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The implications of different approaches to define AT(N) in Alzheimer disease

OBJECTIVE: To compare different β-amyloid (Aβ), tau, and neurodegeneration (AT[N]) variants within the Swedish BioFINDER studies. METHODS: A total of 490 participants were classified into AT(N) groups. These include 53 cognitively unimpaired (CU) and 48 cognitively impaired (CI) participants (14 mild cognitive impairment [MCI] and 34 Alzheimer disease [AD] dementia) from BioFINDER-1 and 389 partic

CXCR4 Signaling Has a CXCL12-Independent Essential Role in Murine MLL-AF9-Driven Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is defined by an accumulation of immature myeloid blasts in the bone marrow. To identify key dependencies of AML stem cells in vivo, here we use a CRISPR-Cas9 screen targeting cell surface genes in a syngeneic MLL-AF9 AML mouse model and show that CXCR4 is a top cell surface regulator of AML cell growth and survival. Deletion of Cxcr4 in AML cells eradicates leukemia c

Spread of pathological tau proteins through communicating neurons in human Alzheimer's disease

Tau is a hallmark pathology of Alzheimer's disease, and animal models have suggested that tau spreads from cell to cell through neuronal connections, facilitated by β-amyloid (Aβ). We test this hypothesis in humans using an epidemic spreading model (ESM) to simulate tau spread, and compare these simulations to observed patterns measured using tau-PET in 312 individuals along Alzheimer's disease co

Radial versus femoral access in patients with acute coronary syndrome undergoing invasive management : A prespecified subgroup analysis from VALIDATE-SWEDEHEART

AIMS: In the Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART), bivalirudin was not superior to unfractionated heparin in patients with

Imaging of the vulnerable carotid plaque : Role of imaging techniques and a research agenda

OBJECTIVES: Atherothrombosis in the carotid arteries is a main cause of ischemic stroke and may depend on plaque propensity to complicate with rupture or erosion, in turn related to vulnerability features amenable to in vivo imaging. This would provide an opportunity for risk stratification and-potentially-local treatment of more vulnerable plaques. We here review current information on this topic

Tau pathology and relative cerebral blood flow are independently associated with cognition in Alzheimer’s disease

Purpose: We aimed to investigate associations between tau pathology and relative cerebral blood flow (rCBF), and their relationship with cognition in Alzheimer’s disease (AD), by using a single dynamic [18F]flortaucipir positron emission tomography (PET) scan. Methods: Seventy-one subjects with AD (66 ± 8 years, mini-mental state examination (MMSE) 23 ± 4) underwent a dynamic 130-min [18F]flortauc

Morphological and structural heterogeneity of solid gliadin food foams modified with transglutaminase and food grade dispersants.

We show in this study the impact of transglutaminase (SB6), glycerol (Gly) and linoleic acid (LA) on the development of gliadin (Glia) solid edible foams. Two concentrations of SB6 were tested, 0.58 U/g and 1.17 U/g, and sufficiently high concentration of SB6 was found essential to crosslink the gliadins. Greater cross-linking in foam prepared with gliadin and 1.17 U/g of SB6 (2-TG-Glia) was follo

Preventing kidney injury among sugarcane workers : Promising evidence from enhanced workplace interventions

Objectives: To assess if improvement of working conditions related to heat stress was associated with improved kidney health outcomes among sugarcane harvest workers in Chichigalpa, Nicaragua, a region heavily affected by the epidemic of chronic kidney disease of non-traditional origin. Methods: Based on our findings during the 2017-2018 harvest (harvest 1), recommendations that enhanced the rest

Ultrastructural evidence for self-replication of alzheimer-associated Aβ42 amyloid along the sides of fibrils

The nucleation of Alzheimer-associated Aβ peptide monomers can be catalyzed by preexisting Aβ fibrils. This leads to autocatalytic amplification of aggregate mass and underlies self-replication and generation of toxic oligomers associated with several neurodegenerative diseases. However, the nature of the interactions between the monomeric species and the fibrils during this key process, and indee

