IgG Serum Antibodies to Shigella sonnei Lipopolysaccharide Are Inversely Associated with the Incidence of Culture-Proven S. sonnei Shigellosis in Israeli Children and Adolescents.

BACKGROUND: Shigella is a leading cause of moderate-to-severe diarrhea globally, with young children most affected. The burden of shigellosis drops increasingly with age, inferring the acquisition of natural immunity. We tested the hypothesis that IgG antibodies elicited against Shigella O-specific polysaccharide (O-SP) are correlates of age-acquired immunity. OBJECTIVES: We examined levels and determinants of serum IgG to S. sonnei LPS and the association with the incidence of S. sonnei shigellosis in Israeli children and adolescents. METHODS: We analyzed 1096 serum samples from 0- to 19-year-olds collected in 2008-2015 for IgG anti-S. sonnei LPS levels by ELISA. Corresponding age-specific incidences of culture-proven S. sonnei shigellosis from 2008 to 2015 were obtained. We compared ecologically IgG levels, prevalence above a proposed protective threshold, and S. sonnei shigellosis incidence. RESULTS: In a multivariable analysis model, children aged 1-4, 5-14, and 15-19 years were 6.71, 27.68, and 48.62 times more likely to have IgG anti-S. sonnei LPS above the threshold than those aged < 1 year, respectively (p < 0.001). Infants 0-3 months old had relatively high IgG anti-S. sonnei LPS levels of maternal origin that dropped thereafter. Children of low socioeconomic status had a 2.73 times higher likelihood of having IgG anti-S. sonnei LPS above the threshold (p < 0.001). A significant inverse correlation between age-specific IgG anti-S. sonnei LPS levels and S. sonnei shigellosis incidence was observed (Spearman rho= -0.76, p = 0.028). CONCLUSIONS: The study results support anti-S. sonnei LPS antibodies as correlates of protection that can inform Shigella vaccine development.

Exposure to Holocaust is associated with chronic morbidity in older adults-Results from national health and nutrition surveys.

BACKGROUND: Although studies have suggested that Holocaust survivors are more likely than their non-Holocaust-exposed counterparts to suffer from mental and chronic morbidity, methodology differences and potential confounders often compromise result replicability and external validity. We examined associations between Holocaust exposure and chronic morbidity, as well as overall risk of mortality. METHODS: Sociodemographic, health-related behavior and nutritional-intake data from two representative National Health and Nutrition Survey Ages 65 and Over-the 2005-2006 MABAT ZAHAV 1 (MZ1) and the 2014-2015 MZ2, including face-to-face interviews and anthropometric measurements-were analyzed. Demographic, health, nutritional and lifestyle characteristics, and exposure to the Holocaust were self-reported. Longitudinal data on overall mortality were obtained by linking the MZ1 population to the population registry dataset. Associations between Holocaust exposure and prevalence of chronic morbidity and risk factors were estimated by multivariable logistic regression analyses, and to risk of overall mortality by Cox regression analysis, both adjusted to significant covariates. RESULTS: Among 2096 study participants aged 75.7 ± 6.1 years, 47.0% male, 518 were Holocaust survivors. In the fully adjusted model, Holocaust exposure was associated with increased prevalence of heart disease (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.07-1.83), metabolic syndrome (OR 2.28, CI 1.23-4.21), and stroke (OR 1.77, CI 1.17-2.69), but not cancer or osteoporosis. Holocaust exposure did not substantially affect the overall risk of mortality (hazard ratio 1.10, CI 0.92-1.32). CONCLUSIONS: Further research is needed to understand the mechanisms governing long-term outcomes of exposure to acute physical or mental trauma.

Menopausal symptoms and attitudes toward hormone replacement therapy among Israeli women.

