Constrained β-Hairpins Targeting the EphA4 Ligand Binding Domain.

The activity of the receptor tyrosine kinase EphA4 has been implicated in several pathologies including oncology (gastric and pancreatic cancers) and neurodegenerative diseases (amyotrophic lateral sclerosis and Alzheimer's disease). However, advances in validating EphA4 as a possible drug target have been limited by the lack of suitable pharmacological inhibitors. Recently, we reported on the design of potent EphA4 agonistic agents targeting its ligand binding domain (LBD).

Covalent Targeting of Histidine Residues with Aryl Fluorosulfates: Application to Mcl-1 BH3 Mimetics.

Covalent drugs provide pharmacodynamic and pharmacokinetic advantages over reversible agents. However, covalent strategies have been developed mostly to target cysteine (Cys) residues, which are rarely found in binding sites. Among other nucleophilic residues that could be in principle used for the design of covalent drugs, histidine (His) has not been given proper attention despite being in principle an attractive residue to pursue but underexplored.

Targeted degradation of Pin1 by protein-destabilizing compounds.

The concept of targeted protein degradation is at the forefront of modern drug discovery, which aims to eliminate disease-causing proteins using specific molecules. In this paper, we explored the idea to design protein degraders based on the section of ligands that cause protein destabilization, hence that facilitate the cellular breakdown of the target. Our studies present covalent agents targeting Pin1, a cis-trans prolyl isomerase that plays a crucial role in tumorigenesis.

Synbiotic supplementation may globally improve non-motor symptoms in patients with stable Parkinson's disease: results from an open label single-arm study.

Gut microbiota changes and brain-gut-axis (BGA) dysregulation are common in people with Parkinson's Disease (PD). Probiotics and prebiotics are emerging as a potential therapeutic approach for PD patients. The aim of this paper was to assess the neurological and gastroenterological effects in PD patients with constipation after the administration of a synbiotic product, with a focus on behavioral and cognitive symptoms.

A window into the mind-brain-body interplay: Development of diagnostic, prognostic biomarkers, and rehabilitation strategies in functional motor disorders.

Background And Aims: Functional motor disorders (FMD) present a prevalent, yet misunderstood spectrum of neurological conditions characterized by abnormal movements (i.e., functional limb weakness, tremor, dystonia, gait impairments), leading to substantial disability and diminished quality of life.

The contribution of white matter changes to clinical phenotype in progressive supranuclear palsy.

White matter hyperintensities (WMH) are considered magnetic brain imaging (MRI) biomarkers of cerebral small vessel disease but their clinical role in neurodegenerative-related disorders is poorly understood. This study describes the distribution of WMH on brain MRI in Progressive Supranuclear Palsy (PSP) in comparison with Parkinson's disease (PD) and explores their possible impact on disease's features. Sixty PSP and 33 PD patients were included.

A multi-constituent qualitative examination of facilitators and barriers to caregiver coaching for autistic children in publicly funded early intervention.

Caregiver coaching is an evidence-based practice for young autistic children, but it is not widely used in community-based early intervention services. Previous research has explored why caregiver coaching is not widespread in early intervention, but only from the perspective of early intervention providers. Caregivers, providers, administrators are all involved in the decision of whether to use caregiver coaching in early intervention.

Histidine-Covalent Stapled Alpha-Helical Peptides Targeting hMcl-1.

Several novel and effective cysteine targeting (Cys) covalent drugs are in clinical use. However, the target area containing a druggable Cys residue is limited. Therefore, methods for creating covalent drugs that target different residues are being looked for; examples of such ligands include those that target the residues lysine (Lys) and tyrosine (Tyr).

Longitudinal change of energy expenditure, body composition and dietary habits in Progressive Supranuclear Palsy patients.

Introduction: Alterations in metabolic status, body composition, and food intake are present in all neurodegenerative diseases. Aim of this study was to detect the progression of these changes in Progressive Supranuclear Palsy (PSP).

Methods: We conducted a longitudinal study of 15 patients with PSP.

