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Purpose: We aim to present a refined thin-film model describing the drug particle dissolution considering radial diffusion in spherical boundary layer, and to demonstrate the ability of the model to describe the dissolution behavior of bulk drug powders. Methods: The dissolution model introduced in this study was refined from a radial diffusion-based model previously published by our laboratory (So et al. in Pharm Res. 39:907–17, 2022). The refined model was created to simulate the dissolution of bulk powders, and to account for the evolution of particle size and diffusion layer thickness during dissolution. In vitro dissolution testing, using fractionated hydrochlorothiazide powders, was employed to assess the performance of the model. Results: Overall, there was a good agreement between the experimental dissolution data and the predicted dissolution profiles using the proposed model across all size fractions of hydrochlorothiazide. The model over-predicted the dissolution rate when the particles became smaller. Notably, the classic Nernst-Brunner formalism led to an under-estimation of the dissolution rate. Additionally, calculation based on the equivalent particle size derived from the specific surface area substantially over-predicted the dissolution rate. Conclusion: The study demonstrated the potential of the radial diffusion-based model to describe dissolution of drug powders. In contrast, the classic Nernst-Brunner equation could under-estimate drug dissolution rate, largely due to the underlying assumption of translational diffusion. Moreover, the study indicated that not all surfaces on a drug particle contribute to dissolution. Therefore, relying on the experimentally-determined specific surface area for predicting drug dissolution is not advisable. [ABSTRACT FROM AUTHOR]

Background: To examine the association of serum 25-hydroxyvitamin D (25[OH]D) with colorectal cancer (CRC) risk in adults with type 2 diabetes (T2D). Methods: Using UK Biobank data, this study included 18,453 adults with T2D. Serum 25(OH)D concentrations were determined by the chemiluminescent immunoassay method. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC outcomes. Results: During a median follow-up of 8.8 years, there were 284 incident CRC cases. Compared with adults with serum 25(OH)D concentrations <25.0 nmol/L, the adjusted HRs (95% CIs) for lower to higher serum 25(OH)D concentrations (25.0 to <50.0, 50.0 to <75.0, and ≥75.0 nmol/L) were 0.61 (0.46–0.82), 0.50 (0.34–0.74), and 0.53 (0.30–0.94), respectively (Ptrend = 0.001). The risk of CRC decreased by 19.0% for per 1-SD increment in serum 25(OH)D concentrations. A nonlinear association of serum 25(OH)D concentrations with CRC risk was observed using a restricted cubic spline analysis (P nonlinearity = 0.002). Conclusions: Higher serum 25(OH)D concentrations were significantly and nonlinearly associated with a lower risk of CRC. These findings highlight the potential benefits of maintaining adequate vitamin D levels in CRC prevention among adults with T2D. [ABSTRACT FROM AUTHOR]

The association between long-term joint exposure to all kinds of ambient air pollutants and the risk of mortality is not known. Our study prospectively assessed the joint associations of various air pollutants with cause-specific and all-cause mortality risk and identified potential modifying factors affecting these associations. A total of 400,259 individuals aged 40–70 years were included in this study. Information on PM10, PM2.5–10, PM2.5, NO2, and NOx was collected. A weighted air pollution score was calculated to assess joint exposure to the above air pollutants. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. During a median of 12.0 years (4,733,495 person-years) of follow-up, 21,612 deaths were recorded, including 7097 deaths from cardiovascular disease and 11,557 deaths from cancer. The adjusted HRs of all-cause mortality were 1.39 (95% CI: 1.29–1.50), 1.86 (95% CI: 1.63–2.13), 1.12 (95% CI: 1.10–1.14), and 1.04 (95% CI: 1.03–1.05) for every 10-ug/m3 increase in PM10, PM2.5, NO2, and NOx, respectively. The adjusted HRs associated with the air pollution score (the highest quintile versus the lowest quintile) were 1.24 (95% CI: 1.19–1.30) for all-cause mortality, 1.33 (95% CI: 1.23–1.43) for cardiovascular mortality, and 1.16 (95% CI: 1.09–1.23) for cancer mortality. Furthermore, we found that the air pollution score was associated with a linear dose–response increase in mortality risk (all P for linearity < 0.001). The findings highlight the importance of a comprehensive assessment of various air pollutants. [ABSTRACT FROM AUTHOR]

Objective: To investigate their compliance with postoperative oral nutritional supplementation and nutritional outcomes. Methods: A total of 84 patients with colorectal cancer surgery with NRS-2002 risk score ≥ 3 who were treated with oral nutritional supplementation were selected and divided into control and observation groups according to the random number table method, with 42 cases in each group. The control group received conventional oral nutritional supplementation and dietary nutrition education; the observation group established a nutrition intervention group based on the Goal Attainment Theory and carried out individualized nutrition education based on the Goal Attainment Theory. The nutritional indicators at 1 day postoperative, 7 days postoperative, oral nutritional supplementation adherence scores at 7 and 14 days postoperative, and the attainment rate of trans-oral nutritional intake at 21 days postoperative were compared between the 2 groups of patients. Results: There was no statistically significant difference between the nutritional status indexes of the 2 groups of patients before the intervention, p > 0.05; when comparing the prealbumin of the 2 groups of patients at 7 days postoperatively, the prealbumin level of the patients in the observation group at 7 days postoperatively (200.25 ± 53.25) was better than that of the control group (165.73 ± 43.00), with a p value of 0.002, and the difference was statistically significant (p < 0.05). Comparison of oral nutritional supplementation adherence scores at 7 and 14 days postoperatively showed that ONS treatment adherence scores were better than those of the control group, with statistically significant differences (p < 0.05). When comparing the attainment rate of oral nutritional intake at 21 days after surgery, the difference was statistically significant (p < 0.05). Conclusion: Nutritional education based on the Goal Attainment Theory can effectively improve the adherence to oral nutritional supplementation therapy and protein intake attainment rate of colorectal cancer patients after surgery and effectively improve the nutritional status of patients. [ABSTRACT FROM AUTHOR]

Immunotherapy based on immune checkpoint inhibitors (ICIs) has provided revolutionary results in treating various cancers. However, its efficacy in colorectal cancer (CRC), especially in microsatellite stability-CRC, is limited. This study aimed to observe the efficacy of personalized neoantigen vaccine in treating MSS–CRC patients with recurrence or metastasis after surgery and chemotherapy. Candidate neoantigens were analyzed from whole-exome and RNA sequencing of tumor tissues. The safety and immune response were assessed through adverse events and ELISpot. The clinical response was evaluated by progression-free survival (PFS), imaging examination, clinical tumor marker detection, circulating tumor DNA (ctDNA) sequencing. Changes in health-related quality of life were measured by the FACT-C scale. A total of six MSS–CRC patients with recurrence or metastasis after surgery and chemotherapy were administered with personalized neoantigen vaccines. Neoantigen-specific immune response was observed in 66.67% of the vaccinated patients. Four patients remained progression-free up to the completion of clinical trial. They also had a significantly longer progression-free survival time than the other two patients without neoantigen-specific immune response (19 vs. 11 months). Changes in health-related quality of life improved for almost all patients after the vaccine treatment. Our results shown that personalized neoantigen vaccine therapy is likely to be a safe, feasible and effective strategy for MSS–CRC patients with postoperative recurrence or metastasis. [ABSTRACT FROM AUTHOR]

