Search

BackgroundIn U.S. states that legalized and commercialized recreational cannabis, cannabis sales in illegal markets are still sizable or even larger than those in legal markets. This study aimed to assess cannabis consumers' preferences for purchasing cannabis from legal and illegal markets and estimate the trade-offs under various policy scenarios.Methods963 adults were recruited, who used cannabis in the past year and lived in a state with recreational cannabis legalization. In a discrete choice experiment, participants chose purchasing cannabis from a legal dispensary or an illegal dealer with varying levels in product attributes including quality, safety, accessibility, potency, and price. Mixed logit models were used to analyze preferences.ResultsThe likelihood of choosing legal cannabis increased with a higher quality, the presence of lab test, a shorter distance to seller, a higher tetrahydrocannabinol level, and a lower price. The likelihood of choosing illegal cannabis increased with a higher quality, a shorter distance to seller, and a lower price. Among product attributes, quality and accessibility were perceived to be the most important for legal cannabis and price was perceived to be the most important for illegal cannabis. Policy simulations predicted that improving quality, ensuring safety, allowing delivery services, increasing dispensary density, and lowering prices/taxes of legal cannabis may reduce illegal cannabis market share.ConclusionsIn the U.S., cannabis consumers' preferences for illegal cannabis were associated with both legal and illegal cannabis product attributes. Policies regulating legal cannabis markets should consider potential spillover effects to illegal markets.

Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense and is invariably fatal unless treated. Current therapies present limitations in their application, parasite resistance, or require further clinical investigation for wider use. Our work, informed by previous findings, presents novel 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidine derivatives with promising antitrypanosomal activity. In particular, 32 exhibits an in vitro EC50 value of 0.5 µM against Trypanosoma brucei rhodesiense, and analogues 29, 30 and 33 show antitrypanosomal activities in the

OBJECTIVE: Multifocal motor neuropathy is a rare chronic immune-mediated neuropathy with impaired grip strength representing a common symptom. While intravenous immunoglobulin G is an effective treatment for the disease, significant variation in treatment response has been observed but not well understood. This analysis characterized dose-exposure-response relationships in multifocal motor neuropathy, using grip strength as a clinical efficacy measure. METHODS: Serum immunoglobulin G trough concentrations and grip strength data for the more affected hand from a Phase 3, randomized, double-blind, placebo-controlled, crossover trial of intravenous immunoglobulin 10% in 44 patients with multifocal motor neuropathy (NCT00666263) were used to develop a population pharmacokinetic-pharmacodynamic model. RESULTS: The model adequately described the observed pharmacokinetic and pharmacodynamic data and relationships between intravenous immunoglobulin 10% dose, serum immunoglobulin G trough levels, grip strength, and inter-patient variabilities in multifocal motor neuropathy. Model-based simulations for various dosing regimens (0.4-2.0 g/kg every 2-4 weeks) indicated that ≥1.6 g/kg/month would achieve clinically meaningful improvements in grip strength (≥4 kg) in ≥70% of patients. More frequent dosing at an equivalent monthly dose led to a more consistent response in grip strength. Furthermore, splitting the dose over multiple days for high doses (>1 g/kg) did not impact grip strength. INTERPRETATION: These findings suggest that the majority of patients with multifocal motor neuropathy would respond rapidly to intravenous immunoglobulin 10% with a range of dosing regimens. Shorter dosing intervals may avoid the diminishing response seen with longer dosing intervals. Dose-splitting provided similar outcomes while offering flexibility and convenience.

BACKGROUND: Amyloid beta protein (Aβ) is a treatment target in Alzheimers Disease (AD). Lowering production of its parent protein, APP, has benefits in preclinical models. Posiphen, an orally administered small molecule, binds to an iron-responsive element in APP mRNA and decreases translation of APP and Aβ. To augment human data for Posiphen, we evaluated safety, tolerability and pharmacokinetic and pharmacodynamic (PD) effects on Aβ metabolism using Stable Isotope Labeling Kinetic (SILK) analysis. METHODS: Double-blind phase 1b randomized ascending dose clinical trial, at five sites, under an IRB-approved protocol. Participants with mild cognitive impairment or mild AD (Early AD) confirmed by low CSF Aβ42/40 were randomized (within each dose arm) to Posiphen or placebo. Pretreatment assessment included lumbar puncture for CSF. Participants took Posiphen or placebo for 21-23 days, then underwent CSF catheter placement, intravenous infusion of 13C6-leucine, and CSF sampling for 36 h. Safety and tolerability were assessed through participant reports, EKG and laboratory tests. CSF SILK analysis measured Aβ40, 38 and 42 with immunoprecipitation-mass spectrometry. Baseline and day 21 CSF APP, Aβ and other biomarkers were measured with immunoassays. The Mini-Mental State Exam and ADAS-cog12 were given at baseline and day 21. RESULTS: From June 2017 to December 2021, 19 participants were enrolled, randomized within dose cohorts (5 active: 3 placebo) of 60 mg once/day and 60 mg twice/day; 1 participant was enrolled and completed 60 mg three times/day. 10 active drug and 5 placebo participants completed all study procedures. Posiphen was safe and well-tolerated. 8 participants had headaches related to CSF catheterization; 5 needed blood patches. Prespecified SILK analyses of Fractional Synthesis Rate (FSR) for CSF Aβ40 showed no significant overall or dose-dependent effects of Posiphen vs. placebo. Comprehensive multiparameter modeling of APP kinetics supported dose-dependent lowering of APP production by Posiphen. Cognitive measures and CSF biomarkers did not change significantly from baseline to 21 days in Posiphen vs. placebo groups. CONCLUSIONS: Posiphen was safe and well-tolerated in Early AD. A multicenter SILK study was feasible. Findings are limited by small sample size but provide additional supportive safety and PK data. Comprehensive modeling of biomarker dynamics using SILK data may reveal subtle drug effects. TRIAL REGISTRATION: NCT02925650 on clinicaltrials.gov (registered on 10-24-2016).

Developmental exposures to PCBs are implicated in the etiology of neurodevelopmental disorders (NDDs). This observation is concerning given the continued presence of PCBs in the human environment and the increasing incidence of NDDs. Previous studies reported that developmental exposure to legacy commercial PCB mixtures (Aroclors) or single PCB congeners found in Aroclors caused NDD-relevant behavioral phenotypes in animal models. However, the PCB congener profile in contemporary human samples is dissimilar to that of the legacy Aroclors, raising the question of whether human-relevant PCB mixtures similarly interfere with normal brain development. To address this question, we assessed the developmental neurotoxicity of the Fox River Mixture (FRM), which was designed to mimic the congener profile identified in fish from the PCB-contaminated Fox River that constitute a primary protein source in the diet of surrounding communities. Adult female C57BL/6 J mouse dams (8-10 weeks old) were exposed to vehicle (peanut oil) or FRM at 0.1, 1.0, or 6.0 mg/kg/d in their diet throughout gestation and lactation, and neurodevelopmental outcomes were assessed in their pups. Ultrasonic vocalizations (USVs) and measures of general development were quantified at postnatal day (P) 7, while performance in the spontaneous alternation task and the 3-chambered social approach/social novelty task was assessed on P35. Triiodothyronine (T3) and thyroxine (T4) were quantified in serum collected from the dams when pups were weaned and from pups on P28 and P35. Developmental exposure to FRM did not alter pup weight or body temperature on P7, but USVs were significantly decreased in litters exposed to FRM at 0.1 or 6.0 mg/kg/d in the maternal diet. FRM also impaired male and female pups' performance in the social novelty task. Compared to sex-matched vehicles, significantly decreased social novelty was observed in male and female pups in the 0.1 and 6.0 mg/kg/d dose groups. FRM did not alter performance in the spontaneous alternation or social approach tasks. FRM increased serum T3 levels but decreased serum T4 levels in P28 male pups in the 1.0 and 6.0 mg/kg/d dose groups. In P35 female pups and dams, serum T3 levels decreased in the 6.0 mg/kg/d dose group while T4 levels were not altered. Collectively, these findings suggest that FRM interferes with the development of social communication and social novelty, but not memory, supporting the hypothesis that contemporary PCB exposures pose a risk to the developing brain. FRM had sex, age, and dose-dependent effects on serum thyroid hormone levels that overlapped but did not perfectly align with the FRM effects on behavioral outcomes. These observations suggest that changes in thyroid hormone levels are not likely the major factor underlying the behavioral deficits observed in FRM-exposed animals.

