Search

BACKGROUND: For faculty in academic health sciences, the balance between research, education, and patient care has been impeded by the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to identify personal and professional characteristics of faculty to understand the impact of the pandemic on faculty and consequent policy implications. METHODS: A 93-question survey was sent to faculty at a large urban public university and medical center. Demographic, family, and academic characteristics, work distribution and productivity before and during the pandemic, stress, and self-care data information were collected. Latent class analysis (LCA) was performed to identify classes of faculty sharing similar characteristics. Comparisons between latent classes were performed using analysis of variance and chi-square analyses. RESULTS: Of 497 respondents, 60% were women. Four latent classes of faculty emerged based on six significant indicator variables. Class 1 individuals were more likely women, assistant professors, nontenured with high work and home stress; Class 2 faculty were more likely associate professors, women, tenured, who reported high home and work stress; Class 3 faculty were more likely men, professors, tenured with moderate work, but low home stress; and Class 4 faculty were more likely adjunct professors, nontenured, and had low home and work stress. Class 2 reported significantly increased administrative and clinical duties, decreased scholarly productivity, and deferred self-care. CONCLUSIONS: The pandemic has not affected faculty equally. Early and mid-career individuals were impacted negatively from increased workloads, stress, and decreased self-care. Academic leaders need to acknowledge these differences and be inclusive of faculty with different experiences when adjusting workplace or promotion policies.

Supplemental Digital Content is available in the text., Background: LNK/SH2B3 inhibits Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling by hematopoietic cytokine receptors. Genome-wide association studies have shown association of a common single nucleotide polymorphism in LNK (R262W, T allele) with neutrophilia, thrombocytosis, and coronary artery disease. We have shown that LNK(TT) reduces LNK function and that LNK-deficient mice display prominent platelet–neutrophil aggregates, accelerated atherosclerosis, and thrombosis. Platelet–neutrophil interactions can promote neutrophil extracellular trap (NET) formation. The goals of this study were to assess the role of NETs in atherosclerosis and thrombosis in mice with hematopoietic Lnk deficiency. Methods: We bred mice with combined deficiency of Lnk and the NETosis-essential enzyme PAD4 (peptidyl arginine deiminase 4) and transplanted their bone marrow into Ldlr–/– mice. We evaluated the role of LNK in atherothrombosis in humans and mice bearing a gain of function variant in JAK2 (JAK2V617F). Results: Lnk-deficient mice displayed accelerated carotid artery thrombosis with prominent NETosis that was completely reversed by PAD4 deficiency. Thrombin-activated Lnk–/– platelets promoted increased NETosis when incubated with Lnk–/– neutrophils compared with wild-type platelets or wild-type neutrophils. This involved increased surface exposure and release of oxidized phospholipids (OxPL) from Lnk–/– platelets, as well as increased priming and response of Lnk–/– neutrophils to OxPL. To counteract the effects of OxPL, we introduced a transgene expressing the single-chain variable fragment of E06 (E06-scFv). E06-scFv reversed accelerated NETosis, atherosclerosis, and thrombosis in Lnk–/– mice. We also showed increased NETosis when human induced pluripotent stem cell–derived LNK(TT) neutrophils were incubated with LNK(TT) platelet/megakaryocytes, but not in isogenic LNK(CC) controls, confirming human relevance. Using data from the UK Biobank, we found that individuals with the JAK2VF mutation only showed increased risk of coronary artery disease when also carrying the LNK R262W allele. Mice with hematopoietic Lnk+/– and Jak2VF clonal hematopoiesis showed accelerated arterial thrombosis but not atherosclerosis compared with Jak2VFLnk+/+ controls. Conclusions: Hematopoietic Lnk deficiency promotes NETosis and arterial thrombosis in an OxPL-dependent fashion. LNK(R262W) reduces LNK function in human platelets and neutrophils, promoting NETosis, and increases coronary artery disease risk in humans carrying Jak2VF mutations. Therapies targeting OxPL may be beneficial for coronary artery disease in genetically defined human populations.

Background Approximately 1000 out-of-hospital cardiac arrest (OHCA) occur each day in the United States. Although sex differences exist for other cardiovascular conditions such as stroke and acute myocardial infarction, they are less well understood for OHCA. Specifically, the extent to which neurological and survival outcomes after OHCA differ between men and women remains poorly characterized in the U.S. Methods and results Within the national Cardiac Arrest Registry to Enhance Survival (CARES) registry, we identified 326,138 adults with an OHCA from 2013 to 2019. Using multivariable logistic regression, we evaluated for sex differences in rates of survival to hospital admission, survival to hospital discharge, and favorable neurological survival (i.e., without severe neurological disability), adjusted for demographics, cardiac arrest characteristics and bystander interventions. Overall, 117,281 (36%) patients were women. Median age was 62 and 65 years for men and women, respectively. An initial shockable rhythm (25.1% vs 14.7%, standardized difference of 0.26) and an arrest in a public location (22.2% vs. 11.3%; standardized difference of 0.30) were more common in men, but there were no meaningful sex differences in rates of witnessed arrests, bystander cardiopulmonary resuscitation, intra-venous access, or use of mechanical devices for delivering cardiopulmonary resuscitation. Overall, the unadjusted rates of all survival outcomes were similar between men and women: survival to hospital admission (27.0% for men vs. 27.9% for women, standardized difference of −0.02), survival to hospital discharge (10.5% for men vs. 8.6% for women, standardized difference of 0.07), and favorable neurological survival (9.0% for men vs. 6.6% for women, standardized difference of 0.09). After multivariable adjustment, however, men were less likely to survive to hospital admission (adjusted OR = 0.75, 95% CI: 0.73, 0.77), survive to hospital discharge (adjusted OR = 0.83, 95% CI: 0.80, 0.85), or have favorable neurological survival (adjusted OR = 0.88, 95% CI: 0.85, 0.91). Conclusions Compared to women, men with OHCA have more favorable cardiac arrest characteristics but were less likely to survive to hospital admission, survive to discharge, nor have favorable neurological survival.