With the advent of continuous direct compression (CDC) process, it becomes increasingly desirable to characterize inherent powder blend heterogeneity at a small batch scale for a robust and CDC-amenable formulation. To accomplish this goal, a near infrared spectroscopy (NIRS)-based characterization approach was developed and implemented on multiple direct compression (DC) blends in this study, with the intended purpose of complementing existing formulation development tools and enabling to build an early CMC data package for late-phased process analytical technology (PAT) method development. Three fumaric acid DC blends, designed to harbor varied degrees of inherent blend heterogeneity, were employed. Near infrared spectral data were collected on a kg-scale batch blender via both time- and angle-based triggering modes. The time-triggered data were used to investigate the blending heterogeneity with respect to rotation angles, while the angle-triggered data were used to provide blending variability characterization and compare against off-line HPLC-based results. The time-triggered data revealed that the greatest blend variability was observed between revolutions, while the blending variability within a single revolution stayed relatively low with respect to rotation angles. This confirmed earlier literature findings that the bottom layer of powder blends tends to move with the blender within each revolution, and the most intense powder mixing takes place across revolutions. This also indicates the use of blending speed and the number of co-adds are not able to increase sampling volume to improve signal-to-noise ratio under a tumble-bin blender as what were typically done in a feedframe application. The angle-triggered data showed that there is a consistent trend between NIRS and HPLC-based methods on characterizing blend heterogeneity across the blends at a given sample size. This study contributes to establishing NIRS as a potential characterization approach for inherent powder blend heterogeneity for early R&D. It also highlights the promise of continuous characterization of inherent powder blend heterogeneity from gram scale to mini-batch CDC scale. [ABSTRACT FROM AUTHOR]

Purpose: We aim to perform a systematic study of the time consolidation effect, i.e. the reduction of powder flowability resulting from at-rest storage, on a diverse array of pharmaceutical powders under different stress, humidity, and length of time. Methods: A ring shear cell-based methodology was employed. An instantaneous flow function was obtained, followed immediately by at-rest consolidation at precisely controlled humidity, stress, and duration. The consolidated powder was then subjected to shear-cell measurement. The difference in flowability between the immediate and consolidated specimens were attributed to the time consolidation effect. Results: Among the six excipients tested, three exhibited time consolidation at varying extents. Citric acid and starch underwent time consolidation only at high relative humidity (RH = 75%), promoted by vapor condensation and liquid bridge formation. For both materials, the flowability decreased with time, and the extent of time consolidation was not sensitive to the stress applied (0.4–2 kPa). Importantly, mannitol was found to time consolidate under both 50% and 75% RH. Given time, mannitol formed cake, giving rise to flow function below unity. Inverse gas chromatography analysis indicated that mannitol possesses high total surface energy among known pharmaceutical powders. Conclusion: While time consolidation is prevalent among pharmaceutical powders, most can be mitigated by controlling the RH to below 75%. Notably, for materials possessing high surface energy, such as mannitol, time consolidation could occur at ambient humidity. Therefore, it is desirable to consider in-depth time consolidation evaluation for high surface energy powders, e.g. those subjected to milling or of amorphous nature. [ABSTRACT FROM AUTHOR]

Assessment and understanding of changes in particle size of active pharmaceutical ingredients (API) and excipients as a function of solid dosage form processing is an important but under-investigated area that can impact drug product quality. In this study, X-ray microscopy (XRM) was investigated as a method for determining the in situ particle size distribution of API agglomerates and an excipient at different processing stages in tablet manufacturing. An artificial intelligence (AI)–facilitated XRM image analysis tool was applied for quantitative analysis of thousands of individual particles, both of the API and the major filler component of the formulation, microcrystalline cellulose (MCC). Domain size distributions for API and MCC were generated along with the calculation of the porosity of each respective component. The API domain size distributions correlated with laser diffraction measurements and sieve analysis of the API, formulation blend, and granulation. The XRM analysis demonstrated that attrition of the API agglomerates occurred secondary to the granulation stage. These results were corroborated by particle size distribution and sieve potency data which showed generation of an API fines fraction. Additionally, changes in the XRM-calculated size distribution of MCC particles in subsequent processing steps were rationalized based on the known plastic deformation mechanism of MCC. The XRM data indicated that size distribution of the primary MCC particles, which make up the larger functional MCC agglomerates, is conserved across the stages of processing. The results indicate that XRM can be successfully applied as a direct, non-invasive method to track API and excipient particle properties and microstructure for in-process control samples and in the final solid dosage form. The XRM and AI image analysis methodology provides a data-rich way to interrogate the impact of processing stresses on API and excipients for enhanced process understanding and utilization for Quality by Design (QbD). [ABSTRACT FROM AUTHOR]

Background: Genetic variation increases the risk of lung cancer, but the extent to which smoking amplifies this effect remains unknown. Therefore, we aimed to investigate the risk of lung cancer in people with different genetic risks and smoking habits. Methods: This prospective cohort study included 345,794 European ancestry participants from the UK Biobank and followed up for 7.2 [6.5–7.8] years. Results: Overall, 26.2% of the participants were former smokers, and 9.8% were current smokers. During follow-up, 1687 (0.49%) participants developed lung cancer. High genetic risk and smoking were independently associated with an increased risk of incident lung cancer. Compared with never-smokers, HR per standard deviation of the PRS increase was 1.16 (95% CI, 1.11–1.22), and HR of heavy smokers (≥40 pack-years) was 17.89 (95% CI, 15.31–20.91). There were no significant interactions between the PRS and the smoking status or pack-years. Population-attributable fraction analysis showed that smoking cessation might prevent 76.4% of new lung cancers. Conclusions: Both high genetic risk and smoking were independently associated with higher lung cancer risk, but the increased risk of smoking was much more significant than heredity. The combination of traditional risk factors and additional PRS provides realistic application prospects for precise prevention. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study is to present a mathematical model capable of describing drug particle dissolution in 3-dimensional (3D) space, and to provide experimental model verification. Through this study, we also aim to elaborate limitations of the classic, 1D-based Nernst-Brunner formalism in dissolution modeling. Methods: The 3D dissolution model was derived by treating the dissolution of a spherical particle as a diffusion-driven process, and by solving Fick's 2nd law of diffusion in spherical coordinates using numerical methods. The resulting model was experimentally verified through analyzing the dissolution behavior of single succinic acid particles in un-stirred water droplet under polarized light microscopy, in combination with image segmentation techniques. Results: A set of working equations was developed to describe drug particle dissolution in 3D space. The predicted dissolution time and profile are in good agreement with the experimental results. The model clearly shows that the concentration gradient within the diffusion layer, in realistic 3D condition, must not be a constant value as implicated in the Nernst-Brunner formalism. The actual concentration profile is a hyperbola, and the concentration gradient at the surface of the particle can be significantly higher than the classic 1D-based dissolution model. Conclusion: The study demonstrates that the classic, 1D-based dissolution models may lead to significant under-estimation of drug dissolution rates. In contrast, modeling dissolution in 3D space yields more reliable results. This study merits further development of comprehensive 3D drug dissolution models, by considering polydispersed particle ensemble and imposing the changes of diffusion layer thickness during dissolution. [ABSTRACT FROM AUTHOR]

Self-healing polymers based on dynamic crosslinkers have drawn rapidly increasing interest over the last decade. Here, a self-healable epoxy network with exchangeable disulfide bonds was synthesized by polymerizing two epoxies with an aromatic amine containing a disulfide bond. The bisphenol A diglycidyl ether (DGEBA) and poly(ethylene glycol) diglycidyl ether (DER736) were used as rigid and soft components, respectively. The crosslinking densities of studied polymers decreased with the increasing amount of DER736, resulting in the lower glassy temperature and weaker mechanical strength. The dynamic covalent network character of disulfide bond and its low active energy were also investigated through stress relaxation experiments at various temperatures. The self-healing performance of healable epoxy resins with varied flexibility was measured by tensile tests. The tensile strength of a full-cut sample was restored to 84% (13 MPa) of the initial values (16 MPa) at moderate temperature. Its healed fracture strain was up to 505%. Moreover, the effect of healing time and temperature on the self-healing properties was also studied. A model was proposed to investigate the self-repairing efficiency evolution with healing time, suggesting that hydrogen bonds mainly contributed to the initial sticking or interfacial adhesion while disulfide links and chain interdiffusion assisted time dependent reformation of networks to restore the original mechanical strength. [ABSTRACT FROM AUTHOR]

