The role of Mediterranean diet in cancer incidence and mortality in the older adults.

The magnitude of benefit of Mediterranean diet in cancer prevention and mortality in older adults is still unclear, therefore we conducted a systematic review and meta-analysis. Outcomes considered were cancer incidence and cancer mortality. In studies evaluating cancer incidence as a time-to-event endpoint and adherence as quantiles, HR was 0.

Quantitative EEG in Parkinson's disease: when REM sleep behavior disorder onset really matters.

Parkinson's Disease (PD) body-first subtype is characterized by prodromal autonomic symptoms and REM sleep behavior disorder (RBD), symmetric dopaminergic degeneration, and increased risk of dementia. On the other hand, the PD brain-first subtype has fewer non-motor symptoms and a milder motor phenotype. The temporal relationship between RBD onset and motor symptoms onset may differentiate these two subtypes.

Vaccinome landscape in nearly 620,000 patients with diabetes.

Introduction: Type 1 (T1D) and type 2 diabetes (T2D) are associated with an elevated incidence of infectious diseases and a higher risk of infections-related hospitalization and death. In this study, we delineated the "vaccinome" landscape obtained with a large immunization schedule offered by the Regional Government of Lombardy in a cohort of 618,396 patients with diabetes (T1D and T2D).

Methods: Between September 2021 and September 2022, immunization coverage for influenza, meningococcus, pneumococcus, and herpes zoster was obtained from the public computerized registry of the healthcare system of Lombardy Region (Italy) in 618,396 patients with diabetes and in 9,534,087 subjects without diabetes.

Type 2 diabetes mellitus pharmacological remission with dapagliflozin plus oral semaglutide.

Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor and semaglutide, a glucagon-like peptide 1 receptor agonist, have both demonstrated efficacy in glycemic control, reducing blood pressure, body weight, risk of renal and heart failure in type 2 diabetes mellitus. In this observational, real-world, study we aimed to investigate the efficacy of the combination therapy with those two agents over glycemic control. We thus obtained the data of 1335 patients with type 2 diabetes followed by 11 Diabetes centers in Lombardia, Italy.

Unaltered hepatic wound healing response in male rats with ancestral liver injury.

The possibility that ancestral environmental exposure could result in adaptive inherited effects in mammals has been long debated. Numerous rodent models of transgenerational responses to various environmental factors have been published but due to technical, operational and resource burden, most still await independent confirmation. A previous study reported multigenerational epigenetic adaptation of the hepatic wound healing response upon exposure to the hepatotoxicant carbon tetrachloride (CCl) in male rats.

The role of laboratory investigations in the classification of tremors.

Introduction: Tremor is the most common movement disorder. Although clinical examination plays a significant role in evaluating patients with tremor, laboratory tests are useful to classify tremors according to the recent two-axis approach proposed by the International Parkinson and Movement Disorders Society.

Methods: In the present review, we will discuss the usefulness and applicability of the various diagnostic methods in classifying and diagnosing tremors.

Retinal Thickness in Essential Tremor and Early Parkinson Disease: Exploring Diagnostic Insights.

Background: Essential tremor (ET) represents a heterogeneous condition which may overlap with Parkinson disease (PD) even at early stages, by sharing some subtle clinical aspects. Longstanding ET demonstrated also higher risk of developing PD, especially with a Tremor-dominant (TD-PD) phenotype. Therefore, differential diagnosis between ET and early PD could be quite challenging.

Brain linear measurements for differentiating normal pressure hydrocephalus from Alzheimer's disease: an exploratory study.

Background And Purpose: Easy and reliable tools for the differential diagnosis between idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD) are needed.

Materials And Methods: In this cross-sectional study iNPH and AD patients referred to the Neurology Unit of the University of Catania from 1 January 2020 to 1 December 2022 were enrolled. The following brain linear measurements (BLMs) were calculated: Evan's index (EI), the parieto-occipital ratio (POR) and the temporal ratio (TR).

Wdr5 is essential for fetal erythropoiesis and hematopoiesis.

WDR5 is a highly conserved protein that performs multiple scaffolding functions in the context of chromatin. However, efforts to understand the function of WDR5 in normal tissues physiologically are quite limited so far. In our study, we explored the function of Wdr5 in erythropoiesis and hematopoiesis by using a hematopoietic-specific Wdr5 knockout mouse model.

Turning and Sitting in Early Parkinsonism: Differences Between Idiopathic Normal Pressure Hydrocephalus Associated with Parkinsonism and Parkinson's Disease.

Background: Differential diagnosis between idiopathic normal pressure hydrocephalus (iNPH) associated with parkinsonism (iNPH-P) and Parkinson's disease (PD) may prove difficult when evaluating patients with early parkinsonism. The objective of this study was to evaluate differences in mobility during standardized tasks between iNPH-P and PD.

Methods: We selected 21 iNPH-P and 21 pharmacologically untreated PD patients.

