Search

The article deals with the implementation of harm reduction methods to combat the opioid crisis in the U.S. and Canada. The two countries have employed multiple public health and treatment strategies, including opioid agonist therapies (OAT), to address the opioid crisis. Studies have compared the effectiveness and safety of three novel harm reduction methods: heroin assisted treatment; injectable hydromorphone and supervised consumption facilities.

Selective growth of CuO nanowires on the etched face of Al2O3/Cu/Al2O3 thin-film multilayer patterns was achieved by ambient oxidation at 400 °C. The nanowires were observed to selectively grow only from the pattern edge with diameter limited by the thickness of Cu thin film. Transmission-electron-microscopy (TEM) characterization confirmed CuO nanowires of a monoclinic CuO growing in the [010] crystallographic direction. Nanowire growth kinetics was studied at 400 °C for different cumulative growth durations with initial growth rates of ~1 nm/min. A base growth mechanism with kinetics limited by oxygen diffusion through defects of a scaling oxide film is consistent with observed kinetics. The oxygen diffusivity is found to be ~10-11 cm2/s, consistent with the grain-boundary diffusion of oxygen through polycrystalline copper oxide. [ABSTRACT FROM AUTHOR]

Patients should be stabilized on sublingual buprenorphine before BUP-XR is initiated Patients can receive BUP-XR if they are stabilized on 8-24 mg of sublingual buprenorphine for at least 7 days. Patient-reported outcomes of treatment of opioid dependence with weekly and monthly subcutaneous depot vs daily sublingual buprenorphine: a randomized clinical trial. In 2018, Health Canada approved the only BUP-XR treatment available in Canada, under the brand name Sublocade. [Extracted from the article]

Carbon nanomaterials such as graphene, carbon nanotubes, and fullerene have drawn great interest during the last decade due to their unique electrical, mechanical, thermal, and optical properties. By further combining these carbon nanomaterials with external nanocrystals of metal, semiconductor, ceramic, and/or quantum dot, it is possible to achieve the evolution of nanoscale hybrids and heterostructures with mutually improved performances and multi-functionalities. In this critical review, we summarize the state-of-the-art of recent researches on the development of nanoscale hybrids and heterostructures by incorporating carbon nanomaterials with foreign nanocrystals. The discussion is also focused on nanocomposites ranging from zero-dimensional to three-dimensional according to their fabrication approaches, structural properties, and applications. With respect to the practical applications of such nano-carbon-based hybrids and heterostructures, further review was presented on the recent development of carbon-tin based nanocomposites as electrode materials for lithium-ion batteries. The behaviors of carbon materials and their interaction with tin components during the charging/discharging of such lithium-ion batteries are summarized in detail. This review article is to provide critical knowledge and inspiration for future development of nano-carbon-based hybrids and heterostructures and their application in energy conversion and storage devices. [ABSTRACT FROM AUTHOR]

Magnetic nanomaterials have been shown to be effective additives to conductive materials for enhancing electromagnetic interference shielding (EMI) shielding performance, but the comprehensive mechanism remains unknown. Herein, a 3D flexible carbon foam composite decorated with Fe 3 O 4 nanoparticles was designed and constructed. The composite exhibited good flexibility and mechanical strength (approximately 45 KPa). Due to the synergistic effect of dielectric and magnetic losses, the composite delivered a shielding effectiveness (SE) of 21 dB in the X-band and a corresponding specific SE (SSE) value of 210 dB cm2/g. The transmission coefficient (T) was discovered to be as low as 0.008, indicating that the composite can successfully shield EM, while the reflection coefficient (R) was found to be higher than the absorption coefficient (A). Moreover, the complicated permittivity, permeability, and magnetism magnetization of the composite were discussed in order to better understand the origin of the composite's shielding behavior. [ABSTRACT FROM AUTHOR]

Abstract: Discrete dipole approximation (DDA) method was utilized to simulate optical properties (extinction spectra and normalized electric field distribution) of multilayer graphene shell encapsulated gold nanoparticles (GNPs) and their heterostructures with carbon nanotube (CNT). The results were also compared with those for gold (Au) nanoparticles and CNT–Au nanoparticle heterostructures. Encapsulation of Au nanoparticle with a multilayer graphene shell in GNPs did not suppress optical properties and surface plasmons of the former. Tunable optical characteristics of GNPs were calculated that showed resonance peak wavelengths, corresponding to encapsulated Au nanoparticle, between ∼527 and ∼663nm as a function of size and multilayer graphene shell thickness. Enhanced optical/plasmonic behavior and intense ‘hot spots’ were estimated for CNT coated with tightly-packed GNPs as compared to CNT coated with bare Au nanoparticles. [Copyright &y& Elsevier]

With the continuous development of information technology and electronic communications, the problems of electromagnetic interference (EMI) and electromagnetic wave pollution becomes more and more serious, and thus the EMI shielding materials have recently attracted numerous attentions. Carbon materials have been deemed as good candidate for novel EMI shielding materials due to their unique properties such as superior conductivity, light weight, stable chemical properties, good thermal properties, environmental friendliness, easy processing, and excellent mechanical properties. And great developments of carbon-based EMI shielding materials have been achieved in the past few years. In the current review article, we mainly focus on the EMI shielding mechanism and EMI shielding performance of various forms of carbon materials. Combining with the current research status, their future development was also prospected. Image 1 [ABSTRACT FROM AUTHOR]

