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BDNF Overexpression Increases Striatal D3 Receptor Level at Striatal Neurons and Exacerbates D1-Receptor Agonist-Induced Dyskinesia

BACKGROUND: We recently showed that striatal overexpression of brain derived neurotrophic factor (BDNF) by adeno-associated viral (AAV) vector exacerbated L-DOPA-induced dyskinesia (LID) in 6-OHDA-lesioned rats. An extensive sprouting of striatal serotonergic terminals accompanied this effect, accounting for the increased susceptibility to LID.OBJECTIVE: We set to investigate whether the BDNF effe

Mammographic density as an image-based biomarker of therapy response in neoadjuvant-treated breast cancer patients

Purpose: Personalized cancer treatment requires predictive biomarkers, including image-based biomarkers. Breast cancer (BC) patients receiving neoadjuvant chemotherapy (NACT) are in a clinically vulnerable situation with the tumor present. This study investigated whether mammographic density (MD), assessed pre-NACT, is predictive of pathological complete response (pCR). Methods: A total of 495 BC

Dietary fatty acids, macronutrient substitutions, food sources and incidence of coronary heart disease: Findings from the EPIC-CVD case-cohort study across nine european countries

BACKGROUND: There is controversy about associations between total dietary fatty acids, their classes (saturated fatty acids [SFAs], monounsaturated fatty acids, and polyunsaturated fatty acids), and risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD associations is uncertain. METHODS AND RESULTS: We conducted a case-cohort study involving 10 529 incide

Telomeres in ecology and evolution : A review and classification of hypotheses

Research on telomeres in the fields of ecology and evolution has been rapidly expanding over the last two decades. This has resulted in the formulation of a multitude of, often name-given, hypotheses related to the associations between telomeres and life-history traits or fitness-facilitating processes (and the mechanisms underlying them). However, the differences (or similarities) between the var

Clustering of blood cell count abnormalities and future risk of death

BACKGROUND: The identification of novel predictors of poor outcome may help stratify cardiovascular risk. Aim was to evaluate the individual contribution of blood cell count parameters, as well as their clustering, on the risk of death and cardiovascular events over the long term in the population-based Malmö Diet and Cancer Study cohort.METHODS: In 30,447 individuals (age 57 ± 8 years), we assess

Family history of breast cancer as a second primary malignancy in relatives : a nationwide cohort study

BACKGROUND: With the increasing number of breast cancer (BC) diagnosed as a second primary malignancy after a first primary non-breast cancer (BCa-2), it is unclear about the familial risk of BC among women with a first-degree relative (FDR, parents or siblings) affected by a BCa-2.METHODS: In this Swedish nationwide cohort study, 5315 women with a FDR affected by BCa-2 and 115,048 women with a FD

A Multi-Biomarker Disease Activity Score and the Choice of Second-Line Therapy in Early Rheumatoid Arthritis After Methotrexate Failure

Objective: To investigate whether the Multi-Biomarker Disease Activity (MBDA) score predicts optimal add-on treatment in patients with early rheumatoid arthritis (RA) who were inadequate responders to MTX (MTX-IRs). Methods: We analyzed data from 157 MTX-IRs (with a Disease Activity Score using the erythrocyte sedimentation rate [DAS28-ESR] >3.2) from the Swedish Pharmacotherapy (SWEFOT) trial who

Human Trials of Stem Cell-Derived Dopamine Neurons for Parkinson's Disease : Dawn of a New Era

Stem cell-based therapies for Parkinson's disease are moving into a new and exciting era, with several groups pursuing clinical trials with pluripotent stem cell (PSC)-derived dopamine neurons. As many groups have ongoing or completed GMP-level cell manufacturing, we highlight key clinical translation considerations from our recent fourth GForce-PD meeting. Stem cell-based therapies for Parkinson'

Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease

To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLADRB5 (odds ratio (

Inflammation and chronic colonization of Haemophilus influenzae in sputum in COPD patients related to the degree of emphysema and bronchiectasis in high-resolution computed tomography

The presence of bacteria in the lower airways in COPD results in inflammation, further airway structural damage, and might lead to repeated exacerbations. We have previously shown that chronic colonization of Haemophilus influenzae during stable disease is related to increased inflammation, and we now aimed to relate previous findings of bacterial colonization and inflammation to the degree of rad

