Preparation and In Vitro Release Property of PLA Microspheres Enclosing Antitumor Agent

Recently, many antitumor agents developed. Irinotecan hycrochloride (CPT) has a great side effect even though it is well effective against the cancer. Drug delivery system (DDS) medicine indicates that the release rate of medicine is constant for a long time. Therefore, in order to materialize the general idea of DDS, we applied microencapsulation technique to prepare biodegradable polymer microspheres (MS) enclosing antitumor drug having no side effect. Polylactide microparticles enclosing antitumor agent were prepared by solvent evaporation method under various operation conditions. The effects of operation parameter on release rate of drug and morphology of microparticles were studied

Design and performance of a gain calibration system for the POLARBEAR-2a receiver system at the Simons Array cosmic microwave background experiment

We present an advanced system for calibrating the detector gain responsivity with a chopped thermal source for POLARBEAR-2a, which is the first receiver system of a cosmic microwave background (CMB) polarimetry experiment: the Simons Array. Intensity-to-polarization leakage due to calibration errors between detectors can be a significant source of systematic error for a polarization-sensitive experiment. To suppress this systematic uncertainty, POLARBEAR-2a calibrates the detector gain responsivities by observing a chopped thermal source before and after each period of science observations. The system includes a high-temperature ceramic heater that emits blackbody radiation covering a wide frequency range and an optical chopper to modulate the radiation signal. We discuss the experimental requirements of gain calibration and system design to calibrate POLARBEAR-2a. We evaluate the performance of our system during the early commissioning of the receiver system. This calibration system is promising for the future generation of CMB ground-based polarization observations

Cell-Surface Protein Profiling Identifies Distinctive Markers of Progenitor Cells in Human Skeletal Muscle

SummarySkeletal muscle contains two distinct stem/progenitor populations. One is the satellite cell, which acts as a muscle stem cell, and the other is the mesenchymal progenitor, which contributes to muscle pathogeneses such as fat infiltration and fibrosis. Detailed and accurate characterization of these progenitors in humans remains elusive. Here, we performed comprehensive cell-surface protein profiling of the two progenitor populations residing in human skeletal muscle and identified three previously unrecognized markers: CD82 and CD318 for satellite cells and CD201 for mesenchymal progenitors. These markers distinguish myogenic and mesenchymal progenitors, and enable efficient isolation of the two types of progenitors. Functional study revealed that CD82 ensures expansion and preservation of myogenic progenitors by suppressing excessive differentiation, and CD201 signaling favors adipogenesis of mesenchymal progenitors. Thus, cell-surface proteins identified here are not only useful markers but also functionally important molecules, and provide valuable insight into human muscle biology and diseases

Mutations in the J domain of DNAJB6 cause dominant distal myopathy

Eight patients from five families with undiagnosed dominant distal myopathy underwent clinical, neurophysiological and muscle biopsy examinations. Molecular genetic studies were performed using targeted sequencing of all known myopathy genes followed by segregation of the identified mutations in the affected families using Sanger sequencing. Two novel mutations in DNAJB6 J domain, c.149C>T (p.A50V) and c.161A>C (p.E54A), were identified as the cause of disease. The muscle involvement with p.A50V was distal calf-predominant, and the p.E54A was more proximo-distal. Histological findings were similar to those previously reported in DNAJB6 myopathy. In line with reported pathogenic mutations in the glycine/phenylalanine (G/F) domain of DNAJB6, both the novel mutations showed reduced anti-aggregation capacity by filter trap assay and TDP-43 disaggregation assays. Modeling of the protein showed close proximity of the mutated residues with the G/F domain. Myopathy-causing mutations in DNAJB6 are not only located in the G/F domain, but also in the J domain. The identified mutations in the J domain cause dominant distal and proximo-distal myopathy, confirming that mutations in DNAJB6 should be considered in distal myopathy cases.Peer reviewe

Optimal Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease

BACKGROUND: Intravascular ultrasound (IVUS) was only rarely used in landmark trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel disease. OBJECTIVES: The authors aimed to evaluate clinical outcomes after optimal IVUS-guided PCI in patients undergoing multivessel PCI. METHODS: The OPTIVUS (OPTimal IntraVascular UltraSound)-Complex PCI study multivessel cohort was a prospective multicenter single-arm study enrolling 1, 021 patients undergoing multivessel PCI, including left anterior descending coronary artery using IVUS, aiming to meet the prespecified criteria (OPTIVUS criteria: minimum stent area > distal reference lumen area [stent length ≥28mm], and minimum stent area >0.8 × average reference lumen area [stent length <28mm]) for optimal stent expansion. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) (death/myocardial infarction/stroke/any coronary revascularization). The predefined performance goals were derived from the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome study in Kyoto) PCI/CABG registry cohort-2 fulfilling the inclusion criteria in this study. RESULTS: In this study, 40.1% of the patients met OPTIVUS criteria in all stented lesions. The cumulative 1-year incidence of the primary endpoint was 10.3% (95% CI: 8.4%-12.2%), which was significantly lower than the predefined PCI performance goal of 27.5% (P < 0.001), and which was numerically lower than the predefined CABG performance goal of 13.8%. The cumulative 1-year incidence of the primary endpoint was not significantly different regardless of meeting or not meeting OPTIVUS criteria. CONCLUSIONS: Contemporary PCI practice conducted in the OPTIVUS-Complex PCI study multivessel cohort was associated with a significantly lower MACCE rate than the predefined PCI performance goal, and with a numerically lower MACCE rate than the predefined CABG performance goal at 1 year