Background: Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with decreased risk of cardiovascular and renal events in type 2 diabetes mellitus (DM) patients. However, no study to date has compared the effect of SGLT-2 inhibitors with that of GLP-1 RAs in type 2 DM patients with chronic kidney disease (CKD). We herein investigated the benefits of SGLT-2 inhibitors and GLP-1 RAs in CKD patients. Methods: We performed a systematic literature search through November 2020. We selected randomized control trials that compared the risk of major adverse cardiovascular events (MACE) and a composite of renal outcomes. We performed a network meta-analysis to compare SGLT-2 inhibitors with GLP-1 RAs indirectly. Risk ratios (RRs) with corresponding 95% confidence intervals (CI) were synthesized. Results: Thirteen studies were selected with a total of 32,949 patients. SGLT-2 inhibitors led to a risk reduction in MACE and renal events (RR [95% CI]; 0.85 [0.75–0.96] and 0.68 [0.59–0.78], respectively). However, GLP-1 RAs did not reduce the risk of cardiovascular or renal adverse events (RR 0.91 [0.80–1.04] and 0.86 [0.72–1.03], respectively). Compared to GLP-1 RAs, SGLT-2 inhibitors did not demonstrate a significant difference in MACE (RR 0.94 [0.78–1.12]), while SGLT-2 inhibitors were associated with a lower risk of renal events compared to GLP-1 RAs (RR 0.79 [0.63–0.99]). A sensitivity analysis revealed that GLP-1 analogues significantly decreased MACE when compared to placebo treatment (RR 0.81 [0.69–0.95]), while exendin-4 analogues did not (RR 1.03 [0.88–1.20]). Conclusions: In patients with type 2 DM and CKD, SGLT-2 inhibitors were associated with a decreased risk of cardiovascular and renal events, but GLP-1 RAs were not. SGLT-2 inhibitors significantly decreased the risk of renal events compared to GLP-1 RAs. Among GLP-1 RAs, GLP-1 analogues showed a positive impact on cardiovascular and renal outcomes, while exendin-4 analogues did not. [ABSTRACT FROM AUTHOR]

• Fever was associated with poor outcomes in patients with COVID-19. • Leukocytosis was associated with severe disease. • Leukopenia was associated with a better prognosis. • CRP was associated with poor prognosis. • Leuocytosis and CRP on arrival may predict severe COVID-19. Since December 2019, coronavirus 2019 (COVID-19) has spread worldwide. Identifying poor prognostic factors is helpful for risk stratification. In this meta-analysis, we investigated the association between severe COVID-19 and a change in white blood cell (WBC) count, an elevation of C-reactive protein (CRP), and fever. Moreover, we aimed to evaluate the diagnostic accuracy of leukocytosis and an elevation of CRP. We performed a systematic search of PubMed, EMBASE, Scopus, and the Cochrane Library through April 20th, 2020. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. A sensitivity analysis was conducted according to the study size (>200 or <200) and median age (>55 or <55). Meta-regression analyses were conducted to examine possible sources of heterogeneity. We calculated the diagnostic accuracy of leukocytosis and CRP. Eighteen studies with 3278 patients were selected. Fever, leukocytosis, and elevated CRP were associated with poor outcomes (OR (95% CI) 1.63 (1.06–2.51), 4.51 (2.53–8.04), and 11.97 (4.97–28.8), respectively). Leukopenia was associated with a better prognosis (OR 0.56, 95% CI 0.40–0.78). Sensitivity analyses showed similar tendencies. Meta-regression analysis for leukocytosis indicated that age, dyspnea, and hypertension contributed to heterogeneity. The pooled area under the leukocytosis and CRP curves were 0.70 (0.64–0.76) and 0.89 (0.80–0.99), respectively. In patients with COVID-19, fever, leukocytosis, and an elevated CRP were associated with severe outcomes. Leukocytosis and CRP on arrival may predict poor outcomes. [ABSTRACT FROM AUTHOR]

Herein, we report the design and preparation of a carbon foam composite with the addition of SiO 2 aerogel, aimed to obtain a novel thermal insulation material. SiO 2 aerogel was formed via a sol-gel process and then mixed with the mesophase pitch, followed by further foaming and carbonization process to synthesize the SiO 2 aerogel/carbon foam composite. The effects of SiO 2 aerogel content on the morphology and performance of composite product were studied to understand the relationship between the microstructure and the thermal insulation performance and mechanical strength of the composite. The results showed that the addition of SiO 2 aerogel had a significantly effect on the microstructure of the pore cells. The composite with SiO 2 aerogel addition showed better thermal insulation performance as compared with the pristine carbon foam; and the composite with 11 wt % SiO 2 aerogel content possessed a minimum thermal conductivity of 0.254 W/m·K. Meanwhile, the mechanical strength of the resultant composite was found co-enhanced with the addition of SiO 2 aerogel. Our study paves a new avenue to realize the simultaneous enhancement of thermal insulation performance and mechanical strength of carbon foam. [ABSTRACT FROM AUTHOR]

Keywords: Alcohol; DXM; NMDA; Naltrexone; gabapentin; case report EN Alcohol DXM NMDA Naltrexone gabapentin case report 266 267 2 04/24/23 20230301 NES 230301 NyQuil SP TM sp is an over-the-counter medication containing the pain reliever, acetaminophen; the antihistamine, doxylamine; and dextromethorphan (DXM), the anti-tussive medication. This case report highlights a potential therapeutic strategy for the treatment of problematic DXM use, which warrants further study, such as collection of additional case reports with either naltrexone or gabapentin, and their combination, to treat DXM use disorder, prior to designing randomized clinical trials. Given DXM's mechanism of action at both NMDA and sigma-1 receptors, it may be possible to treat DXM addiction by targeting these receptors. [Extracted from the article]

