High-level of sialic acid (SA) expression on the surface of cancer cells is observed extremely common. Phenylboronic acids (PBAs) have a high affinity with SA. The cellular uptake efficiency could be enhanced by the strategy of introducing PBA fragments to the compounds. In this work, we synthesized five new probes with the Dicyanomethylene-4H-pyran (DCM) fluorophore, three of them conjugated with different phenylboronic acid fragments. By cellular uptake experiments, DLCB and DLAB showed enhanced cellular uptake abilities compared with DLN and DLO. These two effective phenylboronic acid fragments were then conjugated with SN-38 and the conjugates showed enhanced cellular uptake abilities by 3-fold or 7-fold compared with irinotecan. In summary, the strategy of introducing 4-carboxyphenylboronic acid and 3-amino-benzoxaborole groups shows great potential in drug delivery system. Moreover, the released linkers between boric acid and drugs deserve further studies. PET imaging of α-synuclein (α-syn) deposition in the brain will be an effective tool for earlier diagnosis of Parkinson's disease (PD) due to α-syn aggregation is the widely accepted biomarker for PD. However, the necessary PET radiotracer for imaging is clinically unavailable until now. The lead compound discovery is the first key step for the study. Herein, we initially established an efficient biologically evaluation system well in highthroughput based on SPR technology, and identified a novel class of N, N-dibenzylcinnamamide (DBC) compounds as α-syn ligands through the assay. These compounds were proved to have high affinities against α-syn aggregates (KD  less then  10 nM), which well met the requirement of binding activity for the PET probe. These DBC compounds were firstly reported as α-syn ligands herein and the preliminary obtained structure has been further modified into F-labeled ones. Among them, a high-affinity tracer (5-41) with 1.03 nM (KD) has been acquired, indicating its potential as a new lead compound for developing PET radiotracer. The islet of Langerhans contains at least five types of endocrine cells producing distinct hormones. In response to nutrient or neuronal stimulation, islet endocrine cells release biochemicals including peptide hormones to regulate metabolism and to control glucose homeostasis. It is now recognized that malfunction of islet cells, notably insufficient insulin release of β-cells and hypersecretion of glucagon from α-cells, represents a causal event leading to hyperglycemia and frank diabetes, a disease that is increasing at an alarming rate to reach an epidemic level worldwide. Understanding the mechanisms regulating stimulus-secretion coupling and investigating how islet β-cells maintain a robust secretory activity are important topics in islet biology and diabetes research. To facilitate such studies, a number of biological systems and assay platforms have been developed for the functional analysis of islet cells. These technologies have enabled detailed analyses of individual islets at the cellular level, either in vitro, in situ, or in vivo. INTRODUCTION AND OBJECTIVES Population aging is associated with an increased prevalence of atrial fibrillation (AF) and dementia. This study aimed to analyze the impact of oral anticoagulation in elderly patients with AF and moderate-severe dementia. METHODS We conducted a single-center retrospective study analyzing patients aged ≥ 85 years with a diagnosis of AF between 2013 and 2018. The impact of anticoagulation on mortality, embolisms, and bleeding events was assessed by multivariate Cox analysis. In patients with dementia, this analysis was complemented by propensity score matching, depending on whether the patients were prescribed anticoagulant treatment or not. RESULTS Of the 3549 patients aged ≥ 85 years with AF, 221 had moderate-severe dementia (6.1%), of whom 88 (60.2%) were anticoagulated. During a follow-up of 2.8 ±1.7 years, anticoagulation was associated with lower embolic risk and higher bleeding risk both in patients with dementia (hazard ratio [HR]embolisms, 0.36; 95%CI, 0.15-0.84; HRbleeding, 2.44; 95%CI, 1.04-5.71) and in those without dementia (HRembolisms, 0.58; 95%CI, 0.45-0.74; HRbleeding, 1.55, 95%CI, 1.21-1.98). However, anticoagulation was associated with lower mortality only in patients without dementia (HR, 0.63; 95%CI, 0.53-0.75) and not in those with dementia (adjusted HR, 1.04; 95%CI, 0.63-1.72; P=.541; HR after propensity score matching 0.91, 95%CI, 0.45-1.83; P=.785). CONCLUSIONS In patients aged ≥ 85 years with moderate-severe dementia and AF, oral anticoagulation was significantly associated with a lower embolic risk and a higher bleeding risk, with no differences in total mortality. BACKGROUND A biconcave polyethylene (PE) bearing was developed for mobile-bearing unicompartmental knee arthroplasties (UKA) to reduce PE dislocation. METHODS A modification of the BalanSys Unicompartmental knee system with a biconcave PE and convex tibial component was used in 32 prostheses in 28 patients. Clinical outcomes and five cases of PE fracture are reported and extensively analyzed ex vivo.  https://www.selleckchem.com/products/CP-690550.html  RESULTS Visual Analogue Score of pain and satisfaction, and Knee Society Scores improved for all patients. The passive range of motion was 130°. No PE bearings dislocated. Five bearings fractured with oxidation, cracking and delamination at the thinnest central region of the PE. The combination of increased stress and decreased poly thickness was associated with increased creep. PE oxidation caused embrittlement and contributed to fractures in the thin waist of the implant. CONCLUSIONS The unforeseen consequence of a novel design of a UKA that resulted in a specific mechanical and tribological mode of failure is reported. We conclude the PE failed due to a biconcave design that increased stress on the implant at its region of risk combined with a decrease of the polyethylene thickness by 1 mm in the central area. V.BACKGROUND AND OBJECTIVE The subjective orgasm experience refers to the evaluation of sensations caused by orgasm from a psychological approach. The objective of this study was to examine the subjective orgasm experience in the context of solitary masturbation taking into account sex and age, as well as to compare this experience with perceived experience in the context of a sexual relations. MATERIAL AND METHODS The sample was composed of 874 heterosexual adults from the general Spanish population (441 men [50.5%], 433 women [49.5%]). It was distributed into two age ranges 18-34 and 50-93years. Participants completed a survey composed of a Background questionnaire and the Spanish version of the Orgasm Rating Scale. RESULTS It was shown that sex (p less then .001) and age (p less then .001) influence subjective orgasm experience in the context of solitary masturbation. Women and young people showed greater intensity. Furthermore, significant differences in the subjective orgasm experience between the context of solitary masturbation and the context of a sexual relations were found.