Menopause occurs around midlife and is an inevitable component of women's aging. The study aimed to investigate the associations between the lifetime prevalence of menopausal symptoms and health-related characteristics among Israeli postmenopausal women aged 55-75 years. Additionally, this study aimed to estimate the use of hormone replacement therapy (HRT) and women's attitudes toward this treatment. Data for this study were extracted from a cross-sectional national telephone survey conducted in Israel between 2018 and 2020. For the current study, only postmenopausal women aged 55-75 years were included. Multivariate analyses were used to identify demographic and health-related characteristics associated with menopausal symptoms. The study included 688 participants. Most (68.8%) reported one or more menopausal symptoms, specifically vasomotor symptoms (50.4%). According to the multivariate logistic regression analysis, menopausal symptoms were associated with moderate-high anxiety and/or depression symptoms (OR = 2.01, 95% CI 1.12-3.58) and with osteoporosis (OR = 1.78, 95% CI 1.08-2.92). Although most (78.3%) symptomatic women were bothered by their symptoms, 29.1% received any treatment for symptom relief and only 12.6% reported current or past use of HRT. The findings show that menopausal symptoms were associated with a higher prevalence of anxiety and/or depression symptoms and osteoporosis in the years following menopause. Most symptomatic women did not receive any treatment and the majority were against HRT. Knowledge and awareness about menopause and treatment options should be increased among Israeli women. Additionally, the promotion of positive attitudes toward menopause and HRT use among women and healthcare providers is strongly recommended.

Diet Quality and Incident Frailty in Adults 65 Years or Older: The Israeli Longitudinal Study on Aging.

OBJECTIVE: To prospectively examine the association between diet quality and frailty incidence in the oldest-old age group. METHODS: We studied an older adult (65+ years) cohort participating in the Israeli National Health and Nutrition Survey of Older Adults in 2005-2006 (T1 [N=1799]). Survivors of T1 were contacted, and between 2017 and 2019, an extensive interview and a functional assessment were conducted (T2) of 604 past participants. A 24-hour dietary recall, assessed at T1, was used to calculate the Healthy Eating Index (HEI-2015) score. A frailty index based on an accumulation of deficits, including clinical, functional, and cognitive measures, was computed. Frail participants at T1 were excluded from the analysis. Logistic regression models were constructed to assess the association of HEI-2015 score with frailty incidence. Inverse probability weighting was used to minimize selection bias due to attrition. RESULTS: Of the 479 T2 participants analyzed (mean [SD] age, 84 [5] years; 50% women), 225 (46%) were classified as frail. Frail participants were older, were less educated, and had a lower household income and a higher comorbidity burden at baseline than non-frail participants. After adjustment for sociodemographic and lifestyle factors, a higher HEI-2015 score was associated with decreased odds of incident frailty (odds ratio, 0.57 [95% CI, 0.35 to 0.91] for the upper tertile and 0.66 [95% CI, 0.42 to 1.06] for the middle tertile compared with the lower tertile; Ptrend=.02). CONCLUSION: In this cohort study of oldest-old participants, improved diet quality was inversely associated with frailty incidence in a dose-dependent manner.

COVID-19 Boosters: If The US Had Matched Israel's Speed And Take-Up, An Estimated 29,000 US Lives Would Have Been Saved.

Israel was the first country to launch COVID-19 boosters, in late July 2021, with strong public health messaging. The booster campaign reversed rising infection rates from the Delta variant and reduced hospitalizations and deaths. The US booster rollout was slower, and public health messaging was mixed. We used the Israeli experience to ask the counterfactual question: How many lives could the US have saved if it had authorized boosters sooner? We estimated that through June 30, 2022, if the US had moved at Israel's speed and booster take-up percentages, it would have saved 29,000 lives. US regulatory caution, in the middle of a pandemic, thus had a large, avoidable cost. Yet the US booster rollout still avoided 42,000 deaths. Moving more slowly to approve boosters, as some advocated, would have cost many additional lives.

Association between parental smoking and child exposure to environmental tobacco smoke in Israel.

