The Feasibility of Personalized Endpoints in Assessing Treatment Outcomes in Rare Disease: A Pilot Study of Goal Attainment Scaling in SCN2A-Associated Developmental Epileptic Encephalopathy.

Objectives: For individuals living with rare neurodevelopmental disorders, especially those who are at the most severe end of the spectrum, standardized outcome measures may lack the sensitivity to capture small but meaningful changes. Personalized endpoints such as Goal Attainment Scaling (GAS) allow the assessment of treatment response across variable baseline states and disease manifestations and thus provide a highly sensitive measure of efficacy. The current study tested the feasibility of using GAS in rare SCN2A-associated developmental and epileptic encephalopathy (SCN2A-DEE).

Use of Basket Trials to Solve Sleep Problems in Patients with Rare Diseases.

The need for sleep is universal, and the ability to meet this need impacts the quality of life for patients, families, and caregivers. Although substantial progress has been made in treating rare diseases, many patients have unmet medical sleep needs, and current regulatory policy makes it prohibitively difficult to address those needs medically. This opinion reviews the rare disease experience with sleep disorders and explores potential solutions.

Patient-advocate-led global coalition adapting fit-for-purpose outcomes measures to assure meaningful inclusion of DEEs in clinical trials.

Existing clinical tools that measure non-seizure outcomes lack the range and granularity needed to capture skills in developmental and epileptic encephalopathy (DEE)-affected individuals who also fall in the severe to profound range of intellectual disability. This effectively excludes those with severe impairments from clinical trials, impeding the ability of sponsors to evaluate disease-modifying therapies (DMTs). The Inchstone Project, an international, patient advocate-led collaboration, brings together leading researchers, clinicians, pharmaceutical companies, and advocates to develop an adapted, validated assessment battery within 5 years.

Gram-Negative Bloodstream Infections in Healthcare: The Relationship Between Antibiotic Resistance, Mortality, and Novel Serological Biomarker.

Background: Bloodstream infections caused by Gram-negative bacteria are highly mortal. In this study, we aimed to investigate the relationship between antimicrobial resistance profile and novel serological biomarkers and mortality in bloodstream infections (BSIs) caused by Gram-negative bacteria in intensive care units (ICUs).

Methods: 366 Patients diagnosed with healthcare-associated Gram-negative bloodstream infection in the ICUs of our hospital between February 2015 and December 2021 were included in the study.

Synthesis and Photophysical Characterizations of Benzimidazole Functionalized BODIPY Dyes.

Herein, a series of new BODIPY dyes substituted by 2-phenyl benzimidazole units at the meso (C8) position including methyl/ethyl, phenyl, or p-methoxyphenyl moieties at the distal and proximal positions of the BODIPY core have been successfully synthesized and their photophysical characteristics were analyzed. Experimentally investigating absorption and fluorescence profiles in the THF media was followed by density functional theory (DFT) calculations to clarify photophysical features. Theoretical analyses have revealed that upon excitation, both electrons and holes are confined solely within the BODIPY core.

Photophysical, thermal, and DFT studies on a tetraaryl-azadipyrromethene ligand and its zinc(II) complex.

An azadipyrromethene ligand () and homoleptic zinc(II) () complex were synthesized. The resulting structures were elucidated by NMR, FTIR, and HRMS techniques. The photophysical properties and effects of complexing the zinc(II) atom to azadipyrromethene ligands in solution were studied by means of UV-Vis absorption and fluorescence spectroscopy.

A systematic review of goal attainment scaling implementation practices by caregivers in randomized controlled trials.

Background: Goal attainment scaling (GAS), an established individualized, patient-centred outcome measure, is used to capture the patient's voice. Although first introduced ~60 years ago, there are few published guidelines for implementing GAS, and almost none for its use when caregivers GAS is implemented with caregiver input. We conducted a systematic review of studies that implemented GAS with caregiver input; and examined variations in GAS implementation, analysis, and reporting.

Within-Person Modulation of Neural Networks following Interoceptive Awareness Training through Mindful Awareness in Body-Oriented Therapy (MABT): A Pilot Study.

Interoception, the representation of the body's internal state, is increasingly recognized for informing subjective wellbeing and promoting regulatory behavior. However, few empirical reports characterize interoceptive neural networks, and fewer demonstrate changes to these networks in response to an efficacious intervention. Using a two-group randomized controlled trial, this pilot study explored within-participant neural plasticity in interoceptive networks following Mindful Awareness in Body-oriented Therapy (MABT).

