Mild behavioral impairment in people with mild cognitive impairment: Are the two conditions related?

Background: Mild cognitive impairment (MCI) and mild behavioral impairment (MBI) are both considered potential prodromal stages of dementia, especially Alzheimer's disease. Previous literature has lacked specific information about MBI in individuals with MCI and associations of several aspects of both, MBI and MCI.

Objective: Our aim was to investigate whether associations exist between aspects of MBI and aspects of cognitive performance in certain dimensions of the Montreal Cognitive Assessment (MoCA).

Individualised computerised cognitive training (iCCT) for community-dwelling people with mild cognitive impairment (MCI): results on cognition in the 6-month intervention period of a randomised controlled trial (MCI-CCT study).

Background: Computerised cognitive training (CCT) can improve the cognitive abilities of people with mild cognitive impairment (MCI), especially when the CCT contains a learning system, which is a type of machine learning (ML) that automatically selects exercises at a difficulty that corresponds to the person's peak performance and thus enables individualised training.

Methods: We developed one individualised CCT (iCCT) with ML and one basic CCT (bCCT) for an active control group (CG). The study aimed to determine whether iCCT in the intervention group (IG) resulted in significantly greater enhancements in overall cognitive functioning for individuals with MCI (age 60+) compared with bCCT in the CG across a 6-month period.

The roles of employment status and income in the mental health of informal caregivers in Germany.

Background: Informal caregivers often experience multiple negative consequences as a result of the informal care they provide. Among other factors, employment status, financial resources, and mental health are related to informal caregiving. This analysis examined the association between informal caregivers' employment status and their mental health, as well as the moderating effect of net household income on this relationship.

Wavelength Tuning in Resonant Cavity Interband Cascade Light Emitting Diodes (RCICLEDs) via Post Growth Cavity Length Adjustment.

We demonstrate substrate-emitting resonant cavity interband cascade light emitting diodes (RCICLEDs) based on a single distributed Bragg reflector (DBR). These devices operate in continuous wave mode at room temperature. Compared to standard ICLEDs without a cavity, we achieved an 89% reduction in the emission spectrum width, as indicated by the Full Width Half Maximum (FWHM) of 70 nm.

Highly pure DNA-encoded chemical libraries by dual-linker solid-phase synthesis.

The first drugs discovered using DNA-encoded chemical library (DEL) screens have entered late-stage clinical development. However, DEL technology as a whole still suffers from poor chemical purity resulting in suboptimal performance. In this work, we report a technique to overcome this issue through self-purifying release of the DEL after magnetic bead-based synthesis.

[Reconciling Employment and Informal Caregiving for an Elderly Person at Home: Factors Influencing a Reduction in Employment due to Caregiving and Work-Related Wishes of Informal Caregivers].

Objective: Reconciling informal caregiving and gainful employment is a challenge for many informal caregivers. The goals of this paper are to identify factors influencing care-related employment reduction, and to record work-related wishes for improving the compatibility of informal caregiving and being employed.

Methods: Analyses were based on the cross-sectional Benefits of Being a Caregiver Study of 426 employed caregivers of an older person in need of care.

[Care-related Termination of Employment among Informal Caregivers of Elderly Persons: Identification of a Risk Profile].

Objective: Employed informal caregivers often experience role conflicts between caring for an elderly person in need of care at home and their employment. The goal of this paper was to identify a risk profile of care-related termination of employment.

Methods: Analyses are based on the cross-sectional Benefits of Being a Caregiver Study (October 2019 - March 2020) with data from 481 informal caregivers of elderly persons in need of care.

Brain expression profiles of two antisense RNAs in children and adolescents with epilepsy.

Objective: Heterozygous mutations within the voltage-gated sodium channel α subunit () are responsible for the majority of cases of Dravet syndrome (DS), a severe developmental and epileptic encephalopathy. Development of novel therapeutic approaches is mandatory in order to directly target the molecular consequences of the genetic defect. The aim of the present study was to investigate whether cis-acting long non-coding RNAs (lncRNAs) of are expressed in brain specimens of children and adolescent with epilepsy as these molecules comprise possible targets for precision-based therapy approaches.

Asymmetry of Dual-Display DNA-Encoded Chemical Libraries.

While dual-display DNA-encoded chemical libraries (DELs) are increasingly employed for ligand discovery, some of their fundamental properties have not yet been studied in-depth. Aided with fluorescence polarization experiments, we demonstrate that dual-display DELs are intrinsically asymmetrical entities, and we deduce practical guidelines to perform better-informed on-DNA hit validation from these libraries.

Advancing small-molecule drug discovery by encoded dual-display technologies.

DNA-encoded chemical library technology (DECL or DEL) has become an important pillar for small-molecule drug discovery. The technology rapidly identifies small-molecule hits for relevant target proteins at low cost and with a high success rate, including ligands for targeted protein degradation (TPD). More recently, the setup of DNA- or peptide nucleic acid (PNA)-encoded chemical libraries based on the simultaneous display of ligand pairs, termed dual-display, allows for more sophisticated applications which will be reviewed herein.

[Sometimes, I Also Drink Water… - Alcohol Consumption of People With Mild Cognitive Impairment].

Aim: Risky alcohol consumption increases the risk of dementia for people with mild cognitive impairment (MCI). The aim of this study is to assess alcohol consumption in people with MCI.