BACKGROUND: Environmental tobacco smoke (ETS) exposure in children can cause delayed lung development and lifelong cardiovascular damage. The aim of this study was to measure ETS exposure in children in Israel in 2020-2021 using urinary cotinine (UC) measurements and to assess correlates of ETS exposure, including parental smoking. METHODS: In the framework of the National Human Biomonitoring Program, spot urine samples and questionnaire data were collected from 166 children aged 4-12 years, during the years 2020-2021. We collected urine samples in 233 adults, 69 of whom were parents of children included in the study. Parents of participating children were asked about parental smoking, child's exposure to ETS and smoking policy at home. Cotinine and creatinine were measured in urine. Creatinine-adjusted and unadjusted urine cotinine (UC) geometric means were calculated. Associations between potential correlates and UC concentrations were analyzed in univariate and multivariate analyses. For 69 child-parent pairs, correlation between child and parental UC was analyzed. RESULTS: Based on urinary cotinine measurement, 65.2% of children of smokers are exposed to ETS, compared to 20.7% of children in non-smoking families. Greater numbers of smokers living in the home (beta = 1.27, p < 0.01), and low maternal education (beta = - 2.32, p < 0.01) were associated with higher levels of UC in a multivariate analysis. Spearman correlations showed a positive moderate correlation between UC in 69 child-parent pairs (r = 0.52, p < 0.01). CONCLUSIONS: In order to reduce child exposure to ETS, smoking parents should be urgently targeted for smoking cessation and smoke-free home interventions. Further interventions are needed to protect all children from ETS.

An Increased Risk for Ischemic Stroke in the Short-Term Period following COVID-19 Infection: A Nationwide Population-Based Study.

INTRODUCTION: The association disclosed between coronavirus disease 2019 (COVID-19) infection and ischemic stroke (IS) raises concern. The exact risk periods, which were not consistent between studies, require further investigation. METHODS: We linked two national databases: the COVID-19 database and the Israeli National Stroke Registry. The self-controlled case series method was used to estimate the association between COVID-19 infection and a first IS. The study population included all Israeli residents who had both a first IS event and a first COVID-19 diagnosis during 2020. The date of the PCR test served to define the day of exposure, and the 28 days following it were categorized into three risk periods: days 1-7, 8-14, and 15-28. A relative incidence (RI) with a 95% confidence interval (95% CI) was calculated based on the incidence rate of events in a post-exposure period, compared to the incidence rate in a control period. RESULTS: From January 1, 2020, to December 31, 2020, 308,015 Israelis aged 18+ were diagnosed with COVID-19 and 9,535 were diagnosed with a first IS. Linking the two databases, 555 persons had both diagnoses during 2020. The mean age of the study population was 71.5 ± 13.7, 55.1% were males, 77.8% had hypertension, 73.7% had hyperlipidemia, 51.9% had diabetes, and 28.5% had ischemic heart disease. Comparing the risk period and the control period, we found a very similar distribution of the cardiovascular risk factors. The risk for an acute IS was 3.3-fold higher in the first week following COVID-19 diagnosis, compared with a control period (RI = 3.3; 95% CI: 2.3-4.6). The RI among males (RI = 4.5; 95% CI: 2.9-6.8) was 2.2-fold higher compared to females. The increased risk did not last beyond the first week following exposure. CONCLUSION: Physicians should be aware of the elevated risk for IS among patients experiencing COVID-19, particularly among men with high burden of cardiovascular risk factors.

Trends in the Epidemiology of Non-Typhoidal Salmonellosis in Israel between 2010 and 2021.

Non-typhoidal salmonellosis (NTS) is one of the most common foodborne diseases worldwide. In this study, we aimed to analyze trends in the epidemiology of NTS in the last decade in Israel. Laboratory-confirmed cases of NTS at eight sentinel laboratories were reported to the Israel Sentinel Laboratory-Based Surveillance Network, integrated with the serotype identification performed at the Salmonella National Reference Laboratory of the Ministry of Health. The decrease in NTS incidence since 1999 continued between 2010 and 2014 (16.1 per 100,000 in 2014) and was interrupted by a rise between 2015 and 2017 (39.1 per 100,000 in 2017) associated with outbreaks of Salmonella Enteritidis. The incidence of NTS dropped again thereafter (21.4 per 100,000 in 2021). The 0-4 age group was the most affected by NTS (55.5% of the cases) throughout the surveillance period. The age-adjusted incidence rates were consistently high in the summer months (June-September) and low in the winter months (December-February). The overall decrease in the incidence of NTS in Israel since 1999 was temporarily interrupted in the last decade by country-wide outbreaks involving emerging or re-emerging Salmonella serotypes. Control measures should be enhanced for all risk points of food chain transmission of Salmonella spp. to further reduce the NTS morbidity in Israel.

Food Insecurity in Israeli Elderly is Associated with Sociodemographic Characteristics, Disability, and Depression: Policy Implications.

