The aggregation of Amyloid- (A) peptides is associated with neurodegeneration in Alzheimer's disease (AD). We previously identified novel naphtalene derivatives, including the lead compound Amylovis-201, able to form thermodynamically stable complexes with A species, peptides and fibrils. As the drug showed a chemical scaffold coherent for an effective interaction with the receptor chaperone and as agonists are currently developed as potent neuroprotectants in AD, we investigated the pharmacological action of Amylovis-201 on the receptor.
View Article and Find Full Text PDFClimate change can disrupt animal fitness by reducing survival, fertility, fecundity and altering offspring development and survival. While parental care typically helps offspring cope with harsh environmental conditions, little is known about its role in buffering extreme temperature changes, such as heat waves. In this study, we tested whether parental care mitigates the impact of cold and heat waves on eggs and juveniles in the European earwig.
View Article and Find Full Text PDFIntroduction: The Cohen-Mansfield Agitation Inventory (CMAI) quantifies the frequency of agitation behaviors in elderly persons. This analysis of data from the brexpiprazole clinical program aimed to determine a meaningful within-patient change (MWPC) threshold for CMAI Total score among patients with agitation associated with dementia due to Alzheimer's disease.
Methods: Data were included from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm trials of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease (ClinicalTrials.
Immune checkpoint inhibitors have emerged as a promising cancer treatment, allowing significant and long-term therapeutic responses. Nivolumab, an anti-programmed cell death protein-1, is one of the molecules of this therapeutic class with known and manageable side effects. Giant cell arteritis is a rare immune-related adverse event most often manifested by headaches poorly released by common antalgics and can result in visual loss.
View Article and Find Full Text PDFThe use of herbicides on crops often results in unintentional, low-dose exposure of non-target organisms, such as insects. While these exposures are increasingly known to alter the survival and physiology of insects, it remains unclear whether these effects can vary between populations and modify other fitness-related traits, such as behaviour and immunity. Here, we addressed these questions by testing the effects of sublethal exposure to a glyphosate-based herbicide (GBH) on the behaviour and immunity of European earwig males from six natural populations.
View Article and Find Full Text PDFBackground: Hoverflies are among the most important insect pollinators and there is documented evidence of a recent decline in their populations. To trace the past distributions of hoverfly species, verified records of historical collections are essential.
New Information: Here, we provide data on 1071 specimens of hoverflies collected or received by Jean Timon-David and hosted at the Marseille Natural History Museum, France.
Background: Pruritus, or itch, is a key symptom of atopic dermatitis (AD); as such, mitigating itch is an important outcome of AD treatment. This study explored the content validity and measurement properties of the Pruritus Numeric Rating Scale (Pruritus NRS), a novel single-item scale for assessing itch severity in clinical trials of AD treatments.
Methods: In this mixed-methods study, qualitative interviews were conducted with 21 people with moderate-to-severe AD (n = 15 adult, n = 6 adolescent) to develop a conceptual model of the patient experience in AD and explore the content validity of the Pruritus NRS.
Background: Many insect species have shown dramatic declines over the last decades, as a result of man-related environmental changes. Many species which were formerly widespread are now rare. To document this trend with evidence, old records of collected specimens are vital.
View Article and Find Full Text PDFPlant phytoliths, which represent the main pool of silica (Si) in the form of hydrous Si oxide, are capable of providing valuable information on different aspect of environmental issues including paleo-environmental reconstruction and agricultural sustainability. Phytoliths may have different chemical composition, which, in turn, affects their preservation in soils ad impacts terrestrial cycle of the occluded elements including micro-nutrients and environmental toxicants. Yet, in contrast to sizable work devoted to phytoliths formation, dissolution and physico-chemical properties, the mechanisms that control total (major and trace) elemental composition and the impact that various elements exert on phytolith reactivity and preservation in soils remains poorly known.
View Article and Find Full Text PDFBackground And Aim: By using an in vivo phenotypic screening assay in zebrafish, we identified Convolamine, a tropane alkaloid from Convulvus plauricalis, as a positive modulator of the sigma-1 receptor (S1R). The wfs1ab zebrafish larva, a model of Wolfram syndrome, exhibits an increased visual-motor response due to a mutation in Wolframin, a protein involved in endoplasmic reticulum-mitochondria communication. We previously reported that ligand activating S1R, restored the cellular and behavioral deficits in patient fibroblasts and zebrafish and mouse models.
