Mcbridemahmood1136
Zwitterionic polymers play an attractive role in the application of stealthy nanocarriers for their excellent antifouling property. Herein, a zwitterionic nanogel with temperature sensitivity and redox-responsive degradability prepared by copolymerization of N-vinylcaprolactam (VCL) and 2-(methacryloyloxy) ethyldimethyl-(3-sulfopropyl) ammonium hydroxide (DMAPS) via aqueous precipitation polymerization. The prepared nanogels own ultra-high colloidal stability and non-specific protein adsorption resistance as a result of the incorporation of zwitterionic groups. Meanwhile, they exhibit sensitive temperature-induced swelling/collapse transition in aqueous solution and excellent redox-degradability ascribed to the presence of disulfide bonds. The nanogels loaded with anticancer drug doxorubicin (DOX) exhibit low leakage of DOX under physiological conditions (merely 23.8 % within 24 h), whereas striking release amount of DOX under reducing conditions combined with elevated temperature (93.4 % within 24 h). The measurement of cell viability showed that the cytotoxicity of blank nanogels to tumor cells (HeLa cells) was negligible, while the nanogels loaded with DOX had a prominent inhibitory impact on tumor cells.Peroxidase-like activity of MoS2 quantum dots (QDs) can be reversibly regulated by means of Fe3+/alendronate sodium (ALDS)-induced aggregation/disaggregation of the QDs in solution. Specifically, Fe3+ can selectively aggregate the MoS2 QDs and thus greatly enhance their peroxidase-like activity, while such enhancement can be inhibited in the presence of ALDS owing to the competitive coordination of ALDS with Fe3+. By regulating the enzyme-like activity of MoS2 QDs, different colorimetric signal of a typical substrate of horseradish peroxidase, 3,3΄,5,5΄-tetramethylbenzidine, can be measured in the presence of H2O2. Based on this mechanism, we develop a colorimetric approach for the determination of ALDS and further applied in quality control of pharmaceutical products, utilizing either smartphone or UV-vis spectrometer as a readout. This detection method is rapid and selective, where derivatization of ALDS before detection is not needed. Such a smartphone-based colorimetric detection platform is promising to be applied in point-of-care testing at home, small clinics, or underdeveloped regions.Escherichia coli is one of the most common commensal aerobic bacteria in the gut microbiota of humans (and other mammals). Nevertheless, if left free to proliferate, it can induce a large range of diseases from diarrhoea to extra-intestinal diseases. In recent years, this bacterium had become increasingly resistant to antibiotics. It is therefore essential to implement new approaches able to maintain both bacterial viability and to control their proliferation. In this context, we developed a process to encapsulate Escherichia coli in polymer shells. We took advantage of the fact that this bacterium has a negatively charged surface and modified it via a layer-by-layer process, i.e. with oppositely charged polyelectrolyte pairs (namely chitosan as the polycation and alginate or dextran sulfate as polyanion). We successfully demonstrate the controlled coating of the bacterial surface via zeta potential measurement, the viability of the encapsulated bacteria and a delay in growth due to the multilayer coating. This delay was dependent on the number of polyelectrolyte layers.Despite efforts to achieve a long-acting formulation for human growth hormone (hGH), daily injections are still prescribed for children with growth hormone deficiency. To grapple with the issue, acquiring a deep knowledge of the protein and understanding its interaction mechanism with the carrier can be beneficial. Herein, we designed and synthesized a novel chitosan-based copolymer and investigated its interaction with hGH using a combination of experimental and computational strategies. To construct the amphiphilic triblock copolymers (CDP), we grafted deoxycholic acid (DCA) and polyacrylic acid (PAA) onto the chitosan chains, and Fourier-transform infrared (FTIR) analysis confirmed the proper formation of CDP. Circular dichroism (CD) demonstrated the preservation of the secondary structure of hGH interacting with CDP, and, further, fluorescence spectroscopy proved the stability of the tertiary structure of the protein. Applying molecular dynamics simulation (MD), we examined the dynamics and integrity of hGH in the presence of the copolymer and compared its behavior with the protein in aquatic environments. Additionally, energy and contact analysis illustrated that the residues involved in the interaction were located predominantly in the connecting loops, and van der Waals (vdW) and electrostatic interactions were the main driving forces of the polymer-protein complex formation. selleck kinase inhibitor This research's main aim was to trace the protein-polymer interaction's mechanism. We anticipate that the utility of the copolymer can address the challenges of fabricating a new sustained-release delivery platform for therapeutic proteins.Near the end of 2019, a new betacoronavirus started to efficiently transmit between humans, resulting in the current COVID-19 pandemic. Unprecedented worldwide efforts were made to identify and repurpose antiviral therapeutics from collections of approved drugs and known bioactive compounds. Typical pitfalls of this approach (promiscuous/cytotoxic compounds leading to false positives), combined with bypassing antiviral drug development parameters due to urgency have resulted in often disappointing outcomes. A flood of publications, press-releases, and media posts, created confusion in the general public and sometime mobilized precious resources for clinical trials with minimal prospect of success. Breakthroughs have been made, not in the laboratory but in the clinic, resulting from the empiric identification of mitigators of clinical signs such as the discovery of improved disease management through immunomodulators. This opinion piece will aim to capture some of the lessons that we believe the COVID-19 pandemic has taught about drug repurposing screens.
