Synthesis, Pharmacological Characterization, and Binding Mode Analysis of 8-Hydroxy-Tetrahydroisoquinolines as 5-HT Receptor Inverse Agonists.

The serotonin 7 receptor (5-HTR) regulates various processes in the central nervous system, including mood, learning, and circadian rhythm control, among others. Receptor activation can lead to activation of the Gα protein and a subsequent increase of intracellular cyclic adenosine monophosphate (cAMP). Receptor interaction with inverse agonists results in a decrease of basal cAMP levels and therefore a downstream effect of reduced neuronal excitability and neurotransmission.

Manipulating Fano Coupling in an Opto-Thermoelectric Field.

Fano resonances in photonics arise from the coupling and interference between two resonant modes in structures with broken symmetry. They feature an uneven and narrow and tunable lineshape and are ideally suited for optical spectroscopy. Many Fano resonance structures have been suggested in nanophotonics over the last ten years, but reconfigurability and tailored design remain challenging.

The Calcium-Sensing Receptor in the Thick Ascending Limb and the Renal Response to Hypercalcemia.

Background: The parathyroid calcium-sensing receptor (CASR) controls the release of parathyroid hormone (PTH) in response to changes in serum calcium levels. Activation of the renal CASR increases urinary calcium excretion and is particularly important when CASR-dependent reductions in PTH fail to lower serum calcium. However, the role of the renal CASR in protecting against hypercalcemia and the direct effects of chronic CASR activation on tubular calcium handling remains to be fully elucidated.

Clinical outcomes among COVID-19 patients initiated on molnupiravir in Denmark - A national registry study.

Background: Molnupiravir (MOV) is an orally bioavailable ribonucleoside with antiviral activity against all tested SARS-CoV-2 variants. We describe the demographic, clinical, and treatment characteristics of non-hospitalized Danish patients treated with MOV and their clinical outcomes following MOV initiation.

Method: Among all adults (>18 years) who received MOV between 16 December 2021 and 30 April 2022 in an outpatient setting in Denmark, we summarized their demographic and clinical characteristics at baseline and post-MOV outcomes using descriptive statistics.

Cut-Off Values Able to Identify Migraine Patients With Increased Pressure-Pain Sensitivity Independent of the Migraine Cycle Through a Single Assessment: A Secondary Analysis of a Multicentre, Cross-Sectional, Observational Study.

Aim: Identify values that could predict the presence of increased pressure-pain sensitivity independent of the migraine cycle through a single assessment.

Methods: This was a secondary analysis of a previous study in which 198 episodic and chronic migraine patients were assessed during all phases of the migraine cycle. Pressure pain threshold (PPT) was assessed over the temporalis, cervical spine, hand, and leg.

Effectiveness of Empagliflozin vs Dapagliflozin for Kidney Outcomes in Type 2 Diabetes.

Importance: No large randomized clinical trial has directly compared empagliflozin with dapagliflozin, leaving their comparative effectiveness regarding kidney outcomes unknown.

Objective: To compare kidney outcomes between initiation of empagliflozin vs dapagliflozin in adults with type 2 diabetes who were receiving antihyperglycemic treatment.

Design, Setting, And Participants: This target trial emulation used nationwide, population-based routinely collected Danish health care data to compare initiation of empagliflozin vs dapagliflozin in adults with type 2 diabetes who received antihyperglycemic treatment between June 1, 2014, and October 31, 2020.

High fatigue levels among psychiatric outpatients - the validity of the Danish Patient Reported Outcomes Measurement Information System Fatigue Short-Form (PROMISF-SF).

Background: Patient Reported Outcomes Measurement Information System Fatigue Short-Form (PROMIS-F-SF) is a self-administered, patient reported outcome (PRO) designed to assess fatigue in healthy and clinical populations and for tracking progress during treatment for disorders complicated with fatigue.

Methods: Patients in the Mental Health Service Outpatient Clinics and healthy volunteers were invited to complete a survey, which included the Danish translation of the PROMIS-F-SF, the Chalder Fatigue Scale (CFS-11), and measures of depression and anxiety. We conducted a confirmatory factor analysis of the previously suggested single-factor structure of the instrument.

The value of early root development traits in breeding programs for biomass yield in perennial ryegrass (Lolium perenne L.).

Early root traits, particularly total root length, are heritable and show positive genetic correlations with biomass yield in perennial ryegrass; incorporating them into breeding programs can enhance genetic gain. Perennial ryegrass (Lolium perenne L.) is an important forage grass widely used in pastures and lawns, valued for its high nutritive value and environmental benefits.

