Association between bone mineral metabolism and vascular calcification in end-stage renal disease

Background: Development of vascular calcification is accelerated in patients with end-stage renal disease. In addition to traditional risk factors of cardiovascular disease (CVD) abnormal bone and mineral metabolism together with many other factors contribute to the excess cardiovascular burden in patients on dialysis. Aortic calcification score and coronary calcification score are predictive of CVD and mortality. The aim of this study was to evaluate the possible relationship between arterial calcification and bone metabolism.Methods: Thirty two patients on dialysis were included. All patients underwent a bone biopsy to assess bone histomorphometry and a 18F-NaF PET scan. Fluoride activity was measured in the lumbar spine (L1 - L4) and at the anterior iliac crest. Arterial calcification scores were assessed by computerized tomography for quantification of coronary artery calcification score and lateral lumbar radiography for aortic calcification score.Results: This study group showed high prevalence of arterial calcification and 59% had verified CVD. Both CAC and AAC were significantly higher in patients with verified CVD. Only 22% had low turnover bone disease. There was a weak association between fluoride activity, which reflects bone turnover, measured in the lumbar spine, and CAC and between PTH and CAC. There was also a weak association between erosion surfaces and AAC. No significant association was found between calcification score and any other parameter measured.Conclusions: The results in this study highlight the complexity, when evaluating the link between bone remodeling and vascular calcification in patients with multiple comorbidities and extensive atherosclerosis. Several studies suggest an impact of bone turnover on development of arterial calcification and there is some evidence of reduced progression of vascular calcification with improvement in bone status. The present study indicates an association between vascular calcification and bone turnover, even though many parameters of bone turnover failed to show significance. In the presence of multiple other factors contributing to the development of calcification, the impact of bone remodeling might be diminished.</p

Correlation between 18F-Sodium Fluoride positron emission tomography and bone histomorphometry in dialysis patients

BackgroundThe diagnosis of renal osteodystrophy is challenging. Bone biopsy is the gold standard, but it is invasive and limited to one site of the skeleton. The ability of biomarkers to estimate the underlying bone pathology is limited. 18F-Sodium Fluoride positron emission tomography (18F-NaF PET) is a noninvasive quantitative imaging technique that allows assessment of regional bone turnover at clinically relevant sites. The hypothesis of this study was, that 18F-NaF PET correlates with bone histomorphometry in dialysis patients and could act as a noninvasive diagnostic tool in this patient group.MethodsThis was a cross-sectional diagnostic test study. 26 dialysis patients with biochemical abnormalities indicating mineral and bone disorder were included. All the participants underwent a 18F-NaF PET scan and a bone biopsy. Fluoride activity in the PET scan was measured in the lumbar spine and at the anterior iliac crest. Dynamic and static histomorphometric parameters of the bone biopsy were assessed. As histomorphometric markers for bone turnover we used bone formation rate per bone surface (BFR/BS) and activation frequency per year (Ac.f).ResultsThere was a statistically significant correlation between fluoride activity in the 18F-NaF PET scan and histomorphometric parameters such as bone formation rate, activation frequency and osteoclast and osteoblast surfaces and mineralized surfaces. 18F-NaF PET's sensitivity to recognize low turnover in respect to non-low turnover was 76% and specificity 78%. Because of the small number of patients with high turnover, we were unable to demonstrate significant predictive value in this group.ConclusionsA clear correlation between histomorphometric parameters and fluoride activity in the 18F-NaF PET scan was established. 18F-NaF PET may possibly be a noninvasive diagnostic tool in dialysis patients with low turnover bone disease, but further research is needed.</div

Bone Histomorphometry and 18F‑Sodium Fluoride Positron Emission Tomography Imaging: Comparison Between only Bone Turnover-based and Unified TMV-based Classification of Renal Osteodystrophy

