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The objective of this study was to evaluate predicting factors for supraphysiologic serum estradiol elevation during controlled ovarian stimulation (COS) with administration of letrozole and gonadotropins in patients with estrogen-dependent cancer. Use of aromatase inhibitors is recommended to prevent the potential effects of elevated serum estradiol levels and recurrence of tumor in patients with estrogen-dependent cancers during COS. Although previous studies reported that letrozole have shown an effective lowering of peak estrogen levels, a part of patients shows supraphysiologic levels of estrogen associated with ovarian stimulation despite the administration of letrozole. From January 2009 to December 2019, patients with estrogen-dependent cancer who underwent COS with antagonist protocol using a letrozole (5 mg/ day) to keep estrogen levels low were included in this study. Early monitoring serum estradiol was measured in all patients on the 4-6th day of stimulation. Subjects were classified into two groups according to the serum estradiol level on hCG triggering day, physiologic estradiol group (≤400 pg/mL) and supraphysiologic estradiol group (>400 pg/mL). A total of 96 COS cycles were retrospectively analyzed. Supraphysiologic level of serum estradiol was found in 21.9% of the patients. Mean age, AMH, duration of stimulation, total dose of gonadotropins administered were not different between the two groups. However, early monitoring serum estradiol level was significantly higher in the supraphysiologic estradiol group (67.1±47.9 vs. 115.6±78.1, p = 0.001) and was associated with the occurrence of supraphysiologic elevation of serum estradiol on hCG triggering day. Patients with early monitoring serum estradiol ≥84.5 pg/mL had an odds ratio of 5.376 [95% CI, 1.613-17.913] for supraphysiologic elevation of serum estradiol compared to those with early monitoring serum estradiol below 84.5 pg/mL. In conclusion, early monitoring serum estradiol is an independent predicting factor for supraphysiologic level of serum estradiol on hCG triggering day in the COS cycles using letrozole and gonadotropins.

Real-time PCR, also called quantitative PCR (qPCR), has been powerful analytical tool for detection of nucleic acids since it developed. Not only for biological research but also for diagnostic needs, qPCR technique requires capacity to detect multiple genes in recent years. Solid phase PCR (SP-PCR) where one or two directional primers are immobilized on solid substrates could analyze multiplex genetic targets. However, conventional SP-PCR was subjected to restriction of application for lack of PCR efficiency and quantitative resolution. Here we introduce an advanced qPCR with primer-incorporated network (PIN). One directional primers are immobilized in the porous hydrogel particle by covalent bond and the other direction of primers are temporarily immobilized at so-called 'Supplimers'. Supplimers released the primers to aqueous phase in the hydrogel at the thermal cycling of PCR. It induced the high PCR efficiency over 92% with high reliability. It reduced the formation of primer dimers and improved the selectivity of qPCR thanks to the strategy of 'right primers supplied to right place only'. By conducting a six-plex qPCR of 30 minutes, we analyzed DNA samples originated from malaria patients and successfully identified malaria species in a single reaction.

The aim of this study was to investigate whether supplementation with chitosan (COS) could reduce diarrhea and to explore how COS alleviates intestinal inflammation in weaned pigs. Thirty pigs (Duroc×Landrace×Yorkshire, initial BW of 5.65±0.27) weaned at age 21 d were challenged with enterotoxigenic Escherichia coli during a preliminary trial period, and then divided into three treatment groups. Pigs in individual pens were fed a corn-soybean meal diet, that contained either 0 (control), 50 mg/kg chlortetracycline, or 300 mg/kg COS for 21 days. The post-weaning diarrhea frequency, calprotectin levels and TLR4 protein expression were decreased (P