Acute myeloid leukemia (AML) is a clonal hematopoietic stem and progenitor cell malignancy characterized by poor clinical outcomes. Major histocompatibility complex class I polypeptide-related sequence A and B (MICA/B) are stress proteins expressed by cancer cells, and antibody-mediated inhibition of MICA/B shedding represents a novel approach to stimulate immunity against cancers. We found that the MICA/B antibody 7C6 potently inhibits the outgrowth of AML in 2 models in immunocompetent mice. Macrophages were essential for therapeutic efficacy, and 7C6 triggered antibody-dependent phagocytosis of AML cells. Furthermore, we found that romidepsin, a selective histone deacetylase inhibitor, increased MICB messenger RNA in AML cells and enabled subsequent stabilization of the translated protein by 7C6. This drug combination substantially increased surface MICA/B expression in a human AML line, pluripotent stem cell-derived AML blasts and leukemia stem cells, as well as primary cells from 3 untreated patients with AML. Human macrophages phagocytosed AML cells following treatment with 7C6 and romidepsin, and the combination therapy lowered leukemia burden in a humanized model of AML. Therefore, inhibition of MICA/B shedding promotes macrophage-driven immunity against AML via Fc receptor signaling and synergizes with an epigenetic regulator. These results provide the rationale for the clinical testing of this innovative immunotherapeutic approach for the treatment of AML.

Introduction: Out-of-Hospital cardiac arrest (OHCA) is the leading cause of death with an overall survival rate of less than 10%. Organ failure and metabolic impairment are two critical elements of post-CA syndrome. Taurine and glutamate are amino acids that are expressed primarily in heart and brain. The compensatory release during osmotic stress, as seen in CA, amplifies reperfusion injury, heart stunning and brain edema. Thus, taurine and glutamate concentrations in blood likely reflects the extent of injury in the heart and brain following CA. Hypothesis: Plasma taurine and glutamate concentration correlates with CA outcomes. Methods: Adult OHCA patients (n=37) at an urban academic ED were enrolled from 2018-2019. Among them, 14 were survivors (S) and 23 were nonsurvivors (NS). Blood samples were collected at various time points including the time at hospital arrival, 6, 24, 48, 72 hours after arrival (T0, 6, 24, 48 and 72 h, respectively), and measured. T-test and GEE were used for mean comparison and longitudinal trend analysis, respectively. p < 0.05 was considered as statistically significant. Results: Plasma taurine and glutamate concentrations were compared between S and NS at T0 and across all time points. Both concentrations were significantly higher in NS vs S group at T0 (for taurine: 77.7 ± 40.0 in NS vs. 60.0 ± 31.9 μM in S, p =0.014; for glutamate: 176.4 ± 98.7 in NS vs. 162.8 ± 111.1 μM in S, p =0.0496), and showed a decreasing trend over time. In the first 6 h, taurine and glutamate level decreased more in S group than NS group (over 30% drop in S compared to Conclusions: Blood taurine and glutamate may serve as early biomarkers in predicting OHCA outcomes. Monitoring their change over time can help physicians tailor treatment decisions and patient management.

Introduction: Neurologically guided resuscitation after out-of-hospital cardiac arrest (OHCA) to improve survival has been limited due to knowledge gaps in cerebral edema changes. Point-of-care ultrasound (POCUS) for the assessment of optic nerve sheath diameter (ONSD) is an established modality to characterize the extent of cerebral edema. We aimed to describe ONSD differences by sex, rhythm type, neurological outcome using cerebral performance category (CPC), and overall survival status. Methods: We studied adult OHCA treated at an urban academic ED with return of spontaneous circulation (ROSC) from May 2018 to May 2020. After ROSC, trained emergency physicians obtained bilateral ONSD measurements at 1, 6, 24, 48, and 72 hours, in the transverse, oblique, and sagittal planes for each eye. All the ONSD measurements were averaged for each time point and comparisons were made between each predictor’s categories. To compare the mean at each time point between groups, t-test or ANOVA was used. The trend comparison was done using generalized estimating equations. Statistical analysis was performed using SAS 9.4 under the significance level of 0.05. Results: Out of 62 eligible patients, 35 (56%) were male and 27 (44%) were female, 33 (59%) had a shockable rhythm and 23 (41%) had non-shockable rhythm. At 72 hr, 6 (10%) had a CPC of 1-2 and 57 (90%) had CPC of 3-5. Overall, there were 37 (61%) survivors and 24 (39%) non-survivors. There was a notable sex difference in the mean ONSD across all time points between males and females (p = 0.031), with males showing higher ONSD, and between shockable and non-shockable (p= 0.035), with the shockable group having relatively lower ONSD. There is a statistically significant difference of mean ONSD between CPC 1-2 and CPC 3-5 groups at 6hr, 48hr, and at 72hr, with higher means in the CPC 3-5 group. Across all times, the trend line was statistically significant between non-survivors and survivors (p= 0.015), with non-survivors having higher ONSD. Conclusion: Males, patients with non-shockable rhythm, CPC 3-5 at 72 hr, and non-survivors had higher ONSD. Understanding cerebral edema dynamics during resuscitation will allow for future work to potentially tailor interventions to individual patient cerebral injury patterns.