The use of honey bees (Apis mellifera L.) to monitor airborne particulate matter and assess health effects on pollinators.

The honey bee Apis mellifera has long been recognized as an ideal bioindicator for environmental pollution. These insects are exposed to pollutants during their foraging activities, making them effective samplers of environmental contaminants, including heavy metals, pesticides, radionuclides, and volatile organic compounds. Recently, it has been demonstrated that honey bees can be a valuable tool for monitoring and studying airborne PM pollution, a complex mixture of particles suspended in the air, known to have detrimental effects on human health.

Direct Current Stimulation of Prefrontal Cortex Is Not Effective in Progressive Supranuclear Palsy: A Randomized Trial.

Background: Progressive supranuclear palsy (PSP) is a rare 4R-tauopathy. Transcranial direct current stimulation (tDCS) may improve specific symptoms.

Objectives: This randomized, double-blinded, sham-controlled trial aimed at verifying the short-, mid-, and long-term effect of multiple sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) cortex in PSP.

A mixed-methods evaluation of organization and individual factors influencing provider intentions to use caregiver coaching in community-based early intervention.

Background: Most psycho-social interventions contain multiple components. Practitioners often vary in their implementation of different intervention components. Caregiver coaching is a multicomponent intervention for young autistic children that is highly effective but poorly implemented in community-based early intervention (EI).

Psychometric properties of the Caregiver's inventory neuropsychological diagnosis dementia (CINDD) in mild cognitive impairment and dementia.

Objectives: The Caregiver's Inventory Neuropsychological Diagnosis Dementia (CINDD) is an easy tool designed to quantify cognitive, behavioural and functional deficits of patients with cognitive impairment. Aim of the present study was to analyse the psychometric properties of the CINDD in Mild Cognitive Impairment (MCI) and Dementia (D).

Design, Setting And Participants: The CINDD, composed by 9 sub-domains, was administered to fifty-six caregivers of patients with different types of dementia (D) and 44 caregivers of patients with MCI.

Beyond the Task List: A Proposed Integration of Naturalistic Developmental Behavioral Interventions to BCBA Training.

Naturalistic developmental behavioral intervention (NDBI) is firmly rooted in both the science of ABA as well as developmental science. Research indicates that many practicing board certified behavior analysts (BCBAs) are unfamiliar with NDBI models and do not implement these approaches when working with young autistic children (Hampton and Sandbank (4), 875-888, 2022). In this article we align NDBI to the seven dimensions of ABA, describe their compatibility with the ABA service system, and urge community agencies and insurance funders to support NDBI use.

The effects of safinamide according to gender in Chinese parkinsonian patients.

The incidence and prevalence of Parkinson's disease (PD) is expected to raise dramatically over the next decades. Gender-related differences are not yet widely recognized, particularly regarding the response to dopaminergic medications. To analyse gender differences in the clinical effects of safinamide, compared to placebo, in Chinese PD patients of the pivotal XINDI trial.

The Correlation between Retinal and Choroidal Thickness with Age-Related White Matter Hyperintensities in Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease. Recently, several retinal layers in PSP compared to healthy controls. were found to be thinner.

Development of the Digital Inclusion Questionnaire (DIQUEST) in Parkinson's Disease.

Background: No tool is currently able to measure digital inclusion in clinical populations suitable for telemedicine. We developed the "Digital Inclusion Questionnaire" (DIQUEST) to estimate access and skills in Parkinson's Disease (PD) patients and verified its properties with a pilot study.

Methods: Thirty PD patients completed the initial version of the DIQUEST along with the Mobile Device Proficiency Questionnaire (MDPQ) and a practical computer task.

Parent Coaching in Early Intervention for Autism Spectrum Disorder: A Brief Report.

Coaching caregivers of young children on the autism spectrum is a critical component of parent-mediated interventions. Little information is available about how providers implement parent coaching for children on the autism spectrum in publicly funded early intervention systems. This study evaluated providers' use of parent coaching in an early intervention system.