Health-risk assessments of temperature are central to determine total non-accidental human mortality; however, few studies have investigated the effect of temperature on accidental human mortality. We performed a time-series study combined with a distributed lag non-linear model (DLNM) to quantify the non-linear and delayed effects of daily mean temperature on accidental human mortality between 2013 and 2017 in Shenzhen, China. The threshold for effects of temperature on accidental human mortality occurred between 5.6 °C and 18.5 °C. Cold exposures, but not hot exposures, were significantly associated with accidental human mortality. All of the observed groups were susceptible to cold effects, with the strongest effects presented in females (relative risk [RR]: 3.14, 95% confidence interval (CI) [1.44–6.84]), followed by poorly educated people (RR: 2.63, 95% CI [1.59–4.36]), males (RR: 1.79, 95% CI [1.10–2.92]), and well-educated people (RR: 1.20, 95% CI [0.58–2.51]). Pooled estimates for cold effects at a lag of 0–21 days (d) were also stronger than hot effects at a lag of 0–2 d. Our results indicate that low temperatures increased the risk of accidental human mortality. Females and poorly educated people were more susceptible to the low temperatures. These findings imply that interventions which target vulnerable populations during cold days should be developed to reduce accidental human mortality risk. [ABSTRACT FROM AUTHOR]

Cytidine base editors (CBEs) and adenine base editors (ABEs), composed of a cytidine deaminase or an evolved adenine deaminase fused to Cas9 nickase, enable the conversion of C·G to T·A or A·T to G·C base pair in organisms, respectively. Here, we show that BE3 and ABE7.10 systems can achieve a targeted mutation efficiency of 53–88% and 44–100%, respectively, in both blastocysts and Founder (F0) rabbits. Meanwhile, this strategy can be used to precisely mimic human pathologies by efficiently inducing nonsense or missense mutations as well as RNA mis-splicing in rabbit. In addition, the reduced frequencies of indels with higher product purity are also determined in rabbit blastocysts by BE4-Gam, which is an updated version of the BE3 system. Collectively, this work provides a simple and efficient method for targeted point mutations and generation of disease models in rabbit. DOI: 10.1038/s41467-018-05232-2 OPEN 1 [ABSTRACT FROM AUTHOR]

Shadong deposit is the first large-scale tungsten deposit found in the East Tianshan orogenic belt, and the geologic characteristics of the deposit indicate that the deeply concealed granite body is genetically related with the mineralization. The LA-ICPMS U-Pb age of zircons from the Shadong concealed granite obtained in this research is 239±2.0 Ma, belonging to the Middle Triassic. The whole rock samples are metaluminous to slightly peraluminous (A/CNK=0.95-1.02) with low contents of SiO (64.0 wt.%-68.5 wt.%) and low KO/NaO ratios (0.73-0.96). The samples reveal enrichment of K, Rb, Th and depletion of Nb, Ta, P, Ti and have a negative slope from La to Lu (La/Yb=16.29-36.8) with weak negative Eu anomaly (Eu/Eu*= 0.71-0.82). Initial Sr/Sr ratios of whole rock range of 0.706 59-0.707 75, ε ( t) values range from -1.77 to -2.53 and ε ( t) values of zircon are between 2.54 and 4.90. The lithogeochemistry and Sr-Nd-Hf isotopic characteristics revealed that the concealed granite in Shadong tungsten deposit is I-type granite, and occurs in an intraplate tectonic setting. The magma mixing during intraplating of mantle derived magma intruding into the crust in Indosinian Period is the major formation mechanism of the granite. Of which, the proportion of mantle derived magma ranges from 58% to 60%, and the crustal materials are mainly the metamorphic basement of Xingxingxia Group of Mesoproterozoic Changcheng System, which may provide the main source of ore forming metals of Shadong tungsten deposit. [ABSTRACT FROM AUTHOR]

Novel Mn-Fe-Mg- and Mn-Fe-Ce-loaded alumina (Mn-Fe-Mg/Al2O3 and Mn-Fe-Ce/Al2O3) were developed to catalytically ozonate reverse osmosis concentrates generated from petroleum refinery wastewaters (PRW-ROC). Highly dispersed 100-300-nm deposits of composite multivalent metal oxides of Mn (Mn2+, Mn3+, and Mn4+), Fe (Fe2+ and Fe3+) and Mg (Mg2+), or Ce (Ce4+) were achieved on Al2O3 supports. The developed Mn-Fe-Mg/Al2O3 and Mn-Fe-Ce/Al2O3 exhibited higher catalytic activity during the ozonation of PRW-ROC than Mn-Fe/Al2O3, Mn/Al2O3, Fe/Al2O3, and Al2O3. Chemical oxygen demand removal by Mn-Fe-Mg/Al2O3- or Mn- Fe-Ce/Al2O3-catalyzed ozonation increased by 23.9% and 23.2%, respectively, in comparison with single ozonation. Mn-Fe-Mg/Al2O3 and Mn-Fe-Ce/Al2O3 notably promoted .OH generation and .OH-mediated oxidation. This study demonstrated the potential use of composite metal oxide-loaded Al2O3 in advanced treatment of bio-recalcitrant wastewaters. [ABSTRACT FROM AUTHOR]

With the development of whole genome and transcriptome sequencing technologies, a growing body of long non-coding RNAs (lncRNAs) has been identified and is receiving increasing attention. LncRNAs are non-protein encoding transcripts whose functions are crucial for advancing our comprehensive understanding of biological processes in human health and diseases, specifically glioma. It has been established that lncRNAs are differently expressed in the central nervous system and may play a vital role in glioma. As of June 2016, 20 lncRNAs have been identified that may play a role in glioma pathogenesis. Investigation into the role of lncRNAs in glioma may help to identify potential biomarkers which can improve the diagnosis and treatment of glioma. In this paper, we review current understanding of the function of lncRNAs in glioma initiation and progression. [ABSTRACT FROM AUTHOR]

The purpose of this meta-analysis was to investigate whether serum resistin level was associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) by comparing serum resistin levels between RA or SLE patients and normal controls. PubMed and EMBASE databases (up to May 13, 2014) were used to search all related articles. The weighted mean differences (WMDs) with 95 % confidence interval (CI) were calculated using random-effect model analysis. The Cochrane Q test and I statistic were used to test heterogeneity. To assess publication bias, the Egger's test and visual observation of a funnel plot were used. The Newcastle-Ottawa scale was used to assess the study quality. The STATA statistical software (version 11.0) was applied to deal with statistical data. A total of eight studies of RA including 620 patients and 460 healthy controls, and six studies of SLE including 559 patients and 430 healthy controls were finally included in the meta-analysis. The results revealed that the serum resistin levels in RA were significantly higher than those in normal controls ( WMD = 0.767 ng/ml, 95 % CI = 0.114-1.419, P = 0.021), but there was no significant difference between SLE patients and normal controls ( WMD = 2.771 ng/ml, 95 % CI = −0.521-6.063, P = 0.099). Publication bias was undetected. In conclusion, this meta-analysis indicate that serum resistin level was significantly elevated in RA patients. [ABSTRACT FROM AUTHOR]

