In Vitro and In Vivo Human Herpesvirus 8 Infection of Placenta

Herpesvirus infection of placenta may be harmful in pregnancy leading to disorders in fetal growth, premature delivery, miscarriage, or major congenital abnormalities. Although a correlation between human herpesvirus 8 (HHV-8) infection and abortion or low birth weight in children has been suggested, and rare cases of in utero or perinatal HHV-8 transmission have been documented, no direct evidence of HHV-8 infection of placenta has yet been reported. The aim of this study was to evaluate the in vitro and in vivo susceptibility of placental cells to HHV-8 infection. Short-term infection assays were performed on placental chorionic villi isolated from term placentae. Qualitative and quantitative HHV-8 detection were performed by PCR and real-time PCR, and HHV-8 proteins were analyzed by immunohistochemistry. Term placenta samples from HHV-8-seropositive women were analyzed for the presence of HHV-8 DNA and antigens. In vitro infected histocultures showed increasing amounts of HHV-8 DNA in tissues and supernatants; cyto- and syncitiotrophoblasts, as well as endothelial cells, expressed latent and lytic viral antigens. Increased apoptotic phenomena were visualized by the terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling method in infected histocultures. Ex vivo, HHV-8 DNA and a latent viral antigen were detected in placenta samples from HHV-8-seropositive women. These findings demonstrate that HHV-8, like other human herpesviruses, may infect placental cells in vitro and in vivo, thus providing evidence that this phenomenon might influence vertical transmission and pregnancy outcome in HHV-8-infected women

When the Rules of Discourse Change, but Nobody Tells You: Making Sense of Mathematics Learning From a Commognitive Standpoint

In this article we introduce a research framework grounded in the assumption that thinking is a form of communication and that learning a school subject such as mathematics is modifying and extending one’s discourse. This framework is then applied in the study devoted to the learning of negative numbers. The analysis of data is guided by questions about (a) the discourse on negative numbers as such, and the features that set it apart from the mathematical discourse with which the students have been familiar when the learning began; (b) students’ and teacher’s efforts toward the necessary transition to the new meta-discursive rules, and (c) effects of the learning teaching process, that is, the extent of discursive change resulting from these efforts. Our findings lead to the conclusion that discursive change, rather than being necessitated by an extradiscursive reality, is spurred by communicational conflict, that is, by the situation that arises whenever different interlocutors seem to be acting according to differing discursive rules. Another conclusion is that school learning requires an active lead of an experienced interlocutor and is fuelled by a realistic communicational agreement between her and the learners

P391Estimated glomerular filtration rate levels and risk of stroke in individuals with diabetes mellitus and atrial fibrillation

Abstract Funding Acknowledgements pfizer Background Diabetes mellitus (DM) is associated with increased risk of embolic complications in non-valvular atrial fibrillation (NVAF). Chronic kidney disease (CKD) has been shown in some studies to increase the risk of stroke. This finding is not consistent among all studies. Therefore the relationship between kidney function, diabetes and stroke risk is complex and warrants further investigation. Purpose To assess the incidence rates and risk of ischemic stroke and mortality by baseline Estimated Glomerular Filtration Rate (eGFR) levels among individuals with AF and DM. Methods A prospective, historical cohort study using our electronic medical records database. The study population included all members 21 years old, with a first diagnosis of NVAF between January 1, 2010 to December 31, 2016 and a minimal follow-up period of 1 year. Among those patients identified as diabetics, we compared three groups of patients according to eGFR levels at the time of AF diagnosis: eGFR ≥ 60, between 30-60 and ≤ 30 or chronic dialysis or kidney transplant. Results A total of  17,567 cases were included in the final analysis, of them, 11013 (62.7%) had eGFR ≥ 60, 4930 (28%) with eGFR between 30-60 and 1624 (9.24%) with eGFR ≤30 . The median age was 75 years (IQR 65-83) with a majority of females in all groups, 52.5%, 51.2% and 55.5% respectively. The incidence of stroke per 100 person-years in the three study groups was: 1.88 in patients with eGFR ≥ 60, 2.69 in patients with eGFR between 30-60 and 3.34 in those with eGFR ≤ 30 . Impaired renal function was associated with increased risk of stroke in univariate analysis, but not found in the adjusted model  (Adjusted Hazard Ratio (AHR) = 1.04 {95% 0.89-1.23} for eGFR 30-60  and 1.16 {95% CI 0.88-1.51} for eGFR ≤ 30 compared to GFR ≥ 60). incidence of mortality per 100 person-years was 10.78 in patients with  eGFR ≥ 60, 21.49 in patients with eGFR 30-60 and 41.55 in those with eGFR ≤ 30. In both univariate and multivariate analyses, decreased levels of eGFR were associated with increased mortality risk compared to subjects with normal renal function (AHR 1.22 {95%CI 1.14-1.27} and AHR 2.09 {95%CI 1.95-2.24} for eGFR between 30-60 and for eGFR ≤ 30, respectively). Conclusion In this observational prospective cohort of patients with newly diagnosed NVAF, impaired renal function was not found to be associated with increased risk of stroke. Lower eGFR levels were associated with an increased mortality risk. </jats:sec