Background: Food insecurity (FI) and poor health can turn into a vicious cycle with detrimental effects, especially in the elderly, however, few studies have examined the relationship between FI and health in this age group. Objectives: We investigated associations of FI with physical and mental health and health behaviors among community-dwelling elderly. Methods: We used nationally representative, cross-sectional data from the 2014-2015 Israel National Health and Nutrition Survey of the Elderly (Rav Mabat Zahav) on FI, sociodemographic characteristics, noncommunicable diseases (NCDs), disability, self-assessed physical, oral, and mental health for 1006 individuals aged ≥65 y. Results: FI affected 12.3% of all households with elderly and was significantly higher among late immigrants and Arabs. Bivariate associations of FI with the number of NCDs, depression, disability in all 6 domains (vision, hearing, mobility, self-care, remembering, communication), poor self-assessed physical and oral health, chewing and swallowing problems, feelings of loneliness, insufficient physical activity, and smoking were significant (P < 0.05). In a multivariable logistic regression controlling for population group, household size, age and sex, FI was significantly associated (P < 0.05) with lack of formal education (OR: 6.26; 95% CI: 1.66, 23.65), being in the lowest (OR: 23.56; 95% CI: 3.71, 149.76) or second-lowest (OR: 16.75; 95% CI: 2.68, 104.52) per capita household income quartile, having one (OR: 2.11; 95% CI: 1.05, 4.23) or several disabilities (OR: 4.04; 95% CI: 1.72, 9.45), and having ever been diagnosed with depression (OR: 3.34; 95% CI: 1.35, 8.28). Conclusions: FI is associated with physical and mental health problems, multiple disabilities, and loneliness among Israeli elderly. Providing income support could reduce FI, and subsidized congregate and home-delivered meal services could be expanded to meet the needs of elderly with disabilities and counter social isolation. Because low education, disability, and depression are particularly prevalent among the food insecure and vulnerable groups face language barriers, assistance with applications for these services should be increased.

Effectiveness of BNT162b2 Vaccine against Omicron Variant Infection among Children 5-11 Years of Age, Israel.

We assessed effectiveness of the BNT162b2 vaccine against infection with the B.1.1.529 (Omicron) variant (mostly BA.1 subvariant), among children 5-11 years of age in Israel. Using a matched case-control design, we matched SARS-CoV-2-positive children (cases) and SARS-CoV-2-negative children (controls) by age, sex, population group, socioeconomic status, and epidemiologic week. Vaccine effectiveness estimates after the second vaccine dose were 58.1% for days 8-14, 53.9% for days 15-21, 46.7% for days 22-28, 44.8% for days 29-35, and 39.5% for days 36-42. Sensitivity analyses by age group and period demonstrated similar results. Vaccine effectiveness against Omicron infection among children 5-11 years of age was lower than vaccine efficacy and vaccine effectiveness against non-Omicron variants, and effectiveness declined early and rapidly.

Dialysis in Israeli Children between 1990 and 2020: Trends and International Comparisons.

BACKGROUND: Childhood kidney failure is a rare condition with worldwide clinical variability. We used a nationwide multicenter analysis to study the pretransplant course of the entire Israeli pediatric kidney failure population over 30 years. METHODS: In this nationwide, population-based, historical cohort study, we analyzed medical and demographic data of all children treated with KRT and reported to the Israeli kidney failure registry in 1990-2020. Statistical analysis was performed with incidence rate corrected for age, ethnicity, and calendar year, using the appropriate age-related general population as denominator. RESULTS: During the last 30 years, childhood incidence of kidney failure decreased. Average incidence in 2015-2019 was 9.1 cases per million age-related population (pmarp). Arab and Druze children exhibited higher kidney failure incidence rates than Jewish children (18.4 versus 7.0 cases pmarp for minorities versus Jews). The most common kidney failure etiologies among Arab and Jewish children were congenital anomalies of the kidney and urinary tract (approximately 27%), followed by cystic kidney diseases among Arab children (13%) and glomerulonephritis among Jewish children (16%). The most common etiology among Druze children was primary hyperoxaluria type 1 (33%). Israel's national health insurance provides access to primary health care to all citizens. Accordingly, waiting time for deceased-donor transplantation was equal between all ethnicities. Living-donor kidney transplantation rates among minority populations remained low in comparison with Jews over the entire study period. Although all patient groups demonstrated improvement in survival, overall survival rates were mainly etiology dependent. CONCLUSIONS: In Israel, Arab and Druze children had a higher incidence of kidney failure, a unique etiological distribution, and a lower rate of living-donor kidney transplantations compared with Jewish children.

