Critical comparison of BMD and TD methods for the calculation of acceptable intakes for N-nitroso compounds.

The tumorigenic dose 50 (TD) is a widely used measure of carcinogenic potency which has historically been used to determine acceptable intake limits for carcinogenic compounds. Although broadly used, the TD model was not designed to account for important biological factors such as DNA repair and cell compensatory mechanisms, changes in absorption, etc., leading to the development of benchmark dose (BMD) approaches, which use more flexible dose-response models that are better able to account for these processes.

Nanostructural Analysis of Age-Related Changes Affecting Human Dentin.

Human dentin performs its function throughout life, even though it is not remodeled like bone. Therefore, dentin must have extreme durability against daily repetitive loading. Elucidating its durability requires a comprehensive understanding of its shape, structure, and anisotropy at various levels of its structure.

Kirners deformity - a systematic review and surgery recommendations.

Background: Kirner deformity is a rare anomaly of the little finger in adolescents, characterized by a deformity of the distal phalanx and a radiologically L-shaped epiphysis, along with palmar and radial angulation of the distal phalanx. Due to the rarity of these pathological findings, there are no systematic literature reviews available. This work serves as an overview of the clinical presentation, frequency and age distributions, as well as possible conservative and surgical treatment options.

Visible-light-induced CO-releasing properties and cytotoxicity of a Ru(II) carbonyl complex containing 2-(pyridin-2-yl)-quinoxaline.

The photo-induced CO-releasing properties of the dark-stable complex [RuCl(CO)L] (L = 2-(pyridin-2-yl)quinoxaline) were investigated under 468 nm light exposure in the presence and absence of biomolecules such as histidine, calf thymus DNA and hen egg white lysozyme. The CO release kinetics were consistent regardless of the presence of these biomolecules, suggesting that they did not influence the CO release mechanism. The quinoxaline ligand demonstrated exceptional cytotoxicity against human acute monocytic leukemia cells (THP-1), with evidence of potential DNA damage ascertained by comet assay, while it remained non-toxic to normal kidney epithelial cells derived from African green monkey (Vero) cell lines.

An extra pair of eyes: adopting innovative approaches to detect integrity issues in Naunyn-Schmiedeberg's Archives of Pharmacology.

Scientific integrity has been increasingly challenged by scientific misconduct and paper mills, resulting in an increase in retractions. Naunyn-Schmiedeberg's Archives of Pharmacology has been significantly impacted by fraudulent submissions, resulting in numerous retractions. By analyzing retraction notes and utilizing a post-publication surveillance strategy, this editorial discusses how this journal continues to deal with problematic publications, uncovers image- and physiological-related integrity issues, and responds to fraudulent activity.

Basic Science and Pathogenesis.

Background: In 43-63% of symptomatic Alzheimer's disease (AD) patients, there is an observed accumulation of misfolded alpha-synuclein (αSyn). Two primary αSyn subtypes have been identified based on the underlying spreading pattern of this pathology: caudo-rostral and amygdala-predominant. Interactions between pathological TDP-43, Tau, and αSyn can aggravate their spread and aggregation.

Basic Science and Pathogenesis.

Background: MicroRNAs have been linked to dementia. However, understanding their relation to cognition in the general population is required to determine their potential use for the detection and prevention of age-associated cognitive decline and preclinical dementia. Therefore, we examined the association of circulating microRNAs with cognitive performance in a population-based cohort and the possible underlying mechanisms.

Basic Science and Pathogenesis.

Background: Despite significant advancements in the development of blood biomarkers for AD, challenges persist due to the complex interplay of genetic and environmental risk factors in AD pathogenesis. Epigenetic processes, including non-coding RNAs and especially microRNAs (miRs), have emerged as important players in the molecular mechanisms underlying neurodegenerative diseases. MiRs have the ability to fine-tune gene expression and proteostasis, and microRNAome profiling in liquid biopsies is gaining increasing interest since changes in miR levels can indicate the presence of multiple pathologies.

