Abstract Aims Heart disease might be an independent risk factor for cancer (reverse cardio-oncology). The co-occurrence of these diseases worsens patients' prognoses and limits therapeutic options. However, the cellular and molecular mechanisms that link heart disease to cancer remain elusive. Therefore, we hypothesized that cardiac extracellular vesicles (cEVs) secreted by diseased hearts carry and disseminate factors that promote tumor growth. Methods and results We subjected female mice to myocardial infarction (MI) or sham-MI and 28 days of follow-up. Left ventricular remodeling and dysfunction were assessed by echocardiography. To determine the role of cEVs in tumor growth, we focused on cardiac mesenchymal stromal cells (cMSCs), which play a central role in cardiac repair, remodeling, and fibrosis. We isolated cMSCs from mice hearts 10 or 28 days after MI or sham MI and purified cMSC-EVs from the conditioned medium using size exclusion chromatography. cEVs were characterized by nanoparticle tracking analysis (NTA), the classical EV markers: CD81 and Tumor susceptibility gene 101, and electron microscopy. cMSCs after MI secreted more small EVs than cMSCs from sham-MI (Fig. 1A, p<0.0001). Proteomic and biological process analysis revealed a distinctive profile of cEVs after MI with more EV-encapsulated proteins related to inflammation, angiogenesis, and cell cycle (Fig. 1B). Purified cMSC-EVs were labeled with PKH26 dye and found to target both breast and lung cancer cells in vitro. Colorimetric proliferation assay showed that MI-cEVs facilitated cancer cells proliferation compared with sham-MI cEVs (n=7 in each group, p<0.0001). Furthermore, by scratch assay, MI-cEVs facilitated cancer cell migration two times faster than sham-MI cEVs (Fig. 1C, p=0.0002). Finally, we established 2 models of heart disease with cancer. Lung or breast cancer cells (750x103 or 250x103) were inoculated into the hind limb or mammary pad 10 days before or after MI. Serial ultrasound examinations monitored tumor growth. While MI significantly stimulated lung cancer growth, EV inhibition by GW4869 markedly attenuated the tumorigenic effect of MI and left ventricular (LV) dysfunction (Fig. 1D, p for GW4869 <0.0001). Moreover, we found an inverse correlation between LV ejection fraction (LVEF) and the volume of breast cancer tumors. cEV inhibition by GW4869 attenuated this inverse correlation (for vehicle group: n=14, r=−0.54 and p=0.04. for GW4869 group: n=13, r=−0.43, and p=0.14). Conclusions Our results suggest, for the first time, that cMSCs from the infarcted and failing heart secret EVs that target tumor cells and accelerate tumor growth. We propose cEVs as potential mediators and therapeutic targets in patients with concomitant heart disease and cancer. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Seymour Fefer Grant

Introduction Diabetes as a multifactorial disorder requires prevention measures based upon the modification of several risk factors simultaneously; otherwise, there is insufficient potential for prevention. Following the success of the American Diabetes Prevention Program (DPP), we implemented an intervention program in a large Israeli healthcare organization with an emphasize on Mediterranean Diet (MedDiet) and physical activity. The objective was to evaluate the effectiveness of two types of intervention, individual and group therapies, in reducing risk factors and in preventing or delaying the development of type 2 diabetes. Methods Out of 180 primary care physicians, 85 who agreed to participate, were randomly assigned, between the years 2005 and 2006, into two groups: those who would refer pre-diabetes adult patients for individual therapy and those who would refer for group therapy. The two groups of patients consisted of 111 and 112 in each group. The intervention lasted for 6 months and discussed: the benefits of MedDiet, planning nutritional behavior and mindful eating, and the importance of physical activity. All patients were invited to participate in walking groups. Follow up lasted for 24 months and logistic, mixed models, and Cox regressions were employed. Results No statistically significant differences were detected between the two intervention groups in age; gender and clinical measurements at recruitment. Thirty nine percent of both groups developed diabetes (entered the DR by 2012), including 38.7% from the individual therapy and 39.3% from the group therapy (P = 0.933). The mean time from 2005 until entry to the Diabetes Registry (DR) was 2.9 and 2.5 years for the individual and group therapy respectively (P = 0.542). Conclusion Both interventions were equally effective in achieving the desired outcomes and time until entry to the DR. For large health organizations with a high number of pre-diabetes patients and scarce resources, group therapy, where 12 people are reached out by one team member are preferable and more costly effective, than a one on one therapy.

This paper investigates repetitive purchase decisions of perishable items in the face of uncertain demand (the newsvendor problem). The experimental design includes: high, or low profit levels; and uniform, or normal demand distributions. The results show that in all cases both learning and convergence occur and are effected by: (1) the mean demand; (2) the order-size of the maximal expected profit; and (3) the demand level of the immediately preceding round. In all cases of the experimental design, the purchase order converges to a value between the mean demand and the quantity for maximizing the expected profit.

