2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), a compound manufactured for use as a flame retardant, is a ubiquitous environmental contaminant and suspected endocrine disruptor. Though several studies have explored the reproductive effects of BDE-47 in adult fish, there is a paucity of data regarding the reproductive effects of early life stage exposure. The goal of this study was to assess the reproductive effects of early life stage BDE-47 exposure in fathead minnows (Pimephales promelas). To achieve this, minnows were exposed to either a low (57.68 μg BDE-47/g Artemia) or high (392.59 μg BDE-47/g Artemia) dose of BDE-47 from fertilization to 34 days postfertilization (dpf) via a combination of maternal transfer and dietary exposure. Larvae were then raised on a clean diet until sexual maturity (∼184 dpf) when reproductive function was evaluated using a 21 day breeding study. Fish exposed to BDE-47 had significantly reduced clutch size and fecundity relative to controls. BDE-47 exposed groups also had female-biased sex ratios and exposed males had fewer tubercles. Overall, this study demonstrates that exposure to BDE-47 during early life stages can alter both sexual differentiation and reproductive function.
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http://dx.doi.org/10.1021/acs.est.6b02147 | DOI Listing |
Background: Alzheimer's disease (AD) agitation is a distressing neuropsychiatric symptom characterized by excessive motor activity, verbal aggression, or physical aggression. Agitation is one of the causes of caregiver distress, increased morbidity and mortality, and early institutionalization in patients with AD. Current medications used for the management of agitation have modest efficacy and have substantial side effects.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
EQT Life Sciences Partners, Amsterdam, 1071 DV Amsterdam, Netherlands.
Background: Alzheimer's disease (AD) trials report a high screening failure rate (potentially eligible trial candidates who do not meet inclusion/exclusion criteria during screening) due to multiple factors including stringent eligibility criteria. Here, we report the main reasons for screening failure in the 12-week screening phase of the ongoing evoke (NCT04777396) and evoke+ (NCT04777409) trials of semaglutide in early AD.
Method: Key inclusion criteria were age 55-85 years; mild cognitive impairment due to AD (Clinical Dementia Rating [CDR] global score of 0.
Background: Differences in patient characteristics across geographical regions may result in heterogeneity in clinical trial populations. evoke (NCT04777396) and evoke+ (NCT04777409) are two phase 3, multinational, randomised trials investigating semaglutide versus placebo in individuals with mild cognitive impairment or mild dementia due to Alzheimer's disease (AD) (early AD). We present baseline characteristics across the geographical regions in evoke/evoke+.
View Article and Find Full Text PDFBackground: evoke and evoke+ are phase 3, randomized, placebo-controlled trials currently investigating the glucagon-like peptide-1 receptor agonist semaglutide as disease-modifying therapy (DMT) in persons with early Alzheimer's disease (AD). How the evoke and evoke+ trial populations compare with other phase 3 programs for DMTs in early AD has not been described.
Method: We compare the inclusion/exclusion criteria and baseline characteristics of the evoke/evoke+ trial populations with those of Clarity AD (lecanemab) and TRAILBLAZER-ALZ-2 (donanemab): two recent phase 3 trials assessing anti-amyloid monoclonal antibodies in persons with early AD.
Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to amyloid-beta (Aβ) protofibrils, was formally evaluated as a treatment for early Alzheimer's disease in a phase 2 study (Study 201) and the phase 3 Clarity AD study. These trials both included an 18-month, randomized study (core) and an open-label extension (OLE) phase where eligible participants received open-label lecanemab for up to 30 months to date. Clinical (CDR-SB, ADAS-Cog14, and ADCS-MCI-ADL), biomarker (PET, Aβ42/40 ratio, and ptau181) and safety outcomes were evaluated.
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