Impact of PM2.5 exposure in old age and its interactive effect with smoking on incidence of diabetes.

PURPOSE: To determine the impact of PM2.5 exposure in old age and its interactive effect with smoking on incident diabetes. METHODS: A total of 2766 participants aged ≥60 years in China were interviewed at baseline for disease risk factors in 2001-03 and were then followed up for 10 years to document incident diabetes. They were assessed for daily PM2.5 exposure in 2005. Multivariate Cox regression models were used to examine the association of PM2.5 exposure with incident diabetes and interactive effect between PM2.5 and smoking on incident diabetes. RESULTS: During the cohort follow-up, 176 participants developed diabetes. The incidence of diabetes increased with PM2.5 exposure; the multiple-adjusted hazard ratio (HR) of diabetes was 2.27 (95 % CI 1.36-3.77) in participants with PM2.5 at ≥62.0 µg/m3 compared to those with <62.0 µg/m3. There was a significant interaction effect of PM2.5 with smoking on increased risk of diabetes. The adjusted HR for participants exposed to PM2.5 levels ≥62.0 µg/m3 who smoked was 4.39 (95 % CI 1.72-11.21), while for non-smokers it was 1.65 (95 % CI 0.88-3.09), compared to those with <62.0 µg/m3. CONCLUSIONS: Exposure to PM2.5 in old age was associated with an increased incidence of diabetes and smoking enhanced the impact of PM2.5 on diabetic risk. These findings underscore the urgent need for air quality improvement measures and smoking cessation programs to mitigate the risk of diabetes in aging populations.

Healthy lifestyles ameliorate an increased risk of periodontitis associated with polycyclic aromatic hydrocarbons.

The risk of chronic inflammatory diseases has been linked to exposure to polycyclic aromatic hydrocarbons (PAHs). However, limited data are available regarding their impact on periodontitis. This study aims to explore the association between PAHs and periodontitis while also evaluating the potential modifying effects of healthy lifestyles. We included 17,031 participants from the US National Health and Nutrition Examination Survey (NHANES, 2001-2004 and 2009-2014). A meta-analysis-based environment-wide association study (EWAS) was adopted to identify environmental chemicals for the mean probing pocket depth (PPD) and the mean attachment loss (AL). PAHs were further evaluated concerning the cross-sectional association with Mod/Sev periodontitis using multivariable logistic regression models. Moreover, healthy lifestyle scores were estimated to assess their modifying effect on the PAH-periodontitis association. EWAS analysis identified several urinary PAH metabolites as significant risk factors for the mean PPD and AL (false discovery rate <0.05, Q > 0.05). Periodontitis severity was positively associated with eight individual and total PAH concentrations. Stratifying the participants in terms of healthy lifestyle scores did not reveal any association in the healthy group. Moreover, the association weakened in never-smokers and individuals with sufficient physical activity and normal weight. PAH exposure was a risk factor for periodontitis. A healthier lifestyle was observed to offset the risk potentials of PAHs for periodontitis. Smoking cessation, physical activity, and weight loss might be recommended as a healthy lifestyle strategy for ameliorating PAH-related periodontitis.

The Southern European Atlantic diet and all-cause and cause-specific mortality: a European multicohort study.

AIMS: The Southern European Atlantic diet (SEAD) is the traditional dietary pattern of northwestern Spain and northern Portugal, but it may resemble that of central, eastern, and western European countries. The SEAD has been found associated with lower risk of myocardial infarction and mortality in older adults, but it is uncertain whether this association also exists in other European populations and if it is similar as that found in its countries of origin. METHODS AND RESULTS: We conducted a prospective analysis of four cohorts with 35 917 subjects aged 18-96 years: ENRICA (Spain), HAPIEE (Czechia and Poland), and Whitehall II (United Kingdom). The SEAD comprised fresh fish, cod, red meat and pork products, dairy, legumes and vegetables, vegetable soup, potatoes, whole-grain bread, and moderate wine consumption. Associations were adjusted for sociodemographic variables, energy intake, lifestyle, and morbidity. After a median follow-up of 13.6 years (range = 0-15), we recorded 4 973 all-cause, 1 581 cardiovascular, and 1 814 cancer deaths. Higher adherence to the SEAD was associated with lower mortality in the pooled sample. Fully adjusted hazard ratios and 95% confidence interval per 1-standard deviation increment in the SEAD were 0.92 (0.89, 0.95), 0.91 (0.86, 0.96), and 0.94 (0.89, 0.99) for all-cause, cardiovascular, and cancer mortality, respectively. The association of the SEAD with all-cause mortality was not significantly different between countries [Spain = 0.93 (0.88, 0.99), Czechia = 0.94 (0.89,0.99), Poland = 0.89 (0.85, 0.93), United Kingdom = 0.98 (0.89, 1.07); P for interaction = 0.16]. CONCLUSION: The SEAD was associated with lower all-cause, cardiovascular, and cancer mortality in southern, central, eastern, and western European populations. Associations were of similar magnitude as those found for existing healthy dietary patterns.

