Effects of sirtuin 1 on arterial stiffening in a model of diet-induced obesity

BACKGROUND: Arterial stiffness, or the loss of compliance of the large arteries, is a major independent predictor of cardiovascular events. Obesity induced by a high fat, high sucrose (HFHS) diet, in mice, causes the development of arterial stiffness, diabetes, and hypertension. Along with the resulting metabolic syndrome, inflammation and oxidants are increased in vascular smooth muscle (VSM) cells of HFHS-fed mice. Sirtuin 1 (SirT1), an important cellular homeostatic regulator, has been shown to prevent inflammation and obesity-associated metabolic impairment in animal models. This deacetylase is involved in histone and transcription factor regulation, thereby affecting a wide range of physiological mechanisms. However, whether SirT1 affects obesity-induced arterial stiffness is unknown. Therefore, we aimed to investigate the effects of SirT1 on arterial stiffening in a setting of diet-induced obesity. METHODS: The polyphenolic SirT1 activators, resveratrol and S17834, were added to HFHS diet fed to WT mice for 8 months. Arterial stiffness was measured in vivo, by pulse wave velocity (PWV), at baseline, 4 months, and 8 months. In another experiment, a highly selective SirT1 activator, SRT1720, was administered to mice in HFHS diet for one week following 8 months of HFHS diet, and PWV was measured before and after treatment. To study the role of VSM SirT1 in HFHS-induced arterial stiffness, resveratrol was supplemented to HFHS diet-fed mice lacking SirT1 in VSM (SMKO), and PWV was measured in comparison to control HFHS-fed mice. Additionally, mice overexpressing SirT1 in VSM specifically (SMTG) were generated and placed on HFHS diet, and PWV was measured at baseline, 4 months, and 8 months. The effects of SirT1 on oxidant production and inflammation in the different experimental groups were assessed by staining aortic sections for oxidants and performing Western blots of inflammatory markers (phospho-p65 NFκB, VCAM1) on isolated aortic and VSM cell lysates. RESULTS: Administering resveratrol and S17834 completely prevented the development HFHS-induced arterial stiffness over 8 months. Similarly, elevated PWV due to 8 months of HFHS diet was reversed by one-week treatment with SRT1720. SirT1 knockout in VSM partially prevented resveratrol’s effect in lowering arterial stiffness. Mice overexpressing SirT1 in VSM (SMTG) did not develop arterial stiffness and were protected from HFHS-induced oxidant production and inflammation (upregulation of phospho-p65 NFκB and VCAM1). CONCLUSIONS: VSM SirT1 can prevent the development of arterial stiffness in settings of obesity by opposing oxidants and inflammation in the aortic wall. SirT1 activators represent a potential therapeutic approach to alleviate the burden of cardiovascular disease in obese individuals with metabolic syndrome.2018-06-16T00:00:00

READERS BATTALION IN ABDUL RAHMAN BIN ALASHAATH ARMY

Abdul Rahman bin Alashaath revolution was considered one of the most important and most dangerous revolutions in the Umayyad period, even though it was not doctrinal. This revolution started from the eastern borders of the Islamic state against Iraq. Wali Al-Hajjaj bn Yusuf Thaqafi rose up and took over from Al Khalifa Abdul Malik bin Marwan. What distinguishes this revolution share readers of the people of Iraq in addition to a large number of loyalists who were indignant by the economic and social conditions? Readers played an important role in the revolution and they were able to achieve many victories. However, Al-Hajjaj managed to defeat them at the Battle of Deir Al-jamajem and abolish their revolution

READERS BATTALION IN ABDUL RAHMAN BIN ALASHAATH ARMY

Abdul Rahman bin Alashaath revolution was considered one of the most important and most dangerous revolutions in the Umayyad period, even though it was not doctrinal. This revolution started from the eastern borders of the Islamic state against Iraq. Wali Al-Hajjaj bn Yusuf Thaqafi rose up and took over from Al Khalifa Abdul Malik bin Marwan. What distinguishes this revolution share readers of the people of Iraq in addition to a large number of loyalists who were indignant by the economic and social conditions? Readers played an important role in the revolution and they were able to achieve many victories. However, Al-Hajjaj managed to defeat them at the Battle of Deir Al-jamajem and abolish their revolution

Correlation Between Organizational Thinking & Strategic Vision An Applied Study in Sample Jordanian Organizations

This research aims to consider the correlation between organizational thinking & strategic vision. To do so, a model was designed consisting of four organizational thinking types (Critical Thinking, Creative Thinking, Higher-Order Thinking & Meta-Thinking) and three dimensions of the strategic vision (Vision as Process, Vision as Content, and Vision as Leadership), using data collected from three different Jordanian organizations. The results indicate that there are strong effects and linkages with statistical implication between patterns of organizational thinking and strategic vision. When we have merged organizational thinking with strategic vision, a matrix with four cells. The total sample location within this matrix was defined , where it became clear that the thinking and vision of the sample was limited but balanced so that the bulk of thinking was invested in the production of their vision. Key Words: Organizational Thinking, Critical Thinking, Creative Thinking, Higher-Order Thinking,                                                                                                         Meta-Thinking, Strategic Vision, Vision as Process, Vision as Content, Vision as Leadership

A Critical Study of Ibn-Ma'een's Remark "He Is Nothing" Concerning Hadith Narrators

