Comparison of whole-body MRI and contrast-enhanced CT for treatment response assessment of mixed visceral- and bone-metastasizing breast cancer.

BackgroundTreatment response assessment can be challenging in bone-metastasizing breast cancer. Whole-body magnetic resonance imaging (WB-MRI) is superior to contrast-enhanced computed tomography (CE-CT) for detecting progressive disease (PD) in bone-only metastatic breast cancer; however, the ability to detect PD in mixed visceral- and bone-metastasizing breast cancer remains to be assessed in prospective studies.PurposeTo prospectively compare WB-MRI and CE-CT for detecting PD in mixed visceral- and bone-metastasizing breast cancer and determine if WB-MRI could detect PD earlier than CE-CT.

The Selective Serotonin 5‑HT Receptor Agonist ()‑3-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)piperidine (LPH-5) Induces Persistent and Robust Antidepressant-Like Effects in Rodents.

Psychedelics have emerged as a promising treatment for mental health disease, and the therapeutic potential of psilocybin and lysergic acid diethylamide (LSD) is presently being pursued in numerous clinical trials. This has prompted a search for novel agents with more specific pharmacological activities than the rather promiscuous classical psychedelics. Here we present the detailed pharmacological characterization of one such compound, LPH-5 [()-3-(2,5-dimethoxy-4-(trifluoromethyl)-phenyl)-piperidine].

Proteomic profiling reveals the potential role of allogenic equine platelet-rich plasma and extracellular vesicles in modulating tendon inflammation and repair.

Objective: To determine the protein composition of equine platelet-rich plasma (PRP) and PRP-derived extracellular vesicles (EVs) and evaluate their effects on tendon inflammation in vitro. As tendon injuries are common in horses and treatment with PRP derived from the horse's own blood shows promise, but outcomes vary due to inconsistent composition. PRP contains EVs that facilitate cell communication.

Statin Therapy in Early Breast Cancer: The MASTER Trial; A Randomized Phase III, Placebo-Controlled Comparison of Standard (Neo)Adjuvant Therapy Plus Atorvastatin versus Standard (Neo)Adjuvant Therapy Plus Placebo.

Purpose: Statin use has been consistently associated with improved clinical outcomes (especially recurrence) in breast cancer in multiple observational studies backed by compelling preclinical evidence. The strength of this evidence warrants a clinical trial to test the efficacy of statin exposure on breast cancer recurrence.

Patients And Methods: The double-blind, phase III, randomized, placebo-controlled MASTER (MAmmary cancer STatins in ER positive breast cancer) trial includes women diagnosed with early-stage, estrogen receptor-positive (ER+) breast cancer who are candidates for systemic (neo)adjuvant therapy.

Temporomandibular joint degeneration arises spontaneously in STR/ort mice and is prevented by targeted aggrecanase inhibition.

Objective: Temporomandibular joint osteoarthritis (TMJ-OA) is painful and causes masticatory dysfunction, but current treatment is limited to symptom relief due to an incomplete appreciation of aetiology. Herein, we develop morphological and histological methods for quantitative evaluation of TMJ-OA severity and examine whether STR/Ort mice, which are genetically predisposed to spontaneous knee OA, exhibit protection against TMJ-OA upon genetic gain-of-function modification of an aggrecanase-selective mutant of tissue inhibitor of metalloproteinase (TIMP)-3.

Design: We established morphological changes in mandibular condylar head adapted from human TMJ-OA criteria, and developed and verified the utility of TMJ-OA histological damage scoring adapted from the OARSI system.

Efficacy of 12 months therapy with glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on weight regain after bariatric surgery: a real-world retrospective observational study.

Background: The role of glucagon-like peptide-1 receptor agonists (GLP1-RAs) in patients with weight regain after bariatric surgery remains unclear. The objective of this study was to determine the efficacy and safety of 12 months of GLP1-RA treatment in a real-world patient population with weight regain after bariatric surgery.

Methods: A single-centre retrospective observational study.

The severity of SLC1A2-associated neurodevelopmental disorders correlates with transporter dysfunction.