Cardiac arrest systems of care are successfully coordinating community, emergency medical services, and hospital efforts to improve the process of care for patients who have had a cardiac arrest. As a result, the number of people surviving sudden cardiac arrest is increasing. However, physical, cognitive, and emotional effects of surviving cardiac arrest may linger for months or years. Systematic recommendations stop short of addressing partnerships needed to care for patients and caregivers after medical stabilization. This document expands the cardiac arrest resuscitation system of care to include patients, caregivers, and rehabilitative healthcare partnerships, which are central to cardiac arrest survivorship.

Background Acute chest syndrome (ACS) is the leading cause of death for patients with sickle cell disease (SCD). Early recognition of ACS improves prognosis. Objective Investigate the use of bedside lung ultrasound (BLU) in identification of early pulmonary findings associated with ACS in SCD patients. Methods Prospective, observational study of a convenience sample of SCD patients presenting to the Emergency Department (ED) for a pain crisis. BLU interpretations were made by an emergency physician blinded to the diagnosis of ACS, and were validated by a second reviewer. The electronic medical record was reviewed at discharge and at 30 days. Results Twenty SCD patients were enrolled. Median age was 31 years, median hemoglobin was 7.7 g/dL. Six patients developed ACS. Five patients in the ACS group had lung consolidations on BLU (83%) compared to 3 patients in the non-ACS group (21%), p = 0.0181, (OR = 12.05, 95% CI 1.24 to 116.73). The ACS group was also more likely to have a pleural effusion and B-lines on BLU than the non-ACS group, p = 0.0175; 0.1657, respectively. In the ACS group, peripheral and frank consolidations on BLU was 83% and 50% sensitive, 79% and 100% specific for ACS, respectively; whereas an infiltrate on initial chest X-ray (CXR) was only 17% sensitive. BLU identified lung abnormalities sooner than CXR (median 3.6 vs. 31.8 h). Conclusions Pulmonary abnormalities on BLU of an adult SCD patient presenting to the ED for a painful crisis appear before CXR, and highly suggest ACS. BLU is a promising predictive tool for ACS.

Introduction: Approximately 1,000 out-of-hospital cardiac arrest (OHCA) occur per day in the United States. Although survival rates remains low, the extent to which OHCA neurological outcomes differ between men and women remains poorly characterized. Methods: Within the national Cardiac Arrest Registry to Enhance Survival (CARES) registry, we identified 195,722 adult individuals with an OHCA between 2013-2017. Using multi-variable logistic regression models, we evaluated for sex differences in rates of survival to hospital discharge and favorable neurological outcome (survival with discharge CPC score of 1 or 2), adjusted for cardiac arrest characteristics, race, location, year of arrest, age, and use of targeted temperature management (TTM) and coronary angiography. Results: Overall, 70,767 (31%) patients were women. Median age was 64 and 62 years for women and men, respectively. An initial shockable rhythm (14.9% vs. 25.7%) and a witnessed arrest (40.9% vs. 45.6%) was more common in men. Bystander CPR was provided to 37% of women and 39% of men. Men were less likely to survive to hospital discharge than women (8.7% vs. 10.9%; adjusted OR 0.75, 95% CI 0.73, 0.78). Similarly, men were less likely to have favorable neurological outcome (6.6% vs. 9.2% for women; adjusted OR 0.78, 95% CI 0.74, 0.82). Further interaction analysis for the pre-hospital elements found small, but statistically significant sex differences in favorable neurological survival for witnessed status (among female OR 2.29, 95% CI 2.10, 2.49; among males OR 2.07, 95% CI 1.92, 2.23, p= 0.04) and for bystander CPR (among females OR 1.20, 95% CI 1.11, 1.29; among males OR 1.34, 95% CI 1.27, 1.42, p= 0.01). Interaction of sex with the hospital level variables of TTM and coronary angiography, for the subset of patients that survived to hospital admission, had no sex differences in favorable neurological outcome. Conclusion: Our analysis shows that for OHCA in the United States, women have better survival outcomes than men. There was a sex differences in the pre-hospital variable of BCPR, but not in the other modifiable variables of TTM and coronary angiography. Further study is needed to better understand sex differences in overall survival and neurological outcomes.

A 82-year-old male experiencing headaches, dementia, urinary incontinence and gait instability was diagnosed with normal pressure hydrocephalus (NPH) and underwent a resting state magnetoencephalography (MEG) examination. MEG data were recorded in a magnetically shielded room with a whole-head 122 channel biomagnetometer. Following MEG, a ventriculoperitoneal (VP) shunt was placed in his head and greatly improved his symptomatology. Spontaneous MEG recordings revealed lower magnetic fields at frontal and frontotemporal regions compared to central and posterior regions. This finding correlated well with the significant ventricular distention, and specifically the enlargement of the frontal horns of the lateral ventricles, observed in presurgical CT. The regional pattern of MEG signal decrease in NPH seems to be quite different from that encountered in brain atrophy. In the latter case, a more generalized distribution of low magnetic fields is observed, possibly reflecting the high sensitivity of MEG to activity originating in sulci. Acquired data suggest that MEG may be able to differentiate between NPH and brain atrophy. Furthermore, MEG could potentially constitute a non-invasive, non-imaging tool, useful in the selection of patients with NPH to undergo shunt surgery. The findings of this study warrant further research in patient groups before firm conclusions can be drawn.

