Thioredoxin as a putative biomarker and candidate target in age-related immune decline

The oxidoreductase Trx-1 (thioredoxin 1) is highly conserved and found intra- and extra-cellularly in mammalian systems. There is increasing interest in its capacity to regulate immune function based on observations of altered distribution and expression during ageing and disease. We have investigated previously whether extracellular T-cell or peripheral blood mononuclear cell Trx-1 levels serve as a robust marker of ageing. In a preliminary study of healthy older adults compared with younger adults, we showed that therewas a significant, butweak, relationshipwith age. Interestingly, patientswith rheumatoid arthritis and cancer have been described by others to secrete or express greater surface Trx-1 than predicted. It is interesting to speculate whether a decline in Trx-1 during ageing protects against such conditions, but correspondingly increases risk of disease associated with Trx-1 depletion such as cardiovascular disease. These hypotheses are being explored in the MARK-AGE study, and preliminary findings confirm an inverse correlation of surface Trx-1 with age. We review recent concepts around the role of Trx-1 and its partners in T-cell function on the cell surface and as an extracellular regulator of redox state in a secreted form. Further studies on the redox state and binding partners of surface and secreted Trx-1 in larger patient datasets are needed to improve our understanding of why Trx-1 is important for lifespan and immune function. © The Authors Journal compilation © 2014 Biochemical Society.

Quality Assurance in Extreme Programming

Our previous research about possible quality improvements in Extreme Programming (XP) led us to a conclusion that XP supports many good engineering practices but there is still place for refinements. Our proposal was to add dedicated Quality Assurance (QA) measures, which should be sufficiently effective and at the same time simpler enough in the context of XP. This paper intends to analyze the possibilities for an effective way for applying approved quality assurance practices to XP. The last should not affect negatively to the process and in the meantime must lead to better quality assurance. We aim to make changes to XP that even if would slow down a bit the development process, will make it more suitable for widest range of projects including large and very large projects as well as life critical and highly reliable systems.

A magyar öngondoskodás sajátosságai

A magyar nyugdíjrendszerben 1998 óta egymás mellett működik a felosztó-kirovó és a kötelező tőkefedezeti pillér. Ezt a paradigmatikusnak tekintett reformot követően is több változtatás zajlott az elmúlt években, amelyek lényegében a nyugdíjparaméterek módosítására irányultak. Mára a nyugdíjreformról szóló diskurzus világszerte újra általánossá vált. A magyar nyugdíjviták középpontjában nem elsősorban az idősödő népesség növekvő aránya, hanem az alacsony foglalkoztatás és a csekély jogosultságszerzés áll. A hozzászólások ma már nem a felosztó-kirovó versus tőkefedezeti rendszer kérdéskörét érintik. A vitában újra és újra előkerül az öngondoskodás hangsúlyozása. A tanulmány egy felmérés adatain keresztül elemzi az öngondoskodás különböző formáinak elterjedtségét. A kérdőív tanulsága szerint a megkérdezettek jellemzően nem saját maguk hozták meg döntéseiket a vizsgált kérdésekben - a nyugdíjrendszerről és saját várható nyugdíjas élettartamukról korlátozott (és néha téves) ismeretekkel rendelkeznek. Az emberek öngondoskodásának túlhangsúlyozása a szerzők szerint meg nem engedhető optimizmus. /===/ Unfunded and mandatory funded pillars of the Hungarian pension system have been operating simultaneously since 1998. This reform, seen as paradigmatic, has undergone several changes in recent years, designed essentially to alter the pension parameters. Discourse on pension reform has become general again throughout the world. The pension debates in Hungary have focused less on the rising proportion of the elderly than on low employment and eligibility. Contributions to the debate these days are not about the question of an unfunded versus a funded system. The emphasis has repeatedly been on self-provision. The study analyses by means of survey data the extent of the various forms of self-provision. The survey shows that respondents have not typically made decisions of their own on the matter, for which they have limited (and sometimes false) information about the pension system and their life expectancy as pensioners. According to the authors, it is impermissibly optimistic to place excessive emphasis on people’s ability to provide for themselves.

Gazdasági kórkép alulnézetből 2. rész (Syndrome of Hungarian Economy from Bottom-view - part 2.)

