Erősítik-e a társadalmi kirekesztést a smart cityk?

A fejlesztéspolitikában ma a „smart” címkével minden vonzóbb, eladhatóbb, a kifejezés sokszor a ’környezet- barát’ vagy ’fenntartható’ szinonimájaként is használa- tos. A városfejlesztésben az utóbbi idők egyik legfel- kapottabb paradigmája, globális szintű versengést in- dítva mind a városok, mind az érdekelt vállalatok között a kölcsönösen hasznosnak vélt előnyök reményében. A szerzők egyrészt annak jártak utána, miért éppen most virágzott fel a smart city mint fejlesztési paradigma, és milyen tényezők indukálták gyors előretörését. Más- részt a nemzetközi példák bemutatásán keresztül arra a kérdésre keresik a választ, milyen társadalmi hatásokkal járnak ezek a fejlesztések, milyen kihívásokkal kell szembenézni a smart city fejlesztések kapcsán, és vajon a jövőben a fejlesztési szereplők képesek lesznek-e ta- nulni hibáikból, és tudatosan tervezni a hatások összes- ségével

OVERALL CHARACTERISTICS AND EARLY DIAGNOSIS OF PATIENTS WITH CONNECTIVE TISSUE DISEASES

Najvažnije pitanje sustavnih autoimunih bolesti jest rano prepoznavanje i rano dugotrajno liječenje. U nekim bolestima, uključujući reumatoidni artritis i sistemsku sklerozu, novi revidirani kriteriji mogu pomoći identificirati bolest što je prije moguće. Nakon postavljanja dijagnoze važno je „liječenje prema cilju”. Potrebni su dodatni napori za poboljšanje zasad dostupnih indeksa aktivnosti/oštećenja i mjera ishoda u ovim bolestima, a napose bolji složeni indeksi aktivnosti koji se čine nužnima u budućnosti. Ključno je rano prepoznati tipične simptome i znakove bolesti. Ove su bolesti obično praćene stalnim ili povremenim znakovima upale koja često nastupa u valovima. Najčešći simptomi sustavnih autoimunih bolesti uključuju poliartritis, Raynaudov fenomen, upalne i neupalne simptome kože, „sicca” sindrom (suhe oči, suha usta), plućnu hipertenziju / fibrozu pluća, različite simptome središnjega i perifernoga živčanog sustava te simetričnu slabost i bol proksimalne muskulature. Osim toga, u spektar ovih specifičnih poremećaja pripadaju i proteinurija, hematurija te ponavljajući pleuritis/perikarditis. Simptomi tipični za antifosfolipidni sindrom (ponavljajući trombo-embolijski događaji, fetalni morbiditet i prisutnost antifosfolipidnih protutijela) mogu također biti obilježja ovih poremećaja. Rijetki nalazi uključuju stalne simptome središnjega i perifernoga živčanog sustava, leukopeniju i plućnu hipertenziju. Stoga je ključno rano prepoznati „neobične” kombinacije organskih simptoma.The most important issue in regard to systemic autoimmune diseases is early recognition and early, long-term treatment. In certain disorders, including rheumatoid arthritis and systemic sclerosis, the revised new classification criteria help to identify the cases as early as possible. Once the diagnosis has been established, a “treat-to-target” approach is important. Further work is required to improve the currently available activity damage indexes and outcome measures in these particular disorders; in particular, better composite activity indexes seem to be necessary for the future. Early recognition of the typical symptoms and signs of these particular diseases is crucial. These disorders are usually accompanied by permanent or temporary inflammatory signs, and the inflammation often occurs in waves. The most frequent symptoms of systemic autoimmune disorders include polyarthritis, Raynaud phenomenon, inflammatory and non-inflammatory skin symptoms, sicca syndrome (dry eyes, dry mouth), pulmonary arterial hypertension/lung fibrosis, a variety of central and peripheral nervous system-related symptoms, and symmetric proximal muscle weakness and pain. Furthermore, proteinuria, hematuria, and recurrent pleuritis/pericarditis also belong to the disease spectrum of these disorders. Symptoms representing antiphospholipid syndrome (recurrent thrombo-embolic events, fetal morbidity, and presence of antiphospholipid autoantibodies) can also be typical contributors. There are further rare findings, including persistent peripheral/central nervous system-related symptoms, leukopenia, and pulmonary arterial hypertension. The early recognition of “unusual” associations of organ symptoms is a crucial point

