Maintaining the structural fidelity of DNA origami structures on substrates is a prerequisite for the successful fabrication of hybrid DNA origami/semiconductor-based biomedical sensor devices. Molybdenum disulfide (MoS2) is an ideal substrate for such future sensors due to its exceptional electrical, mechanical and structural properties. In this work, we performed the first investigations into the interaction of DNA origami with the MoS2 surface. In contrast to the structure-preserving interaction of DNA origami with mica, another atomically flat surface, it was observed that DNA origami structures rapidly lose their structural integrity upon interaction with MoS2. In a further series of studies, pyrene and 1-pyrenemethylamine, were evaluated as surface modifications which might mitigate this effect. While both species were found to form adsorption layers on MoS2 via physisorption, 1-pyrenemethylamine serves as a better protective agent and preserves the structures for significantly longer times. These findings will be beneficial for the fabrication of future DNA origami/MoS2 hybrid electronic structures.

Through an integrative literature review involving the CINAHL, Cochrane, Embase, LILACS, PsycINFO, PubMed databases, tools available in the literature for assessing pain in individuals with severe dementia were identified along with versions validated for use in Brazil. We found 1501 relevant articles which, after selection of abstracts and full reading, yielded a final sample of 33 articles. The analysis enabled the identification of 12 instruments: ABBEY PAIN SCALE; ADD; CNPI; CPAT; DOLOPLUS-2; MOBID and MOBID-2; MPS; NOPPAIN; PACSLAC; PADE; PAINAD and PAINE. Despite the wide variety of tools for assessing pain in individuals with severe dementia worldwide, it was observed that only four are available in Portuguese, of which two are culturally adapted for Brazilian Portuguese (NOPPAIN and PACSLAC) and two validated for Portuguese of Portugal (DOLOPLUS and PAINAD), pointing to the need for further validation of instruments for use in Brazil.

Prevalence studies of dementia and cognitive impairment in different cultures and environments are necessary.

The study aimed to investigate correlates of cognition among patients with schizophrenia.

A simple, precise, accurate stability-indicating gradient reversed-phase high-performance liquid chromatographic (RP-HPLC) method was developed for the quantitative determination of zotepine (ZTP) in bulk and pharmaceutical dosage forms in the presence of its degradation products (DPs). The method was developed using Phenomenex C18 column (250 mm×4.6 mm i.d., 5 µm) with a mobile phase containing a gradient mixture of solvents, A (0.05% trifluoroacetic acid (TFA), pH=3.0) and B (acetonitrile). The eluted compounds were monitored at 254 nm; the run time was within 20.0 min, in which ZTP and its DPs were well separated, with a resolution of >1.5. The stress testing of ZTP was carried out under acidic, alkaline, neutral hydrolysis, oxidative, photolytic and thermal stress conditions. ZTP was found to degrade significantly in acidic, photolytic, thermal and oxidative stress conditions and remain stable in basic and neutral conditions. The developed method was validated with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness as per ICH guidelines. This method was also suitable for the assay determination of ZTP in pharmaceutical dosage forms. The DPs were characterized by LC-MS/MS and their fragmentation pathways were proposed.

It is important to understand the adsorption mechanism of chemicals and active pharmaceutical ingredients (API) on sewage sludge since wastewater treatment plants are the last barrier before the release of these compounds to the environment. Adsorption models were developed considering mostly hydrophobic API-sludge interaction. They have poor predictive ability, especially with ionisable compounds. This work proposes a solid-phase extraction (SPE) approach to estimate rapidly the API-sludge interaction. Sludge-filled SPE cartridges could not be percolated with API spiked mobile phases so different powders were tested as SPE sludge supports. Polytetrafluoroethylene (PTFE) was selected and tested at different PTFE/sludge ratios under eight different adsorption conditions with three API ionisable compounds. The PTFE/sludge mixtures with 50% or less sludge could be used in SPE mode for API sorption studies with methanol/water liquid phases. The results gave insights into API-sludge interactions. It was found that π-π, hydrogen-bonding and charge-charge interactions were as important as hydrophobicity in the adsorption mechanism of charged APIs on sludge.

