Early peroxisome proliferator-activated receptor gamma regulated genes involved in expansion of pancreatic beta cell mass.

BACKGROUND: The progression towards type 2 diabetes depends on the allostatic response of pancreatic beta cells to synthesise and secrete enough insulin to compensate for insulin resistance. The endocrine pancreas is a plastic tissue able to expand or regress in response to the requirements imposed by physiological and pathophysiological states associated to insulin resistance such as pregnancy, obesity or ageing, but the mechanisms mediating beta cell mass expansion in these scenarios are not well defined. We have recently shown that ob/ob mice with genetic ablation of PPARγ2, a mouse model known as the POKO mouse failed to expand its beta cell mass. This phenotype contrasted with the appropriate expansion of the beta cell mass observed in their obese littermate ob/ob mice. Thus, comparison of these models islets particularly at early ages could provide some new insights on early PPARγ dependent transcriptional responses involved in the process of beta cell mass expansion RESULTS: Here we have investigated PPARγ dependent transcriptional responses occurring during the early stages of beta cell adaptation to insulin resistance in wild type, ob/ob, PPARγ2 KO and POKO mice. We have identified genes known to regulate both the rate of proliferation and the survival signals of beta cells. Moreover we have also identified new pathways induced in ob/ob islets that remained unchanged in POKO islets, suggesting an important role for PPARγ in maintenance/activation of mechanisms essential for the continued function of the beta cell. CONCLUSIONS: Our data suggest that the expansion of beta cell mass observed in ob/ob islets is associated with the activation of an immune response that fails to occur in POKO islets. We have also indentified other PPARγ dependent differentially regulated pathways including cholesterol biosynthesis, apoptosis through TGF-β signaling and decreased oxidative phosphorylation.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Comparative field performance and adherence to test results of four malaria rapid diagnostic tests among febrile patients more than five years of age in Blantyre, Malawi

<p>Abstract</p> <p>Background</p> <p>Malaria rapid diagnostics tests (RDTs) can increase availability of laboratory-based diagnosis and improve the overall management of febrile patients in malaria endemic areas. In preparation to scale-up RDTs in health facilities in Malawi, an evaluation of four RDTs to help guide national-level decision-making was conducted.</p> <p>Methods</p> <p>A cross sectional study of four histidine rich-protein-type-2- (HRP2) based RDTs at four health centres in Blantyre, Malawi, was undertaken to evaluate the sensitivity and specificity of RDTs, assess prescriber adherence to RDT test results and explore operational issues regarding RDT implementation. Three RDTs were evaluated in only one health centre each and one RDT was evaluated in two health centres. Light microscopy in a reference laboratory was used as the gold standard.</p> <p>Results</p> <p>A total of 2,576 patients were included in the analysis. All of the RDTs tested had relatively high sensitivity for detecting any parasitaemia [Bioline SD (97%), First response malaria (92%), Paracheck (91%), ICT diagnostics (90%)], but low specificity [Bioline SD (39%), First response malaria (42%), Paracheck (68%), ICT diagnostics (54%)]. Specificity was significantly lower in patients who self-treated with an anti-malarial in the previous two weeks (odds ratio (OR) 0.5; p-value < 0.001), patients 5-15 years old versus patients > 15 years old (OR 0.4, p-value < 0.001) and when the RDT was performed by a community health worker versus a laboratory technician (OR 0.4; p-value < 0.001). Health workers correctly prescribed anti-malarials for patients with positive RDT results, but ignored negative RDT results with 58% of patients with a negative RDT result treated with an anti-malarial.</p> <p>Conclusions</p> <p>The results of this evaluation, combined with other published data and global recommendations, have been used to select RDTs for national scale-up. In addition, the study identified some key issues that need to be further delineated: the low field specificity of RDTs, variable RDT performance by different cadres of health workers and the need for a robust quality assurance system. Close monitoring of RDT scale-up will be needed to ensure that RDTs truly improve malaria case management.</p

Effectiveness of Motivational Interviewing in improving lipid level in patients with dyslipidemia assisted by general practitioners: Dislip-EM study protocol