Highlights • A facile and cost-effective methodology was employed to pattern Au nanoparticles. • The density and inter-particle spacing of Au nanoparticles could be controlled. • The substrate for modulating the dispersion and density of plasmonic nanoparticles. Abstract Surface-enhanced Raman spectroscopy (SERS) is a promising technique for future high-sensitivity chemical sensors. The main deficiencies that restrict the large-scale application of SERS lie in its high cost, low reproducibility, and poor signal uniformity. In this letter, we report the primary exploration of a facile dip coating – thermal shrinking method to produce gold (Au) nanoparticle decorated flexible polymer substrate for SERS. Briefly, Au nanoparticles dispersed in DI-water were anchored on to a polystyrene film via controlled dip coating, which was followed by a thermal treatment process to shrink the polymer film. We observe a polymer volume shrinking rate of 20% after heating, which results in a particle density increase of more than 10 times. Significant enhancement of Raman signals was observed for the R6G molecules anchored on the shrunk substrate, demonstrating our methodology is feasible, reliable, and promising for future large-scale application of SERS-based chemical sensors. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Although quantum dots (QDs) based on two dimensional (2D) materials have manifested fascinating properties and promising applications in a wide range of fields, a low cost and non-tedious approach for the preparation of atomically thick 2D QDs with high yield remains elusive. Herein, for the first time, we demonstrate a reflux pretreatment-mediated sonication approach to produce a series of ultrathin 2D QDs (e.g., graphene, TiS 2 , MoS 2 , MoSe 2 , WSe 2 , NbS 2 , SnS 2 , and h-BN QDs) from their bulk counterparts. The solvent molecules, confined in the channels of layered materials during reflux, assist the delamination and fracture of 2D sheets in the process of bath sonication. The resulting 2D QDs exhibited uniform lateral size distribution of 2–7 nm and a mean thickness of 0.8–1 nm, almost identical to the monolayer thickness of layered materials. To demonstrate the unique property of these 2D QDs, the optical limiting activity was studied using open aperture z-scan technique. TiS 2 QDs exhibited appreciable nonlinear optical limiting, reaching 50% by a tapered and sharp absorption at input laser fluence of 4.24 GW/cm2. [ABSTRACT FROM AUTHOR]

Abstract Graphene-encapsulated gold nanoparticles (referred as graphene nanoparticles or GNPs) were recently reported as a potential plasmonic substrate for future bio-compatible devices, chemical sensors and many catalysis systems. However, the desired surface functionality creation of such GNPs is often limited by the insufficient surface area of the 2D graphene shell. In this paper, we report the design and realization of a novel bio-functionalization approach to covalently anchor singled-walled carbon nanotubes (SWCNTs) onto the GNP surface, rendering a unique nanocomposite architecture, namely GNP-CNT, with effectively increased surface functional sites. We found that the theoretical plasmonic "hot-spots" of our GNP-CNT nanoarchitectures were accumulated at the conjunction and interface sites of the GNP and SWCNTs. This further enables their advanced application as a substrate material for the surface-enhanced Raman spectroscopic (SERS) sensing. Experimentally we found that the GNP-CNT substrate exhibited nicely improved SERS performance as compared with the pristine GNP substrate. This paper paves a new bio-compatible avenue for design of future SERS sensing, bio-imaging and other bio-compatible materials. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Hexagonal boron nitride (h-BN), graphene oxide (GO) and hybrid (GO/h-BN) nanosheets were employed as fillers in order to enhance the physical properties of the polymer matrix. Composites based in epoxy and these two-dimensional (2D) nanofillers were produced with different wt% and their microstructure, mechanical and thermal properties were investigated. Increases up to 140% in tensile strength, 177% in ultimate strain and 32% in elastic modulus were observed for the hybrid GO/h-BN composite with 0.5 wt% content. The hybrid nanofiller also contributed to the increase up to 142% on thermal conductivity with respect to the pure epoxy for GO/h-BN composite with 2.0 wt% content. Molecular dynamic simulation was used to predict the behavior of possible stacking arrangements between h-BN and GO nanosheets tensioned by normal and shear forces. The results showed that the hybrid GO/h-BN combination can prevent the re-stacking process of exfoliated layers, demonstrating the synergism between these nanostructures with the final effect of better dispersion in the composite material. The excellent thermal and mechanical performance of these hybrid composites engineered by the combination of different types of the 2D inorganic nanoparticles make them multifunctional candidates for advanced materials applications. [ABSTRACT FROM AUTHOR]

Herein, we demonstrate a novel and flexible Surface enhanced Raman scattering (SERS) substrate comprised of thermally-responsive polymer film coated with ZnO nanowire-Au nanoparticle heterostructures. The heterostructure fabrication involved vapor-solid growth of ZnO nanowires and their subsequent decoration with Au nanoparticles via a wet-chemical and surfactant-free route. These heterostructures were further loaded with an analyte, methylene blue (MB). The mechanism of SERS relied on the Raman laser-based local heating of the thermally-responsive polymer substrate coated with MB-loaded heterostructures. This in-situ heating process caused the substrate to shrink and resulted in suitable hot spots between the heterostructures ("self-closing" mechanism) leading to MB Raman signal enhancement. The SERS effect was studied as a function of the substrate heating duration (0–10 s) and MB concentration (10−5–10−7 M). In addition, SERS substrate reusability was demonstrated by performing multi-spot analysis and photo-decomposition of loaded MB allowed for regeneration of the analyzed spot. The temperature distribution for the polymeric substrate under the incident Raman laser was calculated using finite element method (FEM). The plasmonic characteristics or hot spot formation for the self-closing heterostructures with varying distances between the two heterostructured targets was simulated using discrete dipole approximation (DDA) method. Self-closing ZnO nanowire-Au nanoparticle heterostructures for surface enhanced Raman scattering effect. Unlabelled Image • A novel and flexible SERS substrate composed of polymer film coated with ZnO nanowire-Au nanoparticles heterostructure. • A large area substrate could be realized and allows for multiple detection sites depending on the incident beam spot size. • Finite element method and discrete dipole approximation method were utilized. [ABSTRACT FROM AUTHOR]

