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Raul Vizcardo, Nicholas D Klemen, S M Rafiqul Islam, Devikala Gurusamy, Naritaka Tamaoki, Daisuke Yamada, Haruhiko Koseki, Benjamin L Kidder, Zhiya Yu, Li Jia, Amanda N Henning, Meghan L Good, Marta Bosch-Marce, Takuya Maeda, Chengyu Liu, Zied Abdullaev, Svetlana Pack, Douglas C Palmer, David F Stroncek, Fumito Ito, Francis A Flomerfelt, Michael J Kruhlak, Nicholas P Restifo
Induced pluripotent stem cell (iPSC)-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers for clinical translation. Our data indicate that these iPSC-derived CD8 single-positive T cells are more like CD4+ CD8+ double-positive T cells than mature naive T cells because they display phenotypic markers of developmental arrest and an innate-like phenotype after stimulation. We developed a 3D thymic culture system to avoid these aberrant developmental fates, generating a homogeneous subset of CD8αβ+ antigen-specific T cells, designated iPSC-derived thymic emigrants (iTEs)...
March 20, 2018: Cell Reports
Trine Jul Larsen, Marit Eika Jørgensen, Christina Viskum Lytken Larsen, Inger Katrine Dahl-Petersen, Pernille Falberg Rønn, Peter Bjerregaard, Stine Byberg
BACKGROUND: Studies have found mercury to be associated with cardiovascular disease (CVD), however, primarily in populations with low exposure. The highest levels, and variations in the levels, of whole blood mercury (WBM) worldwide have been found in Greenland. We prospectively assessed the association between WBM and the risk of developing CVD in the Greenlandic population. METHODS: We assessed the effects of WBM levels on incident CVD among 3083 Greenlandic Inuit, participating in a population-based cohort study conducted from 2005 to 2010...
March 16, 2018: Environmental Research
Mihajlo Michael Jakovljevic, Yael Netz, Sandra C Buttigieg, Roza Adany, Ulrich Laaser, Mirjana Varjacic
BACKGROUND: There is a gap in knowledge on long term pace of population aging acceleration and related net-migration rate changes in WHO European Region and its adjacent MENA countries. We decided to compare European Union (EU-28) region with the EU Near Neighborhood Policy Region East and EU Near Neighborhood Policy Region South in terms of these two essential features of third demographic transition. One century long perspective dating back to both historical data and towards reliable future forecasts was observed...
March 16, 2018: Globalization and Health
Ibrahim Batal, Sumit Mohan, Sacha A De Serres, Elena-Rodica Vasilescu, Demetra Tsapepas, Russel J Crew, Shefali S Patel, Geo Serban, Kasi McCune, Syed A Husain, Jae-Hyung Chang, Jan M Herter, Govind Bhagat, Glen S Markowitz, Vivette D D'Agati, Mark A Hardy, Lloyd Ratner, Anil Chandraker
Ischemia-reperfusion injury increases allograft immunogenicity and enhances myeloid dendritic cell maturation and trafficking to recipient's secondary lymphoid tissue. Here, we used postreperfusion biopsies from patients who received kidney allografts from deceased donors between 2006 and 2009 to assess the impact of ischemia-reperfusion damage and myeloid dendritic cell density on subsequent allograft rejection episodes. Histologic changes of severe ischemia-reperfusion damage in postreperfusion biopsies were found to be associated with subsequent rejection episodes and suboptimal allograft survival...
March 13, 2018: Kidney International
S Lauze, B Maurina, V Sidlovska
For several hundred years, the Baltic German families of pharmacists have been the decisive creator of traditions in Latvian pharmacy. A large amount of the oldest pharmacies in Latvia, especially in Riga, were owned by pharmacists of Baltic German origin. Many of these ancient pharmacies ceased to exist in 1939, as a result of the emigration of the Baltic Germans. The agreement on the outward migration of German nationality citizens between Latvia and Germany was signed October 30, 1939. According to the information of the Pharmacy Board of Latvia, the number of employees in the pharmaceutical sector, registered in 1939, was 2068 persons...
March 5, 2018: Die Pharmazie
S O Edeki, O O Akanbi
The datasets contained in this article are simulated data with respect to Sickle Cell Anaemia (SCA) in order to examine the mathematical inheritance formation of the SCA disease. The simulation is done using Monte Carlos Simulation (MCS) Technique to complement the Physical Simulation Smith's Statistical (PSSS) package used as random number generator for birth simulation. One hundred and fifty-six (156) births for seven (7) generations were considered in the simulation alongside non-gestating reproductive females with fertile male adults while immigration and emigration are not permitted...
February 2018: Data in Brief
Jens Sundbøll, Katalin Veres, Erzsébet Horváth-Puhó, Kasper Adelborg, Henrik Toft Sørensen
Background -Venous thromboembolism can be a presenting symptom of cancer, but the association between lower limb arterial thrombosis and cancer is unknown. We therefore examined cancer risk and prognosis of cancer in patients with lower limb arterial thrombosis. Methods -Using nationwide population-based Danish medical registries, we identified all patients diagnosed with first-time lower limb arterial thrombosis (1994-2013) and followed them until the occurrence of any subsequent cancer diagnosis, emigration, death, or 30 November 2013, whichever came first...