OBJECTIVE: The purpose of this study was to determine the in vitro effects of a single exposure of bupivacaine on the mechanical properties of bovine cartilage explants at 3 weeks. DESIGN: Femoral condyle articular cartilage explants were aseptically harvested from juvenile bovine stifle joints before being exposed to chondrogenic medium containing 0.50% (wt/vol) bupivacaine, 0.25% (wt/vol) bupivacaine, or no medication (control) for 1 hour. Explants were then washed and maintained in culture in vitro for 3 weeks before testing. Cell viability, tensile and compressive mechanical properties, histological properties, and biochemical properties were then assessed. RESULTS: Explants exhibited a dose-dependent decrease in mean tensile Youngs modulus with increasing bupivacaine concentration (9.86 MPa in the controls, 6.48 MPa in the 0.25% bupivacaine group [P = 0.048], and 4.72 MPa in the 0.50% bupivacaine group [P = 0.005]). Consistent with these results, collagen content and collagen crosslinking decreased with bupivacaine exposure as measured by mass spectrometry. Compressive properties of the explants were unaffected by bupivacaine exposure. Explants also exhibited a trend toward dose-dependent decreases in viability (51.2% for the controls, 47.3% for the 0.25% bupivacaine-exposed group, and 37.0% for the 0.50% bupivacaine-exposed group [P = 0.072]). CONCLUSIONS: Three weeks after 1-hour bupivacaine exposure, the tensile properties of bovine cartilage explants were significantly decreased, while the compressive properties remained unaffected. These decreases in tensile properties corresponded with reductions in collagen content and crosslinking of collagen fibers. Physicians should be judicious regarding the intra-articular administration of bupivacaine in native joints.

In our paper, we encompass the topic of socioeconomic disparities intrinsic to drug pricing and look at ways to ensure that every individual in the United States can access antibiotics equally and equitably. In the United States, a multitude of individuals find themselves struggling with high, out-of-pocket costs for necessary antibiotics or medications.  These issues are generally caused by factors surrounding monopolistic drug markets, high costs for development, and the severity of disease that an individual is facing. We explore these challenges from a plethora of perspectives, such as; the role of specialty pharmacies, limited distribution networks, and the usage of psychotropic medications among youth with Autism Spectrum Disorders (ASD). High prices and restricted access of certain antibiotics for conditions like Hepatitis C highlight the systemic and intrinsic issues within the pharmaceutical industry and how it affects individuals who suffer from this disease or diseases similar to it. On a similar topic to that, ongoing shortages of ADHD medications continue to show the consistent and heavy impact of supply constraints amongst the pharmaceutical industry in the United States. We discuss potential solutions, including but not limited to, accelerating the approval of basic drugs, implementing ceiling prices to prevent high costs, and better integrating health-system specialty pharmacies. By concentrating on the need for policy reforms within the United States and collaboration amongst the various stakeholders that remain involved with drug pricing disparities, this study aims to offer a varied approach in reducing drug pricing disparities and making necessary medications accessible to every individual in the United States, regardless of socioeconomic or health status.

BACKGROUND: Reference to an intrinsic healing mechanism or an inner healer is commonplace amongst psychedelic drug-using cultures. The inner healer refers to the belief that psychedelic compounds, plants or concoctions have an intrinsically regenerative action on the mind and brain, analogous to intrinsic healing mechanisms within the physical body, for example, after sickness or injury. AIMS: Here, we sought to test and critique this idea by devising a single subjective rating item pertaining to perceived inner healing effects. METHODS: The item was issued to 59 patients after a single high (25 mg, n = 30) or placebo (1 mg, n = 29) dose of psilocybin in a double-blind randomised controlled trial of psilocybin for depression. RESULTS: Inner healer scores were higher after the high versus placebo dose of psilocybin (t = 3.88, p

This study demonstrates that changes in mindfulness predict subsequent changes in well-being in a data set including individuals who recently engaged in psychedelic use.

Methylphenidate (MPH) is highly efficacious in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Generally increased doses are found to result in better symptom control; however, it remains unclear whether this pattern can be observed at the individual level, given the large heterogeneity in individual dose-response relationships and observed placebo responses. A double-blind, randomized, placebo-controlled cross-over trial was used to compare weekly treatment with placebo and 5, 10, 15 and 20 mg of MPH twice daily on parent and teacher ratings of child ADHD symptoms and side effects. Participants were 5-13-year-old children with a DSM-5 diagnosis of ADHD (N = 45). MPH response was assessed at group and individual levels and predictors of individual dose-response curves were examined. Mixed model analysis showed positive linear dose-response curves at group level for parent and teacher rated ADHD symptoms and parent rated side effects, but not for teacher rated side effects. Teachers reported all dosages to improve ADHD symptoms compared to placebo, while parents only reported > 5 mg/dose as effective. At the individual level, most (73-88%) children, but not all, showed positive linear dose-response curves. Higher severity of hyperactive-impulsive symptoms and lower internalizing problems, lower weight, younger age and more positive opinions towards diagnosis and medication partly predicted steeper linear individual dose-response curves. Our study confirms that increased doses of MPH yield greater symptom control at a group level. However, large interindividual variation in the dose-response relationship was found and increased doses did not lead to greater symptom improvement for all children. This trial was registered in the Netherlands trial register (# NL8121).

Steven-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is a rare immunologic hypersensitivity reaction to stimuli that presents as widespread eruption with mucocutaneous detachment and involvement of other organs. Multiple causes have been noted in literature, including numerous medications. In this report, we present a 52-year-old woman who arrived at the emergency department with a complaint of rash, malaise, and pruritus. She subsequently developed diffuse cutaneous and mucosal detachment. Work-up supported a diagnosis of SJS/TEN secondary to her thyroid replacement therapy, derived from desiccated pig thyroid glands. The patient's natural thyroid medication was discontinued and she responded well to appropriate treatment. This case is unique in that thyroid replacement therapy is not a commonly reported trigger of SJS/TEN. Providers should be aware of the potential for natural thyroid and other animal-derived natural medications to cause adverse reactions such as SJS/TEN.

