A randomized controlled trial was conducted to determine whether a manual-based psychodynamic treatment, labeled dynamic deconstructive psychotherapy (DDP), would be feasible and effective for individuals with co-occurring borderline personality disorder (BPD) and alcohol use disorder. Thirty participants were assessed every 3 months during a year of treatment with either DDP or treatment as usual (TAU) in the community. DDP participants showed statistically significant improvement in parasuicide behavior, alcohol misuse, institutional care, depression, dissociation, and core symptoms of BPD, and treatment retention was 67% to 73%. Although TAU participants received higher average treatment intensity, they showed only limited change during the same period. The results support the feasibility, tolerability, and efficacy of DDP for the co-occurring subgroup and highlight the need for further research. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

We report a one-step method to fabricate necklace-like structures from zero-dimensional materials via electrospinning. PVA was used as polymer matrix for accomplishing necklace-like arrays of silica particles. We systemically investigated how the diameter of SiO(2) particles, the weight ratio of PVA to SiO(2), the voltage, and the relative content of PVA/SiO(2)/H(2)O influenced the morphology of electrospun fibers. SiO(2) particles with diameter of 143 nm tended to aggregate into bunches in the fibers, while 265 and 910 nm SiO(2) particles tended to align along the fibers one by one, resembling necklaces. The content of water in the PVA/SiO(2)/H(2)O solution showed critical influence on the diameter of fibers and consequently determined the morphology. Too thin solutions gave birth to blackberry-like structure; too condensed solution was too hard to eject from the orifice of the needle; when the ingredient was elaborately tailored, we obtained necklace-like structures. We believe that these results can serve as references to generating other complex structures involving polymers and particles via electrospinning and that these structures will be potentially useful in photoelectric devices, drug release, and optical components.

No abstract

No abstract

Blood viscosity provides the rheological basis to elucidate shear stress underlying developmental cardiac mechanics and physiology. Zebrafish is a high throughput model for developmental biology, forward-genetics, and drug discovery. The micro-scale posed an experimental challenge to measure blood viscosity. To address this challenge, a microfluidic viscometer driven by surface tension was developed to reduce the sample volume required (3μL) for rapid (<2 min) and continuous viscosity measurement. By fitting the power-law fluid model to the travel distance of blood through the micro-channel as a function of time and channel configuration, the experimentally acquired blood viscosity was compared with a vacuum-driven capillary viscometer at high shear rates (>500 s−1), at which the power law exponent (n) of zebrafish blood was nearly 1 behaving as a Newtonian fluid. The measured values of whole blood from the micro-channel (4.17cP) and the vacuum method (4.22cP) at 500 s−1 were closely correlated at 27 °C. A calibration curve was established for viscosity as a function of hematocrits to predict a rise and fall in viscosity during embryonic development. Thus, our rapid capillary pressure-driven micro-channel revealed the Newtonian fluid behavior of zebrafish blood at high shear rates and the dynamic viscosity during development.

Abstract. The present study aimed to identify the level of programmed death-1 (PD-1) expression in infiltrating cluster of differentiation (CD)4 + and CD8 + T cells isolated from lung cancer tissues, and investigated whether the level of PD-1 expression may be directly regulated by lung cancer cells via prostaglandin E2 (PGE2)-associated signaling pathways in patients with lung cancer. A total of 75 patients with lung cancer were enrolled in the present study. The percentage of infiltrating CD4 + and CD8 + T cells was determined by flow cytometry. ELISA was performed to evaluate the concentration of PGE2 in lung cancer tissue homogenate. The correlation between PGE2 and PD-1 expression levels in CD8 + T cells was assessed by Spearman's rank correlation test. The expression levels of PD-1 and PGE2 receptors were determined by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The level of PD-1 expression in infiltrating CD8 + T cells was gradually increased as the stage of lung cancer increased. The level of PD-1 expression was also positively associated with the concentration of PGE2 in lung cancer tissues. Furthermore, the level of PD-1 expression was closely associated with the PGE2/EP2 and PGE2/EP4 signaling pathways. The activation of PGE2-associated EP2-and EP4-pathways may positively regulate the level of PD-1 in infiltrating CD8 + T cells, which results in immune tolerance in the lung cancer microenvironment.

Purpose: The dense stroma underlies the drug resistance of pancreatic ductal adenocarcinoma (PDA) and has motivated the development of stroma-directed drugs. Our objective is to test the concept that dynamic contrastenhanced (DCE) MRI using FDA-approved contrast media, an imaging method sensitive to the tumor microenvironment, can detect early responses to stroma-directed drug. Experimental Design: Imaging studies were performed in three mouse models exhibiting high desmoplastic reactions: the autochthonous PDA in genetically engineered mice (KPC), an orthotopic model in syngeneic mice, and a xenograft model of human PDA in athymic mice. An investigational drug, PEGPH20 (pegvorhyaluronidase alfa), which degrades hyaluronan (HA) in the stroma of PDA, was injected alone or in combination with gemcitabine. Results: At 24 hours after a single injection of PEGPH20, K trans , a DCE-MRI-derived marker that measures how fast a unit volume of contrast media is transferred from capillaries to interstitial space, increased 56% and 50% from baseline in the orthotopic and xenograft tumors, respectively, compared with a 4% and 6% decrease in vehicle groups (both P < 0.05). Similarly, after three combined treatments, K trans in KPC mice increased 54%, whereas it decreased 4% in controls treated with gemcitabine alone (P < 0.05). Consistently, after a single injection of PEGPH20, tumor HA content assessed by IHC was reduced substantially in all three models while drug delivery (measured by paclitaxel accumulation in tumor) was increased by 2.6-fold. Conclusions: These data demonstrated a DCE-MRI marker, K trans , can detect early responses to stroma-directed drug and reveal the sustained effect of combination treatment (PEGPH20þ gemcitabine).

PURPOSE. To evaluate the effect of diquafosol on corneal epithelium in a dry eye model using Transwell culture and a scopolamine-induced dry eye rat model. METHODS. Desiccation stress induced in an in vitro dry eye model using human corneal epithelial cells was used, and the cells were incubated with or without diquafosol media diluted at 1:100. Reactive oxygen species (ROS) generation was measured using 2 0 ,7 0dichlorofluorescein diacetate (DCFH-DA). Apoptosis was analyzed, and levels of phosphorylated Erk1/2, phosphorylated p90RSK, phosphorylated Akt, IjB-a, and NF-jB-p65 were determined. Levels of IL-1b, TNF-a, IL-6, IL-8, and GM-CSF were quantified. To investigate the in vivo effects of diquafosol, we induced dry eye in Wistar rats using scopolamine hydrobromide. The rats were divided into three groups: control, dry eye, and dry eye diquafosol; topical DIQUAS was applied four times daily for 28 days. We used immunohistochemistry to detect the levels of phosphorylated Erk1/2, phosphorylated p90RSK, and IL-1b, and used the TUNEL assay in corneal tissue. RESULTS. The distribution of highly fluorescent dichlorofluorescein and the proportion of annexin V-and PI-positive cells decreased in the diquafosol medium. Diquafosol increased the levels of phospho-Erk1/2, phospho-90RSK, phospho-Akt, and IjB-a, whereas it significantly decreased the levels of NF-jB-p65, IL-1b, and TNF-a. In vivo, apoptosis was enhanced in dry eye group. This response was markedly reduced and the level of phosphorylated p90RSK and phosphorylated ERK1/2 were upregulated and IL-1b was downregulated by DIQUAS. CONCLUSIONS. Diquafosol treatment reduced intracellular ROS levels, apoptosis, and inflammation, all of which were increased in the dry eye model through desiccation.