The objective was to evaluate the prevalence of osteoporosis among Ethiopian immigrant and Israeli-born women and to determine the risk factors. The study revealed extreme prevalence of osteoporosis among Ethiopian immigrants (38.7). A strong association between calcium intake during adolescence, BMI, lactation duration, physical activity, oral contraceptive and osteoporosis is suggested.

Objectives: To assess the importance of combined use of non-contrast computerized tomography (NCCT) and dynamic renal scintigraphy (DRS) in evaluation of patients with refractory flank pain in the emergency department.Methods: The study involved 64 consecutive patients with refractory renal colic. All patients were evaluated with plain abdominal films kidneys, ureters and bladder (KUB), NCCT and DRS. We assessed the accuracy of different diagnostic procedures and their combinations; in addition, we determined their importance for different steps of evaluation.Results: Urololithiasis was diagnosed in 76.6% (n = 49) of the patients. Twenty-nine percent of calculi were >4 mm. Surgical intervention were performed in 20 patients (40.8%). A combination of NCCT plus DRS yielded the greatest sensitivity (96%) in establishing final diagnosis, however clinical, laboratory and KUB data in combination with DRS, yielded greater specificity (93%) and PPV (97%). Sex (male), WBC (mean 10.2 x 10(3) +/- 3.1) and KUB (calculus > 4 mm) were chosen in the three-step multi-variant analysis, while only male sex was found to be the strongest predictor (p < 0.056) of necessity to perform NCCT. In making decision for definitive treatment NCCT and DRS provided the most important information about stone size and obstruction (kappa = 0.734, p < 0.001 and kappa = 0.625, p < 0.001), while DRS was selected as the most important diagnostic procedure in the emergency department (kappa = 0.527, p < 0.001).Conclusions: In the emergency department, DRS combined with the results of clinical investigation may indicate candidates for hospitalization with emergency intervention. Immediate NCCT must be strongly considered in men with WBC >= 10 x 10(3) and calculi > 4 turn on the KUB. (C) 2005 Elsevier Ireland Ltd. All rights reserved.

Fine particles are thought to pose a risk to health, especially for vulnerable groups such as children with asthma. These children are also known to be affected by meteorological and seasonal changes. We assessed the association between air pollution and lung function via peak expiratory flow (PEF), controlling for seasonal changes, meteorological conditions and personal physiological, clinical and sociodemographic measurements, in a panel of schoolchildren with asthma living near two power plants in Israel. Two hundred and eighty-five children with confirmed asthma performed PEF tests and completed a respiratory symptoms diary twice a day. Particulate matter <10 microm in diameter (PM10), particulate matter <2.5 microm in diameter (PM2.5) and meteorological conditions were measured at six fixed stations. Data were analysed using time series analysis-generalized linear model and generalized estimating equations. The models were built under the assumption that any health outcome belongs to a multivariate hierarchical system and depends on meteorological, geophysical and sociocultural variables and pollution factors. No significant differences were found in the demographic (age, gender, mean parental education level, parental smoking habits, place of birth and housing density), physiological (body mass index) and clinical factors (illness severity) between the communities participating in the study. A significant direct effect of PM2.5 on the PEF was found in Ashdod (P=0.000). In Sderot, this effect was through an interaction between PM10 and the sequential day of the year (P=0.000). The main conclusion of this study is that children with asthma are at risk from air pollution and geophysical conditions. Policy makers should take these results into consideration when setting thresholds for environmental protection.

Objectives. To assess the usefulness of measuring testosterone, free testosterone, and the free/total (f/t) prostate-specific antigen (PSA) ratio with the intention of reducing the number of unnecessary biopsies in the patients with PSA values between 2.0 and 4.0 ng/mL. Cancer detection is not rare among patients with PSA values between 2.0 and 4.0 ng/mL.Methods. A total of 171 men with serum PSA levels of 2.0 to 4.0 ng/mL were enrolled in this study. The f/t PSA ratio and total and free testosterone levels were quantified. All patients underwent transrectal ultrasound-guided biopsy. The cancer detection rate, clinical and pathologic features of the cancers detected, and the probability of cancer detection in relation to the f/t PSA ratio and total and free testosterone levels were estimated. Two-step statistical analysis was used for descriptive purposes and in the detection of cancer predictors. Statistical significance was set at P <= 0.05.Results. The mean patient age was 63.3 years. Cancer was detected in 39 (22.8%) of the 171 patients. Only 15.4% of our patients had insignificant cancer. The f/t PSA ratio and total and free testosterone levels were significantly lower in the patients with prostate cancer (19.3%, 13.68 nmol/L, and 28.4 pmol/L, respectively; P <0.001). The f/t PSA ratio and free testosterone were the strongest predictors of cancer detection (P <0.001).Conclusions. The results of our study have shown that an important number of cancers could be detected in the PSA range of 2.0 to 4.0 ng/mL. The great majority of cancers detected have the features of medically significant tumors. The combination of the f/t PSA ratio and free testosterone measurements may reveal those patients who require biopsy.