Bone biopsy is the gold standard for characterization of renal osteodystrophy (ROD). However, the classification of the subtypes of ROD based on histomorphometric parameters is not unambiguous and the range of normal values for turnover differ in different publications. F-18-Sodium Fluoride positron emission tomography (F-18-NaF PET) is a dynamic imaging technique that measures turnover. F-18-NaF PET has previously been shown to correlate with histomorphometric parameters. In this cross-sectional study, 26 patients on dialysis underwent a F-18-NaF PET and a bone biopsy. Bone turnover-based classification was assessed using Malluche's historical reference values for normal bone turnover. In unified turnover-mineralization-volume (TMV)-based classification, the whole histopathological picture was evaluated and the range for normal turnover was set accordingly. Fluoride activity was measured in the lumbar spine (L1-L4) and at the anterior iliac crest. On the basis of turnover-based classification of ROD, 12% had high turnover and 61% had low turnover bone disease. On the basis of unified TMV-based classification of ROD, 42% had high turnover/hyperparathyroid bone disease and 23% had low turnover/adynamic bone disease. When using unified TMV-based classification of ROD, F-18-NaF PET had an AUC of 0.86 to discriminate hyperparathyroid bone disease from other types of ROD and an AUC of 0.87, for discriminating adynamic bone disease. There was a disproportion between turnover-based classification and unified TMV-based classification. More research is needed to establish normal range of bone turnover in patients with CKD and to establish the role of PET imaging in ROD

Barriers to medication counselling for people with mental health disorders : A six country study

Provision of medication information may improve adherence and prevent medication related problems. People with mental health disorders commonly receive less medication counselling from pharmacists than people with other common long term and persistent disorders. Objective: The objective of this study was to compare and contrast barriers pharmacy students perceive toward providing medication counselling for people with mental health disorders in Australia, Belgium, Estonia, Finland, India and Latvia. Methods: Barriers identified by third-year pharmacy students as part of the International Pharmacy Students' Health Survey were content analysed using a directed approach. Students' responses were categorised as pharmacist related, patient related, health-system related, or social or cultural related. Quantitative data were analysed using SPSS version 14.0. Results: Survey instruments were returned by 649 students. Of the respondents, 480 identified one or more barriers to medication counselling for people with mental health disorders. Patient related factors accounted for between 25.3% and 36.2% of barriers identified by the pharmacy students. Pharmacist related factors accounted for between 17.6% and 45.1% of the barriers identified by the pharmacy students. Students in India were more likely to attribute barriers to pharmacist and social and cultural related factors, and less likely to healthsystem related factors, than students studying in other countries. Conclusion: The nature of barriers identified by pharmacy students differed according to the country in which they studied. Undergraduate and postgraduate pharmacy education programs may need to be amended to address common misconceptions among pharmacy students.publishersversionPeer reviewe

High-Resolution Confocal Fluorescence Imaging of Serine Hydrolase Activity in Cryosections - Application to Glioma Brain Unveils Activity Hotspots Originating from Tumor-Associated Neutrophils

Background Serine hydrolases (SHs) are a functionally diverse family of enzymes playing pivotal roles in health and disease and have emerged as important therapeutic targets in many clinical conditions. Activity-based protein profiling (ABPP) using fluorophosphonate (FP) probes has been a powerful chemoproteomic approach in studies unveiling roles of SHs in various biological systems. ABPP utilizes cell/tissue proteomes and features the FP-warhead, linked to a fluorescent reporter for in-gel fluorescence imaging or a biotin tag for streptavidin enrichment and LC-MS/MS-based target identification. Existing ABPP approaches characterize global SH activity based on mobility in gel or MS-based target identification and cannot reveal the identity of the cell-type responsible for an individual SH activity originating from complex proteomes. Results Here, by using an activity probe with broad reactivity towards the SH family, we advance the ABPP methodology to glioma brain cryosections, enabling for the first time high-resolution confocal fluorescence imaging of global SH activity in the tumor microenvironment. Tumor-associated cell types were identified by extensive immunohistochemistry on activity probe-labeled sections. Tissue-ABPP indicated heightened SH activity in glioma vs. normal brain and unveiled activity hotspots originating from tumor-associated neutrophils (TANs), rather than tumor-associated macrophages (TAMs). Thorough optimization and validation was provided by parallel gel-based ABPP combined with LC-MS/MS-based target verification. Conclusions Our study advances the ABPP methodology to tissue sections, enabling high-resolution confocal fluorescence imaging of global SH activity in anatomically preserved complex native cellular environment. To achieve global portrait of SH activity throughout the section, a probe with broad reactivity towards the SH family members was employed. As ABPP requires no a priori knowledge of the identity of the target, we envisage no imaginable reason why the presently described approach would not work for sections regardless of species and tissue source.Peer reviewe