March 14, 2018: Circulation
Liv Tybjærg Nordestgaard, Anne Tybjærg-Hansen, Katrine Laura Rasmussen, Børge G Nordestgaard, Ruth Frikke-Schmidt
BACKGROUND: Clusterin, also known as apolipoprotein J (apoJ), is one of the most abundantly expressed apolipoproteins in the brain after apolipoprotein E (apoE). Like the ε4 allele of the apolipoprotein E gene (APOE), the clusterin gene (CLU) is a risk locus for Alzheimer's disease, and may play additional roles in atherosclerosis pathogenesis. We tested whether genetic variation in CLU was associated with either Alzheimer's disease or atherosclerosis-related diseases. METHODS: We studied individual data on 103,987 participants from the Copenhagen General Population Study (CGPS) and the Copenhagen City Heart Study (CCHS)...
March 14, 2018: BMC Medicine
Norma Rallón, Marcial García, Javier García-Samaniego, Alfonso Cabello, Beatriz Álvarez, Clara Restrepo, Sara Nistal, Miguel Górgolas, José M Benito
INTRODUCTION: T-cell exhaustion has been involved in the pathogenesis of HIV infection. We have longitudinally analyzed PD1 and Tim3 surrogate markers of T-cells exhaustion, in parallel with other markers of HIV progression, and its potential association with CD4 changes in treated and untreated infection. PATIENTS AND METHODS: 96 HIV patients, 49 of them followed in the absence of cART (cART-naïve group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 [IQR: 31-60] months...
2018: PloS One
Niharika Arora Duggal, Ross D Pollock, Norman R Lazarus, Stephen Harridge, Janet M Lord
It is widely accepted that aging is accompanied by remodelling of the immune system including thymic atrophy and increased frequency of senescent T cells, leading to immune compromise. However, physical activity, which influences immunity but declines dramatically with age, is not considered in this literature. We assessed immune profiles in 125 adults (55-79 years) who had maintained a high level of physical activity (cycling) for much of their adult lives, 75 age-matched older adults and 55 young adults not involved in regular exercise...
March 8, 2018: Aging Cell
Amanda Blubaugh, Daniel Rissi, Deborah Elder, Tara Denley, Sitka Eguiluz-Hernandez, Frane Banovic
BACKGROUND: Topical Janus kinase (JAK) inhibition is a promising therapeutic target for several inflammatory skin diseases of humans. OBJECTIVES: To evaluate the anti-inflammatory effect of tofacitinib, a JAK 1/3 inhibitor, on immediate and late-phase skin reactions in dogs. ANIMALS: Five healthy laboratory beagle dogs. METHODS: Topical tofacitinib (total daily dosage: 0.5 mg/cm2 ) or its gel vehicle were applied on either the left or right lateral thorax of each dog for eight days...
March 6, 2018: Veterinary Dermatology
Susana Beceiro, Attila Pap, Zsolt Czimmerer, Tamer Sallam, Jose A Guillén, Germán Gallardo, Cynthia Hong, Noelia A-Gonzalez, Carlos Tabraue, Mercedes Diaz, Felix Lopez, Jonathan Matalonga, Annabel F Valledor, Pilar Dominguez, Carlos Ardavin, Cristina Delgado-Martin, Santiago Partida-Sanchez, Jose Luis Rodriguez-Fernandez, Laszlo Nagy, Peter Tontonoz, Antonio Castrillo
The liver X receptors (LXRs) are ligand-activated nuclear receptors with established roles in the maintenance of lipid homeostasis in multiple tissues. LXRs exert additional biological functions as negative regulators of inflammation, particularly in macrophages. However, the transcriptional responses controlled by LXRs in other myeloid cells, such as dendritic cells (DC), are still poorly understood. Here we used gain- and loss-of-function models to characterize the impact of LXR deficiency on DC activation programs...
March 5, 2018: Molecular and Cellular Biology
Graham R Serjeant, Nicki Chin, Monika R Asnani, Beryl E Serjeant, Karlene P Mason, Ian R Hambleton, Jennifer M Knight-Madden
Globally, the majority of persons born with sickle cell disease do not have access to hydroxyurea or more expensive interventions. The objectives were to estimate the survival in homozygous sickle cell disease, unbiased by symptomatic selection and to ascertain the causes of death in a pre-hydroxyurea population. The utility of early life biomarkers and genetically determined phenotypes to predict survival was assessed. A cohort study based on neonatal diagnosis was undertaken at the Sickle Cell Unit, a specialist clinic delivering care to persons with sickle cell disease in Jamaica...
