Carpenterhorowitz1090
Background Patients with metastatic radioiodine-refractory papillary thyroid carcinoma (PTC) have limited treatment options and a poor prognosis. There is an urgent need to develop new drugs targeting PTC for clinical application. Apatinib, a novel small-molecule tyrosine kinase inhibitor (TKI), is highly selective for vascular endothelial growth factor receptor-2 (VEGFR2) and exhibits antitumor effects in a variety of solid tumors. Although apatinib has been shown to be safe and efficacious in radioiodine-refractory differentiated thyroid cancer, the mechanism underlying its antitumor effect is unclear. In this report, we explored the effects of apatinib on PTC in vitro and in vivo. Methods VEGFR2 expression levels were evaluated by immunohistochemistry (IHC), qPCR, and western blotting (WB). The effects of apatinib on cell viability, colony formation, and migration in the Transwell assay were assessed in vitro, and its effect on tumor growth rate was assessed in vivo. In addition, the levels of proteins in signaling pathways were determined by WB. Finally, the autophagy level was assessed by WB, immunofluorescence (IF), and transmission electron microscopy. Results We found that high VEGFR2 expression is associated with tumor size, T stage, and lymph node metastasis in patients with PTC and that apatinib inhibits PTC cell growth, promotes apoptosis, and induces cell cycle arrest through the PI3K/Akt/mTOR signaling pathway. Moreover, apatinib induces autophagy, and pharmacological inhibition of autophagy or small interfering RNA (siRNA)-mediated targeting of autophagy-associated gene 5 (ATG5) can further increase PTC cell apoptosis. Conclusion Our data suggest that apatinib can induce apoptosis and autophagy via the PI3K/Akt/mTOR signaling pathway for the treatment of PTC and that autophagy is a potential novel target for future therapy in resistant PTC. Copyright © 2020 Meng, Wang, Zhao, Hu, Zhi, Wei, Ruan, Hou, Li, Zhang, Yang, Qian, Wu, Zhang, Meng, Guan, Zhang, Zheng and Gao.In the twenty-first century, high contagious infectious diseases such as SARS (Severe Acute Respiratory Syndrome), MERS (Middle East Respiratory Syndrome), FMD (Foot-and-Mouth Disease) and AI (Avian Influenza) have become very prevalent, causing treat harm to humans and animals in aspect of public health, and economical issues. The critical problem is that newly-reported infectious diseases that humans firstly experience are expected to continue to emerge, and these diseases will be spreading out rapidly. Therefore, rapid and safe supplies of effective vaccines are most pivotal to prevent the rapid prevalent of new infection, but international standards or assessing protocol the safety of urgent vaccines are not established well. In our previous study, since we established a module to assess the brain safety of urgent vaccines, therefore, it is necessary to verify that this established module for assessing brain safety could work effectively in commercially available two vaccines (one killed- and on live-vaccines). We compared the results of Evans blue (EB) assay and qPCR analysis by injection of two kinds of vaccines, PBS and Lipopolysaccharide (LPS) under the condition of the module previously reported. We confirmed that the brain safety test module for urgent vaccine we established is very reproducible. Therefore, it is believed that this vaccine safety testing method can be used to validate brain safety when prompt supply of a newly developed vaccines is needed. © The Author(s) 2019.This study uses a dictator game with a charitable organization as the donation recipient to test whether empathic concern explains persistent gender differences in charitable giving. We first explore whether we can evoke empathic concern by varying the content of a real-world charitable appeal video that highlights children's stories of struggle with access to clean water. Then we examine whether the evoked feelings help explain gender differences in donations. Despite no gender differences in donation behavior in a baseline control group, we find that females donate 63% more than males in treatments that include the personal stories from children. These treatment videos increase self-reported feelings of empathic concern towards children among both males and females relative to the control; however, the empathic concern that results from the treatment videos increases average donations among females but not males. Causal mediation methods show that empathic concern explains 17% of the observed gender differences in giving. While the treatments evoke other emotions in addition to empathic concern, none of them explain observed gender differences in donations. Our study sheds light on the role of children's personal stories and empathic concern for children in explaining gender-donation gaps.Purpose of Review The goal of this review is to provide a timely overview on efforts to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease (COVID-19). Recent Findings Previous research efforts to develop a severe acute respiratory syndrome coronavirus (SARS-CoV) vaccine in the years following the 2003 pandemic have opened the door for investigators to design vaccine concepts and approaches for the COVID-19 epidemic in China. Both SARS-CoV and SARS-CoV-2 exhibit a high degree of genetic similarity and bind to the same host cell ACE2 receptor. Based on previous experience with SARS-CoV vaccines, it is expected that all COVID-19 vaccines will require careful safety evaluations for immunopotentiation that could lead to increased infectivity or eosinophilic infiltration. Besides this, a COVID-19 vaccine target product profile must address vaccinating at-risk human populations including frontline healthcare workers, individuals over the age of 60, and those with underlying and debilitating chronic conditions. Among the vaccine technologies under evaluation are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. Summary Each current vaccine