Notes

Phlegm.
Altogether, the abovementioned findings indicate that CuSO4 treatment may induce pulmonary fibrosis through the activation of EMT induced by TGF-β1/Smad pathway and MAPKs pathways, revealing the mechanism Cu-caused pulmonary toxicity.Medical reports indicate a prevalence of pain in 50% of patients with cancer. In this context, this article investigated the antinociceptive activity of α-PHE using in vivo Sarcoma-180-induced hypernociception in mice to detail its mechanism(s) of antinociception under different conditions of treatment and tumor progression. Firsty, in vitro cytotoxic action was assessed using melanoma B-16/F-10 and S-180 murine cells and colorimetric MTT assays. For in vivo studies, acute treatment with α-PHE (6.25, 12.5, 25 and 50 mg/kg orally by gavage) was performed on the 1st day after S-180 inoculation. Subacute treatments were performed for 8 days starting on the next day (early protocol) or on day 8 after S-180 inoculation (late protocol). For all procedures, mechanical nociceptive evaluations were carried out by von Frey's technique in the subaxillary region peritumoral tissue (direct nociception) and in right legs of S-180-bearing mice (indirect nociception). α-PHE showed in vitro cytotoxic action on B-16/F-10 and S-180 (CI50 values of 436.0 and 217.9 μg/mL), inhibition of in vivo tumor growth (ranging from 47.3 to 82.7%) and decreased direct (peritumoral tissue in subaxillary region) and indirect (right leg) mechanical nociception in Sarcoma 180-bearing mice with early and advanced tumors under acute or subacute conditions of treatment especially at doses of 25 and 50 mg/kg. It improved serum levels of GSH as well as diminished systemic lipid peroxidation, blood cytokines (interleukin-1β, -4, -6, and tumor necrosis factor-α). Such outcomes highlight α-PHE as a promising lead compound that combines antinociceptive and antineoplasic properties. Its structural simplicity make it a cost-effective alternative, justifying further mechanistic investigations and the development of pharmaceutical formulations. Moreover, the protocols developed and standardized here make it possible to use Sarcoma-180 hypernociception model to evaluate the capacity of new antinociceptive molecules under conditions of cancer-related allodynia.
This study explored affective mechanisms of compensatory health behaviors after acting inconsistently with an important goal. Specifically, we propose and test a model in which regret over being in a situation that inhibits goal pursuit lays at the root of an individual's engagement in compensatory behaviors such as avoiding fatty foods and sweets.

A total of 185 participants committed to being healthy took part in a longitudinal experiment (t
-t
). At t
we measured the extent to which the goal of being healthy was important to participants. At t
in the laboratory setting we manipulated inconsistency with the goal by asking participants to taste foods either more or less calorie-dense. After the manipulation (t
) we measured experienced regret. Twenty-four hours later (t
), participants declared whether they engaged in compensatory health behaviors such as avoiding fat-dense food and sweets.

As predicted, acting inconsistently with a goal was associated with higher levels of experienced regret. Higher regret, in turn, predicted engagement in compensatory health behaviors. Moreover, subjective importance of the goal moderated the effect of inconsistency on experienced regret in such a way that more committed individuals experienced more regret when they acted inconsistently with a goal.

We discuss the results and propose new avenues for research on compensation in broader contexts of situational and individual differences.
We discuss the results and propose new avenues for research on compensation in broader contexts of situational and individual differences.The evolution of tablet strength is mainly influenced by deformability (bonding area) and strength of intermolecular interactions (bonding strength) from the intrinsic material properties and tableting process, respectively. Therefore, understanding of intrinsic material attributes is important for in-silico drug product designs. The present study shows that the separate effect of the above two factors can be better understood by systematic evaluation of pure APIs and their formulations. Using tensile strength, elastic modulus and yield stress as critical material attributes, a proof of concept shown in this work emphasizes that materials with greater deformability tend to possess greater tensile strength at comparable bonding strengths. In contrast, the influence of the deformability parameter is hidden when formulations are used, leading to a scenario where the effects of bonding area and bonding strength are more inseparable.Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been widely used in the clinical treatment of non-small cell lung cancer (NSCLC) patients with EGFR mutations. 3PO clinical trial Previous studies have shown that Aurora kinase A (AURKA) is overexpressed in a broad spectrum of cancer cells, which can induce epithelial-mesenchymal transition (EMT) and contribute to the occurrence of acquired EGFR-TKI resistance. However, whether the inhibition of AURKA could overcome EGFR-TKI resistance or reverse the EMT in TKI-resistant NSCLC cells remains unclear. In the current study, we established three EGFR-TKI-resistant cell lines and analyzed their expression profiles by RNA sequencing. The results revealed that the EMT pathway is significantly upregulated in the three cell lines with EGFR-TKI resistance. The phosphorylation of AURKA at Thr 288 was also upregulated, suggesting that the activation of AURKA plays an important role in the occurrence of EGFR-TKI resistance. Interestingly, the AURKA inhibitor, alisertib treatment restored the susceptibility of resistant cells to EGFR-TKIs and partially reversed the EMT process, thereby reducing migration and invasion in EGFR-TKI-resistant cells. This study provides evidence that targeting AURKA signaling pathway by alisertib may be a novel approach for overcoming EGFR-TKI resistance and for the treatment of metastatic EGFR-TKIs in NSCLC patients.
This study uses a national model of community-based long-term services and supports, the Program of All-inclusive Care for the Elderly (PACE), to identify organizational structures and protocols that can facilitate the delivery of dental examinations.

