Prevention of congenital defects induced by prenatal alcohol exposure (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sheehan, Megan M.; Karunamuni, Ganga; Pedersen, Cameron J.; Gu, Shi; Doughman, Yong Qiu; Jenkins, Michael W.; Watanabe, Michiko; Rollins, Andrew M.

2017-02-01

Nearly 2 million women in the United States alone are at risk for an alcohol-exposed pregnancy, including more than 600,000 who binge drink. Even low levels of prenatal alcohol exposure (PAE) can lead to a variety of birth defects, including craniofacial and neurodevelopmental defects, as well as increased risk of miscarriages and stillbirths. Studies have also shown an interaction between drinking while pregnant and an increase in congenital heart defects (CHD), including atrioventricular septal defects and other malformations. We have previously established a quail model of PAE, modeling a single binge drinking episode in the third week of a woman's pregnancy. Using optical coherence tomography (OCT), we quantified intraventricular septum thickness, great vessel diameters, and atrioventricular valve volumes. Early-stage ethanol-exposed embryos had smaller cardiac cushions (valve precursors) and increased retrograde flow, while late-stage embryos presented with gross head/body defects, and exhibited smaller atrio-ventricular (AV) valves, interventricular septum, and aortic vessels. We previously showed that supplementation with the methyl donor betaine reduced gross defects, improved survival rates, and prevented cardiac defects. Here we show that these preventative effects are also observed with folate (another methyl donor) supplementation. Folate also appears to normalize retrograde flow levels which are elevated by ethanol exposure. Finally, preliminary findings have shown that glutathione, a crucial antioxidant, is noticeably effective at improving survival rates and minimizing gross defects in ethanol-exposed embryos. Current investigations will examine the impact of glutathione supplementation on PAE-related CHDs.

Maternal Autoimmune Disease and Birth Defects in the National Birth Defects Prevention Study

PubMed Central

Howley, Meredith M.; Browne, Marilyn L.; Van Zutphen, Alissa R.; Richardson, Sandra D.; Blossom, Sarah J.; Broussard, Cheryl S.; Carmichael, Suzan L.; Druschel, Charlotte M.

2017-01-01

Background Little is known about the association between maternal autoimmune disease or its treatment and the risk of birth defects. We examined these associations using data from the National Birth Defects Prevention Study, a multi-site, population-based, case–control study. Methods Analyses included 25,116 case and 9897 unaffected control infants with estimated delivery dates between 1997 and 2009. Information on autoimmune disease, medication use, and other pregnancy exposures was collected by means of telephone interview. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for birth defects with five or more exposed cases; crude ORs and exact 95% CIs were estimated for birth defects with three to four exposed cases. Results Autoimmune disease was reported by 373 mothers (279 case and 94 control mothers). The majority of birth defects evaluated were not associated with autoimmune disease; however, a statistically significant association between maternal autoimmune disease and encephalocele was observed (OR, 4.64; 95% CI, 1.95–11.04). Eighty-two mothers with autoimmune disease used an immune modifying/suppressing medication during pregnancy; this was associated with encephalocele (OR, 7.26; 95% CI, 1.37–24.61) and atrial septal defects (OR, 3.01; 95% CI, 1.16–7.80). Conclusion Our findings suggest maternal autoimmune disease and treatment are not associated with the majority of birth defects, but may be associated with some defects, particularly encephalocele. Given the low prevalence of individual autoimmune diseases and the rare use of specific medications, we were unable to examine associations of specific autoimmune diseases and medications with birth defects. Other studies are needed to confirm these findings. PMID:27891777

Characterizing and Targeting Replication Stress Response Defects in Breast Cancer

DTIC Science & Technology

2011-08-01

induced RSR breast cell model, in which cyclin E can be conditionally induced to trigger RSR in normal breast cells. Using this model, we demonstrated...which makes these defects effective targets for both breast cancer prevention and breast cancer treatment. This project is to use cutting-edge...defective RSR; identify drugs that target these defects; and develop RSR-defect-targeting nanoparticles for diagnostic imaging, prevention, and

Prevention of Neural Tube Defects. ARC Q&A #101-45.

ERIC Educational Resources Information Center

Arc, Arlington, TX.

This fact sheet uses a question-and-answer format to summarize issues related to the prevention of neural tube defects. Questions and answers address the following topics: what neural tube defects are and the most common types (spina bifida and anencephaly); occurrence of neural tube defects during the first month of pregnancy; the frequency of…

Risk comparison for prenatal use of analgesics and selected birth defects, National Birth Defects Prevention Study 1997-2011.

PubMed

Interrante, Julia D; Ailes, Elizabeth C; Lind, Jennifer N; Anderka, Marlene; Feldkamp, Marcia L; Werler, Martha M; Taylor, Lockwood G; Trinidad, James; Gilboa, Suzanne M; Broussard, Cheryl S

2017-10-01

To compare the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or opioids to the use of acetaminophen without NSAIDs or opioids with respect to associations with birth defects. We used data from the National Birth Defects Prevention Study (1997-2011). Exposure was self-reported maternal analgesic use from the month before through the third month of pregnancy (periconceptional). Adjusted odds ratios (aORs) were calculated to examine associations with 16 birth defects. Compared to acetaminophen, mothers reporting NSAIDs were significantly more likely to have offspring with gastroschisis, hypospadias, cleft palate, cleft lip with cleft palate, cleft lip without cleft palate, anencephaly, spina bifida, hypoplastic left heart syndrome, pulmonary valve stenosis, and tetralogy of Fallot (aOR range, 1.2-1.6). Opioids were associated with tetralogy of Fallot, perimembranous ventricular septal defect, and ventricular septal defect with atrial septal defect (aOR range, 1.8-2.3), whereas use of both opioids and NSAIDs was associated with gastroschisis, cleft palate, spina bifida, hypoplastic left heart syndrome, and pulmonary valve stenosis (aOR range, 2.0-2.9). Compared to periconceptional use of acetaminophen, selected birth defects occurred more frequently among infants of women using NSAIDs and/or opioids. However, we could not definitely determine whether these risks relate to the drugs or to indications for treatment. Published by Elsevier Inc.

Who Should Be Targeted for the Prevention of Birth Defects? A Latent Class Analysis Based on a Large, Population-Based, Cross-Sectional Study in Shaanxi Province, Western China.

PubMed

Zhu, Zhonghai; Cheng, Yue; Yang, Wenfang; Li, Danyang; Yang, Xue; Liu, Danli; Zhang, Min; Yan, Hong; Zeng, Lingxia

2016-01-01

The wide range and complex combinations of factors that cause birth defects impede the development of primary prevention strategies targeted at high-risk subpopulations. Latent class analysis (LCA) was conducted to identify mutually exclusive profiles of factors associated with birth defects among women between 15 and 49 years of age using data from a large, population-based, cross-sectional study conducted in Shaanxi Province, western China, between August and October, 2013. The odds ratios (ORs) and 95% confidence intervals (CIs) of associated factors and the latent profiles of indicators of birth defects and congenital heart defects were computed using a logistic regression model. Five discrete subpopulations of participants were identified as follows: No folic acid supplementation in the periconceptional period (reference class, 21.37%); low maternal education level + unhealthy lifestyle (class 2, 39.75%); low maternal education level + unhealthy lifestyle + disease (class 3, 23.71%); unhealthy maternal lifestyle + advanced age (class 4, 4.71%); and multi-risk factor exposure (class 5, 10.45%). Compared with the reference subgroup, the other subgroups consistently had a significantly increased risk of birth defects (ORs and 95% CIs: class 2, 1.75 and 1.21-2.54; class 3, 3.13 and 2.17-4.52; class 4, 5.02 and 3.20-7.88; and class 5, 12.25 and 8.61-17.42, respectively). For congenital heart defects, the ORs and 95% CIs were all higher, and the magnitude of OR differences ranged from 1.59 to 16.15. A comprehensive intervention strategy targeting maternal exposure to multiple risk factors is expected to show the strongest results in preventing birth defects.

Assessing congenital malformation risk from medications used in pregnancy: The contribution of NBDPS in pregnancy labeling of prescription drug products.

PubMed

Tassinari, Melissa S; Sahin, Leyla; Yao, Lynne P

2015-08-01

Obtaining human pregnancy data to inform product labeling is important for drug and biological products. Collection and analyses of safety data on their use during pregnancy is usually performed after approval. The Centers for Disease Control National Birth Defects Prevention Study has provided important data on the relationship between drug use in pregnancy and birth defects. The Pregnancy and Lactation Labeling Rule will set new and improved standards for the inclusion of information about the use of prescription drugs and biological products during pregnancy; the National Birth Defects Prevention Study, along with other data sources, will be critical for providing safety data to inform product labeling. © 2015 Wiley Periodicals, Inc.

Effects and safety of periconceptional folate supplementation for preventing birth defects

PubMed Central

Maria De-Regil, Luz; Fernández-Gaxiola, Ana C; Dowswell, Therese; Peña-Rosas, Juan Pablo

2014-01-01

Background It has been reported that neural tube defects can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes of folate supplementation for the prevention of other birth defects and maternal and infant outcomes are unclear. Objectives This review updates and expands a previous Cochrane Review assessing the effects of periconceptional supplementation with folic acid to reduce neural tube defects (NTDs). We examined whether folate supplementation before and during early pregnancy can reduce neural tube and other birth defects (including cleft palate) without causing adverse outcomes for mothers or babies. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (July 2010). Additionally, we searched the international clinical trials registry platform and contacted relevant organisations to identify ongoing and unpublished studies. Selection criteria We included all randomised or quasi-randomised trials evaluating the effect of periconceptional folate supplementation alone, or in combination with other vitamins and minerals, in women independent of age and parity. Data collection and analysis We assessed trials for methodological quality using the standard Cochrane criteria. Two authors independently assessed the trials for inclusion, one author extracted data and a second checked for accuracy. Main results Five trials involving 6105 women (1949 with a history of a pregnancy affected by a NTD and 4156 with no history of NTDs) were included. Overall, the results are consistent in showing a protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.15 to 0.52). Only one study assessed the incidence of NTDs and the effect was not statistically significant (RR 0.08, 95% CI 0.00 to 1.33) although no events were found in the group that received folic acid. Folic acid had a significant protective effect for reoccurrence (RR 0.32, 95% CI 0.17 to 0.60). There is no statistically significant evidence of any effects on prevention of cleft palate, cleft lip, congenital cardiovascular defects, miscarriages or any other birth defects. There were no included trials assessing the effects of this intervention on maternal blood folate or anaemia at term. We found no evidence of short-term side effects. Authors’ conclusions Folic acid, alone or in combination with vitamins and minerals, prevents NTDs but does not have a clear effect on other birth defects. PMID:20927767

Using Bayesian Models to Assess the Effects of Under-reporting of Cannabis Use on the Association with Birth Defects, National Birth Defects Prevention Study, 1997–2005

PubMed Central

van Gelder, Marleen M. H. J.; Rogier, A.; Donders, T.; Devine, Owen; Roeleveld, Nel; Reefhuis, Jennita

2015-01-01

Background Studies on associations between periconceptional cannabis exposure and birth defects have mainly relied on self-reported exposure. Therefore, the results may be biased due to underreporting of the exposure. The aim of this study was to quantify the potential effects of this form of exposure misclassification. Methods Using multivariable logistic regression, we re-analyzed associations between periconceptional cannabis use and 20 specific birth defects using data from the National Birth Defects Prevention Study from 1997–2005 for 13 859 case infants and 6556 control infants. For seven birth defects, we implemented four Bayesian models based on various assumptions concerning the sensitivity of self-reported cannabis use to estimate odds ratios (ORs), adjusted for confounding and underreporting of the exposure. We used information on sensitivity of self-reported cannabis use from the literature for prior assumptions. Results The results unadjusted for underreporting of the exposure showed an association between cannabis use and anencephaly (posterior OR 1.9 [95% credible interval (CRI) 1.1, 3.2]) which persisted after adjustment for potential exposure misclassification. Initially, no statistically significant associations were observed between cannabis use and the other birth defect categories studied. Although adjustment for underreporting did not notably change these effect estimates, cannabis use was associated with esophageal atresia (posterior OR 1.7 [95% CRI 1.0, 2.9]), diaphragmatic hernia (posterior OR 1.8 [95% CRI 1.1, 3.0]) and gastroschisis (posterior OR 1.7 [95% CRI 1.2, 2.3]) after correction for exposure misclassification. Conclusions Underreporting of the exposure may have obscured some cannabis-birth defect associations in previous studies. However, the resulting bias is likely to be limited. PMID:25155701

Using bayesian models to assess the effects of under-reporting of cannabis use on the association with birth defects, national birth defects prevention study, 1997-2005.

PubMed

van Gelder, Marleen M H J; Donders, A Rogier T; Devine, Owen; Roeleveld, Nel; Reefhuis, Jennita

2014-09-01

Studies on associations between periconceptional cannabis exposure and birth defects have mainly relied on self-reported exposure. Therefore, the results may be biased due to under-reporting of the exposure. The aim of this study was to quantify the potential effects of this form of exposure misclassification. Using multivariable logistic regression, we re-analysed associations between periconceptional cannabis use and 20 specific birth defects using data from the National Birth Defects Prevention Study from 1997-2005 for 13 859 case infants and 6556 control infants. For seven birth defects, we implemented four Bayesian models based on various assumptions concerning the sensitivity of self-reported cannabis use to estimate odds ratios (ORs), adjusted for confounding and under-reporting of the exposure. We used information on sensitivity of self-reported cannabis use from the literature for prior assumptions. The results unadjusted for under-reporting of the exposure showed an association between cannabis use and anencephaly (posterior OR 1.9 [95% credible interval (CRI) 1.1, 3.2]) which persisted after adjustment for potential exposure misclassification. Initially, no statistically significant associations were observed between cannabis use and the other birth defect categories studied. Although adjustment for under-reporting did not notably change these effect estimates, cannabis use was associated with esophageal atresia (posterior OR 1.7 [95% CRI 1.0, 2.9]), diaphragmatic hernia (posterior OR 1.8 [95% CRI 1.1, 3.0]), and gastroschisis (posterior OR 1.7 [95% CRI 1.2, 2.3]) after correction for exposure misclassification. Under-reporting of the exposure may have obscured some cannabis-birth defect associations in previous studies. However, the resulting bias is likely to be limited. © 2014 John Wiley & Sons Ltd.

Associations between Maternal Water Consumption and Birth Defects in the National Birth Defects Prevention Study (2000-2005).

PubMed

Alman, Breanna L; Coffman, Evan; Siega-Riz, Anna Maria; Luben, Thomas J

2017-02-15

Water and water-based beverages constitute a major part of daily fluid intake for pregnant women, yet few epidemiologic studies have investigated the role of water consumption on birth outcomes. We used data from the National Birth Defects Prevention Study to conduct a case-control study investigating associations between maternal water consumption during pregnancy and birth defects (BD). We used interview data on water consumption during the first trimester of pregnancy in 14,454 cases (major BDs n ≥ 50) and 5,063 controls. Total water consumption was analyzed as a continuous variable and in quartiles. We evaluated the role of dietary quality and sugar sweetened beverage consumption. Logistic regression models were used to assess effects of water consumption on risk of BDs with adjustment for relevant covariates. Mean daily maternal water consumption among controls was 4.4 eight-ounce glasses. We observed decreases in estimated risk associated with increases in water consumption for several BDs, including neural tube defects (spina bifida), oral clefts (cleft lip), musculoskeletal defects (gastroschisis, limb deficiencies), and congenital heart defects (hypoplastic left heart syndrome, right-sided obstructions, pulmonary valve stenosis). Our results were generally unchanged when an indicator for overall dietary quality was included; however, there was evidence of effect measure modification by heavy consumption of sugar-sweetened beverages for some defects, but not all. These analyses suggest the importance of sufficient water consumption during early pregnancy, above and beyond it being a marker of higher diet quality. Additional analyses are warranted to understand the biological mechanism for this association. Birth Defects Research 109:193-202, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Inositol for prevention of neural tube defects: a pilot randomised controlled trial - CORRIGENDUM

PubMed Central

Greene, Nicholas D. E.; Leung, Kit-Yi; Gay, Victoria; Burren, Katie; Mills, Kevin; Chitty, Lyn S.; Copp, Andrew J.

2016-01-01

Although peri-conceptional folic acid (FA) supplementation can prevent a proportion of neural tube defects (NTDs), there is increasing evidence that many NTDs are FA non-responsive. The vitamin-like molecule inositol may offer a novel approach to preventing FA-non-responsive NTDs. Inositol prevented NTDs in a genetic mouse model, and was well tolerated by women in a small study of NTD recurrence. In the present study, we report the Prevention of Neural Tube Defects by Inositol (PONTI) pilot study designed to gain further experience of inositol usage in human pregnancy as a preliminary trial to a future large-scale controlled trial to evaluate efficacy of inositol in NTD prevention. Study subjects were UK women with a previous NTD pregnancy who planned to become pregnant again. Of 117 women who made contact, ninety-nine proved eligible and forty-seven agreed to be randomised (double-blind) to peri-conceptional supplementation with inositol plus FA or placebo plus FA. In total, thirty-three randomised pregnancies produced one NTD recurrence in the placebo plus FA group (n 19) and no recurrences in the inositol plus FA group (n 14). Of fifty-two women who declined randomisation, the peri-conceptional supplementation regimen and outcomes of twenty-four further pregnancies were documented. Two NTDs recurred, both in women who took only FA in their next pregnancy. No adverse pregnancy events were associated with inositol supplementation. The findings of the PONTI pilot study encourage a large-scale controlled trial of inositol for NTD prevention, but indicate the need for a careful study design in view of the unwillingness of many high-risk women to be randomised. PMID:26917444

Inositol for the prevention of neural tube defects: a pilot randomised controlled trial.

PubMed

Greene, Nicholas D E; Leung, Kit-Yi; Gay, Victoria; Burren, Katie; Mills, Kevin; Chitty, Lyn S; Copp, Andrew J

2016-03-28

Although peri-conceptional folic acid (FA) supplementation can prevent a proportion of neural tube defects (NTD), there is increasing evidence that many NTD are FA non-responsive. The vitamin-like molecule inositol may offer a novel approach to preventing FA-non-responsive NTD. Inositol prevented NTD in a genetic mouse model, and was well tolerated by women in a small study of NTD recurrence. In the present study, we report the Prevention of Neural Tube Defects by Inositol (PONTI) pilot study designed to gain further experience of inositol usage in human pregnancy as a preliminary trial to a future large-scale controlled trial to evaluate efficacy of inositol in NTD prevention. Study subjects were UK women with a previous NTD pregnancy who planned to become pregnant again. Of 117 women who made contact, ninety-nine proved eligible and forty-seven agreed to be randomised (double-blind) to peri-conceptional supplementation with inositol plus FA or placebo plus FA. In total, thirty-three randomised pregnancies produced one NTD recurrence in the placebo plus FA group (n 19) and no recurrences in the inositol plus FA group (n 14). Of fifty-two women who declined randomisation, the peri-conceptional supplementation regimen and outcomes of twenty-two further pregnancies were documented. Two NTD recurred, both in women who took only FA in their next pregnancy. No adverse pregnancy events were associated with inositol supplementation. The findings of the PONTI pilot study encourage a large-scale controlled trial of inositol for NTD prevention, but indicate the need for a careful study design in view of the unwillingness of many high-risk women to be randomised.

Association between antibiotic use among pregnant women with urinary tract infections in the first trimester and birth defects, National Birth Defects Prevention Study 1997 to 2011.

PubMed

Ailes, Elizabeth C; Gilboa, Suzanne M; Gill, Simerpal K; Broussard, Cheryl S; Crider, Krista S; Berry, Robert J; Carter, Tonia C; Hobbs, Charlotte A; Interrante, Julia D; Reefhuis, Jennita

2016-11-01

Previous studies noted associations between birth defects and some antibiotics (e.g., nitrofurantoin, sulfonamides) but not others (e.g., penicillins). It is unclear if previous findings were due to antibiotic use, infections, or chance. To control for potential confounding by indication, we examined associations between antibiotic use and birth defects, among women reporting urinary tract infections (UTIs). The National Birth Defects Prevention Study is a multi-site, population-based case-control study. Case infants/fetuses have any of over 30 major birth defects and controls are live-born infants without major birth defects. We analyzed pregnancies from 1997 to 2011 to estimate the association between maternally reported periconceptional (month before conception through the third month of pregnancy) use of nitrofurantoin, trimethoprim-sulfamethoxazole, or cephalosporins and specific birth defects, among women with periconceptional UTIs. Women with periconceptional UTIs who reported penicillin use served as the comparator. Periconceptional UTIs were reported by 7.8% (2029/26,068) of case and 6.7% (686/10,198) of control mothers. Most (68.2% of case, 66.6% of control mothers) also reported antibiotic use. Among 608 case and 231 control mothers reporting at least one periconceptional UTI and certain antibiotic use, compared with penicillin, nitrofurantoin use was associated with oral clefts in the offspring (adjusted odds ratio, 1.97 [95% confidence interval, 1.10-3.53]), trimethoprim-sulfamethoxazole use with esophageal atresia (5.31 [1.39-20.24]) and diaphragmatic hernia (5.09 [1.20-21.69]), and cephalosporin use with anorectal atresia/stenosis (5.01 [1.34-18.76]). Periconceptional exposure to some antibiotics might increase the risk for certain birth defects. However, because individual birth defects are rare, absolute risks should drive treatment decisions.Birth Defects Research (Part A) 106:940-949, 2016.© 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Thyroid Medication Use and Birth Defects in the National Birth Defects Prevention Study.

PubMed

Howley, Meredith M; Fisher, Sarah C; Van Zutphen, Alissa R; Waller, Dorothy K; Carmichael, Suzan L; Browne, Marilyn L

2017-11-01

Thyroid disorders are common among reproductive-aged women, with hypothyroidism affecting 2 to 3% of pregnancies, and hyperthyroidism affecting an additional 0.1 to 1%. We examined associations between thyroid medications and individual birth defects using data from the National Birth Defects Prevention Study (NBDPS). The NBDPS is a multisite, population-based, case-control study that included pregnancies with estimated delivery dates from 1997 to 2011. We analyzed self-reported thyroid medication use from mothers of 31,409 birth defect cases and 11,536 unaffected controls. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression for birth defects with five or more exposed cases, controlling for maternal age, race/ethnicity, and study center. Crude ORs and exact 95% CIs were estimated for defects with 3 to 4 exposed cases. Thyroid hormone was used by 738 (2.3%) case and 237 (2.1%) control mothers, and was associated with anencephaly (OR = 1.68; 95% CI, 1.03-2.73), holoprosencephaly (OR = 2.48; 95% CI, 1.13-5.44), hydrocephaly (1.77; 95% CI, 1.07-2.95) and small intestinal atresia (OR = 1.81; 95% CI, 1.04-3.15). Anti-thyroid medication was used by 34 (0.1%) case and 10 (<0.1%) control mothers, and was associated with aortic valve stenosis (OR = 6.91; 95% CI, 1.21-27.0). While new associations were identified, our findings are relatively consistent with previous NBDPS analyses. Our findings suggest thyroid medication use is not associated with most birth defects studied in the NBDPS, but may be associated with some specific birth defects. These results should not be interpreted to suggest that medications used to treat thyroid disease are teratogens, as the observed associations may reflect effects of the underlying thyroid disease. Birth Defects Research 109:1471-1481, 2017.© 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Prevention of esophageal strictures after endoscopic submucosal dissection

PubMed Central

Kobayashi, Shinichiro; Kanai, Nobuo; Ohki, Takeshi; Takagi, Ryo; Yamaguchi, Naoyuki; Isomoto, Hajime; Kasai, Yoshiyuki; Hosoi, Takahiro; Nakao, Kazuhiko; Eguchi, Susumu; Yamamoto, Masakazu; Yamato, Masayuki; Okano, Teruo

2014-01-01

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have recently been accepted as less invasive methods for treating patients with early esophageal cancers such as squamous cell carcinoma and dysplasia of Barrett’s esophagus. However, the large defects in the esophageal mucosa often cause severe esophageal strictures, which dramatically reduce the patient’s quality of life. Although preventive endoscopic balloon dilatation can reduce dysphagia and the frequency of dilatation, other approaches are necessary to prevent esophageal strictures after ESD. This review describes several strategies for preventing esophageal strictures after ESD, with a particular focus on anti-inflammatory and tissue engineering approaches. The local injection of triamcinolone acetonide and other systemic steroid therapies are frequently used to prevent esophageal strictures after ESD. Tissue engineering approaches for preventing esophageal strictures have recently been applied in basic research studies. Scaffolds with temporary stents have been applied in five cases, and this technique has been shown to be safe and is anticipated to prevent esophageal strictures. Fabricated autologous oral mucosal epithelial cell sheets to cover the defective mucosa similarly to how commercially available skin products fabricated from epidermal cells are used for skin defects or in cases of intractable ulcers. Fabricated autologous oral-mucosal-epithelial cell sheets have already been shown to be safe. PMID:25386058

Impact of sample collection participation on the validity of estimated measures of association in the National Birth Defects Prevention Study when assessing gene-environment interactions.

PubMed

Jenkins, Mary M; Reefhuis, Jennita; Herring, Amy H; Honein, Margaret A

2017-12-01

To better understand the impact that nonresponse for specimen collection has on the validity of estimates of association, we examined associations between self-reported maternal periconceptional smoking, folic acid use, or pregestational diabetes mellitus and six birth defects among families who did and did not submit buccal cell samples for DNA following a telephone interview as part of the National Birth Defects Prevention Study (NBDPS). Analyses included control families with live born infants who had no birth defects (N = 9,465), families of infants with anorectal atresia or stenosis (N = 873), limb reduction defects (N = 1,037), gastroschisis (N = 1,090), neural tube defects (N = 1,764), orofacial clefts (N = 3,836), or septal heart defects (N = 4,157). Estimated dates of delivery were between 1997 and 2009. For each exposure and birth defect, odds ratios and 95% confidence intervals were calculated using logistic regression stratified by race-ethnicity and sample collection status. Tests for interaction were applied to identify potential differences between estimated measures of association based on sample collection status. Significant differences in estimated measures of association were observed in only four of 48 analyses with sufficient sample sizes. Despite lower than desired participation rates in buccal cell sample collection, this validation provides some reassurance that the estimates obtained for sample collectors and noncollectors are comparable. These findings support the validity of observed associations in gene-environment interaction studies for the selected exposures and birth defects among NBDPS participants who submitted DNA samples. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Lack of periconceptional vitamins or supplements that contain folic acid and diabetes mellitus-associated birth defects.

PubMed

Correa, Adolfo; Gilboa, Suzanne M; Botto, Lorenzo D; Moore, Cynthia A; Hobbs, Charlotte A; Cleves, Mario A; Riehle-Colarusso, Tiffany J; Waller, D Kim; Reece, E Albert

2012-03-01

The purpose of this study was to examine the risk of birth defects in relation to diabetes mellitus and the lack of use of periconceptional vitamins or supplements that contain folic acid. The National Birth Defects Prevention Study (1997-2004) is a multicenter, population-based case-control study of birth defects (14,721 cases and 5437 control infants). Cases were categorized into 18 types of heart defects and 26 noncardiac birth defects. We estimated odds ratios for independent and joint effects of preexisting diabetes mellitus and a lack of periconceptional use of vitamins or supplements that contain folic acid. The pattern of odds ratios suggested an increased risk of defects that are associated with diabetes mellitus in the absence vs the presence of the periconceptional use of vitamins or supplements that contain folic acid. The lack of periconceptional use of vitamins or supplements that contain folic acid may be associated with an excess risk for birth defects due to diabetes mellitus. Published by Mosby, Inc.

Maternal occupational exposure to polycyclic aromatic hydrocarbons and congenital heart defects among offspring in the national birth defects prevention study.

PubMed

Lupo, Philip J; Symanski, Elaine; Langlois, Peter H; Lawson, Christina C; Malik, Sadia; Gilboa, Suzanne M; Lee, Laura J; Agopian, A J; Desrosiers, Tania A; Waters, Martha A; Romitti, Paul A; Correa, Adolfo; Shaw, Gary M; Mitchell, Laura E

2012-11-01

There is evidence in experimental model systems that exposure to polycyclic aromatic hydrocarbons (PAHs) results in congenital heart defects (CHDs); however, to our knowledge, this relationship has not been examined in humans. Therefore, we conducted a case-control study assessing the association between estimated maternal occupational exposure to PAHs and CHDs in offspring. Data on CHD cases and control infants were obtained from the National Birth Defects Prevention Study for the period of 1997 to 2002. Exposure to PAHs was assigned by industrial hygienist consensus, based on self-reported maternal occupational histories from 1 month before conception through the third month of pregnancy. Logistic regression was used to evaluate the association between maternal occupational PAH exposure and specific CHD phenotypic subtypes among offspring. The prevalence of occupational PAH exposure was 4.0% in CHD case mothers (76/1907) and 3.6% in control mothers (104/2853). After adjusting for maternal age, race or ethnicity, education, smoking, folic acid supplementation, and study center, exposure was not associated with conotruncal defects (adjusted odds ratio [AOR], 0.98; 95% confidence interval [CI], 0.58-1.67), septal defects (AOR, 1.28; 95% CI, 0.86-1.90), or with any isolated CHD subtype. Our findings do not support an association between potential maternal occupational exposure to PAHs and various CHDs in a large, population-based study. For CHD phenotypic subtypes in which modest nonsignificant associations were observed, future investigations could be improved by studying populations with a higher prevalence of PAH exposure and by incorporating information on maternal and fetal genotypes related to PAH metabolism. Birth Defects Research (Part A), 2012. Copyright © 2012 Wiley Periodicals, Inc.

[Updates on rickets and osteomalacia. dental diseases in rickets].

PubMed

Kubota, Takuo

2013-10-01

Rickets is characterized by mineralization defect in bone and cartilage. X-linked hypophosphatemic rickets (XLH) is the most common form of inherited rickets. Mineralization defect is observed in dentin as well as in bone and cartilage in XLH. The dominant feature is the occurrence of infectious periradicular abscesses on deciduous and permanent teeth, not associated with trauma or decay. Dental care including the maintenance of good oral hygiene and periodical examinations should be performed. A preventive sealing of occlusal surfaces can be considered. Endodontic treatment or extraction are carried out in the presence of periradicular abscesses. Further studies are necessary for elucidating mechanisms of dentin mineralization defect and the occurrence of periradicular abscesses and for developing preventive and curative measures in XLH.

Lack of periconceptional vitamins or supplements that contain folic acid and diabetes mellitus–associated birth defects

PubMed Central

Correa, Adolfo; Gilboa, Suzanne M.; Botto, Lorenzo D.; Moore, Cynthia A.; Hobbs, Charlotte A.; Cleves, Mario A.; Riehle-Colarusso, Tiffany J.; Waller, D. Kim; Reece, E. Albert

2016-01-01

OBJECTIVE The purpose of this study was to examine the risk of birth defects in relation to diabetes mellitus and the lack of use of periconceptional vitamins or supplements that contain folic acid. STUDY DESIGN The National Birth Defects Prevention Study (1997-2004) is a multicenter, population-based case-control study of birth defects (14,721 cases and 5437 control infants). Cases were categorized into 18 types of heart defects and 26 noncardiac birth defects. We estimated odds ratios for independent and joint effects of preexisting diabetes mellitus and a lack of periconceptional use of vitamins or supplements that contain folic acid. RESULTS The pattern of odds ratios suggested an increased risk of defects that are associated with diabetes mellitus in the absence vs the presence of the periconceptional use of vitamins or supplements that contain folic acid. CONCLUSION The lack of periconceptional use of vitamins or supplements that contain folic acid may be associated with an excess risk for birth defects due to diabetes mellitus. PMID:22284962

Facts about Birth Defects

MedlinePlus

... Defects Language: English (US) Español (Spanish) Recommend on Facebook Tweet Share Compartir On This Page Birth Defects are Common Identifying Birth Defects Causes Prevention References Birth defects are common, costly, and critical conditions that affect 1 in every 33 babies born in the ...

Maternal caffeine intake and risk of selected birth defects in the National Birth Defects Prevention Study.

PubMed

Browne, Marilyn L; Hoyt, Adrienne T; Feldkamp, Marcia L; Rasmussen, Sonja A; Marshall, Elizabeth G; Druschel, Charlotte M; Romitti, Paul A

2011-02-01

Caffeine intake is common during pregnancy, yet few epidemiologic studies have examined the association between maternal caffeine consumption and birth defects. Using data from the National Birth Defects Prevention Study (NBDPS), we examined the association between maternal caffeine consumption and anotia/microtia, esophageal atresia, small intestinal atresia, craniosynostosis, diaphragmatic hernia, omphalocele, and gastroschisis. The NBDPS is a multi-site population-based case-control study. The present analysis included 3,346 case infants and 6,642 control infants born from October 1997 through December 2005. Maternal telephone interview reports of demographic characteristics and conditions and exposures before and during pregnancy were collected. Odds ratios and 95% confidence intervals, adjusted for relevant covariates, were calculated to estimate the associations between maternal dietary caffeine intake (coffee, tea, soda, and chocolate) and maternal use of caffeine-containing medications and each defect. We observed small, statistically significant elevations in adjusted odds ratios ranging from 1.3 to 1.8 for total maternal dietary caffeine intake or specific types of caffeinated beverages and anotia/microtia, esophageal atresia, small intestinal atresia, and craniosynostosis; however, dose-response patterns were absent. Periconceptional use of caffeine-containing medications was infrequent and estimates were imprecise. We did not find convincing evidence of an association between maternal caffeine intake and the birth defects included in this study. The increasing popularity of caffeine-containing energy drinks and other caffeinated products may result in higher caffeine intake among women of childbearing age. Future studies should consider more detailed evaluation of such products. Copyright © 2010 Wiley-Liss, Inc.

Prenatal nitrate intake from drinking water and selected birth defects in offspring of participants in the national birth defects prevention study.

PubMed

Brender, Jean D; Weyer, Peter J; Romitti, Paul A; Mohanty, Binayak P; Shinde, Mayura U; Vuong, Ann M; Sharkey, Joseph R; Dwivedi, Dipankar; Horel, Scott A; Kantamneni, Jiji; Huber, John C; Zheng, Qi; Werler, Martha M; Kelley, Katherine E; Griesenbeck, John S; Zhan, F Benjamin; Langlois, Peter H; Suarez, Lucina; Canfield, Mark A

2013-09-01

Previous studies of prenatal exposure to drinking-water nitrate and birth defects in offspring have not accounted for water consumption patterns or potential interaction with nitrosatable drugs. We examined the relation between prenatal exposure to drinking-water nitrate and selected birth defects, accounting for maternal water consumption patterns and nitrosatable drug exposure. With data from the National Birth Defects Prevention Study, we linked addresses of 3,300 case mothers and 1,121 control mothers from the Iowa and Texas sites to public water supplies and respective nitrate measurements. We assigned nitrate levels for bottled water from collection of representative samples and standard laboratory testing. Daily nitrate consumption was estimated from self-reported water consumption at home and work. With the lowest tertile of nitrate intake around conception as the referent group, mothers of babies with spina bifida were 2.0 times more likely (95% CI: 1.3, 3.2) to ingest ≥ 5 mg nitrate daily from drinking water (vs. < 0.91 mg) than control mothers. During 1 month preconception through the first trimester, mothers of limb deficiency, cleft palate, and cleft lip cases were, respectively, 1.8 (95% CI: 1.1, 3.1), 1.9 (95% CI: 1.2, 3.1), and 1.8 (95% CI: 1.1, 3.1) times more likely than control mothers to ingest ≥ 5.42 mg of nitrate daily (vs. < 1.0 mg). Higher water nitrate intake did not increase associations between prenatal nitrosatable drug use and birth defects. Higher water nitrate intake was associated with several birth defects in offspring, but did not strengthen associations between nitrosatable drugs and birth defects.

Prevention of congenital defects induced by prenatal alcohol exposure (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sheehan, Megan M.; Karunamuni, Ganga; Pedersen, Cameron J.; Gu, Shi; Doughman, Yong Qiu; Jenkins, Michael W.; Watanabe, Michiko; Rollins, Andrew M.

2017-02-01

Over 500,000 women per year in the United States drink during pregnancy, and 1 in 5 of this population also binge drink. Up to 40% of live-born children with prenatal alcohol exposure (PAE) present with congenital heart defects (CHDs) including life-threatening outflow and valvuloseptal anomalies. Previously we established a PAE model in the avian embryo and used optical coherence tomography (OCT) imaging to assay looping-stage (early) cardiac function/structure and septation-stage (late) cardiac defects. Early-stage ethanol-exposed embryos had smaller cardiac cushions (valve precursors) and increased retrograde flow, while late-stage embryos presented with gross head/body defects, and exhibited smaller atrio-ventricular (AV) valves, interventricular septae, and aortic vessels. However, supplementation with the methyl donor betaine reduced gross defects, prevented cardiac defects such as ventricular septal defects and abnormal AV valves, and normalized cardiac parameters. Immunofluorescent staining for 5-methylcytosine in transverse embryo sections also revealed that DNA methylation levels were reduced by ethanol but normalized by co-administration of betaine. Furthermore, supplementation with folate, another methyl donor, in the PAE model appeared to normalize retrograde flow levels which are typically elevated by ethanol exposure. Studies are underway to correlate retrograde flow numbers for folate with associated cushion volumes. Finally, preliminary findings have revealed that glutathione, a key endogenous antioxidant which also regulates methyl group donation, is particularly effective in improving alcohol-impacted survival and gross defect rates. Current investigations will determine whether glutathione has any positive effect on PAE-related CHDs. Our studies could have significant implications for public health, especially related to prenatal nutrition recommendations.

Meeting the challenge: using policy to improve children's health.

PubMed

Brush, Charles Adam; Kelly, Maggie M; Green, Denise; Gaffney, Marcus; Kattwinkel, John; French, Molly

2005-11-01

We reflect on the proceedings of a symposium at a conference of the Centers for Disease Control and Prevention National Center on Birth Defects and Developmental Disabilities. We present examples of bridging the gap between science and policy to achieve improvements in children's health through case studies in early hearing detection and intervention, folic acid fortification to prevent birth defects, sleep positioning recommendations to reduce infant mortality, and workplace lactation support programs. We discuss case studies that present different policy strategies (public health law and voluntary practices) for improving public health. These case studies demonstrate both the power of policy as a tool for improving children's health and the challenges of communicating public health research to policy decisionmakers.

Arsenic is associated with reduced effect of folic acid in myelomeningocele prevention: a case control study in Bangladesh

USDA-ARS?s Scientific Manuscript database

Background: Arsenic induces neural tube defects in several animal models, but its potential to cause neural tube defects in humans is unknown. Our objective was to investigate the associations between maternal arsenic exposure, periconceptional folic acid supplementation, and risk of posterior neura...

Primary prevention of neural-tube defects and some other congenital abnormalities by folic acid and multivitamins: history, missed opportunity and tasks

PubMed Central

Bártfai, Zoltán; Bánhidy, Ferenc

2011-01-01

The history of intervention trials of periconception folic acid with multivitamin and folic acid supplementation in women has shown a recent breakthrough in the primary prevention of structural birth defects, namely neural-tube defects and some other congenital abnormalities. Recently, some studies have demonstrated the efficacy of this new method in reducing congenital abnormalities with specific origin; for example, in the offspring of diabetic and epileptic mothers, and in pregnancy with high fever. The benefits and drawbacks of four possible uses of periconception folate/folic acid and multivitamin supplementation are discussed: we believe there has been a missed opportunity to implement this preventive approach in medical practice. The four methods are as follows: (i) dietary intake of folate and other vitamins, (ii) periconception folic acid/multivitamin supplementation, (iii) food fortification with folic acid, and (iv) the combination of oral contraceptives with 6S-5-methytetrahydrofolate (‘folate’). PMID:25083211

Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines.

PubMed

Cordero, Amy M; Crider, Krista S; Rogers, Lisa M; Cannon, Michael J; Berry, R J

2015-04-24

Neural tube defects (NTDs) such as spina bifida, anencephaly, and encephalocele are serious birth defects of the brain and spine that occur during the first month of pregnancy when the neural tube fails to close completely. Randomized controlled trials and observational studies have shown that adequate daily consumption of folic acid before and during early pregnancy considerably reduces the risk for NTDs. The U.S. Public Health Service recommends that women capable of becoming pregnant consume 400 µg of folic acid daily for NTD prevention. Furthermore, fortification of staple foods (e.g., wheat flour) with folic acid has decreased folate-sensitive NTD prevalence in multiple settings and is a highly cost-effective intervention.

The National Birth Defects Prevention Study: a review of the methods

PubMed Central

Reefhuis, Jennita; Gilboa, Suzanne M.; Anderka, Marlene; Browne, Marilyn L.; Feldkamp, Marcia L.; Hobbs, Charlotte A.; Jenkins, Mary M.; Langlois, Peter H.; Newsome, Kimberly B.; Olshan, Andrew F.; Romitti, Paul A.; Shapira, Stuart K.; Shaw, Gary M.; Tinker, Sarah C.; Honein, Margaret A.

2015-01-01

Background The National Birth Defects Prevention Study (NBDPS) is a large population-based multi-center case-control study of major birth defects in the United States. Methods Data collection took place from 1998 through 2013 on pregnancies ending between October 1997 and December 2011. Cases could be live born, stillborn or induced terminations, and were identified from birth defects surveillance programs in Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas and Utah. Controls were live born infants without major birth defects identified from the same geographical regions and time periods as cases via either vital records or birth hospitals. Computer-assisted telephone interviews were completed with women between 6 weeks and 24 months after the estimated date of delivery. After completion of interviews, families received buccal cell collection kits for the mother, father and infant (if living). Results There were 47,832 eligible cases and 18,272 eligible controls. Among these, 32,187 (67%) and 11,814 (65%) respectively, provided interview information about their pregnancies. Buccal cell collection kits with a cytobrush for at least one family member were returned by 19,065 case and 6,211 control families (65% and 59% of those who were sent a kit). More than 500 projects have been proposed by the collaborators and over 200 manuscripts published using data from the NBDPS through December 2014. Conclusion The NBDPS has made substantial contributions to the field of birth defects epidemiology through its rigorous design, including case classification, detailed questionnaire and specimen collection, large study population, and collaborative activities across Centers. PMID:26033852

The National Birth Defects Prevention Study: A review of the methods.

PubMed

Reefhuis, Jennita; Gilboa, Suzanne M; Anderka, Marlene; Browne, Marilyn L; Feldkamp, Marcia L; Hobbs, Charlotte A; Jenkins, Mary M; Langlois, Peter H; Newsome, Kimberly B; Olshan, Andrew F; Romitti, Paul A; Shapira, Stuart K; Shaw, Gary M; Tinker, Sarah C; Honein, Margaret A

2015-08-01

The National Birth Defects Prevention Study (NBDPS) is a large population-based multicenter case-control study of major birth defects in the United States. Data collection took place from 1998 through 2013 on pregnancies ending between October 1997 and December 2011. Cases could be live born, stillborn, or induced terminations, and were identified from birth defects surveillance programs in Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas, and Utah. Controls were live born infants without major birth defects identified from the same geographical regions and time periods as cases by means of either vital records or birth hospitals. Computer-assisted telephone interviews were completed with women between 6 weeks and 24 months after the estimated date of delivery. After completion of interviews, families received buccal cell collection kits for the mother, father, and infant (if living). There were 47,832 eligible cases and 18,272 eligible controls. Among these, 32,187 (67%) and 11,814 (65%), respectively, provided interview information about their pregnancies. Buccal cell collection kits with a cytobrush for at least one family member were returned by 19,065 case and 6,211 control families (65% and 59% of those who were sent a kit). More than 500 projects have been proposed by the collaborators and over 200 manuscripts published using data from the NBDPS through December 2014. The NBDPS has made substantial contributions to the field of birth defects epidemiology through its rigorous design, including case classification, detailed questionnaire and specimen collection, large study population, and collaborative activities across Centers. © 2015 Wiley Periodicals, Inc.

Folic acid supplementation and the occurrence of congenital heart defects, orofacial clefts, multiple births, and miscarriage.

PubMed

Bailey, Lynn B; Berry, Robert J

2005-05-01

Key research findings relative to the question of whether maternal use of folic acid before and during pregnancy reduces the chance that offspring will be born with a congenital heart defect or an orofacial cleft are reviewed in this paper. Observational studies in general support an association between maternal use of multivitamins containing folic acid and a reduction in the occurrence of congenital heart defects and orofacial clefts. Results from one randomized controlled trial (RCT) provide the strongest evidence that multivitamins prevent congenital heart defects, but this RCT did not provide evidence that multivitamins prevent orofacial clefts. In addition, most observational and interventional studies are not designed to detect an independent effect from folic acid. Early studies suggested that periconceptional multivitamin use was associated with an increased occurrence of both miscarriages and multiple births, which has resulted in a great deal of controversy about the safety of folic acid use during pregnancy. We also review reports that were designed to answer these questions with more definitive data. When more substantial evidence about the effect of periconceptional folic acid on the occurrence of congenital heart defects and orofacial clefts is reported, we will have additional support for promoting folic acid intervention programs. All women capable of becoming pregnant should continue to consume 400 mug/d of folic acid in addition to a healthy diet as advised.

Maternal exposures in the National Birth Defects Prevention Study: time trends of selected exposures

PubMed Central

Dawson, April L.; Razzaghi, Hilda; Arth, Annelise; Canfield, Mark A.; Parker, Samantha E.; Reefhuis, Jennita

2015-01-01

Background Our objective was to describe time trends in selected pregnancy exposures in the National Birth Defects Prevention Study (NBDPS). Methods We analyzed data from the NBDPS, a multi-site case-control study of major birth defects, for mothers of live-born infants without birth defects (controls), with an expected date of delivery (EDD) from 1998 –2011. Mothers from the 10 participating centers across the United States were interviewed by phone between six weeks and two years after the EDD. We focused on maternal race/ethnicity and five maternal risk factors: obesity, use of folic acid-containing multivitamins, opioid analgesics, selective serotonin reuptake inhibitors (SSRIs), and loratadine because of their prevalence of use and some reports of associations with major birth defects. Prevalence time trends were examined using the Kendall’s τβ test statistic. Results The exposure trend analysis included 11,724 control mothers with EDDs from 1998–2011. We observed a significant increase in obesity prevalence among control mothers, as well as use of SSRIs and loratadine. We also observed an increase in periconceptional use of folic acid-containing multivitamins. Some of the time trends varied by race/ethnicity. No remarkable trend in the overall use of opioid analgesics was observed. The racial/ethnic distribution of mothers changed slightly during the study period. Conclusions Long-term, population-based case-control studies continue to be an effective way to assess exposure-birth defects associations and provide guidance to health care providers. However, investigators examining rare outcomes covering many years of data collection need to be cognizant of time trends in exposures. PMID:25884728

Maternal exposures in the National Birth Defects Prevention Study: Time trends of selected exposures.

PubMed

Dawson, April L; Razzaghi, Hilda; Arth, Annelise; Canfield, Mark A; Parker, Samantha E; Reefhuis, Jennita

2015-08-01

Our objective was to describe time trends in selected pregnancy exposures in the National Birth Defects Prevention Study (NBDPS). We analyzed data from the NBDPS, a multi-site case-control study of major birth defects, for mothers of live-born infants without birth defects (controls), with an expected date of delivery (EDD) from 1998 to 2011. Mothers from the 10 participating centers across the United States were interviewed by phone between 6 weeks and 2 years after the EDD. We focused on maternal race/ethnicity and five maternal risk factors: obesity, use of folic acid-containing multivitamins, opioid analgesics, selective serotonin reuptake inhibitors, and loratadine because of their prevalence of use and some reports of associations with major birth defects. Prevalence time trends were examined using the Kendall's τβ test statistic. The exposure trend analysis included 11,724 control mothers with EDDs from 1998 to 2011. We observed a significant increase in obesity prevalence among control mothers, as well as use of selective serotonin reuptake inhibitors and loratadine. We also observed an increase in periconceptional use of folic acid-containing multivitamins. Some of the time trends varied by race/ethnicity. No remarkable trend in the overall use of opioid analgesics was observed. The racial/ethnic distribution of mothers changed slightly during the study period. Long-term, population-based case-control studies continue to be an effective way to assess exposure-birth defects associations and provide guidance to health care providers. However, investigators examining rare outcomes covering many years of data collection need to be cognizant of time trends in exposures. © 2015 Wiley Periodicals, Inc.

Birth Defects. Matrix No. 2.

ERIC Educational Resources Information Center

Brent, Robert L.

This report discusses the magnitude of the problem of birth defects, outlines advances in the birth defects field in the past decade, and identifies those areas where research is needed for the prevention, treatment, and management of birth defects. The problem of birth defects has consumed a greater portion of our health care resources because of…

Supplement use and other characteristics among pregnant women with a previous pregnancy affected by a neural tube defect - United States, 1997-2009.

PubMed

Arth, Annelise; Tinker, Sarah; Moore, Cynthia; Canfield, Mark; Agopian, Aj; Reefhuis, Jennita

2015-01-16

Neural tube defects (NTDs) include anomalies of the brain (anencephaly and encephalocele) and spine (spina bifida). Even with ongoing mandatory folic acid fortification of enriched cereal grain products, the U.S. Preventive Services Task Force recommends that women of childbearing potential consume a daily supplement containing 400 µg-800 µg of folic acid. Women with a prior NTD-affected pregnancy have an increased risk for having another NTD-affected pregnancy, and if they are planning another pregnancy, the recommendation is that they consume high-dosage folic acid supplements (4.0 mg/day) beginning ≥4 weeks before conception and continuing through the first 12 weeks of pregnancy. To learn whether folic acid supplementation (from multivitamins or single- ingredient supplements) was commonly used during pregnancy by women with a previous NTD-affected pregnancy, supplement use was assessed among a convenience sample of women with a previous NTD-affected pregnancy who participated in the National Birth Defects Prevention Study (NBDPS), a case-control study of major birth defects in the United States. Characteristics of women who previously had an NTD-affected pregnancy and whose index pregnancy (pregnancy included in NBDPS) was either affected by an NTD (N = 17) (i.e., recurrence-cases) or resulted in a live-born infant without a major birth defect (N = 10) (i.e., recurrence-controls) were assessed. Taking a supplement that included folic acid was more common among recurrence-control mothers (80%) than recurrence-case mothers (35%). The recommendation that women should take folic acid supplements just before and during early pregnancy is not being followed by many women and offers an opportunity for NTD prevention, especially among women who are at a higher risk because they have had a previous pregnancy affected by an NTD.

Data linkage between the National Birth Defects Prevention Study and the Occupational Information Network (O*NET) to assess workplace physical activity, sedentary behaviors, and emotional stressors during pregnancy.

PubMed

Lee, Laura J; Symanski, Elaine; Lupo, Philip J; Tinker, Sarah C; Razzaghi, Hilda; Pompeii, Lisa A; Hoyt, Adrienne T; Canfield, Mark A; Chan, Wenyaw

2016-02-01

Knowledge of the prevalence of work-related physical activities, sedentary behaviors, and emotional stressors among pregnant women is limited, and the extent to which these exposures vary by maternal characteristics remains unclear. Data on mothers of 6,817 infants without major birth defects, with estimated delivery during 1997 through 2009 who worked during pregnancy were obtained from the National Birth Defects Prevention Study. Information on multiple domains of occupational exposures was gathered by linking mother's primary job to the Occupational Information Network Version 9.0. The most frequent estimated physical activity associated with jobs during pregnancy was standing. Of 6,337 mothers, 31.0% reported jobs associated with standing for ≥75% of their time. There was significant variability in estimated occupational exposures by maternal age, race/ethnicity, and educational level. Our findings augment existing literature on occupational physical activities, sedentary behaviors, emotional stressors, and occupational health disparities during pregnancy. © 2015 Wiley Periodicals, Inc.

Transient inhibition of the ERK pathway prevents cerebellar developmental defects and improves long-term motor functions in murine models of neurofibromatosis type 1.

PubMed

Kim, Edward; Wang, Yuan; Kim, Sun-Jung; Bornhorst, Miriam; Jecrois, Emmanuelle S; Anthony, Todd E; Wang, Chenran; Li, Yi E; Guan, Jun-Lin; Murphy, Geoffrey G; Zhu, Yuan

2014-12-23

Individuals with neurofibromatosis type 1 (NF1) frequently exhibit cognitive and motor impairments and characteristics of autism. The cerebellum plays a critical role in motor control, cognition, and social interaction, suggesting that cerebellar defects likely contribute to NF1-associated neurodevelopmental disorders. Here we show that Nf1 inactivation during early, but not late stages of cerebellar development, disrupts neuronal lamination, which is partially caused by overproduction of glia and subsequent disruption of the Bergmann glia (BG) scaffold. Specific Nf1 inactivation in glutamatergic neuronal precursors causes premature differentiation of granule cell (GC) precursors and ectopic production of unipolar brush cells (UBCs), indirectly disrupting neuronal migration. Transient MEK inhibition during a neonatal window prevents cerebellar developmental defects and improves long-term motor performance of Nf1-deficient mice. This study reveals essential roles of Nf1 in GC/UBC migration by generating correct numbers of glia and controlling GC/UBC fate-specification/differentiation, identifying a therapeutic prevention strategy for multiple NF1-associcated developmental abnormalities.

A somatic T15091C mutation in the Cytb gene of mouse mitochondrial DNA dominantly induces respiration defects.

PubMed

Hayashi, Chisato; Takibuchi, Gaku; Shimizu, Akinori; Mito, Takayuki; Ishikawa, Kaori; Nakada, Kazuto; Hayashi, Jun-Ichi

2015-08-07

Our previous studies provided evidence that mammalian mitochondrial DNA (mtDNA) mutations that cause mitochondrial respiration defects behave in a recessive manner, because the induction of respiration defects could be prevented with the help of a small proportion (10%-20%) of mtDNA without the mutations. However, subsequent studies found the induction of respiration defects by the accelerated accumulation of a small proportion of mtDNA with various somatic mutations, indicating the presence of mtDNA mutations that behave in a dominant manner. Here, to provide the evidence for the presence of dominant mutations in mtDNA, we used mouse lung carcinoma P29 cells and examined whether some mtDNA molecules possess somatic mutations that dominantly induce respiration defects. Cloning and sequence analysis of 40-48 mtDNA molecules from P29 cells was carried out to screen for somatic mutations in protein-coding genes, because mutations in these genes could dominantly regulate respiration defects by formation of abnormal polypeptides. We found 108 missense mutations existing in one or more of 40-48 mtDNA molecules. Of these missense mutations, a T15091C mutation in the Cytb gene was expected to be pathogenic due to the presence of its orthologous mutation in mtDNA from a patient with cardiomyopathy. After isolation of many subclones from parental P29 cells, we obtained subclones with various proportions of T15091C mtDNA, and showed that the respiration defects were induced in a subclone with only 49% T15091C mtDNA. Because the induction of respiration defects could not be prevented with the help of the remaining 51% mtDNA without the T15091C mutation, the results indicate that the T15091C mutation in mtDNA dominantly induced the respiration defects. Copyright © 2015 Elsevier Inc. All rights reserved.

Maternal occupational pesticide exposure and risk of congenital heart defects in the National Birth Defects Prevention Study.

PubMed

Rocheleau, Carissa M; Bertke, Stephen J; Lawson, Christina C; Romitti, Paul A; Sanderson, Wayne T; Malik, Sadia; Lupo, Philip J; Desrosiers, Tania A; Bell, Erin; Druschel, Charlotte; Correa, Adolfo; Reefhuis, Jennita

2015-10-01

Congenital heart defects (CHDs) are common birth defects, affecting approximately 1% of live births. Pesticide exposure has been suggested as an etiologic factor for CHDs, but previous results were inconsistent. We examined maternal occupational exposure to fungicides, insecticides, and herbicides for 3328 infants with CHDs and 2988 unaffected control infants of employed mothers using data for 1997 through 2002 births from the National Birth Defects Prevention Study, a population-based multisite case-control study. Potential pesticide exposure from 1 month before conception through the first trimester of pregnancy was assigned by an expert-guided task-exposure matrix and job history details self-reported by mothers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Maternal occupational exposure to pesticides was not associated with CHDs overall. In examining specific CHD subtypes compared with controls, some novel associations were observed with higher estimated pesticide exposure: insecticides only and secundum atrial septal defect (OR = 1.8; 95% CI, 1.3-2.7, 40 exposed cases); both insecticides and herbicides and hypoplastic left heart syndrome (OR = 5.1; 95% CI, 1.7-15.3, 4 exposed cases), as well as pulmonary valve stenosis (OR = 3.6; 95% CI, 1.3-10.1, 5 exposed cases); and insecticides, herbicides, and fungicides and tetralogy of Fallot (TOF) (OR = 2.2; 95% CI, 1.2-4.0, 13 exposed cases). Broad pesticide exposure categories were not associated with CHDs overall, but examining specific CHD subtypes revealed some increased odds ratios. These results highlight the importance of examining specific CHDs separately. Because of multiple comparisons, additional work is needed to verify these associations. © 2014 Wiley Periodicals, Inc.

Integration of DNA sample collection into a multi-site birth defects case-control study.

PubMed

Rasmussen, Sonja A; Lammer, Edward J; Shaw, Gary M; Finnell, Richard H; McGehee, Robert E; Gallagher, Margaret; Romitti, Paul A; Murray, Jeffrey C

2002-10-01

Advances in quantitative analysis and molecular genotyping have provided unprecedented opportunities to add biological sampling and genetic information to epidemiologic studies. The purpose of this article is to describe the incorporation of DNA sample collection into the National Birth Defects Prevention Study (NBDPS), an ongoing case-control study in an eight-state consortium with a primary goal to identify risk factors for birth defects. Babies with birth defects are identified through birth defects surveillance systems in the eight participating centers. Cases are infants with one or more of over 30 major birth defects. Controls are infants without defects from the same geographic area. Epidemiologic information is collected through an hour-long interview with mothers of both cases and controls. We added the collection of buccal cytobrush DNA samples for case-infants, control-infants, and their parents to this study. We describe here the methods by which the samples have been collected and processed, establishment of a centralized resource for DNA banking, and quality control, database management, access, informed consent, and confidentiality issues. Biological sampling and genetic analyses are important components to epidemiologic studies of birth defects aimed at identifying risk factors. The DNA specimens collected in this study can be used for detection of mutations, study of polymorphic variants that confer differential susceptibility to teratogens, and examination of interactions among genetic risk factors. Information on the methods used and issues faced by the NBDPS may be of value to others considering the addition of DNA sampling to epidemiologic studies.

Comparing Methods for Maintaining the Safety of a Child with Pica.

ERIC Educational Resources Information Center

LeBlanc, Linda A.; Piazza, Cathleen C.; Krug, Mary A.

1997-01-01

A study of 4-year-old girl with severe intellectual disabilities, congenital heart defects, and pulmonary disease investigated the effectiveness of restraint and no-restraint methods to prevent pica. Both methods prevented pica, however, the no restraint condition required less therapist effort and had less negative impact on quality of life.…

Pediatricians' Knowledge, Training, and Experience in the Care of Children with Fetal Alcohol Syndrome

ERIC Educational Resources Information Center

Gahagan, Sheila; Sharpe, Tanya Telfair; Brimacombe, Michael; Fry-Johnson, Yvonne; Levine, Robert; Mengel, Mark; O'Connor, Mary; Paley, Blair; Adubato, Susan; Brenneman, George

2007-01-01

Objectives: Prenatal exposure to alcohol interferes with fetal development and is the leading preventable cause of birth defects and developmental disabilities. The purpose of this study was to identify current knowledge, diagnosis, prevention, and intervention practices related to fetal alcohol syndrome and related conditions by members of the…

T Cells Prevent Hemorrhagic Transformation in Ischemic Stroke by P-Selectin Binding.

PubMed

Salas-Perdomo, Angélica; Miró-Mur, Francesc; Urra, Xabier; Justicia, Carles; Gallizioli, Mattia; Zhao, Yashu; Brait, Vanessa H; Laredo, Carlos; Tudela, Raúl; Hidalgo, Andrés; Chamorro, Ángel; Planas, Anna M

2018-06-14

Hemorrhagic transformation is a serious complication of ischemic stroke after recanalization therapies. This study aims to identify mechanisms underlying hemorrhagic transformation after cerebral ischemia/reperfusion. We used wild-type mice and Selplg -/- and Fut7 -/- mice defective in P-selectin binding and lymphopenic Rag2 -/- mice. We induced 30-minute or 45-minute ischemia by intraluminal occlusion of the middle cerebral artery and assessed hemorrhagic transformation at 48 hours with a hemorrhage grading score, histological means, brain hemoglobin content, or magnetic resonance imaging. We depleted platelets and adoptively transferred T cells of the different genotypes to lymphopenic mice. Interactions of T cells with platelets in blood were studied by flow cytometry and image stream technology. We show that platelet depletion increased the bleeding risk only after large infarcts. Lymphopenia predisposed to hemorrhagic transformation after severe stroke, and adoptive transfer of T cells prevented hemorrhagic transformation in lymphopenic mice. CD4 + memory T cells were the subset of T cells binding P-selectin and platelets through functional P-selectin glycoprotein ligand-1. Mice defective in P-selectin binding had a higher hemorrhagic score than wild-type mice. Adoptive transfer of T cells defective in P-selectin binding into lymphopenic mice did not prevent hemorrhagic transformation. The study identifies lymphopenia as a previously unrecognized risk factor for secondary hemorrhagic transformation in mice after severe ischemic stroke. T cells prevent hemorrhagic transformation by their capacity to bind platelets through P-selectin. The results highlight the role of T cells in bridging immunity and hemostasis in ischemic stroke. © 2018 American Heart Association, Inc.

Analysis of Selected Maternal Exposures and Non-Syndromic Atrioventricular Septal Defects in the National Birth Defects Prevention Study, 1997–2005

PubMed Central

Patel, Sonali S.; Burns, Trudy L.; Botto, Lorenzo D.; Riehle-Colarusso, Tiffany J.; Lin, Angela E.; Shaw, Gary M.; Romitti, Paul A.

2015-01-01

Although the descriptive epidemiology of atrioventricular septal defects (AVSDs), a group of serious congenital heart defects (CHDs), has been recently reported, non-genetic risk factors have not been consistently identified. Using data (1997–2005) from the National Birth Defects Prevention Study, an ongoing multisite population-based case–control study, the association between selected non-genetic factors and non-syndromic AVSDs was examined. Data on periconceptional exposures to such factors were collected by telephone interview from 187 mothers of AVSD case infants and 6,703 mothers of unaffected infants. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated from logistic regression models. Mothers who reported cigarette smoking during the periconceptional period were more likely to have infants with AVSDs compared with non-smokers, independent of maternal age, periconceptional alcohol consumption, infant gestational age, family history of CHDs, and study site (aOR 1.5, 95% CI 1.1–2.4). The association was strongest in mothers who smoked more than 25 cigarettes/day. In addition, mothers with periconceptional passive smoke exposure were more likely to have infants with AVSDs than unexposed mothers, independent of maternal age, active periconceptional smoking, infant gestational age, and family history of CHDs (aOR 1.4, 95% CI 1.0–2.0). No associations were observed between AVSDs and maternal history of a urinary tract infection or pelvic inflammatory disease, maternal use of a wide variety of medications, maternal occupational exposure, parental drug use, or maternal alcohol consumption. If the results of this preliminary study can be replicated, minimizing maternal active and passive smoke exposure may decrease the incidence of AVSDs. PMID:22903798

Complex cardiac defects after ethanol exposure during discrete cardiogenic events in zebrafish: Prevention with folic acid

PubMed Central

Sarmah, Swapnalee; Marrs, James A.

2014-01-01

BACKGROUND Fetal alcohol spectrum disorder (FASD) describes a range of birth defects including various congenital heart defects (CHDs). Mechanisms of FASD-associated CHDs are not understood. Whether alcohol interferes with a single critical event or with multiple events in heart formation is not known. RESULTS Our zebrafish embryo experiments showed that ethanol interrupts different cardiac regulatory networks and perturbed multiple steps of cardiogenesis (specification, myocardial migration, looping, chamber morphogenesis and endocardial cushion formation). Ethanol exposure during gastrulation until cardiac specification or during myocardial midline migration did not produce severe or persistent heart development defects. However, exposure comprising gastrulation until myocardial precursor midline fusion or during heart patterning stages produced aberrant heart looping and defective endocardial cushions. Continuous exposure during entire cardiogenesis produced complex cardiac defects leading to severely defective myocardium, endocardium, and endocardial cushions. Supplementation of retinoic acid with ethanol partially rescued early heart developmental defects, but the endocardial cushions did not form correctly. In contrast, supplementation of folic acid rescued normal heart development, including the endocardial cushions. CONCLUSIONS Our results indicate that ethanol exposure interrupted divergent cardiac morphogenesis events causing heart defects. Folic acid supplementation was effective in preventing a wide spectrum of ethanol-induced heart developmental defects. PMID:23832875

Assessing bottled water nitrate concentrations to evaluate total drinking water nitrate exposure and risk of birth defects.

PubMed

Weyer, Peter J; Brender, Jean D; Romitti, Paul A; Kantamneni, Jiji R; Crawford, David; Sharkey, Joseph R; Shinde, Mayura; Horel, Scott A; Vuong, Ann M; Langlois, Peter H

2014-12-01

Previous epidemiologic studies of maternal exposure to drinking water nitrate did not account for bottled water consumption. The objective of this National Birth Defects Prevention Study (NBDPS) (USA) analysis was to assess the impact of bottled water use on the relation between maternal exposure to drinking water nitrate and selected birth defects in infants born during 1997-2005. Prenatal residences of 1,410 mothers reporting exclusive bottled water use were geocoded and mapped; 326 bottled water samples were collected and analyzed using Environmental Protection Agency Method 300.0. Median bottled water nitrate concentrations were assigned by community; mothers' overall intake of nitrate in mg/day from drinking water was calculated. Odds ratios for neural tube defects, limb deficiencies, oral cleft defects, and heart defects were estimated using mixed-effects models for logistic regression. Odds ratios (95% CIs) for the highest exposure group in offspring of mothers reporting exclusive use of bottled water were: neural tube defects [1.42 (0.51, 3.99)], limb deficiencies [1.86 (0.51, 6.80)], oral clefts [1.43 (0.61, 3.31)], and heart defects [2.13, (0.87, 5.17)]. Bottled water nitrate had no appreciable impact on risk for birth defects in the NBDPS.

Assessing bottled water nitrate concentrations to evaluate total drinking water nitrate exposure and risk of birth defects

PubMed Central

Weyer, Peter J.; Brender, Jean D.; Romitti, Paul A.; Kantamneni, Jiji R.; Crawford, David; Sharkey, Joseph R.; Shinde, Mayura; Horel, Scott A.; Vuong, Ann M.; Langlois, Peter H.

2016-01-01

Previous epidemiologic studies of maternal exposure to drinking water nitrate did not account for bottled water consumption. The objective of this National Birth Defects Prevention Study (NBDPS) (USA) analysis was to assess the impact of bottled water use on the relation between maternal exposure to drinking water nitrate and selected birth defects in infants born during 1997–2005. Prenatal residences of 1,410 mothers reporting exclusive bottled water use were geocoded and mapped; 326 bottled water samples were collected and analyzed using Environmental Protection Agency Method 300.0. Median bottled water nitrate concentrations were assigned by community; mothers’ overall intake of nitrate in mg/day from drinking water was calculated. Odds ratios for neural tube defects, limb deficiencies, oral cleft defects, and heart defects were estimated using mixed-effects models for logistic regression. Odds ratios (95% CIs) for the highest exposure group in offspring of mothers reporting exclusive use of bottled water were: neural tube defects [1.42 (0.51, 3.99)], limb deficiencies [1.86 (0.51, 6.80)], oral clefts [1.43 (0.61, 3.31)], and heart defects [2.13, (0.87, 5.17)]. Bottled water nitrate had no appreciable impact on risk for birth defects in the NBDPS. PMID:25473985

Prevention and Treatment of Esophageal Stenosis after Endoscopic Submucosal Dissection for Early Esophageal Cancer

PubMed Central

Wen, Jing; Lu, Zhongsheng; Liu, Qingsen

2014-01-01

Endoscopic submucosal dissection (ESD) for the treatment of esophageal mucosal lesions is associated with a risk of esophageal stenosis, especially for near-circumferential or circumferential esophageal mucosal defects. Here, we review historic and modern studies on the prevention and treatment of esophageal stenosis after ESD. These methods include prevention via pharmacological treatment, endoscopic autologous cell transplantation, endoscopic esophageal dilatation, and stent placement. This short review will focus on direct prevention and treatment, which may help guide the way forward. PMID:25386186

Associations between maternal periconceptional exposure to secondhand tobacco smoke and major birth defects.