Potential for enhancing efficacy of screening colonoscopy by lowering starting ages and extending screening intervals: A modelling study for Germany.

Studies aimed to evaluate the expected impact of alternative screening strategies are essential for optimizing colorectal cancer (CRC) screening offers, but such studies are lacking in Germany, where two screening colonoscopies (CS) 10 years apart are offered for men from age 50 and women from age 55. Our aim was to explore whether and to what extent the efficacy of utilizing two CS could be enhanced by alternative starting ages and screening intervals. We modeled the expected numbers of CRC cases, CRC deaths, years of potential life lost (YPLL), and disability-adjusted life years (DALYs) due to CRC in hypothetical cohorts of 100,000 men and women aged 45-85 using COSIMO, a validated Markov-based multi-state simulation model.

Two Patients with Therapy-Resistant Pemphigus Vulgaris and Severe Underlying Disease Showing Good Response to a New IVIg Preparation.

Pemphigus vulgaris is a severe and often therapy-resistant bullous autoimmune disease. Standard therapy with steroids often administered together with another immunosuppressant does not respond in all patients or may not be a good therapeutic option in patients with severe underlying diseases. Intravenous immunoglobulins (IVIgs) represent a treatment alternative, often showing a rapid response which allows one to reduce concomitant immunosuppression.

Association of mental health in childhood, adolescence and young adulthood with cardiovascular risk factors and carotid remodeling below age 30 - results from the KiGGS cohort study.

An association of mental health and in particular depression with cardiovascular disease has been shown in adults and to a lesser extent in the young. Recently improved measurement methods of carotid-intima media thickness (CIMT) and carotid stiffness (CS) allow more differentiated analyses of this link. We examined 4,361 participants of the nationwide KiGGS cohort aged 3-17 years at baseline and 14-28 years at follow-up.

Large language models can segment narrative events similarly to humans.

Humans perceive discrete events such as "restaurant visits" and "train rides" in their continuous experience. One important prerequisite for studying human event perception is the ability of researchers to quantify when one event ends and another begins. Typically, this information is derived by aggregating behavioral annotations from several observers.

Impact of acetylsalicylic acid on perioperative bleeding complications in deceased donor kidney transplantation.

Purpose: The objective of this study was to evaluate the perioperative outcomes and complications associated with the use of acetylsalicylic acid (ASA) in deceased donor kidney transplantation (KTX), with a particular focus on bleeding events.

Methods: We retrospectively analyzed 157 kidney transplant recipients (KTRs) who underwent KTX at Charité Berlin, Department for Urology, between February 2014 and December 2017. Patients were divided into two groups: patients with ASA in their preoperative medication (Group A, n = 59) and patients without ASA use (Group B, n = 98).

Do perilunate dislocations and fracture-dislocations result in different radiological outcomes following wrist alignment reconstruction? A single-center retrospective study including 51 patients with perilunate injuries.

Introduction: Perilunate dislocations (PLD) and perilunate fracture-dislocations (PLFD) are high-energy wrist injuries often linked to significant post-traumatic osteoarthritis. This study aims to determine whether PLD and PLFD yield different radiological outcomes following surgical treatment while identifying prognostic factors for worse outcomes.

Materials And Methods: We retrospectively analyzed 51 patients treated for perilunate injuries between 2000 and 2022.

Basic Science and Pathogenesis.

Background: The TMEM106B protein is critical for proper functioning of the endolysomal system, which is utilised by all cells to traffic and degrade molecular cargo. Genome-wide association studies identified a haplotype in the TMEM106B gene that is associated with increased risk for Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal lobar degeneration with TAR DNA binding protein inclusions (FTLD-TDP). However, the causal variant that drives the association has thus far remained elusive.

Basic Science and Pathogenesis.

