Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB.

BACKGROUND: Isoniazid (INH) is an important drug in many TB regimens, and unfavorable treatment outcomes can be caused by suboptimal pharmacokinetics. Dose adjustment can be personalized by measuring peak serum concentrations; however, the process involves cold-chain preservation and laboratory techniques such as liquid chromatography (LC)/mass spectrometry (MS), which are unavailable in many high-burden settings. Urine spectrophotometry could provide a low-cost alternative with simple sampling and quantification methods. METHODS: We enrolled 56 adult patients on treatment for active TB. Serum was collected at 0, 1, 2, 4, 6, and 8 h for measurement of INH concentrations using validated LC-MS/MS methods. Urine was collected at 0-4, 4-8, and 8-24 h intervals, with INH concentrations measured using colorimetric methods. RESULTS: The median peak serum concentration and total serum exposure over 24 h were 4.8 mg/L and 16.4 mg*hour/L, respectively. Area under the receiver operator characteristic curves for urine values predicting a subtherapeutic serum concentration (peak <3.0 mg/L) were as follows: 0-4 h interval (AUC 0.85, 95% CI 0.7-0.96), 0-8 h interval (AUC 0.85, 95% CI 0.71-0.96), and 0-24 h urine collection interval (AUC 0.84, 95% CI 0.68-0.96). CONCLUSION: Urine spectrophotometry may improve feasibility of personalized dosing in high TB burden regions but requires further study of target attainment following dose adjustment based on a urine threshold.

CONTEXTE: L'isoniazide (INH) est un médicament important dans de nombreux schémas thérapeutiques contre la TB, et des résultats thérapeutiques défavorables peuvent être dus à une pharmacocinétique sous-optimale. L'ajustement de la dose peut être personnalisé en mesurant les concentrations sériques maximales ; cependant, le processus implique la conservation de la chaîne du froid et des techniques de laboratoire telles que la chromatographie liquide (LC)/spectrométrie de masse (MS), qui ne sont pas disponibles dans de nombreuses régions à forte charge de morbidité. La spec-trophotométrie urinaire pourrait constituer une alternative peu coûteuse avec des méthodes d'échantillonnage et de quantification simples. MÉTHODES: Nous avons recruté 56 patients adultes sous traitement pour une TB active. Le sérum a été prélevé à 0, 1, 2, 4, 6 et 8 h pour mesurer les concentrations d'INH à l'aide de méthodes LC-MS/MS validées. L'urine a été prélevée à des intervalles de 0­4, 4­8 et 8­24 h, et les concentrations d'INH ont été mesurées à l'aide de méthodes colorimétriques. RÉSULTATS: La concentration sérique maximale médiane et l'exposition sérique totale sur 24 h étaient respectivement de 4,8 mg/L et de 16,4 mg*heure/L. L'aire sous les courbes caractéristiques de l'opérateur récepteur a été mesurée à l'aide de méthodes color-imétriques. Les aires sous les courbes caractéristiques des récepteurs pour les valeurs urinaires prédisant une concentration sérique sous-thérapeutique (pic <3,0 mg/L) étaient les suivantes : intervalle 0­4 h (AUC 0,85 ; IC 95% 0,7­0,96), intervalle 0­8 h (AUC 0,85 ; IC 95% 0,71­0,96), et intervalle de collecte d'urine 0­24 h (AUC 0,84 ; IC 95% 0,68­0,96). CONCLUSION: La spectrophotométrie urinaire peut améliorer la faisabilité d'un dosage personnalisé dans les régions à forte charge de TB, mais nécessite une étude plus approfondie de l'atteinte de la cible après l'ajustement de la dose sur la base d'un seuil urinaire.

Impact of COVID-19 pandemic on cross-country runners: changes in training, sleep, diet, and mental health.