PubMed

Hoyt, Adrienne T; Canfield, Mark A; Romitti, Paul A; Botto, Lorenzo D; Anderka, Marlene T; Krikov, Sergey V; Tarpey, Morgan K; Feldkamp, Marcia L

2016-11-01

While associations between secondhand smoke and a few birth defects (namely, oral clefts and neural tube defects) have been noted in the scientific literature, to our knowledge, there is no single or comprehensive source of population-based information on its associations with a range of birth defects among nonsmoking mothers. We utilized data from the National Birth Defects Prevention Study, a large population-based multisite case-control study, to examine associations between maternal reports of periconceptional exposure to secondhand smoke in the household or workplace/school and major birth defects. The multisite National Birth Defects Prevention Study is the largest case-control study of birth defects to date in the United States. We selected cases from birth defect groups having >100 total cases, as well as all nonmalformed controls (10,200), from delivery years 1997 through 2009; 44 birth defects were examined. After excluding cases and controls from multiple births and whose mothers reported active smoking or pregestational diabetes, we analyzed data on periconceptional secondhand smoke exposure-encompassing the period 1 month prior to conception through the first trimester. For the birth defect craniosynostosis, we additionally examined the effect of exposure in the second and third trimesters as well due to the potential sensitivity to teratogens for this defect throughout pregnancy. Covariates included in all final models of birth defects with ≥5 exposed mothers were study site, previous live births, time between estimated date of delivery and interview date, maternal age at estimated date of delivery, race/ethnicity, education, body mass index, nativity, household income divided by number of people supported by this income, periconceptional alcohol consumption, and folic acid supplementation. For each birth defect examined, we used logistic regression analyses to estimate both crude and adjusted odds ratios and 95% confidence intervals for both isolated and total case groups for various sources of exposure (household only; workplace/school only; household and workplace/school; household or workplace/school). The prevalence of secondhand smoke exposure only across all sources ranged from 12.9-27.8% for cases and 14.5-15.8% for controls. The adjusted odds ratios for any vs no secondhand smoke exposure in the household or workplace/school and isolated birth defects were significantly elevated for neural tube defects (anencephaly: adjusted odds ratio, 1.66; 95% confidence interval, 1.22-2.25; and spina bifida: adjusted odds ratio, 1.49; 95% confidence interval, 1.20-1.86); orofacial clefts (cleft lip without cleft palate: adjusted odds ratio, 1.41; 95% confidence interval, 1.10-1.81; cleft lip with or without cleft palate: adjusted odds ratio, 1.24; 95% confidence interval, 1.05-1.46; cleft palate alone: adjusted odds ratio, 1.31; 95% confidence interval, 1.06-1.63); bilateral renal agenesis (adjusted odds ratio, 1.99; 95% confidence interval, 1.05-3.75); amniotic band syndrome-limb body wall complex (adjusted odds ratio, 1.66; 95% confidence interval, 1.10-2.51); and atrial septal defects, secundum (adjusted odds ratio, 1.37; 95% confidence interval, 1.09-1.72). There were no significant inverse associations observed. Additional studies replicating the findings are needed to better understand the moderate positive associations observed between periconceptional secondhand smoke and several birth defects in this analysis. Increased odds ratios resulting from chance (eg, multiple comparisons) or recall bias cannot be ruled out. Copyright © 2016 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spencer, B. W.; Williamson, R. L.; Stafford, D. S.

One of the important roles of cladding in light water reactor fuel rods is to prevent the release of fission products. To that end, it is essential that the cladding maintain its integrity under a variety of thermal and mechanical loading conditions. Local geometric irregularities in fuel pellets caused by manufacturing defects known as missing pellet surfaces (MPS) can in some circumstances lead to elevated cladding stresses that are sufficiently high to cause cladding failure. Accurate modeling of these defects can help prevent these types of failures. The BISON nuclear fuel performance code developed at Idaho National Laboratory can bemore » used to simulate the global thermo-mechanical fuel rod behavior, as well as the local response of regions of interest, in either 2D or 3D. In either case, a full set of models to represent the thermal and mechanical properties of the fuel, cladding and plenum gas is employed. A procedure for coupling 2D full-length fuel rod models to detailed 3D models of the region of the rod containing a MPS defect is detailed in this paper. The global and local model each contain appropriate physics and behavior models for nuclear fuel. This procedure is demonstrated on a simulation of a boiling water reactor (BWR) fuel rod containing a pellet with an MPS defect, subjected to a variety of transient events, including a control blade withdrawal and a ramp to high power. The importance of modeling the local defect using a 3D model is highlighted by comparing 3D and 2D representations of the defective pellet region. Finally, parametric studies demonstrate the effects of the choice of gaseous swelling model and of the depth and geometry of the MPS defect on the response of the cladding adjacent to the defect.« less

Data Linkage Between the National Birth Defects Prevention Study and the Occupational Information Network (O*NET) to Assess Workplace Physical Activity, Sedentary Behaviors, and Emotional Stressors During Pregnancy

PubMed Central

Lee, Laura J.; Symanski, Elaine; Lupo, Philip J.; Tinker, Sarah C.; Razzaghi, Hilda; Pompeii, Lisa A.; Hoyt, Adrienne T.; Canfield, Mark A.; Chan, Wenyaw

2016-01-01

Background Knowledge of the prevalence of work-related physical activities, sedentary behaviors, and emotional stressors among pregnant women is limited, and the extent to which these exposures vary by maternal characteristics remains unclear. Methods Data on mothers of 6,817 infants without major birth defects, with estimated delivery during 1997 through 2009 who worked during pregnancy were obtained from the ‘National Birth Defects Prevention Study. Information on multiple domains of occupational exposures was gathered by linking mother’s primary job to the Occupational Information Network Version 9.0. Results The most frequent estimated physical activity associated with jobs during pregnancy was standing. Of 6,337 mothers, 31.0% reported jobs associated with standing for ≥ 75% of their time. There was significant variability in estimated occupational exposures by maternal age, race/ethnicity, and educational level. Conclusions Our findings augment existing literature on occupational physical activities, sedentary behaviors, emotional stressors, and occupational health disparities during pregnancy. PMID:26681357

Transient inhibition of the ERK pathway prevents cerebellar developmental defects and improves long-term motor functions in murine models of neurofibromatosis type 1

PubMed Central

Kim, Edward; Wang, Yuan; Kim, Sun-Jung; Bornhorst, Miriam; Jecrois, Emmanuelle S; Anthony, Todd E; Wang, Chenran; Li, Yi E; Guan, Jun-Lin; Murphy, Geoffrey G; Zhu, Yuan

2014-01-01

Individuals with neurofibromatosis type 1 (NF1) frequently exhibit cognitive and motor impairments and characteristics of autism. The cerebellum plays a critical role in motor control, cognition, and social interaction, suggesting that cerebellar defects likely contribute to NF1-associated neurodevelopmental disorders. Here we show that Nf1 inactivation during early, but not late stages of cerebellar development, disrupts neuronal lamination, which is partially caused by overproduction of glia and subsequent disruption of the Bergmann glia (BG) scaffold. Specific Nf1 inactivation in glutamatergic neuronal precursors causes premature differentiation of granule cell (GC) precursors and ectopic production of unipolar brush cells (UBCs), indirectly disrupting neuronal migration. Transient MEK inhibition during a neonatal window prevents cerebellar developmental defects and improves long-term motor performance of Nf1-deficient mice. This study reveals essential roles of Nf1 in GC/UBC migration by generating correct numbers of glia and controlling GC/UBC fate-specification/differentiation, identifying a therapeutic prevention strategy for multiple NF1-associcated developmental abnormalities. DOI: http://dx.doi.org/10.7554/eLife.05151.001 PMID:25535838

Improving the Quality of Cast Ingot for the Production of Defect-Free Rolled and Polished Blanks of Silver-Copper Coinage Alloy

NASA Astrophysics Data System (ADS)

Chakrabarti, Debalay; Chakrabarti, Ajit Kumar; Roy, Sanat Kumar

2018-05-01

The causes of defect generation in Ag-7.5 wt% Cu coinage alloy billets and in rolled and polished blanks were evaluated in this paper. Microstructural and compositional study of the as-cast billets indicated that excessive formation of gas-porosity and shrinkage cavity was responsible for crack formation during rolling. Carbon pick-up from charcoal flux cover used during melting, formation of CuS inclusions due to high-S content and rapid work-hardening also contributed to cracking during rolling. In order to prevent the defect generation, several measures were adopted. Those measures significantly reduced the defect generation and improved the surface luster of the trial rolled strips.

Risk reduction using DDP (Defect Detection and Prevention): Software support and software applications

NASA Technical Reports Server (NTRS)

Feather, M. S.

2001-01-01

Risk assessment and mitigation is the focus of the Defect Detection and Prevention (DDP) process, which has been applied to spacecraft technology assessments and planning, both hardware and software. DDP's major elements and their relevance to core requirement engineering concerns are summarized. The accompanying research demonstration illustrates DDP's tool support, and further customizations for application to software.

77 FR 6669 - Airworthiness Directives; Honeywell International Inc. TPE331-10 and TPE331-11 Series Turboprop...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-09

... failure of a first stage turbine disk that had a metallurgical defect. This AD requires inspecting certain...-1. We are issuing this AD to prevent uncontained failure of the first stage turbine disk and damage... failure of a first stage turbine disk that had a metallurgical defect. We are issuing this AD to prevent...

Estimated Maternal Pesticide Exposure from Drinking Water and Heart Defects in Offspring

PubMed Central

Kim, Jihye; Swartz, Michael D.; Langlois, Peter H.; Romitti, Paul A.; Weyer, Peter; Mitchell, Laura E.; Ramakrishnan, Anushuya; Malik, Sadia; Lupo, Philip J.; Feldkamp, Marcia L.; Meyer, Robert E.; Winston, Jennifer J.; Reefhuis, Jennita; Blossom, Sarah J.; Bell, Erin; Agopian, A. J.

2017-01-01

Our objective was to examine the relationship between estimated maternal exposure to pesticides in public drinking water and the risk of congenital heart defects (CHD). We used mixed-effects logistic regression to analyze data from 18,291 nonsyndromic cases with heart defects from the Texas Birth Defects Registry and 4414 randomly-selected controls delivered in Texas from 1999 through 2005. Water district-level pesticide exposure was estimated by linking each maternal residential address to the corresponding public water supply district’s measured atrazine levels. We repeated analyses among independent subjects from the National Birth Defects Prevention Study (NBDPS) (1620 nonsyndromic cases with heart defects and 1335 controls delivered from 1999 through 2005). No positive associations were observed between high versus low atrazine level and eight CHD subtypes or all included heart defects combined. These findings should be interpreted with caution, in light of potential misclassification and relatively large proportions of subjects with missing atrazine data. Thus, more consistent and complete monitoring and reporting of drinking water contaminants will aid in better understanding the relationships between pesticide water contaminants and birth defects. PMID:28786932

Estimated Maternal Pesticide Exposure from Drinking Water and Heart Defects in Offspring.

PubMed

Kim, Jihye; Swartz, Michael D; Langlois, Peter H; Romitti, Paul A; Weyer, Peter; Mitchell, Laura E; Luben, Thomas J; Ramakrishnan, Anushuya; Malik, Sadia; Lupo, Philip J; Feldkamp, Marcia L; Meyer, Robert E; Winston, Jennifer J; Reefhuis, Jennita; Blossom, Sarah J; Bell, Erin; Agopian, A J

2017-08-08

Our objective was to examine the relationship between estimated maternal exposure to pesticides in public drinking water and the risk of congenital heart defects (CHD). We used mixed-effects logistic regression to analyze data from 18,291 nonsyndromic cases with heart defects from the Texas Birth Defects Registry and 4414 randomly-selected controls delivered in Texas from 1999 through 2005. Water district-level pesticide exposure was estimated by linking each maternal residential address to the corresponding public water supply district's measured atrazine levels. We repeated analyses among independent subjects from the National Birth Defects Prevention Study (NBDPS) (1620 nonsyndromic cases with heart defects and 1335 controls delivered from 1999 through 2005). No positive associations were observed between high versus low atrazine level and eight CHD subtypes or all included heart defects combined. These findings should be interpreted with caution, in light of potential misclassification and relatively large proportions of subjects with missing atrazine data. Thus, more consistent and complete monitoring and reporting of drinking water contaminants will aid in better understanding the relationships between pesticide water contaminants and birth defects.

Maternal Antihypertensive Medication Use and Congenital Heart Defects: Updated Results From the National Birth Defects Prevention Study.

PubMed

Fisher, Sarah C; Van Zutphen, Alissa R; Werler, Martha M; Lin, Angela E; Romitti, Paul A; Druschel, Charlotte M; Browne, Marilyn L

2017-05-01

Previous NBDPS (National Birth Defects Prevention Study) findings from 1997 to 2003 suggested that maternal antihypertensive use was associated with congenital heart defects (CHDs). We re-examined associations between specific antihypertensive medication classes and specific CHDs with additional NBDPS data from 2004 to 2011. After excluding mothers missing hypertension information or who reported pregestational diabetes mellitus, a multiple birth, or antihypertensive use but no hypertension, we compared self-reported maternal exposure data on 10 625 CHD cases and 11 137 nonmalformed controls. We calculated adjusted odds ratios [95% confidence intervals] to estimate the risk of specific CHDs associated with antihypertensive use during the month before conception through the third month of pregnancy, controlling for maternal age, race/ethnicity, body mass index, first trimester cigarette smoking, and NBDPS site. Overall, 164 (1.5%) case mothers and 102 (0.9%) control mothers reported early pregnancy antihypertensive use for their hypertension. We observed increased risk of 4 CHD phenotypes, regardless of antihypertensive medication class reported: coarctation of the aorta (2.50 [1.52-4.11]), pulmonary valve stenosis (2.19 [1.44-3.34]), perimembranous ventricular septal defect (1.90 [1.09-3.31]), and secundum atrial septal defect (1.94 [1.36-2.79]). The associations for these phenotypes were statistically significant for mothers who reported β-blocker use or renin-angiotensin system blocker use; estimates for other antihypertensive medication classes were generally based on fewer exposed cases and were less stable but remained elevated. Our results support and expand on earlier NBDPS findings that antihypertensive medication use may be associated with increased risk of specific CHDs, although we cannot completely rule out confounding by underlying disease characteristics. © 2017 American Heart Association, Inc.

Periconceptional folic acid prevents miscarriage in Irish families with neural tube defects.

PubMed

Byrne, J

2011-03-01

Miscarriages occur to excess in sibships with neural tube defects (NTDs) and among maternal versus paternal relatives in NTD families. Folic acid prevents most NTDs. Its potential to prevent miscarriages has been controversial. We evaluated the relationship of maternal line and periconceptional folic acid with miscarriage. First cousins in Irish families with NTDs were interviewed about pregnancy outcomes and the health of their offspring. Miscarriages were not more frequent among pregnancies of maternal versus paternal first cousins. Folic acid intake during early pregnancy significantly reduced the risk of miscarriage from 15.7 to 9.6%, for an adjusted odds ratio of 0.37 (95% confidence interval 0.19, 0.72, p = 0.005). Folic acid during pregnancy was associated with a reduction of approximately 60% in miscarriages. Miscarriages are common-one in every eight pregnancies in this study. If incorporated into pre-pregnancy counseling, these results could have significant public health impact.

An exploratory analysis of the relationship between ambient ...

EPA Pesticide Factsheets

Background: Associations between ozone (O3) and fine particulate matter (PM2.5) concentrations and birth outcomes have been previously demonstrated. We perform an exploratory analysis of O3 and PM2.5 concentrations during early pregnancy and multiple types of birth defects. Methods: Data on births were obtained from the Texas Birth Defects Registry and the National Birth Defects Prevention Study (NBDPS) in Texas. Air pollution concentrations were determined using a Bayesian hierarchical model that combined modeled air pollution concentrations with air monitoring data to create bias-corrected concentrations and matched to residential address at birth. Average air pollution concentrations during the first trimester were calculated. Results: The analysis generated hypotheses for future, confirmatory studies; although many of the observed associations between the air pollutants and birth defects were null. The hypotheses are provided by an observed association between O3 and craniosynostosis [adjusted OR 1.28 (95% CI 1.04, 1.58) per 13.3 ppb increase) and observed inverse associations between PM2.5 concentrations and septal heart defects and obstructive heart defects [adjusted ORs 0.79 (95% CI 0.75, 0.82) and 0.88 (95% CI 0.79, 0.97) per 5.0 µg/m3 increase, respectively] in the Texas Birth Defects Registry study. Septal heart defects and ventricular outflow tract obstructions were also examined using the NBDPS but the associations with PM2.5 were null [adj

Inherited hypothyroidism.

PubMed

Jackson, I M

1976-03-01

Familial hypothyroidism results from both thyroidal and extrathyroidal dysfunction. Specific intrathyroidal abnormalities in thyroid hormone synthesis causing goitrous hypothyroidism are iodide trap defect, organification defect, "coupling" defect, iodoprotein defect, and dehalogenase defect. The diagnostic studies for each are outlined utilizing radioiodine(131I) studies. Other causes of cretinism include failure of the thyroid gland to respond to TSH and lack of pituitary TSH (or hypothalamic TRH). The syndrome of peripheral resistance to thyroid hormone is discussed. The diagnosis of inherited hypothyrodism rests on an adequate family history and measurement of both T4 and TSH levels which can be determined in cord blood or peripheral blood from the infant. The importance of early treatment of hypothyroidism in the neonatal period to prevent brain damage is emphasized. The rec:nt discovery of the importance of reverse T3 (RT3) in fetal thyroid metabolism is described, and the possibility of amniocentesis as an aid in prenatal diagnosis is considered. The place of intrauterine administration of thyroid hormone to the fetus at risk from hypothyroidism is uncertain at this time and requires carefully controlled studies and long-term follow-up.

Maternal diet supplementation with methyl donors and increased parity affect the incidence of craniofacial defects in the offspring of twisted gastrulation mutant mice.

PubMed

Billington, Charles J; Schmidt, Brian; Zhang, Lei; Hodges, James S; Georgieff, Michael K; Schotta, Gunnar; Gopalakrishnan, Rajaram; Petryk, Anna

2013-03-01

Diets rich in methyl-donating compounds, including folate, can provide protection against neural tube defects, but their role in preventing craniofacial defects is less clear. Mice deficient in Twisted gastrulation (TWSG1), an extracellular modulator of bone morphogenetic protein signaling, manifest both midline facial defects and jaw defects, allowing study of the effects of methyl donors on various craniofacial defects in an experimentally tractable animal model. The goal of this study was to examine the effects of maternal dietary supplementation with methyl donors on the incidence and type of craniofacial defects among Twsg1(-/-) offspring. Nulliparous and primiparous female mice were fed an NIH31 standard diet (control) or a methyl donor supplemented (MDS) diet (folate, vitamin B-12, betaine, and choline). Observed defects in the pups were divided into those derived mostly from the first branchial arch (BA1) (micrognathia, agnathia, cleft palate) and midline facial defects in the holoprosencephaly spectrum (cyclopia, proboscis, and anterior truncation). In the first pregnancy, offspring of mice fed the MDS diet had lower incidence of BA1-derived defects (12.8% in MDS vs. 32.5% in control; P = 0.02) but similar incidence of midline facial defects (6.4% in MDS vs. 5.2% in control; P = 1.0). Increased maternal parity was independently associated with increased incidence of craniofacial defects after adjusting for diet (from 37.7 to 59.5% in control, P = 0.04 and from 19.1 to 45.3% in MDS, P = 0.045). In conclusion, methyl donor supplementation shows protective effects against jaw defects, but not midline facial defects, and increased parity can be a risk factor for some craniofacial defects.

A Knowledge-Based System For Analysis, Intervention Planning and Prevention of Defects in Immovable Cultural Heritage Objects and Monuments

NASA Astrophysics Data System (ADS)

Valach, J.; Cacciotti, R.; Kuneš, P.; ČerÅanský, M.; Bláha, J.

2012-04-01

The paper presents a project aiming to develop a knowledge-based system for documentation and analysis of defects of cultural heritage objects and monuments. The MONDIS information system concentrates knowledge on damage of immovable structures due to various causes, and preventive/remedial actions performed to protect/repair them, where possible. The currently built system is to provide for understanding of causal relationships between a defect, materials, external load, and environment of built object. Foundation for the knowledge-based system will be the systemized and formalized knowledge on defects and their mitigation acquired in the process of analysis of a representative set of cases documented in the past. On the basis of design comparability, used technologies, materials and the nature of the external forces and surroundings, the developed software system has the capacity to indicate the most likely risks of new defect occurrence or the extension of the existing ones. The system will also allow for a comparison of the actual failure with similar cases documented and will propose a suitable technical intervention plan. The system will provide conservationists, administrators and owners of historical objects with a toolkit for defect documentation for their objects. Also, advanced artificial intelligence methods will offer accumulated knowledge to users and will also enable them to get oriented in relevant techniques of preventive interventions and reconstructions based on similarity with their case.

Use of Family History Information for Neural Tube Defect Prevention: Integration into State-Based Recurrence Prevention Programs

ERIC Educational Resources Information Center

Green, Ridgely Fisk; Ehrhardt, Joan; Ruttenber, Margaret F.; Olney, Richard S.

2011-01-01

A family history of neural tube defects (NTDs) can increase the risk of a pregnancy affected by an NTD. Periconceptional folic acid use decreases this risk. Purpose: Our objective was to determine whether second-degree relatives of NTD-affected children showed differences in folic acid use compared with the general population and to provide them…

Agrichemicals in surface water and birth defects in the United States

PubMed Central

Winchester, Paul D; Huskins, Jordan; Ying, Jun

2009-01-01

Objectives: To investigate if live births conceived in months when surface water agrichemicals are highest are at greater risk for birth defects. Methods: Monthly concentrations during 1996–2002 of nitrates, atrazine and other pesticides were calculated using United States Geological Survey's National Water Quality Assessment data. Monthly United States birth defect rates were calculated for live births from 1996 to 2002 using United States Centers for Disease Control and Prevention natality data sets. Birth defect rates by month of last menstrual period (LMP) were then compared to pesticide/nitrate means using logistical regression models. Results: Mean concentrations of agrichemicals were highest in April–July. Total birth defects, and eleven of 22 birth defect subcategories, were more likely to occur in live births with LMPs between April and July. A significant association was found between the season of elevated agrichemicals and birth defects. Conclusion: Elevated concentrations of agrichemicals in surface water in April–July coincided with higher risk of birth defects in live births with LMPs April–July. While a causal link between agrichemicals and birth defects cannot be proven from this study an association might provide clues to common factors shared by both variables. PMID:19183116

Research of Medication Use during Pregnancy

MedlinePlus

... Podcasts and Videos Buttons CDC’s Work Pregnancy Homepage Research Recommend on Facebook Tweet Share Compartir CDC and ... registration. Studies from the Centers for Birth Defects Research and Prevention CDC funds the Centers for Birth ...

Effect of point defects and disorder on structural phase transitions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toulouse, J.

1997-06-01

Since the beginning in 1986, the object of this project has been Structural Phase Transitions (SPT) in real as opposed to ideal materials. The first stage of the study has been centered around the role of Point Defects in SPT`s. Our intent was to use the previous knowledge we had acquired in the study of point defects in non-transforming insulators and apply it to the study of point defects in insulators undergoing phase transitions. In non-transforming insulators, point defects, in low concentrations, marginally affect the bulk properties of the host. It is nevertheless possible by resonance or relaxation methods tomore » study the point defects themselves via their local motion. In transforming solids, however, close to a phase transition, atomic motions become correlated over very large distances; there, even point defects far removed from one another can undergo correlated motions which may strongly affect the transition behavior of the host. Near a structural transition, the elastic properties win be most strongly affected so as to either raise or decrease the transition temperature, prevent the transition from taking place altogether, or simply modify its nature and the microstructure or domain structure of the resulting phase. One of the well known practical examples is calcium-stabilized zirconia in which the high temperature cubic phase is stabilized at room temperature with greatly improved mechanical properties.« less

K-RasV14I recapitulates Noonan syndrome in mice

PubMed Central

Hernández-Porras, Isabel; Fabbiano, Salvatore; Schuhmacher, Alberto J.; Aicher, Alexandra; Cañamero, Marta; Cámara, Juan Antonio; Cussó, Lorena; Desco, Manuel; Heeschen, Christopher; Mulero, Francisca; Bustelo, Xosé R.; Guerra, Carmen; Barbacid, Mariano

2014-01-01

Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, craniofacial dysmorphism, and congenital heart defects. NS also is associated with a risk for developing myeloproliferative disorders (MPD), including juvenile myelomonocytic leukemia (JMML). Mutations responsible for NS occur in at least 11 different loci including KRAS. Here we describe a mouse model for NS induced by K-RasV14I, a recurrent KRAS mutation in NS patients. K-RasV14I–mutant mice displayed multiple NS-associated developmental defects such as growth delay, craniofacial dysmorphia, cardiac defects, and hematologic abnormalities including a severe form of MPD that resembles human JMML. Homozygous animals had perinatal lethality whose penetrance varied with genetic background. Exposure of pregnant mothers to a MEK inhibitor rescued perinatal lethality and prevented craniofacial dysmorphia and cardiac defects. However, Mek inhibition was not sufficient to correct these defects when mice were treated after weaning. Interestingly, Mek inhibition did not correct the neoplastic MPD characteristic of these mutant mice, regardless of the timing at which the mice were treated, thus suggesting that MPD is driven by additional signaling pathways. These genetically engineered K-RasV14I–mutant mice offer an experimental tool for studying the molecular mechanisms underlying the clinical manifestations of NS. Perhaps more importantly, they should be useful as a preclinical model to test new therapies aimed at preventing or ameliorating those deficits associated with this syndrome. PMID:25359213

3D modeling of missing pellet surface defects in BWR fuel

DOE PAGES

Spencer, B. W.; Williamson, R. L.; Stafford, D. S.; ...

2016-07-26

One of the important roles of cladding in light water reactor fuel rods is to prevent the release of fission products. To that end, it is essential that the cladding maintain its integrity under a variety of thermal and mechanical loading conditions. Local geometric irregularities in fuel pellets caused by manufacturing defects known as missing pellet surfaces (MPS) can in some circumstances lead to elevated cladding stresses that are sufficiently high to cause cladding failure. Accurate modeling of these defects can help prevent these types of failures. The BISON nuclear fuel performance code developed at Idaho National Laboratory can bemore » used to simulate the global thermo-mechanical fuel rod behavior, as well as the local response of regions of interest, in either 2D or 3D. In either case, a full set of models to represent the thermal and mechanical properties of the fuel, cladding and plenum gas is employed. A procedure for coupling 2D full-length fuel rod models to detailed 3D models of the region of the rod containing a MPS defect is detailed in this paper. The global and local model each contain appropriate physics and behavior models for nuclear fuel. This procedure is demonstrated on a simulation of a boiling water reactor (BWR) fuel rod containing a pellet with an MPS defect, subjected to a variety of transient events, including a control blade withdrawal and a ramp to high power. The importance of modeling the local defect using a 3D model is highlighted by comparing 3D and 2D representations of the defective pellet region. Finally, parametric studies demonstrate the effects of the choice of gaseous swelling model and of the depth and geometry of the MPS defect on the response of the cladding adjacent to the defect.« less

Radiation damage and defect behavior in proton irradiated lithium-counterdoped n+p silicon solar cells

NASA Technical Reports Server (NTRS)

Stupica, John; Goradia, Chandra; Swartz, Clifford K.; Weinberg, Irving

1987-01-01

Two lithium-counterdoped n+p silicon solar cells with different lithium concentrations were irradiated by 10-MeV protons. Cell performance was measured as a function of fluence, and it was found that the cell with the highest concentration of lithium had the highest radiation resistance. Deep level transient spectroscopy which showed two deep level defects that were lithium related. Relating the defect energy levels obtained from this study with those from earlier work using 1-MeV electron irradiation shows no correlation of the defect energy levels. There is one marked similarity: the absence of the boron-interstitial-oxygen-interstitial defect. This consistency strengthens the belief that lithium interacts with oxygen to prevent the formation of the boron interstitial-oxygen interstitial defect. The results indicate that, in general, addition of lithium in small amounts to the p-base of a boron doped silicon solar cell such that the base remains p-type, tends to increase the radiation resistance of the cell.

Do Cartilage Repair Procedures Prevent Degenerative Meniscus Changes? Longitudinal T1ρ and Morphological Evaluation at 3.0T

PubMed Central

Jungmann, Pia M.; Li, Xiaojuan; Nardo, Lorenzo; Subburaj, Karupppasamy; Lin, Wilson; Ma, C. Benjamin; Majumdar, Sharmila; Link, Thomas M.

2014-01-01

Background Cartilage repair (CR) procedures are widely accepted for treatment of isolated cartilage defects at the knee joint. However, it is not well known whether these procedures prevent degenerative joint disease. Hypothesis/Purpose CR procedures prevent accelerated qualitative and quantitative progression of meniscus degeneration in individuals with focal cartilage defects. Study Design Cohort Study; Level of evidence 2b Methods A total of 94 subjects were studied. CR procedures were performed on 34 patients (n=16 osteochondral transplantation, n=18 microfracture); 34 controls were matched. An additional 13 patients received CR and anterior cruciate ligament (ACL) reconstruction (CR&ACL) and 13 patients received only ACL reconstruction. 3.0T MRI with T1ρ mapping and sagittal fat-saturated intermediate-weighted fast spin echo (FSE) sequences was performed to analyze menisci quantitatively and qualitatively (Whole-Organ Magnetic Resonance Imaging Score, WORMS). CR and CR&ACL patients were examined 4 months (n=34; n=13), 1 (n=21; n=8) and 2 (n=9; n=5) years post CR. Control subjects were scanned at baseline and after 1 and 2 years, ACL patients after 1 and 2 years. Results At baseline, global meniscus T1ρ values were higher in individuals with CR (14.2±0.6ms; P=0.004) and in individuals with CR&ACL (17.1±0.9ms; P<0.001) when compared to controls (12.8±0.6ms). After two years, there was a statistical difference between T1ρ at the overlying meniscus above cartilage defects (16.4±1.0ms) and T1ρ of the subgroup of control knees without cartilage defects (12.1±0.8ms; P<0.001) and a statistical trend to the CR group (13.3±1.0 ms; P=0.088). At baseline, 35% of subjects with CR showed morphological meniscus tears at the overlying meniscus; 10% of CR subjects showed an increase of WORMS meniscus score within the first year, none progressed in the second year. Control subjects with (without) cartilage defects showed meniscus tears in 30% (5%) at baseline; 38% (19%) increased within the first, and 15% (10%) within the second year. Conclusions This study identified more severe meniscus degeneration after CR surgery compared to controls. However, progression of T1ρ values was not observed from 1 to 2 years after surgery. These results suggest, that CR may prevent degenerative meniscus changes. PMID:23104606

NMDA Receptor Signaling Is Important for Neural Tube Formation and for Preventing Antiepileptic Drug-Induced Neural Tube Defects.

PubMed

Sequerra, Eduardo B; Goyal, Raman; Castro, Patricio A; Levin, Jacqueline B; Borodinsky, Laura N

2018-05-16

Failure of neural tube closure leads to neural tube defects (NTDs), which can have serious neurological consequences or be lethal. Use of antiepileptic drugs (AEDs) during pregnancy increases the incidence of NTDs in offspring by unknown mechanisms. Here we show that during Xenopus laevis neural tube formation, neural plate cells exhibit spontaneous calcium dynamics that are partially mediated by glutamate signaling. We demonstrate that NMDA receptors are important for the formation of the neural tube and that the loss of their function induces an increase in neural plate cell proliferation and impairs neural cell migration, which result in NTDs. We present evidence that the AED valproic acid perturbs glutamate signaling, leading to NTDs that are rescued with varied efficacy by preventing DNA synthesis, activating NMDA receptors, or recruiting the NMDA receptor target ERK1/2. These findings may prompt mechanistic identification of AEDs that do not interfere with neural tube formation. SIGNIFICANCE STATEMENT Neural tube defects are one of the most common birth defects. Clinical investigations have determined that the use of antiepileptic drugs during pregnancy increases the incidence of these defects in the offspring by unknown mechanisms. This study discovers that glutamate signaling regulates neural plate cell proliferation and oriented migration and is necessary for neural tube formation. We demonstrate that the widely used antiepileptic drug valproic acid interferes with glutamate signaling and consequently induces neural tube defects, challenging the current hypotheses arguing that they are side effects of this antiepileptic drug that cause the increased incidence of these defects. Understanding the mechanisms of neurotransmitter signaling during neural tube formation may contribute to the identification and development of antiepileptic drugs that are safer during pregnancy. Copyright © 2018 the authors 0270-6474/18/384762-12$15.00/0.

Collection, use, and protection of population-based birth defects surveillance data in the united states.

PubMed

Mai, Cara T; Law, David J; Mason, Craig A; McDowell, Bradley D; Meyer, Robert E; Musa, Debra

2007-12-01

Birth defects surveillance systems collect population-based birth defects data from multiple sources to track trends in prevalence, identify risk factors, refer affected families to services, and evaluate prevention efforts. Strong state and federal public health and legal mandates are in place to govern the collection and use of these data. Despite the prima facie appeal of "opt-in" and similar strategies to those who view data collection as a threat to privacy, the use of these strategies in lieu of population-based surveillance can severely limit the ability of public health agencies to accurately access the health status of a group within a defined geographical area. With the need for population-based data central to their mission, birth defects programs around the country take their data stewardship role seriously, recognizing both moral and legal obligations to protect the data by employing numerous safeguards. Birth defects surveillance systems are shaped by the needs of the community they are designed to serve, with the goal of preventing birth defects or alleviating the burdens associated with them. (c) 2007 Wiley-Liss, Inc.

Use of Antihistamine Medications During Early Pregnancy and Isolated Major Malformations

PubMed Central

Gilboa, Suzanne M.; Strickland, Matthew J.; Olshan, Andrew F.; Werler, Martha M.; Correa, Adolfo

2013-01-01

BACKGROUND Antihistamines are commonly used during pregnancy. There is little evidence that they have teratogenic effects, but there are knowledge gaps with respect to newer products, as well as the relationship between specific antihistamines and specific birth defects. METHODS Using the National Birth Defects Prevention Study (1997-2003), the authors examined associations between maternal use of 14 antihistamines during early pregnancy and 26 isolated major birth defects. A Bayesian analysis incorporating prior knowledge about the relationships between the antihistamines, birth defects, and measured covariates was conducted. RESULTS Of the 364 associations investigated, 24 had 95% posterior intervals excluding 1.0. All 24 associations were positive; 23 associations were of weak to moderate magnitude (posterior odds ratio [OR] < 3.0) and one was strong (OR > 6.0) but very imprecise. Of the 24 associations, 20 were with non-cardiac defects. Eight associations involved the antihistamine diphenhydramine. CONCLUSIONS The results of this study generally were consistent with no association between birth defects and antihistamine use during early pregnancy. Several of the findings might warrant further investigation, although the observed elevated associations should be interpreted in the context of the number of associations investigated and the analysis of retrospective, self-reported data. PMID:19161158

Maternal occupation and the risk of major birth defects: A follow-up analysis from the National Birth Defects Prevention Study

PubMed Central

Lin, Shao; Herdt-Losavio, Michele L.; Chapman, Bonnie R.; Munsie, Jean-Pierre; Olshan, Andrew F.; Druschel, Charlotte M.

2013-01-01

This study further examined the association between selected maternal occupations and a variety of birth defects identified from prior analysis and explored the effect of work hours and number of jobs held and potential interaction between folic acid and occupation. Data from a population-based, multi-center case-control study was used. Analyses included 45 major defects and specific sub-occupations under five occupational groups: healthcare workers, cleaners, scientists, teachers and personal service workers. Both logistic regression and Bayesian models (to minimize type-1 errors) were used, adjusted for potential confounders. Effect modification by folic acid was also assessed. More than any other occupation, nine different defects were positively associated with maids or janitors [odds ratio (OR) range: 1.72-3.99]. Positive associations were also seen between the following maternal occupations and defects in their children (OR range: 1.35-3.48): chemists/conotruncal heart and neural tube defects (NTDs), engineers/conotruncal defects, preschool teachers/cataracts and cleft lip with/without cleft palate (CL/P), entertainers/athletes/gastroschisis, and nurses/hydrocephalus and left ventricular outflow tract heart defects. Non-preschool teachers had significantly lower odds of oral clefts and gastroschisis in their offspring (OR range: 0.53-0.76). There was a suggestion that maternal folic acid use modified the effects with occupations including lowering the risk of NTDs and CL/P. No consistent patterns were found between maternal work hours or multiple jobs by occupation and the risk of birth defects. Overall, mothers working as maids, janitors, biologists, chemists, engineers, nurses, entertainers, child care workers and preschool teachers had increased risks of several malformations and non-preschool teachers had a lower risk of some defects. Maternal folic acid use reduced the odds of NTDs and CL/P among those with certain occupations. This hypothesis-generating study will provide clues for future studies with better exposure data. PMID:22695106

Risk factors for isolated biliary atresia, National Birth Defects Prevention Study, 1997-2002.

PubMed

The, Natalie S; Honein, Margaret A; Caton, Alissa R; Moore, Cynthia A; Siega-Riz, Anna Maria; Druschel, Charlotte M

2007-10-01

Biliary atresia is a rare birth defect that affects 1 in 12,000 to 1 in 19,500 live births. We used data from the National Birth Defects Prevention Study, a multistate case-control study, to identify potential risk factors for isolated biliary atresia (no additional unrelated major birth defects diagnosed). Infants were identified from eight states from 1997 to 2002, with clinical information abstracted from medical records. Potential risk factors assessed include: demographic factors, seasonality, preterm birth, maternal smoking, maternal alcohol use, maternal illicit drug use, maternal health, maternal medication use, maternal vitamin use, and maternal nutrition. Infants of non-Hispanic black mothers were more likely to have biliary atresia than infants of non-Hispanic white mothers (adjusted odds ratio (aOR) = 2.29, 95% confidence interval (CI) 1.07-4.93) and infants conceived during the spring season were more likely to have biliary atresia than infants conceived in winter (aOR = 2.33, 95%CI 1.05-5.16). Low intakes of vitamin E, copper, phosphorus, and beta tocopherol were associated with the occurrence of isolated biliary atresia (borderline significance). Low iron intake had a borderline inverse association with biliary atresia. While this analysis provides support for previous reports of a possible association between seasonal variation and the occurrence of biliary atresia, more data are needed to evaluate whether the seasonal variation is related to infectious agents. The role of nutrients in the development of biliary atresia remains unclear. Further studies of genetic, infectious, and nutrient exposures and the association of biliary atresia are warranted. 2007 Wiley-Liss, Inc

Prevention of internal hernias and pelvic adhesions following laparoscopic left-sided colorectal resection: the role of fibrin sealant.

PubMed

Angelini, Pierluigi; Sciuto, Antonio; Cuccurullo, Diego; Pirozzi, Felice; Reggio, Stefano; Corcione, Francesco

2017-07-01

Laparoscopy has increasingly become the standard of care for patients who undergo colorectal surgery for both benign and malignant diseases. This growing experience has also resulted in more reports of postoperative complications from the minimally invasive approach to primary colorectal resection. Small bowel obstruction from internal hernias and pre-sacral adhesions is an uncommon but not negligible complication. However, there is little literature specific to this topic with recommendations for different methods to prevent it. We report our original technique of closing the mesenteric defect and covering the pre-sacral fascia by using fibrin sealant to prevent this complication. From January 2005 to December 2014, a total of 1079 patients underwent elective laparoscopic left colorectal resection (left hemicolectomy or anterior rectal resection) in our department. In the first 298 procedures, the mesenteric defect was left open, while in the following 781 procedures, it was closed using fibrin sealant with the aim of preventing postoperative small bowel obstruction. Among the first 298 patients, three (1%) required reoperation for small bowel obstruction due to internal hernia (0.33%) or critical pre-sacral adhesions (0.66%). These complications did not occur in the subsequent series in which all 781 patients were treated with fibrin sealant prophylactic closure of the mesenteric defect. In our experience, fibrin sealant closure of the mesenteric defect has demonstrated to be safe and effective in preventing postoperative small bowel obstruction that remains a complication both in open and in laparoscopic colorectal surgeries.

Transcatheter Retrieval of Embolized Atrial Septal Defect Occluder Device by Waist Capture Technique.

PubMed

Her, Ae-Young; Lim, Kyung-Hun; Shin, Eun-Seok

2018-01-27

This case study describes the successful percutaneous transcatheter retrieval of an embolized Amplatzer occluder device using the "waist capture technique" in a patient with an atrial septal defect. This technique allowed for stability of the Amplatzer device, compression of the atrial discs for easier removal, prevention of further embolization, and minimal injury to vasculature during device retrieval. This novel and effective technique can be used safely for the retrieval of Amplatzer devices in the venous system.

Pathophysiology of Corneal Scarring in Persistent Epithelial Defects After PRK and Other Corneal Injuries.

PubMed

Wilson, Steven E; Medeiros, Carla S; Santhiago, Marcony R

2018-01-01

To analyze corneal persistent epithelial defects that occurred at 3 to 4 weeks after -4.50 diopter (D) photorefractive keratectomy (PRK) in rabbits and apply this pathophysiology to the treatment of persistent epithelial defects that occur after any corneal manipulations or diseases. Two of 168 corneas that had -4.50 D PRK to study epithelial basement membrane regeneration developed spontaneous persistent epithelial defects that did not heal at 3 weeks after PRK. These were studied with slit-lamp photographs, immunohistochemistry for the myofibroblast marker alpha-smooth muscle actin (α-SMA), and transmission electron microscopy. Myofibroblasts developed at the stromal surface within the persistent epithelial defect and for a short distance peripheral to the leading edge of the epithelium. No normal epithelial basement membrane was detectable within the persistent epithelial defect or for up to 0.3 mm behind the leading edge of the epithelium, although epithelial basement membrane had normally regenerated in other areas of the zone ablated by an excimer laser where the epithelium healed promptly. A persistent epithelial defect in the cornea results in the development of myofibroblasts and disordered extracellular matrix produced by these cells that together cause opacity within, and a short distance beyond, the persistent epithelial defect. Clinicians should treat persistent epithelial defects within 10 days of non-closure of the epithelium to facilitate epithelial healing to prevent long-term stromal scarring (fibrosis). [J Refract Surg. 2018;34(1):59-64.]. Copyright 2018, SLACK Incorporated.

Early Intervention and Nonpharmacological Therapy of Myopia in Young Adults

PubMed Central

Gładysiak, Aleksandra; Ślęzak, Daniel

2018-01-01

Myopia is a condition of the eye where parallel rays focus in front of, instead of on, the retina, which results in excessive refractive power of the cornea or the lens or eyeball elongation. Studies carried out in recent years show that the etiology of myopia is complex with genetic and environmental factors playing a role. Refraction defects decrease the quality of vision, while progressing myopia can lead to partial loss of vision, which can be particularly dramatic in young adults. Therefore, it is so crucial to take appropriate actions aimed at preventing myopia progression. This is a review of nonpharmacological therapeutic possibilities of refraction defect prevention in young adults, with special regard to myofascial therapy, osteopathy, and massage of acupuncture points surrounding the eye. PMID:29576878

Agricultural chemical exposures and birth defects in the Eastern Cape Province, South Africa A case – control study

PubMed Central

Heeren, Gudrun A; Tyler, Joanne; Mandeya, Andrew

2003-01-01

Background South Africa is one of the major users of pesticides on the African continent. The Eastern Cape is the second largest province in South Africa. There has been growing concern about the occurrence of certain birth defects which seemed to have increased in the past few years. In this paper we investigate associations between exposure to agricultural chemicals and certain birth defects. Few such studies have been undertaken in the developing world previously. Methods Between September 2000 and March 2001 a case – control study was conducted among rural women in the area of the Eastern cape to investigate the association between women's exposure to pesticides and the occurrence of birth defects. Information on birth defects was obtained from the register of the Paediatrics Department at the Cecilia Makiwane Hospital in Mdantsane, one of the largest referral hospitals in the province. The cases were children who were diagnosed with selected birth defects. The controls were children born in the same areas as the cases. Exposure information on the mothers was obtained by interview concerning from their activities in gardens and fields. Data were analysed using conditional logistic regression. Results A total of 89 case mothers and 178 control mothers was interviewed. Babies with birth defects were seven times more likely to be born to women exposed to chemicals used in gardens and fields compared to no reported exposure (Odds Ratio 7.18, 95% CI 3.99, 13.25); and were almost twice as likely to be born to women who were involved in dipping livestock used to prevent ticks (OR 1.92, 95% CI 1.15, 3.14). They were also 6.5 times more likely to be born to women who were using plastic containers for fetching water (OR 6.5, 95% CI 2.2, 27.9). Some of these containers had previously contained pesticides (OR 1.87, 95% CI 1.06, 3.31). Conclusions These findings suggest a link between exposure to pesticides and certain birth defects among the children of rural South African women who work on the land. Education programmes for women alerting them to the dangers to their babies from the use of pesticides and alternative farming methods and elimination of the reuse of pesticide containers are indicated as preventive measures. PMID:14613490

Some studies to prevent the production of some types of moire effects in fabrics

NASA Astrophysics Data System (ADS)

Serrano, Alfonso; Ponce, Rodrigo; Serroukh, Ibrahim

2004-09-01

The symmetry concerning the fabric pattern is not always suitable for the quality that we expected from fabric textile. The moire effects produced by a periodic structure may be caused by various and diverse factors as folds, lines, etc. The defect that we are concern is bright and dark fringes appearing in the Nylon Fabric are viewed with necked eye, from a particular angle using white light. To prevent these annoying effects, one should be focusing the research basically on geometrical fabric structure, physical, optical and dyeing. We start this work by an exhaustive study made to obtain enough information in order to identify and analyze the problem in order to identify, explain and prevent it appearance. To realize that we may define the factors that causes the phenomena. Concerning the experimental results, we begin with a conventional experiment called "Flat table examination" using Fluorescent white light bulb as types of illumination. We have used as well a microscope examination. It is useful to inspect the fiber and yarns which may have different characteristics of size and form. The light interaction with the fiber will produce especially kind of reflection and absorption. We finish the work by designing and developing an optical system able not only for detecting those kinds of fringes. As well to allow some defects inspection. We believe that some measurements are necessary during some process of fabrication (dyeing, spinning and knitting), at least to reduce this types of defects.

National Birth Defects Prevention Study (NBDPS)

MedlinePlus

... it was not very common for women to work in places with PAHs. PAH exposure occurred most often among women working in food preparation and serving. Pregnant women who worked in places with any PAHs were more likely to have ...

Long-term effect on tooth vitality of regenerative therapy in deep periodontal bony defects: a retrospective study.

PubMed

de Sanctis, Massimo; Goracci, Cecilia; Zucchelli, Giovanni

2013-01-01

Over the last few decades, many authors have investigated the effect of periodontal disease and treatment on pulpal status with controversial results. This study was conducted to verify whether periodontal disease in a deep intrabony defect and complex therapy, including aggressive root planing such as in periodontal regeneration, have an influence on tooth vitality. One hundred thirty-seven patients who fulfilled the requirements were included. The collected data did not support the need for "preventive" root canal treatment in severely compromised teeth that are planned to undergo periodontal regenerative surgery.

Folic Acid

MedlinePlus

... help prevent other types of birth defects and early pregnancy loss (miscarriage). Since about half of all pregnancies ... correctly every time you have sex. In a survey by the Centers for Disease Control and ... pregnancies were using birth control. 8 Birth defects of ...

Recurrent neural tube defects, risk factors and vitamins.

PubMed Central

Wild, J; Read, A P; Sheppard, S; Seller, M J; Smithells, R W; Nevin, N C; Schorah, C J; Fielding, D W; Walker, S; Harris, R

1986-01-01

Data from our trial of periconceptional vitamin supplementation for the prevention of neural tube defects have been analysed to assess the influence of various factors on recurrence rates of neural tube defect. Our data suggest that the risk of recurrence of neural tube defect is influenced by the number of previous neural tube defects, area of residence, immediately prior miscarriage, and interpregnancy interval. None of these factors, however, contributed any significant differential risk between supplemented and unsupplemented mothers. Hence we conclude that the highly significant difference in recurrence rates of neural tube defect between supplemented and unsupplemented mothers was due to vitamin supplementation. PMID:3521496

Enzyme replacement prevents enamel defects in hypophosphatasia mice

PubMed Central

Yadav, Manisha C.; de Oliveira, Rodrigo Cardoso; Foster, Brian L.; Fong, Hanson; Cory, Esther; Narisawa, Sonoko; Sah, Robert L.; Somerman, Martha; Whyte, Michael P.; Millán, José Luis

2012-01-01

Hypophosphatasia (HPP) is the inborn error of metabolism characterized by deficiency of alkaline phosphatase activity leading to rickets or osteomalacia and to dental defects. HPP occurs from loss-of-function mutations within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNAP). TNAP knockout (Alpl−/−, a.k.a. Akp2−/−) mice closely phenocopy infantile HPP, including the rickets, vitamin B6-responsive seizures, improper dentin mineralization, and lack of acellular cementum. Here, we report that lack of TNAP in Alpl−/− mice also causes severe enamel defects, which are preventable by enzyme replacement with mineral-targeted TNAP (ENB-0040). Immunohistochemistry was used to map the spatiotemporal expression of TNAP in the tissues of the developing enamel organ of healthy mouse molars and incisors. We found strong, stage-specific expression of TNAP in ameloblasts. In the Alpl−/− mice, histological, μCT, and scanning electron microscopy analysis showed reduced mineralization and disrupted organization of the rods and inter-rod structures in enamel of both the molars and incisors. All of these abnormalities were prevented in mice receiving from birth daily subcutaneous injections of mineral-targeting, human TNAP (sALP-FcD10, a.k.a. ENB-0040) at 8.2 mg/kg/day for up to 44 days. These data reveal an important role for TNAP in enamel mineralization, and demonstrate the efficacy of mineral-targeted TNAP to prevent enamel defects in HPP. PMID:22461224

Use of direct washing of chemical dispense nozzle for defect control

NASA Astrophysics Data System (ADS)

Linnane, Michael; Mack, George; Longstaff, Christopher; Winter, Thomas

2006-03-01

Demands for continued defect reduction in 300mm IC manufacturing are driving process engineers to examine all aspects of the chemical apply process for improvement. Historically, the defect contribution from photoresist apply nozzles has been minimized through a carefully controlled process of "dummy dispenses" to keep the photoresist in the tip "fresh" and remove any solidified material, a preventive maintenance regime involving periodic cleaning or replacing of the nozzles, and reliance on a pool of solvent within the nozzle storage block to keep the photoresist from solidifying at the nozzle tip. The industry standard has worked well for the most part but has limitations in terms of cost effectiveness and absolute defect elimination. In this study, we investigate the direct washing of the chemical apply nozzle to reduce defects seen on the coated wafer. Data is presented on how the direct washing of the chemical dispense nozzle can be used to reduce coating related defects, reduce material costs from the reduction of "dummy dispense", and can reduce equipment downtime related to nozzle cleaning or replacement.

Maternal obesity and tobacco use modify the impact of genetic variants on the occurrence of conotruncal heart defects.

PubMed

Tang, Xinyu; Nick, Todd G; Cleves, Mario A; Erickson, Stephen W; Li, Ming; Li, Jingyun; MacLeod, Stewart L; Hobbs, Charlotte A

2014-01-01

Conotruncal heart defects (CTDs) are among the most severe birth defects worldwide. Studies of CTDs indicate both lifestyle behaviors and genetic variation contribute to the risk of CTDs. Based on a hybrid design using data from 616 case-parental and 1645 control-parental triads recruited for the National Birth Defects Prevention Study between 1997 and 2008, we investigated whether the occurrence of CTDs is associated with interactions between 921 maternal and/or fetal single nucleotide polymorphisms (SNPs) and maternal obesity and tobacco use. The maternal genotypes of the variants in the glutamate-cysteine ligase, catalytic subunit (GCLC) gene and the fetal genotypes of the variants in the glutathione S-transferase alpha 3 (GSTA3) gene were associated with an elevated risk of CTDs among obese mothers. The risk of delivering infants with CTDs among obese mothers carrying AC genotype for a variant in the GCLC gene (rs6458939) was 2.00 times the risk among those carrying CC genotype (95% confidence interval: 1.41, 2.38). The maternal genotypes of several variants in the glutathione-S-transferase (GST) family of genes and the fetal genotypes of the variants in the GCLC gene interacted with tobacco exposures to increase the risk of CTDs. Our study suggests that the genetic basis underlying susceptibility of the developing heart to the adverse effects of maternal obesity and tobacco use involve both maternal and embryonic genetic variants. These results may provide insights into the underlying pathophysiology of CTDs, and ultimately lead to novel prevention strategies.

Tuning of defects in ZnO nanorod arrays used in bulk heterojunction solar cells

PubMed Central

2012-01-01

With particular focus on bulk heterojunction solar cells incorporating ZnO nanorods, we study how different annealing environments (air or Zn environment) and temperatures impact on the photoluminescence response. Our work gives new insight into the complex defect landscape in ZnO, and it also shows how the different defect types can be manipulated. We have determined the emission wavelengths for the two main defects which make up the visible band, the oxygen vacancy emission wavelength at approximately 530 nm and the zinc vacancy emission wavelength at approximately 630 nm. The precise nature of the defect landscape in the bulk of the nanorods is found to be unimportant to photovoltaic cell performance although the surface structure is more critical. Annealing of the nanorods is optimum at 300°C as this is a sufficiently high temperature to decompose Zn(OH)2 formed at the surface of the nanorods during electrodeposition and sufficiently low to prevent ITO degradation. PMID:23186280

Delamination initiated by a defect

NASA Astrophysics Data System (ADS)

Biel, A.; Toftegaard, H.

2016-07-01

Composite materials in wind turbines are mainly joined with adhesives. Adhesive joining is preferable since it distributes the stresses over a larger area. This study shows how a defect can influence the fracture behaviour of adhesively joined composite. Repeated experiments are performed using double cantilever beam specimens loaded with bending moments. The specimens consist of two 8 mm thick GFRP-laminates which are joined by a 3 mm thick epoxy adhesive. A thin foil close to one of the laminates is used to start the crack. For some of the specimens a defect is created by an initial load-unload operation. During this operation, a clamp is used in order to prevent crack propagation in the main direction. For the specimens without defect, the crack propagates in the middle of the adhesive layer. For the specimens with defect, the crack directly deviates into the laminate. After about 25 mm propagation in the laminate, the crack returns to the adhesive. Compared to the adhesive the fracture energy for the laminate is significantly higher.

EUV patterning improvement toward high-volume manufacturing

NASA Astrophysics Data System (ADS)

Kuwahara, Yuhei; Matsunaga, Koichi; Kawakami, Shinichiro; Nafus, Kathleen; Foubert, Philippe; Goethals, Anne-Marie

2015-03-01

Extreme ultraviolet lithography (EUVL) technology is a promising candidate for a semiconductor process for 18nm half pitch and beyond. So far, the studies of EUV for manufacturability have been focused on particular aspects. It still requires fine resolution, uniform and smooth patterns, and low defectivity, not only after lithography but also after the etch process. Tokyo Electron Limited and imec are continuously collaborating to improve manufacturing quality of the process of record (POR) on a CLEAN TRACKTM LITHIUS ProTMZ-EUV. This next generation coating/developing system has been upgraded with defectivity reduction enhancements which are applied along with TELTM best known methods. We have evaluated process defectivity post lithography and post etch. Apart from defectivity, FIRMTM rinse material and application compatibility with sub 18nm patterning is improved to prevent line pattern collapse and increase process window on next generation resist materials. This paper reports on the progress of defectivity and patterning performance optimization towards the NXE:3300 POR.

Knowledge and periconceptional use of folic acid for the prevention of neural tube defects in ethnic communities in the United Kingdom: systematic review and meta-analysis.

PubMed

Peake, Jordana N; Copp, Andrew J; Shawe, Jill

2013-07-01

It is widely accepted that periconceptional supplementation with folic acid can prevent a significant proportion of neural tube defects (NTDs). The present study evaluated how folic acid knowledge and periconceptional use for NTD prevention varies by ethnicity in the United Kingdom (U.K.). A literature search was conducted to identify studies that included assessment of folic acid knowledge or use in U.K. women of different ethnicities. Only research and referenced sources published after 1991, the year of the landmark Medical Research Council's Vitamin Study, were included. A meta-analysis was performed of studies that assessed preconceptional folic acid use in Caucasians and non-Caucasians. Five studies met the inclusion criteria for assessment of knowledge and/or use of folic acid supplements in U.K. women including non-Caucasians. The available evidence indicates that South Asians specifically have less knowledge and lower periconceptional use of folic acid than Caucasians; one study found that West Indian and African women also had lower folic acid uptake. A synthesis of results from three of the studies, in a meta-analysis, shows that Caucasians are almost three times more likely to take folic acid before conception than non-Caucasians. From the limited evidence available, U.K. women of non-Caucasian ethnicity appear to have less knowledge and a lower uptake of folic acid supplementation than Caucasians during the periconceptional period. Implementing targeted, innovative education campaigns together with a mandatory fortification policy, including the fortification of ethnic minority foods, will be required for maximum prevention of folic acid-preventable NTDs across different ethnic groups. Copyright © 2013 Wiley Periodicals, Inc.

Noble Logic for Preventing Scratch on Roll-to-Roll Printed Layers in Noncontacting Transportation

NASA Astrophysics Data System (ADS)

Lee, Changwoo; Kang, Hyunkyoo; Kim, Hojoon; Shin, Keehyun

2010-05-01

The use of roll-to-roll (R2R) printed electronics is a relatively new method of mass producing flexible electronic devices while keeping production costs down. The geometrical qualities of a printed pattern, such as surface roughness and uniformity, could deteriorate. Moreover, the geometric qualities of a printed layer affect the functional qualities of a printed electronic device directly. Therefore, the functional qualities (conductivity and mobility) of a multilayer electronic device could deteriorate in the presence of a scratch defect on the printed layer. In general, a scratch on a printed pattern on a flexible substrate is induced by contact between the rolls and printed pattern in R2R printing systems. To prevent such contact, one of the best solutions is to use an air flotation unit. However, a scratch defect could be induced even though an air flotation process is used to minimize contact, because the flotation height of a moving web is affected by web tension. In this paper, we discuss an analytical model of an air-floated moving substrate. For the noncontacting transfer of a moving web without a scratch defect, a mathematical tension model has been developed by considering an induced strain due to aerodynamic forces and verified by numerical and experimental studies. Additionally, the correlation between the flotation height of an air-floated moving web and speed compensation used to control the tension are investigated. The analysis shows that tension fluctuations can cause the substrate to touch the air-flotation subsystem, which is installed to prevent contact, resulting in defects such as scratches on the printed layer. On the basis of the proposed model, a logic is developed to minimize scratch defects on R2R printed layers in noncontacting transportation. Through a guideline based on this logic, the scratched area density on R2R printed layers can be reduced by approximately 70%.

Neural Tube Defects

PubMed Central

Greene, Nicholas D.E.; Copp, Andrew J.

2015-01-01

Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as have possibilities for prevention by maternal folic acid supplementation. Mechanisms underlying neural tube closure and NTDs may be informed by experimental models, which have revealed numerous genes whose abnormal function causes NTDs and have provided details of critical cellular and morphological events whose regulation is essential for closure. Such models also provide an opportunity to investigate potential risk factors and to develop novel preventive therapies. PMID:25032496

[Cartilage regeneration surgery on the hip : What is feasible?

PubMed

Landgraeber, Stefan; Jäger, Marcus; Fickert, Stefan

2017-11-01

Localized cartilage defects at the hip are mainly caused by pre-arthritic deformities, particularly by cam-type femoroacetabular impingement (FAI). Timely elimination of symptomatic deformities can prevent further progression such as cartilage defects. As the defects mostly occur in the anterolateral part of the acetabulum, they can be easily treated either by open surgery or by arthroscopy. To date the most effective methods of treatment are bone marrow stimulation, with or without a covering of biomaterials, and autologous chondrocyte transplantation. In selected cases, readaptation of the damaged cartilage can be attempted by biological procedures. In the present article, the findings reported in current studies on these procedures are summarized and discussed in detail. An outlook is given regarding possible future treatment concepts.

Anti-site defected MoS2 sheet for catalytic application

NASA Astrophysics Data System (ADS)

Sharma, Archana; Husain, Mushahid; Khan, Mohd. Shahid

2018-04-01

To prevent harmful and poisonous CO gas molecules, catalysts are needed for converting them into benign substances. Density functional theory (DFT) calculations have been used to investigate CO oxidation on the surface of MoS2 monolayer with Mo atom embedded at S-vacancy site (anti-site defect). The stronger interaction between Mo metal with O2 molecule as compared with CO molecule suggests high catalytic activity. The complete oxidation of CO is studied in a two-step procedure using Langmuir-Hinshelwood (LH) and Eley-Rideal (ER) mechanisms with a low overall energy barrier of 0.35 eV. Creation of anti-site defect makes the surface of MoS2 nanosheet catalytically active for the CO oxidation to take place.

Association between Prenatal Exposure to Antiretroviral Therapy and Birth Defects: An Analysis of the French Perinatal Cohort Study (ANRS CO1/CO11)

PubMed Central

Sibiude, Jeanne; Mandelbrot, Laurent; Blanche, Stéphane; Le Chenadec, Jérôme; Boullag-Bonnet, Naima; Faye, Albert; Dollfus, Catherine; Tubiana, Roland; Bonnet, Damien; Lelong, Nathalie; Khoshnood, Babak; Warszawski, Josiane

2014-01-01

Background Antiretroviral therapy (ART) has major benefits during pregnancy, both for maternal health and to prevent mother-to-child transmission of HIV. Safety issues, including teratogenic risk, need to be evaluated. We estimated the prevalence of birth defects in children born to HIV-infected women receiving ART during pregnancy, and assessed the independent association of birth defects with each antiretroviral (ARV) drug used. Methods and Findings The French Perinatal Cohort prospectively enrolls HIV-infected women delivering in 90 centers throughout France. Children are followed by pediatricians until 2 y of age according to national guidelines. We included 13,124 live births between 1994 and 2010, among which, 42% (n = 5,388) were exposed to ART in the first trimester of pregnancy. Birth defects were studied using both European Surveillance of Congenital Anomalies (EUROCAT) and Metropolitan Atlanta Congenital Defects Program (MACDP) classifications; associations with ART were evaluated using univariate and multivariate logistic regressions. Correction for multiple comparisons was not performed because the analyses were based on hypotheses emanating from previous findings in the literature and the robustness of the findings of the current study. The prevalence of birth defects was 4.4% (95% CI 4.0%–4.7%), according to the EUROCAT classification. In multivariate analysis adjusting for other ARV drugs, maternal age, geographical origin, intravenous drug use, and type of maternity center, a significant association was found between exposure to zidovudine in the first trimester and congenital heart defects: 2.3% (74/3,267), adjusted odds ratio (AOR) = 2.2 (95% CI 1.3–3.7), p = 0.003, absolute risk difference attributed to zidovudine +1.2% (95% CI +0.5; +1.9%). Didanosine and indinavir were associated with head and neck defects, respectively: 0.5%, AOR = 3.4 (95% CI 1.1–10.4), p = 0.04; 0.9%, AOR = 3.8 (95% CI 1.1–13.8), p = 0.04. We found a significant association between efavirenz and neurological defects (n = 4) using the MACDP classification: AOR = 3.0 (95% CI 1.1–8.5), p = 0.04, absolute risk +0.7% (95% CI +0.07%; +1.3%). But the association was not significant using the less inclusive EUROCAT classification: AOR = 2.1 (95% CI 0.7–5.9), p = 0.16. No association was found between birth defects and lopinavir or ritonavir with a power >85% for an odds ratio of 1.5, nor for nevirapine, tenofovir, stavudine, or abacavir with a power >70%. Limitations of the present study were the absence of data on termination of pregnancy, stillbirths, tobacco and alcohol intake, and concomitant medication. Conclusions We found a specific association between in utero exposure to zidovudine and heart defects; the mechanisms need to be elucidated. The association between efavirenz and neurological defects must be interpreted with caution. For the other drugs not associated with birth defects, the results were reassuring. Finally, whatever the impact that some ARV drugs may have on birth defects, it is surpassed by the major role of ART in the successful prevention of mother-to-child transmission of HIV. Please see later in the article for the Editors' Summary PMID:24781315

Intensity compensation for on-line detection of defects on fruit

NASA Astrophysics Data System (ADS)

Wen, Zhiqing; Tao, Yang

1997-10-01

A machine-vision sorting system was developed that utilizes the difference in light reflectance of fruit surfaces to distinguish the defective and good apples. To accommodate to the spherical reflectance characteristics of fruit with curved surface like apple, a spherical transform algorithm was developed that converts the original image to a non-radiant image without losing defective segments on the fruit. To prevent high-quality dark-colored fruit form being classified into the defective class and increase the defect detection rate for light-colored fruit, an intensity compensation method using maximum propagation was used. Experimental results demonstrated the effectiveness of the method based on maximum propagation and spherical transform for on-line detection of defects on apples.

A case–control study of maternal bathing habits and risk for birth defects in offspring

PubMed Central

2013-01-01

Background Nearly all women shower or take baths during early pregnancy; however, bathing habits (i.e., shower and bath length and frequency) may be related to the risk of maternal hyperthermia and exposure to water disinfection byproducts, both of which are suspected to increase risk for multiple types of birth defects. Thus, we assessed the relationships between bathing habits during pregnancy and the risk for several nonsyndromic birth defects in offspring. Methods Data for cases with one of 13 types of birth defects and controls from the National Birth Defects Prevention Study delivered during 2000–2007 were evaluated. Logistic regression analyses were conducted separately for each type of birth defect. Results There were few associations between shower frequency or bath frequency or length and risk for birth defects in offspring. The risk for gastroschisis in offspring was increased among women who reported showers lasting ≥15 compared to <15 minutes (adjusted odds ratio: 1.43, 95% confidence interval: 1.18-1.72). In addition, we observed modest increases in the risk for spina bifida, cleft lip with or without cleft palate, and limb reduction defects in offspring of women who showered ≥15 compared to <15 minutes. The results of comparisons among more specific categories of shower length (i.e., <15 minutes versus 15–19, 20–29, and ≥ 30 minutes) were similar. Conclusions Our findings suggest that shower length may be associated with gastroschisis, but the modest associations with other birth defects were not supported by analyses of bath length or bath or shower frequency. Given that showering for ≥15 minutes during pregnancy is very common, further evaluation of the relationship between maternal showering habits and birth defects in offspring is worthwhile. PMID:24131571

Damage of composite structures: Detection technique, dynamic response and residual strength

NASA Astrophysics Data System (ADS)

Lestari, Wahyu

2001-10-01

Reliable and accurate health monitoring techniques can prevent catastrophic failures of structures. Conventional damage detection methods are based on visual or localized experimental methods and very often require prior information concerning the vicinity of the damage or defect. The structure must also be readily accessible for inspections. The techniques are also labor intensive. In comparison to these methods, health-monitoring techniques that are based on the structural dynamic response offers unique information on failure of structures. However, systematic relations between the experimental data and the defect are not available and frequently, the number of vibration modes needed for an accurate identification of defects is much higher than the number of modes that can be readily identified in the experiment. These motivated us to develop an experimental data based detection method with systematic relationships between the experimentally identified information and the analytical or mathematical model representing the defective structures. The developed technique use changes in vibrational curvature modes and natural frequencies. To avoid misinterpretation of the identified information, we also need to understand the effects of defects on the structural dynamic response prior to developing health-monitoring techniques. In this thesis work we focus on two type of defects in composite structures, namely delamination and edge notch like defect. Effects of nonlinearity due to the presence of defect and due to the axial stretching are studied for beams with delamination. Once defects are detected in a structure, next concern is determining the effects of the defects on the strength of the structure and its residual stiffness under dynamic loading. In this thesis, energy release rate due to dynamic loading in a delaminated structure is studied, which will be a foundation toward determining the residual strength of the structure.

MTHFR polymorphisms in Puerto Rican children with isolated congenital heart disease and their mothers

PubMed Central

García-Fragoso, Lourdes; García-García, Inés; Leavitt, Gloria; Renta, Jessicca; Ayala, Miguel A.; Cadilla, Carmen L.

2010-01-01

Congenital heart defects (CHD) are among the most common birth defects. There is evidence suggesting that polymorphisms in folate metabolism could alter susceptibility to CHD. The MTHFR 677TT genotype has been associated with the development of structural congenital heart malformations. The objective of this study was to identify common polymorphisms in the MTHFR gene in children with isolated CHD and their mothers. The DNA analysis for the C677T and A1298C mutations was performed. The study group included 27 mothers, 27 children with CHD, and 220 controls. The prevalence of the TT polymorphism was higher in mothers (22%) than in controls (10%). Compound heterozygosity for both polymorphisms was 3.7 times more common in children with CHD than in the newborn controls. Mothers of children with CHD were more likely to be compound heterozygotes. The higher prevalence of C677T polymorphisms in mothers of children with CHD and of compound heterozygosity for both polymorphisms suggests the possible role of folic acid in the prevention of CHD. Due to the relation of this enzyme to folate metabolism, current folate recommendations for women in childbearing age in Puerto Rico to reduce neural tube defects may need to be extended to the prevention of CHD. PMID:20657745

MTHFR polymorphisms in Puerto Rican children with isolated congenital heart disease and their mothers.

PubMed

García-Fragoso, Lourdes; García-García, Inés; Leavitt, Gloria; Renta, Jessicca; Ayala, Miguel A; Cadilla, Carmen L

2010-03-01

Congenital heart defects (CHD) are among the most common birth defects. There is evidence suggesting that polymorphisms in folate metabolism could alter susceptibility to CHD. The MTHFR 677TT genotype has been associated with the development of structural congenital heart malformations. The objective of this study was to identify common polymorphisms in the MTHFR gene in children with isolated CHD and their mothers. The DNA analysis for the C677T and A1298C mutations was performed. The study group included 27 mothers, 27 children with CHD, and 220 controls. The prevalence of the TT polymorphism was higher in mothers (22%) than in controls (10%). Compound heterozygosity for both polymorphisms was 3.7 times more common in children with CHD than in the newborn controls. Mothers of children with CHD were more likely to be compound heterozygotes. The higher prevalence of C677T polymorphisms in mothers of children with CHD and of compound heterozygosity for both polymorphisms suggests the possible role of folic acid in the prevention of CHD. Due to the relation of this enzyme to folate metabolism, current folate recommendations for women in childbearing age in Puerto Rico to reduce neural tube defects may need to be extended to the prevention of CHD.

Unclosed fascial defect: is it the risk to develop port-site hernia after laparoscopic cholecystectomy?

