Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient

Kualitas Hidup Pasien Diabetes Melitus Tipe 2 di Puskesmas Se Kota Kupang

Diabetes Mellitus is well known as a chronic disease which can lead to a decrease in quality of life in all domains. The study aims to explore the diabetic type 2 patient\u27s quality of life and find out the factors affecting in type 2 diabetic mellitus patients. The cross-sectional study design is used that included 65 patient with type 2 diabetes mellitus, in 11 public health centers of Kupang City. Data were collected by using Short Form Survey (SF-36) that assessed 8-scale health profile. Independent sample t-test is used to analyze the correlation between the factors affecting and the quality of life. the study showed that the QoL of DM patients decreased in all 8- health profile including physical functioning, social functioning, mental health, general health, pain, change in the role due to physical problems and emotional problems. The Study also showed there was a relationship between gender, duration of suffering from Diabetes mellitus, and complications to the quality of life. Male perceived a better quality of life than female

Exploring Public Sector’s Roles in Collaborative Consumption – A Research Agenda

Part 2: Digital Collaboration and Social MediaInternational audienceMotivated by the growing significance of sharing economy within our society, we here discuss which role the public sector may have within collaborative consumption (CC). CC refers to a business model grounded on peer-to-peer based sharing of goods and services through community-based online services. While public sector to a large extent has transformed from formalised bureaucratic structures into more hybrid organisations, focusing on the co-creation between public and private stakeholders, public sector’s role within the sharing economy is still in need for further investigation. We reflect on the need for studying how public sector could benefit from a more active role within CC for public service provision in the e-government area. Based on current literature on CC, we argue that the public sector can take on three main roles in CC: the customers, the service providers, and the platform providers. We further develop suggestions for a research agenda in this area and raise questions for a further discussion on the role of public sector within CC

Why medical students do not choose a career in geriatrics: a systematic review

Background: While the demand for doctors specialised in the medical care of elderly patients is increasing, the interest among medical students for a career in geriatrics is lagging behind. Methods: To get an overview of the different factors reported in the literature that affect the (low) interest among medical students for a career in geriatrics, a systematic literature search was conducted using PubMed, Embase, PsycINFO, and ERIC. Quality assessment criteria were applied. Results: Twenty studies met the criteria and were included in the review. In relation to the nature of the work, the preference of medical students is young patients, and acute somatic diseases that can be cured. The complexity of the geriatric patient deters students from choosing this specialty. Exposure by means of pre-clinical and particularly clinical education increases interest. The lack of status and the financial aspects have a negative influence on interest. Conclusion: Exposure to geriatrics by means of education is necessary. The challenge in geriatric education is to show the rewarding aspects of the specialty