Objective: Functional outcomes following facial and ocular trauma are time-sensitive and require prompt evaluation to minimise long-term vision loss, yet few studies have systematically evaluated disparities in the management of these cases. This study investigates whether a patient's race/ethnicity, primary language, insurance status, gender or age affects receipt of ophthalmology consultation for facial trauma., Methods and Analysis: This study was a retrospective cohort analysis of patients from the Elmhurst City Hospital Trauma Registry in Queens, New York who were seen for facial trauma including open globe injuries and orbital fractures between January 2014 and May 2016., Results: Of the 264 patients included, 43% reported as Hispanic, 23% white, 11% Asian, 8% black and 15% other/unknown. After controlling for confounding variables by multivariable logistic regression, neither race/ethnicity, gender, nor primary language were significantly associated with the likelihood of receiving an ophthalmology consult. However, patients with private insurance had 2.57 times greater odds of receiving an ophthalmology consultation than those with Medicaid or state corrections insurance (95% CI 1.37 to 4.95). As age increased, the likelihood of receiving an ophthalmology consultation decreased (p=0.009); patients 60 years of age and older had one-third the odds of ophthalmology consultation as younger patients (OR 0.33; 95% CI 0.16 to 0.68)., Conclusions: This study highlights that lack of ophthalmology consultation in patients with facial trauma is linked to age and underinsurance. Extra attention must be paid during primary assessments to ensure elderly patients and those with public insurance have equitable access to timely and appropriate care for facial trauma., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Alcohol use disorder and gastric bypass surgery are highly comorbid. Alcohol withdrawal syndrome (AWS) is a common and potentially life-threatening event, requiring nuanced and individually tailored management depending on various clinical factors including patient history, alcohol consumption, comorbidities, and timeline of use. Although increasingly common, the literature for managing alcohol withdrawal in the gastric bypass population is quite limited. We present the case of a 45-year-old woman with a past history of Roux-en-Y gastric bypass admitted for alcohol withdrawal at a psychiatric hospital who experienced a complicated withdrawal despite adhering to standard management guidelines. She had been consuming 8 to 12 standard drinks daily, and she was therefore monitored on a Clinical Institute Withdrawal Assessment for Alcohol. She experienced only minimal withdrawal symptoms up to 48 hours following cessation of alcohol consumption. At 70 hours postcessation, she experienced a witnessed tonic-clonic seizure with associated head trauma with internal bleeding, requiring acute medical intervention. This timeline of withdrawal symptoms is atypical, yet perhaps understood in the context of her past medical history which included gastric bypass surgery. We discuss the potential complicating factors inherent in individuals who have received Roux-en-Y gastric bypass in the past with respect to alcohol metabolism. We discuss the similar considerations with respect to altered metabolism of therapeutics commonly used in managing this condition. Lastly, we include a review of the extent literature on this topic and propose possible considerations for managing this unique but increasingly prevalent clinical scenario., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Background  Peer physical examination learning is commonly practiced in medical schools during preclinical curricula and has been shown to improve empathy for patients. While there is literature regarding medical student attitudes toward peer physical exam learning, no studies to date have specifically examined student attitudes toward fundoscopy and dilation of the eyes for the purposes of learning fundoscopy. This study evaluates medical student preferences with regards to learning fundoscopy on peers and explores attitudes toward alternate approaches. Methods  First year medical students at the Icahn School of Medicine at Mount Sinai participated in a 2-hour fundoscopy skills workshop in March 2020. Following the session, the authors administered a voluntary survey querying students on attitudes toward peer physical exam learning and its use in learning peer fundoscopy. Primary study endpoints evaluated (1) student attitudes toward the use of peer physical exam learning, (2) learning benefit of the session, including student comfort with conducting the fundoscopy exam, and (3) empathy toward patients experiencing dilation. Secondary endpoints focused on alternative teaching methods and preferences for nonmydriatic fundoscopy. Analysis of survey data was performed using nonparametric Spearman's correlations, chi-square tests, t -tests, and Mann-Whitney U tests. Results  A total of 51/138 (37%) students completed the survey, with 78% indicating they felt peer physical exam learning was a helpful instructional method, including for the fundoscopic exam. The session led to improved self-rated fundoscopy skills and empathy for patients. However, when considering learning with dilation versus alternative nonmydriatic techniques, 96% of students indicated a preference for using alternative nonmydriatic techniques. Conclusion  This study found that students' attitudes toward fundoscopy generally aligned with their overall peer physical exam preferences. However, they preferred not using dilation and learning with nonmydriatic fundoscopic techniques. Assessing student learning preferences and incorporating novel instructional tools can help facilitate more successful fundoscopy skills acquisition. These considerations are particularly important in the context of COVID-19 and with advances in teleophthalmology., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration., Competing Interests: In the last 3 years, the following authors had no conflict of interest: Drs. de Leon, Schoretsanitis, Molden, Smith, Solismaa, Švancer, Olmos, Ricciardi, Iglesias-Garcia, Iglesias-Alonso, Spina, Ruan, Chuan-Yue Wang, Gang Wang, Tang, Lin, Lane, Rajkumar, González-Esquivel, Jung-Cook, Baptista, Rohde, Nielsen, Verdoux, Quiles, Sanz, De las Cuevas, Cohen, Schulte, Chopra, McCollum, Shelton, Kaithi, Farooq, McGrane, Lana, Arrojo-Romero, Rădulescu, Every-Palmer, Bebawi, Bhattacharya, Otsuka, Lazary, Torres, Yecora, Motuca, Chan, Zolezzi, Ouanes, De Berardis, Grover, Kirilochev, Soloviev, Ayub, Silva, Bonelli, Temmingh, Decloedt, Pedro, Pacheco Palha, LLerena, Fernandez-Egea, Siskind, Masmoudi, Mohd Saffian, Leung and Buckley. In the last 3 years several authors report conflicts of interests. Dr. Seppälä is permanent medical advisor, received lecture fees and is an advisory board member from Viatris that markets clozapine in Finland and other European countries. Dr. Kopeček participated in speakers/advisory boards and lectured with the support of Angelini, Janssen Pharmaceuticals, Lundbeck and Richter Gedeon. Dr. Yong Sik Kim received grants, research support and honoraria from Janssen, Otsuka, Whan in Pharm and Bukwang Pharm (Sumitomo Dannipon Pharma). Dr. Se Hyun Kim received research grants from and/or served as a lecturer for Janssen, Eli Lilly, and Dongwha. Dr. Ertuğrul has received speaker’s honoraria from Abdi İbrahim Otsuka. Dr. Anıl Yağcıoğlu has received speaker’s honoraria and consulting fees from Janssen and Abdi İbrahim Otsuka. Dr. Cotes has received research funding from Otsuka, Lundbeck, Roche, Alkermes, and is a consultant for Saladax Biomedical. Dr. Kane reports personal fees from Alkermes, personal fees from Allergan, personal fees from Bristol-Myers Squibb, personal fees from IntraCellular Therapies, Janssen, Lundbeck, Minerva, Neurocrine, Otsuka, Pierre Fabre, Reviva, Sunovion, Takeda, Teva, outside-the-submitted work from LB Pharma, MedAvante and The Vanguard Research Group. Dr. Ng had served as consultant for Grunbiotics, Lundbeck, Servier, and Janssen-Cilag, and received research speaker honoraria from Servier, Janssen-Cilag and Pfizer.IMcG received royalties from Hogrefe Publishing Corp. T.L. Dr. Bilbily is supported by the National Institute on Drug Abuse training grant 5T32DA007261-30 (MPI). Dr. Hiemke received speaker’s honoraria from Otsuka. Dr. López-Jaramillo reports financial support for research from Financial support from the National Institute of Mental Health, USA, MinCiencias, Colombia and the Universidad de Antioquia, Colombia. Dr. Eap received honoraria for conferences or teaching CME courses from Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Vifor-Pharma, and Zeller. Dr. Seifritz has received honoraria from Schwabe GmbH for educational lectures. He has further received educational grants and consulting fees from Janssen Cilag, Lundbeck, Angelini, Otsuka, Servier, Recordati, Vifor, Sunovion, and Mepha. Dr. Bousman is a member of the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Pharmacogene Variation Consortium (PharmVar). Dr. Kelly has served as a consultant for Alkermes, Lyndra and Sunovion. Dr. Procyshyn has been on the speaker's bureau and attended advisory board meetings for Janssen, Lundbeck, and Otsuka. Dr. Adebayo was on the advisory board of Janssen for a Long Acting Injectable Paliperidone palmitate in Nigeria. Janssen is not involved in Clozapine in Nigeria. Dr. Fountoulakis has received grants in the past, served as consultant, advisor or CME speaker, or received support to attend congresses by the following entities: AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka, Pfizer, the Pfizer Foundation, Sanofi-Aventis, Servier, Shire and others. Since January 2020 he has been the director of Cochrane Greece and completely free from any conflict of interest. Dr. Wilkowska has received research support from Angelini, Biogen, Eli Lilly and Company, Janssen-Cilag, Lundbeck, Polpharma, Sanofi and Valeant. Dr. Cubała has received research support from Alkermes, Allergan, Auspex, Biogen, Celon, Ferrier, Forest Laboratories, Janssen, Otsuka, and Sanofi; he has served on speaker bureaus for Angelini, Celon, Janssen, and Sanofi, and he has served as a consultant for GW Pharmaceuticals, Janssen, Celon and Sanofi. Dr. Villagrán-Moreno has received speakerʼs honoraria from Janssen and have developed lectures and presented clozapine lectures for Adamed, which sells clozapine in Spain; he has participated in advisory boards for Rovi and in research projects for Otsuka. Dr. Crespo-Facorro has received funding unrelated to the present work for research projects and/or honoraria as a consultant or speaker from the following entities: Angelini, Janssen-Cilag, Lundbeck, Otsuka, Mylan, Sanofi-Aventis, ADAMED, Agencia Española de Investigacion, Instituto de Salud Carlos III, the EU Seventh Framework Program and Horizon 2020. Dr. Takeuchi has received speaker’s fees from EA Pharma, Kyowa, Janssen, Lundbeck, Meiji Seika Pharma, Mochida, Otsuka, Sumitomo Dainippon Pharma, Takeda, and Yoshitomiyakuhin. Dr. Tsukahara has received speaker's honoraria from Eisai Inc. Dr. Gründer has served as a consultant for Allergan (Dublin, Ireland), Boehringer Ingelheim (Ingelheim, Germany), Institute for Quality and Efficiency in Health Care (IQWiG, Cologne, Germany), Janssen-Cilag (Neuss, Germany), Lundbeck (Copenhagen, Denmark), Otsuka (Chiyoda, Japan), Recordati (Milan, Italy), Sage (Cambridge, USA), and Takeda (Osaka, Japan). He has served on the speakers’ bureau of Gedeon Richter (Budapest, Hungary), Janssen Cilag, Lundbeck, Otsuka, Recordati. He has received grant support from Boehringer Ingelheim, Lundbeck and Saladax (Bethlehem, USA). He is co-founder and/or shareholder of Mind and Brain Institute GmbH (Zornheim, Germany), Brainfoods GmbH (Zornheim, Germany), OVID Health Systems GmbH (Berlin, Germany) and MIND Foundation gGmbH (Berlin, Germany). Dr. Sagud participated in lectures for the following companies: Alkaloid, Belupo, Elli Lilly, Gedeon Richter, Jadran Galenski Laboratorij, Johnson / Johnson, Lundbeck, Makpharm, Pliva, Stada and participated in the clinical trial: Eli Lilly, Krka and Gedeon Richter. Dr. Celofiga received speaker’s honoraria from Ely Lilly, Lundbeck, Richter Gedeon, Krka, Lek, Pliva, Angelini Pharma and participated in advisory boards for Janssen Pharmaceuticals and Lundbeck. Dr. Ignjatovic Ristic developed and presented clozapine lectures with the support of Mylan, received speakerʼs honoraria from Mylan, Teva Serbia, Pharm Swiss, Krka and Janssen. Dr. Ortiz has been a consultant and has received honoraria from Janssen-Cilag. Dr. Elkis received research grants from the São Paulo Research Support Foundation (FAPESP) and honoraria for participation as a member of advisory boards, speaker, or travel support from the following pharmaceutical companies: Aché, Cristalia, Daiichi-Sankyo, Janssen, Mantecorp-Hypera, Sandoz, and Teva. Dr. Weizman received speakerʼs honoraria from Lundbeck, Lilly, Teva, Trima, Jansen, Medison, Novartis and AstraZeneca. These activities were unrelated to the current study. Dr Marder reports consultation fees from Roche, Sunovion, Merck, Boehringer Ingelheim and Otsuka. He reports research support from Boehringer-Ingelheim, and GW Pharma. Dr. Citrome has engaged in collaborative research with, or received consulting or speaking fees, from: AbbVie, Acadia, Alexza, Alkermes, Allergan, Angelini, Astellas, AstraZeneca, Avanir, Axsome, BioXcel, Boehringer Ingelheim, Bristol-Myers Squibb, Cadent Therapeutics, Eisai, Eli Lilly, Forum, Genentech, Impel, Indivior, Intra-Cellular Therapies, Janssen, Jazz, Karuna, Lundbeck, Luye, Lyndra, Medavante-Prophase, Meiji, Merck, Medivation, Mylan, Neurocrine, NeuroRx, Novartis, Noven, Osmotica, Otsuka, Pfizer, Reckitt Benckiser, Relmada, Reviva, Sage, Shire, Sunovion, Takeda, Teva, University of Arizona, Valeant, Vanda, and one-off ad hoc consulting for individuals/entities conducting marketing, commercial, or scientific scoping research. Dr. Freudenreich has the following financial relationship with a commercial interest to disclose (recipient SELF; content area SCHIZOPHRENIA): Alkermes – Research grant (to institution), consultant honoraria (Advisory Board); Avanir – Research grant (to institution); Janssen – Research grant (to institution), consultant honoraria (Advisory Board); Integral - Consultant honoraria; Neurocrine – Consultant honoraria (Advisory Board); Novartis – Consultant honoraria; Otsuka – Research grant (to institution); Roche – Consultant honoraria; Springer Verlag – Royalties (medical writer); Elsevier – Honoraria (medical editing); Global Medical Education – Honoraria (CME speaker and content developer); Medscape – Honoraria (CME speaker); American Psychiatric Association – Consultant honoraria (SMI Adviser); Wolters-Kluwer – Royalties (content developer); UpToDate – Royalties, honoraria (content developer and editor, including for a chapter on clozapine). Dr. Correll has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Axsome, Damitsa, Gedeon Richter, Hikma, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Medscape, Merck, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of LB Pharma. Dr. Müller reports he has been a co-investigator for two pharmacogenetic studies where genetic test kits were provided as an in-kind contribution by Myriad Neuroscience. He did not receive any payments or any equity, stocks, or options from any pharmacogenetic companies. He is also a co-inventor of two patents assessing risk for antipsychotic-induced weight gain (pending)., (Thieme. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Manufacturing has been the key factor limiting rollout of vaccination during the COVID-19 pandemic, requiring rapid development and large-scale implementation of novel manufacturing technologies. ChAdOx1 nCoV-19 (AZD1222, Vaxzevria) is an efficacious vaccine against SARS-CoV-2, based upon an adenovirus vector. We describe the development of a process for the production of this vaccine and others based upon the same platform, including novel features to facilitate very large-scale production. We discuss the process economics and the "distributed manufacturing" approach we have taken to provide the vaccine at globally-relevant scale and with international security of supply. Together, these approaches have enabled the largest viral vector manufacturing campaign to date, providing a substantial proportion of global COVID-19 vaccine supply at low cost., (© 2021 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Direct encapsulation of graphene shells on noble metal nanoparticles via chemical vapor deposition (CVD) has been recently reported as a unique way to design and fabricate new plasmonic heterostructures. But currently, the fundamental nature of the growth mechanism of graphene layers on metal nanostructures is still unknown. Herein, we report a systematic investigation on the CVD growth of graphene-encapsulated Au nanoparticles (Au@G) by combining an experimental parameter study and theoretical modeling. We studied the effect of growth temperature, duration, hydrocarbon precursor concentration, and extent of reducing (H 2 ) environment on the morphology of the products. In addition, the influence of plasma oxidation conditions for the surface oxidation of gold nanoparticles on the graphene shell growth is evaluated in combination with thermodynamic calculations. We find that these parameters critically aid in the evolution of graphene shells around gold nanoparticles and allow for controlling shell thickness, graphene shell quality and morphology, and hybrid nanoparticle diameter. An optimized condition including the growth temperature of ∼675 °C, duration of 30 min, and xylene feed rate of ∼10 mL/h with 10% H 2 /Ar carrier gas was finally obtained for the best morphology evolution. We further performed finite-element analysis (FEA) simulations to understand the equivalent von Mises stress distribution and discrete dipolar approximation (DDA) calculation to reveal the optical properties of such new core-shell heterostructures. This study brings new insight to the nature of CVD mechanism of Au@G and might help guiding their controlled growth and future design and application in plasmonic applications.

