Nanoscale Photoluminescence Manipulation in Monolithic Porous Silicon Oxide Microcavity Coated with Rhodamine-Labeled Polyelectrolyte via Electrostatic Nanoassembling

Porous silicon (PSi) is a promising material for future integrated nanophotonics when coupled with guest emitters, still facing challenges in terms of homogenous distribution and nanometric thickness of the emitter coating within the silicon nanostructure. Herein, it is shown that the nanopore surface of a porous silicon oxide (PSiO2) microcavity (MC) can be conformally coated with a uniform nm-thick layer of a cationic light-emitting polyelectrolyte, e.g., poly(allylamine hydrochloride) labeled with Rhodamine B (PAH-RhoB), leveraging the self-tuned electrostatic interaction of the positively-charged PAH-RhoB polymer and negatively-charged PSiO2 surface. It is found that the emission of PAH-RhoB in the PSiO2 MC is enhanced (≈2.5×) and narrowed (≈30×) at the resonant wavelength, compared with that of PAH-RhoB in a non-resonant PSiO2 reference structure. The time-resolved photoluminescence analysis highlights a shortening (≈20%) of the PAH-RhoB emission lifetime in the PSiO2 MC at the resonance versus off-resonance wavelengths, and with respect to the reference structure, thereby proving a significant variation of the radiative decay rate. Remarkably, an experimental Purcell factor Fp = 2.82 is achieved. This is further confirmed by the enhancement of the photoluminescence quantum yield of the PAH-RhoB in the PSiO2 MC with respect to the reference structure. Application of the electrostatic nanoassembling approach to other emitting dyes, nanomaterials, and nanophotonic systems is envisaged

Modulating the luminance of organic light emitting diodes Via optical stimulation of a photochromic molecular monolayer at transparent oxide electrode

Self-assembled monolayers (SAMs) deposited on bottom electrodes are commonly used to tune charge carrier injection or blocking in optoelectronic devices. Beside the enhancement of device performance, the fabrication of multifunctional devices in which the output can be modulated by multiple external stimuli remains a challenging target. In this work, we report the functionalization of an indium tin oxide (ITO) electrode with a SAM of a diarylethene derivative designed for optically control the electronic properties. Following the demonstration of dense SAM formation and its photochromic activity, as a proof-of-principle, an organic light-emitting diode (OLED) embedding the light-responsive SAM-covered electrode was fabricated and characterized. Optically addressing the two-terminal device by irradiation with ultraviolet light doubles the electroluminescence. The original value can be restored reversibly by irradiation with visible light. This expanded functionality is based on the photoinduced modulation of the electronic structure of the diarylethene isomers, which impact the charge carriers' confinement within the emissive layer. This approach could be successfully exploited in the field of opto-communication technology, for example to fabricate opto-electronic logic circuits

Clinical variability in spinal muscular atrophy type III

Objective: We report natural history data in a large cohort of 199 patients with spinal muscular atrophy (SMA) type III assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE). The aim of the study was to establish the annual rate and possible patterns of progression according to a number of variables, such as age of onset, age at assessment, SMN2 copy number, and functional status. Methods: HFMSE longitudinal changes were assessed using piecewise linear mixed‐effects models. The dependency in the data due to repeated measures was accounted for by a random intercept per individual and an unstructured covariance R matrix was used as correlation structure. An additional descriptive analysis was performed for 123 patients, for a total of 375 12‐month assessments. Results: A break point at age 7 years was set for the whole cohort and for SMA IIIA and IIIB. Age, SMA type, and ambulatory status were significantly associated with changes in mean HFMSE score, whereas gender and SMN2 copy number were not. The increase in response before the break point of age 7 years is significant only for SMA IIIA (β = 1.79, p < 0.0001). After the break point, the change in the rate of HFMSE score significantly decrease for both SMA IIIA (β = −1.15, p < 0.0001) and IIIB (β = −0.69, p = 0.002). Interpretation: Our findings contribute to the understanding of the natural history of SMA type III and will be helpful in the interpretation of the real‐world data of patients treated with commercially available drugs. ANN NEUROL 2020;88:1109–111

The Novel μ-Opioid Receptor Antagonist GSK1521498 Decreases Both Alcohol Seeking and Drinking: Evidence from a New Preclinical Model of Alcohol Seeking.

Distinct environmental and conditioned stimuli influencing ethanol-associated appetitive and consummatory behaviors may jointly contribute to alcohol addiction. To develop an effective translational animal model that illuminates this interaction, daily seeking responses, maintained by alcohol-associated conditioned stimuli (CSs), need to be dissociated from alcohol drinking behavior. For this, we established a procedure whereby alcohol seeking maintained by alcohol-associated CSs is followed by a period during which rats have the opportunity to drink alcohol. This cue-controlled alcohol-seeking procedure was used to compare the effects of naltrexone and GSK1521498, a novel selective μ-opioid receptor antagonist, on both voluntary alcohol-intake and alcohol-seeking behaviors. Rederived alcohol-preferring, alcohol-nonpreferring, and high-alcohol-drinking replicate 1 line of rats (Indiana University) first received 18 sessions of 24 h home cage access to 10% alcohol and water under a 2-bottle choice procedure. They were trained subsequently to respond instrumentally for access to 15% alcohol under a second-order schedule of reinforcement, in which a prolonged period of alcohol-seeking behavior was maintained by contingent presentations of an alcohol-associated CS acting as a conditioned reinforcer. This seeking period was terminated by 20 min of free alcohol drinking access that achieved significant blood alcohol concentrations. The influence of pretreatment with either naltrexone (0.1-1-3 mg/kg) or GSK1521498 (0.1-1-3 mg/kg) before instrumental sessions was measured on both seeking and drinking behaviors, as well as on drinking in the 2-bottle choice procedure. Naltrexone and GSK1521498 dose-dependently reduced both cue-controlled alcohol seeking and alcohol intake in the instrumental context as well as alcohol intake in the choice procedure. However, GSK1521498 showed significantly greater effectiveness than naltrexone, supporting its potential use for promoting abstinence and preventing relapse in alcohol addiction.The present study was funded by Medical Research Council Programme Grant (no. G1002231) and by GlaxoSmithKline (GSK), which has a commercial interest in GSK1521498. Charles R. Goodlett was funded by a grant from the IUPUI International Development Fund, which supported his sabbatical leave at the University of Cambridge. Maria Pilar Garcia-Pardo was funded by Val+id para investigadores en formación (Conselleria de educacion, Generalitat Valenciana), which also supported her stay at the University of Cambridge (January-April 2014) as a Visiting Student.This is the accepted manuscript. The final version is available from NPG at http://dx.doi.org/10.1038/npp.2015.15

