Correction: The final plague outbreak in Scotland 1644-1649: Historical, archaeological, and genetic evidence.

[This corrects the article DOI: 10.1371/journal.pone.

The final plague outbreak in Scotland 1644-1649: Historical, archaeological, and genetic evidence.

This paper has several aims: to determine if Yersinia pestis was the causative agent in the last Scottish plague outbreak in the mid-17th century; map the geographic spread of the epidemic and isolate potential contributing factors to its spread and severity; and examine funerary behaviours in the context of a serious plague epidemic in early modern Scotland. Results confirm the presence of Y. pestis in individuals associated with a mid-17th century plague pit in Aberdeen.

Safety and efficacy of viltolarsen in ambulatory and nonambulatory males with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by mutations in the dystrophin gene, causing motor and pulmonary function decline. Viltolarsen is indicated for patients with dystrophin gene mutations amenable to exon 53 skipping. Here, we report safety, motor function, and the first pulmonary function results from the open-label, phase II Galactic53 trial of viltolarsen (NCT04956289).

JNK signaling during IL-3-mediated differentiation contributes to the c-kit-potentiated allergic inflammatory capacity of mast cells.

Mast cells are leukocytes that mediate various aspects of immunity and drive allergic hypersensitivity pathologies. Mast cells differentiate from hematopoietic progenitor cells in a manner that is largely IL-3 dependent. However, molecular mechanisms, including the signaling pathways that control this process, have yet to be thoroughly investigated.

Prescribing Patterns and Outcomes of Edoxaban in Atrial Fibrillation: One-Year Data from the Global ETNA-AF Program.

Non-recommended dosing occurs in ~25-50% of non-vitamin K antagonist oral anticoagulant prescriptions, with limited data for edoxaban. We analyzed edoxaban dosing patterns in atrial fibrillation patients from the Global ETNA-AF program, relating patterns to baseline characteristics and 1-year clinical outcomes. The following dosing groups were compared: non-recommended 60 mg ("overdosed") vs.

Acute activation of SERCA with CDN1163 attenuates IgE-mediated mast cell activation through selective impairment of ROS and p38 signaling.

Mast cells are granulocytic immune sentinels present in vascularized tissues that drive chronic inflammatory mechanisms characteristic of allergic pathologies. IgE-mediated mast cell activation leads to a rapid mobilization of Ca from intracellular stores, which is essential for the release of preformed mediators via degranulation and de novo synthesized proinflammatory cytokines and chemokines. Given its potent signaling capacity, the dynamics of Ca localization are highly regulated by various pumps and channels controlling cytosolic Ca concentrations.

Carnosic acid inhibits secretion of allergic inflammatory mediators in IgE-activated mast cells via direct regulation of Syk activation.

Mast cells are essential regulators of inflammation most recognized for their central role in allergic inflammatory disorders. Signaling via the high-affinity immunoglobulin E (IgE) receptor, FcεRI, leads to rapid degranulation of preformed granules and the sustained release of newly synthesized proinflammatory mediators. Our group recently established rosemary extract as a potent regulator of mast cell functions, attenuating MAPK and NF-κB signaling.

Targeting glycogen synthase kinase 3 with CHIR99021 negatively regulates allergen-induced mast cell activation.

Mast cells are granulated immune sentinels responsible for allergic inflammation. Allergen-induced FcεRI-signaling leads to rapid degranulation in the early-phase and sustained production and release of pro-inflammatory mediators in the late phase. Glycogen synthase kinase 3 (GSK3) is a constitutively active serine/threonine kinase and a central molecular convergence point for several pro-inflammatory pathways.

Does primary trauma lead to developmental defects in permanent teeth?

Introduction A systematic review of existing evidence to determine if trauma in the primary dentition causes alteration in the development of the underlying permanent dentition.Data sources Six electronic databases (PubMed, Medline, MEDES, Scopus, Lilacs and Embase) were used to search a range of dental terms relating to dental trauma to locate studies between 1972-2020.Study selection Study selection was carried out by two authors by reviewing title, abstract and then full articles.

Zika Virus Replication in a Mast Cell Model is Augmented by Dengue Virus Antibody-Dependent Enhancement and Features a Selective Immune Mediator Secretory Profile.

Zika virus and dengue virus are evolutionarily related and structurally similar mosquito-borne . These congruencies can lead to cross-reactive antibody binding, whereby antibodies generated from previous dengue virus immunity can augment Zika virus replication . This phenomenon, termed antibody-dependent enhancement, may participate in the clinical manifestations detected in areas with cocirculations where Zika virus is endemic; however, a causal relationship has yet to be determined.

Amplification of input differences by dynamic heterogeneity in the spiral ganglion.

A defining feature of type I primary auditory afferents that compose ∼95% of the spiral ganglion is their intrinsic electrophysiological heterogeneity. This diversity is evident both between and within unitary, rapid, and slow adaptation (UA, RA, and SA) classes indicative of specializations designed to shape sensory receptor input. But to what end? Our initial impulse is to expect the opposite: that auditory afferents fire uniformly to represent acoustic stimuli with accuracy and high fidelity.

Are RMGIC restorations as effective with or without selective caries removal in primary molars?

Design A two-arm parallel group, tooth-randomised, controlled, non-inferiority clinical trial.Case selection Participants were cooperative 3-9-year-old children of good health, presenting with at least one International Caries Detection and Assessment System (ICDAS) Grade 5 cavitated dentine occlusal carious lesion, with radiographic depth into dentine. Teeth included were symptom-free, non-mobile and had no more than one-third root resorption.