Real-world evidence on methotrexate-free subcutaneous tocilizumab therapy in patients with rheumatoid arthritis : 24-week data from the SIMPACT study

The aim of the SIMPACT study was to evaluate the efficacy and safety of MTX-free s.c. tocilizumab (TCZ) therapy in RA patients.SIMPACT was an open-label, non-controlled, non-randomized, non-interventional study, in which RA patients for whom the treating physicians ordered s.c. TCZ were observed during a 24-week treatment period in Hungarian centres. Although the use of MTX was avoided during the study period, other conventional synthetic DMARDs, oral CSs and NSAIDs were allowed. Study endpoints included the change in DAS28 and clinical activity index (CDAI) scores, the proportion of patients achieving remission in the whole population and in subgroups defined based on prior RA treatment history, and age, weight or biological sex post hoc. The extent of supplementary medication use was monitored.Three hundred and thirty-seven RA patients were enrolled in 18 study centres. TCZ therapy significantly decreased the disease activity measured by both DAS28 (P = 0.0001) and CDAI (P = 0.0001). Clinical response was more pronounced in biologic-naïve patients and was lower in patients >75 years of age. In the whole population, DAS28 ESR or CRP and CDAI remission rates were 70.10%, 78.95% and 33.59%, respectively. In patients <45 years of age, the CDAI remission rate doubled (67.86%). A significant decrease in the frequency of co-administered medication was reported, including oral CSs and DMARDs.Real-world clinical evidence on s.c. TCZ reported here is in line with the efficacy outcomes of randomized clinical trials. Subgroup analysis revealed that TCZ was more effective in biologic-naïve patients and in those <75 years old.ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT02402686

SURVIVAL AND SUBSET CLASSIFICATION ANALYSIS OF 82 PATIENTS WITH INFLAMMATORY MYOPATHY

Background: Idiopathic inflammatory myopathies (IIM) are characterised by chronic muscle inflammation, various organ involvements and the presence of certain specific autoantibodies. Objectives: We assessed survival and characterized subsets based on muscle biopsy and myositis specific autoantibodies (MSAs). Methods: Eighty-two patients with muscle biopsy proven IIM were included in the study. All cases had MSA and myositis associated antibody (MAA) tests (Jo-1, PL-7, PL-12, Mi-2, SRP, Pm-Scl, Ku, ribosomal, AMA-M2) using Western-blot kits. Survival analysis was performed by Kaplan Meier test. Results: Fift y-nine women and 23 men with a mean age of 49.3 ± 14.6 years and with 7.5 ± 4.5 years of mean follow-up time were included. Interstitial lung disease (ILD) (51.2%), arthritis (51.2%), Raynaud’s phenomenon (42.7%), skin symptoms (45.1%), dysphagia (24.4%) and significant cardiac involvement (15.9%) were the most prevalent disease manifestations. 15 cases were associated with malignancies. Myositis subsets were as follow: 26.8% (n=22) polymyositis /PM/, 30.5% (n=25) dermatomyositis/DM/, 1.2% (n=1) juvenile PM/DM, 8.5% (n=7) inclusion body myositis /IBM/, 22% (n=18) overlap myositis /OM/, and 11% (n=9) immune mediated necrotizing myopathy /IMNM/. Malignancy was most frequently associated with IMNM (7 out of 9 patients). Altogether 18 patients died from which 15 deaths can be connected to myositis related events. Eight patients died of malignancies, 5 patients due to cardiac events (heart failure, arrythmia), 2 due to lung fibrosis and 3 by unknown causes. The worst prognosis with a 10-year survival of 31 % was in the IMNM subgroup (p<0.01), followed by patients with PM (68%), IBM (84%) OM (85.1%) and DM (85.3%). Mi-2 positive patients had a favourable prognosis with a 10-year survival of 100%. Patients with IMNM had the worst prognosis (10-year survival of 31.1%), followed by PM (76%), DM and IBM (85.7% each). Patients with antisynthetase antibody-positivity had worse prognosis compared to patients with other antibodies or no identifiable antibodies (10-year survival of 55%, n=16) (p<0.05). Conclusions: Th e worst survivals were seen in the IMNM and PM groups, due to the high frequency of the underlying malignancies and cardiac manifestations. Although ILD was the most frequent involvement, it was not the main cause of death