Oral estrogens are directly associated with changes in plasma levels of coagulation proteins. Thus, the detection of any variation in protein concentrations due to estrogen contraceptives, by a simultaneous analysis of both coagulation proteins and estrogens, would be a very informative tool. In the present study, the merit of photo-selected reaction monitoring (SRM), a new analytical tool, was evaluated towards estrogens detection in plasma. Then, SRM and photo-SRM detection modes were combined for the simultaneous analysis of estrogen molecules together with heparin co-factor and factor XIIa, two proteins involved in the coagulation cascade. This study shows that photo-SRM could open new multiplexed analytical routes.

A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed for simultaneous quantification of ezetimibe and simvastatin in rat plasma. The deuterium isotopes: ezetimibe d4 and simvastatin d6 were used as internal standards for ezetimibe and simvastatin, respectively. MS/MS detection involved a switch of electron spray ionization mode from negative to positive at retention time 3.01 min. Samples were extracted from plasma by liquid-liquid extraction using tertiary butyl methyl ether. Chromatographic separation was achieved with Agilent Eclipse XBD-C18 column using mobile phase that consisted of a mixture of ammonium acetate (pH4.5; 10 mM)-acetonitrile (25:75 v/v). The method was linear and validated over the concentration range of 0.2-40.0 ng/mL for simvastatin and 0.05-15.0 ng/mL for ezetimibe. The transitions selected were m/z 408.3→271.1 and m/z 412.0→275.10 for ezetimibe and ezetimibe d4, and m/z 419.30→285.20 and m/z 425.40→199.20 for simvastatin and simvastatin d6. Intra- and inter-batch precisions for ezetimibe were 1.6-14.8% and 2.1-13.4%; and for simvastatin 0.94-9.56% and 0.79-12%, respectively. The proposed method was sensitive, selective, precise and accurate for the quantification of ezetimibe and simvastatin simultaneously in rat plasma. The method was successfully applied to a pharmacokinetic study by oral co-administration of ezetimibe and simvastatin in SD rats.

A gas chromatography mass spectrometry (GC-MS) method has been developed and fully validated for the simultaneous determination of natural borneol (NB) and its metabolite, camphor, in rat plasma. Following a single liquid-liquid extraction, the analytes were separated using an HP-5MS capillary column (0.25 mm×30 m×0.25 μm) and analyzed by MS in the selected ion monitoring mode. Selected ion monitor (m/z) of borneol, camphor and internal standard was 95, 95 and 128, respectively. Linearity, accuracy, precision and extraction recovery of the analytes were all satisfactory. The method was successfully applied to pharmacokinetic studies of NB after oral administration to Wistar rats.

This systematic review examined 140 outcome evaluations of primary prevention strategies for sexual violence perpetration. The review had two goals: 1) to describe and assess the breadth, quality, and evolution of evaluation research in this area; and 2) to summarize the best available research evidence for sexual violence prevention practitioners by categorizing programs with regard to their evidence of effectiveness on sexual violence behavioral outcomes in a rigorous evaluation. The majority of sexual violence prevention strategies in the evaluation literature are brief, psycho-educational programs focused on increasing knowledge or changing attitudes, none of which have shown evidence of effectiveness on sexually violent behavior using a rigorous evaluation design. Based on evaluation studies included in the current review, only three primary prevention strategies have demonstrated significant effects on sexually violent behavior in a rigorous outcome evaluation: Safe Dates (Foshee et al., 2004); Shifting Boundaries (building-level intervention only, Taylor, Stein, Woods, Mumford, & Forum, 2011); and funding associated with the 1994 U.S. Violence Against Women Act (VAWA; Boba & Lilley, 2009). The dearth of effective prevention strategies available to date may reflect a lack of fit between the design of many of the existing programs and the principles of effective prevention identified by Nation et al. (2003).