Objective Methods Results Conclusions This study examined prescription trends for benign prostatic hyperplasia (BPH) drug therapy in Japan over the past decade, focusing on drugs rated as grade A according to Japanese clinical guidelines.Using the National Database Open Data, this study analyzed prescription data from the fiscal years of 2014 to 2021, tracking α1‐blockers, 5α‐reductase inhibitors, and phosphodiesterase type 5 inhibitors. We adjusted for demographics and calculated medication costs to determine prescribing patterns and changes in drug utilization.Prescriptions for α1‐blockers increased from 9898 per 1000 males in 2014 to 12 613 in 2021. Prescriptions for 5α‐reductase inhibitors rose from 1441 per 1000 males in 2014 to 2310 in 2021. Tadalafil prescriptions saw a significant increase, from 900 in 2015 to 2520 in 2021. Despite these increases, the overall market size for BPH drugs decreased from 664 million dollars in 2014 to 279 million dollars in 2021, indicating a shift toward generic medications driven by healthcare policies.Although BPH medication prescriptions are increasing, driven by Japan's aging population and clinical guidelines, market dynamics are shifting owing to generic and government price adjustments. This analysis underscores the changing BPH treatment landscape in Japan, highlighting the importance of continuous evaluation of treatment efficacy and cost‐effectiveness in evolving healthcare policies and demographics. [ABSTRACT FROM AUTHOR]

Retinoic acid receptor B2 (RARẞ2) is an emerging therapeutic target for spinal cord injuries (SCIs) with a unique multimodal regenerative effect. We have developed a first-in-class RARẞ agonist drug, C286, that modulates neuron- glial pathways to induce functional recovery in a rodent model of sensory root avulsion. Here, using genome-wide and pathway enrichment analysis of avulsed rats' spinal cords, we show that C286 also influences the extracellular milieu (ECM). Protein expression studies showed that C286 upregulates tenascin-C, integrin-a9, and osteopontin in the injured cord. Similarly, C286 remodulates these ECM molecules, hampers inflammation and prevents tissue loss in a rodent model of spinal cord contusion C286. We further demonstrate C286's efficacy in human iPSC-derived neurons, with treatment resulting in a significant increase in neurite outgrowth. Additionally, we identify a putative efficacy biomarker, S100B, which plasma levels correlated with axonal regeneration in nerve- injured rats. We also found that other clinically available retinoids, that are not RARẞ specific agonists, did not lead to functional recovery in avulsed rats, demonstrating the requirement for RARẞ specific pathways in regeneration. In a Phase 1 trial, the single ascending dose (SAD) cohorts showed increases in expression of RARẞ2 in white blood cells correlative to increased doses and at the highest dose administered, the pharmacokinetics were similar to the rat proof of concept (POC) studies. Collectively, our data suggests that C286 signalling in neurite/axonal outgrowth is conserved between species and across nerve injuries. This warrants further clinical testing of C286 to ascertain POC in a broad spectrum of neurodegenerative conditions. [ABSTRACT FROM AUTHOR]

3D printing technologies confer an unparalleled degree of control over the material distribution on the structures they produce, which has led them to become an extremely attractive research topic in pharmaceutical dosage form development, especially for the design of personalized treatments. With fine tuning in material selection and careful design, these technologies allow to tailor not only the amount of drug administered but the biopharmaceutical behaviour of the dosage forms as well. While fused deposition modelling (FDM) is still the most studied 3D printing technology in this area, others are gaining more relevance, which has led to many new and exciting dosage forms developed during 2022 and 2023. Considering that these technologies, in time, will join the current manufacturing methods and with the ever-increasing knowledge on this topic, our review aims to explore the advantages and limitations of 3D printing technologies employed in the design and development of pharmaceutical oral dosage forms, giving special focus to the most important aspects governing the resulting drug release profiles. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Actualités Pharmaceutiques is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Human immunodeficiency virus (HIV) is no longer considered a contraindication for kidney transplantation (KT). KT management in HIV patients is a complex process with challenges, such as drug interactions between immunosuppression and antiretroviral (ARV) therapy. In our country, no KT has been performed thus far in this category of patients. We present the case of a 29-year-old female patient with HIV and end-stage renal disease (ESRD) who performed a KT from a related living donor in March 2022. KT immediate evolution was favorable. No transplant-related complications were reported. HIV viral load remained undetectable and CD4+ T cells were constantly > 500 cell/ μL, during the 18 months of follow-up. The main challenge in our case was the drug interaction between the protease inhibitor-based regimen and tacrolimus. This led to tacrolimus overdose, and, subsequently, change in ARV therapy. ARV switching was performed on a regimen based on integrase inhibitor and nucleoside reverse transcriptase inhibitors. After the ARV change, the therapeutic level of tacrolimus was easily reached and maintained. Kidney graft function remained normal during follow-up, despite tacrolimus overexposure, and no rejection or anti-HLA antibodies were observed. Another challenge was related to the donor's hepatitis C virus status (positive antibodies, negative nucleic acid test). The recipient did not develop seroconversion or detectable viremia at 3-, 6-, 12- and 18-months post-KT. We reported the first case of a successful KT in an ESRD patient with HIV in Romania, in whom the post-transplant evolution was favorable. [ABSTRACT FROM AUTHOR]

Background: Benzodiazepines are the preferred treatment for alcohol withdrawal. Phenobarbital is an alternative in the setting of prescriber expertise or benzodiazepine contraindication. Objective: To evaluate the efficacy and safety of a phenobarbital dosing strategy aimed at treating a spectrum of alcohol withdrawal symptoms across various patient populations. Methods: Retrospective review of patients admitted with concerns of alcohol withdrawal between May 2018 and November 2022. Patients were separated into a before-after cohort of lorazepam or phenobarbital. The primary outcome was hospital length of stay (LOS). Secondary outcomes were intensive care unit (ICU) LOS, escalation of respiratory support, increased level of care (LOC), and incidence of delirium tremens and/or seizures. Results: Two hundred and seventy-seven patients received lorazepam and 198 received phenobarbital. Hospital LOS was longer in the phenobarbital cohort compared with the lorazepam cohort (6.9 vs 9.3 days). There was no difference in ICU LOS. Level of care increases were fewer in the phenobarbital cohort (4 events vs 19 events). There were higher rates of non-invasive respiratory interventions in the lorazepam cohort and higher rates of mechanical ventilation in the phenobarbital cohort. Utilization of phenobarbital was attributed to a reduction in delirium tremens and seizures. Conclusion and Relevance: This study is novel because of the broad application of a phenobarbital order set across multiple levels of care and patient admission diagnoses. A risk targeted split load intravenous phenobarbital order set can safely be administered to patients with fewer escalations of care, seizures, delirium tremens, and respiratory care escalation. [ABSTRACT FROM AUTHOR]

Red fluorescent dyes are usually charged, lipophilic molecules with relatively high molecular weight, which tend to localize in specific intracellular locations, e. g., a cyanine dye Cy5 is biased towards mitochondria. They are often used as markers of biomolecules including nucleic acids and proteins. Since the molecular weight of the dyes is much smaller than that of the biomolecules, the labelling has a negligible effect on the properties of the biomolecules. In contrast, conjugation of the dyes to low molecular weight (pro)drugs can dramatically alter their properties. For example, conjugates of Cy5 with lysosome‐targeting aminoferrocenes accumulate in mitochondria and exhibit no intracellular effects characteristic for the parent (pro)drugs. Herein we tested several neutral and negatively charged dyes for labelling lysosome‐targeting aminoferrocenes 7 and 8 as well as a non‐targeted control 3. We found that a BODIPY derivative BDP‐TR exhibits the desired unbiased properties: the conjugation does not disturb the intracellular localization of the (pro)drugs, their mode of action, and cancer cell specificity. We used the conjugates to clarify the mechanism of action of the aminoferrocenes. In particular, we identified new intermediates, explained why lysosome‐targeting aminoferrocenes are more potent than their non‐targeted counterparts, and evaluated their distribution in vivo. [ABSTRACT FROM AUTHOR]