PubMed

Tangjaroen, Somard; Watanapa, Prasit

2014-02-01

Port-site hernia (PSH) is one of the complications after laparoscopic cholecystectomy (LC). Closure of the fascial defect has been mentioned to prevent such complication. However, the results are still controversial. The present study was done to clarify whether unclosed fascial defect was actually the risk factor for the development of PSH MATERIAL AND METHOD: Two hundred ninety four patients underwent LC by a single surgeon at Kalasin Hospital between 2007 and 2010. The procedure was done by using a four-port technique without closure of any fascial defects. The male:female ratio was 85:209, and the mean body mass index was 24.38 +/- 3.33 (SD). The mean operative time was 18.71 +/- 3.76 minutes and there was no postoperative wound infection. Patients were regularly followed-up and underwent both supine and upright physical examination. The mean duration of follow-up period was 4.94 +/- 1.31 years with the shortest follow-up period of two years. None of the patients in the present study developed PSH in any port sites during the follow-up period. Unclosed fascial defect may not have the significant risk factor of developing PSH after LC.

Mastoid cortex plasty using bone pate.

PubMed

Yanagihara, Naoaki; Hinohira, Yasuyuki; Sato, Hidemitu

2002-07-01

To describe the surgical technique of mastoid cortex plasty using bone pate and its clinical significance. Retrospective. Tertiary medical center. Bone pate collected while drilling the mastoid cortex was mixed with fibrin glue to make a pate plate. The mastoid cortex defect was closed with a pate plate cut to the desired shape and size. Mastoid cortex plasty was included in the first-stage operation in 49 patients who underwent staged tympanoplasty. The second-stage operation was an inspection to see whether the mastoid cortex was reconstructed and the ingrowth of fibrous soft tissue was prevented. In 35 patients, the mastoid cortex was reconstructed completely, and soft tissue ingrowth into the mastoid cavity was blocked completely. In the remaining 14 patients, a defect of varying size occurred at the site of drainage-tube insertion. This defect was small enough to prevent soft tissue ingrowth into the mastoid cavity. Mastoid cortex plasty is a simple and rapid procedure for preventing postoperative deformity of the mastoid process and is valuable for restoring mastoid cavity function.

The Aurora-B-dependent NoCut checkpoint prevents damage of anaphase bridges after DNA replication stress.

PubMed

Amaral, Nuno; Vendrell, Alexandre; Funaya, Charlotta; Idrissi, Fatima-Zahra; Maier, Michael; Kumar, Arun; Neurohr, Gabriel; Colomina, Neus; Torres-Rosell, Jordi; Geli, María-Isabel; Mendoza, Manuel

2016-05-01

Anaphase chromatin bridges can lead to chromosome breakage if not properly resolved before completion of cytokinesis. The NoCut checkpoint, which depends on Aurora B at the spindle midzone, delays abscission in response to chromosome segregation defects in yeast and animal cells. How chromatin bridges are detected, and whether abscission inhibition prevents their damage, remain key unresolved questions. We find that bridges induced by DNA replication stress and by condensation or decatenation defects, but not dicentric chromosomes, delay abscission in a NoCut-dependent manner. Decatenation and condensation defects lead to spindle stabilization during cytokinesis, allowing bridge detection by Aurora B. NoCut does not prevent DNA damage following condensin or topoisomerase II inactivation; however, it protects anaphase bridges and promotes cellular viability after replication stress. Therefore, the molecular origin of chromatin bridges is critical for activation of NoCut, which plays a key role in the maintenance of genome stability after replicative stress.

Minimally Invasive Surgical Device for Precise Application of Bioadhesives to Prevent iPPROM.

PubMed

Devaud, Yannick Robert; Züger, Silvia; Zimmermann, Roland; Ehrbar, Martin; Ochsenbein-Kölble, Nicole

2018-06-19

The benefits of endoscopic fetal surgery are deteriorated by the high risk of iatrogenic preterm prelabor rupture of fetal membranes (iPPROM). While previous studies have reported good sealing candidates to prevent membrane rupture, the delivery of these materials to the location of membrane puncture remains unsolved. We describe an approach to apply sealing materials onto the amnion through the fetoscopy port. We developed a device composed of an umbrella-shaped polyester coated nitinol mesh and an applicator. The spontaneously unfolding umbrella is pushed through the port, pulled against the amnion, and glued onto the amnion defect site. We tested the adhesion strength of multiple glues and tested the feasibility and reproducibility of this fetal membrane sealing approach in an ex vivo model. The umbrella unfolded and was well positioned in all tests (n = 18). When applied via the fetoscopy port, umbrellas were successfully glued onto the fetal membrane, and all of them completely covered the defect (n = 5). The mean time needed for the whole procedure was 3 min. This study is a proof of concept presenting a potential future solution for the precise local application of bioadhesives for the prevention of iPPROM. © 2018 S. Karger AG, Basel.

Neuronal Dysfunction Associated with Cholesterol Deregulation

PubMed Central

Loganes, Claudia; Bilel, Sabrine; Celeghini, Claudio; Tommasini, Alberto

2018-01-01

Cholesterol metabolism is crucial for cells and, in particular, its biosynthesis in the central nervous system occurs in situ, and its deregulation involves morphological changes that cause functional variations and trigger programmed cell death. The pathogenesis of rare diseases, such as Mevalonate Kinase Deficiency or Smith–Lemli–Opitz Syndrome, arises due to enzymatic defects in the cholesterol metabolic pathways, resulting in a shortage of downstream products. The most severe clinical manifestations of these diseases appear as neurological defects. Expanding the knowledge of this biological mechanism will be useful for identifying potential targets and preventing neuronal damage. Several studies have demonstrated that deregulation of the cholesterol pathway induces mitochondrial dysfunction as the result of respiratory chain damage. We set out to determine whether mitochondrial damage may be prevented by using protective mitochondria-targeted compounds, such as MitoQ, in a neuronal cell line treated with a statin to induce a biochemical block of the cholesterol pathway. Evidence from the literature suggests that mitochondria play a crucial role in the apoptotic mechanism secondary to blocking the cholesterol pathway. Our study shows that MitoQ, administered as a preventive agent, could counteract the cell damage induced by statins in the early stages, but its protective role fades over time. PMID:29783748

Shared molecular networks in orofacial and neural tube development.

PubMed

Kousa, Youssef A; Mansour, Tamer A; Seada, Haitham; Matoo, Samaneh; Schutte, Brian C

2017-01-30

Single genetic variants can affect multiple tissues during development. Thus it is possible that disruption of shared gene regulatory networks might underlie syndromic presentations. In this study, we explore this idea through examination of two critical developmental programs that control orofacial and neural tube development and identify shared regulatory factors and networks. Identification of these networks has the potential to yield additional candidate genes for poorly understood developmental disorders and assist in modeling and perhaps managing risk factors to prevent morbidly and mortality. We reviewed the literature to identify genes common between orofacial and neural tube defects and development. We then conducted a bioinformatic analysis to identify shared molecular targets and pathways in the development of these tissues. Finally, we examine publicly available RNA-Seq data to identify which of these genes are expressed in both tissues during development. We identify common regulatory factors in orofacial and neural tube development. Pathway enrichment analysis shows that folate, cancer and hedgehog signaling pathways are shared in neural tube and orofacial development. Developing neural tissues differentially express mouse exencephaly and cleft palate genes, whereas developing orofacial tissues were enriched for both clefting and neural tube defect genes. These data suggest that key developmental factors and pathways are shared between orofacial and neural tube defects. We conclude that it might be most beneficial to focus on common regulatory factors and pathways to better understand pathology and develop preventative measures for these birth defects. Birth Defects Research 109:169-179, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Facts about Anencephaly

MedlinePlus

... for Prevention Birth Defects are Common, Costly, and Critical Videos & Podcasts Buttons Prevent to Protect PACT Quiz ... front part of the brain (forebrain) and the thinking and coordinating part of the brain (cerebrum). The ...

Birth defects among a cohort of infants born to HIV-infected women on antiretroviral medication

PubMed Central

Watts, D. Heather; Huang, Sharon; Culnane, Mary; Kaiser, Kathleen A.; Scheuerle, Angela; Mofenson, Lynne; Stanley, Kenneth; Newell, Marie-Louise; Mandelbrot, Laurent; Delfraissy, Jean-Francois; Cunningham, Coleen K.

2011-01-01

Objective To determine rate of and risk factors for birth defects in infants born to HIV-infected women receiving nucleoside and protease inhibitor antiretroviral (ARV) therapy. Methods Birth defects were evaluated among infants on the Pediatric AIDS Clinical Trials Group 316 trial that studied addition of peripartum nevirapine to established ARV regimen for prevention of mother-to-child transmission. Maternal therapy was categorized by trimester of earliest exposure. Birth defects were coded using conventions of the Antiretroviral Pregnancy Registry. Results Birth defects were detected in 60/1414 (4.2%; 95% CI 3.3–5.4%) infants including 30/636 (4.7%; 95% CI 3.2–6.7%) with first trimester ARV exposure and 30/778 (3.9%; 95% CI 2.6–5.5%) with exposure only after the first trimester (P=0.51). Rates of classes of defects were similar between first trimester compared to later exposure groups except heart defects which occurred in 16 (2.5%; 95% CI 1.4–4.1%) with first trimester ARV exposure and in six (0.8%; 95% CI 0.3–1.7%) infants with later exposure (P=0.02). Exposure to ARV was not associated with specific types of heart defects. Two cases of cardiomyopathy were noted. Conclusion ARV use in early pregnancy was not associated with an increased risk of birth defects overall. The possible association of ARV exposure with heart defects requires further surveillance. PMID:21142844

Characterisation and modelling of defect formation in direct-chill cast AZ80 alloy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mackie, D.; Robson, J.D.; Withers, P.J.

2015-06-15

Wrought magnesium alloys for demanding structural applications require high quality defect free cast feedstock. The aim of this study was to first identify and characterise typical defects in direct chill cast magnesium–aluminium–zinc (AZ) alloy billet and then use modelling to understand the origins of these defects so they can be prevented. Defects were first located using ultrasonic inspection and were then characterised using X-ray computed tomography (XCT) and serial sectioning, establishing the presence of oxide films and intermetallic particles Al{sub 8}Mn{sub 5} in all defects. A model was developed to predict the flow patterns and growth kinetics of the intermetallicmore » phases during casting, which influence the formation of defects. Simulation of the growth of the intermetallic particles demonstrated that precipitation from the liquid occurs in the mould. The combination of the entrained oxide films and intermetallic particles recirculates in the liquid metal and continues to grow, until large enough to settle, which is predicted to occur at the centre of the mould where the flow is the slowest. Based on these predictions, strategies to reduce the susceptibility to defect formation are suggested. - Highlights: • Casting defects in magnesium direct chill casting have been imaged and characterised in 3-dimensions. • The occurrences of co-located clusters of particles and oxide films have been characterised and explained. • A coupled model has been developed to help interpret the observed trend for defects located towards the centre of billets.« less

Relating Risk and Reliability Predictions to Design and Development Choices

NASA Technical Reports Server (NTRS)

Feather, Martin S.; Cornford, Steven L.

2006-01-01

In this context there are many possible assurance activities. Some focus on the prevention of defects - for example, up-front planning, adoption of design standards, configuration management, training, etc. Others focus on the detection of defects - either to detect latent defects in a system (and so be able to correct them before actual deployment of the system), or to increase confidence that such defects are not present. For example, a wide gamut of reviews, design walkthroughs, tests, inspections, analyses, etc. can be applied to systems and their components.

Insights from Parents about Caring for a Child with Birth Defects

PubMed Central

Lemacks, Jodi; Fowles, Kristin; Mateus, Amanda; Thomas, Kayte

2013-01-01

Birth defects affect 1 in 33 babies. Having a child with a birth defect impacts the whole family. Parents of children who have birth defects face unique challenges and desire to make life better for their kids. They also want to help to prevent birth defects in the future. Some of the challenges parents face involve communication with healthcare professionals, quality of life issues, creating awareness and advocating for research and funding, finding resources and support, and helping teens transition to appropriate, specialized adult care. This paper addresses these issues and their sub-issues, provides examples, and makes suggestions for improvement and research. PMID:23965922

The combined oral contraceptive pill containing drospirenone and ethinyl estradiol plus levomefolate calcium.

PubMed

Rapkin, Rachel B; Creinin, Mitchell D

2011-10-01

Neural tube defects are the second most common congenital anomaly in the United States, although their incidence may be decreased by periconception folic acid supplementation. A new oral contraceptive containing drospirenone and ethinyl estradiol plus levomefolate calcium was formulated to decrease the risk of neural tube defects in pregnancies conceived while taking or shortly after discontinuing this pill. Because of its novelty, very few studies have been performed to evaluate the efficacy, side effects and safety related to contraception, premenstrual dysphoric disorder and acne; therefore, literature evaluating similar contraceptives without levomefolate is reviewed. Additionally, we review studies evaluating the addition of levomefolate calcium to oral contraceptives containing 3 mg drospirenone and either 20 or 30 μg ethinyl estradiol. To date, no study has been performed to evaluate the effect this new oral contraceptive has on reducing the incidence of neural tube defects. This new pill has similar contraceptive efficacy, side effect, safety and benefits profile to other drospirenone-containing contraceptives. While also approved to prevent neural tube defects, no studies validate this claim and physician time is better spent counseling women, regardless of contraceptive choice, on the importance of folic acid supplementation during the child-bearing years.

Maternal use of folic acid supplements and infant risk of neural tube defects in Norway 1999-2013.

PubMed

Gildestad, Trude; Øyen, Nina; Klungsøyr, Kari; Nilsen, Roy Miodini; Daltveit, Anne Kjersti; Vollset, Stein Emil

2016-08-01

Like most European countries, Norway has refrained from mandatory food fortification with folic acid to reduce the number of neural tube defects. We explored the role of folic acid and multivitamin supplements in the prevention of neural tube defects among newborn infants. We used data from the Medical Birth Registry of Norway, 1999-2013. A total of 528,220 women had 880,568 pregnancies resulting in 896,674 live- and stillborn infants, of whom 270 had neural tube defects. Relative risks were estimated with log-binomial regression. From 1999 to 2013, intake of folic acid supplements increased from 4.8% to 27.4%. Vitamin supplement use was more frequent in older, married or cohabiting women and those with lower parity, as well as women who did not smoke during pregnancy. The overall adjusted relative risk of infant neural tube defects associated with maternal vitamin intake before pregnancy relative to no intake was 0.76 (95% confidence interval: 0.53-1.10). When we divided our study period in two (1999-2005 and 2006-2013), we found a significantly reduced risk of neural tube defects overall by vitamin use in the second time period, but not in the first: adjusted relative risk 0.54 (95% confidence interval: 0.31-0.91) and 1.02 (95% confidence interval: 0.63-1.65), respectively. OVER THE FULL STUDY PERIOD, WE FOUND NO STATISTICALLY SIGNIFICANT ASSOCIATION BETWEEN VITAMIN USE AND NEURAL TUBE DEFECTS OVERALL HOWEVER, VITAMIN USE WAS ASSOCIATED WITH A SIGNIFICANTLY LOWER RISK OF NEURAL TUBE DEFECTS IN THE SECOND HALF OF THE STUDY PERIOD, 2006-2013. © 2016 the Nordic Societies of Public Health.

Maternal occupational exposure to polycyclic aromatic hydrocarbons and craniosynostosis among offspring in the National Birth Defects Prevention Study.

PubMed

O'Brien, Jacqueline L; Langlois, Peter H; Lawson, Christina C; Scheuerle, Angela; Rocheleau, Carissa M; Waters, Martha A; Symanski, Elaine; Romitti, Paul A; Agopian, A J; Lupo, Philip J

2016-01-01

Evidence in animal models and humans suggests that exposure to polycyclic aromatic hydrocarbons (PAHs) may lead to birth defects. To our knowledge, this relationship has not been evaluated for craniosynostosis, a birth defect characterized by the premature closure of sutures in the skull. We conducted a case-control study to examine associations between maternal occupational exposure to PAHs and craniosynostosis. We used data from craniosynostosis cases and control infants in the National Birth Defects Prevention Study (NBDPS) with estimated delivery dates from 1997 to 2002. Industrial hygienists reviewed occupational data from the computer-assisted telephone interview and assigned a yes/no rating of probable occupational PAH exposure for each job from 1 month before conception through delivery. We used logistic regression to assess the association between occupational exposure to PAHs and craniosynostosis. The prevalence of exposure was 5.3% in case mothers (16/300) and 3.7% in control mothers (107/2,886). We observed a positive association between exposure to PAHs during the 1 month before conception through the third month of pregnancy and craniosynostosis (odds ratio [OR] = 1.75; 95% confidence interval [CI], 1.01-3.05) after adjusting for maternal age and maternal education. The number of cases for each craniosynostosis subtype limited subtype analyses to sagittal craniosynostosis; the odds ratio remained similar (OR = 1.76, 95% CI, 0.82-3.75), but was not significant. Our findings support a moderate association between maternal occupational exposure to PAHs and craniosynostosis. Additional work is needed to better characterize susceptibility and the role PAHs may play on specific craniosynostosis subtypes. © 2015 Wiley Periodicals, Inc.

Ambient Air Pollution and Traffic Exposures and Congenital Heart Defects in the San Joaquin Valley of California

PubMed Central

Padula, Amy M.; Tager, Ira B.; Carmichael, Suzan L.; Hammond, S. Katharine; Yang, Wei; Lurmann, Frederick; Shaw, Gary M.

2013-01-01

Background Congenital anomalies are a leading cause of infant morbidity and mortality. Studies suggest associations between environmental contaminants and some anomalies, although evidence is limited. Methods We used data from the California Center of the National Birth Defects Prevention Study and the Children's Health and Air Pollution Study to estimate the odds of 27 congenital heart defects with respect to quartiles of 7 ambient air pollutant and traffic exposures in California during the first two months of pregnancy, 1997–2006 (N=813 cases and N=828 controls). Results Particulate matter <10 microns (PM10) was associated with pulmonary valve stenosis (aOR4th Quartile=2.6; 95% CI: 1.2, 5.7) and perimembranous ventricular septal defects (aOR3rd Quartile=2.1; 95% CI: 1.1, 3.9) after adjusting for maternal race-ethnicity, education and multivitamin use. PM2.5 was associated with transposition of the great arteries (aOR3rd Quartile=2.6; 95% CI: 1.1, 6.5) and inversely associated with perimembranous ventricular septal defects (aOR4th Quartile=0.5; 95% CI: 0.2, 0.9). Secundum atrial septal defects were inversely associated with carbon monoxide (aOR4th Quartile=0.4; 95% CI: 0.2, 0.8) and PM2.5 (aOR4th Quartile=0.5; 95% CI: 0.3, 0.8). Traffic density was associated with muscular ventricular septal defects (aOR4th Quartile=3.0, 95% CI: 1.2, 7.8) and perimembranous ventricular septal defects (aOR3rd Quartile =2.4; 95% CI: 1.3, 4.6), and inversely associated with transposition of the great arteries (aOR4th Quartile=0.3; 95% CI: 0.1, 0.8). Conclusions PM10 and traffic density may contribute to the occurrence of pulmonary valve stenosis and ventricular septal defects, respectively. The results were mixed for other pollutants and had little consistency with previous studies. PMID:23772934

Eliminating "Hotspots" in Digital Image Processing

NASA Technical Reports Server (NTRS)

Salomon, P. M.

1984-01-01

Signals from defective picture elements rejected. Image processing program for use with charge-coupled device (CCD) or other mosaic imager augmented with algorithm that compensates for common type of electronic defect. Algorithm prevents false interpretation of "hotspots". Used for robotics, image enhancement, image analysis and digital television.

Osteogenic Activity of Locally Applied Small Molecule Drugs in a Rat Femur Defect Model

PubMed Central

Cottrell, Jessica A.; Vales, Francis M.; Schachter, Deborah; Wadsworth, Scott; Gundlapalli, Rama; Kapadia, Rasesh; O'Connor, J. Patrick

2010-01-01

The long-term success of arthroplastic joints is dependent on the stabilization of the implant within the skeletal site. Movement of the arthroplastic implant within the bone can stimulate osteolysis, and therefore methods which promote rigid fixation or bone growth are expected to enhance implant stability and the long-term success of joint arthroplasty. In the present study, we used a simple bilateral bone defect model to analyze the osteogenic activity of three small-molecule drug implants via microcomputerized tomography (micro-CT) and histomorphometry. In this study, we show that local delivery of alendronate, but not lovastatin or omeprazole, led to significant new bone formation at the defect site. Since alendronate impedes osteoclast-development, it is theorized that alendronate treatment results in a net increase in bone formation by preventing osteoclast mediated remodeling of the newly formed bone and upregulating osteoblasts. PMID:20625499

[Spatial distribution of birth defects among children aged 0 to 5 years and its relationship with soil chemical elements in Chongqing].

PubMed

Dong, Yan; Zhong, Zhao-hui; Li, Hong; Li, Jie; Wang, Ying-xiong; Peng, Bin; Zhang, Mao-zhong; Huang, Qiao; Yan, Ju; Xu, Fei-long

2013-10-01

To explore the correlation between the incidence of birth defects and the contents of soil elements so as to provide a scientific basis for screening the related pathogenic factors that inducing birth defects for the development of related preventive and control strategies. MapInfo 7.0 software was used to draw the maps on spatial distribution regarding the incidence rates of birth defects and the contents of 11 chemical elements in soil in the 33 studied areas. Variables on the two maps were superposed for analyzing the spatial correlation. SAS 8.0 software was used to analyze single factor, multi-factors and principal components as well as to comprehensively evaluate the degrees of relevance. Different incidence rates of birth defects showed in the maps of spatial distribution presented certain degrees of negative correlation with anomalies of soil chemical elements, including copper, chrome, iodine, selenium, zinc while positively correlated with the levels of lead. Results from the principal component regression equation indicating that the contents of copper(0.002), arsenic(-0.07), cadmium(0.05), chrome (-0.001), zinc (0.001), iodine(-0.03), lead (0.08), fluorine(-0.002)might serve as important factors that related to the prevalence of birth defects. Through the study on spatial distribution, we noticed that the incidence rates of birth defects were related to the contents of copper, chrome, iodine, selenium, zinc, lead in soil while the contents of chrome, iodine and lead might lead to the occurrence of birth defects.

Effects of Radioprotective Agents on Foot Deformities and Gait Defects in the Prenatally X-Irradiated Rat.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ershoff, B. H.; Steers, C. W.; Kruger, L.

1962-11-01

The radioprotective agents AET, cysteamine, and MEG largely prevented the occurrence of foot deformities and a defect in gait in the young of rats exposed to a single dose of 150 r total-body x irradiation on the 14th day og pregnancy'. These substances also prevented in part the occurrence of an abnormality in development of the cerebral hemispheres of such young but were without significant effect in altering an attendant reduction in the ratio of brain to body weight.

Mechanisms of oxygen permeation through plastic films and barrier coatings

NASA Astrophysics Data System (ADS)

Wilski, Stefan; Wipperfürth, Jens; Jaritz, Montgomery; Kirchheim, Dennis; Mitschker, Felix; Awakowicz, Peter; Dahlmann, Rainer; Hopmann, Christian

2017-10-01

Oxygen and water vapour permeation through plastic films in food packaging or other applications with high demands on permeation are prevented by inorganic barrier films. Most of the permeation occurs through small defects (<3 µm) in the barrier coating. The defects were visualized by etching with reactive oxygen in a capacitively coupled plasma and subsequent SEM imaging. In this work, defects in SiO x -coatings deposited by plasma-enhanced chemical vapour deposition on polyethylene terephthalate (PET) are investigated and the mass transport through the polymer is simulated in a 3D approach. Calculations of single defects showed that there is no linear correlation between the defect area and the resulting permeability. The influence of adjacent defects in different distances was observed and led to flow reduction functions depending on the defect spacing and defect area. A critical defect spacing where no interaction between defects occurs was found and compared to other findings. According to the superposition principle, the permeability of single defects was added up and compared to experimentally determined oxygen permeation. The results showed the same trend of decreasing permeability with decreasing defect densities.

Folic acid and birth defect prevention

MedlinePlus

Preconceptional counseling. In: Cunningham FG, Leveno KL, Bloom SL, et al, eds. Williams Obstetrics. 24th ed. New York, NY: McGraw-Hill; 2014:chap 8. US Preventive Services Task Force. Folic acid for ...

Internal Prosthetic Replacement of Skeletal Segments Lost in Combat Injuries.

DTIC Science & Technology

1973-08-31

osteo- articular bone grafts. Clin. Ortho., 87: 156, 1972. 8. Tuli, S. M.: Bridging of bone defects by massive bone grafts in tumorous conditions. Clin...fashion in its proximal one-third to "prevent distractic ,n of the fragments. The fiber metal segment was then placed in the appropriate defect and the...defect slightly oversized and also osteotomizing the fibula to delete any possible distracting forces or angulating forces. The only complication in

Temporal and Spatial Analysis of Neural Tube Defects and Detection of Geographical Factors in Shanxi Province, China

PubMed Central

He, Lei; Wang, Jinfeng; Liu, Xin; Zhang, Ningxu; Xu, Bing

2016-01-01

Background Neural tube defects (NTDs) are congenital birth defects that occur in the central nervous system, and they have the highest incidence among all birth defects. Shanxi Province in China has the world’s highest rate of NTDs. Since the 1990s, China’s government has worked on many birth defect prevention programs to reduce the occurrence of NTDs, such as pregnancy planning, health education, genetic counseling, antenatal ultrasonography and serological screening. However, the rate of NTDs in Shanxi Province is still higher than the world’s average morbidity rate after intervention. In addition, Shanxi Province has abundant coal reserves, and is the largest coal production province in China. The objectives of this study are to determine the temporal and spatial variation of the NTD rate in rural areas of Shanxi Province, China, and identify geographical environmental factors that were associated with NTDs in the risk area. Methods In this study, Heshun County and Yuanping County in Shanxi Province, which have high incidence of NTDs, were selected as the study areas. Two paired sample T test was used to analyze the changes in the risk of NTDs from the time dimension. Ripley’s k function and spatial filtering were combined with geographic information system (GIS) software to study the changes in the risk of NTDs from the spatial dimension. In addition, geographical detectors were used to identify the risk geographical environmental factors of NTDs in the study areas, especially the areas close to the coal sites and main roads. Results In both Heshun County and Yuanping County, the incidence of NTDs was significantly (P<0.05) reduced after intervention. The results from spatial analysis showed that significant spatial heterogeneity existed in both counties. NTD clusters were still identified in areas close to coal sites and main roads after interventions. This study also revealed that the elevation, fault and soil types always had a larger influence on the incidence of NTDs in our study areas. In addition, distance to the river was a risk factor of NTDs in areas close to the coal sites and main roads. Conclusion The existing interventions may have played an important role to reduce the incidence of NTDs. However, there is still spatial heterogeneity in both counties after using the traditional intervention methods. The government needs to take more measures to strengthen the environmental restoration to prevent the occurrence of NTDs, especially those areas close to coal sites and main roads. The outcome of this research provides an important theoretical basis and technical support for the government to prevent the occurrence of NTDs. PMID:27100082

Hydroxyapatite nanobelt/polylactic acid Janus membrane with osteoinduction/barrier dual functions for precise bone defect repair.

PubMed

Ma, Baojin; Han, Jing; Zhang, Shan; Liu, Feng; Wang, Shicai; Duan, Jiazhi; Sang, Yuanhua; Jiang, Huaidong; Li, Dong; Ge, Shaohua; Yu, Jinghua; Liu, Hong

2018-04-15

Controllable osteoinduction maintained in the original defect area is the key to precise bone repair. To meet the requirement of precise bone regeneration, a hydroxyapatite (HAp) nanobelt/polylactic acid (PLA) (HAp/PLA) Janus membrane has been successfully prepared in this study by coating PLA on a paper-like HAp nanobelt film by a casting-pervaporation method. The Janus membrane possesses dual functions: excellent osteoinduction from the hydrophilic HAp nanobelt side and barrier function originating from the hydrophobic PLA film. The cell viability and osteogenic differentiation ability of human adipose-derived stem cells (hADSCs) on the Janus membrane were assessed. The in vitro experimental results prove that the HAp nanobelt side presents high cell viability and efficient osteoinduction without any growth factor and that the PLA side can prohibit cell attachment. The in vivo repair experiments on a rat mandible defect model prove that the PLA side can prevent postoperative adhesion between bone and adjacent soft tissues. Most importantly, the HAp side has a strong ability to promote defect repair and bone regeneration. Therefore, the HAp/PLA Janus membrane will have wide applications as a kind of tissue engineering material in precise bone repair because of its unique dual osteoinduction/barrier functions, biocompatibility, low cost, and its ability to be mass-produced. Precise bone defect repair to keeping tissue integrity and original outline shape is a very important issue for tissue engineering. Here, we have designed and prepared a novel HAp/PLA Janus membrane using a casting-pervaporation method to form a layer of PLA film on paper-like HAp nanobelt film. HAp nanobelt side of the Janus membrane can successfully promote osteogenic differentiation. PLA side of the Janus membrane exhibits good properties as a barrier for preventing the adhesion of cells in vitro. Mandible repair experiments in vivo have shown that the HAp/PLA Janus membrane can promote rat mandible repair on the HAp side and can successfully prevent postoperative adhesion on the PLA side at the same time. Therefore, the HAp/PLA Janus membrane with its osteoinduction/barrier dual functions can be applied to repair bone defect precisely. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

77 FR 24960 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [30Day-12-0010... Description CDC has been monitoring the occurrence of serious birth defects and genetic diseases in Atlanta... early warning system for new teratogens. In 1997, the Birth Defects Risk Factor Surveillance (BDRFS...

Ion beam collimating grid to reduce added defects

DOEpatents

Lindquist, Walter B.; Kearney, Patrick A.

2003-01-01

A collimating grid for an ion source located after the exit grid. The collimating grid collimates the ion beamlets and disallows beam spread and limits the beam divergence during transients and steady state operation. The additional exit or collimating grid prevents beam divergence during turn-on and turn-off and prevents ions from hitting the periphery of the target where there is re-deposited material or from missing the target and hitting the wall of the vessel where there is deposited material, thereby preventing defects from being deposited on a substrate to be coated. Thus, the addition of a collimating grid to an ion source ensures that the ion beam will hit and be confined to a specific target area.

Cartilage repair and joint preservation: medical and surgical treatment options.

PubMed

Madry, Henning; Grün, Ulrich Wolfgang; Knutsen, Gunnar

2011-10-01

Articular cartilage defects are most often caused by trauma and osteoarthritis and less commonly by metabolic disorders of the subchondral bone, such as osteonecrosis and osteochondritis dissecans. Such defects do not heal spontaneously in adults and can lead to secondary osteoarthritis. Medications are indicated for symptomatic relief. Slow-acting drugs in osteoarthritis (SADOA), such as glucosamine and chondroitin, are thought to prevent cartilage degeneration. Reconstructive surgical treatment strategies aim to form a repair tissue or to unload compartments of the joint with articular cartilage damage. In this article, we selectively review the pertinent literature, focusing on original publications of the past 5 years and older standard texts. Particular attention is paid to guidelines and clinical studies with a high level of evidence, along with review articles, clinical trials, and book chapters. There have been only a few randomized trials of medical versus surgical treatments. Pharmacological therapies are now available that are intended to treat the cartilage defect per se, rather than the associated symptoms, yet none of them has yet been shown to slow or reverse the progression of cartilage destruction. Surgical débridement of cartilage does not prevent the progression of osteoarthritis and is thus not recommended as the sole treatment. Marrow-stimulating procedures and osteochondral grafts are indicated for small focal articular cartilage defects, while autologous chondrocyte implantationis mainly indicated for larger cartilage defects. These surgical reconstructive techniques play a lesser role in the treatment of osteoarthritis. Osteotomy near the knee joint is indicated for axial realignment when unilateral osteoarthritis of the knee causes axis deviation. Surgical reconstructive techniques can improve joint function and thereby postpone the need for replacement of the articular surface with an artificial joint.

A Multivariate Dynamic Spatial Factor Model for Speciated Pollutants and Adverse Birth Outcomes

DOE PAGES

Kaufeld, Kimberly Ann; Fuentes, Montse; Reich, Brian J.; ...

2017-09-11

Evidence suggests that exposure to elevated concentrations of air pollution during pregnancy is associated with increased risks of birth defects and other adverse birth outcomes. While current regulations put limits on total PM2.5 concentrations, there are many speciated pollutants within this size class that likely have distinct effects on perinatal health. However, due to correlations between these speciated pollutants, it can be difficult to decipher their effects in a model for birth outcomes. To combat this difficulty, we develop a multivariate spatio-temporal Bayesian model for speciated particulate matter using dynamic spatial factors. These spatial factors can then be interpolated tomore » the pregnant women’s homes to be used to model birth defects. The birth defect model allows the impact of pollutants to vary across different weeks of the pregnancy in order to identify susceptible periods. Here, the proposed methodology is illustrated using pollutant monitoring data from the Environmental Protection Agency and birth records from the National Birth Defect Prevention Study.« less

A Multivariate Dynamic Spatial Factor Model for Speciated Pollutants and Adverse Birth Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaufeld, Kimberly Ann; Fuentes, Montse; Reich, Brian J.

Evidence suggests that exposure to elevated concentrations of air pollution during pregnancy is associated with increased risks of birth defects and other adverse birth outcomes. While current regulations put limits on total PM2.5 concentrations, there are many speciated pollutants within this size class that likely have distinct effects on perinatal health. However, due to correlations between these speciated pollutants, it can be difficult to decipher their effects in a model for birth outcomes. To combat this difficulty, we develop a multivariate spatio-temporal Bayesian model for speciated particulate matter using dynamic spatial factors. These spatial factors can then be interpolated tomore » the pregnant women’s homes to be used to model birth defects. The birth defect model allows the impact of pollutants to vary across different weeks of the pregnancy in order to identify susceptible periods. Here, the proposed methodology is illustrated using pollutant monitoring data from the Environmental Protection Agency and birth records from the National Birth Defect Prevention Study.« less

Improving surveillance for injuries associated with potential motor vehicle safety defects

PubMed Central

Whitfield, R; Whitfield, A

2004-01-01

Objective: To improve surveillance for deaths and injuries associated with potential motor vehicle safety defects. Design: Vehicles in fatal crashes can be studied for indications of potential defects using an "early warning" surveillance statistic previously suggested for screening reports of adverse drug reactions. This statistic is illustrated with time series data for fatal, tire related and fire related crashes. Geographic analyses are used to augment the tire related statistics. Results: A statistical criterion based on the Poisson distribution that tests the likelihood of an expected number of events, given the number of events that actually occurred, is a promising method that can be readily adapted for use in injury surveillance. Conclusions: Use of the demonstrated techniques could have helped to avert a well known injury surveillance failure. This method is adaptable to aid in the direction of engineering and statistical reviews to prevent deaths and injuries associated with potential motor vehicle safety defects using available databases. PMID:15066972

Preventing neural tube defects in Europe: a missed opportunity.

PubMed

Busby, Araceli; Abramsky, Lenore; Dolk, Helen; Armstrong, Ben; Addor, Marie-Claude; Anneren, Goran; Armstrong, Nicola; Baguette, Andre; Barisic, Ingeborg; Berghold, Andrea; Bianca, Sebastiano; Braz, Paula; Calzolari, Elisa; Christiansen, Marianne; Cocchi, Guido; Daltveit, Anne Kjersti; De Walle, Hermien; Edwards, Grace; Gatt, Miriam; Gener, Blanca; Gillerot, Yves; Gjergja, Romana; Goujard, Janine; Haeusler, Martin; Latos-Bielenska, Anna; McDonnell, Robert; Neville, Amanda; Olars, Birgitta; Portillo, Isabel; Ritvanen, Annukka; Robert-Gnansia, Elizabeth; Rösch, Christine; Scarano, Gioacchino; Steinbicker, Volker

2005-01-01

Each year, more than 4500 pregnancies in the European Union are affected by neural tube defects (NTD). Unambiguous evidence of the effectiveness of periconceptional folic acid in preventing the majority of neural tube defects has been available since 1991. We report on trends in the total prevalence of neural tube defects up to 2002, in the context of a survey in 18 European countries of periconceptional folic acid supplementation (PFAS) policies and their implementation. EUROCAT is a network of population-based registries in Europe collaborating in the epidemiological surveillance of congenital anomalies. Representatives from 18 participating countries provided information about policy, health education campaigns and surveys of PFAS uptake. The yearly total prevalence of neural tube defects including livebirths, stillbirths and terminations of pregnancy was calculated from 1980 to 2002 for 34 registries, with UK and Ireland estimated separately from the rest of Europe. A meta-analysis of changes in NTD total prevalence between 1989-1991 and 2000-2002 according to PFAS policy was undertaken for 24 registries. By 2005, 13 countries had a government recommendation that women planning a pregnancy should take 0.4mg folic acid supplement daily, accompanied in 7 countries by government-led health education initiatives. In the UK and Ireland, countries with PFAS policy, there was a 30% decline in NTD total prevalence (95% CI 16-42%) but it was difficult to distinguish this from the pre-existing strong decline. In other European countries with PFAS policy, there was virtually no decline in NTD total prevalence whether a policy was in place by 1999 (2%, 95% CI 28% reduction to 32% increase) or not (8%, 95% CI 26% reduction to 16% increase). The potential for preventing NTDs by periconceptional folic acid supplementation is still far from being fulfilled in Europe. Only a public health policy including folic acid fortification of staple foods is likely to result in large-scale prevention of NTDs.

How genetics came to the unborn: 1960-2000.

PubMed

Löwy, Ilana

2014-09-01

Prenatal diagnosis (PND) is frequently identified with genetic testing. The termination of pregnancy for foetal malformation was called 'genetic abortion', in spite of the fact that in many cases the malformation does not result from changes in the genetic material of the cell. This study argues that the 'geneticization' of PND reflected the transformation of the meaning of the term 'genetics' in the 1960s and 70s. Such transformation was linked with the definition of Down syndrome as a genetic condition, and to the key role of search for this condition in the transformation of PND into a routine approach. The identification of PND with the polysemic term 'genetics' was also favoured by hopes that cytogenetic studies will lead to cures or prevention of common birth defects, the association of genetic counsellors with prenatal diagnosis, and the raising prestige of clinical genetics. In spite of the impressive achievements of the latter specialty, more than fifty years after the first prenatal diagnoses, the main 'cure' of a severe foetal malformation remains the same as it was in the 1960s: the termination of a pregnancy. The identification of PND with genetics deflects attention from the gap between scientists' capacity to elucidate the causes of numerous birth defects and their ability (as for now) to prevent or treat these defects, and favours the maintenance of a powerful regimen of hope. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impact of Time to Maternal Interview on Interview Responses in the National Birth Defects Prevention Study

PubMed Central

Tinker, Sarah C.; Gibbs, Cassandra; Strickland, Matthew J.; Devine, Owen J.; Crider, Krista S.; Werler, Martha M.; Anderka, Marlene T.; Reefhuis, Jennita

2013-01-01

Prenatal exposures often are assessed using retrospective interviews. Time from exposure to interview may influence data accuracy. We investigated the association of time to interview (TTI) with aspects of interview responses in the National Birth Defects Prevention Study, a population-based case-control study of birth defects in 10 US states. Mothers completed a computer-assisted telephone interview 1.5–24 months after their estimated date of delivery. Proxy metrics for interview quality were whether certain exposures were reported, whether the start month of reported medication use or illness was reported, or whether responses were missing. Interaction by case status was assessed. Interviews were completed with 30,542 mothers (22,366 cases and 8,176 controls) who gave birth between 1997 and 2007. Mothers of cases were interviewed later than were mothers of controls (11.7 months vs. 9.5 months, respectively). In adjusted analyses, having a TTI that was greater than 6 months was associated with only a few aspects of interview responses (e.g., start month of pseudoephedrine use). Interaction by case-control status was observed for some exposures; mothers of controls had a greater reduction in interview quality with increased TTI in these instances (e.g., report of morning sickness, start month of acetaminophen use and ibuprofen use). The results suggest that TTI might impact interview responses; however, the impact may be minimal and specific to the type of exposure. PMID:23645625

Impact of time to maternal interview on interview responses in the National Birth Defects Prevention Study.

PubMed

Tinker, Sarah C; Gibbs, Cassandra; Strickland, Matthew J; Devine, Owen J; Crider, Krista S; Werler, Martha M; Anderka, Marlene T; Reefhuis, Jennita

2013-06-01

Prenatal exposures often are assessed using retrospective interviews. Time from exposure to interview may influence data accuracy. We investigated the association of time to interview (TTI) with aspects of interview responses in the National Birth Defects Prevention Study, a population-based case-control study of birth defects in 10 US states. Mothers completed a computer-assisted telephone interview 1.5-24 months after their estimated date of delivery. Proxy metrics for interview quality were whether certain exposures were reported, whether the start month of reported medication use or illness was reported, or whether responses were missing. Interaction by case status was assessed. Interviews were completed with 30,542 mothers (22,366 cases and 8,176 controls) who gave birth between 1997 and 2007. Mothers of cases were interviewed later than were mothers of controls (11.7 months vs. 9.5 months, respectively). In adjusted analyses, having a TTI that was greater than 6 months was associated with only a few aspects of interview responses (e.g., start month of pseudoephedrine use). Interaction by case-control status was observed for some exposures; mothers of controls had a greater reduction in interview quality with increased TTI in these instances (e.g., report of morning sickness, start month of acetaminophen use and ibuprofen use). The results suggest that TTI might impact interview responses; however, the impact may be minimal and specific to the type of exposure.

Microcomputed tomographic and histomorphometric analyses of novel titanium mesh membranes for guided bone regeneration: a study in rat calvarial defects.

PubMed

Rakhmatia, Yunia Dwi; Ayukawa, Yasunori; Furuhashi, Akihiro; Koyano, Kiyoshi

2014-01-01

The objective of this study was to evaluate the optimal thickness and porosity of novel titanium mesh membranes to enhance bone augmentation, prevent soft tissue ingrowth, and prevent membrane exposure. Six types of novel titanium meshes with different thicknesses and pore sizes, along with three commercially available membranes, were used to cover surgically created calvarial defects in 6-week-old Sprague-Dawley rats. The animals were killed after 4 or 8 weeks. Microcomputed tomographic analyses were performed to analyze the three-dimensional bone volume and bone mineral density. Soft tissue ingrowth was also evaluated histologically and histomorphometrically. The novel titanium membranes used in this study were as effective at augmenting bone in the rat calvarial defect model as the commercially available membranes. The greatest bone volume was observed on 100-μm-thick membranes with larger pores, although these membranes promoted growth of bone with lower mineral density. Soft tissue ingrowth when 100-μm membranes were used was increased at 4 weeks but decreased again by 8 weeks to a level not statistically significantly different from other membranes. Membrane thickness affects the total amount of new bone formation, and membrane porosity is an essential factor for guided bone regeneration, especially during the initial healing period, although the final bone volume obtained is essentially the same. Newly developed titanium mesh membranes of 100 μm in thickness and with large pores appear to be optimal for guided bone regeneration.

Developing effective campaign messages to prevent neural tube defects: a qualitative assessment of women's reactions to advertising concepts.

PubMed

Massi Lindsey, Lisa L; Silk, Kami J; Von Friederichs-Fitzwater, Marlene M; Hamner, Heather C; Prue, Christine E; Boster, Franklin J

2009-03-01

The incidence of neural tube defects (NTDs), serious birth defects of the brain and spine that affect approximately 3,000 pregnancies in the United States each year, can be reduced by 50-70% with daily periconceptional consumption of the B vitamin folic acid. Two studies were designed to assess college women's reactions to and perceptions of potential campaign advertising concepts derived from preproduction formative research to increase folic acid consumption through the use of a daily multivitamin. Study one assessed draft advertising concepts in eight focus groups (N = 71) composed of college-enrolled women in four cities geographically dispersed across the United States. Based on study one results, the concepts were revised and reassessed in study two with a different sample (eight focus groups; N = 73) of college women in the same four cities. Results indicated that participants generally responded favorably to concepts in each of the two studies, and provided insight into individual concepts to increase their overall appeal and effectiveness. The specific findings and implications of these results are discussed.

Topology and strong four fermion interactions in four dimensions

NASA Astrophysics Data System (ADS)

Catterall, Simon; Butt, Nouman

2018-05-01

We study massless fermions interacting through a particular four-fermion term in four dimensions. Exact symmetries prevent the generation of bilinear fermion mass terms. We determine the structure of the low-energy effective action for the auxiliary field needed to generate the four-fermion term and find it has an novel structure that admits topologically nontrivial defects with nonzero Hopf invariant. We show that fermions propagating in such a background pick up a mass without breaking symmetries. Furthermore, pairs of such defects experience a logarithmic interaction. We argue that a phase transition separates a phase where these defects proliferate from a broken phase where they are bound tightly. We conjecture that, by tuning one additional operator, the broken phase can be eliminated with a single BKT-like phase transition separating the massless from massive phases.

HOW to Recognize Hazardous Defects in Trees

Treesearch

Minnesota Department of Natural Resources; USDA Forest Service

1996-01-01

Trees add to our enjoyment of outdoor experiences whether in forests, parks, or urban landscapes. Too often, we are unaware of the risks associated with defective trees, which can cause personal injury and property damage. Interest in hazard tree management has increased in recent years due to safety and liability concerns resulting from preventable accidents....

Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets

PubMed Central

Muralidharan, Pooja; Sarmah, Swapnalee; Zhou, Feng C.; Marrs, James A.

2013-01-01

Fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection. PMID:24961433

Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets.

PubMed

Muralidharan, Pooja; Sarmah, Swapnalee; Zhou, Feng C; Marrs, James A

2013-06-19

Fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection.

Neural circuit architecture defects in a Drosophila model of Fragile X syndrome are alleviated by minocycline treatment and genetic removal of matrix metalloproteinase

PubMed Central

Siller, Saul S.; Broadie, Kendal

2011-01-01

SUMMARY Fragile X syndrome (FXS), caused by loss of the fragile X mental retardation 1 (FMR1) product (FMRP), is the most common cause of inherited intellectual disability and autism spectrum disorders. FXS patients suffer multiple behavioral symptoms, including hyperactivity, disrupted circadian cycles, and learning and memory deficits. Recently, a study in the mouse FXS model showed that the tetracycline derivative minocycline effectively remediates the disease state via a proposed matrix metalloproteinase (MMP) inhibition mechanism. Here, we use the well-characterized Drosophila FXS model to assess the effects of minocycline treatment on multiple neural circuit morphological defects and to investigate the MMP hypothesis. We first treat Drosophila Fmr1 (dfmr1) null animals with minocycline to assay the effects on mutant synaptic architecture in three disparate locations: the neuromuscular junction (NMJ), clock neurons in the circadian activity circuit and Kenyon cells in the mushroom body learning and memory center. We find that minocycline effectively restores normal synaptic structure in all three circuits, promising therapeutic potential for FXS treatment. We next tested the MMP hypothesis by assaying the effects of overexpressing the sole Drosophila tissue inhibitor of MMP (TIMP) in dfmr1 null mutants. We find that TIMP overexpression effectively prevents defects in the NMJ synaptic architecture in dfmr1 mutants. Moreover, co-removal of dfmr1 similarly rescues TIMP overexpression phenotypes, including cellular tracheal defects and lethality. To further test the MMP hypothesis, we generated dfmr1;mmp1 double null mutants. Null mmp1 mutants are 100% lethal and display cellular tracheal defects, but co-removal of dfmr1 allows adult viability and prevents tracheal defects. Conversely, co-removal of mmp1 ameliorates the NMJ synaptic architecture defects in dfmr1 null mutants, despite the lack of detectable difference in MMP1 expression or gelatinase activity between the single dfmr1 mutants and controls. These results support minocycline as a promising potential FXS treatment and suggest that it might act via MMP inhibition. We conclude that FMRP and TIMP pathways interact in a reciprocal, bidirectional manner. PMID:21669931

[Errors in medical care rendered by military treatment and prevention institutions (according to the data of forensic medical expertise].

PubMed

Kolkutin, V V; Fetisov, V A

2003-12-01

The authors discuss one of the important aspects of military medicolegal laboratory activities connected with the quality control of medical care rendered in the military treatment-and-prophylactic institutions in the nineties of the XX century. The example of medical care defects (MCD) permitted to reveal their nature, causes and sites of origin at pre-hospital (PHS) and hospital (HS) stages. Despite some decrease in the total number of MCD revealed HS defects prevail (more than 75%); the organizational defects at PHS and diagnostic defects at HS are predominant. The main MCD causes are inadequate qualification of medical workers, defects in organization of treatment-and-diagnostic process and inadequate examination of patients.

Attaining human dignity for people with birth defects: a historical perspective.

PubMed

Christianson, Arnold L

2013-10-11

People with birth defects have been stigmatised, marginalised and discriminated against for millennia, diminishing their human dignity and abrogating their human rights. Beginning with the United Nations Universal Declaration of Human Rights, promulgated in 1947, the circumstances in which human dignity in healthcare for people with birth defects could be achieved arose, and this was accomplished over the next 65 years through the insight, hard work and dedication of a select group of people and organisations. In 2010 the World Health Organization prioritised services for the care and prevention of birth defects, particularly in middle- and low-income countries. Translating what has been achieved into human rights in healthcare for people with birth defects is the next objective. 

Defective Reduction in Frozen Pie Manufacturing Process

NASA Astrophysics Data System (ADS)

Nooted, Oranuch; Tangjitsitcharoen, Somkiat

2017-06-01

The frozen pie production has a lot of defects resulting in high production cost. Failure mode and effect analysis (FMEA) technique has been applied to improve the frozen pie process. Pareto chart is also used to determine the major defects of frozen pie. There are 3 main processes that cause the defects which are the 1st freezing to glazing process, the forming process, and the folding process. The Risk Priority Number (RPN) obtained from FMEA is analyzed to reduce the defects. If RPN of each cause exceeds 45, the process will be considered to be improved and selected for the corrective and preventive actions. The results showed that RPN values decreased after the correction. Therefore, the implementation of FMEA technique can help to improve the performance of frozen pie process and reduce the defects approximately 51.9%.

Reconstruction of a pelvic floor defect using a pedicled tensor fascia lata flap: a new technique to prevent radiation injury for pediatric patients with advanced pelvic tumors.

PubMed

Ohno, Yasuharu; Tanaka, Katsumi; Kanematsu, Takashi; Noguchi, Mitsuru; Okada, Masahiko; Kamitamari, Akira; Hayashi, Nobuyuki

2008-05-01

In the treatment of pelvic tumors, pelvic floor defects owing to a wide excision tend to increase the occurrence of such morbidities as radiation injury. The reconstruction of these defects would minimize the risk of such morbidities. Authors introduce a new technique for repairing a pelvic floor defect using a tensor fascia lata flap. Two boys, 4 years old and 10 months old, presenting with pelvic rhabdomyosarcoma underwent a tumor extirpation associated with a wide excision of the pelvic organs. After the removal of the tumor, a tensor fascia lata flap was designed on the right thigh. The pedicled rotation flap was subcutaneously elevated, guided to the intraperitoneal cavity, and was fixed to cover the superior aperture of the lesser pelvis. The flaps functioned well, and postoperative radiation therapies consisting of 45 and 41.4 Gy to the lesser pelvic cavity were carried out without any complications. As a result, the necessary postoperative protocol combination therapies could be successfully performed in a timely manner. The pedicled tensor fascia lata flap is considered to be an alternative option for the stable repair of pelvic floor defects to prevent radiation injury.

[Experimental study on long-term prevention effect of chitosan electrospun membrane on cerebrospinal fluid leakage].

PubMed

Guo, Xingfeng; Hou, Chunlin; Dou, Yuandong; Lin, Ye; Lei, Deqiao

2014-08-01

To study the long-term prevention effect of self-developed chitosan electrospun membrane on cerebrospinal fluid leakage. Twenty-five healthy adult New Zealand rabbits were selected to prepare the bilateral dural defect (0.8 cem x 0.8 cm in size) via midline incision of head. Defect of the right was repaired with chitosan electrospun membrane as the experimental group; defect of the left was not repaired as the control group. At 2-16 weeks after operation, one rabbit was sacrificed for the general observation of inflammatory response surrounding bone window and absorption of chitosan electrospun membrane; at 3 and 6 weeks after operation, 5 rabbits were sacrificed for sampling to observe histological change and collagen expression by_HE and Masson staining, and to measure the expressions of epidermal growth factor receptor (EGFR) and basic fibroblast growth factor (bFGF) by immunohistochemical staining. No inflammatory reaction of swelling, exudation, and sppuration appeared in the skin and subcutaneous tissue after operation in 2 groups. There was no adhesion around the chitosan electrospun membrane, and new fiber membrane formed under the chitosan electrospun membrane in the experimental group; no cerebrospinal fluid leakage happened; the chitosan electrospun membrane was gradually degraded with time, and was completely absorbed at 16 weeks. There was uneven scar around the dural detect in control group. Histological observation showed less inflammatory cell infiltration in the experimental group, showing significant difference in the number of inflammatory cells compared with control group at 3, 6 weeks (P < 0.05); capillary, granulation tissue and collagen fiber massively proliferated; collagen fiber arranged in line, and there was a clear borderline between chitosan electrospurn membrane and adjacent collagen fiber. The immunohistochemical staining showed that there were high expressions of bFGF and EGFR in the experimental group, and low expressions of bFGF and EGFR in the control group. Chitosan electrospun membrane for dural defect of rabbit can effectively reconstruct the dura, and it has exact long-term prevention effect on cerebrospinal fluid leakage.

Birth defects: Risk factors and consequences

PubMed Central

Oliveira, Camila Ive Ferreira; Fett-Conte, Agnes Cristina

2013-01-01

Birth defects (BDs) or congenital anomalies include all structural and functional alterations in embryonic or fetal development resulting from genetic, environmental or unknown causes, which result in physical and/or mental impairment. BDs occur in about 3% of newborn babies and in most cases of pregnancy loss. BDs are a very complex and heterogeneous group of single or multiple changes that, in most cases, are of unknown etiology. Among the risk factors are advanced maternal and paternal ages, parental consanguinity, teratogenic agents such as infectious agents and drugs, and poor nutrition, in particular folic acid deficiency. One of the consequences of these defects is the high death rate within the first year of life. Information on BDs is becoming increasingly more important throughout the world so that preventive measures can be taken. Knowledge of BDs enables the development of therapeutic and preventive strategies besides adequate genetic counseling. PMID:27625844

Child Care Provider Awareness and Prevention of Cytomegalovirus and Other Infectious Diseases

ERIC Educational Resources Information Center

Thackeray, Rosemary; Magnusson, Brianna M.

2016-01-01

Background: Child care facilities are prime locations for the transmission of infectious and communicable diseases. Children and child care providers are at high risk for cytomegalovirus (CMV) infection which causes severe birth defects and developmental delays. Objective: The goals of study were: (1) to determine the level of cytomegalovirus…

Conditions for Further Study: Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure

ERIC Educational Resources Information Center

Hart, Shelley R.; Harrison, Molly J.

2017-01-01

The Alcohol Abuse and Alcoholism branch of the National Institute of Health (NIH) indicates that there is no known safe level of alcohol consumption during pregnancy (NIH, 2015). Prenatal alcohol exposure (PAE) is the leading preventable cause of birth defects and neurodevelopmental abnormalities in the United States, which is not surprising given…

TNFalpha-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, Akt and NFkappaB signaling.

PubMed

Amasheh, Maren; Fromm, Anja; Krug, Susanne M; Amasheh, Salah; Andres, Susanne; Zeitz, Martin; Fromm, Michael; Schulzke, Jörg-Dieter

2010-12-01

TNFα-mediated tight junction defects contribute to diarrhea in inflammatory bowel diseases (IBDs). In our study, the signaling pathways of the TNFα effect on barrier- or pore-forming claudins were analyzed in HT-29/B6 human colon monolayers. Berberine, a herbal therapeutic agent that has been recently established as a therapy for diabetes and hypercholesterinemia, was able to completely antagonize the TNFα-mediated barrier defects in the cell model and in rat colon. Ussing chamber experiments and two-path impedance spectroscopy revealed a decrease of paracellular resistance after TNFα to 11±4%, whereas transcellular resistance was unchanged. The permeability of the paracellular marker fluorescein was increased fourfold. Berberine alone had no effect while it fully prevented the TNFα-induced barrier defects. This effect on resistance was confirmed in rat colon. TNFα removed claudin-1 from the tight junction and increased claudin-2 expression. Berberine prevented TNFα-induced claudin-1 disassembly and upregulation of claudin-2. The effects of berberine were mimicked by genistein plus BAY11-7082, indicating that they are mediated via tyrosine kinase, pAkt and NFκB pathways. In conclusion, the anti-diarrheal effect of berberine is explained by a novel mechanism, suggesting a therapeutic approach against barrier breakdown in intestinal inflammation.

Ambient air pollution and traffic exposures and congenital heart defects in the San Joaquin Valley of California.

PubMed

Padula, Amy M; Tager, Ira B; Carmichael, Suzan L; Hammond, S Katharine; Yang, Wei; Lurmann, Frederick; Shaw, Gary M

2013-07-01

Congenital anomalies are a leading cause of infant morbidity and mortality. Studies suggest associations between environmental contaminants and some anomalies, although evidence is limited. We used data from the California Center of the National Birth Defects Prevention Study and the Children's Health and Air Pollution Study to estimate the odds of 27 congenital heart defects with respect to quartiles of seven ambient air pollutant and traffic exposures in California during the first 2 months of pregnancy, 1997-2006 (n = 822 cases and n = 849 controls). Particulate matter < 10 microns (PM10 ) was associated with pulmonary valve stenosis [adjusted odds ratio (aOR)Fourth Quartile  = 2.6] [95% confidence intervals (CI) 1.2, 5.7] and perimembranous ventricular septal defects (aORThird Quartile  = 2.1) [95% CI 1.1, 3.9] after adjusting for maternal race/ethnicity, education and multivitamin use. PM2.5 was associated with transposition of the great arteries (aORThird Quartile  = 2.6) [95% CI 1.1, 6.5] and inversely associated with perimembranous ventricular septal defects (aORFourth Quartile  = 0.5) [95% CI 0.2, 0.9]. Secundum atrial septal defects were inversely associated with carbon monoxide (aORFourth Quartile  = 0.4) [95% CI 0.2, 0.8] and PM2.5 (aORFourth Quartile  = 0.5) [95% CI 0.3, 0.8]. Traffic density was associated with muscular ventricular septal defects (aORFourth Quartile  = 3.0) [95% CI 1.2, 7.8] and perimembranous ventricular septal defects (aORThird Quartile  = 2.4) [95% CI 1.3, 4.6], and inversely associated with transposition of the great arteries (aORFourth Quartile  = 0.3) [95% CI 0.1, 0.8]. PM10 and traffic density may contribute to the occurrence of pulmonary valve stenosis and ventricular septal defects, respectively. The results were mixed for other pollutants and had little consistency with previous studies. © 2013 John Wiley & Sons Ltd.

Congenital Abnormalities: Consequence of Maternal Zika Virus Infection: A Narrative Review.

PubMed

Hassan, Fatima I; Niaz, Kamal; Maqbool, Faheem; Khan, Fazlullah; Abdollahi, Mohammad

2017-01-01

Zika virus (ZIKV) is a deadly flavivirus that has spread from Africa to Asia and European countries. The virus is associated with other viruses in the same genus or family, transmitted by the same mosquito species with known history of fatality. A sudden increase in the rate of infection from ZIKV has made it a global health concern, which necessitates close symptom monitoring, enhancing treatment options, and vaccine production. This paper reviewed current reports on birth defects associated with ZIKV, mode of transmission, body fluids containing the virus, diagnosis, possible preventive measures or treatments, and vaccine development. Google scholar was used as the major search engine for research and review articles, up to July, 2016. Search terms such as "ZIKV", "ZIKV infection", "ZIKV serotypes", "treatment of ZIKV infection", "co-infection with zika virus", "flavivirus", "microcephaly and zika", "birth defects and Zika", as well as "ZIKV vaccine" were used. ZIKV has been detected in several body fluids such as saliva, semen, blood, and amniotic fluid. This reveals the possibility of sexual and mother to child transmission. The ability of the virus to cross the placental barrier and the blood brain barrier (BBB) has been associated with birth defects such as microcephaly, ocular defects, and Guillian Barre syndrome (GBS). Preventive measures can reduce the spread and risk of the infection. Available treatments only target symptoms while vaccines are still under development. Birth defects are associated with ZIKV infection in pregnant women; hence the need for development of standard treatments, employment of strict preventive measures and development of effective vaccines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

College women's reported behaviors and beliefs regarding fish and folic acid and their roles in birth defects.

PubMed

Burak, Lydia J; Costello, Pamela

2006-10-01

The purpose of the current study was to examine college women's beliefs and behaviors regarding birth defect prevention via folic acid intake and avoidance of fish with high mercury levels. We surveyed 313 college women and found that the majority of them reported eating fish despite their awareness that certain types of fish contained levels of mercury that are dangerous for women of childbearing age. We also found that the majority of the women did not comply with dietary guidelines for vegetable and legume consumption, and more than half of them did not take vitamin supplements that provide folic acid.

Differences in risk factors for 2nd and 3rd degree hypospadias in the National Birth Defects Prevention Study

PubMed Central

in 't Woud, Sander Groen; van Rooij, Iris A.L.M.; van Gelder, Marleen M.H.J.; Olney, Richard S.; Carmichael, Suzan L.; Roeleveld, Nel; Reefhuis, Jennita

2015-01-01

Background Hypospadias is a frequent birth defect with three phenotypic subtypes. With data from the National Birth Defects Prevention Study, a large, multi-state, population-based, case-control study, we compared risk factors for second and third degree hypospadias. Methods A wide variety of data on maternal and pregnancy-related risk factors for isolated second and third degree hypospadias was collected via computer-assisted telephone interviews to identify potential etiological differences between the two phenotypes. Logistic regression was used to calculate odds ratios including a random effect by study center. Results In total, 1547 second degree cases, 389 third degree cases, and 5183 male controls were included in our study. Third degree cases were more likely to have a non-Hispanic black or Asian/Pacific Islander mother, be delivered preterm, have a low birth weight, be small for gestational age, and be conceived with fertility treatments than second degree cases and controls. Associations with both second and third degree hypospadias were observed for maternal age, family history, parity, plurality, and hypertension during pregnancy. Risk estimates were generally higher for third degree hypospadias except for family history. Conclusions Most risk factors were associated with both or neither phenotype. Therefore, it is likely that the underlying mechanism is at least partly similar for both phenotypes. However, some associations were different between 2nd and 3rd degree hypospadias, and went in opposite directions for second and third degree hypospadias for Asian/Pacific Islander mothers. Effect estimates for subtypes of hypospadias may be over- or underestimated in studies without stratification by phenotype. PMID:25181604

A new, treatable source of recurrent meningitis: basioccipital meningocele.

PubMed

Hemphill, M; Freeman, J M; Martinez, C R; Nager, G T; Long, D M; Crumrine, P

1982-12-01

A 19-month-old boy suffered eight episodes of bacterial meningitis. During the ninth episode a meningocele of the basioccipital clivus communicating with the nasopharynx was discovered. Identification of the organism causing the episodes of meningitis was not helpful in pointing to the site of this congenital anatomic defect. Surgical closure of the defect has prevented further recurrences.

Maternal caffeine consumption and risk of cardiovascular malformations.

PubMed

Browne, Marilyn L; Bell, Erin M; Druschel, Charlotte M; Gensburg, Lenore J; Mitchell, Allen A; Lin, Angela E; Romitti, Paul A; Correa, Adolfo

2007-07-01

The physiologic effects and common use of caffeine during pregnancy call for examination of maternal caffeine consumption and risk of birth defects. Epidemiologic studies have yielded mixed results, but such studies have grouped etiologically different defects and have not evaluated effect modification. The large sample size and precise case classification of the National Birth Defects Prevention Study allowed us to examine caffeine consumption and specific cardiovascular malformation (CVM) case groups. We studied consumption of caffeinated coffee, tea, soda, and chocolate to estimate total caffeine intake and separately examined exposure to each caffeinated beverage. Smoking, alcohol, vasoactive medications, folic acid supplement use, and infant gender were evaluated for effect modification. Maternal interview reports for 4,196 CVM case infants overall and 3,957 control infants were analyzed. We did not identify any significant positive associations between maternal caffeine consumption and CVMs. For tetralogy of Fallot, nonsignificant elevations in risk were observed for moderate (but not high) caffeine intake overall and among nonsmokers (ORs of 1.3 to 1.5). Risk estimates for both smoking and consuming caffeine were less than the sum of the excess risks for each exposure. We observed an inverse trend between coffee intake and risk of atrial septal defect; however, this single significant pattern of association might have been a chance finding. Our study found no evidence for an appreciable teratogenic effect of caffeine with regard to CVMs. (c) 2007 Wiley-Liss, Inc.

Venous Thromboembolism Quality Measures Fail to Accurately Measure Quality.

PubMed

Lau, Brandyn D; Streiff, Michael B; Pronovost, Peter J; Haut, Elliott R

2018-03-20

Venous thromboembolism (VTE) is 1 of the most common causes of preventable harm for patients in hospitals. Consequently, the Joint Commission, the Centers for Medicare and Medicaid Services, the Agency for Healthcare Research and Quality, the United Kingdom Care Quality Commission, the Australian Commission on Safety and Quality in Health Care, the Maryland Health Services Cost Review Commission, and the American College of Surgeons have prioritized measuring and reporting VTE outcomes with the goal of reducing the incidence of and preventable harm from VTE. We developed a rubric for defect-free VTE prevention, graded each organizational VTE quality measure, and found that none of the current VTE-related quality measures adequately characterizes VTE prevention efforts or outcomes in hospitalized patients. Effective VTE prevention is multifactorial: clinicians must assess patients' risk for VTE and prescribe therapy appropriate for each patient's risk profile, patients must accept the prescribed therapy, and nurses must administer the therapy as prescribed. First, an ideal, defect-free VTE prevention process measure requires: (1) documentation of a standardized VTE risk assessment; (2) prescription of optimal, risk-appropriate VTE prophylaxis; and (3) administration of all risk-appropriate VTE prophylaxis as prescribed. Second, an ideal VTE outcome measure should define potentially preventable VTE as VTE that developed in patients who experienced any VTE prevention process failures. © 2018 American Heart Association, Inc.

The use of folic acid for the prevention of birth defects in Puerto Rico

PubMed Central

García-Fragoso, Lourdes; García-García, Inés; Rivera, Cynthia E.

2009-01-01

Introduction The occurrence of neural tube defects (NTD) has been shown to vary by race/ethnicity, with the highest rates among women of Hispanic ethnicity. Women of reproductive age are advised to use folic acid to prevent NTD and other birth defects. Since 1994, Puerto Rico has a campaign to promote the use of folic acid and since 1998 there is fortification of enriched grain products. After fortification, there has been a reduction in the incidence of NTD in the island. The objective of this study is to assess the use of folic acid by women of reproductive age in Puerto Rico and determine factors associated to its use. Methods A self-administered questionnaire was answered by 964 women around the island. Results Folic acid consumption was reported by 30% of the participants, 21% reported to consume it at least 4 times per week, and only 14% consumed it the day before the survey. Knowledge about the recommendation for women to consume folic acid was reported by 97% of the participants. The use of folic acid was lower among women of lower education and lower social class. Women with higher education were 8.3 times more likely to consume folic acid. Conclusion The folic acid campaign has improved women’s knowledge about the recommendation for folic acid supplementation. Nevertheless, its use is lower than desired to continue reducing the incidence of birth defects in Puerto Rico. Education and social class continue to represent barriers to eliminate the disparities in the pre-conception health of our population. PMID:18646342

Wet particle source identification and reduction using a new filter cleaning process

NASA Astrophysics Data System (ADS)

Umeda, Toru; Morita, Akihiko; Shimizu, Hideki; Tsuzuki, Shuichi

2014-03-01

Wet particle reduction during filter installation and start-up aligns closely with initiatives to reduce both chemical consumption and preventative maintenance time. The present study focuses on the effects of filter materials cleanliness on wet particle defectivity through evaluation of filters that have been treated with a new enhanced cleaning process focused on organic compounds reduction. Little difference in filter performance is observed between the two filter types at a size detection threshold of 60 nm, while clear differences are observed at that of 26 nm. It can be suggested that organic compounds can be identified as a potential source of wet particles. Pall recommends filters that have been treated with the special cleaning process for applications with a critical defect size of less than 60 nm. Standard filter products are capable to satisfy wet particle defect performance criteria in less critical lithography applications.

Neural tube defects – recent advances, unsolved questions and controversies

PubMed Central

Copp, Andrew J.; Stanier, Philip; Greene, Nicholas D. E.