It is clinically important to be able to detect influenza A/H1N1 virus using a fast, portable, and accurate system that has high specificity and sensitivity. To achieve this goal, it is necessary to develop a highly specific primer set that recognizes only influenza A viral genes and a rapid real-time PCR system that can detect even a single copy of the viral gene. In this study, we developed and validated a novel fluidic chip-type real-time PCR (LabChip real-time PCR) system that is sensitive and specific for the detection of influenza A/H1N1, including the pandemic influenza strain A/H1N1 of 2009. This LabChip realtime PCR system has several remarkable features: (1) It allows rapid quantitative analysis, requiring only 15 min to perform 30 cycles of real-time PCR. (2) It is portable, with a weight of only 5.5 kg. (3) The reaction cost is low, since it uses disposable plastic chips. (4) Its high efficiency is equivalent to that of commercially available tube-type real-time PCR systems. The developed disposable LabChip is an economic, heat-transferable, light-transparent, and easy-to-fabricate polymeric chip compared to conventional silicon- or glass-based labchip. In addition, our LabChip has large surface-to-volume ratios in micro channels that are required for overcoming time consumed for temperature control during real-time PCR. The efficiency of the LabChip real-time PCR system was confirmed using novel primer sets specifically targeted to the hemagglutinin (HA) gene of influenza A/H1N1 and clinical specimens. Eighty-five human clinical swab samples were tested using the LabChip real-time PCR. The results demonstrated 100% sensitivity and specificity, showing 72 positive and 13 negative cases. These results were identical to those from a tube-type real-time PCR system. This indicates that the novel LabChip real-time PCR may be an ultra-fast, quantitative, point-of-care-potential diagnostic tool for influenza A/H1N1 with a high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Heat shock proteins (Hsps) are a set of molecular chaperones involved in cellular repair. They provide protective mechanisms that allow cells to survive potentially lethal insults, In response to a conditioning stress their expression is increased. Here we examined the connection between Hsps and Aβ42, the amyloid peptide involved in the pathological sequence of Alzheimer's disease (AD). Extracellular Aβ42 associates with neuronal cells and is a major constituent of senile plaques, one of the hallmarks of AD. Although Hsps are generally thought to prevent accumulation of misfolded proteins, there is a lack of mechanistic evidence that heat shock chaperones directly modulate Aβ42 toxicity. In this study we show that neither extracellular Aβ42 nor Aβ42/PrPC trigger the heat shock response in neurons. To address the influence of the neuroprotective heat shock response on cellular Aβ42, Western analysis of Aβ42 was performed following external Aβ42 application. Five hours after a conditioning heat shock, Aβ42 association with CAD cells was increased compared to control neurons. However, at forty-eight hours following heat shock Aβ42 levels were reduced compared to that found for control cells. Moreover, transient transfection of the stress induced Hsp40, decreased CAD levels of Aβ42. In contrast to CAD cells, hippocampal neurons transfected with Hsp40 retained Aβ42 indicating that Hsp40 modulation of Aβ42 proteostasis is cell specific. Mutation of the conserved HPD motif within Hsp40 significantly reduced the Hsp40-mediated Aβ42 increase in hippocampal cultures indicating the importance of this motif in regulating cellular Aβ42. Our data reveal a biochemical link between Hsp40 expression and Aβ42 proteostasis that is cell specific. Therefore, increasing Hsp40 therapeutically with the intention of interfering with the pathogenic cascade leading to neurodegeneration in AD should be pursued with caution. [ABSTRACT FROM AUTHOR]

PurposeThis study aimed to evaluate the dosimetric accuracy of respiratory gated volumetric modulated arc therapy (VMAT) for lung stereotactic body radiation therapy (SBRT) under simulation conditions similar to the actual clinical situation using patient-specific lung phantoms and realistic target movements.MethodsSix heterogeneous lung phantoms were fabricated using a 3D-printer (3DISON, ROKIT, Seoul, Korea) to be dosimetrically equivalent to actual target regions of lung SBRT cases treated via gated VMAT. They were designed to move realistically via a motion device (QUASAR, Modus Medical Devices, Canada). Using the lung phantoms and a homogeneous phantom (model 500-3315, Modus Medical Devices), film dosimetry was performed with and without respiratory gating for VMAT delivery (TrueBeam STx; Varian Medical Systems, Palo Alto, CA, USA). The measured results were analyzed with the gamma passing rates (GPRs) of 2%/1 mm criteria, by comparing with the calculated dose via the AXB and AAA algorithms of the Eclipse Treatment Planning System (version 10.0.28; Varian Medical Systems).ResultsGPRs were greater than the acceptance criteria 80% for all film measurements with the stationary and homogeneous phantoms in conventional QAs. Regardless of the heterogeneity of phantoms, there were no significant differences (p > 0.05) in GPRs obtained with and without target motions; the statistical significance (p = 0.031) was presented between both algorithms under the utilization of heterogeneous phantoms.ConclusionsDosimetric verification with heterogeneous patient-specific lung phantoms could be successfully implemented as the evaluation method for gated VMAT delivery. In addition, it could be dosimetrically confirmed that the AXB algorithm improved the dose calculation accuracy under patient-specific simulations using 3D printed lung phantoms.