Background: Substance use disorders are a widely recognized problem among hepatitis C-infected patients; moreover, substance abuse by intravenous injection is a common mode of transmission of the hepatitis C virus worldwide. The frequency of substance use disorders and their relation to hepatitis C infection are still unknown in Iraq. This cross-sectional study, conducted among a sample of hepatitis C- infected patients attending the Gastrointestinal Tract Center in Baghdad Medical City, aimed to examine the prevalence of substance use disorders, the sociodemographic characteristics of the abusers, and the relation between intravenous drug abuse and hepatitis C virus infection. All participants were subjected to an Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) questionnaire and a data form to determine sociodemographic characteristics and hepatitis C virus-related risk factors. Results: In a total of 300 hepatitis C virus-infected patients, the prevalence of substance use disorders was 53.6%. Among these patients, 43.6% abused nicotine, 6% abused licit drugs, and 4% abused alcohol. No one reported illicit drug abuse. Intravenous drug abuse was rare, and there was no relationship found between intravenous drug abuse and hepatitis C infection. Cupping (23%) and blood transfusion (20.3%) were both significantly associated with hepatitis C transmission in this study (p > 0.001). Conclusion: This study revealed a high prevalence (53.6%) of substance abuse in this sample of hepatitis C-infected patients, with nicotine being the most commonly abused substance. However, there was no relationship between hepatitis C infection and intravenous drug abuse. Common risk factors that might contribute to hepatitis C transmission among this population include cupping and blood transfusion. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) constitutes an important contributor to fatalities. Coronavirus disease 2019 (COVID-19) frequently presents with complications such as respiratory distress, systemic inflammatory responses, and damage to various organs. Several studies have investigated the relationship between COVID-19 and mortality in patients with liver cancer, but there are few research on the relationship between them. This study is to explore the correlation between the two diseases and drugs treating them. Methods: The Gene Expression Omnibus (GEO) database provides gene datasets of COVID-19 patients and HCC patients. Through differential gene analysis and weighted gene co-expression network analysis, we determined 223 genes represented in HCC and COVID-19. We then used functional annotation, protein–protein interaction network construction, predictive model development and verification, prognostic value analysis, and miRNA–gene network construction. Besides, we created a drug–hub–gene network by predicting possible medications that interact with hub genes using the Drug–Gene Interaction Database (DGIdb). Ultimately, we applied immunohistochemistry to ascertain the hub genes expression. Results: This study revealed that eight core genes (RRM2, TPX2, DTL, CDT1, TYMS, CDCA5, CDC25C, and HJURP) co-existed in both HCC and COVID-19 and were differentially expressed in both HCC and normal tissues.CDC25C, RRM2, CDCA5, and HJURP had diagnostic value (AUC > 0.8) and prognostic value (adjusted P-value < 0.05). Genome enrichment analysis indicated that eight genes may function in liver cancer through engagement in the cell cycle, DNA replication, etc. In liver cancer samples, these genes were significantly and adversely associated with plasma cells while RRM2 was positively associated with neutrophil and NK cell activation and with dendritic cell resting. Using the miRNAnet database and DGIdb, 9 transcription factors, 7 miRNAs, and 51 drugs or molecular compounds were predicted to interact with the hub genes. Finally, RRM2 expression showed significant variation in clinical specimens, and analysis of the association of RRM2 with immunomodulators indicated that RRM2 was closely connected to MICB and CD276. Conclusions: Our study revealed several metabolic genes related to HCC and COVID-19. Moreover, potential drugs related to central genes were predicted. These findings may provide new ideas for treating COVID-19 and HCC. [ABSTRACT FROM AUTHOR]

Introduction: Prion diseases are deadly neurodegenerative disorders in both animals and humans, causing the destruction of neural tissue and inducing behavioral manifestations. Heat shock proteins (Hsps), act as molecular chaperones by supporting the appropriate folding of proteins and eliminating the misfolded proteins as well as playing a vital role in cell signaling transduction, cell cycle, and apoptosis control. SW02 is a potent activator of Hsp 70 kDa (Hsp70). Methods: In the current study, the protective effects of SW02 against prion protein 106-126 (PrP106-126)-induced neurotoxicity in human neuroblastoma cells (SH-SY5Y) were investigated. In addition, the therapeutic effects of SW02 in ME7 scrapie-infected mice were evaluated. Results: The results showed that SW02 treatment significantly increased Hsp70 mRNA expression levels and Hsp70 ATPase activity (p < 0.01). SW02 also significantly inhibited cytotoxicity and apoptosis induced by PrP106-126 (p < 0.01) and promoted neurite extension. In vivo, intraperitoneal administration of SW02 did not show a statistically significant difference in survival time (p = 0.16); however, the SW02-treated group exhibited a longer survival time of 223.6 ± 6.0 days compared with the untreated control group survival time of 217.6 ± 5.4 days. In addition, SW02 reduced the PrPSc accumulation in ME7 scrapie-infected mice at 5 months post-injection (p < 0.05). A significant difference was not observed in GFAP expression, an astrocyte marker, between the treated and untreated groups. Conclusion: In conclusion, the potential therapeutic role of the Hsp70 activator SW02 was determined in the present study and may be a novel and effective drug to mitigate the pathologies of prion diseases and other neurodegenerative diseases. Further studies using a combination of two pharmacological activators of Hsp70 are required to maximize the effectiveness of each intervention. [ABSTRACT FROM AUTHOR]

Ferroptosis is a nonapoptotic form of cell death characterized by iron dependence and lipid peroxidation. Ferroptosis is involved in a range of pathological processes, such as cancer. Many studies have confirmed that ferroptosis plays an essential role in inhibiting cancer cell proliferation. In addition, a series of small-molecule compounds have been developed, including erastin, RSL3, and FIN56, which can be used as ferroptosis inducers. The combination of ferroptosis inducers with anticancer drugs can produce a significant synergistic effect in cancer treatment, and patients treated with these combinations exhibit a better prognosis than patients receiving traditional therapy. Therefore, a thorough understanding of the roles of ferroptosis in cancer is of great significance for the treatment of cancer. This review mainly elaborates the molecular biological characteristics and mechanism of ferroptosis, summarizes the function of ferroptosis in cancer development and treatment, illustrates the application of ferroptosis in patient's prognosis prediction and drug discovery, and discusses the prospects of targeting ferroptosis. [ABSTRACT FROM AUTHOR]

Oxytetracycline impregnated XAD-4 resin was prepared and then used for the online preconcentration of zirconium (IV) from aqueous solution. HCl was used for the elution of zirconium from the complex retained on XAD-4 resin. Arsenazo-III solution was used as chromogenic reagent for the spectrophotometric determination of eluted zirconium (IV) ions. The developed system showed greater sensitivity and selectivity as compared to many reported methods. The current study achieved a detection limit of 0.47 and 0.10 µgL−1, preconcentration factor of 52 and 247 and sample throughput of 40 and 10 samples per hour for concentration range from 10 to 60 µg L−1 (60s preconcentration time) and from 2 to 12 µgL−1 (300s preconcentration time) respectively. The method was successfully applied for the determination of Zirconium (IV) from spiked water and IAEA-soil sample. [ABSTRACT FROM AUTHOR]

