Examining predictors of suicide by firearm in young, middle, and late adulthood.

INTRODUCTION: Suicide remains a leading cause of death in the U.S., and firearms are one of the most lethal methods of suicide. This study examines personal and contextual factors that predict suicide with a firearm compared to other methods across stages of adulthood. METHODS: Data on adult suicide decedents from 2009 to 2019 were obtained from Colorado's National Violent Death Reporting System (NVDRS) data (N = 11,512). The dataset includes incident and person characteristics collected by law enforcement and coroners. Zip code level data were integrated from the American Community Survey. RESULTS: Age, sex, race, marital status, military service, substance use, suicide attempt history, mental health, and location characteristics (population density, as well as age, education, veteran status, and household status of population) predicted suicide by firearm. Risk was particularly high for males in older adulthood. We further explored age-specific models (young, middle-aged, and older adults) to determine salient risk factors for each group. CONCLUSION: This study highlights the need for comprehensive suicide prevention approaches that consider both individual and contextual risk factors, as well as unique risks in each stage of adulthood.

Guanidines: Synthesis of Novel Histamine H3R Antagonists with Additional Breast Anticancer Activity and Cholinesterases Inhibitory Effect.

This study examines the properties of novel guanidines, designed and synthesized as histamine H3R antagonists/inverse agonists with additional pharmacological targets. We evaluated their potential against two targets viz., inhibition of MDA-MB-231, and MCF-7 breast cancer cells viability and inhibition of AChE/BuChE. ADS10310 showed micromolar cytotoxicity against breast cancer cells, combined with nanomolar affinity at hH3R, and may represent a promising target for the development of an alternative method of cancer therapy. Some of the newly synthesized compounds showed moderate inhibition of BuChE in the single-digit micromolar concentration ranges. H3R antagonist with additional AChE/BuChE inhibitory effect might improve cognitive functions in Alzheimer's disease. For ADS10310, several in vitro ADME-Tox parameters were evaluated and indicated that it is a metabolically stable compound with weak hepatotoxic activity and can be accepted for further studies.

Cardioprotective Effect of Centaurea castriferrei Borbás & Waisb Extract against Doxorubicin-Induced Cardiotoxicity in H9c2 Cells.

Doxorubicin (DOX) is one of the most used chemotherapeutic agents in the treatment of various types of cancer. However, a continual problem that is associated with its application in therapeutic regimens is the development of dose-dependent cardiotoxicity. The progression of this process is associated with a range of different mechanisms, but especially with the high level of oxidative stress. The aim of the study was to evaluate the effects of the water and methanol-water extracts from the plant Centaurea castriferrei (CAS) obtained by the ultrasound-assisted extraction method on the DOX-induced cardiotoxicity in the rat embryonic cardiomyocyte cell line H9c2. The H9c2 cells were treated for 48 h with the DOX and water or methanol-water extracts, or a combination (DOX + CAS H2O/CAS MeOH). The MTT assay, cell cycle analysis, and apoptosis detection revealed that both the tested extracts significantly abolished the cytotoxic effect caused by DOX. Moreover, the detection of oxidative stress by the CellROX reagent, the evaluation of the number of AP sites, and the expressions of the genes related to the oxidative stress defense showed substantial reductions in the oxidative stress levels in the H9c2 cells treated with the combination of DOX and CAS H2O/CAS MeOH compared with the DOX administered alone. The tested extracts did not affect the cytotoxic effect of DOX on the MCF-7 breast cancer cell line. The obtained results constitute the basis for further research in the context of the application of C. castriferrei extracts as adjuvants in the therapy regiments of cancer patients treated with DOX.

Anticancer and antimicrobial activity of new copper (II) complexes.

In this study, three new organic ligands N'-(benzylidene)-6-chloropyrazine-2-carbohydrazonamide (L1), 6-chloro-N'-(4-nitrobenzylidene)picolinohydrazonamide(L2), and N'-(benzylidene)-4-chloropicolinohydrazonamide (L3) and three copper coordination compounds (Cu(L1)Cl2, Cu(L2)Cl2 and Cu(L3)Cl2) based on them were synthesized. All obtained compounds were characterized using appropriate analytical techniques: elemental analysis (EA), thermogravimetric analysis (TG-DTG), Fourier transform infrared spectroscopy (FTIR) and flame-atomic absorption spectrometry (F-AAS). These methods of physicochemical analyses helped to assume that the complexation in three cases proceeds in a bidentate manner. The X-ray investigation confirmed the synthesis pathway and molecular structures for L1 and L3 ligands. The antimicrobial activity of the obtained compounds was then comprehensively investigated, where Cu(L3)Cl2 showed the strongest antibacterial properties against all tested bacteria (Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli). LN229 human glioma cells and BJ human normal fibroblasts cells were treated with tested compounds and their cytotoxicity was evaluated with MTT test. The effect of complexing on antitumor activity has been investigated. The ligand L1 and its complex showed similar activity against normal cells while complexation increases toxicity against cancer cells in concentrations of 50 and 100 µM. For the one pair of ligand/complex compounds the apoptosis detection, cell cycle analysis and gene expression analysis (qRT-PCR) were performed. Cu(L1)Cl2 showed the stronger toxic effect in comparison with L1 due to the population of early apoptotic cells which revealed metabolic activity in MTT assay.

Phytochemical Analysis and Anti-Cancer Properties of Extracts of Centaurea castriferrei Borbás & Waisb Genus of Centaurea L.