Discovery of the Clinical Candidate MAK683: An EED-Directed, Allosteric, and Selective PRC2 Inhibitor for the Treatment of Advanced Malignancies.

Polycomb Repressive Complex 2 (PRC2) plays an important role in transcriptional regulation during animal development and in cell differentiation, and alteration of PRC2 activity has been associated with cancer. On a molecular level, PRC2 catalyzes methylation of histone H3 lysine 27 (H3K27), resulting in mono-, di-, or trimethylated forms of H3K27, of which the trimethylated form H3K27me3 leads to transcriptional repression of polycomb target genes. Previously, we have shown that binding of the low-molecular-weight compound EED226 to the H3K27me3 binding pocket of the regulatory subunit EED can effectively inhibit PRC2 activity in cells and reduce tumor growth in mouse xenograft models.

Clinical-Instrumental patterns of neurodegeneration in Essential Tremor: A data-driven approach.

Introduction: Essential Tremor (ET) is increasingly recognized as a complex disorder with additional clinical signs other than tremor. It is still unknown whether a unique pathophysiologic or neurodegenerative process underlies progression and prognosis of the disease. The aim of the study was to identify ET phenotypes through a clinical-instrumental data-driven approach and to characterize possible patterns of neurodegeneration.

BET bromodomain inhibitors regulate keratinocyte plasticity.

Although most acute skin wounds heal rapidly, non-healing skin ulcers represent an increasing and substantial unmet medical need that urgently requires effective therapeutics. Keratinocytes resurface wounds to re-establish the epidermal barrier by transitioning to an activated, migratory state, but this ability is lost in dysfunctional chronic wounds. Small-molecule regulators of keratinocyte plasticity with the potential to reverse keratinocyte malfunction in situ could offer a novel therapeutic approach in skin wound healing.

iNPH with parkinsonism: response to lumbar CSF drainage and ventriculoperitoneal shunting.

Objectives: To evaluate clinical response after external lumbar drainage (ELD) and ventriculoperitoneal shunting (VPS) in a cohort of patients with idiopathic normal pressure hydrocephalus associated with parkinsonism (iNPH-P), considering parkinsonism as clinical primary outcome.

Methods: Patients underwent long-term 72-h intracranial pressure-controlled CSF ELD. Clinical motor response before and after ELD was evaluated using changes in UPDRS-ME as outcome measure.

Drug-induced chromatin accessibility changes associate with sensitivity to liver tumor promotion.

Liver cancer susceptibility varies amongst humans and between experimental animal models because of multiple genetic and epigenetic factors. The molecular characterization of such susceptibilities has the potential to enhance cancer risk assessment of xenobiotic exposures and disease prevention strategies. Here, using DNase I hypersensitivity mapping coupled with transcriptomic profiling, we investigate perturbations in -acting gene regulatory elements associated with the early stages of phenobarbital (PB)-mediated liver tumor promotion in susceptible versus resistant mouse strains (B6C3F1 versus C57BL/6J).

IRF2 is a master regulator of human keratinocyte stem cell fate.

Resident adult epithelial stem cells maintain tissue homeostasis by balancing self-renewal and differentiation. The stem cell potential of human epidermal keratinocytes is retained in vitro but lost over time suggesting extrinsic and intrinsic regulation. Transcription factor-controlled regulatory circuitries govern cell identity, are sufficient to induce pluripotency and transdifferentiate cells.

Electrocortical networks in Parkinson's disease patients with Mild Cognitive Impairment. The PaCoS study.

Introduction: Parkinson's Disease (PD) is frequently associated with cognitive dysfunction ranging from Mild Cognitive Impairment (PD-MCI) to dementia. Few electrophysiological studies are available evaluating potential pathogenetic mechanisms linked to cognitive impairment in PD since its initial phases. The objective of the study is to analyze electrocortical networks related with cognitive decline in PD-MCI for identifying possible early electrophysiological markers of cognitive impairment in PD.

Constitutive androstane receptor 1 is constitutively bound to chromatin and 'primed' for transactivation in hepatocytes.

The constitutive androstane receptor (CAR) is a xenobiotic sensor expressed in hepatocytes that activates genes involved in drug metabolism, lipid homeostasis, and cell proliferation. Much progress has been made in understanding the mechanism of activation of human CAR by drugs and xenobiotics. However, many aspects of the activation pathway remain to be elucidated.

Chromatin dynamics underlying latent responses to xenobiotics.

Pleiotropic xenobiotics can trigger dynamic alterations in mammalian chromatin structure and function but many of these are likely non-adverse and simply reflect short-term changes in DNA transactions underlying normal homeostatic, adaptive and protective cellular responses. However, it is plausible that a subset of xenobiotic-induced perturbations of somatic tissue or germline epigenomes result in delayed-onset and long-lasting adverse effects, in particular if they occur during critical stages of growth and development. These could include reprogramming, dedifferentiation, uncontrolled growth, and cumulative toxicity effects through molecular memory of prior xenobiotic exposures or altered susceptibility to subsequent xenobiotic exposures.