Objective This study aimed to describe our experience with universal urine drug screening (UDS) with rapid confirmation (RC) via liquid chromatography mass spectrometry (LC-MS) before infant's discharge, in efforts to increase detection of neonates at risk of neonatal opioid withdrawal syndrome (NOWS) while reducing patient burden related to false positive results. Study Design Two-phase retrospective study of all pregnant women admitted to our labor and delivery (L&D) unit before (phase 1, April 2018–March 2019) and after (phase 2, October 2019–September 2020) RC of UDS was initiated. Urine samples were obtained on admission and screened for drugs using an enzyme immunoassay with positive results reflexed to confirmation via LC-MS. The turnaround time for LC-MS was 1 week in phase 1 and 24 hours in phase 2. For mothers with positive LC-MS confirmation, the infant's meconium was sent for drug screening. Positive results were determined to be true or false positive based on urinary LC-MS results. The primary outcome was the rate of opioid-positive mothers who were unanticipated. The secondary outcome was the difference in rate of neonates who were observed for NOWS, before and after implementation of RC with LC-MS. Results In phase 2, a total of 2,395 deliveries occurred of which 2,122 (88.6%) had available UDS results. Fifty-two (2.5%) women had a positive UDS for at least one drug with LC-MS confirmation. Of those, 25 were true positive and 27 were false positive. Twenty-one (84%) true positive mothers were taking opioids and 8 (37%) of them were unanticipated positives. Among mothers with positive UDS for opioids, the neonatal observation rate for development of NOWS was 100% (22/22) and 48% (21/44) before and after implementation of LC-MS RC, respectively. Conclusion Universal UDS and LC-MS RC in L&D may improve detection of unanticipated positive mothers whose infants are at risk of NOWS. RC of positive results allows intervention only for confirmed cases. Key Points Universal UDS can detect more infants at risk of NOWS. Rapid confirmation of positive UDS reduces burden. Only confirmed infants should be observed in the neonatal intensive care unit. Child Protective Services should only be notified of confirmed opioid-positive results. [ABSTRACT FROM AUTHOR]

High dropout rates, particularly among intimate partner violence (IPV) perpetrators with alcohol and other drug use problems (ADUPs), challenge IPV perpetrator programs' effectiveness. This study sought to examine factors associated with goal setting, a motivational strategy to promote engagement, in a sample of IPV perpetrators (n = 285), including participants with ADUPs (n = 127) and investigated whether goal setting predicted lower dropout by adjusting for relevant variables. Results revealed goal setting could be an effective strategy to reduce dropout in IPV perpetrators and those with ADUPs and support the need to tailor interventions to participants' needs to enhance effectiveness. [ABSTRACT FROM AUTHOR]

Background: Ophiopogon D is an important natural organic compound in Ophiopogon japonicus, which often has significant biological activity. Purpose: The purpose of this review is to systemically summarize and discuss the pharmacological activity and underlying mechanisms of OP-D in recent years. Method: PubMed and Web of Science were searched with the keywords: "Ophiopogon japonicus", "Ophiopogon D" "pharmacology", and "pharmacokinetics". There was no restriction on the publication year, and the last search was conducted on 1 Jan 2024. Results: Emerging evidence suggests that OP-D possess numerous pharmacological activities, including bone protection, cardiovascular protection, immune regulation, anti-cancer, anti-atherosclerosis, antiinflammatory and anti-NAFLD. Conclusion: OP-D has a potential value in the prevention and treatment of many diseases. We hope that this review will contribute to therapeutic development and future studies of OP-D. [ABSTRACT FROM AUTHOR]

Copyright of Mediterranean Nursing & Midwifery is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Drug‐associated acute kidney injury (D‐AKI) constitutes approximately 19%–26% of all acute kidney injury (AKI) cases in hospitalized patients. Notably, there is often a deficiency in optimal drug management after D‐AKI diagnosis, with only about half of the patients experiencing discontinuation of nephrotoxins and one‐fifth avoiding further nephrotoxin administration. Nephrotoxin stewardship involves the application of coordinated care management strategies to ensure the safe utilization of nephrotoxins and renally eliminated medications. The purpose of this paper is to review nephrotoxin stewardship strategies and highlight contemporary considerations for estimating kidney function and the use of novel biomarkers as part of the stewardship program. The Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) 2021 serum creatinine formula is now recommended for estimating kidney function for adults in most clinical situations in the United States. It is time to reevaluate how healthcare professionals think of estimating kidney function for drug dosing with the use of the non‐indexed, race‐free, CKDEPI 2021 equation. In addition, widespread use of serum cystatin C (CysC) is anticipated so estimated glomerular filtration rate equations that incorporate serum CysC will need to be further evaluated for drug dosing recommendations and how the use of serum CysC can complement serum creatinine‐based equations. Lastly, novel kidney stress/damage biomarkers should be viewed as a piece of a complex scenario of D‐AKI prediction, diagnosis, and prognosis and should be interpreted along with other diagnostic criteria in relation to the clinical condition of the patient. These contemporary considerations for drug dosing and D‐AKI management are important components of nephrotoxin stewardship. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is still the second leading cause of cancer-related deaths and thus biomarkers allowing prediction of the resistance of patients to therapy and estimating their prognosis are needed. We designed a panel of 558 genes with pharmacogenomics records related to 5-fluorouracil resistance, genes important for sensitivity to other frequently used drugs, major oncodrivers, and actionable genes. We performed a target enrichment sequencing of DNA from tumors and matched blood samples of patients, and compared the results with patient prognosis stratified by systemic adjuvant chemotherapy. Results: The median number of detected variants per tumor sample was 18.5 with 4 classified as having a high predicted functional effect and 14.5 moderate effect. APC, TP53, and KRAS were the most frequent mutated genes (64%, 59%, and 42% of mutated samples, respectively) followed by FAT4 (23%), FBXW7, and PIK3CA (16% for both). Patients with advanced stage III had more frequently APC, TP53, or KRAS mutations than those in stages I or II. KRAS mutation counts followed an increasing trend with grade (G1 < G2 < G3). The response to adjuvant therapy was worse in carriers of frameshift mutations in APC or 12D variant in KRAS, but none of these oncodrivers had prognostic value. Carriage of somatic mutations in any of the genes ABCA13, ANK2, COL7A1, NAV3, or UNC80 had prognostic relevance for worse overall survival (OS) of all patients. In contrast, mutations in FLG, GLI3, or UNC80 were prognostic in the same direction for patients untreated, and mutations in COL6A3, LRP1B, NAV3, RYR1, RYR3, TCHH, or TENM4 for patients treated with adjuvant therapy. The first association was externally validated. From all germline variants with high or moderate predicted functional effects (median 326 per patient), > 5% frequency and positive Manhattan plot based on 3-year RFS, rs72753407 in NFACS, rs34621071 in ERBB4, and rs2444274 in RIF1 were significantly associated with RFS, OS or both. Conclusions: The present study identified several putative somatic and germline genetic events with prognostic potential for colorectal cancer that should undergo functional characterization. [ABSTRACT FROM AUTHOR]

Background: Amorphous calcium carbonate (ACC) is a potential new treatment for canine osteoarthritis (OA) with novel mechanisms based on local pH modulation and targeting bone remodeling, inflammation, and pain. The aim of this pilot exploratory clinical study was to obtain initial data on the potential efficacy and safety of ACC in OA dogs and to determine if further investigation was appropriate using similar assessment methods. Materials and methods: In this prospective, randomized, double-blind, controlled pilot study, 41 client-owned dogs were allocated in a 2:1 ratio to ACC: placebo given orally for 56 days. Efficacy assessments included improvements in pain and mobility using owner questionnaires [Canine Brief Pain Inventory (CBPI), Client Specific Outcome Measure (CSOM), and Veterinary Orthopedic Scores (VOS)]. Safety in the study population was monitored by veterinary examinations, clinical pathology, and adverse events. Results: Fifty-three dogs were screened, of which 41 enrolled and served for the safety assessment. Thirty-six dogs were found evaluable for initial efficacy assessment. Three dogs given placebo (21.4%) and one given ACC (4.5%) were removed before day 56 due to owner-perceived pain and were considered treatment failures. There were no serious adverse events or clinically significant treatment-related effects in the study. Overall, ACC was found safe in the small study population. On day 56, proportionally more ACC than placebo dogs were treatment successes based on CBPI (45.5% vs. 21.4%) and CSOM (63.6% vs. 30.8%, respectively); however, these differences were not statistically significant (p = 0.15 and 0.06, respectively). On day 56, within the ACC group but not the placebo group, the CBPI, CSOM, and VOS assessments were lower compared to day 0 and day 14 (p < 0.05). Limitations: The relatively small number of dogs limited the statistical power of the pilot study in evaluating the efficacy and safety of ACC. Conclusion: Study results support the conduct of larger, appropriately powered studies using similar assessments to confirm whether ACC may be a safe and effective treatment for OA in dogs. [ABSTRACT FROM AUTHOR]

