Rational Design of Molecularly Imprinted Polymers for Curcuminoids Binding: Computational and Experimental Approaches for the Selection of Functional Monomers.

Molecularly imprinted polymers (MIPs) have emerged as bespoke materials with versatile molecular applications. In this study, we propose a proof of concept for a methodology employing molecular dynamics (MD) simulations to guide the selection of functional monomers for curcuminoid binding in MIPs. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin are phenolic compounds widely employed as spices, pigments, additives, and therapeutic agents, representing the three main curcuminoids of interest. Through MD simulations, we investigated prepolymerization mixtures composed of various functional monomers, including acrylamide (ACA), acrylic acid (AA), methacrylic acid (MAA), and N-vinylpyrrolidone (NVP), with ethylene glycol dimethacrylate (EGDMA) as the cross-linker and acetonitrile as the solvent. Curcumin was selected as the template molecule due to its structural similarity to the other curcuminoids. Notably, the prepolymerization mixture containing NVP as the functional monomer demonstrated superior molecular recognition capabilities toward curcumin. This observation was supported by higher functional monomer molecules surrounding the template, a lower total nonbonded energy between the template and monomer, and a greater number of hydrogen bonds in the aggregate. These findings suggest a stronger affinity between the functional monomer NVP and the template. We synthesized, characterized, and conducted binding tests on the MIPs to validate the MD simulation results. The experimental binding tests confirmed that the MIP-NVP exhibited higher binding capacity. Consequently, based on MD simulations, our computational methodology effectively guided the selection of the functional monomer, leading to MIPs with binding capacity for curcuminoids. The outcomes of this study provide a valuable reference for the rational design of MIPs through MD simulations, facilitating the selection of components for MIPs. This computational approach holds the potential for extension to other templates, establishing a robust methodology for the rational design of MIPs.

Ionic-Liquid Gating in Two-Dimensional TMDs: The Operation Principles and Spectroscopic Capabilities.

Ionic-liquid gating (ILG) is able to enhance carrier densities well above the achievable values in traditional field-effect transistors (FETs), revealing it to be a promising technique for exploring the electronic phases of materials in extreme doping regimes. Due to their chemical stability, transition metal dichalcogenides (TMDs) are ideal candidates to produce ionic-liquid-gated FETs. Furthermore, as recently discovered, ILG can be used to obtain the band gap of two-dimensional semiconductors directly from the simple transfer characteristics. In this work, we present an overview of the operation principles of ionic liquid gating in TMD-based transistors, establishing the importance of the reference voltage to obtain hysteresis-free transfer characteristics, and hence, precisely determine the band gap. We produced ILG-based bilayer WSe2 FETs and demonstrated their ambipolar behavior. We estimated the band gap directly from the transfer characteristics, demonstrating the potential of ILG as a spectroscopy technique.

Regulation of Adaptive Tumor Immunity by Non-Coding RNAs.

Cancer immunology research has mainly focused on the role of protein-coding genes in regulating immune responses to tumors. However, despite more than 70% of the human genome is transcribed, less than 2% encodes proteins. Many non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have been identified as critical regulators of immune cell development and function, suggesting that they might play important roles in orchestrating immune responses against tumors. In this review, we summarize the scientific advances on the role of ncRNAs in regulating adaptive tumor immunity, and discuss their potential therapeutic value in the context of cancer immunotherapy.

Skin Cancer and Dermoscopy Training for Primary Care Physicians: A Pilot Study.

INTRODUCTION: The primary objective of this study was to determine the diagnostic accuracy and effect of an educational training on skin cancer course and dermoscopy use among primary care physicians in rural areas of Colombia. The secondary objective was to assess the diagnostic accuracy of skin cancer diagnosis and detection rate after 3 months of the initial training. METHODS: Twenty-one primary care physicians from 6 rural areas of Colombia participated in a 2-day skin cancer and dermoscopy training, followed by a day-long hands-on session on dermoscopy at a free skin cancer screening event. Pre- and post-tests were performed using clinical and dermoscopic images to evaluate the user's ability to diagnose and differentiate benign and malignant neoplasms. In addition, participants' levels of confidence were assessed. RESULTS: After the training, the sensitivity and specificity of characterizing skin lesions as benign or malignant or providing a specific diagnosis (ie, angioma, seborrheic keratosis, basal cell carcinoma, etc.) increased by 23.6% (62.9% to 86.5%; P < 0.0001) and 21% (54.7% to 75.7%; P < 0.0017), respectively. In addition, levels of confidence when diagnosing skin lesions changed from extremely low or low, to high or extremely high by 20.7% (38.3% to 59%) using dermoscopic images (odds ratio (OR) 3.22; 95% confidence interval (CI): 2.67-3.86; P < 0.0001). The secondary objective was not achieved due to loss of follow-up of the majority of participants. CONCLUSION: Providers serving populations with limited healthcare access may benefit from education in diagnosing and differentiating skin cancer with the use of dermoscopy, which may ultimately improve patient care and reduce healthcare costs.

