Stevensonbarnett1547

Modern Western diets are rich in acidogenic foods. Human and

studies suggest a potential link between dietary acid load and cancer risk. However, no epidemiologic studies have investigated the association of dietary acid load with the risk of pancreatic cancer. Therefore, we conducted a prospective cohort study to fill this gap.

A population-based cohort of 95,708 American adults was identified. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) were used to assess dietary acid load of each subject, with greater values indicating greater dietary acid load. Cox regression was used to estimate risk estimates for pancreatic cancer incidence. Predefined subgroup analysis was used to identify the potential effect modifiers.

A total of 337 pancreatic cancer cases were observed during 848,534.0 person-years of follow-up. PRAL score was found to be positively associated with the risk of pancreatic cancer [fully adjusted HR

1.73; 95% confidence interval (95% CI), 1.21-2.48;



= 0.001] in a nonlinear dose-response pattern (



= 0.012). Subgroup analysis found that the positive association of PRAL score with the risk of pancreatic cancer was more pronounced in subjects aged <65 years than in those ≥65 years (



= 0.018). Similar results were obtained for NEAP score.

Higher dietary acid load is associated with a higher risk of pancreatic cancer. Future studies should validate our findings in other populations and settings.

This is the first epidemiologic study suggesting that reducing dietary acid load may be useful in primary prevention of pancreatic cancer.

This is the first epidemiologic study suggesting that reducing dietary acid load may be useful in primary prevention of pancreatic cancer.Emerging three-dimensional (3D) cultures of glioblastoma are becoming powerful models to study glioblastoma stem cell behavior and the impact of cell-cell and cell-microenvironment interactions on tumor growth and invasion. Here we describe a method for culturing human glioblastoma stem cells (GSCs) in 3D by co-culturing them with pluripotent stem cell-derived brain organoids. This requires multiple coordinated steps, including the generation of cerebral organoids, and the growth and fluorescence tagging of GSCs. We highlight how to recognize optimal organoid generation and how to efficiently mark GSCs, before describing optimized co-culture conditions. We show that GSCs can efficiently integrate into brain organoids and maintain a significant degree of cell fate heterogeneity, paving the way for the analysis of GSC fate behavior and lineage progression. These results establish the 3D culture system as a viable and versatile GBM model for investigating tumor cell biology and GSC heterogeneity.This article has an associated First Person interview with the first author of the paper.

Valproate is a known teratogen. In April 2018, the Medicines and Healthcare products Regulatory Agency (MHRA) restricted its use in women and banned use in pregnancy, except for epilepsy with no other effective treatment. To date, there is limited information on valproate prescribing within primary care.

To characterise valproate prescribing to women of childbearing age, recorded advice or GP prescribed contraception, and recorded pregnancies.

A cross-sectional study of patients from all 141 general practices across three clinical commissioning groups (CCGs) in East London.

Women aged 15-44 years prescribed valproate between 1 October 2017 and 1 January 2020 were included. Exclusion criteria were early menopause, sterilisation procedures, or hysterectomy. Pseudonymised data on valproate indication, pregnancy, pre-conception, and contraception advice were retrospectively extracted from general practice consultation data. Data were analysed by quarter using univariate statistics.

Of the total 1 042 46formed reproductive choices and safeguard future pregnancies from valproate exposure.

The lung clearance index (LCI) is increasingly used as an outcome in clinical trials of patients with mild cystic fibrosis (CF) lung disease. Yet, understanding the impact of standard CF respiratory therapy on LCI is needed. We assessed to what degree withdrawal of nebulised dornase alfa affected LCI in school-age children with CF not receiving CFTR modulators or hydrator therapy.

A single-centre, randomised, controlled, parallel group study to determine effects of one month's withdrawal of nebulised dornase alfa (intervention) in 5-18 years old children with CF. Remaining chronic maintenance therapy stayed unchanged. Outcome measures were assessed at two visits one month apart. Primary outcome was absolute change in LCI. Secondary outcomes were FEV

, FEF

and CF Questionnaire-revised (CFQ-R) respiratory symptom score. Possible harmful effects were assessed by comparing the occurrence of pulmonary exacerbations between groups.

Twenty-eight children (median age 10.4 [interquartile range 7.6; 13.5] yearm clinical trials.Highly effective CFTR modulator drug therapy is increasingly available to those with cystic fibrosis. Multiple observational research studies are now being conducted to better understand the impacts of this important therapeutic milestone on long-term outcomes, patient care needs, and future research priorities. PROMISE is a large, multi-disciplinary academic study focused on the broad impacts of starting elexacaftor/tezacaftor/ivacaftor in the US population age 6 years and older. Eganelisib purchase The many areas of investigation and rationale for each are discussed by organ systems, along with recognition of remaining important questions that will not be addressed by this study alone. Knowledge gained through this and multiple complementary studies around the world will help to understand important health outcomes, clinical care priorities, and research needs for a large majority of people treated with these or similarly effective medications targeting the primary cellular impairment in cystic fibrosis.

Atrial fibrillation (AF) with rapid ventricular response frequently complicates the management of critically ill patients with sepsis and may necessitate the initiation of medication to avoid hemodynamic compromise. However, the optimal medication to achieve rate control for AF with rapid ventricular response in sepsis is unclear.

What is the comparative effectiveness of frequently used AF medications (β-blockers, calcium channel blockers, amiodarone, and digoxin) on heart rate (HR) reduction among critically ill patients with sepsis and AF with rapid ventricular response?

We conducted a multicenter retrospective cohort study among patients with sepsis and AF with rapid ventricular response (HR > 110 beats/min). We compared the rate control effectiveness of β-blockers to calcium channel blockers, amiodarone, and digoxin using multivariate-adjusted, time-varying exposures in competing risk models (for death and addition of another AF medication), adjusting for fixed and time-varying confounders.

Among 666 included patients, 50.