Drug Development.

Background: Evidence suggests glucagon-like peptide 1 receptor agonists (GLP-1RAs) may have therapeutic potential in Alzheimer's disease (AD). Cumulative evidence has indicated a potential reduction in cognitive decline in people with AD, while real-world evidence has shown decreased dementia risk in patients with type 2 diabetes. Non-clinical data reveal that GLP-1RAs impact neuroinflammation and other biological processes believed to be involved in AD pathophysiology, including effects on central and peripheral immune cells.

Proteomic changes upon treatment with semaglutide in individuals with obesity.

Obesity and type 2 diabetes are prevalent chronic diseases effectively managed by semaglutide. Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645). We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways.

coexpressing neurons modulate the suppression of food intake and body weight by a GLP-1/leptin dual agonist.

Glucagon-like peptide-1 (GLP-1) and leptin signal recent feeding and long-term energy stores, respectively, and play complementary roles in the modulation of energy balance. Previous work using single-cell techniques in mice revealed the existence of a population of leptin receptor ()-containing dorsomedial hypothalamus (DMH) neurons marked by the expression of GLP-1 receptor (; LepR neurons) that play important roles in the control of feeding and body weight by leptin. Here, we demonstrate the existence of a population of LepR neurons in the DMHs of nonhuman primates (NHPs), suggesting the potential translational relevance of these neurons.

The effectiveness of diabetes training of psychiatric health professionals on individuals with diabetes and psychiatric disorders - a pragmatic controlled trial in Denmark.

Background: Individuals with diabetes and co-existing psychiatric disorders have more diabetes complications and lower life expectancy than those with diabetes but no co-existing psychiatric disorders. Psychiatric health professionals may have a role in improving these outcomes but often lack diabetes knowledge and skills. This study aims to examine the effectiveness of a diabetes training course for psychiatric health professionals on their diabetes knowledge and skills and clinical outcomes, diabetes support and diabetes distress among individuals with diabetes and psychiatric disorders treated in psychiatric outpatient clinics.

Fuzzy ripple artifact in high resolution fMRI: identification, cause, and mitigation.

Purpose: High resolution fMRI is a rapidly growing research field focused on capturing functional signal changes across cortical layers. However, the data acquisition is limited by low spatial frequency EPI artifacts; termed here as Fuzzy Ripples. These artifacts limit the practical applicability of acquisition protocols with higher spatial resolution, faster acquisition speed, and they challenge imaging in lower brain areas.

Facilitators and challenges of implementing a digital patient education programme for rheumatoid arthritis into clinical practice.

Background: The integration of telehealth interventions into clinical practice is frequently delayed, hindering the full adoption. Previously, we developed a digital patient education (PE) programme for self-management in rheumatoid arthritis (RA). While the programme design considered crucial factors to ensure the likelihood of success in clinical practice, there is a need for a systematic evaluation of implementation perspectives.

AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer.

Castration resistant prostate cancer (CRPC) remains an incurable disease stage with ineffective treatments options. Here, the androgen receptor (AR) coactivators CBP/p300, which are histone acetyltransferases, were identified as critical mediators of DNA damage repair (DDR) to potentially enhance therapeutic targeting of CRPC. Key findings demonstrate that CBP/p300 expression increases with disease progression and selects for poor prognosis in metastatic disease.

Insight into protein crosslinking and casein polymerization in pre- and posthydrolyzed lactose-free ultra-high-temperature milk during long-term storage.

During processing and storage of both conventional and lactose-hydrolyzed UHT milk (LHM), aggregation of milk proteins occurs. Protein aggregation can inter alia occur via nonreducible covalent cross-links derived from either Maillard or dehydroalanine (DHA) pathways. To study this further in relation to processing method and lactase enzyme purity, LHM was produced using 3 different lactase preparations, with lactase enzymes added in a dairy setting either before (prehydrolysis) or after (posthydrolysis) UHT treatment.

Objectives and achievements of the HUMN project on its 26th anniversary.

Micronuclei (MN) are a nuclear abnormality that occurs when chromosome fragments or whole chromosomes are not properly segregated during mitosis and consequently are excluded from the main nuclei and wrapped within nuclear membrane to form small nuclei. This maldistribution of genetic material leads to abnormal cellular genomes which may increase risk of developmental defects, cancers, and accelerated aging. Despite the potential importance of MN as biomarkers of genotoxicity, very little was known about the optimal way to measure MN in humans, the normal ranges of values of MN in healthy humans and the prospective association of MN with developmental and degenerative diseases prior to the 1980's.

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Infections in pregnancy are common, and although often not harmful to the woman or her unborn child, some infections may be associated with severe adverse outcomes. Pregnancy causes physiological and immunological adaptations which may make pregnant women more susceptible to infections and at increased risk of more severe illness. Infections in pregnancy represent a challenging area of concern for many specialists and general practitioners.

Exposure to bisphenol A in European women from 2007 to 2014 using human biomonitoring data - The European Joint Programme HBM4EU.

