Grafted human pluripotent stem cell-derived cortical neurons integrate into adult human cortical neural circuitry

Several neurodegenerative diseases cause loss of cortical neurons, leading to sensory, motor, and cognitive impairments. Studies in different animal models have raised the possibility that transplantation of human cortical neuronal progenitors, generated from pluripotent stem cells, might be developed into a novel therapeutic strategy for disorders affecting cerebral cortex. For example, we have shown that human longterm neuroepithelial-like stem (lt-NES) cell-derived cortical neurons, produced from induced pluripotent stem cells and transplanted into stroke-injured adult rat cortex, improve neurological deficits and establish both afferent and efferent morphological and functional connections with host cortical neurons. So far, all studies with human pluripotent stem cell-derived neurons have been carried out using xenotransplantation in animal models. Whether these neurons can integrate also into adult human brain circuitry is unknown. Here, we show that cortically fated lt-NES cells, which are able to form functional synaptic networks in cell culture, differentiate to mature, layer-specific cortical neurons when transplanted ex vivo onto organotypic cultures of adult human cortex. The grafted neurons are functional and establish both afferent and efferent synapses with adult human cortical neurons in the slices as evidenced by immuno-electron microscopy, rabies virus retrograde monosynaptic tracing, and whole-cell patch-clamp recordings. Our findings provide the first evidence that pluripotent stem cell-derived neurons can integrate into adult host neural networks also in a human-to-human grafting situation, thereby supporting their potential future clinical use to promote recovery by neuronal replacement in the patient's diseased brain

Direct Reader Address in Health-related Online News Articles: Imposing Problems and Projecting Desires for Action and Change onto Readers

The digitalisation and commercialisation of the news mean journalistic practices are changing. Traditionally, readers are not addressed in written news stories. This study documents practices of direct reader address in online news headlines on health topics from three Nordic countries. The study focuses on the linguistic means of constructing the reader and journalist-reader relationship through forms of direct address. For this purpose, we take pragmatic-interactional and discourse-analytical approaches. Building on a discursive view on news values, the paper analyses three practices of addressing readers in headlines, outlines how news values are discursively constructed through these practices, and examines how journalists construct their target audience discursively by imposing problems and projecting desires for action and change onto readers, indicating assumptions about the readers' knowledge. We argue that, by using such practices, journalists construct journalistic authority

Photoperiod induced obesity in the Brandt's vole (Lasiopodomys brandtii) : a model of 'healthy obesity'?

Funding This work was funded by the Strategic Priority Research Program of the Chinese Academy of Sciences [XDB13030000 to J.R.S.], a small grant to J.R.S. and D.-H.W., and a Great Wall professorship to J.R.S., both from the Chinese Academy of Sciences–Novo Nordisk UK Research Foundation. J.R.S. was also supported by a 1000 Talents professorship and a Wolfson merit award from the Royal Society. D.B.Y. was supported by a project from China Postdoctoral Science Foundation [2013M541078].Peer reviewedPublisher PD

Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) rationale and design

Cardiovascular disease (CVD) is a major cause of morbidity and mortality. Although it has been widely appreciated that obesity is a major risk factor for CVD, treatments that produce effective, durable weight loss and the impact of weight reduction in reducing cardiovascular risk have been elusive. Instead, progress in CVD risk reduction has been achieved through medications indicated for controlling lipids, hyperglycemia, blood pressure, heart failure, inflammation, and/or thrombosis. Obesity has been implicated as promoting all these issues, suggesting that sustained, effective weight loss may have independent cardiovascular benefit. GLP-1 receptor agonists (RAs) reduce weight, improve glycemia, decrease cardiovascular events in those with diabetes, and may have additional cardioprotective effects. The GLP-1 RA semaglutide is in phase 3 studies as a medication for obesity treatment at a dose of 2.4 mg subcutaneously (s.c.) once weekly. Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) is a randomized, double-blind, parallel-group trial testing if semaglutide 2.4 mg subcutaneously once weekly is superior to placebo when added to standard of care for preventing major adverse cardiovascular events in patients with established CVD and overweight or obesity but without diabetes. SELECT is the first cardiovascular outcomes trial to evaluate superiority in major adverse cardiovascular events reduction for an antiobesity medication in such a population. As such, SELECT has the potential for advancing new approaches to CVD risk reduction while targeting obesity

Effects of needs-based patient education on self-efficacy and health outcomes in people with rheumatoid arthritis: A multicentre, single blind, randomised controlled trial

