Longer breastfeeding duration is associated with lower consumption of ultraprocessed foods in a sample of spanish preschoolers: The SENDO project

Background: Breastfeeding has been linked to a higher consumption of fruit and vegetables at ages 4 to 5 years. More recently, it has been suggested that it may also be associated with lower ultraprocessed food (UPF) consumption in childhood. Objective: The aim of this study was to assess whether breastfeeding duration was associated with consumption of UPF in a sample of Mediterranean preschoolers. Design: This study involved a cross-sectional analysis of baseline information of children in the Child Follow-Up for Optimal Development cohort. Children were enrolled at ages 4 to 5 years and information was gathered through an online questionnaire completed by parents. Dietary information was collected with a previously validated semi-quantitative food frequency questionnaire and foods were classified based on the degree of processing according to the NOVA classification. Participants/setting: This study used baseline information for 806 participants enrolled in the Child Follow-Up for Optimal Development cohort between January 2015 and June 2021 in Spain. Main outcomes measures: Main study outcome measures were difference in grams per day and in the percentage of total energy intake from UPF consumption related to breastfeeding duration, and odds ratio that UPF represents a high percentage of total energy intake. Statistical analyses: Crude and multivariable adjusted estimates were calculated with generalized estimating equations to account for intracluster correlation between siblings. Results: The prevalence of breastfeeding in the sample was 84%. After adjusting for potential confounders, children who were breastfed for some time reported significantly lower consumption of UPF than children who were not breastfed at all. The mean differences were -19.2 g (95% CI -44.2 to 10.8) for children who were breastfed for <6 months, -42.5 g (95% CI -77.2 to -7.80) for those who were breastfed for 6 to 12 months, and -43.6 g (95% CI -79.8 to -7.48) for those who were breastfed for 12 months or more (P value for trend = 0.01). After adjusting for potential confounders, compared with children who were not breastfed, those who were breastfed for ≥12 months had consistently lower odds of UPF representing more than 25%, 30%, 35%, and 40% of total energy intake. Conclusions: Breastfeeding is associated with lower consumption of UPF in Spanish preschoolers

Gene expression profiling identifies IL-13 receptor alpha 2 chain as a therapeutic target in prostate tumor cells overexpressing adrenomedullin

Human adrenomedullin (AM) is a 52 amino acid peptide, which shares homology with the calcitonin gene-related peptide. Overexpression of AM in the prostate carcinoma cell line PC-3 results in growth inhibition with a 20% (for human AM) and 35% (for rat AM) increase in doubling time compared to parental or mock-transfected cells. We demonstrate by gene expression profiling that AM overexpression results in the dysregulation of approximately 100 genes. Examples of such genes include many involved in the formation of the cytoskeleton, cell adhesion and the extracellular matrix, as well as regulators of the cell cycle and apoptosis, cytokines and transcription factors. Several genes related to cell growth arrest, such as GADD45, IGF-BP6 and RUNX-3, are upregulated by AM. Interestingly, interleukin-13 receptor alpha 2 (IL-13R alpha 2) transcripts were significantly increased in clones overexpressing AM, which was confirmed by semiquantitative RT-PCR analysis. In addition, PC-3 cells treated with AM showed an overexpression of IL-13R alpha 2, which was abolished when cells were preincubated with an anti-AM blocking antibody. When PC-3 cells overexpressing AM and the IL-13R alpha 2 were treated with the highly specific IL13-PE38 cytotoxin, which binds to this receptor, a concentration-dependent inhibition of protein synthesis was observed. The IC(50) (concentration of cytotoxin inhibiting protein synthesis by 50%) ranged from 1 to 4 ng/ml. This cytotoxicity was specific as it was neutralized by the excess of IL-13 and confirmed by clonogenic assays. This study describes a novel AM-induced mechanism of tumor sensitization through the upregulation of functional IL-13R alpha 2 chain, an ideal target for the highly specific recombinant chimeric cytotoxin IL13-PE38

Identification of VEGF-regulated genes associated with increased lung metastatic potential: functional involvement of tenascin-C in tumor growth and lung metastasis

Metastasis is the primary cause of death in patients with breast cancer. Overexpression of c-myc in humans correlates with metastases, but transgenic mice only show low rates of micrometastases. We have generated transgenic mice that overexpress both c-myc and vascular endothelial growth factor (VEGF) (Myc/VEGF) in the mammary gland, which develop high rates of pulmonary macrometastases. Gene expression profiling revealed a set of deregulated genes in Myc/VEGF tumors compared to Myc tumors associated with the increased metastatic phenotype. Cross-comparisons between this set of genes with a human breast cancer lung metastasis gene signature identified five common targets: tenascin-C(TNC), matrix metalloprotease-2, collagen-6-A1, mannosidase-alpha-1A and HLA-DPA1. Signaling blockade or knockdown of TNC in MDA-MB-435 cells resulted in a significant impairment of cell migration and anchorage-independent cell proliferation. Mice injected with clonal MDA-MB-435 cells with reduced expression of TNC demonstrated a significant decrease (P<0.05) in (1) primary tumor growth; (2) tumor relapse after surgical removal of the primary tumor and (3) incidence of lung metastasis. Our results demonstrate that VEGF induces complex alterations in tissue architecture and gene expression. The TNC signaling pathway plays an important role in mammary tumor growth and metastases, suggesting that TNC may be a relevant target for therapy against metastatic breast cancer