Introduction: Contrast-induced acute kidney injury (CI-AKI) is a major complication after coronary angiography (CAG) or percutaneous coronary intervention (PCI) and is associated with increased morbidity and mortality. It remains controversial whether renin-angiotensin system (RAS) blockers increase or decrease CI-AKI. In this meta-analysis, we investigated the association between RAS blockers and CI-AKI in patients with normal kidney function or mild-to-moderate chronic kidney disease (CKD)., Materials and Methods: We performed a systematic search of PubMed, EMBASE, clinicaltrials.gov, and the Cochrane Library up to December 2019 for studies that assessed the association between RAS blockers and CI-AKI events after CAG/PCI. The primary outcome was the development of CI-AKI. Odds ratios (ORs) with corresponding 95% confidence interval (CI) were synthesized., Results: Five randomized controlled trials (RCTs) and five observational studies were included, accounting for a total of 7,420 patients. Unstratified, RAS blocker administration was significantly associated with an increased risk of CI-AKI (pooled OR = 1.63, 95% CI 1.19 - 2.25, p = 0.003). However, the effect was not observed in RCTs (pooled OR = 1.22, 95% CI 0.54 - 2.74, p = 0.63). Sensitivity analysis in observational studies showed significant association (pooled OR = 1.77, 95% CI 1.22 - 2.55, p = 0.003) with high heterogeneity and evidence of publication bias., Conclusion: In patients with relatively-preserved renal function, the association of RAS blockers with an increased risk of CI-AKI after contrast media exposure was inconclusive, as sensitivity analysis showed conflicting results and bias. Although this study did not demonstrate significant evidence, it indicated that clinicians need to be vigilant in assessing the potential risk for RAS blockers to cause CI-AKI in low-risk patients.

