Circulating levels of inflammation-associated miR-155 and endothelial-enriched miR-126 in patients with end-stage renal disease

Circulating microRNAs (miRNAs) may represent a potential noninvasive molecular biomarker for various pathological conditions. Moreover, the detection of circulating miRNAs can provide important novel disease-related information. In particular, inflammation-associated miR-155 and endothelial-enriched miR-126 are reported to be associated with vascular homeostasis. Vascular damage is a common event described in end-stage renal disease (ESRD). We hypothesized that miR-155 and miR-126 may be detectable in the circulation and serve as potential biomarkers for risk stratification. In this study, we assessed miR-155 and miR-126 in the plasma of 30 ESRD patients and 20 healthy controls using real-time quantification RT-PCR. The circulating levels of miR-155 and miR-126 were significantly reduced in patients with ESRD compared to healthy controls. However, there was no significant difference of circulating miR-155 and miR-126 levels between prehemodialysis and posthemodialysis patients. Furthermore, both circulating miR-126 and miR-155 correlated positively with estimated glomerular filtration rate (miR-126: r = 0.383, P = 0.037; miR-155: r = 0.494, P = 0.006) and hemoglobin (miR-126: r = 0.515, P = 0.004; miR-155: r = 0.598, P < 0.001) and correlated inversely with phosphate level (miR-126: r = -0.675, P < 0.001; miR-155: r = -0.399, P = 0.029). Pearson’s correlation was used to compare circulating levels of miRNAs with clinical parameters. These results suggested that circulating miR-155 and miR-126 might be involved in the development of ESRD. Further studies are needed to demonstrate the role of circulating miR-155 and miR-126 as candidate biomarkers for risk estimation.

Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

Cocaine/levamisole-induced systemic vasculitis with retiform purpura and pauci-immune glomerulonephritis

Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes.

Thoughts on work-in-progress crowdsourcing metrics of digital collections

The presentation consists of work-in-progress metrics of #digitalkoot, the crowdsourcing project launched by National Library of Finland

Challenges of user-driven innovations on late stages of innovation process: evidence from ICT companies

The goal of this thesis is to study user-driven innovations and user involvement throughout the innovation process in context of B2B companies. Significant emphasis in the analysis put onto the late stages of innovation process and commercialization of innovations. Thesis includes detailed review of theoretical concepts and underlying frameworks of innovation process, lead users and user-driven innovations. The empirical part of the thesis consist of interviews of the four companies from ICT industry, followed by the comprehensive analysis and comparison of the results. The presented findings indicate common challenges, which ICT companies face, when shifting towards innovation by users paradigm. Linkages and connections among current situation and theoretical frameworks presented in the discussion part of the thesis allow to draw practical managerial implications. The results of the research emphasize valuable insights and challenges of user interactions within innovation process as well as output and participation related benefits for the companies and users. The research points out current state of the user involvement techniques and tools used for user interactions as well as suggests the possibilities for improvement in the future.

Skaalautuvan grafiikka- ja käyttöliittymäkirjaston valinta ja hyödyntäminen reaaliaikaisessa web-sovelluksessa

Skaalautuvien web-sivujen merkitys kasvaa nykypäivänä, koska web-sivuja katsotaan hyvin erikokoisilla ja -resoluutiosilla laitteilla. Sivujen skaalautuessa eri laitteille ei tarvitse erikseen tehdä mobiilisivuja tai perinteistä natiivia ohjelmistoa joka laitteelle, vaan yksi sivu toimii kaikilla laitteilla. Ongelmana on saada web-sovellukset toimimaan eri laitteilla, koska laitteiden selaimissa saattaa olla pieni eroja, joiden vuoksi on työlästä saada skaalautuva käyttöliittymä toimimaan kaikilla eri laitteilla. Skaalautuvien sivujen kehittämisen avuksi on luotu erilaisia käyttöliittymä- ja grafiikkakirjastoja, jotka auttavat sivun skaalautuvuuden toteuttamisessa. Kirjastoja käyttämällä säästetään kehitystyöhön käytettävää aikaa ja ulkoistetaan kirjaston ylläpito kolmannelle osapuolelle. Tällöin jää enemmän aikaa varsinaisten sovelluksen kehitystyölle. Tässä työssä tutkitaan eri käyttöliittymä- ja grafiikkakirjastovaihtoehtoja käyttöliittymän toteuttamiseksi. Työssä toteutetaan yksinkertainen verkkoseurantajärjestelmän prototyyppi ja valitaan sille skaalautuva käyttöliittymä- ja grafiikkakirjasto. Järjestelmä koostuu kolmesta osasta: käyttöliittymästä, palvelusta ja tietolähteistä, joista palvelu kerää tietoa käyttöliittymälle näytettäväksi.