High-Resolution Confocal Fluorescence Imaging of Serine Hydrolase Activity in Cryosections - Application to Glioma Brain Unveils Activity Hotspots Originating from Tumor-Associated Neutrophils

Background Serine hydrolases (SHs) are a functionally diverse family of enzymes playing pivotal roles in health and disease and have emerged as important therapeutic targets in many clinical conditions. Activity-based protein profiling (ABPP) using fluorophosphonate (FP) probes has been a powerful chemoproteomic approach in studies unveiling roles of SHs in various biological systems. ABPP utilizes cell/tissue proteomes and features the FP-warhead, linked to a fluorescent reporter for in-gel fluorescence imaging or a biotin tag for streptavidin enrichment and LC-MS/MS-based target identification. Existing ABPP approaches characterize global SH activity based on mobility in gel or MS-based target identification and cannot reveal the identity of the cell-type responsible for an individual SH activity originating from complex proteomes. Results Here, by using an activity probe with broad reactivity towards the SH family, we advance the ABPP methodology to glioma brain cryosections, enabling for the first time high-resolution confocal fluorescence imaging of global SH activity in the tumor microenvironment. Tumor-associated cell types were identified by extensive immunohistochemistry on activity probe-labeled sections. Tissue-ABPP indicated heightened SH activity in glioma vs. normal brain and unveiled activity hotspots originating from tumor-associated neutrophils (TANs), rather than tumor-associated macrophages (TAMs). Thorough optimization and validation was provided by parallel gel-based ABPP combined with LC-MS/MS-based target verification. Conclusions Our study advances the ABPP methodology to tissue sections, enabling high-resolution confocal fluorescence imaging of global SH activity in anatomically preserved complex native cellular environment. To achieve global portrait of SH activity throughout the section, a probe with broad reactivity towards the SH family members was employed. As ABPP requires no a priori knowledge of the identity of the target, we envisage no imaginable reason why the presently described approach would not work for sections regardless of species and tissue source.Peer reviewe

Perehdytyskansio Finnair Shop-myymälälle

Tämä opinnäytetyö on toiminnallinen kehittämisprojekti, jonka toimeksiantaja on Finnair Catering Oy. Työn tavoitteena oli tuottaa perehdytyskansio Helsinki-Vantaan lentoasemalla toimivien Tax Free Shop-myymälöiden uusille työntekijöille. Perehdytyskansion sisältö koostuu perehdytysoppaasta sekä perehdytyksen tarkistuslis-tasta. Koska perehdyttäminen perustuu vuorovaikutteisuuteen, haluttiin kansioon lisätä myös perehdyttämisen palautelomake, jossa työntekijät arvioivat omaa perehdyttämis-tään sekä siihen liittyviä toimintoja. Palautteista saadun tiedon avulla koko perehdyttämisprosessia voidaan kehittää edelleen. Projektin tavoitteena oli myymälän perehdyttämisen yhtenäistäminen, laadun paranta-minen sekä oppimisen seuranta, jonka perusteella perehdytysprosessia on mahdollista kehittää. Työn viitekehys sisältää perehdytystä sekä työnopastusta koskevaa syventävää tietoa, johon koko projektin toteuttaminen pohjautuu. Itse perehdytysprosessia on pyritty tar-kastelemaan toimialakohtaisesta näkökulmasta. Empiiriseen osioon on koottu kappaleita koskien tiedonkeruuta sekä selvitys koko hankkeen toteutuksesta, työn suunnittelusta lopputulokseen. Projektille asetetut tavoitteet savutettiin ja projektin tuotos, perehdytyskansio, otettiin käyttöön Finnair Shop-myymälöissä syksyllä 2011. Perehdytyskansion voidaan katsoa parantaneen myymälän perehdyttämisen laatua. Opinnäytetyöhön ei voitu liittää produktia, perehdytyskansiota, sen sisältämän salaisena pidettävän tiedon vuoksi.This Bachelor’s thesis is a practice- based development project commissioned by Fin-nair Catering Oy. The objective was to produce an initiation folder for new employees of the Finnair Shop which operates at the airport of Helsinki-Vantaa. The initiation folder consists of the initiation guidebook and the checklist of initiation. Because initiation is based on interaction, the feedback form of the initiation was also added. In the feedback form the employees are asked to estimate their own initiation process and functions which are related to it. The information received of the feedback can be used to further develop of the whole process. The objective of this project was to unify the initiation of the Finnair Shop as well as to improve the quality and the follow-up of the learning. The realization of the whole project is based on the theoretical framework which con-tains information on initiation and work guidance. The aim was to examine the orientation process from a branch-specific point of view. The empirical section includes data of collecting the information and the analysis of the implementation of the whole project. The objectives set for this project were ac-hieved and the output of the project, the initiation folder, was taken into use in the autumn 2011 in the Finnair Shop. The initiation folder can be considered to have im-proved the quality of the initiation of the Finnair shop. It was not possible to enclose the product of the project itself, the initiation folder, because it contains confidential information