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Repetitive nicotine exposure leads to a more malignant and metastasis-prone phenotype of SCLC: a molecular insight into the importance of quitting smoking during treatment

Cigarette smoking is strongly correlated with the onset of lung cancer. Nicotine, a major component in cigarette smoke, has been found to promote tumor growth and angiogenesis, as well as protect cancer cells from apoptosis. Among all lung cancer cases, small cell lung cancer (SCLC) is found almost exclusively in smokers; metastasis and chemoresistance are the main reasons for the high mortality rates associated with SCLC. Retrospective studies have shown that patients with tobacco-related cancers who continue to smoke after their diagnosis display lower response rates and a shorter median survival compared with those who stop smoking. In the current work, we examined the effects of acute and repetitive exposure to nicotine, in the concentrations found in the lungs of active smokers, on the malignant properties of N417 SCLC cells in vitro. We observed that repetitive nicotine exposure induced a neuronal-like appearance in N417 cells along with increased adhesion to the extracellular matrix and chemoresistance. These changes were accompanied by enhanced migration through collagen matrices and adhesion to and transmigration across lymphatic endothelial cell monolayers. SCLC differentiation reverted after cessation of nicotine exposure. Here, we provide evidence for the leading role of the CXCR4/CXCL12 axis in these phenomena. Finally, we show how nicotine-differentiated N417 cells produced bigger and more vascularized tumors in mice, with lower apoptotic rates, than their nondifferentiated counterparts. In short, these findings identify the mechanisms through which nicotine increases SCLC malignancy and provide further evidence that CXCR4 is a potential anticancer target for nicotine-associated SCLC

Repetitive nicotine exposure leads to a more malignant and metastasis-prone phenotype of SCLC: a molecular insight into the importance of quitting smoking during treatment

Cigarette smoking is strongly correlated with the onset of lung cancer. Nicotine, a major component in cigarette smoke, has been found to promote tumor growth and angiogenesis, as well as protect cancer cells from apoptosis. Among all lung cancer cases, small cell lung cancer (SCLC) is found almost exclusively in smokers; metastasis and chemoresistance are the main reasons for the high mortality rates associated with SCLC. Retrospective studies have shown that patients with tobacco-related cancers who continue to smoke after their diagnosis display lower response rates and a shorter median survival compared with those who stop smoking. In the current work, we examined the effects of acute and repetitive exposure to nicotine, in the concentrations found in the lungs of active smokers, on the malignant properties of N417 SCLC cells in vitro. We observed that repetitive nicotine exposure induced a neuronal-like appearance in N417 cells along with increased adhesion to the extracellular matrix and chemoresistance. These changes were accompanied by enhanced migration through collagen matrices and adhesion to and transmigration across lymphatic endothelial cell monolayers. SCLC differentiation reverted after cessation of nicotine exposure. Here, we provide evidence for the leading role of the CXCR4/CXCL12 axis in these phenomena. Finally, we show how nicotine-differentiated N417 cells produced bigger and more vascularized tumors in mice, with lower apoptotic rates, than their nondifferentiated counterparts. In short, these findings identify the mechanisms through which nicotine increases SCLC malignancy and provide further evidence that CXCR4 is a potential anticancer target for nicotine-associated SCLC

Longer breastfeeding duration is associated with lower consumption of ultraprocessed foods in a sample of spanish preschoolers: The SENDO project