This paper presents a digital three-dimensional reconstruction method based on a set of small-baseline elemental images captured with a micro-lens array and a CCD sensor. In this paper, we adopt the ASIFT (Affine Scale-invariant feature transform) operator as the image registration method. Among the set of captured elemental images, the elemental image located in the middle of the overall image field is used as the reference and corresponding matching points in each elemental image around the reference elemental are calculated, which enables to accurately compute the depth value of object points relatively to the reference image frame. Using optimization algorithm with redundant matching points can achieve 3D reconstruction finally. Our experimental results are presented to demonstrate excellent performance in accuracy and speed of the proposed algorithm. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the effect of naringenin on protection in lipopolysaccharide (LPS)-induced injury in normal human bronchial epithelium (NHBE) and to provide insights into the possible underlying mechanisms. NHBE were stimulated by LPS in the presence or absence of the narigenin. In vitro treatment with naringenin led to a significant attenuation in the LPS-induced NHBE secretion of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), superoxidase dismutase (SOD), nitricoxide synthase (NOS), myeloperoxidase (MPO), and nitric oxide (NO). RT-qPCR demonstrated that naringenin significantly reduced the LPS-induced upregulation of TNF-α, IL-6, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 mRNA expression in a dose-dependent manner. Additionally, Western blot analysis revealed that naringenin effectively suppressed NF-κB activation by inhibiting the degradation of IκB-α and the translocation of p65. Naringenin also attenuated mitogen-activated protein kinase (MAPK) activation by inhibiting the phosphorylation of ERK1/2, c-Jun NH(2)-terminal kinase (JNK), and p38 MAPK. Taken together, these demonstrate that naringenin reduces TNF-α and IL-6 secretion and mRNA expression, possibly by blocking the activation of the NF-κB and MAPK signaling pathways in LPS-treated NHBE. These results indicated that naringenin had a protective effect on LPS-induced injury in NHBE. [ABSTRACT FROM AUTHOR]

To determine whether methylenetetrahydrofolate reductase ( MTHFR) C677T and A1298C polymorphisms are associated with pre-eclampsia susceptibility. Literature searches of the Pubmed, Embase, BIOSIS Previews and Web of Science were conducted to identify all eligible articles up to January 18th, 2013. The pooled odds ratios (ORs) with 95 % confidence intervals (CIs) of five genetic models were calculated by fixed-effects or random-effects model. Publication bias, subgroup analysis, meta-regression and sensitivity analysis were also performed. A number of 49 studies including 51 samples consisted of 18,009 subjects (6,238 patients and 11,771 controls) were finally included. MTHFR C677T allele (TT or CT) carriers were 1.12 times more likely to develop pre-eclampsia (95 % CI 1.04-1.21) compared with 677CC homozygous individuals. Similar results were obtained under other genetic models. Restricted to severe pre-eclampsia, there was an increased risk for 677TT homozygotes compared with 677CC homozygotes (OR 1.43; 95 % CI 1.12-1.83). Subgroup analysis revealed a significant positive association between the C677T polymorphism (TT or CT) and pre-eclampsia in Asians (OR 1.41; 95 % CI 1.11-1.79) and white population (OR 1.14; 95 % CI 1.03-1.25). Meta-regression showed that study population, blinded genotyping, matching of cases and controls were not substantial sources of heterogeneity. For the MTHFR A1298C, ORs for all genetic models yielded a null association. This meta-analysis suggests that the MTHFR 677T allele might be associated with increased pre-eclampsia risk in Asian and white ethnicity and the subgroup of severe pre-eclampsia, while no association is observed between the MTHFR A1298C polymorphism and pre-eclampsia. [ABSTRACT FROM AUTHOR]

Background: Resistance and aerobic exercises are both recommended as effective treatments for people with type 2 diabetes. However, the optimum type of exercise for the disease remains to be determined to inform clinical decision-making and facilitate personalized exercise prescription. Objectives: Our objective was to investigate whether resistance exercise is comparable to aerobic exercise in terms of effectiveness and safety in people with type 2 diabetes. Data sources: PubMed, EMBASE, CENTRAL, CINAHL, and SPORTdiscus were systematically searched up to March 2013. The reference lists of eligible studies and relevant reviews were also checked. Study Selection: We used the following criteria to select studies for inclusion in the review: (i) the study was a randomized controlled trial; (ii) the participants were people with type 2 diabetes aged 18 years or more; (iii) the trial compared resistance exercise with aerobic exercise for a duration of at least 8 weeks, with pre-determined frequency, intensity, and duration; and (iv) the trial provided relevant data on at least one of the following: glycaemic control, blood lipids, anthropometric measures, blood pressure, fitness, health status, and adverse events. Study Appraisal and Synthesis Methods: The assessment of study quality was based on the Cochrane Risk of Bias tool. For effectiveness measures, differences (resistance group minus aerobic group) in the changes from baseline with the two exercises were combined, using a random-effects model wherever possible. For adverse events, the relative risks (resistance group vs. aerobic group) were combined. Results: Twelve trials ( n = 626) were included. Following the exercise interventions, there was a greater reduction of glycosylated hemoglobin with aerobic exercise than with resistance exercise (difference 0.18 % (1.97 mmol/mol), 95 % confidence interval (CI) 0.01, 0.36). This difference became non-significant with sensitivity analysis ( p = 0.14). The differences in changes from baseline were also statistically significant for body mass index (difference 0.22, 95 % CI 0.06, 0.39), peak oxygen consumption (difference −1.84 mL/kg/min, 95 % CI −3.07, −0.62), and maximum heart rate (difference 3.44 beats per minute, 95 % CI 2.49, 4.39). Relative risks for adverse events (all) and serious adverse events were 1.17 (95 % CI 0.77, 1.79) and 0.89 (95 % CI 0.18, 4.39), respectively. Limitations: Most included trials were short term (8 weeks to 6 months), and seven had important methodological limitations. Additionally, the meta-analyses for some of the secondary outcomes had a small number of participants or substantial statistical heterogeneity. Conclusions: Although differences in some diabetic control and physical fitness measures between resistance exercise and aerobic exercise groups reached statistical significance, there is no evidence that they are of clinical importance. There is also no evidence that resistance exercise differs from aerobic exercise in impact on cardiovascular risk markers or safety. Using one or the other type of exercise for type 2 diabetes may be less important than doing some form of physical activity. Future long-term studies focusing on patient-relevant outcomes are warranted. [ABSTRACT FROM AUTHOR]

Background: Although interleukin-10 (IL-10) is a potent inhibitor of allergic diseases, the association between promoter −1082/−819/−592 polymorphisms and asthma susceptibility remains inconclusive. We sought to determine if IL-10 promoter −1082/−819/−592 polymorphisms contribute to asthma susceptibility and are associated with phenotypes of atopic asthma. Methods: Systematic computerized searches were performed. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated by using random-effect and fixed-effect models, based on between-study heterogeneity. Subgroup analyses were performed according to age, ethnicity, and atopy. Publication bias was detected by funnel plot using Egger's test. Results: A total of 4,716 asthmatic patients and 5,093 controls were included. The asthma susceptibility correlated significantly with IL-10 promoter gene −1082 polymorphism [OR (95 % CI) 1.26 (1.02, 1.55) for AA vs. AG + GG] and −592 polymorphism [OR (95 % CI) 1.12 (1.07, 1.34) for AC + AA vs. CC] (both P < 0.05), but not with −819 polymorphism ( P > 0.05). Subgroup analyzes suggested that the AA versus AG + GG genotype of −1082A/G polymorphism and AC + AA versus CC genotype of −592A/C polymorphism contributed significantly to increased asthma susceptibility in adults [OR (95 % CI) 1.39 (1.03, 1.87) for −1082A/G and 1.53 (1.25, 1.87) for −592A/C polymorphism]. The Asian population [OR (95 % CI) 1.35 (1.1, 1.7) for −1082A/G and 1.4 (1.12, 1.64) for −592A/C polymorphism] and subjects with atopic asthma [OR (95 % CI) 1.49 (1.18, 1.88) for −1082A/G and 1.23 (1.01, 1.48) for −592A/C polymorphism] also had an increased susceptibility of asthma. No publication bias was detected. Conclusions: IL-10 promoter −1028A/G, −592A/C polymorphisms and their haplotypes, but not −819T/C polymorphism, correlate with asthma susceptibility. [ABSTRACT FROM AUTHOR]