Objectives The Educational Needs Assessment Tool (ENAT) is a self-completed questionnaire, which allows patients with arthritis to prioritise their educational needs. The aim of this study was to evaluate the effects of needs-based patient education on self-efficacy, health outcomes and patient knowledge in people with rheumatoid arthritis (RA). Methods Patients with RA were enrolled into this multicentre, single-blind, parallel-group, pragmatic randomised controlled trial. Patients were randomised to either the intervention group (IG) where patients completed ENAT, responses of which were used by the clinical nurse specialist to guide patient education; or control group (CG) in which they received patient education without the use of ENAT. Patients were seen at weeks 0, 16 and 32. The primary outcome was selfefficacy (Arthritis Self Efficacy Scale (ASES)-Pain and ASES-Other symptoms). Secondary outcomes were health status (short form of Arthritis Impact Measurement Scale 2, AIMS2-SF) and patient knowledge questionnaire-RA. We investigated between-group differences using analysis of covariance, adjusting for baseline variables. Results A total of 132 patients were recruited (IG=70 and CG=62). Their mean (SD) age was 54 (12.3) years, 56 (13.3) years and disease duration 5.2 (4.9) years, 6.7 (8.9) years for IG and CG, respectively. There were significant between-group differences, in favour of IG at week 32 in the primary outcomes, ASES-Pain, mean difference (95% CI) -4.36 (1.17 to 7.55), t=-2.72, p=0.008 and ASES-Other symptoms, mean difference (95% CI) -5.84 (2.07 to 9.62), t=-3.07, p=0.003. In secondary outcomes, the between-group differences favoured IG in AIMS2-SF Symptoms and AIMS2-SF Affect. There were no between-group differences in other secondary outcomes. Conclusions The results suggest that needs-based education helps improve patients' self-efficacy and some aspects of health status

GATA-1 testis activation region is essential for Sertoli cell-specific expression of GATA-1 gene in transgenic mouse

Background: The erythroid transcription factor GATA-1 is also expressed in Sertoli cells of the testis. The testicular expression of GATA-1 is regulated in a developmental and spermatogenic stage-specific manner. To further clarify the regulatory mechanisms of testicular GATA-1 gene expression, we carried out transgenic reporter gene expression analyses. Results: We found that GATA-1 expression in Sertoli cells is markedly decreased concomitant with the emergence of elongated spermatids in the seminiferous tubules. Transgenic reporter mouse analyses revealed that a 15 kb GATA-1 genomic region is sufficient to recapitulate the gene expression profile in Sertoli cells. While the GATA-1 haematopoietic enhancer and the proximal first exon are included within the 15 kb genomic region, these regulatory elements are not essential for GATA-1 expression in Sertoli cells. Further analyses using deletion constructs revealed that a 1.5 kb region 5′ to the GATA-1 haematopoietic enhancer is essential for gene expression in Sertoli cells and this region is referred to as the GATA-1 testis activation region. Conclusion: These results thus demonstrated that the GATA-1 testis activation region is essential for Sertoli cell-specific expression of GATA-1 gene. The 15 kb genomic region is applicable and useful for the expression vector system specific for adult Sertoli cells in stage VII to IX.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71393/1/j.1365-2443.2003.00658.x.pd

Teams between Neo-Taylorism and Anti-Taylorism

The concept of teamworking is the product of two distinct developments. One: a neo- Tayloristic form of organization of work, of which Toyota has shown that it can be very profitable, was packaged and reframed to make it acceptable to the Western public. Two: anti-Tayloristic ways of organizing work, inspired by ideals of organizational democracy, were relabeled to make these acceptable to profit-oriented managers. Drawing on empirical research in Scandinavia, Germany, The Netherlands and the UK, as well as on published case studies of Japanese companies, the paper develops a neo-Tayloristic and an anti-Tayloristic model of teamworking. Key concerns in the teamworking literature are intensification of work and the use of shop floor autonomy as a cosmetic or manipulative device. Indeed, all the features of neo-Tayloristic teamworking are geared towards the intensification of work. However, one of the intensification mechanisms, the removal of Tayloristic rigidities in the division of labor, applies to anti-Tayloristic teamworking as well. This poses a dilemma for employee representatives. In terms of autonomy, on the other hand, the difference between neo-Tayloristic and anti-Tayloristic teamworking is real. In anti-Tayloristic teamworking, there is no supervisor inside the team. The function of spokesperson rotates. All team members can participate in decision-making. Standardization is not relentlessly pursued; management accepts some measure of worker control. There is a tendency to alleviate technical discipline, e.g. to find alternatives for the assembly line. Buffers are used. Remuneration is based on proven skill level; there are no group bonuses. In contrast, in neo-Tayloristic teamworking, a permanent supervisor is present in the team as team leader. At most, only the team leader can participate in decision-making. Standardization is relentlessly pursued. Management prerogatives are nearly unlimited. Job designers treat technical discipline, e.g. short-cycled work on the assembly line, as unproblematic. There are no buffers. A substantial part of wages consists of individual bonuses based on assessments by supervisors on how deeply workers cooperate in the system. Group bonuses are also given. The instability and vulnerability of anti-Tayloristic teamworking imply that it can only develop and flourish when managers and employee representatives put determined effort into it. The opportunity structure for this contains both economic and political elements. In mass production, the economic success of Toyota, through skillful mediation by management gurus, makes the opportunity structure for anti-Tayloristic teamworking relatively unfavorable