We developed an online survey instrument and conceptual model for this study representing 10 domains believed to characterize a quality PACE dental program.

The Qualtrics survey was distributed nationally to all 124 PACE programs in the 31 states PACE was available. Respondents in this study represented 35 programs (program response rate=28.2%) in 23 states (state response rate=74.2%).

Selected independent variables from each of the 10 domains were tested against the reported delivery of dental examinations variable using the Kendall τ and χ
. Twenty-nine programs were included in the final analysis.

Most programs mandated a dental examination within 31-60days of enrollment (63.6%). Few programs had a dental manual (15.6%) or any quality assurance forovative models of community-based long-term services and supports. Implementing these domains can facilitate effective delivery of dental examinations that have the potential to support positive oral health and general health outcomes.Multiple sources contribute to nitrogen(N) and phosphorus (P) pollution in lowland urban rivers, and apportioning the sources of N and P pollution is essential for improving the ecological health of urban environments. Three urban polders in Jiaxing were selected to investigate the temporal variations of N and P pollutants in lowland urban river waters under dry and wet conditions. Moreover, the main potential sources of N and P pollution were identified through the correlations of pollutants and components of dissolved organic matter (DOM) derived from excitation-emission matrix (EEM) and parallel factor analysis (PARAFAC). The results indicate that the main pollution sources identified with PCA method were consistent with the potential sources revealed by DOM's EEM-PARAFAC components. Furthermore, absolute principal components score combined with multivariate linear regression (APCS-MLR) was conducted. The results illustrated that domestic wastewater contributes more than 70% of N pollution and river-bottom sediments contribute more than 50% of P pollution under dry conditions. On the contrary, discharged water from the stormwater outlets contributes more than 41% of P and 75% of N under wet conditions. Specifically, about 48% of them come from domestic wastewater, and about 38% come from urban surface runoff. This study highlights the effectiveness of DOM components derived from EEM-PARAFAC in identifying the sources of N and P pollution and the PCA-APCS-MLR in apportioning the contributions of each potential pollution source in lowland urban rivers.
Gestational exposure to chemical mixtures, which is prevalent among pregnant women, may be associated with adverse childhood neurodevelopment. However, few studies have examined relations between gestational chemical mixture exposure and children's cognitive abilities.

In a cohort of 253 pregnant women and their children from Cincinnati, OH (enrolled 2003-2006), we quantified biomarker concentrations of 43 metals, phthalates, phenols, polybrominated diphenyl ethers, organophosphate and organochlorine pesticides, polychlorinated biphenyls, perfluoroalkyl substances, and environmental tobacco smoke in blood or urine. Using k-means clustering and principal component (PC) analysis, we characterized chemical mixtures among pregnant women. We assessed children's cognitive abilities using the Wechsler Preschool and Primary Scale of Intelligence-III and Wechsler Intelligence Scale for Children-IV at ages 5 and 8 years, respectively. We estimated covariate-adjusted differences in children's cognitive ability scoreith children's cognition, but some individual chemical biomarker concentrations were not. Additional studies should determine if the aggregate impact of these chemicals on cognition is different from their individual effects.This paper evaluates the scientific basis for the adoption of the linear non-threshold (LNT) dose response model for radiation-induced leukemia. This LNT risk assessment application for leukemia is significant because it (1) was generalized for all tumor types induced by ionizing radiation and chemical carcinogens at relatively high doses and; (2) it was based on the mechanistic assumption of low dose linearity for somatic cell mutations as determined from responses in mature spermatozoa of fruit flies. A serious problem with the latter assumption is that those spermatozoa lack DNA repair. The acceptance of the LNT dose response model for cancer risk assessment was based on the convergence of recommendations of the BEAR I Genetics Panel (1956a) for reproductive cell gene mutations and those of Lewis (1957a) for somatic cell mutation and its capacity to explain apparent and/or predicted linear dose responses of ionizing radiation-induced leukemia in multiple and diverse epidemiological investigations. Use of that model and related dose response beliefs achieved rapid, widespread and enduring acceptance in the scientific and regulatory communities.
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