2014-01-01

Neural tube defects (NTDs) are severe congenital malformations affecting around 1 in every 1000 pregnancies. Here we review recent advances and currently unsolved issues in the NTD field. An innovation in clinical management has come from the demonstration that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention by folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in UK. Genetic predisposition comprises the majority of NTD risk, and genes that regulate folate one-carbon metabolism and planar cell polarity have been strongly implicated. The sequence of human neural tube closure events remains controversial, but study of mouse NTD models shows that anencephaly, open spina bifida and craniorachischisis result from failure of primary neurulation, while skin-covered spinal dysraphism results from defective secondary neurulation. Other ‘NTD’ malformations, such as encephalocele, are likely to be post-neurulation disorders. PMID:23790957

Etiology and clinical presentation of birth defects: population based study

PubMed Central

Carey, John C; Byrne, Janice L B; Krikov, Sergey; Botto, Lorenzo D

2017-01-01

Objective To assess causation and clinical presentation of major birth defects. Design Population based case cohort. Setting Cases of birth defects in children born 2005-09 to resident women, ascertained through Utah’s population based surveillance system. All records underwent clinical re-review. Participants 5504 cases among 270 878 births (prevalence 2.03%), excluding mild isolated conditions (such as muscular ventricular septal defects, distal hypospadias). Main outcome measures The primary outcomes were the proportion of birth defects with a known etiology (chromosomal, genetic, human teratogen, twinning) or unknown etiology, by morphology (isolated, multiple, minors only), and by pathogenesis (sequence, developmental field defect, or known pattern of birth defects). Results Definite cause was assigned in 20.2% (n=1114) of cases: chromosomal or genetic conditions accounted for 94.4% (n=1052), teratogens for 4.1% (n=46, mostly poorly controlled pregestational diabetes), and twinning for 1.4% (n=16, conjoined or acardiac). The 79.8% (n=4390) remaining were classified as unknown etiology; of these 88.2% (n=3874) were isolated birth defects. Family history (similarly affected first degree relative) was documented in 4.8% (n=266). In this cohort, 92.1% (5067/5504) were live born infants (isolated and non-isolated birth defects): 75.3% (4147/5504) were classified as having an isolated birth defect (unknown or known etiology). Conclusions These findings underscore the gaps in our knowledge regarding the causes of birth defects. For the causes that are known, such as smoking or diabetes, assigning causation in individual cases remains challenging. Nevertheless, the ongoing impact of these exposures on fetal development highlights the urgency and benefits of population based preventive interventions. For the causes that are still unknown, better strategies are needed. These can include greater integration of the key elements of etiology, morphology, and pathogenesis into epidemiologic studies; greater collaboration between researchers (such as developmental biologists), clinicians (such as medical geneticists), and epidemiologists; and better ways to objectively measure fetal exposures (beyond maternal self reports) and closer (prenatally) to the critical period of organogenesis. PMID:28559234

Systems Engineering Case Studies, Synopsis of the Learning Principles

DTIC Science & Technology

2009-08-24

TBMCS refers to the Theater Battle Management Core System Systems Engineering Case Study Peacekeeper refers to the Peacekeeper Intercontinental...primary mirror defect going to orbit undetected in spite of substantial evidence that could have been used to prevent this occurrence. TBMCS /1...The requirements baseline was volatile up to system acceptance, which took place after TBMCS passed operational test and evaluation. Approved for

Maternal Medication and Herbal Use and Risk for Hypospadias: Data from the National Birth Defects Prevention Study, 1997--2007

PubMed Central

Lind, Jennifer N.; Tinker, Sarah C.; Broussard, Cheryl S.; Reefhuis, Jennita; Carmichael, Suzan L.; Honein, Margaret A.; Olney, Richard S.; Parker, Samantha E.; Werler, Martha M.

2014-01-01

Purpose Investigate associations between maternal use of common medications and herbals during early pregnancy and risk for hypospadias in male infants. Methods We used data from the National Birth Defects Prevention Study, a multi-site, population-based, case-control study. We analyzed data from 1,537 infants with second-or third-degree isolated hypospadias and 4,314 liveborn male control infants without major birth defects, with estimated dates of delivery from 1997–2007. Exposure was reported use of prescription or over-the-counter medications or herbal products, from 1 month before to 4 months after conception. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were estimated using multivariable logistic regression, adjusting for maternal age, race/ethnicity, education, pre-pregnancy BMI, previous live births, maternal sub-fertility, study site, and year. Results We assessed 64 medication and 24 herbal components. Maternal uses of most components were not associated with an increased risk of hypospadias. Two new associations were observed for venlafaxine (aOR 2.4; 95% CI 1.0, 6.0) and progestin only oral contraceptives (aOR 1.9, 95% CI 1.1, 3.2). The previously reported association for clomiphene citrate was confirmed (aOR 1.9, 95% CI 1.2, 3.0). Numbers were relatively small for exposure to other specific patterns of fertility agents, but elevated aORs were observed for the most common of them. Conclusions Overall, findings were reassuring that hypospadias is not associated with most medication components examined in this analysis. New associations will need to be confirmed in other studies. Increased risks for hypospadias associated with various fertility agents raises the possibility of confounding by underlying subfertility. PMID:23620412

Variation in practice patterns in device closure of atrial septal defects and patent ductus arteriosus: An analysis of data from the IMproving Pediatric and Adult Congenital Treatment (IMPACT) registry.

PubMed

O'Byrne, Michael L; Kennedy, Kevin F; Rome, Jonathan J; Glatz, Andrew C

2018-02-01

Practice variation is a potentially important measure of healthcare quality. The IMPACT registry provides a representative national sample with which to study practice variation in trans-catheter interventions for congenital heart disease. We studied cases for closure of atrial septal defect (ASD) and patent ductus arteriosus (PDA) in IMPACT between January 1, 2011, and September 30, 2015, using hierarchical multivariate models studying (1) the distribution of indications for closure and (2) in patients whose indication for closure was left (LVVO) or right ventricular volume overload (RVVO), the factors influencing probability of closure of a small defect (either in size or in terms of the magnitude of shunt). Over the study period, 5233 PDA and 4459 ASD cases were performed at 77 hospitals. The indications for ASD closure were RVVO in 84% and stroke prevention in 13%. Indications for PDA closure were LVVO in 57%, endocarditis prevention in 36%, and pulmonary hypertension in 7%. There was statistically significant variability in indications between hospitals for PDA and ASD procedures (median rate ratio (MRR): 1.3 and 1.1; both P<.001). The proportion of cases for volume overload with a Qp:Qs <1.5:1 decreased with increasing PDA and ASD procedural volume (P=.04 and 0.05). For ASD, the proportion was higher at hospitals with a larger proportion of adult cases (P=.0007). There was significant variation in practice in the risk of closing PDA <2 mm for LVVO (MRR: 1.4, P<.001). There is measurable variation in transcatheter closure of PDA and ASD. Further research is necessary to study whether this affects outcomes or resource utilization. Copyright © 2017 Elsevier Inc. All rights reserved.

Myo-inositol soft gel capsules may prevent the risk of coffee-induced neural tube defects.

PubMed

De Grazia, Sara; Carlomagno, Gianfranco; Unfer, Vittorio; Cavalli, Pietro

2012-09-01

Neural tube defects (NTDs) are classified as folate sensitive (about 70%) and folate resistant (about 30%); although folic acid is able to prevent the former, several data have shown that inositol may prevent the latter. It has recently been proposed that coffee intake might represent a risk factor for NTD, likely by interfering with the inositol signaling. In the present study, we tested the hypothesis that, beside affecting the inositol signaling pathway, coffee also interferes with inositol absorption. In order to evaluate coffee possible negative effects on inositol gastrointestinal absorption, a single-dose bioavailability trial was conducted. Pharmacokinetics (PK) parameters of myo-inositol (MI) powder and MI soft gelatin capsules swallowed with water and with a single 'espresso' were compared. PK profiles were obtained by analysis of MI plasma concentration, and the respective MI bioavailability was compared. Myo-inositol powder administration was negatively affected by coffee intake, thus suggesting an additional explanation to the interference between inositol deficiency and coffee consumption. On the contrary, the concomitant single 'espresso' consumption did not affect MI absorption following MI soft gelatin capsules administration. Furthermore, it was observed that MI soft gelatin capsule administration resulted in improved bioavailability compared to the MI powder form. Myo-inositol soft gelatin capsules should be considered for the preventive treatment of NTDs in folate-resistant subjects due to their higher bioavailability and to the capability to reduce espresso interference.

Exploring the seasonality of birth defects in the New York State Congenital Malformations Registry.

PubMed

Caton, Alissa R

2012-06-01

Examining seasonal patterns of birth defects may help to identify environmental risk factors. Because the teratogenic window for most birth defects is during gestational weeks 3 to 8, investigating exposures closer to the timing of conception is important. However, studies are usually based on month of birth, which is not the biologically relevant exposure period and does not account for differences in gestational length. We aimed to determine whether the occurrence of birth defects varied by month of conception using the population-based New York State Congenital Malformations Registry (CMR). We merged live birth certificates (n = 2,044,091) with CMR records for mothers residing in New York State, excluding New York City, for the years 1992 through 2006. We categorized birth defects according to the National Birth Defects Prevention Network guidelines and performed Cochran-Armitage trend, Hewitt-Rogerson, and Walter-Elwood tests on month of conception and chi-square tests on season of conception. We graphed seasonal distributions and seasonality test results. We performed stratified analyses by maternal and infant characteristics. Of 42 groups examined in the 15-year period, 24 (57%) had at least one statistically significant test result, suggesting a trend or seasonal variation: Cochran-Armitage (18), Hewitt-Rogerson (17), Walter-Elwood (4), and chi-square (5). Ventricular septal defect showed the most consistent results: Cochran-Armitage (p = 0.0006), Hewitt-Rogerson (December to May; p = 0.0130), Walter-Elwood (March 14; p = 0.0027), and chi-square (winter; p = 0.0046). Congenital cataract, pulmonary valve atresia/stenosis, coarctation of aorta, biliary atresia, and renal agenesis or hypoplasia had at least three significant tests. These results may help to generate hypotheses about environmental factors that vary by season for further studies. Copyright © 2012 Wiley Periodicals, Inc.

Evaluation of the Effectiveness and Efficiency of Preventive Dentistry Programs: Assessment of the Relationship between Past Dental Experience and Dental Sick Call in the Field

DTIC Science & Technology

1981-09-01

of the emergencies (41.2%) followed by third molar /pericoronitis (15.9%), defective filling or fractured tooth (11.0%), gingival and periodcntal...cause of the emergencies (41.2%J followed by third molar /pericoronitis (15.9%), defective filling or fractured tooth (11.0%), gingival and periodontal...EXERCISES AT FORt IRWIN, CA 1981 CONDITION FREQUENCY PERCENT CARIES 75 41.2 THIRD MOLARS /PERICORONITIS 29 15.9 DEFECTIVE FILLING/FRACTURED TOOTH 20 11.0

Modeling Anterior Development in Mice: Diet as Modulator of Risk for Neural Tube Defects

PubMed Central

Kappen, Claudia

2014-01-01

Head morphogenesis is a complex process that is controlled by multiple signaling centers. The most common defects of cranial development are craniofacial defects, such as cleft lip and cleft palate, and neural tube defects, such as anencephaly and encephalocoele in humans. More than 400 genes that contribute to proper neural tube closure have been identified in experimental animals, but only very few causative gene mutations have been identified in humans, supporting the notion that environmental influences are critical. The intrauterine environment is influenced by maternal nutrition, and hence, maternal diet can modulate the risk for cranial and neural tube defects. This article reviews recent progress toward a better understanding of nutrients during pregnancy, with particular focus on mouse models for defective neural tube closure. At least four major patterns of nutrient responses are apparent, suggesting that multiple pathways are involved in the response, and likely in the underlying pathogenesis of the defects. Folic acid has been the most widely studied nutrient, and the diverse responses of the mouse models to folic acid supplementation indicate that folic acid is not universally beneficial, but that the effect is dependent on genetic configuration. If this is the case for other nutrients as well, efforts to prevent neural tube defects with nutritional supplementation may need to become more specifically targeted than previously appreciated. Mouse models are indispensable for a better understanding of nutrient–gene interactions in normal pregnancies, as well as in those affected by metabolic diseases, such as diabetes and obesity. PMID:24124024

Maternal and infant genetic variants, maternal periconceptional use of selective serotonin reuptake inhibitors, and risk of congenital heart defects in offspring: population based study.

PubMed

Nembhard, Wendy N; Tang, Xinyu; Hu, Zhuopei; MacLeod, Stewart; Stowe, Zachary; Webber, Daniel

2017-03-06

Objective  To evaluate whether the association between maternal periconceptional use of selective serotonin reuptake inhibitors (SSRIs) and increased risk of congenital heart defects in offspring is modified by maternal or infant genetic variants in folate, homocysteine, or transsulfuration pathways. Design  Population based study. DNA from mothers, fathers, and infants was genotyped with an Illumina GoldenGate custom single nucleotide polymorphism panel. A hybrid design based on a log linear model was used to calculate relative risks and Bayesian false discovery probabilities (BFDP) to identify polymorphisms associated with congenital heart defects modified by SSRI use. Data sources  Data from the US National Birth Defects Prevention Study on 1180 liveborn infants with congenital heart defects and 1644 controls, born 1997-2008. Main outcome measures  Cases included infants with selected congenital heart defects and control infants had no major defects. SSRI use was obtained from telephone interviews with mothers. Results  For women who reported taking SSRIs periconceptionally, maternal SHMT1 (rs9909104) GG and AGgenotypes were associated with a 5.9 and 2.4 increased risk of select congenital heart defects in offspring, respectively, versus the AA genotype (BFDP=0.69). Compared with the AA genotype, BHMT (rs492842 and rs542852) GG and AG genotypes were associated with twice the riskof congenital heart defects (BFDP=0.74 and 0.79, respectively). MGST1 (rs2075237) CC and ACgenotypes were associated with an increased risk compared with the GG genotype (8.0 and 2.8, respectively; BFDP=0.79). Single nucleotide polymorphism in infant genes in the folate (MTHFS rs12438477), homocysteine (TRDMT1 rs6602178 and GNMT rs11752813) and transsulfuration (GSTP1 rs7941395 and MGST1 rs7294985) pathways were also associated with an increased risk of congenital heart defects. Conclusions  Common maternal or infant genetic variants in folate, homocysteine, or transsulfuration pathways are associated with an increased risk of certain congenital heart defects among children of women taking SSRIs during cardiogenesis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The value of case reports in human teratology.

PubMed

Goldberg, J D; Golbus, M S

1986-03-01

Birth defects caused by human teratogens are an important and potentially preventable cause of perinatal morbidity and mortality. Case reports provide an initial suggestion that a specific agent may be a human teratogen and provide the basis for further study. This review discusses the importance of case reports in human teratology and provides guidance in evaluating new case reports.

Folic acid awareness among female college students: neural tube defects prevention.

PubMed

Kari, Jameela A; Bardisi, Ekhlas S; Baitalmal, Rabaa M; Ageely, Ghofran A

2008-12-01

To investigate the level of awareness among female college students on the importance of preconception folic acid supplementation in preventing neural tube defects (NTDs). We have also studied their response after educating them. This is a questionnaire-based study. Five hundreds questionnaires were distributed to the female students of the 3 colleges, namely, Humanities, Sciences, and Health in Jeddah, Kingdom of Saudi Arabia in April 2008. The questions included an enquiry on their knowledge regarding the importance of folic acid preconception, and if they will implement what they learned after listening to lectures, delivered by the 4th year medical students, who were trained and supervised by the faculty members of the King Abdul-Aziz University. Two hundred and seventeen questionnaires were filled, and returned (43.4%). Mean age +/- SD was 20.96 +/- 2.25 years. Almost 88% were not aware of the importance of folic acid in preventing NTDs. After listening to the lecture, 82.9% thought that they will surely use folic acid preconception, and 98.6% will relay the important message about the importance of folic acid to others. There is a need to increase the awareness of the importance of folic acid among females' childbearing age. Medical students' involvement in educating college students was an effective way to increase their awareness. Similar educating programs are required, in order to reduce the high incidence of NTDs.

A first-principles study of the preventive effects of Al and Mg doping on the degradation in LiNi0.8Co0.1Mn0.1O2 cathode materials.

PubMed

Min, Kyoungmin; Seo, Seung-Woo; Song, You Young; Lee, Hyo Sug; Cho, Eunseog

2017-01-18

First-principles calculations have been used to investigate the effects of Al and Mg doping on the prevention of degradation phenomena in Li(Ni 0.8 Co 0.1 Mn 0.1 )O 2 cathode materials. Specifically, we have examined the effects of dopants on the suppression of oxygen evolution and cation disordering, as well as their correlation. It is found that Al doping can suppress the formation of oxygen vacancies effectively, while Mg doping prevents the cation disordering behaviors, i.e., excess Ni and Li/Ni exchange, and Ni migration. This study also demonstrates that formation of oxygen vacancies can facilitate the construction of the cation disordering, and vice versa. Delithiation can increase the probabilities of formation of all defect types, especially oxygen vacancies. When oxygen vacancies are present, Ni can migrate to the Li site during delithiation. However, Al and Mg doping can inhibit Ni migration, even in structures with preformed oxygen defects. The analysis of atomic charge variations during delithiation demonstrates that the degree of oxidation behavior in oxygen atoms is alleviated in the case of Al doping, indicating the enhanced oxygen stability in this structure. In addition, changes in the lattice parameters during delithiation are suppressed in the Mg-doped structure, which suggests that Mg doping may improve the lattice stability.

Proceedings of the Conference on Birth Defects for Educators (May 4, 1978).

ERIC Educational Resources Information Center

Davidson, Michael S., Ed.; Davidson, Mary W., Ed.

Six papers from a 1978 conference on birth defects focus on prevention. G. Stickle ("The Health of America's Babies: How Do We Stack Up?'" reviews risk in pregnancy, cites inadequate prenatal care and maternal nutrition, and discusses examples of how the United States is not applying its knowledge of how to improve pregnancy outcome. In "Genetic…

Study of Incidence and Prevalence of Musculoskeletal Anomalies in a Tertiary Care Hospital of Eastern India

PubMed Central

Mohanty, Biswa Bhusan; Sarangi, Rachita; Kumar, Sanjay; Mahapatra, Susanta Kumar; Chinara, Prafulla Kumar

2014-01-01

Introduction: Congenital anomalies or malformations are anatomical. Structural or functional defects present at birth leads to physical and mental disabilities. With the advent of newer drugs, infectious diseases have taken the backseat and congenital defects have emerged as an important cause of neonatal morbidity and mortality. In India, anomalies of musculoskeletal system have been most commonly reported. Aims and Objectives: With this in view, the present study was carried out to find the incidence and types of musculoskeletal defects in a tertiary care hospital in Eastern India. Various maternal factors were also correlated and analyzed. The purpose of this communication is to report these defects so as to help doctors and parents to prevent unexpected fetal loss and better parental counseling. Materials and Methods: This study was done in the Department of Obstetrics and Gynaecology in association with Department of Paediatrics of a tertiary care hospital in Odisha from for a period of 1 year. The newborns were examined within 1st three days of delivery for congenital malformations. The study group included all live borns along with still borns after 28 weeks of gestation or those dead babies whose weight was about 1kg. A thorough physical examination from head to toe was done to look for musculoskeletal defects within 24hrs of delivery. Observation and Results: Out of total 7268 babies delivered, 116 babies were found to have anomalies. Thirty two of these had musculoskeletal defects. Talipes equinovarus was the commonest anomaly observed followed by polydactyly. The ratio of male babies with musculoskeletal defects to female babies was found to be 1.28:1.The malformed babies were mainly born to term mothers (77.6%), who were mostly unbooked (62.5%) and belonged to lower or middle class. But no significant relationship could be established between these factors and defects. Most mothers were in the age group of 20-35 years and there was no history of drug addiction, smoking, trauma or irradiation that could be related to the occurrence of congenital malformations. Conclusion: It is concluded that better maternal care and improved standards of living have very little effect on the overall frequency of congenital malformations. For the better future of neonates an early recognition of correctable lesions is essential, which calls for a systematic approach to the study of musculoskeletal defects. PMID:24995167

Histologic Evaluation of Osseous Regeneration Following Combination Therapy With Platelet-Rich Plasma and Bio-Oss in a Rat Calvarial Critical-Size Defect Model.

PubMed

DeNicolo, Philip J; Guyton, M Kelly; Cuenin, Michael F; Hokett, Steven D; Sharawy, Mohamed; Borke, James; McPherson, James C

2015-10-01

Platelet-rich plasma (PRP) is an autogenous source of growth factors shown to facilitate human bone growth. Bio-Oss, an osteoconductive xenograft, is used clinically to regenerate periodontal defects, restore dental alveolar ridges, and facilitate sinus-lift procedures. The purpose of this study was to analyze whether a combination of PRP and Bio-Oss would enhance bone regeneration better than either material alone. PRP and/or Bio-Oss were administered in an 8-mm critical-size defect (CSD) rat calvarial model of bone defect between 2 polytetrafluoroethylene membranes to prevent soft tissue incursion. Eight weeks after the induction of the CSD, histologic sections were stained with hematoxylin and eosin stain and analyzed via light microscopy. Qualitative analyses revealed new bone regeneration in all 4 groups. The Bio-Oss and PRP plus Bio-Oss groups demonstrated greater areas of closure in the defects than the control or PRP-only groups because of the space-maintaining ability of Bio-Oss. The groups grafted with Bio-Oss showed close contact with new bone growth throughout the defects, suggesting a stronger graft. The use of PRP alone or in combination with Bio-Oss, however, did not appear to enhance osseous regeneration at 8 weeks. Areas grafted with Bio-Oss demonstrated greater space-maintaining capacity than controls, and PRP was an effective vehicle for placement of the Bio-Oss. However, at 8 weeks this study was unable to demonstrate a significant advantage of using PRP plus Bio-Oss over using Bio-Oss alone.

Public Health Practice of Population-Based Birth Defects Surveillance Programs in the United States.

PubMed

Mai, Cara T; Kirby, Russell S; Correa, Adolfo; Rosenberg, Deborah; Petros, Michael; Fagen, Michael C

2016-01-01

Birth defects remain a leading cause of infant mortality in the United States and contribute substantially to health care costs and lifelong disabilities. State population-based surveillance systems have been established to monitor birth defects, yet no recent systematic examination of their efforts in the United States has been conducted. To understand the current population-based birth defects surveillance practices in the United States. The National Birth Defects Prevention Network conducted a survey of US population-based birth defects activities that included questions about operational status, case ascertainment methodology, program infrastructure, data collection and utilization, as well as priorities and challenges for surveillance programs. Birth defects contacts in the United States, including District of Columbia and Puerto Rico, received the survey via e-mail; follow-up reminders via e-mails and telephone were used to ensure a 100% response rate. Forty-three states perform population-based surveillance for birth defects, covering approximately 80% of the live births in the United States. Seventeen primarily use an active case-finding approach and 26 use a passive case-finding approach. These programs all monitor major structural malformations; however, passive case-finding programs more often monitor a broader list of conditions, including developmental conditions and newborn screening conditions. Active case-finding programs more often use clinical reviewers, cover broader pregnancy outcomes, and collect more extensive information, such as family history. More than half of the programs (24 of 43) reported an ability to conduct follow-up studies of children with birth defects. The breadth and depth of information collected at a population level by birth defects surveillance programs in the United States serve as an important data source to guide public health action. Collaborative efforts at the state and national levels can help harmonize data collection and increase utility of birth defects programs.

78 FR 18986 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [60Day-13-0733... on proposed data collection projects, the Centers for Disease Control and Prevention (CDC) will... Center on Birth Defects and Developmental Disabilities (NCBDDD), Centers for Disease Control and...

Defective prevention of immune precipitation in autoimmune diseases is independent of C4A*Q0

PubMed Central

Arason, G J; Kolka, R; Hreidarsson, A B; Gudjonsson, H; Schneider, P M; Fry, L; Arnason, A

2005-01-01

Increased prevalence of C4 null alleles is a common feature of autoimmune diseases. We have shown previously that complement-dependent prevention of immune precipitation (PIP) is defective in patients with systemic lupus erythematosus (SLE), and correlated this defect with C4A*Q0 and low levels of the C4A isotype. To further clarify the role of C4A in the aetiology of SLE, we now extend our studies to other diseases which have been associated with C4A*Q0. The frequency of C4A*Q0 was increased in Icelandic patients with coeliac disease (0·50; P < 0·001), Grave's disease (0·30; P = 0·002) and insulin-dependent diabetes mellitus (0·23; P = 0·04) and in British patients with dermatitis herpetiformis (0·42; P = 0·002) and this was reflected in low levels of C4A. In spite of this, PIP was normal in these patients, and in marked contrast to our previous observations on connective tissue diseases, PIP measurements in these patient groups correlated more strongly with levels of C4B (r = 0·51, P = 0·0000004) than C4A. Patients with increased levels of anti-C1q antibodies had significantly lower PIP than patients without such antibodies (P < 0·01) and a negative association of PIP with anti-C1q antibodies was also reflected in an increased prevalence (P = 0·006) and levels (P = 0·006) of anti-C1q antibodies in patients with subnormal PIP, as well as a negative correlation between PIP and anti-C1q antibodies (r = − 0·25, P = 0·02). These results show that the PIP defect cannot be explained by low levels of C4A alone and suggest that measurements of anti-C1q antibodies may be useful in future studies on the molecular cause of the PIP defect in autoimmune connective tissue disease. PMID:15932521

Defect Detection and Segmentation Framework for Remote Field Eddy Current Sensor Data

PubMed Central

2017-01-01

Remote-Field Eddy-Current (RFEC) technology is often used as a Non-Destructive Evaluation (NDE) method to prevent water pipe failures. By analyzing the RFEC data, it is possible to quantify the corrosion present in pipes. Quantifying the corrosion involves detecting defects and extracting their depth and shape. For large sections of pipelines, this can be extremely time-consuming if performed manually. Automated approaches are therefore well motivated. In this article, we propose an automated framework to locate and segment defects in individual pipe segments, starting from raw RFEC measurements taken over large pipelines. The framework relies on a novel feature to robustly detect these defects and a segmentation algorithm applied to the deconvolved RFEC signal. The framework is evaluated using both simulated and real datasets, demonstrating its ability to efficiently segment the shape of corrosion defects. PMID:28984823

Maternal diet modulates the risk for neural tube defects in a mouse model of diabetic pregnancy

PubMed Central

Kappen, Claudia; Kruger, Claudia; MacGowan, Jacalyn; Salbaum, J. Michael

2010-01-01

Pregnancies complicated by maternal diabetes have long been known to carry a higher risk for congenital malformations, such as neural tube defects. Using the FVB inbred mouse strain and the Streptozotocin-induced diabetes model, we tested whether the incidence of neural tube defects in diabetic pregnancies can be modulated by maternal diet. In a comparison of two commercial mouse diets, which are considered nutritionally replete, we found that maternal consumption of the unfavorable diet was associated with a more than three-fold higher rate of neural tube defects. Our results demonstrate that maternal diet can act as a modifier of the risk for abnormal development in high-risk pregnancies, and provide support for the possibility that neural tube defects in human diabetic pregnancies might be preventable by optimized maternal nutrition. PMID:20868740

Defect Detection and Segmentation Framework for Remote Field Eddy Current Sensor Data.

PubMed

Falque, Raphael; Vidal-Calleja, Teresa; Miro, Jaime Valls

2017-10-06

Remote-Field Eddy-Current (RFEC) technology is often used as a Non-Destructive Evaluation (NDE) method to prevent water pipe failures. By analyzing the RFEC data, it is possible to quantify the corrosion present in pipes. Quantifying the corrosion involves detecting defects and extracting their depth and shape. For large sections of pipelines, this can be extremely time-consuming if performed manually. Automated approaches are therefore well motivated. In this article, we propose an automated framework to locate and segment defects in individual pipe segments, starting from raw RFEC measurements taken over large pipelines. The framework relies on a novel feature to robustly detect these defects and a segmentation algorithm applied to the deconvolved RFEC signal. The framework is evaluated using both simulated and real datasets, demonstrating its ability to efficiently segment the shape of corrosion defects.

GaAs on Si epitaxy by aspect ratio trapping: Analysis and reduction of defects propagating along the trench direction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Orzali, Tommaso, E-mail: tommaso.orzali@sematech.org; Vert, Alexey; O'Brien, Brendan

2015-09-14

The Aspect Ratio Trapping technique has been extensively evaluated for improving the quality of III-V heteroepitaxial films grown on Si, due to the potential for terminating defects at the sidewalls of SiO{sub 2} patterned trenches that enclose the growth region. However, defects propagating along the trench direction cannot be effectively confined with this technique. We studied the effect of the trench bottom geometry on the density of defects of GaAs fins, grown by metal-organic chemical vapor deposition on 300 mm Si (001) wafers inside narrow (<90 nm wide) trenches. Plan view and cross sectional Scanning Electron Microscopy and Transmission Electron Microscopy, togethermore » with High Resolution X-Ray Diffraction, were used to evaluate the crystal quality of GaAs. The prevalent defects that reach the top surface of GaAs fins are (111) twin planes propagating along the trench direction. The lowest density of twin planes, ∼8 × 10{sup 8 }cm{sup −2}, was achieved on “V” shaped bottom trenches, where GaAs nucleation occurs only on (111) Si planes, minimizing the interfacial energy and preventing the formation of antiphase boundaries.« less

Revisiting the relevance of using a constant voltage step to improve electrochemical performances of Li-rich lamellar oxides

NASA Astrophysics Data System (ADS)

Pradon, A.; Caldes, M. T.; Petit, P.-E.; La Fontaine, C.; Elkaim, E.; Tessier, C.; Ouvrard, G.; Dumont, E.

2018-03-01

A Li-rich lamellar oxide was cycled at high potential and the relevance of using a constant voltage step (CVS) at the end of the charge, needed for industrial application, was investigated by electrochemical performance, X-ray diffraction (XRD) and high resolution transmission electron microscopy (HRTEM). Electrochemical studies at 4.7 and 4.5 V with and without CVS showed that capacity and voltage fading occurred mostly when cells operated at high potential. After cycling, 3D-type defects involving transition metals trapped in lithium layer were observed by HRTEM into the electrode bulk. These defects are responsible for the voltage fading. XRD microstrain parameter was used to evaluate defects rate in aged materials subjected to a CVS, showing more 3D-type defects when cycled at 4.7 V than at 4.5 V. The time spent at high potential at the end of the charge as well as the value of the upper potential limit, are both relevant parameters to voltage decay. The use of a CVS at the end of the charge needs at the same time, a reduced upper potential window in order to minimize 3D-type defects occurrence. Unfortunately, this approach is still not sufficient to prevent voltage fading.

Transplantation of mature adipocyte-derived dedifferentiated fat cells into three-wall defects in the rat periodontium induces tissue regeneration.

PubMed

Suzuki, Daigo; Akita, Daisuke; Tsurumachi, Niina; Kano, Koichiro; Yamanaka, Katsuyuki; Kaneko, Tadashi; Kawano, Eisuke; Iguchi, Shinya; Toriumi, Taku; Arai, Yoshinori; Matsumoto, Taro; Sato, Shuichi; Honda, Masaki

2017-01-01

The transplantation of dedifferentiated fat (DFAT) cells in combination with poly(d,l-lactic-co-glycolic acid) (PLGA) scaffolds has previously been proven as an effective approach in promoting periodontal tissue regeneration in a rat fenestration defect model. The aim of this study was to assess the regenerative potential of DFAT cells in a rat model of three-wall periodontal bone defect. Three-wall bone defects were created bilaterally on the mesial side of rat maxillary first molars and were either left untreated or treated by implantation of PLGA scaffolds with DFAT cells or PLGA alone. Four weeks after surgery, the tissues were processed for micro-computed tomography (micro-CT) and histomorphometric examination. Micro-CT revealed that the PLGA/DFAT group had significantly higher rates of bone regeneration than the other groups, while histomorphometric analysis showed that the PLGA/DFAT group had significantly higher densities of collagen fiber bundles in acellular and cellular cementum than the PLGA group. Moreover, the results indicate that the placement of the PLGA scaffold prevented the downgrowth of the junctional epithelium. These findings suggest that DFAT cells contribute to tissue regeneration in three-wall periodontal defects, while PLGA provides space necessary for periodontal tissue restoration.

Synovial Mesenchymal Stem Cells Promote Meniscus Regeneration Augmented by an Autologous Achilles Tendon Graft in a Rat Partial Meniscus Defect Model

PubMed Central

Ozeki, Nobutake; Muneta, Takeshi; Matsuta, Seiya; Koga, Hideyuki; Nakagawa, Yusuke; Mizuno, Mitsuru; Tsuji, Kunikazu; Mabuchi, Yo; Akazawa, Chihiro; Kobayashi, Eiji; Saito, Tomoyuki; Sekiya, Ichiro

2015-01-01

Although meniscus defects and degeneration are strongly correlated with the later development of osteoarthritis, the promise of regenerative medicine strategies is to prevent and/or delay the disease's progression. Meniscal reconstruction has been shown in animal models with tendon grafting and transplantation of mesenchymal stem cells (MSCs); however, these procedures have not shown the same efficacy in clinical studies. Here, our aim was to investigate the ability of tendon grafts pretreated with exogenous synovial-derived MSCs to prevent cartilage degeneration in a rat partial meniscus defect model. We removed the anterior half of the medial meniscus and grafted autologous Achilles tendons with or without a 10-minute pretreatment of the tendon with synovial MSCs. The meniscus and surrounding cartilage were evaluated at 2, 4, and 8 weeks (n = 5). Tendon grafts increased meniscus size irrespective of synovial MSCs. Histological scores for regenerated menisci were better in the tendon + MSC group than in the other two groups at 4 and 8 weeks. Both macroscopic and histological scores for articular cartilage were significantly better in the tendon + MSC group at 8 weeks. Implanted synovial MSCs survived around the grafted tendon and native meniscus integration site by cell tracking assays with luciferase+, LacZ+, DiI+, and/or GFP+ synovial MSCs and/or GFP+ tendons. Flow cytometric analysis showed that transplanted synovial MSCs retained their MSC properties at 7 days and host synovial tissue also contained cells with MSC characteristics. Synovial MSCs promoted meniscus regeneration augmented by autologous Achilles tendon grafts and prevented cartilage degeneration in rats. Stem Cells 2015;33:1927–1938 PMID:25993981

Periodontal healing in one-wall intra-bony defects in dogs following implantation of autogenous bone or a coral-derived biomaterial.

PubMed

Kim, Chang-Sung; Choi, Seong-Ho; Cho, Kyoo-Sung; Chai, Jung-Kiu; Wikesjö, Ulf M E; Kim, Chong-Kwan

2005-06-01

Autogenous bone grafts and bone biomaterials are being used as part of protocols aiming at reconstruction of periodontal defects. There is a limited biologic information on the effect of such materials on periodontal healing, in particular aberrant healing events that may prevent their general use. The objective of this study was, using histological techniques, to evaluate periodontal healing with focus on root resorption and ankylosis following implantation of autogenous bone and a coral-derived biomaterial into intra-bony defects in dogs. One-wall intra-bony periodontal defects were surgically created at the distal aspect of the second and the mesial aspect of the fourth mandibular premolars in either right or left jaw quadrants in four Beagle dogs. Each animal received particulated autogenous bone and the resorbable calcium carbonate biomaterial into discrete one-wall intra-bony defects. The mucoperiosteal flaps were positioned and sutured to their pre-surgery position. The animals were euthanized 8 weeks post-surgery when block sections of the defect sites were collected and prepared for qualitative histological analysis. There were no significant differences in periodontal healing between sites receiving autograft bone and the coral-derived biomaterial. A well-organized periodontal ligament bridging new bone and cementum regeneration was observed extending coronal to a notch prepared to delineate the apical extent of the defect. Osteoid and bone with enclosed osteocytes were formed onto the surface of both autograft and coral particles. Although small resorption pits were evident in most teeth, importantly none of the biomaterials provoked marked root resorption. Ankylosis was not observed. Particulated autogenous bone and the coral-derived biomaterial may be implanted into periodontal defects without significant healing aberrations such as root resorption and ankylosis. The histopathological evaluation suggests that the autogenous bone graft has a limited osteogenic potential as demonstrated in this study model.

Fas/CD95 prevents autoimmunity independently of lipid raft localization and efficient apoptosis induction

PubMed Central

Cruz, Anthony C.; Ramaswamy, Madhu; Ouyang, Claudia; Klebanoff, Christopher A.; Sengupta, Prabuddha; Yamamoto, Tori N.; Meylan, Françoise; Thomas, Stacy K.; Richoz, Nathan; Eil, Robert; Price, Susan; Casellas, Rafael; Rao, V. Koneti; Lippincott-Schwartz, Jennifer; Restifo, Nicholas P.; Siegel, Richard M.

2016-01-01

Mutations affecting the apoptosis-inducing function of the Fas/CD95 TNF-family receptor result in autoimmune and lymphoproliferative disease. However, Fas can also costimulate T-cell activation and promote tumour cell growth and metastasis. Palmitoylation at a membrane proximal cysteine residue enables Fas to localize to lipid raft microdomains and induce apoptosis in cell lines. Here, we show that a palmitoylation-defective Fas C194V mutant is defective in inducing apoptosis in primary mouse T cells, B cells and dendritic cells, while retaining the ability to enhance naive T-cell differentiation. Despite inability to efficiently induce cell death, the Fas C194V receptor prevents the lymphoaccumulation and autoimmunity that develops in Fas-deficient mice. These findings indicate that induction of apoptosis through Fas is dependent on receptor palmitoylation in primary immune cells, and Fas may prevent autoimmunity by mechanisms other than inducing apoptosis. PMID:28008916

Epidemiology, prenatal management, and prevention of neural tube defects

PubMed Central

Salih, Mustafa A.; Murshid, Waleed R.; Seidahmed, Mohammed Z.

2014-01-01

This review article discusses the epidemiology, risk factors, prenatal screening, diagnosis, prevention potentials, and epidemiologic impact of neural tube defects (NTDs). The average incidence of NTDs is 1/1000 births, with a marked geographic variation. In the developed countries, the incidence of NTDs has fallen over recent decades. However, it still remains high in the less-developed countries in Latin America, Africa, the Middle East, Asia, and the Far East (>1 to 11/1000 births). Recognized NTDs risks include maternal diabetes, obesity, lower socioeconomic status, hyperthermia, and exposure to certain teratogens during the periconceptional period. Periconceptional folic acid supplementation decreased the prevalence of NTDs by 50-70%, and an obligatory folic acid fortification of food was adopted in several countries to reach women with unplanned pregnancies and those facing social deprivation. Prevention of NTDs can be accelerated if more, especially low income countries, adopted fortification of the staple food in their communities. PMID:25551106

An investigation on defect-generation conditions in immersion lithography

NASA Astrophysics Data System (ADS)

Tomita, Tadatoshi; Shimoaoki, Takeshi; Enomoto, Masashi; Kyoda, Hideharu; Kitano, Junichi; Suganaga, Toshifumi

2006-03-01

As a powerful candidate for a lithography technique that can accommodate the scaling-down of semiconductors, 193-nm immersion lithography-which realizes a high numerical aperture (NA) and uses deionized water as the medium between the lens and wafer in the exposure system-has been developing at a rapid pace and has reached the stage of practical application. In regards to defects that are a cause for concern in the case of 193-nm immersion lithography, however, many components are still unclear and many problems remain to be solved. It has been pointed out, for example, that in the case of 193-nm immersion lithography, immersion of the resist film in deionized water during exposure causes infiltration of moisture into the resist film, internal components of the resist dissolve into the deionized water, and residual water generated during exposure affects post-processing. Moreover, to prevent this influence of directly immersing the resist in de-ionized water, application of a protective film is regarded as effective. However, even if such a film is applied, it is still highly likely that the above-mentioned defects will still occur. Accordingly, to reduce these defects, it is essential to identify the typical defects occurring in 193-nm immersion lithography and to understand the condition for generation of defects by using some kinds of protective films and resist materials. Furthermore, from now onwards, with further scaling down of semiconductors, it is important to maintain a clear understanding of the relation between defect-generation conditions and critical dimensions (CD). Aiming to extract typical defects occurring in 193-nm immersion lithography, the authors carried out a comparative study with dry exposure lithography, thereby confirming several typical defects associated with immersion lithography. We then investigated the conditions for generation of defects in the case of some kinds of protective films. In addition to that, by investigating the defect-generation conditions and comparing the classification data between wet and dry exposure, we were able to determine the origin of each particular defect involved in immersion lithography. Furthermore, the comparison of CD for wet and dry processing could indicate the future defectivity levels to be expected with shrinking immersion process critical dimensions.

49 CFR 238.303 - Exterior calendar day mechanical inspection of passenger equipment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... to prevent the pin from falling out of place in case of breakage. (5) The suspension system... pneumatic suspension system component inflates or deflates, as applicable, correctly and otherwise operates... secondary braking system is in operating mode and does not have any known defective condition which prevents...

Prevention of Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Floyd, R. Louise; Weber, Mary Kate; Denny, Clark; O'Connor, Mary J.

2009-01-01

Alcohol use among women of childbearing age is a leading, preventable cause of birth defects and developmental disabilities in the United States. Although most women reduce their alcohol use upon pregnancy recognition, some women report drinking during pregnancy and others may continue to drink prior to realizing they are pregnant. These findings…

Diet and asthma: an update.

PubMed

Han, Yueh-Ying; Forno, Erick; Holguin, Fernando; Celedón, Juan C

2015-08-01

Our objective was to provide an overview and discussion of recent experimental studies, epidemiologic studies, and clinical trials of diet and asthma. We focus on dietary sources and vitamins with antioxidant properties [vitamins (A, C, and E), folate, and omega-3 and omega-6 polyunsaturated fatty acids (n-3 and n-6 PUFAs)]. Current evidence does not support the use of vitamin A, vitamin C, vitamin E, or PUFAs for the prevention or treatment of asthma or allergies. Current guidelines for prenatal use of folate to prevent neural tube defects should be followed, as there is no evidence of major effects of this practice on asthma or allergies. Consumption of a balanced diet that is rich in sources of antioxidants (e.g. fruits and vegetables) may be beneficial in the primary prevention of asthma. None of the vitamins or nutrients examined is consistently associated with asthma or allergies. In some cases, further studies of the effects of a vitamin or nutrient on specific asthma phenotypes (e.g. vitamin C to prevent viral-induced exacerbations) are warranted. Clinical trials of 'whole diet' interventions to prevent asthma are advisable on the basis of existing evidence.

Multivitamins, Folic Acid and Birth Defects: Knowledge, Beliefs and Behaviors of Hispanic Women in North Carolina

ERIC Educational Resources Information Center

deRosset, Leslie; Mullenix, Amy; Zhang, Lei

2009-01-01

Background: Consumption of folic acid prior to conception can prevent up to 70% of neural tube defect (NTD)-affected pregnancies. In 1992, the U.S. Public Health Service (USPHS) issued a recommendation that all women of childbearing age capable of becoming pregnant consume 400 [mu]g of folic acid daily to reduce their risk for a NTD-affected…

Cost effectiveness of teratology counseling - the Motherisk experience.

PubMed

Koren, Gideon; Bozzo, Pina

2014-01-01

While the benefits of evidence-based counseling to large numbers of women and physicians are intuitively evident, there is an urgent need to document that teratology counseling, in addition to improving the quality of life of women and families, also leads to cost saving. The objective of the present study was to calculate the cost effectiveness of the Motherisk Program, a large teratology information and counseling service at The Hospital for Sick Children and the University of Toronto. We analyzed data from the Motherisk Program on its 2012 activities in two domains: 1) Calculation of cost-saving in preventing unjustified pregnancy terminations; and 2) prevention of major birth defects. Cost of pregnancy termination and lifelong cost of specific birth defects were identified from primary literature and prorated for cost of living for the year 2013. Prevention of 255 pregnancy terminations per year led to cost savings of $516,630. The total estimated number of major malformations prevented by Motherisk counseling in 2012 was 8.41 cases at a total estimated cost of $9,032,492. With an estimated minimum annual prevention of 8 major malformations, and numerous unnecessary terminations of otherwise- wanted pregnancies, a cost saving of $10 million can be calculated. In 2013 the operating budget of Motherisk counseling totaled $640,000. Even based on the narrow range of activities for which we calculated cost, this service is highly cost- effective. Because most teratology counseling services are operating in a very similar method to Motherisk, it is fair to assume that these results, although dependent on the size of the service, are generalizable to other countries.

Synthesis of photochromic nanoparticles and determination of the mechanism of photochromism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, Shuhei, E-mail: shu18@hiroshima-u.ac.jp; Matsumura, Yukihiko; Kawamoto, Takahiro

2016-05-15

Photochromic nanoparticles of zinc-silicon oxide were synthesized using plasma enhanced chemical vapor deposition. These particles turned black upon irradiating with ultraviolet light. We investigated this phenomenon using density functional theory calculations. Silicon inclusions create trap levels and oxygen defects that reduce the ionization potential of ZnO. This forms a quantum potential between ZnO and zinc-silicon oxide, and the excited electron is stable. Because oxygen defects also increase the bond overlap population between the zinc atoms in a ZnO crystal, they introduce further defects and help in the formation of quantum potentials. Growth of a perfect crystal of ZnO prevents themore » formation of oxygen defects, which is not desirable for photochromism.« less

Effect of hydrogen adsorption on the formation and annealing of Stone-Wales defects in graphene

NASA Astrophysics Data System (ADS)

Podlivaev, A. I.; Openov, L. A.

2015-12-01

The heights of energy barriers preventing the formation and annealing of Stone-Wales defects in graphene with a hydrogen atom adsorbed on the defect or in its immediate vicinity have been calculated using the atomistic computer simulation. It has been shown that, in the presence of hydrogen, both barriers are significantly lower than those in the absence of hydrogen. Based on the analysis of the potential energy surface, the frequency factors have been calculated for two different paths of the Stone-Wales transformation, and the temperature dependences of the corresponding annealing times of the defects have been found. The results obtained have been compared with the first-principles calculations and molecular dynamics data.

Folate receptor 1 is necessary for neural plate cell apical constriction during Xenopus neural tube formation

PubMed Central

Balashova, Olga A.; Visina, Olesya

2017-01-01

Folate supplementation prevents up to 70% of neural tube defects (NTDs), which result from a failure of neural tube closure during embryogenesis. The elucidation of the mechanisms underlying folate action has been challenging. This study introduces Xenopus laevis as a model to determine the cellular and molecular mechanisms involved in folate action during neural tube formation. We show that knockdown of folate receptor 1 (Folr1; also known as FRα) impairs neural tube formation and leads to NTDs. Folr1 knockdown in neural plate cells only is necessary and sufficient to induce NTDs. Folr1-deficient neural plate cells fail to constrict, resulting in widening of the neural plate midline and defective neural tube closure. Pharmacological inhibition of folate action by methotrexate during neurulation induces NTDs by inhibiting folate interaction with its uptake systems. Our findings support a model in which the folate receptor interacts with cell adhesion molecules, thus regulating the apical cell membrane remodeling and cytoskeletal dynamics necessary for neural plate folding. Further studies in this organism could unveil novel cellular and molecular events mediated by folate and lead to new ways of preventing NTDs. PMID:28255006

Oral administration of the antioxidant, N-acetylcysteine, abrogates diabetes-induced endothelial dysfunction.

PubMed

Pieper, G M; Siebeneich, W

1998-07-01

Oxidative stress is believed to play an important role in the development of vascular complications associated with diabetes mellitus. In this study, we examined the efficacy of long-term treatment with the antioxidant, N-acetylcysteine, in preventing the development of defective endothelium-dependent relaxation in streptozotocin-induced, Sprague-Dawley diabetic rats. At 48 h after injection of streptozotocin, a portion of diabetic rats received 250 mg/L N-acetylcysteine in drinking water for a total duration of 8 weeks. Oral administration did not alter the increase in blood glucose or the reduction in serum insulin but did modestly reduce total glycosylated hemoglobin. In precontracted thoracic aortic rings suspended in isolated tissue baths, endothelium-dependent relaxation to acetylcholine was impaired in diabetic rings compared with control rings. Endothelium-independent relaxation to nitroglycerin was unaltered. Long-term oral administration of N-acetylcysteine did not alter responses to nitroglycerin but completely prevented the defective relaxation to acetylcholine. These studies indicate a dissociation between glycemic control and correction of endothelial dysfunction and suggest that long-term exposure to reactive oxygen subsequent to diabetes rather than hyperglycemia per se is responsible for the development of endothelial dysfunction in diabetes mellitus.

Traffic-Related Air Pollution and Selected Birth Defects in the San Joaquin Valley of California

PubMed Central

Padula, Amy M.; Tager, Ira B.; Carmichael, Suzan L.; Hammond, S. Katharine; Yang, Wei; Lurmann, Frederick W.; Shaw, Gary M.

2014-01-01

BACKGROUND Birth defects are a leading cause of infant morbidity and mortality. Studies suggest associations between environmental contaminants and some structural anomalies, although evidence is limited and several anomalies have not been investigated previously. METHODS We used data from the California Center of the National Birth Defects Prevention Study and the Children's Health and Air Pollution Study to estimate the odds of 26 congenital birth defect phenotypes with respect to quartiles of seven ambient air pollutant and traffic exposures in California during the first 2 months of pregnancy, 1997 to 2006 (874 cases and 849 controls). We calculated odds ratios (adjusted for maternal race/ethnicity, education, and vitamin use; aOR) for 11 phenotypes that had at least 40 cases. RESULTS Few odds ratios had confidence intervals that did not include 1.0. Odds of esophageal atresia were increased for the highest versus lowest of traffic density (aOR = 2.8, 95% confidence interval [CI], 1.1–7.4) and PM10 exposure (aOR 4.9; 95% CI, 1.4–17.2). PM10 was associated with a decreased risk of hydrocephaly (aOR= 0.3; 95% CI, 0.1–0.9) and CO with decreased risk of anotia/microtia (aOR = 0.4; 95% CI, 0.2–0.8) and transverse limb deficiency (aOR = 0.4; 95% CI, 0.2–0.9), again reflecting highest versus lowest quartile comparisons. CONCLUSION Most analyses showed no substantive association between air pollution and the selected birth defects with few exceptions of mixed results. PMID:24108522

Traffic-related air pollution and selected birth defects in the San Joaquin Valley of California.

PubMed

Padula, Amy M; Tager, Ira B; Carmichael, Suzan L; Hammond, S Katharine; Yang, Wei; Lurmann, Frederick W; Shaw, Gary M

2013-11-01

Birth defects are a leading cause of infant morbidity and mortality. Studies suggest associations between environmental contaminants and some structural anomalies, although evidence is limited and several anomalies have not been investigated previously. We used data from the California Center of the National Birth Defects Prevention Study and the Children's Health and Air Pollution Study to estimate the odds of 26 congenital birth defect phenotypes with respect to quartiles of seven ambient air pollutant and traffic exposures in California during the first 2 months of pregnancy, 1997 to 2006 (874 cases and 849 controls). We calculated odds ratios (adjusted for maternal race/ethnicity, education, and vitamin use; aOR) for 11 phenotypes that had at least 40 cases. Few odds ratios had confidence intervals that did not include 1.0. Odds of esophageal atresia were increased for the highest versus lowest of traffic density (aOR = 2.8, 95% confidence interval [CI], 1.1-7.4) and PM10 exposure (aOR 4.9; 95% CI, 1.4-17.2). PM₁₀ was associated with a decreased risk of hydrocephaly (aOR= 0.3; 95% CI, 0.1-0.9) and CO with decreased risk of anotia/microtia (aOR = 0.4; 95% CI, 0.2-0.8) and transverse limb deficiency (aOR = 0.4; 95% CI, 0.2-0.9), again reflecting highest versus lowest quartile comparisons. Most analyses showed no substantive association between air pollution and the selected birth defects with few exceptions of mixed results. Copyright © 2013 Wiley Periodicals, Inc.

Pharmacological Correction of Trafficking Defects in ATP-sensitive Potassium Channels Caused by Sulfonylurea Receptor 1 Mutations*

PubMed Central

Martin, Gregory M.; Rex, Emily A.; Devaraneni, Prasanna; Denton, Jerod S.; Boodhansingh, Kara E.; DeLeon, Diva D.; Stanley, Charles A.; Shyng, Show-Ling

2016-01-01

ATP-sensitive potassium (KATP) channels play a key role in mediating glucose-stimulated insulin secretion by coupling metabolic signals to β-cell membrane potential. Loss of KATP channel function due to mutations in ABCC8 or KCNJ11, genes encoding the sulfonylurea receptor 1 (SUR1) or the inwardly rectifying potassium channel Kir6.2, respectively, results in congenital hyperinsulinism. Many SUR1 mutations prevent trafficking of channel proteins from the endoplasmic reticulum to the cell surface. Channel inhibitors, including sulfonylureas and carbamazepine, have been shown to correct channel trafficking defects. In the present study, we identified 13 novel SUR1 mutations that cause channel trafficking defects, the majority of which are amenable to pharmacological rescue by glibenclamide and carbamazepine. By contrast, none of the mutant channels were rescued by KATP channel openers. Cross-linking experiments showed that KATP channel inhibitors promoted interactions between the N terminus of Kir6.2 and SUR1, whereas channel openers did not, suggesting the inhibitors enhance intersubunit interactions to overcome channel biogenesis and trafficking defects. Functional studies of rescued mutant channels indicate that most mutants rescued to the cell surface exhibited WT-like sensitivity to ATP, MgADP, and diazoxide. In intact cells, recovery of channel function upon trafficking rescue by reversible sulfonylureas or carbamazepine was facilitated by the KATP channel opener diazoxide. Our study expands the list of KATP channel trafficking mutations whose function can be recovered by pharmacological ligands and provides further insight into the structural mechanism by which channel inhibitors correct channel biogenesis and trafficking defects. PMID:27573238

Elevated body mass index and decreased diet quality among women and risk of birth defects in their offspring.

PubMed

Carmichael, Suzan L; Yang, Wei; Gilboa, Suzanne; Ailes, Elizabeth; Correa, Adolfo; Botto, Lorenzo D; Feldkamp, Marcia L; Shaw, Gary M

2016-03-01

We examined whether risks of 32 birth defects were higher than expected in the presence of overweight or obese body mass index (BMI) and low diet quality, based on estimating individual and joint effects of these factors and calculating relative excess risk due to interaction. Analyses included mothers of 20,250 cases with birth defects and 8617 population-based controls without birth defects born from 1997 to 2009 and interviewed for the National Birth Defects Prevention Study. We used logistic regression to generate adjusted odds ratios (AORs) reflecting the combined effects of BMI and diet quality. We focused analyses on 16 birth defects (n = 11,868 cases, 8617 controls) for which initial results suggested an association with BMI or diet quality. Relative to the reference group (normal weight women with not low diet quality, i.e., >lowest quartile), AORs for low diet quality among normal weight women tended to be >1, and AORs for overweight and obese women tended to be stronger among women who had low diet quality than not low diet quality. For 9/16 birth defects, AORs for obese women who had low diet quality-the group we hypothesized to have highest risk-were higher than other stratum-specific AORs. Most relative excess risk due to interactions were positive but small (<0.5), with confidence intervals that included zero. These findings provide evidence for the hypothesis of highest birth defect risks among offspring to women who are obese and have low diet quality but insufficient evidence for an interaction of these factors in their contribution to risk. © 2015 Wiley Periodicals, Inc.

Glucose counterregulation, hypoglycemia, and intensive insulin therapy in diabetes mellitus.

PubMed

Cryer, P E; Gerich, J E

1985-07-25

The prevention or correction of hypoglycemia is the result of both dissipation of insulin and activation of counterregulatory systems. In the models studied to date, glucagon and epinephrine have been shown to be the key counterregulatory factors; the potential roles of other hormones, neural factors, or substrate mechanisms in other models and during more gradual recovery from hypoglycemia remain to be defined. Deficient glucagon responses to decrements in plasma glucose, which are common in patients with IDDM and occur in some patients with NIDDM, result in altered counterregulation. But counterregulation is generally adequate, because epinephrine compensates for it. Defective glucose counterregulation due to combined deficiencies of glucagon and epinephrine secretory responses occurs in many patients, typically those with longstanding diabetes, and must be added to the list of factors known to increase the risk of hypoglycemia, at least during intensive therapy. From the material reviewed, it should be apparent that much has been learned about glucose counterregulation. It should be equally clear that much remains to be learned. Among the many possibilities, we consider four worthy of emphasis. First of all, we need to examine the physiology and pathophysiology of glucose counterregulation in additional models (e.g., during exercise) and over longer periods. Secondly, we need to determine whether central nervous system adaptation to antecedent glycemia occurs and, if so, identify its mechanisms. Thirdly, we need to develop better methods of insulin delivery or learn to correct or compensate for defective counterregulatory systems, if we are to achieve euglycemia safely in diabetic patients with defective glucose counterregulation. Finally, we need to know whether effective control of diabetes mellitus prevents development of defective glucose counterregulation.

Imaging of cardiovascular dynamics in early mouse embryos with swept source optical coherence tomography

NASA Astrophysics Data System (ADS)

Larina, Irina V.; Liebling, Michael; Dickinson, Mary E.; Larin, Kirill V.

2009-02-01

Congenital cardiovascular defects are very common, occurring in 1% of live births, and cardiovascular failures are the leading cause of birth defect-related deaths in infants. To improve diagnostics, prevention and treatment of cardiovascular abnormalities, we need to understand not only how cells form the heart and vessels but also how physical factors such as heart contraction and blood flow influence heart development and changes in the circulatory network. Mouse models are an excellent resource for studying cardiovascular development and disease because of the resemblance to humans, rapid generation time, and availability of mutants with cardiovascular defects linked to human diseases. In this work, we present results on development and application of Doppler Swept Source Optical Coherence Tomography (DSS-OCT) for imaging of cardiovascular dynamics and blood flow in the mouse embryonic heart and vessels. Our studies demonstrated that the spatial and temporal resolution of the DSS-OCT makes it possible to perform sensitive measurements of heart and vessel wall movements and to investigate how contractile waves facilitate the movement of blood through the circulatory system.

Quality Control System using Simple Implementation of Seven Tools for Batik Textile Manufacturing

NASA Astrophysics Data System (ADS)

Ragil Suryoputro, Muhammad; Sugarindra, Muchamad; Erfaisalsyah, Hendy

2017-06-01

In order to produce better products and mitigate defect in products, every company must implement a quality control system. Company will find means to implement a quality control system that is capable and reliable. One of the methods is using the simple implementation of the seven tools in quality control defects. The case studied in this research was the level of disability xyz grey fabric on a shuttle loom 2 on the Batik manufacturing company. The seven tools that include: flowchart, check sheet, histogram, scatter diagram combined with control charts, Pareto diagrams and fishbone diagrams (causal diagram). Check sheet results obtained types of defects in the grey fabric was woven xyz is warp, double warp, the warp break, double warp, empty warp, warp tenuous, ugly edges, thick warp, and rust. Based on the analysis of control chart indicates that the process is out of control. This can be seen in the graph control where there is still a lot of outlier data. Based on a scatter diagram shows a positive correlation between the percentage of disability and the number of production. Based on Pareto diagram, repair needs priority is for the dominant type of defect is warp (44%) and based on double warp value histogram is also the highest with a value of 23635.11 m. In addition, based on the analysis of the factors causing defect by fishbone diagram double warp or other types of defects originating from the materials, methods, machines, measurements, man and environment. Thus the company can take to minimize the prevention and repair of defects and improve product quality.

Congenital abnormalities in newborns of women with pregestational diabetes: A time-trend analysis, 1994 to 2009.

PubMed

Agha, Mohammad M; Glazier, Richard H; Moineddin, Rahim; Booth, Gillian

2016-10-01

The main objective of the current study is to examine the trend of congenital abnormalities among children born by women with and without diabetes, and to explore the impact of food fortification by folic acid on the rate of birth defects among these two groups of mothers. All children born alive in Ontario, Canada, during 1994 to 2009 and their mothers were included in study. Diagnosis of pregestational diabetes among mothers was identified using Diabetes registry, and diagnosis of birth defects among children were identified using hospital records. The prevalence of births among diabetic mothers increased by almost 200% during the study period. Among children born to mothers with diabetes, the prevalence for all anomalies combined was approximately 47% higher and for various cardiac and central nervous system anomalies up to a three- to fivefold higher than those born to nondiabetic mothers. While the rate of birth defects in both groups observed a considerable decline after food fortification in 1999, but the gap between two groups remained unchanged over time. While the prevalence of birth defects among diabetic pregnancies is still considerably higher that nondiabetic pregnancies, results of the current study indicate a declining trend in the prevalence of some congenital abnormalities among babies born to both diabetic and nondiabetic mothers after 1999. We need to be more aggressive in implementing preventive measures, including a national diabetes plan or the proposed universal policy of supra-dietary folic acid supplementation for women with diabetes who are of reproductive age. Birth Defects Research (Part A) 106:831-839, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Silk fibroin hydrogel as physical barrier for prevention of post hernia adhesion.

PubMed

Konar, S; Guha, R; Kundu, B; Nandi, S; Ghosh, T K; Kundu, S C; Konar, A; Hazra, S

2017-02-01

Adhesion formation remains a major complication following hernia repair surgery. Physical barriers though effective for adhesion prevention in clinical settings are associated with major disadvantages, therefore, needs further investigation. This study evaluates silk fibroin hydrogel as a physical barrier on polypropylene mesh for the prevention of adhesion following ventral hernia repair. Peritoneal explants were cultured on silk fibroin scaffold to evaluate its support for mesothelial cell growth. Full thickness uniform sized defects were created on the ventral abdominal wall of rabbits, and the defects were covered either with silk hydrogel coated polypropylene mesh or with plain polypropylene mesh as a control. The animals were killed after 1 month, and the adhesion formation was graded; healing response of peritoneum was evaluated by immunohistochemistry with calretinin, collagen staining of peritoneal sections, and expression of PCNA, collagen-I, TNFα, IL6 by real time PCR; and its adverse effect if any was determined. Silk fibroin scaffold showed excellent support for peritoneal cell growth in vitro and the cells expressed calretinin. A remarkable prevention of adhesion formation was observed in the animals implanted with silk hydrogel coated mesh compared to the control group; in these animals peritoneal healing was complete and predominantly by mesothelial cells with minimum fibrotic changes. Expression of inflammatory cytokines decreased compared to control animals, histology of abdominal organs, haematological and blood biochemical parameters remained normal. Therefore, silk hydrogel coating of polypropylene mesh can improve peritoneal healing, minimize adhesion formation, is safe and can augment the outcome of hernia surgery.

Melatonin protects against maternal obesity-associated oxidative stress and meiotic defects in oocytes via the SIRT3-SOD2-dependent pathway.

PubMed

Han, Longsen; Wang, Haichao; Li, Ling; Li, Xiaoyan; Ge, Juan; Reiter, Russel J; Wang, Qiang

2017-10-01

Maternal obesity in humans is associated with poor outcomes across the reproductive spectrum. Emerging evidence indicates that these defects are likely attributed to factors within the oocyte. Although various molecules and pathways may contribute to impaired oocyte quality, prevention of fertility issues associated with maternal obesity is a challenge. Using mice fed a high-fat diet (HFD) as an obesity model, we document spindle disorganization, chromosome misalignment, and elevated reactive oxygen species (ROS) levels in oocytes from obese mice. Oral administration of melatonin to HFD mice not only reduces ROS generation, but also prevents spindle/chromosome anomalies in oocytes, consequently promoting the developmental potential of early embryos. Consistent with this finding, we find that melatonin supplement during in vitro maturation also markedly attenuates oxidative stress and meiotic defects in HFD oocytes. Finally, by performing morpholino knockdown and acetylation-mimetic mutant overexpression assays, we reveal that melatonin ameliorates maternal obesity-induced defective phenotypes in oocytes through the SIRT3-SOD2-dependent mechanism. In sum, our data uncover the marked beneficial effects of melatonin on oocyte quality from obese females; this opens a new area for optimizing culture system as well as fertility management. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Congenital heart defects in newborns with apparently isolated single gastrointestinal malformation: A retrospective study.

PubMed

Schierz, Ingrid Anne Mandy; Pinello, Giuseppa; Giuffrè, Mario; La Placa, Simona; Piro, Ettore; Corsello, Giovanni

2016-12-01

Congenital gastrointestinal system malformations/abdominal wall defects (GISM) may appear as isolated defects (single or complex), or in association with multiple malformations. The high incidence of association of GISM and congenital heart defects (CHD) in patients with syndromes and malformative sequences is known, but less expected is the association of apparently isolated single GISM and CHD. The aim of this study was to investigate the frequency of CHD in newborns with isolated GISM, and the possibility to modify the diagnostic-therapeutic approach just before the onset of cardiac symptoms or complications. Anamnestic, clinical, and imaging data of newborns requiring abdominal surgery for GISM, between 2009 and 2014, were compared with a control group of healthy newborns. Distribution of GISM and cardiovascular abnormalities were analyzed, and risk factors for adverse outcomes were identified. Seventy-one newborns with isolated GISM were included in this study. More frequent GISM were intestinal rotation and fixation disorders. CHD were observed in 15.5% of patients, augmenting their risk for morbidity. Risk factors for morbidity related to sepsis were identified in central venous catheter, intestinal stoma, and H2-inhibitor-drugs. Moreover, 28.2% of newborns presented only functional cardiac disorders but an unexpectedly higher mortality. The high incidence of congenital heart disease in infants with apparently isolated GISM confirms the need to perform an echocardiographic study before surgery to improve perioperative management and prevent complications such as sepsis and endocarditis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Genetic Engineering and the Amelioration of Genetic Defect

ERIC Educational Resources Information Center

Lederberg, Joshua

1970-01-01

Discusses the claims for a brave new world of genetic manipulation" and concludes that if we could agree upon applying genetic (or any other effective) remedies to global problems we probably would need no rescourse to them. Suggests that effective methods of preventing genetic disease are prevention of mutations and detection and…

Generation of an immortalized mouse embryonic palatal mesenchyme cell line

PubMed Central

Soriano, Philippe

2017-01-01

Palatogenesis is a complex morphogenetic process, disruptions in which result in highly prevalent birth defects in humans. In recent decades, the use of model systems such as genetically-modified mice, mouse palatal organ cultures and primary mouse embryonic palatal mesenchyme (MEPM) cultures has provided significant insight into the molecular and cellular defects underlying cleft palate. However, drawbacks in each of these systems have prevented high-throughput, large-scale studies of palatogenesis in vitro. Here, we report the generation of an immortalized MEPM cell line that maintains the morphology, migration ability, transcript expression and responsiveness to exogenous growth factors of primary MEPM cells, with increased proliferative potential over primary cultures. The immortalization method described in this study will facilitate the generation of palatal mesenchyme cells with an unlimited capacity for expansion from a single genetically-modified mouse embryo and enable mechanistic studies of palatogenesis that have not been possible using primary culture. PMID:28582446

Brain abscess of odontogenic origin in a man with interatrial defect.

PubMed

Milli, Bruna; Rocci, Anna; Paganelli, Enrico; Degli Antoni, Gino; Monaco, Delio; Quintavalla, Roberto

2010-12-01

A 65-year-old man with previous surgery for cyanotic congenital heart disease was admitted to our hospital with fever, headache and visual disturbances due to a right occipital brain abscess as shown through CT-scan. A comprehensive workup looking for a source of infection was negative except for an orthopantomogram showing multiple dental caries. A transesophageal echocardiogram (TEE) bubble study revealed the permanence of an atrial septal defect with a moderate right-to-left shunt. The culture of the abscess content showed flora commonly found in the oropharynx that responded to antimicrobial therapy. We hypothesize that the underlying mechanism is a significant bacterial load from dental infections that enters the arterial circulation through the interatrial defect. If a brain abscess is identified without any adjacent source of infection, then a transesophageal echocardiogram is indicated to exclude right to left shunt. If a shunt is found, then hematogenous spread of flora normally found in the oropharynx should be suspected. Surgical evacuation followed by antimicrobial therapy is warranted. Once the infection is eliminated, long term anticoagulation or anatomic closure of the interatrial defect with good oral hygiene could be valid strategies for preventing recurrence.

Promotora de salud: promoting folic acid use among Hispanic women.

PubMed

deRosset, Leslie; Mullenix, Amy; Flores, Alina; Mattia-Dewey, Daniel; Mai, Cara T

2014-06-01

The U.S. Public Health Service recommends that all women in the United States capable of becoming pregnant consume 400 μg of folic acid daily to reduce their risk of having a pregnancy affected by a neural tube defect (NTD). However, disparities exist in the consumption of folic acid, with Hispanic women having lower rates of folic acid consumption than non-Hispanic white women. A community-based feasibility study was designed to assess the utility of the promotora de salud model to promote consumption of multivitamins containing folic acid for the prevention of NTDs among Spanish-speaking Hispanic women in North Carolina. The study consisted of an educational intervention given by a promotora (a lay, community health worker), with data collection occurring at baseline and four months post-intervention to measure changes in knowledge and behavior. Overall, 52% (n=303) of participants completed all components of the study. Self-reported daily multivitamin consumption increased from 24% at baseline to 71% four months post-intervention. During the same time frame, awareness of folic acid increased from 78% to 98% and knowledge of the role of folic acid in the prevention of birth defects increased from 82% to 92%. The results of this study indicate that the promotora de salud model may be effective in reaching a subpopulation of women with the folic acid message. Additional studies with larger population sizes are warranted to validate these findings.

Barrier mechanism of multilayers graphene coated copper against atomic oxygen irradiation

NASA Astrophysics Data System (ADS)

Zhang, Haijing; Ren, Siming; Pu, Jibin; Xue, Qunji

2018-06-01

Graphene has been demonstrated as a protective coating for Cu under ambient condition because of its high impermeability and light-weight oxidation barrier. However, it lacks the research of graphene as a protective coating in space environment. Here, we experimentally and theoretically study the oxidation behavior of graphene-coated Cu in vacuum atomic oxygen (AO) condition. After AO irradiation, the experimental results show multilayer graphene has better anti-oxidation than monolayer graphene. Meanwhile, the calculation results show the oxidation appeared on the graphene's grain boundaries or the film's vacancy defects for the monolayer graphene coated Cu foil. Moreover, the calculation results show the oxidation process proceeds slowly in multilayers because of the matched defects overlaps each other to form a steric hindrance to suppress the O atom diffusion in the vertical direction, and the mismatched defects generates potential energy barriers for interlayer to suppress the O atom diffusion in the horizontal direction. Hence, multilayer graphene films could serve as protection coatings to prevent diffusion of O atom.

Vitrectomy-assisted phacoemulsification for lenticular coloboma.

