A cluster-randomized crossover trial of organic diet impact on biomarkers of exposure to pesticides and biomarkers of oxidative stress/inflammation in primary school children

Despite suggestive observational epidemiology and laboratory studies, there is limited experimental evidence regarding the effect of organic diet on human health. A cluster-randomized 40-day-organic (vs. 40-day-conventional) crossover trial was conducted among children (11–12 years old) from six schools in Cyprus. One restaurant provided all organic meals, and adherence to the organic diet intervention was measured by parent-provided diet questionnaire/diary data. Biomarkers of pyrethroid and neonicotinoid pesticide exposures were measured using tandem mass spectrometry, and oxidative stress/inflammation (OSI) biomarkers using immunoassays or spectrophotometry. Associations were assessed using mixed-effect regression models including interactions of treatment with time. Seventy-two percent of neonicotinoid biomarkers were non-detectable and modeled as binary (whether detectable). In post-hoc analysis, we considered the outcome of age-and-sex-standardized BMI. Multiple comparisons were handled using Benjamini-Hochberg correction for 58 regression parameters. Outcome data were available for 149 children. Children had lower pesticide exposures during the organic period (pyrethroid geometric mean ratio, GMR = 0.297; [95% confidence interval (95% CI): 0.237, 0.373], Q-value < 0.05); odds for detection of neonicotinoids (OR = 0.651; [95% CI: 0.463, 0.917), Q-value < 0.05); and decreased OSI biomarker 8-OHdG (GMR = 0.888; [95% CI: 0.808, 0.976], Q-value < 0.05). An initial increase was followed by a countervailing decrease over time in the organic period for OSI biomarkers 8-iso-PGF2a and MDA. BMI z-scores were lower at the end of the organic period (β = -0.131; [95% CI: 0.179, -0.920], Q-value < 0.05). Energy intake during the conventional period was reported to be higher than the recommended reference levels. The organic diet intervention reduced children’s exposure to pyrethroid and neonicotinoid pesticides and, over time lowered biomarkers of oxidative stress/inflammation (8-iso-PGF2a, 8-OHdG and MDA). The several-week organic diet intervention also reduced children’s age- and-sex-standardized BMI z-scores, but causal inferences regarding organic diet’s physiological benefits are limited by the confounding of the organic diet intervention with caloric intake reduction and possible lifestyle changes during the trial

Les phlébotomes (Diptera-Psychodidae) de l'île de Chypre.II - Presence de Leishmania (Leishmania) infantum Nicolle, 1908 (zymodeme MON 1) chez Phlebotomus (Larroussius) tobbi Adler et Theodor, 1930

Dans le foyer leishmanien cypriote, les auteurs ont disseque 2910 femelles de phlebotomes appartenant a 11 especes : Phlebotomus papatasi, P. sergenti, P. jacusieli, P. alexandri, P. tobbi, P. galilaeus, P. mascittii, P. economidesi, Sergentomyia fallax, S. minuta et S. azizi . Les deux larroussius (P. galilaeus et P. tobbi ) sont les especes les plus abondantes. Elles representent plus de 60 % des captures realisees avec des pieges CDC. Des promastigotes ont ete observees chez un seul specimen appartenant a l'espece P. tobbi . Elles ont ete mises en culture puis identifiees selon la methode isoenzymatique. La souche de Leishmania isolee appartient a l'espece Leishmania infantum , zymodeme MON 1. Le meme zymodeme a ete aussi isole et identifie chez quatre chiens de l'ile. En l'absence des vecteurs habituels de L. infantum dans l'est mediterraneen (P. neglectus ef P. syriacus) et en raison de sa repartition a Chypre, P. tobbi constitue vraisemblablement un bon vecteur local. Sa faible anthropophilie expliquerait peut-etre le tres faible nombre de cas humains. Le role de P. galilaeus dans la transmission de la leishmaniose a Chypre reste a preciser

Oral Ingestion of Hexavalent Chromium through Drinking Water and Cancer Mortality in an Industrial Area of Greece - An Ecological Study

