Reduction in orofacial clefts following folic acid fortification of the U.S. grain supply

BACKGROUND: Folic acid fortification in the United States became mandatory January 1, 1998, to reduce the occurrence of neural tube defects (NTDs). We evaluated the impact of folic acid fortification on orofacial clefts using United States birth certificate data for 45 states and the District of Columbia. METHODS: Prevalence ratios (PRs) were calculated comparing orofacial cleft prevalence among births prefortification (1/1990-12/1996) and postfortification (10/1998-12/2002), based on fortification status at conception. The JoinPoint Regression Program and exponentially weighted moving average charts (EWMA) were used to assess the timing of any statistically significant changes in prevalence. Data were stratified by maternal race/ethnicity, age, smoking, and timing of prenatal care. RESULTS: Orofacial clefts declined following folic acid fortification (PR=0.94; 95% CI: 0.92-0.96). The EWMA chart flagged a significant decrease in the fourth quarter of 1998. The JoinPoint graph had one change in slope, with a significant quarterly percent change (-0.34) between 1996 and 2002. The decline in orofacial clefts occurred in non-Hispanic Whites but not other racial/ethnic groups, nonsmokers but not women who reported smoking during pregnancy, and women who received prenatal care in the first trimester but not women who began receiving care later in pregnancy. CONCLUSION: Folic acid fortification in the United States was associated with a small decrease in orofacial cleft prevalence, with the timing of the decline consistent with the introduction of fortification. The decline is much smaller than that observed for NTDs, but nonetheless suggests an additional benefit of this public health intervention.     

Efficiency of ultrafiltration/diafiltration in removing organic and elemental process equipment related leachables from biological therapeutics

In the production of biological therapeutics such as monoclonal antibodies (mAbs), ultrafiltration and diafiltration (UF/DF) are widely regarded as effective downstream processing steps capable of removing process equipment related leachables (PERLs) introduced upstream of the UF/DF step. However, clearance data available in the literature are limited to species with low partition coefficients (log P) such as buffer ions, hydrophilic organic compounds, and some metal ions. Additional data for a wide range of PERLs including hydrophobic compounds and elemental impurities are needed to establish meaningful, comprehensive safety risk assessments. Herein, we report the results from studies investigating the clearance of seven different organic PERLs representing a wide range of characteristics (i.e., log P (−0.3 to 18)), and four model elements with different chemical properties spiked into a mAb formulation at 10 ppm and analyzed during clearance using gas chromatography–mass spectrometry (GC–MS), liquid chromatography-photodiode-array-mass spectrometry (LC-PDA-MS), and inductively coupled plasma mass spectrometry (ICP-MS). The clearance data showed ideal clearance and sieving of spiked organic PERLs with log P < 4, partial clearance of PERLs with 4 < log P < 9, and poor clearance of highly hydrophobic PERLs (log P > 9) after nine diafiltration volumes (DVs). Supplemental clearance studies on seven additional PERLs present at much lower concentration levels (0.1–1.5 ppm) in the mAb formulation upstream of UF/DF and three PERLs associated with the tangential flow filtration (TFF) equipment also demonstrated the similar correlations between log P and % clearance. For model elements, the findings suggest that UF/DF in general provides ideal clearance for elements. Evidence showed that the UF/DF process does not only help mitigate leachables risk from PERLs introduced upstream of UF/DF, but also from the TFF operation itself as all three TFF-related PERLs were effectively cleared. Overall, the UF/DF clearance presented in this work demonstrated whereas highly hydrophobic PERLs and elements that exist as charged species, particularly transition metal ions, may not be as effectively cleared and thus warrant further risk assessment; hydrophilic and some hydrophobic PERLs (log P < 4) are indeed well-cleared and thus present a lower overall safety risk.     

Effect of low-level laser therapy on experimental wounds of hard palate mucosa in mice

Under general anesthesia and sterile conditions, incision wound was induced in the hard palate mucosa of adult male mice. The wounds of groups 1 and 2 were irradiated daily with He-Ne laser at 3 and 7.5 J/cm2 for 120 and 300 s, respectively, while the incision wound of group 3 not exposed served as controls. On day 3 of injury, the laser-treated wounds contained significantly lower neutrophils than the wounds in the control group. By day 7 after injury, the laser-treated wounds contained significantly more fibroblasts and at the same time contained significantly fewer macrophages. In conclusion, an acceleration of the wound healing process of experimental wounds in the hard palate mucosa of mice at low-level laser therapy with a He-Ne laser at energy densities of 3 and 7.5 J/cm2 was observed.     

Optimizing Conditions for Rat Pancreatic Islets Isolation

Many procedures have been described for rat pancreatic islet isolation. Several factors contribute to the pancreatic islet isolation outcome. One of the main problems in islet isolation procedure is the formation of a viscouse, gellike structure during collagenase digestion which entraps the free islets and decrease islet yield after density gradient purification. This issue has not been addressed in most techniques described for rat islet isolation. We examined effect of various factors to eliminate formation of gellike material and improve the islets yields. Islet isolation was performed on 26 adult male Wistar Albino rats weighing between 280 and 350 g. We have observed that several factors affect pancreatic islet isolation. Optimum Collagenase enzyme concentration, maintaining pH range between 7.7 and 7.9 in digestion solution, incubation temperature at 38±1 °C and addition of Calcium ion decreased the formation of gellike materials and increased islet yield. Addition of Glycerol as a gelatin solvent has also been helpful in the reduction or complete elimination of gellike material. Precise optimization of rat islet isolation procedure is useful to improve the islet yield in islet transplantation studies.     