Macroscopic quantum systems (MQS) are macroscopic systems driven by quantum rather than classical mechanics, a long studied area with minimal success till recently. Harnessing the benefits of quantum mechanics on a macroscopic level would revolutionize fields ranging from telecommunication to biology, the latter focused on here for reasons discussed. Contrary to misconceptions, there are no known physical laws that prevent the development of MQS. Instead, they are generally believed universally lost in complex systems from environmental entanglements (decoherence). But we argue success is achievable MQS with decoherence compensation developed, naturally or artificially, from top-down rather current reductionist approaches. This paper advances the MQS field by a complex systems approach to decoherence. First, why complex system decoherence approaches (top-down) are needed is discussed. Specifically, complex adaptive systems (CAS) are not amenable to reductionist models (and their master equations) because of emergent behaviour, approximation failures, not accounting for quantum compensatory mechanisms, ignoring path integrals, and the subentity problem. In addition, since MQS must exist within the context of the classical world, where rapid decoherence and prolonged coherence are both needed. Nature has already demonstrated this for quantum subsystems such as photosynthesis and magnetoreception. Second, we perform a preliminary study that illustrates a top-down approach to potential MQS. In summary, reductionist arguments against MQS are not justifiable. It is more likely they are not easily detectable in large intact classical systems or have been destroyed by reductionist experimental set-ups. This complex systems decoherence approach, using top down investigations, is critical to paradigm shifts in MQS research both in biological and non-biological systems.

Metabolically healthy obese phenotype is defined by high insulin sensitivity and lack of metabolic syndrome, parameters regulated by omental adipose tissue inflammation, ectopic fat deposition and adipose tissue dysfunction. Our study aimed to identify novel metabolic and inflammatory markers in serum and omental adipose tissue which characterize the "unhealthy" obese patients and distinguish them from obese patients with better metabolic profile.

Silver nanoparticles (Ag NPs) are increasingly used in biomedical applications because of their large antimicrobial spectrum. Data in the literature on the ability of Ag NPs to perform their desired function without eliciting undesirable effects on blood elements are very limited and contradictory. We studied the impact of Ag NPs on erythrocyte integrity, platelet function and blood coagulation. Erythrocyte integrity was assessed by spectrophotometric measurement of haemoglobin release. Platelet adhesion and aggregation was determined by light transmission aggregometry and scanning electron microscopy. The calibrated thrombin generation test was used to study the impact on coagulation cascade. We demonstrated that Ag NPs induced haemolysis. They also increase platelet adhesion without having any impact on platelet aggregation. Finally, they also had procoagulant potential. Bringing all data from these tests together, the no observed effect concentration is 5 μg/mL.

Aiming to reduce the potential in vivo hepato-and nephrotoxicity of Ag/Au bimetallic nanoparticles (NPs) stabilized by sodium dodecyl sulphate (SDS), an approach involving a simultaneous reduction of silver nitrate and tetrachlorauratic acid using tryptophan (Trp) as a reducing/stabilizing agent was applied during NP synthesis. The obtained Ag/Au/Trp NPs (5-15 nm sized) were able to form stable aggregates with an average size of 370-450 nm and were potentially less toxic than Ag/Au/SDS in relation to a mouse model system based on clinical biochemical parameters and oxidative damage product estimation. Ag/Au/Trp NPs were shown to exhibit anticancer activity in relation to a Lewis lung carcinoma model. The data generated from the present study support the fact that the use of tryptophan in NP synthesis is effective in attenuating the potential hepatotoxicity and nephrotoxicity of NPs during their in vivo application.

Iron oxide nanoparticles have received sustained interest for biomedical applications as synthetic approaches are continually developed for control of nanoparticle properties. However, many approaches focus solely on the material, rather than the complete optimization of synthesis and functionalization together to enhance translation into biological systems. Presented herein is a modified seed growth method designed for obtaining optimal nanoparticle properties and ease of surface functionalization for long term stability. With a one or two addition process, iron oxide nanoparticles were produced in crystallite sizes ranging from 5-15 nm using only benzyl alcohol and an iron precursor. In the functionalization process, concentration variations were required for stabilizing different nanoparticle sizes. Radio frequency induction heating experiments of various crystallite and hydrodynamic sizes verified that the heating efficiency greatly increased while approaching the 15 nm crystallite, and suggested an important role of the overall particle size on heating efficiency. Initial in vitro experiments with the functionalized nanoparticles showed success in providing hyperthermia-induced tumour cell killing without an increase in the temperature of the cell suspension medium. This demonstrates the potential for nanoparticle-based hyperthermia to provide a therapeutic effect while limiting normal tissue damage.