Background: Excessive daytime sleepiness is a common and early symptom of Alzheimer's disease (AD). The subcortical wake-promoting neurons in the lateral hypothalamic area, tuberomammillary nucleus (TMN), and locus coeruleus synchronize to maintain wakefulness/arousal. Although significant neuronal decline occurs in wake-promoting regions, the TMN histaminergic neurons remain relatively more intact than orexinergic and nor-adrenergic neurons.

Basic Science and Pathogenesis.

Background: Progranulin (PGRN) haploinsufficiency is a major risk factor for frontotemporal lobar degeneration with TDP-43 pathology (FTLD-GRN). Multiple therapeutic strategies are in clinical development to restore PGRN levels in the CNS, including gene therapy. However, a limitation of current gene therapy approaches aimed to alleviate FTLD-associated pathologies may be their inefficient brain exposure and biodistribution.

Basic Science and Pathogenesis.

Background: Memory consolidation is an essential process for our everyday lives that is severely disrupted in Alzheimer's Disease (AD). Memories are initially encoded in the hippocampus before being consolidated in the neocortex by synaptic plasticity processes that depend on protein synthesis. However, how molecular pathways affect synaptic signalling during memory consolidation in health and disease is unclear.

Basic Science and Pathogenesis.

Background: Peripheral metabolic health status can reflect and/or contribute to the risk of Alzheimer's disease (AD). Peripheral metabolic health status can be indicated by metabolic health markers, such as inflammatory biomarker glycoprotein acetyls (GlycA) and specific components of lipoproteins (e.g.

Basic Science and Pathogenesis.

Background: Lewy body pathology (LBP) is common in autosomal dominant (ADAD) or sporadic Alzheimer disease (sAD). LBP seems to be the most frequent co-pathology in sAD and even in the relatively young ADAD population, where other co-pathologies are rare. Knowledge of neuropathological distribution patterns of LBP and associated survival and genetic characteristics in both AD variants is incomplete.

Basic Science and Pathogenesis.

Background: Argonaute2 (Ago2) plays an essential role in RISC-mediated silencing of target mRNAs, which are critical for cellular functions. Argonaute2 Syndrome, also known as Ago2 Syndrome, is a rare neurological disorder recently discovered in humans. It has significant implications for brain development, yet it remains unstudied to date METHOD: To study this effect, we deleted the Ago2 gene in GABAergic (Slc32a1 cre) and Glutamatergic (Slc17a6 cre) mice.

Basic Science and Pathogenesis.

Background: A significant proportion of individuals preserve cognitive function despite meeting neuropathological criteria for Alzheimer's disease (AD) at autopsy, known as cognitive resilience. We aimed to define the molecular and cellular signatures of cognitive resilience against AD.

Method: We integrated multi-modal data from the Religious Order Study and Memory and Aging Project (ROSMAP), including bulk (n = 631) and multi-regional single nucleus (n = 48) RNA sequencing.

Basic Science and Pathogenesis.

Background: Despite recent breakthroughs, Alzheimer's disease (AD) remains untreatable. In addition, we are still lacking robust biomarkers for early diagnosis and promising novel targets for therapeutic intervention. To enable utilizing the entirety of molecular evidence in the discovery and prioritization of potential novel biomarkers and targets, we have developed the AD Atlas, a network-based multi-omics data integration platform.

Basic Science and Pathogenesis.

Background: Anti-amyloid antibodies have been associated with amyloid-related-imaging-abnormalities (ARIA) in AD patients, causing vasogenic edema and microhemorrhages, especially in ApoE4 carriers. Here, we compared recombinant 3D6-L, a murine version of bapineuzumab, and an isotype control IgG2a monoclonal antibody (mAb) to investigate potential mechanisms, including complement activation, involved in these side effects (ARIA-H or microhemorrhages) following passive immunization.

Method: Plaque-rich 16.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) related pathologies (i.e., neurofibrillary tangles [NFTs], amyloid-β plaques, and phosphorylated-TAR-DNA-binding-protein-43 [pTDP-43]) differ across sexes.