Background: Hexavalent chromium is a known carcinogen when inhaled, but its carcinogenic potential when orally ingested remains controversial. Water contaminated with hexavalent chromium is a worldwide problem, making this a question of significant public health importance. Methods: We conducted an ecological mortality study within the Oinofita region of Greece, where water has been contaminated with hexavalent chromium. We calculated gender, age, and period standardized mortality ratios (SMRs) for all deaths, cancer deaths, and specific cancer types of Oinofita residents over an 11-year period (1999 - 2009), using the greater prefecture of Voiotia as the standard population. Results: A total of 474 deaths were observed. The SMR for all cause mortality was 98 (95% CI 89-107) and for all cancer mortality 114 (95% CI 94-136). The SMR for primary liver cancer was 1104 (95% CI 405-2403, p-value < 0.001). Furthermore, statistically significantly higher SMRs were identified for lung cancer (SMR = 145, 95% CI 100-203, p-value = 0.047) and cancer of the kidney and other genitourinary organs among women (SMR = 368, 95% CI 119-858, p-value = 0.025). Elevated SMRs for several other cancers were also noted (lip, oral cavity and pharynx 344, stomach 121, female breast 134, prostate 128, and leukaemias 168), but these did not reach statistical significance. Conclusions: Elevated cancer mortality in the Oinofita area of Greece supports the hypothesis of hexavalent chromium carcinogenicity via the oral ingestion pathway of exposure. Further studies are needed to determine whether this association is causal, and to establish preventive guidelines and public health recommendations

Genetic risk of progression to type 2 diabetes and response to intensive lifestyle or metformin in prediabetic women with and without a history of gestational diabetes mellitus.

OBJECTIVE The Diabetes Prevention Program (DPP) trial investigated rates of progression to diabetes among adults with prediabetes randomized to treatment with placebo, metformin, or intensive lifestyle intervention. Among women in the DPP, diabetes risk reduction with metformin was greater in women with prior gestational diabetes mellitus (GDM) compared with women without GDM but with one or more previous live births. RESEARCH DESIGN AND METHODS We asked if genetic variability could account for these differences by comparing β-cell function and genetic risk scores (GRS), calculated from 34 diabetes-associated loci, between women with and without histories of GDM. RESULTS β-Cell function was reduced in women with GDM. The GRS was positively associated with a history of GDM; however, the GRS did not predict progression to diabetes or modulate response to intervention. CONCLUSIONS These data suggest that a diabetes-associated GRS is associated with development of GDM and may characterize women at risk for development of diabetes due to β-cell dysfunction

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Effects of a healthy lifestyle intervention and COVID-19-adjusted training curriculum on firefighter recruits

There are knowledge gaps regarding healthy lifestyle (HLS) interventions in fire academy settings and also concerning the impacts of the pandemic on training. We enrolled fire recruits from two fire academies (A and B) in New England in early 2019 as the historical control group, and recruits from academies in New England (B) and Florida (C), respectively, during the pandemic as the intervention group. The three academies have similar training environments and curricula. The exposures of interest were a combination of (1) an HLS intervention and (2) impacts of the pandemic on training curricula and environs (i.e. social distancing, masking, reduced class size, etc.). We examined the health/fitness changes throughout training. The follow-up rate was 78%, leaving 92 recruits in the historical control group and 55 in the intervention group. The results show an HLS intervention improved the effects of fire academy training on recruits healthy behaviors (MEDI-lifestyle score, 0.5 ± 1.4 vs. - 0.3 ± 1.7), systolic blood pressure (- 7.2 ± 10.0 vs. 2.9 ± 12.9 mmHg), and mental health (Beck Depression score, - 0.45 ± 1.14 vs. - 0.01 ± 1.05) (all P < 0.05). The associations remained significant after multivariable adjustments. Moreover, a 1-point MEDI-lifestyle increment during academy training is associated with about 2% decrement in blood pressures over time, after multivariable adjustments (P < 0.05). Nonetheless, the impacts of pandemic restrictions on academy procedures compromised physical fitness training, namely in percent body fat, push-ups, and pull-ups

A preliminary assessment of low level arsenic exposure and diabetes mellitus in Cyprus

<p>Abstract</p> <p>Background</p> <p>A preliminary study was undertaken in a community of Cyprus where low-level arsenic (As) concentrations were recently detected in the groundwater that was chronically used to satisfy potable needs of the community. The main objective of the study was to assess the degree of association between orally-ingested As and self-reported type-2 diabetes mellitus (DM) in 317 adult (≥18 years old) volunteers.</p> <p>Methods</p> <p>Cumulative lifetime As exposure (CLAEX) (mg As) was calculated using the median As concentrations in water, individual reported daily water consumption rates, and lifetime exposure duration. Logistic regression models were used to model the probability of self-reported DM and calculate odds ratios (OR) in univariate and multivariate models.</p> <p>Results</p> <p>Significantly higher (p <it><</it> 0.02) CLAEX values were reported for the diabetics (median = 999 mg As) versus non-diabetics (median = 573 mg As), suggesting that As exposure could perhaps be related to the prevalence of DM in the study area, which was 6.6%. The OR for DM, comparing participants in the 80^th versus the 20^th percentiles of low-level As CLAEX index values, was 5.0 (1.03, 24.17), but after adjusting for age, sex, smoking, education, and fish consumption, the As exposure effect on DM was not significant.</p> <p>Conclusions</p> <p>Further research is needed to improve As exposure assessment for the entire Cypriot population while assessing the exact relationship between low-level As exposure and DM.</p

Breast and other cancer dormancy as a therapeutic endpoint: speculative recombinant T cell receptor ligand (RTL) adjuvant therapy worth considering?

