pH-responsive drug delivery system based on hollow silicon dioxide micropillars coated with polyelectrolyte multilayers

We report on the fabrication of polyelectrolyte multilayer-coated hollow silicon dioxide micropillars as pH-responsive drug delivery systems. Silicon dioxide micropillars are based on macroporous silicon formed by electrochemical etching. Due to their hollow core capable of being loaded with chemically active agents, silicon dioxide micropillars provide additional function such as drug delivery system. The polyelectrolyte multilayer was assembled by the layer-by-layer technique based on the alternative deposition of cationic and anionic polyelectrolytes. The polyelectrolyte pair poly(allylamine hydrochloride) and sodium poly(styrene sulfonate) exhibited pH-responsive properties for the loading and release of a positively charged drug doxorubicin. The drug release rate was observed to be higher at pH 5.2 compared to that at pH 7.4. Furthermore, we assessed the effect of the number of polyelectrolyte bilayers on the drug release loading and release rate. Thus, this hybrid composite could be potentially applicable as a pH-controlled system for localized drug release.     

Identification of miR-20a-5p as Robust Normalizer for Urine microRNA Studies in Renal Cell Carcinoma and a Profile of Dysregulated microRNAs

Renal cell carcinoma (RCC) is the third most frequent urinary malignancy and one of the most lethal. Current diagnostic and follow-up techniques are harmful and unspecific in low-grade tumors. Novel minimally invasive markers such as urine microRNAs (miRNAs) are under study. However, discrepancies arise among studies in part due to lack of consent regarding normalization. We aimed to identify the best miRNA normalizer for RCC studies performed in urine samples together with a miRNA profile with diagnostic value and another for follow-up. We evaluated the performance of 120 candidate miRNAs in the urine of 16 RCC patients and 16 healthy controls by RT-qPCR followed by a stability analysis with RefFinder. In this screening stage, miR-20a-5p arose as the most stably expressed miRNA in RCC and controls, with a good expression level. Its stability was validated in an independent cohort of 51 RCC patients and 32 controls. Using miR-20a-5p as normalizer, we adjusted and validated a diagnostic model for RCC with three miRNAs (miR-200a-3p, miR-34a-5p and miR-365a-3p) (AUC = 0.65; Confidence Interval 95% [0.51, 0.79], p = 0.043). let-7d-5p and miR-205-5p were also upregulated in patients compared to controls. Comparing RCC samples before surgery and fourteen weeks after, we identified let-7d-5p, miR-152-3p, miR-30c-5p, miR-362-3p and miR-30e-3p as potential follow-up profile for RCC. We identified validated targets of most miRNAs in the renal cell carcinoma pathway. This is the first study that identifies a robust normalizer for urine RCC miRNA studies, miR-20a-5p, which may allow the comparison of future studies among laboratories. Once confirmed in a larger independent cohort, the miRNAs profiles identified may improve the non-invasive diagnosis and follow-up of RCC.     

Role of Receptor Protein Tyrosine Phosphatases (RPTPs) in Insulin Signaling and Secretion

Changes in lifestyle in developed countries have triggered the prevalence of obesity and type 2 diabetes mellitus (T2DM) in the latest years. Consequently, these metabolic diseases associated to insulin resistance, and the morbidity associated with them, accounts for enormous costs for the health systems. The best way to face this problem is to identify potential therapeutic targets and/or early biomarkers to help in the treatment and in the early detection. In the insulin receptor signaling cascade, the activities of protein tyrosine kinases and phosphatases are coordinated, thus, protein tyrosine kinases amplify the insulin signaling response, whereas phosphatases are required for the regulation of the rate and duration of that response. The focus of this review is to summarize the impact of transmembrane receptor protein tyrosine phosphatase (RPTPs) in the insulin signaling cascade and secretion, and their implication in metabolic diseases such as obesity and T2DM.     

Cell Death Mechanisms Induced by CLytA-DAAO Chimeric Enzyme in Human Tumor Cell Lines

The combination of the choline binding domain of the amidase N-acetylmuramoyl-L-alanine (CLytA)-D-amino acid oxidase (DAAO) (CLytA-DAAO) and D-Alanine induces cell death in several pancreatic and colorectal carcinoma and glioblastoma cell lines. In glioblastoma cell lines, CLytA-DAAO-induced cell death was inhibited by a pan-caspase inhibitor, suggesting a classical apoptotic cell death. Meanwhile, the cell death induced in pancreatic and colon carcinoma cell lines is some type of programmed necrosis. In this article, we studied the mechanisms that trigger CLytA-DAAO-induced cell death in pancreatic and colorectal carcinoma and glioblastoma cell lines and we acquire a further insight into the necrotic cell death induced in pancreatic and colorectal carcinoma cell lines. We have analyzed the intracellular calcium mobilization, mitochondrial membrane potential, PARP-1 participation and AIF translocation. Although the mitochondrial membrane depolarization plays a crucial role, our results suggest that CLytA-DAAO-induced cell death is context dependent. We have previously detected pancreatic and colorectal carcinoma cell lines (Hs766T and HT-29, respectively) that were resistant to CLytA-DAAO-induced cell death. In this study, we have examined the putative mechanism underlying the resistance in these cell lines, evaluating both detoxification mechanisms and the inflammatory and survival responses. Overall, our results provide a better understanding on the cell death mechanism induced by CLytA-DAAO, a promising therapy against cancer.     

