Pre-eclampsia (PE) is a serious multi-factorial disorder of human pregnancy. It is associated with changes in the expression of placental genes. Recent transcription profiling of placental genes with ...microarray analyses have offered better opportunities to define the molecular pathology of this disorder. However, the extent to which placental gene expression changes in PE is not fully understood. We conducted a systematic review of published PE and normal pregnancy (NP) control placental RNA microarrays to describe the similarities and differences between NP and PE placental gene expression, and examined how these differences could contribute to the molecular pathology of the disease. A total of 167 microarray samples were available for meta-analysis. We found the expression pattern of one group of genes was the same in PE and NP. The review also identified a set of genes (PE unique genes) including a subset, that were significantly (p < 0.05) down-regulated in pre-eclamptic placentae only. Using class prediction analysis, we further identified the expression of 88 genes that were highly associated with PE (p < 0.05), 10 of which (LEP, HTRA4, SPAG4, LHB, TREM1, FSTL3, CGB, INHA, PROCR, and LTF) were significant at p < 0.001. Our review also suggested that about 30% of genes currently being investigated as possibly of importance in PE placenta were not consistently and significantly affected in the PE placentae. We recommend further work to confirm the roles of the PE unique and associated genes, currently not being investigated in the molecular pathology of the disease.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims
The presence of diabetic foot ulcers is strongly associated with an increased risk of death. In this study, we investigate whether the effects of diabetes‐associated complications can explain ...the apparent relationship between diabetic foot ulcers and death.
Methods
We analysed data from 414 523 people with diabetes enrolled in practices associated with The Health Improvement Network in the United Kingdom. Our methods were designed to control for potential confounders in order to isolate the relationship between diabetic foot ulcers and death. Using proportional hazards models and the area under the receiver operator curve, we evaluated the effects of diabetic foot ulcers and the covariates on death.
Results
Among the patients, 20 737 developed diabetic foot ulcers; 5.0% of people with new ulcers died within 12 months of their first foot ulcer visit and 42.2% of people with foot ulcers died within 5 years. After controlling for major known complications of diabetes that might influence mortality, the correlation between diabetic foot ulcers and death remained strong with a fully adjusted hazard ratio of 2.48 (95% confidence interval: 2.43, 2.54). Geographic variance existed but was not spatially associated.
Conclusions
Diabetic foot ulcers are linked to an increased risk of death. This cannot be explained by other common risk factors. These results suggest that either there are major unknown risk factors associated with both diabetic foot ulcers and death, or that diabetic foot ulceration itself is a serious threat, which seems unlikely. A diabetic foot ulcer should be seen as a major warning sign for mortality, necessitating closer medical follow‐up.
What's new?
This is the largest patient cohort study ever to study the association between diabetic foot ulcers and risk of death in adults with diabetes.
Our findings support the hypothesis that diabetic foot ulcers are a marker associated with a risk to patients’ longevity independent of other complications of diabetes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We search for the signature of parity-violating physics in the cosmic microwave background, called cosmic birefringence, using the Planck data release 4. We initially find a birefringence angle of ...β=0.30°±0.11° (68% C.L.) for nearly full-sky data. The values of β decrease as we enlarge the Galactic mask, which can be interpreted as the effect of polarized foreground emission. Two independent ways to model this effect are used to mitigate the systematic impact on β for different sky fractions. We choose not to assign cosmological significance to the measured value of β until we improve our knowledge of the foreground polarization.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Ectopic lymphoid follicles are hallmarks of chronic autoimmune inflammatory diseases such as multiple sclerosis (MS), rheumatoid arthritis, Sjögren's syndrome, and myasthenia gravis. However, the ...effector cells and mechanisms that induce their development are unknown. Here we showed that in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, Th17 cells specifically induced ectopic lymphoid follicles in the central nervous system (CNS). Development of ectopic lymphoid follicles was partly dependent on the cytokine interleukin 17 (IL-17) and on the cell surface molecule Podoplanin (Pdp), which was expressed on Th17 cells, but not on other effector T cell subsets. Pdp was also crucial for the development of secondary lymphoid structures: Pdp-deficient mice lacked peripheral lymph nodes and had a defect in forming normal lymphoid follicles and germinal centers in spleen and lymph node remnants. Thus, Th17 cells are uniquely endowed to induce tissue inflammation, characterized by ectopic lymphoid follicles within the target organ.