The global impact of drug shortages on healthcare systems is a concerning issue that needs urgent attention. These shortages not only jeopardize patient care, public health, and healthcare delivery but also pose distinct challenges for pediatric populations due to their specific medication requirements and vulnerabilities. It is imperative to address this issue to safeguard the health and wellbeing of this specific age group. This review Gaimed to conduct a systematic analysis of strategies for addressing drug shortages in pediatric care from 2014 to 2024. The search included five databases: PubMed, Reaxys, Embase, Scopus, and Science Direct, using the keywords "drug shortage" and "pediatric". The final protocol was developed following the guidelines outlined in the " The PRISMA 2020 statement: An updated guideline for reporting systematic reviews". In total, 234 publications were identified. After screening the search results and applying inclusion and exclusion measures, a total of 27 original research papers were included. The primary finding indicates that a comprehensive approach rooted in risk management can significantly mitigate drug shortages in pediatric settings. This approach should address underlying causes such as manufacturer and delivery challenges and focus on prevention through enhanced forecasting and vigilant shortage monitoring. The most prevalent response involved seeking alternative treatment options. It is imperative to implement institutional and national guidelines, foster communication, and provider education, and minimize waste to effectively mitigate drug shortages in pediatric settings. [ABSTRACT FROM AUTHOR]

Background: Many national studies fail to account for discordance between sexual orientation dimensions (e.g. a mismatch between sexual identity and sexual attraction) or sexual identity fluidity (e.g. changes in sexual identity over time). Objective: To examine the longitudinal relationships among sexual identity fluidity/stability, sexual orientation discordance/concordance, and alcohol and other drug use disorder symptoms. Methods: The study used nationally representative longitudinal data from Waves 1–5 (2013–2019) of the Population Assessment of Tobacco and Health (PATH) study of US adolescents and adults (N = 24,591). Results: Substance use disorder symptoms were most prevalent (45.8%) among bisexual-stable females relative to all other sexual identity subgroups. The adjusted odds ratios (AORs) of substance use disorder symptoms were significantly higher among bisexual-stable females vs. heterosexual-stable females in all models (AOR range: 1.94–2.32), while no such associations were found for males. Sexual identity-attraction discordant females had significantly greater AORs (17/20 instances) of substance use disorder symptoms compared to concordant females; this finding was not as consistent for males (6/20 instances). Conclusion: Sexual orientation discordance was significantly associated with substance use disorder symptoms, especially among females discordant in their sexual identity and attraction. Bisexual-stable and discordant females are at highest risk of developing symptomatic substance use; it is vital that they receive screening, no matter where they are in their coming out process. This study highlights pitfalls of relying solely on cross-sectional data using a single sexual orientation dimension to understand the relationship between sexual orientation and substance use disorder. [ABSTRACT FROM AUTHOR]

A sensitive, easy, and low-cost method used in the determination of pure forms of losartan and mebeverine hydrochloride, also in pharmaceutical preparations with derivative spectrometry using UV-Vis technology. This method depends on measuring the first derivative of the spectrum using zero cross, peak to base line, and peak area. The linear range of concentrations used was equal to 2–14 ppm for losartan, whereas for mebeverine hydrochloride it was equal to 2–16 ppm in a mixture. For losartan, in the presence of mebeverine hydrochloride, 12 ppm by utilizing peak to baseline correlation coefficients 0.9984, 0.9994, and peak area 0.9972, whereas for mebeverine hydrochloride in the presence of losartan, 12 ppm by utilizing peak to fundamental correlation coefficients 0.9952, 0.9966, 0.9957, and peak area 0.9970, 0.9971, 0.9968, 0.9971. The limit of detection for each drug, losartan and mebeverine hydrochloride, is equal to 0.0113 ppm. The accuracy and precision of the method were estimated by calculating relative standard deviation (%RSD) values less than 3% while maintaining a recovery percentage of acceptable value. The proposed method proved effective and efficient at estimating both losartan and mebeverine hydrochloride, in the presence of the other in a mixture of the two without interference, despite the closeness of their spectral absorption peaks. There are no other more accurate methods for estimating the two in a mixture than the proposed method. The proposed method is considered one of the most direct and economical methods that do not require reagents or additional materials for conducting reactions and studying the optimal conditions for those interactions. Thus, it is considered one of the green chemistry techniques that reduce the use of chemicals and reagents in the process of estimating these drugs in a mixture and in a shorter period of time. The proposed method can be used to estimate the different properties in a mixture of the two compounds whose absorption spectra are close. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a condition that affects the nervous system and that requires considerably more in-depth study. Abnormal Nicotinamide Adenine Dinucleotide (NAD+) metabolism and disulfide levels have been demonstrated in AD. This study investigated novel hub genes for disulfide levels and NAD+ metabolism in relation to the diagnosis and therapy of AD. Methods: Data from the gene expression omnibus (GEO) database were analyzed. Hub genes related to disulfide levels, NAD+ metabolism, and AD were identified from overlapping genes for differentially expressed genes (DEGs), genes in the NAD+ metabolism or disulfide gene sets, and module genes obtained by weighted gene co-expression network analysis (WGCNA). Pathway analysis of these hub genes was performed by Gene Set Enrichment Analysis (GSEA). A diagnostic model for AD was constructed based on the expression level of hub genes in brain samples. CIBERSORT was used to evaluate immune cell infiltration and immune factors correlating with hub gene expression. The DrugBank database was also used to identify drugs that target the hub genes. Results: We identified 3 hub genes related to disulfide levels in AD and 9 related to NAD+ metabolism in AD. Pathway analysis indicated these 12 genes were correlated with AD. Stepwise regression analysis revealed the area under the curve (AUC) for the predictive model based on the expression of these 12 hub genes in brain tissue was 0.935, indicating good diagnostic performance. Additionally, analysis of immune cell infiltration showed the hub genes played an important role in AD immunity. Finally, 33 drugs targeting 10 hub genes were identified using the DrugBank database. Some of these have been clinically approved and may be useful for AD therapy. Conclusion: Hub genes related to disulfide levels and NAD+ metabolism are promising biomarkers for the diagnosis of AD. These genes may contribute to a better understanding of the pathogenesis of AD, as well as to improved drug therapy. [ABSTRACT FROM AUTHOR]

