Development of Zalfermin, a Long-Acting Proteolytically Stabilized FGF21 Analog.

Here, we describe the development of the FGF21 analog zalfermin (NNC0194-0499, ), intended for once-weekly sc dosing. Protein engineering was needed to address inherent druggability issues of the natural FGF21 hormone. Thus, deamidation of Asp121 was solved by mutation to glutamine, and oxidation of Met168 was solved by mutation to leucine.

MAS and MANS Predicts Repeated Sprint Ability in Youth Soccer Players.

Unlabelled: The study investigated the impact of maximal aerobic speed (MAS) and maximal anaerobic sprint (MANS) on repeated sprint ability (RSA) in soccer.

Methods: 17 amateur-to semi-professional soccer players, age 19 (± 4) years, were tested for maximal oxygen consumption (VO), oxygen cost of running (C), RSA consisting of 15·20m sprint each divided by a 100 seconds dribble track, and 40-meter sprint performance. MAS was calculated as VO · C, and MANS was defined as the highest velocity in the 40-meter sprint.

Health profession students' outlooks on the medical profession during the COVID-19 pandemic: a global perspective.

Background: This article summarizes a global study of the effect of the COVID-19 pandemic on junior health professions students' outlook on medicine. The pandemic has significantly affected health professions education. There is limited understanding of how students' pandemic experiences will affect them, and what impact these events may have on their career paths or the future of the professions.

A thematic analysis of students' discussions on death and body donation in international online focus groups.

Historically, Anatomy education is an in-person discipline involving exposure to human body donors that facilitates personal and professional growth through, in part, the initiation of reflection on the topic of death. However, during the COVID-19 pandemic the decreased exposure to cadaveric anatomy for many health professions students may have influenced the depth of their individual reflections on this topic. Accordingly, this study aimed to investigate the effect of an alternate approach-focus group discussions between peers with varying degrees of exposure to cadaveric material-that may offer one strategy to stimulate deep reflection on the topic of death.

The Anatomy Course During COVID-19: The Impact of Cadaver-Based Learning on the Initiation of Reflection on Death.

Background: During the COVID-19 pandemic, in-person cadaveric dissection laboratories for teaching anatomy were omitted by many schools around the world. While knowledge domains can be easily evaluated via remote exams, non-traditional discipline-independent skills such as those encouraged through reflection on the topic of death are often overlooked. This study investigated how different anatomy course formats played a role in initiating students' reflections on death during the COVID-19 pandemic.

Colorectal cancer-associated SNP rs17042479 is involved in the regulation of NAF1 promoter activity.

A novel risk locus at 4q32.2, located between the Nuclear Assembly Factor 1 (NAF1) and Follistatin Like 5 (FSTL5) genes, was associated with increased risk of developing colorectal cancer (CRC), with SNP rs17042479 being the most associated. However, the link between CRC development and the risk locus at 4q32.

Contemporary N and SF multiple breath washout in infants and toddlers with cystic fibrosis.

Introduction: Multiple breath washout (MBW) is used for early detection of cystic fibrosis (CF) lung disease, with SF MBW commonly viewed as the reference method. The use of N MBW in infants and toddlers has been questioned for technical and physiological reasons, but a new correction of the N signal has minimized the technical part. The present study aimed to assess the remaining differences and the contributing mechanisms for the differences between SF and N MBW,corrected-such as tidal volume reduction during N washout with pure O .

The effect of fatty diacid acylation of human PYY on Y receptor potency and half-life in minipigs.

Peptides are notoriously known to display very short in vivo half-lives often measured in minutes which in many cases greatly reduces or eliminates sufficient in vivo efficacy. To obtain long half-lives allowing for up to once-weekly dosing regimen, fatty acid acylation (lipidation) have been used to non-covalently associate the peptide to serum albumin thus serving as a circulating depot. This approach is generally considered in the scientific and patent community as a standard approach to protract almost any given peptide.

Alternatives to Student Outbound Mobility-Improving Students' Cultural Competency Skills Online to Improve Global Health Without Travel.

Introduction: Student outbound mobility is a major element in internationalization of medical education and global health education. However, this approach is often criticized, as it is inherently inequitable. Internationalization is a newer concept that aims to provide students with international skills and experiences without exchange travel.

Intestinal Growth in Glucagon Receptor Knockout Mice Is Not Associated With the Formation of AOM/DSS-Induced Tumors.

Treatment with exogenous GLP-2 has been shown to accelerate the growth of intestinal adenomas and adenocarcinomas in experimental models of colonic neoplasia, however, the role of endogenous GLP-2 in tumor promotion is less well known. Mice with a global deletion of the glucagon receptor (Gcgr) display an increase in circulating GLP-1 and GLP-2. Due to the intestinotrophic nature of GLP-2, we hypothesized that Gcgr mice would be more susceptible to colonic dysplasia in a model of inflammation-induced colonic carcinogenesis.

Initiating Students' Reflections on Life's Passing in the Anatomy Course - an International Observation at 14 Universities.

Background: Medical and dental students' feelings and thoughts about the topic of death and life's passing are often associated with learning in the gross anatomy course, when students begin working with a deceased body donor in order to study human anatomy. Little is known of whether the format of anatomy teaching has an impact on these experiences. An observational study was performed to capture the initiation of students' sentiments on the topic of life's passing during the anatomy course at 14 international universities, identify common themes regarding these thoughts, and to study the connection to variations in anatomy course formats and included elements.