Mental health professionals' adaptive responses to racial microaggressions: An exploratory study.

This study examines adaptive responses that mental health professionals of color use to cope with racial microaggressions in their professional lives. Twenty-four mental health professionals from diverse ethnic backgrounds in the United States and Canada participated in focus groups discussing their experiences with racial microagressions and how they cope with them. Results of the analysis indicated that 8 primary coping themes illustrated strategies used by the participants. These include: identifying key issues in responding to racial microaggressions, self-care, spirituality, confrontation, support, documentation, mentoring, and collective organizing. Suggestions for mentoring professionals of color are offered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preserved monitoring and control processes in temporal lobe epilepsy.

Objective: The aim of this study was to assess an aspect of metamemory never examined before in patients with temporal lobe epilepsy (TLE): the ability to upgrade the accuracy of one's memory predictions after study. Method: Four lists of different levels of difficulty and relatedness were presented to 15 TLE patients and 15 control participants, who were asked to predict their subsequent recall both before and after studying each list. Results: The results showed clear impairment in recall in TLE patients. However, both TLE patients and controls showed an improvement in accuracy in their poststudy predictions compared with their prestudy predictions, showing that both groups were able to upgrade their metamemory predictions. Unexpectedly, prediction accuracy was overall higher in TLE patients than in controls. Moreover, study time was allocated in both groups taking into account the characteristics of the list. Conclusion: These results confirm and extend findings of Howard et al. (2010) of intact metamemory in TLE patients, and provide further support to the dissociation between memory and metamemory in this clinical population. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Toward the DSM-V: The Withdrawal-Gate Model versus the DSM-IV in the diagnosis of alcohol abuse and dependence.

The Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) classifies as dependent many cases of mild alcohol problems. DSM-IV diagnoses have modest relationships with predictive and some concurrent validators and often improperly sequence the onset of abuse vs dependence, perhaps due to insufficient emphasis on physiological features. Testing reliability, syndrome prevalence, syndrome sequencing, and concurrent and predictive validity, this study contrasted the DSM-IV with the Withdrawal-Gate Model (WGM), in which alcohol withdrawal is necessary and sufficient for the dependence diagnosis. Clinical samples of adults (baseline n?=?318) and adolescents (baselinen?=?214) meeting abuse or dependence were assessed for DSM-IV alcohol symptoms and external measures of problem severity and reinterviewed at 6 (adults) and 12 mo (adults and adolescents). Among DSM-IV dependent cases, the WGM shifted 32% of adults and 80% of adolescents to the abuse category, making both categories more symptomatically severe, but had a negligible effect on prevalence of total alcohol diagnoses. The WGM was more reliable than the DSM-IV and temporally sequenced abuse before dependence in a greater number of cases. The WGM was superior to the DSM-IV in concurrent and predictive validity on most measures. Future diagnostic systems may be more reliable and valid if they require evidence of withdrawal for substance dependence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reinforcing effect of a kaolin surface-treated with diallyldimethylammonium in SBR vulcanizates

This paper examines the physico-chemical characteristics of a natural kaolin, its textural properties, pores, morphology, chemical surface, as well as chemical surface modification through treatment with quaternary ammonium salts in SBR mixes. Diallyldimethylammonium chloride was used as a quaternary alkali for surface modification of the kaolin, thus allowing the unsaturated allyl portion to covulcanize with the rubber. This achieved strong rubber-filler bonds with consequential enhancement of the technological properties of the vulcanizate.     

Response surface methodology multivariate analysis of properties of high-pressure-induced fish mince gel

 Factorial analyses were performed to determine the effect of high-pressure treatment on the characteristics of blue whiting mince of good gel-forming quality. Pressure, time and temperature independently influenced gel characteristics. Temperature had the greatest influence of the three. High-pressure gels were generally distinguished by lower adhesiveness, higher water-holding capacity and less yellowness than heat-induced gels. The combination of pressure and temperature produced more elastic gels, whereas gels made under high pressure at chilling temperatures were much harder, more deformable and more cohesive. There was no correlation between elasticity and deformability.