The theory that D-dimer level might has a predictive or diagnostic role in preeclampsia needs to be explored. Aim of the study was to evaluate the association between serum D-dimer level and the ...occurrence of placenta-mediated complications (PMC) in a pregnant population at high risk.
A prospective multicenter cohort study including 200 pregnant women was conducted.
Serum D-dimer increases throughout pregnancy, with the highest levels at the end of gestation. Serum D-dimer level was similar for women with PMC and with no complication. Serum D-dimer level was not different in women with preeclampsia
uncomplicated women. Serum D-dimer level was not different in women with early or late preeclampsia
uncomplicated women.
This result suggests that serum D-dimer level was not predictive of the PMC occurrence. This corroborates the fact that the origin of PMC based more on immunity than in hemostasis.
Infection of cells by respiratory syncytial virus induces the formation of cytoplasmic inclusion bodies (IBs) where all the components of the viral RNA polymerase complex are concentrated. However, ...the exact organization and function of these IBs remain unclear. In this study, we use conventional and super-resolution imaging to dissect the internal structure of IBs. We observe that newly synthetized viral mRNA and the viral transcription anti-terminator M2-1 concentrate in IB sub-compartments, which we term "IB-associated granules" (IBAGs). In contrast, viral genomic RNA, the nucleoprotein, the L polymerase and its cofactor P are excluded from IBAGs. Live imaging reveals that IBAGs are highly dynamic structures. Our data show that IBs are the main site of viral RNA synthesis. They further suggest that shortly after synthesis in IBs, viral mRNAs and M2-1 transiently concentrate in IBAGs before reaching the cytosol and suggest a novel post-transcriptional function for M2-1.Respiratory syncytial virus (RSV) induces formation of inclusion bodies (IBs) sheltering viral RNA synthesis. Here, Rincheval et al. identify highly dynamic IB-associated granules (IBAGs) that accumulate newly synthetized viral mRNA and the viral M2-1 protein but exclude viral genomic RNA and RNA polymerase complexes.
This article is the first part of a two-part manuscript addressing the DME/TACAN multipath (MP) impact on the future airborne GNSS Dual-Frequency Multi-Constellation (DFMC) GNSS L5/E5a receiver ...correlator input. GNSS L5/E5a signals and DME/TACAN pulsed signals share the same Aeronautical Radionavigation Service (ARNS) frequency band with consequent interference between the two systems. The current GNSS signal C/NO degradation model for future airborne GNSS DFMC receivers due to DME/TACAN pulsed signals is expressed at the DMFC correlator input and is standardized in different civil aviation documents. This model considers the introduction of a temporal blanker at the DMFC Radio-Frequency Front-End (RFFE) block output to mitigate the DME/TACAN pulsed signals and thus, relies on the definition of the above blanker pulse width (pweq) and the below blanker equivalent pulse width (PWeq) . However, this model did not consider the presence of DME/TACAN pulsed signals MP. Indeed, the DME/TACAN MP impact on the GNSS signal C/NO degradation was never inspected while it could be significant, especially at low altitude. The objective of this paper is thus to update the C/NO degradation model by considering DME/TACAN MP impact generated by ground scatterers. This is done by updating pweq and PWeq formulas which require the knowledge of the MP delays and Peak Envelope Powers. In particular, this paper proposes two models of the DME/TACAN MP impact, the statistical and the fixed environment models, where the main difference is the modelling of the additional phase generated by the channel environmental condition θe as an uniform variable in the statistical model and as a constant in the fixed environment model. As a consequence, the Pulse Independency Condition (PIC) is satisfied (power of the sum of received DME/TACAN pulses is equal to the sum of the received pulses power) for the statistical model, which is not always true for the fixed environment model. The two models are proposed to cover different needs. The statistical model is a low complexity model completely defined by closed-form formulas, and is proposed to be used for standardization purposes. The fixed environment model is a higher complexity model with two main purposes. First, the fixed environment model is able to provide the C/NO degradation for one specific set of DME/TACAN signal conditions. Second, the fixed environment model is used to inspect the limitations of the statistical model by identifying geographical zones where the received power of the DME/TACAN MP signals generated by the ground scatterers only loosely fulfills the PIC.