Mindfulness training and exercise differentially impact fear extinction neurocircuitry.

Background: The ability to extinguish a maladaptive conditioned fear response is crucial for healthy emotional processing and resiliency to aversive experiences. Therefore, enhancing fear extinction learning has immense potential emotional and health benefits. Mindfulness training enhances both fear conditioning and recall of extinguished fear; however, its effects on fear extinction learning are unknown.

BRD9-containing non-canonical BAF complex maintains somatic cell transcriptome and acts as a barrier to human reprogramming.

Epigenetic reprogramming to pluripotency requires extensive remodeling of chromatin landscapes to silence existing cell-type-specific genes and activate pluripotency genes. ATP-dependent chromatin remodeling complexes are important regulators of chromatin structure and gene expression; however, the role of recently identified Bromodomain-containing protein 9 (BRD9) and the associated non-canonical BRG1-associated factors (ncBAF) complex in reprogramming remains unknown. Here, we show that genetic or chemical inhibition of BRD9, as well as ncBAF complex subunit GLTSCR1, but not the closely related BRD7, increase human somatic cell reprogramming efficiency and can replace KLF4 and c-MYC.

Two-photon absorption and triplet excited state quenching of near-IR region aza-BODIPY photosensitizers a triphenylamine moiety despite heavy bromine atoms.

Aza-BODIPY compounds with methoxy groups at -3 and -5 and triphenylamine moieties at -1 and -7 positions with and without heavy bromine atoms at -2 and -6 positions have been designed and synthesized. The chemical structures of the novel compounds were fully characterized using H NMR, C NMR, FTIR, and HRMS-TOF-ESI techniques. Steady-state absorption and emission features were investigated to analyze ground-state interactions.

Rates of underreported needlestick and sharps injuries among healthcare workers in Turkey: in the light of Infection Control Committee data.

Objective: Doctors and nurses are frequently exposed to needlestick and sharps injuries (NSIs) because of their work. It is estimated that NSIs are more common than the rates reported to Infection Control Committee. The purpose of this study was to determine the incidence and reporting rates of NSIs in our hospital.

Mindfulness Training Improves Cognition and Strengthens Intrinsic Connectivity Between the Hippocampus and Posteromedial Cortex in Healthy Older Adults.

Maintaining optimal cognitive functioning throughout the lifespan is a public health priority. Evaluation of cognitive outcomes following interventions to promote and preserve brain structure and function in older adults, and associated neural mechanisms, are therefore of critical importance. In this randomized controlled trial, we examined the behavioral and neural outcomes following mindfulness training ( = 72), compared to a cognitive fitness program ( = 74) in healthy, cognitively normal, older adults (65-80 years old).

Age differences in intuitive moral decision-making: Associations with inter-network neural connectivity.

Positions of power involving moral decision-making are often held by older adults (OAs). However, little is known about age differences in moral decision-making and the intrinsic organization of the aging brain. In this study, younger adults (YAs; = 117, = 22.

Synthetic review of financial capacity in cognitive disorders: Foundations, interventions, and innovations.

Purpose Of Review: Financial capacity (FC) is a complex, multi-dimensional construct that changes over the lifespan and commonly becomes impaired as individuals age and develop dementia. Impaired FC results in several important negative outcomes including loss of independence and increased victimization and abuse. The goal of this review is to synthesize current knowledge of the assessment and intervention of impaired financial capacity in order to propose its further development in the context of technological advancements.

3, 3,5 and 2,6 Expanded Aza-BODIPYs Via Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling Reactions: Synthesis and Photophysical Properties.

Novel symmetrical aza-borondipyrromethene (aza-BODIPY) compounds bearing 4-methoxyphenyl, 4-methoxybiphenyl, 2,4-dimethoxybipheny, 4-bromophenyl and N,N-diphenyl-4-biphenylamine groups on the 3, 3,5 and 2,6 positions of aza-BODIPY core were synthesized via Suzuki-Miyaura coupling reactions while unsymmetrical analogues were obtained from the starting mono Br-substituted aza-BODIPY material which was obtained from nitrosolated pyrrole derivative. The characterizations were performed by means of H-NMR, C-NMR, FTIR and HRMS-TOF-ESI techniques. The spectral properties of the aza-BODIPY derivatives were investigated using absorption and fluorescence spectroscopy.