Background: There are current clinical observations that atorvastatin may promote subdural hematoma resorption. We aimed to assess the causal effects of lipid-lowering agents 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors, Proproteinconvertase subtilisin/kexin type 9 (PCSK9) inhibitors and Niemann-Pick C1-like protein 1 (NPC1L1) inhibitors on traumatic subdural hematomas. Methods: We used genetic instruments to proxy lipid-lowering drug exposure, with genetic instruments being genetic variants within or near low-density lipoprotein (LDL cholesterol)-associated drug target genes. These were analyzed by using a two-sample Mendelian randomization (MR) study. Results: A causal relationship was found between HMGCR inhibitors and traumatic subdural hematoma (Inverse variance weighted (β = -0.7593341 (Odds Ratio (OR) = 0.4679779), p = 0.008366947<0.05)). However, no causal relationship was found between PCSK9 inhibitors and NPC1L1 inhibitors and traumatic subdural hematoma (PCSK9 inhibitors: Inverse variance weighted (β = 0.23897796 (OR = 1.2699505), p = 0.1126327), NPC1L1 inhibitors: Inverse variance weighted (β = -0.02118558 (OR = 0.9790373), p = 0.9701686)). Sensitivity analysis of the data revealed good stability of the results. Conclusions: This two-sample MR study suggests a potential causal relationship between HMGCR inhibition (atorvastatin) and traumatic subdural hemorrhage. [ABSTRACT FROM AUTHOR]

The drug addiction problem in Vietnam is becoming increasingly complicated, especially for the group of addicts using Amphetamine-Type Stimulants (ATS). The trading market and ATS user increase quickly with an estimated 36 million people using ATS globally. Long-term use of ATS may have unwanted psychological effects such as mood changes, depression, paranoia, hallucinations, insomnia, and anxiety. From there, are unwanted behaviors such as violence and aggression. The use of ATS also has caused many negative effects for families, communities, and society. The current problem is that these narcotics and psychotropic substances have very serious effects on the brain. Many deaths caused by psychotropic drugs also stem from the abuse of these toxins. It is also a challenge because the intervention of Methadone, which is an effective treatment for heroin users, is not effective with ATS users. Very concerned about this issue, in 2019, Vietnam issued the guidelines for intervention on drug abuse in the form of ATS including social and psychological intervention. It is a comprehensive approach with the expectation of more effective intervention and support for ATS users. The study used psychological and social experimental study for 45 ATS users in 3 ATS treatment clinics in Hanoi and Haiphong-Vietnam. The results showed that psychological and social intervention has brought positive effects for ATS users, both in terms of reducing ATS use as well as having positive results on mental health problems. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Intraneuronal inclusions composed of tau protein are found in Alzheimer's disease (AD) and other tauopathies. Tau normally binds microtubules (MTs), and its disengagement from MTs and misfolding in AD is thought to result in MT abnormalities. We previously identified triazolopyrimidine‐containing MT‐stabilizing compounds that provided benefit in AD mouse models and herein describe the characterization and efficacy testing of an optimized candidate, CNDR‐51997. METHODS: CNDR‐51997 underwent pharmacokinetic, pharmacodynamic, safety pharmacology, and mouse tolerability testing. In addition, the compound was examined for efficacy in 5XFAD amyloid beta (Aβ) plaque mice and PS19 tauopathy mice. RESULTS: CNDR‐51997 significantly reduced Aβ plaques in 5XFAD mice and tau pathology in PS19 mice, with the latter also showing attenuated axonal dystrophy and gliosis. CNDR‐51997 was well tolerated at doses that exceeded efficacy doses, with a good safety pharmacology profile. DISCUSSION: CNDR‐51997 may be a candidate for advancement as a potential therapeutic agent for AD and/or other tauopathies. Highlights: There is evidence of microtubule alterations (MT) in Alzheimer's disease (AD) brain and in mouse models of AD pathology.Intermittent dosing with an optimized, brain‐penetrant MT‐stabilizing small‐molecule, CNDR‐51997, reduced both Aβ plaque and tau inclusion pathology in established mouse models of AD.CNDR‐51997 attenuated axonal dystrophy and gliosis in a tauopathy mouse model, with a strong trend toward reduced hippocampal neuron loss.CNDR‐51997 is well tolerated in mice at doses that are meaningfully greater than required for efficacy in AD mouse models, and the compound has a good safety pharmacology profile. [ABSTRACT FROM AUTHOR]

Fungi cause diseases in a variety of marine animal hosts. The need for new antifungal agents arises from the rising prevalence of invasive fungal infections (IFI) and the ineffectiveness, severe side effects, and high mortality of the current antifungal agents. The present study aims to assess Caulerpa scalpelliformis seaweed extract's antifungal efficacy against human fungal infections. Using methanol solvents, the antifungal activity of marine macroalgae C.scalpelliformis was assessed against Candida albicans, Aspergillus fumigatus, Aspergillus niger, Aspergillus flavus, and Cryptococcus neoformans. C. scalpelliformis showed strong fungal activity against A. fumigatus, A. niger, and A. flavus compared to C. albicans and C. neoformans, similar to the positive control drug Amphotericin B in the current study.This is the first report from Tuticorin's Periyathalai coast. These results point to the use of green seaweed, C. scalpelliformis methanol extract as a natural antibiotic in conjunction with synthetic antibiotics, which has paved the way for the development of new anti-aspergillus, anti-cryptococcal, and anti-candidal compounds. [ABSTRACT FROM AUTHOR]

The current 2019–2021 marine pharmacology literature review provides a continuation of previous reviews covering the period 1998 to 2018. Preclinical marine pharmacology research during 2019–2021 was published by researchers in 42 countries and contributed novel mechanism-of-action pharmacology for 171 structurally characterized marine compounds. The peer-reviewed marine natural product pharmacology literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral mechanism-of-action studies for 49 compounds, 87 compounds with antidiabetic and anti-inflammatory activities that also affected the immune and nervous system, while another group of 51 compounds demonstrated novel miscellaneous mechanisms of action, which upon further investigation, may contribute to several pharmacological classes. Thus, in 2019–2021, a very active preclinical marine natural product pharmacology pipeline provided novel mechanisms of action as well as new lead chemistry for the clinical marine pharmaceutical pipeline targeting the therapy of several disease categories. [ABSTRACT FROM AUTHOR]

The field of electrochemistry at the interface between two immiscible electrolyte solutions (ITIES) has been continuously expanding over the years due to their vast number of applications, including to investigate the partitioning of ionizable drugs at liquid‐liquid systems. The aim of this Review is to highlight the great potential of ITIES as simple model of biological membranes to gather information on drug partition, lipophilicity, and pharmacokinetics that can be very useful for researchers in the field of drug discovery for development of new drugs with enhanced permeability. Relevant contributions and perspectives to improve the applicability of ITIES in partition studies were highlighted and discussed. The second part of this Review pretends to highlight the application of electrochemistry at the ITIES as experimental technique to investigate interactions between small ligands, including drugs, and DNA, a topic of high research interest in pharmaceutical and biological sciences, which remains with lots of opportunities to explore. [ABSTRACT FROM AUTHOR]

Copyright of Baghdad Science Journal is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