A magyar gazdaság új növekedési pályára állása a kilencvenes évek végére tehető, s ebben meghatározó szerepe volt a pótlólagos erőforrásként szolgáló külföldi működőtőke-befektetéseknek. A nemzetközi tőkeáramlás ezredfordulót követő módosulása (csökkenő volumen, változó irányultság) kedvezőtlenül érintette a hazai gazdaságot, aminek egyik következménye a beruházások csökkenése és a növekedési ütem lassulása, másik következménye viszont – a jövedelemkiáramlást semlegesítő hatás elmaradása miatt – a fizetési mérleg romlása. Ebben a helyzetben halaszthatatlanná vált az államháztartási egyensúlyromlás megállítása, illetve a gazdasági fejlődés új alapokra helyezése. A szerző elemzésében – a hazai versenyszektor eredményességi és vagyoni jellemzőinek értékelésével – azt szeretné jelezni, hogy az egyensúlytalansági állapot megszüntetése nem szorítkozhat az államháztartási rendszerre, vagyis az ország helyzetének stabilizálása, majd új növekedési pályára állás nem képzelhető el a gazdaság átfogó modernizációja nélkül. Vizsgálata a ténylegesen működő (343 ezer) hazai társas vállalkozás 2000–2008. évi pénzügyi beszámolóinak adataira épül. Álláspontja szerint a mintavétel nagysága ellensúlyozza az esetleges torzító hatásokat (lásd: helyenként előforduló kreatív beszámolók), így a vállalkozások mennyiségi gyarapodása, méret szerinti megoszlása, a gazdasági tevékenység jellege, a teljesítmények és eredmények alakulása, a vállalkozói vagyon módosulása megbízhatóan értékelhető, illetve a tapasztalatok alapján a korrekciós intézkedések igénye és azok tartalma is jól körvonalazható. Tanulmányát így ajánljuk a téma iránt érdeklődőknek, a versenyszektor szereplőinek, de leginkább a gazdaságpolitika formálóinak. _________ The economic performance during the transition period was characterized by the alternations of fulfilled hopes and unrealized expectations. The economic restructuring and changes in market relations took place during the first decade, while new – mostly foreign – investment groups entered on the new market. As a result the economy was stabilized and was put to a new growth path. But after the millennium the foreign investment based economy development strategy was no more adequate. The new engine for the growth should have been the domestic small and medium enterprise sector (SsME), but despite the subsidies this sector was not strengthened to take this role. The author – the researcher of BCE, and the ex-president of APpEH – analyses the characteristics of the domestic business demography, performance and effectiveness, based on the 2000–2008 annual financial statements of the business sector. In the author’s analysis – with assessment of the domestic business sector and financial performance characteristicst - he would like to point out that the imbalance can not be confined to the elimination of state government system, that is, the country’s situation to stabilize, and then post a new growth path is not conceivable without the modernization of the economy overall. In his view, the sample size outweighed the possible distortionary effects (see occurring in places of creative accounts), so the growth of business volume, size distribution, the nature of economic activity, the evolution of performance and results, a reliable assessment of changes in the business of property and the experience on the basis of the need for corrective action, and its contents are also well delineated. Sstudy it is recommended for those interested in the topic, the business sector actors, but most of the economic policy makers.

Vertical profiles of environmental parameters measured on discrete water samples collected with Niskin bottles at station TARA_085 during the Tara Oceans expedition 2009-2013

The Tara Oceans Expedition (2009-2013) was a global survey of ocean ecosystems aboard the Sailing Vessel Tara. It carried out extensive measurements of evironmental conditions and collected plankton (viruses, bacteria, protists and metazoans) for later analysis using modern sequencing and state-of-the-art imaging technologies. Tara Oceans Data are particularly suited to study the genetic, morphological and functional diversity of plankton. The present data set includes properties of seawater, particulate matter and dissolved matter that were measured from discrete water samples collected with Niskin bottles during the 2009-2013 Tara Oceans expedition. Properties include pigment concentrations from HPLC analysis (10 depths per vertical profile, 25 pigments per depth), the carbonate system (Surface and 400m; pH (total scale), CO2, pCO2, fCO2, HCO3, CO3, Total alkalinity, Total carbon, OmegaAragonite, OmegaCalcite, and dosage Flags), nutrients (10 depths per vertical profile; NO2, PO4, N02/NO3, SI, quality Flags), DOC, CDOM, and dissolved oxygen isotopes. The Service National d'Analyse des Paramètres Océaniques du CO2, at the Université Pierre et Marie Curie, determined CT and AT potentiometrically. More than 200 vertical profiles of these properties were made across the world ocean. DOC, CDOM and dissolved oxygen isotopes are available only for the Arctic Ocean and Arctic Seas (2013).