Effective interventions to identify and treat uncontrolled hypertension (HTN), particularly in underrepresented populations that use the emergency department (ED) for primary care, are critically needed. Uncontrolled HTN contributes significantly to cardiovascular morbidity and mortality and is more frequently encountered among patients presenting to the ED as compared to the primary care setting. EDs serve as the point of entry into the health care system for high-risk patient populations, including minority and low-income patients. Previous studies have demonstrated that the prevalence of uncontrolled/undiagnosed HTN in patients presenting to the ED is alarmingly high. Thus ED engagement and early risk assessment/stratification is a feasible innovation to help close health disparity gaps in HTN. A Hypertension Emergency Department Intervention Aimed at Decreasing Disparities (AHEAD2) trial, funded by the National Heart, Lung, and Blood Institute (NHLBI) is a three-arm single site randomized clinical pilot trial of adults presenting to the ED with Stage 2 hypertension (blood pressure [BP] >160/100) comparing (1) an ED-initiated Screening, Brief Intervention, and Referral for Treatment (SBIRT) focused on HTN, (2) the same ED-initiated SBIRT coupled with a Post-Acute Care Hypertension Transition Consultation by ED Clinical Pharmacists, and (3) usual care. The primary outcome is mean BP differences between study arms. Secondary outcomes are proportion of participants with BP control (BP

INTRODUCTION The objective of this study was to determine the effects of chorioamnionitis on the extracellular matrix (ECM) structural glycoproteins of the developing human fetal spleen, and their influence on the haematopoiesis and spleen immune system compared to controls. MATERIALS AND METHODS After elective induced pregnancy termination due to chorioamnionitis or voluntary abortion, paraffin-embedded specimens from the spleen and respective fetal membranes of 90 fetuses were investigated by immunohistochemistry for presence of ECM structural glycoproteins, haematopoietic, and lymphoid cells. Conventional histological examination of the relative fetal membranes was performed. RESULTS The present results showed no quantitative variations in the expression of the ECM glycoproteins and haematopoietic lineages of the fetal spleen parenchyma at the end of first trimester (in both groups). At the second and third trimesters, acute chorioamnionitis showed a decreased number of the aforementioned proteins, with an increase of granulopoiesis and CD34 progenitor/stem haematopoietic cells. The immune system of the spleen during the third trimester demonstrated a decrease of both B and T lymphocytes, in comparison with controls. CONCLUSIONS These results suggest that toxins and cytokines generated during chorioamnionitis, seem to influence ECM structural glycoproteins synthesis and release in fetal splenic parenchyma by reducing them, and probably cause further disorders of haematopoiesis and lymphopoiesis.

Sex- and gender-based differences are emerging as clinically significant in the epidemiology and resuscitation of patients with out-of-hospital cardiac arrest (OHCA). Female patients tend to be older, experience arrest in private locations, and have fewer initial shockable rhythms (ventricular fibrillation/ventricular tachycardia). Despite standardized algorithms for the management of OHCA, women are less likely to receive evidence-based interventions, including advanced cardiac life support medications, percutaneous coronary intervention, and targeted temperature management. While some data suggest a protective mechanism of estrogen in the heart, brain, and kidney, its role is incompletely understood. Female patients experience higher mortality from OHCA, prompting the need for sex-specific research.

MEG data for five cerebral palsy patients were taken using a whole-head 122-channel MEG system. An experiment was designed to identify the possible effect of external pico-Tesla weak magnetic fields. The subjects were five male volunteers 17-46 years of age. External stimulation, field amplitude 1-7.5 pico-Tesla, was applied to each subject at their alpha-rhythm frequency. Fast Fourier transforms were applied to the data of all MEG channels and the rhythms of the patients were evaluated before and after pico-Tesla transcranial magnetic stimulation. The appliance of pico-Tesla weak magnetic fields showed the brains of the cerebral palsy patients had an enhance of the frequencies of (2-7 Hz) for each patient. This was followed by an improvement and normalization of their MEG. The results had a statistical significance in four out of five subjects (80%) and suggested the stimulation provided a positive contribution to the management of the symptoms of cerebral palsy patients.

Hypertensive emergency is a life-threatening state. End-organ damage affecting the heart accounts for up to 52% of hypertensive emergencies commonly encountered in the emergency department. Recent evidence indicates that strain echocardiography with computerized speckle-tracking is more sensitive at identifying hypertension induced changes in the left ventricle (LV) mechanical function than traditional 2-D echocardiography. We present a case demonstrating the use of emergency physician performed point-of-care strain echocardiography to identify and quantify LV mechanical dysfunction during a hypertensive crisis and to monitor improvement over 6 h.

Implementation of postarrest care by individual physicians and systems has been slow. Deadoption, or discontinuation of therapeutic hypothermia (TH) treatment targets, after recent prospective study results has not been well reported. This study assesses practices in the early stages of postarrest care across emergency departments (EDs) in Michigan. A 27-question Internet-based survey was distributed to EDs in Michigan in September 2013. To assess changes in practice after publication of Nielsen et al., we sent follow-up questions to all original respondents a year later. Observational data and descriptive statistics are reported. From the 142 EDs identified, we excluded critical access hospitals (N = 35), free standing EDs (N = 7), EDs that transfer critical patients to tertiary centers (N = 21), and exclusive children's hospitals (N = 3). Of the remaining 76 hospitals, we received 64 (84.2%) responses. We identified 15 respondents with a protocol to specifically initiate ED TH and transfer patients to a higher level of care. The 49 remaining were mostly teaching institutions (N = 34, 69%) and gave the ED physician the ability to initiate TH (N = 40, 82%). On follow-up 12 months later, we received 33/40 (83%) responses, of which only 5 indicated formal or informal change in TH practice or target temperature. There is substantial variation in the practice of ED postarrest care and initiation of TH across the state of Michigan, but few ED TH protocols were changed in a year's time. The consequences of postarrest treatment variability at the state and ED levels are likely under-recognized as an influence on outcome variation between regions.