PubMed

Agarwal, Ashvin; Narang, Priya; Agarwal, Amar

2017-02-01

We describe a technique to prevent continuous vitreous hydration during phacoemulsification in eyes with lenticular coloboma. The hydration results from communication between the anterior and posterior chambers from the edges of the colobomatous defect. To avoid this, a valved trocar is placed at the pars plana site around the area of the lenticular defect, which allows a limited dry vitrectomy during phacoemulsification. Intermittent vitrectomy with a moderate cutting rate and low vacuum parameters accompanied by temporary halting of the phacoemulsification procedure prevents vitreous herniation into the anterior chamber and limits the extension of zonular compromise, facilitating safe phacoemulsification with appropriate capsule expansion and fixation devices and implantation of an intraocular lens. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

The role of diet and nutrition in the etiology and prevention of oral diseases.

PubMed

Moynihan, Paula J

2005-09-01

Diet plays an important role in preventing oral diseases including dental caries, dental erosion, developmental defects, oral mucosal diseases and, to a lesser extent, periodontal disease. This paper is intended to provide an overview of the evidence for an association between diet, nutrition and oral diseases and to clarify areas of uncertainty. Undernutrition increases the severity of oral mucosal and periodontal diseases and is a contributing factor to life-threatening noma. Undernutrition is associated with developmental defects of the enamel which increase susceptibility to dental caries. Dental erosion is perceived to be increasing. Evidence suggests that soft drinks, a major source of acids in the diet in developed countries, are a significant causative factor. Convincing evidence from experimental, animal, human observational and human intervention studies shows that sugars are the main dietary factor associated with dental caries. Despite the indisputable role of fluoride in the prevention of caries, it has not eliminated dental caries and many communities are not exposed to optimal quantities of fluoride. Controlling the intake of sugars therefore remains important for caries prevention. Research has consistently shown that when the intake of free sugars is < 15 kg/person/year, the level of dental caries is low. Despite experimental and animal studies suggesting that some starch-containing foods and fruits are cariogenic, this is not supported by epidemiological data, which show that high intakes of starchy staple foods, fruits and vegetables are associated with low levels of dental caries. Following global recommendations that encourage a diet high in starchy staple foods, fruit and vegetables and low in free sugars and fat will protect both oral and general health.

The role of diet and nutrition in the etiology and prevention of oral diseases.

PubMed Central

Moynihan, Paula J.

2005-01-01

Diet plays an important role in preventing oral diseases including dental caries, dental erosion, developmental defects, oral mucosal diseases and, to a lesser extent, periodontal disease. This paper is intended to provide an overview of the evidence for an association between diet, nutrition and oral diseases and to clarify areas of uncertainty. Undernutrition increases the severity of oral mucosal and periodontal diseases and is a contributing factor to life-threatening noma. Undernutrition is associated with developmental defects of the enamel which increase susceptibility to dental caries. Dental erosion is perceived to be increasing. Evidence suggests that soft drinks, a major source of acids in the diet in developed countries, are a significant causative factor. Convincing evidence from experimental, animal, human observational and human intervention studies shows that sugars are the main dietary factor associated with dental caries. Despite the indisputable role of fluoride in the prevention of caries, it has not eliminated dental caries and many communities are not exposed to optimal quantities of fluoride. Controlling the intake of sugars therefore remains important for caries prevention. Research has consistently shown that when the intake of free sugars is < 15 kg/person/year, the level of dental caries is low. Despite experimental and animal studies suggesting that some starch-containing foods and fruits are cariogenic, this is not supported by epidemiological data, which show that high intakes of starchy staple foods, fruits and vegetables are associated with low levels of dental caries. Following global recommendations that encourage a diet high in starchy staple foods, fruit and vegetables and low in free sugars and fat will protect both oral and general health. PMID:16211161

Insights into Metabolic Mechanisms Underlying Folate-Responsive Neural Tube Defects: A Minireview

PubMed Central

Beaudin, Anna E.; Stover, Patrick J.

2015-01-01

Neural tube defects (NTDs), including anencephaly and spina bifida, arise from the failure of neurulation during early embryonic development. Neural tube defects are common birth defects with a heterogenous and multifactorial etiology with interacting genetic and environmental risk factors. Although the mechanisms resulting in failure of neural tube closure are unknown, up to 70% of NTDs can be prevented by maternal folic acid supplementation. However, the metabolic mechanisms underlying the association between folic acid and NTD pathogenesis have not been identified. This review summarizes our current understanding of the mechanisms by which impairments in folate metabolism might ultimately lead to failure of neural tube closure, with an emphasis on untangling the relative contributions of nutritional deficiency and genetic risk factors to NTD pathogenesis. PMID:19180567

Emergent presentation of decompensated mitral valve prolapse and atrial septal defect.

PubMed

Kang, Jessie; Das, Bijon

2015-05-01

Mitral valve prolapse is not commonly on the list of differential diagnosis when a patient presents in the emergency department (ED) in severe distress, presenting with non-specific features such as abdominal pain, tachycardia and dyspnea. A healthy 55-year-old man without significant past medical history arrived in the ED with a unique presentation of a primary mitral valve prolapse with an atrial septal defect uncommon in cardiology literature. Early recognition of mitral valve prolapse in high-risk patients for severe mitral regurgitation or patients with underlying cardiovascular abnormalities such as an atrial septal defect is crucial to prevent morbid outcomes such as sudden cardiac death.

Challenges in the reconstruction of bilateral maxillectomy defects.

PubMed

Joseph, Shawn T; Thankappan, Krishnakumar; Buggaveeti, Rahul; Sharma, Mohit; Mathew, Jimmy; Iyer, Subramania

2015-02-01

Bilateral maxillectomy defects, if not adequately reconstructed, can result in grave esthetic and functional problems. The purpose of this study was to investigate the outcome of reconstruction of such defects. This is a retrospective case series. The defects were analyzed for their components and the flaps used for reconstruction. Outcomes for flap loss and functional indices, including oral diet, speech, and dental rehabilitation, also were evaluated. Ten consecutive patients who underwent bilateral maxillectomy reconstruction received 14 flaps. Six patients had malignancies of the maxilla, and 4 patients had nonmalignant indications. Ten bony free flaps were used. Four soft tissue flaps were used. The fibula free flap was the most common flap used. Three patients had total flap loss. Seven patients were alive and available for functional evaluation. Of these, 4 were taking an oral diet with altered consistency and 2 were on a regular diet. Speech was intelligible in all patients. Only 2 patients opted for dental rehabilitation with removable dentures. Reconstruction after bilateral maxillectomy is essential to prevent esthetic and functional problems. Bony reconstruction is ideal. The fibula bone free flap is commonly used. The complexity of the defect makes reconstruction difficult and the initial success rate of free flaps is low. Secondary reconstructions after the initial flap failures were successful. A satisfactory functional outcome can be achieved. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Growth and analysis of micro and nano CdTe arrays for solar cell applications

NASA Astrophysics Data System (ADS)

Aguirre, Brandon Adrian

CdTe is an excellent material for infrared detectors and photovoltaic applications. The efficiency of CdTe/CdS solar cells has increased very rapidly in the last 3 years to ˜20% but is still below the maximum theoretical value of 30%. Although the short-circuit current density is close to its maximum of 30 mA/cm2, the open circuit voltage has potential to be increased further to over 1 Volt. The main limitation that prevents further increase in the open-circuit voltage and therefore efficiency is the high defect density in the CdTe absorber layer. Reducing the defect density will increase the open-circuit voltage above 1 V through an increase in the carrier lifetime and concentration to tau >10 ns and p > 10 16 cm-3, respectively. However, the large lattice mismatch (10%) between CdTe and CdS and the polycrystalline nature of the CdTe film are the fundamental reasons for the high defect density and pose a difficult challenge to solve. In this work, a method to physically and electrically isolate the different kinds of defects at the nanoscale and understand their effect on the electrical performance of CdTe is presented. A SiO2 template with arrays of window openings was deposited between the CdTe and CdS to achieve selective-area growth of the CdTe via close-space sublimation. The diameter of the window openings was varied from the micro to the nanoscale to study the effect of size on nucleation, grain growth, and defect density. The resulting structures enabled the possibility to electrically isolate and individually probe micrometer and nanoscale sized CdTe/CdS cells. Electron back-scattered diffraction was used to observe grain orientation and defects in the miniature cells. Scanning and transmission electron microscopy was used to study the morphology, grain boundaries, grain orientation, defect structure, and strain in the layers. Finally, conducting atomic force microscopy was used to study the current-voltage characteristics of the solar cells. An important part of this work was the ability to directly correlate the one-to-one relationship between the electrical performance and defect structure of individual nanoscale cells. This method is general and can be applied to other material systems to study the electrical-microstructure relationship on a one-to-one basis with nanoscale resolution.

The Eyesight of School Children: Defective Vision as Related to School Environment, and Methods of Prevention and Correction. Bulletin, 1919, No. 65

ERIC Educational Resources Information Center

Berkowitz, J. H.

1920-01-01

Competent authorities seem to agree as to the causes of eye strain in school children other than congenital defects. Standard works on diseases of the eye are practically unanimous in declaring that myopia results from the protracted and unhygienic use of the eyes in near work. Most of the factors tending to cause eye strain exist in the schools.…

Pharmacological Correction of Trafficking Defects in ATP-sensitive Potassium Channels Caused by Sulfonylurea Receptor 1 Mutations.

PubMed

Martin, Gregory M; Rex, Emily A; Devaraneni, Prasanna; Denton, Jerod S; Boodhansingh, Kara E; DeLeon, Diva D; Stanley, Charles A; Shyng, Show-Ling

2016-10-14

ATP-sensitive potassium (K ATP ) channels play a key role in mediating glucose-stimulated insulin secretion by coupling metabolic signals to β-cell membrane potential. Loss of K ATP channel function due to mutations in ABCC8 or KCNJ11, genes encoding the sulfonylurea receptor 1 (SUR1) or the inwardly rectifying potassium channel Kir6.2, respectively, results in congenital hyperinsulinism. Many SUR1 mutations prevent trafficking of channel proteins from the endoplasmic reticulum to the cell surface. Channel inhibitors, including sulfonylureas and carbamazepine, have been shown to correct channel trafficking defects. In the present study, we identified 13 novel SUR1 mutations that cause channel trafficking defects, the majority of which are amenable to pharmacological rescue by glibenclamide and carbamazepine. By contrast, none of the mutant channels were rescued by K ATP channel openers. Cross-linking experiments showed that K ATP channel inhibitors promoted interactions between the N terminus of Kir6.2 and SUR1, whereas channel openers did not, suggesting the inhibitors enhance intersubunit interactions to overcome channel biogenesis and trafficking defects. Functional studies of rescued mutant channels indicate that most mutants rescued to the cell surface exhibited WT-like sensitivity to ATP, MgADP, and diazoxide. In intact cells, recovery of channel function upon trafficking rescue by reversible sulfonylureas or carbamazepine was facilitated by the K ATP channel opener diazoxide. Our study expands the list of K ATP channel trafficking mutations whose function can be recovered by pharmacological ligands and provides further insight into the structural mechanism by which channel inhibitors correct channel biogenesis and trafficking defects. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

How to minimize ischemic complication related to swollen temporalis muscle following indirect revascularization surgery in moyamoya disease: a technical report.

PubMed

Joo, Sung Pil; Kim, Tae Sun; Moon, Hyung Sik

2014-05-01

There are several reports in the literature of postoperative ischemic events due to swelling of the temporalis muscle after indirect revascularization surgery. Here, we report our surgical technique for preventing ischemic events during the acute postoperative recovery period in moyamoya patients. We used various types of titanium mesh to cover the bony defect area in 8 patients (10 operations) with moyamoya disease. The mesh was cut and manipulated according to the shape of the bony defect. Surgical results were favorable, with no newly developed ischemic event or infarction in the acute recovery period. The mesh formed an outer table of skull, so there was no compressive effect on the temporalis muscle and no cosmetic defects. The titanium mesh appears to be effective and useful for prevention of ischemic insult in the treatment of moyamoya disease. The choice of this procedure depends on both the operative findings of temporalis muscle thickness and the status of ischemic vulnerability of moyamoya brain. Georg Thieme Verlag KG Stuttgart · New York.

Progesterone Prevents High-Grade Serous Ovarian Cancer by Inducing Necroptosis of p53-Defective Fallopian Tube Epithelial Cells.

PubMed

Wu, Na-Yiyuan; Huang, Hsuan-Shun; Chao, Tung Hui; Chou, Hsien Ming; Fang, Chao; Qin, Chong-Zhen; Lin, Chueh-Yu; Chu, Tang-Yuan; Zhou, Hong Hao

2017-03-14

High-grade serous ovarian carcinoma (HGSOC) originates mainly from the fallopian tube (FT) epithelium and always carries early TP53 mutations. We previously reported that tumors initiate in the FT fimbria epithelium because of apoptotic failure and the expansion of cells with DNA double-strand breaks (DSB) caused by bathing of the FT epithelial cells in reactive oxygen species (ROSs) and hemoglobin-rich follicular fluid (FF) after ovulation. Because ovulation is frequent and HGSOC is rare, we hypothesized that luteal-phase progesterone (P4) could eliminate p53-defective FT cells. Here we show that P4, via P4 receptors (PRs), induces necroptosis in Trp53 -/- mouse oviduct epithelium and in immortalized human p53-defective fimbrial epithelium through the TNF-α/RIPK1/RIPK3/MLKL pathway. Necroptosis occurs specifically at diestrus, recovers at the proestrus phase of the estrus cycle, and can be augmented with P4 supplementation. These results reveal the mechanism of the well-known ability of progesterone to prevent ovarian cancer. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Cyclin Kinase-independent role of p21CDKN1A in the promotion of nascent DNA elongation in unstressed cells

PubMed Central

Mansilla, Sabrina F; Bertolin, Agustina P; Bergoglio, Valérie; Pillaire, Marie-Jeanne; González Besteiro, Marina A; Luzzani, Carlos; Miriuka, Santiago G; Hoffmann, Jean-Sébastien; Gottifredi, Vanesa

2016-01-01

The levels of the cyclin-dependent kinase (CDK) inhibitor p21 are low in S phase and insufficient to inhibit CDKs. We show here that endogenous p21, instead of being residual, it is functional and necessary to preserve the genomic stability of unstressed cells. p21depletion slows down nascent DNA elongation, triggers permanent replication defects and promotes the instability of hard-to-replicate genomic regions, namely common fragile sites (CFS). The p21’s PCNA interacting region (PIR), and not its CDK binding domain, is needed to prevent the replication defects and the genomic instability caused by p21 depletion. The alternative polymerase kappa is accountable for such defects as they were not observed after simultaneous depletion of both p21 and polymerase kappa. Hence, in CDK-independent manner, endogenous p21 prevents a type of genomic instability which is not triggered by endogenous DNA lesions but by a dysregulation in the DNA polymerase choice during genomic DNA synthesis. DOI: http://dx.doi.org/10.7554/eLife.18020.001 PMID:27740454

Dental Caries and Enamel Defects in Very Low Birth Weight Adolescents

PubMed Central

Nelson, S.; Albert, J.M.; Lombardi, G.; Wishnek, S.; Asaad, G.; Kirchner, H.L.; Singer, L.T.

2011-01-01

Objectives The purpose of this study was to examine developmental enamel defects and dental caries in very low birth weight adolescents with high risk (HR-VLBW) and low risk (LR-VLBW) compared to full-term (term) adolescents. Methods The sample consisted of 224 subjects (80 HR-VLBW, 59 LR-VLBW, 85 term adolescents) recruited from an ongoing longitudinal study. Sociodemographic and medical information was available from birth. Dental examination of the adolescent at the 14-year visit included: enamel defects (opacity and hypoplasia); decayed, missing, filled teeth of incisors and molars (DMFT-IM) and of overall permanent teeth (DMFT); Simplified Oral Hygiene Index for debris/calculus on teeth, and sealant presence. A caregiver questionnaire completed simultaneously assessed dental behavior, access, insurance status and prevention factors. Hierarchical analysis utilized the zero-inflated negative binomial model and zero-inflated Poisson model. Results The zero-inflated negative binomial model controlling for sociodemographic variables indicated that the LR-VLBW group had an estimated 75% increase (p < 0.05) in number of demarcated opacities in the incisors and first molar teeth compared to the term group. Hierarchical modeling indicated that demarcated opacities were a significant predictor of DMFT-IM after control for relevant covariates. The term adolescents had significantly increased DMFT-IM and DMFT scores compared to the LR-VLBW adolescents. Conclusion LR-VLBW was a significant risk factor for increased enamel defects in the permanent incisors and first molars. Term children had increased caries compared to the LR-VLBW group. The effect of birth group and enamel defects on caries has to be investigated longitudinally from birth. PMID:20975268

The role of precisely matching fascicles in the quick recovery of nerve function in long peripheral nerve defects

PubMed Central

Yan, Liwei; Yao, Zhi; Lin, Tao; Zhu, Qingtang; Qi, Jian; Gu, Liqiang; Fang, Jintao; Zhou, Xiang

2017-01-01

Peripheral nerve injury therapy in the clinic remains less than satisfactory. The gold standard of treatment for long peripheral nerve defects is autologous nerve grafts; however, numerous clinical complications are associated with this treatment. As tissue engineering has developed, tissue-engineered nerve grafts (TENGs) have shown potential applications as alternatives to autologous nerve grafts. To verify the important role of the biomimetic pathway of fascicle design in TENGs, we designed an animal model to study the role of the precise matching of fascicles in the effectiveness of nerve function recovery. 24 Sprague-Dawley rats were divided randomly into three groups (eight/group) that corresponded to 100% fascicle matching (100%FM), 50%FM and 0%FM. We selected Sprague–Dawley rat long-gap (15 mm) sciatic nerve defects. In the 6 weeks after surgery, we found that the 100%FM group showed the most effective functional recovery among the three groups. The 100%FM group showed better functional recovery on the basis of the sciatic functional index than the 50%FM and 0%FM groups. According to histological evaluation, the 100%FM group showed more regenerating nerve fibres. Moreover, in terms of the prevention of muscle atrophy, the 100%FM group showed excellent physiological outcomes. The 100%FM as tissue-engineered scaffolds can enhance nerve regeneration and effective functional recovery after the repair of large nerve defects. The results of this study provide a theoretical basis for future TENG designs including biomimetic fascicle pathways for repairing long nerve defects. PMID:28914740

Spectrum of prenatally detected central nervous system malformations: Neural tube defects continue to be the leading foetal malformation.

PubMed

Siddesh, Anjurani; Gupta, Geetika; Sharan, Ram; Agarwal, Meenal; Phadke, Shubha R

2017-04-01

Prenatal diagnosis of malformations is an important method of prevention and control of congenital anomalies with poor prognosis. Central nervous system (CNS) malformations amongst these are the most common. The information about the prevalence and spectrum of prenatally detected malformations is crucial for genetic counselling and policymaking for population-based preventive programmes. The objective of this study was to study the spectrum of prenatally detected CNS malformations and their association with chromosomal abnormalities and autopsy findings. This retrospective study was conducted in a tertiary care hospital in north India from January 2007 to December 2013. The details of cases with prenatally detected CNS malformations were collected and were related with the foetal chromosomal analysis and autopsy findings. Amongst 6044 prenatal ultrasonographic examinations performed; 768 (12.7%) had structural malformations and 243 (31.6%) had CNS malformations. Neural tube defects (NTDs) accounted for 52.3 per cent of CNS malformations and 16.5 per cent of all malformations. The other major groups of prenatally detected CNS malformations were ventriculomegaly and midline anomalies. Chromosomal abnormalities were detected in 8.2 per cent of the 73 cases studied. Foetal autopsy findings were available for 48 foetuses. Foetal autopsy identified additional findings in eight foetuses and the aetiological diagnosis changed in two of them (4.2%). Amongst prenatally detected malformations, CNS malformations were common. NTD, which largely is a preventable anomaly, continued to be the most common group. Moreover, 60 per cent of malformations were diagnosed after 20 weeks, posing legal issues. Chromosomal analysis and foetal autopsy are essential for genetic counselling based on aetiological diagnosis.

Folate and human reproduction.

PubMed

Tamura, Tsunenobu; Picciano, Mary Frances

2006-05-01

The influence of folate nutritional status on various pregnancy outcomes has long been recognized. Studies conducted in the 1950s and 1960s led to the recognition of prenatal folic acid supplementation as a means to prevent pregnancy-induced megaloblastic anemia. In the 1990s, the utility of periconceptional folic acid supplementation and folic acid food fortification emerged when they were proven to prevent the occurrence of neural tube defects. These distinctively different uses of folic acid may well be ranked among the most significant public health measures for the prevention of pregnancy-related disorders. Folate is now viewed not only as a nutrient needed to prevent megaloblastic anemia in pregnancy but also as a vitamin essential for reproductive health. This review focuses on the relation between various outcomes of human reproduction (ie, pregnancy, lactation, and male reproduction) and folate nutrition and metabolism, homocysteine metabolism, and polymorphisms of genes that encode folate-related enzymes or proteins, and we identify issues for future research.

Medications Used to Treat Nausea and Vomiting of Pregnancy and the Risk of Selected Birth Defects

PubMed Central

Anderka, Marlene; Mitchell, Allen A.; Louik, Carol; Werler, Martha M.; Hernández-Diaz, Sonia; Rasmussen, Sonja A.

2012-01-01

Background Nausea and vomiting of pregnancy (NVP) occurs in up to 80% of pregnant women, yet its association with birth outcomes is not clear. Several medications are used for the treatment of NVP; however, data are limited on their possible associations with birth defects. Methods Using data from the National Birth Defects Prevention Study (NBDPS), a multi-site population-based case-control study, we examined whether NVP or its treatment was associated with the most common non-cardiac defects in the NBDPS (non-syndromic cleft lip with or without cleft palate (CL/P), cleft palate alone (CP), neural tube defects (NTDs), and hypospadias) compared to randomly-selected non-malformed live births. Results Among the 4524 cases and 5859 controls included in this study, 67.1% reported first trimester NVP, and 15.4% of them reported using at least one agent for NVP. Nausea and vomiting of pregnancy was not associated with CP or NTDs, but modest risk reductions were observed for CL/P (aOR=0.87, 0.77–0.98), and hypospadias (OR=0.84, 0.72–0.98). In regards to treatments for NVP in the first trimester, the following adjusted associations were observed with an increased risk: proton pump inhibitors and hypospadias (aOR=4.36, 1.21–15.81), steroids and hypospadias (aOR=2.87, 1.03–7.97), and ondansetron and CP (aOR=2.37, 1.18–4.76), while antacids were associated with a reduced risk for CL/P (aOR=0.58, 0.38–0.89). Conclusions Nausea and vomiting of pregnancy was not observed to be associated with an increased risk of birth defects, but possible risks related to three treatments (i.e. proton pump inhibitors, steroids and ondansetron), which could be chance findings, warrant further investigation. PMID:22102545

Fetal Alcohol Spectrum Disorders.

PubMed

Williams, Janet F; Smith, Vincent C

2015-11-01

Prenatal exposure to alcohol can damage the developing fetus and is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities. In 1973, fetal alcohol syndrome was first described as a specific cluster of birth defects resulting from alcohol exposure in utero. Subsequently, research unequivocally revealed that prenatal alcohol exposure causes a broad range of adverse developmental effects. Fetal alcohol spectrum disorder (FASD) is the general term that encompasses the range of adverse effects associated with prenatal alcohol exposure. The diagnostic criteria for fetal alcohol syndrome are specific, and comprehensive efforts are ongoing to establish definitive criteria for diagnosing the other FASDs. A large and growing body of research has led to evidence-based FASD education of professionals and the public, broader prevention initiatives, and recommended treatment approaches based on the following premises:▪ Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.▪ Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.▪ Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.▪ During pregnancy:◦no amount of alcohol intake should be considered safe;◦there is no safe trimester to drink alcohol;◦all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and◦binge drinking poses dose-related risk to the developing fetus. Copyright © 2015 by the American Academy of Pediatrics.

Making birth defects 'preventable': pre-conceptional vitamin supplements and the politics of risk reduction.

PubMed

Al-Gailani, Salim

2014-09-01

Since the mid-1990s, governments and health organizations around the world have adopted policies designed to increase women's intake of the B-vitamin 'folic acid' before and during the first weeks of pregnancy. Building on initial clinical research in the United Kingdom, folic acid supplementation has been shown to lower the incidence of neural tube defects (NTDs). Recent debate has focused principally on the need for mandatory fortification of grain products with this vitamin. This article takes a longer view, tracing the transformation of folic acid from a routine prenatal supplement to reduce the risk of anaemia to a routine 'pre-conceptional' supplement to 'prevent' birth defects. Understood in the 1950s in relation to social problems of poverty and malnutrition, NTDs were by the end of the century more likely to be attributed to individual failings. This transition was closely associated with a second. Folic acid supplements were initially prescribed to 'high-risk' women who had previously borne a child with a NTD. By the mid-1990s, they were recommended for all women of childbearing age. The acceptance of folic acid as a 'risk-reducing drug' both relied upon and helped to advance the development of preventive and clinical practices concerned with women's health before pregnancy. Copyright © 2013 The Author. Published by Elsevier Ltd.. All rights reserved.

Detecting Submicron Pattern Defects On Optical Photomasks Using An Enhanced El-3 Electron-Beam Lithography Tool

NASA Astrophysics Data System (ADS)

Simpson, R. A.; Davis, D. E.

1982-09-01

This paper describes techniques to detect submicron pattern defects on optical photomasks with an enhanced direct-write, electron-beam lithographic tool. EL-3 is a third generation, shaped spot, electron-beam lithography tool developed by IBM to fabricate semiconductor devices and masks. This tool is being upgraded to provide 100% inspection of optical photomasks for submicron pattern defects, which are subsequently repaired. Fixed-size overlapped spots are stepped over the mask patterns while a signal derived from the back-scattered electrons is monitored to detect pattern defects. Inspection does not require pattern recognition because the inspection scan patterns are derived from the original design data. The inspection spot is square and larger than the minimum defect to be detected, to improve throughput. A new registration technique provides the beam-to-pattern overlay required to locate submicron defects. The 'guard banding" of inspection shapes prevents mask and system tolerances from producing false alarms that would occur should the spots be mispositioned such that they only partially covered a shape being inspected. A rescanning technique eliminates noise-related false alarms and significantly improves throughput. Data is accumulated during inspection and processed offline, as required for defect repair. EL-3 will detect 0.5 um pattern defects at throughputs compatible with mask manufacturing.

Serine biosynthesis and transport defects.

PubMed

El-Hattab, Ayman W

2016-07-01

l-serine is a non-essential amino acid that is biosynthesized via the enzymes phosphoglycerate dehydrogenase (PGDH), phosphoserine aminotransferase (PSAT), and phosphoserine phosphatase (PSP). Besides its role in protein synthesis, l-serine is a potent neurotrophic factor and a precursor of a number of essential compounds including phosphatidylserine, sphingomyelin, glycine, and d-serine. Serine biosynthesis defects result from impairments of PGDH, PSAT, or PSP leading to systemic serine deficiency. Serine biosynthesis defects present in a broad phenotypic spectrum that includes, at the severe end, Neu-Laxova syndrome, a lethal multiple congenital anomaly disease, intermediately, infantile serine biosynthesis defects with severe neurological manifestations and growth deficiency, and at the mild end, the childhood disease with intellectual disability. A serine transport defect resulting from deficiency of the ASCT1, the main transporter for serine in the central nervous system, has been recently described in children with neurological manifestations that overlap with those observed in serine biosynthesis defects. l-serine therapy may be beneficial in preventing or ameliorating symptoms in serine biosynthesis and transport defects, if started before neurological damage occurs. Herein, we review serine metabolism and transport, the clinical, biochemical, and molecular aspects of serine biosynthesis and transport defects, the mechanisms of these diseases, and the potential role of serine therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

[Prevention of neural tube defects. An important health and social problem].

PubMed

Czochańska, J; Lech, M

1998-01-01

Central neural system congenital malformations in the form of neural tube defects (ntd) belong to the most common diseases leading to very serious childrens' disability and mortality. As it has been calculated, the number of children affected with ntd, delivered in Poland every year is in the range of 800-1150. Children with encephalocele participate in this number in app. 50%. As it has been found, morbidity and mortality caused by the ntd remain high and stable in Poland for the last 20 years. In the view of very limited possibilities of the treatment offered by health services, prophylactic measures remain the best methods for limitation of the problem. The primary prevention of ntd was discovered in late seventies. It has been found that folic acid added to the diet of women in the reproductive age reduced number of children born with ntd by 70%. Authors present the Programme of Primary Prevention of ntd in Poland. This Programme has been incorporated in the National Programme of Health for the Nation 1996-2005.

Back-irradiation photonic sintering for defect-free high-conductivity metal patterns on transparent plastic

NASA Astrophysics Data System (ADS)

Kwak, Ji Hye; Chun, Su Jin; Shon, Chae-Hwa; Jung, Sunshin

2018-04-01

Photonic sintering has attracted considerable attention for printed electronics. It irradiates high-intensity light onto the front surface of metal nanoparticle patterns, which often causes defects such as delamination, cavities, and cracks in the patterns. Here, a back-irradiation photonic sintering method is developed for obtaining defect-free high-conductivity metal patterns on a transparent plastic substrate, through which high-intensity light is irradiated onto the back surface of the patterns for a few milliseconds. Ag patterns back-irradiated with ˜10.0 J cm-2 are defect-free in contrast to front-irradiated patterns and exhibited an electrical conductivity of ˜2.3 × 107 S m-1. Furthermore, real-time high-speed observation reveals that the mechanisms that generate defects in the front-irradiated patterns and prevent defects in the back-irradiated patterns are closely related to vapor trapping. In contrast to the latter, in the former, vapor is trapped and delaminates the patterns from the substrate because the front of the patterns acts as a barrier to vapor venting.

Diet and asthma: an update

PubMed Central

Han, Yueh-Ying; Forno, Erick; Holguin, Fernando; Celedón, Juan C.

2015-01-01

Purpose of review Our objective is to provide an overview and discussion of recent experimental studies, epidemiologic studies, and clinical trials of diet and asthma. We focus on dietary sources and vitamins with antioxidant properties (vitamins (A, C, and E), folate, and omega-3 and omega-6 polyunsaturated fatty acids (n-3 and n-6 PUFAs). Recent findings Current evidence does not support the use of vitamin A, vitamin C, vitamin E or PUFAs for the prevention or treatment of asthma or allergies. Current guidelines for prenatal use of folate to prevent neural tube defects should be followed, as there is no evidence of major effects of this practice on asthma or allergies. Consumption of a balanced diet that is rich in sources of antioxidants (e.g. fruits and vegetables) may be beneficial in the primary prevention of asthma. Summary None of the vitamins or nutrients examined is consistently associated with asthma or allergies. In some cases, further studies of the effects of a vitamin or nutrient on specific asthma phenotypes (e.g. vitamin C to prevent viral-induced exacerbations) are warranted. Clinical trials of “whole diet” interventions to prevent asthma are advisable on the basis of existing evidence. PMID:26110689

Inherited trombophilic states and pulmonary embolism

PubMed Central

Konecny, Filip

2009-01-01

Pulmonary embolism (PE) and deep vein thrombosis (DVT) are associated with considerable morbidity and mortality, mostly, in case of PE for its lack of sensitivity of its early detection. For as much as twenty-five percent of PE patients the primary clinical appearance is unexpected death. While PE is one of the most avertable causes of hospital associated deaths, its diagnostics can be extremely difficult. Newly increased interest in an inherited thrombophilic states has been provoked by the discovery of several common inherited abnormalities, i.e. the prothrombin (PT) gene G20210A, Factor V Leiden (FVL) mutation (Arg506Gln), hyperhomocystenemia and homocysteiuria, Wein-Penzing defect, Sticky Platelet Syndrome (SPS), Quebec platelet disorder (QPD) and Sickle Cell Disease (SCD). PE incidence rates increase exponentially with age for both men and women, as they might harbor more than one thrombophilic state. Although the impact of genetic factors on PE is to some extent documented with lacking taxonomy, its genetic testing as its prevention strategy fall short. In this review thrombophilic states are divided into inherited or acquired, and only the inherited and newly documented are more closely followed. Factors are further grouped based on its thrombophilic taxonomy into; inherited defects of coagulation, inherited defects of fibrinolysis, inherited defects of enzymatic pathway in relation to development of VTE and PE and inherited defects of platelets in relation to PE. It was beyond the scope of this review to follow all inherited and newly recognized factors and its association to VTE and PE; however the overall taxonomy makes this review clinically valuable i.e. in relation to genetic testing as PE prevention. PMID:21772860

Inherited trombophilic states and pulmonary embolism.

PubMed

Konecny, Filip

2009-01-01

Pulmonary embolism (PE) and deep vein thrombosis (DVT) are associated with considerable morbidity and mortality, mostly, in case of PE for its lack of sensitivity of its early detection. For as much as twenty-five percent of PE patients the primary clinical appearance is unexpected death. While PE is one of the most avertable causes of hospital associated deaths, its diagnostics can be extremely difficult. Newly increased interest in an inherited thrombophilic states has been provoked by the discovery of several common inherited abnormalities, i.e. the prothrombin (PT) gene G20210A, Factor V Leiden (FVL) mutation (Arg506Gln), hyperhomocystenemia and homocysteiuria, Wein-Penzing defect, Sticky Platelet Syndrome (SPS), Quebec platelet disorder (QPD) and Sickle Cell Disease (SCD). PE incidence rates increase exponentially with age for both men and women, as they might harbor more than one thrombophilic state. Although the impact of genetic factors on PE is to some extent documented with lacking taxonomy, its genetic testing as its prevention strategy fall short.In this review thrombophilic states are divided into inherited or acquired, and only the inherited and newly documented are more closely followed. Factors are further grouped based on its thrombophilic taxonomy into; inherited defects of coagulation, inherited defects of fibrinolysis, inherited defects of enzymatic pathway in relation to development of VTE and PE and inherited defects of platelets in relation to PE. It was beyond the scope of this review to follow all inherited and newly recognized factors and its association to VTE and PE; however the overall taxonomy makes this review clinically valuable i.e. in relation to genetic testing as PE prevention.

Splice-Site Mutations Cause Rrp6-Mediated Nuclear Retention of the Unspliced RNAs and Transcriptional Down-Regulation of the Splicing-Defective Genes

PubMed Central

Eberle, Andrea B.; Hessle, Viktoria; Helbig, Roger; Dantoft, Widad; Gimber, Niclas; Visa, Neus

2010-01-01

Background Eukaryotic cells have developed surveillance mechanisms to prevent the expression of aberrant transcripts. An early surveillance checkpoint acts at the transcription site and prevents the release of mRNAs that carry processing defects. The exosome subunit Rrp6 is required for this checkpoint in Saccharomyces cerevisiae, but it is not known whether Rrp6 also plays a role in mRNA surveillance in higher eukaryotes. Methodology/Principal Findings We have developed an in vivo system to study nuclear mRNA surveillance in Drosophila melanogaster. We have produced S2 cells that express a human β-globin gene with mutated splice sites in intron 2 (mut β-globin). The transcripts encoded by the mut β-globin gene are normally spliced at intron 1 but retain intron 2. The levels of the mut β-globin transcripts are much lower than those of wild type (wt) ß-globin mRNAs transcribed from the same promoter. We have compared the expression of the mut and wt β-globin genes to investigate the mechanisms that down-regulate the production of defective mRNAs. Both wt and mut β-globin transcripts are processed at the 3′, but the mut β-globin transcripts are less efficiently cleaved than the wt transcripts. Moreover, the mut β-globin transcripts are less efficiently released from the transcription site, as shown by FISH, and this defect is restored by depletion of Rrp6 by RNAi. Furthermore, transcription of the mut β-globin gene is significantly impaired as revealed by ChIP experiments that measure the association of the RNA polymerase II with the transcribed genes. We have also shown that the mut β-globin gene shows reduced levels of H3K4me3. Conclusions/Significance Our results show that there are at least two surveillance responses that operate cotranscriptionally in insect cells and probably in all metazoans. One response requires Rrp6 and results in the inefficient release of defective mRNAs from the transcription site. The other response acts at the transcription level and reduces the synthesis of the defective transcripts through a mechanism that involves histone modifications. PMID:20634951

Reconstruction of palatal defect using mucoperiosteal hinge flap and pushback palatoplasty.

PubMed

Lee, S I; Lee, H S; Hwang, K

2001-11-01

This article describes a simple, new surgical technique to provide a complete two-layer closure of palatal defect resulting from a surgical complication of trans palatal resection of skull base chordoma. The nasal layer was reconstructed with triangular shape oral mucoperiosteal turn over hinge flap based on anterior margin of palatal defect and rectangular shaped lateral nasal mucosal hinge flaps. The oral layer was reconstructed with conventional pushback V-Y advancement 2-flaps palatoplasty. Each layer of the flaps were secured with two key mattress suture for flap coaptation. This technique has some advantages: simple, short operation time, one-stage procedure, no need of osteotomy. It can close small- to medium-sized palatal defect of palate or wide cleft palate and can prevent common complication of oronasal fistula, which could be caused by tension.

Relief of Headache by Cranioplasty After Skull Base Surgery

PubMed Central

Fetterman, Bruce L.; Lanman, Todd H.; House, John W.

1997-01-01

Headache after skull base surgery can cause profound morbidity in certain patients, resulting in significant impairment of their quality of life. Several methods to prevent postoperative headache have been described, including a modification of the skin/muscle incision replacing the craniotomy bone flap replacing the bone flap and filling in the residual defect with methyl methacrylate, using hydroxyapatite cement (HAC) to fill the craniectomy defect, and wiring hardened methyl methacrylate (MMA) into the defect. Ten patients with severe headache following craniectomy for a posterior fossa lesion underwent cranioplasty with MMA, which was placed exactly within the craniectomy defect and secured rigidly with miniplates and screws. The headache decreased in severity in all patients and resolved completely in 90%. Also, 78% of patients with dizziness improved. The procedure and its effect on headache and dizziness will be described. PMID:17171000

Triple surveillance: a proposal for an integrated strategy to support and accelerate birth defect prevention

PubMed Central

Mastroiacovo, Pierpaolo

2018-01-01

Abstract Preventing neural tube defects (NTDs) easily qualifies as a high‐value opportunity to improve childhood survival and health: the unmet need is significant (major preventable burden), the intervention is transformative (providing sufficient folic acid), and delivery strategies (e.g., fortification) are effective in low‐resource countries. Yet, NTD prevention is lagging. Can public health surveillance help fix this problem? Critics contend that surveillance is largely unnecessary, that limited resources are best spent on interventions, and that surveillance is unrealistic in developing countries. The counterargument is twofold: (1) in the absence of surveillance, interventions will provide fewer benefits and cost more and (2) effective surveillance is likely possible nearly everywhere, with appropriate strategies. As a base strategy, we propose “triple surveillance:” integrating surveillance of cause (folate insufficiency), of disease occurrence (NTD prevalence), and of health outcomes (morbidity, mortality, and disability). For better sustainability and usefulness, it is crucial to refocus and streamline surveillance activities (no recreational data collection), weave surveillance into clinical care (integrate in clinical workflow), and, later, work on including additional risk factors and pediatric outcomes (increase benefits at low marginal cost). By doing so, surveillance becomes not a roadblock but a preferential path to prevention and better care. PMID:29532515

Biallelic mutations in CYP24A1 or SLC34A1 as a cause of infantile idiopathic hypercalcemia (IIH) with vitamin D hypersensitivity: molecular study of 11 historical IIH cases.

PubMed

Pronicka, Ewa; Ciara, Elżbieta; Halat, Paulina; Janiec, Agnieszka; Wójcik, Marek; Rowińska, Elżbieta; Rokicki, Dariusz; Płudowski, Paweł; Wojciechowska, Ewa; Wierzbicka, Aldona; Książyk, Janusz B; Jacoszek, Agnieszka; Konrad, Martin; Schlingmann, Karl P; Litwin, Mieczysław

2017-08-01

Idiopathic infantile hypercalcemia (IIH) is a mineral metabolism disorder characterized by severe hypercalcemia, failure to thrive, vomiting, dehydration, and nephrocalcinosis. The periodical increase in incidence of IIH, which occurred in the twentieth century in the United Kingdom, Poland, and West Germany, turned out to be a side effect of rickets over-prophylaxis. It was recently discovered that the condition is linked to two genes, CYP24A1 and SLC34A1. The aim of the study was to search for pathogenic variants of the genes in adult persons who were shortlisted in infancy as IIH caused by "hypersensitivity to vit. D". All persons were found to carry mutations in CYP24A1 or SLC34A1, nine and two persons respectively. The changes were biallelic, with one exception. Incidence of IIH in Polish population estimated on the basis of allele frequency of recurrent p.R396W CYP24A1 variant, is 1:32,465 births. It indicates that at least a thousand homozygotes and compound heterozygotes with risk of IIH live in the country. Differences in mechanism of developing hypercalcemia indicate that its prevention may vary in both IIH defects. Theoretically, vit. D restriction is a first indication for CYP24A1 defect (which disturbs 1,25(OH) 2 D degradation) and phosphate supplementation for SLC34A1 defect (which impairs renal phosphate transport). In conclusion, we suggest that molecular testing for CYP24A1 and SLC34A1 mutations should be performed in each case of idiopathic hypercalcemia/hypercalciuria, both in children and adults, to determine the proper way for acute treatment and complications prevention.

Plasma folate levels and associated factors in women planning to become pregnant in a population with high prevalence of neural tube defects.

PubMed

Ma, Rui; Wang, Linlin; Jin, Lei; Li, Zhiwen; Ren, Aiguo

2017-07-17

Optimal blood folate levels of women before pregnancy are critical to the prevention of neural tube defects (NTDs). However, few studies have focused on blood folate levels of women planning to become pregnant. The aims of this study were to assess plasma folate levels in women who planned to become pregnant in a population with high prevalence of NTDs, to identify factors associated with plasma folate levels, and to evaluate the risk of NTDs at the population level. A total of 2065 women were enrolled at the time of premarital health check-up in two rural counties in northern China from November 2009 to December 2012. Fasting venous blood samples were collected and plasma folate concentrations were measured by microbiological method. The overall median of plasma folate was 10.5 nmol/L. 50% of the women had a plasma folate level below 10.5 nmol/L, a cutoff for megaloblastic anemia, and 88% below 18 nmol/L, a proposed optimal plasma folate level for the prevention of NTDs. Folic acid supplementation was the only factor to be associated with plasma folate concentrations, but only 1.9% of the women reported having taken folic acid supplements. A population risk of 29.3 NTD cases per 10,000 births was predicted. Women who planned to become pregnant had very low plasma folate in the population. Folic acid supplementation was the only factor to be associated with a high plasma folate concentration. High NTD risk would remain if women would get pregnant without having taken folic acid supplements. Birth Defects Research 109:1039-1047, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana – A Cohort Study

PubMed Central

Owusu, Ruth; Asante, Kwaku Poku; Mahama, Emmanuel; Awini, Elizabeth; Anyorigiya, Thomas; Dosoo, David; Amu, Alberta; Jakpa, Gabriel; Ofei, Emmanuel; Segbaya, Sylvester; Oduro, Abraham Rexford; Gyapong, Margaret; Hodgson, Abraham; Bart-Plange, Constance; Owusu-Agyei, Seth

2015-01-01

Background Sulphadoxine-Pyrimethamine (SP) is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp) in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb) drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp. Methods and Findings Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb) levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women).The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia. Conclusions There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin drop post SP-IPTp but a larger study is required to confirm consistency of findings. PMID:26327623

Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana - A Cohort Study.

PubMed

Owusu, Ruth; Asante, Kwaku Poku; Mahama, Emmanuel; Awini, Elizabeth; Anyorigiya, Thomas; Dosoo, David; Amu, Alberta; Jakpa, Gabriel; Ofei, Emmanuel; Segbaya, Sylvester; Oduro, Abraham Rexford; Gyapong, Margaret; Hodgson, Abraham; Bart-Plange, Constance; Owusu-Agyei, Seth

2015-01-01

Sulphadoxine-Pyrimethamine (SP) is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp) in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb) drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp. Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb) levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women).The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia. There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin drop post SP-IPTp but a larger study is required to confirm consistency of findings.

[Case-control study on influence factors of birth defects].

PubMed

Xiu, Xin-hong; Yuan, Li; Wang, Xiao-ming; Chen, Yu-hua; Wan, Ai-hua; Fu, Ping

2011-07-01

To investigate the influence factors of birth defects. The congenital malformational fetuses born from 13 week of gestation to 7 days after birth were selected as the study group between April 1st, 2009 and March 31st, 2010. The health born fetuses were set as control in the same period. Case-control and the three-level of monitor network of birth defects were used in the study in the participating 75 hospitals (Qingdao Women and Children's Medical Center, Affiliated Hospital of Medical College Qingdao University, Qingdao Municipal Hospital, etc.). The study and control group's parents were interviewed by an uniformed questionnaire which was designed specially with influence factors of birth defects. (1) There are 466 congenital malformational fetuses in the total of 77 231 fetuses collected in 75 hospitals. The congenital malformational rate accounts for about 6.034‰. The top six defect diseases were congenital heart disease (112 cases), total harelip (cleft lip; cleft lip with palate: 85 cases), polydactyly (53 cases), neural tube defects (38 cases), congenital hydrocephalus (37 cases) and limb reduction defect (27 cases) in turn, which amounts to 353 cases (54.48%, 353/648). (2) Their mother education level in the birth-defect group (25.6%) were significantly lower than that in control group (30.0%, P<0.05). (3) The rate of passive smoking, drinking, raising pets of the parents in birth-defect group were significantly higher than that in control group (P<0.05). (4) The rate of exposure to harmful chemical and physical factors of mothers in birth defects group (13.9% and 20.5%, respectively) was higher than that in control group (1.1% and 11.7%, respectively), the difference between which were significant (P<0.01). The rate of disease (34.3%), fever (13.1%), taking drugs (33.8%) in pregnancy period in birth defect group were higher than that in control group (13.5%, 1.5% and 9.9%, respectively), the difference between which were significant (P<0.01). The rate of bad moral irritation to the mother in pregnancy in birth defect group (11.3%) was significantly higher than that in control group (1.4%, P<0.01). (5) There were 19 cases (2.9%, 19/648) with family heredity medical history in birth defect group, but there were none in the control group, the difference between which were significant (P<0.01). There were 89 cases (13.7%, 89/648) with unusual birth history of their mothers in birth defect group, but there were 31 cases (4.8%, 31/650) in control group, the difference between which were significant (P<0.01). (6) Conditional Logistic Regression model was used for univalent and multivariate analysis. The results showed that main influence factors were identified as having important effect on birth defects, including mothers' exposure to harmful chemical factors (OR=13.46), disease (OR=3.37), taking drugs (OR=2.20), exposure to bad moral irritation (OR=5.44), food-choosy (OR=1.90), anemia (OR=1.52) in gestational period, polyembryony (OR=4.40), father drinking (OR=1.55). While it was protective factors to supplement microelements such as the calcium iron and nutrient, etc.in pregnancy period (OR=0.45). First, the main birth defects were congenital heart disease, total harelip(cleft lip; cleft lip with palate), polydactyly, neural tube defects, congenital hydrocephalus and limb reduction defect in turn. Second, the main influence factors identified as having important effect on birth defects were mothers' exposure to harmful chemical factors, ill, taking drugs, exposure to bad moral irritation, food-choosy, anemia in gestational period, polyembryony, father drinking. But it is protective factors to supplement microelements such as the calcium iron and nutrient, etc. in pregnancy period. Finally, it is the important part to prevent the birth defects by reducing and controlling dangerous factors in pregnancy period.

Epidemiological Evaluation of Rubella Virus Infection among Pregnant Women in Ibadan, Nigeria.

PubMed

Adewumi, Olubusuyi M; Olayinka, Oluseyi A; Olusola, Babatunde A; Faleye, Temitope O C; Sule, Waidi F; Adesina, Olubukola

2015-01-01

Rubella is a vaccine-preventable, mild rash-inducing viral disease with complications that include a spectrum of birth defects in the developing fetus, especially if the infection is acquired in the early months of pregnancy. Consequently, the primary objective of global rubella control programs is prevention of congenital rubella infection and associated birth defects. Despite the availability of safe and effective vaccines, and the elimination of the rubella virus in many developed countries, substantial commitment to rubella control has not been demonstrated in developing countries. This study appraises immunity to rubella, and consequently makes appropriate recommendations aimed at facilitating effective control. A cross-sectional sero-surveillance study was carried out among defined 272 consenting ante-natal clinic attendees in south-western, Nigeria. Prevalence rates of 91.54% and 1.84% were recorded for the anti-rubella virus (anti-RV) IgG and IgM, respectively. Also, 90.7% and 92.3% of the women aged ≤30 years and >30 years, respectively, had detectable anti-RV IgG. No significant association (p = 0.94) was recorded between anti-RV IgG detection and age of the women. Previous exposure and susceptibility of significant fraction of the population to rubella infection were confirmed. Considerable political commitment and promotion of free rubella immunization specifically for women with childbearing potential were recommended.

Punishment can promote defection in group-structured populations.

PubMed

Powers, Simon T; Taylor, Daniel J; Bryson, Joanna J

2012-10-21

Pro-social punishment, whereby cooperators punish defectors, is often suggested as a mechanism that maintains cooperation in large human groups. Importantly, models that support this idea have to date only allowed defectors to be the target of punishment. However, recent empirical work has demonstrated the existence of anti-social punishment in public goods games. That is, individuals that defect have been found to also punish cooperators. Some recent theoretical studies have found that such anti-social punishment can prevent the evolution of pro-social punishment and cooperation. However, the evolution of anti-social punishment in group-structured populations has not been formally addressed. Previous work has informally argued that group-structure must favour pro-social punishment. Here we formally investigate how two demographic factors, group size and dispersal frequency, affect selection pressures on pro- and anti-social punishment. Contrary to the suggestions of previous work, we find that anti-social punishment can prevent the evolution of pro-social punishment and cooperation under a range of group structures. Given that anti-social punishment has now been found in all studied extant human cultures, the claims of previous models showing the co-evolution of pro-social punishment and cooperation in group-structured populations should be re-evaluated. Copyright © 2012 Elsevier Ltd. All rights reserved.

Probing Photoexcited Carriers in a Few-Layer MoS2 Laminate by Time-Resolved Optical Pump-Terahertz Probe Spectroscopy.

PubMed

Kar, Srabani; Su, Y; Nair, R R; Sood, A K

2015-12-22

We report the dynamics of photoinduced carriers in a free-standing MoS2 laminate consisting of a few layers (1-6 layers) using time-resolved optical pump-terahertz probe spectroscopy. Upon photoexcitation with the 800 nm pump pulse, the terahertz conductivity increases due to absorption by the photoinduced charge carriers. The relaxation of the non-equilibrium carriers shows fast as well as slow decay channels, analyzed using a rate equation model incorporating defect-assisted Auger scattering of photoexcited electrons, holes, and excitons. The fast relaxation time occurs due to the capture of electrons and holes by defects via Auger processes, resulting in nonradiative recombination. The slower relaxation arises since the excitons are bound to the defects, preventing the defect-assisted Auger recombination of the electrons and the holes. Our results provide a comprehensive understanding of the non-equilibrium carrier kinetics in a system of unscreened Coulomb interactions, where defect-assisted Auger processes dominate and should be applicable to other 2D systems.

Enzyme Replacement for Craniofacial Skeletal Defects and Craniosynostosis in Murine Hypophosphatasia

PubMed Central

Liu, Jin; Campbell, Cassie; Nam, Hwa Kyung; Caron, Alexandre; Yadav, Manisha C; Millán, José Luis; Hatch, Nan E.

2015-01-01

Hypophosphatasia (HPP) is an inborn-error-of-metabolism disorder characterized by deficient bone and tooth mineralization due to loss-of function mutations in the gene (Alpl) encoding tissue-nonspecific alkaline phosphatase (TNAP). Alpl−/− mice exhibit many characteristics seen in infantile HPP including long bone and tooth defects, vitamin B6 responsive seizures and craniosynostosis. Previous reports demonstrated that a mineral-targeted form of TNAP rescues long bone, verterbral and tooth mineralization defects in Alpl−/− mice. Here we report that enzyme replacement with mineral-targeted TNAP (asfotase-alfa) also prevents craniosynostosis (the premature fusion of cranial bones) and additional craniofacial skeletal abnormalities in Alpl−/− mice. Craniosynostosis, cranial bone volume and density, and craniofacial shape abnormalities were assessed by microsocopy, histology, digital caliper measurements and micro CT. We found that craniofacial shape defects, cranial bone mineralization and craniosynostosis were corrected in Alpl−/− mice injected daily subcutaneously starting at birth with recombinant enzyme. Analysis of Alpl−/− calvarial cells indicates that TNAP deficiency leads to aberrant osteoblastic gene expression and diminished proliferation. Some but not all of these cellular abnormalities were rescued by treatment with inorganic phosphate. These results confirm an essential role for TNAP in craniofacial skeletal development and demonstrate the efficacy of early postnatal mineral-targeted enzyme replacement for preventing craniofacial abnormalities including craniosynostosis in murine infantile HPP. PMID:25959417

Failure Analysis of Cracked FS-85 Tubing and ASTAR-811C End Caps

DOE Office of Scientific and Technical Information (OSTI.GOV)

ME Petrichek

2006-02-09

Failure analyses were performed on cracked FS-85 tubing and ASTAR-811C and caps which had been fabricated as components of biaxial creep specimens meant to support materials testing for the NR Space program. During the failure analyses of cracked FS-85 tubing, it was determined that the failure potentially could be due to two effects: possible copper contamination from the EDM (electro-discharge machined) recast layer and/or an insufficient solution anneal. to prevent similar failures in the future, a more formal analysis should be done after each processing step to ensure the quality of the material before further processing. During machining of themore » ASTAR-811FC rod to form end caps for biaxial creep specimens, linear defects were observed along the center portion of the end caps. These defects were only found in material that was processed from the top portion of the ingot. The linear defects were attributed to a probable residual ingot pipe that was not removed from the ingot. During the subsequent processing of the ingot to rod, the processing temperatures were not high enough to allow self healing of the ingot's residual pipe defect. To prevent this from occurring in the future, it is necessary to ensure that complete removal of the as-melted ingot pipe is verified by suitable non-destructive evaluation (NDE).« less

Using "Rebar" to Stabilize Rigid Chest Wall Reconstruction.

PubMed

Robinson, Lary A; Grubbs, Deanna M

2016-04-01

After major chest wall resection, reconstruction of the bony defect with a rigid prosthesis is mandatory to protect the underlying thoracic organs, and to prevent flail chest physiology. Although many methods have been described for chest wall reconstruction, a commonly used technique employs a composite Marlex (polypropylene) mesh with methyl-methacrylate cement sandwiched between two layers of mesh (MMS), which is tailored to the defect size and shape. In building construction, steel "rebar" is used to strengthen and reinforce masonry structures. To avoid the initial residual motion of the rigid prosthesis used to reconstruct very large defects, particularly the sternum, we devised a simple technique of adding one or more Steinmann steel pins as "rebar" to strengthen and immediately stabilize the prosthesis to the surrounding ribs and sternum. For the very large defects, particularly over the heart and great vessels, titanium mesh may also be readily added into the sandwich construction for increased strength and to prevent late prosthetic fractures. Short- and long-term results of this inexpensive modification of the MMS reconstruction technique are excellent. This modified MMS tailor-made prosthesis is only one-third the cost of the recently popular prosthetic titanium systems, takes much less operative time to create and implant, and avoids the well-described complications of late titanium bar fracture and erosion/infection as well as loosening of screws and/or titanium bars. Georg Thieme Verlag KG Stuttgart · New York.

Stability of boron-doped graphene/copper interface: DFT, XPS and OSEE studies

NASA Astrophysics Data System (ADS)

Boukhvalov, D. W.; Zhidkov, I. S.; Kukharenko, A. I.; Slesarev, A. I.; Zatsepin, A. F.; Cholakh, S. O.; Kurmaev, E. Z.

2018-05-01

Two different types of boron-doped graphene/copper interfaces synthesized using two different flow rates of Ar through the bubbler containing the boron source were studied. X-ray photoelectron spectra (XPS) and optically stimulated electron emission (OSEE) measurements have demonstrated that boron-doped graphene coating provides a high corrosion resistivity of Cu-substrate with the light traces of the oxidation of carbon cover. The density functional theory calculations suggest that for the case of substitutional (graphitic) boron-defect only the oxidation near boron impurity is energetically favorable and creation of the vacancies that can induce the oxidation of copper substrate is energetically unfavorable. In the case of non-graphitic boron defects oxidation of the area, a nearby impurity is metastable that not only prevent oxidation but makes boron-doped graphene. Modeling of oxygen reduction reaction demonstrates high catalytic performance of these materials.

Nutrition during Pregnancy

MedlinePlus

... meals during pregnancy? The United States Department of Agriculture has made it easier to plan meals during ... of folic acid daily to help prevent major birth defects of the fetal brain and spine called ...

Evaluating the effectiveness of gel formulation of irradiated seed lectin Cratylia mollis during bone repair in rats

PubMed Central

Santos-Oliveira, Ralph; Lima-Ribeiro, Maria Helena Madruga; Carneiro-Leão, Ana Maria dos Anjos; Cruz, Adriana Ferreira; de Santana, Mauricélia Firmino; Cavalcanti, Carmelita de Lima Bezerra; de Pontes Filho, Nicodemos Teles; Coelho, Luana Cassandra Breitenbach Barroso; dos Santos Correia, Maria Tereza

2013-01-01

Context: Regeneration corresponds to the replacement of damaged cells with ones that have the same morphology and function. For experimental evaluation of materials that may favor the process of bone healing, defects are created with dimensions that prevent spontaneous regeneration. For the development and use of new drugs, it is necessary to study its effects in vitro, which depends on the formulation, concentration, and rate of irradiation in vivo and the route and frequency of administration; thus, it is possible to characterize the physiological and molecular mechanisms involved in the response and cellular effects. Objective: The objective of this study was to assess the effect of Cramoll-1,4 on the process of bone repair. Materials and Methods: A formulation of biopharmaceutical lectin Cramoll-1,4 at a concentration of 300 mg/100 mL was applied in a single application via gamma radiation and its effect on the process of bone repair in rats was assessed. Results: Histologically, it was observed that the bone defect is coated by loose connective tissue rich in fibroblasts, providing a range similar to the thick bone original and competing with site of new bone formation. This prevented direct contact between the formulation and experimental bone tissue, as, despite its proven effectiveness in experiments on the repair of skin lesions, the formulation used did not promote bone stimulation that would have promoted the tissue repair process. Conclusion: Because of the direct interference of loose tissue repair that prevented direct contact of the implant with the bone interface, the formulation did not promote bone stimulation. PMID:24083142

Optimizing the technological and informational relationship of the health care process and of the communication between physician and patient. The impact of Preventive Medicine and social marketing applied in Health Care on youth awareness–Preliminary study

PubMed Central

Gheorghe, IR; Petrescu, GD

2011-01-01

Rationale. In this case study we wanted to find out the impact of Preventive Medicine and implicitly social marketing upon young students with the average age of 19, belonging to the academic environment in Romania. Methods The study lasted one month and consisted of a questionnaire that was conceived and applied to 304 adolescents. The questionnaire contained demographic and personal information, such as age, origin, gender, marital status and some questions related to the respondents' attitude towards several issues that are inserted in the preventive medicine discipline, such as the date of their last consultation, if the respondents were registered to a family physician, suffered from chronic diseases, what was the rate of doing physical exercises, if they ate salty and fat meals, if they were on a diet, their rate of alcohol, caffeine and tobacco consumption. Discussion. Ostium secundum defect is the most common type of atrial septal defect and accounts for 60–70% of all cases. The malformation often goes unnoticed for decades because symptoms may be absent and because physical signs are subtle. Symptoms usually take 30–40 years to develop. They are the consequences of pulmonary hypertension, atrial tachyarrhythmias and, sometimes, associated mitral valve disease. ResultsThe panel was made up of more female respondents than male, with the average age rate of 19, who had medical consultations in the last 3 months, are included in the evidence of a family physician, had no chronic diseases, usually do workout exercises moderately, are not on a diet and have 3 meals per day. The meals are medium salty and rarely rich in fats. They drink 2 cups of tea per day and are non–alcohol drinkers and non-smokers. DiscussionAfter applying several statistical tests to find a correlation between our variables, we reached the conclusion that even if the results are encouraging; there is no correlation between the impact of Preventive Medicine and the respondents' health behavior. Abbreviations: PM–Preventive Medicine, UNICEF–United Nations Children's Fund PMID:21505585

Missing defects? A comparison of microscopic and macroscopic approaches to identifying linear enamel hypoplasia.

PubMed

Hassett, Brenna R

2014-03-01

Linear enamel hypoplasia (LEH), the presence of linear defects of dental enamel formed during periods of growth disruption, is frequently analyzed in physical anthropology as evidence for childhood health in the past. However, a wide variety of methods for identifying and interpreting these defects in archaeological remains exists, preventing easy cross-comparison of results from disparate studies. This article compares a standard approach to identifying LEH using the naked eye to the evidence of growth disruption observed microscopically from the enamel surface. This comparison demonstrates that what is interpreted as evidence of growth disruption microscopically is not uniformly identified with the naked eye, and provides a reference for the level of consistency between the number and timing of defects identified using microscopic versus macroscopic approaches. This is done for different tooth types using a large sample of unworn permanent teeth drawn from several post-medieval London burial assemblages. The resulting schematic diagrams showing where macroscopic methods achieve more or less similar results to microscopic methods are presented here and clearly demonstrate that "naked-eye" methods of identifying growth disruptions do not identify LEH as often as microscopic methods in areas where perikymata are more densely packed. Copyright © 2013 Wiley Periodicals, Inc.

Interest of proviral HIV-1 DNA genotypic resistance testing in virologically suppressed patients candidate for maintenance therapy.

PubMed

Allavena, C; Rodallec, A; Leplat, A; Hall, N; Luco, C; Le Guen, L; Bernaud, C; Bouchez, S; André-Garnier, E; Boutoille, D; Ferré, V; Raffi, F

2018-01-01

Switch of antiretroviral therapy in virologically suppressed HIV-infected patients is frequent, to prevent toxicities, for simplification or convenience reasons. Pretherapeutic genotypic resistance testing on RNA can be lacking in some patients, which could enhance the risk of virologic failure, if resistance-associated mutations of the new regimen are not taken into account. Proviral DNA resistance testing in 69 virologically suppressed patients on antiretroviral treatment with no history of virological failure were pair-wised compared with pre-ART plasma RNA resistance testing. The median time between plasma (RNA testing) and whole blood (proviral DNA testing) was 47 months (IQR 29-63). A stop codon was evidenced in 23% (16/69) of proviral DNA sequences; these strains were considered as defective, non-replicative, and not taken into consideration. Within the non defective strains, concordance rate between plasma RNA and non-defective proviral DNA was high both on protease (194/220 concordant resistance-associated mutations=88%) and reverse transcriptase (28/37 concordant resistance-associated mutations=76%) genes. This study supports that proviral DNA testing might be an informative tool before switching antiretrovirals in virologically suppressed patients with no history of virological failure, but the interpretation should be restricted to non-defective viruses. Copyright © 2017 Elsevier B.V. All rights reserved.

Estimate of the potential impact of folic acid fortification of corn masa flour on the prevention of neural tube defects.

PubMed

Tinker, Sarah C; Devine, Owen; Mai, Cara; Hamner, Heather C; Reefhuis, Jennita; Gilboa, Suzanne M; Dowling, Nicole F; Honein, Margaret A

2013-10-01

Hispanics in the US have a higher prevalence of neural tube defect (NTD) -affected pregnancies than non-Hispanic whites, and lower median total folic acid (FA) intake. FA fortification of corn masa flour (CMF) is a policy-level intervention for NTD prevention; however, the impact on NTD prevalence has not been estimated. We developed a model to estimate the percentage reduction in prevalence of spina bifida and anencephaly (NTDs) that could occur with FA fortification of CMF. Model inputs included estimates of the percentage reduction in United States NTD prevalence attributed to FA fortification of enriched cereal grain products (1995-1996 vs. 1998-2002), the increase in median FA intake after enriched cereal grain product fortification, and the estimated increase in median FA intake that could occur with CMF fortification at the same level as enriched cereal grain products (140 μg/100 g). We used Monte Carlo simulation to quantify uncertainty. We stratified analyses by racial/ethnic group and rounded results to the nearest 10. We estimated CMF fortification could prevent 30 Hispanic infants from having spina bifida (95% uncertainty interval: 0, 80) and 10 infants from having anencephaly (95% uncertainty interval: 0, 40) annually. The estimated impact among non-Hispanic whites and blacks was smaller. CMF fortification with FA could prevent from 0 to 120 infants, with the most likely value of approximately 40, from having spina bifida or anencephaly among Hispanics, the population most likely to benefit from the proposed intervention. While this estimated reduction is unlikely to be discernible using current birth defect surveillance methods, it still suggests an important benefit to the target population. Copyright © 2013 Wiley Periodicals, Inc.

Preliminary investigations on the antibacterial activity of zinc oxide nanostructures

NASA Astrophysics Data System (ADS)

Ramani, Meghana; Ponnusamy, S.; Muthamizhchelvan, C.

2013-04-01

In this study, we present a systematic investigation on the evolution of nanorods of diameter 35-40 nm and 1-2 μm length from nanoparticles of diameter 30-35 nm by varying the concentration of 2,6-lutidine which acts as a shape-directing agent in the synthesis process. This variation in morphology was studied using transmission electron microscopy. The surface capping agent was subsequently removed by heating during the synthesis process and confirmed using Fourier Transform Infra-red spectroscopy. Sufficient quantity of surface defects in the form of oxygen vacancies was observed from the photoluminescence analysis of the synthesized nanostructures. The concentration of defects decreased as the shape transits from nanoparticles to nanorods. The synthesized samples were preliminarily studied for their antibacterial activity against four model (gram-positive and gram-negative) pathogens by disk diffusion method and growth curve analysis. The calculated generation time indicates higher activity for nanoparticles than nanorods. However, the difference in the activity against different pathogens and their dependence on the concentration of defects indicate oxidative stress in addition to mechanical membrane damage as the major toxicity mechanism. Overall, the experimental findings are preliminary evidence supporting the possibility of developing zinc oxide nanostructures as antibacterial agents against a wide range of microorganisms to control and prevent the spreading of bacterial infections.

[The international communication and cooperation of prevention and treatment of epidemics in the Republican period of China].

PubMed

Zhang, Tai-shan

2008-07-01

During the Republican period of China, either the Northern Warlords Government or the National Government at Nanking, to different extent, all conducted international communication and cooperation in the prevention and treatment of epidemics. Firstly, they communicated and cooperated with International League in epidemic information, establishment of new health organization, health investigation and prevention and treatment of epidemics. Secondly, with WHO in epidemic information, live prevention and treatment of epidemics and personnel training. In addition, with international medical academic society by the initiative means of selecting and sending returned students abroad, dispatching overseas staff to study and attend international academic meeting. These communications and cooperations not only created good circumstances of international society for the prevention and treatment of epidemics in the Republican period of China, but also open a special window for the mutual understanding between China and the world, at the same time, promoted and reinforced independent research and development forces of prevention and treatment technology of infectious disease of our nation. Unfortunately, the inherent defects of the society of Republic of China greatly detracted from the effects of these endeavor.

Atrial Septal Defect (For Parents)

MedlinePlus

... dental work or surgical procedures to prevent infective endocarditis (an infection of the inner surface of the ... need to worry about the risk of infective endocarditis. Your doctor will discuss other possible risks and ...

Acquired platelet function defect

MedlinePlus

... Some cases cannot be prevented. Alternative Names Acquired qualitative platelet disorders; Acquired disorders of platelet function Images ... Todd Gersten, MD, Hematology/Oncology, Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by VeriMed Healthcare ...

The bitter taste of infection.

PubMed

Prince, Alice

2012-11-01

The human innate immune response to pathogens is complex, and it has been difficult to establish the contribution of epithelial signaling in the prevention of upper respiratory tract infection. The prevalence of chronic sinusitis in the absence of systemic immune defects indicates that there may be local defects in innate immunity associated with such mucosal infections. In this issue of the JCI, Cohen and colleagues investigate the role of the bitter taste receptors in airway epithelial cells, and find that these are critical to sensing the presence of invading pathogens.

[Surgical Techniques for Patella Replacement in Cases of Deficient Bone Stock in Revision TKA].

PubMed

Ritschl, P; Machacek, F; Strehn, L; Kloiber, J

2015-06-01

The patella replacement in revision surgery is a challenge especially in cases of unsufficient bone stock. Depending on the extent of the bone defect, the following videos demonstrate different approaches: Video 1: bone sparing removal of the patella implant: onlay-type patella implants. Video 2: complete cortical bone rim of the patella, residual thickness between 6 to 10 mm: biconvex patella implant. Video 3 and 4: small defects of the cortical bone rim of the patella, residual thickness 1 to 5 mm (patella shell): gull-wing osteotomy, patella bone grafting techniques. Video 5: partial necrosis/defect of the patella shell with incomplete cortical bone rim: porous tantalum patella prosthesis. On account of the various surgical options for different bone defects of the patella, patellectomy and pure patelloplasty should be avoided to prevent functional shortcomings. Georg Thieme Verlag KG Stuttgart · New York.

Silicide formation process of Er films with Ta and TaN capping layers.

