The organic food market has grown rapidly worldwide in the past 15 years. However, evidence concerning the health effects of organic foods is scarce. We evaluated the cross-sectional association of ...organic food purchase, as a proxy of organic food consumption, with diabetes in a nationally representative population.
We included 8199 participants aged ≥20 years from the National Health and Nutrition Examination Survey 2007⁻2008 and 2009⁻2010. Organic food purchase and frequency were ascertained by questionnaires. Diabetes was defined as a self-reported physician diagnosis or a hemoglobin A1c level ≥6.5% or both. We used logistic regression with sample weights to estimate the odds ratios (ORs) and 95% confidence intervals (CIs).
Individuals who reported purchasing organic foods were less likely to have diabetes compared to those who did not report organic food purchase. After adjustment for age, gender, race/ethnicity, family history of diabetes, socioeconomic status, and dietary and lifestyle factors, the OR of diabetes associated with organic food purchase was 0.80 (95% CI 0.68⁻0.93). The association remained significant after additional adjustment for BMI with OR of 0.80 (0.69⁻0.94).
In a nationally representative population, frequent organic food purchase was inversely associated with diabetes prevalence in adults in the United States.
Dynamin 2 (Dyn2), a large GTPase, is involved in receptor tyrosine kinase (RTK)-promoted cell migration. However, the molecular mechanisms by which Dyn2 regulates RTK-induced cell migration have not ...been established. Recently, we reported that tyrosine-protein phosphatase non-receptor type 11 (SHP-2) and phosphatidylinositol 3-kinase (PI3K) mediate platelet-derived growth factor receptor-α (PDGFRα)-promoted glioma tumor growth and invasion. Here, we show that Dyn2 is an effector downstream of the PDGFRα-PI3K/SHP-2 signaling in glioma cells. Depletion of endogenous Dyn2 by short hairpin RNAs (shRNAs) inhibited PDGFRα-stimulated phosphorylation of Akt, Erk1/2, Rac1 and Cdc42 activities, glioma cell migration and survival in vitro and tumor growth and invasion in the brains of mice. Dyn2 binds to SHP-2 and PI3K and colocalizes with PDGFRα at the invasive fronts in PDGF-A-stimulated glioma cells. Inhibition of SHP-2 by siRNA knockdown abrogated Dyn2 association with activated PDGFRα and PDGFRα activation of Rac1 and Cdc42, and glioma cell migration, thereby establishing a link between SHP-2 interaction with Dyn2 and the PDGFRα signaling. Furthermore, a dominant-negative SHP-2 C459S mutant inhibited PDGF-A-stimulated glioma cell migration, phosphorylation of Dyn2 and concomitantly blocked PDGFRα-induced Src activation. Inhibition of Src by Src inhibitors attenuated PDGF-A-stimulated phosphorylation of Akt and Dyn2 and glioma cell migration. Additionally, mutations of binding sites to PI3K, SHP-2 or Src of PDGFRα impaired PDGFRα-stimulated phosphorylation of Akt and Dyn2, and Dyn2 association with activated PDGFRα. Taken together, this study identifies Dyn2 as an effector that mediates PDGFRα-SHP-2-induced glioma tumor growth and invasion, suggesting that targeting the PDGFRα-SHP-2-Dyn2 pathway may be beneficial to patients with malignant glioblastomas.
Abstract
Background and objective
Head-up tilt test (HUTT) is clinically advantageous for diagnosing patients with vasovagal syncope (VVS). Nitroglycerin is mainly used as a stimulant during HUTT, ...and mitochondrial aldehyde dehydrogenase 2 (ALDH2) is involved in the metabolism of nitroglycerin (NTG). ALDH2 Glu487Lys polymorphism (ALDH2 rs671) is the most common variant in the East Asian population. This study aimed to assess the effects of ALDH2 rs671 on VVS patients undergoing HUTT supplemented with sublingual NTG (HUTT-NTG).