Hippocampal circuits underlie improvements in self-reported anxiety following mindfulness training.

Introduction: Mindfulness meditation has successfully been applied to cultivate skills in self-regulation of emotion, as it employs the unbiased present moment awareness of experience. This heightened attention to and awareness of sensory experience has been postulated to create an optimal therapeutic exposure condition and thereby improve extinction learning. We recently demonstrated increased connectivity in hippocampal circuits during the contextual retrieval of extinction memory following mindfulness training.

Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling.

Organoid technologies have become a powerful emerging tool to model liver diseases, for drug screening, and for personalized treatments. These applications are, however, limited in their capacity to generate functional hepatocytes in a reproducible and efficient manner. Here, we generated and characterized the hepatic organoid (eHEPO) culture system using human induced pluripotent stem cell (iPSC)-derived EpCAM-positive endodermal cells as an intermediate.

Strengthened Hippocampal Circuits Underlie Enhanced Retrieval of Extinguished Fear Memories Following Mindfulness Training.

Background: The role of hippocampus in context-dependent recall of extinction is well recognized. However, little is known about how intervention-induced changes in hippocampal networks relate to improvements in extinction learning. In this study, we hypothesized that mindfulness training creates an optimal exposure condition by heightening attention and awareness of present moment sensory experience, leading to enhanced extinction learning, improved emotion regulation, and reduced anxiety symptoms.

Beyond consensus: Embracing heterogeneity in curated neuroimaging meta-analysis.

Coordinate-based meta-analysis can provide important insights into mind-brain relationships. A popular approach for curated small-scale meta-analysis is activation likelihood estimation (ALE), which identifies brain regions consistently activated across a selected set of experiments, such as within a functional domain or mental disorder. ALE can also be utilized in meta-analytic co-activation modeling (MACM) to identify brain regions consistently co-activated with a seed region.

How does mindfulness training improve moral cognition: a theoretical and experimental framework for the study of embodied ethics.

Mindfulness meditation has been primarily studied within the context of individual's psychological well being and/or in relation to it's potential to enhance cognitive skills such as attention and working memory. However, in Buddhism, mindfulness is used as a tool to cultivate wholesome actions, and as a means to promote virtuous, prosocial qualities. In this article, we postulate that heightened awareness of physiological and mental phenomena following mindfulness training may contribute to altered processing of morally relevant information and promote moral action.

Compassionate Hearts Protect Against Wandering Minds: Self-compassion Moderates the Effect of Mind-Wandering on Depression.

Depression is associated with high levels of mind-wandering and low levels of self-compassion. However, little is known about whether and how these two factors interact with one another to influence depressive symptoms. The current study examined the interaction between mind-wandering, self-compassion and depressive symptoms in a depressed sample and tested the effects of an eight-week Mindfulness Based Cognitive Therapy (MBCT) program on these constructs.

Retrospective investigation of 9 years of data on needlestick and sharps injuries: Effect of a hospital infection control committee.

Background: The risk of occupational transmission of bloodborne pathogens to health care workers is primarily associated with needlestick and sharps injuries (NSIs). However, most NSIs are not reported, and most health care workers are not aware of postexposure procedures.

Methods: Data for NSIs reported in our hospital between 2008 and 2016 were reviewed retrospectively.

Common and Dissociable Neural Activity After Mindfulness-Based Stress Reduction and Relaxation Response Programs.

Objective: We investigated common and dissociable neural and psychological correlates of two widely used meditation-based stress reduction programs.

Methods: Participants were randomized to the Relaxation Response (RR; n = 18; 56% female) or the Mindfulness-Based Stress Reduction (MBSR; n = 16; 56% female) programs. Both programs use a "bodyscan" meditation; however, the RR program explicitly emphasizes physical relaxation during this practice, whereas the MBSR program emphasizes mindful awareness with no explicit relaxation instructions.

Salience network engagement with the detection of morally laden information.

Moral cognition is associated with activation of the default network, regions implicated in mentalizing about one's own actions or the intentions of others. Yet little is known about the initial detection of moral information. We examined the neural correlates of moral processing during a narrative completion task, which included an implicit moral salience manipulation.