Background: Excitatory amino acid transporter 2 (EAAT2) is the predominant glutamate transporter and a key mediator of excitatory neurotransmission in the human brain. Here we present a cohort of 18 individuals harbouring 13 different SLC1A2 variants, who all present with neurodevelopmental impairment with variable symptoms and disease severities, and we delineate the impact of these variants on EAAT2 function.

Methods: The consequences of nine novel missense SLC1A2 variants for expression, transport and anion channel properties of EAAT2 expressed in mammalian cells were characterized by confocal microscopy, enzyme-linked immunosorbent and [H]-D-aspartate uptake assays, and electrophysiological recordings.

Virus Monitoring in Denmark: A Community-Based Self-Sampling System to Surveil Respiratory Viruses and Associated Symptoms.

This study presents findings captured in the first 1.5 years of the Virus Monitoring in Denmark (VMD) surveillance system. It describes trends in respiratory viruses, related symptoms, and participant demographics and behaviors.

The Heterogeneous Kinetic Origins of the Binding Properties of Orthosteric Ligands at Heteromeric Nicotinic Acetylcholine Receptors.

A plethora of agonists and competitive antagonists have been developed to explore the therapeutic potential in neuronal nicotinic acetylcholine receptors (nAChRs). Based on equilibrium and kinetic [H]epibatidine binding studies, we report that the kinetic fingerprints of [H]epibatidine at five heteromeric αβ nAChRs and of seven classical agonists at α4β2 and α3β4 nAChRs differ substantially. While this diversity depends on both the agonist and receptor subtype, the overall pattern of kinetic determinants emerging from this profiling is complex.

Chronic chemotherapy-induced peripheral neuropathy and pain following paclitaxel versus docetaxel in breast cancer survivors: A cross-sectional study.

Chemotherapy-induced peripheral neuropathy (CIPN) is a concerning late effect of taxane treatment. This study aimed to explore and compare long-term symptoms and consequences of CIPN after docetaxel and paclitaxel treatment. Patients with breast cancer who had followed Danish recommended adjuvant docetaxel or paclitaxel treatment regimens completed an online questionnaire 2-3 years after treatment.

Ibogalogs decrease neuropathic pain in mice through a mechanism involving crosstalk between 5-HT and mGlu receptors.

The objective of this study was to determine the anti-neuropathic activity of a variety of ibogalogs, including tabernanthalog (TBG), ibogaminalog (DM506), ibogainalog (IBG), nor-IBG, catharanthalog (CAG), and PNU-22394 using the oxaliplatin (OXA) neuropathic pain model in mice, and to investigate whether there is crosstalk between the 5-HT and mGlu receptors. All tested ibogalogs induce pain-relieving activity using both cold plate and paw pressure tests, without toxic effects. The most potent ibogalogs were IBG and CAG, whereas nor-IBG and DM506 were the longest-acting compounds.

Comparative modeling of risk factors for near-crashes from crowdsourced bicycle airbag helmet data and crashes from conventional police data.

Introduction: Conventional cycling crash data is valuable for shaping safe cycling environments but has limitations due to the rarity and under-reporting of cycling crashes. However, recent technological developments can provide information from near-crashes. the subheads should be italic, not bf.

Characterisation of equine odontoclastic tooth resorption and hypercementosis: A comparative study using microCT and radiography in age-matched controls.

Background: Equine odontoclastic tooth resorption and hypercementosis (EOTRH) is a painful disorder primarily affecting the incisor teeth of horses over 15 years of age. Clinical signs of the disease include prehension problems, halitosis and in severe cases weight loss. The disease predominately affects the reserve crown and presents as a loss of dental tissue and excessive build-up of cementum.

Inflammation and response to bacterial infection as potential drivers of equine odontoclastic tooth resorption and hypercementosis: A proteomics insight.

Background: Equine dental diseases significantly impact a horse's overall health, performance and quality of life. They can result in secondary infections and digestive disturbances, potentially leading to colic. A recently described disease affecting the incisors of horses is equine odontoclastic tooth resorption and hypercementosis (EOTRH).

Complete genome sequence of a penicillin-resistant subsp. from a tonsillitis patient.

We report the complete genome sequence of a penicillin-resistant subsp. isolate, AJ79, from a tonsillitis patient. The AJ79 genome consists of a chromosome (2,440,359 bp) and plasmid (9,887 bp), providing insights into the genetic basis of penicillin resistance in and its implications for treating tonsillitis.

