Low-Dose Chidamide Treatment Displays Sex-Specific Differences in the 3xTg-AD Mouse.

Epigenetic compounds have become attractive small molecules for targeting the multifaceted aspects of Alzheimer's disease (AD). Although AD disproportionately affects women, most of the current literature investigating epigenetic compounds for the treatment of AD do not report sex-specific results. This is remarkable because there is rising evidence that epigenetic compounds intrinsically affect males and females differently.

APOE and immunity: Research highlights.

Introduction: At the Alzheimer's Association's APOE and Immunity virtual conference, held in October 2021, leading neuroscience experts shared recent research advances on and inspiring insights into the various roles that both the apolipoprotein E gene (APOE) and facets of immunity play in neurodegenerative diseases, including Alzheimer's disease and other dementias.

Methods: The meeting brought together more than 1200 registered attendees from 62 different countries, representing the realms of academia and industry.

Results: During the 4-day meeting, presenters illuminated aspects of the cross-talk between APOE and immunity, with a focus on the roles of microglia, triggering receptor expressed on myeloid cells 2 (TREM2), and components of inflammation (e.

Functional Drug Screening of Small Molecule Inhibitors of Epigenetic Modifiers in Refractory AML Patients.

The use of inhibitors of epigenetic modifiers in the treatment of acute myeloid leukemia (AML) has become increasingly appealing due to the highly epigenetic nature of the disease. We evaluated a library of 164 epigenetic compounds in a cohort of 9 heterogeneous AML patients using an ex vivo drug screen. AML blasts were isolated from bone marrow biopsies according to established protocols and treatment response to the epigenetic library was evaluated.

Ipilimumab/Nivolumab Therapy in Patients With Metastatic Pancreatic or Biliary Cancer With Homologous Recombination Deficiency Pathogenic Germline Variants.

This case series describes ipilimumab/nivolumab therapy in patients with metastatic pancreatic or biliary cancer with homologous recombination deficiency (HRD) pathogenic germline variants (PGVs).

JOTROL, a Novel Formulation of Resveratrol, Shows Beneficial Effects in the 3xTg-AD Mouse Model.

Background: Alzheimer's disease (AD) has minimally effective treatments currently. High concentrations of resveratrol, a polyphenol antioxidant found in plants, have been reported to affect several AD-related and neuroprotective genes. To address the low bioavailability of resveratrol, we investigated a novel oral formulation of resveratrol, JOTROL™, that has shown increased pharmacokinetic properties compared to non-formulated resveratrol in animals and in humans.

Sexual Dimorphism in the 3xTg-AD Mouse Model and Its Impact on Pre-Clinical Research.

Female sex is a leading risk factor for developing Alzheimer's disease (AD). Sexual dimorphism in AD is gaining attention as clinical data show that women are not only more likely to develop AD but also to experience worse pathology and faster cognitive decline. Pre-clinical AD research in animal models often neglects to address sexual dimorphism in evaluation of behavioral or molecular characteristics and outcomes.

Serum and macular response to carotenoid-enriched egg supplementation in human subjects: the Egg Xanthophyll Intervention clinical Trial (EXIT).

The macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) accumulate at the macula, where they are collectively referred to as macular pigment (MP). Augmentation of this pigment, typically achieved through diet and supplementation, enhances visual function and protects against progression of age-related macular degeneration. However, it is known that eggs are a rich dietary source of L and Z, in a highly bioavailable matrix.

Enrichment of Macular Pigment Enhances Contrast Sensitivity in Subjects Free of Retinal Disease: Central Retinal Enrichment Supplementation Trials - Report 1.

Purpose: The high-performance visual function associated with central vision is mediated by the macula (the central retina), which accumulates three diet-derived pigments (the carotenoids lutein [L], zeaxanthin [Z], and meso-zeaxanthin [MZ]). Our study sought to investigate the impact on visual function, including contrast sensitivity (CS), of supplementation with these naturally occurring carotenoids, in individuals with low retinal concentrations.

Methods: Subjects consumed daily a formulation containing 10 mg L, 2 mg Z, and 10 mg MZ (active group; n = 53) or placebo (n = 52) for a period of 12 months.

The Photobiology of Lutein and Zeaxanthin in the Eye.

Lutein and zeaxanthin are antioxidants found in the human retina and macula. Recent clinical trials have determined that age- and diet-related loss of lutein and zeaxanthin enhances phototoxic damage to the human eye and that supplementation of these carotenoids has a protective effect against photoinduced damage to the lens and the retina. Two of the major mechanisms of protection offered by lutein and zeaxanthin against age-related blue light damage are the quenching of singlet oxygen and other reactive oxygen species and the absorption of blue light.