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Most individuals who died of trauma were found to harbour microscopic primary cancers at autopsies. Surgical excision of the primary tumour, unfortunately, seems to disturb tumour dormancy in over half of all metastatic relapses. PRESENTATION OF THE HYPOTHESIS: A recently developed immune model suggested that the evolutionary pressure driving the creation of a T cell receptor repertoire was primarily the homeostatic surveillance of the genome. The model is based on the homeostatic role of T cells, suggesting that molecular complementarity between the positively selected T cell receptors and the self peptide-presenting major histocompatibility complex molecules establishes and regulates homeostasis, strictly limiting variations of its components. The repertoire is maintained by continuous peripheral stimulation via soluble forms of self-peptide-presenting major histocompatibility complex molecules governed by the law of mass action. The model states that foreign peptides inhibit the complementary interactions between the major histocompatibility complexes and T cell receptors. Since the vast majority of clinically detected cancers present self-peptides the model assumes that tumour cells are, paradoxically, under homeostatic T cell control.The novelty of our hypothesis therefore is that resection of the primary tumour mass is perceived as loss of 'normal' tissue cells. Consequently, T cells striving to reconstitute homeostasis stimulate rather than inhibit the growth of dormant tumour cells and avascular micrometastases. Here we suggest that such kick-start growths could be prevented by a recombinant T cell receptor ligand therapy that modifies T cell behaviour through a partial activation mechanism. TESTING THE HYPOTHESIS: The homeostatic T cell regulation of tumours can be tested in a tri-transgenic mice model engineered to express potent oncogenes in a doxycycline-dependent manner. We suggest seeding dissociated, untransformed mammary cells from doxycycline naïve mice into the lungs of two mice groups: one carries mammary tumours, the other does not. Both recipient groups to be fed doxycycline in order to activate the oncogenes of the untransformed mammary cells in the lungs, where solitary nodules are expected to develop 6 weeks after injection. We expect that lung metastasis development will be stimulated following resection of the primary tumour mass compared to the tumour-free mice. A recombinant T cell receptor ligand therapy, starting at least one day before resection and continuing during the entire experimental period, would be able to prevent the stimulating effect of surgery. IMPLICATIONS OF THE HYPOTHESIS: Recombinant T cell receptor ligand therapy of diagnosed cancer would keep all metastatic deposits microscopic for as long as the therapy is continued without limit and could be pursued as one method of cancer control. Improving the outcome of therapy by preventing the development of metastases is perhaps achievable more readily than curing patients with overt metastases

Ambient temperature and subsequent COVID-19 mortality in the OECD countries and individual United States

Epidemiological studies have yielded conflicting results regarding climate and incident SARS-CoV-2 infection, and seasonality of infection rates is debated. Moreover, few studies have focused on COVD-19 deaths. We studied the association of average ambient temperature with subsequent COVID-19 mortality in the OECD countries and the individual United States (US), while accounting for other important meteorological and non-meteorological co-variates. The exposure of interest was average temperature and other weather conditions, measured at 25 days prior and 25 days after the first reported COVID-19 death was collected in the OECD countries and US states. The outcome of interest was cumulative COVID-19 mortality, assessed for each region at 25, 30, 35, and 40 days after the first reported death. Analyses were performed with negative binomial regression and adjusted for other weather conditions, particulate matter, sociodemographic factors, smoking, obesity, ICU beds, and social distancing. A 1 °C increase in ambient temperature was associated with 6% lower COVID-19 mortality at 30 days following the first reported death (multivariate-adjusted mortality rate ratio: 0.94, 95% CI 0.90, 0.99, p = 0.016). The results were robust for COVID-19 mortality at 25, 35 and 40 days after the first death, as well as other sensitivity analyses. The results provide consistent evidence across various models of an inverse association between higher average temperatures and subsequent COVID-19 mortality rates after accounting for other meteorological variables and predictors of SARS-CoV-2 infection or death. This suggests potentially decreased viral transmission in warmer regions and during the summer season