The divide expand consolidate scheme for unrestricted second order Møller-Plesset perturbation theory ground state energies.

The linear scaling divide-expand-consolidate (DEC) framework is expanded to include unrestricted Hartree-Fock references. By partitioning the orbital space and employing local molecular orbitals, the full molecular calculation can be performed as independent calculations on individual fragments, making the method well-suited for massively parallel implementations. This approach also incorporates error control through the fragment optimization threshold (FOT), which maintains precision and consistency throughout the calculations.

Deletion of and genes in serovars induces a comparable immune response to wild-type infection in different chicken lineages.

It was previously reported that utilization of tetrathionate and 1,2-propanediol by spp. through the metabolic pathways encoded by and operons are related to overgrowth and out-competing microbiota in an anaerobic environment. However, recent knowledge demonstrated which strains in the absence of and genes provoke both higher intestinal colonization and spreading bacteria on faeces in relation to their respective wild-type strain, and generate more prominent inflammation as well.

Draft genome sequence of sp. CC302I with non-canonical biosynthetic gene clusters for codon-readthrough activity.

sp. CC302I was isolated from a highly oligothrophic environment. High-throughput screening shows high codon-readthrough activity for the isolate with no canonical biosynthetic gene cluster responsible.

Safety and Tolerability of Pivmecillinam During More Than Four Decades of Clinical Experience: A Systematic Review.

The recent US Food and Drug Administration approval of pivmecillinam-an oral prodrug of the amidinopenicillin antibiotic mecillinam-presents a valuable opportunity to address the need for new treatments for uncomplicated urinary tract infection (uUTI). We report findings of a systematic literature review of the safety profile of pivmecillinam/mecillinam based on more than 40 years' experience, mainly in Europe and Canada, to describe its tolerability profile and identify any important safety signals. In total, 110 eligible publications were identified describing use of pivmecillinam/mecillinam as monotherapy or in combination, for treatment of uUTI or other infectious conditions.

Endopiriform neurons projecting to ventral CA1 are a critical node for recognition memory.

The claustrum complex is viewed as fundamental for higher-order cognition; however, the circuit organization and function of its neuroanatomical subregions are not well understood. We demonstrated that some of the key roles of the CLA complex can be attributed to the connectivity and function of a small group of neurons in its ventral subregion, the endopiriform (EN). We identified a subpopulation of EN neurons by their projection to the ventral CA1 (EN.

Annexin A8 deficiency delays atherosclerosis progression.

Background: Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids and leukocytes within the arterial wall. By studying the aortic transcriptome of atherosclerosis-prone apolipoprotein E (ApoE) mice, we aimed to identify novel players in the progression of atherosclerosis.

Methods: RNA-Seq analysis was performed on aortas from ApoE and wild-type mice.

Very low levels of physical activity among patients hospitalized following hip fracture surgery: a prospective cohort study.

Purpose: The evidence supports early and intensive mobilization and physical activity for patients who are hospitalized following hip fracture. The objectives were to determine levels of physical activity among patients hospitalized following hip fracture surgery, and to explore the association between levels of physical activity and 30-day post-discharge readmission, and mortality.

Materials And Methods: We collected data at two university hospitals in Denmark from March-June 2023.

mTOR Ser1261 is an AMPK-dependent phosphosite in mouse and human skeletal muscle not required for mTORC2 activity.

The kinases AMPK, and mTOR as part of either mTORC1 or mTORC2, are major orchestrators of cellular growth and metabolism. Phosphorylation of mTOR Ser1261 is reportedly stimulated by both insulin and AMPK activation and a regulator of both mTORC1 and mTORC2 activity. Intrigued by the possibilities that Ser1261 might be a convergence point between insulin and AMPK signaling in skeletal muscle, we investigated the regulation and function of this site using a combination of human exercise, transgenic mouse, and cell culture models.

Circumpolar Population Structure, Diversity and Recent Evolutionary History of the Bearded Seal in Relation to Past and Present Icescapes.

The Arctic environment plays a critical role in the global climate system and marine biodiversity. The region's ice-covered expanses provide essential breeding and feeding grounds for a diverse assemblage of marine species, who have adapted to thrive in these harsh conditions and consequently are under threat from global warming. The bearded seal (Erignathus barbatus), including two subspecies (E.

Outdoor experiences and outdoor-based activities and interventions for individuals with spinal cord injury: a systematic scoping review.

Study Design: Systematic scoping review.

Objectives: The aim was to identify and synthesize empirical studies exploring outdoor experiences, activities, and interventions in people with spinal cord injury (SCI).

Methods: Systematic searches were performed in 7 bibliometric databases.