In this study of 35 917 subjects from southern, central, eastern, and western European countries, the Southern European Atlantic diet (traditional dietary pattern of northwestern Spain and northern Portugal) was associated with lower 13.6-year mortality from any cause, cardiovascular disease, and cancer. The associations of the Southern European Atlantic diet with lower mortality were not significantly different between countries (Spain, Czechia, Poland, and the United Kingdom). Study associations were similar as those found for existing healthy dietary patterns, suggesting that rather different diets could confer comparable benefits on health.

Comparison of functional and oncological outcome of conformal sphincter preservation operation, low anterior resection, and abdominoperineal resection in very low rectal cancer: a retrospective comparative cohort study with propensity score matching.

PURPOSE: Conformal sphincter preservation operation (CSPO) procedure is a sphincter preservation procedure for preserving the anal canal function for very low rectal cancers. This study investigated the functional and oncological outcome of conformal sphincter preservation operation by comparing with low anterior resection (LAR) and abdominoperineal resection (APR). METHODS: This is a retrospective comparative study. Patients who received conformal sphincter preservation operation (n = 52), low anterior resection (n = 54), or abdominoperineal resection (n = 69) were included between 2011 and 2016 in a tertiary referral hospital. Propensity score matching was applied to adjust the baseline characteristics which may influence the choice of the surgical procedure. RESULTS: Twenty-one pairs of conformal sphincter preservation operation vs. low anterior resection and 29 pairs of conformal sphincter preservation operation vs. abdominoperineal resection were selected. The first group had a higher tumor location than the second group. Compared with the low anterior resection group, the conformal sphincter preservation operation group had shorter distal resection margins; however, no significant differences were identified in daily stool frequency, Wexner incontinence score, local recurrence, distant metastasis, overall survival, and disease-free survival between both groups. Compared with the abdominoperineal resection group, the conformal sphincter preservation operation group had shorter operative time and shorter postoperative hospital stay. No significant differences were identified in local recurrence, distant metastasis, overall survival, and disease-free survival. CONCLUSION: Conformal sphincter preservation operation is oncologically safe compared to APR and LAR, and has similar functional findings to LAR. Studies comparing CSPO with intersphincteric resection should be performed.

Serum Antioxidant Vitamins Mediate the Association between Periodontitis and Metabolically Unhealthy Overweight/Obesity.

BACKGROUND: Periodontal disease is associated with metabolic syndrome and obesity. This cross-sectional study aimed to investigate whether serum antioxidant vitamins could mediate the association between periodontitis and a metabolically unhealthy phenotype in the overweight and obese population; Methods: We included 6158 Americans (body mass index (BMI) ≥ 25 kg/m2) from the Third National Health and Nutrition Examination Survey (NHANES III). Periodontitis was defined using a half-reduced CDC/AAP (Centers for Disease Control and Prevention/American Academy of Periodontology) definition. Having two or more metabolic abnormalities was defined as a metabolically unhealthy overweight and obese (MUO) phenotype. Mediation analysis of four oxidative stress biomarkers (serum antioxidant vitamins A, C, D, and E) was conducted; Results: Of participants with overweight and obesity, 2052 (33.3%) Americans were categorized as having periodontitis. Periodontitis increased dyslipidemia risk and systemic inflammation in the overweight and obese population. In the multivariable logistic regression model, periodontitis was positively associated with MUO (adjusted odds ratio = 1.238; 95% confidence interval: 1.091 to 1.406). These findings were validated in an independent cohort. Serum vitamins C and D were estimated to mediate 19.3% and 8.4% of the periodontitis-MUO association. CONCLUSIONS: Periodontitis might decrease serum vitamins C and D and induce a metabolically unhealthy state among adults with overweight and obesity.