Serological and Genetic Evidence for Altered Complement System Functionality in Systemic Lupus Erythematosus: Findings of the GAPAID Consortium.

Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption we examined ex vivo immune complex formation on autoantigen arrays. We recruited patients with SLE (n = 211), with other systemic autoimmune diseases (n = 65) and non-autoimmune control subjects (n = 149). Standard clinical and laboratory data were collected and serum complement levels were determined. The genotype of SNP rs1143679 in the ITGAM gene was also determined. Ex vivo formation of immune complexes, with respect to IgM, IgG, complement C4 and C3 binding, was examined using a functional immunoassay on autoantigen microarray comprising nucleic acids, proteins and lipids. Complement consumption of nucleic acids increased upon binding of IgM and IgG even when serum complement levels were decreased due to consumption in SLE patients. A negative correlation between serum complement levels and ex vivo complement deposition on nucleic acid autoantigens is demonstrated. On the contrary, complement deposition on tested protein and lipid autoantigens showed positive correlation with C4 levels. Genetic analysis revealed that the non-synonymous variant rs1143679 in complement receptor type 3 is associated with an increased production of anti-dsDNA IgG antibodies. Notwithstanding, homozygous carriers of the previously reported susceptible allele (AA) had lower levels of dsDNA specific IgM among SLE patients. Both the non-synonymous variant rs1143679 and the high ratio of nucleic acid specific IgG/IgM were associated with multiple organ involvement. In summary, secondary complement deficiency in SLE does not impair opsonization of nucleic-acid-containing autoantigens but does affect other antigens and potentially other complement dependent processes. Dysfunction of the receptor recognizing complement opsonized immune complexes promotes the development of class-switched autoantibodies targeting nucleic acids

Klinikai - immunológiai vizsgálatok szisztémás autoimmun kórképekben = Clinical-epidemiological studies in systemic autoimmune diseases