Steroid-resistant idiopathic nephrotic syndrome in children: long-term follow-up and risk factors for end-stage renal disease

INTRODUTION: Steroid resistant idiopathic nephrotic syndrome (SRINS) in children is one of the leading causes of progression to chronic kidney disease stage V (CKD V)/end stage renal disease (ESRD). OBJECTIVE: The aim of this retrospective study is to evaluate the efficacy of immunosuppressive drugs (IS) and to identify risk factors for progression to ESRD in this population. METHODS: Clinical and biochemical variables at presentation, early or late steroid resistance, histological pattern and response to cyclosporine A (CsA) and cyclophosfamide (CP) were reviewed in 136 children with SRINS. The analyzed outcome was the progression to ESRD. Univariate as well as multivariate Cox-regression analysis were performed. RESULTS: Median age at onset was 5.54 years (0.67-17.22) and median follow up time was 6.1 years (0.25-30.83). Early steroid-resistance was observed in 114 patients and late resistance in 22. Resistance to CP and CsA was 62.9% and 35% respectively. At last follow-up 57 patients reached ESRD. The renal survival rate was 71.5%, 58.4%, 55.3%, 35.6% and 28.5% at 5, 10, 15, 20 and 25 years respectively. Univariate analysis demonstrated that older age at onset, early steroid-resistance, hematuria, hypertension, focal segmental glomerulosclerosis (FSGS), and resistance to IS were risk factors for ESRD. The Cox proportional-hazards regression identified CsAresistance and FSGS as the only predictors for ESRD. CONCLUSION: Our findings showed that CsA-resistance and FSGS were risk factors for ESRD.

Purple urine bag syndrome in end-stage chronic kidney disease

Introduction: When faced with violet, purple or purplish-blue urine, clinicians should consider urinary tract infection in their differential diagnosis. Case report: A 60-year-old woman with end-stage kidney disease and non-adherence to renal replacement therapy was admitted to our hospital for placement of hemodialysis catheter. During her hospitalization she had purple urine, and purple urine bag syndrome (PUBS) was diagnosed. She was effectively treated with antibiotics and her urine returned to a dark yellow color. Discussion: Although this condition is often easily treated, diagnosing PUBS in chronic renal patients probably means an increased serum concentration of indoxyl sulfate, metabolite that is involved in the progression of both CKD and cardiovascular disease. Conclusion: Hence, in the context of our renal patients, perhaps PUBS is not as benign as supposed.

Erythropoietin resistance in end-stage renal disease patient with gastric antral vascular ectasia

AbstractWe observed a case of recombinant human erythropoietin resistance caused by Gastric Antral Vascular Ectasia in a 40-year-old female with ESRD on hemodialysis. Some associated factors such as autoimmune disease, hemolysis, heart and liver disease were discarded on physical examination and complementary tests. The diagnosis is based on the clinical history and endoscopic appearance of watermelon stomach. The histologic findings are fibromuscular proliferation and capillary ectasia with microvascular thrombosis of the lamina propria. However, these histologic findings are not necessary to confirm the diagnosis. Gastric Antral Vascular Ectasia is a serious condition and should be considered in ESRD patients on hemodialysis with anemia and resistance to recombinant human erythropoietin because GAVE is potentially curable with specific endoscopic treatment method or through surgical procedure.

Erythropoietin resistance in end-stage renal disease patient with gastric antral vascular ectasia

AbstractWe observed a case of recombinant human erythropoietin resistance caused by Gastric Antral Vascular Ectasia in a 40-year-old female with ESRD on hemodialysis. Some associated factors such as autoimmune disease, hemolysis, heart and liver disease were discarded on physical examination and complementary tests. The diagnosis is based on the clinical history and endoscopic appearance of watermelon stomach. The histologic findings are fibromuscular proliferation and capillary ectasia with microvascular thrombosis of the lamina propria. However, these histologic findings are not necessary to confirm the diagnosis. Gastric Antral Vascular Ectasia is a serious condition and should be considered in ESRD patients on hemodialysis with anemia and resistance to recombinant human erythropoietin because GAVE is potentially curable with specific endoscopic treatment method or through surgical procedure.

Modelling of changes in electricity end-use and their impacts on electricity distribution

The electricity distribution sector will face significant changes in the future. Increasing reliability demands will call for major network investments. At the same time, electricity end-use is undergoing profound changes. The changes include future energy technologies and other advances in the field. New technologies such as microgeneration and electric vehicles will have different kinds of impacts on electricity distribution network loads. In addition, smart metering provides more accurate electricity consumption data and opportunities to develop sophisticated load modelling and forecasting approaches. Thus, there are both demands and opportunities to develop a new type of long-term forecasting methodology for electricity distribution. The work concentrates on the technical and economic perspectives of electricity distribution. The doctoral dissertation proposes a methodology to forecast electricity consumption in the distribution networks. The forecasting process consists of a spatial analysis, clustering, end-use modelling, scenarios and simulation methods, and the load forecasts are based on the application of automatic meter reading (AMR) data. The developed long-term forecasting process produces power-based load forecasts. By applying these results, it is possible to forecast the impacts of changes on electrical energy in the network, and further, on the distribution system operator’s revenue. These results are applicable to distribution network and business planning. This doctoral dissertation includes a case study, which tests the forecasting process in practice. For the case study, the most prominent future energy technologies are chosen, and their impacts on the electrical energy and power on the network are analysed. The most relevant topics related to changes in the operating environment, namely energy efficiency, microgeneration, electric vehicles, energy storages and demand response, are discussed in more detail. The study shows that changes in electricity end-use may have radical impacts both on electrical energy and power in the distribution networks and on the distribution revenue. These changes will probably pose challenges for distribution system operators. The study suggests solutions for the distribution system operators on how they can prepare for the changing conditions. It is concluded that a new type of load forecasting methodology is needed, because the previous methods are no longer able to produce adequate forecasts.