Methods: Socio-demographics, 12-month prevalence, 30-d prevalence, prevalence of risky consumption (>10 g/20 g/d pure alcohol for women/men) and binge drinking (≥50 g pure alcohol on one occasion) were recorded in 270 people (≥60 years) with MCI from the German RCT "Brainfit-Nutrition" in 2022.

Computational methods to analyze and predict the binding mode of inhibitors targeting both human and mushroom tyrosinase.

Tyrosinase, a copper-containing enzyme critical in melanin biosynthesis, is a key drug target for hyperpigmentation and melanoma in humans. Testing the inhibitory effects of compounds using tyrosinase from Agaricus bisporus (AbTYR) has been a common practice to identify potential therapeutics from synthetic and natural sources. However, structural diversity among human tyrosinase (hTYR) and AbTYR presents a challenge in developing drugs that are therapeutically effective.

Are Protective Activities and Limitations in Practical Skills of Daily Living Associated with the Cognitive Performance of People with Mild Cognitive Impairment? Baseline Results from the BrainFit-Nutrition Study.

Limitations in daily living have not yet been described adequately for mild cognitive impairment (MCI). In this study, we investigated first, time spent on protective activities (social, mental, and physical) and second, limitations in practical skills of daily living, both for people with MCI. We used baseline data from 270 individuals who participated in the randomized controlled trial BrainFit-Nutrition.

A Portable Infrared Attenuated Total Reflection Spectrometer for Food Analysis.

The analytical performance of a compact infrared attenuated total reflection spectrometer using a pyroelectric detector array has been evaluated and compared to a conventional laboratory Fourier transform infrared system for applications in food analysis. Analytical characteristics including sensitivity, repeatability, linearity of the calibration functions, signal-to-noise ratio, and spectral resolution have been derived for both approaches. Representative analytes of relevance in food industries (i.

Site-Specific Chemical Modification of a Cytokine Mimic for Small Molecule-Based Tumor Targeting.

The targeted delivery of bioactive proteins, such as cytokines, for cancer immunotherapy approaches mostly relies on antibodies or antibody fragments. However, fusion proteins may display low tissue penetration due to a large molecular size. Small molecule ligands with high affinity toward tumor-associated antigens provide a promising alternative for the selective delivery of cytokines to tumor lesions.

A DNA-encoded chemical library based on chiral 4-amino-proline enables stereospecific isozyme-selective protein recognition.

DNA-encoded chemical libraries (DELs) consist of large chemical compound collections individually linked to DNA barcodes, facilitating pooled construction and screening. However, screening campaigns often fail if the molecular arrangement of the building blocks is not conducive to an efficient interaction with a protein target. Here we postulated that the use of rigid, compact and stereo-defined central scaffolds for DEL synthesis may facilitate the discovery of very specific ligands capable of discriminating between closely related protein targets.

RGD Cyclopeptide Equipped with a Lysine-Engaging Salicylaldehyde Showing Enhanced Integrin Affinity and Cell Detachment Potency.

Salicylaldehyde (SA) derivatives are emerging as useful fragments to obtain reversible-covalent inhibitors interacting with the lysine residues of the target protein. Here the SA installation at the C terminus of an integrin-binding cyclopeptide, leading to enhanced ligand affinity for the receptor as well as stronger biological activity in cultured glioblastoma cells is reported.

Predictors of expressed, felt, and normative needs for informal caregiver counseling : Domestic care for people aged 65+ years.

Background: Informal caregivers (CGs) often fail to recognize or express a need for informal caregiver counseling (ICC) but ICC is an essential but relatively rarely used support service for CGs.

Objective: Our aim is to identify predictors of CGs' need for ICC. Stirling et al.

Isolation of a Natural Killer Group 2D Small-Molecule Ligand from DNA-Encoded Chemical Libraries.

Natural Killer Group 2D (NKG2D) is a homo-dimeric transmembrane protein which is typically expressed on the surface of natural killer (NK) cells, natural killer T (NKT) cells, gamma delta T (γδT) cells, activated CD8 positive T-cells and activated macrophages. Bispecific molecules, capable of bridging NKG2D with a target protein expressed on the surface of tumor cells, may be used to redirect the cytotoxic activity of NK-cells towards antigen-positive malignant T-cells. In this work, we report the discovery of a novel NKG2D small molecule binder [K =(410±60) nM], isolated from a DNA-Encoded Chemical Library (DEL).

Computerised cognitive training tools and online nutritional group counselling for people with mild cognitive impairment: study protocol of a completely digital, randomised, controlled trial.

Introduction: People with mild cognitive impairment (MCI) are at increased risk of decreasing cognitive functioning. Computerised cognitive training (CCT) and nutrition have been shown to improve the cognitive capacities of people with MCI. For each variable, we developed two kinds of interventions specialised for people with MCI (CCT: 'individualised' CCT; nutrition: a whole-food, plant-based diet).

LncRNA shapes the gene expression program towards neurogenesis.

The evolution of brain complexity correlates with an increased expression of long, noncoding (lnc) RNAs in neural tissues. Although prominent examples illustrate the potential of lncRNAs to scaffold and target epigenetic regulators to chromatin loci, only few cases have been described to function during brain development. We present a first functional characterization of the lncRNA , which we term for "RNA upstream of Slitrk3.