Methods
Patients with recurrent VVS (at least 2 times) who were admitted to the syncope center of our hospital were enrolled. All VVS patients have undergone HUTT. The polymorphism of Glu487Lys gene of ALDH2 was measured by the DNA Microarray Chip Method. The results of HUTT-NTG of VVS patients with different ALDH2 genotypes were compared and their hemodynamic characteristics were assessed.
Results
A total of 199 VVS patients were enrolled, including 101 patients in the ALDH2*1/*1 group and 98 patients in the ALDH2*2 group. Among patients undergoing HUTT-NTG, 70.3% of patients in the ALDH2*1/*1 group and 68.4% of patients in the ALDH2*2 group were positive, and the difference between the two groups was not statistically significant (
P
= 0.77). The proportions of VASIS I, VASIS II, and VASIS III were 40.6%, 8.9%, and 20.8% in the ALDH2*1/*1 group, respectively, and the corresponding proportions in the ALDH2*2 group were 36.7%, 11.2%, and 20.4%, respectively. There was no statistically significant difference between the two groups (
P
= 0.91). The hemodynamic characteristics of different genotypes in VVS patients undergoing HUTT-NTG were compared, and no statistically significant difference was found. The median time of syncopal episode occurred after NTG administration in the ALDH2*1/*1 group was 6 min (interquartile range IQR: 5.0–9.0), and it was 6.0 min in the ALDH2*2 group (IQR: 4.25–8.0,
P
= 0.64).
Conclusion
ALDH2 Glu487Lys polymorphism did not affect the outcome of VVS patients undergoing HUTT-NTG, and no significant change in the hemodynamic characteristics of different genotypes was found.
Obesity induced inflammation may promote periodontal tissue destruction and bone resorption inducing tooth loss. We examined the association between measures of adiposity and self‐reported ...periodontal disease, using data from 36,910 healthy male participants of the Health Professionals Follow‐Up Study (HPFS) who were free of periodontal disease at baseline and followed for ≤20 years (1986–2006). Self‐reported height, weight, and periodontal disease data were collected at baseline, weight and periodontal disease were additionally collected on biennial follow‐up questionnaires and waist and hip circumference were self‐reported in 1987. These self‐reported measures have been previously validated. The multivariable adjusted associations between BMI (kg/m2), waist circumference (WC), waist‐to‐hip ratio (WHR), and first report of periodontal disease diagnosis were evaluated using time‐varying Cox models. We observed 2,979 new periodontal disease diagnoses during 596,561 person‐years of follow‐up. Significant associations and trends were observed between all measures of adiposity and periodontal disease after adjusting for age, smoking, race, dental profession, physical activity, fruit and vegetable intake, alcohol consumption, and diabetes status at baseline. BMI ≥30 kg/m2 compared to BMI 18.5–24.9 kg/m2 was significantly associated with greater risk of periodontal disease (hazard ratios (HR) = 1.30; 95% confidence interval (CI): 1.17–1.45). Elevated WC and WHR were significantly associated with a greater risk of periodontal disease (HR for extreme quintiles: WC = 1.27, 95% CI: 1.11–1.46; WHR = 1.34, 95% CI: 1.17–1.54). The associations of BMI and WC were significant even among nondiabetics and never smokers. Given the high prevalence of overweight, obesity, and periodontal disease this association may be of substantial public health importance.
Conventional coarse-grained (CG) biomedical austenitic stainless steel with grain size in the micrometer range was subjected to a novel phase reversion concept involving severe cold deformation, ...followed by annealing, when the cold deformed martensite reverts to austenite with grain size in the nanometer/ultrafine (NG/UFG) regime (~200–400 nm). The mechanical behavior of CG and NG/UFG steels was studied via load-controlled and displacement-controlled experiments using a nanoindentation technique with the aim to simulate micromotion. The plastic zone associated with the indentation-induced deformed region was characterized by post-mortem electron microscopy of the deformed region to elucidate the deformation mechanism. Nanoscale twinning was the deformation mechanism in steel with grain size in the NG/UFG regime, and contributed to the ductility of high strength steel. In contrast, strain-induced martensite contributed to the ductility of low strength CG steel with micrometer grain size. Interestingly, besides the differences in the mechanical behavior, the biological functions of the two steels were remarkably different. Higher cell attachment, proliferation and higher expression level of prominent proteins, fibronection, actin and vinculin were favored by a surface with grain size in the nanometer regime and was in striking contrast with the surface with micrometer grain size. This behavior is attributed to the differences in the fraction of grain boundaries that are high energy two-dimensional defects. The study advances our understanding of the mechanical behavior of biomaterials and their cellular functions.