Objective: Determine the impact of the COVID-19 pandemic on the changes in training, sleep, diet, and mental health of cross-country runners. Participants: Cross-country runners from NCAA Division II institutes. Methods: Wilcoxon signed-rank test was performed to analyze survey responses to ordinal questions on the survey while Spearman's rank correlation analysis (ρ) was used to calculate correlation between after the start of pandemic questions. Data was marked significant at p < 0.05. Results: Analysis of the survey responses revealed that cross-country runners were more likely to experience feelings of depression (p < 0.001), lack of motivation (p < 0.001), and higher daily stress (p < 0.001) after the start of the pandemic. After the start of the pandemic, runners running less days per week were more likely to report an increased feeling of depression (ρ=-0.315, p = 0.008) and lack of motivation (ρ=-0.458, p < 0.001). Conclusions: The present study underscores the importance of training, sleep, diet, and mental health amongst cross-country runners.

Cannabinoid-induced changes in the immune system: The role of microRNAs.

Naturally occurring cannabinoids have been used by humans for their medicinal benefits for over several millennia. While the use of cannabinoids has been strictly regulated in the past century, easing of state regulations has been associated with an increase in use of cannabinoids in the United States. The potential therapeutic applications of cannabinoids have been explored and the anti-inflammatory effect of cannabis-derived cannabinoids has been well-documented. The pharmacological effects of cannabinoids are governed by the modulation of cannabinoid receptors, CB1 and CB2, expressed in the central and peripheral tissues. Moreover, growing scientific evidence suggests that the cannabinoid-mediated changes in the immune system involves change in expression of microRNAs (miRNAs). MiRNAs are short non-coding, single-stranded RNA which have the ability to affect post-translational regulation of gene expression. Studies over the past decade have investigated the changes in expression of miRNAs following treatment of various components of the immune system with different chemical modulators of the cannabinoid receptors. Such studies have highlighted the key role played by various miRNAs in driving the observed immunomodulatory effects of cannabinoids. The aim of this review article, therefore, is to summarize the role of miRNAs behind the observed effects of cannabinoids on the overall immune system, rather than focusing on a single disease state.

Dynamic spatio-temporal patterns of metapopulation occupancy in patchy habitats.

Spatio-temporal dynamics in habitat suitability and connectivity among mosaics of heterogeneous wetlands are critical for biological diversity and species persistence in aquatic patchy landscapes. Despite the recognized importance of stochastic hydroclimatic forcing in driving wetlandscape hydrological dynamics, linking such effects to emergent dynamics of metapopulation poses significant challenges. To fill this gap, we propose here a dynamic stochastic patch occupancy model (SPOM), which links parsimonious hydrological and ecological models to simulate spatio-temporal patterns in species occupancy in wetlandscapes. Our work aims to place ecological studies of patchy habitats into a proper hydrologic and climatic framework to improve the knowledge about metapopulation shifts in response to climate-driven changes in wetlandscapes. We applied the dynamic version of the SPOM (D-SPOM) framework in two wetlandscapes in the US with contrasting landscape and climate properties. Our results illustrate that explicit consideration of the temporal dimension proposed in the D-SPOM is important to interpret local- and landscape-scale patterns of habitat suitability and metapopulation occupancy. Our analyses show that spatio-temporal dynamics of patch suitability and accessibility, driven by the stochasticity in hydroclimatic forcing, influence metapopulation occupancy and the topological metrics of the emergent wetlandscape dispersal network. D-SPOM simulations also reveal that the extinction risk in dynamic wetlandscapes is exacerbated by extended dry periods when suitable habitat decreases, hence limiting successful patch colonization and exacerbating metapopulation extinction risks. The proposed framework is not restricted only to wetland studies but could also be applied to examine metapopulation dynamics in other types of patchy habitats subjected to stochastic external disturbances.

Strong hydroclimatic controls on vulnerability to subsurface nitrate contamination across Europe.

Subsurface contamination due to excessive nutrient surpluses is a persistent and widespread problem in agricultural areas across Europe. The vulnerability of a particular location to pollution from reactive solutes, such as nitrate, is determined by the interplay between hydrologic transport and biogeochemical transformations. Current studies on the controls of subsurface vulnerability do not consider the transient behaviour of transport dynamics in the root zone. Here, using state-of-the-art hydrologic simulations driven by observed hydroclimatic forcing, we demonstrate the strong spatiotemporal heterogeneity of hydrologic transport dynamics and reveal that these dynamics are primarily controlled by the hydroclimatic gradient of the aridity index across Europe. Contrasting the space-time dynamics of transport times with reactive timescales of denitrification in soil indicate that ~75% of the cultivated areas across Europe are potentially vulnerable to nitrate leaching for at least one-third of the year. We find that neglecting the transient nature of transport and reaction timescale results in a great underestimation of the extent of vulnerable regions by almost 50%. Therefore, future vulnerability and risk assessment studies must account for the transient behaviour of transport and biogeochemical transformation processes.

