Early Improvements With Atogepant for the Preventive Treatment of Migraine: Results From 3 Randomized Phase 3 Trials.

Background And Objectives: Three phase 3 trials demonstrated the efficacy and safety of atogepant in episodic migraine (EM) and chronic migraine (CM) across 12-week treatment periods. This analysis evaluates improvements in efficacy and functional outcomes in the first 4 weeks of treatment with the oral calcitonin gene-related peptide receptor antagonist, atogepant, for the preventive treatment of migraine.

Methods: ADVANCE, ELEVATE, and PROGRESS were phase 3, multicenter, randomized, double-blind, placebo-controlled 12-week trials.

JRM-28, a Novel HDAC2 Inhibitor, Upregulates Plasticity-Associated Proteins in Hippocampal Neurons and Enhances Morphological Plasticity via Activation of CREB: Implications for Alzheimer's Disease.

Enhancement of neuronal plasticity by small-molecule therapeutics protects cognitive skills and also ameliorates progressive neurodegenerative pathologies like Alzheimer's disease (AD) and dementia. One such compound, a novel histone deacetylase 2 (HDAC2) inhibitor named JRM-28, was shown here to enhance dendritic strength, augment spine density, and upregulate post-synaptic neurotransmission in hippocampal neurons. The molecular basis for this effect correlates with JRM-28-induced upregulation of the transcription of cAMP response element-binding protein(CREB), induction of its transcriptional activity, and subsequent stimulation of expressions of CREB-dependent plasticity-associated genes, such as those encoding N-methyl-D-aspartate (NMDA) receptor subunit NR2A and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1.

Effect of preventive treatment with atogepant on quality of life, daily functioning, and headache impact across the spectrum of migraine: Findings from three double-blind, randomized, phase 3 trials.

Background: We aimed to assess the effects of preventive migraine treatment with atogepant vs. placebo on patient-reported quality of life and functioning.

Methods: Analyses of patient-reported outcomes from three 12-week, randomized, placebo-controlled trials evaluating preventive migraine treatment with atogepant 60 mg once-daily: ADVANCE (low-frequency episodic migraine [LFEM], 4-8 monthly migraine days [MMDs] and high-frequency episodic migraine [HFEM], 8-14 MMDs), PROGRESS (chronic migraine, CM) and ELEVATE (episodic migraine in those previously failed by two to four classes of oral preventive treatments).

Feed-induced hypersalivation in horses from Austria, Germany and Switzerland.

Background: While previous reports come mostly from the southern Americas, several outbreaks of hypersalivation in horses were observed in Middle Europe from 2016 to 2018.

Objective: To describe feed-induced hypersalivation in European horses.

Study Design: Analysis of feedstuffs.

Over a century of pear breeding at the USDA.

The U.S. Department of Agriculture (USDA) has performed European pear ( L.

Dysregulation of tetrahydrobiopterin metabolism in myalgic encephalomyelitis/chronic fatigue syndrome by pentose phosphate pathway.

Background: Tetrahydrobiopterin (BH4) and its oxidized derivative dihydrobiopterin (BH2) were found to be strongly elevated in ME/CFS patients with orthostatic intolerance (ME + OI).

Objective: However, the molecular mechanism of biopterin biogenesis is poorly understood in ME + OI subjects. Here, we report that the activation of the non-oxidative pentose phosphate pathway (PPP) plays a critical role in the biogenesis of biopterins (BH4 and BH2) in ME + OI subjects.

Dose-response study on the transfer of pyrrolizidine alkaloids from a tansy ragwort extract ( Gaertn.) to bovine milk.

Ragworts like tansy ragwort ( Gaertn., syn. L.

The Near-Gapless Genome Enables the Discovery of Lifestyle Features as an Emerging Post-Harvest Phytopathogen.

spp. occupy many diverse biological niches that include plant pathogens, opportunistic human pathogens, saprophytes, indoor air contaminants, and those selected specifically for industrial applications to produce secondary metabolites and lifesaving antibiotics. Recent phylogenetic studies have established as a synonym for which is an indoor air contaminant and toxin producer and can infect apple fruit during storage.

A case of pulmonary melioidosis in Germany: a rare differential diagnosis in returning travelers from South-East Asia.

Background: Melioidosis is a bacterial infection associated with high mortality. The diagnostic approach to this rare disease in Europe is challenging, especially because pulmonary manifestation of melioidosis can mimic pulmonary tuberculosis (TB). Antibiotic therapy of melioidosis consists of an initial intensive phase of 2-8 weeks followed by an eradication therapy of 3-6 months.

Pyrrolizidine alkaloids and tropane alkaloids in milk samples from individual dairy farms of the German federal states of Bavaria and Schleswig-Holstein.