The Centaurea L. (Asteraceae) genus includes many plant species with therapeutic properties. Centaurea castriferrei Borbás & Waisb is one of the least known and least described plants of this genus. The aim of the study was the phytochemical analysis of water and methanol-water extracts (7:3 v/v) obtained from the aerial parts of the plant as well as evaluation of their anticancer activity. Quantitative determinations of phenolic compounds and flavonoids were performed, and the antioxidant potential was measured using the CUPRAC method. The RP-HPLC/DAD analysis and HPLC-ESI-QTOF-MS mass spectroscopy were performed, to determine the extracts' composition. The antiproliferative activity of the obtained extracts was tested in thirteen cancer cell lines and normal skin fibroblasts using MTT test. Regardless of the extraction method and the extractant used, similar cytotoxicity of the extracts on most cancer cell lines was observed. However, the methanol-water extracts (7:3 v/v) contained significantly more phenolic compounds and flavonoids as well as showing stronger antioxidant properties in comparison to water extracts. Centaurea castriferrei Borbás & Waisb is a rich source of apigenin and its derivatives. In all tested extracts, chlorogenic acid and centaurein were also identified. In vitro research revealed that this plant may be a potential source of compounds with anticancer activity.

Targeting Energy Metabolism in Cancer Treatment.

Cancer is the second most common cause of death worldwide after cardiovascular diseases. The development of molecular and biochemical techniques has expanded the knowledge of changes occurring in specific metabolic pathways of cancer cells. Increased aerobic glycolysis, the promotion of anaplerotic responses, and especially the dependence of cells on glutamine and fatty acid metabolism have become subjects of study. Despite many cancer treatment strategies, many patients with neoplastic diseases cannot be completely cured due to the development of resistance in cancer cells to currently used therapeutic approaches. It is now becoming a priority to develop new treatment strategies that are highly effective and have few side effects. In this review, we present the current knowledge of the enzymes involved in the different steps of glycolysis, the Krebs cycle, and the pentose phosphate pathway, and possible targeted therapies. The review also focuses on presenting the differences between cancer cells and normal cells in terms of metabolic phenotype. Knowledge of cancer cell metabolism is constantly evolving, and further research is needed to develop new strategies for anti-cancer therapies.

Influence of Complexation of Thiosemicarbazone Derivatives with Cu (II) Ions on Their Antitumor Activity against Melanoma Cells.

A series of thiosemicarbazone derivatives was prepared and their anti-tumor activity in vitro was tested. The X-ray investigation performed for compounds T2, T3 and T5 confirmed the synthesis pathway and assumed molecular structures of analyzed thiosemicarbazones. The conformational preferences of the thiosemicarbazone system were characterized using theoretical calculations by AM1 method. Selected compounds were converted into complexes of Cu (II) ions. The effect of complexing on anti-tumor activity has been investigated. The copper(II) complexes, with Schiff bases T1, T10, T12, T13, and T16 have been synthesized and characterized by chemical and elemental analysis, FTIR spectroscopy and TGA method. Thermal properties of coordination compounds were studied using TG-DTG techniques under dry air atmosphere. G361, A375, and SK-MEL-28 human melanoma cells and BJ human normal fibroblast cells were treated with tested compounds and their cytotoxicity was evaluated with MTT test. The compounds with the most promising anti-tumour activity were then selected and their cytotoxicity was verified with cell cycle analysis and apoptosis/necrosis detection. Additionally, DNA damages in the form of a basic sites presence and the expression of oxidative stress and DNA damage response genes were evaluated. The obtained results indicate that complexation of thiosemicarbazone derivatives with Cu (II) ions improves their antitumor activity against melanoma cells. The observed cytotoxic effect is associated with DNA damage and G2/M phase of cell cycle arrest as well as disorders of the antioxidant enzymes expression.

The impact of childhood maltreatment on adolescent gang involvement.

BACKGROUND: A number of risk factors for gang involvement have been identified in the literature, such as victimization, poor parental monitoring, aggressive behavior, and affiliation with delinquent peers. However, few studies have examined the influence of maltreatment experiences during childhood on gang involvement later in adolescence. OBJECTIVE: This study examines how differential experiences of maltreatment might impact future gang involvement. PARTICIPANTS AND SETTING: We analyze self-report data and official maltreatment records on 611 youth (52% female; 76% non-white) in the US, from a larger dataset (Longitudinal Studies on Childhood Abuse and Neglect; N = 1354). METHODS: Multinomial logistic regression models were used to examine the influence of experiencing different types of maltreatment on gang involvement. RESULTS: Results show that childhood experiences of maltreatment (p = .005) generally and neglect (p = .013) specifically were significantly associated with an increased risk of involvement in stable gang affiliations later in adolescence. CONCLUSIONS: These findings demonstrate the value of considering gang involvement as an outcome of maltreatment and tailoring best practice interventions to support maltreated youth at risk of gang involvement.

Early maltreatment is associated with greater risk of conduct problems and lack of guilt in adolescence.

Previous research indicates a link between childhood maltreatment and elevated conduct problems. Yet the literature is less clear on associations between maltreatment and callousness (e.g., lack of empathy or guilt). This is a critical gap given that callousness is a robust predictor of serious aggressive and violent behavior. We examine the association between substantiated maltreatment events in childhood and adolescence (up to age 13) and conduct problems and lack of guilt at age 14. We analyze self- and parent-report data along with official maltreatment records on 557 youth (50% female; 69% non-white) from a larger dataset (Longitudinal Studies on Childhood Abuse and Neglect; N = 1354). Results of multinomial logistic regression models indicate that youth with histories of substantiated maltreatment events are more likely to have elevated conduct problems and decreased guilt at age 14, particularly if they experienced maltreatment before the age of four years old. Youth who exhibit conduct problems and also appear to lack guilt are more likely to have a personal history of substantiated maltreatment. We discuss our results in terms of their implications for theory and practice.