To examine whether youth and young adult e-cigarette use is associated with initiation of cigars, little cigars, or cigarillos (CLCCs) and current use of flavored CLCCs.
The sample is drawn from the Truth Longitudinal Cohort, a probability-based longitudinal cohort of youth and young adults recruited at ages 15-21 and surveyed every six months. The sample for this study was CLCC-naïve defined as those who had never used CLCCs as of 2017 (N = 5586). The outcomes were the odds of (1) initiating any CLCC use and (2) reporting current (past 30-day) use of flavored CLCCs from 2018 to late 2019. The main predictor was use of e-cigarettes by 2018.
The odds of initiating a CLCC was greater for those who had used ever used JUUL (OR 3.30, p < 0.001) or were current users of another type of e-cigarette by 2018 (OR 3.57, p < 0.001). Odds of CLCC initiation was also greater for those who had ever used combustible cigarettes (OR 1.62, p < 0.05), were current smokers (OR 3.12, p < 0.001) or had used marijuana (OR 1.92, p < 0.001) by 2018. E-cigarette use that occurred by 2018 was associated with greater odds of current use of flavored CLCCs compared to non-flavored CLCCs (ever users of JUUL OR 2.57, p < 0.01; current users of some other e-cigarette OR 3.06, p < 0.05).
This study raises new concerns about the effects of e-cigarette use on subsequent combustible tobacco use. Restrictions on CLCCs should be considered in conjunction with current policies designed to reduce the youth vaping epidemic.
This study raises new concerns about the effects of e-cigarette use on subsequent combustible tobacco use. Restrictions on CLCCs should be considered in conjunction with current policies designed to reduce the youth vaping epidemic.
Four million individuals in the U.S. criminal-legal system are supervised in the community under probation or parole. Sentences to community supervision often mandate participation in substance use treatment. Yet evidence-based treatment with medication (i.e., methadone, buprenorphine, or naltrexone) is rarely offered to people under community supervision with opioid use disorder (OUD). This qualitative study explores the structural and organizational factors shaping OUD medication treatment use in community supervision.
We conducted in-depth interviews with 31 community supervision professionals. Thematic analysis characterized interview participants' perceptions of the key factors shaping use of OUD medications in community supervision.
Findings indicate that authorities making decisions about OUD treatment include community supervision agencies, treatment providers, judges and courts, and jails and prisons. Agencies with more rehabilitative cultural orientations are more forgiving of relapse and suppn reincarceration, morbidity, and mortality among individuals with OUD under supervision.
The objectives of this study were to (1) investigate racial/ethnic differences in being offered information on alcohol treatment options by a health care provider; and (2) conduct stratified subgroup analyses to explore racial/ethnic differences in the use of alcohol treatment utilization among those who have received information on alcohol treatment services by a health care provider.
Data from National Survey on Drug Use and Health (2015-2017) was used. Analyses were restricted to adult White, Black, and Latino participants who met diagnostic criteria for a past-year alcohol use disorder (AUD) and reported visiting a health care provider in the past-year (n = 4,939). A multivariable logistic regression model was estimated to investigate differences in being offered information on alcohol treatment by a health care provider by race/ethnicity. A sub analysis that was limited to participants who reported receiving information on alcohol treatment services by a health care provider (n = 481) was also conducted to explore racial/ethnic differences in treatment utilization.
Overall, health care providers rarely provided information on alcohol treatment services to persons with AUD. In multivariable analyses, Latinos were less likely to receive information on alcohol treatment services than Whites, but no White-Black differences were documented. When analyses were restricted to those who had received information on alcohol treatment options, no racial/ethnic differences in the use of alcohol treatment services were found.
Health care providers can potentially encourage use of alcohol treatment among those in need and contribute to reducing existing alcohol-related racial/ethnic disparities.
Health care providers can potentially encourage use of alcohol treatment among those in need and contribute to reducing existing alcohol-related racial/ethnic disparities.
Drug overdoses have contributed to considerable years of life lost. However, focusing solely on drug overdoses, whereby drug poisoning defines the underlying cause of death, obscures the wider burden of the drug mortality crisis. We aim to describe 21 years of trends in "psychotropic-drug-implicated deaths," those where psychotropic drugs are a contributing (but not the underlying) cause of death.
We analyze deaths extracted from CDC WONDER from 1999-2019 to generate annual counts and rates for psychotropic-drug-implicated deaths in the United States, including by underlying cause of death and drug implicated.
Over 21 years, 51,446 psychotropic-drug-implicated deaths occurred (33,885 medical; 17,561 external). Both medical and external psychotropic-drug-implicated deaths rose dramatically, increasing 2.5 and 5.0 times, respectively. Diseases of the circulatory system predominated underlying causes of medical deaths (74 %). Non-drug suicide, transport accidents, and drownings constitute 54 % of external underlying causes.
