Bringing Gratitude to Aphasia Intervention: A Scoping Review of Gratitude Interventions for Adults with Chronic Health Conditions.

Aphasia negatively impacts mental health, disrupting social connections and meaningful life activities. Gratitude interventions for healthy adults positively impact well-being, physical health, and mental health. A systematic review of gratitude interventions for people living with chronic health conditions was conducted to identify current practices and existing gaps and to map the literature for incorporating gratitude interventions into aphasia rehabilitation.

Supporting Participation Through Project-Based Intervention: A Tutorial for Working With People With Aphasia in Individual Sessions.

Purpose: Participation is an integral focus of services to people with aphasia and is considered best practice within the scope of practice for speech-language pathology. The Life Participation Approach to Aphasia encourages meaningful participation in life for people living with aphasia. In theory, providing participation-based services to people with aphasia seems logical; however, embedding these constructs of participation into practice can be challenging for speech-language pathologists (SLPs).

"I Could Not Talk . . . She Did Everything . . . She's Now My Sister": People With Aphasia's Perspectives on Friends Who Stuck Around.

Purpose: Aphasia may decrease the capacity to develop and maintain friendships. The aim of this study was to better understand the perspectives of people with aphasia on why some friendship bonds remain strong and some do not. Furthermore, we wanted to explore how age and aphasia severity shape views on friendship.

"It's not often that people want to hear me talk about my life": Storytelling experiences of people with aphasia in an interdisciplinary songwriting project.

Purpose: Storytelling is an integral part of human life, providing opportunities for social closeness, relationship development, and identity exploration. Having aphasia can disrupt the ability to convey stories across a variety of settings. Structured songwriting frameworks may provide people with aphasia an opportunity to successfully engage in this medium for storytelling.

A scoping review of friendship intervention for older adults: lessons for designing intervention for people with aphasia.

Purpose: Map the landscape of friendship interventions/programs for older adults to guide intervention/program development inclusive of the unique needs of older people with aphasia (PWA).

Methods: A search query of multiple databases was completed for articles published before 4 January 2021. Studies included all the following: (1) participants aged 55 years or older; (2) addressed an intervention/program designed to prevent social isolation and/or friendship loss; (3) used an outcome variable related to social isolation and/or friendship; and (4) published in a peer-reviewed journal.

How Do You Do Talk Therapy With Someone Who Can't Talk? Perspectives From Mental Health Providers on Delivering Services to Individuals With Aphasia.

Purpose Aphasia is correlated with depression and anxiety, and it has a negative impact on quality of life. Aphasia is also frequently misunderstood among mental health care providers. The aim of this study was to explore the experiences of mental health providers who provide services to people living with aphasia.

Recurrent seizure-related GRIN1 variant: Molecular mechanism and targeted therapy.

Objective: Genetic variants in the GRIN genes that encode N-methyl-D-aspartate receptor (NMDAR) subunits have been identified in various neurodevelopmental disorders, including epilepsy. We identified a GRIN1 variant from an individual with early-onset epileptic encephalopathy, evaluated functional changes to NMDAR properties caused by the variant, and screened FDA-approved therapeutic compounds as potential treatments for the patient.

Methods: Whole exome sequencing identified a missense variant in GRIN1.

Distinct GluN1 and GluN2 Structural Determinants for Subunit-Selective Positive Allosteric Modulation of -Methyl-d-aspartate Receptors.

-Methyl-d-aspartate receptors (NMDARs) are ionotropic ligand-gated glutamate receptors that mediate fast excitatory synaptic transmission in the central nervous system (CNS). Several neurological disorders may involve NMDAR hypofunction, which has driven therapeutic interest in positive allosteric modulators (PAMs) of NMDAR function. Here we describe modest changes to the tetrahydroisoquinoline scaffold of GluN2C/GluN2D-selective PAMs that expands activity to include GluN2A- and GluN2B-containing recombinant and synaptic NMDARs.

Discovery of Dihydropyrrolo[1,2-]pyrazin-3(4)-one-Based Second-Generation GluN2C- and GluN2D-Selective Positive Allosteric Modulators (PAMs) of the -Methyl-d-Aspartate (NMDA) Receptor.

The -methyl-d-aspartate receptor (NMDAR) is an ion channel that mediates the slow, Ca-permeable component of glutamatergic synaptic transmission in the central nervous system (CNS). NMDARs are known to play a significant role in basic neurological functions, and their dysfunction has been implicated in several CNS disorders. Herein, we report the discovery of second-generation GluN2C/D-selective NMDAR-positive allosteric modulators (PAMs) with a dihydropyrrolo[1,2-]pyrazin-3(4)-one core.

More Than a Story: My Life Came Back to Life.

Purpose: Social models of aphasia rehabilitation emphasize the importance of supporting identity renegotiation, which can be accomplished in part through personal narrative construction. The purpose of this study was to examine the experiences of persons who had engaged in a project to coconstruct personal narratives about life with aphasia.

Method: Qualitative interviews were conducted with 3 participants with aphasia who completed a 4-week personal narrative coconstruction project, which included preadministration and postadministration of the Communication Confidence Rating Scale for Aphasia (Cherney & Babbitt, 2011).