View Article and Find Full Text PDFPerformance outcome (PerfO) measures are based on tasks performed by patients in a controlled environment, making their meaningful interpretation challenging to establish. Co-calibrating PerfO and patient-reported outcome (PRO) measures of the same target concept allow for interpretation of the PerfO with the item content of the PRO. The Rasch model applied to the discretized PerfO measure together with the PRO items allows expressing parameters related to the PerfO measure in the PRO metric for it to be linked to the PRO responses.
View Article and Find Full Text PDFThis study aims to examine geometric models of the corneal surface that can be used to reduce in reasonable time the dimensionality of datasets of normal anterior corneas. Polynomial models (P) like Zernike polynomials (ZP) and spherical harmonic polynomials (SHP) were obvious candidates along with their rational function (R) counterparts, namely Zernike rational functions (ZR) and spherical harmonic rational functions (SHR, new model). Knowing that both SHP and ZR were more accurate than ZP for the modeling of normal and keratoconus corneas, it was expected that both spherical harmonic (SH) models (SHP and SHR) would be more accurate than their Zernike (Z) counterparts (ZP and ZR, respectively), and both rational (R) models (SHR and ZR) more accurate than their polynomial counterparts (SHP and ZP, respectively) for a low dimensional space (coefficient number J < 30).
View Article and Find Full Text PDFBackground: Trials of disease-modifying therapies (DMTs) for multiple sclerosis (MS) often include patients with minimal disability. Patient-reported outcome instruments used in these trials have often not captured physical and psychological treatment effects concomitant with observed clinical benefits.
Objective: To examine whether the Multiple Sclerosis Impact Scale-29 (MSIS-29) captures changes in the impact of MS in a sample of patients enrolled in the Phase 3 ASCLEPIOS studies (ofatumumab vs.
Earwigs are often known for the forceps-like appendage at the end of their abdomen, urban legends about them crawling into human ears, and their roles as pest and biological control agents. However, they are much less known for their social life. This is surprising, as many of the 1,900 species of earwigs show social behaviors toward eggs, juveniles, and adults.
View Article and Find Full Text PDFIntroduction: The use of complementary therapies within oncology is a clinical issue, and their evaluation a methodological challenge. This paper reports the findings of a qualitative study exploring the lived experience of a French program of complementary therapies combining structured physical activity and MBSR among women with breast cancer.
Methods: This French exploratory qualitative study followed the five stages of the Inductive Process to analyze the Structure of lived Experience (IPSE) approach.
Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8 and CD4 T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation.
View Article and Find Full Text PDFBackground: Hereditary angioedema (HAE) is associated with a substantial disease burden. Lanadelumab reduced the HAE attack rate during 132 weeks of follow-up in the HELP open-label extension (OLE) Study (NCT02741596).
Objective: To measure the impact of long-term lanadelumab treatment on patient-reported outcomes (PROs).
Objectives: To quantify and describe flare-ups of house dust mite allergic rhinitis (HDM-AR) which had occurred during the last 12 months in a population of adults and children candidate for Allergen ImmunoTherapy (AIT). Next, to identify associated clinical features.
Materials And Methods: This was an observational, multicenter, cross-sectional study that included patients aged ≥ 5 years with HDM-AR eligible for AIT and without prior AIT for at least 12 months.
A P300-based speller can be used to control a home automation system via brain activity. Evaluation of the visual stimuli used in a P300-based speller is a common topic in the field of brain-computer interfaces (BCIs). The aim of the present work is to compare, using the usability approach, two types of stimuli that have provided high performance in previous studies.
View Article and Find Full Text PDFAim: The oral anti-angiogenic therapy nintedanib prolongs progression-free survival (PFS) when combined with chemotherapy after primary surgery for advanced epithelial ovarian cancer. The randomized phase II CHIVA trial evaluated the impact of combining nintedanib with neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer.
Methods: Patients with newly diagnosed unresectable FIGO stage IIIC-IV epithelial ovarian cancer received 3-4 cycles of carboplatin plus paclitaxel every 3 weeks as NACT before interval debulking surgery (IDS), followed by 2-3 post-operative cycles.
Although delirium in patients with acute respiratory failure (ARF) may evolve in any hospital setting, previous studies on the impact of delirium on ARF were restricted to those in the intensive care unit (ICU). The data about the impact of delirium on ARF hospitalizations outside of the ICU is limited. Therefore, we conducted the first national study to examine the effect-magnitude of delirium on ARF in all hospital settings, that is, in the ICU as well as on the general medical floor.
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