PubMed

Choi, Juyun; Choi, Seongheum; Kim, Jungwoo; Na, Sekwon; Lee, Hoo-Jeong; Lee, Seok-Hee; Kim, Hyoungsub

2013-12-11

The phase development and defect formation during the silicidation reaction of sputter-deposited Er films on Si with ∼20-nm-thick Ta and TaN capping layers were examined. TaN capping effectively prevented the oxygen incorporation from the annealing atmosphere, which resulted in complete conversion to the ErSi2-x phase. However, significant oxygen penetration through the Ta capping layer inhibited the ErSi2-x formation, and incurred the growth of several Er-Si-O phases, even consuming the ErSi2-x layer formed earlier. Both samples produced a number of small recessed defects at an early silicidation stage. However, large rectangular or square-shaped surface defects, which were either pitlike or pyramidal depending on the capping layer identity, were developed as the annealing temperature increased. The origin of different defect generation mechanisms was suggested based on the capping layer-dependent silicidation kinetics.

Advanced in-production hotspot prediction and monitoring with micro-topography

NASA Astrophysics Data System (ADS)

Fanton, P.; Hasan, T.; Lakcher, A.; Le-Gratiet, B.; Prentice, C.; Simiz, J.-G.; La Greca, R.; Depre, L.; Hunsche, S.

2017-03-01

At 28nm technology node and below, hot spot prediction and process window control across production wafers have become increasingly critical to prevent hotspots from becoming yield-limiting defects. We previously established proof of concept for a systematic approach to identify the most critical pattern locations, i.e. hotspots, in a reticle layout by computational lithography and combining process window characteristics of these patterns with across-wafer process variation data to predict where hotspots may become yield impacting defects [1,2]. The current paper establishes the impact of micro-topography on a 28nm metal layer, and its correlation with hotspot best focus variations across a production chip layout. Detailed topography measurements are obtained from an offline tool, and pattern-dependent best focus (BF) shifts are determined from litho simulations that include mask-3D effects. We also establish hotspot metrology and defect verification by SEM image contour extraction and contour analysis. This enables detection of catastrophic defects as well as quantitative characterization of pattern variability, i.e. local and global CD uniformity, across a wafer to establish hotspot defect and variability maps. Finally, we combine defect prediction and verification capabilities for process monitoring by on-product, guided hotspot metrology, i.e. with sampling locations being determined from the defect prediction model and achieved prediction accuracy (capture rate) around 75%

Neuropilin-2 mediates VEGF-C–induced lymphatic sprouting together with VEGFR3

PubMed Central

Xu, Yunling; Yuan, Li; Mak, Judy; Pardanaud, Luc; Caunt, Maresa; Kasman, Ian; Larrivée, Bruno; del Toro, Raquel; Suchting, Steven; Medvinsky, Alexander; Silva, Jillian; Yang, Jian; Thomas, Jean-Léon; Koch, Alexander W.; Alitalo, Kari

2010-01-01

Vascular sprouting is a key process-driving development of the vascular system. In this study, we show that neuropilin-2 (Nrp2), a transmembrane receptor for the lymphangiogenic vascular endothelial growth factor C (VEGF-C), plays an important role in lymphatic vessel sprouting. Blocking VEGF-C binding to Nrp2 using antibodies specifically inhibits sprouting of developing lymphatic endothelial tip cells in vivo. In vitro analyses show that Nrp2 modulates lymphatic endothelial tip cell extension and prevents tip cell stalling and retraction during vascular sprout formation. Genetic deletion of Nrp2 reproduces the sprouting defects seen after antibody treatment. To investigate whether this defect depends on Nrp2 interaction with VEGF receptor 2 (VEGFR2) and/or 3, we intercrossed heterozygous mice lacking one allele of these receptors. Double-heterozygous nrp2vegfr2 mice develop normally without detectable lymphatic sprouting defects. In contrast, double-heterozygote nrp2vegfr3 mice show a reduction of lymphatic vessel sprouting and decreased lymph vessel branching in adult organs. Thus, interaction between Nrp2 and VEGFR3 mediates proper lymphatic vessel sprouting in response to VEGF-C. PMID:20065093

Detecting defective electrical components in heterogeneous infra-red images by spatial control charts

NASA Astrophysics Data System (ADS)

Jamshidieini, Bahman; Fazaee, Reza

2016-05-01

Distribution network components connect machines and other loads to electrical sources. If resistance or current of any component is more than specified range, its temperature may exceed the operational limit which can cause major problems. Therefore, these defects should be found and eliminated according to their severity. Although infra-red cameras have been used for inspection of electrical components, maintenance prioritization of distribution cubicles is mostly based on personal perception and lack of training data prevents engineers from developing image processing methods. New research on the spatial control chart encouraged us to use statistical approaches instead of the pattern recognition for the image processing. In the present study, a new scanning pattern which can tolerate heavy autocorrelation among adjacent pixels within infra-red image was developed and for the first time combination of kernel smoothing, spatial control charts and local robust regression were used for finding defects within heterogeneous infra-red images of old distribution cubicles. This method does not need training data and this advantage is crucially important when the training data is not available.

Congenital diaphragmatic hernias: from genes to mechanisms to therapies

PubMed Central

McCulley, David J.; Shen, Yufeng; Wynn, Julia; Shang, Linshan; Bogenschutz, Eric; Sun, Xin

2017-01-01

ABSTRACT Congenital diaphragmatic hernias (CDHs) and structural anomalies of the diaphragm are a common class of congenital birth defects that are associated with significant morbidity and mortality due to associated pulmonary hypoplasia, pulmonary hypertension and heart failure. In ∼30% of CDH patients, genomic analyses have identified a range of genetic defects, including chromosomal anomalies, copy number variants and sequence variants. The affected genes identified in CDH patients include transcription factors, such as GATA4, ZFPM2, NR2F2 and WT1, and signaling pathway components, including members of the retinoic acid pathway. Mutations in these genes affect diaphragm development and can have pleiotropic effects on pulmonary and cardiac development. New therapies, including fetal endoscopic tracheal occlusion and prenatal transplacental fetal treatments, aim to normalize lung development and pulmonary vascular tone to prevent and treat lung hypoplasia and pulmonary hypertension, respectively. Studies of the association between particular genetic mutations and clinical outcomes should allow us to better understand the origin of this birth defect and to improve our ability to predict and identify patients most likely to benefit from specialized treatment strategies. PMID:28768736

Prevention of valproic acid-induced neural tube defects by sildenafil citrate.

PubMed

Tiboni, Gian Mario; Ponzano, Adalisa

2015-08-15

This study was undertaken to test the effects of sildenafil citrate (SC), a type 5 phosphodiesterase inhibitor, on valproic acid (VPA)-induced teratogenesis. On gestation day (GD) 8, ICR (CD-1) mice were treated by gastric intubation with SC at 0 (vehicle), 1.0, 2.5, 5.0 or 10mg/kg. One hour later, animals received a teratogenic dose of VPA (600mg/kg) or vehicle. Developmental endpoints were evaluated near the end of gestation. Twenty-eighth percent of fetuses exposed to VPA had neural tube defects (exencephaly). Pretreatment with SC at 2.5, 5.0 or 10mg/kg significantly reduced the rate of VPA-induced exencephaly to 15.9%, 13.7%, and 10.0%, respectively. Axial skeletal defects were observed in 75.8% of VPA-exposed fetuses. Pre-treatment with SC at 10mg/kg, but not at lower doses, significantly decreased the rate of skeletally affected fetuses to 61.6%. These results show that SC, which prolongs nitric oxide (NO) signaling action protects from VPA-induced teratogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Vascular Surgery, Microsurgery and Supramicrosurgery for Treatment of Chronic Diabetic Foot Ulcers to Prevent Amputations

PubMed Central

Schirmer, Steffen; Ritter, Ralf-Gerhard; Fansa, Hisham

2013-01-01

Introduction Diabetic foot ulcers occur in approximately 2,5% of patients suffering from diabetes and may lead to major infections and amputation. Such ulcers are responsible for a prolonged period of hospitalization and co- morbidities caused by infected diabetic foot ulcers. Small, superficial ulcers can be treated by special conservative means. However, exposed bones or tendons require surgical intervention in order to prevent osteomyelitis. In many cases reconstructive surgery is necessary, sometimes in combination with revascularization of the foot. There are studies on non surgical treatment of the diabetic foot ulcer. Most of them include patients, classified Wagner 1-2 without infection. Patients presenting Wagner 3D and 4D however are at a higher risk of amputation. The evolution of microsurgery has extended the possibilities of limb salvage. Perforator based flaps can minimize the donorsite morbidity. Patients and Methods 41 patients were treated with free tissue transfer for diabetic foot syndrome and chronic defects. 44 microvascular flaps were needed. The average age of patients was 64.3 years. 18 patients needed revascularization. 3 patients needed 2 microvascular flaps. In 6 cases supramicrosurgical technique was used. Results There were 2 flap losses leading to amputation. 4 other patients required amputation within 6 months postoperatively due to severe infection or bypass failure. Another 4 patients died within one year after reconstruction. The remaining patients were ambulated. Discussion Large defects of the foot can be treated by free microvascular myocutaneous or fasciocutaneous tissue transfer. If however, small defects, exposing bones or tendons, are not eligible for local flaps, small free microvascular flaps can be applied. These flaps cause a very low donor site morbidity. Arterialized venous flaps are another option for defect closure. Amputation means reduction of quality of life and can lead to an increased mortality postoperatively. PMID:24058622

Reliability of extended dorsal intercostal artery perforator propeller flaps for reconstruction of large myelomeningocele defects.

PubMed

Tenekeci, Goktekin; Basterzi, Yavuz

2017-01-01

Reconstruction of large myelomeningocele defects using extended (elongated beyond the lateral margin of the latissimus dorsi muscle) dorsal intercostal artery perforator (DICAP) propeller flaps is not recommended by previous studies. However, to provide tension-free and successful closure of a defect, the DICAP propeller flaps must sometimes be elongated beyond this margin. Our experience and results in this issue are discussed. In this article, reconstruction of 11 consecutive cases, with large myelomeningocele defects in which standard DICAP propeller flaps were incapable to close the defect, was achieved using extended DICAP propeller flaps between June 2013 and November 2015. At least two reliable perforators of the neighboring intervertebral spaces are included to supply the flap. Intramuscular dissection of perforators is performed to free the perforators from the surrounding muscle and to gain pedicle length as much as possible to prevent twisting and vascular compromise. All the flaps survived completely except for one patient who had superficial skin necrosis on the most distal part of the flap and had severe accompanying systemic disorders and died on postoperative 14th day. In 7 of 11 patients, venous congestion was noted, which resolved spontaneously. No hematoma or seroma formation was observed during the postoperative follow-up period. Dissection of multiple DICAPs supplying flaps enable us to harvest larger DICAP flaps possibly by providing better arterial supply and venous drainage. We use microsurgical instruments and 4.3× loupe magnification for pedicle dissection in this newborn population. This study shows the reliability of extended DICAP propeller flaps when multiple perforators at sixth or more cranial adjacent intercostal spaces are included in DICAP propeller flaps. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

CD22ΔE12 as a molecular target for corrective repair using a RNA trans-splicing strategy: Anti-leukemic activity of a rationally designed RNA trans-splicing molecule

PubMed Central

Uckun, Fatih M.; Qazi, Sanjive; Ma, Hong; Reaman, Gregory H.; Mitchell, Lloyd G.

2015-01-01

Our recent studies have demonstrated that the CD22 exon 12 deletion (CD22ΔE12) is a characteristic genetic defect of therapy-refractory clones in pediatric B-precursor acute lymphoblastic leukemia (BPL) and implicated the CD22ΔE12 genetic defect in the aggressive biology of relapsed or therapy-refractory pediatric BPL. The purpose of the present study was to further evaluate the biologic significance of the CD22ΔE12 molecular lesion and determine if it could serve as a molecular target for corrective repair using RNA trans-splicing therapy. We show that both pediatric and adult B-lineage lymphoid malignancies are characterized by a very high incidence of the CD22ΔE12 genetic defect. We provide experimental evidence that the correction of the CD22ΔE12 genetic defect in human CD22ΔE12+ BPL cells using a rationally designed CD22 RNA trans-splicing molecule (RTM) caused a pronounced reduction of their clonogenicity. The RTM-mediated correction replaced the downstream mutation-rich segment of Intron 12 and remaining segments of the mutant CD22 pre-mRNA with wildtype CD22 Exons 10-14, thereby preventing the generation of the cis-spliced aberrant CD22ΔE12 product. The anti-leukemic activity of this RTM against BPL xenograft clones derived from CD22ΔE12+ leukemia patients provides the preclinical proof-of-concept that correcting the CD22ΔE12 defect with rationally designed CD22 RTMs may provide the foundation for therapeutic innovations that are needed for successful treatment of high-risk and relapsed BPL patients. PMID:25567759

Assessment of frontal lobe sagging after endoscopic endonasal transcribriform resection of anterior skull base tumors: is rigid structural reconstruction of the cranial base defect necessary?

PubMed

Eloy, Jean Anderson; Shukla, Pratik A; Choudhry, Osamah J; Singh, Rahul; Liu, James K

2012-12-01

The endoscopic endonasal transcribriform approach (EETA) is a viable alternative option for resection of selected anterior skull base (ASB) tumors. However, this technique results in the creation of large cribriform defects. Some have reported the use of a rigid substitute for ASB reconstruction to prevent postoperative frontal lobe sagging. We evaluate the degree of frontal lobe sagging using our triple-layer technique [fascia lata, acellular dermal allograft, and pedicled nasoseptal flap (PNSF)] without the use of rigid structural reconstruction for large cribriform defects. Retrospective analysis. Nine patients underwent an EETA for resection of large ASB tumors from August 2010 to November 2011. The degree of frontal lobe displacement after EETA, defined as the ASB position, was calculated based on the most inferior position of the frontal lobe relative to the nasion-sellar line defined on preoperative and postoperative imaging. A positive value signified upward displacement, and a negative value represented inferior displacement of the frontal lobe. The average cribriform defect size was 9.3 cm(2) (range, 5.0-13.8 cm(2) ). The average distance of postoperative frontal lobe displacement was 0.2 mm (range, -3.9 to 2.9 mm) without any cases of significant brain sagging. The mean follow-up period was 10.1 months (range, 4-19 months). There were no postoperative CSF leaks. Rigid structural repair may not be necessary for ASB defect repair after endoscopic endonasal resection of the cribriform plate. Our technique for multilayer cranial base reconstruction appears to be satisfactory in preventing delayed frontal lobe sagging. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Nutrition Update, 1978.

ERIC Educational Resources Information Center

Weininger, Jean; Briggs, George M.

1978-01-01

Reviews current nutrition research areas with important practical applications. Topics include hypertension, preventable birth defects, phenylketonuria and genetic diseases, new molecular genetics techniques, and saccharin and sweetners. Entries are brief and a 65-reference list is given. (MA)

Identifying environmental risk factors for human neural tube defects before and after folic acid supplementation

PubMed Central

Liao, Yilan; Wang, Jinfeng; Li, Xinhu; Guo, Yaoqin; Zheng, Xiaoying

2009-01-01

Background Birth defects are a major cause of infant mortality and disability in many parts of the world. Neural tube defects (NTDs) are one of the most common types of birth defects. In 2001, the Chinese population and family planning commission initiated a national intervention program for the prevention of birth defects. A key step in the program was the introduction of folic acid supplementation. Of interest in the present study was to determine whether folic acid supplementation has the same protective effect on NTDs under various geographical and socioeconomic conditions within the Chinese population and the nature in which the influence of environmental factors varied after folic acid supplementation. Methods In this study, Heshun was selected as the region of interest as a surrogate for helping to answer some of the questions raised in this study on the impact of the intervention program. Spatial filtering in combination with GIS software was used to detect annual potential clusters from 1998 to 2005 in Heshun, and Kruskal-wallis test and multivariate regression were applied to identify the environmental risk factors for NTDs among various regions. Results In 1998, a significant (p < 0.100) NTDs cluster was detected in the west of Heshun. After folic acid supplementation, the significant clusters gradually moved from west to east. However, during the study period, most of the clusters appeared in the middle region of Heshun where more than 95 percent of the coal mines of Heshun are located. For the analysis, buffer regions of the coal mine zone were built in a GIS environment. It was found that the correlations between environmental risk factors and NTDs vary among the buffer regions. Conclusion This suggests that the government needs to adapt the intervention measures according to local conditions. More attention needs to be paid to the poor and to people living in areas near coal mines. PMID:19835574

Base Excision Repair of Oxidative DNA Damage

PubMed Central

David, Sheila S.; O’Shea, Valerie L.; Kundu, Sucharita

2010-01-01

Base excision repair plays an important role in preventing mutations associated with the common product of oxidative damage, 8-oxoguanine. Recent structural studies have shown that 8-oxoguanine glycosylases use an intricate series of steps to efficiently search and locate 8-oxoguanine lesions within the multitude of undamaged bases. The importance of prevention of mutations associated with 8-oxoguanine has also been illustrated by direct connections between defects in the BER glycosylase MUTYH and colorectal cancer. In addition, the properties of other guanine oxidation products and the BER glycosylases that remove them are being uncovered. This work is providing surprising and intriguing new insights into the process of base excision repair. PMID:17581577

Potential health economic benefits of vitamin supplementation.

PubMed Central

Bendich, A; Mallick, R; Leader, S

1997-01-01

This study used published relative risk estimates for birth defects, premature birth, and coronary heart disease associated with vitamin intake to project potential annual cost reductions in U.S. hospitalization charges. Epidemiological and intervention studies with relative risk estimates were identified via MEDLINE. Preventable fraction estimates were derived from data on the percentage of at-risk Americans with daily vitamin intake levels lower than those associated with disease risk reduction. Hospitalization rates were obtained from the 1992 National Hospital Discharge Survey. Charge data from the 1993 California Hospital Discharge Survey were adjusted to 1995 national charges using the medical component of the Consumer Price Index. Based on published risk reductions, annual hospital charges for birth defects, low-birth-weight premature births, and coronary heart disease could be reduced by about 40, 60, and 38%, respectively. For the conditions studied, nearly $20 billion in hospital charges were potentially avoidable with daily use of folic acid and zinc-containing multivitamins by all women of childbearing age and daily vitamin E supplementation by those over 50. PMID:9217432

Low carbohydrate diets may increase risk of neural tube defects.

PubMed

Desrosiers, Tania A; Siega-Riz, Anna Maria; Mosley, Bridget S; Meyer, Robert E

2018-01-25

Folic acid fortification significantly reduced the prevalence of neural tube defects (NTDs) in the United States. The popularity of "low carb" diets raises concern that women who intentionally avoid carbohydrates, thereby consuming fewer fortified foods, may not have adequate dietary intake of folic acid. To assess the association between carbohydrate intake and NTDs, we analyzed data from the National Birth Defects Prevention Study from 1,740 mothers of infants, stillbirths, and terminations with anencephaly or spina bifida (cases), and 9,545 mothers of live born infants without a birth defect (controls) conceived between 1998 and 2011. Carbohydrate and folic acid intake before conception were estimated from food frequency questionnaire responses. Restricted carbohydrate intake was defined as ≤5th percentile among controls. Odds ratios were estimated with logistic regression and adjusted for maternal race/ethnicity, education, alcohol use, folic acid supplement use, study center, and caloric intake. Mean dietary intake of folic acid among women with restricted carbohydrate intake was less than half that of other women (p < .01), and women with restricted carbohydrate intake were slightly more likely to have an infant with an NTD (AOR = 1.30, 95% CI: 1.02, 1.67). This is the first study to examine the association between carbohydrate intake and NTDs among pregnancies conceived postfortification. We found that women with restricted carbohydrate intake were 30% more likely to have an infant with anencephaly or spina bifida. However, more research is needed to understand the pathways by which restricted carbohydrate intake might increase the risk of NTDs. © 2018 Wiley Periodicals, Inc.

Transparency and damage tolerance of patternable omniphobic lubricated surfaces based on inverse colloidal monolayers

DOE PAGES

Vogel, Nicolas; Belisle, Rebecca A.; Hatton, Benjamin; ...

2013-07-31

A transparent coating that repels a wide variety of liquids, prevents staining, is capable of self-repair and is robust towards mechanical damage can have a broad technological impact, from solar cell coatings to self-cleaning optical devices. Here we employ colloidal templating to design transparent, nanoporous surface structures. A lubricant can be firmly locked into the structures and, owing to its fluidic nature, forms a defect-free, self-healing interface that eliminates the pinning of a second liquid applied to its surface, leading to efficient liquid repellency, prevention of adsorption of liquid-borne contaminants, and reduction of ice adhesion strength. We further show howmore » this method can be applied to locally pattern the repellent character of the substrate, thus opening opportunities to spatially confine any simple or complex fluids. The coating is highly defect-tolerant due to its interconnected, honeycomb wall structure, and repellency prevails after the application of strong shear forces and mechanical damage. The regularity of the coating allows us to understand and predict the stability or failure of repellency as a function of lubricant layer thickness and defect distribution based on a simple geometric model.« less

Tricho-Dento-Osseous Syndrome: Diagnosis and Dental Management

PubMed Central

Al-Batayneh, Ola B.

2012-01-01

Tricho-dento-osseous (TDO) syndrome is a rare, autosomal dominant disorder principally characterised by curly hair at infancy, severe enamel hypomineralization and hypoplasia and taurodontism of teeth, sclerotic bone, and other defects. Diagnostic criteria are based on the generalized enamel defects, severe taurodontism especially of the mandibular first permanent molars, an autosomal dominant mode of inheritance, and at least one of the other features (i.e., nail defects, bone sclerosis, and curly, kinky or wavy hair present at a young age that may straighten out later). Confusion with amelogenesis imperfecta is common; however, taurodontism is not a constant feature of any of the types of amelogenesis imperfecta. Management of TDO requires a team approach, proper documentation, and a long-term treatment and follow-up plan. The aim of treatment is to prevent problems such as sensitivity, caries, dental abscesses, and loss of occlusal vertical dimension through attrition of hypoplastic tooth structure. Another aim is to restore function of the dentition and enhance the esthetics and self-esteem of the patient. This paper proposes treatment approaches that include preventive, restorative, endodontic, prosthetic, and surgical options to management. In addition, it sheds light on the difficulties faced during dental treatment of such cases. PMID:22969805

SPR4-peptide Alters Bone Metabolism of Normal and HYP Mice

PubMed Central

Zelenchuk, Lesya V; Hedge, Anne-Marie; Rowe, Peter S N

2015-01-01

Context ASARM-peptides are substrates and ligands for PHEX, the gene responsible for X-linked hypophosphatemic rickets (HYP). PHEX binds to the DMP1-ASARM-motif to form a trimeric-complex with α5β3-integrin on the osteocyte surface and this suppresses FGF23 expression. ASARM-peptide disruption of this complex increases FGF23 expression. We used a 4.2 kDa peptide (SPR4) that binds to ASARM-peptide and ASARM-motif to study DMP1-PHEX interactions and to assess SPR4 for treating inherited hypophosphatemic rickets. Design Subcutaneously transplanted osmotic pumps were used to infuse SPR4-peptide or vehicle into wild-type mice (WT) and HYP-mice for 4 weeks. Results Asymmetrically distributed mineralization defects occurred with WT-SPR4 femurs. Specifically, SPR4 induced negative effects on trabecular bone and increased bone volume and mineralization in cortical-bone. Markedly increased sclerostin and reduced active β-catenin occurred with HYP mice. SPR4-infusion suppressed sclerostin and increased active β-catenin in WT and HYP mice and improved HYP-mice trabecular mineralization defects but not cortical mineralization defects. Conclusions SPR4-peptide has bimodal activity and acts by: (1) preventing DMP1 binding to PHEX and (2) sequestering an inhibitor of DMP1-PHEX binding, ASARM-peptide. In PHEX defective HYP-mice the second pathway predominates. Although SPR4-peptide improved trabecular calcification defects, decreased sclerostin and increased active β-catenin it did not correct HYP-mice cortical mineralization defects on a normal phosphate diet. Thus, for inherited hypophosphatemic rickets patients on a normal phosphate diet, SPR4-peptide is not a useful therapeutic. PMID:25460577

Laser Engineered Net Shape (LENS) Technology for the Repair of Ni-Base Superalloy Turbine Components

NASA Astrophysics Data System (ADS)

Liu, Dejian; Lippold, John C.; Li, Jia; Rohklin, Stan R.; Vollbrecht, Justin; Grylls, Richard

2014-09-01

The capability of the laser engineered net shape (LENS) process was evaluated for the repair of casting defects and improperly machined holes in gas turbine engine components. Various repair geometries, including indentations, grooves, and through-holes, were used to simulate the actual repair of casting defects and holes in two materials: Alloy 718 and Waspaloy. The influence of LENS parameters, including laser energy density, laser scanning speed, and deposition pattern, on the repair of these defects and holes was studied. Laser surface remelting of the substrate prior to repair was used to remove machining defects and prevent heat-affected zone (HAZ) liquation cracking. Ultrasonic nondestructive evaluation techniques were used as a possible approach for detecting lack-of-fusion in repairs. Overall, Alloy 718 exhibited excellent repair weldability, with essentially no defects except for some minor porosity in repairs representative of deep through-holes and simulated large area casting defects. In contrast, cracking was initially observed during simulated repair of Waspaloy. Both solidification cracking and HAZ liquation cracking were observed in the repairs, especially under conditions of high heat input (high laser power and/or low scanning speed). For Waspaloy, the degree of cracking was significantly reduced and, in most cases, completely eliminated by the combination of low laser energy density and relatively high laser scanning speeds. It was found that through-hole repairs of Waspaloy made using a fine powder size exhibited excellent repair weldability and were crack-free relative to repairs using coarser powder. Simulated deep (7.4 mm) blind-hole repairs, representative of an actual Waspaloy combustor case, were successfully produced by the combination use of fine powder and relatively high laser scanning speeds.

Regional bias in birth defect prevalence rates for Arkansas: influence of incomplete ascertainment along surveillance system borders.

PubMed

Mosley, Bridget S; Simmons, Caroline J; Cleves, Mario A; Hobbs, Charlotte A

2002-01-01

As part of the continuing evaluation of the Arkansas Reproductive Health Monitoring System (ARHMS), we assessed the effects on birth defect prevalence rates introduced by incomplete case ascertainment along surveillance boundaries. Using data from ARHMS and Arkansas Vital Statistics for 1993-1998, we determined birth defect prevalence rates (per 10,000 live births), stratified by race, among three geographic comparison groups of counties. These included: (1) the Northeast Group, near the state border at Memphis, Tennessee; (2) the Central Group, surrounding Little Rock, Arkansas; and (3) the Southwest Group, near Texarkana, Texas. These counties have similar socioeconomic measures and proximity to health care facilities, but are differentiated by limitations imposed by ARHMS' surveillance borders. Maternal age-standardized rates from the control groups were used to impute expected rates, for the Northeast Group and statewide, which were compared with reported rates. We found that there were 620 fewer reported birth defect cases than expected for the Northeast Group. The Northeast Group's prevalence rates were approximately half of the control groups' rates (310.6 vs. 529.8, respectively, for Whites, and 240.8 vs. 550.1, respectively, for African-Americans). Incorporating the missed cases into statewide prevalence calculations could increase prevalence rates from 502.6 to 523.2 for Whites and from 527.4 to 590.7 for African-Americans. This study identified significant regional differences in reported birth defect rates in Arkansas. Case ascertainment might be incomplete in other surveillance systems lacking the means to share data with neighboring systems. Regional inaccuracy can hinder evaluation of localized birth defect trends or targeted prevention efforts. Copyright 2002 Wiley-Liss, Inc.

Triple surveillance: a proposal for an integrated strategy to support and accelerate birth defect prevention.

PubMed

Botto, Lorenzo D; Mastroiacovo, Pierpaolo

2018-02-01

Preventing neural tube defects (NTDs) easily qualifies as a high-value opportunity to improve childhood survival and health: the unmet need is significant (major preventable burden), the intervention is transformative (providing sufficient folic acid), and delivery strategies (e.g., fortification) are effective in low-resource countries. Yet, NTD prevention is lagging. Can public health surveillance help fix this problem? Critics contend that surveillance is largely unnecessary, that limited resources are best spent on interventions, and that surveillance is unrealistic in developing countries. The counterargument is twofold: (1) in the absence of surveillance, interventions will provide fewer benefits and cost more and (2) effective surveillance is likely possible nearly everywhere, with appropriate strategies. As a base strategy, we propose "triple surveillance:" integrating surveillance of cause (folate insufficiency), of disease occurrence (NTD prevalence), and of health outcomes (morbidity, mortality, and disability). For better sustainability and usefulness, it is crucial to refocus and streamline surveillance activities (no recreational data collection), weave surveillance into clinical care (integrate in clinical workflow), and, later, work on including additional risk factors and pediatric outcomes (increase benefits at low marginal cost). By doing so, surveillance becomes not a roadblock but a preferential path to prevention and better care. © 2018 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

Hypospadias and maternal exposure to atrazine via drinking water in the National Birth Defects Prevention study.

PubMed

Winston, Jennifer J; Emch, Michael; Meyer, Robert E; Langlois, Peter; Weyer, Peter; Mosley, Bridget; Olshan, Andrew F; Band, Lawrence E; Luben, Thomas J

2016-07-15

Hypospadias is a relatively common birth defect affecting the male urinary tract. It has been suggested that exposure to endocrine disrupting chemicals might increase the risk of hypospadias by interrupting normal urethral development. Using data from the National Birth Defects Prevention Study, a population-based case-control study, we considered the role of maternal exposure to atrazine, a widely used herbicide and potential endocrine disruptor, via drinking water in the etiology of 2nd and 3rd degree hypospadias. We used data on 343 hypospadias cases and 1,422 male controls in North Carolina, Arkansas, Iowa, and Texas from 1998-2005. Using catchment level stream and groundwater contaminant models from the US Geological Survey, we estimated atrazine concentrations in public water supplies and in private wells. We assigned case and control mothers to public water supplies based on geocoded maternal address during the critical window of exposure for hypospadias (i.e., gestational weeks 6-16). Using maternal questionnaire data about water consumption and drinking water, we estimated a surrogate for total maternal consumption of atrazine via drinking water. We then included additional maternal covariates, including age, race/ethnicity, parity, and plurality, in logistic regression analyses to consider an association between atrazine and hypospadias. When controlling for maternal characteristics, any association between hypospadias and daily maternal atrazine exposure during the critical window of genitourinary development was found to be weak or null (odds ratio for atrazine in drinking water = 1. 00, 95 % CI = 0.97 to 1.03 per 0.04 μg/day increase; odds ratio for maternal consumption = 1.02, 95 % CI = 0.99 to 1.05; per 0.05 μg/day increase). While the association that we observed was weak, our results suggest that additional research into a possible association between atrazine and hypospadias occurrence, using a more sensitive exposure metric, would be useful.

Implementation of surgical quality improvement: auditing tool for surgical site infection prevention practices.

PubMed

Hechenbleikner, Elizabeth M; Hobson, Deborah B; Bennett, Jennifer L; Wick, Elizabeth C

2015-01-01

Surgical site infections are a potentially preventable patient harm. Emerging evidence suggests that the implementation of evidence-based process measures for infection reduction is highly variable. The purpose of this work was to develop an auditing tool to assess compliance with infection-related process measures and establish a system for identifying and addressing defects in measure implementation. This was a retrospective cohort study using electronic medical records. We used the auditing tool to assess compliance with 10 process measures in a sample of colorectal surgery patients with and without postoperative infections at an academic medical center (January 2012 to March 2013). We investigated 59 patients with surgical site infections and 49 patients without surgical site infections. First, overall compliance rates for the 10 process measures were compared between patients with infection vs patients without infection to assess if compliance was lower among patients with surgical site infections. Then, because of the burden of data collection, the tool was used exclusively to evaluate quarterly compliance rates among patients with infection. The results were reviewed, and the key factors contributing to noncompliance were identified and addressed. Ninety percent of process measures had lower compliance rates among patients with infection. Detailed review of infection cases identified many defects that improved following the implementation of system-level changes: correct cefotetan redosing (education of anesthesia personnel), temperature at surgical incision >36.0°C (flags used to identify patients for preoperative warming), and the use of preoperative mechanical bowel preparation with oral antibiotics (laxative solutions and antibiotics distributed in clinic before surgery). Quarterly compliance improved for 80% of process measures by the end of the study period. This study was conducted on a small surgical cohort within a select subspecialty. The infection auditing tool is a useful strategy for identifying defects and guiding quality improvement interventions. This is an iterative process requiring dedicated resources and continuous patient and frontline provider engagement.

The Detection of Burn-Through Weld Defects Using Noncontact Ultrasonics

PubMed Central

Abbasi, Zeynab; Yuhas, Donald; Zhang, Lu; Basantes, Alexandra-Del-Carmen; Tehrani, Niloofar Nabili; Ozevin, Didem; Indacochea, Ernesto

2018-01-01

Nearly all manufactured products in the metal industry involve welding. The detection and correction of defects during welding improve the product reliability and quality, and prevent unexpected failures. Nonintrusive process control is critical for avoiding these defects. This paper investigates the detection of burn-through damage using noncontact, air-coupled ultrasonics, which can be adapted to the immediate and in-situ inspection of welded samples. The burn-through leads to a larger volume of degraded weld zone, providing a resistance path for the wave to travel which results in lower velocity, energy ratio, and amplitude. Wave energy dispersion occurs due to the increase of weld burn-through resulting in higher wave attenuation. Weld sample micrographs are used to validate the ultrasonic results. PMID:29342875

Repair of Postoperative Abdominal Hernia in a Child with Congenital Omphalocele Using Porcine Dermal Matrix

PubMed Central

Mylona, E.; Tsakalidis, C.; Spyridakis, I.; Mitsiakos, G.; Karagianni, P.

2016-01-01

Introduction. Incisional hernias are a common complication appearing after abdominal wall defects reconstruction, with omphalocele and gastroschisis being the most common etiologies in children. Abdominal closure of these defects represents a real challenge for pediatric surgeons with many surgical techniques and various prosthetic materials being used for this purpose. Case Report. We present a case of repair of a postoperative ventral hernia occurring after congenital omphalocele reconstruction in a three-and-a-half-year-old child using an acellular, sterile, porcine dermal mesh. Conclusion. Non-cross-linked acellular porcine dermal matrix is an appropriate mesh used for the reconstruction of abdominal wall defects and their postoperative complications like large ventral hernias with success and preventing their recurrence. PMID:27110247

Repair of Postoperative Abdominal Hernia in a Child with Congenital Omphalocele Using Porcine Dermal Matrix.

PubMed

Lambropoulos, V; Mylona, E; Mouravas, V; Tsakalidis, C; Spyridakis, I; Mitsiakos, G; Karagianni, P

2016-01-01

Introduction. Incisional hernias are a common complication appearing after abdominal wall defects reconstruction, with omphalocele and gastroschisis being the most common etiologies in children. Abdominal closure of these defects represents a real challenge for pediatric surgeons with many surgical techniques and various prosthetic materials being used for this purpose. Case Report. We present a case of repair of a postoperative ventral hernia occurring after congenital omphalocele reconstruction in a three-and-a-half-year-old child using an acellular, sterile, porcine dermal mesh. Conclusion. Non-cross-linked acellular porcine dermal matrix is an appropriate mesh used for the reconstruction of abdominal wall defects and their postoperative complications like large ventral hernias with success and preventing their recurrence.

Method of detecting defects in ion exchange membranes of electrochemical cells by chemochromic sensors

DOEpatents

Brooker, Robert Paul; Mohajeri, Nahid

2016-01-05

A method of detecting defects in membranes such as ion exchange membranes of electrochemical cells. The electrochemical cell includes an assembly having an anode side and a cathode side with the ion exchange membrane in between. In a configuration step a chemochromic sensor is placed above the cathode and flow isolation hardware lateral to the ion exchange membrane which prevents a flow of hydrogen (H.sub.2) between the cathode and anode side. The anode side is exposed to a first reactant fluid including hydrogen. The chemochromic sensor is examined after the exposing for a color change. A color change evidences the ion exchange membrane has at least one defect that permits H.sub.2 transmission therethrough.

Guidance for Preventing Birth Defects

MedlinePlus

... of no safe level of marijuana use during pregnancy, women who are pregnant, or considering becoming pregnant, should ... for her during pregnancy. Learn about vaccinations during pregnancy » Pregnant women are more prone to severe illness from the ...

Effect of point defects on the amorphization of metallic alloys during ion implantation. [NiTi

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pedraza, D.F.; Mansur, L.K.

1985-01-01

A theoretical model of radiation-induced amorphization of ordered intermetallic compounds is developed. The mechanism is proposed to be the buildup of lattice defects to very high concentrations, which destabilizes the crystalline structure. Because simple point defects do not normally reach such levels during irradiation, a new defect complex containing a vacancy and an interstitial is hypothesized. Crucial properties of the complex are that the interstitial sees a local chemical environment similar to that of an atom in the ordered lattice, that the formation of the complex prevents mutual recombination and that the complex is immobile. The evolution of a disordermore » based on complexes is not accompanied by like point defect aggregation. The latter leads to the development of a sink microstructure in alloys that do not become amorphous. For electron irradiation, the complexes form by diffusional encounters. For ion irradiation, complexes are also formed directly in cascades. The possibility of direct amorphization in cascades is also included. Calculations for the compound NiTi show reasonable agreement with measured amorphization kinetics.« less

Evaluation of applied public health emergency system at Prince Mohammed International Airport in Almedinah during Hajj season 2014: a qualitative case study.

PubMed

Gosadi, Ibrahim M; BinSaeed, Abdulaziz; Al-Hazmi, Ali M; Fadl, Amin A; Alharbi, Khalid H; Swarelzahab, Mazin M

2015-09-12

During the Hajj season 2014, several public health measures were applied by the Ministry of Health at Prince Mohammed International Airport in Almedinah. However, several operational defects affected the provision of preventive health services for passengers and airport workers. This study aims to evaluate the applied public health emergency system at the airport, detect any potential gaps and to provide appropriate operational solutions. This is a qualitative case study conducted at Prince Mohammed International Airport in Almedinah during the 2014 Hajj season, September 2014. Data were collected via semi-structured interviews, focus groups and policy document reviews. Interviews were conducted with the 14 individuals of the airport's decision makers and relevant health practitioners. Data were recorded via taking notes during interviews and data coding was performed to produce the main themes and subthemes of the study. The main findings of the study revealed three main defects affecting the applied public health emergency system at the airport. The main themes were mainly related to shortage in logistics related to public health emergency systems, shortage in proper documentation of policies and lack of documented protocols of communications among airport stakeholders. The study highlighted the main factors hindering the application of public health emergency measures at the airport. A Public Health Emergency Contingency Plan was proposed as a method to regulate the process of providing logistics for public health preventive services, the method of producing documented policies and methods of producing Memoranda of Understandings as communication regulators.

Maternal mortality in Syria: causes, contributing factors and preventability.

PubMed

Bashour, Hyam; Abdulsalam, Asmaa; Jabr, Aisha; Cheikha, Salah; Tabbaa, Mohammed; Lahham, Moataz; Dihman, Reem; Khadra, Mazen; Campbell, Oona M R

2009-09-01

To describe the biomedical and other causes of maternal death in Syria and to assess their preventability. A reproductive age mortality study (RAMOS) design was used to identify pregnancy related deaths. All deaths among women aged 15-49 reported to the national civil register for 2003 were investigated through home interviews. Verbal autopsies were used to ascertain the cause of death among pregnancy related maternal deaths, and causes and preventability of deaths were assessed by a panel of doctors. A total of 129 maternal deaths were identified and reviewed. Direct medical causes accounted for 88%, and haemorrhage was the main cause of death (65%). Sixty nine deaths (54%) occurred during labour or delivery. Poor clinical skills and lack of clinical competency were behind 54% of maternal deaths. Ninety one percent of maternal deaths were preventable. The causes of maternal death in Syria and their contributing factors reflect serious defects in the quality of maternal care that need to be urgently rectified.

CERAMENT treatment of fracture defects (CERTiFy): protocol for a prospective, multicenter, randomized study investigating the use of CERAMENT™ BONE VOID FILLER in tibial plateau fractures

PubMed Central

2014-01-01

Background Bone graft substitutes are widely used for reconstruction of posttraumatic bone defects. However, their clinical significance in comparison to autologous bone grafting, the gold-standard in reconstruction of larger bone defects, still remains under debate. This prospective, randomized, controlled clinical study investigates the differences in pain, quality of life, and cost of care in the treatment of tibia plateau fractures-associated bone defects using either autologous bone grafting or bioresorbable hydroxyapatite/calcium sulphate cement (CERAMENT™|BONE VOID FILLER (CBVF)). Methods/Design CERTiFy (CERament™ Treatment of Fracture defects) is a prospective, multicenter, controlled, randomized trial. We plan to enroll 136 patients with fresh traumatic depression fractures of the proximal tibia (types AO 41-B2 and AO 41-B3) in 13 participating centers in Germany. Patients will be randomized to receive either autologous iliac crest bone graft or CBVF after reduction and osteosynthesis of the fracture to reconstruct the subchondral bone defect and prevent the subsidence of the articular surface. The primary outcome is the SF-12 Physical Component Summary at week 26. The co-primary endpoint is the pain level 26 weeks after surgery measured by a visual analog scale. The SF-12 Mental Component Summary after 26 weeks and costs of care will serve as key secondary endpoints. The study is designed to show non-inferiority of the CBVF treatment to the autologous iliac crest bone graft with respect to the physical component of quality of life. The pain level at 26 weeks after surgery is expected to be lower in the CERAMENT bone void filler treatment group. Discussion CERTiFy is the first randomized multicenter clinical trial designed to compare quality of life, pain, and cost of care in the use of the CBVF and the autologous iliac crest bone graft in the treatment of tibia plateau fractures. The results are expected to influence future treatment recommendations. Trial registration number ClinicalTrials.gov: NCT01828905 PMID:24606670

Self-expanding nanoplatinum-coated nitinol devices for atrial septal defect and patent ductus arteriosus closure: a swine model.

PubMed

Lertsapcharoen, Pornthep; Khongphatthanayothin, Apichai; La-orkhun, Vidhavas; Supachokchaiwattana, Pentip; Charoonrut, Phingphol

2006-01-01

Our purpose was to evaluate self-expanding nanoplatinum-coated nitinol devices for transcatheter closure of atrial septal defects and patent ductus arteriosus in a swine model. The devices were braided from platinum-activated nitinol wires and filled with polyester to enhance thrombogenicity. The platinum activation of the nitinol wires was carried out with the help of Nanofusion technology. The coating of platinum covers the exposed surface of the nitinol wires and prevents the release of nickel into the blood stream after the implantation of the device but does not affect its shape memory, which makes the device self-expanding after it is loaded from the catheter. Atrial septal defects were created in 12 piglets by balloon dilation of the patent foramen ovale. The size of the device was selected on the basis of the diameter of the balloon and the size of the defect, measured by transthoracic echocardiography. The devices were successfully deployed in all 12 piglets under fluoroscopic study. Transthoracic color Doppler echocardiograms showed complete closure of the atrial septal defect within 15 minutes of device implantation. Twelve patent ductus arteriosus closure devices were deployed in the right or left subclavian arteries in 10 piglets. Angiograms showed complete occlusion of the subclavian arteries within a few minutes of device deployment. In the atrial septal defect cases, the autopsy findings showed complete organizing fibrin thrombus formation and complete neo-endothelialization on the outer surface of the devices within one week and six weeks of implantation, respectively. The use of self-expanding nanoplatinum-coated nitinol devices for the transcatheter closure of atrial septal defects and patent ductus arteriosus is feasible. The excellent occlusion result and complete neo-endothelialization of the devices in the swine model is an indication of the potential of these devices in human application.

Risk of central nervous system defects in offspring of women with and without mental illness.

PubMed

Ayoub, Aimina; Fraser, William D; Low, Nancy; Arbour, Laura; Healy-Profitós, Jessica; Auger, Nathalie

2018-02-22

We sought to determine the relationship between maternal mental illness and the risk of having an infant with a central nervous system defect. We analyzed a cohort of 654,882 women aged less than 20 years between 1989 and 2013 who later delivered a live born infant in any hospital in Quebec, Canada. The primary exposure was mental illness during pregnancy or hospitalization for mental illness before pregnancy. The outcomes were neural and non-neural tube defects of the central nervous system in any offspring. We computed risk ratios (RR) and 95% confidence intervals (CI) for the association between mental disorders and risk of central nervous system defects in log-binomial regression models adjusted for age at delivery, total parity, comorbidity, socioeconomic deprivation, place of residence, and time period. Maternal mental illness was associated with an increased risk of nervous system defects in offspring (RR 1.76, 95% CI 1.64-1.89). Hospitalization for any mental disorder was more strongly associated with non-neural tube (RR 1.84, 95% CI 1.71-1.99) than neural tube defects (RR 1.31, 95% CI 1.08-1.59). Women at greater risk of nervous system defects in offspring tended to be diagnosed with multiple mental disorders, have more than one hospitalization for mental disease, or be 17 or older at first hospitalization. A history of mental illness is associated with central nervous system defects in offspring. Women hospitalized for mental illness may merit counseling at first symptoms to prevent central nervous system defects at pregnancy.

The critical size of focal articular cartilage defects is associated with strains in the collagen fibers.

PubMed

Heuijerjans, A; Wilson, W; Ito, K; van Donkelaar, C C

2017-12-01

The size of full-thickness focal cartilage defect is accepted to be predictive of its fate, but at which size threshold treatment is required is unclear. Clarification of the mechanism behind this threshold effect will help determining when treatment is required. The objective was to investigate the effect of defect size on strains in the collagen fibers and the non-fibrillar matrix of surrounding cartilage. These strains may indicate matrix disruption. Tissue deformation into the defect was expected, stretching adjacent superficial collagen fibers, while an osteochondral implant was expected to prevent these deformations. Finite element simulations of cartilage/cartilage contact for intact, 0.5 to 8mm wide defects and 8mm implant cases were performed. Impact, a load increase to 2MPa in 1ms, and creep loading, a constant load of 0.5MPa for 900s, scenarios were simulated. A composition-based material model for articular cartilage was employed. Impact loading caused low strain levels for all models. Creep loading increased deviatoric strains and collagen strains in the surrounding cartilage. Deviatoric strains increased gradually with defect size, but the surface area at which collagen fiber strains exceeded failure thresholds, abruptly increased for small increases of defect size. This was caused by a narrow distribution of collagen fiber strains resulting from the non-linear stiffness of the fibers. We postulate this might be the mechanism behind the existence of a critical defect size. Filling of the defect with an implant reduced deviatoric and collagen fiber strains towards values for intact cartilage. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quality of medicines in Canada: a retrospective review of risk communication documents (2005–2013)

PubMed Central

Almuzaini, Tariq; Sammons, Helen; Choonara, Imti

2014-01-01

Objective To explore the quality and safety of medicines in Canada. Design A retrospective review of drug recalls and risk communication documents conveying issues relating to defective (ie, substandard and falsified) medicines. Setting The Health Canada website search for drug recalls and risk communication documents issued between 2005 and 2013. Eligibility criteria Drug recalls and risk communication documents related to quality defect in medicinal products. Main outcome measure Relevant data about defective medicines reported in drug recalls and risk communication documents, including description of the defect, type of formulation, year of the recall and category of the recall or the document. Results There were 653 defective medicines of which 649 were substandard. The number of defective medicines reported by Health Canada increased from 42 in 2005 to 143 in 2013. The two most frequently reported types of defects were stability (205 incidents) and contamination issues (139 incidents). Some of these defects were found to be more prominent and repetitive over other types within some manufacturers. Tablet formulation (251 incidents) was the formulation most frequently compromised. No significant differences were observed between the manufacturers and distributors in the number of substandard medicines reported under each defect type. There were only four falsified medicines reported over the 9-year period. Conclusions Substandard medicines are a problem in Canada and have resulted in an increasing number of recalled medicines. Most of the failures were related to stability issues, raising the need to investigate the root causes and for stringent preventative measures to be implemented by manufacturers. PMID:25361839

Prescription Drugs, Over-the-Counter Drugs, Supplements and Herbal Products

MedlinePlus

... at risk? Zika virus and pregnancy Folic acid Medicine safety and pregnancy Birth defects prevention Learn how ... the-counter drugs, supplements and herbal products Prescription drugs, over-the-counter drugs, supplements and herbal products ...

Birth Defects Prevention, Risk Reduction, and Awareness Act of 2011

THOMAS, 112th Congress

Sen. Hagan, Kay R. [D-NC

2011-05-26

Senate - 05/26/2011 Read twice and referred to the Committee on Health, Education, Labor, and Pensions. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Birth Defects Prevention, Risk Reduction, and Awareness Act of 2010

THOMAS, 111th Congress

Sen. Hagan, Kay R. [D-NC

2010-06-10

Senate - 06/10/2010 Read twice and referred to the Committee on Health, Education, Labor, and Pensions. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Rubella

MedlinePlus

... dangerous for a pregnant woman's baby. It can cause miscarriage or birth defects. Rubella spreads when an infected person coughs or sneezes. People without symptoms can still spread it. There is no treatment, but the measles-mumps-rubella (MMR) vaccine can prevent it. Centers ...

Knowledge, attitudes, and practices of women of childbearing age testing negative for Zika virus in Kentucky, 2016.

PubMed

Heitzinger, Kristen; Thoroughman, Douglas A; Porter, Kimberly A

2018-06-01

Because infection with Zika virus during pregnancy can cause microcephaly and other birth defects, women of childbearing age are an important population for targeting of Zika-related public health messaging. To improve Zika-related communication and outreach in Kentucky, we conducted a survey to assess Zika knowledge, attitudes, and practices among all women of childbearing age who received a negative Zika test result from the state public health laboratory during February to July 2016. Although >90% of the 55 respondents knew the virus could be transmitted by mosquitoes and caused birth defects, just 56% (31/55) knew the virus could be sexually transmitted. These findings underscore the importance of continued efforts by CDC and state and local health departments to educate female travelers of childbearing age about risks for and prevention of Zika virus infection, particularly emphasizing use of condoms and abstinence to prevent transmission.

[POSSIBILITIES OF VACUUM THERAPY APPLICATION IN DISORDERS OF VENOUS OUTFLOW IN ISLET GRAFTS].

PubMed

Badyul, P O; Samoylenko, G E; Nor, N M; Slesarenko, K S

2015-07-01

The experience of "distressed" (problematic) flaps application in 33 patients with soft tissue defects over 2010-2014 years were analysed. It was proposed to use the local negative pressure for the prevention and treatment of complications associated with venous insufficiency or trombosis in using of plastics with vascularised complexes of tissues. Vacuum-therapy was conducted with the help of negative pressure apparatus "AGATE-Dnepr" (Ukraine) by attaching silver-containing polyurethane sponge on the operating zone, covering the flap with the surrounding skin netting band "Grassolind". The recommended standard of negative pressure of 75-125 mm Hg, both in impulse and in continuous mode was used. The high efficiency of vacuum-therapy for survival of grafts has been demonstrated. Thus, it might be considered as an effective element of prevention and treatment of complications associated with venous insufficiency or trombosis using of vascularised tissue complex plastics of defects.

Single closed contact for 0.18-micron photolithography process

NASA Astrophysics Data System (ADS)

Cheung, Cristina; Phan, Khoi A.; Chiu, Robert J.

2000-06-01

With the rapid advances of deep submicron semiconductor technology, identifying defects is converted into a challenge for different modules in the fabrication of chips. Yield engineers often do bitmap on a memory circuit array (SRAM) to identify the failure bits. This is followed by a wafer stripback to look for visual defects at each deprocessed layer for feedback to the Fab. However, to identify the root cause of a problem, Fab engineers must be able to detect similar defects either on the product wafers in process or some short loop test wafers. In the photolithography process, we recognize that the detection of defects is becoming as important as satisfying the critical dimension (CD) of the device. For a multi-level metallization chemically mechanical polish backend process, it is very difficult to detect missing contacts or via at the masking steps due to metal grain roughness, film color variation and/or previous layer defects. Often, photolithography engineer must depend on Photo Cell Monitor (PCM) and short loop experiments for controlling baseline defects and improvement. In this paper, we discuss the findings on the Poly mask PCM and the Contact mask PCM. We present the comparison between the Poly mask and the Contact mask of the I-line Phase Shifted Via mask and DUV mask process for a 0.18 micron process technology. The correlation and the different type of defects between the Contact PCM and the Poly Mask are discussed. The Contact PCM was found to be more sensitive and correlated to contact failure at sort yield better. We also dedicate to study the root cause of a single closed contact hole in the Contact mask short loop experiment for a 0.18 micron process technology. A single closed contact defect was often caused by the developer process, such as bubbles in the line, resist residue left behind, and the rinse mechanism. We also found surfactant solution helps to improve the surface tension of the wafer for the developer process and this prevents/eliminates a single closed contact hole defects. The applications and effects of using different substrates like SiON, different thicknesses of Oxides, and Poly in the Contact Photo Mask is shown. Finally, some defect troubleshooting techniques and the root cause analysis are also discussed.

Improvement of formability of high strength steel sheets in shrink flanging

NASA Astrophysics Data System (ADS)

Hamedon, Z.; Abe, Y.; Mori, K.

2016-02-01

In the shrinkage flanging, the wrinkling tends to occur due to compressive stress. The wrinkling will cause a difficulty in assembling parts, and severe wrinkling may leads to rupture of parts. The shrinkage flange of the ultra-high strength steel sheets not only defects the product by the occurrence of the wrinkling but also causes seizure and wear of the dies and shortens the life of dies. In the present study, a shape of a punch having gradual contact was optimized in order to prevent the wrinkling in shrinkage flanging of ultra-high strength steel sheets. The sheet was gradually bent from the corner of the sheet to reduce the compressive stress. The wrinkling in the shrink flanging of the ultra-high strength steel sheets was prevented by the punch having gradual contact. It was found that the punch having gradual contact is effective in preventing the occurrence of wrinkling in the shrinkage flanging.

Formate supplementation enhances folate-dependent nucleotide biosynthesis and prevents spina bifida in a mouse model of folic acid-resistant neural tube defects.

PubMed

Sudiwala, Sonia; De Castro, Sandra C P; Leung, Kit-Yi; Brosnan, John T; Brosnan, Margaret E; Mills, Kevin; Copp, Andrew J; Greene, Nicholas D E

2016-07-01

The curly tail mouse provides a model for neural tube defects (spina bifida and exencephaly) that are resistant to prevention by folic acid. The major ct gene, responsible for spina bifida, corresponds to a hypomorphic allele of grainyhead-like 3 (Grhl3) but the frequency of NTDs is strongly influenced by modifiers in the genetic background. Moreover, exencephaly in the curly tail strain is not prevented by reinstatement of Grhl3 expression. In the current study we found that expression of Mthfd1L, encoding a key component of mitochondrial folate one-carbon metabolism (FOCM), is significantly reduced in ct/ct embryos compared to a partially congenic wild-type strain. This expression change is not attributable to regulation by Grhl3 or the genetic background at the Mthfd1L locus. Mitochondrial FOCM provides one-carbon units as formate for FOCM reactions in the cytosol. We found that maternal supplementation with formate prevented NTDs in curly tail embryos and also resulted in increased litter size. Analysis of the folate profile of neurulation-stage embryos showed that formate supplementation resulted in an increased proportion of formyl-THF and THF but a reduction in proportion of 5-methyl THF. In contrast, THF decreased and 5-methyl THF was relatively more abundant in the liver of supplemented dams than in controls. In embryos cultured through the period of spinal neurulation, incorporation of labelled thymidine and adenine into genomic DNA was suppressed by supplemental formate, suggesting that de novo folate-dependent biosynthesis of nucleotides (thymidylate and purines) was enhanced. We hypothesise that reduced Mthfd1L expression may contribute to susceptibility to NTDs in the curly tail strain and that formate acts as a one-carbon donor to prevent NTDs. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Challenges of nickel silicidation in CMOS technologies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Breil, Nicolas; Lavoie, Christian; Ozcan, Ahmet

2015-04-01

In our paper, we review some of the key challenges associated with the Ni silicidation process in the most recent CMOS technologies. The introduction of new materials (e.g.SiGe), and of non-planar architectures bring some important changes that require fundamental investigation from a material engineering perspective. Following a discussion of the device architecture and silicide evolution through the last CMOS generations, we focus our study on a very peculiar defect, termed NiSi-Fangs. We describe a mechanism for the defect formation, and present a detailed material analysis that supports this mechanism. We highlight some of the possible metal enrichment processes of themore » nickel monosilicide such as oxidation or various RIE (Reactive Ion Etching) plasma process, leading to a metal source available for defect formation. Furthermore, we investigate the NiSi formation and re-formation silicidation differences between Si and SiGe materials, and between (1 0 0) and (1 1 1) orientations. Finally, we show that the thermal budgets post silicidation can lead to the formation of NiSi-Fangs if the structure and the processes are not optimized. Beyond the understanding of the defect and the discussion on the engineering solutions used to prevent its formation, the interest of this investigation also lies in the fundamental learning within the Ni–Pt–Si–Ge system and some additional perspective on Ni-based contacts to advanced microelectronic devices.« less

Methods for Measuring Lung Volumes: Is There a Better One?

PubMed

Tantucci, Claudio; Bottone, Damiano; Borghesi, Andrea; Guerini, Michele; Quadri, Federico; Pini, Laura

2016-01-01

Accurate measurement of lung volumes is of paramount importance to establish the presence of ventilatory defects and give insights for diagnostic and/or therapeutic purposes. It was the aim of this study to measure lung volumes in subjects with respiratory disorders and in normal controls by 3 different techniques (plethysmographic, dilutional and radiographic methods), in an attempt to clarify the role of each of them in performing such a task, without any presumptive 'a priori' superiority of one method above others. Patients andMethods: In different groups of subjects with obstructive and restrictive ventilatory defects and in a normal control group, total lung capacity, functional residual capacity (FRC) and residual volume were measured by body plethysmography, multi-breath helium (He) dilution and radiographic CT scan method with spirometric gating. The 3 methods gave comparable results in normal subjects and in patients with a restrictive defect. In patients with an obstructive defect, CT scan and plethysmography showed similar lung volumes, while on average significantly lower lung volumes were obtained with the He dilution technique. Taking into account that the He dilution technique does primarily measure FRC during tidal breathing, our data suggest that in some patients with an obstructive defect, a number of small airways can be functionally closed at end-expiratory lung volume, preventing He to reach the lung regions subserved by these airways. In all circumstances, both CT scan with spirometric gating and plethysmographic methods provide similar values of lung volumes. In contrast, the He dilution method can measure lower lung volumes in some patients with chronic airflow obstruction. © 2016 S. Karger AG, Basel.

In vivo characterization of Hyalonect, a novel biodegradable surgical mesh.

PubMed

Rhodes, Nicholas P; Hunt, John A; Longinotti, Cristina; Pavesio, Alessandra

2011-06-01

Musculoskeletal reconstructive surgery often requires removal of significant quantities of bone tissue, such as the periosteum, causing critical problems following surgery like friction between different tissues and adhesion of soft tissues to the underlying bone. We studied the long-term host response and closure of large bone defects for periosteal reconstruction using Hyalonect, a novel membrane comprising knitted fibers of esterified hyaluronan, (HYAFF11). For biological characterization, 162 rats were used in a defect model in which a section of the dorsal muscular fascia was removed, and the membrane behavior observed over 540 d using conventional histology, with sham operated rats as controls. In addition, Hyalonect was used to cover defects made in the humeri of 7 dogs, filled with a variety of conventional bone filling compounds, and the regeneration process observed after 6 wks using histology. Low levels of inflammation were observed in the dorsal muscle fascia defect model, with cellular colonization of the mesh by 30 d, vascularization by 120 days, matrix fiber organization by 270 d, and the appearance of connective tissue identical to the surrounding tissue between 365 and 540 d, without the formation of fibrotic tissue. In addition, Hyalonect was shown to allow the regeneration of bone within the humeral defects whilst preventing fibrotic tissue in-growth, and allowing regeneration of tissue which, by 6 wk, had begun to resemble natural periosteal tissue. Hyalonect is suitable for improving the outcome of the final phases of orthopedic and trauma reconstructive surgical procedures, especially in the reconstruction of periosteal tissue. Copyright © 2011. Published by Elsevier Inc.

Estimates of global and regional prevalence of neural tube defects for 2015: a systematic analysis.

PubMed

Blencowe, Hannah; Kancherla, Vijaya; Moorthie, Sowmiya; Darlison, Matthew W; Modell, Bernadette

2018-02-01

Neural tube defects (NTDs) are associated with substantial mortality, morbidity, disability, and psychological and economic costs. Many are preventable with folic acid, and access to appropriate services for those affected can improve survival and quality of life. We used a compartmental model to estimate global and regional birth prevalence of NTDs (live births, stillbirths, and elective terminations of pregnancy) and subsequent under-5 mortality. Data were identified through web-based reviews of birth defect registry databases and systematic literature reviews. Meta-analyses were undertaken where appropriate. For 2015, our model estimated 260,100 (uncertainty interval (UI): 213,800-322,000) NTD-affected birth outcomes worldwide (prevalence 18.6 (15.3-23.0)/10,000 live births). Approximately 50% of cases were elective terminations of pregnancy for fetal anomalies (UI: 59,300 (47,900-74,500)) or stillbirths (57,800 (UI: 35,000-88,600)). Of NTD-affected live births, 117,900 (∼75%) (UI: 105,500-186,600) resulted in under-5 deaths. Our systematic review showed a paucity of high-quality data in the regions of the world with the highest burden. Despite knowledge about prevention, NTDs remain highly prevalent worldwide. Lack of surveillance and incomplete ascertainment of affected pregnancies make NTDs invisible to policy makers. Improved surveillance of all adverse outcomes is needed to improve the robustness of total NTD prevalence estimation, evaluate effectiveness of prevention through folic acid fortification, and improve outcomes through care and rehabilitation. © 2018 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of New York Academy of Sciences.

Taurine protects methamphetamine-induced developmental angiogenesis defect through antioxidant mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shao, Xue; Hu, Zhengtao; Hu, Chunyan

Investigations have characterized addictive drug-induced developmental cardiovascular malformation in human, non-human primate and rodent. However, the underlying mechanism of malformation caused by drugs during pregnancy is still largely unknown, and preventive and therapeutic measures have been lacking. Using {sup 1}H NMR spectroscopy, we profiled the metabolites from human embryo endothelial cells exposed to methamphetamine (METH) and quantified a total of 226 peaks. We identified 11 metabolites modified robustly and found that taurine markedly increased. We then validated the hypothesis that this dramatic increase in taurine could attribute to its effect in inhibiting METH-induced developmental angiogenesis defect. Taurine supplement showed amore » more significant potential than other metabolites in protecting against METH-induced injury in endothelial cells. Taurine strongly attenuated METH-induced inhibition of proliferation and migration in endothelial cells. Furthermore, death rate and vessel abnormality of zebrafish embryos treated with METH were greatly reversed by taurine. In addition, taurine supplement caused a rapid decrease in reactive oxygen species generation and strongly attenuated the excitable arise of antioxidase activities in the beginning of METH exposure prophase. Dysregulations of NF-κB, p-ERK as well as Bax, which reflect apoptosis, cell cycle arrest and oxidative stress in vascular endothelium, were blocked by taurine. Our results provide the first evidence that taurine prevents METH-caused developmental angiogenesis defect through antioxidant mechanism. Taurine could serve as a potential therapeutic or preventive intervention of developmental vascular malformation for the pregnant women with drug use. Highlights: ► Metabonomics findings. ► Abnormal development. ► Dysregulations of key proteins.« less

The challenge of developing a herpes simplex virus 2 vaccine

PubMed Central

Dropulic, Lesia K; Cohen, Jeffrey I

2013-01-01

HSV infections are prevalent worldwide. A vaccine to prevent genital herpes would have a significant impact on this disease. Several vaccines have shown promise in animal models; however, so far these have not been successful in human clinical studies. Prophylactic HSV vaccines to prevent HSV infection or disease have focused primarily on eliciting antibody responses. Potent antibody responses are needed to result in sufficiently high levels of virus-specific antibody in the genital tract. Therapeutic vaccines that reduce recurrences need to induce potent T-cell responses at the site of infection. With the increasing incidence of HSV-1 genital herpes, an effective herpes vaccine should protect against both HSV-1 and HSV-2. Novel HSV vaccines, such as replication-defective or attenuated viruses, have elicited humoral and cellular immune responses in preclinical studies. These vaccines and others hold promise in future clinical studies. PMID:23252387

A synchrotron study of microstructure gradient in laser additively formed epitaxial Ni-based superalloy

DOE PAGES

Xue, Jiawei; Zhang, Anfeng; Li, Yao; ...

2015-10-08

Laser additive forming is considered to be one of the promising techniques to repair single crystal Ni-based superalloy parts to extend their life and reduce the cost. Preservation of the single crystalline nature and prevention of thermal mechanical failure are two of the most essential issues for the application of this technique. Here we employ synchrotron X-ray microdiffraction to evaluate the quality in terms of crystal orientation and defect distribution of a Ni-based superalloy DZ125L directly formed by a laser additive process rooted from a single crystalline substrate of the same material. We show that a disorientation gradient caused bymore » a high density of geometrically necessary dislocations and resultant subgrains exists in the interfacial region between the epitaxial and stray grains. This creates a potential relationship of stray grain formation and defect accumulation. In conclusion, the observation offers new directions on the study of performance control and reliability of the laser additive manufactured superalloys.« less

Formin homology 1 (OsFH1) regulates submergence-dependent root hair development in rice plants.

PubMed

Huang, Jin; Liu, Jingmiao; Han, Chang-Deok

2013-08-01

By using a forward genetic approach, a formin homology 1 gene (OsFH1) was identified as a critical regulator of rice root hair development. The phenotypic effect of OsFH1 on root hair development was verified by using three independent mutants, one point mutation and two T-DNA insertions. The study showed that OsFH1 is required for the elongation of root-hairs. However, Osfh1 exhibited growth defect of root hairs only when roots were grown submerged in solution. To understand how OsFH1 impinges on plant responses to root submergence, the growth responses of Osfh1 root hairs to anoxia, carbohydrate supplementation and exogenous hormones (auxin and ethylene) and nutrients (Fe and Pi) were examined. However, none of these treatments rescued the growth defects of Osfhl1 root hairs. This study demonstrates that OsFH1 could be involved in preventing submergence-induced inhibition of root hair growth.

Dietary intake of choline and neural tube defects in Mexican Americans.

PubMed

Lavery, Amy M; Brender, Jean D; Zhao, Hongwei; Sweeney, Anne; Felkner, Marilyn; Suarez, Lucina; Canfield, Mark A

2014-06-01

Low maternal intake of dietary choline and betaine (a choline derivative) has recently been investigated as a possible risk factor for neural tube defects (NTDs). This case-control study examined the NTD risk associated with choline and betaine in 409 Mexican-American women who gave birth during 1995 to 2000 in the 14-county border region of Texas. Using data from the food frequency questionnaire and the lowest quartiles of intake as the reference categories, a protective association was suggested between higher intakes of choline and betaine and NTD risk although the 95% confidence intervals for all risk estimates included 1.0. For choline intake in the second, third, and fourth quartiles, adjusted odds ratios were 1.2, 0.80, and 0.89, respectively. Betaine appeared more protective with odds ratios of 0.62, 0.73, and 0.61, respectively, for the second, third, and fourth quartiles of intake. Study findings suggest that dietary betaine may help to prevent NTDs. © 2014 Wiley Periodicals, Inc.

A synchrotron study of microstructure gradient in laser additively formed epitaxial Ni-based superalloy.

PubMed

Xue, Jiawei; Zhang, Anfeng; Li, Yao; Qian, Dan; Wan, Jingchun; Qi, Baolu; Tamura, Nobumichi; Song, Zhongxiao; Chen, Kai

2015-10-08

Laser additive forming is considered to be one of the promising techniques to repair single crystal Ni-based superalloy parts to extend their life and reduce the cost. Preservation of the single crystalline nature and prevention of thermal mechanical failure are two of the most essential issues for the application of this technique. Here we employ synchrotron X-ray microdiffraction to evaluate the quality in terms of crystal orientation and defect distribution of a Ni-based superalloy DZ125L directly formed by a laser additive process rooted from a single crystalline substrate of the same material. We show that a disorientation gradient caused by a high density of geometrically necessary dislocations and resultant subgrains exists in the interfacial region between the epitaxial and stray grains. This creates a potential relationship of stray grain formation and defect accumulation. The observation offers new directions on the study of performance control and reliability of the laser additive manufactured superalloys.

A synchrotron study of microstructure gradient in laser additively formed epitaxial Ni-based superalloy

PubMed Central

Xue, Jiawei; Zhang, Anfeng; Li, Yao; Qian, Dan; Wan, Jingchun; Qi, Baolu; Tamura, Nobumichi; Song, Zhongxiao; Chen, Kai

2015-01-01

Laser additive forming is considered to be one of the promising techniques to repair single crystal Ni-based superalloy parts to extend their life and reduce the cost. Preservation of the single crystalline nature and prevention of thermal mechanical failure are two of the most essential issues for the application of this technique. Here we employ synchrotron X-ray microdiffraction to evaluate the quality in terms of crystal orientation and defect distribution of a Ni-based superalloy DZ125L directly formed by a laser additive process rooted from a single crystalline substrate of the same material. We show that a disorientation gradient caused by a high density of geometrically necessary dislocations and resultant subgrains exists in the interfacial region between the epitaxial and stray grains. This creates a potential relationship of stray grain formation and defect accumulation. The observation offers new directions on the study of performance control and reliability of the laser additive manufactured superalloys. PMID:26446425

Genetic epistasis between heparan sulfate and FGF-Ras signaling controls lens development

PubMed Central

Qu, Xiuxia; Hertzler, Kristina; Pan, Yi; Grobe, Kay; Robinson, Michael L.; Zhang, Xin

2011-01-01

Vertebrate lens development depends on a complex network of signaling molecules to coordinate cell proliferation, migration and differentiation. In this study, we have studied the role of heparan sulfate in lens specific signaling by generating a conditional ablation of heparan sulfate modification genes, Ndst1 and Ndst2. In this mutant, N-sulfation of heparan sulfate was disrupted after the lens induction stage, resulting in reduced lens cell proliferation, increased cell death and defective lens fiber differentiation in later lens development. The loss of Ndst function also prevented the assembly of Fgf/Fgfr complexes on the lens cell surface and disrupted ERK signaling within the lens. We further demonstrated that Ndst mutation completely inhibited the FGF1 and Fgf3 overexpression phenotypes, but Kras reactivation was sufficient to reverse the Ndst deficient lens differentiation defect. The epistatic relationship between Ndst and FGF-Ras signaling demonstrates that FGF signaling is the predominant signaling pathway controlled by Ndst in lens development. PMID:21536023

Replication fork reversal triggers fork degradation in BRCA2-defective cells.

