Hammasperäiset bakteerit aivoinfarktipotilaiden aivoveritulpissa

Aivoverenkiertohäiriö on huomattava työvuosien sekä itsenäisen toimintakyvyn menetyksen aiheuttaja. Suomessa 18 000 ihmistä sairastuu aivoinfarktiin vuosittain. Infektion ja kroonisen inflammaation merkitystä akuutin iskeemisen aivoinfarktin synnyssä on korostettu viime vuosina, erityisesti hammasbakteereilla on arveltu olevan roolia sairauden kehittymisessä. Parodontaalisairauksien ja huonon hammashygienian on pitkäaikaistutkimuksissa näytetty provosoivan kardiovaskulaari- ja aivoverenkiertohäiriösairauksien syntyä. Mittasimme bakteeriperäisen DNA:n pitoisuudet mekaanisella trombektomialla hoidettujen aivoverenkiertohäiriöpotilaiden aspiroiduista aivoveritulpista. Näytemateriaalina oli käytettävissä aivoveritulpat ja valtimoverinäytteet 75 aivoinfarktipotilaalta (69% miehiä; ikämediaani 67 vuotta), joista eristettiin humaani- ja bakteeriperäinen DNA. Kvantitatiivisellä PCR:a selvitettiin Streptococcus spp., (lähinnä S. mitis ryhmä), Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans ja muiden bakteerien pitoisuudet näytteissä. Bakteeri DNA:n suhteellinen osuus laskettiin vertailemalla veritulpan ja valtimoverinäytteen bakteeripitoisuuksia (comparative Ct method). Positiivisiksi tuloksiksi katsottiin näytteet, joiden N-kertaiset arvot olivat yli 2,0. Bakteeriperäistä DNA:ta löytyi 84% (n=63) veritulpista ja 16% (n=12) näytteistä olivat negatiivisia. Streptococcus spp. (lähinnä S. mitis ryhmä) löytyi 79% (n=59) näytteistä. Streptococcus spp. (lähinnä S. mitis ryhmä) suhteellinen osuus oli 5,10-kertainen verrattuna valtimoverinäytteisiin. Veritulpista ei löytynyt Porphyromonas gingivalis tai Aggregatibacter actinomycetemcomitans bakteerien DNA:ta. Tämä on ensimmäinen tutkimus, joka näyttää odontogeenisten bakteerien olemassaolon aivoveritulpissa. Hammasperäisillä bakteereilla saattaa olla huomattava rooli veritulpan kehittymisessä

Market innovation: A literature review and new research directions

Over the past three decades, a rapidly expanding academic literature has investigated how new markets are created and how existing markets are transformed, phenomena this article refers to as “market innovation”. The literature on market innovation is currently fragmented and characterized by heterogeneity of terminology, theoretical paradigms, and empirical research settings. The purpose of this article is to map the field, identify distinct research clusters, and uncover shifts in the literature’s underpinning conceptual perspectives. Specifically, using bibliometric mapping, the article identifies six clusters of market innovation research. Further analysis reveals three major shifts in the literature over time: (1) a shift from reductionism to emergence, (2) a shift from central agency to distributed agency, and (3) a shift from linearity to non-linearity. To advance the understanding of all three shifts and move theory development forward, complexity theory offers a valuable meta-theoretical framework. Future research directions are derived from complexity theory

Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms

Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, n(effective) = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (vertical bar r(g)vertical bar > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range vertical bar r(g)vertical bar = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.Peer reviewe

C-reactive Protein and Temperament: An Instrumental Variable Analysis

BACKGROUND: Temperament is associated with circulating inflammatory biomarkers, such as C-reactive protein (CRP), which has been associated with various health conditions, including depression. This study aims to investigate whether genetic disposition for increased circulating CRP concentration may influence temperament over the life-course. METHODS: Using a longitudinal cohort that began in 1980—the Cardiovascular Risk in Young Finns Study (YFS)—we included 920 participants (59.8% female) aged 3–12 years old at baseline (childhood), and the same participants again at ages 30–39 years old (adulthood) in this study. We used both ordinary least-squares regression (OLS linear regression) and instrumental variable (IV) regression to assess associations between CRP concentration and temperament dimensions (negative emotionality, activity, and sociability). To represent genetically determined risk for increase in circulating CRP concentration, we calculated a weighted genetic risk score (GRS) which reflects risk for increased circulating CRP concentration. RESULTS: In OLS linear regression analyses, we found that increased circulating CRP concentration in childhood was associated with slightly higher scores for sociability in childhood (19% increase, CI ​= ​7–32%) and adulthood (13% increase, CI ​= ​2–27%), and lower activity scores in adulthood (15% decrease, CI ​= ​3–25%). For all IV regressions, there were no apparent associations between GRS and temperament in either childhood or adulthood (all p>0.3). The Durbin-Wu-Hausman test for endogeneity produced p-values (all>0.05) that suggest there is no evidence for disagreement between the OLS and IV estimates. CONCLUSIONS: We found no clear evidence for an association of GRS for elevated CRP with childhood or adulthood emotionality, activity, or sociability, although circulating CRP was associated with some of these traits

C-reactive protein and temperament: An instrumental variable analysis

Cited by: 0; All Open Access, Gold Open Access, Green Open AccessPeer reviewe

Cranioplasty with Adipose-Derived Stem Cells, Beta-Tricalcium Phosphate Granules and Supporting Mesh : Six-Year Clinical Follow-Up Results