Peripheral nerve regeneration can be enhanced by chemical and mechanical cues for neurite growth. Aligned and randomly oriented electrospun nanofibers of poly(ε-caprolactone) (PCL) or a blend of PCL and elastin were fabricated to test their potential to provide contact guidance to embryonic chick dorsal root ganglia for peripheral nerve regeneration. Scanning electron microscopy was used to analyze the fiber diameter. Fiber diameter was found to be significantly smaller when elastin was incorporated into the scaffold (934 ± 58 nm for PCL and 519 ± 36 nm for PCL:elastin). After 24 h in culture, there was preferential cell attachment and neurite extension along the fibers of the elastin-containing scaffolds (average neurite extension 173.4 ± 20.7 μm), indicating that the presence of elastin promotes neurite outgrowth on electrospun scaffolds.

Aortic valve disease is a burgeoning public health problem associated with significant mortality. Loss of function mutations in NOTCH1 cause bicuspid aortic valve (BAV) and calcific aortic valve disease. Because calcific nodules manifest on the fibrosa side of the cusp in low fluidic oscillatory shear stress (OSS), elucidating pathogenesis requires approaches that consider both molecular and mechanical factors. Therefore, we examined the relationship between NOTCH loss of function (LOF) and biomechanical indices in healthy and diseased human aortic valve interstitial cells (AVICs). An orbital shaker system was used to apply cyclic OSS, which mimics the cardiac cycle and hemodynamics experienced by AVICs in vivo. NOTCH LOF blocked OSS-induced cell alignment in human umbilical vein endothelial cells (HUVECs), whereas AVICs did not align when subjected to OSS under any conditions. In healthy AVICs, OSS resulted in decreased elastin (ELN) and α-SMA (ACTA2). NOTCH LOF was associated with similar changes, but in diseased AVICs, NOTCH LOF combined with OSS was associated with increased α-SMA expression. Interestingly, AVICs showed relatively higher expression of NOTCH2 compared to NOTCH1. Biomechanical interactions between endothelial and interstitial cells involve complex NOTCH signaling that contributes to matrix homeostasis in health and disorganization in disease.

There have been no previous reports that apolipoprotein (apo) A-I mimetic peptide improves survival rate after myocardial infarction (MI).

Aortic elastic properties are determinants of left ventricular function by means of ventriculo-arterial coupling and indicators of cardiovascular risk. Aortic valve stenosis surgical replacement temporary reduces aortic function damaging vasa vasorum, while transcatheter aortic valve implantation (TAVI) does not influence it in the short term. We studied aortic distensibility, stiffness, M-mode strain and tissue strain after 6 and 12 months from TAVI.

Timothy Syndrome (TS) is caused by very rare exonic mutations of the CACNA1C gene that produce delayed inactivation of Cav1.2 voltage-gated calcium channels during cellular action potentials, with greatly increased influx of calcium into the activated cells. The major clinical feature of this syndrome is a long QT interval that results in cardiac arrhythmias. However, TS also includes cognitive impairment, autism and major developmental delays in many of the patients. We observed the appearance of bipolar disorder (BD) in a patient with a previously reported case of TS, who is one of the very few patients to survive childhood. This is most interesting because the common single-nucleotide polymorphism (SNP) most highly associated with BD is rs1006737, which we show here is a cis-expression quantitative trait locus for CACNA1C in human cerebellum, and the risk allele (A) is associated with decreased expression. To combine the CACNA1C perturbations in the presence of BD in this patient and in patients with the common CACNA1C SNP risk allele, we would propose that either increase or decrease in calcium influx in excitable cells can be associated with BD. In treatment of BD with calcium channel blocking drugs, we would predict better response in patients without the risk allele, because they have increased CACNA1C expression.