Notes

Employing inside vivo animal versions regarding understanding SARS-CoV-2.
Maltreatment victimization history is an established risk factor for child maltreatment across generations. However, many parents with a victimization history do not maltreat, and many parents with no victimization history do have victimized children.

To understand differences in demographic and maltreatment risk factors across the following intergenerational patterns of maltreatment cycle maintainers, cycle breakers, cycle initiators, and a comparison group (no maltreatment).

Data were drawn from a large population-based cohort in Queensland, Australia and included 32,574 biological parents and their children. Maltreatment experiences as a victim or person responsible for harm towards a child were obtained from the Queensland Child Protection System.

Multinomial regression was completed with the full sample to compare the three maltreatment groups with the comparison group. Logistic regressions were conducted on all pairwise combinations of maltreatment groups. Models accounted for several demographic and maltreatment factors.

Compared with breakers, maintainers were more likely to be Indigenous (OR = 1.86), never married (OR = 0.34), younger at first birth (OR = 0.87), have ≥3 children (OR = 1.99), be younger at first-and older at last-maltreatment victimization (ORs = 0.97 and 1.07, respectively), and experience a higher frequency of victimization (OR = 1.05). Amongst maltreaters, males were significantly more likely to be initiators while females were more likely to be maintainers (OR = .62). There were few other differences between initiators and maintainers.

Meaningful differences among the three maltreatment groups were revealed suggesting that research should focus on the intergenerational discontinuity of maltreatment.
Meaningful differences among the three maltreatment groups were revealed suggesting that research should focus on the intergenerational discontinuity of maltreatment.
The translation of research on adverse childhood experiences (ACEs) into effective prevention and treatment of psychopathology requires examination of how ACEs impact mental health. Moreover, increased attention to more marginalized populations, such as immigration-affected ethnic-minority young adults, is greatly needed.

The current study tested the hypothesis that greater ACEs would be related to greater generalized anxiety symptoms directly and indirectly, via ACE-related deficits in coping efficacy, self-compassion, and perceived support, above and beyond immigration-related family stress.

Participants included ethnic minority young adults (n=322) attending a public university who reported having at least one family member living in the United States without legal protection and/or being undocumented themselves.

Data was collected online using validated measures of the primary study variables. Participants also completed a pilot measure of immigration-related stress in their family. A multiple mediation model was tested in a structural equation modeling framework.

A substantial percentage of young adults experienced 4 or more ACEs and clinically-significant generalized anxiety symptoms (38.5% and 20.5%, respectively); a greater number of ACEs were directly (β=0.33, p<.001) and indirectly, via lower self-compassion (standardized indirect effect 95% CI 0.04, 0.14), associated with significantly greater generalized anxiety symptoms, above and beyond immigration-related family stress and other indicators of socioemotional functioning.