Acute pancreatitis is associated with acute lung injury. The aim of the present study is to evaluate alterations of lungs in an experimental model of acute pancreatitis (AP) following both bilio-pancreatic duct obstruction close to the duodenum. Acute pancreatitis is a common disease with significant mortality. This situation makes the need of finding protective factors for the lung parenchyma, imperative. In the present study there is an effort to clarify the role of apigenin, a substance which is well known for its antioxidant and anti-inflammatory effects, on lung injury, following acute pancreatitis in rats.In the present study, 126 male Wistar-type rats 3-4 months old and 220-350 g weight were used. At time 0 we randomly assigned the following groups: Group Sham: Rats were subjected to virtual surgery. Group Control: Rats were subjected to surgery for induction of acute pancreatitis. Group Apigenin: Rats were subjected to surgery for induction of acute pancreatitis and enteral feeding with apigenin. Immunochemistry for TNF-α and IL-6 as well as MPO activity were measured at predetermined time intervals 6, 12, 24, 48, and 72 h, in order to evaluate architectural disturbances of the lung tissue.From the pathological reports we realized that comparing the control group with the apigenin group, there is an improvement of lung tissue damage following apigenin administration, with statistical significance. Apigenin reduces most histopathological alterations of the pulmonary tissue, reduces MPO and TNF-α activity at 48 hours and, furthermore, reduces IL-6 activity at 72 hours post-administration.Oral Apigenin administration in rats, following experimental induced acute pancreatitis, seems to be protective on the lung tissue. Apigenin administration to humans could potentially ameliorate acute lung injuries. However, special caution is required for humans' use, as more detailed studies are needed.

Introduction This study evaluates the agreement between emergency physician (EP) assessment of diastolic dysfunction (DD) by a simplified approach using average peak mitral excursion velocity (eʹA) and an independent cardiologist’s diagnosis of DD by estimating left atrial (LA) pressure using American Society of Echocardiography (ASE) guidelines. Methods This was a secondary analysis of 48 limited bedside echocardiograms (LBE) performed as a part of a research study of patients presenting to the Emergency Department (ED) with elevated blood pressure but without decompensated heart failure. EPs diagnosed DD based on eʹA

Purpose/aim: To examine with immunohistochemical assay MTA1 protein expression levels in pancreatic cancer tissues defining its prognostic value.The specimens derived from 51 patients who underwent surgery. The levels of MTA1 protein were compared with the age of the patients, their survival, and prognosis. Also, we studied clinical and histopathological factors such as the degree of tumor differentiation and its stage in correlation with MTA1 protein levels. In parallel, there was correlation between the expression of the ΜΤΑ1 protein and the aforementioned factors regarding survival rate. Furthermore, we independently correlated the patient's survival in relation to whether they had undergone adjuvant chemotherapy or not.It has been found to be low, moderate, or high expression of MTA1 levels in 48 out of 51 cancer tissues. Specifically, 49.0% of patients had low expression, 33.3% moderate, and 11.8% high expression of MTA1. Regarding the expression of MTA1 protein in correlation with various clinical and histopathological factors, a statistically significant correlation was observed with the degree of differentiation (p = 0.0068) and with the stage of the disease (p = 0.0173), but not with survival (p = 0.0740) or the age of them (p = 0.1547). Finally, it was found that overexpression of the MTA1protein is a prognostic factor for shorter survival in patients with pancreatic cancer (average 4.67 ± 0.95 months).MTA 1 protein may constitute an important prognostic marker in pancreatic cancer and could improve prognosis and treatment.

The purpose of this study was to use magnetoencephalography (MEG) to identify epileptic zones in patients with brain tumors before undergoing tumor surgery. The MEG data were recorded with a 122-channel biomagnetometer. Equivalent current dipoles (ECD) were calculated for epileptic spikes on MEG recordings according to the single dipole model. Eight patients (five males and three females) within the age range (43-73 years; mean ± SD = 55.12 ± 9.77) were examined by MEG before neurosurgery operation. Four patients had meningioma grade I, three had glioblastoma grade IV and one had astrocytoma grade II. All the patients showed ECD at their MEG's before surgical operation except a female one with meningioma who showed no ECD. Tumors observed in the frontal areas show posteriorly located ECD. We conclude that the MEG is a valuable clinical tool for the localization of epileptic foci in patients with brain tumors before surgical tumor operation.

Background:Improvement of the management of pancreatic cancer requires a better understanding of the genetic and molecular changes responsible for the development of the disease. The family of p21-activated kinases (PAKs) and especially PAK1 appears to mediate many cellular processes that contribute to the development and progression of pancreatic cancer, but the clinical relevance of PAK1 expression with the disease still remains unclear. Aim of the study was to assess the clinical value and the potential prognostic significance of PAK1 in pancreatic adenocarcinoma.Methods:We investigated the relationship between the PAK1 expression and the clinical and histopathologic characteristics of pancreatic cancer patients and the potential significance of PAK1 on survival. We examined tissue samples from 51 patients operated for pancreatic cancer. PAK1 expression was investigated with immunohistochemistry and correlated to clinicopathological parameters.Results:PAK1 was detected in all tumor samples and high expression was found in most patients. High PAK1 expression was also associated with younger age and well-differentiated tumors, but no association was found between PAK1 expression and Tumor-Node-Metastasis stage as well as deceased or alive status on follow-up. Moderate to high PAK1 expression favored higher 6-month and 1-year survival and low PAK1 expression 2-year survival but without statistical significance.ConclusionsOur results indicate that PAK1 could potentially be used as a prognostic marker in pancreatic cancer. Further studies could clarify whether utilization of PAK1 in therapeutic protocols for the treatment of pancreatic cancer will render them more effective.