Epidemiological studies have evaluated the association between ATM 5557G>A (p.D1853N) polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of PubMed and Medline databases were performed. A total of nine studies included 3155 cases and 2752 controls were identified. When all nine studies were pooled into the meta-analysis, there was no evidence for significant association between 5557G>A mutation and breast cancer risk(for G/A vs. G/G: OR = 1.05, 95% CI = 0.83-1.34; for A/A vs. G/G: OR = 0.77, 95% CI = 0.58-1.03; for dominant model: OR = 1.04, 95% CI = 0.82-1.31; for recessive model: OR = 0.87, 95% CI = 0.69-1.09). In the subgroup analyses by family history and ethnicity, significant associations were found among Amerindians (for G/A vs. G/G: OR = 2.19, 95% CI = 1.38-3.47; for dominant model: OR = 2.15, 95% CI = 1.37-3.38). In summary, the meta-analysis suggest that ATM 5557G>A polymorphism is associated with increased breast cancer risk among Amerindians. However, due to the small subjects included in analysis and the selection bias existed in some studies, the results for Amerindians should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Several polymorphisms of vascular endothelial growth factor (VEGF) such as 936 C/T, −2578 C/A, −406 C/T, and −1154 G/A polymorphism have been identified. Published data on the association between VEGF polymorphisms and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude OR with 95% CI was used to assess the strength of association between them. For VEGF 936C/T polymorphism, a total of 10 studies including 7,685 cases and 7,915 controls were involved in this meta-analysis. Overall, no significant associations were found between VEGF 936C/T polymorphism and breast cancer risk when all studies pooled into the meta-analysis (TC vs. CC: OR = 0.904, 95% CI = 0.797-1.024; TT vs. CC: OR = 0.974, 95% CI = 0.786-1.205; dominant model: OR = 0.911, 95% CI = 0.811-1.024; and recessive model: OR = 0.991, 95% CI = 0.801-1.226). In the subgroup analysis by ethnicity, still no significant associations were found for all comparison models. For −2578 C/A, −406 C/T, and −1154 G/A polymorphism, there were too limited data to perform a meta-analysis. In conclusion, this meta-analysis suggests that the VEGF 936C/T polymorphism may be not associated with breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding. [ABSTRACT FROM AUTHOR]

The ecological implications on biological control of insecticidal transgenic plants, which produce crystal (Cry) proteins from the soil bacterium Bacillus thuringiensis (Bt), remain a contentious issue and affect risk assessment decisions. In this study, we used a unique system of resistant insects, Bt plants and a parasitoid to critically evaluate this issue. The effects of broccoli type (normal or expressing Cry1Ac protein) and insect genotype (susceptible or Cry1Ac-resistant) of Plutella xylostella L. (Lepidoptera: Plutellidae) were examined for their effects on the development and host foraging behavior of the parasitoid, Diadegma insulare (Cresson) (Hymenoptera: Ichneumonidae) over two generations. Parasitism rate and development of D. insulare were not significantly different when different genotypes (Bt-resistant or susceptible) of insect host larvae fed on non-Bt broccoli plants. D. insulare could not discriminate between resistant and susceptible genotypes of P. xylostella, nor between Bt and normal broccoli plants with different genotypes of P. xylostella feeding on them. No D. insulare could emerge from Bt broccoli-fed susceptible and heterozygous P. xylostella larvae because these larvae were unable to survive on Bt broccoli. The parasitism rate, developmental period, pupal and adult weights of D. insulare that had developed on Bt broccoli-fed Cry1Ac-resistant P. xylostella larvae were not significantly different from those that developed on non-Bt broccoli-fed larvae. Female D. insulare emerged from Cry1Ac-resistant P. xylostella that fed on Bt plants could successfully parasitize P. xylostella larvae. The life parameters of the subsequent generation of D. insulare from P. xylostella reared on Bt broccoli were not significantly different from those from non-Bt broccoli. The Cry1Ac protein was detected in P. xylostella and in D. insulare when hosts fed on Bt broccoli. These results are the first to indicate that Cry1Ac did not harm the development or host acceptance of an important endoparasitoid after two generations of exposure. We suggest that using other Bt crops and resistant insect species would likely lead to similar conclusions about the safety of the presently used Bt proteins on parasitoids. [ABSTRACT FROM AUTHOR]

Published data on the association between three polymorphisms (Lys939Gln, Ala499Val, and PAT±) of Xeroderma Pigmentosum group C (XPC) and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 11 studies including 5,090 cases and 5,214 controls were involved in this meta-analysis. For XPC Lys939Gln polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis (Lys/Gln vs. Lys/Lys: OR = 1.00, 95% CI 0.92-1.10; Gln/Gln vs. Lys/Lys: OR = 0.96, 95% CI 0.84-1.09; dominant model: OR = 0.99, 95% CI 0.91-1.08; and recessive model: OR = 0.97, 95% CI 0.86-1.09). In the subgroup analysis by ethnicity or study design, still no obvious associations were found. For XPC Ala499Val polymorphism, also no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis (Val/Ala vs. Ala/Ala: OR = 0.91, 95% CI 0.79-1.05; Val/Val vs. Ala/Ala: OR = 1.07, 95% CI 0.80-1.44; dominant model: OR = 0.93, 95% CI 0.81-1.06; and recessive model: OR = 1.11, 95% CI 0.84-1.48). For XPC PAT± polymorphism, obvious associations were found for recessive model when all studies were pooled into the meta-analysis (OR = 1.41, 95% CI 1.05-1.89). In conclusion, this meta-analysis suggests that the XPC PAT± polymorphism allele may be a low-penetrant risk factor for developing breast cancer. [ABSTRACT FROM AUTHOR]

Epidemiological studies have evaluated the association between ATM C.1066-6T > G (IVS10-6T > G) mutation and breast cancer risk. However, the results remain conflicting rather than conclusive. In order to derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of PubMed and Medline databases were performed. A total of 11 studies including 8,831 cases and 4,957 controls were identified. The carrier frequency of the ATM C.1066-6T > G mutation was 0.5% (45/8,831) in patients with breast cancer and 0.7% (38/4,957) in healthy controls. When all the 11 studies were pooled into the meta-analysis, there was no evidence for significant association between C.1066-6T > G mutation and breast cancer risk (OR 0.87, 95% CI 0.55-1.37). In the subgroup analyses by source of controls and family history with BRCA1/2 status, no significant association were found in any subgroup of population. When sensitivity analyses were performed, all the results were not materially altered. In summary, the meta-analysis strongly suggests that ATM C.1066-6T > G mutation is not associated with increased breast cancer risk. [ABSTRACT FROM AUTHOR]

Published data on the association between Xeroderma Pigmentosum complementation group D (XPD) Lys751Gln polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 30 studies including 14,283 cases and 14,426 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with XPD 751Gln allele when all studies were pooled into the meta-analysis (Lys/Gln vs. Lys/Lys: OR = 1.13, 95% CI = 1.02-1.25; Gln/Gln vs. Lys/Lys: OR = 1.21, 95% CI = 1.06-1.38; dominant model: OR = 1.16, 95% CI = 1.05-1.29; and recessive model: OR = 1.14, 95% CI = 1.02-1.27). In the subgroup analysis by ethnicity, borderline significantly increased risks were found for Caucasians (Lys/Gln vs. Lys/Lys: OR = 1.09, 95% CI = 0.98-1.22; dominant model: OR = 1.10, 95% CI = 0.99-1.22) and significantly increased risks were found for Africans in dominant model (OR = 1.10, 95% CI = 1.04-1.15). When stratified by study design, statistically significantly elevated risk was found in population-based studies (Lys/Gln vs. Lys/Lys: OR = 1.10, 95% CI = 1.01-1.20; Gln/Gln vs. Lys/Lys: OR = 1.15, 95% CI = 1.01-1.31; dominant model: OR = 1.12, 95% CI = 1.03-1.23). In conclusion, this meta-analysis suggests that the XPD 751Gln allele is a low-penetrant risk factor for developing breast cancer. [ABSTRACT FROM AUTHOR]

