Assembly of Nucleic Acid-Based Nanoparticles by Gas-Liquid Segmented Flow Microfluidics

The development of novel and efficient mixing methods is important for optimizing the efficiency of many biological and chemical processes. Tuning the physical and performance properties of nucleic acid-based nanoparticles is one such example known to be strongly affected by mixing efficiency. The characteristics of DNA nanoparticles (such as size, polydispersity, ζ-potential, and gel shift) are important to ensure their therapeutic potency, and new methods to optimize these characteristics are of significant importance to achieve the highest efficacy. In the present study, a simple segmented flow microfluidics system has been developed to augment mixing of pDNA/bPEI nanoparticles. This DNA and cationic polymer pair (plasmid DNA and branched poly(ethylenimine)) was chosen due to bPEI’s well-known ability to spontaneously condense plasmid DNA. The system fabricated in this project utilizes silastic tubing (1.6 mm ID) as the reaction channels, nitrogen gas as the continuous phase, and the aqueous components as the dispersed phase. Drop flow has been characterized using UV/Vis spectrophotometry, and the relationships between continuous and dispersed phase flow and drop rate and size have been documented. Drops have been successfully formed using two different types of drop generation (cross-flow and co-flow). Physical properties of the nanoparticles were analyzed using dynamic light scattering (DLS) measurements and agarose gel electrophoresis. Biological performance of the nanoparticles was analyzed using DNase I protection, unincorporated bPEI quantitation, mammalian cell transfection, and cell viability assays. The nitrogen-to-phosphate (N/P) ratio (5 and 20), flow rate, and flow-path geometry (linear, serpentine, and coiled) have been explored for their effect on mixing and particle uniformity. The results show a significant decrease in nanoparticle size compared with bulk-mixed methods at an N/P ratio of 5 and an observable difference in nanoparticle properties and performance when adjusting the nature of mixing using the developed microfluidics system

Verspreiding inlaatwater in beeld met nieuwe tracer

Inlaatwater heeft in de polder Quarles van Ufford zelfs in een droge periode geen invloed op de waterkwaliteit van kleine landbouwsloten. Dat blijkt uit metingen van de concentratie gadolinium, die zijn uitgevoerd voor het project Monitoring Stroomgebieden. Hiermee komt voor dit gebied een einde aan de twijfel over de invloed van inlaatwater op de oppervlaktewaterkwaliteit en is er meer duidelijkheid over de belasting vanuit de landbouw

Reliability and validity of the Dutch dimensional assessment of personality pathology-short form(DAPP-SF), a shortened version of the DAPP-Basic questionnaire

The Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ) appears to be a good choice for the assessment of personality pathology. However, due to its length, administration of the instrument is rather time-consuming, hindering standard inclusion of the DABB-BQ in a battery of assessment instruments at intake. We developed the 136-item DAPP-SF (Short Form), and investigated its psychometric characteristics in various samples, i.e., a community-based sample (n = 487), patients with mood-, anxiety-, and somatoform disorders (n = 1,329), and patients with personality disorders (n = 1,393). Results revealed high internal consistency for almost all dimensions. The factor structure appeared almost identical as compared to the factor structure of the original DAPP-BQ, and was shown to be invariant across the various patient and community samples. Indices for convergent, discriminant and criterion related validity were satisfactory. It is concluded that the good psychometric characteristics of the original DAPP-BQ were preserved in the shortened version of the instrument

The association between attention-deficit/hyperactivity (ADHD) symptoms and self-employment

Attention-deficit/hyperactivity (ADHD) symptoms have been associated with the decision to become self-employed. Although these symptoms are generally regarded as disadvantageous, there may also be a bright side. To our knowledge, however, there has been no systematic, epidemiological evidence to support this claim. This paper examines the association between ADHD symptoms and self-employment in a population-based sample from the STAGE cohort of the Swedish Twin Registry (N = 7208). For replication, we used a sample of Dutch students who participated in the Global University Entrepreneurial Spirit Students’ Survey (N = 13,112). In the Swedish sample, we found a positive association with self-employment for both general ADHD symptoms [odds ratio (OR) 1.13; 95 % confidence intervals (CI) 1.04–1.23] and hyperactivity symptoms [OR 1.19; 95 % CI 1.08–1.32], whereas no association was found for attention-deficit symptoms [OR 0.99; 95 % CI 0.89–1.10]. The positive association between hyperactivity and self-employment was replicated in the Dutch student sample [OR 1.09; 95 % CI 1.03–1.15]. Our results show that certain aspects of ADHD, in particular hyperactivity, can have a bright side, as they are positively associated with self-employment

Stereotactic cyst aspiration directly followed by Gamma Knife radiosurgery for large cystic brain metastases

Background: Gamma Knife radiosurgery (GKRS) has been proven to be a successful primary treatment for metastatic brain tumors (BM). BM can come in cystic lesions and are often too large for GKRS. An alternative approach to treat cystic BM is stereotactic cyst aspiration (SCA) for volume reduction, making it suitable for GKRS afterwards. Objective: Our objective is evaluation of volumetric reduction after SCA, tumor control, and complications after SCA directly followed by GKRS. Methods: We performed a retrospective analysis of all patients who underwent SCA directly followed by GKRS at the Gamma Knife Center of the Elisabeth-Tweesteden Hospital in Tilburg between 2002 and 2015. In total, 54 patients had undergone this combined approach. Two patients were excluded because of prior intracranial treatment. The other 52 patients were included for analysis. Results: SCA resulted in a mean volumetric reduction of 56.5% (range 5.50–87.00%). In 83.6% of the tumors (46 tumors), SCA led to sufficient volumetric reduction making GKRS possible. The overall local tumor control (OLTC) of the aspirated lesions post-GKRS was 60.9% (28 out of 46 tumors). Median progression-free survival (PFS) and overall survival (OS) for all patients were 3 (range 5 days–14 months) and 12 months (range 5 days–58 months), respectively. Leptomeningeal disease was reported in 5 (9.6%) cases. Conclusion: SCA directly followed by GKRS is an effective and time-efficient treatment for large cystic BM in selected patients in which surgery is contraindicated and those with deeply located lesions.</p

Tracing the spatial propagation of river inlet water into an agricultural polder area using anthropogenic gadolinium

Diverting river water into agricultural areas or nature reserves is a frequently applied management strategy to prevent fresh water shortage. However, the river water might have negative consequences for chemical and ecological water quality in the receiving water bodies. This study aimed to obtain a spatial image of the diverted river water propagation into a hydrologically complex polder area, the polder Quarles van Ufford in The Netherlands. We used anthropogenic gadolinium (Gd-anomaly) as a tracer for river water that was diverted into the polder. A clear reduction in the river water contribution was found between very dry conditions on 5 August 2010 and very wet conditions on 22 October. Despite the large river water impact on 5 August, the diverted river water did not propagate up into the small agricultural headwater ditches. Gadolinium proved to be an effective tracer for diverted river water in a polder system. We applied our results to upgrade the interpretation of water quality monitoring data and to validate an integrated nutrient transport mode