Mobile learning is becoming increasingly popular. Educational web sites can be used as supporting learning tools for students who wish to supplement their knowledge without restrictions of time and place. The continuously increasing demand for enhanced remote and mobile services, as well as the difficulty in easily incorporating current learning services for mobile users, renders essential the adaptation of educational material for these requirements. The objective of this work is to present and evaluate a methodology for producing content semantics from learning material. The proposed approach results in recommending links, which are relevant to the mobile users’ interests, by exploiting the recorded usage of an educational portal and the semantics of the learning content. The implementation results reveal enhanced capabilities in mobile learners’ web experience and usability.

Background Magnetoencephalography (MEG) is a well-established noninvasive method for investigating human brain activity. Objectives The present study aimed at identifying any change in the brain state after pico- Tesla Transcranial Magnetic Stimulation (pT-TMS) on patients with multiple sclerosis (MS). Methods A whole-head 122 - channel MEG system in a magnetically shielded room with low magnetic noise was used. The study population comprised of 2 male and 8 female volunteers with MS, with a mean age of 41.3 ± 9.5 years. External magnetic field of pT-TMS was applied on the above patients with proper field characteristics (magnetic field amplitude: 1 - 7.5 pT, frequency: the alpha rhythm of the patient 8 - 13 Hz), obtained prior to the application of pT-TMS. Results A significant effect was observed with an increase of frequencies in the range of 2 - 7 Hz among the participants. The results were statistically significant in 7 out of 10 patients (70%). Conclusions The pT-TMS has the prospective to be a significant noninvasive secure and effective means in managing MS symptoms.

Magnetoencephalographic (MEG) recordings of 10 multiple sclerosis (MS) patients (2 men, 8 women, mean 41.3±9.5 years, mean disease duration 12.7±7.2 years) were obtained using a whole-head 122 - channel MEG system in a magnetically shielded room of low magnetic noise. Our experimental design was double-blind in order to look for possible effect of external pico - Tesla Transcranial Magnetic Stimulation (pT-TMS). The external pT-TMS was applied on the MS patients with proper field characteristics (magnetic field amplitude: 1-7.5pT, frequency: the alpha-rhythm of the patient 8-13Hz) which were obtained prior to the application of pT-TMS. Each MS patient had two separate recording sessions consisting of 3 runs in between where were given real or sham pT-TMS. It was then tried to predict the real and sham stimulation sessions based on the changes in the mean peak frequency difference (MPFD) observed in the brain of the patients in the 2-7Hz frequency band. After unblinding it was found a significant effect of an increase of frequencies in the range of 2-7Hz across the subjects followed by an improvement and normalization of the MEG.

Endometrial cancer is the sixth most common cancer in women. Galectin-3 (GAL-3) and CRIP-1 are multifunctional proteins which seem to be involved in many neoplasias. This study aims to point out correlations between clinicopathological findings and endometrial cancer patient survival to GAL-3 and CRIP-1 expression in order to enfold their diagnostic/prognostic potential. Tissues from 46 patients diagnosed with endometrial cancer were studied by immunohistochemistry, using monoclonal antibodies for GAL-3 and CRIP-1, and expression levels were correlated with clinicopathological findings and survival. Analysis was performed at single protein level or as co-expression. High expression of GAL-3 and CRIP-1 was independently associated with tumor depth and histological grade, respectively. Also, there was a significant correlation between high co-expression of the two proteins and the histological grade (aOR 2.66), the tumor depth (aOR 0.32) and the histological type (aOR 1.32), but not with the patients' age. Moreover, high expression of both proteins was observed in patients with shorter survival times. Interestingly, the co-expression of the two proteins exhibited some degree of monotony (Spearman's ρ = 0.768), indicating a common molecular pathway. This study provides evidence for a prognostic clinical potential of the combined study of GAL-3 and CRIP-1 in endometrial cancer. These factors are poorly studied in endometrium, and their role in the carcinogenetic process and on effective therapy awaits further elucidation.

Magnetoencephalographic recordings were evaluated in five different states: normal condition, sweet, bitter, sour, and salt taste. Twenty-eight healthy volunteers, 14 male and 14 female, ranging from 12 to 50 years of age, were included in the study. The results showed that, in the normal condition, as well as in the sweet and the bitter taste, the male volunteers exhibited a higher count of low-frequency than high-frequency channels compared to the femal ones; in the case of the sour taste, there was no clear differentiation between the genders; with the salt taste, the female volunteers exhibited a higher count of low-frequency channels whereas there was no clear differentiation in the number of high frequencies between the gender. A discrimination in the spatial distribution of the frequencies provides novel insights into the identification of gender-related taste sensation.

A Web-based platform to support the economic planning and growth of rural areas is currently being developed as part of the Agricultural Observatory project of a typical Greek region. The main goal is to provide a structural tool for municipality- and community-based groups for the identification and provision of any information needed to residents of rural areas. The application described also has international relevance for other local communities where agriculture is an important component of rural development. Work is now under way to expand the platform to include additional online tools in order to provide new applications to support the economic growth of the study and other areas.

The aim of this study is to assess any cerebral dysfunction in young children, who experienced febrile seizures, by means of magnetoencephalography. Our study population included 15 children (9 boys, 6 girls) within the age range of 2 to 7 years. The magnetoencephalography data were recorded with a 122-channel biomagnetometer. Equivalent current dipoles were calculated for epileptic spikes on magnetoencephalography recordings according to the single dipole model. Of 15 children, 8 showed equivalent current dipoles that located at the left—temporal, right—temporal, occipital, and frontal lobe, as active regions responsible for febrile seizures. We assumed that the interictal epileptiform discharges are a consequence of febrile seizures. Of course, further study in a larger number of patients is needed to evaluate the exact role of the equivalent current dipoles, in young children, who experienced febrile seizures.