We use the optimized skew-spectrum as well as the skew-spectra associated with the Minkowski functionals to test the possibility of using the cross-correlation of the integrated Sachs–Wolfe effect ...(ISW) and lensing of the cosmic microwave background (CMB) radiation to detect deviations in the theory of gravity away from General Relativity (GR). We find that the although both statistics can put constraints on modified gravity, the optimized skew-spectra are especially sensitive to the parameter B
0 that denotes the Compton wavelength of the scalaron at the present epoch. We investigate three modified gravity theories, namely the post-parametrized Friedmann formalism; the Hu–Sawicki model and the Bertschinger–Zukin (BZ) formalism. Employing a likelihood analysis for an experimental setup similar to ESA's Planck mission, we find that, assuming GR to be the correct model, we expect the constraints from the first two skew-spectra,
$S_{\ell }^{(0)}$
and
$S_{\ell }^{(1)}$
, to be the same: B
0 < 0.45 at 95 per cent confidence level (CL) and B
0 < 0.67 at 99 per cent CL in the BZ model. The third skew-spectrum does not give any meaningful constraint. We find that the optimal skew-spectrum provides much more powerful constraint, giving B
0 < 0.071 at 95 per cent CL and B
0 < 0.15 at 99 per cent CL, which is essentially identical to what can be achieved using the full bispectrum.
Although it is widely believed that type 2 diabetes mellitus is the result of a complex interplay between genetic and environmental factors, compelling evidence from epidemiologic studies indicates ...that the current worldwide diabetes epidemic is largely due to changes in diet and lifestyle. Prospective cohort studies and randomized clinical trials have demonstrated that type 2 diabetes can be prevented largely through moderate diet and lifestyle modifications. Excess adiposity is the most important risk factor for diabetes, and thus, maintaining a healthy body weight and avoiding weight gain during adulthood is the cornerstone of diabetes prevention. Increasing physical activity and reducing sedentary behaviors such as prolonged TV watching are important both for maintaining body weight and improving insulin sensitivity. There is increasing evidence that the quality of fat and carbohydrate plays a more important role than does the quantity, and thus, public health strategies should emphasize replacing saturated and trans fats with unsaturated fats and replacing refined grain products with whole grains. Recent studies have also suggested a potential role for coffee, dairy, nuts, magnesium, and calcium in preventing diabetes. Overall, a healthy diet, together with regular physical activity, maintenance of a healthy weight, moderate alcohol consumption, and avoidance of sedentary behaviors and smoking, could nearly eliminate type 2 diabetes. However, there is still a wide gap between what we know and what we practice in the field of public health; how to narrow that gap remains a major public health challenge.
Worldwide, the burden of morbidity and mortality from diet-related chronic diseases is increasing, driven by poor diet quality and overconsumption of calories. At the same time, the global food ...production system is draining our planet's resources, jeopardizing the environment and future food security. Personal, population, and planetary health are closely intertwined and will all continue to be vulnerable to these threats unless action is taken. Fortunately, shifting current global dietary patterns towards high-quality, plant-based diets could alleviate these health and environmental burdens. Compared with typical Western diets with high amounts of animal products, healthy plant-based diets are not only more sustainable, but have also been associated with lower risk of chronic diseases such as obesity, type 2 diabetes, cardiovascular disease, and some cancers. For personalized disease management and prevention, precision nutrition has the potential to offer more effective approaches tailored to individual characteristics such as the genome, metabolome, and microbiome. However, this area of research is in the early stages and is not yet ready for widespread clinical use. Therefore, it must not overshadow public health nutrition strategies, which have the power to improve health and sustainability on a larger scale. If widely implemented, interventions and policy changes that shift the globe towards healthy plant-based dietary patterns could be instrumental in ensuring future personal, population, and planetary health.