Conhecimento da doença renal crônica entre médicos conforme as diretrizes práticas

INTRODUCTION: Chronic kidney disease (CKD) is a global health problem, with increasing prevalence in its terminal stage and one of the factors that can contribute is the failure to recognize the disease and its risk factors. OBJECTIVE: To evaluate the knowledge of medical residents (MR) and medical preceptors (MP) in hospitals in the Federal University of Rio Grande do Norte in Natal-RN - Brazil, on the DRC, based on the policy of the Kidney Disease Improving Global Outcomes (KDIGO ). METHODS: Cross-sectional study where 64 MR (R1 = 32; R2 = 15; R3 = 17) and 63 MP answered a questionnaire divided into seven sessions that addressed aspects of the DRC since the setting up referral to a nephrologist. RESULTS: Only 20 participants (15.7%) reported using any guidelines for the management of CKD. The scores obtained by session were: Definition and classification (46.1 ± 47.8); Risk factors (70.5 ± 27.9); Laboratory evaluation (58.2 ± 8.8); Clinical action plan (57.6 ± 19.9); Reduction in proteinuria (68.3 ± 15.0); Complications (64.8 ± 19.9); Referral to a nephrologist (73.0 ± 44.6). There was a statistically significant difference between the knowledge of MR and MP in the sessions: Laboratory evaluation (MR 61.5 ± 8.4 vs 54.8 ± 7.9 MP; p <0.001); Reduction in proteinuria (73.1 ± 11.4 vs MR MP 63.5 ± 16.7; p <0.001) and Referral to a nephrologist (MR 81.2 ± 39.3 vs 64.5 ± 48.2 MP; p = 0.035). Among the MR, the R2 obtained the best score (63.9 ± 22.6 vs R1 R2 R3 71.9 ± 17.2 vs 63.5 ± 22.5, p = 0.445). It identified a low percentage of success of the doctors on the definition of CKD (MP = 46%; R1 = 40.6%; R2 = 60%; R3 = 52.9%; p = 0.623) and classification (MP = 34.9%; R1 = 53.1%, R2 = 60%; R3 = 52.9%; p = 0.158). CONCLUSION: The study showed that most doctors do not use any guidelines for clinical management of CKD and that there are gaps in knowledge on the subject, even among physicians who work in the university environment. In this sense, we propose the realization of mini-workshops for participants and students from boarding UFRN, using Case-Based Learning Strategy (CBL), with small group discussion, to strengthen the incorporation of CKD guidelines in undergraduate teaching and in clinical medical practice in general.

Conhecimento da doença renal crônica entre médicos conforme as diretrizes práticas

INTRODUCTION: Chronic kidney disease (CKD) is a global health problem, with increasing prevalence in its terminal stage and one of the factors that can contribute is the failure to recognize the disease and its risk factors. OBJECTIVE: To evaluate the knowledge of medical residents (MR) and medical preceptors (MP) in hospitals in the Federal University of Rio Grande do Norte in Natal-RN - Brazil, on the DRC, based on the policy of the Kidney Disease Improving Global Outcomes (KDIGO ). METHODS: Cross-sectional study where 64 MR (R1 = 32; R2 = 15; R3 = 17) and 63 MP answered a questionnaire divided into seven sessions that addressed aspects of the DRC since the setting up referral to a nephrologist. RESULTS: Only 20 participants (15.7%) reported using any guidelines for the management of CKD. The scores obtained by session were: Definition and classification (46.1 ± 47.8); Risk factors (70.5 ± 27.9); Laboratory evaluation (58.2 ± 8.8); Clinical action plan (57.6 ± 19.9); Reduction in proteinuria (68.3 ± 15.0); Complications (64.8 ± 19.9); Referral to a nephrologist (73.0 ± 44.6). There was a statistically significant difference between the knowledge of MR and MP in the sessions: Laboratory evaluation (MR 61.5 ± 8.4 vs 54.8 ± 7.9 MP; p <0.001); Reduction in proteinuria (73.1 ± 11.4 vs MR MP 63.5 ± 16.7; p <0.001) and Referral to a nephrologist (MR 81.2 ± 39.3 vs 64.5 ± 48.2 MP; p = 0.035). Among the MR, the R2 obtained the best score (63.9 ± 22.6 vs R1 R2 R3 71.9 ± 17.2 vs 63.5 ± 22.5, p = 0.445). It identified a low percentage of success of the doctors on the definition of CKD (MP = 46%; R1 = 40.6%; R2 = 60%; R3 = 52.9%; p = 0.623) and classification (MP = 34.9%; R1 = 53.1%, R2 = 60%; R3 = 52.9%; p = 0.158). CONCLUSION: The study showed that most doctors do not use any guidelines for clinical management of CKD and that there are gaps in knowledge on the subject, even among physicians who work in the university environment. In this sense, we propose the realization of mini-workshops for participants and students from boarding UFRN, using Case-Based Learning Strategy (CBL), with small group discussion, to strengthen the incorporation of CKD guidelines in undergraduate teaching and in clinical medical practice in general.

