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Components of specialised Mental Health Care Used in holland: A Scoping Assessment Implementing Andersen-Newman's Attention Utilization Design.
Further, specific differences in potential needs, wishes and barriers for future campaigns or interventions were observed between demographic strata. The majority of the respondents (89%) indicated that they would welcome more information on improving their brain-health. learn more More than half (54%) also believed that they lacked the necessary knowledge to make brain-healthy behavior changes. In conclusion, effective public awareness campaigns on the topic of dementia risk reduction are feasible and timely, given the state of the evidence. Special efforts need to be made to develop effective campaigns, tailored towards low-educated individuals.
The Janus kinase (JAK) pathway mediates the activity of many asthma-relevant cytokines, including IL-4 and IL-13. GDC-0214 is a potent, inhaled, small-molecule JAK inhibitor being developed for the treatment of asthma.

We sought to determine whether GDC-0214 reduces fractional exhaled nitric oxide (Feno), a JAK1-dependent biomarker of airway inflammation, in patients with mild asthma.

We conducted a double-blind, randomized, placebo-controlled, phase 1 proof-of-activity study in adults with mild asthma and Feno higher than 40 parts per billion (ppb). Subjects were randomized 21 (GDC-0214placebo) into 4 sequential ascending-dose cohorts (1 mg once daily [QD], 4 mg QD, 15 mg QD, or 15 mg twice daily). All subjects received 4 days of blinded placebo, then 10 days of either active drug or placebo. The primary outcome was placebo-corrected percent reduction in Feno from baseline to day 14. Baseline was defined as the average Feno during the blinded placebo period. Pharmacokinetics, safety, and tolerability were also assessed.

Thirty-six subjects (mean age, 28 years; 54% females) were enrolled. Mean Feno at baseline across all subjects was 93± 43 ppb. At day 14, placebo-corrected difference in Feno was -23% (95% CI, -37.3 to -9) for 15 mg QD and -42% (95% CI, -57 to -27.4) for 15 mg twice daily. Higher plasma exposure was associated with greater Feno reduction. No dose-limiting adverse events, serious adverse events, or treatment discontinuations occurred. There were no major imbalances in adverse events or laboratory findings, or evidence of systemic JAK inhibition.

GDC-0214, an inhaled JAK inhibitor, caused dose-dependent reductions in Feno in mild asthma and was well tolerated without evidence of systemic toxicity.
GDC-0214, an inhaled JAK inhibitor, caused dose-dependent reductions in Feno in mild asthma and was well tolerated without evidence of systemic toxicity.
The aim of this study was to explore the antitumor effect of citrate on prostate cancer and its underlying mechanism.

CCK-8 and Colony formation assay were performed to detect the anti-proliferative effect of citrate on prostate cancer. Flow cytometry analysis was conducted to investigate the pro-apoptosis effect of citrate on prostate cancer. Immunofluorescence assay was taken to detect whether citrate induced autophagy in prostate cancer. Western blot and Immunohistochemical assay were performed to explore the underlying mechanism by which citrate activates autophagic death in prostate cancer cells. Xenograft tumorigenicity assay was conducted to explore whether citrate suppressed the growth of xenograft prostate tumors in vivo.

We found citrate could significantly induce apoptosis and autophagy of prostate cancer cells in vitro and in vivo. Furthermore, treatment with autophagy inhibitor (chloroquine) drastically suppresses the apoptosis rate of prostate cancer induced by citrate. Based on the Ca
-chelating property of citrate, the further study suggested that citrate activates autophagic cell death in prostate cancer cells via downregulation CaMKII/AKT/mTOR pathway. Finally, citrate suppresses the growth of xenograft prostate tumors without remarkable toxicity in mice.

Our study elucidated a novel molecular mechanism about the anti-cancer activities of citrate. That citrate activates autophagic cell death of prostate cancer via downregulation CaMKII/AKT/mTOR pathway and without remarkable toxicity in mice. This study suggests that citrate might be a promising therapeutic agent for the treatment of prostate cancer.
Our study elucidated a novel molecular mechanism about the anti-cancer activities of citrate. That citrate activates autophagic cell death of prostate cancer via downregulation CaMKII/AKT/mTOR pathway and without remarkable toxicity in mice. This study suggests that citrate might be a promising therapeutic agent for the treatment of prostate cancer.
Gentamicin (GM) is an aminoglycoside antibiotic effectively used for severe/life-threatening infections. However, the clinical application of GM is limited by nephrotoxic side effects. Diosmin (DS) is a flavonoid with a wide range of bioactivities. However, its therapeutic potential in GM-induced nephrotoxicity remains unclear.

Rats received GM (100mg/kg, i.p.) for 7days either separately or in combination with oral DS (50mg/kg).

GM injection disrupted kidney function along with oxidant/antioxidant imbalance. Also, GM significantly decreased renal nuclear factor erythroid 2-related factor 2 (Nrf2), glutamyl cysteine synthetase (GCLC), heme oxygenase-1 (HO-1), superoxide dismutase3 (SOD-3), protein kinase B (AKT), and p-AKT expressions along with Kelch-like ECH-associated protein 1 (KEAP1) up-regulation. On the contrary, DS administration significantly attenuated GM-induced kidney dysfunction and restored kidney oxidant/antioxidant status. In addition, co-treatment with DS plus GM significantly enhanced Nrf2, GCLC, HO-1, SOD3, AKT, and p-AKT expressions along with KEAP1 down-regulation. Additionally, GM-treated rats exhibited a significant decrease in the expressions of renal peroxisome-proliferator activated receptor-gamma (PPAR-γ) and this reduction was alleviated by DS treatment. Furthermore, histopathological findings demonstrated that DS significantly reduced the GM-induced histological abrasions. Besides, an in-silico study was conducted to confirm our biochemical results. Interestingly, in-silico results strongly supported our biochemical investigation by studying the binding affinity of DS to KEAP1, AKT, and PPAR-γ proteins.

DS could be a promising protective agent against GM-induced nephrotoxicity through targeting of KEAP1/Nrf2/ARE, AKT, and PPAR-γ signaling pathways.
DS could be a promising protective agent against GM-induced nephrotoxicity through targeting of KEAP1/Nrf2/ARE, AKT, and PPAR-γ signaling pathways.
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