Remission of lymphoblastic leukaemia in an intravascular fluidic environment by pliable drug carrier with a sliding target ligand

A polyrotaxane-based nanoconstruct with pliable structure carrying a chemotherapeutic drug was developed for targeting circulating lymphoblastic leukaemia cells in a fluidic environment of blood vessels in vivo. By introducing lymphoblast targeting aptamer DNA through cyclodextrin, threaded in poly(ethylene glycol) as polyrotaxane, target aptamer slides along the long polymeric chain and actively search for target ligand, leading to active targeting in dynamic fluidic system which is enhanced by up to 6-fold compared with that of control carriers with non-sliding targeting ligands. Moreover, the drug carrier was made stimuli-responsive by employing i-motif DNA to selective releases of its payload at intracellular acidic condition. These combined features resulted in the effective remission of lymphoblastic leukaemia both in vitro and in dynamic blood vessels in vivo.1142Ysciescopu

anti-9,10-Di(1-naphth­yl)anthracene pyridine disolvate

In the title compound, C34H22·2C5H5N, there is a crystallographic inversion center in the middle of the anthracene ring system. The dihedral angle between the mean planes of the anthracene and naphthalene ring systems is 83.96 (4)°. The crystal structure is stabilized by weak inter­molecular C—H⋯N and C—H⋯π inter­actions

Self-assembled nanocomplex between polymerized phenylboronic acid and doxorubicin for efficient tumor-targeted chemotherapy

Since the discovery that nano-scaled particulates can easily be incorporated into tumors via the enhanced permeability and retention (EPR) effect, such nanostructures have been exploited as therapeutic small molecule delivery systems. However, the convoluted synthetic process of conventional nanostructures has impeded their feasibility and reproducibility in clinical applications. Herein, we report an easily prepared formulation of self-assembled nanostructures for systemic delivery of the anti-cancer drug doxorubicin (DOX). Phenylboronic acid (PBA) was grafted onto the polymeric backbone of poly(maleic anhydride). pPBA-DOX nanocomplexes were prepared by simple mixing, on the basis of the strong interaction between the 1,3-diol of DOX and the PBA moiety on pPBA. Three nanocomplexes (1, 2, 4) were designed on the basis of [PBA]:[DOX] molar ratios of 1: 1, 2: 1, and 4: 1, respectively, to investigate the function of the residual PBA moiety as a targeting ligand. An acid-labile drug release profile was observed, owing to the intrinsic properties of the phenylboronic ester. Moreover, the tumor-targeting ability of the nanocomplexes was demonstrated, both in vitro by confocal microscopy and in vivo by fluorescence imaging, to be driven by an inherent property of the residual PBA. Ligand competition assays with free PBA pre-treatment demonstrated the targeting effect of the residual PBA from the nanocomplexes 2 and 4. Finally, the nanocomplexes 2 and 4, compared with the free DOX, exhibited significantly greater anti-cancer effects in vitro and even in vivo. Our pPBA-DOX nanocomplex enables a new paradigm for self-assembled nanostructures with potential biomedical applications.115Ysciescopu

A case of dermatomyositis in a patient with central core disease: unusual association with autoimmunity and genetic muscle disease

Background Dermatomyositis is an inflammatory muscle disease caused by immune-mediated muscle injury, and central core disease (CCD) is a congenital myopathy associated with disturbed intracellular calcium homeostasis and excitation-contraction coupling. To date, CCD has not been reported to have autoantibodies or coexist with inflammatory myopathy. Case presentation Here, we described the case of a 25-year-old woman who had progressive proximal muscle weakness, myalgia, pruritic macular rash, skin ulcers, and calcinosis. Dermatomyositis was initially suspected based on the clinical symptoms accompanied by elevated muscle enzyme levels, electromyography abnormalities, and a positive antinuclear antibody test. However, the patients muscle biopsy revealed the characteristic findings of both dermatomyositis and CCD, suggesting that dermatomyositis occurred in this patient with previously asymptomatic CCD. The patient did not have any pathogenic gene mutations associated with congenital myopathy, including RYR1 and SEPN1 in targeted next-generation sequencing. She received high-dose glucocorticoid therapy and azathioprine with a significant improvement in muscle strength. Conclusions We present a case of rare coexistence of dermatomyositis and CCD. Clinicians should be aware that patients with CCD may have inflammatory myopathy that responds well to immunosuppressive therapy.This study was funded by a grant from the Ministry of Science, ICT, and Future Planning (NRF-2020M3E5E2037430 to Y-W.S.)

Prognosis Prediction for Class III Malocclusion Treatment by Feature Wrapping Method

Objective: To use the feature wrapping (FW) method to identify which cephalometric markers show the highest classification accuracy in prognosis prediction for Class III malocclusion and to compare the prediction accuracy between the FW method and conventional statistical methods such as discriminant analysis (DA). Materials and Methods: The sample set consisted of 38 patients (15 boys and 23 girls, mean age 8.53 ± 1.36 years) who were diagnosed with Class III malocclusion and received both first-phase (orthopedic) and second-phase (fixed orthodontic) treatments. Lateral cephalograms were taken before (T0) and after first-phase treatment (T1) and after second-phase treatment and retention (T2). Based on the measurements taken at the T2 stage, the patients were allocated into good (n = 20) or poor (n = 18) prognosis groups. Forty-six cephalometric variables on T0 lateral cephalograms were analyzed by the FW method to identify key determinants for discriminating between the two groups. Sequential forward search (SFS) algorism and support vector machine (SVM) were used in conjunction with the FW method to improve classification accuracy. To compare the prediction accuracy of the FW method with conventional statistical methods, DA was performed for the same data set. Results: AB to mandibular plane angle (°) and A to N-perpendicular (mm) were selected as the most accurate cephalometric predictors by both the FW and DA methods. However, classification accuracy was higher with the FW method (97.2%) compared with DA (92.1%), because the FW method with SFS and SVM has a more precise classification algorithm. Conclusions: The FW method, which uses a learning algorithm, might be an effective alternative to DA for prognosis prediction