PubMed

Mijic, Sofija; Zellweger, Ralph; Chappidi, Nagaraja; Berti, Matteo; Jacobs, Kurt; Mutreja, Karun; Ursich, Sebastian; Ray Chaudhuri, Arnab; Nussenzweig, Andre; Janscak, Pavel; Lopes, Massimo

2017-10-16

Besides its role in homologous recombination, the tumor suppressor BRCA2 protects stalled replication forks from nucleolytic degradation. Defective fork stability contributes to chemotherapeutic sensitivity of BRCA2-defective tumors by yet-elusive mechanisms. Using DNA fiber spreading and direct visualization of replication intermediates, we report that reversed replication forks are entry points for fork degradation in BRCA2-defective cells. Besides MRE11 and PTIP, we show that RAD52 promotes stalled fork degradation and chromosomal breakage in BRCA2-defective cells. Inactivation of these factors restores reversed fork frequency and chromosome integrity in BRCA2-defective cells. Conversely, impairing fork reversal prevents fork degradation, but increases chromosomal breakage, uncoupling fork protection, and chromosome stability. We propose that BRCA2 is dispensable for RAD51-mediated fork reversal, but assembles stable RAD51 nucleofilaments on regressed arms, to protect them from degradation. Our data uncover the physiopathological relevance of fork reversal and illuminate a complex interplay of homologous recombination factors in fork remodeling and stability.BRCA2 is involved in both homologous recombination (HR) and the protection of stalled replication forks from degradation. Here the authors reveal how HR factors cooperate in fork remodeling, showing that BRCA2 supports RAD51 loading on the regressed arms of reversed replication forks to protect them from degradation.

Hydrophilic Graphene Preparation from Gallic Acid Modified Graphene Oxide in Magnesium Self-Propagating High Temperature Synthesis Process

NASA Astrophysics Data System (ADS)

Cao, Lei; Li, Zhenhuan; Su, Kunmei; Cheng, Bowen

2016-10-01

Hydrophilic graphene sheets were synthesized from a mixture of magnesium and gallic acid (GA) modified graphene oxide (GO) in a self-propagating high-temperature synthesis (SHS) process, and hydrophilic graphene sheets displayed the higher C/O ratio (16.36), outstanding conductivity (~88900 S/m) and excellent water-solubility. GO sheets were connected together by GA, and GA was captured to darn GO structure defects through the formation of hydrogen bonds and ester bonds. In SHS process, the most oxygen ions of GO reacted with magnesium to prevent the escape of carbon dioxide and carbon monoxide to from the structure defects associated with vacancies, and GA could take place the high-temperature carbonization, during which a large-area graphene sheets formed with a part of the structure defects being repaired. When only GO was reduced by magnesium in SHS process, and the reduced GO (rGO) exhibited the smaller sheets, the lower C/O ratio (15.26), the weaker conductivity (4200 S/m) and the poor water-solubility because rGO inevitably left behind carbon vacancies and topological defects. Therefore, the larger sheet, less edge defects and free structure defects associated with vacancies play a key role for graphene sheets good dispersion in water.

Recognizing anterior metaphyseal femoral bone loss during uncemented total hip arthroplasty: the skylight sign.

PubMed

Harwin, Steven F

2007-03-01

During preparation for uncemented femoral arthroplasty, a phenomenon has been observed that indicates thinning of anterior metaphyseal bone to a critical level. Light can be seen from within the canal passing through the anterior cortex. This skylight sign alerts the surgeon that a cortical defect or fracture can occur on reaming, broaching, or component insertion. In 420 consecutive arthroplasties, a skylight sign was noted in 97 (23%) hips. In 5 of those hips an oval cortical defect was created and in 3 hips a fracture occurred during broaching or insertion. Loosening developed in 1 hip with fracture. No fractures or defects occurred in hips without a skylight sign. If a skylight sign is present, the femur is at risk and preventive measures should be taken.

Integrated circuit failure analysis by low-energy charge-induced voltage alteration

DOEpatents

Cole, E.I. Jr.

1996-06-04

A scanning electron microscope apparatus and method are described for detecting and imaging open-circuit defects in an integrated circuit (IC). The invention uses a low-energy high-current focused electron beam that is scanned over a device surface of the IC to generate a charge-induced voltage alteration (CIVA) signal at the location of any open-circuit defects. The low-energy CIVA signal may be used to generate an image of the IC showing the location of any open-circuit defects. A low electron beam energy is used to prevent electrical breakdown in any passivation layers in the IC and to minimize radiation damage to the IC. The invention has uses for IC failure analysis, for production-line inspection of ICs, and for qualification of ICs. 5 figs.

Integrated circuit failure analysis by low-energy charge-induced voltage alteration

DOEpatents

Cole, Jr., Edward I.

1996-01-01

A scanning electron microscope apparatus and method are described for detecting and imaging open-circuit defects in an integrated circuit (IC). The invention uses a low-energy high-current focused electron beam that is scanned over a device surface of the IC to generate a charge-induced voltage alteration (CIVA) signal at the location of any open-circuit defects. The low-energy CIVA signal may be used to generate an image of the IC showing the location of any open-circuit defects. A low electron beam energy is used to prevent electrical breakdown in any passivation layers in the IC and to minimize radiation damage to the IC. The invention has uses for IC failure analysis, for production-line inspection of ICs, and for qualification of ICs.

[X-linked adrenoleukodystrophy: a report of three cases. The importance of early diagnosis].

PubMed

López Úbeda, Marta; de Arriba Muñoz, Antonio; Ferrer Lozano, Marta; Labarta Aizpún, José I; García Jiménez, María C

2017-10-01

X-linked adrenoleukodystrophy is the most common peroxisomal disorder. This disease is caused by a defect in the ABCD1 gen. Saturated very long chain fatty acids are accumulated in serum, adrenal cortex and central nervous system white matter. The clinical spectrum is characterized by progressive neurological dysfunction and adrenal insufficiency with a devastating prognosis. We report a first case of X-linked adrenoleukodystrophy with fatal evolution which identified two asymptomatic family members and established a preventive treatment. Although there is no definitive cure, we stress the importance of family study and evaluation of the individual in situation of risk to establish an early preventive treatment and to give in each particular situation suitable professional advice. Sociedad Argentina de Pediatría.

Errors prevention in manufacturing process through integration of Poka Yoke and TRIZ

NASA Astrophysics Data System (ADS)

Helmi, Syed Ahmad; Nordin, Nur Nashwa; Hisjam, Muhammad

2017-11-01

Integration of Poka Yoke and TRIZ is a method of solving problems by using a different approach. Poka Yoke is a trial and error method while TRIZ is using a systematic approach. The main purpose of this technique is to get rid of product defects by preventing or correcting errors as soon as possible. Blame the workers for their mistakes is not the best way, but the work process should be reviewed so that every workers behavior or movement may not cause errors. This study is to demonstrate the importance of using both of these methods in which everyone in the industry needs to improve quality, increase productivity and at the same time reducing production cost.

Implant and clinical characteristics for pediatric and congenital heart patients in the national cardiovascular data registry implantable cardioverter defibrillator registry.

PubMed

Jordan, Christopher P; Freedenberg, Vicki; Wang, Yongfei; Curtis, Jeptha P; Gleva, Marye J; Berul, Charles I

2014-12-01

In 2010, the National Cardiovascular Data Registry enhanced pediatric, nonatherosclerotic structural heart disease and congenital heart disease (CHD) data collection. This report characterizes CHD and pediatric patients undergoing implantable cardioverter defibrillator implantation. In this article, we report implantable cardioverter defibrillator procedures (April 2010 to December 2012) in the registry for 2 cohorts: (1) all patients with CHD (atrial septal defect, ventricular septal defect, tetralogy of Fallot, Ebstein anomaly, transposition of the great vessels, and common ventricle) and (2) patients <21 years. We evaluated indications and characteristics to include transvenous and nontransvenous lead implants, CHD type, and New York Heart Association class. There were 3139 CHD procedures, 1601 for patients <21 years and 126 for CHD <21 years. Implantable cardioverter defibrillator indications for patients with CHD were primary prevention in 1943 (61.9%) and secondary prevention in 1107 (35.2%). Pediatric patients had 935 (58.4%) primary prevention and 588 (36.7%) secondary prevention devices. Primary prevention had higher New York Heart Association class. Nontransvenous age (35.9 ± 23.2 versus 40.1 ± 24.6 years; P=0.05) and nontransvenous height (167.1 ± 18.9 cm; range, 53-193 cm versus 170.4 ± 13.1 cm; range, 61-203 cm; P<0.01) were lower than for transvenous patients. CHD and pediatrics had similar rates of transvenous (97%) and nontransvenous (3%) leads and did not differ from the overall registry. Transposition of the great vessels and common ventricle had higher rates of nontransvenous leads. Primary prevention exceeds secondary prevention for CHD and pediatrics. Nontransvenous lead patients were younger, with higher rates of transposition of the great vessels and common ventricle patients compared with transvenous lead patients. © 2014 American Heart Association, Inc.

Integrated light maintenance and inspection system for high-mast poles.

DOT National Transportation Integrated Search

2005-01-01

Virginia highway high-mast light poles must be inspected periodically for structural defects to prevent failures. The visual inspection methods currently used include use of binoculars and telescopes and up-close inspection with bucket trucks. These ...

Functional defect in regulatory T cells in myasthenia gravis

PubMed Central

Thiruppathi, Muthusamy; Rowin, Julie; Jiang, Qin Li; Sheng, Jian Rong; Prabhakar, Bellur S.; Meriggioli, Matthew N.

2012-01-01

Forkhead box P3 (FOXP3)+ is a transcription factor necessary for the function of regulatory T cells (Treg cells). Treg cells maintain immune homeostasis and self-tolerance, and play an important role in the prevention of autoimmune disease. Here, we discuss the role of Treg cells in the pathogenesis of myasthenia gravis (MG) and review evidence indicating that a significant defect in Treg cell in vitro suppressive function exists in MG patients, without an alteration in circulating frequency. This functional defect is associated with a reduced expression of key functional molecules such as FOXP3 on isolated Treg cells and appears to be more pronounced in immunosuppression-naive MG patients. In vitro administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced the suppressive function of Treg cells and up-regulated FOXP3 expression. These findings indicate a clinically relevant Treg cell–intrinsic defect in immune regulation in MG that may reveal a novel therapeutic target. PMID:23252899

Proteomic approach to characterize biochemistry of meat quality defects.

PubMed

Schilling, M W; Suman, S P; Zhang, X; Nair, M N; Desai, M A; Cai, K; Ciaramella, M A; Allen, P J

2017-10-01

Proteomics can be used to characterize quality defects including pale, soft, and exudative (PSE) meat (pork and poultry), woody broiler breast meat, reddish catfish fillets, meat toughness, and beef myoglobin oxidation. PSE broiler meat was characterized by 15 proteins that differed in abundance in comparison to normal broiler breast meat, and eight proteins were differentially expressed in woody breast meat in comparison to normal breast meat. Hemoglobin was the only protein that was differentially expressed between red and normal catfish fillets. However, inducing low oxygen and/or heat stress conditions to catfish fillets did not lead to the production of red fillets. Proteomic data provided information pertaining to the protein differences that exist in meat quality defects. However, these data need to be evaluated in conjunction with information pertaining to genetics, nutrition, environment of the live animal, muscle to meat conversion, meat quality analyses and sensory attributes to understand causality, protein biomarkers, and ultimately how to prevent quality defects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enthalpy Landscape Dictates the Irradiation-Induced Disordering of Quartz

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krishnan, N. M. Anoop; Wang, Bu; Yu, Yingtian

Here, under irradiation, minerals tend to experience an accumulation of structural defects, ultimately leading to a disordered atomic network. Despite the critical importance of understanding and predicting irradiation-induced damage, the physical origin of the initiation and saturation of defects remains poorly understood. Here, based on molecular dynamics simulations of α-quartz, we show that the topography of the enthalpy landscape governs irradiation-induced disordering. Specifically, we show that such disordering differs from that observed upon vitrification in that, prior to saturation, irradiated quartz accesses forbidden regions of the enthalpy landscape, i.e., those that are inaccessible by simply heating and cooling. Furthermore, wemore » demonstrate that damage saturates when the system accesses a local region of the enthalpy landscape corresponding to the configuration of an allowable liquid. At this stage, a sudden decrease in the heights of the energy barriers enhances relaxation, thereby preventing any further accumulation of defects and resulting in a defect-saturated disordered state.« less

Enthalpy Landscape Dictates the Irradiation-Induced Disordering of Quartz

DOE PAGES

Krishnan, N. M. Anoop; Wang, Bu; Yu, Yingtian; ...

2017-07-28

Here, under irradiation, minerals tend to experience an accumulation of structural defects, ultimately leading to a disordered atomic network. Despite the critical importance of understanding and predicting irradiation-induced damage, the physical origin of the initiation and saturation of defects remains poorly understood. Here, based on molecular dynamics simulations of α-quartz, we show that the topography of the enthalpy landscape governs irradiation-induced disordering. Specifically, we show that such disordering differs from that observed upon vitrification in that, prior to saturation, irradiated quartz accesses forbidden regions of the enthalpy landscape, i.e., those that are inaccessible by simply heating and cooling. Furthermore, wemore » demonstrate that damage saturates when the system accesses a local region of the enthalpy landscape corresponding to the configuration of an allowable liquid. At this stage, a sudden decrease in the heights of the energy barriers enhances relaxation, thereby preventing any further accumulation of defects and resulting in a defect-saturated disordered state.« less

Maternal caffeine intake during pregnancy and orofacial clefts.

PubMed

Collier, Sarah A; Browne, Marilyn L; Rasmussen, Sonja A; Honein, Margaret A

2009-10-01

Moderate caffeine intake during pregnancy is common, but little is known about its potential association with birth defects. The National Birth Defects Prevention Study is a population-based, case-control study of major birth defects, excluding infants with single-gene disorders and chromosomal abnormalities. This analysis includes infants with cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO), excluding infants whose cleft was secondary to holoprosencephaly or amniotic band sequence. Mothers reported dietary caffeine intake from coffee, tea, sodas, and chocolate in the year before pregnancy and reported intake of medications containing caffeine during pregnancy. We assessed the association between dietary caffeine intake, frequency of consuming each type of caffeinated beverage, medications containing caffeine, and CL/P or CPO among infants born from October 1997 through December 2004. This analysis included 1531 infants with CL/P, 813 infants with CPO, and 5711 infants with no major birth defects (controls). Examining dietary sources among control mothers, 11% reported consuming at least 300 mg of caffeine per day and 17% reported consuming less than 10 mg of caffeine per day; high consumption (>or=3 servings per day) was reported by 8% (coffee), 4% (tea), and 15% (sodas); medications containing at least 100 mg caffeine/dose were reported by less than 1%. Although some effect estimates were elevated for moderate caffeine intake from all beverages, estimates were closer to the null for high caffeine levels. Isolated CL/P was associated with use of medications containing at least 100 mg of caffeine per dose. Our data do not suggest an association between maternal dietary caffeine intake and orofacial clefts, but caffeine-containing medications merit further study.

Efficacy and safety of non-suture dural closure using a novel dural substitute consisting of polyglycolic acid felt and fibrin glue to prevent cerebrospinal fluid leakage-A non-controlled, open-label, multicenter clinical trial.

PubMed

Terasaka, Shunsuke; Taoka, Toshiaki; Kuroda, Satoshi; Mikuni, Nobutaka; Nishi, Toru; Nakase, Hiroyuki; Fujii, Yukihiko; Hayashi, Yasuhiko; Murata, Jun-Ichi; Kikuta, Ken-Ichiro; Kuroiwa, Toshihiko; Shimokawa, Sachie; Houkin, Kiyohiro

2017-05-01

The objective of this study is to evaluate the efficacy and safety of non-suture dural closure using a novel dural substitute (GM111) consisting of polyglycolic acid felt with a fibrin-glue-coated area commensurate in size with the dural defect. This was a non-controlled, open-label, multicenter clinical trial. The efficacy evaluation endpoints were (1) GM111's intra-operative capability to close dural defects and (2) prevention of cerebrospinal fluid (CSF) leakage and subcutaneous CSF retention throughout the postoperative period (evaluated by diagnostic imaging). Patients meeting the following three preoperative and two intra-operative selection criteria were enrolled: (1) between 12 and <75 years of age; (2) the dura is surmised to be defective and in need of reconstruction; (3) informed written consent was obtained from the patient; (4) the surgical wound is class 1; and (5) the size of duraplasty is ≥0.2 cm 2 to <100 cm 2 . Sixty patients were enrolled. The craniotomy site was supratentorial in 77.2%, infratentorial in 12.3% and sellar in 10.5%. The GM111 prosthesis size ranged from 0.24 to 42 cm 2 . To evaluate the efficacy, intra-operative closure was confirmed by Valsalva's maneuver, water infusion, etc., in all patients. CSF leakage and subcutaneous CSF retention throughout the postoperative period were found in four patients. Adverse events for which a causal relationship with GM111 could not be ruled out occurred in 8.8% of the patients. There were no instances of postoperative infection due to GM111. GM111 showed good closure capability and safety when used for non-suture dural closure.

Reconstruction of Midface and Orbital Wall Defects After Maxillectomy and Orbital Content Preservation With Titanium Mesh and Fascia Lata: 3-Year Follow-Up.

PubMed

Motiee-Langroudi, Maziar; Harirchi, Iraj; Amali, Amin; Jafari, Mehrdad

2015-12-01

To describe the authors' experience in the reconstruction of patients after total maxillectomy with preservation of orbital contents for maxillary tumors using titanium mesh and autogenous fascia lata, where no setting for free flap reconstruction is available. Twelve consecutive patients with paranasal sinus tumors underwent total maxillectomy without orbital exenterations and primary reconstruction. The defects were reconstructed by titanium mesh in combination with autogenous fascia lata in the orbital floor performed by 1 surgical team. Titanium mesh (0.2 mm thick) was contoured and fixed to reconstruct the orbital floor and obtain midface projection. Fascia lata was used to cover the titanium mesh along the orbital floor to prevent fat entrapment in the mesh holes. The most common pathology was squamous cell carcinoma (50%). Patients' mean age was 45.66 years (33 to 74 yr). The mean follow-up period was 35.2 months (30 to 49 months). During follow-up, no infection or foreign body reaction was encountered. Extrusion of titanium mesh occurred in 4 patients who underwent postoperative radiotherapy. Two cases of mild diplopia at extreme gaze occurred early during the postoperative period that resolved after a few months. Placing fascia lata between the titanium mesh surface of the orbital implant and the orbital contents was successful in preventing long-term diplopia or dystopia. Nevertheless, exposure of the titanium implant through the skin surface represented a complication of this technique in 25% of patients. Further studies are required with head-to-head comparisons of artificial materials and free flaps for reconstruction of maxillectomy defects. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Influence of angiographic collateral circulation on myocardial perfusion in patients with chronic total occlusion of a single coronary artery and no prior myocardial infarction.

PubMed

Aboul-Enein, Fatma; Kar, Saibal; Hayes, Sean W; Sciammarella, Maria; Abidov, Aiden; Makkar, Raj; Friedman, John D; Eigler, Neal; Berman, Daniel S

2004-06-01

The functional role of various angiographic grades for coronary collaterals remains controversial. The aim of this study was to assess the influence of the Rentrop angiographic grading of coronary collaterals on myocardial perfusion in patients with single-vessel chronic total occlusion (CTO) and no prior myocardial infarction (MI). The study included 56 patients with single-vessel CTO and no prior MI who underwent rest-stress myocardial perfusion SPECT and coronary angiography within 6 mo. All patients had angiographic evidence of coronary collaterals. Patients were divided according to the Rentrop classification: Group I had grade 1 or 2 (n = 25) and group II had grade 3 collaterals (n = 31). Group I had a higher frequency of resting regional wall motion abnormalities on left ventriculography (52.6% vs. 19.2% [P = 0.019]). The mean perfusion scores of the overall population showed severe and extensive stress perfusion defects (summed stress score of 14.1 +/- 7.1 and summed difference score of 12.9 +/- 6.9) but minimal resting perfusion defects (summed rest score of 1.0 +/- 2.7). No perfusion scores differed between the 2 groups. The perfusion findings suggested that chronic stunning rather than hibernation is the principal cause of regional wall motion abnormalities in these patients. In the setting of single-vessel CTO and no prior MI, coronary collaterals appear to protect against resting perfusion defects. Excellent angiographic collaterals may prevent resting regional wall motion abnormalities but do not appear to protect against stress-induced perfusion defects.

Programmed Application of Transforming Growth Factor β3 and Rac1 Inhibitor NSC23766 Committed Hyaline Cartilage Differentiation of Adipose-Derived Stem Cells for Osteochondral Defect Repair.

PubMed

Zhu, Shouan; Chen, Pengfei; Wu, Yan; Xiong, Si; Sun, Heng; Xia, Qingqing; Shi, Libing; Liu, Huanhuan; Ouyang, Hong Wei

2014-10-01

Hyaline cartilage differentiation is always the challenge with application of stem cells for joint repair. Transforming growth factors (TGFs) and bone morphogenetic proteins can initiate cartilage differentiation but often lead to hypertrophy and calcification, related to abnormal Rac1 activity. In this study, we developed a strategy of programmed application of TGFβ3 and Rac1 inhibitor NSC23766 to commit the hyaline cartilage differentiation of adipose-derived stem cells (ADSCs) for joint cartilage repair. ADSCs were isolated and cultured in a micromass and pellet culture model to evaluate chondrogenic and hypertrophic differentiation. The function of Rac1 was investigated with constitutively active Rac1 mutant and dominant negative Rac1 mutant. The efficacy of ADSCs with programmed application of TGFβ3 and Rac1 inhibitor for cartilage repair was studied in a rat model of osteochondral defects. The results showed that TGFβ3 promoted ADSCs chondro-lineage differentiation and that NSC23766 prevented ADSC-derived chondrocytes from hypertrophy in vitro. The combination of ADSCs, TGFβ3, and NSC23766 promoted quality osteochondral defect repair in rats with much less chondrocytes hypertrophy and significantly higher International Cartilage Repair Society macroscopic and microscopic scores. The findings have illustrated that programmed application of TGFβ3 and Rac1 inhibitor NSC23766 can commit ADSCs to chondro-lineage differentiation and improve the efficacy of ADSCs for cartilage defect repair. These findings suggest a promising stem cell-based strategy for articular cartilage repair. ©AlphaMed Press.

Obstructive heart defects associated with candidate genes, maternal obesity, and folic acid supplementation.

PubMed

Tang, Xinyu; Cleves, Mario A; Nick, Todd G; Li, Ming; MacLeod, Stewart L; Erickson, Stephen W; Li, Jingyun; Shaw, Gary M; Mosley, Bridget S; Hobbs, Charlotte A

2015-06-01

Right-sided and left-sided obstructive heart defects (OHDs) are subtypes of congenital heart defects, in which the heart valves, arteries, or veins are abnormally narrow or blocked. Previous studies have suggested that the development of OHDs involved a complex interplay between genetic variants and maternal factors. Using the data from 569 OHD case families and 1,644 control families enrolled in the National Birth Defects Prevention Study (NBDPS) between 1997 and 2008, we conducted an analysis to investigate the genetic effects of 877 single nucleotide polymorphisms (SNPs) in 60 candidate genes for association with the risk of OHDs, and their interactions with maternal use of folic acid supplements, and pre-pregnancy obesity. Applying log-linear models based on the hybrid design, we identified a SNP in methylenetetrahydrofolate reductase (MTHFR) gene (C677T polymorphism) with a main genetic effect on the occurrence of OHDs. In addition, multiple SNPs in betaine-homocysteine methyltransferase (BHMT and BHMT2) were also identified to be associated with the occurrence of OHDs through significant main infant genetic effects and interaction effects with maternal use of folic acid supplements. We also identified multiple SNPs in glutamate-cysteine ligase, catalytic subunit (GCLC) and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) that were associated with elevated risk of OHDs among obese women. Our findings suggested that the risk of OHDs was closely related to a combined effect of variations in genes in the folate, homocysteine, or glutathione/transsulfuration pathways, maternal use of folic acid supplements and pre-pregnancy obesity. © 2015 Wiley Periodicals, Inc.

Dietary Milk Sphingomyelin Prevents Disruption of Skin Barrier Function in Hairless Mice after UV-B Irradiation.

PubMed

Oba, Chisato; Morifuji, Masashi; Ichikawa, Satomi; Ito, Kyoko; Kawahata, Keiko; Yamaji, Taketo; Asami, Yukio; Itou, Hiroyuki; Sugawara, Tatsuya

2015-01-01

Exposure to ultraviolet-B (UV-B) irradiation causes skin barrier defects. Based on earlier findings that milk phospholipids containing high amounts of sphingomyelin (SM) improved the water content of the stratum corneum (SC) in normal mice, here we investigated the effects of dietary milk SM on skin barrier defects induced by a single dose of UV-B irradiation in hairless mice. Nine week old hairless mice were orally administrated SM (146 mg/kg BW/day) for a total of ten days. After seven days of SM administration, the dorsal skin was exposed to a single dose of UV-B (20 mJ/cm2). Administration of SM significantly suppressed an increase in transepidermal water loss and a decrease in SC water content induced by UV-B irradiation. SM supplementation significantly maintained covalently-bound ω-hydroxy ceramide levels and down-regulated mRNA levels of acute inflammation-associated genes, including thymic stromal lymphopoietin, interleukin-1 beta, and interleukin-6. Furthermore, significantly higher levels of loricrin and transglutaminase-3 mRNA were observed in the SM group. Our study shows for the first time that dietary SM modulates epidermal structures, and can help prevent disruption of skin barrier function after UV-B irradiation.

[CONE BEAM COMPUTED TOMOGRAPHY IN DIAGNOSTICS OF ODONTOGENIC MAXILLARY SINUSITIS (CASE REPORTS)].

PubMed

Demidova, E; Khurdzidze, G

2017-06-01

Diagnostic studies performed by cone beam computed tomography Morita 3D made possible to obtain high resolution images of hard tissues of upper jawbone and maxillary sinus, to detect bony tissue defects, such as odontogenic cysts, cystogranulomas and granulomas. High-resolution and three dimensional tomographic image reconstructions allowed for optimal and prompt determination of the scope of surgical treatment and planning of effective conservative treatment regimen. Interactive diagnostics helped to estimate cosmetic and functional results of surgical treatment, to prevent the occurrence of surgical complications, and to evaluate the efficacy of conservative treatment. The obtained data contributed to determination of particular applications of cone beam computed tomography in the diagnosis of odontogenic maxillary sinusitis, detection of specific defects with cone beam tomography as the most informative method of diagnosis; as well as to determination of weak and strong sides, and helped to offer mechanisms of x-ray diagnostics to dental surgeons and ENT specialists.

Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency

PubMed Central

Shen, Siming; Sandoval, Juan; Swiss, Victoria A; Li, Jiadong; Dupree, Jeff; Franklin, Robin J M; Casaccia-Bonnefil, Patrizia

2009-01-01

The efficiency of remyelination decreases with age, but the molecular mechanisms responsible for this decline remain only partially understood. In this study, we show that remyelination is regulated by age-dependent epigenetic control of gene expression. In demyelinated young brains, new myelin synthesis is preceded by downregulation of oligodendrocyte differentiation inhibitors and neural stem cell markers, and this is associated with recruitment of histone deacetylases (HDACs) to promoter regions. In demyelinated old brains, HDAC recruitment is inefficient, and this allows the accumulation of transcriptional inhibitors and prevents the subsequent surge in myelin gene expression. Defective remyelination can be recapitulated in vivo in mice receiving systemic administration of pharmacological HDAC inhibitors during cuprizone treatment and is consistent with in vitro results showing defective differentiation of oligodendrocyte progenitors after silencing specific HDAC isoforms. Thus, we suggest that inefficient epigenetic modulation of the oligodendrocyte differentiation program contributes to the age-dependent decline in remyelination efficiency. PMID:19160500

Social networking between cells of the foetal skeleton: the importance of thyroid hormones.

PubMed

Farquharson, Colin

2011-08-01

In this issue of Journal of Endocrinology, Lanham et al. investigated the effects of hypothyroidism on the developing skeleton of the ovine foetus in utero. Their analyses indicated that, following thyroidectomy, bone growth, structure and mechanical properties were all altered at late gestation or at term. Adrenalectomy, whilst preventing the prepartum rise in triiodothyronine, did not modify skeletal development. The hypothyroid-mediated skeletal defects of the developing foetus described in this study may have clinical implications for bone health in later life.

Superiority of Graphene over Polymer Coatings for Prevention of Microbially Induced Corrosion

NASA Astrophysics Data System (ADS)

Krishnamurthy, Ajay; Gadhamshetty, Venkataramana; Mukherjee, Rahul; Natarajan, Bharath; Eksik, Osman; Ali Shojaee, S.; Lucca, Don A.; Ren, Wencai; Cheng, Hui-Ming; Koratkar, Nikhil

2015-09-01

Prevention of microbially induced corrosion (MIC) is of great significance in many environmental applications. Here, we report the use of an ultra-thin, graphene skin (Gr) as a superior anti-MIC coating over two commercial polymeric coatings, Parylene-C (PA) and Polyurethane (PU). We find that Nickel (Ni) dissolution in a corrosion cell with Gr-coated Ni is an order of magnitude lower than that of PA and PU coated electrodes. Electrochemical analysis reveals that the Gr coating offers ~10 and ~100 fold improvement in MIC resistance over PU and PA coatings respectively. This finding is remarkable considering that the Gr coating (1-2 nm) is ~25 and ~4000 times thinner than the PA (40-50 nm), and PU coatings (20-80 μm), respectively. Conventional polymer coatings are either non-conformal when deposited or degrade under the action of microbial processes, while the electro-chemically inert graphene coating is both resistant to microbial attack and is extremely conformal and defect-free. Finally, we provide a brief discussion regarding the effectiveness of as-grown vs. transferred graphene films for anti-MIC applications. While the as-grown graphene films are devoid of major defects, wet transfer of graphene is shown to introduce large scale defects that make it less suitable for the current application.

Reconstruction of Heel With Propeller Flap in Postfasciotomy and Popliteal Artery Revascularization State.

PubMed

Kang, Jin Seok; Choi, Hwan Jun; Tak, Min Sung

2016-06-01

Free flaps are still the gold standard for large defects of the lower limb, but propeller perforator flaps have become a simpler and faster alternative to free flaps because of some advantages such as reliable vascular pedicle, wide mobilization and rotation, great freedom in design, low donor site morbidity, and easy harvest with no requirement for anastomosis. But when the vessels show insufficient findings in preoperative evaluation using a Doppler probe or the vessel is injured, the surgeon should avoid performing free flap surgery to prevent flap failure and should select a propeller perforator flap as an alternative method on the condition that more than one perforator is intact. In this study, we report reconstruction of soft tissue defects of the heel with a pedicled propeller flap in postfasciotomy and popliteal artery revascularization state by making an incision on the central portion above the Achilles tendon, which can be covered by the posterior tibial artery perforator or the peroneal artery perforator based flaps. In conclusion, we showed that although the popliteal artery was injured, the soft tissue defect can be reconstructed using a perforator propeller flap if intact distal flow in the anastomosis site was confirmed. © The Author(s) 2015.

Epidemiology of neural tube defects in Saudi Arabia.

PubMed

AlShail, Essam; De Vol, Edward; Yassen, Ahsan; Elgamal, Essam A

2014-12-01

To evaluate the distribution and pattern of neural tube defects in Saudi Arabia by creating a hospital based registry. All cases registered in the King Faisal Specialist Hospital and Research Center (KFSH&RC) neural tube defect (NTD) registry since it was established in October 2000 until December 2012 were studied through active surveillance comprising a registrar who collects NTD information by reviewing the patient's medical records, and interviewing patient's families. The total number of patients registered from October 2000 to December 2012 was 718 patients. There were more females (417, 58%) than males (301, 42%). Of 620 mothers who underwent antenatal ultrasonography; 392 (63%) were diagnosed at birth, and 204 (33%) were diagnosed with antenatal hydrocephalus. In our registry sample, most mothers (95%) did not take folic acid 3 months prior to pregnancy, and 76% did not take folic acid during the 3 months after conception with the affected child. Only 5% received folic acid prior to conception. The KFSH&RC-NTD registry has met its objectives as a source of data that may significantly contribute to the prevention of NTDs, and improving quality of care for NTD patients through active publication of registry findings and management approaches.

SHINING A LIGHT ON XERODERMA PIGMENTOSUM

PubMed Central

DiGiovanna, John J.; Kraemer, Kenneth H.

2012-01-01

Xeroderma pigmentosum (XP) is a rare, autosomal recessive disorder of DNA repair characterized by sun sensitivity and ultraviolet (UV) induced skin and mucous membrane cancers. Described in 1874 by Moriz Kaposi in Vienna, nearly 100 years later James Cleaver in San Francisco reported defective DNA repair in XP cells. This eventually provided the basis for a mechanistic link between sun exposure, DNA damage, somatic mutations and skin cancer. XP cells were found to have defects in 7 of the proteins of the nucleotide excision repair pathway and in DNA polymerase eta. XP cells are hypersensitive to killing by UV and XP cancers have characteristic “UV signature” mutations. Clinical studies at NIH found a nearly 10,000-fold increase in skin cancer in XP patients under age 20 years demonstrating the substantial importance of DNA repair in cancer prevention in the general population. About 25 % of XP patients have progressive neurological degeneration with progressive loss of neurons, probably from DNA damage induced by oxidative metabolism which kills non-dividing cells in the nervous system. Interestingly, patients with another disorder, trichothiodystrophy have defects in some of the same genes as XP but they have primary developmental abnormalities without an increase in skin cancer. PMID:22217736

Impact of Co-Occurring Birth Defects on the Timing of Newborn Hearing Screening and Diagnosis

PubMed Central

Chapman, Derek A.; Stampfel, Caroline C.; Bodurtha, Joann N.; Dodson, Kelley M.; Pandya, Arti; Lynch, Kathleen B.; Kirby, Russell S.

2016-01-01

Purpose Early detection of hearing loss in all newborns and timely intervention are critical to children's cognitive, verbal, behavioral, and social development. The initiation of appropriate early intervention services before 6 months of age can prevent or reduce negative developmental consequences. The purpose of this study was to assess, using large, population-based registries, the effect of co-occurring birth defects (CBDs) on the timing and overall rate of hearing screening and diagnosis. Method The authors linked statewide data from newborn hearing screenings, a birth defects registry, and birth certificates to assess the timeliness of newborn hearing screening and diagnosis of hearing loss (HL) for infants with and without CBDs in 485 children with confirmed HL. Results Nearly one third (31.5%) of children with HL had 1 or more CBDs. The presence of CBDs prolonged the time of the initial infant hearing screening, which contributed to further delays in the subsequent diagnosis of HL. Conclusions Better coordination of HL assessment into treatment plans for children with CBDs may enable earlier diagnosis of HL and provide opportunities for intervention that will affect long-term developmental outcomes for these children. PMID:21940980

[Clinical research progress of mesenteric internal hernia after Roux-en-Y reconstruction].

PubMed

Xu, Zhengrong; Guo, Wenjun

2017-03-25

Postoperative internal hernia is a rare clinical complication which often occurs after digestive tract reconstruction. Roux-en-Y anastomosis is a common type of digestive tract reconstruction. Internal hernia after Roux-en-Y reconstruction, which occurs mainly in the mesenteric defect caused by incomplete closure of mesenteric gaps in the process of digestive tract reconstruction, is systematically called, in our research, as mesenteric internal hernia after Roux-en-Y reconstruction. Such internal hernia can be divided, according to the different structures of mesentric defect, into 3 types: the type of mesenteric defect at the jejunojejunostomy (J type), the type of Petersen's defect (P type), and the type of mesenteric defect in the transverse mesocolon (M type). Because of huge differences in the number of cases and follow-up time among existing research reports, the morbidity of internal hernia after LRYGB fluctuates wildly between 0.2% and 9.0%. Delayed diagnosis and treatment of mesenteric internal hernia after Roux- en-Y reconstruction may result in disastrous consequences such as intestinal necrosis. Clinical manifestations of internal hernia vary from person to person: some, in mild cases, may have no symptoms at all while others in severe cases may experience acute intestinal obstruction. Despite the difference, one common manifestation of internal hernia is abdominal pain. Surgical treatment should be recommended for those diagnosed as internal hernia. A safer and more feasible way to conduct the manual reduction of the incarcerated hernia is to start from the distal normal empty bowel and trace back to the hernia ring mouth, enabling a faster identification of hernia ring and its track. The prevention of mesenteric internal hernia after Roux-en-Y reconstruction is related to the initial surgical approach and the technique of mesenteric closure. Significant controversy remains on whether or not the mesenteric defect should be closed in laparoscopic Roux-en-Y anastomosis. This article is to review the reports and researches on internal hernia resulting from the mesenteric defect after Roux-en-Y digestive tract reconstruction in recent years, so as to promote understanding and attention on this disease. And more active preventive measures are strongly suggested to be taken in operations where digestive tract reconstruction is involved.

Imaging of the Unstable Shoulder

PubMed Central

Baudi, Paolo; Rebuzzi, Manuela; Matino, Giovanni; Catani, Fabio

2017-01-01

Background: Unstable shoulder can occur in different clinical scenarios with a broad spectrum of symptoms and presentations: first-time (or recurrent) traumatic acute shoulder anterior dislocation or chronic anterior instability after repeated dislocations. Imaging in unstable shoulder is fundamental for choosing the right treatment preventing recurrence. The goal of imaging depends on clinical scenario and patient characteristics. Method: Careful selection and evaluation of the imaging procedures is therefore essential to identify, characterize and quantify the lesions. Proper imaging in unstable shoulder cases is critical to the choice of treatment to prevent recurrence, and to plan surgical intervention. Results: In acute setting, radiographs have to roughly detect and characterize the bone defects present. At about 7 days, it is recommended to perform a MR to demonstrate lesions to labrum and/or ligaments and bone defects: in acute setting, the MRA is not necessary, because of effusion and hemarthrosis that behave as the contrast medium. In recurrence, it is fundamental not only to detect lesions but characterize them for planning the treatment. The first study to do is the MRI (with a magnetic field of at least 1.5 Tesla), and if possible MRA, above all in younger patients. Then, on the basis of the pathologic findings as bipolar lesion or severity of bone defects, CT can be performed. PICO method on 2D or 3D CT is helpful if you need to study a glenoid bone loss, with the “en face view” of glenoid, while a 3D CT reconstruction with the humeral head “en face view” is the gold standard to assess an Hill-Sachs lesion. Conclusion: The clinical diagnoses of anterior shoulder instability can be different and acknowledgement of imaging findings is essential to guide the treatment choice. Imaging features are quite different in chronic than in acute scenario. This requires appropriate indications of many different imaging techniques. PMID:29114335

Integral ceramic superstructure evaluation using time domain optical coherence tomography

NASA Astrophysics Data System (ADS)

Sinescu, Cosmin; Bradu, Adrian; Topala, Florin I.; Negrutiu, Meda Lavinia; Duma, Virgil-Florin; Podoleanu, Adrian G.

2014-02-01

Optical Coherence Tomography (OCT) is a non-invasive low coherence interferometry technique that includes several technologies (and the corresponding devices and components), such as illumination and detection, interferometry, scanning, adaptive optics, microscopy and endoscopy. From its large area of applications, we consider in this paper a critical aspect in dentistry - to be investigated with a Time Domain (TD) OCT system. The clinical situation of an edentulous mandible is considered; it can be solved by inserting 2 to 6 implants. On these implants a mesostructure will be manufactured and on it a superstructure is needed. This superstructure can be integral ceramic; in this case materials defects could be trapped inside the ceramic layers and those defects could lead to fractures of the entire superstructure. In this paper we demonstrate that a TD-OCT imaging system has the potential to properly evaluate the presence of the defects inside the ceramic layers and those defects can be fixed before inserting the prosthesis inside the oral cavity. Three integral ceramic superstructures were developed by using a CAD/CAM technology. After the milling, the ceramic layers were applied on the core. All the three samples were evaluated by a TD-OCT system working at 1300 nm. For two of the superstructures evaluated, no defects were found in the most stressed areas. The third superstructure presented four ceramic defects in the mentioned areas. Because of those defects the superstructure may fracture. The integral ceramic prosthesis was send back to the dental laboratory to fix the problems related to the material defects found. Thus, TD-OCT proved to be a valuable method for diagnosing the ceramic defects inside the integral ceramic superstructures in order to prevent fractures at this level.

Active infrared thermal imaging technology to detect the corrosion defects in aircraft cargo door

NASA Astrophysics Data System (ADS)

Chen, Dapeng; Zhang, Cunlin; Zeng, Zhi; Xing, Chunfei; Li, Yanhong

2009-11-01

Aircraft fuselage material corrosion problems have been major aviation security issues, which hinder the development of aviation industry. How can we use non-destructive testing methods to detect the internal corrosion defects from the outside of the fuselage, to find the hidden safety problems in advance and update the defective equipment and materials, has great significance for the prevention of accidents. Nowadays, the active infrared thermal imaging technology as a new nondestructive technology has been gradually used on a wide variety of materials, such as composite, metal and so on. This article makes use of this technology on an aircraft cargo door specimen to detect the corrosion defects. Firstly, use High-energy flash pulse to excite the specimen, and use the thermal image processing software to splice the thermal images, so the thermal images of the overall specimen can be showed. Then, heat the defects by ultrasonic excitation, this will cause vibration and friction or thermoelastic effects in the places of defects, so the ultrasonic energy will dissipate into heat and manifested in the uneven temperature of surface. An Infrared camera to capture the changes of temperature of material surface, send data to the computer and records the thermal information of the defects. Finally, extracting data and drawing infrared radiation-time curve of some selected points of interest to analyze the signal changes in heat of defects further more. The results of the experiments show that both of the two ways of heat excitation show a clear position and shape of defects, and the ultrasonic method has more obvious effect of excitation to the defects, and a higher signal to noise ratio than the flash pulse excitation, but flash pulse method do not contact the specimen in the process of excitation, and shows the location and shape of defects in the overall of the specimen has its advantages.

Facts about Gastroschisis

MedlinePlus

... 2013 Aug; 122 (2 Pt 1):275-81. Jones AM, Isenburg J, Salemi JL, et al.; for the National Birth Defects Prevention Network. Increasing prevalence of gastroschisis—14 States, 1995-2012. MMWR morb Mortal Wkly Rep. 2016 Jan 22;65(2):23-6. Bird TM, ...

How Many People Are Affected By or Are at Risk for Neural Tube Defects?

MedlinePlus

... of the Scientific Director (OSD) Affinity Groups & Labs (AG&L) Scientists Emeriti National Center for Medical Rehabilitation ... for Disease Control and Prevention. (2011). Spina bifida: Data and statistics. Retrieved May 19, 2012, from http:// ...

Betaine supplementation reduces congenital defects after prenatal alcohol exposure (Conference Presentation)

NASA Astrophysics Data System (ADS)

Karunamuni, Ganga; Gu, Shi; Doughman, Yong Qiu; Sheehan, Megan M.; Ma, Pei; Peterson, Lindsy M.; Linask, Kersti K.; Jenkins, Michael W.; Rollins, Andrew M.; Watanabe, Michiko

2016-03-01

Over 500,000 women per year in the United States drink during pregnancy, and 1 in 5 of this population also binge drink. As high as 20-50% of live-born children with prenatal alcohol exposure (PAE) present with congenital heart defects including outflow and valvuloseptal anomalies that can be life-threatening. Previously we established a model of PAE (modeling a single binge drinking episode) in the avian embryo and used optical coherence tomography (OCT) imaging to assay early-stage cardiac function/structure and late-stage cardiac defects. At early stages, alcohol/ethanol-exposed embryos had smaller cardiac cushions and increased retrograde flow. At late stages, they presented with gross morphological defects in the head and chest wall, and also exhibited smaller or abnormal atrio-ventricular (AV) valves, thinner interventricular septae (IVS), and smaller vessel diameters for the aortic trunk branches. In other animal models, the methyl donor betaine (found naturally in many foods such as wheat bran, quinoa, beets and spinach) ameliorates neurobehavioral deficits associated with PAE but the effects on heart structure are unknown. In our model of PAE, betaine supplementation led to a reduction in gross structural defects and appeared to protect against certain types of cardiac defects such as ventricular septal defects and abnormal AV valvular morphology. Furthermore, vessel diameters, IVS thicknesses and mural AV leaflet volumes were normalized while the septal AV leaflet volume was increased. These findings highlight the importance of betaine and potentially methylation levels in the prevention of PAE-related birth defects which could have significant implications for public health.

Light-activation of the Archaerhodopsin H+-pump reverses age-dependent loss of vertebrate regeneration: sparking system-level controls in vivo

PubMed Central

Adams, Dany Spencer; Tseng, Ai-Sun; Levin, Michael

2013-01-01

Summary Optogenetics, the regulation of proteins by light, has revolutionized the study of excitable cells, and generated strong interest in the therapeutic potential of this technology for regulating action potentials in neural and muscle cells. However, it is currently unknown whether light-activated channels and pumps will allow control of resting potential in embryonic or regenerating cells in vivo. Abnormalities in ion currents of non-excitable cells are known to play key roles in the etiology of birth defects and cancer. Moreover, changes in transmembrane resting potential initiate Xenopus tadpole tail regeneration, including regrowth of a functioning spinal cord, in tails that have been inhibited by natural inactivity of the endogenous H+-V-ATPase pump. However, existing pharmacological and genetic methods allow neither non-invasive control of bioelectric parameters in vivo nor the ability to abrogate signaling at defined time points. Here, we show that light activation of a H+-pump can prevent developmental defects and induce regeneration by hyperpolarizing transmembrane potentials. Specifically, light-dependent, Archaerhodopsin-based, H+-flux hyperpolarized cells in vivo and thus rescued Xenopus embryos from the craniofacial and patterning abnormalities caused by molecular blockade of endogenous H+-flux. Furthermore, light stimulation of Arch for only 2 days after amputation restored regenerative capacity to inhibited tails, inducing cell proliferation, tissue innervation, and upregulation of notch1 and msx1, essential genes in two well-known endogenous regenerative pathways. Electroneutral pH change, induced by expression of the sodium proton exchanger, NHE3, did not rescue regeneration, implicating the hyperpolarizing activity of Archaerhodopsin as the causal factor. The data reveal that hyperpolarization is required only during the first 48 hours post-injury, and that expression in the spinal cord is not necessary for the effect to occur. Our study shows that complex, coordinated sets of stable bioelectric events that alter body patterning—prevention of birth defects and induction of regeneration—can be elicited by the temporal modulation of a single ion current. Furthermore, as optogenetic reagents can be used to achieve that manipulation, the potential for this technology to impact clinical approaches for preventive, therapeutic, and regenerative medicine is extraordinary. We expect this first critical step will lead to an unprecedented expansion of optogenetics in biomedical research and in the probing of novel and fundamental biophysical determinants of growth and form. PMID:23519324

Internal Hernia Following Laparoscopic Roux-en-Y Gastric Bypass: Prevention and Tips for Intra-operative Management.

PubMed

Nimeri, Abdelrahman A; Maasher, Ahmed; Al Shaban, Talat; Salim, Elnazeer; Gamaleldin, Maysoon M

2016-09-01

Laparoscopic Roux-en-Y gastric bypass (LRYGB) is considered the golden standard for bariatric surgery. However, the potential risk for internal hernia after LRYGB remains a significant concern to both patients and surgeons. In addition, patients presenting with abdominal pain after LRYGB warrant careful attention to avoid missing or delaying the diagnosis of internal hernia. The aim of this study was to describe our technique to prevent internal hernia after LRYGB, intra-operative findings, and our management strategies for patients with internal hernia after LRYGB. In this video, we review different technical tips and tricks to explore patients with suspected internal hernia after RYGB, how to reduce obstructed small bowel, and effectively close mesenteric defects to prevent internal hernia after LRYGB. A high index of suspicion and evaluation of the CT scan of the patient by an experienced bariatric surgeon is essential to avoid missing cases of internal hernia after LRYGB. In addition, patients presenting with incarcerated small bowel due to an internal hernia are best managed by standing on the left side of the patient with the left arm tucked and starting at the ileocecal valve and running the small bowel backwards towards the ligament of Treitz. Furthermore, patients with bowel obstruction due to internal hernia may need to have a gastrostomy placed at the remnant of the stomach. Recurrent abdominal pain is not uncommon after LRYGB. Systematic closure of mesenteric defects, the use of diagnostic laparoscopy, and high index of suspicion are all necessary to avoid delay in diagnosis.

Self-expanding platinum-coated nitinol devices for transcatheter closure of atrial septal defect: prevention of nickel release.

PubMed

Lertsapcharoen, Pornthep; Khongphatthanayothin, Apichai; Srimahachota, Suphot; Leelanukrom, Ruenreong

2008-06-01

A variety of nitinol-containing devices for transcatheter closure of atrial septal defects (ASD) has been widely used. However, there is concern about the release of nickel after nitinol device implantation. In this study, a platinum-coated nitinol device was braided from nanoplatinum-coated nitinol wires in order to prevent nickel release. The serum nickel levels before and after device implantation and the 1-year results were evaluated. Thirty-one patients, aged 4-59 years, and weighing 13.7-90.0 kg, underwent transcatheter closure. Blood samples for serum nickel levels were taken before, 1 day, 1 week, 1 month and 3 months after implantation. Twenty-nine (93.6%) patients had a successful implantation. The mean ASD diameter was 19.7 +/- 4.8 mm (range 10-30 mm). Procedure-related complications included transient brachial plexus injury in 1 patient and transient dysrhythmia in 4 patients. All 29 patients had complete closure within 1 month after implantation. The mean serum nickel levels at baseline and at 1 day, 1 week, 1 month and 3 months after implantation were 0.65 +/- 0.28, 0.63 +/- 0.18, 0.67 +/- 0.34, 0.55 +/- 0.16, 0.52 +/- 0.14 ng/ml, respectively. There was no significant difference in serum nickel levels before and after implantation. There were no device-related complications at 1-year follow up. Transcatheter ASD closure using a platinum-coated nitinol device can be performed safely and successfully with good outcomes. Nano-coating of platinum on nitinol wires can prevent nickel release following device implantation.

Distribution of Argon Arc Contaminated with Nitrogen as Function of Frequency in Pulsed TIG Welding

NASA Astrophysics Data System (ADS)

Takahashi, Hiroki; Tanaka, Tatsuro; Yamamoto, Shinji; Iwao, Toru

2016-09-01

TIG arc welding is the high-quality and much applicable material joining technology. However, the current has to be small because the cathode melting should be prevented. In this case, the heat input to the welding pool becomes low, then, the welding defect sometimes occurs. The pulsed TIG arc welding is used to improve this disadvantage This welding can be controlled by some current parameters such as frequency However, few report has reported the distribution of argon arc contaminated with nitrogen It is important to prevent the contamination of nitrogen because the melting depth increases in order to prevent the welding defects. In this paper, the distribution of argon arc contaminated as function of frequency with nitrogen in pulsed TIG welding is elucidated. The nitrogen concentration, the radial flow velocity, the arc temperature were calculated using the EMTF simulation when the time reached at the base current. As a result, the nitrogen concentration into the arc became low with increasing the frequency The diffusion coefficient decreased because of the decrement of temperature over 4000 K. In this case, the nitrogen concentration became low near the anode. Therefore, the nitrogen concentration became low because the frequency is high.

Studying heat-affected zone deformations of electric arc welding

NASA Astrophysics Data System (ADS)

Suleimanov, R. I.; Zainagalina, L. Z.; Khabibullin, M. Ya; Zaripova, L. M.; Kovalev, N. O.

2018-03-01

The paper studies the influence of the most common defects in permanent electric arc welds made during the welding butt joints in infield oil pipelines, onto the strength characteristics of the welded pipe material around the heat-affected zone. A specimen of a butt weld with an obvious defect was used as a subject of the study. The changes in the geometric parameters of the weld were measured with the standard means; Rockwell hardness in the heat-affected zone was determined in certain areas with justification for the weld process modes. The cause of softening was found to be an increased width of the hot spot on the one side of the weld, where an enlarged crystalline structure appears as a result of the pipe material recrystallization under the influence of heat. Changes in the geometry of the thermal action area are determined by accumulation of molten filler on the one side of the weld when the welding rate is decreased. Some recommendations are given to prevent destruction of the welded structures and appearance of emergencies in infield oil pipelines.

Biomechanical testing of a polymer-based biomaterial for the restoration of spinal stability after nucleotomy

PubMed Central

Hegewald, Aldemar A; Knecht, Sven; Baumgartner, Daniel; Gerber, Hans; Endres, Michaela; Kaps, Christian; Stüssi, Edgar; Thomé, Claudius

2009-01-01

Background Surgery for disc herniations can be complicated by two major problems: painful degeneration of the spinal segment and re-herniation. Therefore, we examined an absorbable poly-glycolic acid (PGA) biomaterial, which was lyophilized with hyaluronic acid (HA), for its utility to (a) re-establish spinal stability and to (b) seal annulus fibrosus defects. The biomechanical properties range of motion (ROM), neutral zone (NZ) and a potential annulus sealing capacity were investigated. Methods Seven bovine, lumbar spinal units were tested in vitro for ROM and NZ in three consecutive stages: (a) intact, (b) following nucleotomy and (c) after insertion of a PGA/HA nucleus-implant. For biomechanical testing, spinal units were mounted on a loading-simulator for spines. In three cycles, axial loading was applied in an excentric mode with 0.5 Nm steps until an applied moment of ± 7.5 Nm was achieved in flexion/extension. ROM and NZ were assessed. These tests were performed without and with annulus sealing by sewing a PGA/HA annulus-implant into the annulus defect. Results Spinal stability was significantly impaired after nucleotomy (p < 0.001). Intradiscal implantation of a PGA-HA nucleus-implant, however, restored spinal stability (p < 0.003). There was no statistical difference between the stability provided by the nucleus-implant and the intact stage regarding flexion/extension movements (p = 0.209). During the testing sequences, herniation of biomaterial through the annulus defect into the spinal canal regularly occurred, resulting in compression of neural elements. Sewing a PGA/HA annulus-implant into the annulus defect, however, effectively prevented herniation. Conclusion PGA/HA biomaterial seems to be well suited for cell-free and cell-based regenerative treatment strategies in spinal surgery. Its abilities to restore spinal stability and potentially close annulus defects open up new vistas for regenerative approaches to treat intervertebral disc degeneration and for preventing implant herniation. PMID:19604373

Enzyme Replacement Therapy Prevents Dental Defects in a Model of Hypophosphatasia

PubMed Central

McKee, M.D.; Nakano, Y.; Masica, D.L.; Gray, J.J.; Lemire, I.; Heft, R.; Whyte, M.P.; Crine, P.; Millán, J.L.

2011-01-01

Hypophosphatasia (HPP) occurs from loss-of-function mutation in the tissue-non-specific alkaline phosphatase (TNALP) gene, resulting in extracellular pyrophosphate accumulation that inhibits skeletal and dental mineralization. TNALP-null mice (Akp2-/-) phenocopy human infantile hypophosphatasia; they develop rickets at 1 week of age, and die before being weaned, having severe skeletal and dental hypomineralization and episodes of apnea and vitamin B6-responsive seizures. Delay and defects in dentin mineralization, together with a deficiency in acellular cementum, are characteristic. We report the prevention of these dental abnormalities in Akp2-/- mice receiving treatment from birth with daily injections of a mineral-targeting, human TNALP (sALP-FcD10). sALP-FcD10 prevented hypomineralization of alveolar bone, dentin, and cementum as assessed by micro-computed tomography and histology. Osteopontin – a marker of acellular cementum – was immuno-localized along root surfaces, confirming that acellular cementum, typically missing or reduced in Akp2-/- mice, formed normally. Our findings provide insight concerning how acellular cementum is formed on tooth surfaces to effect periodontal ligament attachment to retain teeth in their osseous alveolar sockets. Furthermore, they provide evidence that this enzyme-replacement therapy, applied early in post-natal life – where the majority of tooth root development occurs, including acellular cementum formation – could prevent the accelerated tooth loss seen in individuals with HPP. PMID:21212313

Enzyme replacement therapy prevents dental defects in a model of hypophosphatasia.

PubMed

McKee, M D; Nakano, Y; Masica, D L; Gray, J J; Lemire, I; Heft, R; Whyte, M P; Crine, P; Millán, J L

2011-04-01

Hypophosphatasia (HPP) occurs from loss-of-function mutation in the tissue-non-specific alkaline phosphatase (TNALP) gene, resulting in extracellular pyrophosphate accumulation that inhibits skeletal and dental mineralization. TNALP-null mice (Akp2(-/-)) phenocopy human infantile hypophosphatasia; they develop rickets at 1 week of age, and die before being weaned, having severe skeletal and dental hypomineralization and episodes of apnea and vitamin B(6)-responsive seizures. Delay and defects in dentin mineralization, together with a deficiency in acellular cementum, are characteristic. We report the prevention of these dental abnormalities in Akp2(-/-) mice receiving treatment from birth with daily injections of a mineral-targeting, human TNALP (sALP-FcD(10)). sALP-FcD(10) prevented hypomineralization of alveolar bone, dentin, and cementum as assessed by micro-computed tomography and histology. Osteopontin--a marker of acellular cementum--was immuno-localized along root surfaces, confirming that acellular cementum, typically missing or reduced in Akp2(-/-) mice, formed normally. Our findings provide insight concerning how acellular cementum is formed on tooth surfaces to effect periodontal ligament attachment to retain teeth in their osseous alveolar sockets. Furthermore, they provide evidence that this enzyme-replacement therapy, applied early in post-natal life--where the majority of tooth root development occurs, including acellular cementum formation--could prevent the accelerated tooth loss seen in individuals with HPP.

Design and Analysis of a Triple Stop-band Filter Using Ratioed Periodical Defected Microstrip Structure

NASA Astrophysics Data System (ADS)

Jiang, Tao; Wang, Yanyan; Li, Yingsong

2017-07-01

In this paper, a triple stop-band filter with a ratioed periodical defected microstrip structure is proposed for wireless communication applications. The proposed ratioed periodical defected microstrip structures are spiral slots, which are embedded into a 50 Ω microstrip line to obtain multiple stop-bands. The performance of the proposed triple stop-band filter is investigated numerically and experimentally. Moreover, the equivalent circuit model of the proposed filter is also established and discussed. The results are given to verify that the proposed triple stop-band filter has three stop bands at 3.3 GHz, 5.2 GHz, 6.8 GHz to reject the unwanted signals, which is promising for integrating into UWB communication systems to efficiently prevent the potential interferences from unexpected narrowband signals such as WiMAX, WLAN and RFID communication systems.

Skin signs of primary immunodeficiencies: how to find the genes to check.

PubMed

Ettinger, M; Schreml, J; Wirsching, K; Berneburg, M; Schreml, S

2018-02-01

Primary immunodeficiencies (PIDs) are a heterogeneous group of rare diseases that result from defects in immune system development and/or function. The clinical manifestations of PIDs are highly variable, but most disorders involve at least an increased susceptibility to infection. Furthermore, cutaneous manifestations are very common in PIDs. As an easily accessible organ, the skin can be crucial for early diagnosis and treatment. This is relevant for preventing significant disease-associated morbidity and mortality. We provide a table that enables the reader to find the possible diseases and corresponding gene defects based on the skin manifestations of the suspected PIDs. To our knowledge, this is the first review that allows the reader to find relevant PIDs and the respective gene defects through solitary or combined skin signs. © 2017 British Association of Dermatologists.

Radiation damage in cubic ZrO 2 and yttria-stabilized zirconia from molecular dynamics simulations

DOE PAGES

Aidhy, Dilpuneet S.; Zhang, Yanwen; Weber, William J.

2014-11-20

Here, we perform molecular dynamics simulation on cubic ZrO 2 and yttria-stabilized zirconia (YSZ) to elucidate defect cluster formation resulting from radiation damage, and evaluate the impact of Y-dopants. Interstitial clusters composed of split-interstitial building blocks, i.e., Zr-Zr or Y-Zr are formed. Moreover, oxygen vacancies control cation defect migration; in their presence, Zr interstitials aggregate to form split-interstitials whereas in their absence Zr interstitials remain immobile, as isolated single-interstitials. Y-doping prevents interstitial cluster formation due to sequestration of oxygen vacancies.

Trends in liability affecting technical writers

NASA Technical Reports Server (NTRS)

Driskill, L. P.

1981-01-01

Liability of technical writers for defective products is explored. Documents generated during a product's life cycle (including design memos, design tests, clinical trials, trial use reports, letters, and proposals) become relevant because they are likely to become the only available means of showing that the product was not defectively designed. These documents become the evidence that the product underwent balanced and well considered planning, development, testing, quality control, and field testing. The predicted increased involvement of technical writers in the prevention and defense of product liability claims is cited in view of a greater number of cases turning on "failure to warn".

Birth Defects Prevention, Risk Reduction, and Awareness Act of 2010

THOMAS, 111th Congress

Rep. DeLauro, Rosa L. [D-CT-3

2010-05-28

Senate - 11/15/2010 Received in the Senate and Read twice and referred to the Committee on Health, Education, Labor, and Pensions. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

Analysis of minimum rail size in heavy axle load environment

DOT National Transportation Integrated Search

2013-04-15

The effects of increasing axle loads on rail integrity are examined in this paper. In the present context, rail integrity refers to the prevention and control of rail failures. Rail failures usually occur because cracks or defects develop and grow fr...

Prevention of congenital abnormalities by periconceptional multivitamin supplementation.

PubMed Central

Czeizel, A E

1993-01-01

OBJECTIVE--To study the effect of periconceptional multivitamin supplementation on neural tube defects and other congenital abnormality entities. DESIGN--Randomised controlled trial of supplementation with multivitamins and trace elements. SETTING--Hungarian family planning programme. SUBJECTS--4156 pregnancies with known outcome and 3713 infants evaluated in the eighth month of life. INTERVENTIONS--A single tablet of a multivitamin including 0.8 mg of folic acid or trace elements supplement daily for at least one month before conception and at least two months after conception. MAIN OUTCOME MEASURES--Number of major and mild congenital abnormalities. RESULTS--The rate of all major congenital abnormalities was significantly lower in the group given vitamins than in the group given trace elements and this difference cannot be explained totally by the significant reduction of neural tube defects. The rate of major congenital abnormalities other than neural tube defects and genetic syndromes was 9.0/1000 in pregnancies with known outcome in the vitamin group and 16.6/1000 in the trace element group; relative risk 1.85 (95% confidence interval 1.02 to 3.38); difference, 7.6/1000. The rate of all major congenital abnormalities other than neural tube defects and genetic syndromes diagnosed up to the eighth month of life was 14.7/1000 informative pregnancies in the vitamin group and 28.3/1000 in the trace element group; relative risk 1.95 (1.23 to 3.09); difference, 13.6/1000. The rate of some congenital abnormalities was lower in the vitamin group than in the trace element group but the differences for each group of abnormalities were not significant. CONCLUSIONS--Periconceptional multivitamin supplementation can reduce not only the rate of neural tube defects but also the rate of other major non-genetic syndromatic congenital abnormalities. Further studies are needed to differentiate the chance effect and vitamin dependent effect. PMID:8324432

Periodontal Defects in the A116T Knock-in Murine Model of Odontohypophosphatasia.

PubMed

Foster, B L; Sheen, C R; Hatch, N E; Liu, J; Cory, E; Narisawa, S; Kiffer-Moreira, T; Sah, R L; Whyte, M P; Somerman, M J; Millán, J L

2015-05-01

Mutations in ALPL result in hypophosphatasia (HPP), a disease causing defective skeletal mineralization. ALPL encodes tissue nonspecific alkaline phosphatase (ALP), an enzyme that promotes mineralization by reducing inorganic pyrophosphate, a mineralization inhibitor. In addition to skeletal defects, HPP causes dental defects, and a mild clinical form of HPP, odontohypophosphatasia, features only a dental phenotype. The Alpl knockout (Alpl (-/-)) mouse phenocopies severe infantile HPP, including profound skeletal and dental defects. However, the severity of disease in Alpl (-/-) mice prevents analysis at advanced ages, including studies to target rescue of dental tissues. We aimed to generate a knock-in mouse model of odontohypophosphatasia with a primarily dental phenotype, based on a mutation (c.346G>A) identified in a human kindred with autosomal dominant odontohypophosphatasia. Biochemical, skeletal, and dental analyses were performed on the resulting Alpl(+/A116T) mice to validate this model. Alpl(+/A116T) mice featured 50% reduction in plasma ALP activity compared with wild-type controls. No differences in litter size, survival, or body weight were observed in Alpl(+/A116T) versus wild-type mice. The postcranial skeleton of Alpl(+/A116T) mice was normal by radiography, with no differences in femur length, cortical/trabecular structure or mineral density, or mechanical properties. Parietal bone trabecular compartment was mildly altered. Alpl(+/A116T) mice featured alterations in the alveolar bone, including radiolucencies and resorptive lesions, osteoid accumulation on the alveolar bone crest, and significant differences in several bone properties measured by micro-computed tomography. Nonsignificant changes in acellular cementum did not appear to affect periodontal attachment or function, although circulating ALP activity was correlated significantly with incisor cementum thickness. The Alpl(+/A116T) mouse is the first model of odontohypophosphatasia, providing insights on dentoalveolar development and function under reduced ALP, bringing attention to direct effects of HPP on alveolar bone, and offering a new model for testing potential dental-targeted therapies in future studies. © International & American Associations for Dental Research 2015.

Pain associated with the musculoskeletal system in children from Warsaw schools.

PubMed

Słowińska, Iwona; Kwiatkowska, Małgorzata; Jednacz, Ewa; Mańczak, Małgorzata; Rutkowska-Sak, Lidia; Raciborski, Filip

2015-01-01

To assess the prevalence of pain in the musculoskeletal system and possible reasons for these complaints among early age children from Warsaw schools. The study was conducted in 34 randomly selected primary schools in Warsaw in 2011. 2748 survey-questionnaires were given to parents or legal guardians by children. Of these, 1509 surveys were subject to a final analysis. The survey included 66 questions regarding, among other things, pain in the musculoskeletal system in children. Additionally, there were questions about possibly occurring diseases, any postural defects, significant obesity, as well as effects of these complaints on the child's physical activity. Survey data regarded 6-7-year-old children. In the group of 1509 respondents, 242 children (16%) complained about pain in the musculoskeletal system. Pain was located most frequently in the knee joints, and more rarely in the spine and joints in the upper extremities. In the group of children who complained about pain, moderate physical activity was statistically significantly limited. According to parents, physicians did not diagnose any medical conditions in 106 children. Joint disease was diagnosed in 33 children. Postural defects were diagnosed in 589 children. In 123 children complaining about pain at least one postural defect was diagnosed. Such defects were diagnosed statistically significantly more rarely (p = 0.011) in 1234 children who did not complain about pain (460 children). Platypodia or other foot deformation was observed in 25% of these children, spinal curvature in 12%, abnormal knee joint position in 11% and uneven hip position in 2% children. Of note, 17% of all children were significantly overweight. In overweight children the prevalence of pain, especially in the knee joints and feet, was significantly higher. This study aims to underline the problem of musculoskeletal pain in early-age children which limits their physical activity. Also the authors draw attention to the issue of postural defects in a large group of school children. This issue undoubtedly requires more attention and a plan how to create more effective methods of prevention.

Biodegradable and thermosensitive monomethoxy poly(ethylene glycol)-poly(lactic acid) hydrogel as a barrier for prevention of post-operative abdominal adhesion.

PubMed

Fu, Shao Zhi; Li, Zhi; Fan, Jun Ming; Meng, Xiao Hang; Shi, Kun; Qu, Ying; Yang, Ling Lin; Wu, Jing Bo; Fan, Juan; Luot, Feng; Qian, Zhi Yong

2014-03-01

Post-operative peritoneal adhesions are serious consequences of abdominal or pelvic surgery and cause severe bowel obstruction, chronic pelvic pain and infertility. In this study, a novel nano-hydrogel system based on a monomethoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) di-block copolymer was studied for its ability to prevent abdominal adhesion in rats. The MPEG-PLA hydrogel at a concentration of 40% (w/v) was injected and was able to adhere to defect sites at body temperature. The ability of the hydrogel to inhibit adhesion of post-operative tissues was evaluated by utilizing a rat model of abdominal sidewall-cecum abrasion. It was possible to heal wounded tissue through regeneration of neo-peritoneal tissues ten days after surgery. Our data showed that this hydrogel system is equally as effective as current commercialized anti-adhesive products.

Preconceptional motivational interviewing interventions to reduce alcohol-exposed pregnancy risk.