Published data on the association between BRCA2 N372H polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 22 studies including 22,515 cases and 22,388 controls were involved in this meta-analysis. Overall, no significant associations were found between BRCA2 N372H polymorphism and breast cancer risk when all studies pooled into the meta-analysis (NH versus NN: OR = 1.01, 95% CI = 0.97–1.05; HH versus NN: OR = 1.05, 95% CI = 0.97–1.13; dominant model: OR = 1.01, 95% CI = 0.98–1.05; and recessive model: OR = 1.05, 95% CI = 0.98–1.13). In the subgroup analysis by ethnicity, still no significant associations were found for Caucasians, Asians, or Africans. When stratified by study design, statistically significantly elevated risk was found for 372H allele based on population-based studies (HH versus NN: OR = 1.11, 95% CI = 1.01–1.21; dominant model: OR = 1.05, 95% CI = 1.00–1.10; recessive model: OR = 1.09, 95% CI = 1.00–1.18). In conclusion, this meta-analysis suggests that the BRCA2 372H allele may be a low-penetrant risk factor for developing breast cancer. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding. [ABSTRACT FROM AUTHOR]

Published data on the association between MnSOD Val16Ala polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the MnSOD Val16Ala polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (Val/Ala vs. Val/Val, Ala/Ala vs. Val/Val), dominant model (Ala/Ala + Val/Ala vs. Val/Val), and recessive model (Ala/Ala vs. Val/Ala + Val/Val), respectively. A total of 32 studies including 26,022 cases and 32,426 controls were involved in this meta-analysis. Overall, no significant associations were found between MnSOD Val16Ala polymorphism and breast cancer risk when all studies pooled into the meta-analysis (Val/Ala vs. Val/Val: OR = 1.022, 95% CI = 0.981–1.064; Ala/Ala vs. Val/Val: OR = 1.006, 95% CI = 0.934–1.083; dominant model: OR = 1.013, 95% CI = 0.962–1.066; and recessive model: OR = 0.985, 95% CI = 0.931–1.042). In the subgroup analysis by ethnicity or study design, still no significant associations were found for all comparison models. In conclusion, this meta-analysis suggests that the MnSOD Val16Ala polymorphism may be not associated with breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding. [ABSTRACT FROM AUTHOR]

Published data on the association between TGFB1 L10P polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 30 studies including 20,401 cases and 27,416 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with TGFB1 10P allele when all studies were pooled into the meta-analysis (LP vs. LL: OR = 1.046, 95% CI = 1.003–1.090; dominant model: OR = 1.052, 95% CI = 1.012–1.095). In the subgroup analysis by ethnicity, statistically significantly elevated risk was found in Caucasians (dominant model: OR = 1.045, 95% CI = 1.001–1.091). When stratified by study design, statistically significantly elevated risk was found based on population-based studies (dominant model: OR = 1.076, 95% CI = 1.019–1.136). In conclusion, this meta-analysis suggests that the TGFB1 10P allele may be a low-penetrant risk factor for developing breast cancer. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding. [ABSTRACT FROM AUTHOR]

Published data on the association between insulin-like growth factor binding protein 3 (IGFBP3) A-202C polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 27 studies including 33,557 cases and 45,254 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with IGFBP3 C allele when all studies were pooled into the meta-analysis (CC vs. AA: OR = 1.06, 95% CI = 1.02–1.11; dominant model: OR = 1.04, 95% CI = 1.00–1.07). In the subgroup analysis by ethnicity, significantly increased risk was found for Caucasians (AC vs. AA: OR = 1.04, 95% CI = 1.00–1.08; CC vs. AA: OR = 1.05, 95% CI = 1.01–1.10; dominant model: OR = 1.04, 95% CI = 1.00–1.08) and Asians (CC vs. AA: OR = 1.35, 95% CI = 1.02–1.78; recessive model: OR = 1.38, 95% CI = 1.05–1.82). When stratified by study design, statistically significantly elevated risk was found among population-based studies (CC vs. AA: OR = 1.06, 95% CI = 1.01–1.11; dominant model: OR = 1.03, 95% CI = 1.00–1.07). In the subgroup analysis by menopausal status, no statistically significantly increased risk was found among premenopausal or postmenopausal women. In conclusion, this meta-analysis suggests that the IGFBP3 C allele is a low-penetrant risk factor for developing breast cancer. [ABSTRACT FROM AUTHOR]

Published data on the association between XRCC3 5′-UTR and IVS5-14 polymorphisms and breast cancer risk are inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between these polymorphisms and breast cancer risk. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. A total of four studies were involved in the meta-analysis with 6,303 cases and 6,563 controls for XRCC3 5′-UTR polymorphism and with 6,270 cases and 6,682 controls for XRCC3 IVS5-14 polymorphism. For XRCC3 5′-UTR A/G polymorphism, significantly elevated breast cancer risk was associated with variant genotype when all studies were pooled into the meta-analysis (AG vs. AA: OR = 1.11, 95% CI = 1.03–1.19; dominant model: OR = 1.09, 95% CI = 1.01–1.17). For XRCC3 IVS5-14 A/G polymorphism, significantly decreased breast cancer risk was associated with variant genotype (GG vs. AA: OR = 0.86, 95% CI = 0.77–0.96). In conclusion, this meta-analysis suggests that the variant G allele of XRCC3 5′-UTR polymorphism is a low-penetrant risk factor for developing breast cancer, while the variant G allele of XRCC3 IVS5-14 polymorphism has a protective effect on breast cancer development. [ABSTRACT FROM AUTHOR]

Published data on the association between cytochrome P-450 1A2 (CYP1A2)-164 A/C polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between CYP1A2-164 A/C polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (AC versus AA, CC versus AA), dominant model (CC + AC versus AA), and recessive model (CC versus AA + AC), respectively. A total of 9 studies including 7,580 cases and 10,020 controls were involved in this meta-analysis. Overall, no significantly elevated breast cancer risk was found in all genetic models when all studies were pooled into the meta-analysis (AC versus AA: OR = 1.02, 95% CI = 0.92–1.13; CC versus AA: OR = 1.17, 95% CI = 0.83–1.64; dominant model: OR = 1.07, 95% CI = 0.93–1.23; and recessive model: OR = 1.13, 95% CI = 0.82–1.55). In the subgroup analysis by ethnicity or source of controls, there was still no significant association detected in all genetic models. In conclusion, upto date, there is still no enough evidence to indicate the association of CYP1A2-164 A/C polymorphism and breast cancer development. [ABSTRACT FROM AUTHOR]

Fusarium head blight (FHB) is a serious wheat disease all over the world. In this study, the relationships between plant height (PH) and FHB were investigated across the whole wheat genome by QTL meta-analysis from fifty-six experiments. Coincident meta-QTL (MQTL) for PH and FHB were found on chromosomes 2D, 3A, 4B, 4D and 7A. Rht-B1, Rht-D1, Rht8, MQTLs P7 and P26 were consistent with FHB MQTLs. The meta-analysis results confirmed the negative associations of Rht-B1, Rht-D1, and Rht8 with FHB resistance. The associations of PH and FHB resistance on chromosomes 3A and 7A have not been reported and need further investigation. These regions should be given attention in breeding programs. MQTLs derived from several resistance sources were also observed. Some FHB MQTLs for different types of resistance overlapped. These findings could be useful for improving wheat varieties with resistance to FHB. [ABSTRACT FROM AUTHOR]