2018: PloS One
Shu-Fang Hsu, Yu-Bin Lee, Ying-Chu Lee, Ai-Ling Chung, Maria Karmella Apaya, Lie-Fen Shyur, Ching-Feng Cheng, Feng-Ming Ho, Tzu-Ching Meng
Tumor necrosis factor (TNF)-α activates a diverse array of signaling pathways in vascular endothelial cells (ECs), leading to the inflammatory phenotype that contributes to the vascular dysfunction and neutrophil emigration in patients with sepsis. To date, it is not well understood what key regulator might coordinate signaling pathways to achieve inflammatory response in TNF-α-stimulated ECs. This study investigated the role of dual specificity phosphatase-6 (DUSP6) in the regulation of endothelial inflammation...
March 1, 2018: FEBS Journal
José M Benito, María C Ortiz, Agathe León, Luis A Sarabia, José M Ligos, María Montoya, Marcial Garcia, Ezequiel Ruiz-Mateos, Rosario Palacios, Alfonso Cabello, Clara Restrepo, Carmen Rodriguez, Jorge Del Romero, Manuel Leal, María A Muñoz-Fernández, José Alcamí, Felipe García, Miguel Górgolas, Norma Rallón
BACKGROUND: Despite long-lasting HIV replication control, a significant proportion of elite controller (EC) patients may experience CD4 T-cell loss. Discovering perturbations in immunological parameters could help our understanding of the mechanisms that may be operating in those patients experiencing loss of immunological control. METHODS: A case-control study was performed to evaluate if alterations in different T-cell homeostatic parameters can predict CD4 T-cell loss in ECs by comparing data from EC patients showing significant CD4 decline (cases) and EC patients showing stable CD4 counts (controls)...
February 28, 2018: BMC Medicine
Niamh Humphries, Sophie Crowe, Ruairí Brugha
BACKGROUND: The failure of high-income countries, such as Ireland, to achieve a self-sufficient medical workforce has global implications, particularly for low-income, source countries. In the past decade, Ireland has doubled the number of doctors it trains annually, but because of its failure to retain doctors, it remains heavily reliant on internationally trained doctors to staff its health system. To halve its dependence on internationally trained doctors by 2030, in line with World Health Organisation (WHO) recommendations, Ireland must become more adept at retaining doctors...
February 27, 2018: BMC Health Services Research
Matti Seppänen, Inari Laaksonen, Pekka Pulkkinen, Antti Eskelinen, Ari-Pekka Puhto, Jukka Kettunen, Jarkko Leskinen, Mikko Manninen, Keijo Mäkelä
BACKGROUND: Large-diameter head metal-on-metal (MoM) THA has largely been abandoned as a result of higher than anticipated revision rates. However, the majority of these implants are still in situ. Although earlier reports from the Finnish Arthroplasty Register noted similar short-term survivorship between large-diameter head MoM THA and conventional cemented THA, longer term survivorship of this population is unclear. Although reported revision rates for this implant group have been high, the majority of these implants have not been revised and followup is important to improve long-term management...
February 14, 2018: Clinical Orthopaedics and related Research
Kristin L Laidre, Erik W Born, Stephen N Atkinson, Øystein Wiig, Liselotte W Andersen, Nicholas J Lunn, Markus Dyck, Eric V Regehr, Richard McGovern, Patrick Heagerty
Climate change is expected to result in range shifts and habitat fragmentation for many species. In the Arctic, loss of sea ice will reduce barriers to dispersal or eliminate movement corridors, resulting in increased connectivity or geographic isolation with sweeping implications for conservation. We used satellite telemetry, data from individually marked animals (research and harvest), and microsatellite genetic data to examine changes in geographic range, emigration, and interpopulation connectivity of the Baffin Bay (BB) polar bear ( Ursus maritimus ) subpopulation over a 25-year period of sea-ice loss...
February 2018: Ecology and Evolution
Lalit K Beura, Sathi Wijeyesinghe, Emily A Thompson, Marissa G Macchietto, Pamela C Rosato, Mark J Pierson, Jason M Schenkel, Jason S Mitchell, Vaiva Vezys, Brian T Fife, Steven Shen, David Masopust
Immunosurveillance of secondary lymphoid organs (SLO) is performed by central memory T cells that recirculate through blood. Resident memory T (Trm) cells remain parked in nonlymphoid tissues and often stably express CD69. We recently identified Trm cells within SLO, but the origin and phenotype of these cells remains unclear. Using parabiosis of "dirty" mice, we found that CD69 expression is insufficient to infer stable residence of SLO Trm cells. Restimulation of nonlymphoid memory CD8+ T cells within the skin or mucosa resulted in a substantial increase in bona fide Trm cells specifically within draining lymph nodes...
February 20, 2018: Immunity
Anne G Ording, Katalin Veres, Dóra K Farkas, Kasper Adelborg, Henrik T Sørensen
BACKGROUND: Respiratory tract bleeding may be a marker of cancer. We quantified the risk of specific cancer types among patients with hospital-based diagnoses of epistaxis and haemoptysis relative to risk in the general population. METHODS: We used Danish, nationwide databases to conduct a population-based cohort study of 80460 patients diagnosed with epistaxis and 18487 patients presenting with haemoptysis (1995-2013). We followed patients until a cancer diagnosis, emigration, death, or 31 December 2013, whichever came first...
February 20, 2018: British Journal of Cancer
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