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A series of rhodium complexes bearing sterically and electronically tunable cyclopentadienyl ligands, prepared by utilizing Co2(CO)8-mediated [2+2+1] cyclization as a key step, were synthesized. In the presence of 2.5 mol% of CpmRh4, unprecedented enantioselective [4+1] annulation reaction of benzamides and alkenes was achieved with a broad substrate scope under mild reaction conditions, providing a variety of isoindolinones with excellent regio- and enantioselectivity (up to 94% yield, 973 er). Preliminary mechanistic studies suggest that the reaction involves an oxidative Heck reaction and an intramolecular enantioselective alkene hydroamination reaction.Compared with lithium, magnesium shows a low propensity toward dendritic deposition due to its low surface self-diffusion barriers. However, due to the intrinsic surface roughness of the metal and the nonuniformity of the formed solid-electrolyte interphase, uneven deposition of Mg still happens, which brings about high local current density and continuous proliferation of the interphase, greatly exacerbating the passivation. Unfortunately, little attention has been paid to the deposition uniformity and the interfacial stability of Mg metal anodes, which result in a potential penalty. Herein, we modify the electrolyte with cathodically stable cations to guide smooth deposition via an electrostatic shielding strategy. The cations adsorbed on the initial protuberances effectively homogenize the charge flux by repulsing the incoming Mg2+ away from the tips. Importantly, we prove the lateral growth can benefit the interphase stability and electrochemical reversibility.It aimed to provide the change of accreditation standards of medical schools in Korea by the Korean Institute of Medical Education and Evaluation (KIMEE) from 2000 to 2019. Specifically, the following was explained the development process, setting principle and direction, items of evaluation, characteristics of the standards, and validity test of 4 cycles. NVP-BEZ235 research buy The first cycle of accreditation (2000-2005) was a process to secure the minimum requirement of the educational environment. The evaluation criteria emphasized the evaluation of the core elements of medical education, including facilities and human resources. The second cycle of accreditation (2007-2010) was a process in which the university emphasized its commitment to social accountability and the pursuit of excellence in medical education. It raised the importance of the qualitative standard for judging the contents and fidelity of education. In the post-2nd cycle of accreditation (2012-2018), the certification criteria were developed to standardize the educational environment and educational programs and to use them in the development of curriculum, to continually improve the quality of basic medical education. The ASK2019 accreditation aimed at qualitative evaluation following the World Federation of Medical Education's accreditation criteria to reach the international level of basic medical education, which stresses the student-centered curriculum, communication with the society, and evaluation through whole basic medical education course. KIMEE has developed the basic medical education evaluation and certification system step by step as above. Understanding the previous process will help to develop the accreditation criteria of medical school in Korea.The Snellen chart assesses binocular and monocular visual acuity.In the near future, clinicians may face scenarios in which there are not have enough resources (ventilators, ECMO machines, etc) available for the number of critically sick COVID-19 patients. There may not be enough healthcare workers, as those who are positive for COVID-19 or those who have been exposed to the virus and need to be quarantined. During these worst-case scenarios, new crisis standards of care and thresholds for intensive care unit (ICU) admissions will be needed. Clinical decision scores may support the clinician's decision-making, especially if properly adapted for this unique pandemic and for the patient being treated. This review discusses the use of clinical prediction scores for pneumonia severity at 3 main decision points to examine which scores may provide value in this unique situation. Initial data from a cohort of over 44,000 COVID-19 patients in China, including risk factors for mortality, were compared with data from cohorts used to study the clinical scores, in order to estimate the potential appropriateness of each score and determine how to best adjust results at the bedside.BACKGROUND/AIMS The cardiac current IKs is carried by the KCNQ1/KCNE1-channel complex. Genetic aberrations that affect the activity of KCNQ1/KCNE1 can lead to the Long QT Syndrome 1 and 5 and, thereby, to a predisposition to sudden cardiac death. This might be prevented by pharmacological modulation of KCNQ1/KCNE1. The prototypic KCNQ1/KCNE1 activator 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) represents a candidate drug. Here, we study the mechanism of DIDS action on KCNQ1/KCNE1. METHODS Channels were expressed in Xenopus oocytes and iPSC cardiomyocytes. The role of the central S6 region was investigated by alanin-screening of KCNQ1 residues 333-338. link2 DIDS effects were measured by TEVC and MEA. RESULTS DIDS-action is influenced by the presence of KCNE1 but not by KCNQ1/KCNE1 stochiometry. V334A produces a significant higher increase in current amplitude, whereas deactivation (slowdown) DIDS-sensitivity is affected by residues 334-338. CONCLUSION We show that the central S6 region serves as a hub for allosteric channel activation by the drug and that DIDS shortens the pseudo QT interval in iPSC cardiomyocytes. The elucidation of the structural and mechanistic underpinnings of the DIDS action on KCNQ1/KCNE1 might allow for a targeted design of DIDS derivatives with improved potency and selectivity. © Copyright by the Author(s). Published