Findings suggest that ACEs and generalized anxiety are prevalent in ethnic minority young adults from mixed legal status families and their association may be partially accounted for by ACE-related deficits in self-compassion.
Findings suggest that ACEs and generalized anxiety are prevalent in ethnic minority young adults from mixed legal status families and their association may be partially accounted for by ACE-related deficits in self-compassion.In this work, a UHPLC-HRMS method using a quadrupole-orbitrap mass spectrometer has been developed for the detection and quantification of 47 compounds. These compounds include a range of chemical structures and properties and are popularly referred to as active pharmaceutical ingredients (API). The APIs selected have historically been incorporated into a variety of products commonly marketed towards acne, hair loss, male erectile dysfunction, and skin whitening. A fast ultrasound-assisted extraction (UAE) procedure without sample cleanup was developed and a high-resolution product ion spectral library was generated for compound verification in complex matrices. Collision energies were optimized for all analytes to overcome the limitations by applying stepped collision energies, such as insufficient fragmentation and excessive fragmentation without molecular ion information. Higher HRMS2 spectra matching scores (0.6 or above) were obtained for the analytes in the tested complex matrices. Eleven representative stable isotopically labeled API analogs were used as internal standards to compensate for the influence of complex matrices, such as shampoo and creams, and as an instrument quality control. One-hundred products with complex matrices were analyzed using the validated UHPLC-HRMS method. Eight APIs (ketoconazole, hydroquinone, salicylic acid, benzocaine, progesterone, azelaic acid, lidocaine, and minoxidil) were identified in 26 out of 100 products ranging from 103 μg/g to 156,000 μg/g.Curcumae Rhizoma (Ezhu in Chinese) is a multi-origin herbal medicine with excellent clinical efficacy. For fast discrimination and quantification analysis of Ezhu from three botanical origins (Curcuma kwangsiensis, Curcuma phaeocaulis, and Curcuma wenyujin), ultra-violet (UV) spectroscopy and high performance liquid chromatography (HPLC) combined with chemometric tools were employed in this study. Firstly, the analysis method for the simultaneous determination of eleven compounds in Ezhu was developed by HPLC, and the UV spectra of thirty-eight batches of Ezhu were acquired. Then, principal component analysis (PCA), an unsupervised pattern recognition method, was applied on the HPLC and UV spectral data. PCA did not show a clear separation between C. phaeocaulis and C. 8-Bromo-cAMP wenyujin samples with HPLC data. By contrast, the supervised techniques, decision tree (DT) and linear discriminant analysis (LDA), achieved the complete discrimination for the three species of Ezhu with 100 % correct classification rate (CCR),hydroxyphenyl)-heptane contents in Ezhu, which will help a lot in the quality control of Ezhu and other multi-origin herbal medicines.We report an accelerator mass spectrometry (AMS) assay to quantify azacitidine (Aza) incorporation into DNA and RNA from human acute myeloid leukemia (AML) cells, mouse bone marrow (BM) and peripheral blood mononuclear cells (PBMCs). Aza, a cytidine nucleoside analogue, is a disease modifying pharmacological agent used for treatment of myelodysplastic syndromes (MDS) and AML. Our assay was able to directly quantify the complex of Aza incorporated into DNA/RNA, via isolation of DNA/RNA from matrix (i.e., cancer cells, BM and PBMC) and subsequent measurement of total radioactivity (i.e., 14C-Aza) by using AMS. The sensitivity of the method was able to quantify as little as a single Aza molecule incorporated into DNA with approximately 2 × 107 nucleotides from PBMCs. link2 An in vivo mouse model was used for establishing the lower limits of quantification (LLOQs) for Aza incorporated into DNA/RNA in mouse PBMCs (∼ 3.7 × 105) and BM (∼27.8 mg) collected 24 h post-dose after total exposure of 18 nCi/mouse (Aza 1 mg/kg). The LLOQs for PBMC analysis were 2.5 picogram equivalents per microgram (pgEq/μg) DNA and 0.22 pgEq/μg RNA, and for BM analysis were 1.7 pgEq/μg DNA and 0.22 pgEq/μg RNA. A linear relationship (i.e., ∼10-fold) was established of radioactive dose from 14C-Aza 17 nCi/mouse to 188 nCi/mouse and AMS response (i.e., 14C/12C ratio ranging from 2.45 × 10-11 to 2.50 × 10-10), as Aza was incorporated into DNA in mouse BM. The current method enables the direct measurement of Aza incorporation into DNA and RNA from patient PBMCs and BM to provide dosing optimization, and to assess target engagement with as little as ∼5 mL whole blood and ∼3 mL of BM from patients.Previously, our cooperative team confirmed the chemical composition and anti-rheumatoid arthritis (RA) efficacy of Juanbi-Tang (JBT), a clinically and historically used traditional Chinese medicine formula, in two model animals. In this study, we developed an in vivo-in silico strategy to elucidate the anti-RA material basis and mechanism of JBT. With the aid of high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF), the metabolic profiles were investigated in normal and collagen-induced arthritis RA rats following oral administration of JBT. Based on the absorbed constituents in RA rats, network pharmacology was employed to predict the anti-RA mechanisms, followed by molecular docking validation. Consequently, there were 18 absorbed compounds with 6 chemical structures, which were absolutely identified by matching with standard compounds in plasma, and 17 generated metabolites involved of 7 biotransformation pathways, including glucuronidation, sulfation, hydroxylation, deglycosylation, methylation, taurine, and glycine conjugation. link3 Moreover, RA disease affected the absorption and metabolism of the constituents in JBT, given the undetected 2 absorbed compounds and 4 metabolites in RA rats. The analysis of network pharmacology indicated that those absorbed compounds in JBT may fight against RA through the MAPK, FoxO, and Rap1 pathways. Molecular docking also validated these results. Overall, this is the first study to describe the metabolic profiles of JBT-treated healthy and RA rats, and it provides a possible anti-RA mechanism through multiple absorbed compounds and targets by network pharmacology.Curcumae Rhizoma (Ezhu), a multi-origin Chinese medicine, originates from the dry rhizomes of C. kwangsiensis, C. phaeocaulis and C. wenyujin. The three species have great variation in chemical components and therapeutic effects. To improve safety and effectiveness in clinical use, a strategy integrating chromatographic analysis and chemometrics for the species authentication of Ezhu was proposed. Firstly, systematic analysis of chemical compositions in Ezhu was achieved using high performance liquid chromatography (HPLC) fingerprint and headspace gas chromatography-mass spectrometry (HS-GC-MS). HPLC fingerprints showed that seventeen peaks in common for C. kwangsiensis and eleven peaks in common for C. wenyujin both presented a good similarity (> 0.9, only several samples less then 0.8). Eleven common peaks in C. phaeocaulis and the similarity values of most samples were higher than 0.700. Additionally, there were ten common peaks in all Ezhu samples and they had relatively poor similarity with the correlaues higher than 1 in the OPLS-DA model were selected as potential chemical markers for the species authentication of Ezhu. And the constructed OPLS-DA model using these markers obtained 100 % accuracy. Consequently, a rapid, precise and feasible strategy was established for the discrimination and quality control of Ezhu with different species.
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