Characterization of the main transition of dinervonoylphosphocholine liposomes by fluorescence spectroscopy

AbstractThe structural dynamics of the main phase transition of large unilamellar dinervonoylphosphocholine (DNPC) vesicles was investigated by steady state and time-resolved fluorescence spectroscopy of the membrane incorporated fluorescent lipid analog, 1-palmitoyl-2[10-(pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine (PPDPC). These data were supplemented by differential scanning calorimetry (DSC) and fluorescence anisotropy measured for 1-palmitoyl-2-(3-(diphenylhexatrienyl) propanoyl)-sn-glycero-3-phosphocholine (DPHPC). The collected data displayed several discontinuities in the course of the main transition and the pretransition. The discontinuities seen in the fluorescence properties may require modification of the existing models for phospholipid main transition as a first order process. From our previous study on dipalmitoylphosphocholine (DPPC), we concluded the transition to involve a first-order process resulting in the formation of an intermediate phase, which then converts into the liquid crystalline state by a second order process. Changes in the physical properties of the DNPC matrix influencing probe behavior were similar to those reported previously for PPDPC in DPPC. In gel state DNPC [(T−Tm)<−10] the high values for excimer/monomer emission ratio (Ie/Im) suggest enrichment of the probe in clusters. In this temperature range, excimer fluorescence for PPDPC (mole fraction XPPDPC=0.02) is described by two formation times up to (T−Tm)≈−10, with a gradual disappearance of the fractional intensity (IR1) of the shorter formation time (τR1) with increasing temperature up to (T–Tm)≈−10. This would be consistent with the initiation of the bilayer melting at the PPDPC clusters and the subsequent dispersion of the one population of PPDPC domains. A pronounced decrement in Ie starts at (T–Tm)=−10, continuing until Tm is reached. No decrease was observed in fluorescence quantum yield in contrast to our previous study on DPPC/PPDPC large unilamellar vesicles (LUVs) [J. Phys. Chem., B 107 (2003) 1251], suggesting that a lack of proper hydrophobic mismatch may prevent the formation of the previously reported PPDPC superlattice. With further increase in temperature and starting at (T−Tm)≈−1, Ie, τR2, and excimer decay times (τD) reach plateaus while increment in trans→gauche isomerization continues. This behavior is in keeping with an intermediate phase existing in the temperature range −1<(T−Tm)<4 and transforming into the liquid disordered phase as a second order process, the latter being completed when (T−Tm)→4 and corresponding to ≈50% of the total transition enthalpy

Hormonaalisesti aktiivisen lisämunuaiskasvaimen diagnostiikka ja perioperatiivinen hoito

Lisämunuaiskasvaimen poistoa harkitaan, jos se erittää hormoneja tai sen hyvänlaatuista luonnetta ei pystytä kuvantamalla varmistamaan. Yleensä leikataan myös yli 4 cm:n kokoiset kasvaimet. Hormonaalisesti aktiiviset lisämunuaiskasvaimet voivat erittää adrenaliinia, noradrenaliinia, kortisolia tai aldosteronia. Primaarinen lisämunuaisen kuorikerroksen adrenokortikaalinen karsinooma voi erittää kortisolia tai aldosteronia sekä harvinaisissa tapauksissa myös androgeeneja ja estrogeeneja. Hormonaalisesti aktiivisten lisämunuaiskasvainten leikkaushoitoon liittyy lisääntynyt kirurgisten komplikaatioiden vaara hormonierityksen aiheuttamien hemodynaamisten muutosten ja liitännäissairauksien vuoksi. Lisämunuaiskasvainten huolellinen leikkausta edeltävä selvittely, hormonierityksen vaikutusten hallinta, anestesian aikainen seuranta ja hoito sekä siirtyminen laparo- tai retroperitoneoskooppisiin leikkausmenetelmiin vähentää perioperatiivisia komplikaatioita. Hormonaalisesti aktiivisten lisämunuaiskasvainten leikkaamisesta päätetään moniammatillisessa kokouksessa, ja leikkaukset tekee perioperatiiviseen hoitoon perehtynyt tiimi. Hoidon laatua tulee seurata ja raportoida.publishedVersionPeer reviewe

Genetic testing for familial hypercholesterolemia in a Finnish cohort of patients with premature coronary artery disease and elevated LDL-C levels