Objective: To determine the impact of near-peer teaching experiences in the ophthalmology branch of the East Harlem Health Outreach Program (EHHOP), a student-run clinic, on teaching skills of fourth-year medical student Teaching Seniors (TS)., Design: Mixed-methods observational study, including online survey and telephone interview., Setting: Student-run ophthalmology clinic affiliated with the Icahn School of Medicine at Mount Sinai and Mount Sinai Hospital, a tertiary-care center in New York, NY., Participants: All EHHOP TS alumni from 2014 to 2019 were eligible for inclusion in our study. All 14 alumni participated in the survey, and 8 participated in the follow-up interview., Methods: EHHOP ophthalmology TS alumni were surveyed via an online survey and subsequent, optional, individual telephone interview. The web survey queried former TS on the impact of EHHOP ophthalmology experiences on self-reported teaching skills and comfort with teaching. Quantitative analysis of survey questions and qualitative analysis of telephone responses was performed and analyzed for themes., Results: Majority of participants reported increased comfort teaching ophthalmology concepts, teaching the slit-lamp exam, and serving as mentors as a result of their experience. Qualitative analysis of telephone interviews revealed 4 major themes: (1) TS were a self-selected group of individuals with prior interest in teaching, (2) Teaching experiences in EHHOP had a positive impact in many teaching-related domains, (3) TS perceptions of teaching skills gained did not necessarily align with junior students' perceptions of teaching received, and (4) despite increased confidence and satisfaction with teaching experiences, TS desired more formal instruction in teaching., Conclusions: While TS perceptions of teaching skills gained in EHHOP ophthalmology were overwhelmingly positive, TS still desired formal instruction in teaching. Additionally, the effectiveness of near-peer education in a subspecialty like ophthalmology, with limited formal curricular time, may be more effective later in training, when a more solid foundation of knowledge is acquired., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Outcomes in acute decompensated heart failure (ADHF) have remained poor. Worsening renal function (WRF) is common among patients with ADHF. However, the impact of WRF on the prognosis is controversial. We hypothesized that in patients with ADHF, the achievement of concomitant decongestion would diminish the signal for harm associated with WRF., Methods: We performed a systematic search of PubMed, EMBASE, and the Cochrane Library up to December 2019 for studies that assessed signs of decongestion in patients with WRF during ADHF admission. The primary outcome was all-cause mortality and heart transplantation., Results: Thirteen studies were selected with a pooled population of 8138 patients. During the follow-up period of 60-450 days, 19.2% of patients died. Unstratified, patients with WRF versus no WRF had a higher risk for mortality (odds ratio [OR], 1.71 [95% confidence interval {CI}, 1.45-2.01]; P  < 0.0001). However, patients who achieved decongestion had a similar prognosis (OR, 1.15 [95% CI, 0.89-1.49]; P  = 0.30). Moreover, patients with WRF who achieved decongestion had a better prognosis compared with those without WRF or decongestion (OR, 0.63 [95% CI, 0.46-0.86]; P  = 0.004). This tendency persisted for the sensitivity analyses., Conclusions: Decongestion is a powerful effect modifier that attenuates harmful associations of WRF with mortality. Future studies should not assess WRF as an endpoint without concomitant assessment of achieved volume status., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: In the last 20 years of clinical practice, the senior author has identified these 2 rare cases in which the patients needed extremely high doses of drugs metabolized by CYP3A4 to reach and maintain serum therapeutic concentrations., Methods: The high metabolic ability of these 2 patients was demonstrated by the low concentration-to-dose ratios (C/D ratios) of several drugs metabolized by CYP3A4., Results: Case 1 was characterized by a history of high carbamazepine doses (up to 2,000mg/day) and needed 170 mg/day of diazepam in 2 days to cooperate with dental cleaning. The high activity of the CYP3A4 isoenzyme was manifested by fast metabolism for quetiapine and diazepam, which took more than 1 year to normalize after the inducer, phenytoin, was stopped. Case 2 was also very sensitive to CYP3A4 inducers as indicated by very low C/D ratios for carbamazepine, risperidone and paliperidone. The carbamazepine (2,800 mg/day) and risperidone (20 mg/day) dosages for this second patient are the highest doses ever seen for these drugs by the senior author. Risperidone induction appeared to last for many months and metabolism was definitively normal 3 years after stopping carbamazepine. On the other hand, olanzapine C/D ratios were normal for induction., Conclusions: The literature has never described similar cases of very high doses of drugs metabolized by CYP3A4. We speculate that these 2 patients may have unusual genetic profiles at the nuclear receptor levels; these receptors regulate induction of drugs., (Copyright © 2018 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