This research studies Ibn-Ma'een's use of the remark "He is nothing" when describing some Haidth narrators. It attempts to show the remark's meaning, and if it indicates the small number of Hadiths narrated or the narrator's unreliability. The research aims to establish what Ibn-Ma'een meant by the remark and to investigate the arguments for interpreting it as other than stating a narrator's unreliability. The research follows an analytical deductive-inductive approach. The following are its most important findings: Al-Haakim was the first to interpret Ibn-Ma'een's remark "He is nothing" as meaning the narrator narrated a small number of Hadiths, not meaning the unreliability of the narrator. Al-Haakim was followed by Ibn-Al-Qattaan Al-Faassy, then by Ibn-Hajar, through whom that interpretation was spread. Al-Haakim's interpretation was not based on well-established evidences. In fact, evidences from the study of the narrators in question supported the interpretation as an unreliability judgment. Only a small number of narrators were criticized by Ibn-Ma'een as having narrated few Hadiths; he just mentioned the number of Hadiths they narrated or how small the number of Hadiths was, without remarking any as being "nothing". Ibn-Ma'een's use of the remark in context could be only interpreted as an expression of narrators' "unreliability". This was the meaning understood by his students, none of whom interpreted it as a reference to the small number of narrated Hadiths. The research recommends that the terms and expressions used by Hadith critics in establishing reliability or unreliability of narrators should be thoroughly studied so that their meanings can be properly understood

Evaluating Differences of Erosion Patterns in Natural and Anthropogenic Basins through Scenario Testing: A Case Study of the Claise, France and Nahr Ibrahim, Lebanon

This study assessed soil erosion risks of two basins representing different geographical, topographical, climatological and land occupation/management settings. A comparison and an evaluation of site-specific factors influencing erosion in the French Claise and the Lebanese Nahr Ibrahim basins were performed. The Claise corresponds to a natural park with a flat area and an oceanic climate, and is characterized by the presence of 2179 waterbodies (mostly ponds) considered as hydro-sedimentary alternating structures, while Nahr Ibrahim represents an orographic Mediterranean basin characterized by a random unequal land occupation distribution. The Claise was found to be under 12.48% no erosion (attributed to the dense pond network), 65.66% low, 21.68% moderate and 0.18% high erosion risks; while Nahr Ibrahim was found to be under 4, 39.5 and 56.4%, low, moderate and high erosion risks, along with 66% land degradation determined from the intersection of land capability and land occupation maps. Under the alternative scenario for the Claise where ponds were considered dried, erosion risks became 1.12, 0.52, 76.8 and 21.56%, no erosion, low, moderate and high risks, respectively. For Nahr Ibrahim, and following the Land Degradation Neutrality intervention, high erosion risks decreased by 13.9%, while low and moderate risks increased by 3 and 10.8%

The Degree of Achieving Organizational Rigidity at Umm Al-Qura and Ajloun National Universities: Faculty Members’ Perspective

The paper pinpoints the degree of achieving organizational rigidity at Umm Al-Qura University and Ajloun National University from the faculty members’ viewpoint in line with the faculty, academic rank, and number of years of experience. The nature of the research necessitates using the descriptive survey research approach. A questionnaire adopted as a research instrument is applied to a 410-member sample of (410) randomly designated from the two universities. It is found that the organizational rigidity achievement is of a medium degree with a mean of (3.48). The results also show no statistically significant differences thanks to the variables of the number of years of experience and academic rank. However, it is found that there are differences caused by the faculty variable in favor of scientific faculties. The research recommends activating the methods of evaluating job performance, activating accountability and accounting systems, dividing work at the university according to the competence and experience of workers, and defining the tasks and duties of employees

Polymerization-based signal amplification for paper-based immunoassays

Diagnostic tests in resource-limited settings require technologies that are affordable and easy to use with minimal infrastructure. Colorimetric detection methods that produce results that are readable by eye, without reliance on specialized and expensive equipment, have great utility in these settings. We report a colorimetric method that integrates a paper-based immunoassay with a rapid, visible-light-induced polymerization to provide high visual contrast between a positive and a negative result. Using Plasmodium falciparum histidine-rich protein 2 as an example, we demonstrate that this method allows visual detection of proteins in complex matrices such as human serum and provides quantitative information regarding analyte levels when combined with cellphone-based imaging. It also allows the user to decouple the capture of analyte from signal amplification and visualization steps.Bill & Melinda Gates Foundation (Award 51308)United States. Defense Advanced Research Projects Agency (HR0011-12-2-0010)National Science Foundation (U.S.). Graduate Research FellowshipBurroughs Wellcome Fund (Career Award at the Scientific Interface

Challenges and Opportunities: What Can We Learn from Patients Living with Chronic Musculoskeletal Conditions, Health Professionals and Carers about the Concept of Health Literacy Using Qualitative Methods of Inquiry?

The field of health literacy continues to evolve and concern public health researchers and yet remains a largely overlooked concept elsewhere in the healthcare system. We conducted focus group discussions in England UK, about the concept of health literacy with older patients with chronic musculoskeletal conditions (mean age = 73.4 years), carers and health professionals. Our research posed methodological, intellectual and practical challenges. Gaps in conceptualisation and expectations were revealed, reiterating deficiencies in predominant models for understanding health literacy and methodological shortcomings of using focus groups in qualitative research for this topic. Building on this unique insight into what the concept of health literacy meant to participants, we present analysis of our findings on factors perceived to foster and inhibit health literacy and on the issue of responsibility in health literacy. Patients saw health literacy as a result of an inconsistent interactive process and the implications as wide ranging; healthcare professionals had more heterogeneous views. All focus group discussants agreed that health literacy most benefited from good inter-personal communication and partnership. By proposing a needs-based approach to health literacy we offer an alternative way of conceptualising health literacy to help improve the health of older people with chronic conditions