Tumor-derived exosomes: Potential biomarkers and therapeutic target in the treatment of colorectal cancer

Colorectal cancer (CRC) is the third most common cause of cancer-related death in men and women in many countries. Early detection of CRC helps to prevent the advanced stages of the disease, and may thereby improve the survival of these patients. A noninvasive test with high specificity and sensitivity is required for this. Exosomes are lipid bilayer membrane nanovesicles that are released into most body fluids and especially in the microenvironment of cancer. They carry various proteins, lipids, and nucleic materials such as DNA, RNA, messenger RNA (mRNA), and microRNA (miRNA), and may also alter the function of target cells. In this review, we aimed to describe the biogenesis, composition, function, and the role of tumor-derived exosomes in cancer progression. Moreover, their applications in tumor diagnosis and treatment are described, with a particular focus on CRC.     

Ethanethiol degradation by Ralstonia eutropha

In the present study, a pure culture of Ralstonia eutropha was used to degrade gaseous ethanethiol. Ethane thiol at various initial concentrations ranging from 115 to 320 mg/m³ was degraded almost completely within 120 ～ 168 h, while at higher concentrations up to 452 mg/m³, removal efficiency declined. It was likely that ethanethiol was used as the source of energy by R. eutropha, since no clear increase in the biomass concentration was observed. Kinetic data of ethanethiol bidegradation could be fitted using the Monod model. The kinetic parameters were q _m = 0.23 (mg ethanethiol/g biomass/h), and K _s = 1.379 (mg/L). The mineralization pathway of ethanethiol through sulphate, as the detected product, and the energy production were discussed in some detail.     

Sex Specific Incidence Rates of Type 2 Diabetes and Its Risk Factors over 9 Years of Follow-Up: Tehran Lipid and Glucose Study

Objective

To investigate the population-based incidence of type 2 diabetes and its potential risk factors in a sex-split cohort of Iranian population.

Materials and Methods

A total of 8400 non-diabetic participants, aged ≥20 years (3620 men and 4780 women) entered the study. Crude and age standardized incidence rates per 1000 person-years were calculated for whole population and each sex separately. Cox proportional hazard models were used to evaluate hazard ratios (HR) and 95% confidence intervals for all potential risk factors in both uni-variable and multivariable models.

Results

During a median follow-up of 9.5 years, 736 new cases of diabetes were identified, including 433 women and 303 men. The annual crude and age-standardized incidence rates (95% CI) of diabetes in the total population were 10.6 (9.92–11.4) and 9.94 (7.39–13.6) per 1000 person-years of follow-up and the corresponding sex specific rates were 10.2 (9.13–11.4) and 9.36 (5.84–14.92) in men and 11.0 (9.99–12.0) and 10.1 (7.24–13.9) in women, respectively. In the multivariable model, the risk for incident diabetes was significantly associated with fasting and 2 hour post challenge plasma glucose as well as family history of diabetes in both men and women. However, among women, only the contribution of wrist circumference to incident diabetes achieved statistical significance [HR: 1.16 (1.03–1.31)] with waist/height ratio being marginally significant [HR: 1.02 (0.99–1.04)]; while among men, only body mass index was a significant predictor [HR: 1.12 (1.02–1.22)]. Additionally, low education level conferred a higher risk for incident diabetes only among men [HR: 1.80 (1.23–2.36); P for interaction with sex = 0.003].

Conclusion

Overall, sex did not significantly modify the impact of risk factors associated with diabetes among Iranian adults; however, among modifiable risk factors, the independent role of lower education and general adiposity in men and central adiposity in women might require different preventive strategies.     

Organ specific optical imaging of mitochondrial redox state in a rodent model of hereditary hemorrhagic telangiectasia‐1

Hereditary Hemorrhagic Telangiectasia‐1 (HHT‐1) is a vascular disease caused by mutations in the endoglin (Eng)/CD105 gene. The objective of this study was to quantify the oxidative state of a rodent model of HHT‐1 using an optical imaging technique. We used a cryofluorescence imaging instrument to quantitatively assess tissue metabolism in this model. Mitochondrial redox ratio (FAD/NADH), FAD RR, was used as a quantitative marker of the metabolic status and was examined in the kidneys, and eyes of wild‐type and Eng +/– mice. Kidneys and eyes from wild‐type P21, 6W, and 10M old mice showed, respectively, a 9% (±2), 24% (±0.4), 15% (±1), and 23% (±4), 33% (±0.6), and 30% (±2) change in the mean FAD RR compared to Eng +/– mice at the same age. Thus, endoglin haploinsufficiency is associated with less oxidative stress in various organs and mitigation of angiogenesis. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Exosomal noncoding RNAs: key players in glioblastoma drug resistance

Molecular and Cellular Biochemistry - Glioma, as one of the most severe human malignancies, is defined as the Central Nervous System’s (CNS) tumors. Glioblastoma (GBM) in this regard, is the...