A Cyclic Phosphoramidate Prodrug of 2'-Deoxy-2'-Fluoro-2'-C-Methylguanosine for the Treatment of Dengue Virus Infection.

Monophosphate prodrug analogs of 2'-deoxy-2'-fluoro-2'-C-methylguanosine have been reported as potent inhibitors of hepatitis C virus (HCV) RNA-dependent RNA polymerase. These prodrugs also display potent anti-dengue virus activities in cellular assays although their prodrug moieties were designed to produce high levels of triphosphate in the liver. Since peripheral blood mononuclear cells (PBMCs) are among the major targets of dengue virus, different prodrug moieties were designed to effectively deliver 2'-deoxy-2'-fluoro-2'-C-methylguanosine monophosphate prodrugs and their corresponding triphosphates into PBMCs after oral administration. We identified a cyclic phosphoramidate, prodrug 17, demonstrating well-balanced anti-dengue virus cellular activity and in vitro stability profiles. We further determined the PBMC concentration of active triphosphate needed to inhibit virus replication by 50% (TP50). Compound 17 was assessed in an AG129 mouse model and demonstrated 1.6- and 2.2-log viremia reductions at 100 and 300 mg/kg twice a day (BID), respectively. At 100 mg/kg BID, the terminal triphosphate concentration in PBMCs exceeded the TP50 value, demonstrating TP50 as the target exposure for efficacy. In dogs, oral administration of compound 17 resulted in high PBMC triphosphate levels, exceeding the TP50 at 10 mg/kg. Unfortunately, 2-week dog toxicity studies at 30, 100, and 300 mg/kg/day showed that "no observed adverse effect level" (NOAEL) could not be achieved due to pulmonary inflammation and hemorrhage. The preclinical safety results suspended further development of compound 17. Nevertheless, present work has proven the concept that an efficacious monophosphate nucleoside prodrug could be developed for the potential treatment of dengue virus infection.

Emergent dispersal networks in dynamic wetlandscapes.

The connectivity among distributed wetlands is critical for aquatic habitat integrity and to maintain metapopulation biodiversity. Here, we investigated the spatiotemporal fluctuations of wetlandscape connectivity driven by stochastic hydroclimatic forcing, conceptualizing wetlands as dynamic habitat nodes in dispersal networks. We hypothesized that spatiotemporal hydrologic variability influences the heterogeneity in wetland attributes (e.g., size and shape distributions) and wetland spatial organization (e.g., gap distances), in turn altering the variance of the dispersal network topology and the patterns of ecological connectivity. We tested our hypotheses by employing a DEM-based, depth-censoring approach to assess the eco-hydrological dynamics in a synthetically generated landscape and three representative wetlandscapes in the United States. Network topology was examined for two end-member connectivity measures: centroid-to-centroid (C2C), and perimeter-to-perimeter (P2P), representing the full range of within-patch habitat preferences. Exponentially tempered Pareto node-degree distributions well described the observed structural connectivity of both types of networks. High wetland clustering and attribute heterogeneity exacerbated the differences between C2C and P2P networks, with Pareto node-degree distributions emerging only for a limited range of P2P configuration. Wetlandscape network topology and dispersal strategies condition species survival and biodiversity.

Novel therapeutic agents for the treatment of diabetic kidney disease.