Conversion to complete resection with mFOLFOX6 with bevacizumab or cetuximab based on K‐RAS status for unresectable colorectal liver metastasis (BECK study): Long‐term results of survival

[Background/Purpose]To investigate the long‐term outcome and entire treatment course of patients with technically unresectable CRLM who underwent conversion hepatectomy and to examine factors associated with conversion to hepatectomy. [Methods]Recurrence and survival data with long‐term follow‐up were analyzed in the cohort of a multi‐institutional phase II trial for technically unresectable colorectal liver metastases (the BECK study). [Results]A total of 22/12 patients with K‐RAS wild‐type/mutant tumors were treated with mFOLFOX6 + cetuximab/bevacizumab. The conversion R0/1 hepatectomy rate was significantly higher in left‐sided primary tumors than in right‐sided tumors (75.0% vs 30.0%, P = .022). The median follow‐up was 72.6 months. The 5‐year overall survival (OS) rate in the entire cohort was 48.1%. In patients who underwent R0/1 hepatectomy (n = 21), the 5‐year RFS rate and OS rate were 19.1% and 66.3%, respectively. At the final follow‐up, seven patients had no evidence of disease, five were alive with disease, and 20 had died from their original cancer. All 16 patients who achieved 5‐year survival underwent conversion hepatectomy, and 11 of them underwent further resection for other recurrences (median: 2, range: 1‐4). [Conclusions]Conversion hepatectomy achieved a similar long‐term survival to the results of previous studies in initially resectable patients, although many of them experienced several post‐hepatectomy recurrences. Left‐sided primary was found to be the predictor for conversion hepatectomy

Transgenic Monkey Model of the Polyglutamine Diseases Recapitulating Progressive Neurological Symptoms

Age-associated neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and the polyglutamine (polyQ) diseases, are becoming prevalent as a consequence of elongation of the human lifespan. Although various rodent models have been developed to study and overcome these diseases, they have limitations in their translational research utility owing to differences from humans in brain structure and function and in drug metabolism. Here, we generated a transgenic marmoset model of the polyQ diseases, showing progressive neurological symptoms including motor impairment. Seven transgenic marmosets were produced by lentiviral introduction of the human ataxin 3 gene with 120 CAG repeats encoding an expanded polyQ stretch. Although all offspring showed no neurological symptoms at birth, three marmosets with higher transgene expression developed neurological symptoms of varying degrees at 3–4 months after birth, followed by gradual decreases in body weight gain, spontaneous activity, and grip strength, indicating time-dependent disease progression. Pathological examinations revealed neurodegeneration and intranuclear polyQ protein inclusions accompanied by gliosis, which recapitulate the neuropathological features of polyQ disease patients. Consistent with neuronal loss in the cerebellum, brain MRI analyses in one living symptomatic marmoset detected enlargement of the fourth ventricle, which suggests cerebellar atrophy. Notably, successful germline transgene transmission was confirmed in the second-generation offspring derived from the symptomatic transgenic marmoset gamete. Because the accumulation of abnormal proteins is a shared pathomechanism among various neurodegenerative diseases, we suggest that this new marmoset model will contribute toward elucidating the pathomechanisms of and developing clinically applicable therapies for neurodegenerative diseases.ArticleeNeuro.4(2):e0250(2017)journal articl

Single-Session Versus Staged Multivessel Optimal IVUS-Guided PCI in Patients With CCS or NSTE-ACS

[Background] There are no studies comparing single-session vs staged multivessel intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with chronic coronary syndrome (CCS) or non–ST-segment-elevation acute coronary syndrome (NSTE-ACS). [Objectives] The authors aimed to compare single-session vs staged multivessel IVUS-guided PCI in patients with CCS or NSTE-ACS. [Methods] The OPTIVUS-Complex PCI study multivessel cohort was a prospective multicenter single-arm trial enrolling 1, 021 patients with CCS or NSTE-ACS undergoing multivessel PCI including left anterior descending coronary artery using IVUS aiming to meet the prespecified OPTIVUS criteria for optimal stent expansion. We compared single-session vs staged multivessel PCI. The primary endpoint was a composite of death, myocardial infarction, stroke, or any coronary revascularization. [Results] There were 246 patients (24.1%) undergoing single-session multivessel PCI, and 775 patients (75.9%) undergoing staged multivessel PCI. There was a wide variation in the prevalence of single-session multivessel PCI across the participating centers. The staged multivessel PCI group more often had complex coronary anatomy such as 3-vessel disease, chronic total occlusion, and calcified lesions requiring an atherectomy device compared with the single-session multivessel PCI group. The rates of PCI success, procedural complications, and meeting OPTIVUS criteria were not different between groups. The cumulative 1-year incidence of the primary endpoint was not different between single-session and staged multivessel PCI groups (9.0% vs 10.8%, log-rank P = 0.42). After adjusting confounders, the effect of single-session multivessel PCI relative to staged multivessel PCI was not significant for the primary endpoint (HR: 0.95; 95% CI: 0.58-1.55; P = 0.84). [Conclusions] Single-session and staged multivessel IVUS-guided PCI had similar 1-year outcomes