Judon ogoshi- lonkkaheiton voimantuoton ymmärtäminen ja heittovoiman kehittäminen

Opinnäytetyö lähestyy judon ogoshi- lonkkaheittoa Vierumäellä vuonna 2013 tehdyn taitolajien liikeanalyysin kautta. Analysoitava lonkkaheitto toteutettiin Makikomi- tek-niikkana, jossa heittäjä tulee heiton mukana mattoon asti (Marwood 1992, 96-97). Opinnäytetyön tavoitteena on ymmärtää ogoshi- lonkkaheiton voimantuottoa. Kun ymmärretään millaisista osatekijöistä heitto rakentuu, ja mistä siihen tarvittava voima aikaansaadaan, pystytään heittoa kehittämään tehokkaammaksi. Opinnäytetyön teoreettisena viitekehyksenä toimivat fysiikan lait, biomekaniikka ja kansainväliset judotutkimukset. Tutkimusten ja kirjallisuuden perusteella selvisi, että judo vaatii harrastajaltaan paljon voima-, nopeus- ja kestävyysominaisuuksia: ylävartalon voima on otetaistelusta johtuen pääasiassa isometristä ja jalkojen voimantuotto dynaamista. Tutkimusten perusteella voidaan myös päätellä ogoshin tuottavan sekä vaativan heittäjältä paljon voimaa, joten se todennäköisesti suosii voimakkaita heittäjiä. Jotta ogoshi tapahtuisi räjähtävästi, on myös heiton horjutuksessa tapahtuvan käsivedon tapahduttava räjähtävällä ja suurella voimalla (uken eli heitettävän vauhti saattaa harai-goshi- lonkkaheiton horjutuksessa kiihtyä jopa liki 53 (kgxm)/s). Biomekaanisesti tarkasteltuna ogoshi- luokitellaan viputekniikka- ryhmään, jossa lonkka toimii vipuna. Ogoshi- lonkkaheiton onnistuminen edellyttää, että torin eli heittäjän tukipiste on siirryttävä uken eli heitettävän vyötärön alapuolelle. Näin heittossa tarvitaan myös liikkuvuutta sekä jalkojen voimaa, etenkin etureisien lihaksista ja lonkkanivelen ojentajalihaksista. Heitettävän tukipisteen alle pääseminen suosii mahdollisesti lyhyitä heittäjiä. Heiton aikana myös selän ja keskivartalon tulee pysyä jännityksessä, kuten painonnostoliikkeissä. Se mitä harjoitellaan kehittyy – voimaa hankitaan nimenomaan lajisuoritusta varten (Keränen 2006). Valmennuksen haasteena on kehittää voimaominaisuuksia siten, että ne siirtyisivät mahdollisimman hyvin lajisuoritukseen (Mero, Nummela, Keskinen & Häkkinen 2004, 251). Työn lopussa olevat harjoitusliikkeet on suunniteltu kehittämään torin valmiuksia tehdä ogoshi- lonkkaheitto tehokkaammin; työskentelevät lihakset, liikkeiden nivelkulmat ja voimantuottosuunnat ovat heiton kanssa saman suuntaiset