Two receptors for vasopressin (Avp) are expressed in the brain, the Avp 1a receptor (Avpr1a) and the Avp 1b receptor (Avpr1b). To investigate the role of Avpr1a in behaviors in mice more extensively, ...we generated a line of mice lacking a functional Avpr1a (knockout, Avpr1a−/−). We first performed a baseline phenotypic screen of the Avpr1a knockouts followed by a more detailed analysis of their circadian rhythms and olfactory function. When free‐running in constant darkness, the Avpr1a−/− mice have a longer circadian tau than the wild types. There are also subtle olfactory deficits in Avpr1a−/− mice as measured in an olfactory habituation/dishabituation test and in the discrimination of female urine from male urine using an operant testing paradigm. An extensive body of research has shown that manipulation of the Avpr1a alters behavior, including aggression and social recognition. Therefore, we expected profound behavioral deficits in mice lacking the Avpr1a gene. Contrary to our expectations, social aggression, anxiety‐like behavior and social recognition are unaffected in this line of Avpr1a knockout mice. These data suggest either that the Avpr1a is not as critical as we thought for social behavior in mice or, more likely, that the neural circuitry underlying aggression and other social behaviors compensates for the life‐long loss of the Avpr1a. However, the olfactory deficits observed in the Avpr1a−/− mice suggest that Avp and Avpr1a drugs may affect behavior, in part, by modulation of chemosensory systems.
The mother-child inheritance of DNA methylation (DNAm) variations could contribute to the inheritance of disease susceptibility across generations. However, no study has investigated patterns of ...mother-child associations in DNAm at the genome-wide scale. It remains unknown whether there are sex differences in mother-child DNAm associations.
Using genome-wide DNAm profiling data (721,331 DNAm sites, including 704,552 on autosomes and 16,779 on the X chromosome) of 396 mother-newborn pairs (54.5% male) from the Boston Birth Cohort, we found significant sex differences in mother-newborn correlations in genome-wide DNAm patterns (Spearman's rho = 0.91-0.98; p = 4.0 × 10
), with female newborns having stronger correlations. Sex differences in correlations were attenuated but remained significant after excluding X-chromosomal DNAm sites (Spearman's rho = 0.91-0.98; p = 0.035). Moreover, 89,267 DNAm sites (12.4% of all analyzed, including 88,051 12.5% of analyzed autosomal and 1,216 7.2% of analyzed X-chromosomal sites) showed significant mother-newborn associations in methylation levels, and the top autosomal DNAm sites had high heritability than the genome-wide background (e.g., the top 100 autosomal DNAm sites had a medium h
of 0.92). Additionally, significant interactions between newborn sex and methylation levels were observed for 11 X-chromosomal and 4 autosomal DNAm sites that were mapped to genes that have been associated with sex-specific disease/traits or early development (e.g., EFHC2, NXY, ADCYAP1R1, and BMP4). Finally, 18,769 DNAm sites (14,482 77.2% on the X chromosome) showed mother-newborn differences in methylation levels that were significantly associated with newborn sex, and the top autosomal DNAm sites had relatively small heritability (e.g., the top 100 autosomal DNAm sites had a medium h
of 0.23). These DNAm sites were mapped to 2,532 autosomal genes and 978 X-chromosomal genes with significant enrichment in pathways involved in neurodegenerative and psychological diseases, development, neurophysiological process, immune response, and sex-specific cancers. Replication analysis in the Isle of Wight birth cohort yielded consistent results.
In two independent birth cohorts, we demonstrated strong mother-newborn correlations in whole blood DNAm on both autosomes and ChrX, and such correlations vary substantially by sex. Future studies are needed to examine to what extent our findings contribute to developmental origins of pediatric and adult diseases with well-observed sex differences.
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