Background: Breastfeeding has been linked to a higher consumption of fruit and vegetables at ages 4 to 5 years. More recently, it has been suggested that it may also be associated with lower ultraprocessed food (UPF) consumption in childhood. Objective: The aim of this study was to assess whether breastfeeding duration was associated with consumption of UPF in a sample of Mediterranean preschoolers. Design: This study involved a cross-sectional analysis of baseline information of children in the Child Follow-Up for Optimal Development cohort. Children were enrolled at ages 4 to 5 years and information was gathered through an online questionnaire completed by parents. Dietary information was collected with a previously validated semi-quantitative food frequency questionnaire and foods were classified based on the degree of processing according to the NOVA classification. Participants/setting: This study used baseline information for 806 participants enrolled in the Child Follow-Up for Optimal Development cohort between January 2015 and June 2021 in Spain. Main outcomes measures: Main study outcome measures were difference in grams per day and in the percentage of total energy intake from UPF consumption related to breastfeeding duration, and odds ratio that UPF represents a high percentage of total energy intake. Statistical analyses: Crude and multivariable adjusted estimates were calculated with generalized estimating equations to account for intracluster correlation between siblings. Results: The prevalence of breastfeeding in the sample was 84%. After adjusting for potential confounders, children who were breastfed for some time reported significantly lower consumption of UPF than children who were not breastfed at all. The mean differences were -19.2 g (95% CI -44.2 to 10.8) for children who were breastfed for <6 months, -42.5 g (95% CI -77.2 to -7.80) for those who were breastfed for 6 to 12 months, and -43.6 g (95% CI -79.8 to -7.48) for those who were breastfed for 12 months or more (P value for trend = 0.01). After adjusting for potential confounders, compared with children who were not breastfed, those who were breastfed for ≥12 months had consistently lower odds of UPF representing more than 25%, 30%, 35%, and 40% of total energy intake. Conclusions: Breastfeeding is associated with lower consumption of UPF in Spanish preschoolers

Longer breastfeeding duration is associated with lower consumption of ultraprocessed foods in a sample of Spanish preschoolers: The SENDO Project

Background Breastfeeding has been linked to a higher consumption of fruit and vegetables at ages 4 to 5 years. More recently, it has been suggested that it may also be associated with lower ultraprocessed food (UPF) consumption in childhood. Objective The aim of this study was to assess whether breastfeeding duration was associated with consumption of UPF in a sample of Mediterranean preschoolers. Design This study involved a cross-sectional analysis of baseline information of children in the Child Follow-Up for Optimal Development cohort. Children were enrolled at ages 4 to 5 years and information was gathered through an online questionnaire completed by parents. Dietary information was collected with a previously validated semi-quantitative food frequency questionnaire and foods were classified based on the degree of processing according to the NOVA classification. Participants/setting This study used baseline information for 806 participants enrolled in the Child Follow-Up for Optimal Development cohort between January 2015 and June 2021 in Spain. Main outcomes measures Main study outcome measures were difference in grams per day and in the percentage of total energy intake from UPF consumption related to breastfeeding duration, and odds ratio that UPF represents a high percentage of total energy intake. Statistical analyses Crude and multivariable adjusted estimates were calculated with generalized estimating equations to account for intracluster correlation between siblings. Results The prevalence of breastfeeding in the sample was 84%. After adjusting for potential confounders, children who were breastfed for some time reported significantly lower consumption of UPF than children who were not breastfed at all. The mean differences were –19.2 g (95% CI –44.2 to 10.8) for children who were breastfed for <6 months, –42.5 g (95% CI -77.2 to –7.80) for those who were breastfed for 6 to 12 months, and –43.6 g (95% CI –79.8 to –7.48) for those who were breastfed for 12 months or more (P value for trend = 0.01). After adjusting for potential confounders, compared with children who were not breastfed, those who were breastfed for ≥12 months had consistently lower odds of UPF representing more than 25%, 30%, 35%, and 40% of total energy intake. Conclusions Breastfeeding is associated with lower consumption of UPF in Spanish preschoolers

Identification of VEGF-regulated genes associated with increased lung metastatic potential: functional involvement of tenascin-C in tumor growth and lung metastasis

Metastasis is the primary cause of death in patients with breast cancer. Overexpression of c-myc in humans correlates with metastases, but transgenic mice only show low rates of micrometastases. We have generated transgenic mice that overexpress both c-myc and vascular endothelial growth factor (VEGF) (Myc/VEGF) in the mammary gland, which develop high rates of pulmonary macrometastases. Gene expression profiling revealed a set of deregulated genes in Myc/VEGF tumors compared to Myc tumors associated with the increased metastatic phenotype. Cross-comparisons between this set of genes with a human breast cancer lung metastasis gene signature identified five common targets: tenascin-C(TNC), matrix metalloprotease-2, collagen-6-A1, mannosidase-alpha-1A and HLA-DPA1. Signaling blockade or knockdown of TNC in MDA-MB-435 cells resulted in a significant impairment of cell migration and anchorage-independent cell proliferation. Mice injected with clonal MDA-MB-435 cells with reduced expression of TNC demonstrated a significant decrease (P<0.05) in (1) primary tumor growth; (2) tumor relapse after surgical removal of the primary tumor and (3) incidence of lung metastasis. Our results demonstrate that VEGF induces complex alterations in tissue architecture and gene expression. The TNC signaling pathway plays an important role in mammary tumor growth and metastases, suggesting that TNC may be a relevant target for therapy against metastatic breast cancer