Similar Age Preference but Different Attentional Control in Mandatory Hospitalized Individuals who Have Committed Sexual Offenses Against Children and Non-hospitalized Individuals With Self-Reported Sexual Interest in Children.

Thirty-two forensic persons who have committed sexual offenses against children (FP-SOC), 26 non-forensic persons of whom most have committed sexual offenses against children (NFP-SOC), 14 forensic persons who have not committed sexual offenses against children but have committed other offenses (FP-NSOC), and 53 non-forensic persons who have not committed sexual offenses against children (NFP-NSOC) were instructed to solve a cognitive task, while sexual distractors were presented simultaneously. Behavioral performance and eye movements were measured. FP-SOC and NFP-SOC exhibit same age preference patterns for children and adults, but both groups differ significantly with respect to sexual attentional control.

Apolipoprotein E aggregation in microglia initiates Alzheimer's disease pathology by seeding β-amyloidosis.

The seeded growth of pathogenic protein aggregates underlies the pathogenesis of Alzheimer's disease (AD), but how this pathological cascade is initiated is not fully understood. Sporadic AD is linked genetically to apolipoprotein E (APOE) and other genes expressed in microglia related to immune, lipid, and endocytic functions. We generated a transgenic knockin mouse expressing HaloTag-tagged APOE and optimized experimental protocols for the biochemical purification of APOE, which enabled us to identify fibrillary aggregates of APOE in mice with amyloid-β (Aβ) amyloidosis and in human AD brain autopsies.

An appeal for strengthening genomic pathogen surveillance to improve pandemic preparedness and infection prevention: the German perspective.

The SARS-CoV-2 pandemic has highlighted the importance of viable infection surveillance and the relevant infrastructure. From a German perspective, an integral part of this infrastructure, genomic pathogen sequencing, was at best fragmentary and stretched to its limits due to the lack or inefficient use of equipment, human resources, data management and coordination. The experience in other countries has shown that the rate of sequenced positive samples and linkage of genomic and epidemiological data (person, place, time) represent important factors for a successful application of genomic pathogen surveillance.

Brain Region-Specific Differences in Amyloid-β Plaque Composition in 5XFAD Mice.

Senile plaques consisting of amyloid-beta (Aβ) peptides are a major pathological hallmark of Alzheimer's disease (AD). Aβ peptides are heterogeneous regarding the exact length of their amino- and carboxy-termini. Aβ1-40 and Aβ1-42 are often considered to represent canonical "full-length" Aβ species.

Search Strategy Analysis of 5xFAD Alzheimer Mice in the Morris Water Maze Reveals Sex- and Age-Specific Spatial Navigation Deficits.

Spatial disorientation and navigational impairments are not only some of the first memory deficits in Alzheimer's disease, but are also very disease-specific. In rodents, the Morris Water Maze is used to investigate spatial navigation and memory. Here, we examined the spatial memory in the commonly used 5xFAD Alzheimer mouse model in a sex- and age-dependent manner.

A Combination of Caffeine Supplementation and Enriched Environment in an Alzheimer's Disease Mouse Model.

A variety of factors has been associated with healthy brain aging, and epidemiological studies suggest that physical activity and nutritional supplements such as caffeine may reduce the risk of developing dementia and, in particular, Alzheimer's disease (AD) in later life. Caffeine is known to act as a cognitive enhancer but has been also shown to positively affect exercise performance in endurance activities. We have previously observed that chronic oral caffeine supplementation and a treatment paradigm encompassing physical and cognitive stimulation by enriched environment (EE) housing can improve learning and memory performance and ameliorate hippocampal neuron loss in the Tg4-42 mouse model of AD.

Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study.

Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients ( = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score.

Combined long-term enriched environment and caffeine supplementation improve memory function in C57Bl6 mice.

Regular physical activity has been associated with healthy brain aging, reflected by beneficial effects on cognition and learning and memory. Nutritional supplements such as caffeine have been shown to act as cognitive enhancers and may possess neuroprotective properties. Interestingly, caffeine also improves athletic capabilities and is widely used by athletes because of its performance-enhancing effect, while information on potential additive beneficial effects of physical activity and caffeine on cognitive performance is scarce.

Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach.

Background: Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.

Aims: To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.

Estimating the effect of practicing nursing professionals density on cumulative carbapenem-resistance prevalence in gram-negative invasive Isolates: a 30 European country observational modeling study.

Background: The burden of antimicrobial-resistance, specifically carbapenem-resistance in gram-negative bacteria (CRGN), presents a serious public health threat worldwide. In Europe, Southern and Eastern countries (SEC) display a higher CRGN-prevalence as compared to Northern and Western countries (NWC). Since SEC also display lower nurse-density on average, we hypothesized that the occurrence of CRGN might correlate with nurse understaffing and therefore aimed at quantifying a potential independent effect of nurse-density on total CRGN in Europe.

Long-term caffeine treatment of Alzheimer mouse models ameliorates behavioural deficits and neuron loss and promotes cellular and molecular markers of neurogenesis.

Epidemiological studies indicate that the consumption of caffeine, the most commonly ingested psychoactive substance found in coffee, tea or soft drinks, reduces the risk of developing Alzheimer's disease (AD). Previous treatment studies with transgenic AD mouse models reported a reduced amyloid plaque load and an amelioration of behavioral deficits. It has been further shown that moderate doses of caffeine have the potential to attenuate the health burden in preclinical mouse models of a variety of brain disorders (reviewed in Cunha in J Neurochem 139:1019-1055, 2016).

Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients.

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes.

HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders.

Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region.

Characterization of a Mouse Model of Alzheimer's Disease Expressing Aβ4-42 and Human Mutant Tau.

The relationship between the two most prominent neuropathological hallmarks of Alzheimer's Disease (AD), extracellular amyloid-β (Aβ) deposits and intracellular accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFT), remains at present not fully understood. A large body of evidence places Aβ upstream in the cascade of pathological events, triggering NFTs formation and the subsequent neuron loss. Extracellular Aβ deposits were indeed causative of an increased tau phosphorylation and accumulation in several transgenic models but the contribution of soluble Aβ peptides is still controversial.

Evaluation of cerebrospinal fluid glycoprotein NMB (GPNMB) as a potential biomarker for Alzheimer's disease.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder associated with extracellular amyloid-β peptide deposition and progressive neuron loss. Strong evidence supports that neuroinflammatory changes such as the activation of astrocytes and microglia cells are important in the disease process. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a transmembrane glycoprotein that has recently been associated with an emerging role in neuroinflammation, which has been reported to be increased in post-mortem brain samples from AD and Parkinson's disease patients.

Accuracy and reproducibility of automated white matter hyperintensities segmentation with lesion segmentation tool: A European multi-site 3T study.

Brain vascular damage accumulate in aging and often manifest as white matter hyperintensities (WMHs) on MRI. Despite increased interest in automated methods to segment WMHs, a gold standard has not been achieved and their longitudinal reproducibility has been poorly investigated. The aim of present work is to evaluate accuracy and reproducibility of two freely available segmentation algorithms.

Neuron Loss in Alzheimer's Disease: Translation in Transgenic Mouse Models.

Transgenic mouse models represent an essential tool for the exploration of Alzheimer's disease (AD) pathological mechanisms and the development of novel treatments, which at present provide only symptomatic and transient effects. While a variety of mouse models successfully reflects the main neuropathological hallmarks of AD, such as extracellular amyloid-β (Aβ) deposits, intracellular accumulation of Tau protein, the development of micro- and astrogliosis, as well as behavioral deficits, substantial neuron loss, as a key feature of the disease, seems to be more difficult to achieve. In this review, we summarize information on classic and more recent transgenic mouse models for AD, focusing in particular on loss of pyramidal, inter-, and cholinergic neurons.

Physical activity and cognitive stimulation ameliorate learning and motor deficits in a transgenic mouse model of Alzheimer's disease.

Epidemiological studies suggest that physical exercise or cognitive stimulation might contribute to lower the risk of developing dementia disorders such as Alzheimer's disease (AD). Here, we used the well-established enrichment environment (EE) paradigm to study the impact of prolonged physical activity and cognitive stimulation in a mouse model of AD overexpressing only Aβ peptides. These mice display age-dependent memory and motor deficits, in the absence of human amyloid precursor protein (APP) overexpression.

Chronic Memantine Treatment Ameliorates Behavioral Deficits, Neuron Loss, and Impaired Neurogenesis in a Model of Alzheimer's Disease.

Memantine, a non-competitive NMDA receptor antagonist possessing neuroprotective properties, belongs to the small group of drugs which have been approved for the treatment of Alzheimer's disease (AD). While several preclinical studies employing different transgenic AD mouse models have described beneficial effects with regard to rescued behavioral deficits or reduced amyloid plaque pathology, it is largely unknown whether memantine might have beneficial effects on neurodegeneration. In the current study, we assessed whether memantine treatment has an impact on hippocampal neuron loss and associated behavioral deficits in the Tg4-42 mouse model of AD.

Development and Technical Validation of an Immunoassay for the Detection of APP (Aβ) in Biological Samples.

The ratio of amyloid precursor protein (APP) (Aβ)/Aβ in blood plasma was reported to represent a novel Alzheimer's disease biomarker. Here, we describe the characterization of two antibodies against the N-terminus of Aβ and the development and "fit-for-purpose" technical validation of a sandwich immunoassay for the measurement of Aβ. Antibody selectivity was assessed by capillary isoelectric focusing immunoassay, Western blot analysis, and immunohistochemistry.

N-terminal heterogeneity of parenchymal and vascular amyloid-β deposits in Alzheimer's disease.

Aims: The deposition of amyloid-β (Aβ) peptides in the form of extracellular plaques in the brain represents one of the classical hallmarks of Alzheimer's disease (AD). In addition to 'full-length' Aβ starting with aspartic acid (Asp-1), considerable amounts of various shorter, N-terminally truncated Aβ peptides have been identified by mass spectrometry in autopsy samples from individuals with AD.

Methods: Selectivity of several antibodies detecting full-length, total or N-terminally truncated Aβ species has been characterized with capillary isoelectric focusing assays using a set of synthetic Aβ peptides comprising different N-termini.

Controlling incisor torque with completely customized lingual appliances.

Purpose: To test the null hypothesis of no significant deviation between the center of rotation (C) and the center of resistance (C) during space closure in Angle class II division 2 subjects achieved using a completely customized lingual appliance (CCLA) in combination with class II elastics and elastic chains.

Methods: This retrospective study included 29 patients (male/female 11/18; mean age 15.6 [13-27] years) with inclusion criteria of an Angle class II/2 occlusion of least of half of a cusp, maxillary dental arch spacing, completed CCLA treatment (WIN, DW Lingual Systems, Bad Essen, Germany) in one center with a standardized archwire sequence and use of class II elastics and elastic chains only.