: Reporting of intoxication and withdrawal from aberrant use of over-the-counter medication has been sparse and inconsistent in literature. Attributed to their anticholinergic properties, medications such as dimenhydrinate (Gravol) taken in supratherapeutic doses have been associated with euphoria, anxiolysis, and hallucinations. We present a case of a woman in her forties, with a psychiatric history of bipolar disorder, and complex concurrent medical history including familial Mediterranean fever (FMF), and fibromyalgia, admitted for withdrawal management of her intravenous dimenhydrinate use. As a result of her FMF, there were numerous hospital admissions and treatment which required intravenous access. Hence, a physician-inserted intravenous access port was placed on her chest. The port was maintained monthly with the help of a community agency. In this port, she was injecting 100 to 200 mg of dimenhydrinate hourly for its euphoric and calming effects, consuming upwards of 2400 mg/d. Comprehensive laboratory work-up and urine drug screening were unremarkable. Vital signs were stable. Her mental status at time of admission was lethargic, unfocused, but calm. Her withdrawal symptoms included severe nausea, vomiting, sedation, headaches, dizziness, anxiety, and muscle stiffness. Her detoxification was managed with benztropine and lorazepam, and was well tolerated. The patient was discharged to a community inpatient rehabilitation center. Urine drug testing before discharge was negative. This case draws attention to the addictive potential of dimenhydrinate and offers a regime for its medical withdrawal management. Additionally, this case highlights that screening and management of over-the-counter medications warrants further clinical consideration and investigation.

