Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions

Control of phosphate metabolism is crucial to regulate aging in mammals. Klotho is a well-known anti-aging factor that regulates phosphate metabolism: mice mutant or deficient in Klotho exhibit phenotypes resembling human aging. Here we show that ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) is required for Klotho expression under phosphate overload conditions. Loss-of-function Enpp1 ttw/ttw mice under phosphate overload conditions exhibited phenotypes resembling human aging and Klotho mutants, such as short life span, arteriosclerosis and osteoporosis, with elevated serum 1,25(OH)2D3 levels. Enpp1ttw/ttw mice also exhibited significantly reduced renal Klotho expression under phosphate overload conditions, and aging phenotypes in these mice were rescued by Klotho overexpression, a low vitamin D diet or vitamin D receptor knockout. These findings indicate that Enpp1 plays a crucial role in regulating aging via Klotho expression under phosphate overload conditions

Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization

The mobilization of hematopoietic stem cells does not require osteoclasts, which may even have an inhibitory effect

Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus : A randomized, crossover trial

Aims: We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range. Methods: This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR; <70 mg/dL). Results: The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001). Conclusions: The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM

ICAR: endoscopic skull‐base surgery

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Reflexões visuais...Um portofolio do artista

A pesquisa que apresento, sob forma de Trabalho Equivalente, investiga os procedimentos artísticos envolvidos na produção de um portfólio, a partir a partir do estudo de alguns conjuntos de trabalhos plásticos produzidos ou orientados por mim. A primeira etapa do processo consistiu em analisar os dez anos iniciais de minha produção artística, partindo das primeiras composições, realizadas em 1996, e chegando ate as pinturas mais recentes executadas durante o primeiro ano de mestrado em 2006. Organizei os trabalhos mais significativos, cronologicamente, em quatro portfolios que traduzem os interesses, as necessidades e as expectativas de períodos específicos. O segundo momento da pesquisa foi dedicado ao relado de algumas das minhas experiências no ensino de arte, ocorridas nos anos de 2006 e 2007, através das quais tive a oportunidade de orientar a produção de uma série de visualidades. Como produto final dessa sistematização propus a elaboração de um novo portfólio que sintetiza o meu percurso como artista visual e como professora na área de Artes. As imagens presentes neste relatório circunstanciado não desempenham função ilustrativa; elas constituem o verdadeiro substrato desta reflexão comunicada, essencialmente, através da linguagem visual.The research that I present, in a form of Equivalent Work, investigates the artistic procedures envolved in the production of a portfolio from the study of some plastic art work set produced of orientated by me. The first stage of the process consisted in analyse the first ten years of my artistic production starting from ghe first composition, realizead in 1996 and finishid until the most recent paitings executed durint the first year of the Visual Art Masters, in 2006. I organized the most significant works chronologically, in four portfolios that express the intersts, needs and expectationsa of specific periods. The second stage was dedicated the report of some art teaching experiences of mine, occured in the years of 2006 and 2007, through them I had the opportunity to orientate the production of visualitics. As the result of this system I propused an elaboration of a new portfolio that systhetizes my trajectory as a visual and as a teacher in the art area. The present imges in the written repor don't represent illustrative function; they compose the real abstracat of this communicated reflection essentiallly through the visual language

Evaluation of Clinical Practice Guidelines for Rare Diseases in Japan

INTRODUCTION: The insufficient quantity and quality of clinical epidemiological evidence in the field of rare diseases have posed methodological challenges to develop clinical practice guidelines (CPGs). Guideline development groups struggle to provide patients and their families with beneficial guidance, such as that for medical care and in complex circumstances. Motivated by the challenges, we focused on information on resources for supporting the daily and social life to improve the CPGs for users. We aimed to assess the methodological quality of CPGs for rare diseases in Japan and to evaluate information on resources to support the daily and social life in the CPGs. METHODS: We conducted a systematic search using PubMed, three electronic Japanese databases, and two hand-searched sources in Japan. The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument with six domains was used to assess the methodological quality of the CPGs. A content analysis of the CPG text was conducted using five keywords as information on non-medical resources, e.g., "Intractable Disease Consultation Support Center, " "Japan Intractable Disease Information Center, " and "Patient Association." RESULTS: A total of 55 CPGs met the inclusion criteria. Among four domains of AGREE II with low scores (Stakeholder Involvement, Rigor of Development, Applicability, and Editorial Independence), Rigor of Development had the lowest median score. As for information on non-medical resources, 41 CPGs included at least 1 of the 5 keywords, while 14 CPGs included none. CONCLUSIONS: At the Rigor of Development domain, methodological challenges may have resulted in an insufficient description of items regarding the translation evidence to recommendations. As the sufficiency of five keywords as information on non-medical resources could be improved, the information will be advocative as clues to provide pragmatic guidance, particularly for rare diseases with limited medical evidence

Bezafibrate attenuates immobilization-induced muscle atrophy in mice

Abstract Muscle atrophy due to fragility fractures or frailty worsens not only activity of daily living and healthy life expectancy, but decreases life expectancy. Although several therapeutic agents for muscle atrophy have been investigated, none is yet in clinical use. Here we report that bezafibrate, a drug used to treat hyperlipidemia, can reduce immobilization-induced muscle atrophy in mice. Specifically, we used a drug repositioning approach to screen 144 drugs already utilized clinically for their ability to inhibit serum starvation-induced elevation of Atrogin-1, a factor related to muscle atrophy, in myotubes in vitro. Two candidates were selected, and here we demonstrate that one of them, bezafibrate, significantly reduced muscle atrophy in an in vivo model of muscle atrophy induced by leg immobilization. In gastrocnemius muscle, immobilization reduced muscle weight by an average of ~ 17.2%, and bezafibrate treatment prevented ~ 40.5% of that atrophy. In vitro, bezafibrate significantly inhibited expression of the inflammatory cytokine Tnfa in lipopolysaccharide-stimulated RAW264.7 cells, a murine macrophage line. Finally, we show that expression of Tnfa and IL-1b is induced in gastrocnemius muscle in the leg immobilization model, an activity significantly antagonized by bezafibrate administration in vivo. We conclude that bezafibrate could serve as a therapeutic agent for immobilization-induced muscle atrophy