Epidemiological studies have evaluated the association between CYP17 MspA1 polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of the PubMed and Medline databases were performed. A total of 35 studies including 22,090 cases and 28,498 controls were identified. Genotype distributions of CYP17 in the controls of all studies were in agreement with Hardy–Weinberg equilibrium (HWE) except for three studies. When all 35 studies were pooled into the meta-analysis, there was no evidence for significant association between CYP17 MspA1 polymorphism and breast cancer risk (for A1/A2 vs. A1/A1: OR = 1.00, 95% CI = 0.96–1.04; for A2/A2 vs. A1/A1: OR = 1.03, 95% CI = 0.97–1.08; for dominant model: OR = 1.01, 95% CI = 0.97–1.05; for recessive model: OR = 1.03, 95% CI = 0.98–1.08). In the subgroup analyses by ethnicity, menopausal status and source of controls, no significant associations were found in all genetic models. When sensitivity analyses were performed by excluding HWE-violating studies, all the results were not materially altered. In summary, the meta-analysis strongly suggests that CYP17 MspA1 polymorphism is not associated with increased breast cancer risk. [ABSTRACT FROM AUTHOR]

Published data on the association between present/null polymorphism of glutathione S-transferase M1 (GSTM1) and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the GSTM1 present/null polymorphism and breast cancer risk. The pooled ORs were performed for null versus present genotype. A total of 59 studies including 20,993 cases and 25,288 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with null genotype when all studies were pooled into the meta-analysis (OR = 1.10, 95% CI = 1.04–1.16). In the subgroup analysis by ethnicity, significantly increased risks were found for Caucasians (OR = 1.05, 95% CI = 1.00–1.10) and Asians (OR = 1.21, 95% CI = 1.08–1.35). When stratified by population-based studies or hospital-based studies, statistically significantly elevated risks were found among population-based studies (OR = 1.11, 95% CI = 1.03–1.20). In the subgroup analysis by menopausal status, statistically significantly increased risks were found among postmenopausal women (OR = 1.15, 95% CI = 1.04–1.28). In conclusion, this meta-analysis suggests that the GSTM1 null genotype is a low-penetrant risk factor for developing breast cancer. [ABSTRACT FROM AUTHOR]

Epidemiological studies have evaluated the association between catechol- O-methyltransferase (COMT) Val108/158Met polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. In order to derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of the PubMed and Medline databases were performed. A total of 41 studies including 25,627 cases and 34,222 controls were identified. Genotype distributions of COMT in the controls of all studies were in agreement with the Hardy–Weinberg equilibrium (HWE) except for three studies. When all 41 studies were pooled into the meta-analysis, there was no evidence for significant association between COMT Val108/158Met polymorphism and breast cancer risk (for Val/Met vs. Val/Val: OR = 0.99, 95% CI = 0.93–1.04; for Met/Met vs. Val/Val: OR = 0.96, 95% CI = 0.88–1.04; for dominant model: OR = 0.97, 95% CI = 0.92–1.03; for recessive model: OR = 0.97, 95% CI = 0.90–1.04). In the subgroup analyses by ethnicity, menopausal status, no significant associations were found in all genetic models. When sensitivity analyses were performed by excluding HWE-violating studies, all the results were not materially altered. In summary, the meta-analysis strongly suggests that COMT Val108/158Met polymorphism is not associated with increased breast cancer risk. [ABSTRACT FROM AUTHOR]

Increased intra-abdominal pressure (IAP) is common in intensive care patients, affecting aerated lung volume distribution. The current study deals with the effect of increased IAP and decompressive laparotomy on aerated lung volume distribution. The serial whole-lung computed tomography scans of 16 patients with increased IAP were retrospectively analyzed between July 2006 and July 2008 and compared to controls. The IAP increased from (12.1±2.3) mmHg on admission to (25.2±3.6) mmHg ( P<0.01) before decompressive laparotomy and decreased to (14.7±2.8) mmHg after decompressive laparotomy. Mean time from admission to decompressive laparotomy and length of intensive-care unit (ICU) stay were 26 h and 16.2 d, respectively. The percentage of normally aerated lung volume on admission was significantly lower than that of controls ( P<0.01). Prior to decompressive laparotomy, the total lung volume and percentage of normally aerated lung were significantly less in patients compared to controls ( P<0.01), and the absolute volume of non-aerated lung and percentage of non-aerated lung were significantly higher in patients ( P<0.01). Peak inspiratory pressure, partial pressure of carbon dioxide in arterial blood, and central venous pressure were higher in patients, while the ratio of partial pressure of arterial O2 to the fraction of inspired O2 (PaO2/FIO2) was decreased relative to controls prior to laparotomy. An approximately 1.8 cm greater cranial displacement of the diaphragm in patients versus controls was observed before laparotomy. The sagittal diameter of the lung at the T6 level was significantly increased compared to controls on admission ( P<0.01). After laparotomy, the volume and percentage of non-aerated lung decreased significantly while the percentage of normally aerated lung volume increased significantly ( P<0.01). In conclusion, increased IAP decreases total lung volume while increasing non-aerated lung volume. Decompressive laparotomy is associated with resolution of these effects on lung volumes. [ABSTRACT FROM AUTHOR]

The tea weevil, Myllocerinus aurolineatus (Voss) (Coleoptera: Curculionidae), is a leaf-feeding pest of Camellia sinensis (O.Ktze.) with aggregative behaviors that can seriously reduce tea yield and quality. Although herbivore-induced host plant volatiles have been shown to attract conspecific individuals of some beetle pests, especially members of the Chrysomelidae family, little is known about the volatiles emitted from tea plants infested by M. aurolineatus adults and their roles in mediating interactions between conspecifics. The results of behavioral bioassays revealed that volatile compounds emitted from tea plants infested by M. aurolineatus were attractive to conspecific weevils. Volatile analyses showed that infestations dramatically increased the emission of volatiles, ( Z)-3-hexenal, (Z)-3-hexenol, ( E)-β-ocimene, linalool, phenylethyl alcohol, benzyl nitrile, indole, ( E, E)-α-farnesene, ( E)-nerolidol, and 31 other compounds. Among the induced volatiles, 12 chemicals, including γ-terpinene, benzyl alcohol, ( Z)-3-hexenyl acetate, myrcene, benzaldehyde, ( Z)-3-hexenal, and ( E, E)-α-farnesene, elicited antennal responses from both sexes of the herbivore, whereas ( E)-β-ocimene elicited antennal responses only from males. Using a Y-tube olfactometer, we found that six of the 13 chemicals, γ-terpinene, benzyl alcohol, ( Z)-3-hexenyl acetate, myrcene, benzaldehyde, and ( Z)-3-hexenal, were attractive to both males and females; two chemicals, ( E/Z)-β-ocimene and ( E, E)-α-farnesene, were attractive only to males; and four chemicals, ( E)-4,8-dimethyl-1,3,7-nonatriene, phenylethyl alcohol, linalool, and (Z)-3-hexenol, were attractive only to females. The findings provide new insights into the interactions between tea plants and their herbivores, and may help scientists develop new strategies for controlling the herbivore. [ABSTRACT FROM AUTHOR]