INTRODUCTION: Diabetic kidney disease (DKD) involves multifaceted pathophysiology which increases the risk of cardiorenal events and mortality. Conventional therapy is limited to renin-angiotensin aldosterone system inhibition and management of hyperglycemia and hypertension. Recent clinical trials have demonstrated promising nephroprotective effects of antihyperglycemic agents thus modifying guideline treatment recommendations for type 2 diabetic patients with chronic kidney disease. AREAS OF COVERED: Relevant studies and clinical trials were searched via PubMed and clinicaltrials.gov through August 2020. Authors offer an update on clinical evidence regarding nephroprotective effects and side effects of sodium-glucose-cotransporter-2 (SGLT2) inhibitors, glucagon-like-peptide-1 (GLP1) agonists and dipeptidylpeptidase-4 (DPP4) inhibitors. They discuss the potential benefits of novel therapy targeting DKD pathogenic processes including inflammation, oxidative stress, fibrosis, and vasoconstriction shown in early phases of clinical trials and offer an opinion on key challenges and directions for future progress. EXPERT OPINION: SGLT2 inhibitors are the most promising agents for DKD and improving cardiorenal outcomes. Mineralocorticoid-receptor antagonists and janus kinase inhibitors are also promising investigational therapies that target oxidative stress, nitric oxide synthesis, and inflammation. Novel therapeutic targets and the identification of clinically useful biomarkers may provide future therapies that detect early stages of DKD enabling a slower kidney function decline.

Author Correction: Global and regional trends of atmospheric sulfur.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Surveys of pharmacy students and pharmacy educators regarding medical marijuana.

INTRODUCTION: In this study, a cohort of Ohio pharmacy students were surveyed about knowledge and attitudes regarding medical marijuana (MMJ). Pharmacy educators in legalized states were asked how MMJ education was incorporated into pharmacy curricula. METHODS: Pharmacy students from six colleges were emailed surveys. Pharmacy educators from 79 colleges in states with legal MMJ programs were emailed regarding curricular content covering MMJ. RESULTS: A total of 319 student respondents received scores between 50 and 60% on knowledge-based questions. Students favored legalization of medical, but not recreational marijuana; they are not confident in ability to counsel; they believe little education on MMJ is provided in pharmacy school; and feel that more education is needed on MMJ. Students supporting MMJ were more likely to support recreational use of marijuana (p < 0.001), and education about MMJ (p < 0.001). Students in advanced years were less willing to dispense medical marijuana (p < 0.01), and less likely to support pharmacist availability for counseling (p < 0.05). Sixty-two percent of colleges who responded to the survey in legalized states provided education on MMJ to pharmacy students. Sixty-four percent of colleges responding who provided MMJ education offered a required course; 84.6% educated on indications and misuse/abuse; 92.3% on side effects, and adverse drug reactions; 53.8% on drug interactions. CONCLUSION: Ohio pharmacy student knowledge regarding medical marijuana is low. Students believe pharmacists should be available for counseling on MMJ; they feel unprepared to dispense MMJ, and would like more education on MMJ. Some colleges of pharmacy in the US report providing MMJ education; extent is unknown.

The structural, DC resistivity and magnetic properties of Zr and Co co-substituted Ni0.5Zn0.5Fe2O4.

The Zr and Co co-substituted Ni0.5Zn0.5Fe2O4 have been synthesized by sol-gel auto combustion method. The XRD patterns provide single phase cubic spinel with ( F d 3 ¯ m ( O h 7 )) space group and extra peaks found in XRD patterns from x = 0.24 to x = 0.4. The experimental lattice parameter is increased from 8.3995Å to 8.4129 Å and the theoretical lattice parameter is increased from 8.3948Å to 8.4130Å with increasing dopant concentration. The substitute ions in place of ferric ions cause the significant changes in all structural parameters. The D.C resistivity is increased from 126597 Ω-cm to 684229 Ω-cm and the drift mobility is decreased from 4.9×10-36 cm2/V-s to 1.88× 10-36cm2/V-s with increasing dopant concentration. The activation energy is decreased from 0.2108 eV to 0.0905 eV with increasing doping concentration. The saturation magnetization is decreased from 71.1559 emu/gm to 28.2405 emu/gm and the net magnetic moment is decreased from 6.3556 Bhor magnetons to 2.5523 Bhor magnetons with increasing dopant concentration. The Y-K angles are increased from 20.0723̊ to 59.4274̊ with increasing dopant concentration. The anisotropy constant has increased from 100 to 351 with increasing dopant concentration. The permeability is decreased from 117 to 19.4524 with increasing dopant concentration.

Design, synthesis, and biological evaluation of lipophilically modified bisphenol Z derivatives.