We investigated the localization of current sources in the time and frequency domain from spontaneous MEG data recorded from nine epileptic patients (six females; three males) randomly selected, who had a mean age of 41 years old (range of 17–78 years old), with different types of epilepsy. The MEG data were recorded in a magnetically shielded room with a whole-head 122 channel biomagnetometer. For each MEG spike, we calculated the single Equivalent Current Dipole (ECD) sources at the initial spike peaks with a spherical model. MRI and EEG findings were available in patients' records. Prominent low frequencies can be seen in the majority of channels. For each patient there was an increase of the frequency range after the ECD in comparison with the frequency range before the ECD, in the whole study group due to epileptic discharge which is statistically significant (p = 0.02). There was also a statistical significant difference in the increase of the frequency range in four patients with pathologic MRI (p = 0.05), in five patients with normal MRI (p = 0.02), in five patients with a high incidence of seizures (p = 0.04) and in four patients with onset < 10 years (p = 0.04). The MEG analysis of neuromagnetic data gives information about the modification of the frequency range in the epileptic brains.

Magnetoencephalographic (MEG) recordings of patients with CNS disorders were obtained using a whole-head 122-channel magnetometer SQUID and analyzed using Fourier statistical analysis. External transcranial magnetic stimulation in the order of pico Tesla (pTMS) was applied to the above patients with proper characteristics (magnetic intensity 1-7.5 pT; frequency: 8-13 Hz) which were obtained with MEG recordings prior to pTMS. The MEG recordings after the application of pTMS showed a rapid attenuation of the high abnormal activity followed by an increase in the number of the low frequency components toward the patients alpha-rhythm. The possible mechanisms of the effects of external magnetic stimulation on the pineal gland in the brain are presented.

Objectives To elucidate the hemodynamics of the uterine artery in normal and abnormal pregnancies by use of Doppler ultrasound and SQUID biomagnetometry. Method Two hundred and three women (gestational age 28–42 weeks) were included in the study. Forty-three of them had preeclampsia and/or intrauterine growth restriction and 160 were normal. Uterine artery waveform measurements were evaluated by use of pulsatility index (PI) (normal value PI

Objective: To improve the detection rates in the determination of signs consistent with ulcerative cervicitis against signs of intraepithelial neoplasia, in PAP smears. Study design: We investigated the frequency of establishing a diagnosis of a simple ulcerative cervicitis by histology in a cohort of 58 females with cervical cytology suggestive of intraepithelial neoplasia. Results: There was found a detection rate of 81.58% in the determination of ulcerative cervicitis by cytology and a rate of 100% in the determination of HPV-infection, CIN1, CIN2 and CIN3 respectively. There was no statistically significant difference between cytology and histology in the diagnosis of ultracerative cervicitis (p>0.5, chi-square). Conclusions: There is an overestimation of the cytological signs in the diagnosis of ulcerative cervicitis 18.42 %). There is also an excellent agreement in the diagnosis of HPV-infection and CIN grades (100 %) between cytology and histology, discordant with the literature (2.4 %–71 %).

Aim: Polymorphous low grade adenocarcinoma of the salivary glands (PLGA) is a low grade neoplasm that predominantly occurs in the minor salivary glands. In this site is amenable to biopsy and histologic diagnosis. However, experience with cytological findings in these tumors is limited. We describe the cytology of this entity. Experimental design: Touch imprint cytology of a primary parotid PLGA is specified and correlated with histology. Results: Smears were hypercellular showing branching papillae, sheets and clusters of uniform cells with bland nuclei, dispersed chromatin and no nucleoli. The cells had a scant to moderate amount of eosinophilic cytoplasm. They formed tubular structures containing hyaline globules. Conclusions. The cytologic differential diagnosis of PLGA includes adenoid cystic carcinoma, pleomorphic adenoma, and monomorphic adenoma. PLGA should be considered in the differential diagnosis of head and neck tumors, where the cytology suggests on of the above mentioned tumors, even when the clinical findings (involvement of a major salivary gland, lymph node metastasis) is not typical of PLGA.

To evaluate the biomagnetic activity of a low-grade mucosa-associated lymphoid tissue (MALT-) type gastric lymphoma, and to determine if this procedure could be an adjunct to endoscopic ultrasonography (EUS) in the assessment of the disease pre- and postsurgically.A 47-year-old female with a 2-year clinical history of a low-grade MALT-type gastric lymphoma associated with Helicobacter pylori was examined. The disease showed no histologic remission after eradication of the H. pylori infection and subsequent treatment with chemotherapy and the patient was classified as stage II EA. A decision for surgical resection was made. Biomagnetic waveform recordings were made in the target area before and after surgery and the Fourier analysis of these recordings was performed.The gastric lymphoma biomagnetic waveforms showed high amplitudes (1.8 pT) before and low amplitudes (0.6 pT) after resection. The corresponding Fourier analysis demonstrated that the maximum spectral power of the presurgical measurement was elevated (mean 235 +/- 847 pT2/Hz) compared with that obtained postsurgically (mean 725 +/- 89 pT2/Hz). The difference was of statistical significance ( p0.0001, t-test).Biomagnetic monitoring of gastric lymphoma, which is an entirely new diagnostic modality, could be a supplement to EUS for assessing remission or persistence of disease with medical treatment during follow up.