Risk Prediction of Second Primary Malignancies in Primary Early-Stage Ovarian Cancer Survivors: A SEER-Based National Population-Based Cohort Study.

Purpose: This study aimed to characterize the clinical features of early-stage ovarian cancer (OC) survivors with second primary malignancies (SPMs) and provided a prediction tool for individualized risk of developing SPMs. Methods: Data were obtained from the Surveillance, Epidemiology and End Results (SEER) database during 1998-2013. Considering non-SPM death as a competing event, the Fine and Gray model and the corresponding nomogram were used to identify the risk factors for SPMs and predict the SPM probabilities after the initial OC diagnosis. The decision curve analysis (DCA) was performed to evaluate the clinical utility of our proposed model. Results: A total of 14,314 qualified patients were enrolled. The diagnosis rate and the cumulative incidence of SPMs were 7.9% and 13.6% [95% confidence interval (CI) = 13.5% to 13.6%], respectively, during the median follow-up of 8.6 years. The multivariable competing risk analysis suggested that older age at initial cancer diagnosis, white race, epithelial histologic subtypes of OC (serous, endometrioid, mucinous, and Brenner tumor), number of lymph nodes examined (<12), and radiotherapy were significantly associated with an elevated SPM risk. The DCA revealed that the net benefit obtained by our proposed model was higher than the all-screening or no-screening scenarios within a wide range of risk thresholds (1% to 23%). Conclusion: The competing risk nomogram can be potentially helpful for assisting physicians in identifying patients with different risks of SPMs and scheduling risk-adapted clinical management. More comprehensive data on treatment regimens and patient characteristics may help improve the predictability of the risk model for SPMs.

Efficacy and safety of 3D printing-assisted percutaneous nephrolithotomy in complex renal calculi.

This study evaluated the efficacy and safety of 3D printing technology combined with percutaneous nephrolithotomy in the treatment of complex renal calculi. Ninety patients with complex renal calculi were randomly divided into a 3D printing group (45 patients) and a control group (45 patients). In the 3D printing group, a patient-specific 1:1 3D printing model was established based on the patient's thin-layer CT scanning data. A 3D printing model was used for preoperative communication between doctors and patients. Preoperative puncture training, channel design, residual stone prediction, and percutaneous nephrolithotomy were performed under the guidance of a 3D printing model and B-ultrasound. The control group was treated with the conventional B-ultrasound-guided puncture method. Results suggest that there was a statistically significant difference between the two groups (P < 0.05). The overall score of the doctor-patient communication objects in the 3D printing group was 19.32 ± 1.57 points, and in the control group, it was 14.51 ± 2.13 points. The operation time of the 3D printing group was 103.21 ± 13.49 min, and that of the control group was 126.12 ± 25.87 min. The calculi clearance rate of the 3D printing group was 96%, while that of the control group was 80%. The incidence of postoperative complications was 6.67% in the 3D printing group and 22.22% in the control group. Compared with traditional percutaneous nephrolithotomy, 3D printing technology combined with percutaneous nephrolithotomy can significantly enhance the effectiveness of doctor-patient communication, shorten operation time, reduce operation bleeding, improve the stone clearance rate, reduce the incidence of complications and shorten the length of hospital stay. The proposed method is thus a safe and effective method to treat complex renal calculi.

The development and performance of a perforated plate burner to produce vitiated flow with negligible swirl under engine-relevant gas turbine conditions.

The development and performance of a perforated plate burner (PPB) operating using premixed natural gas and air at engine-relevant inlet temperatures and combustor pressures with thermal powers up to 1 MW is discussed. A significant benefit of using burners with simplified flow fields, such as the PPB, for experimental studies in the laboratory is the potential for decoupling the complex fluid dynamics in typical combustors from the chemical kinetics. The primary motivation for developing this burner was to use it as a source of vitiated flow with negligible swirl for reacting jet in vitiated crossflow experiments. The design methodology for the PPB is described, including plate geometry selection and flashback mitigation features. The stable operation of the PPB within a high-pressure test rig was validated: successful ignition, effective use of red-lines for flashback mitigation, and long duration steady-state operation in both piloted and nonpiloted modes were all observed. Exhaust gas emissions measured using a Fourier-transform infrared (FTIR) spectrometer showed very good performance of the PPB in terms of the combustion efficiency (based on measured CO and UHC), and a stability diagram of the PPB was developed as a function of the equivalence ratio and the PPB hole velocity. FTIR measurements also showed very low levels of NOX in nonpiloted operation that were generally within 3 ppm (reported dry and referenced to 15% O2). The capability for steady-state operation, high combustion efficiency, and low levels of NOX makes this PPB an excellent burner candidate for combustion experiments in the laboratory.