• Doxycycline was more toxic, than norfloxacin on tested aquatic organisms: plants and crustaceans. • The effect concentration (EC 20) of doxycycline reduced by 20 % growth of L. minor was more than twice lower than for norfloxacin. • The leaf chlorophyll content was an early and sensitive indicator of the phytoxic effects of doxycycline in L. minor , before morphological changes were observed. • The effect concentration (EC 20 in 180. min) of doxycycline immobilizing of daphnia by 20 % was almost twice lower as for norfloxacin. The main reason for the appearance of pharmaceutical compounds in the aquatic environment is their regular excretion by humans and animals in an unchanged form or slightly metabolized. Pharmaceuticals limit the habitable living environment for aquatic organisms, because they can be toxic not only to bacteria but also to non-target organisms. Plants of the Lemnoideae subfamily and crustaceans Daphniindae family are widely used as bioindicators in freshwater environmental risk assessments. This study aimed to use biotests (Lemna test and Daphtoxkit) to determine the effect of two pharmaceuticals: antibiotic – Doxycycline (DOX) and semi-synthetic chemotherapeutic drug – Norfloxacin (NOR) on plants Lemna minor and crustaceans Daphnia magna. Standard Lemna test was extended to include pharmaceutical effects on plant chlorophyll content (LCC) and fluorescence (Fo, Fm, and Fv/Fm), and the confirmation of drug toxicity was the biotest Daphtoxkit assessing the immobilization (IM) of organisms. Studies have shown that DOX was more toxic than NOR on tested aquatic organisms: plants and crustaceans. The lowest observed effect concentration (EC 20) of DOX and NOR reduced by 20 % LCC and Iy of L. minor was 2.14 and 8.11 mg × L −1, respectively. The LCC was an early and sensitive indicator of the phytotoxic effects of DOX in L. minor before morphological changes were observed. Confirmation of drug toxicity was the Daphtoxkit. The EC 20 (180. min) of DOX and NOR, IM of daphnia by 20 % was 117.18 and 215.42 mg × L −1, respectively. In conclusion, DOX and NOR in aquatic environments may have significant implications for tested organisms and their ecosystems. [ABSTRACT FROM AUTHOR]

A simple mathematical model based on product's moisture sorption isotherm and package's moisture transmission was developed to predict moisture content of dry solid tablets during consumers' use, which is useful for determination of in-use shelf life (ISL) or secondary shelf life. The moisture increase depending on amount of product remaining in the package was accounted for in the mass balance equation on the package. The model was first verified by literature data of desiccant canisters in a plastic bottle of high density polyethylene exposed to two environmental conditions (25 °C and 60% relative humidity (RH); 40 °C and 75% RH) simulating in-use of removing one canister each day. Then an experimental work was conducted on dry refresher candies in a polyethylene terephthalate bottle at 25 °C with two tablets taken out every day, which confirmed the model's capability to predict the product moisture content during in-use storage of 76% and 90% RH. Its use can provide science-based accurate determination of ISL, which may work as consumer guideline. The model is also expected to be helpful for recommending management scheme of whole product life. [ABSTRACT FROM AUTHOR]

The preventive policy is the best way to envisage the existence of the criminal personality, and since the phenomenon of illicit drug dealing is increasing in Iraqi society; We chose it from this aspect, especially after the issuance of the Narcotic Drugs and Psychotropic Substances Law No. (50) for the year 2017 AD, by examining the legislator’s preventive policy in this law and in the legislations subject to comparison.The criminalization contained in the law is of the type of preventive (precautionary) criminalization, and the criminal behavior in the drug law is such as crimes of danger and not harm. Therefore, objective prevention (the subject of our discussion) aims to prevent harm that affects the health of individuals, the decline of human energy in society and the economy and the spread of crime and others, the law also included many forms of behavior that the legislator incriminated,

Abstract Background Substance use disorders are a widely recognized problem among hepatitis C-infected patients; moreover, substance abuse by intravenous injection is a common mode of transmission of the hepatitis C virus worldwide. The frequency of substance use disorders and their relation to hepatitis C infection are still unknown in Iraq. This cross-sectional study, conducted among a sample of hepatitis C- infected patients attending the Gastrointestinal Tract Center in Baghdad Medical City, aimed to examine the prevalence of substance use disorders, the sociodemographic characteristics of the abusers, and the relation between intravenous drug abuse and hepatitis C virus infection. All participants were subjected to an Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) questionnaire and a data form to determine sociodemographic characteristics and hepatitis C virus-related risk factors. Results In a total of 300 hepatitis C virus-infected patients, the prevalence of substance use disorders was 53.6%. Among these patients, 43.6% abused nicotine, 6% abused licit drugs, and 4% abused alcohol. No one reported illicit drug abuse. Intravenous drug abuse was rare, and there was no relationship found between intravenous drug abuse and hepatitis C infection. Cupping (23%) and blood transfusion (20.3%) were both significantly associated with hepatitis C transmission in this study (p > 0.001). Conclusion This study revealed a high prevalence (53.6%) of substance abuse in this sample of hepatitis C-infected patients, with nicotine being the most commonly abused substance. However, there was no relationship between hepatitis C infection and intravenous drug abuse. Common risk factors that might contribute to hepatitis C transmission among this population include cupping and blood transfusion.

Abstract Background Hepatocellular carcinoma (HCC) constitutes an important contributor to fatalities. Coronavirus disease 2019 (COVID-19) frequently presents with complications such as respiratory distress, systemic inflammatory responses, and damage to various organs. Several studies have investigated the relationship between COVID-19 and mortality in patients with liver cancer, but there are few research on the relationship between them. This study is to explore the correlation between the two diseases and drugs treating them. Methods The Gene Expression Omnibus (GEO) database provides gene datasets of COVID-19 patients and HCC patients. Through differential gene analysis and weighted gene co-expression network analysis, we determined 223 genes represented in HCC and COVID-19. We then used functional annotation, protein–protein interaction network construction, predictive model development and verification, prognostic value analysis, and miRNA–gene network construction. Besides, we created a drug–hub–gene network by predicting possible medications that interact with hub genes using the Drug–Gene Interaction Database (DGIdb). Ultimately, we applied immunohistochemistry to ascertain the hub genes expression. Results This study revealed that eight core genes (RRM2, TPX2, DTL, CDT1, TYMS, CDCA5, CDC25C, and HJURP) co-existed in both HCC and COVID-19 and were differentially expressed in both HCC and normal tissues.CDC25C, RRM2, CDCA5, and HJURP had diagnostic value (AUC > 0.8) and prognostic value (adjusted P-value

Jiankang Wu,1– 4 Yan Chen1– 4 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, People’s Republic of China; 3Clinical Medical Research Center for Pulmonary and Critical Care Medicine, Changsha, Hunan, People’s Republic of China; 4Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Yan Chen, Email chenyan99727@csu.edu.cnAbstract: Extracellular vesicles (EVs) are nanoscale lipid bilayer vesicles released during cell activation, cellular damage, or apoptosis. They carry nucleic acids, proteins, and lipids facilitating intercellular communication and activate signaling pathways in target cells. In non-small cell lung cancer (NSCLC), EVs may contribute to tumor growth and metastasis by modulating immune responses, facilitating epithelial-mesenchymal transition, and promoting angiogenesis, while potentially contributing to resistance to chemotherapy drugs. EVs in liquid biopsies serve as non-invasive biomarkers for early cancer detection and diagnosis. Due to their small size, inherent molecular transport properties, and excellent biocompatibility, EVs also act as natural drug delivery vehicles in NSCLC therapy. Keywords: extracellular vesicles, non-small cell lung cancer, immunity, metastasis, drug, biomarkers

Objective: Nursing students attended distance learning due to the pandemic, which made it more difficult for them to learn how to calculate the right dose because drug dose calculation requires constant practice. This study investigated whether Padlet helped nursing students to learn how to calculate the right dose. Method: This study adopted a single-group pretest-posttest experimental research design. This study was conducted in the nursing department of a university in Turkey. The sample consisted of 42 first-year nursing students. Students participating in the research answered the “form for promotional features” and “drug dose calculation knowledge test” sent via Google Forms. Then, the researcher and participants shared and discussed the questions, pictures, and videos they prepared for drug dose calculation on Padlet for three weeks. At the end of three weeks, all participants filled out the knowledge test again. Number, percentage, and Wilcoxon test were used for data analysis. Results: It was determined that the students’ test score average regarding drug dose calculation skills increased at a statistically significant level (p