Two-dimensional (2D) nanomaterials as molybdenum disulfide (MoS 2 ), hexagonal boron nitride (h-BN), and their hybrid (MoS 2 /h-BN) were employed as fillers to improve the physical properties of epoxy composites. Nanocomposites were produced in different concentrations and studied in their microstructure, mechanical and thermal properties. The hybrid 2D mixture imparted efficient reinforcement to the epoxy leading to increases of up to 95% in tensile strength, 60% in ultimate strain, and 58% in Young's modulus. Moreover, an enhancement of 203% in thermal conductivity was achieved for the hybrid composite as compared to the pure polymer. The incorporation of MoS 2 /h-BN mixture nanofillers in epoxy resulted in nanocomposites with multifunctional characteristics for applications that require high mechanical and thermal performance.

Opioid use disorder is a growing epidemic, with an alarming number of associated deaths. In 2014, in the United States, 18,893 lethal overdoses were related to prescription opioids and 10,574 due to heroin. Despite the growing number of treatment options for substance use disorders, which are chronic, relapsing-remitting conditions, relapse rates remain as high as 91%. In the United States, 7.5 million children reside with at least one patient who abuses drugs or alcohol. Mothers are twice as likely to lose custody of their children. They have higher rates of comorbid abuse and psychopathology and limited social supports. Child service agencies, commonly involved in these scenarios, are often pressured to find permanent placement for children, within an expedited timeframe, inconsistent with the need for sufficient time for recovery and goals of family inclusion and unity. We present the complicated case of a 25-year-old woman with a history of opioid use disorder and depression, who, after being in and out of treatment programs for years, had a lethal overdose. She had a significant family history of addiction and had lost custody of her children. This challenging, but common presentation draws attention to challenges in providing treatment during this opioid epidemic.

Nanoscale structures that could mimic the selective transport and extraordinarily fast flow possible in biological cellular channels would have a wide range of potential applications. Here we show that liquid flow through a membrane composed of an array of aligned carbon nanotubes is four to five orders of magnitude faster than would be predicted from conventional fluid-flow theory. This high fluid velocity results from an almost frictionless interface at the carbon-nanotube wall.

An array of aligned carbon nanotubes (CNTs) was incorporated across a polymer film to form a well-ordered nanoporous membrane structure. This membrane structure was confirmed by electron microscopy, anisotropic electrical conductivity, gas flow, and ionic transport studies. The measured nitrogen permeance was consistent with the flux calculated by Knudsen diffusion through nanometer-scale tubes of the observed microstructure. Data on Ru(NH3)6(3+) transport across the membrane in aqueous solution also indicated transport through aligned CNT cores of the observed microstructure. The lengths of the nanotubes within the polymer film were reduced by selective electrochemical oxidation, allowing for tunable pore lengths. Oxidative trimming processes resulted in carboxylate end groups that were readily functionalized at the entrance to each CNT inner core. Membranes with CNT tips that were functionalized with biotin showed a reduction in Ru(NH3)6(3+) flux by a factor of 15 when bound with streptavidin, thereby demonstrating the ability to gate molecular transport through CNT cores for potential applications in chemical separations and sensing.