BackgroundBased on Finnish LDLR-founder variations, the prevalence of familial hypercholesterolemia (FH) in Finland is estimated to be at least 1:600. Patients with FH have increased risk of premature coronary artery disease (CAD) and thus the prevalence of FH is expected to be higher in this subgroup.ObjectiveTo assess the prevalence of monogenic FH in a Finnish cohort of patients with premature CAD and elevated low-density lipoprotein cholesterol (LDL-C) levels.MethodsAmong 28,295 patients undergoing angiography at Heart Hospital at Tampere University Hospital between 2007 and 2017, we identified 162 patients diagnosed with premature CAD (men aged &lt;55 years and women aged &lt;60 years) and history of high LDL-C (≥5 mmol/L) levels without secondary causes of hypercholesterolemia. Clinical probability of FH was estimated, and genetic testing of FH was carried out in 80 patients with informed consent.ResultsOf the 80 patients with premature CAD and history of high LDL-C levels, 70% were men; the age at diagnosis of CAD for male and female patients was 48 and 53 years, respectively. In total, 58 (73%) patients had probable (n = 54) or definite (n = 4) FH based on Dutch Lipid Clinic Network criteria. A pathogenic variant of FH was found in five (6%) patients. Prevalence of the genetically verified FH was 1:16. The FH variant was found in 75% of patients with definite FH.ConclusionsThe prevalence of genetically verified FH was 1:16 among patients with premature CAD and elevated LDL-C level, which is 38 times higher than the estimated prevalence of 1:600 in the general Finnish population

Spiritual well-being correlates with quality of life of both cancer and non-cancer patients in palliative care - further validation of EORTC QLQ-SWB32 in Finnish

Publisher Copyright: © 2023. The Author(s).BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) has developed the Spiritual Well-being Questionnaire (EORTC QLQ-SWB32), a measure of spiritual well-being validated with people receiving palliative care for cancer, although its usefulness is not restricted to that population. We aimed to translate and validate this tool in Finnish and to study the relationship between spiritual well-being (SWB) and quality of life (QOL). METHODS: A Finnish translation was produced according to the guidelines of EORTC and included forward- and back-translations. Face, content, construct and convergence/divergence validity and reliability were studied in a prospective manner. QOL was assessed with EORTC QLQ-C30 and 15D questionnaires. Sixteen individuals participated in the pilot testing. 101 cancer patients drawn from oncology units, and 89 patients with other chronic diseases drawn from religious communities in different parts of the country participated in the validation stage. Retest was obtained from 16 individuals (8 cancer and 8 non-cancer patients). Inclusion criteria included patients with either a well-defined palliative care plan, or who would benefit from palliative care, as well as the capacity to understand and communicate in Finnish. RESULTS: The translation appeared understandable and acceptable. Factorial analysis identified four scoring scales with high Cronbach alfa values: Relationship with Self (0.73), Relationship with Others (0.84), Relationship with Something Greater (0.82), Existential (0.81), and, additionally, a scale on Relationship with God (0.85). There was a significant correlation between SWB and QOL in all participants. CONCLUSIONS: The Finnish translation of EORTC QLQ-SWB32 is a valid and reliable measure both for research and clinical practice. SWB is correlated with QOL in cancer and non-cancer patients undergoing palliative care or who are eligible for it.Peer reviewe

Antiplatelets versus Anticoagulants for the Treatment of Cervical Artery Dissection: Bayesian Meta-Analysis

Peer reviewe

Type 2 diabetes enhances arterial uptake of choline in atherosclerotic mice: an imaging study with positron emission tomography tracer 18F-fluoromethylcholine

Additional file 1. Supplemental data

Time-resolved fluorescence based direct two-site apoA-I immunoassays and their clinical application in patients with suspected obstructive coronary artery disease

Objective: High-density lipoprotein (HDL) is a heterogeneous group of subpopulations differing in protein/lipid composition and in their anti-atherogenic function. There is a lack of assays that can target the functionality of HDL particles related to atherosclerosis. The objective of this study was to construct two-site apolipoprotein A-I (apoA-I) assays and to evaluate their clinical performance in patients with suspected obstructive coronary artery disease (CAD).Approach and results: Direct two-site apoA-I assays (named 109–121 and 110–525) were developed to identify the presence of apoA-I in the HDL of patients with CAD using apoA-I antibodies as a single-chain variable fragment fused with alkaline phosphatase. ApoA-I109−121 and apoA-I110−525 were measured in 197 patients undergoing coronary computed tomography angiography (CTA) and myocardial positron emission tomography perfusion imaging due to suspected obstructive CAD. Among patients not using lipid-lowering medication (LLM, n = 125), the level of apoA-I110−525 was higher in the presence than in the absence of coronary atherosclerosis [21.88 (15.89–27.44) mg/dl vs. 17.66 (13.38–24.48) mg/dl, P = 0.01)], whereas there was no difference in apoA-I109−121, HDL cholesterol, and apoA-I determined using a polyclonal apoA-I antibody. The levels of apoA-I109−121 and apoA-I110−525 were similar in the presence or absence of obstructive CAD. Among patients not using LLM, apoA-I110−525 adjusted for age and sex identified individuals with coronary atherosclerosis with a similar accuracy to traditional risk factors [area under the curve [AUC] (95% CI): 0.75(0.66–0.84) 0.71 (0.62–0.81)]. However, a combination of apoA-I110−525 with risk factors did not improve the accuracy [AUC (95% CI): 0.73 (0.64–0.82)].Conclusion: Direct two-site apoA-I assays recognizing heterogeneity in reactivity with apoA-I could provide a potential approach to identify individuals at a risk of coronary atherosclerosis. However, their clinical value remains to be studied in larger cohorts.</p

