Activity

The size, shape, and underlying chemistries of drug delivery particles are key parameters which govern their ultimate performance in vivo. Responsive particles are desirable for triggered drug delivery, achievable through architecture change and biodegradation to control in vivo fate. Here, polymeric materials are synthesized with linear, hyperbranched, star, and micellar-like architectures based on 2-hydroxypropyl methacrylamide (HPMA), and the effects of 3D architecture and redox-responsive biodegradation on biological transport are investigated. Variations in “stealth” behavior between the materials are quantified in vitro and in vivo, whereby reduction-responsive hyperbranched polymers most successfully avoid accumulation within the liver, and none of the materials target the spleen or lungs. Functionalization of selected architectures with doxorubicin (DOX) demonstrates enhanced efficacy over the free drug in 2D and 3D in vitro models, and enhanced efficacy in vivo in a highly aggressive orthotopic breast cancer model when dosed over schedules accounting for the biodistribution of the carriers. These data show it is possible to direct materials of the same chemistries into different cellular and physiological regions via modulation of their 3D architectures, and thus the work overall provides valuable new insight into how nanoparticle architecture and programmed degradation can be tailored to elicit specific biological responses for drug delivery.

To compare the clinical outcomes of plate fixation and arthroscopic-assisted plate fixation in patients with displaced isolated medium-sized fractures of the greater tuberosity.

From July 2013 to October 2017, patients with displaced isolated medium-sized fractures of the greater tuberosity who underwent arthroscopic-assisted plate fixation (ASPF group) or open reduction and internal plate fixation (ORIF group) were retrospectively reviewed and analyzed. There were 19 patients in the ASPF group and 27 patients in the ORIF group, with comparable demographic characteristics. The average age of patients was 49.4 ± 12.1 years in the ASPF group and 46.9 ± 11.4 years in the ORIF group. The shoulder function reflected by the Constant-Murley (CS) scores, the American Shoulder and Elbow Surgeons (ASES) scores, and the range of motion (ROM) in the both groups at the last follow-up were analyzed in the study. Surgery time, postoperative pain, and postoperative complications were also reviewed.

A total of 46 eligibacture nonunion, pullout of the suture anchor, and screw penetration, were not observed in either group.

Arthroscopic-assisted plate fixation is effective and may be an alternative in the treatment of displaced isolated medium-sized fractures of the greater tuberosity.

Arthroscopic-assisted plate fixation is effective and may be an alternative in the treatment of displaced isolated medium-sized fractures of the greater tuberosity.

Like other autoimmune diseases, systemic sclerosis (SSc) has been described to be associated with accelerated atherosclerosis (ATS). Before clinical manifestations of cardiovascular disease (CVD) occur, subclinical ATS can be investigated in different ways.

To evaluate the presence of subclinical ATS in a group of patients with SSc, and to identify different risk profiles among patients.

Subclinical ATS was reviewed in 43 SSc patients and 27 healthy controls, using 2 methods carotid ultrasound and flow mediated dilation (FMD) of the brachial artery.

Plaques were statistically more frequent in SSc patients than in controls (65% vs 30%, P=.006); intima-media thickness of common carotid artery (CCA-IMT) resulted in statistically higher (median value 0.8mm vs 0.55mm; P<.0001) while FMD was significantly lower (median value 9% vs 14%; P=.0086) in patients compared to healthy controls. Among the SSc patients, thickening of CCA-IMT was significantly associated with the presence of diastolic dysfunction of left ventricle (absence of diastolic dysfunction odds ratio [OR] 0.2, 95% CI 0.04-0.92, P=.038) and with a higher Framingham score (OR 1.3, 95% CI 1.03-1.6], P=.024). The diffuse cutaneous form was slightly protective against pathological FMD (OR 0.12, 95% CI 0.022-0.71, P=.019).

This study confirms the involvement of macrocirculation in SSc patients, detecting the presence of subclinical ATS markers more frequently in patients compared to healthy controls. selleck chemicals llc Framingham score, diastolic dysfunction of left ventricle and limited cutaneous form of the disease appeared to be associated with a higher risk of developing ATS.

This study confirms the involvement of macrocirculation in SSc patients, detecting the presence of subclinical ATS markers more frequently in patients compared to healthy controls. Framingham score, diastolic dysfunction of left ventricle and limited cutaneous form of the disease appeared to be associated with a higher risk of developing ATS.Fetuin-A is a serum glycoprotein synthesized and secreted into blood by the liver and whose main physiological function is the inhibition of ectopic calcification. However, a number of studies have demonstrated that it is a multifunctional protein. For example, endocytic uptake of fetuin-A by tumor cells resulting in rapid cellular adhesion and spreading has been reported. The precise uptake mechanism, however, has been elusive. The present studies were done to determine whether Toll-like receptor-4 (TLR4), which has been previously shown to be a receptor for fetuin-A and is commonly expressed in immune cells, could take part in the rapid uptake ( less then 3 min) of fetuin-A by tumor cells. Rapid uptake of fetuin-A was inhibited by the specific TLR4 inhibitor CLI-095 and also attenuated in TLR4 knockdown prostate tumor cells. Inhibition of TLR4 by CLI-095 also attenuated the rapid adhesion of tumor cells as well as invasion through a bed of Matrigel. The data suggest mechanisms by which TLR4 modulates the adhesion and growth of tumor cells.

The diagnosis of gallbladder (GB) lesions is occasionally difficult. Recently, superb microvascular imaging (SMI) of ultrasound has been developed as a novel microvascular imaging technique. We evaluated the feasibility of SMI for the diagnosis of GB lesions and compared microvascular imaging between benign and malignant GB lesions.

Twenty patients with GB-protruded lesions or wall thickening who underwent SMI from August 2015 to July 2017 were included in this retrospective study. The measured outcomes were the quality of microvascular imaging when compared between normal SMI (N-SMI) and contrast-enhanced SMI (CE-SMI), and the microvascular findings (vascularity, vascular morphology, presence of branching, and presence of caliber change) when compared between benign and malignant GB lesions.

The quality of microvascular imaging of CE-SMI was evaluated as better than that of N-SMI, showing a significant difference (P<.001). From the CE-SMI microvascular findings, the evaluation of vascular morphology and the presence of caliber change showed a significant difference between benign and malignant GB lesions (P=.