Rise in depression and anxiety during the COVID-19 pandemic: results from a cross-sectional national survey.

The Coronavirus disease 2019 (COVID-19) pandemic has introduced many mental stressors. This study aimed to evaluate the prevalence of depression and anxiety during the pandemic and characterize those at higher risk. We conducted a national cross-sectional telephone interview survey among Israeli adults from May to September 2020, between the first two national lockdowns. Mental health status was measured using the 5-item Mental Health Inventory (MHI-5). A score of ≤60 was defined as poor mental health with moderate to high anxiety and depression symptoms. Multivariate analysis was used to identify demographic, health-related, and COVID-19-related risk factors associated with poor mental health. From 4,712 households that were eligible for inclusion in this study, 2,634 participants (55.9%) completed the survey. Levels of anxiety and depression symptoms increased significantly throughout the pandemic (from 12.9% to 20.3%, P < 0.001). Loneliness also increased over time (from 48.8% to 58.8%, P < 0.001), and fear of the pandemic remained high (66.5%) throughout the study. According to the multivariate analysis, poor mental health was associated with younger age, female gender, lower education, Arab ethnicity, decrease in household income during the pandemic, having a pre-existing chronic illness, obesity, smoking, ever being quarantined, feeling lonely and fear of the pandemic. Our findings show an increase in anxiety and depression over time among the Israeli population during the COVID-19 pandemic. These findings highlight the need for strengthened mental health services and the flexibility of reallocation of funds and health resources to support the growing mental health needs during the health crisis.

Vaccine Coverage Associated With Ending a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Wave: A Retrospective Longitudinal Analysis.

BACKGROUND: Two SARS-CoV-2 waves in Israel ended while a substantial number of individuals remained unvaccinated or partially vaccinated. The indirect protective effect of the first BNT162b2 vaccination campaign in Israel was evaluated between 22 December 2020 and 18 May 2021. METHODS: The daily percentage of new polymerase chain reaction (PCR)-confirmed SARS-CoV-2 cases among unvaccinated individuals was analyzed for trends. Major shifts were identified using piecewise linear regression analysis. At these shifts, the percentage of naturally vaccinated (past SARS-CoV-2 cases) and the percentage of actively vaccinated (by inoculation) individuals were weighted and summed to determine the percentage of natural and active vaccination (NAV). RESULTS: A first decline among unvaccinated individuals occurred during a lockdown period, when the percentage of NAV was 8.16%. The major decline occurred after the end of the lockdown when the percentage of NAV reached 52.05%. SARS-CoV-2 cases ultimately declined among unvaccinated individuals when the percentage of NAV reached 63.55%. During the study period, the Alpha variant was prevalent and the use of nonpharmaceutical interventions, including social distancing, existed to varying degrees. CONCLUSIONS: The vaccination campaign played a major role in the decline of SARS-CoV-2 infection among unvaccinated individuals, leading to the end of the first 2021 SARS-CoV-2 wave (Alpha variant) in Israel. Infection in unvaccinated individuals stopped when two-thirds of the population were naturally or actively vaccinated. Any change in characteristics of the virus or the population can lead to a new outbreak.

Estimated Infection and Vaccine Induced SARS-CoV-2 Seroprevalence in Israel among Adults, January 2020-July 2021.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerged in Israel in February 2020 and spread from then. In December 2020, the FDA approved an emergency use authorization of the Pfizer-BioNTech vaccine, and on 20 December, an immunization campaign began among adults in Israel. We characterized seropositivity for IgG anti-spike antibodies against SARS-CoV-2 between January 2020 and July 2021, before and after the introduction of the vaccine in Israel among adults. We tested 9520 serum samples, collected between January 2020 and July 2021. Between January and August 2020, seropositivity rates were lower than 5.0%; this rate increased from September 2020 (6.3%) to April 2021 (84.9%) and reached 79.1% in July 2021. Between January and December 2020, low socio-economic rank was an independent, significant correlate for seropositivity. Between January and July 2021, the 40.00-64.99-year-old age group, Jews and others, and residents of the Northern district were significantly more likely to be seropositive. Our findings indicate a slow, non-significant increase in the seropositivity rate to SARS-CoV-2 between January and December 2020. Following the introduction of the Pfizer-BioNTech vaccine in Israel, a significant increase in seropositivity was observed from January until April 2021, with stable rates thereafter, up to July 2021.