Abstract  To investigate the association between Fc receptor-like 3 (FCRL3) C169T polymorphism and susceptibility to systemic lupus erythematosus (SLE). We surveyed studies on the FCRL3 C169T polymorphism and SLE using comprehensive Medline search and review of the references. Meta-analysis was performed for genotypes CC (recessive effect), CC+CT (dominant effect) and C allele in fixed effects model or random effects model. Five identified studies included 1,944 SLE patients and 4,528 non-SLE controls. Three out of five identified studies included populations of Asian descent, and two included populations of European descent. The overall odds ratio (OR) of the CC genotype was 1.21(95% confidence interval [CI], 1.04–1.40). Stratification by ethnicity indicated that the CC genotype was associated with SLE in Asian-derived population (OR, 1.23; 95% CI, 1.03–1.47). No association was detected in European-derived population (OR, 1.17; 95% CI, 0.90–1.52). This meta-analysis fails to show significant association of CC+CT genotypes and C allele with SLE in overall, European-derived and Asian-derived populations. In summary, this meta-analysis demonstrates that the FCRL3 169CC genotype (recessive effect) may confer susceptibility to SLE, especially in Asian-derived population. [ABSTRACT FROM AUTHOR]

Abstract  The aim of this study to determine whether serum p53 protein and antibodies are associated with malignant tumors. A case–control study was conduct in 569 patients with various types of malignant tumors and 879 healthy controls. Serum p53 protein and antibodies were analyzed by enzyme-linked immunosorbent assay (ELISA).The rate of positive p53 protein in patients with various malignant tumors was 4.22% compared with 0.34% in healthy controls (P P  [ABSTRACT FROM AUTHOR]

Published data on the association between STK15 F31I polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, Web of Science, and Chinese Biomedicine Database were searched. Crude ORs with 95% CIs were used to assess the strength of association between the STK15 F31I polymorphism and breast cancer risk. The pooled ORs were performed for codominant model (FI vs. FF; II vs. FF), dominant model (FI + II vs. FF), and recessive model (II vs. FI + FF), respectively. A total of 10 studies including 10,537 cases and 14,477 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with II variant genotype in homozygote comparison and recessive genetic model when all studies were pooled into the meta-analysis (for II vs. FF: OR = 1.23, 95% CI = 1.10–1.37; for recessive model: OR = 1.21, 95% CI = 1.05–1.40). In the subgroup analysis by ethnicity, significantly increased risks were found for II allele carriers among Caucasians (for II vs. FF: OR = 1.24, 95% CI = 1.08–1.43; for recessive model: OR = 1.21, 95% CI = 1.00–1.45); significantly increased risks were also found among Asians for II versus FF (OR = 1.21; 95% CI = 1.01–1.45). In conclusion, this meta-analysis suggests that the STK15 31II allele is a low-penetrant risk factor for developing breast cancer. [ABSTRACT FROM AUTHOR]

Lessons from organophosphorus pesticides, which could be bioaccumulated in non-target organisms at different trophic levels and caused unexpected negative impacts, necessitate a study of the possibility of biotransfer and bioaccumulation of Bacillus thuringiensis (Bt) insecticidal toxin(s) expressed in Bt plants. Using ELISA, we evaluated the transfer of Cry1Ab toxin in a food chain of Bt rice (KMD1 and KMD2), the target insect, Cnaphalocrocis medinalis, and its predator, Pirata subpiraticus. Cry1Ab was detected in C. medinalis and P. subpiraticus. However, the concentration of Cry1Ab detected from C. medinalis and P. subpiraticus did not increase as feeding or preying time increased. A binding study of Cry1Ab to the brush border membrane vesicle of C. medinalis and P. subpiraticus indicated that P. subpiraticus does not have binding receptors in its midgut to Cry1Ab, while C. medinalis does. Survivorship and fecundity of P. subpiraticus preying on Bt rice-fed C. medinalis were not significantly different from those preying on non-Bt rice-fed C. medinalis. Developmental time of P. subpiraticus was significantly longer when it preyed on Bt rice-fed C. medinalis than on non-Bt rice-fed prey. However, a 3-year field trial indicated that Bt rice did not significantly affect the density of P. subpiraticus. [ABSTRACT FROM AUTHOR]

Abstract  Transgenic brassica crops producing insecticidal proteins from Bacillus thuringiensis (Bt) are being investigated as candidates for field release to control lepidopteran pests. Information on the potential impact of Bt brassica crops on pests and non-target natural enemies is needed as part of an environmental risk assessment prior to the commercial release. This first tier study provides insight into the tritrophic interactions among Bt broccoli plants, the herbivore Pieris rapae and its parasitoid Pteromalus puparum. We first evaluated the efficacy of three types of Bt broccoli plants, cry1Ac, cry1C and cry1Ac + cry1C, on different instars of P. rapae. Bt broccoli effectively controlled P. rapae larvae, although later instars were more tolerant. The efficacy of different Bt broccoli plants on P. rapae larvae was consistently cry1Ac > cry1Ac  + cry1C > cry1C. When the parasitoid P. puparum developed in a P. rapae pupa (host) that had developed from Bt plant-fed older larvae, developmental time, total number and longevity of the P. puparum generated from the Bt plant-fed host were significantly affected compared with those generated from the non-Bt control plant-fed host. Simultaneously, negative effects on P. rapae pupae were found, i.e. pupal length, width and weight were significantly reduced after older P. rapae larvae fed on different Bt plants for 1 or 2 days. Cry1C toxin was detected using ELISA in P. rapae pupae after older larvae fed on cry1C broccoli. However, no Cry1C toxin was detected in newly emerged P. puparum adults developing in Bt-fed hosts. Only a trace amount of toxin was detected from entire P. puparum pupae dissected from the Bt plant-fed host. Moreover, no negative effect was found on the progeny of P. puparum developing from the Bt plant-fed host when subsequently supplied with a healthy host, P. rapae pupae. The reduced quality of the host appears to be the only reason for the observed deleterious effects on P. puparum. Our data suggest that the effects on P. puparum developing in Bt plant-fed P. rapae are mediated by host quality rather than by direct toxicity. [ABSTRACT FROM AUTHOR]

The Hopf bifurcations of an airfoil flutter system with a cubic nonlinearity are investigated, with the flow speed as the bifurcation parameter. The center manifold theory and complex normal form method are used to obtain the bifurcation equation. Interestingly, for a certain linear pitching stiffness the Hopf bifurcation is both supercritical and subcritical. It is found, mathematically, this is caused by the fact that one coefficient in the bifurcation equation does not contain the first power of the bifurcation parameter. The solutions of the bifurcation equation are validated by the equivalent linearization method and incremental harmonic balance method. [ABSTRACT FROM AUTHOR]

To evaluate the effect of tetramethylpyrazine (TMP) injection on retinal damage induced by N-methyl- N-nitrosourea (MNU) in rats and on nuclear factorkappa B (NF-κB) family members. Female Sprague-Dawley (SD) rats were randomly divided into groups: (i), control group; (ii), model group; and (iii), TMP-injection groups, in which the rats were subdivided into 40 mg/kg, 80 mg/kg and 160 mg/kg groups. Drugs were injected ip into 47-day-old SD rats once a day. At 50 days of age, all rats in the model group and drug groups also received a single ip injection of 60 mg/kg MNU. Rats in group 1 received ip injection of physiological saline. All rats were killed at different times after MNU or physiological saline treatment. The apoptotic index of photoreceptor cells was calculated by TUNEL labeling; retinal damage was evaluated based on retinal thickness and the expression of NF-κB family members was detected by Western blot. TMP injections, in a dose-dependent manner, suppressed photoreceptor cell apoptosis and decreased its loss in the peripheral retina. As compared with the MNU-treated group, TMP injection at a dose of 160 mg/kg also time-dependently upregulated the NF-κB/p65 protein level in the nucleus and downregulated the IκBαprotein level in the cytoplasm. However, no protective effect of TMP injection on MNU-induced central retinal damage was found. TMP injection partially protects against MNU-induced retinal damage by upregulating the nuclear translocation of p65 to inhibit photoreceptor cells apoptosis. [ABSTRACT FROM AUTHOR]