Aim: To determine the immunoreactivity of pancreatic-polypeptide (PP) during the development of the human fetal pancreas and ductal pancreatic adenocarcinoma, given that, PP positive cells were demonstrated either into its embryonic anlage or into pancreatic cancer. Methods: Tissue sections from 15 pancreatic fetal specimens, and equal number of ductal adenocarcinoma specimens, were assessed. Results: The density of positive cells in the primitive exocrine ductal epithelium and endocrine epithelium was significantly higher than the relevant density in the neoplastic pancreatic tissue of mixed (ductal – endocrine) and pure ductal type (p1=0.001, p2

Aim: The maturation of most T- lymphocyte precursors takes place within the meshwork of thymic epithelial cells. Different steps of this process can be defined by immunologic phenotyping. The prothymocytes are positive for the terminal deoxynucleotidyl transferase (TdT) and give rise to cortical thymocytes, which express CD1, CD2, CD3, CD5, and both CD4 and CD8. These CD4 and CD8 double-positive cortical thymocytes differentiate into two lineages: CD4+ or CD8+ lymphocytes of the thymic medulla, by the tenth week of gestation. Our study points towards the determination of the CD8 cytotoxic/suppressor capacity of the fetal thymus in Down’s syndrome. Experimental design: A quantitative comparison of T-lymphocytes (CD3, CD4, and CD8) in the thymic parenchyme in embryos after voluntary abortion during 2nd trimester of gestation and embryos with Down’s syndrome, respectively, was performed. Results: Our results showed: 1) A statistically significant depletion in the total number of T-cells (CD3 positive) in the cases of embryos with Down’s syndrome over those after voluntary abortion, during the second trimester of gestation (p

Objective To assess the value of biomagnetic recordings of the umbilical artery over Doppler ultrasound screening in order to predict complications of impaired uteroplacental blood flow in fetuses with intrauterine growth restriction (IUGR). Methods Our study population included 11 IUGR preeclamptic (34–37-weeks gestation; birth weight 1969 ± 129 g) and 19 normal pregnancies (34–37-weeks gestation; birth weight 3195 ± 229 g). Umbilical artery Doppler ultrasound waveform measurements were expressed in terms of pulsatility index (PI). Biomagnetic signals (waveforms) recorded from the IUGR umbilical artery were expressed in terms of magnetic power spectral amplitudes. Results In all cases, the frequency band considered was 2 to 7 Hz. The spectral amplitudes were low (mean: 117±24 fT/√Hz) in most (90.9%) IUGR pregnancies and high (mean: 224±37 fT/√Hz) in most normal pregnancies (89.5%). There was a statistically significant difference between normal and IUGR pregnancies with respect to spectral amplitudes (p < 0.0001), Doppler PI (p < 0.0005), pH (p < 0.0005) and Apgar score (p < 0.0005). Multiple linear regression analysis revealed an influence of PI, pH and Apgar scores on the biomagnetic values (ANOVA: p < 0.0005). Conclusion Our data imply that biomagnetic values of the umbilical artery flow could prove to be a helpful method for the evaluation of fetal well being especially in pregnancies complicated with preeclampsia and growth restriction. Copyright © 2003 John Wiley & Sons, Ltd.

Objective To investigate the fetal brain activity in pre-eclamptic and normal pregnancies. Biomagnetic measurements were performed by means of a superconducting quantum interference device (SQUID) in an electrically shielded room of low magnetic noise. Methods The study population included 28 pre-eclamptic (34–37 weeks' gestation) and 19 normal pregnancies (34–37 weeks' gestation). The pre-eclamptic group consisted of 11 cases with birth weight below the 10th percentile (1969 ± 129 g) and 17 cases above the 10th percentile (2496 ± 257 g). Biomagnetic signals (waveforms) recorded from fetal brains were expressed in terms of magnetic power spectral amplitudes. Results The total corresponding spectral amplitudes in the frequency range 2–7 Hz were high (719 ± 69 Ft/√Hz in neonates 10th percentile) in most (82%) pre-eclamptic pregnancies and low (382 ± 35 Ft/√Hz) in most normal pregnancies (95%). The difference between normal and all pre-eclamptic pregnancies was highly significant (Student's t-test: p < 0.0001). Comparing the two groups of pre-eclampsia we found also a highly significant difference (Student's t-test: p < 0.0001). Conclusion Biomagnetic measurements of fetal brain activity could be useful in the assessment of fetal central nervous system development. Copyright © 2002 John Wiley & Sons, Ltd.

There have been no published recommendations for the management of low-risk chest pain in emergency departments (EDs) across India. This is despite the fact that chest pain continues to be one of the most common presenting complaints in EDs. Risk stratification of patients utilizing an accelerated diagnostic protocol has been shown to decrease hospitalizations by approximately 40% with a low 30-day risk of major adverse cardiac events. The experts group of academic leaders from the Indian College of Cardiology and Academic College of Emergency Experts in India partnered with academic experts in emergency medicine and cardiology from leading institutions in the UK and USA collaborated to study the scientific evidence and make recommendations to guide emergency physicians working in EDs across India.

Computational thinking resembles a new philosophy in order to approach not only scientific problems but also challenges of everyday life. In recent years, computational thinking reveals more and more as a fundamental skill for everyone. Observing that, the educational community has been interested in the designing of appropriate teaching and pedagogical strategies by incorporating procedures for the cultivation and development of computational thinking during the learning process. In this context, the utilization of gamification aims at activating the participation of students. In particular, a common application of gamification is the empowerment of extrinsic motivation through the integration of grading characteristics comparable with those of video games, such as points, levels, and achievements. However, the activation of external motives, while disregarding the internal ones, may lead to the declination of interest in learning. This work defines a student-centered framework for strengthening the active participation of students using intrinsic motivation for learning and develops a framework for designing educational activities. As a guide to framework application, three prototype scenarios and the corresponding correlations to the computational thinking, gamification and constructivist learning theory goals throughout the learning activities are presented.