► Th17 cells but not other T cell subsets induce ectopic follicles in the CNS ► Th17 cells but not other T cell subsets express Podoplanin ► Formation of ectopic follicles depends on IL-17 and on Podoplanin ► Podoplanin is also crucial for formation of organized secondary lymphoid structures
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Objective To develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis (OA), intended to inform patients, physicians, ...and allied healthcare professionals worldwide. Method Thirteen experts from relevant medical disciplines (primary care, rheumatology, orthopedics, physical therapy, physical medicine and rehabilitation, and evidence-based medicine), three continents and ten countries (USA, UK, France, Netherlands, Belgium, Sweden, Denmark, Australia, Japan, and Canada) and a patient representative comprised the Osteoarthritis Guidelines Development Group (OAGDG). Based on previous OA guidelines and a systematic review of the OA literature, 29 treatment modalities were considered for recommendation. Evidence published subsequent to the 2010 OARSI guidelines was based on a systematic review conducted by the OA Research Society International (OARSI) evidence team at Tufts Medical Center, Boston, USA. Medline, EMBASE, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials were initially searched in first quarter 2012 and last searched in March 2013. Included evidence was assessed for quality using Assessment of Multiple Systematic Reviews (AMSTAR) criteria, and published criticism of included evidence was also considered. To provide recommendations for individuals with a range of health profiles and OA burden, treatment recommendations were stratified into four clinical sub-phenotypes. Consensus recommendations were produced using the RAND/UCLA Appropriateness Method and Delphi voting process. Treatments were recommended as Appropriate, Uncertain, or Not Appropriate, for each of four clinical sub-phenotypes and accompanied by 1–10 risk and benefit scores. Results Appropriate treatment modalities for all individuals with knee OA included biomechanical interventions, intra-articular corticosteroids, exercise (land-based and water-based), self-management and education, strength training, and weight management. Treatments appropriate for specific clinical sub-phenotypes included acetaminophen (paracetamol), balneotherapy, capsaicin, cane (walking stick), duloxetine, oral non-steroidal anti-inflammatory drugs (NSAIDs; COX-2 selective and non-selective), and topical NSAIDs. Treatments of uncertain appropriateness for specific clinical sub-phenotypes included acupuncture, avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip, transcutaneous electrical nerve stimulation, and ultrasound. Treatments voted not appropriate included risedronate and electrotherapy (neuromuscular electrical stimulation). Conclusion These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Students and their parents wonder if college is worth the investment. Employers want graduates with the skills they need. The public wonders if higher education is preparing future generations for an ...era of dynamic change. In his latest book, William Sullivan offers a model of higher education that answers all these questions in the affirmative, through the power of integrated learning. Drawing on examples from the 25 members of the New American Colleges & Universities (NAC&U) consortium, the book makes the case for an approach that combines the strengths of the liberal arts, professional studies, and civic responsibility in order to give students the combination of skills and experience that will prepare them for success in all aspects of life after graduation.NAC&U campuses place emphasis upon enabling their students to know themselves and their abilities, as well as providing them with opportunities to develop a sophisticated understanding of the world. To achieve these goals, the academic programs focus on developing students' intellectual and practical skills, such as analytical ability, problem solving, facility in written and spoken communication, and an appreciation for human diversity and creativity. These have traditionally been identified as the goals of a liberal arts education, and are the same ones identified in a national employer survey as giving job-seekers an edge.These institutions also invest a great deal of effort to provide their students with state-of-the-art preparation for professional life and occupational success in diverse fields. These range from the technical - science and technology fields, with disciplines such as engineering and computer science - through business, and across the human service fields, such as education, nursing, pre-medicine, and pre-law, to architecture, and the performing and visual arts. In these courses of study, students begin to shape their future careers.The important third value of a NAC&U education is fos
Genome-wide association studies (GWAS) have revealed risk alleles for ulcerative colitis (UC). To understand their cell type specificities and pathways of action, we generate an atlas of 366,650 ...cells from the colon mucosa of 18 UC patients and 12 healthy individuals, revealing 51 epithelial, stromal, and immune cell subsets, including BEST4+ enterocytes, microfold-like cells, and IL13RA2+IL11+ inflammatory fibroblasts, which we associate with resistance to anti-TNF treatment. Inflammatory fibroblasts, inflammatory monocytes, microfold-like cells, and T cells that co-express CD8 and IL-17 expand with disease, forming intercellular interaction hubs. Many UC risk genes are cell type specific and co-regulated within relatively few gene modules, suggesting convergence onto limited sets of cell types and pathways. Using this observation, we nominate and infer functions for specific risk genes across GWAS loci. Our work provides a framework for interrogating complex human diseases and mapping risk variants to cell types and pathways.