by Cell Physiol Biochem Press.BACKGROUND/AIMS Chromosomal instability is a well-known factor in the progression of different types of cancer, including colorectal cancer. link3 Chromosomal instability results in severely rearranged karyotypes and aneuploidy. Tetraploidy constitutes an intermediate phase during the polyploidy/aneuploidy cascade in oncogenesis, and tetraploid cells are particularly resistant to chemotherapy. Whether inhibition of the mitotic protein polo-like kinase 1 (PLK1) prevents the survival of tetraploid colon cancer cells is unknown. METHODS Diploid and tetraploid cells were transfected with siPLK1 or treated with PLK1 inhibitor Bi2536 in combination with spindle poison. Cell toxicity was assessed via crystal violet staining and clonogenic assay. Flow cytometry assessment analyzed numerous cell apoptotic parameters and cell cycle phases. Synergistic activity between Bi2536 and paclitaxel, vincristine or colchicine was calculated using the CompuSyn software. RESULTS Inhibition or abrogation of PLK1 prevented the survival of colon cancer cells, specifically tetraploid cells. The cell death induced by PLK inhibition was due to mitotic slippage, followed by the activation of the intrinsic pathway of apoptosis. We further demonstrated that co-treatment of the tetraploid colon cancer cells with a PLK1 inhibitor and the microtubule polymerisation inhibitor vincristine or colchicine, but not the microtubule depolymerisation inhibitor paclitaxel, provoked a lethal synergistic effect. CONCLUSION PLK1 inhibition together with microtubule-targeting chemicals, serve as a potent therapeutic strategy for targeting tetraploid cancer cells. © Copyright by the Author(s). Published by Cell Physiol Biochem Press.PURPOSE Two studies evaluated the efficacy and safety of a single dose of naproxen sodium 440 mg (NS) compared to the combination of acetaminophen 600 mg and codeine phosphate 60 mg (AC) in subjects with postoperative dental pain. METHODS The two studies were single center, randomized, double-blind and double-dummy trials. In both studies, subjects were randomized into one of the following three treatments in a 221 ratio, respectively NS, AC, or placebo (PBO). Subjects were administered study medication when they had at least moderate pain following the surgical removal of three or four impacted molars, at least one of which was a mandibular partial or complete bony impaction. Efficacy assessments were completed over an 8-hour evaluation period. The co-primary efficacy assessments in both studies were time-weighted sum of categorical pain intensity differences over 4 hours (SPID4) and time-weighted sum of pain relief scores over 4 hours (TOTPAR4). Other efficacy assessments such as summed scores over 8 hours,) are effective analgesics for relieving postoperative pain. Copyright©American Journal of Dentistry.PURPOSE To review the scientific evidence for the efficacy of stabilized stannous fluoride (SnF₂) dentifrice in relation to dental caries, dental erosion and dentin hypersensitivity. METHODS Medline OVID, Embase.com, and the Cochrane Library were searched until January 2018. Two researchers independently selected studies according to inclusion and exclusion criteria, data were extracted, the risk of bias in eligible studies was assessed and a meta-analysis was performed wherever feasible. RESULTS Three studies on dental caries, eight studies on dental erosion and 11 on dentin hypersensitivity were included. Risk of bias was judged as high for most of the caries and erosion studies and low or medium for the hypersensitivity studies. A similar or slightly higher anti-caries activity compared with non-stannous fluoride dentifrices was observed. Stannous fluoride showed a greater anti-erosive potential in seven of the eight studies. A mean difference score in favor of stannous fluoride dentifrices compared with controls was found in a meta-analysis including six 8-week hypersensitivity studies. CLINICAL SIGNIFICANCE The use of stabilized stannous fluoride dentifrices to relieve dentin hypersensitivity and to prevent the initiation of dental erosion speaks in favor of this treatment strategy. Copyright©American Journal of Dentistry.PURPOSE This crossover study evaluated the hydrogen (HP) and carbamide (CP) peroxide degradation of bleaching gels in prefilled (PT) and customized trays (CT). METHODS Volunteers were randomly allocated to treatments (n=10) PT-HP/OGO (Opalescence GO-10%); CT-HP/WTC (White Class-10%) or CT-CP/OPF (Opalescence PF-10%). Gel samples were collected from the upper and lower trays in each period (baseline, 15, 30, 50 and 120 minutes). HP concentration was determined with the potassium permanganate titration method. Degradation was calculated based on initial concentration of gels. Repeated measures two-way ANOVA and Tukey's test (5%) were applied. RESULTS Bleaching gels exhibited exponential degradation over time. In 30 minutes, no significant differences in degradation among them were detected (P= 0.13). After 2 hours, lower degradation of CT-CP/OPF (61.85±10.65), compared with hydrogen peroxide in PT and CT (71.55±8.24 and 78.69±9.33, respectively) was observed. The gels showed higher degradation rate in lower trays than in upper trays in all evaluated times. In general, the bleaching gels in lower trays degraded more than in upper trays. The carbamide peroxide gel presented lower degradation than hydrogen peroxide after 2 hours. The degradation of the 10% hydrogen peroxide gel used in prefilled trays was higher than the one in customized trays after 30 minutes, but after 120 minutes, the degradation rate was similar for both. CLINICAL SIGNIFICANCE Bleaching gels degraded faster in lower arches than in upper arches. The degradation process was faster in the first 15 minutes of use and depended on the gel's composition, time of use, and tray position in the dental arches. Copyright©American Journal of Dentistry.

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