Klinikai - immunológiai vizsgálatok szisztémás autoimmun kórképekben Czirják László A populációs alapú vizsgálatainkat lezártuk, és a szisztémás sclerosis, Raynaud jelenség illetve rheumatoid arthritis prevalencia értékeit publikáltuk. A michrochimérismus vizsgálataink nem zárultak interpretálható eredményekkel. Megjegyzendő, hogy más nemzetközi munkacsoportoknak is problámát okozott a kimutathatósági határon levő vizsgálat reprodukálható elvégzése. Az indukált köpet vizsgálat nem bizonyult reprodukálhatónak. Más, alternatív módszert (surfactans D, KL-6) használunk a tüdőmanifesztáció vizsgálatára illetve követésére. Alapmunkánkat közlésre elfogadták, követéses vizsgálatunk publikálása folyamatban van. A hosszutávú követéses vizsgálataink eredményeit szisztémás sclerosisban publikáltuk, kimutattuk, hogy rossz prognozissal jár a papaneopláziás szindróma formájában jelentkező systemás sclerosis. Emellett kidolgoztunk és validáltunk egy a bőrfolyamat aktivitását mérő beteg önkitöltő kérdőívet. Az aktivitás vizsgálatához szükséges kérdőíveket (scleroderma-HAQ, DASH) magyar nyelven validáltuk. Az európai scleroderma aktivitási kritériumok validálása és egy új aktivitási kritériumrendszer kialakítása folyamatban van, már rendelkezésre áll egy igen nagyszámú betegből álló egyéves követéses vizsgálat adatsora (1. sz. melléklet). Gyulladásos izombetegségekben a prógnózist vizsgáló munkánat szintén lezártuk. | Clinical epidemiological studies on systemic autoimmune diseases We have finished our population-based studies on the prevalence of connective tissue diseases. With regard to rheumatoid arthritis, Raynaud?s phenomenon and systemic sclerosis we have published our results. Investigation of microchimesism in systemic sclerosis did not give conclusive results, we had detectability problems with this particular method, similar to other groups . The induced sputum investigations did not show reproducible results therefore we worked out other alternative methods for the evaluation of interstitial lung involvement in connective tissue diseases. Detection of surfactant D and KL-6 markers are good surrogate markers for the severity of lung disease. Our long term follow up studies on systemic sclerosis indicated that the presence of paraneoplastic syndrome and gastric antral ectasia (watermelon stomach) are poor prognostic signs besides the well known organ manifestations in systemic sclerosis. We worked out and validated a patient self assessment questionnaire measuring the skin thickness of scleroderma patients. We have also completed our clinical epidemiological studies on inflammatory myopathies. The presence of cancer associated myositis caused a poor prognosis. Conversely, interstitial lung disease did not cause an unfavourable prognosis in our cohort

Szisztémás autoimmun betegségek pulmonális érintettségének klinikai és laboratóriumi vizsgálata = Clinical and laboratory investigation of the pulmonary manifestation of systemic autoimmune diseases

Systemás sclerosis (SSc) tüdőérintettsége alapvető hatású a betegség kimenetelére. Szérumban is mérhető anyagok - mint pl. a KL-6 - jelentőségét vizsgáltuk a PF-ra nézve. A KL-6 PF-ra vonatkoztatott szenzitivitása emelkedő értéket mutatott a PF súlyosságának fokozódásával. Sok olyan beteg is volt, akinél a PF ellenére normál KL-6 szintet mértünk, azaz a szérummarkerek nem helyettesítik a konvencionális módszereket. Prospektív vizsgálatunk elején mért KL-6 szintek szignifikánsan magasabbak voltak azokban, akik később elhunytak, mint akik életben maradtak. A követés során mért KL-6 változás nem jelezte a PF súlyosságában bekövetkezett változásokat. A módosított Rodnan-féle bőrpontszámot tartják a legalkalmazhatóbb vizsgálati módszernek a bőrérintettség vizsgálatára. Alternatív módszer kifejlesztése fontos. Az általunk kialakított önkitöltős betegkérdőív validálhatóan alkalmasnak bizonyult a bőrfolyamat megítélésére. Az ún. European Scleroderma Study Group aktivitási index kellően jó validitásúnak mutatkozott vizsgálatunkban, azonban nem tükrözte megfelelően a tüdőérintettség állapotát. Egy új 12 pontos aktivitási indexet alakítottunk ki (a FVC/DLCO, DLCO-változás, bőrfekély-változás, a HAQ-DI és az új önkitöltős bőrpontszám hozzáadásával). Az új index szorosabb összefüggést mutatott a tüdőfolyamattal, mint az eredeti. Különböző biomarkerek, mint pl. a KL-6 hozzáadása az új indexhez azonban nem javította az index használhatóságát. | Lung involvement plays an important role in the outcome of systemic sclerosis (SSc). We investigated the notability of distinct serum markers, such as KL-6 in characterization of lung involvement. The sensitivity of KL-6 for pulmonary fibrosis (PF) is increased with the severity of PF. Significant number of patients with PF had normal level of these markers; therefore we conclude that the use of these markers can not replace the conventional techniques. In our prospective study, we measured significantly higher initial serum levels of KL-6 in patients who died than in survivors. However, any change of serum level of KL-6 during the follow up not predicts the alteration of severity of PF. The modified Rodnan skin score (mRSS) is considered the most appropriate technique for measuring skin involvement. There is a need for an alternative method. We established and validated a patient self assessment questionnaire for the evaluation of skin thickening in SSc. The validity of the European Scleroderma Study Group (EScSG) activity index is good, though the lung-related disease activity may not be sufficiently represented. We constructed a 12 point activity index (by adding the FVC/DLCO, change in DLCO, change in the ulcer scores, HAQ-DI and our new patient reported skin score), which showed closer correlation with lung involvement. Biomarkers - including KL-6 - were related to both the EScSG and the 12 point index, though they did not improve the total variance of the model