Longitudinal association between housing accessibility and activities of daily living : The role of self-efficacy and control in people ageing with Parkinson's disease

Background: External housing-related control beliefs (HCB) and general self-efficacy (GSE) influence different health outcomes in the general ageing population, but there is no information of their role in people ageing with Parkinson's disease (PD). This study aimed to longitudinally assess the role of external HCB and GSE on the association between housing accessibility and activities of daily l

Developing ActivABLES for community-dwelling stroke survivors using the Medical Research Council framework for complex interventions

Background: Novel technical solutions are called for to promote home-based exercise among community-dwelling stroke survivors supported by their caregivers. Lack of resources and knowledge about how to accomplish it, has been demonstrated. The objective of this study is to describe in detail the development of ActivABLES, a technical intervention to promote home-based exercise and physical activit

Removal of phosphorus and nitrogen in sediments of the eutrophic Stockholm archipelago, Baltic Sea

Coastal systems can act as filters for anthropogenic nutrient input into marine environments. Here, we assess the processes controlling the removal of phosphorus (P) and nitrogen (N) for four sites in the eutrophic Stockholm archipelago. Bottom water concentrations of oxygen (O2) and P are inversely correlated. This is attributed to the seasonal release of P from iron-oxide-bound (Fe-oxidebound) P

Synthesis of tricyclic carbohydrate-benzene hybrids as selective inhibitors of galectin-1 and galectin-8 N-terminal domains

As the galactoside binding family of galectin proteins is involved in many physiological and pathological processes, the inhibitors of these proteins are considered to be of significant interest in the treatment of diseases such as cancer and fibrosis. Herein, fused tricyclic carbohydrate-benzene hybrid core structures are reported to be the selective inhibitors of galectin-1 and the N-terminal do

Added value of contrast-enhanced mammography (CEM) in staging of malignant breast lesions - A feasibility study

Objectives: The aim of this feasibility study was to evaluate the added value of contrast-enhanced mammography (CEM) in preoperative staging of malignant breast lesions, beyond standard assessment with digital mammography and ultrasound, as a base for a future prospective randomized trial. Materials and methods: Forty-seven patients, with confirmed or strongly suspected malignant breast lesions af

Development and validation of a prediction model for incident hand osteoarthritis in the HUNT study

Objective: To develop and externally validate prediction models for incident hand osteoarthritis (OA) in a large population-based cohort of middle aged and older men and women. Design: We included 17,153 men and 18,682 women from a population-based cohort, aged 35–70 years at baseline (1995–1997). Incident hand OA were obtained from diagnostic codes in the Norwegian National Patient Register (1995

Neutrophil and lymphocyte counts are associated with different immunopathological mechanisms in systemic lupus erythematosus

Objective: Neutrophils contribute to the SLE pathogenesis. Neutrophil to lymphocyte ratio (NLR) is reported to correlate with disease activity in SLE. The aim of the study was to evaluate whether NLR reflects underlying immunopathogenic activity in SLE, as well as to determine the contribution of each component of NLR, neutrophil and lymphocyte count. Methods: Data were obtained from a cohort of p

A pre-specified model based on four kallikrein markers in blood improves predictions of adverse pathology and biochemical recurrence after radical prostatectomy

Background: A pre-specified model based on four kallikrein markers in blood, commercially available as 4Kscore, predicts Gleason Grade (GG) 3 + 4 or higher prostate cancer on biopsy. However, sampling error and variation in pathology reporting may miss aggressive disease. Methods: The 4Kscore was measured in cryopreserved blood from 2330 men obtained before prostatectomy at a single institution be

Controlling photoionization using attosecond time-slit interferences

When small quantum systems, atoms or molecules, absorb a high-energy photon, electrons are emitted with a well-defined energy and a highly symmetric angular distribution, ruled by energy quantization and parity conservation. These rules are based on approximations and symmetries which may break down when atoms are exposed to ultrashort and intense optical pulses. This raises the question of their