Novel intranasal treatment for anxiety disorders using amiloride, an acid-sensing ion channel antagonist: Pharmacokinetic modeling and simulation.

OBJECTIVE: To develop a physiologically based pharmacokinetic (PBPK) model for amiloride, an acid-sensing ion channel (ASIC) antagonist, and to simulate its pharmacokinetics in plasma and the central nervous system following intranasal administration in a virtual human population. MATERIALS AND METHODS: We first developed a PBPK model of amiloride after oral administration and optimized the model using data from five clinical studies. Next, we added a nasal compartment to the amiloride oral PBPK model and parameterized using data from previous clinical studies. We simulated amiloride's pharmacokinetics in plasma, brain, and cerebrospinal fluid (CSF) after intranasal administration of amiloride at various doses in a virtual human population. RESULTS: The target amiloride concentration in the central nervous system required for maximal ASIC inhibition was achieved with a 75-mg intranasal amiloride dose. However, this finding is based on simulations performed using a mathematical model and needs to be further validated with appropriate clinical data. CONCLUSION: The nasal PBPK model of amiloride could be used to design future clinical studies and allow for successful clinical translation of intranasal amiloride formulation.

The Distribution of Colorectal Surgeons in the United States.

BACKGROUND: Surgical resection is a mainstay of colorectal cancer treatment, and prior studies have shown improved outcomes in patients undergoing surgery for colorectal cancer by colorectal surgical specialists compared with nonspecialized surgeons. Here, we examine the geographic distribution of colorectal surgeons in the United States and its relationship with sociodemographic characteristics of the served population. METHODS: The Area Health Resource File from 2017 to 2018 was used to identify the number and location of colorectal surgeons practicing throughout the United States and sociodemographic characteristics at the county and hospital referral region (HRR) level. The main outcomes of interest were the density of colorectal surgeons per 100,000 population and associations with sociodemographic characteristics at the county and HRR level based on multivariable linear regression. RESULTS: In multivariable analysis, regions with higher proportion of nonwhite individuals and college-educated individuals had significantly more colorectal surgeons per 100,000 population, whereas regions with higher proportions of uninsured individuals had significantly fewer colorectal surgeons per 100,000 population at both the county and HRR levels. CONCLUSIONS: Geographic and sociodemographic variability exists in the distribution of colorectal surgeons in the United States. Such variability may be contributing to disparities in access to specialized colorectal care.

Prevalence of High-Risk Disordered Eating Amongst Adolescents and Young Adults in the Middle East: A Scoping Review.

High-risk disordered eating (HRDE) negatively affects physical, mental, and social wellbeing. This scoping review aimed to estimate the prevalence of HRDE amongst adolescents and young adults in the Middle East. MEDLINE database was searched for studies published in English or Arabic from 1 January 2000 to 30 September 2020, estimating HRDE prevalence (using the Eating Attitudes Test 26 or 40 item questionnaire) in the Middle East. Two reviewers independently screened abstracts and full texts of potentially eligible records, followed by data extraction from eligible studies. Nineteen studies (n = 16,288; 65.8% female) from Egypt, Iran, Israel, Jordan, Kuwait, Libya, Oman, Palestine, Saudi Arabia, Syria, Turkey, and the United Arab Emirates were included. Prevalence of HRDE varied considerably across countries and was lowest amongst adolescents in Israel (F 8.2%; M 2.8%) and highest amongst university students in Egypt (F 75.8%; M 69.6%). Prevalence of high-risk for anorexia nervosa ranged from 0.0% in Jordan to 9.5% in Oman; high-risk for bulimia nervosa from 0.6% in Jordan to 1.0% in the United Arab Emirates; and high-risk for binge eating disorder was 1.0% and 1.8% in Turkey and Jordan, respectively. Future studies should employ a standardized two-stage design with clinical diagnosis to verify the prevalence of abnormal eating behaviours in the Middle East.

Reconnoitering the Therapeutic Role of Curcumin in Disease Prevention and Treatment: Lessons Learnt and Future Directions.

Turmeric is a plant with a very long history of medicinal use across different cultures. Curcumin is the active part of turmeric, which has exhibited various beneficial physiological and pharmacological effects. This review aims to critically appraise the corpus of literature associated with the above pharmacological properties of curcumin, with a specific focus on antioxidant, anti-inflammatory, anticancer and antimicrobial properties. We have also reviewed the different extraction strategies currently in practice, highlighting the strengths and drawbacks of each technique. Further, our review also summarizes the clinical trials that have been conducted with curcumin, which will allow the reader to get a quick insight into the disease/patient population of interest with the outcome that was investigated. Lastly, we have also highlighted the research areas that need to be further scrutinized to better grasp curcumin's beneficial physiological and medicinal properties, which can then be translated to facilitate the design of better bioactive therapeutic leads.