In operando evidence of deoxygenation in ionic liquid gating of YBa2Cu3O7-X.

Field-effect experiments on cuprates using ionic liquids have enabled the exploration of their rich phase diagrams [Leng X, et al. (2011) Phys Rev Lett 107(2):027001]. Conventional understanding of the electrostatic doping is in terms of modifications of the charge density to screen the electric field generated at the double layer. However, it has been recently reported that the suppression of the metal to insulator transition induced in VO2 by ionic liquid gating is due to oxygen vacancy formation rather than to electrostatic doping [Jeong J, et al. (2013) Science 339(6126):1402-1405]. These results underscore the debate on the true nature, electrostatic vs. electrochemical, of the doping of cuprates with ionic liquids. Here, we address the doping mechanism of the high-temperature superconductor YBa2Cu3O7-X (YBCO) by simultaneous ionic liquid gating and X-ray absorption experiments. Pronounced spectral changes are observed at the Cu K-edge concomitant with the superconductor-to-insulator transition, evidencing modification of the Cu coordination resulting from the deoxygenation of the CuO chains, as confirmed by first-principles density functional theory (DFT) simulations. Beyond providing evidence of the importance of chemical doping in electric double-layer (EDL) gating experiments with superconducting cuprates, our work shows that interfacing correlated oxides with ionic liquids enables a delicate control of oxygen content, paving the way to novel electrochemical concepts in future oxide electronics.

Chronic dietary chlorpyrifos causes long-term spatial memory impairment and thigmotaxic behavior.

Little is known about the long-term effects of chronic exposure to low-level organophosphate (OP) pesticides, and the role of neurotransmitter systems, other than the cholinergic system, in mediating OP neurotoxicity. In this study, rats were administered 5mg/kg/day of chlorpyrifos (CPF) for 6 months commencing at 3-months-of-age. The animals were examined 7 months later (at 16-months-of-age) for spatial learning and memory in the Morris water maze (MWM) and locomotor activity. In addition, we assessed the chronic effects of CPF on glutamatergic and gamma-aminobutyric acid (GABAergic) function using pharmacological challenges with dizocilpine (MK801) and diazepam. Impaired performance related to altered search patterns, including thigmotaxis and long-term spatial memory was noted in the MWM in animals exposed to CPF, pointing to dietary CPF-induced behavioral disturbances, such as anxiety. Twenty-four hours after the 31st session of repeated acquisition task, 0.1mg/kg MK801, an N-methyl-d-aspartate (NMDA) antagonist was intraperitoneally (i.p.) injected for 4 consecutive days. Decreased latencies in the MWM in the control group were noted after two sessions with MK801 treatment. Once the MWM assessment was completed, animals were administered 0.1 or 0.2mg/kg of MK801 and 1 or 3mg/kg of diazepam i.p., and tested for locomotor activity. Both groups, the CPF dietary and control, displayed analogous performance in motor activity. In conclusion, our data point to a connection between the long-term spatial memory, thigmotaxic response and CPF long after the exposure ended.

Cognitive and histological disturbances after chlorpyrifos exposure and chronic Aß(1-42) infusions in Wistar rats.

Exposure to pesticides has been linked to an increased vulnerability to neurodegenerative diseases. In order to study whether the exposure to the organophosphate chlorpyrifos renders the brain prone to amyloid-beta peptide deposition and accelerates its neuropathological and behavioural effects, Wistar rats were injected a single subcutaneous dose of chlorpyrifos (250 mg/kg) and subsequently infused with Aß(1-42) peptide (i.c.v.) for 15 days. No effects of either treatment were noted in the classic water maze test. The animals infused with Aß peptide showed worse performance when the platform was both hidden and moved from trial to trial. Both groups showed worse performance when the platform was visible and moved from trial to trial. No amyloid deposition was observed in hippocampus or cerebral cortex after the infusion period, although microtubule-associated protein 1A (MAP1A) immunoreactivity was significantly reduced in hippocampus and prefrontal cortex, whereas chlorpyrifos exposure produced a significant reduction of microtubule-associated protein 2 (MAP2) in the prefrontal cortex. Therefore, behavioural deficits could be related to a loss of dendrite and spine processes in these brain regions.