<p>Abstract</p> <p>Background</p> <p>The non-pharmacological approach to cholesterol control in patients with hyperlipidemia is based on the promotion of a healthy diet and physical activity. Thus, to help patients change their habits, it is essential to identify the most effective approach. Many efforts have been devoted to explain changes in or adherence to specific health behaviors. Such efforts have resulted in the development of theories that have been applied in prevention campaigns, and that include brief advice and counseling services. Within this context, Motivational Interviewing has proven to be effective in changing health behaviors in specific cases. However, more robust evidence is needed on the effectiveness of Motivational Interviewing in treating chronic pathologies -such as dyslipidemia- in patients assisted by general practitioners. This article describes a protocol to assess the effectiveness of MI as compared with general practice (brief advice), with the aim of improving lipid level control in patients with dyslipidemia assisted by a general practitioner.</p> <p>Methods/Design</p> <p>An open, two-arm parallel, multicentre, cluster, controlled, randomized, clinical trial will be performed. A total of 48-50 general practitioners from 35 public primary care centers in Spain will be randomized and will recruit 436 patients with dyslipidemia. They will perform an intervention based either on Motivational Interviewing or on the usual brief advice. After an initial assessment, follow-ups will be performed at 2, 4, 8 and 12 months. Primary outcomes are lipid levels (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and cardiovascular risk. The study will assess the degree of dietary and physical activity improvement, weight loss in overweight patients, and adherence to treatment guidelines.</p> <p>Discussion</p> <p>Motivational interview skills constitute the primary strategies GPs use to treat their patients. Having economical, simple, effective and applicable techniques is essential for primary care professionals to help their patients change their lifestyle and improve their health. This study will provide scientific evidence on the effectiveness of Motivational interviewing, and will be performed under strict control over the data collected, ensuring the maintenance of therapeutic integrity.</p> <p>Trials Registration</p> <p>ClinicalTrials.gov (<a href="http://www.clinicaltrials.gov/ct2/show/NCT01282190">NCT01282190</a>).</p

The 2018 report of the Lancet Countdown on health and climate change: shaping the health of nations for centuries to come

The Lancet Countdown: tracking progress on health and climate change was established to provide an independent, global monitoring system dedicated to tracking the health dimensions of the impacts of, and the response to, climate change. The Lancet Countdown tracks 41 indicators across five domains: climate change impacts, exposures, and vulnerability; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; finance and economics; and public and political engagement. This report is the product of a collaboration of 27 leading academic institutions, the UN, and intergovernmental agencies from every continent. The report draws on world-class expertise from climate scientists, ecologists, mathematicians, geographers, engineers, energy, food, livestock, and transport experts, economists, social and political scientists, public health professionals, and. doctors. The Lancet Countdown’s work builds on decades of research in this field, and was first proposed in the 2015 Lancet Commission on health and climate change,1 which documented the human impacts of climate change and provided ten global recommendations to respond to this public health emergency and secure the public health benefits available (panel 1)

Clinical Practice Guideline for the Evaluation of Fever and Infection in Older Adult Residents of Long-Term Care Facilities: 2008 Update by the Infectious Diseases Society of America

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65801/1/j.1532-5415.2009.02175.x.pd

What Lies behind the Wish to Hasten Death? A Systematic Review and Meta-Ethnography from the Perspective of Patients

BACKGROUND: There is a need for an in-depth approach to the meaning of the wish to hasten death (WTHD). This study aims to understand the experience of patients with serious or incurable illness who express such a wish. METHODS AND FINDINGS: Systematic review and meta-ethnography of qualitative studies from the patient's perspective. Studies were identified through six databases (ISI, PubMed, PsycINFO, CINAHL, CUIDEN and the Cochrane Register of Controlled Trials), together with citation searches and consultation with experts. Finally, seven studies reporting the experiences of 155 patients were included. The seven-stage Noblit and Hare approach was applied, using reciprocal translation and line-of-argument synthesis. Six main themes emerged giving meaning to the WTHD: WTHD in response to physical/psychological/spiritual suffering, loss of self, fear of dying, the desire to live but not in this way, WTHD as a way of ending suffering, and WTHD as a kind of control over one's life ('having an ace up one's sleeve just in case'). An explanatory model was developed which showed the WTHD to be a reactive phenomenon: a response to multidimensional suffering, rather than only one aspect of the despair that may accompany this suffering. According to this model the factors that lead to the emergence of WTHD are total suffering, loss of self and fear, which together produce an overwhelming emotional distress that generates the WTHD as a way out, i.e. to cease living in this way and to put an end to suffering while maintaining some control over the situation. CONCLUSIONS: The expression of the WTHD in these patients is a response to overwhelming emotional distress and has different meanings, which do not necessarily imply a genuine wish to hasten one's death. These meanings, which have a causal relationship to the phenomenon, should be taken into account when drawing up care plans

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)