEV status of the farm was HEV RNA analysis of serum samples randomly collected from 40 animals on each farm.
Twenty-one HEV-positive farms were detected by invasive and non-invasive methods. No positive serum or stool samples were detected on five intensive farms. A high intertest agreement (
=1; P<0.00001) was observed between both methodologies, showing the stool screening approach a 100 per cent of sensitivity and specificity with respect to the invasive method. Likewise, a significant negative relationship was observed between the HEV within-farm prevalence and the number of the first HEV-positive stool sample found (Spearman's rho=-0.64; P=0.0004). This negative relationship was higher in intensively managed farms.
This non-invasive screening approach could be reliably applied in a large-scale surveillance programme for determining the HEV status of pig farms under different management systems.
Background & Aims Colorectal cancers (CRCs) with microsatellite instability (MSI) and a mismatch repair (MMR) immunohistochemical deficit without hypermethylation of the MLH1 promoter are likely to ...be caused by Lynch syndrome. Some patients with these cancers have not been found to have pathogenic germline mutations and are considered to have Lynch-like syndrome (LLS). The aim of this study was to determine the risk of cancer in families of patients with LLS. Methods We studied a population-based cohort of 1705 consecutive patients, performing MSI tests and immunohistochemical analyses of MMR proteins. Patients were diagnosed with Lynch syndrome when they were found to have pathogenic germline mutations. Patients with MSI and loss of MSH2 and/or MSH6 expression, isolated loss of PMS2 or loss of MLH1 without MLH1 promoter hypermethylation, and no pathogenic mutation were considered to have LLS. The clinical characteristics of patients and the age- and sex-adjusted standardized incidence ratios (SIRs) of cancer in families were compared between groups. Results The incidence of CRC was significantly lower in families of patients with LLS than in families with confirmed cases of Lynch syndrome (SIR for Lynch syndrome, 6.04; 95% confidence interval CI, 3.58–9.54; SIR for LLS, 2.12; 95% CI, 1.16–3.56; P < .001). However, the incidence of CRC was higher in families of patients with LLS than in families with sporadic CRC (SIR for sporadic CRC, 0.48; 95% CI, 0.27–0.79; P < .001). Conclusions The risk of cancer in families with LLS is lower that of families with Lynch syndrome but higher than that of families with sporadic CRC. These results confirm the need for special screening and surveillance strategies for these patients and their relatives.
The establishment of Alternate Care Sites (ACS) helped the most severely impacted countries expand their response capability. The aim of this study was to evaluate the clinical characteristics and ...risk factors associated with the mortality of hospitalized COVID-19 patients at Alternate Care Site in Mexico City.
A monocentric cohort study was conducted at Mexico City's Temporary Unit COVID-19 (UTC-19). Sociodemographic, clinical, laboratory and treatment variables were included in the analysis.
A total of 4865 patients were included, with a mean age of 49.33 years ± SD 15.28 years (IQR 38 to 60 years); 50.53% were women. 63.53% of the patients presented at least one comorbidity, the most frequent being: obesity (39.94%), systemic arterial hypertension (25.14%), and diabetes mellitus (21.52%). A total of 4549 patients (93.50%) were discharged due to improvement, 64 patients (1.31%) requested voluntary discharge, 39 patients (0.80%) were referred to another unit, and 213 patients (4.37%) died. Factors that were independently and significantly associated with death included male gender (odds ratio OR, 1.60), age ≥ 50 years (OR 14.75), null or low schooling (OR 3.47), have at least one comorbidity (OR 3.26), atrial fibrillation (OR 22.14). In the multivariate analysis, the lymphopenia ≤ 1 × 10
3/
μL (OR 1.91), and having required steroid treatment (OR 2.85), supplemental oxygen with high-flow nasal cannula (OR 3.12) or invasive mechanical ventilation (OR 42.52), was significantly associated with an increased risk of death.
This study identified the clinical characteristics and risk factors for mortality of hospitalized COVID-19 patients at ACS in Mexico City.
KEY MESSAGES
An Alternate Care Site (ACS) is any building or structure that is temporarily converted or constructed for healthcare use during a public health emergency.
Factors associated with death included male gender, age over 50 years, and lower educational attainment (elementary school or less).
The findings corroborate the utility of the CALL score as a predictor of mortality; lymphopenia ≤1 × 10
3
/μL was the most relevant biomarker.