In the present study, a small library of bisphenol Z (BPZ) derivatives was synthesized and investigated for anti-proliferative effects in cultured breast and glioblastoma cell lines. Synthesized BPZ derivatives varied in molecular size, polarity, and lipophilicity. Of the 8 derivatives tested, compounds 4 and 6, both of which displayed the highest degree of lipophilicity, were most active at inducing cell death as determined by the XTT assay. Cell membranes were interrogated using trypan blue staining and were shown to remain intact during treatments with 4 and 6. Activation of caspase enzymes (3 and/or 7) was noted to occur following treatment with compound 4. Polar BPZ derivatives, those with a substituted amine or alcohol, were devoid of any inhibitory or proliferative effects. The remaining derivatives seem to lack sufficient lipophilicity to execute an overt toxic effect. Our results suggest that increasing the lipophilic character of BPZ enhances the cytotoxic effects.

Global and regional trends of atmospheric sulfur.

The profound changes in global SO2 emissions over the last decades have affected atmospheric composition on a regional and global scale with large impact on air quality, atmospheric deposition and the radiative forcing of sulfate aerosols. Reproduction of historical atmospheric pollution levels based on global aerosol models and emission changes is crucial to prove that such models are able to predict future scenarios. Here, we analyze consistency of trends in observations of sulfur components in air and precipitation from major regional networks and estimates from six different global aerosol models from 1990 until 2015. There are large interregional differences in the sulfur trends consistently captured by the models and observations, especially for North America and Europe. Europe had the largest reductions in sulfur emissions in the first part of the period while the highest reduction came later in North America and East Asia. The uncertainties in both the emissions and the representativity of the observations are larger in Asia. However, emissions from East Asia clearly increased from 2000 to 2005 followed by a decrease, while in India a steady increase over the whole period has been observed and modelled. The agreement between a bottom-up approach, which uses emissions and process-based chemical transport models, with independent observations gives an improved confidence in the understanding of the atmospheric sulfur budget.

Dispensing Naloxone Without a Prescription: Survey Evaluation of Ohio Pharmacists.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) reports a 200% escalation in the rate of opioid overdose deaths in the United States. Unfortunately, Ohio has been deemed the epicenter of the nation's opioid epidemic. In 2015, Ohio passed a bill that permits a pharmacist to distribute naloxone without a prescription. OBJECTIVES: This survey was aimed to discover pharmacists' knowledge of naloxone and Ohio law, perceived barriers that may prohibit naloxone dispensing, and Ohio pharmacists' general confidence, comfort, perception, and experience dispensing naloxone per physician protocol. METHODS: Pharmacists' knowledge of naloxone and Ohio law pertaining to dispensing naloxone; perceived barriers to naloxone distribution; and overall experience, willingness, comfort, and perceptions of personally supplying naloxone were assessed using multiple-choice and Likert-type scale questions through an e-mail survey. RESULTS: Overall, Ohio pharmacists were knowledgeable about naloxone and displayed confidence in their training and ability to provide patient education on naloxone. Pharmacists were less certain about Ohio law pertaining to naloxone distribution, especially those who have been in practice longer. Pharmacists indicated several barriers to dispensing naloxone and the need for more training. Younger pharmacists were more likely to report a concern with clientele who would frequent their pharmacy and moral and ethical concerns as barriers to dispensing naloxone. CONCLUSION: Additional educational programs should be delivered to Ohio pharmacists to inform them of the state law and policies. Continuing education programs that review substance abuse and attempt to reduce social stigma may assist with increasing naloxone distribution to those in need, especially, if directed toward younger pharmacists in Ohio.

The role of cytochrome P450 2E1 on ethanol-mediated oxidative stress and HIV replication in human monocyte-derived macrophages.