Several alternative techniques exist to reconstruct skull defects. The complication rate of the cranioplasty procedure is high and the search for optimal materials and techniques continues. To report long-term results of patients who have received a cranioplasty using autologous adipose-derived stem cells (ASCs) seeded on beta-tricalcium phosphate (betaTCP) granules. Between 10/2008 and 3/2010, five cranioplasties were performed (four females, one male; average age 62.0 years) using ASCs, betaTCP granules and titanium or resorbable meshes. The average defect size was 8.1 x 6.7 cm(2). Patients were followed both clinically and radiologically. The initial results were promising, with no serious complications. Nevertheless, in the long-term follow-up, three of the five patients were re-operated due to graft related problems. Two patients showed marked resorption of the graft, which led to revision surgery. One patient developed a late infection (7.3 years post-operative) that required revision surgery and removal of the graft. One patient had a successfully ossified graft, but was re-operated due to recurrence of the meningioma 2.2 years post-operatively. One patient had an uneventful clinical follow-up, and the cosmetic result is satisfactory, even though skull x-rays show hypodensity in the borders of the graft. Albeit no serious adverse events occurred, the 6-year follow-up results of the five cases are unsatisfactory. The clinical results are not superior to results achieved by conventional cranial repair methods. The use of stem cells in combination with betaTCP granules and supporting meshes in cranial defect reconstruction need to be studied further before continuing with clinical trials.Peer reviewe

Effect of blood pressure and glycemic control on the plasma cell-free DNA in hemodialysis patients

AbstractBackgroundThe plasma levels of cell-free DNA (cfDNA) are known to be elevated under inflammatory or apoptotic conditions. Increased cfDNA levels have been reported in hemodialysis (HD) patients. The aim of this study was to investigate the clinical significance of cfDNA in HD patients.MethodsA total of 95 patients on HD were enrolled. We measured their predialysis cfDNA levels using real-time EIF2C1 gene sequence amplification and analyzed its association with certain clinical parameters.ResultsThe mean plasma cfDNA level in the HD patients was 3,884 ± 407 GE/mL, and the mean plasma cfDNA level in the control group was 1,420 ± 121 GE/mL (P < 0.05). Diabetic patients showed higher plasma cfDNA levels compared with nondiabetic patients (P < 0.01). Patients with cardiovascular complications also showed higher plasma cfDNA levels compared with those without cardiovascular complication (P < 0.05). In univariable analysis, the cfDNA level was associated with 3-month mean systolic blood pressure (SBP), white blood cell, serum albumin, creatinine (Cr), normalized protein catabolic rate in HD patients. In diabetic patients, it was significantly correlated with SBP, hemoglobin A1c, and serum albumin. In multivariate analysis, SBP was the independent determinant for the cfDNA level. In diabetic patients, cfDNA level was independently associated with hemoglobin A1c and SBP.ConclusionsIn patients with HD, cfDNA is elevated in diabetic patients and patients with cardiovascular diseases. Uncontrolled hypertension and poor glycemic control are independent determinants for the elevated cfDNA. Our data suggest that cfDNA might be a marker of vascular injury rather than proinflammatory condition in HD patients

Airborne olive pollen counts are not representative of exposure to the major olive allergen Ole e 1

Pollen is routinely monitored, but it is unknown whether pollen counts represent allergen exposure. We therefore simultaneously determined olive pollen and Ole e 1 in ambient air in C ordoba, Spain, and Evora, Portugal, using Hirst-type traps for pollen and high-volume cascade impactors for allergen. Pollen from different days released 12-fold different amounts of Ole e 1 per pollen (both locations P < 0.001). Average allergen release from pollen (pollen potency) was much higher in C ordoba (3.9 pg Ole e 1/pollen) than in Evora (0.8 pg Ole e 1/pollen, P = 0.004). Indeed, yearly olive pollen counts in C ordoba were 2.4 times higher than in Evora, but Ole e 1 concentrations were 7.6 times higher. When modeling the origin of the pollen, >40% of Ole e 1 exposure in Evora was explained by high-potency pollen originating from the south of Spain. Thus, olive pollen can vary substantially in allergen release, even though they are morphologically identical

Management of acute mesenteric ischaemia: Results of a worldwide survey

Acute mesenteric ischaemia; Intestinal failure; SurveyIsquemia mesentérica aguda; Insuficiencia intestinal; EncuestaIsquèmia mesentèrica aguda; Insuficiència intestinal; EnquestaBackground Acute mesenteric ischaemia (AMI) is a condition with high mortality. This survey assesses current attitudes and practices to manage AMI worldwide. Methods A questionnaire survey about the practices of diagnosing and managing AMI, endorsed by several specialist societies, was sent to different medical specialists and hospitals worldwide. Data from individual health care professionals and from medical teams were collected. Results We collected 493 individual forms from 71 countries and 94 team forms from 34 countries. Almost half of respondents were surgeons, and most of the responding teams (70%) were led by surgeons. Most of the respondents indicated that diagnosis of AMI is often delayed but rarely missed. Emergency revascularisation is often considered for patients with AMI but rarely in cases of transmural ischaemia (intestinal infarction). Responses from team hospitals with a dedicated special unit (14 team forms) indicated more aggressive revascularisation. Abdominopelvic CT-scan with intravenous contrast was suggested as the most useful diagnostic test, indicated by approximately 90% of respondents. Medical history and risk factors were thought to be more important in diagnosis of AMI without transmural ischaemia, whereas for intestinal infarction, plasma lactate concentrations and surgical exploration were considered more useful. In elderly patients, a palliative approach is often chosen over extensive bowel resection. There was a large variability in anticoagulant treatment, as well as in timing of surgery to restore bowel continuity. Conclusions Delayed diagnosis of AMI is common despite wide availability of an adequate imaging modality, i.e. CT-scan. Large variability in treatment approaches exists, indicating the need for updated guidelines. Increased awareness and knowledge of AMI may improve current practice until more robust evidence becomes available. Adherence to the existing guidelines may help in improving differences in treatment and outcomes