strategy has distinct advantages and disadvantages. Therefore, it is paramount that multiple strategies be advanced quickly and then evaluated for safety and efficacy. Ultimately, the safety studies to minimize undesired immunopotentiation will become the most significant bottleneck in terms of time. © Springer Nature Switzerland AG 2020.The representation of land use (LU) in meteorological modeling strongly influences the simulation of fluxes of heat, moisture, and momentum; affecting the accuracy of 2-m temperature and precipitation. Here, the Weather Research and Forecasting (WRF) model is used with the Noah land surface model to compare a mosaic approach, which accounts for subgrid scale variability of LU types, to the default option which only considers the dominant category in each grid cell. Three-year historical dynamically downscaled WRF simulations are generated using a 12-km domain over the contiguous U.S. to assess the sensitivities to using mosaic LU and to changes to parameters associated with LU and soil categories. Compared to dominant LU, mosaic LU features decreased coverage of forest and agricultural types and increased low-density urban LU throughout much of the eastern and central U.S. However, highly urbanized areas show the opposite trend, as mosaic LU represents partial greenspace within areas that are exclusively urban within dominant LU. Mosaic LU results in widespread increases in sensible heat fluxes and 2-m temperatures, with reductions in latent heat flux, 2-m mixing ratio, and monthly precipitation across the central and eastern U.S. These changes exacerbate an existing warm bias found with dominant LU but reduce overestimations of precipitation. Highly urbanized areas in the eastern U.S. tend to have cooler, more realistic temperatures with mosaic LU relative to dominant LU. A pair of runs with updated surface parameters corroborates these results. Overall, differences between the simulations are largely attributable to their representations of urban LU.Eosinophilic gastroenteritis (EGE) is a rare idiopathic disease affecting multiple organs (stomach and small intestine) of the digestive tract. It is characterized by eosinophilic infiltration of the bowel wall to a variable depth and symptoms associated with gastrointestinal tract disease. The prevalence of this condition is ranging from 8 and 28 per 100,000. We present a rare presentation of EGE manifesting as upper GI bleeding. A 28-year-old male with PMH of EGE, duodenal ulcers, and stricture presented to the hospital with the chief complaints of three episodes of dizziness and melena over one day. His home medications included prednisone, montelukast, and pantoprazole. On admission, he was found to be tachycardic (150) while other vital signs were stable. Physical examination revealed cold, pale and clammy skin but was otherwise normal on examination. Initial labs showed hemoglobin (hgb) of 9.3. His hospital course was complicated with 1 episode of large volume hematemesis >1.5 L and brief loss of conscwithin 1 week. The purpose of this case report is to increase awareness about this clinical condition among medical professionals. Copyright © 2020, Priyadarshni et al.Neuromyelitis optica (NMO) is a disease of central nervous system, characterized by demyelination and axonal damage mostly involving optic nerves and spinal cord. Usually these patients present with symptoms related to optic neuritis or myelitis with a typical relapsing course. Some patients present with less common symptoms involving brain stem like nausea and vomiting, especially those involving area postrema (AP) located in dorsal medulla. International panel for NMO diagnosis revised criteria in 2015 and came up with a unifying term NMO spectrum disorders (NMOSD) instead of NMO. Patients with NMO having AP involvement are grouped under area postrema syndrome (APS). Usually patients with AP symptoms also have neurological symptoms upon presentation. Here we present a rare case of an NMO who presented with isolated APS with no other neurological symptoms. Copyright © 2020, Dandu et al.Mastocytosis is an uncommon disease involving the proliferation of mast cells within at least one organ system, most commonly the skin. One rare variant is telangiectasia macularis eruptive perstans (TMEP). The telangiectatic tan-brown macules are highly characteristic, although a biopsy is indicated to confirm the diagnosis. We present a 33-year-old white woman who presented for a skin check with concern for a four- to six-year history of "moles" present on the majority of body surface area. Her lesions presented shortly after her first pregnancy and spared sun-exposed face, neck, and extremities. Both of these features are rather unusual in TMEP. In this asymptomatic patient, workup focused on excluding systemic manifestations and discussion of cosmetic treatments. Punch biopsies revealed nests of CD117+ mast cells as well as increased basal melanocytes. Because the lesions spared sun-exposed regions, sunbathing was advised for initial treatment. Copyright © 2020, Fris et al.Acute mucus plugging is a pulmonary emergency associated with increased mortality and often requires rapid bronchoscopic intervention which may not be readily available in all centers. Furthermore, the role and efficacy of alternate conventional measures such as mechanical percussive therapies are uncertain. Herein, we present a patient who rapidly progressed to respiratory distress; a chest X-ray revealed left lobar atelectasis highly suggestive of acute mucus plugging. In the absence of rapid bronchoscopic intervention, bedside chest percussion was initiated with improvement in clinical status. Our case demonstrates the successful utilization of chest physiotherapy in the resolution of acute mucus plugging in an urgent situation and highlights the need for careful attention to respiratory status in high-risk patients who are also undergoing fluid removal with dialysis therapies. Copyright © 2020, Kaur et al.