BACKGROUND: Alcohol consumption is considered to be a major health problem among people living with HIV/AIDS. Our previous reports have shown that ethanol reduced intracellular concentrations of antiretroviral drugs elvitegravir and darunavir in the HIV-1-infected U1 cell line. Ethanol also increased HIV-1 replication despite the presence of elvitegravir. Our previous finding has also shown that the levels of cytochrome P450 enzyme 2E1 (CYP2E1) and oxidative stress in blood monocytes were induced, while the concentration of alcohol in the plasma was reduced in HIV-1-infected alcohol users compared to uninfected alcohol users. However, the role of CYP2E1 in ethanol-enhanced oxidative stress and HIV-1 replication is still unclear. METHODS: This study examined the chronic effects (14 days) of ethanol on HIV viral load, oxidative DNA damage, expression of CYP2E1, expression of antioxidant enzymes (AOEs), expression of reactive oxygen species (ROS) in human monocyte-derived macrophages (MDM). Further, to evaluate the role of CYP2E1 in mediating ethanol-induced viral replication, CYP2E1 siRNA and CYP2E1 selective inhibitor were used in the HIV-1-infected U1 cell line following ethanol treatment. RESULTS: Chronic ethanol exposure demonstrated an increase in oxidative DNA damage and CYP2E1 expression in both non-infected and HIV-1-infected MDM. Our results showed that ethanol chronic exposure increased HIV-1 replication by ~3-fold in HIV-1-infected MDM. This ethanol-enhanced HIV-1 replication was associated with an increased oxidative DNA damage, an increased expression of CYP2E1, and a decreased expression of antioxidant enzyme PRDX6. In HIV-1-infected U1 cell line, we observed a decreased viral replication (~30%) and a decreased DNA damage (~100%) after repression of CYP2E1 by siRNA, upon ethanol exposure. We also observed a decreased viral replication (~25%) after inhibition of CYP2E1 by using selective CYP2E1 inhibitor. CONCLUSIONS: The data suggest that chronic ethanol exposure increases HIV-1 replication in MDM, at least in part, through CYP2E1-mediated oxidative stress. These results are clinically relevant to potentially find effective treatment strategies for HIV-1-infected alcohol users.

Spatial patterns of water quality impairments from point source nutrient loads in Germany's largest national River Basin (Weser River).

We employed the well-established Horton-Strahler, hierarchical, stream-order (ω) scheme to investigate scaling of nutrient loads (P and N) from ~845 wastewater treatment plants (WWTPs) distributed along the river network in urbanized Weser River, the largest national basin in Germany (~46K km2; ~8.4 million population). We estimated hydrologic and water quality impacts at the reach- and basin-scales, at two steady river discharge conditions (median flow, QR50; low-flow, QR90). Of the five WWTPs class-sizes (1 ≤ k ≤ 5), ~68% discharge to small low-order streams (ω < 3). We found large variations in capacity to dilute WWTP nutrient loads because of variability in (1) treated wastewater discharge (QU) within and among different class-sizes, and (2) river discharge (QR) within low-order streams (ω < 3) resulting from differences in drainage areas. For QR50, reach-scale water quality impairment assessed by nutrient concentration was likely at 136 (~16%) locations for P and 15 locations (~2%) for N. About 90% of these locations were lower-order streams (ω < 3). At QR50 and only with dilution, basin-scale cumulative nutrient loads from multiple upstream WWTPs increase impaired locations to 266 (~32% of total) for P. Considering in-stream uptake decreased P-impaired streams to 225 (~27%), suggesting the dominant role of dilution in the Weser River basin. Role of in-stream uptake diminished along the flow paths, while dilution in larger streams (4 ≤ ω ≤ 7) minimizes the impact of WWTP loads. Under QR90 conditions [(QR50/QR90) ~ 2.5], water quality impaired locations will likely double for the basin-scale analyses. Long-term water quality data suggested that diffuse sources are the primary contributors for water quality impairments in large streams. Our data-modeling synthesis approach is transferable to other urbanized river basins and extends understanding of point source impacts on water quality across spatial scales.

Peri-adolescent drinking of ethanol and/or nicotine modulates astroglial glutamate transporters and metabotropic glutamate receptor-1 in female alcohol-preferring rats.