Cognitive Function and Its Relationship with Macular Pigment Optical Density and Serum Concentrations of its Constituent Carotenoids.

Background: Macular pigment (MP) levels correlate with brain concentrations of lutein (L) and zeaxanthin (Z), and have also been shown to correlate with cognitive performance in the young and elderly.

Objective: To investigate the relationship between MP, serum concentrations of L and Z, and cognitive function in subjects free of retinal disease with low MP (Group 1, n = 105) and in subjects with AMD (Group 2, n = 121).

Methods: MP was measured using customized heterochromatic flicker photometry and dual-wavelength autofluorescence; cognitive function was assessed using a battery of validated cognition tests; serum L and Z concentrations were determined by HPLC.

Measuring Visual Function Using the MultiQuity System: Comparison with an Established Device.

Purpose. To compare measures of visual acuity (VA) and contrast sensitivity (CS) from the Thompson Xpert 2000 and MultiQuity (MiQ) devices. Methods.

The impact of supplemental macular carotenoids in Alzheimer's disease: a randomized clinical trial.

Background: Patients with Alzheimer's disease (AD) exhibit significantly less macular pigment (MP) and poorer vision when compared to control subjects.

Objective: To investigate supplementation with the macular carotenoids on MP, vision, and cognitive function in patients with AD versus controls.

Methods: A randomized, double-blind clinical trial with placebo and active arms.

Macular pigment, visual function, and macular disease among subjects with Alzheimer's disease: an exploratory study.

Background: The macula (central retina) contains a yellow pigment, comprising the dietary carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin, known as macular pigment (MP). The concentrations of MP's constituent carotenoids in retina and brain tissue correlate, and there is a biologically-plausible rationale, supported by emerging evidence, that MP's constituent carotenoids are also important for cognitive function.

Objective: To investigate if patients with Alzheimer's disease (AD) are comparable to controls in terms of MP and visual function.

Central Retinal Enrichment Supplementation Trials (CREST): design and methodology of the CREST randomized controlled trials.

Purpose: The Central Retinal Enrichment Supplementation Trials (CREST) aim to investigate the potential impact of macular pigment (MP) enrichment, following supplementation with a formulation containing 10 mg lutein (L), 2 mg zeaxanthin (Z) and 10 mg meso-zeaxanthin (MZ), on visual function in normal subjects (Trial 1) and in subjects with early age-related macular degeneration (AMD; Trial 2).

Methods: CREST is a single center, double-blind, randomized clinical trial. Trial 1 (12-month follow-up) subjects are randomly assigned to a formulation containing 10 mg L, 10 mg MZ and 2 mg Z (n = 60) or placebo (n = 60).

Concordance of macular pigment measurements obtained using customized heterochromatic flicker photometry, dual-wavelength autofluorescence, and single-wavelength reflectance.

This study compares in vivo measurements of macular pigment (MP) obtained using customized heterochromatic flicker photometry (cHFP; Macular Metrics Densitometer(™)), dual-wavelength fundus autofluorescence (Heidelberg Spectralis(®) HRA + OCT MultiColor) and single-wavelength fundus reflectance (Zeiss Visucam(®) 200). MP was measured in one eye of 62 subjects on each device. Data from 49 subjects (79%) was suitable for analysis.

An effective electronic surgical referral system.

Introduction: Electronic booking of out-patient appointments is being rolled out in England under the 'Choose and Book' programme. We set up and ran a local electronic surgical referral service before this. This paper assesses the effect of the electronic surgical referral service on patient waiting times and attendance rates.

Both dorsal and ventral spinal cord pathways contribute to overground locomotion in the adult rat.

Identification of long tracts responsible for spontaneous locomotion is critical for spinal cord injury (SCI) repair strategies. We recently demonstrated that extensive demyelination of adult rat thoracic ventral columns, ventromedial, and ventrolateral white matter produces persistent, significant open-field hindlimb locomotor deficits. Locomotor movements resulting from stimulation of the pontomedullary locomotor region are inhibited by dorsolateral funiculus (DLF) lesions suggesting that important pathways for locomotion may also exist in the dorsal white matter.

Differentiation of engrafted neuronal-restricted precursor cells is inhibited in the traumatically injured spinal cord.

Differentiation of pluripotent neural stem cells engrafted into the adult normal and injured spinal cord is restricted to the glial lineage, suggesting that in vitro induction toward a neuronal lineage prior to transplantation and/or modification of the host environment may be necessary to initiate and increase the differentiation of neurons. In the present study, we investigated the differentiation of neuronal-restricted precursors (NRPs) grafted into the normal and contused adult rat spinal cord. NRPs proliferated through multiple passages in the presence of FGF2 and NT3 and differentiated into only neurons in vitro in the presence of retinoic acid and the absence of FGF2.