The presence of autoantibodies in systemic lupus erythematosus, particularly those of the IgG subclass, have long been associated with disease onset and activity. Here we explored the prevalence of ...autoreactive IgE in SLE and its relevance to disease in French (n = 79) and United States (US) (n = 117) cohorts with a mean age of 41.5 ± 12.7 and 43.6 ± 15.3 years and disease duration of 13.5 ± 8.5 and 16.6 ± 11.9 years, respectively. Our findings show that approximately 65% of all SLE subjects studied produced IgE antibodies to the seven autoantigens tested. This positivity was increased to almost 83% when only those subjects with active disease were considered. SLE subjects who were positive for anti-dsDNA, -Sm, and -SSB/La -specific IgE showed a highly significant association in the levels of these antibodies with disease activity similar to that of the corresponding IgG's. A strong association of IgE autoantibodies with active nephritis was also found in the combined cohort analysis. A test of the predictive value of autoreactive IgE's and IgGs for disease activity (SLE Disease Activity Index (SLEDAI) ≥ 4) revealed that the best predictors were dsDNA-specific IgE and IgG, and that the age of an SLE subject influenced this predictive model. The finding argue that the overall levels of IgE autoantibodies, independently or in combination with IgG autoantibodies, may serve as indicators of active disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human and murine skin wounding commonly results in fibrotic scarring, but the murine wounding model wound-induced hair neogenesis (WIHN) can frequently result in a regenerative repair response. Here, ...we show in single-cell RNA sequencing comparisons of semi-regenerative and fibrotic WIHN wounds, increased expression of phagocytic/lysosomal genes in macrophages associated with predominance of fibrotic myofibroblasts in fibrotic wounds. Investigation revealed that macrophages in the late wound drive fibrosis by phagocytizing dermal Wnt inhibitor SFRP4 to establish persistent Wnt activity. In accordance, phagocytosis abrogation resulted in transient Wnt activity and a more regenerative healing. Phagocytosis of SFRP4 was integrin-mediated and dependent on the interaction of SFRP4 with the EDA splice variant of fibronectin. In the human skin condition hidradenitis suppurativa, phagocytosis of SFRP4 by macrophages correlated with fibrotic wound repair. These results reveal that macrophages can modulate a key signaling pathway via phagocytosis to alter the skin wound healing fate.
Studies of the responses of hematopoietic stem and progenitor cells (HSPCs) to low doses of ionizing radiation formed an important aspect of the RISK-IR project (
www.risk-ir.eu
). A brief overview ...of these studies is presented here. The findings confirm the sensitivity of HSPCs to radiation even at low doses, and illustrate the substantial impact that differentiation state has upon cell sensitivity. The work provides mechanistic support for epidemiological findings of leukemia risk at dose levels used in diagnostic CT imaging, and further suggests that low-dose irradiation may facilitate bone marrow transplantation, a finding that could lead to refinements in clinical practice.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is debate over the effects of long-term oral fluoroquinolone therapy in patients with advanced cirrhosis. We performed a randomized controlled trial to evaluate the effects of long-term ...treatment with the fluoroquinolone norfloxacin on survival of patients with cirrhosis.
We performed a double-blind trial of 291 patients with Child-Pugh class C cirrhosis who had not received recent fluoroquinolone therapy. The study was performed at 18 clinical sites in France from April 2010 through November 2014. Patients were randomly assigned to groups given 400 mg norfloxacin (n = 144) or placebo (n = 147) once daily for 6 months. Patients were evaluated monthly for the first 6 months and at 9 months and 12 months thereafter. The primary outcome was 6-month mortality, estimated by the Kaplan–Meier method, censoring spontaneous bacterial peritonitis, liver transplantation, or loss during follow-up.
The Kaplan–Meier estimate for 6-month mortality was 14.8% for patients receiving norfloxacin and 19.7% for patients receiving placebo (P = .21). In competing risk analysis that took liver transplantation into account, the cumulative incidence of death at 6 months was significantly lower in the norfloxacin group than in the placebo group (subdistribution hazard ratio, 0.59; 95% confidence interval, 0.35–0.99). The subdistribution hazard ratio for death at 6 months with norfloxacin vs placebo was 0.35 (95% confidence interval, 0.13–0.93) in patients with ascites fluid protein concentrations <15 g/L and 1.39 (95% confidence interval, 0.42–4.57) in patients with ascites fluid protein concentrations ≥15 g/L. Norfloxacin significantly decreased the incidence of any and Gram-negative bacterial infections without increasing infections caused by Clostridium difficile or multiresistant bacteria.