Characteristics and Outcomes of 79 Patients with an Insulinoma : A Nationwide Retrospective Study in Finland

Objective. Insulinomas are rare pancreatic tumours. Population-based data on their incidence, clinical picture, diagnosis, and treatment are almost nonexistent. The aim of this study was to clarify these aspects in a nationwide cohort of insulinoma patients diagnosed during three decades. Design and Methods. Retrospective analysis on all adult patients diagnosed with insulinoma in Finland during 1980-2010. Results. Seventy-nine patients were diagnosed with insulinoma over the research period. The median follow-up from diagnosis to last control visit was one (min 0, max 31) year. The incidence increased from 0.5/million/year in the 1980s to 0.9/million/year in the 2000s (p = 0 002). The median diagnostic delay was 13 months and did not change over the study period. The mean age at diagnosis was 52 (SD 16) years. The overall imaging sensitivity improved from 39% in the 1980s to 98% in the 2000s (p <0 001). Seventy- one (90%) of the patients underwent surgery with a curative aim, two (3%) had palliative surgery, and 6 (8%) were inoperable. There were no significant differences in the types of surgical procedures between the 1980s, 1990s, and 2000s; tumour enucleations comprised 43% of the operations, distal pancreatic resections 45%, and pancreaticoduodenectomies 12%, over the whole study period. Of the patients who underwent surgery with a curative aim, 89% had a full recovery. Postoperative complications occurred in half of the patients, but postoperative mortality was rare. Conclusions. The incidence of insulinomas has increased during the past three decades. Despite the improved diagnostic options, diagnostic delay has remained unchanged. To shorten the delay, clinicians should be informed and alert to consider the possibility of hypoglycemia and insulinoma, when symptomatic attacks are investigated in different sectors of the healthcare system. Developing the surgical treatment is another major target, in order to lower the overall complication rate, without compromising the high cure rate of insulinomas.Peer reviewe

Characteristics and Outcomes of 79 Patients with an Insulinoma: A Nationwide Retrospective Study in Finland

Objective. Insulinomas are rare pancreatic tumours. Population-based data on their incidence, clinical picture, diagnosis, and treatment are almost nonexistent. The aim of this study was to clarify these aspects in a nationwide cohort of insulinoma patients diagnosed during three decades. Design and Methods. Retrospective analysis on all adult patients diagnosed with insulinoma in Finland during 1980-2010. Results. Seventy-nine patients were diagnosed with insulinoma over the research period. The median follow-up from diagnosis to last control visit was one (min 0, max 31) year. The incidence increased from 0.5/million/year in the 1980s to 0.9/million/year in the 2000s (p = 0 002). The median diagnostic delay was 13 months and did not change over the study period. The mean age at diagnosis was 52 (SD 16) years. The overall imaging sensitivity improved from 39% in the 1980s to 98% in the 2000s (p < 0 001). Seventy- one (90%) of the patients underwent surgery with a curative aim, two (3%) had palliative surgery, and 6 (8%) were inoperable. There were no significant differences in the types of surgical procedures between the 1980s, 1990s, and 2000s; tumour enucleations comprised 43% of the operations, distal pancreatic resections 45%, and pancreaticoduodenectomies 12%, over the whole study period. Of the patients who underwent surgery with a curative aim, 89% had a full recovery. Postoperative complications occurred in half of the patients, but postoperative mortality was rare. Conclusions. The incidence of insulinomas has increased during the past three decades. Despite the improved diagnostic options, diagnostic delay has remained unchanged. To shorten the delay, clinicians should be informed and alert to consider the possibility of hypoglycemia and insulinoma, when symptomatic attacks are investigated in different sectors of the healthcare system. Developing the surgical treatment is another major target, in order to lower the overall complication rate, without compromising the high cure rate of insulinomas