Current Use of Physiologically Based Pharmacokinetic modeling in New Medicinal Product Approvals at EMA.

Physiologically Based Pharmacokinetic (PBPK) Models are routinely used in drug development and therefore appear frequently in marketing authorization applications (MAAs) to the European Medicines Agency (EMA). For a model to be a key source of evidence for a regulatory decision, it must be considered qualified for the intended use. Advice on the data expected to allow qualification of a PBPK model or platform is provided in the EMA Guideline on the reporting of PBPK modeling and simulation.

The Evolution of NCI's Health Information National Trends Survey: Methods, Data, and Future Directions.

The National Cancer Institute's (NCI) Health Information National Trends Survey® (HINTS®), was conceived in 1997 during a multidisciplinary conference focused on risk communication that included attendees representing the fields of psychology, health behavior, health education, public health, clinical medicine, and health journalism. The key recommendation from the conference was for NCI to develop a premiere communication-specific population survey to track health and cancer communication-related phenomena. This led to NCI developing and launching HINTS in 2003.

Understanding diagnostic delays and health outcomes for inflammatory bowel disease: a mixed-methods study of patients' perspectives.

Purpose: Inflammatory bowel disease (IBD) is a chronic condition affecting the digestive system with symptoms that are often episodic, unpredictable, socially stigmatizing, and impact quality of life. While a timely diagnosis reduces the risk of complications and improves health outcomes, diagnostic delays (DDs) are common. Our study used narratives and data from patient-reported outcome measures (PROMs) of individuals diagnosed with IBD to examine: (1) What factors helped or hindered achieving a timely diagnosis of IBD? and (2) how do DDs relate to PROMs?

Methods: We conducted a mixed-methods study of 296 individuals diagnosed with IBD in Canada.

Implementing a global mentoring program: A call to action for mentorship in surgery.

Background: The Gender Equity Initiative in Global Surgery organization launched a mentorship program to address the limited opportunities available in low-and-middle-income countries (LMICs). We aimed to evaluate the utility of the virtual program in bridging this critical gap.

Methods: A retrospective review of program surveys containing quantitative and qualitative questions from 2022 to 2023 was performed.

Analysis of the immunomodulatory properties of mycobacterium cell wall fraction on the cytokine production of peripheral blood mononuclear cells of healthy dogs.

Background: Mycobacterium cell wall fraction (MCWF) is derived from nonpathogenic Mycobacterium phlei and is used as an immunomodulatory compound in clinical practice, yet its mode-of-action requires further research.

Objective: To evaluate the host response to MCWF in canine peripheral blood mononuclear cells (PBMCs) by using enzyme-linked immunosorbent assays (ELISA) and quantitative reverse transcription (qRT)-PCR for assessment of cytokines.

Animals: Eight healthy Labrador retrievers.

The effect of dietary sodium octanoate on Ghrelin concentration and feed intake in chickens and turkeys: a comparative study.

Active ghrelin (AG) is produced through the post-translational addition of n-octanoic acid to the amino residue Ser-3, making it the natural ligand for the ghrelin receptor. The synthesis of AG is contingent upon specific dietary fatty acids as substrates for the acylation process. Prior studies have demonstrated that AG infusion can lead to reduced feed intake (FI) in broiler chickens, suggesting that manipulating AG may serve as an alternative to quantitative feed restriction in broiler breeders.

High economic inequality is linked to greater moralization.

Throughout the 21st century, economic inequality is predicted to increase as we face new challenges, from changes in the technological landscape to the growing climate crisis. It is crucial we understand how these changes in inequality may affect how people think and behave. We propose that economic inequality threatens the social fabric of society, in turn increasing moralization-that is, the greater tendency to employ or emphasize morality in everyday life-as an attempt to restore order and control.

Exploring Within-Gender Differences in Friendships Using an Online Social Network.

People tend to befriend others similar to themselves, generating a pattern called homophily. However, existing studies on friendship patterns often rely on surveys that assess the perspective of relatively few participants on their friendships but do not measure actualized friendship patterns. Here, we used data from a large Slovakian online social network to assess the role of gender, age, and body mass index (BMI) in same-gender online connections among more than 400,000 users.

A Two-Way Proposal for the Determination of Bioequivalence for Narrow Therapeutic Index Drugs in the European Union.

In the European Union, bioequivalence (BE) for narrow therapeutic index (NTI) drugs is currently demonstrated when the 90% confidence interval for the ratio of the population geometric means of the test and reference products for AUC, and in some cases for Cmax, falls within the acceptance range of 90.00% to 111.11%.

A modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived molecules.

Halogen-containing molecules are ubiquitous in modern society and present unique chemical possibilities. As a whole, de novo fermentation and synthetic pathway construction for these molecules remain relatively underexplored and could unlock molecules with exciting new applications in industries ranging from textiles to agrochemicals to pharmaceuticals. Here, we report a mix-and-match co-culture platform to de novo generate a large array of halogenated tryptophan derivatives in Escherichia coli from glucose.

Sequence-structure-function characterization of the emerging tetracycline destructase family of antibiotic resistance enzymes.

Tetracycline destructases (TDases) are flavin monooxygenases which can confer resistance to all generations of tetracycline antibiotics. The recent increase in the number and diversity of reported TDase sequences enables a deep investigation of the TDase sequence-structure-function landscape. Here, we evaluate the sequence determinants of TDase function through two complementary approaches: (1) constructing profile hidden Markov models to predict new TDases, and (2) using multiple sequence alignments to identify conserved positions important to protein function.

Small-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders.

Glycogen synthase 1 (GYS1), the rate-limiting enzyme in muscle glycogen synthesis, plays a central role in energy homeostasis and has been proposed as a therapeutic target in multiple glycogen storage diseases. Despite decades of investigation, there are no known potent, selective small-molecule inhibitors of this enzyme. Here, we report the preclinical characterization of MZ-101, a small molecule that potently inhibits GYS1 in vitro and in vivo without inhibiting GYS2, a related isoform essential for synthesizing liver glycogen.

How intrasexual competitiveness shapes attitudes towards cosmetic surgery recipients.

Cosmetic surgery is extremely popular. Despite this, negative attitudes towards cosmetic surgery recipients prevail. Across two pre-registered studies, we examined whether intrasexual competitiveness explains these negative attitudes.

Rationale, Procedures, and Response Rates for a Pilot Study to Sample Cancer Survivors for NCI's Health Information National Trends Survey: HINTS-SEER 2021.

The National Cancer Institute's (NCI) Health Information National Trends Survey (HINTS) is a nationally representative survey of U.S. adults in which 12-17% of respondents report a cancer history.

Association of Sputum Eosinophilia With Easily Measured Type-2 Inflammatory Biomarkers in Untreated Mild Persistent Asthma.

Background: A multicenter clinical trial in patients with mild persistent asthma indicated that response to inhaled corticosteroids (ICS) is limited to those with sputum eosinophilia. However, testing for sputum eosinophilia is impractical in most clinical settings.

Objective: We examined associations between sputum eosinophilia and type 2 inflammatory biomarkers in untreated mild persistent asthma.

Gut microbiome and antibiotic resistance effects during travelers' diarrhea treatment and prevention.

The travelers' gut microbiome is potentially assaulted by acute and chronic perturbations (e.g., diarrhea, antibiotic use, and different environments).

S. aureus drives itch and scratch-induced skin damage through a V8 protease-PAR1 axis.

Itch is an unpleasant sensation that evokes a desire to scratch. The skin barrier is constantly exposed to microbes and their products. However, the role of microbes in itch generation is unknown.