In a randomized controlled trial of patients with advanced cirrhosis without recent fluoroquinolone therapy, norfloxacin did not reduce 6-month mortality, estimated by the Kaplan–Meier method. Norfloxacin, however, appears to increase survival of patients with low ascites fluid protein concentrations. ClinicalTrials.gov ID: NCT01037959.
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The composition and site occupancy of Mg within ordered δ′ precipitates in a model Al–Mg–Li alloy have been characterized by atom probe microscopy and first-principles simulations. The concentration ...in the precipitates is found to be almost the same as that of the matrix; however, we show evidence that Mg partitions to the sites normally occupied by Li in the L12 structure. Density functional calculations demonstrate that this partitioning is energetically favorable, in agreement with experimental results.
SARS-CoV-2 is a coronavirus causing a globalized outbreak called COVID-19. SARS-CoV-2 transmission is associated with inhalation of contaminated respiratory droplets and could causes severe ...complications. Until today several “waves” of infections have been observed despite implementation of strict health policies. Decisions for such sanitary measures are based on population health monitoring. Unfortunately, for COVID-19, a significant proportion of individuals are asymptomatic but play a role in the virus transmission.
To overcome these limitations, several strategies were developed including genome quantification in wastewater that could allow monitoring of the health status of population, since shedding of SARS-CoV-2 in patient stool is frequent. Wastewater-based epidemiology (WBE) was established and several countries implemented this approach to allow COVID-19 outbreak monitoring. In France, the OBEPINE project performed a quantitative analysis of SARS-CoV-2 in raw wastewater samples collected from major wastewater treatment plants (WWTP) since March 2020.
In the greater Paris area 1101 samples (507 for five WWTP and 594 for sewer) were collected. This 16 months monitoring allows us to observe the outbreak dynamics. Comparison of WBE indicators with health data lead to several important observation; the good level of correlation with incidence rates, the average 3 days lead time, and the sensitivity (WBE change when incidence is > to 7/100000 inhabitants). We also compared the local monitoring (city level) with the regional monitoring, to help cluster identification.
Moreover, variants of concern (VOC) emerged due to the selection pressure. We developed a specific RT-qPCR method targeting the deletion H69-V70 in the spike protein, using this deletion as a proxy of the B.1.1.7 presence in the wastewater. With this data we demonstrate the predominant role played by this strain in the third wave.
All these results allow a better description and understanding of the pandemic and highlight the role of such WBE indicators.
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•Genome quantification of pathogens in wastewater allow monitoring of the health status of population.•Bi weekly sampling allows description of WBE indicators lag with incidence and sensibility at the regional or local level.•RT qPCR tools, targeting specific mutations allow dynamic monitoring of VOC in wastewater and population.•Variant monitoring in Wastewater demonstrates the important role played by some strains in the third wave.
Most people with type 2 diabetes (T2DM) and nonalcoholic steatohepatitis (NASH) or advanced fibrosis (AF) remain undiagnosed, resulting in missed opportunities for early intervention. This ...multicenter, prospective study assessed the yield of using routinely available data to identify these patients.
A total of 713 outpatients with T2DM, screened in four diabetology clinics for nonalcoholic fatty liver disease according to American Diabetes Association criteria, were referred to hepatologists for further work-up (Fibrosis-4 and vibration-controlled transient elastography VCTE). A liver biopsy was proposed when ALT levels were persistently >20 IU/L in female patients or >30 IU/L in male patients, in the absence of other liver disease.
Liver biopsies were performed in 360 patients and considered adequate for reading after central review for 330 specimens (median patient age, 59 years; male patients, 63%; median BMI and HbA1c values, 32 and 7.5%, respectively). Prevalence of NASH, AF, and cirrhosis were 58%, 38%, and 10%, respectively. Liver lesions were independently associated with the components of metabolic syndrome but not with the micro- and macrovascular complications of T2DM. Models based on routinely available data with or without VCTE had good accuracy to predict AF (respectively: area under the receiver operating characteristic curve AUROC, 0.84 and 0.77; and correctly classified 59% and 45%) and NASH (respectively: AUROC, 0.82 and 0.81; 44% and 42%).
Despite the use of a low ALT threshold, prevalence of NASH (58%) or AF (38%) was high. Routinely available data had a high yield in identifying patients with T2DM with AF and/or NASH requiring further liver assessment.
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