P997Risk of stroke and mortality in patients with atrial fibrillation and insulin dependent versus non-insulin dependent diabetes mellitus

Abstract Funding Acknowledgements Pfizer pharmaceutical corporation Background Diabetes is a known risk factor for thromboembolic events in patients with non-valvular atrial fibrillation (NVAF). Whether patients on insulin therapy are at an increased risk for stroke compered to patients treated solely by oral antidiabetic medications is not yet established. Aim To assess the risk of ischemic stroke and mortality in patients with NVAF and diabetes mellitus (DM) treated by insulin vs. oral antidiabetic treatment. Methods A prospective, historical cohort study based on the Clalit Health Services (CHS) electronic medical records database, including all individuals age ≥ 21 years with a first diagnosis of NVAF between January 2010 to December 2016 and a minimal follow-up period of 1 year. Patients were divided into two groups based on their diabetes therapy regiment (insulin vs. oral antidiabetic medications). Results Overall study population included 12,231 patients with AF and DM, of them 3510 (28.7%) had an insulin-requiring diabetes. The median age was 72.4 years (IQR 65-80) in the insulin- treated group and 75.2 (IQR 68-83) in the orally treated group, with a slight majority of women in both groups, 51.6% and 53.5% respectively. Patients in the insulin group had significantly higher co-morbidity rates including hypertension (HTN) (93.6% vs. 91.2%; p &amp;lt; 0.001), congestive heart failure (CHF) (38% vs. 22.2%%; p &amp;lt; 0.001), previous cerebrovascular accident/ transient ischemic attack (CVA/TIA) (23.1% vs.14.5%;  p &amp;lt; 0.001) and vascular diseases (62.1% vs. 46.5%; p &amp;lt; 0.001). Moreover, patient on insulin therapy were significantly less treated with anticoagulation medications at baseline compered to patients not treated with insulin (38.9% vs. 46.6%; p &amp;lt; 0.001). The incidence of stroke per 100 person-years was 2.62 in the insulin-treated group and 2.02 in the oral-treated group. Although, diabetes patients on insulin therapy had a significantly increased risk for stroke compared to patients not treated with insulin in the univariate analysis (HR: 1.34; 95%CI: 1.13- 1.60), this association was not found to be significant after adjusting for confounding variables (HR: 1.17; 95%CI: 0.96- 1.41). The rate of mortality per 100 person-years was 19 in the insulin-treated group and 12.6 in the oral-treated group. The risk for overall mortality was significantly higher in the insulin-treated group compared to the non-insulin group (HR: 1.38; 95%CI: 1.29- 1.48), as found in the multivariate Cox model, adjusted for age, gender, Creatinine clearance, HTN, CHF , CVA/TIA, vascular diseases, duration of diabetes and use of anticoagulation therapy. Conclusion In this cohort of patients with newly diagnosed NVAF and DM, patients on insulin are at increased risk of all cause mortality and a have a trend of increased risk of stroke after accounting for other recognized risk factors for stroke and mortality in this population. </jats:sec

Sex differences in acute coronary syndrome symptom presentation in young patients

IMPORTANCE Little is known about whether sex differences in acute coronary syndrome (ACS) presentation exist in young patients and what factors determine absence of chest pain in ACS presentation. OBJECTIVES To evaluate sex differences in ACS presentation and to estimate associations between sex, sociodemographic, gender identity, psychosocial and clinical factors, markers of coronary disease severity, and absence of chest pain in young patients with ACS. DESIGN, SETTING, PARTICIPANTS We conducted a prospective cohort study of 1015 patients (30% women) 55 years or younger, hospitalized for ACS and enrolled in the GENESIS PRAXY (Gender and Sex Determinants of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary Syndrome) study (January 2009-September 2012). MAIN OUTCOMES AND MEASURES The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey was administered during hospitalization. RESULTS The median age for both sexes was 49 years. Women were more likely to have non-ST-segment elevation myocardial infarction (37.5 vs 30.7; P = .03) and present without chest pain compared with men (19.0% vs 13.7%; P = .03). Patients without chest pain reported fewer symptoms overall and no discernable pattern of non-chest pain symptoms was found. In the multivariate model, being a woman (odds ratio [OR], 1.95 [95% CI, 1.23-3.11]; P = .005) and tachycardia (OR, 2.07 [95% CI, 1.20-3.56]; P = .009) were independently associated with ACS presentation without chest pain. Patients without chest pain did not differ significantly from those with chest pain in terms of ACS type, troponin level elevation, or coronary stenosis. CONCLUSIONS AND RELEVANCE Chest pain was the most common ACS symptom in both sexes. Although women were more likely to present without chest pain than men, absence of chest pain was not associated with markers of coronary disease severity. Strategies that explicitly incorporate assessment of common non-chest pain symptoms need to be evaluated