Understanding paralogous epilepsy-associated GABA receptor variants: Clinical implications, mechanisms, and potential pitfalls.

Recent discoveries have revealed that genetic variants in γ-aminobutyric acid type A (GABA) receptor subunits can lead to both gain-of-function (GOF) and loss-of-function (LOF) receptors. GABA receptors, however, have a pseudosymmetrical pentameric assembly, and curiously diverse functional outcomes have been reported for certain homologous variants in paralogous genes (paralogous variants). To investigate this, we assembled a cohort of 11 individuals harboring paralogous M1 proline missense variants in , , and Seven mutations (α1, α1, β2, β3, β3, γ2, and γ2) in α1β2/3γ2 receptors were analyzed using electrophysiological examinations and molecular dynamics simulations.

Antiviral combination treatment of SARS-CoV-2 after repeated treatment failures of remdesivir monotherapy: A case report.

Immunocompromised patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can have a longer duration of viral shedding and persistence of symptoms. The optimal treatment strategy for these patients remains to be established. This case describes a male in his late sixties with follicular lymphoma and persistent symptoms of infection with SARS-CoV-2 variant BA.

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This review investigates that effective cancer treatment enhances the number of survivors in Denmark, but late complications like chemotherapy-induced peripheral neuropathy (CIPN) are a challenge. CIPN affects sensory nerves and can persist post-treatment. Diagnosis relies on symptoms and the medical history.

Detailed functional characterization of four nanobodies as positive allosteric modulators of the human calcium-sensing receptor.

The calcium-sensing receptor (CaSR) plays a key role in calcium homeostasis, and small-molecule and peptide positive allosteric modulators (PAMs) of CaSR, so-called calcimimetics, are used in the treatment of hyperparathyroidism and hypocalcemic disorders. In this study, four monovalent nanobodies - representing four distinct nanobody families with CaSR PAM activity - were subjected to elaborate pharmacological profiling at the receptor. While Nb5 displayed negligible PAM activity at CaSR in all assays, Nb4, Nb10 and Nb45 all potently potentiated Ca-evoked signalling through a myc epitope-tagged CaSR expressed in HEK293 or HEK293T cells in Gα and Gα protein activation assays and in a Ca/Fluo-4 assay.

Heterogeneous Origins of Calcium Homeostasis Disorders Arising From 5 Heterozygous Calcium-Sensing Receptor Variants.

Context: The human calcium-sensing receptor (CaSR) plays a key role in calcium homeostasis, and most identified CASR variants are associated with hypercalcemic and hypocalcemic disorders.

Objective: Here we characterized the pharmacological implications of 5 heterozygous CASR variants from individuals with familial hypocalciuric hypercalcemia 1 (FHH1: Y63C, I81T, Q459R, W818stop) or autosomal dominant hypocalcemia 1 (ADH1: R955stop).

Methods: Total and cell surface expression levels of wild-type (WT) and variant CaSRs expressed in human embryonic kidney 293T (HEK293T) cells were determined using enzyme-linked immunosorbent assay, and the pharmacological properties of the receptors were delineated in 2 functional assays.

Distinct neurodevelopmental and epileptic phenotypes associated with gain- and loss-of-function GABRB2 variants.

Background: Variants in GABRB2, encoding the β2 subunit of the γ-aminobutyric acid type A (GABA) receptor, can result in a diverse range of conditions, ranging from febrile seizures to severe developmental and epileptic encephalopathies. However, the mechanisms underlying the risk of developing milder vs more severe forms of disorder remain unclear. In this study, we conducted a comprehensive genotype-phenotype correlation analysis in a cohort of individuals with GABRB2 variants.

Novel insights into the multifaceted and tissue-specific roles of the endocytic receptor LRP1.

Receptor-mediated endocytosis provides a mechanism for the selective uptake of specific molecules thereby controlling the composition of the extracellular environment and biological processes. The low-density lipoprotein receptor-related protein 1 (LRP1) is a widely expressed endocytic receptor that regulates cellular events by modulating the levels of numerous extracellular molecules via rapid endocytic removal. LRP1 also participates in signalling pathways through this modulation as well as in the interaction with membrane receptors and cytoplasmic adaptor proteins.