El acceso a artículos de publicaciones especializadas en enfermería: bases de datos para su identificación y localización / Access to articles in publications specialized in nursing: databases for their identification and retrieval

El objetivo de este estudio es describir las principales bases de datos bibliográficas especializadas en enfermería y medicina que sirven como herramienta para la identificación y localización de artículos publicados en revistas científicas de enfermería. Finalmente, se percibe un aumento del libre acceso a las bases de datos fruto de un proceso de globalización y cooperación entre los países latinoamericanos, y del acceso gratuito a éstas por parte de las instituciones productoras públicas y de las creadas sin ánimos de lucro. Además, se observa un crecimiento de bases de datos especializadas en enfermería y una mayor incorporación de artículos en las bases de datos de cobertura internacional

The objective of this study is to describe the main bibliographical databases specialized in nursing and medicine serving as tool for the identification and retrieval of articles published in scientific journal of nursing. An increase of free database access as a consequence of both the process of globalization and the cooperation among Latin American countries is perceived. Also, increasingly more public institutions as well as non-profit organizations are making their databases freely available to the public. Furthermore, a growth of databases specialized in nursing is observed as well as the inclusion of a greater proportion of nursing-related articles in databases of international scope

Glial overexpression of heme oxygenase-1: a histochemical marker for early stages of striatal damage.

The level of heme oxygenase-1 (HO-1) in the normal striatum is below the limit of immunodetection. However, HO-1 is overexpressed in both neural and non-neural cells in response to a wide range of lesions. We induced different types of lesions affecting the striatal cells or the main striatal afferent systems in rats to investigate if overexpression of HO-1 could be a useful histochemical marker of striatal damage. Thirty-six hours after intrastriatal or intraventricular injection of excitotoxins that affect striatal neurons (ibotenic acid) or of neurotoxins that affect striatal dopaminergic (6-hydroxydopamine) or serotonergic (5,7-dihydroxytriptamine) afferent terminals, or after surgical lesioning of cortico-striatal projections, there was intense induction of striatal HO-1 immunoreactivity (HO-1-ir). Double immunolabeling revealed that the HO-1-ir was located in glial cells. After intrastriatal injection of ibotenic acid, a central zone of neuronal degeneration contained numerous round and pseudopodic HO-1-ir cells, and was surrounded by a ring of HO-1-ir cells, most of which were immunoreactive for astroglial markers. Intraventricular injection of neurotoxins induced astroglial HO-1-ir cells which were more evenly distributed throughout the lesioned or denervated areas. HO-1-ir microglial cells were also observed in areas subjected to mechanical damage. The HO-1-ir was markedly lower or absent 1 week after lesion, and even more so 3 weeks after, although some HO-1-ir cells were still observed after intrastriatal injection of ibotenic acid or surgical corticostriatal deafferentation. The results indicate that determination of glial HO-1-ir is a useful histochemical marker for early stages of striatal damage.

Systemic administration of N-acetylcysteine protects dopaminergic neurons against 6-hydroxydopamine-induced degeneration.

The results of several in vitro studies have shown that cysteine prodrugs, particularly N-acetylcysteine, are effective antioxidants that increase the survival of dopaminergic neurons. N-acetylcysteine can be systemically administered to deliver cysteine to the brain and is of potential use for providing neuroprotection in the treatment of Parkinson's disease. However, it has also been reported that an excess of cysteine may induce neurotoxicity. In the present study, we injected adult rats intrastriatally with 2.5 microl of 6-hydroxydopamine (7.5 microg) and N-acetylcysteine (240 mM) or cysteine (240 mM) or intraventricularly with 6-hydroxydopamine (200 microg) and subcutaneously with N-acetylcysteine (10 and 100 mg/kg). We studied the effects of these compounds on both the nigrostriatal dopaminergic terminals and the surrounding striatal tissue. The tissue was stained with fluoro-jade (a marker of neuronal degeneration) and processed by immunohistochemistry to detect tyrosine hydroxylase, neuronal and glial markers, and the stress protein heme-oxygenase-1. After intrastriatal injection, both cysteine and N-acetylcysteine had clear neuroprotective effects on the striatal dopaminergic terminals, but also led to neuronal degeneration (as revealed by fluoro-jade staining) and astroglial and microglial activation, as well as intense induction of heme-oxygenase-1 in astrocytes and microglial cells. Subcutaneous administration of N-acetylcysteine also induced significant reduction of the dopaminergic lesion (about 30% reduction). However, we did not observe appreciable N-acetylcysteine-induced fluoro-jade labeling in striatal neurons or any of the above-mentioned changes in striatal glial cells. The results suggest that low doses of cysteine prodrugs may be useful neuroprotectors in the treatment of Parkinson's disease.