Purpose: To evaluate emergency SWL for the treatment of upper urinary-tract stones causing renal colic.Patients and Methods: Between January 1999 and June 2003, 53 patients with a mean age of 46.6 years (range 22-65 years) were enrolled. The inclusion criteria were acute renal colic, radiopaque 5-mm to 1.5-cm calculi in the ureteropelvic junction (N = 10) or upper ureter (N = 43), and no evidence of urinary-tract infection or acute renal failure. The mean stone size was 7.14 mm (range 5-13 mm). Patients were randomly assigned to the control (N = 28) and study (N = 25) groups using previously prepared cards in envelopes. Patients in the study group underwent emergency SWL, while patients in the control group underwent scheduled SWL within 30 days. Stone status was evaluated 4 weeks after lithotripsy. There was no significant difference between the control and study groups with respect to age, sex, stone location or volume, renal obstruction, or days spent in the hospital for pain control. Available fragments of stones were sent for infrared spectroscopy. Preoperative and postoperative data were compared in the two groups using SPSS 10.0 statistical software.Results: The SWL treatment lasted 50 +/- 11 minutes. The stone-free rates were 72% and 64% and the efficiency quotients were 53% and 44% in study and control groups, respectively. Patients in the control group spent more time in the hospital (P = 0.014) and in recovery at home (P = 0.011).Conclusion: Emergency SWL for acute renal colic caused by upper-ureteral stones is a safe procedure and offers effective release from pain and obstruction. It also decreases hospitalization days and hastens return to normal activity.

In the paper, we present the methodology of construction and interpretation of the models, which consider effects of air pollution, and also their applications. The study of air-pollution health effects is a very important component in estimating health risk of air pollution and improving environmental quality. On other hand, such study is very complicated because of complexity of factors involved and their relationships. That explains why the effects of air pollution have not been deeply studied yet.

A method is presented, geared to separating signals from different sources which are convoluted and mixed by the mechanical systems before being measured. The method is based on an automatically operating blind deconvolution separation method, with Kurtosis of the separated signals as the measure to be maximised. The application described involves bearings diagnostics, whereas with many classical diagnostic methods, Kurtosis is traditionally one of the accepted criteria for fault detection. The method is tested on simulation and experimental cases. Results show that separation is possible even when measurements are distanced from the vibration exciting sources of the faulty bearing. Furthermore, the method eliminates the effect of structural resonances, which often causes severe problems in classical diagnostic methods.

ISEE-44 Objectives: To assess the relationship between air pollution by fine particles (PM10 PM2.5) and lung function in asthmatic school children living near two power plants in Israel. Methods: 232 asthmatic school children and 60 Healthy children were arbitrarily divided into 5 subgroups. Every subgroup participated in the study for 4 weeks during the spring and autumn of 2000. Each child performed a self peak flow test (PEF) twice a day and completed a respiratory simptoms diary. In addition to meteorological conditions, fine particles were measured by 5 fixed stations in the corresponding areas. The meteorological and pollution data were averaged over hours in order to get one-record-per-day data file including PEF measurments. Statistical methods: First stage: multivariate regression models aiming to remove possible variance of the individual parameters (age, gender, weight, height). Dependent variable was PEF. Second stage: adjustment for seasonality-a sort of generalized linear time series model based on pairs of sin/cos functions with year, half-year, seasonal and other periods:harmonic analysis model. The dependent variable was a residual of the dependent from the first model. The same procedure was executed for all the pollution and meteorological variables. Third stage: generalized estimating equations (GEE) models trying to identify potential effects of pollution. The dependent variable was a residual of the dependent variable after the second stage of modeling while independent variables were residuals of the meteorological and pollution variables after the second stage. Results: In most of the communities under study an association between air pollution and lung function was ibserved in the sick children. In two communities this effect was significantly found in the healthy children. Conclusion: There is a significant effect of air pollution by fine particles on lung functions of asthmatic and healthy children.

OBJECTIVE:To determine whether lower uterine segment involvement (LUSI) correlates with recurrence and survival in women with stage I endometrial adenocarcinoma who do not receive postoperative radiotherapy on the basis of this histologic criterion.STUDY DESIGN:Eighty patients with endometrial adenocarcinoma stage I who underwent surgery between 1989 and 2002 were divided into 2 groups according to the presence of LUSI. Group 1 consisted of 25 patients with LUSI; group 2 consisted of 55 patients without LUSI. The 2 groups were compared with regard to prognostic factors and outcome measures.RESULTS:There were no statistically significant differences between the 2 groups with regard to the following parameters: age and proportion of patients who underwent complete surgical staging and postoperative adjuvant radiotherapy. Pathologic parameters of the 2 groups, such as histologic type, grade and deep myometrial invasion, were comparable. A greater proportion of patients with LUSI had capillary space-like involvement. The patients were followed for a median of 48 months (range, 11-168) from the date of surgery. The overall 5-year recurrence-free survival, disease-specific survival and overall survival rates were 91% (SE .04), 94% (SE .03) and 77% (SE .06), respectively. There was no significant difference between the two groups with regards to these measures (P < .05).CONCLUSION:In patients with state I endometrial cancer, the presence of lower uterine segment involvement does not correlate with their outcome.