The Bioactive Protein-Ligand Conformation of GluN2C-Selective Positive Allosteric Modulators Bound to the NMDA Receptor.

-methyl-d-aspartate (NMDA) receptors are ligand-gated, cation-selective channels that mediate a slow component of excitatory synaptic transmission. Subunit-selective positive allosteric modulators of NMDA receptor function have therapeutically relevant effects on multiple processes in the brain. A series of pyrrolidinones, such as PYD-106, that selectively potentiate NMDA receptors that contain the GluN2C subunit have structural determinants of activity that reside between the GluN2C amino terminal domain and the GluN2C agonist binding domain, suggesting a unique site of action.

The Structure-Activity Relationship of a Tetrahydroisoquinoline Class of N-Methyl-d-Aspartate Receptor Modulators that Potentiates GluN2B-Containing N-Methyl-d-Aspartate Receptors.

We have identified a series of positive allosteric NMDA receptor (NMDAR) modulators derived from a known class of GluN2C/D-selective tetrahydroisoquinoline analogues that includes CIQ. The prototypical compound of this series contains a single isopropoxy moiety in place of the two methoxy substituents present in CIQ. Modifications of this isopropoxy-containing scaffold led to the identification of analogues with enhanced activity at the GluN2B subunit.

Mechanistic Insight into NMDA Receptor Dysregulation by Rare Variants in the GluN2A and GluN2B Agonist Binding Domains.

Epilepsy and intellectual disability are associated with rare variants in the GluN2A and GluN2B (encoded by GRIN2A and GRIN2B) subunits of the N-methyl-D-aspartate receptor (NMDAR), a ligand-gated ion channel with essential roles in brain development and function. By assessing genetic variation across GluN2 domains, we determined that the agonist binding domain, transmembrane domain, and the linker regions between these domains were particularly intolerant to functional variation. Notably, the agonist binding domain of GluN2B exhibited significantly more variation intolerance than that of GluN2A.

GluN2D-Containing N-methyl-d-Aspartate Receptors Mediate Synaptic Transmission in Hippocampal Interneurons and Regulate Interneuron Activity.

N-methyl-d-aspartate receptors (NMDARs) are ionotropic glutamatergic receptors that have been implicated in learning, development, and neuropathological conditions. They are typically composed of GluN1 and GluN2A-D subunits. Whereas a great deal is known about the role of GluN2A- and GluN2B-containing NMDARs, much less is known about GluN2D-containing NMDARs.

NMDA receptor modulators: an updated patent review (2013-2014).

Introduction: The NMDA receptor mediates a slow component of excitatory synaptic transmission, and NMDA receptor dysfunction has been implicated in numerous neurological disorders. Thus, interest in developing modulators that are capable of regulating the channel continues to be strong. Recent research has led to the discovery of a number of compounds that hold therapeutic and clinical value.

Synthesis and structure activity relationship of tetrahydroisoquinoline-based potentiators of GluN2C and GluN2D containing N-methyl-D-aspartate receptors.

We describe here the synthesis and evaluation of a series of tetrahydroisoquinolines that show subunit-selective potentiation of NMDA receptors containing the GluN2C or GluN2D subunits. Bischler-Napieralski conditions were employed in the key step for the conversion of acyclic amides to the corresponding tetrahydroisoquinoline-containing analogs. Compounds were evaluated using both two-electrode voltage clamp recordings from Xenopus laevis oocytes and imaging of mammalian BHK cells loaded with Ca(2+)-sensitive dyes.

Novel NMDA receptor modulators: an update.

Introduction: The NMDA receptor is a ligand-gated ion channel that plays a critical role in higher level brain processes and has been implicated in a range of neurological and psychiatric conditions. Although initial studies for the use of NMDA receptor antagonists in neuroprotection were unsuccessful, more recently, NMDA receptor antagonists have shown clinical promise in other indications such as Alzheimer's disease, Parkinson's disease, pain and depression. Based on the clinical observations and more recent insights into receptor pharmacology, new modulatory approaches are beginning to emerge, with potential therapeutic benefit.

Activator recruitment by the general transcription machinery: X-ray structural analysis of the Oct-1 POU domain/human U1 octamer/SNAP190 peptide ternary complex.

Transcriptional activation of the human U1 snRNA genes is dependent on a noncanonical octamer element contained within an upstream enhancer. The U1 octamer only weakly recruits the Oct-1 POU domain, although recruitment is stimulated by a peptide containing the Oct-1-binding domain of SNAP190. Structural analysis of the Oct-1 POU domain/U1 octamer/SNAP190 peptide complex revealed that SNAP190 makes extensive protein contacts with the Oct-1 POU-specific domain and with the DNA phosphate backbone within the enhancer.

Crystallization of the Oct-1/SNAP190 peptide/DNA complex.

Crystals of the Oct-1 POU/SNAP190 peptide/DNA tertiary complex have been obtained by hanging-drop vapor diffusion at 293K in 20% 2-propanol, 20% PEG 4000 and 0.1M sodium citrate pH 5.6.