Langleydyer9833

Organic anion transporter 3 (OAT3) plays an important role in the disposition of various anionic drugs which impacts the pharmacokinetics and pharmacodynamics of the therapeutics, thus influencing the pharmacological effects and toxicity of the drugs. In this study, we investigated the effect of insulin on the regulation of OAT3 function, expression, and SUMOylation. We demonstrated that insulin induced an increase in OAT3 transport activity through a dose- and time-dependent manner in COS-7 cells. The insulin-induced elevation in OAT3 function was blocked by PKA inhibitor H89, which correlated well with OAT3 protein expression. Moreover, both PKA activator Bt2-cAMP-induced increase and insulin-induced increase in OAT3 function were blocked by PKB inhibitor AKTi1/2. To further investigate the involvement of SUMOylation, we treated OAT3-expressing cells with insulin in presence or absence of H89 or AKTi1/2 followed by examining OAT3 SUMOylation. We showed that insulin enhanced OAT3 SUMOylation, and such enhancement was abrogated by H89 and AKTi1/2. Lastly, insulin increased OAT3 function and SUMOylation in rat kidney slice. In conclusion, our investigations demonstrated that insulin regulated OAT3 function, expression, and SUMOylation through PKA/PKB signaling pathway. Graphical abstract.

There are growing discussions regarding the term "cancer survivor," particularly how patients with cancer relate to it.

To assess how individuals diagnosed with colorectal cancer (CRC) perceive the term "cancer survivor."

We conducted an international cross-sectional study and, using social media, invited individuals who were ≥18 years; received a diagnosis for CRC; and can communicate in English. We administered an online survey comprising both quantitative (e.g., multiple choice) and qualitative (e.g., open-ended) questions. We used logistic regression to assess determinants of participants' perspectives towards the term "cancer survivor." Qualitative responses were analyzed using content analysis.

In all, 539 participants with CRC completed the survey, including 122 (22.6%) undergoing treatment and 417 (77.4%) who completed treatment. selleck Participants who had completed treatment were four times more likely to relate with term "cancer survivor" compared to those undergoing treatment (adjusted odds ratio (aOR), 4.0; 95% confidence interval (CI) 2.4 to 6.7). Participants diagnosed with CRC ≥50 years were also more likely to relate with the term compared to those diagnosed < 50 years (aOR, 1.88; 95% (CI) 1.2 to 3.0). Analysis of open-ended survey responses revealed aversion, discomfort, indifference, reluctance, and acceptance as themes which capture the spectrum of feelings towards the term "cancer survivor."

Perspectives of individuals with CRC towards the term "cancer survivor" differ according to treatment status and age of diagnosis.

Our study amplifies voices of the CRC community towards reconsideration of the term "cancer survivor", considering the implications of treatment status and age in highlighting the importance of language.

Our study amplifies voices of the CRC community towards reconsideration of the term "cancer survivor", considering the implications of treatment status and age in highlighting the importance of language.

Although metastatic breast cancer (MBC) survival is improving, symptoms remain a significant burden. Returning to a cancer center for symptom management can be challenging. Technology-enabled supportive care platforms are worth exploration.

Seventeen patients with MBC were randomized to immediate or delayed start for a 3-month intervention that included daily tablet-based guideline-concordant self-care for pain, distress, fatigue, and sleep disturbance, as well as weekly calls with a patient navigator. The primary outcome was patient acceptability. We also assessed feasibility, patient satisfaction, and cost and compared between group differences for symptoms. RM-ANOVA examined between group differences over time. Hedges' d effect sizes quantified magnitude of differences in change between immediate and delayed start.

Sixty-eight percent of patients approached accepted the tablet-based intervention. Patients interacted with the tablet 48% of possible days. Patient satisfaction ranged from 83 for walking to 49% for the psychological interventions. The cost of delivering Nurse AMIE for 3 months was $570.23. Small nonsignificant improvements were found for fatigue (d=0.24). Nonsignificant, but potentially clinically meaningful, moderate reductions were found for sleep (d=0.65) and distress (d=0.74).

A tablet-based supportive care platform that offers guideline-concordant self-care for pain, fatigue, sleep, and distress was observed to be highly acceptable and feasible for patients with metastatic breast cancer. Patient satisfaction scores and initial evaluation of efficacy are promising, and the platform warrants further investigation.

Technology-based self-care is a promising option to address symptoms in patients with metastatic breast cancer.

Technology-based self-care is a promising option to address symptoms in patients with metastatic breast cancer.Management of cystic fibrosis (CF) patients colonized with Pseudomonas aeruginosa is challenging due to its virulence and multi-drug resistance. Ceftolozane/tazobactam (C/T) is a promising new antipseudomonal agent, and clinical data on CF are limited. We describe our experience in the use of C/T for P. aeruginosa-related pulmonary exacerbations (PE) in CF adults admitted within 2016 and 2019 at Careggi Hospital, Florence, Italy. PE was diagnosed as deterioration of respiratory function, worsening cough, and increasing of sputum. C/T was given at the dose of 3 g every 8 h. C/T was used in ten patients. Mean length of C/T treatment was 16.3 days, and tobramycin was the most frequently combined antipseudomonal agent. All patients were successfully treated although susceptibility testing on sputum sample showed C/T resistance in two cases. No adverse effects related to C/T were reported. To our knowledge this is the largest case series on CF patients treated with C/T. Clinical responses were encouraging even where C/T resistant P.