COVID-19 vaccine hesitancy among Israeli adults before and after vaccines' availability: A cross-sectional national survey.

Vaccine hesitancy (VH) is a major health threat to the efforts to tackle COVID-19 morbidity and mortality. This study's objectives were to assess COVID-19VH before and after vaccines' availability and to analyze the associations between COVID-19VH and participants' characteristics. A national cross-sectional telephone interview survey among Israeli adults aged 21 and older was conducted from September 2020 through May 2021. Attitudes towards COVID-19 vaccines were assessed pre/post vaccines' availability. Multivariate logistic regression analyses were used to identify associations between demographic and health-related characteristics and COVID-19 VH. Most study participants (72.0 % of 2,998) were willing to be vaccinated against COVID-19 across the survey period. The COVID-19 VH declined significantly from 45.6 % pre-vaccine availability to 16.3 % post-vaccine availability (P < 0.001). The multivariable analysis demonstrated that post-vaccine availability, COVID-19 VH was associated with younger age, Arab ethnicity, higher level of religiosity, lower education, past diagnosis of COVID-19, and influenza VH. The main reasons for VH after the vaccine availability included insufficient data on the vaccine (37.4 %) and fear of the vaccine's side effects (33.8 %). Despite the significant decrease in COVID-19 VH following vaccine availability, 16.3% of the population still refuses to get vaccinated. As Israel may face additional waves of the COVID-19 pandemic and booster vaccinations, multimedia vaccine promotions targeting the above-mentioned hesitant populations and their reasons for VH are urgently needed.

Varicocoele in adolescence and testicular cancer in young adulthood.

BACKGROUND: Elevated intrascrotal temperature has been suggested as a risk factor for testicular cancer, which is the most common neoplasm among young men. Varicocoele was linked to increased intrascrotal temperature, but whether it is associated with testicular cancer is unclear. OBJECTIVE: To explore the possible association between varicocoele at adolescence and the incidence of testicular cancer at adulthood. DESIGN, SETTING, AND PARTICIPANTS: This nationwide, population-based, historical cohort study includes 1,521,661 Israeli male adolescents (mean age 17.5 ± 0.4 years), who were screened for varicocoele during the years 1967-2012, as part of their medical assessment prior to compulsory military service. The mean follow-up was 18 ± 4.2 years. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The diagnosis of testicular cancer was ascertained from linkage of records to the the Israeli National Cancer Registry. Survival analysis was applied. RESULTS: In total, 53,210 adolescents were diagnosed with varicocoele stages 2 and 3 prior to military service. Of 1988 (0.13% of the total cohort) men who were diagnosed with testicular cancer during follow-up, 54 (0.1%) had varicocoele prior to military service, while 1934 (99.9%) did not; p = 0.213. The age at cancer diagnosis and the distribution of seminomas versus non-seminomas did not differ significantly between those with and without varicocoele in adolescence. In a multivariable analysis controlling for sociodemographic factors, varicocoele was not associated with testicular cancer; odds ratio = 0.816 (CI: 0.615-1.083). CONCLUSIONS: Varicocoele in adolescents was not found to be associated with testicular cancer in young adults. PATIENT SUMMARY: In light of the theoretical association between varicocoele and testicular cancer, we conducted this large population study. We found no association between varicocoele in young adulthood and testicular cancer later in life.

An Exercise-Induced Metabolic Shield in Distant Organs Blocks Cancer Progression and Metastatic Dissemination.

