Francoryberg0272
Activated protein C (APC) resistance is a major risk factor of venous thrombosis which may be acquired by hormonal therapy or other causes. The FibWave, a sensitive global clot-based assay design to analyze the coagulation kinetics in plasma, may be a good candidate to assess this prothrombotic state. This study aims to assess the suitability of the FibWave to differentiate the coagulation kinetics of women on oral contraceptives.
Fifty-four healthy volunteers were divided into 5 groups men [n=13], women not using hormonal contraception [n=12], women using second [n=12] or third generation [n=12] combined oral contraceptives, and women using progestin only contraceptive [n=5]. Patients with coagulation abnormalities were also assessed [n=8]. The APC resistance was assessed on the FibWave using exogenous APC or Protac, and on the Calibrated Automated Thrombogram using the ETP-based APC resistance assay.
Either in presence or in absence of APC or Protac, the FibWave was able to detect a hypercoagulable state in plasma samples. All combined oral contraceptives showed a lower FW-Max
, FW-Max
and FW-Min
percentage of inhibition and a lower FW-Ttpeak ratio than the other groups. The sensitivity of the FibWave was similar to the one of the ETP-based APC resistance assay.
The FibWave is able to differentiate APC resistance levels observed in women on combined oral contraceptive. The FW-Max
, FW-Max
and to a lesser degree FW-Min
were identified as the most sensitive parameters with a similar performance to the ETP-based APC resistance assay.
The FibWave is able to differentiate APC resistance levels observed in women on combined oral contraceptive. The FW-Max1 , FW-Max2, and to a lesser degree FW-Min2 were identified as the most sensitive parameters with a similar performance to the ETP-based APC resistance assay.
Oncogenic alterations of epidermal growth factor receptor (EGFR) signaling are frequently noted in non-small cell lung cancer (NSCLC). In recent decades, EGFR tyrosine kinase inhibitors (TKIs) have been developed, although the therapeutic efficacy of these inhibitor is restricted to EGFR-mutant patients. In this study, we investigated that clathrin-mediated EGFR endocytosis hampers the effects of gefitinib and sustains NSCLC cells with wild-type EGFR.
NSCLC cell lines (H358, Calu-3, SNU-1327, and H1703) were stimulated with the EGF and treated with gefitinib and endocytosis inhibitors (phenylarsine oxide (PAO) and Filipin III). Growth inhibition and apoptosis were evaluated. Immunofluorescence, immunoprecipitation, and western blot assay were performed to investigate EGFR endocytosis and determine the signaling pathway. Xenograft mouse models were used to verify the combination effect of gefitinib and PAO in vivo.
We confirmed the differences in EGFR endocytosis according to gefitinib response in wild-tbined with gefitinib could be an option in treatment of wild-type EGFR NSCLC.Atypical porcine pestivirus (APPV) was identified and associated with congenital tremor (CT) type A-II in new born piglets and has been reported in many countries. In China, the first APPV identification in swine herds was reported in Guangdong province in 2016. To investigate the genetic characteristics of APPV in Guangxi province, 53 tissue samples from neonatal piglets with CT were collected and detected from October 2017 to May 2019. Five APPV strains which were named as GX04/2017, GX01-2018, GX02-2018, GX01-2019 and GX02-2019 were obtained. Sequence analysis revealed that all six APPV strains from Guangxi province, including five strains from this study and one from a previous report, shared 83.3%-97.5% nucleotide identity of complete genome and 91.7%-99.1% amino acid identity of the open reading frame (ORF), and shared 77.7%-97.7% nucleotide identity of complete genome and 90.6%-99.3% amino acid identity of ORF with reference strains. Phylogenetic analysis indicated that all APPV strains could be divided into three clades based on the complete genome, Npro , Erns and E2 gene sequences, respectively; and the APPV strains from Guangxi province distributed in two clades (clades I and II). No sign of recombination was observed from Guangxi strains. Evolution analysis performed on the complete genome of 58 APPV strains showed that America, Europe and Asia strains during 2006-2019 evolved at a mean rate of 1.37 × 10-4 substitutions/site/year, and the most recent common ancestor (tMRCA) of them was estimated as 1,700.5 years ago. The findings of this study indicated that there existed a high degree of genetic diversity of APPV from Guangxi province, Southern China, which provided important information on the epidemiological features and evolutionary relationships of APPV.Q fever is a zoonotic disease caused by the intracellular bacterium, Coxiella burnetii. Its primary mode of transmission is by inhalation of aerosols originating from infected animals and contaminated environments. The organism has a very low infective dose, can persist in the environment for long periods of time and large outbreaks fuelled by windborne spread have been previously reported. Detection of C. burnetii in the environment is therefore important during human and animal outbreak investigations and for the control and prevention of Q fever. This study aimed to systematically review and critically appraise the published literature on sampling methods used to detect C. burnetii from different environmental samples. A search of four electronic databases with subsequent hand searching identified 47 eligible articles published since 1935. These articles described sampling of dust, air, soil and liquids in attempts to detect C. burnetii during 19 Q fever outbreaks and in 28 endemic settings. Environmental positivity was most commonly associated with ruminant livestock populations. Evidence describing spatio-temporal characteristics and associated geographical dispersion gradients was limited. The most commonly tested sample type was dust which also yielded the highest bacterial loads of >108 bacteria/cloth. The MD8 (Sartorius) air sampler was used widely for air sampling. Soil was the only sample type for which a validated laboratory protocol was established specifically for C. burnetii. Each environmental sample type has its advantages and limitations which are discussed in detail and a simplified framework to guide decisions around environmental sampling for C. burnetii is provided. In any type of environmental sampling, it is recommended to use standardized and validated methods and to match the most ideal sampling strategy and timing with the research context. These conditions are essential to be considered when designing future Q fever management plans that involve environmental sampling for C. RVX-208 manufacturer burnetii.