An Evolutionary Conserved Role for Anaplastic Lymphoma Kinase in Behavioral Responses to Ethanol

Anaplastic lymphoma kinase (Alk) is a gene expressed in the nervous system that encodes a receptor tyrosine kinase commonly known for its oncogenic function in various human cancers. We have determined that Alk is associated with altered behavioral responses to ethanol in the fruit fly Drosophila melanogaster, in mice, and in humans. Mutant flies containing transposon insertions in dAlk demonstrate increased resistance to the sedating effect of ethanol. Database analyses revealed that Alk expression levels in the brains of recombinant inbred mice are negatively correlated with ethanol-induced ataxia and ethanol consumption. We therefore tested Alk gene knockout mice and found that they sedate longer in response to high doses of ethanol and consume more ethanol than wild-type mice. Finally, sequencing of human ALK led to the discovery of four polymorphisms associated with a low level of response to ethanol, an intermediate phenotype that is predictive of future alcohol use disorders (AUDs). These results suggest that Alk plays an evolutionary conserved role in ethanol-related behaviors. Moreover, ALK may be a novel candidate gene conferring risk for AUDs as well as a potential target for pharmacological intervention

Personalizing Cancer Pain Therapy: Insights from the Rational Use of Analgesics (RUA) Group

Introduction: A previous Delphi survey from the Rational Use of Analgesics (RUA) project involving Italian palliative care specialists revealed some discrepancies between current guidelines and clinical practice with a lack of consensus on items regarding the use of strong opioids in treating cancer pain. Those results represented the basis for a new Delphi study addressing a better approach to pain treatment in patients with cancer. Methods: The study consisted of a two-round multidisciplinary Delphi study. Specialists rated their agreement with a set of 17 statements using a 5-point Likert scale (0 = totally disagree and 4 = totally agree). Consensus on a statement was achieved if the median consensus score (MCS) (expressed as value at which at least 50% of participants agreed) was at least 4 and the interquartile range (IQR) was 3–4. Results: This survey included input from 186 palliative care specialists representing all Italian territory. Consensus was reached on seven statements. More than 70% of participants agreed with the use of low dose of strong opioids in moderate pain treatment and valued transdermal route as an effective option when the oral route is not available. There was strong consensus on the importance of knowing opioid pharmacokinetics for therapy personalization and on identifying immediate-release opioids as key for tailoring therapy to patients’ needs. Limited agreement was reached on items regarding breakthrough pain and the management of opioid-induced bowel dysfunction. Conclusion: These findings may assist clinicians in applying clinical evidence to routine care settings and call for a reappraisal of current pain treatment recommendations with the final aim of optimizing the clinical use of strong opioids in patients with cancer

Nanoscale Photoluminescence Manipulation in Monolithic Porous Silicon Oxide Microcavity Coated with Rhodamine-Labeled Polyelectrolyte via Electrostatic Nanoassembling

Porous silicon (PSi) is a promising material for future integrated nanophotonics when coupled with guest emitters, still facing challenges in terms of homogenous distribution and nanometric thickness of the emitter coating within the silicon nanostructure. Herein, it is shown that the nanopore surface of a porous silicon oxide (PSiO2) microcavity (MC) can be conformally coated with a uniform nm-thick layer of a cationic light-emitting polyelectrolyte, e.g., poly(allylamine hydrochloride) labeled with Rhodamine B (PAH-RhoB), leveraging the self-tuned electrostatic interaction of the positively-charged PAH-RhoB polymer and negatively-charged PSiO2 surface. It is found that the emission of PAH-RhoB in the PSiO2 MC is enhanced (≈2.5×) and narrowed (≈30×) at the resonant wavelength, compared with that of PAH-RhoB in a non-resonant PSiO2 reference structure. The time-resolved photoluminescence analysis highlights a shortening (≈20%) of the PAH-RhoB emission lifetime in the PSiO2 MC at the resonance versus off-resonance wavelengths, and with respect to the reference structure, thereby proving a significant variation of the radiative decay rate. Remarkably, an experimental Purcell factor Fp&nbsp;= 2.82 is achieved. This is further confirmed by the enhancement of the photoluminescence quantum yield of the PAH-RhoB in the PSiO2 MC with respect to the reference structure. Application of the electrostatic nanoassembling approach to other emitting dyes, nanomaterials, and nanophotonic systems is envisaged