An Observation of Healthcare Professions Students' Perceptions During the COVID-19 Pandemic.

This study conveys preclinical healthcare professions students' sentiments at 14 universities during the 2020 COVID-19 pandemic. Essays about students' thoughts and experiences were thematically sorted and revealed a variety of sentiments spanning from positive (e.g.

An International Partnership of 12 Anatomy Departments - Improving Global Health through Internationalization of Medical Education.

Background: At a time of global interconnectedness, the internationalization of medical education has become important. Anatomy as an academic discipline, with its close connections to the basic sciences and to medical education, can easily be connected with global health and internationalization of medical education. Here the authors present an international program based on a partnership between twelve anatomy departments in ten countries, on four continents.

Short-term tissue permeability actions of dextran sulfate sodium studied in a colon organ culture system.

Dextran sulfate sodium (DSS)-induced colitis is the most commonly used animal model for inflammatory bowel diseases. However, the precise molecular action of DSS, in particular its initial effect on the epithelial tissue permeability, is still poorly understood. In the present work, organ culture of mouse - and pig colon explants were performed for 1-2 h in the presence/absence of 2% DSS together with polar- and lipophilic fluorescent probes.

Upregulation of PD-1 follows tumour development in the AOM/DSS model of inflammation-induced colorectal cancer in mice.

Chronic inflammation may drive development of cancer as observed in inflammation-induced colorectal cancer (CRC). Though immune cells can infiltrate the tumour microenvironment, cancer cells seem to evade anti-tumour responses, which is one of the established hallmarks of cancer. Targeting the programmed cell death protein-1 (PD-1)/PD-L1 signalling pathway is currently at the forefront in the development of anti-tumour immunity-based therapies for multiple malignancies.

Socioeconomic inequality in cancer survival - changes over time. A population-based study, Denmark, 1987-2013.

Socioeconomic inequality in survival after cancer have been reported in several countries and also in Denmark. Changes in cancer diagnostics and treatment may have changed the gap in survival between affluent and deprived patients and we investigated if the differences in relative survival by income has changed in Danish cancer patients over the past 25 years. The 1- and 5-year relative survival by income quintile is computed by comparing survival among cancer patients diagnosed 1987-2009 to the survival of a cancer-free matched sample of the background population.

Radiation Therapy for Treatment of Adolescent and Young Adult Hodgkin Lymphoma and Risk for Cardiovascular Disease and Cancer.

Purpose: To estimate the risk for hospitalizations among survivors of Hodgkin lymphoma diagnosed in adolescence or young adulthood according to exposure to treatment with radiation therapy.

Methods: Through the files of the Danish Cancer Registry, we identified 1684 five-year survivors of Hodgkin lymphoma, diagnosed at age 15-39 years during the period 1943-2004, and for whom information on radiation therapy was available in the Cancer Registry. Population-based comparisons were identified through the Danish Civil Registration System and matched to the survivors on year of birth and sex.

Rectal Insulin Instillation Inhibits Inflammation and Tumor Development in Chemically Induced Colitis.

Background And Aims: Epithelial expression of the insulin receptor in the colon has previously been reported to correlate with extent of colonic inflammation. However, the impact of insulin signalling in the intestinal mucosa is still unknown. Here, we investigated the effects of inactivating the epithelial insulin receptor in the intestinal tract, in an experimental model of inflammation-induced colorectal cancer.

Neurologic disorders in 4858 survivors of central nervous system tumors in childhood-an Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study.

Background: A comprehensive overview of neurologic complications among survivors of central nervous system (CNS) tumors in childhood is lacking. We aimed to investigate the risk for these disorders in a large, population-based study with outcome measures from nationwide hospital registries.

Methods: We identified 4858 five-year survivors with diagnoses of CNS tumor in childhood in Denmark, Iceland, Finland, and Sweden in 1943-2007, and 166658 matched population comparison subjects.

Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4.

Cancer incidence is rising and this global challenge is further exacerbated by tumour resistance to available medicines. A promising approach to meet the need for improved cancer treatment is drug repurposing. Here we highlight the potential for repurposing disulfiram (also known by the trade name Antabuse), an old alcohol-aversion drug that has been shown to be effective against diverse cancer types in preclinical studies.

Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): A population-based cohort study of 32,839 one-year survivors.

Information on late onset liver complications after childhood cancer is scarce. To ensure an appropriate follow-up of childhood cancer survivors and reducing late liver complications, the need for comprehensive and accurate information is presented. We evaluate the risk of liver diseases in a large childhood cancer survivor cohort.

Long-term inpatient disease burden in the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study: A cohort study of 21,297 childhood cancer survivors.

Background: Survivors of childhood cancer are at increased risk for a wide range of late effects. However, no large population-based studies have included the whole range of somatic diagnoses including subgroup diagnoses and all main types of childhood cancers. Therefore, we aimed to provide the most detailed overview of the long-term risk of hospitalisation in survivors of childhood cancer.

In vivo measurement and biological characterisation of the diabetes-associated mutant insulin p.R46Q (GlnB22-insulin).

Aims/hypothesis: Heterozygous mutations in the insulin gene that affect proinsulin biosynthesis and folding are associated with a spectrum of diabetes phenotypes, from permanent neonatal diabetes to MODY. In vivo studies of these mutations may lead to a better understanding of insulin mutation-associated diabetes and point to the best treatment strategy. We studied an 18-year-old woman with MODY heterozygous for the insulin mutation p.