Exercise prevents cancer incidence and recurrence, yet the underlying mechanism behind this relationship remains mostly unknown. Here we report that exercise induces the metabolic reprogramming of internal organs that increases nutrient demand and protects against metastatic colonization by limiting nutrient availability to the tumor, generating an exercise-induced metabolic shield. Proteomic and ex vivo metabolic capacity analyses of murine internal organs revealed that exercise induces catabolic processes, glucose uptake, mitochondrial activity, and GLUT expression. Proteomic analysis of routinely active human subject plasma demonstrated increased carbohydrate utilization following exercise. Epidemiologic data from a 20-year prospective study of a large human cohort of initially cancer-free participants revealed that exercise prior to cancer initiation had a modest impact on cancer incidence in low metastatic stages but significantly reduced the likelihood of highly metastatic cancer. In three models of melanoma in mice, exercise prior to cancer injection significantly protected against metastases in distant organs. The protective effects of exercise were dependent on mTOR activity, and inhibition of the mTOR pathway with rapamycin treatment ex vivo reversed the exercise-induced metabolic shield. Under limited glucose conditions, active stroma consumed significantly more glucose at the expense of the tumor. Collectively, these data suggest a clash between the metabolic plasticity of cancer and exercise-induced metabolic reprogramming of the stroma, raising an opportunity to block metastasis by challenging the metabolic needs of the tumor. SIGNIFICANCE: Exercise protects against cancer progression and metastasis by inducing a high nutrient demand in internal organs, indicating that reducing nutrient availability to tumor cells represents a potential strategy to prevent metastasis. See related commentary by Zerhouni and Piskounova, p. 4124.

Preventable Cancer in Israel.

Background: The cancer burden in Israel is substantial. Recently calculated population attributable fractions (PAFs) for modifiable cancer risk factors in the US and the UK have indicated much room for prevention. Our aim was to estimate PAFs for selected modifiable cancer risk factors in Israel. Methods: Exposure data on selected modifiable risk factors were based on national health surveys conducted in 2013-2015. Data on invasive cancer incidence in 2015 were retrieved from the Israel National Cancer Registry (INCR). Relative risks (RRs) for specific cancer sites were retrieved from the scientific literature. PAFs were calculated for selected modifiable risk factors using an approximate formula. Results: In 2015, 21% of all invasive cancer cases in Israel were attributed to smoking, 9% to excess body weight, and 1.5% to alcohol intake. Moreover, 32% of all invasive cancer cases were attributed to all modifiable risk factors (combined) included in our study. Conclusions: Quantifying the contribution of modifiable risk factors to the incidence of certain cancer types in Israel offers an opportunity for primary prevention and enables informed decision-making with respect to the prioritization of interventions.

Wastewater-derived organic contaminants in fresh produce: Dietary exposure and human health concerns.

Irrigation with reclaimed wastewater is a growing practice aimed at conserving freshwater sources, especially in arid and semiarid regions. Despite the apparent advantages to water management, the practice of irrigation with reclaimed wastewater exposes the agroenvironment to contaminants of emerging concern (CECs). In this report, we estimated the unintentional dietary exposure of the Israeli population (2808 participants) to CECs from consumption of produce irrigated with reclaimed wastewater using detailed dietary data obtained from a National Health and Nutrition Survey (Rav Mabat adults; 2014-2016). Human health risk analyses were conducted based on acceptable daily intake (ADI) and threshold of toxicological concern (TTC) approaches. The highest unintentional exposure to wastewater-borne CECs was found to occur through the consumption of leafy vegetables. All analyzed CECs exhibited hazard quotients <1 for the mean- and high-exposure scenarios, indicating no human health concerns. However, for the extreme exposure scenario, the anticonvulsant agents lamotrigine and carbamazepine, and the carbamazepine metabolite epoxide-carbamazepine exhibited the highest exposure levels of 29,100, 27,200, and 19,500 ng/person (70 kg) per day, respectively. These exposure levels exceeded the TTC of lamotrigine and the metabolite epoxide-carbamazepine, and the ADI of carbamazepine, resulting in hazard quotients of 2.8, 1.1, and 1.9, respectively. According to the extreme estimated scenario, consumption of produce irrigated with reclaimed wastewater (leafy vegetables in particular) may pose a threat to human health. Minimizing irrigation of leafy vegetables using reclaimed wastewater and/or improving the quality of the reclaimed wastewater using an advanced treatment would significantly reduce human dietary exposure to CECs.