Background: Bisphenol A (BPA; or 4,4'-isopropylidenediphenol) is an endocrine disrupting chemical. It was widely used in a variety of plastic-based manufactured products for several years. The European Food Safety Authority (EFSA) recently reduced the Tolerable Daily Intake (TDI) for BPA by 20,000 times due to concerns about immune-toxicity.

Liraglutide Impacts Iron Homeostasis in a Murine Model of Hereditary Hemochromatosis.

Classic hereditary hemochromatosis (HH) is an autosomal recessive iron-overload disorder resulting from loss-of-function mutations of the HFE gene. Patients with HH exhibit excessive hepatic iron accumulation that predisposes these patients to liver disease, including the risk for developing liver cancer. Chronic iron overload also poses a risk for the development of metabolic disorders such as obesity, type 2 diabetes, and insulin resistance.

Ethylene Oxide Hemoglobin Adducts in Cord Blood and Offspring's Size at Birth: The NewGeneris European Cohort Study.

Background: Prenatal ethylene oxide exposure may have adverse effects on fetal development. We examined the relationships between ethylene oxide hemoglobin (Hb) adduct levels and offspring's size at birth in a prospective European mother-child study.

Methods: This study included 1106 singletons from the NewGeneris project (2006-2010) with ethylene oxide Hb adducts measured in cord blood.

Repetitive invasive lung function maneuvers do not accentuate experimental fibrosis in mice.

Assessment of lung function is an important clinical tool for the diagnosis and monitoring of chronic lung diseases, including idiopathic pulmonary fibrosis (IPF). In mice, lung function maneuvers use algorithm-based ventilation strategies including forced oscillation technique (FOT), negative pressure-driven forced expiratory (NPFE) and pressure-volume (PV) maneuvers via the FlexiVent system. This lung function test (LFT) is usually performed as end-point measurement only, requiring several mice for each time point to be analyzed.

COVID-19 pandemic influence on perceived exposure to chemical substances in Latvia: data from a focus group discussion and the HBM4EU citizen survey.

Introduction: The COVID-19 pandemic has globally influenced the exposure of populations to chemical substances through various channels. This study aims to evaluate the tendencies of the use of chemical products in Latvia amidst the pandemic. Answers from 597 respondents (26.

Development of antibody levels and subsequent decline in individuals with vaccine induced and hybrid immunity to SARS-CoV-2.

Objectives: This study aimed to compare antibody trajectories among individuals with SARS-CoV-2 hybrid and vaccine-induced immunity.

Methods: Danish adults receiving three doses of BTN162b2 or mRNA-1237 were included prior to first vaccination (Day 0). SARS-CoV-2 anti-spike IgG levels were assessed before each vaccine dose, at Day 90, Day 180, 28 days after 3rd vaccination (Day 251), Day 365, and prior to 4th vaccination (Day 535).

Low-volume ventilation of preinjured lungs degrades lung function via stress concentration and progressive alveolar collapse.

Mechanical ventilation can cause ventilation-induced lung injury (VILI). The concept of stress concentrations suggests that surfactant dysfunction-induced microatelectases might impose injurious stresses on adjacent, open alveoli and function as germinal centers for injury propagation. The aim of the present study was to quantify the histopathological pattern of VILI progression and to test the hypothesis that injury progresses at the interface between microatelectases and ventilated lung parenchyma during low-positive end-expiratory pressure (PEEP) ventilation.

Clinical and Metabolic Characterization of Women With Gestational Diabetes Mellitus Within the First Year Postpartum.

Context: Women with gestational diabetes mellitus (GDM) have an increased risk of long-term complications, including impaired glucose metabolism, type 2 diabetes (T2DM), cardiovascular disease, and obesity. In current clinical practice, a 1 size fits all approach to GDM is applied, although heterogeneity among women with GDM has been recognized.

Objective: To give the most adequate preventive care and postpartum (PP) guidance, we aimed to make a metabolic characterization and identify subgroups of women with previous GDM within the first year PP.

The E3 ubiquitin ligase ITCH negatively regulates intercellular communication via gap junctions by targeting connexin43 for lysosomal degradation.

Intercellular communication via gap junctions has a fundamental role in regulating cell growth and tissue homeostasis, and its dysregulation may be involved in cancer development and radio- and chemotherapy resistance. Connexin43 (Cx43) is the most ubiquitously expressed gap junction channel protein in human tissues. Emerging evidence indicates that dysregulation of the sorting of Cx43 to lysosomes is important in mediating the loss of Cx43-based gap junctions in cancer cells.

Which self-reported measures are useful to explore diabetes support needs among adults with diabetes and severe mental illness?

Objectives: To construct and test patient-reported outcome measures (PROMs) for identifying diabetes support needs of adults with co-existing diabetes and severe mental illness (SMI) provided by mental health professionals at psychiatric outpatient clinics.

Methods: Design thinking was used to identify, select, and modify PROMs in collaboration with 18 adults with type 1 or type 2 diabetes and SMI and 10 healthcare experts. The PROMs were then tested with 86 adults with diabetes and SMI recruited from eight psychiatric outpatient clinics in Denmark.