Impairment in glutamate neurotransmission mediates the development of dependence upon nicotine (NIC) and ethanol (EtOH). Previous work indicates that continuous access to EtOH or phasic exposure to NIC reduces expression of the glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT) but not the glutamate/aspartate transporter (GLAST). Additionally, metabotropic glutamate receptors (mGluRs) expression was affected following exposure to EtOH or NIC. However, little is known about the effects of EtOH and NIC co-consumption on GLT-1, xCT, GLAST, and mGluR1 expression. In this study, peri-adolescent female alcohol preferring (P) rats were given binge-like access to water, sucrose (SUC), SUC-NIC, EtOH, or EtOH-NIC for four weeks. The present study determined the effects of these reinforcers on GLT-1, xCT, GLAST, and mGluR1 expression in the nucleus accumbens (NAc), hippocampus (HIP) and prefrontal cortex (PFC). GLT-1 and xCT expression were decreased in the NAc following both SUC-NIC and EtOH-NIC. In addition, only xCT expression was downregulated in the HIP in both of these latter groups. Also, glutathione peroxidase (GPx) activity in the HIP was reduced following SUC, SUC-NIC, EtOH, and EtOH-NIC consumption. Similar to previous work, GLAST expression was not altered in any brain region by any of the reinforcers. However, mGluR1 expression was increased in the NAc in the SUC-NIC, EtOH, and EtOH-NIC groups. These results indicate that peri-adolescent binge-like drinking of EtOH or SUC with or without NIC may exert differential effects on astroglial glutamate transporters and receptors. Our data further parallel some of the previous findings observed in adult rats.

Potential Role of Extracellular Vesicles in the Pathophysiology of Drug Addiction.

Extracellular vesicles (EVs) are small vesicles secreted by cells and are known to carry sub-cellular components including microRNA, proteins, and lipids. Due to their ability to transport cargo between cells, EVs have been identified as important regulators of various pathophysiological conditions and can therefore influence treatment outcomes. In particular, the significance of microRNAs in EV-mediated cell-cell communication is well-documented. While the influence of EVs and the cargo delivered by EVs has been extensively reviewed in other neurological disorders, the available literature on the potential role of EVs in the pathophysiology of drug addiction has not been reviewed. Hence, in this article, the known effects of commonly abused drugs (ethanol, nicotine, opiates, cocaine, and cannabinoids) on EV secretion have been reviewed. In addition, the potential role of drugs of abuse in affecting the delivery of EV-packaged microRNAs, and the subsequent impact on neuronal health and continued drug dependence, has been discussed.

Green synthesis and characterization of Ag nanoparticles from Mangifera indica leaves for dental restoration and antibacterial applications.

Green synthesis has gained a wide recognition as clean synthesis technique in the recent years. In the present investigation, silver nanoparticles were prepared by a novel green synthesis technique using Mangifera indica (Mango leaves) and found to be successfully used in dental applications. The prepared samples were spectroscopically characterized by XRD, PSA, SEM with EDS, and UV-Vis spectroscopy. The crystalline size and lattice strain were analyzed from the XRD data which were counter-verified by W-H plots and particle size analyzer. The XRD peaks revealed that average crystalline size of the as-synthesized Ag nanoparticles was of 32.4 nm with face-centered cubic structure. This was counter-verified by particle size analyzer and Williamson-Hall plots and found to be 31.7 and 33.21 nm in the former and latter, and the crystalline size of Ag NPs could be concluded as 32 ± 2 nm. The morphological structure of the prepared sample was studied through SEM images and the chemical composition was analyzed by the EDS data. The band energy was calculated as 393 nm from UV-Vis, which confirmed the synthesized sample as Ag nanoparticles. To improve the mechanical bonding and hardness of the dentally used glass ionomer cement (GIC), the synthesized silver nanoparticles were incorporated into GIC in 2% weight ratio. The morphology of the prepared specimens was studied using optical microscope images. Vickers microhardness and Monsanto hardness tests were performed on GIC, GIC reinforced with microsilver particles and GIC reinforced with nanosilver particles and the latter derived a promising results. The results of the Monsanto tests confirmed the increase in hardness of the GIC reinforced with AgNps as 14.2 kg/cm2 compared to conventional GIC and GIC reinforced with silver microparticle as 11.7 and 9.5 kg/cm2. Similarly the Vickers hardness results exhibited the enhanced hardness of GIC-reinforced AgNps as 82 VHN compared to GIC as 54 and GIC-reinforced silver microparticles as 61 VHN. The antibacterial activity of AgNPs was tested by a well-diffusion method on Escherichia coli and Staphylococcus aureus bacteria, and the obtained results exhibited a promising antibacterial activity of the as-synthesized nanoparticles.