The changes in pain which mediate Reductions in fatigue likely reflect central not peripheral mechanisms : Results from the BSRBR-RA

Peer reviewed

The impact of statin use on fetal development:a meta-analysis

INTRODUCTION: Statin use inadvertently during pregnancy and proposed use of statins for the treatment of preeclampsia, led us to question the evidence behind their current contraindicated status. Several studies have evaluated the relationship between statin use in pregnancy with fetal outcome but their results have not been quantitatively assessed by meta-analysis. Our objective was to undertake a systematic review of all published clinical evidence to assess the effects of statin use in pregnancy on subsequent fetal wellbeing. METHODS: A comprehensive search strategy was performed of all electronic databases and the Merck reporting database for studies published from 1966 to 2014. Two reviewers independently screened citations and undertook study quality assessment and data extraction. We obtained summary estimates of adverse fetal events that were classified as potentially fatal, clinically significant morbidity or minor adverse event. We identified 602 titles and reviewed 30 articles for inclusion and exclusion criteria. Meta-analysis was performed on seven studies (3 cohort, 3 case-series and 1 case-control). RESULTS: Of the 922 cases of statin exposure in pregnancy, 27 exposures were associated with lethal or clinically significant fetal morbidity and 10 with minor adverse events. Statin exposure was limited to the first trimester in all but two cases. The pooled rate of lethal or clinically significant fetal abnormalities in pregnant women exposed to statins was 0.01 (95% CI 0.00-0.04), less than the European rate of 0.026 (95% CI 2.54- 2.57)EUROCAT. The rate of fetal abnormality for simvastatin was 0.03 (95% CI 0.00-0.08), atorvostatin 0.11 (95% CI 0.00-0.52), pravastatin 0.01 (95% CI 0.00-0.2) and lovastatin use 0.04 (95% CI 0.00-0.28). Systems based anomalies were also calculated, congenital heart disease was 0.8 (95% CI 0.02-0.12) compared with the background rate of 0.79 (95% CI 0.78- 0.80). CONCLUSIONS: The published data suggests that statins may not be teratogenic when given inadvertently during pregnancy and prospective studies such as The StAmP Trial may provide more data

Young students' use of the internet for mental health information and support

It is recognized that young people experience difficulties in accessing mainstream mental health services particularly because of the stigma that remains associated with mental health problems. One potential solution is to use the many websites available offering information and support for mental health problems, such support and information could be offered by Psychiatric Nurses. However, young peoples' usage and views on using the Internet for this purpose has yet to be examined. This quantitative descriptive study aimed to elicit the views of 922 University students, aged between 18 and 24 years, on using the Internet for mental health information and support. Data were collected using a 30-item self-designed questionnaire and analysed using descriptive statistics. The findings indicated that 72.4% of participants used the Internet several times a day. In addition, 30.8% had previously searched for mental health information online, predominantly on depression. While it was found that 68% of participants indicated that they would use the Internet for mental health support if they needed to, 79.4% would still prefer face to face support. It is concluded that young people are willing to use the Internet for mental health information and that it represents a viable source of support for this age group.

Control of the innate immune response by the mevalonate pathway.

Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-translational modification that is catalyzed by protein geranylgeranyl transferase I (GGTase I). Pyrin is an innate immune sensor that forms an active inflammasome in response to bacterial toxins. Mutations in MEFV (encoding human PYRIN) result in autoinflammatory familial Mediterranean fever syndrome. We found that protein geranylgeranylation enabled Toll-like receptor (TLR)-induced activation of phosphatidylinositol-3-OH kinase (PI(3)K) by promoting the interaction between the small GTPase Kras and the PI(3)K catalytic subunit p110δ. Macrophages that were deficient in GGTase I or p110δ exhibited constitutive release of interleukin 1β that was dependent on MEFV but independent of the NLRP3, AIM2 and NLRC4 inflammasomes. In the absence of protein geranylgeranylation, compromised PI(3)K activity allows an unchecked TLR-induced inflammatory responses and constitutive activation of the Pyrin inflammasome.