Analog transmission of action potential fine structure in spiral ganglion axons.

Action potential waveforms generated at the axon initial segment (AIS) are specialized between and within neuronal classes. But is the fine structure of each electrical event retained when transmitted along myelinated axons or is it rapidly and uniformly transmitted to be modified again at the axon terminal? To address this issue, action potential axonal transmission was evaluated in a class of primary sensory afferents that possess numerous types of voltage-gated ion channels underlying a complex repertoire of endogenous firing patterns. In addition to their signature intrinsic electrophysiological heterogeneity, spiral ganglion neurons are uniquely designed.

Tafazzin Modulates Allergen-Induced Mast Cell Inflammatory Mediator Secretion.

Allergic inflammatory diseases are a steadily growing health concern. Mast cells, a driving force behind allergic pathologies, modulate metabolic pathways to carry out various functions following IgE-FcεRI-mediated activation. Tafazzin (TAZ) is a cardiolipin transacylase that functions to remodel, and thereby mature, cardiolipin, which is important for efficient energy production through oxidative phosphorylation.

Effect of social structure and introduction history on genetic diversity and differentiation.

Invasive species are a global threat to biodiversity, and understanding their history and biology is a major goal of invasion biology. Population-genetic approaches allow insights into these features, as population structure is shaped by factors such as invasion history (number, origin and age of introductions) and life-history traits (e.g.

Attenuation of allergen-mediated mast cell activation by rosemary extract (Rosmarinus officinalis L.).

Mast cells are immune sentinels and a driving force in both normal and pathological contexts of inflammation, with a prominent role in allergic hypersensitivities. Crosslinking of FcεRI by allergen-bound IgE Abs leads to mast cell degranulation, resulting in an early-phase response and release of newly synthesized pro-inflammatory mediators in the late-phase. The MAPK and NF-κB pathways are established as critical intracellular mechanisms directing mast cell-induced inflammation.

TAK1 signaling activity links the mast cell cytokine response and degranulation in allergic inflammation.

Mast cells drive the inappropriate immune response characteristic of allergic inflammatory disorders via release of pro-inflammatory mediators in response to environmental cues detected by the IgE-FcεRI complex. The role of TGF-β-activated kinase 1 (TAK1), a participant in related signaling in other contexts, remains unknown in allergy. We detect novel activation of TAK1 at Ser412 in response to IgE-mediated activation under SCF-c-kit potentiation in a mast cell-driven response characteristic of allergic inflammation, which is potently blocked by TAK1 inhibitor 5Z-7-oxozeaenol (OZ).

Long-term treatment with plecanatide was safe and tolerable in patients with irritable bowel syndrome with constipation.

This open-label, multi-center, fixed-dose study (NCT02706483) evaluated the long-term safety and tolerability of plecanatide for the treatment of adults with irritable bowel syndrome with constipation (IBS-C). Safety and tolerability of once-daily plecanatide 6 mg for up to 53 weeks was assessed in patients with IBS-C who either had been enrolled in one of the phase 3 studies or were study-naïve but met eligibility criteria of the double-blind studies. Safety was assessed by treatment-emergent adverse events (AEs).

Better Understanding and Recognition of the Disconnects, Experiences, and Needs of Patients with Irritable Bowel Syndrome with Constipation (BURDEN IBS-C) Study: Results of an Online Questionnaire.

Introduction: The BURDEN IBS-C study was conducted to better understand the experiences, attitudes, and unmet needs of sufferers of irritable bowel syndrome with constipation (IBS-C) in comparison to the perceptions and challenges of healthcare providers (HCPs) who treat IBS-C patients.

Methods: This was an author-developed, online questionnaire using KnowledgePanel to survey individuals with IBS-C (N = 1311). HCPs participated in a complementary online questionnaire and were recruited separately (N = 331).

Efficacy, safety, and tolerability of plecanatide in patients with irritable bowel syndrome with constipation: results of two phase 3 randomized clinical trials.

Objectives: Two identical, phase 3, randomized, double-blind, placebo-controlled trials evaluated the efficacy and safety of plecanatide in patients with irritable bowel syndrome with constipation (IBS-C).

Methods: Adults meeting Rome III criteria for IBS-C were randomized (1:1:1) to placebo or plecanatide (3 or 6 mg) for 12 weeks. The primary efficacy end point was the percentage of overall responders (patients reporting ≥30% reduction from baseline in worst abdominal pain plus an increase of ≥1 complete spontaneous bowel movement (CSBM)/week from baseline in the same week for ≥6 of 12 treatment weeks).

A newly assembled human skeletal reference collection of modern and identified Filipinos.

A collection of 75 modern skeletons from the Philippines has recently been created, and is being housed at the Archaeological Studies Program of the University of the Philippines, Diliman, Philippines. All individuals lived during the 20th century, and almost all died within the 21st century. These individuals were accessioned from exhumed and abandoned tombs at the Manila North Cemetery, and most have documented age and sex from tombstone inscriptions.

Dynamic firing properties of type I spiral ganglion neurons.

Spiral ganglion neurons, the first neural element in the auditory system, possess complex intrinsic properties, possibly required to process frequency-specific sensory input that is integrated with extensive efferent regulation. Together with their tonotopically-graded sizes, the somata of these neurons reveal a sophisticated electrophysiological profile. Type I neurons, which make up ~95 % of the ganglion, have myriad voltage-gated ion channels that not only vary along the frequency contour of the cochlea, but also can be modulated by regulators such as voltage, calcium, and second messengers.