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•51 cell subsets in colon mucosa of 18 ulcerative colitis and 12 healthy individuals•M-like cells, inflammatory monocytes and fibroblasts, and CD8+IL-17+ T cells expand in disease•Oncostatin M circuit in inflammatory monocytes and fibroblasts may affect drug response•Co-expression of genes within cells allows inference of causal genes across risk loci
Single-cell analyses of colon biopsy specimens from patients with ulcerative colitis delineate how expression patterns and shifting cell populations may shape disease and drug resistance, and provide a framework for linking GWAS risk loci with specific cell types and functional pathways.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There has been a substantial number of systematic reviews of stress, coping and interventions for people with dementia and their caregivers. This paper provides a meta-review of this literature ...1988-2014.
A meta-review was carried out of systematic reviews of stress, coping and interventions for people with dementia and their caregivers, using SCOPUS, Google Scholar and CINAHL Plus databases and manual searches.
The meta-review identified 45 systematic reviews, of which 15 were meta-analyses. Thirty one reviews addressed the effects of interventions and 14 addressed the results of correlational studies of factors associated with stress and coping. Of the 31 systematic reviews dealing with intervention studies, 22 focused on caregivers, 6 focused on people with dementia and 3 addressed both groups. Overall, benefits in terms of psychological measures of mental health and depression were generally found for the use of problem focused coping strategies and acceptance and social-emotional support coping strategies. Poor outcomes were associated with wishful thinking, denial, and avoidance coping strategies. The interventions addressed in the systematic reviews were extremely varied and encompassed Psychosocial, Psychoeducational, Technical, Therapy, Support Groups and Multicomponent interventions. Specific outcome measures used in the primary sources covered by the systematic reviews were also extremely varied but could be grouped into three dimensions, viz., a broad dimension of "Psychological Well-Being v. Psychological Morbidity" and two narrower dimensions of "Knowledge and Coping" and of "Institutionalisation Delay".
This meta-review supports the conclusion that being a caregiver for people with dementia is associated with psychological stress and physical ill-health. Benefits in terms of mental health and depression were generally found for caregiver coping strategies involving problem focus, acceptance and social-emotional support. Negative outcomes for caregivers were associated with wishful thinking, denial and avoidance coping strategies. Psychosocial and Psychoeducational interventions were beneficial for caregivers and for people with dementia. Support groups, Multicomponent interventions and Joint Engagements by both caregivers and people with dementia were generally found to be beneficial. It was notable that virtually all reviews addressed very general coping strategies for stress broadly considered, rather than in terms of specific remedies for specific sources of stress. Investigation of specific stressors and remedies would seem to be a useful area for future research.
Discovering the stress-buffering effects of social relationships has been one of the major findings in psychobiology in the last century. However, an understanding of the underlying neurobiological ...and psychological mechanisms of this buffering is only beginning to emerge. An important avenue of this research concerns the neurocircuitry that can regulate the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. The present review is a translational effort aimed at integrating animal models and human studies of the social regulation of the HPA axis from infancy to adulthood, specifically focusing on the process that has been named social buffering. This process has been noted across species and consists of a dampened HPA axis stress response to threat or challenge that occurs with the presence or assistance of a conspecific. We describe aspects of the relevant underlying neurobiology when enough information exists and expose major gaps in our understanding across all domains of the literatures we aimed to integrate. We provide a working conceptual model focused on the role of oxytocinergic systems and prefrontal neural networks as 2 of the putative biological mediators of this process, and propose that the role of early experiences is critical in shaping later social buffering effects. This synthesis points to both general future directions and specific experiments that need to be conducted to build a more comprehensive model of the HPA social buffering effect across the life span that incorporates multiple levels of analysis: neuroendocrine, behavioral, and social.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Natural odors, generally composed of many monomolecular components, are analyzed by peripheral receptors into component features and translated into spatiotemporal patterns of neural activity in the ...olfactory bulb. Here, we will discuss the role of the olfactory cortex in the recognition, separation and completion of those odor-evoked patterns, and how these processes contribute to odor perception. Recent findings regarding the neural architecture, physiology, and plasticity of the olfactory cortex, principally the piriform cortex, will be described in the context of how this paleocortical structure creates odor objects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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