Hennekam Syndrome: A Case Report

Hennekam syndrome is a rare autosomal recessive disorder resulting from malformation of the lymphatic system. The characteristic signs of Hennekam syndrome are lymphangiectasia, lymph edema, facial anomalies, and mental retardation. This is a case in which a patient presented with left-arm lymphedema, facial-feature anomalies, and multiple organ lymphangiectasia consistent with symptoms of Hennekam syndrome. There is no curative therapy at this time, but rehabilitative treatments including complete decongestive therapy for edema control appeared to be beneficial

Gene-based copy number variation study reveals a microdeletion at 12q24 that influences height in the Korean population

AbstractHeight is a classic polygenic trait with high heritability (h2=0.8). Recent genome-wide association studies have revealed many independent loci associated with human height. In addition, although many studies have reported an association between copy number variation (CNV) and complex diseases, few have explored the relationship between CNV and height. Recent studies reported that single nucleotide polymorphisms (SNPs) are highly correlated with common CNVs, suggesting that it is warranted to survey CNVs to identify additional genetic factors affecting heritable traits such as height.This study tested the hypothesis that there would be CNV regions (CNVRs) associated with height nearby genes from the GWASs known to affect height. We identified regions containing >1% copy number deletion frequency from 3667 population-based cohort samples using the Illumina HumanOmni1-Quad BeadChip. Among the identified CNVRs, we selected 15 candidate regions that were located within 1Mb of 283 previously reported genes. To assess the effect of these CNVRs on height, statistical analyses were conducted with samples from a case group of 370 taller (upper 10%) individuals and a control group of 1828 individuals (lower 50%).We found that a newly identified 17.7kb deletion at chromosomal position 12q24.33, approximately 171.6kb downstream of GPR133, significantly correlated with height; this finding was validated using quantitative PCR. These results suggest that CNVs are potentially important in determining height and may contribute to height variation in human populations

Feasibility of hemispatial neglect rehabilitation with virtual reality-based visual exploration therapy among patients with stroke: randomised controlled trial

BackgroundHemispatial neglect (HSN) was diagnosed using a virtual reality-based test (FOPR test) that explores the field of perception (FOP) and field of regard (FOR). Here, we developed virtual reality-visual exploration therapy (VR-VET) combining elements from the FOPR test and visual exploration therapy (VET) and examined its efficacy for HSN rehabilitation following stroke.MethodsEleven participants were randomly assigned to different groups, training with VR-VET first then waiting without VR-VET training (TW), or vice versa (WT). The TW group completed 20 sessions of a VR-VET program using a head-mounted display followed by 4 weeks of waiting, while the WT group completed the opposite regimen. Clinical HSN measurements [line bisection test (LBT), star cancellation test (SCT), Catherine Bergego Scale (CBS), CBS perceptual-attentional (CBS-PA), and CBS motor-explanatory (CBS-ME)] and FOPR tests [response time (RT), success rate (SR), and head movement (HM) for both FOP and FOR] were assessed by blinded face-to-face assessments.ResultsFive and six participants were allocated to the TW and WT groups, respectively, and no dropout occurred throughout the study. VR-VET considerably improved LBT scores, FOR variables (FOR-RT, FOR-SR), FOP-LEFT variables (FOP-LEFT-RT, FOP-LEFT-SR), and FOR-LEFT variables (FOR-LEFT-RT, FOR-LEFT-SR) compared to waiting without VR-VET. Additionally, VR-VET extensively improved FOP-SR, CBS, and CBS-PA, where waiting failed to make a significant change. The VR-VET made more improvements in the left hemispace than in the right hemispace in FOP-RT, FOP-SR, FOR-RT, and FOR-SR.ConclusionThe observed improvements in clinical assessments and FOPR tests represent the translatability of these improvements to real-world function and the multi-dimensional effects of VR-VET training.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03463122, identifier NCT03463122

Effects of a Postnatal Care Program on Self-efficacy, Self-management, and Glycemic Control in Women with Gestational Diabetes Mellitus

PURPOSE: To examine effects of a postnatal care program on self-efficacy, self-management, and glycemic control in women with gestational diabetes mellitus (GDM). METHODS: A non-equivalent control group non-synchronized quasi-experimental design was used. Sixty-two women with GDM were enrolled and assigned to either an experimental group (n=30) or a control group (n=32). The experimental group received an intervention which was postnatal care program for women with GDM. The postnatal care program for GDM included an individual education with leaflet and mobile web-based video with three times of telephone counseling. Effects of the intervention were measured with self-efficacy, self-management questionnaire, and a 75 g oral glucose tolerance test (75g OGTT). Statistical significance was examined using independent t-test and χ2-test. RESULTS: Although there was no significant difference in 75g OGTT (χ2=.11, p=.748) or self-management (t=−1.28, p=.206), there was a statistically significant increase in self-efficacy (t=−2.02, p=.048) in the experimental group compared to that in the control group. CONCLUSION: A postnatal care program is needed for women with GDM to improve their self-efficacy. Further studies are warranted to improve self-management and glycemic control through tailored education for GDM postpartum women