1,2-Dehydro-pyrrolizidine alkaloids (PA), their corresponding -oxides (PANO) and tropane alkaloids (TA), are toxic plant metabolites. If plant material, containing these toxins, is present in the feed of dairy cows these toxins can be transferred into milk. Here, milk was sampled directly from dairy farms in the German federal states of Bavaria and Schleswig-Holstein in 2020-2022 in order to investigate a possible contamination of milk at the production stage.

Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial.

Background: In a recent randomized, double-blind, placebo-controlled study, we observed a nonsignificant reduction of attack frequency in cluster headache after pulse administration of psilocybin (10 mg/70 kg, 3 doses, 5 days apart each). We carried out a blinded extension phase to consider the safety and efficacy of repeating the pulse regimen.

Methods: Eligible participants returned to receive a psilocybin pulse at least 6 months after their first round of study participation.

Short-term exposure of dairy cows to pyrrolizidine alkaloids from tansy ragwort ( Gaertn.): effects on health and performance.

The increasing spread of ragworts is observed with concern. Ragworts like tansy ragwort ( Gaertn.) or marsh ragwort () contain pyrrolizidine alkaloids (PA) which may induce hepatotoxic effects.

Confocal micro X-ray fluorescence analysis for the non-destructive investigation of structured and inhomogeneous samples.

Confocal micro X-ray fluorescence (CMXRF) spectroscopy is a non-destructive, depth-resolved, and element-specific technique that is used to analyze the elemental composition of a sample. For this, a focused beam of mono- or polychromatic X-rays is applied to excite the atoms in the sample, causing them to emit fluorescence radiation which is detected with focusing capillary optics. The confocal design of the instrument allows for depth-resolved analysis, in most cases with a resolution in the lower micrometer dimension after collecting X-rays from a predefined volume within the sample.

Detection of Elevated Level of Tetrahydrobiopterin in Serum Samples of ME/CFS Patients with Orthostatic Intolerance: A Pilot Study.

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a multisystem chronic illness characterized by severe muscle fatigue, pain, dizziness, and brain fog. Many patients with ME/CFS experience orthostatic intolerance (OI), which is characterized by frequent dizziness, light-headedness, and feeling faint while maintaining an upright posture. Despite intense investigation, the molecular mechanism of this debilitating condition is still unknown.

Conservation and divergence of expression of homeologs in apple ( x Borkh.).

In domesticated apple ( x Borkh.) and other woody perennials, floral initiation can be repressed by gibberellins (GAs). The associated mechanism is a major unanswered question in plant physiology, and understanding organismal aspects of GA signaling in apple has important commercial applications.

Altered Fatty Acid Oxidation in Lymphocyte Populations of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling multisystem illness in which individuals are plagued with fatigue, inflammatory symptoms, cognitive dysfunction, and the hallmark symptom, post-exertional malaise. While the cause of this disease remains unknown, there is evidence of a potential infectious component that, along with patient symptoms and common onsets of the disease, implicates immune system dysfunction. To further our understanding of the state of ME/CFS lymphocytes, we characterized the role of fatty acids in isolated Natural Killer cells, CD4+ T cells, and CD8+ T cells in circulation and after overnight stimulation, through implicit perturbations to fatty acid oxidation.

Potential molecular mechanisms of chronic fatigue in long haul COVID and other viral diseases.

Historically, COVID-19 emerges as one of the most devastating diseases of humankind, which creates an unmanageable health crisis worldwide. Until now, this disease costs millions of lives and continues to paralyze human civilization's economy and social growth, leaving an enduring damage that will take an exceptionally long time to repair. While a majority of infected patients survive after mild to moderate reactions after two to six weeks, a growing population of patients suffers for months with severe and prolonged symptoms of fatigue, depression, and anxiety.

Exploratory investigation of a patient-informed low-dose psilocybin pulse regimen in the suppression of cluster headache: Results from a randomized, double-blind, placebo-controlled trial.

Objective: Using a patient-informed regimen, we conducted an exploratory randomized, double-blind, placebo-controlled study to systematically investigate the effects of psilocybin in cluster headache.

Background: Sustained reductions in cluster headache burden after limited quantities of psilocybin-containing mushrooms are anecdotally reported, although to date there are no controlled studies investigating these effects.

Methods: Participants were randomized to receive psilocybin (0.

First Report of Fusarium avenaceum Causing Postharvest Decay of European Pear in Mid-Atlantic United States.

Fruit losses due to postharvest decay caused by several fungal species is a major challenge for pear production (Sardella et al. 2016). In December 2021, a European pear (Pyrus communis L.