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Direct conversion of human fibroblasts to functional excitatory cortical neurons integrating into human neural networks
Background: Human fibroblasts can be directly converted to several subtypes of neurons, but cortical projection neurons have not been generated. Methods: Here we screened for transcription factor combinations that could potentially convert human fibroblasts to functional excitatory cortical neurons. The induced cortical (iCtx) cells were analyzed for cortical neuronal identity using immunocytochem
Secular trends in sickness absence among Swedish patients with ankylosing spondylitis and psoriatic arthritis
The aim was to investigate whether secular trends in sickness absence (SA) were present in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) receiving their diagnosis between 2002 and 2011. A repeated cross-sectional study design was used. Patients were identified in the Skåne Healthcare Register (SHR). A washout period of 18 months was applied. The general population seeking
Treatment with the WNT5A-mimicking peptide Foxy-5 effectively reduces the metastatic spread of WNT5A-low prostate cancer cells in an orthotopic mouse model
Prostate cancer patients with high WNT5A expression in their tumors have been shown to have more favorable prognosis than those with low WNT5A expression. This suggests that reconstitution of Wnt5a in low WNT5A-expressing tumors might be an attractive therapeutic approach. To explore this idea, we have in the present study used Foxy-5, a WNT5A mimicking peptide, to investigate its impact on primar
Association analysis identifies 65 new breast cancer risk loci
Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of
Incident diabetes mellitus may explain the association between sleep duration and incident coronary heart disease
Aims/hypothesis: Sleep duration is a risk factor for incident diabetes mellitus and CHD. The primary aim of the present study was to investigate, in sex-specific analyses, the role of incident diabetes as the possible biological mechanism for the reported association between short/long sleep duration and incident CHD. Considering that diabetes is a major risk factor for CHD, we hypothesised that a
Obesity, metabolic factors and risk of different histological types of lung cancer : A Mendelian randomization study
BACKGROUND: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.METHODS AND FINDINGS: We identified genetic instruments for potential metabolic risk factors and eval
The stem cell regulator PEDF is dispensable for maintenance and function of hematopoietic stem cells
Pigment epithelium derived factor (PEDF), a ubiquitously expressed 50 kDa secreted glycoprotein, was recently discovered to regulate self-renewal of neural stem cells and have a supportive effect on human embryonic stem cell growth. Here, we analyzed expression of PEDF in the murine hematopoietic stem cell (HSC) compartments and found that PEDF is highly expressed in primary long-term HSCs. Theref
Midlife risk factor exposure and incidence of cardiac arrest depending on cardiac or non-cardiac origin
Objective: Little is known about midlife risk factors of future cardiac arrest. Our objective was to evaluate cardiovascular risk factors in midlife in relation to the risk of cardiac arrest (CA) of cardiac and non-cardiac origin later in life. Methods: We cross-matched individuals of the population based Malmö Diet and Cancer study (n = 30,447) with the local CA registry of the city of Malmö. Bas
Female white-collar workers remain at higher risk of breast cancer after adjustments for individual risk factors related to reproduction and lifestyle
Objectives The aim was to investigate the variation in risk of breast cancer between occupational groups with a focus on white-collar and blue-collar workers and to investigate to what extent the differences were explained by risk factors related to reproduction and lifestyle. Methods Between 1991 and 1996, 14 119 women born between 1923 and 1950 and residents of Malmö, Sweden, were included in th
Practical and methodological issues in register-based research
Habits and self-assessed quality of life, negative intrusive thoughts and depressed mood in patients with prostate cancer : a longitudinal study
Objective: The aim of this study was to evaluate the association of self-assessed preoperative physical activity, alcohol consumption and smoking with self-assessed quality of life, negative intrusive thoughts and depressed mood after radical prostatectomy. Materials and methods: The Laparoscopic Prostatectomy Robot Open (LAPPRO) trial was a prospective, controlled, non-randomized longitudinal tri
Incisional negative pressure wound therapy in the prevention of surgical site infection after vascular surgery with inguinal incisions: rational and design of a randomized controlled trial (INVIPS-Trial).
Background/Aims: Inguinal incisions are a common route of access in vascular surgery. Due to anatomical challenges and a diverse bacterial flora in this area, surgical site infections (SSI) represent a common, debilitating and sometimes life-threatening complication. The INVIPS-Trial evaluates the role of Negative Pressure Wound Therapy (NPWT) on closed inguinal incisions in elective vascular surg
The gut microbiota-related metabolite phenylacetylglutamine associates with increased risk of incident coronary artery disease
OBJECTIVE: The gut microbiota is increasingly being implicated in cardiovascular health. Metabolites produced by bacteria have been suggested to be mediators in the bacterial action on cardiovascular health. We aimed to identify gut microbiota-related plasma metabolites and test whether these metabolites associate with future risk of coronary artery disease (CAD). METHODS: Nontargeted metabolomics
Alpha-amylase 1A copy number variants and the association with memory performance and Alzheimer’s dementia
Background: Previous studies have shown that copy number variation (CNV) in the alpha (α)-amylase gene (AMY1A) is associated with body mass index, insulin resistance, and blood glucose levels, factors also shown to increase the risk of Alzheimer’s dementia (AD). We have previously demonstrated the presence of α-amylase in healthy neuronal dendritic spines and a reduction of the same in AD patients
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Stem Cell Therapy as an Emerging Paradigm for Stroke (STEPS) II
Cell-based therapies represent a new therapeutic approach for stroke. In 2007, investigators from academia, industry leaders, and members of the National Institutes of Health crafted recommendations to facilitate the translational development of cellular therapies as a novel, emerging modality for stroke from animal studies to clinical trials. This meeting was called Stem Cell Therapies as an Emer
The STAT3 inhibitor galiellalactone inhibits the generation of MDSC-like monocytes by prostate cancer cells and decreases immunosuppressive and tumorigenic factors
Background: The transcription factor signal transducer and activator of transcription 3 (STAT3) is implicated in cancer drug resistance, metastasis, and immunosuppression and has been identified as a promising therapeutic target for new anticancer drugs. Myeloid-derived suppressor cells (MDSCs) play a major role in the suppression of antitumor immunity and STAT3 is involved in the accumulation, ge
The risk of symptomatic knee osteoarthritis after arthroscopic meniscus repair vs partial meniscectomy vs the general population
Objective: To compare consultation rate for knee osteoarthritis (OA) after meniscus repair, arthroscopic partial meniscectomy (APM), and in general population, respectively. Method: We identified patients aged 16-45 years having had meniscus surgery due to traumatic meniscus tear in 1998-2010 in southern Sweden by a healthcare register. Patients were followed from surgery until a diagnosis of knee
Normal Reference Ranges for Transthoracic Echocardiography Following Heart Transplantation
Background: Heart function following heart transplantation (HTx) is influenced by numerous factors. It is typically evaluated using transthoracic echocardiography, but reference values are currently unavailable for this context. The primary aim of the present study was to derive echocardiographic reference values for chamber size and function, including cardiac mechanics, in clinically stable HTx