A szeronegatív spondylarthritisek és a szisztémás kötőszöveti betegségek gastrointestinalis vonatkozásai = Gastrointestinal involvement of spondylarthropathies and systemic connective tissue disorders

A szisztémás autoimmun betegségek gyomor-bélrendszeri érintettségére vonatkozóan 3 kiemelt területen végeztünk kutatásokat: (1.) kísérletes állatmodellben a gastrointestinum különböző funkcióinak regulációjában részt vevő citokinek és neuropeptidek szerepe, (2.) a szeronegatív spondylarthritisek kialakulásában szerepet játszó genetikai jellegzetességek és (3.) a kötőszöveti betegségek (primer Sjögren szindróma és szisztémás sclerosis) gasztrointesztinális manifesztációinak vizsgálata Eredmények: (1.) Az interferon-α, amely egy hatékony antivirális és tumorellenes citokin, mind intravenásan, mind intracysternálisan adva csökkenti a gyomorszekréciót. A gyomorszekréciót gátló hatás kialakulása nitrogén monoxid felszabadulásán keresztül történik, és a központi idegrendszeri CRF ( 2-es típusú) receptort is magába foglalja. (2.) Crohn betegségben a CARD15/NOD2 intracelluláris receptor fehérjék polimorfizmusánakvizsgálata során azt találtuk, hogy a betegek 33.78 %ában van jelen a NOD2/CARD15 mutációja a control populációban észlelt 16.23 %-hoz képest. Arthropathia psoriaticaban szenvedő betegeknél ezeknek a géneknek a polymorphismusa nem játszik szerepet. (3.) Primer Sjögren szindrómában a májenzimek a beteget 20%-ában mutattak eltérés, 8 %-a autoimmun májbetegséghez kapcsolódik. A májenzim eltérésben szenvedő betegeknél a betegség korábbi életkorban jelentkezik, és gyakrabban van polyarthritisük. | Connective tisue diseases involve gastrointestinal tract. The major aims of our investigations were: (1.) examination of the role of different cytokines and neuropeptides in thr regulation of different functions of the gastrointestinal tract, (2.) genetic predisposition of and the role of mucosal integrity of seronegative spondylarthropathies, and (3.) gastrointestinal manifestations of connective tissuse diseases: liver involvement of primary Sjögren?s syndrome and disturbed gastrointestinal motility of systemic sclerosis. Results: (1.) Interferon-?, a potent antiviral and antitumor cytokine given intravenously and intracisternally decreases gastric secretion. The inhibition of gastric secretion involves nitrogen monoxide and central CRF type-2 receptors. (2.) CARD/15NOD2 polymorphism is present in 33.78 % of patient suffernig from Crohn?s disease. The presence of psoriatic arthritis is not associated with polkymorphism of CARD15/NOD2 proteins. (3.) Primary Sjögren?s syndrome is accompanied by elevation of liver enzymes in 20 % of patients. 8% of liver enzyme disturbences is duo to autoimmune liever diseases: autoimmune hepatitis or primary biliary cirrhosis. Patients having elevated liver enzymes show an early onset of disease and have polyarthritis much frequently in comparison with those having normal liver enzymes

Improved Calcium Homeostasis and Force by Selenium Treatment and Training in Aged Mouse Skeletal Muscle

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