The antiangiogenic activity of the multidomain plasma protein histidine-proline-rich glycoprotein (HPRG) is localized to its histidine-proline-rich (H/P) domain and has recently been shown to be ...mediated, at least partially, through binding to cell-surface tropomyosin in fibroblast growth factor-2-activated endothelial cells (X. Guan et al., Thromb Haemost, in press). HPRG and its H/P domain, but not the other domains of HPRG, bind specifically and with high affinity to tropomyosin. In this study, we characterize the interaction of the H/P domain with tropomyosin and delineate the region within the H/P domain responsible for that interaction. The H/P domain of HPRG consists mostly of repetitions of the consensus sequence H/PH/PPHG. Applying an in vitro tropomyosin binding assay, we demonstrate that the synthetic peptide HHPHG binds to tropomyosin in vitro and inhibits angiogenesis and tumor growth in vivo. The affinity for tropomyosin increases exponentially upon multimerization of the HHPHG sequence, with a concurrent increase in antiangiogenic activity. Specifically, the tetramer (HHPHG)4 has significant antiangiogenic activity in the Matrigel plug model (IC50 approximately 600 nm) and antitumor effects in two syngeneic mouse tumor models. Thus, we show that a 16-mer peptide analogue mimics the antiangiogenic activity of intact HPRG and is also able to inhibit tumor growth, suggesting that cell surface tropomyosin may represent a novel antiangiogenic target for the treatment of cancer.
The anti-angiogenic properties of the histidine-proline-rich (H/P) domain of HPRG have recently been described (Juarez JC, et al. Cancer Research 2002; 62: 5344-50). However, the binding site that ...mediates these properties is unknown. HPRG is evolutionarily, functionally and structurally related to cleaved high molecular weight kininogen (HKa), an anti-angiogenic polypeptide that stimulates apoptosis of proliferating endothelial cells through binding to cell-surface tropomyosin (Zhang J-C, et al. Proc Natl Acad Sci USA 2002; 99: 12224-9). In this study, we demonstrate that HPRG binds with high affinity to FGF-2-stimulated human umbilical vein endothelial cells (HUVEC) and immobilized tropomyosin in a Zn2+ or pH-dependent manner, and that this interaction is mediated by the H/P domain of HPRG. At least two binding sites for HPRG, tropomyosin and heparan sulfate proteoglycans (HSPs), were identified on the surface of FGF-2-activated endothelial cells. Translocation of tropomyosin to the surface of HUVEC occurred in response to FGF-2, and the anti-angiogenic activity of HPRG in a Matrigel plug model was partially inhibited by soluble tropomyosin. These results suggest that HPRG binds to endothelial cell surface tropomyosin which at least partially mediates the antiangiogenic effects of HPRG.
Three salts of 5-amino-2-sulfonamide-1,3,4-thiadiazole (Hats) were prepared and characterized by physico-chemical methods. The p-toluensulfonate, the methylsulfonate, and the chlorhydrate monohydrate ...salts of Hats were evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs) and as anticonvulsants and diuretics, since many CAIs are clinically used as pharmacological agents. The three Hats salts exhibited diuretic and anticonvulsant activities with little neurotoxicity. The human (h) isoforms hCA I, II, IV, VII, IX, and XII were inhibited in their micromolar range by these salts, whereas pathogenic beta and gamma CAs showed similar, weak inhibitory profiles.
The Rover Environmental Monitoring Station (REMS) will investigate environmental factors directly tied to current habitability at the Martian surface during the Mars Science Laboratory (MSL) mission. ...Three major habitability factors are addressed by REMS: the thermal environment, ultraviolet irradiation, and water cycling. The thermal environment is determined by a mixture of processes, chief amongst these being the meteorological. Accordingly, the REMS sensors have been designed to record air and ground temperatures, pressure, relative humidity, wind speed in the horizontal and vertical directions, as well as ultraviolet radiation in different bands. These sensors are distributed over the rover in four places: two booms located on the MSL Remote Sensing Mast, the ultraviolet sensor on the rover deck, and the pressure sensor inside the rover body. Typical daily REMS observations will collect 180 minutes of data from all sensors simultaneously (arranged in 5 minute hourly samples plus 60 additional minutes taken at times to be decided during the course of the mission). REMS will add significantly to the environmental record collected by prior missions through the range of simultaneous observations including water vapor; the ability to take measurements routinely through the night; the intended minimum of one Martian year of observations; and the first measurement of surface UV irradiation. In this paper, we describe the scientific potential of REMS measurements and describe in detail the sensors that constitute REMS and the calibration procedures.
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