Cancer risks and survival in patients with multiple primary melanomas : Association with family history of melanoma and germline CDKN2A mutation status

Background Worse outcomes have been noted in patients with multiple primary melanomas (MPMs) than in patients with single primary melanomas. Objective We investigated how family history of melanoma and germline CDKN2A mutation status of MPM patients affects risks of developing subsequent melanomas and other cancers and survival outcomes. Methods Comprehensive data on cancer diagnoses and deaths of

Simultaneous Control of Soot Emissions and Pressure Rise Rate in Gasoline PPC Engine

Partially Premixed Combustion (PPC) is an advanced combustion concept resulting in high efficiencies and low emission levels by the use of high levels of EGR and pilot injections. The main limitation of PPC to use in practice lies in the high pressure rise rate, which causes issues on engine noise and durability. In addition, soot emissions face with the overshoot problem during the transient oper

Constitutively Active SMAD2/3 Are Broad-Scope Potentiators of Transcription-Factor-Mediated Cellular Reprogramming

Reprogramming of cellular identity using exogenous expression of transcription factors (TFs) is a powerful and exciting tool for tissue engineering, disease modeling, and regenerative medicine. However, generation of desired cell types using this approach is often plagued by inefficiency, slow conversion, and an inability to produce mature functional cells. Here, we show that expression of constit

Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate Cancer

There is a demand for novel targets and approaches to diagnose and treat prostate cancer (PCA). In this context, serum and plasma samples from a total of 609 individuals from two independent patient cohorts were screened for IgG reactivity against a sum of 3833 human protein fragments. Starting from planar protein arrays with 3786 protein fragments to screen 80 patients with and without PCA diagno

Direct Reprogramming of Resident NG2 Glia into Neurons with Properties of Fast-Spiking Parvalbumin-Containing Interneurons

Converting resident glia into functional and subtype-specific neurons in vivo by delivering reprogramming genes directly to the brain provides a step forward toward the possibility of treating brain injuries or diseases. To date, it has been possible to obtain GABAergic and glutamatergic neurons via in vivo conversion, but the precise phenotype of these cells has not yet been analyzed in detail. H

Inflammation and Stem Cell Therapy for Stroke

Ischemic stroke is a leading cause of death and disability worldwide. Currently, there is no treatment that can promote recovery in the chronic phase. It has been shown that neurogenesis occurs in ischemic striatum in rodents and probably also in humans. Moreover, blood-borne macrophages have been found to enhance spontaneous post- stroke recovery in mice. These findings have suggested potential n

Evaluation of an iterative model-based reconstruction of pediatric abdominal CT with regard to image quality and radiation dose

Background In pediatric patients, computed tomography (CT) is important in the medical chain of diagnosing and monitoring various diseases. Because children are more radiosensitive than adults, they require minimal radiation exposure. One way to achieve this goal is to implement new technical solutions, like iterative reconstruction. Purpose To evaluate the potential of a new, iterative, model-basBackgroundIn pediatric patients, computed tomography (CT) is important in the medical chain of diagnosing and monitoring various diseases. Because children are more radiosensitive than adults, they require minimal radiation exposure. One way to achieve this goal is to implement new technical solutions, like iterative reconstruction.PurposeTo evaluate the potential of a new, iterative, model-based

Hypoxia-inducible factor 1a predicts recurrence in high-grade soft tissue sarcoma of extremities and trunk wall

Background and aim Sarcomas are of mesenchymal origin and typically show abundant tumour stroma and presence of necrosis. In search for novel biomarkers for personalised therapy, we determined the prognostic impact of stromal markers, hypoxia and neovascularity in high-grade soft tissue leiomyosarcoma and pleomorphic undifferentiated sarcoma. Method We evaluated CD163, colony-stimulating factor (C

Blood Metabolic Signatures of Body Mass Index : A Targeted Metabolomics Study in the EPIC Cohort

Metabolomics is now widely used to characterize metabolic phenotypes associated with lifestyle risk factors such as obesity. The objective of the present study was to explore the associations of body mass index (BMI) with 145 metabolites measured in blood samples in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolites were measured in blood from 392 men from t