A varying-coefficient cox model for the effect of CA19-9 kinetics on overall survival in patients with advanced pancreatic cancer.

PURPOSE: To evaluate the relationship between serum CA19-9 and overall survival in patients with advanced pancreatic cancer. METHODS: 109 advanced pancreatic cancer patients with gemcitabine based first-line chemotherapy were included. The effect of pretreatment CA19-9 level on overall survival was modeled by Cox proportional hazard regression. The effect of CA19-9 kinetics on overall survival was modeled by an extended Cox regression with a time varying coefficient and a time varying covariate. RESULTS: Univariate analysis indicated that baseline CA19-9 correlated with OS (HR = 1.66, p < 0.01) and this association remained significant within multivariate analysis (HR = 1.56, P < 0.01). For the analysis of CA19-9 kinetics, the extended Cox model showed that the effect of CA19-9 on overall survival changed with time: increased in the first two months and reached the top at a HR of about 2, then decreased for the next two months to a HR of about 1.56 and finally tended to be stable. The combination of pretreatment CA19-9 and CA19-9 at 2 month may better evaluate the patients' prognosis compared to pretreatment CA19-9 alone. CONCLUSION: Pretreatment CA19-9 and CA19-9 kinetics may serve as a useful serum biomarker in advanced pancreatic cancer.

Stem cells in brain tumor development.

Gliomas are highly infiltrative and aggressive brain tumors that are resistant to conventional therapies. Recent studies have implicated neural stem cells (NSCs) in brain tumor initiation and development. Subpopulations of stem-like cancer cells have also been isolated from brain tumors, and are purported to be important mediators of malignant behavior and therapeutic resistance. Similar signaling pathways may be operative in both neural and cancer stem cells, suggesting that neural developmental systems may provide important clues on brain tumorigenesis. Transcriptional regulators such as microRNAs may also contribute to NSC and brain tumor development. Understanding the biology of neural and cancer stem cells and their regulatory mechanisms may directly impact current efforts for more directed therapeutics against these highly aggressive tumors.

Developmental abnormalities of myelin basic protein expression in fyn knock-out brain reveal a role of Fyn in posttranscriptional regulation.

Fyn protein-tyrosine kinase (PTK), a member of the Src-PTK family, is essential for myelin development in the central nervous system (CNS). The absence of Fyn activity results in defects in the morphogenesis of oligodendrocyte precursors (OPCs) and CNS hypomyelination. However, molecular mechanisms for Fyn to control CNS myelinogenesis remain elusive. Here we show that Fyn-PTK is significantly up-regulated in early OPC differentiation, concentrated in the compact myelin, and declines during myelin development. Despite the high levels of Fyn-PTK expression during early OPC differentiation, Fyn deficiency does not affect the expression of mRNAs that encode myelin structural proteins, including that for the myelin basic protein (MBP), until postnatal day 13 (P13). However, the accumulation rate of MBP mRNA is significantly attenuated during the most active period of myelinogenesis (P13 and P20). Interestingly, the absence of Fyn causes a preferential reduction of the exon-2 containing MBP mRNA isoforms derived from alternative splicing, providing the first evidence that Fyn is required for posttranscriptional regulation of MBP. Consistent with this idea, Fyn phosphorylates the selective RNA-binding protein QKI, which likely modulates the activity of QKI in binding and stabilizing the MBP mRNA. Furthermore, Fyn deficiency exerts an opposing influence on MBP isoform patterning in comparison to that by QKI deficiency. These observations collectively suggest that Fyn plays critical roles in promoting accelerated MBP expression during myelinogenesis in a MBP isoform-preferential manner, and QKI may act in the same pathway downstream of Fyn for MBP mRNA homeostasis.