PubMed

Ingersoll, Karen S; Ceperich, Sherry D; Hettema, Jennifer E; Farrell-Carnahan, Leah; Penberthy, J Kim

2013-04-01

Alcohol exposed pregnancy (AEP) is a leading cause of preventable birth defects. While randomized controlled trials (RCTs) have shown that multi-session motivational interviewing-based interventions reduce AEP risk, a one-session intervention could facilitate broader implementation. The purposes of this study were to: (1) test a one-session motivational AEP prevention intervention for community women and (2) compare outcomes to previous RCTs. Participants at risk for AEP (N=217) were randomized to motivational interviewing+assessment feedback (EARLY), informational video, or informational brochure conditions. Outcomes were drinks per drinking day (DDD), ineffective contraception rate, and AEP risk at 3 and 6 months. All interventions were associated with decreased DDD, ineffective contraception rate, and AEP risk. Participants who received EARLY had larger absolute risk reductions in ineffective contraception and AEP risk, but not DDD. Effect sizes were compared to previous RCTs. The one-session EARLY intervention had less powerful effects than multi-session AEP prevention interventions among community women, but may provide a new option in a continuum of preventive care. Copyright © 2013 Elsevier Inc. All rights reserved.

Bayesian multinomial probit modeling of daily windows of ...

EPA Pesticide Factsheets

Past epidemiologic studies suggest maternal ambient air pollution exposure during critical periods of the pregnancy is associated with fetal development. We introduce a multinomial probit model that allows for the joint identification of susceptible daily periods during the pregnancy for 12 individual types of CHDs with respect to maternal PM2.5 exposure. We apply the model to a dataset of mothers from the National Birth Defect Prevention Study where daily PM2.5 exposures from weeks 2-8 of pregnancy are assigned (specific to each location and pregnancy date) using predictions from the downscaler pollution model. Results are compared to an aggregated exposure model which defines exposure as the average value over pregnancy weeks 2-8. Increased PM2.5 exposure during pregnancy days 53 and 50-51 for pulmonary valve stenosis and tetralogy of Fallot, respectively, are associated with an increased probability of development of each CHD. The largest estimated effect is seen for atrioventricular septal defects on pregnancy day 14. The aggregated exposure model fails to identify any significant windows of susceptibility during pregnancy weeks 2-8 for the considered CHDs. Considering daily PM2.5 exposures in a new modeling framework revealed positive associations for defects that the standard aggregated exposure model was unable to identify. Disclaimer: The views expressed in this manuscript are those of the authors and do not necessarily represent the views or policie

Mean Glenoid Defect Size and Location Associated With Anterior Shoulder Instability

PubMed Central

Gottschalk, Lionel J.; Bois, Aaron J.; Shelby, Marcus A.; Miniaci, Anthony; Jones, Morgan H.

2017-01-01

Background: There is a strong correlation between glenoid defect size and recurrent anterior shoulder instability. A better understanding of glenoid defects could lead to improved treatments and outcomes. Purpose: To (1) determine the rate of reporting numeric measurements for glenoid defect size, (2) determine the consistency of glenoid defect size and location reported within the literature, (3) define the typical size and location of glenoid defects, and (4) determine whether a correlation exists between defect size and treatment outcome. Study Design: Systematic review; Level of evidence, 4. Methods: PubMed, Ovid, and Cochrane databases were searched for clinical studies measuring glenoid defect size or location. We excluded studies with defect size requirements or pathology other than anterior instability and studies that included patients with known prior surgery. Our search produced 83 studies; 38 studies provided numeric measurements for glenoid defect size and 2 for defect location. Results: From 1981 to 2000, a total of 5.6% (1 of 18) of the studies reported numeric measurements for glenoid defect size; from 2001 to 2014, the rate of reporting glenoid defects increased to 58.7% (37 of 63). Fourteen studies (n = 1363 shoulders) reported defect size ranges for percentage loss of glenoid width, and 9 studies (n = 570 shoulders) reported defect size ranges for percentage loss of glenoid surface area. According to 2 studies, the mean glenoid defect orientation was pointing toward the 3:01 and 3:20 positions on the glenoid clock face. Conclusion: Since 2001, the rate of reporting numeric measurements for glenoid defect size was only 58.7%. Among studies reporting the percentage loss of glenoid width, 23.6% of shoulders had a defect between 10% and 25%, and among studies reporting the percentage loss of glenoid surface area, 44.7% of shoulders had a defect between 5% and 20%. There is significant variability in the way glenoid bone loss is measured, calculated, and reported. PMID:28203591

Prevention of type 2 Diabetes Mellitus: Potential of pharmacological agents.

PubMed

Samson, Susan L; Garber, Alan J

2016-06-01

People with impaired glucose tolerance or impaired fasting glucose, or "pre-diabetes", are at high risk for progression to type 2 diabetes, as are those with metabolic syndrome or a history of gestational diabetes. Both glucose-lowering and anti-obesity pharmacotherapies have been studied to determine if the onset of type 2 diabetes can be delayed or prevented. Here we review the available data in the field. The most common theme is the reduction in insulin resistance, such as with weight loss, decreasing demands on the beta cell to improve insulin secretion and prolong its function. Overall, therapies which decrease diabetes incidence in high-risk populations delay the onset of diabetes but do not correct the underlying beta cell defect. Copyright © 2016 Elsevier Ltd. All rights reserved.

Elp3 and Dph3 of Schizosaccharomyces pombe mediate cellular stress responses through tRNALysUUU modifications.

PubMed

Villahermosa, Desirée; Fleck, Oliver

2017-08-03

Efficient protein synthesis in eukaryotes requires diphthamide modification of translation elongation factor eEF2 and wobble uridine modifications of tRNAs. In higher eukaryotes, these processes are important for preventing neurological and developmental defects and cancer. In this study, we used Schizosaccharomyces pombe as a model to analyse mutants defective in eEF2 modification (dph1Δ), in tRNA modifications (elp3Δ), or both (dph3Δ) for sensitivity to cytotoxic agents and thermal stress. The dph3Δ and elp3Δ mutants were sensitive to a range of drugs and had growth defects at low temperature. dph3Δ was epistatic with dph1Δ for sensitivity to hydroxyurea and methyl methanesulfonate, and with elp3Δ for methyl methanesulfonate and growth at 16 °C. The dph1Δ and dph3Δ deletions rescued growth defects of elp3Δ in response to thiabendazole and at 37 °C. Elevated tRNA Lys UUU levels suppressed the elp3Δ phenotypes and some of the dph3Δ phenotypes, indicating that lack of tRNA Lys UUU modifications were responsible. Furthermore, we found positive genetic interactions of elp3Δ and dph3Δ with sty1Δ and atf1Δ, indicating that Elp3/Dph3-dependent tRNA modifications are important for efficient biosynthesis of key factors required for accurate responses to cytotoxic stress conditions.

Preconceptional folic acid-containing supplement use in the National Birth Defects Prevention Study.

PubMed

Khodr, Zeina G; Lupo, Philip J; Agopian, A J; Canfield, Mark A; Case, Amy P; Carmichael, Suzan L; Mitchell, Laura E

2014-06-01

Despite public health campaigns encouraging women to take a daily folic acid supplement, the proportion of reproductive age women, in the United States, who comply with this recommendation is less than optimal. The objective of this analysis was to identify predictors of preconceptional folic acid-containing supplement use to define subgroups of women who may benefit from targeted folic acid campaigns. This study included 6570 mothers of live born infants from the control population of National Birth Defects Prevention Study (1997-2005). Logistic regression analyses were used to identify predictors of preconceptional folic acid supplementation. A classification and regression tree (CART) analysis was used to define subgroups of women with different patterns of preconceptional folic acid supplementation. Race/ethnicity, education, age at delivery, nativity, employment, income, number of dependents, smoking, and birth control use were significantly associated with preconceptional folic acid-containing supplement use. Based on a CART analysis, education, race/ethnicity, and age were the most distinguishing factors between women with different preconceptional supplementation patterns. Non-white women with <4 years of a college education were the least likely to use folic acid-containing supplements (11%). However, even in the most compliant subgroup (women with ≥4 years of college), only 60% of women supplemented with folic acid. These results demonstrate the need for continued efforts to increase folic acid supplementation among all reproductive aged women. However, the success of such efforts may be improved if maternal characteristics such as education, race/ethnicity, and age, are considered in the development of future interventions. © 2014 Wiley Periodicals, Inc.

Prevention of Tartrate Crystallization in Wine by Hydrocolloids: The Mechanism Studied by Dynamic Light Scattering.

PubMed

Lankhorst, Peter P; Voogt, Benjamin; Tuinier, Remco; Lefol, Blandine; Pellerin, Patrice; Virone, Cristiana

2017-10-11

Young wines are supersaturated in potassium bitartrate, which induces rather uncontrolled crystallization processes. Delayed crystallization may occur even after bottling of the young wines, which is undesirable because it gives rise to a visual defect in the wine. Colloids such as mannoproteins, metatartaric acid, and carboxymethylcellulose are available on the market and may be added to delay crystallization. It has been a matter of debate whether such hydrocolloids prevent nucleation, growth of crystals, or both. It was the objective of this investigation to study the crystallization event by a new approach using dynamic light scattering and to clarify the mode of action of these hydrocolloids. To achieve this, model solutions and standardized wines were enriched with potassium bitartrate (KHT) to trigger crystallization. In this way, it was possible to distinguish between the influence of the hydrocolloids on nucleation and on crystal growth. It was found that the hydrocolloids do not prevent KHT nucleation. Instead, these compounds delay or even arrest the outgrowth of the crystals to a macroscopic, visual size.

Academic Success Through Quality-Managed Course Design.

ERIC Educational Resources Information Center

Reese, Andy C.; Mobley, Mary F.

1996-01-01

Principles of quality management, focusing on defect prevention rather than correction, were applied to the design of a graduate biomedicine course in immunology. The principles require clearly stated course mission and objectives, numerous intermediate steps to achieving objectives, immediate feedback on student performance, and immediate…

Educating Health Professionals about Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

American Journal of Health Education, 2007

2007-01-01

Prenatal exposure to alcohol is a leading preventable cause of birth defects and developmental disabilities. Individuals exposed to alcohol during fetal development can have physical, mental, behavioral, and learning disabilities, with lifelong implications. These conditions are known as fetal alcohol spectrum disorders (FASDs). Health care…

Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation.

PubMed

Sakai, Daisuke; Dixon, Jill; Achilleos, Annita; Dixon, Michael; Trainor, Paul A

2016-01-21

Craniofacial anomalies account for approximately one-third of all birth defects and are a significant cause of infant mortality. Since the majority of the bones, cartilage and connective tissues that comprise the head and face are derived from a multipotent migratory progenitor cell population called the neural crest, craniofacial disorders are typically attributed to defects in neural crest cell development. Treacher Collins syndrome (TCS) is a disorder of craniofacial development and although TCS arises primarily through autosomal dominant mutations in TCOF1, no clear genotype-phenotype correlation has been documented. Here we show that Tcof1 haploinsufficiency results in oxidative stress-induced DNA damage and neuroepithelial cell death. Consistent with this discovery, maternal treatment with antioxidants minimizes cell death in the neuroepithelium and substantially ameliorates or prevents the pathogenesis of craniofacial anomalies in Tcof1(+/-) mice. Thus maternal antioxidant dietary supplementation may provide an avenue for protection against the pathogenesis of TCS and similar neurocristopathies.

Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation

PubMed Central

Sakai, Daisuke; Dixon, Jill; Achilleos, Annita; Dixon, Michael; Trainor, Paul A.

2016-01-01

Craniofacial anomalies account for approximately one-third of all birth defects and are a significant cause of infant mortality. Since the majority of the bones, cartilage and connective tissues that comprise the head and face are derived from a multipotent migratory progenitor cell population called the neural crest, craniofacial disorders are typically attributed to defects in neural crest cell development. Treacher Collins syndrome (TCS) is a disorder of craniofacial development and although TCS arises primarily through autosomal dominant mutations in TCOF1, no clear genotype–phenotype correlation has been documented. Here we show that Tcof1 haploinsufficiency results in oxidative stress-induced DNA damage and neuroepithelial cell death. Consistent with this discovery, maternal treatment with antioxidants minimizes cell death in the neuroepithelium and substantially ameliorates or prevents the pathogenesis of craniofacial anomalies in Tcof1+/− mice. Thus maternal antioxidant dietary supplementation may provide an avenue for protection against the pathogenesis of TCS and similar neurocristopathies. PMID:26792133

Advanced pigment dispersion glaucoma secondary to phakic intraocular collamer lens implant.

PubMed

Ye, Clara; Patel, Cajal K; Momont, Anna C; Liu, Yao

2018-06-01

We report a case of pigment dispersion glaucoma secondary to uncomplicated phakic intraocular collamer lens (ICL) (Visian ICL™, Staar Inc., Monrovia, CA) implant that resulted in advanced visual field loss. A 50-year-old man presented for routine follow-up status post bilateral phakic intraocular collamer lens (ICL) placement 8 years earlier. He was incidentally found to have a decline in visual acuity from an anterior subcapsular cataract and elevated intraocular pressure (IOP) in the left eye. There were signs of pigment dispersion and no evidence of angle closure. Diffuse optic nerve thinning was consistent with advanced glaucomatous visual field defects. Pigment dispersion was also present in the patient's right eye, but without elevated IOP or visual field defects. The patient was treated with topical glaucoma medications and the phakic ICL in the left eye was removed concurrently with cataract surgery to prevent further visual field loss. Pigment dispersion glaucoma is a serious adverse outcome after phakic ICL implantation and regular post-operative monitoring may prevent advanced visual field loss.

Impact of Missing Data for Body Mass Index in an Epidemiologic Study.

PubMed

Razzaghi, Hilda; Tinker, Sarah C; Herring, Amy H; Howards, Penelope P; Waller, D Kim; Johnson, Candice Y

2016-07-01

Objective To assess the potential impact of missing data on body mass index (BMI) on the association between prepregnancy obesity and specific birth defects. Methods Data from the National Birth Defects Prevention Study (NBDPS) were analyzed. We assessed the factors associated with missing BMI data among mothers of infants without birth defects. Four analytic methods were then used to assess the impact of missing BMI data on the association between maternal prepregnancy obesity and three birth defects; spina bifida, gastroschisis, and cleft lip with/without cleft palate. The analytic methods were: (1) complete case analysis; (2) assignment of missing values to either obese or normal BMI; (3) multiple imputation; and (4) probabilistic sensitivity analysis. Logistic regression was used to estimate crude and adjusted odds ratios (aOR) and 95 % confidence intervals (CI). Results Of NBDPS control mothers 4.6 % were missing BMI data, and most of the missing values were attributable to missing height (~90 %). Missing BMI data was associated with birth outside of the US (aOR 8.6; 95 % CI 5.5, 13.4), interview in Spanish (aOR 2.4; 95 % CI 1.8, 3.2), Hispanic ethnicity (aOR 2.0; 95 % CI 1.2, 3.4), and <12 years education (aOR 2.3; 95 % CI 1.7, 3.1). Overall the results of the multiple imputation and probabilistic sensitivity analysis were similar to the complete case analysis. Conclusions Although in some scenarios missing BMI data can bias the magnitude of association, it does not appear likely to have impacted conclusions from a traditional complete case analysis of these data.

Functional antigen binding by the defective B cells of CBA/N mice.

PubMed

Snippe, H; Merchant, B; Lizzio, E F; Inman, J K

1982-01-01

CBA/N mice have an X-linked B cell defect which prevents them from responding to nonmitogenic thymic independent (TI-2) antigens such as dinitrophenylated DNP-Ficoll (1,2). The F1 male progeny of CBA/N female mice express the same defect. Spleen cell suspensions from such defective mice (CBA/N X C3H/HeN F1 males) could not respond to DNP-Ficoll following in vitro immunization and subsequent transfer into irradiated, syngeneic, F1 male recipients as expected. In contrast, normal CBA/N X C3H/HeN F1 female spleen cells could respond and effect a "rescue"; they mounted strong plaque-forming cell responses 7 days after in vitro exposure to DNP-Ficoll and subsequent transfer into irradiated F1 male recipients. Defective F1 male spleen cells, however, could bind significant quantities of 125I-DNP-Ficoll after in vitro exposure. Extensive washing of these spleen cells could not reverse this binding. Such DNP-Ficoll-exposed and washed F1 male spleen cells could, after transfer, aid normal untreated F1 female cells in their rescue function. The defective F1 male spleen cells could convey immunogenic quantities of DNP-Ficoll to the "rescuing" F1 female cells. Mitomycin treatment of F1 male cells did not interfere with their conveyor function. Goat anti-mouse mu serum impeded the passive antigen conveyor function of defective F1 male cells as did prior exposure to high concentrations of free DNP hapten. Our data support the view that the B cell defect of CBA/N X C3H/HeN F1 male mice does not relate to antigen binding, but rather to an inability to be effectively triggered by certain cell-bound polymeric antigens.

Integrated arc suppression unit for defect reduction in PVD applications

NASA Astrophysics Data System (ADS)

Li, Jason; Narasimhan, Murali K.; Pavate, Vikram; Loo, David; Rosenblum, Steve; Trubell, Larry; Scholl, Richard; Seamons, Scott; Hagerty, Chris; Ramaswami, Sesh

1997-09-01

Arcing between the target and plasma during PVD deposition causes substantial damage to the target and splats and other contamination on the deposited films. Arc-related damages and defects are frequently encountered in microelectronics manufacturing and contributes largely to reduced wafer yields. Arcing is caused largely by the charge buildup at the contaminated sites on the target surface that contains either nonconducting inclusions or nodules. Arc suppression is a key issue for defect reduction, yield improvement and for reliable high quality metallization. An Integrated Arc Suppression Unit (IASU) has been designed for Endura HP PVDTM sputtering sources. The integrated design reduces cable length from unit to source and reduces electrical energy stored in the cable. Active arc handling mode, proactive arc prevention mode, and passive by-pass arc counting mode are incorporated into the same unit. The active mode is designed to quickly respond to chamber conditions, like a large chamber voltage drop, that signals a arc. The self run mode is designed to proactively prevent arc formation by pulsing and reversing target voltage at 50 kHz. The design of the IASU, also called mini small package arc repression circuit--low energy unit (mini Sparc-le), has been optimized for various DC magnetron sources, plasma stability, chamber impedance, power matching, CE MARK test, and power dissipation. Process characterization with Ti, TiN and Al sputtering indicates that the unit has little adverse impact on film properties. Mini Sparc-le unit has been shown here to significantly reduce splats occurrence in Al sputtering. Marathon test of the unit with Ti/TiN test demonstrated the unit's reliability and its ability to reduce sensitivity of defects to target characteristics.

Fibrin-Genipin Adhesive Hydrogel for Annulus Fibrosus Repair: Performance Evaluation with Large Animal Organ Culture, In Situ Biomechanics, and In Vivo Degradation Tests

PubMed Central

Likhitpanichkul, M.; Dreischarf, M.; Illien-Junger, S.; Walter, B. A.; Nukaga, T.; Long, R. G; Sakai, D.; Hecht, A. C.; Iatridis, J. C.

2015-01-01

Annulus fibrosus (AF) defects from annular tears, herniation, and discectomy procedures are associated with painful conditions and accelerated intervertebral disc (IVD) degeneration. Currently, no effective treatments exist to repair AF damage, restore IVD biomechanics and promote tissue regeneration. An injectable fibrin-genipin adhesive hydrogel (Fib-Gen) was evaluated for its performance repairing large AF defects in a bovine caudal IVD model using ex vivo organ culture and biomechanical testing of motion segments, and for its in vivo longevity and biocompatibility in a rat model by subcutaneous implantation. Fib-Gen sealed AF defects, prevented IVD height loss, and remained well-integrated with native AF tissue following approximately 14,000 cycles of compression in 6-day organ culture experiments. Fib-Gen repair also retained high viability of native AF cells near the repair site, reduced nitric oxide released to the media, and showed evidence of AF cell migration into the gel. Biomechanically, Fib-Gen fully restored compressive stiffness to intact levels validating organ culture findings. However, only partial restoration of tensile and torsional stiffness was obtained, suggesting opportunities to enhance this formulation. Subcutaneous implantation results, when compared with the literature, suggested Fib-Gen exhibited similar biocompatibility behaviour to fibrin alone but degraded much more slowly. We conclude that injectable Fib-Gen successfully sealed large AF defects, promoted functional restoration with improved motion segment biomechanics, and served as a biocompatible adhesive biomaterial that had greatly enhanced in vivo longevity compared to fibrin. Fib-Gen offers promise for AF repairs that may prevent painful conditions and accelerated degeneration of the IVD, and warrants further material development and evaluation. PMID:25036053

Fibrin-genipin adhesive hydrogel for annulus fibrosus repair: performance evaluation with large animal organ culture, in situ biomechanics, and in vivo degradation tests.

PubMed

Likhitpanichkul, M; Dreischarf, M; Illien-Junger, S; Walter, B A; Nukaga, T; Long, R G; Sakai, D; Hecht, A C; Iatridis, J C

2014-07-18

Annulus fibrosus (AF) defects from annular tears, herniation, and discectomy procedures are associated with painful conditions and accelerated intervertebral disc (IVD) degeneration. Currently, no effective treatments exist to repair AF damage, restore IVD biomechanics and promote tissue regeneration. An injectable fibrin-genipin adhesive hydrogel (Fib-Gen) was evaluated for its performance repairing large AF defects in a bovine caudal IVD model using ex vivo organ culture and biomechanical testing of motion segments, and for its in vivo longevity and biocompatibility in a rat model by subcutaneous implantation. Fib-Gen sealed AF defects, prevented IVD height loss, and remained well-integrated with native AF tissue following approximately 14,000 cycles of compression in 6-day organ culture experiments. Fib-Gen repair also retained high viability of native AF cells near the repair site, reduced nitric oxide released to the media, and showed evidence of AF cell migration into the gel. Biomechanically, Fib-Gen fully restored compressive stiffness to intact levels validating organ culture findings. However, only partial restoration of tensile and torsional stiffness was obtained, suggesting opportunities to enhance this formulation. Subcutaneous implantation results, when compared with the literature, suggested Fib-Gen exhibited similar biocompatibility behaviour to fibrin alone but degraded much more slowly. We conclude that injectable Fib-Gen successfully sealed large AF defects, promoted functional restoration with improved motion segment biomechanics, and served as a biocompatible adhesive biomaterial that had greatly enhanced in vivo longevity compared to fibrin. Fib-Gen offers promise for AF repairs that may prevent painful conditions and accelerated degeneration of the IVD, and warrants further material development and evaluation.

Detection and Prevention of Perinatal Infection: Cytomegalovirus and Zika Virus.

PubMed

Wood, Amber M; Hughes, Brenna L

2018-06-01

Congenital cytomegalovirus is the most common viral congenital infection, and affects up to 2% of neonates. Significant sequelae may develop after congenital cytomegalovirus, including hearing loss, cognitive defects, seizures, and death. Zika virus is an emerging virus with perinatal implications; a congenital Zika virus syndrome has been identified, and includes findings such as microcephaly, fetal nervous system abnormalities, and neurologic sequelae after birth. Screening, diagnosis, prevention, and treatment of these perinatal infections are reviewed in this article. Copyright © 2018 Elsevier Inc. All rights reserved.

Modulation of nuclear factor-κB signaling and reduction of neural tube defects by quercetin-3-glucoside in embryos of diabetic mice.

PubMed

Tan, Chengyu; Meng, Fantong; Reece, E Albert; Zhao, Zhiyong

2018-05-04

Diabetes mellitus in early pregnancy increases the risk of birth defects in infants. Maternal hyperglycemia stimulates the expression of nitric oxide (NO) synthase 2 (NOS2), which can be regulated by transcription factors of the nuclear factor-κB (NF-κB) family. Increases in reactive nitrogen species (RNS) generate intracellular stress conditions, including nitrosative, oxidative, and endoplasmic reticulum (ER) stresses, and trigger programmed cell death (or apoptosis) in the neural folds, resulting in neural tube defects (NTDs) in the embryo. Inhibiting NOS2 can reduce NTDs; however, the underlying mechanisms require further delineation. Targeting NOS2 and associated nitrosative stress using naturally occurring phytochemicals is a potential approach to preventing birth defects in diabetic pregnancies. This study aims to investigate the effect of quercetin-3-glucoside (Q3G), a polyphenol flavonoid found in fruit, in reducing maternal diabetes-induced NTDs in an animal model, and to delineate the molecular mechanisms underlying Q3G action in regulating NOS2 expression. Female mice (C57BL/6) were induced to develop diabetes using streptozotocin before pregnancy. Diabetic pregnant mice were administered Q3G (100 mg/kg) daily via gavage feeding, introduction of drug to the stomach directly via a feeding needle, during neurulation from embryonic (E) day 6.5 to E9.5. After treatment, E10.5 embryos were collected and examined for the presence of NTDs and apoptosis in the neural tube. Expression of Nos2 and superoxide dismutase 1 (Sod1; an antioxidative enzyme) was quantified using Western blot assay. Nitrosative, oxidative, and endoplasmic reticulum (ER) stress conditions were assessed using specific biomarkers. Expression and posttranslational modification of factors in the NF-κB system were investigated. Treatment with Q3G (suspended in water) significantly decreased NTD rate (24.7%) and apoptosis in the embryos of diabetic mice, compared with those in the water-treated diabetic group (3.1%; p<0.001). Q3G decreased the expression of Nos2 and nitrosative stress (p<0.05). It also increased the levels of Sod1 (p<0.05), further increasing the antioxidative capacity of the cells. Q3G treatment also alleviated of ER stress in the embryos of diabetic mice (p<0.05). Q3G reduced the levels of p65 (RelA; p<0.05), a member of the NF-κB transcription factor family, but augmented the levels of the inhibitor of κBα (IκBα; p<0.05), which suppresses p65 nuclear translocation. In association with these changes, the levels of IκB kinase α (Ikkα) and IκBα phosphorylation were elevated (p<0.05). Q3G reduces the NTD rate in the embryos of diabetic dams. Q3G suppresses Nos2 and increases Sod1 expression, leading to alleviation of nitrosative, oxidative, and ER stress conditions. Q3G may regulate the expression of Nos2 via modulating the NF-κB transcription regulation system. Q3G, a naturally occurring polyphenol that has high bioavailability and low toxicity, is a promising candidate agent to prevent birth defects in diabetic pregnancies. The phytochemical quercetin-3-glucoside prevents neural tube defects in embryos of diabetic mice by alleviating nitrosative stress via suppression of the nuclear factor κB-regulated nitric oxide synthase 2 expression. Copyright © 2018 Elsevier Inc. All rights reserved.

Prosthetic Rehabilitation of Defects of the Head and Neck

PubMed Central

Salinas, Thomas J.

2010-01-01

Patients afflicted with head and neck cancer, traumatic injuries to the head and neck, or those with congenital or developmental defects benefit from multidisciplinary team management. The head and neck region participates in complex physiologic processes that can often be impeded by these circumstances. Evaluation of the patient by the maxillofacial prosthodontist can assist the other members of the team in providing treatment planning options for the patients. Intraoral defects arising from these circumstances can be treated with prosthodontics that serve to assist with speech, swallowing, and to some degree mastication. If chemotherapeutic or radiation modalities are also used to treat the head and neck, assessment of the patient by the maxillofacial prosthodontist may prove to identify factors that may predispose to undesirable sequelae. Preventive treatment by elective tooth extraction, prosthodontic assessment, and patient education prove to assist in predictable management of these oftentimes complex presenting conditions. Facial defects arising from similar circumstances can be an alternative or adjunct to plastic surgical reconstruction and offer the added advantage of tumor surveillance in susceptible patients. PMID:22550451

Overlap of copper and iron uptake systems in mitochondria in Saccharomyces cerevisiae

PubMed Central

Wang, Jing; Gammon, Micah G.; Maynard, Margaret K.; White, Olivia L.; Cobine, Jai A.; Mahone, Wilkerson K.

2016-01-01

In Saccharomyces cerevisiae, the mitochondrial carrier family protein Pic2 imports copper into the matrix. Deletion of PIC2 causes defects in mitochondrial copper uptake and copper-dependent growth phenotypes owing to decreased cytochrome c oxidase activity. However, copper import is not completely eliminated in this mutant, so alternative transport systems must exist. Deletion of MRS3, a component of the iron import machinery, also causes a copper-dependent growth defect on non-fermentable carbon. Deletion of both PIC2 and MRS3 led to a more severe respiratory growth defect than either individual mutant. In addition, MRS3 expressed from a high copy number vector was able to suppress the oxygen consumption and copper uptake defects of a strain lacking PIC2. When expressed in Lactococcus lactis, Mrs3 mediated copper and iron import. Finally, a PIC2 and MRS3 double mutant prevented the copper-dependent activation of a heterologously expressed copper sensor in the mitochondrial intermembrane space. Taken together, these data support a role for the iron transporter Mrs3 in copper import into the mitochondrial matrix. PMID:26763345

Persistent left superior vena cava in association with sinus venosus defect type of atrial septal defect and partial pulmonary venous return on 64-MDCT

PubMed Central

Disha, Bansal; Prakashini, Koteshwara; Shetty, Ranjan K

2014-01-01

The most common venous abnormality of the thorax is persistent left superior vena cava (PLSVC), incidence being less than 0.5%. However, with congenital heart disease, it is about 6.1%. When the coronary sinus is dilated always search for PLSVC. The coronary sinus may communicate with the left atrium. This is known as an unroofed coronary sinus (UCS) and preoperatively documenting it is important. Of all the congenital cardiac anomalies, the sinus venosus defect (SVD) type of atrial septal defect (ASD) is most commonly associated with PLSVC and accounts for 4–11% of all ASDs. Multidetector CT can easily show all these abnormalities along with haemodynamics. On transoesophageal echocardiography it is difficult to characterise SVD and visualise a coronary sinus because of a limited window, contrast resolution and poor patient compliance. The complex of UCS and PLSVC is one such abnormality and its treatment requires careful assessment of other concomitant cardiac abnormalities to prevent post-treatment haemodynamic complications. PMID:24850552

Mouse Models for Investigating the Developmental Bases of Human Birth Defects

PubMed Central

MOON, ANNE M.

2006-01-01

Clinicians and basic scientists share an interest in discovering how genetic or environmental factors interact to perturb normal development and cause birth defects and human disease. Given the complexity of such interactions, it is not surprising that 4% of human infants are born with a congenital malformation, and cardiovascular defects occur in nearly 1%. Our research is based on the fundamental hypothesis that an understanding of normal and abnormal development will permit us to generate effective strategies for both prevention and treatment of human birth defects. Animal models are invaluable in these efforts because they allow one to interrogate the genetic, molecular and cellular events that distinguish normal from abnormal development. Several features of the mouse make it a particularly powerful experimental model: it is a mammalian system with similar embryology, anatomy and physiology to humans; genes, proteins and regulatory programs are largely conserved between human and mouse; and finally, gene targeting in murine embryonic stem cells has made the mouse genome amenable to sophisticated genetic manipulation currently unavailable in any other model organism. PMID:16641221

The Development of Skull Prosthesis Through Active Contour Model.

PubMed

Chen, Yi-Wen; Shih, Cheng-Ting; Cheng, Chen-Yang; Lin, Yu-Cheng

2017-09-09

Skull defects result in brain infection and inadequate brain protection and pose a general danger to patient health. To avoid these situations and prevent re-injury, a prosthesis must be constructed and grafted onto the deficient region. With the development of rapid customization through additive manufacturing and 3D printing technology, skull prostheses can be fabricated accurately and efficiently prior to cranioplasty. However, an unfitted skull prosthesis made with a metal implant can cause repeated infection, potentially necessitating secondary surgery. This paper presents a method of creating suitably geometric graphics of skull defects to be applied in skull repair through active contour models. These models can be adjusted in each computed tomography slice according to the graphic features, and the curves representing the skull defect can be modeled. The generated graphics can adequately mimic the natural curvature of the complete skull. This method will enable clinical surgeons to rapidly implant customized prostheses, which is of particular importance in emergency surgery. The findings of this research can help surgeons provide patients with skull defects with treatment of the highest quality.

Face off against ROS: Tcof1/Treacle safeguards neuroepithelial cells and progenitor neural crest cells from oxidative stress during craniofacial development.

PubMed

Sakai, Daisuke; Trainor, Paul A

2016-09-01

One-third of all congenital birth defects affect the head and face, and most craniofacial anomalies are considered to arise through defects in the development of cranial neural crest cells. Cranial neural crest cells give rise to the majority of craniofacial bones, cartilages and connective tissues. Therefore, understanding the events that control normal cranial neural crest and subsequent craniofacial development is important for elucidating the pathogenetic mechanisms of craniofacial anomalies and for the exploring potential therapeutic avenues for their prevention. Treacher Collins syndrome (TCS) is a congenital disorder characterized by severe craniofacial anomalies. An animal model of TCS, generated through mutation of Tcof1, the mouse (Mus musculus) homologue of the gene primarily mutated in association with TCS in humans, has recently revealed significant insights into the pathogenesis of TCS. Apoptotic elimination of neuroepithelial cells including neural crest cells is the primary cause of craniofacial defects in Tcof1 mutant embryos. However, our understanding of the mechanisms that induce tissue-specific apoptosis remains incomplete. In this review, we describe recent advances in our understanding of the pathogenesis TCS. Furthermore, we discuss the role of Tcof1 in normal embryonic development, the correlation between genetic and environmental factors on the severity of craniofacial abnormalities, and the prospect for prenatal prevention of craniofacial anomalies. © 2016 Japanese Society of Developmental Biologists.

Face off against ROS: Tcof1/Treacle safeguards neuroepithelial cells and progenitor neural crest cells from oxidative stress during craniofacial development

PubMed Central

Sakai, Daisuke; Trainor, Paul A.

2016-01-01

One-third of all congenital birth defects affect the head and face, and most craniofacial anomalies are considered to arise through defects in the development of cranial neural crest cells. Cranial neural crest cells give rise to the majority of craniofacial bones, cartilages and connective tissues. Therefore understanding the events that control normal cranial neural crest and subsequent craniofacial development is important for elucidating the pathogenetic mechanisms of craniofacial anomalies and for the exploring potential therapeutic avenues for their prevention. Treacher Collins syndrome (TCS) is a congenital disorder characterized by severe craniofacial anomalies. An animal model of TCS, generated through mutation of Tcof1, the mouse (Mus musculus) homologue of the gene primarily mutated in association with TCS in humans, has recently revealed significant insights into the pathogenesis of TCS. Apoptotic elimination of neuroepithelial cells including neural crest cells is the primary cause of craniofacial defects in Tcof1 mutant embryos. However our understanding of the mechanisms that induce tissue-specific apoptosis remains incomplete. In this review, we describe recent advances in our understanding of the pathogenesis TCS. Furthermore, we discuss the role of Tcof1 in normal embryonic development, the correlation between genetic and environmental factors on the severity of craniofacial abnormalities, and the prospect for prenatal prevention of craniofacial anomalies. PMID:27481486

Superiority of Graphene over Polymer Coatings for Prevention of Microbially Induced Corrosion

PubMed Central

Krishnamurthy, Ajay; Gadhamshetty, Venkataramana; Mukherjee, Rahul; Natarajan, Bharath; Eksik, Osman; Ali Shojaee, S.; Lucca, Don A.; Ren, Wencai; Cheng, Hui-Ming; Koratkar, Nikhil

2015-01-01

Prevention of microbially induced corrosion (MIC) is of great significance in many environmental applications. Here, we report the use of an ultra-thin, graphene skin (Gr) as a superior anti-MIC coating over two commercial polymeric coatings, Parylene-C (PA) and Polyurethane (PU). We find that Nickel (Ni) dissolution in a corrosion cell with Gr-coated Ni is an order of magnitude lower than that of PA and PU coated electrodes. Electrochemical analysis reveals that the Gr coating offers ~10 and ~100 fold improvement in MIC resistance over PU and PA coatings respectively. This finding is remarkable considering that the Gr coating (1–2 nm) is ~25 and ~4000 times thinner than the PA (40–50 nm), and PU coatings (20–80 μm), respectively. Conventional polymer coatings are either non-conformal when deposited or degrade under the action of microbial processes, while the electro-chemically inert graphene coating is both resistant to microbial attack and is extremely conformal and defect-free. Finally, we provide a brief discussion regarding the effectiveness of as-grown vs. transferred graphene films for anti-MIC applications. While the as-grown graphene films are devoid of major defects, wet transfer of graphene is shown to introduce large scale defects that make it less suitable for the current application. PMID:26350049

Nebula/DSCR1 upregulation delays neurodegeneration and protects against APP-induced axonal transport defects by restoring calcineurin and GSK-3β signaling.

PubMed

Shaw, Jillian L; Chang, Karen T

2013-01-01

Post-mortem brains from Down syndrome (DS) and Alzheimer's disease (AD) patients show an upregulation of the Down syndrome critical region 1 protein (DSCR1), but its contribution to AD is not known. To gain insights into the role of DSCR1 in AD, we explored the functional interaction between DSCR1 and the amyloid precursor protein (APP), which is known to cause AD when duplicated or upregulated in DS. We find that the Drosophila homolog of DSCR1, Nebula, delays neurodegeneration and ameliorates axonal transport defects caused by APP overexpression. Live-imaging reveals that Nebula facilitates the transport of synaptic proteins and mitochondria affected by APP upregulation. Furthermore, we show that Nebula upregulation protects against axonal transport defects by restoring calcineurin and GSK-3β signaling altered by APP overexpression, thereby preserving cargo-motor interactions. As impaired transport of essential organelles caused by APP perturbation is thought to be an underlying cause of synaptic failure and neurodegeneration in AD, our findings imply that correcting calcineurin and GSK-3β signaling can prevent APP-induced pathologies. Our data further suggest that upregulation of Nebula/DSCR1 is neuroprotective in the presence of APP upregulation and provides evidence for calcineurin inhibition as a novel target for therapeutic intervention in preventing axonal transport impairments associated with AD.

Nebula/DSCR1 Upregulation Delays Neurodegeneration and Protects against APP-Induced Axonal Transport Defects by Restoring Calcineurin and GSK-3β Signaling

PubMed Central

Shaw, Jillian L.; Chang, Karen T.

2013-01-01

Post-mortem brains from Down syndrome (DS) and Alzheimer's disease (AD) patients show an upregulation of the Down syndrome critical region 1 protein (DSCR1), but its contribution to AD is not known. To gain insights into the role of DSCR1 in AD, we explored the functional interaction between DSCR1 and the amyloid precursor protein (APP), which is known to cause AD when duplicated or upregulated in DS. We find that the Drosophila homolog of DSCR1, Nebula, delays neurodegeneration and ameliorates axonal transport defects caused by APP overexpression. Live-imaging reveals that Nebula facilitates the transport of synaptic proteins and mitochondria affected by APP upregulation. Furthermore, we show that Nebula upregulation protects against axonal transport defects by restoring calcineurin and GSK-3β signaling altered by APP overexpression, thereby preserving cargo-motor interactions. As impaired transport of essential organelles caused by APP perturbation is thought to be an underlying cause of synaptic failure and neurodegeneration in AD, our findings imply that correcting calcineurin and GSK-3β signaling can prevent APP-induced pathologies. Our data further suggest that upregulation of Nebula/DSCR1 is neuroprotective in the presence of APP upregulation and provides evidence for calcineurin inhibition as a novel target for therapeutic intervention in preventing axonal transport impairments associated with AD. PMID:24086147

Sphenoid dysplasia in neurofibromatosis type 1: a new technique for repair.

PubMed

Concezio, Di Rocco; Amir, Samii; Gianpiero, Tamburrini; Luca, Massimi; Mario, Giordano

2017-06-01

Sphenoid bone dysplasia in neurofibromatosis type 1 is characterized by progressive exophthalmos and facial disfiguration secondary to herniation of meningeal and cerebral structures. We describe a technique for reconstruction of the sphenoid defect apt at preventing or correcting the ocular globe dislocation. After placement of spinal cerebrospinal fluid drainage to reduce intracranial pressure, the temporal pole is posteriorly dislocated extradurally. The greater sphenoid wing defect is identified. A titanium mesh covered by lyophilized dura, modeled in a curved fashion, is interposed between the bone defect and the cerebro-meningeal structures with its convex surface over the retracted temporal pole. The particular configuration of the titanium mesh allows a self-maintaining position due to the pressure exerted by the brain over its convex central part with its lateral margins consequently pushed and self-anchored against the medial and lateral walls of the temporal fossa. Screw fixation is not needed. The technique utilized in four cases proved to be reliable at the long-term clinical and neuroradiological controls (6 to 19 years). Sphenoid bone dysplasia in NF1, resulting in proptosis and exophthalmos, is usually progressive. It can be surgically repaired using a curved titanium mesh with the convexity faced to the temporal pole that is in the opposite fashion from all the techniques previously introduced. When utilized early in life, the technique can prevent the occurrence of the orbital and facial disfiguration.

Further Studies of Porcine Malignant Hyperthermia

PubMed Central

Hall, L. W.; Trim, Cynthia M.; Woolf, N.

1972-01-01

A non-lethal procedure for identifying pigs apt to develop malignant hyperthermia is described. Susceptible animals were exposed to a variety of anaesthetic and other agents and it was shown that thiopentone sodium and CT 1341 (Glaxo) afforded a measure of protection against the development of the syndrome. Pretreatment with procaine did not prevent the onset of the condition and the administration of procaine when muscle rigidity was present failed to prevent a fatal outcome. The syndrome was induced in susceptible animals by halothane, chloroform, and a combination of halothane with suxamethonium. The effects of cyclopropane in susceptible pigs could not be predicted, and other tests showed that suxamethonium alone would not induce muscle contracture. Pretreatment with lignocaine failed to prevent induction of the syndrome by halothane. We believe that the porcine syndrome may result from more than one defect and that in one particular type the most effective treatment is immediate cooling coupled with the administration of sodium bicarbonate. PMID:5017306

Should the dose of folic acid be adjusted for Mexican population? The pilot prevention program implemented in Nuevo Leon, Mexico.

PubMed

Martinez de Villarreal, Laura E

2017-12-11

In 1980 Smithells et al. reported that the intake of folic acid (FA) prevents the recurrence of neural tube defects (NTDs) [1]. After this and several other studies were conducted, the intake of 400 micrograms of folic acid per day, at least three months before and three months during pregnancy for prevention of NTD, was proposed [2,3,4]. Other strategies were also developed to increase folate blood levels in woman of childbearing age such as promoting the consumption of folate rich foods and food fortification (flour and most recently rice) [5]. Nevertheless, results have not been as expected due to poor consumption of folic acid supplements [6]. As a result, in the year 2000, a novel strategy was developed in order to increase folate blood levels in Mexican women. The results of the strategy are presented, as well as, a discussion about how to personalize a program for different populations.

Signification of distal urinary acidification defects in hypocitraturic patients

PubMed Central

Forni Ogna, Valentina; Blanchard, Anne; Vargas-Poussou, Rosa; Ogna, Adam; Baron, Stéphanie; Bertocchio, Jean-Philippe; Prot-Bertoye, Caroline; Nevoux, Jérôme; Dubourg, Julie; Maruani, Gérard; Mendes, Margarida; Garcia-Castaño, Alejandro; Treard, Cyrielle; Lepottier, Nelly; Houillier, Pascal; Courbebaisse, Marie

2017-01-01

Background and objectives Hypocitraturia has been associated with metabolic acidosis and mineral disorders. The aim of this study was to investigate the occurrence of urinary acidification defects underlying hypocitraturia. Materials and methods This retrospective observational study included 67 patients (32 men), aged 40.7±15.1 years with hypocitraturia (<1.67 mmol/24-h) and nephrolithiasis, nephrocalcinosis, and/or bone demineralization, referred to our center from 2000 to 2015. We aimed to assess renal distal acidification capacity, prevalence and mechanisms of urinary acidification defects. Patients with low baseline plasma HCO3- (<22 mmol/L) were studied by bicarbonate loading or furosemide/fludrocortisone tests. Patients with normal baseline plasma HCO3- had an ammonium-chloride challenge test. A normal response was a decrease in urinary pH <5.3 and an increase in urinary NH4+ ≥33 μmol/min and defined idiopathic hypocitraturia. Results Eleven patients (16.4%) had low HCO3- and overt distal acidification defect. Three had a mutation in the gene encoding AE1, 4 had Gougerot-Sjögren syndrome and no cause was found in the remaining 4 cases. Fifty-six patients (83.6%) had normal HCO3-; of those, 33 (58.9%) had idiopathic hypocitraturia. Among the 23 (41%) remaining patients, 12 were unable to increase urinary NH4+ excretion (among them, 8 were able to decrease urinary pH and 4 were not) whereas 11 were able to increase urinary NH4+ excretion but unable to decrease urinary pH. These 11 patients had higher fasting urinary calcium, reflecting bone resorption, than the other 12 patients: median 0.41 [0.24–0.47] vs. 0.22 [0.08–0.37] mmol/mmol creatinine (P = 0.04). Conclusions Patients with hypocitraturia and normal plasma HCO3- frequently show a latent acidification defect that can be further dissected into one of several subtypes based on urinary pH and NH4+ response to the acid load. Those patients with impaired urine acidification capacity but preserved NH4+ excretion exhibit particularly high calciuria and should be identified to optimize nephrolithiasis prevention. PMID:28542241

Suppression of planar defects in the molecular beam epitaxy of GaAs/ErAs/GaAs heterostructures

NASA Astrophysics Data System (ADS)

Crook, Adam M.; Nair, Hari P.; Ferrer, Domingo A.; Bank, Seth R.

2011-08-01

We present a growth method that overcomes the mismatch in rotational symmetry of ErAs and conventional III-V semiconductors, allowing for epitaxially integrated semimetal/semiconductor heterostructures. Transmission electron microscopy and reflection high-energy electron diffraction reveal defect-free overgrowth of ErAs layers, consisting of >2× the total amount of ErAs that can be embedded with conventional layer-by-layer growth methods. We utilize epitaxial ErAs nanoparticles, overgrown with GaAs, as a seed to grow full films of ErAs. Growth proceeds by diffusion of erbium atoms through the GaAs spacer, which remains registered to the underlying substrate, preventing planar defect formation during subsequent GaAs growth. This growth method is promising for metal/semiconductor heterostructures that serve as embedded Ohmic contacts to epitaxial layers and epitaxially integrated active plasmonic devices.

Mitochondrial Translation and Beyond: Processes Implicated in Combined Oxidative Phosphorylation Deficiencies

PubMed Central

Smits, Paulien; Smeitink, Jan; van den Heuvel, Lambert

2010-01-01

Mitochondrial disorders are a heterogeneous group of often multisystemic and early fatal diseases, which are amongst the most common inherited human diseases. These disorders are caused by defects in the oxidative phosphorylation (OXPHOS) system, which comprises five multisubunit enzyme complexes encoded by both the nuclear and the mitochondrial genomes. Due to the multitude of proteins and intricacy of the processes required for a properly functioning OXPHOS system, identifying the genetic defect that underlies an OXPHOS deficiency is not an easy task, especially in the case of combined OXPHOS defects. In the present communication we give an extensive overview of the proteins and processes (in)directly involved in mitochondrial translation and the biogenesis of the OXPHOS system and their roles in combined OXPHOS deficiencies. This knowledge is important for further research into the genetic causes, with the ultimate goal to effectively prevent and cure these complex and often devastating disorders. PMID:20396601

Robust binarization of degraded document images using heuristics

NASA Astrophysics Data System (ADS)

Parker, Jon; Frieder, Ophir; Frieder, Gideon

2013-12-01

Historically significant documents are often discovered with defects that make them difficult to read and analyze. This fact is particularly troublesome if the defects prevent software from performing an automated analysis. Image enhancement methods are used to remove or minimize document defects, improve software performance, and generally make images more legible. We describe an automated, image enhancement method that is input page independent and requires no training data. The approach applies to color or greyscale images with hand written script, typewritten text, images, and mixtures thereof. We evaluated the image enhancement method against the test images provided by the 2011 Document Image Binarization Contest (DIBCO). Our method outperforms all 2011 DIBCO entrants in terms of average F1 measure - doing so with a significantly lower variance than top contest entrants. The capability of the proposed method is also illustrated using select images from a collection of historic documents stored at Yad Vashem Holocaust Memorial in Israel.

Multiple cutaneous malignancies in a patient of xeroderma pigmentosum.

PubMed

Grampurohit, Vandana U; Dinesh, U S; Rao, Ravikala

2011-01-01

Xeroderma pigmentosum is a genodermatosis characterized by photosensitivity and the development of cutaneous and internal malignancies at an early age. The basic defect underlying the clinical manifestations is a nucleotide excision repair defect, leading to defective repair of DNA damaged by ultraviolet radiation. These patients exhibit enhanced sensitivity to ionizing radiation. Patients with xeroderma pigmentosum who are younger than 20 years of age have a greater than 1000-fold increased risk of developing skin cancer. Early detection of these malignancies is necessary because they are fast growing, metastasize early and lead to death. Although, early detection and treatment of cutaneous malignancies will reduce the morbidity and mortality, genetic counseling remains the most important measure for preventing xeroderma pigmentosum. We report a case of xeroderma pigmentosum in an 18-year-old male presenting with multiple cutaneous malignancies: squamous cell carcinoma, malignant melanoma and pigmented basal cell carcinoma.

Inversin relays Frizzled-8 signals to promote proximal pronephros development

PubMed Central

Lienkamp, Soeren; Ganner, Athina; Boehlke, Christopher; Schmidt, Thorsten; Arnold, Sebastian J.; Schäfer, Tobias; Romaker, Daniel; Schuler, Julia; Hoff, Sylvia; Powelske, Christian; Eifler, Annekathrin; Krönig, Corinna; Bullerkotte, Axel; Nitschke, Roland; Kuehn, E. Wolfgang; Kim, Emily; Burkhardt, Hans; Brox, Thomas; Ronneberger, Olaf; Gloy, Joachim; Walz, Gerd

2010-01-01

Mutations of inversin cause type II nephronophthisis, an infantile autosomal recessive disease characterized by cystic kidney disease and developmental defects. Inversin regulates Wnt signaling and is required for convergent extension movements during early embryogenesis. We now show that Inversin is essential for Xenopus pronephros formation, involving two distinct and opposing forms of cell movements. Knockdown of Inversin abrogated both proximal pronephros extension and distal tubule differentiation, phenotypes similar to that of Xenopus deficient in Frizzled-8. Exogenous Inversin rescued the pronephric defects caused by lack of Frizzled-8, indicating that Inversin acts downstream of Frizzled-8 in pronephros morphogenesis. Depletion of Inversin prevents the recruitment of Dishevelled in response to Frizzled-8 and impeded the accumulation of Dishevelled at the apical membrane of tubular epithelial cells in vivo. Thus, defective tubule morphogenesis seems to contribute to the renal pathology observed in patients with nephronophthisis type II. PMID:21059920

Maternal hypertension, medication use, and hypospadias in the National Birth Defects Prevention Study.

PubMed

Van Zutphen, Alissa R; Werler, Martha M; Browne, Marilyn M; Romitti, Paul A; Bell, Erin M; McNutt, Louise-Anne; Druschel, Charlotte M; Mitchell, Allen A

2014-02-01

To investigate whether antihypertensive classes and specific medications in early pregnancy increase the risk of severe hypospadias and to assess prior associations detected for late-treated and untreated hypertension in the National Birth Defects Prevention Study. Using telephone interviews from mothers of 2,131 children with severe hypospadias and 5,129 nonmalformed male control children for 1997-2009 births in a population-based case-control study, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with multivariable logistic regression. We adjusted P values to account for multiple testing. Forty-eight (2.3%) case and 70 (1.4%) control mothers reported early pregnancy antihypertensive treatment, 45 (2.1%) case and 31 (0.6%) control mothers reported late treatment, and 315 (14.8%) case and 394 (7.7%) control mothers reported untreated hypertension. Selective β-blockers, centrally acting agents, renin-angiotensin system-acting agents, diuretics, and specific medications, methyldopa and atenolol, were not associated with hypospadias. Nonselective β-blockers (adjusted OR 3.22, 95% CI 1.47-7.05) were associated with hypospadias; however, P values adjusted for multiple testing were not statistically significant. We confirmed prior findings for associations between hypospadias and untreated hypertension (adjusted OR 2.09, 95% CI 1.76-2.48) and late initiation of treatment (adjusted OR 3.98, 95% CI 2.41-6.55). The increased risks would translate to severe hypospadias prevalences of 11.5, 17.7, and 21.9 per 10,000 births for women with untreated hypertension, nonselective β-blocker use, and late initiation of treatment, respectively. Our study suggests a relationship between hypospadias and the severity of hypertension. II.

Mediterranean diet, folic acid, and neural tube defects.

PubMed

Fischer, Maximilian; Stronati, Mauro; Lanari, Marcello

2017-08-17

The Mediterranean diet has been for a very long time the basis of food habits all over the countries of the Mediterranean basin, originally founded on rural models and low consumption of meat products and high-fat/high-processed foods. However, in the modern era, the traditional Mediterranean diet pattern is now progressively eroding due to the widespread dissemination of the Western-type economy, life-style, technology-driven culture, as well as the globalisation of food production, availability and consumption, with consequent homogenisation of food culture and behaviours. This transition process may affect many situations, including pregnancy and offspring's health. The problem of the diet during pregnancy and the proper intake of nutrients are nowadays a very current topic, arousing much debate. The Mediterranean dietary pattern, in particular, has been associated with the highest risk reduction of major congenital anomalies, like the heterogeneous class of neural tube defects (NTDs). NTDs constitute a major health burden (0.5-2/1000 pregnancies worldwide) and still remain a preventable cause of still birth, neonatal and infant death, or significant lifelong disabilities. Many studies support the finding that appropriate folate levels during pregnancy may confer protection against these diseases. In 1991 one randomised controlled trial (RCT) demonstrated for the first time that periconceptional supplementation of folic acid is able to prevent the recurrence of NTDs, finding confirmed by many other subsequent studies. Anyway, the high rate of unplanned/unintended pregnancies and births and other issues hindering the achievement of adequate folate levels in women in childbearing age, induced the US government and many other countries to institute mandatory food fortification with folic acid. The actual strategy adopted by European Countries (including Italy) suggests that women take 0,4 mg folic acid/die before conception. The main question is which intervention, between folic acid supplementation, foods fortification or both, linked to a healthy life-style and diet pattern may represent the best method in preventing NTDs. The aim of this review is to describe the actual situation in NTDs prevention, with a special attention to the Italiancontext concerning this delicate and controversial subject.

The defectiveness of measurement data in the inclinometer mesurement in the insertion-type aperture and an introduction about the crrection

NASA Astrophysics Data System (ADS)

Homma, H.; Fujisawa, K.; Chiba, S.; Ootsuka, Y.; Higuchi, K.; Suganuma, T.

2010-12-01

Since 1975, the insertion type borehole inclinometer has been used to measure an underground lateral deformation in the civil engineering works field in Japan. The borehole inclinometer is used for a lot of landslide investigations as an effective measuring instrument to judge the slide surface position and the rate of slip. On the other hand, it became popular to be able to gather cores at 100% collection rate by the core-pack-tube method having been developed in the drilling survey. As a result, because the grasp accuracy of geological features had improved greatly, it became clear there was a case where the measurement data of the borehole inclinometer did not obviously show the displacement of the ground. As a result,to correct data even if the method of setting up the guide pipe is examined so as not to generate defective data , some engineers where such the realities were understood have been examining it about the correction method. Therefore, there is a case where there is no standards united about the methods of measuring the insertion type borehole inclinometer, and defective data is used still as a result of the observation though the ratio of defective data has decreased. The Pubic Works Research Institute landslide team and three private company companies of Japan did a joint research from these on the generation of defective data between fiscal year 2008 and fiscal year 2009 to prevent it. And, they made the manual that brought the matter to do an appropriate borehole inclinometer (Insertion type borehole inclinometer measurement manual on the landslide ground). In various experiments executed by a joint research, to prevent defective data being generated, it has been understood that the installation of the guide pipe is most important. The following two problems occur if a defective installation of the guide pipe is caused. (1)S shape data in graph (2)Disorder of flat direction of displacement (1) Because filling work at the time of the guide pipe setting is not enough, a gap occurs between a drill hole and a guide pipe. The grout material of the cement system is used standard in Japan. However, the landslide mass flows out easily in general because there are a lot of cracks in addition to low the groundwater level. Therefore we work on filling with paccar, and it is necessary to let a guide pipe and the ground. (2)The direction of the displacement that data shows is different from the direction of the movement of the actual ground. In this data, the product of the guide pipe twists, and both of the twist when setting it up are causes of generation. However, it is almost impossible to prevent this. Therefore, the twist is corrected measuring the azimuth of the guide tube with a simple type borehole camera. The insertion type clinometer in the aperture is a measure used in many landslide, but a guide pipe and revision of certain setting of the ground and the torsion of the guide pipe are necessary to get right data. And, this manual may be useful internationally.

Management of a large mucosal defect after duodenal endoscopic resection

PubMed Central

Fujihara, Shintaro; Mori, Hirohito; Kobara, Hideki; Nishiyama, Noriko; Matsunaga, Tae; Ayaki, Maki; Yachida, Tatsuo; Masaki, Tsutomu

2016-01-01

Duodenal endoscopic resection is the most difficult type of endoscopic treatment in the gastrointestinal tract (GI) and is technically challenging because of anatomical specificities. In addition to these technical difficulties, this procedure is associated with a significantly higher rate of complication than endoscopic treatment in other parts of the GI tract. Postoperative delayed perforation and bleeding are hazardous complications, and emergency surgical intervention is sometimes required. Therefore, it is urgently necessary to establish a management protocol for preventing serious complications. For instance, the prophylactic closure of large mucosal defects after endoscopic resection may reduce the risk of hazardous complications. However, the size of mucosal defects after endoscopic submucosal dissection (ESD) is relatively large compared with the size after endoscopic mucosal resection, making it impossible to achieve complete closure using only conventional clips. The over-the-scope clip and polyglycolic acid sheets with fibrin gel make it possible to close large mucosal defects after duodenal ESD. In addition to the combination of laparoscopic surgery and endoscopic resection, endoscopic full-thickness resection holds therapeutic potential for difficult duodenal lesions and may overcome the disadvantages of endoscopic resection in the near future. This review aims to summarize the complications and closure techniques of large mucosal defects and to highlight some directions for management after duodenal endoscopic treatment. PMID:27547003

Prenatal Care Training.

ERIC Educational Resources Information Center

Hagen, Michael

Described is the development and evaluation of a prenatal instructional program designed to prevent birth defects. It is explained that the program, composed of five slide tape units on such topics as nutrition and environmental factors, was field tested and found effective with 97 participants (pregnant high school students, nursing students, and…

Potential use of G-CSF for protection against Streptococcus suis infection in swine

USDA-ARS?s Scientific Manuscript database

The use of immunomodulators is a promising alternative to the use of antibiotics for therapeutic, prophylactic, and metaphylactic use to prevent and combat infectious disease. We developed a replication-defective adenovirus vector that expresses porcine granulocyte colony-stimulating factor (G-CSF) ...

Do defects in ion channel glycosylation set the stage for lethal cardiac arrhythmias?

PubMed

Fozzard, Harry A; Kyle, John W

2002-04-30

Many ion channels are modified by the addition of carbohydrate residues. Fozzard and Kyle discuss evidence that sialic acid residues on glycosylated cardiac sodium and potassium channels may be important for preventing early after-depolarizations that can result in cardiac arrhythmias.

38 CFR 4.15 - Total disability ratings.

Code of Federal Regulations, 2010 CFR

2010-07-01

... must be given to unusual physical or mental effects in individual cases, to peculiar effects of occupational activities, to defects in physical or mental endowment preventing the usual amount of success in overcoming the handicap of disability and to the effect of combinations of disability. Total disability will...

The dev Operon Regulates the Timing of Sporulation during Myxococcus xanthus Development.

PubMed

Rajagopalan, Ramya; Kroos, Lee

2017-05-15

Myxococcus xanthus undergoes multicellular development when starved. Thousands of rod-shaped cells coordinate their movements and aggregate into mounds in which cells differentiate into spores. Mutations in the dev operon impair development. The dev operon encompasses a clustered regularly interspaced short palindromic repeat-associated (CRISPR-Cas) system. Null mutations in devI , a small gene at the beginning of the dev operon, suppress the developmental defects caused by null mutations in the downstream devR and devS genes but failed to suppress defects caused by a small in-frame deletion in devT We provide evidence that the original mutant has a second-site mutation. We show that devT null mutants exhibit developmental defects indistinguishable from devR and devS null mutants, and a null mutation in devI suppresses the defects of a devT null mutation. The similarity of DevTRS proteins to components of the CRISPR-associated complex for antiviral defense (Cascade), together with our molecular characterization of dev mutants, support a model in which DevTRS form a Cascade-like subcomplex that negatively autoregulates dev transcript accumulation and prevents DevI overproduction that would strongly inhibit sporulation. Our results also suggest that DevI transiently inhibits sporulation when regulated normally. The mechanism of transient inhibition may involve MrpC, a key transcription factor, whose translation appears to be weakly inhibited by DevI. Finally, our characterization of a devI devS mutant indicates that very little exo transcript is required for sporulation, which is surprising since Exo proteins help form the polysaccharide spore coat. IMPORTANCE CRISPR-Cas systems typically function as adaptive immune systems in bacteria. The dev CRISPR-Cas system of M. xanthus has been proposed to prevent bacteriophage infection during development, but how dev controls sporulation has been elusive. Recent evidence supported a model in which DevR and DevS prevent overproduction of DevI, a predicted 40-residue inhibitor of sporulation. We provide genetic evidence that DevT functions together with DevR and DevS to prevent DevI overproduction. We also show that spores form about 6 h earlier in mutants lacking devI than in the wild type. Only a minority of natural isolates appear to have a functional dev promoter and devI , suggesting that a functional dev CRISPR-Cas system evolved recently in niches where delayed sporulation and/or protection from bacteriophage infection proved advantageous. Copyright © 2017 American Society for Microbiology.

The dev Operon Regulates the Timing of Sporulation during Myxococcus xanthus Development

PubMed Central

Rajagopalan, Ramya

2017-01-01

ABSTRACT Myxococcus xanthus undergoes multicellular development when starved. Thousands of rod-shaped cells coordinate their movements and aggregate into mounds in which cells differentiate into spores. Mutations in the dev operon impair development. The dev operon encompasses a clustered regularly interspaced short palindromic repeat-associated (CRISPR-Cas) system. Null mutations in devI, a small gene at the beginning of the dev operon, suppress the developmental defects caused by null mutations in the downstream devR and devS genes but failed to suppress defects caused by a small in-frame deletion in devT. We provide evidence that the original mutant has a second-site mutation. We show that devT null mutants exhibit developmental defects indistinguishable from devR and devS null mutants, and a null mutation in devI suppresses the defects of a devT null mutation. The similarity of DevTRS proteins to components of the CRISPR-associated complex for antiviral defense (Cascade), together with our molecular characterization of dev mutants, support a model in which DevTRS form a Cascade-like subcomplex that negatively autoregulates dev transcript accumulation and prevents DevI overproduction that would strongly inhibit sporulation. Our results also suggest that DevI transiently inhibits sporulation when regulated normally. The mechanism of transient inhibition may involve MrpC, a key transcription factor, whose translation appears to be weakly inhibited by DevI. Finally, our characterization of a devI devS mutant indicates that very little exo transcript is required for sporulation, which is surprising since Exo proteins help form the polysaccharide spore coat. IMPORTANCE CRISPR-Cas systems typically function as adaptive immune systems in bacteria. The dev CRISPR-Cas system of M. xanthus has been proposed to prevent bacteriophage infection during development, but how dev controls sporulation has been elusive. Recent evidence supported a model in which DevR and DevS prevent overproduction of DevI, a predicted 40-residue inhibitor of sporulation. We provide genetic evidence that DevT functions together with DevR and DevS to prevent DevI overproduction. We also show that spores form about 6 h earlier in mutants lacking devI than in the wild type. Only a minority of natural isolates appear to have a functional dev promoter and devI, suggesting that a functional dev CRISPR-Cas system evolved recently in niches where delayed sporulation and/or protection from bacteriophage infection proved advantageous. PMID:28264995

Assessing the association between natural food folate intake and blood folate concentrations: a systematic review and Bayesian meta-analysis of trials and observational studies.

PubMed

Marchetta, Claire M; Devine, Owen J; Crider, Krista S; Tsang, Becky L; Cordero, Amy M; Qi, Yan Ping; Guo, Jing; Berry, Robert J; Rosenthal, Jorge; Mulinare, Joseph; Mersereau, Patricia; Hamner, Heather C

2015-04-10

Folate is found naturally in foods or as synthetic folic acid in dietary supplements and fortified foods. Adequate periconceptional folic acid intake can prevent neural tube defects. Folate intake impacts blood folate concentration; however, the dose-response between natural food folate and blood folate concentrations has not been well described. We estimated this association among healthy females. A systematic literature review identified studies (1 1992-3 2014) with both natural food folate intake alone and blood folate concentration among females aged 12-49 years. Bayesian methods were used to estimate regression model parameters describing the association between natural food folate intake and subsequent blood folate concentration. Seven controlled trials and 29 observational studies met the inclusion criteria. For the six studies using microbiologic assay (MA) included in the meta-analysis, we estimate that a 6% (95% Credible Interval (CrI): 4%, 9%) increase in red blood cell (RBC) folate concentration and a 7% (95% CrI: 1%, 12%) increase in serum/plasma folate concentration can occur for every 10% increase in natural food folate intake. Using modeled results, we estimate that a natural food folate intake of ≥ 450 μg dietary folate equivalents (DFE)/day could achieve the lower bound of an RBC folate concentration (~ 1050 nmol/L) associated with the lowest risk of a neural tube defect. Natural food folate intake affects blood folate concentration and adequate intakes could help women achieve a RBC folate concentration associated with a risk of 6 neural tube defects/10,000 live births.

Etude des defauts apparaissant dans les amenagements interieurs des avions d'affaires

NASA Astrophysics Data System (ADS)

Charette, Emilie

The evolution of the aeronautic industry led to the development of new materials for these high performance applications. Among other examples, composite sandwich structures are increasingly used for interior body panels of business airplanes. These structures are assembled and fixed to the fuselage using metallic inserts bonded inside the sandwich panels with an epoxy resin adhesive. A thin film of wood veneer covers the visible side of interior furniture in order to bring sophistication and esthetic to the interior design. However, due to multiple factors, surface defects frequently appear on the veneered side of the panel where inserts are located. Moreover the defects tend to appear months after the airplane delivery causing costly reparations. The sources of defects can be mechanical ( deformation due to an excessive tightening), chemical (shrinkage of the epoxy adhesive) or the result of hygrothermal exposition. It is therefore important to understand the source of such surface defects and ultimately prevent or control their appearance. The present thesis deals with defects from chemical and hygrothermal sources appearing on the composite panels used on the interior body of business jets after aging. The main objective was to identify and quantify phenomena causing the defects on the interior panels of business planes. This research project is the first part of a project sponsored by CRIAQ and NSERC. The interaction of several materials can lead to various phenomena causing the apparition of surface defects. The project was thus divided into three parts in order to study an increasingly complex problem. the first study deals with the characterization of the different constitutive materials taken separately. This first part focused on thermal, rheological and mechanical aspects of epoxy adhesives. It was shown that the two adhesives used have different mechanical properties and cure kinetic reactions. In addition, the mechanical properties of sandwich composites panels were studied. The second study focused on the analysis of hygrothermal influence on the adhesive and the composite sandwich panels taken separately. Humidity and temperature can have an important effect on the constitutive materials, it is therefore important to know their influence. Finally, the third part deals with the influence of hygrothermal aging on a structure combining all the different materials. Sample panels including fixing zones (insert and resin) were made at the industrial partner's facility according to the industrial procedure. Subsequently, the samples have undergone an accelerated aging. By using deflectometry system, changes in local curvatures with respect to the aging conditions were observed. A correlation between the material characterization results, the aging effects and the surface defect gravity was performed to evaluate the sources and the occurrence of defects. Recommendations have also been made to ensure the project continuity. This project, carried out in an industrial context with the collaboration of Centre de Recherche Industrielle du Quebec ( CRIQ), 3M Canada and the Chaire de recherche sur les composites hautes performances (CCHP) of the department of mechanical engineering of Ecole Polytechnique de Montreal, highlights the importance of the choice of methods and materials in the manufacturing of composite structures.

Mechanical Restoration and Failure Analyses of a Hydrogel and Scaffold Composite Strategy for Annulus Fibrosus Repair

PubMed Central

Long, Rose G; Bürki, Alexander; Zysset, Philippe; Eglin, David; Grijpma, Dirk W.; Blanquer, Sebastien BG; Hecht, Andrew C; Iatridis, James C

2015-01-01

Unrepaired defects in the annulus fibrosus of intervertebral discs are associated with degeneration and persistent back pain. A clinical need exists for a disc repair strategy that can seal annular defects, be easily delivered during surgical procedures, and restore biomechanics with low risk of herniation. Multiple annulus repair strategies were developed using poly(trimethylene carbonate) scaffolds optimized for cell delivery, polyurethane membranes designed to prevent herniation, and fibrin-genipin adhesive tuned to annulus fibrosus shear properties. This three-part study evaluated repair strategies for biomechanical restoration, herniation risk and failure mode in torsion, bending and compression at physiological and hyper-physiological loads using a bovine injury model. Fibrin-genipin hydrogel restored some torsional stiffness, bending ROM and disc height loss, with negligible herniation risk and failure was observed histologically at the fibrin-genipin mid-substance following rigorous loading. Scaffold-based repairs partially restored biomechanics, but had high herniation risk even when stabilized with sutured membranes and failure was observed histologically at the interface between scaffold and fibrin-genipin adhesive. Fibrin-genipin was the simplest annulus fibrosus repair solution evaluated that involved an easily deliverable adhesive that filled irregularly-shaped annular defects and partially restored disc biomechanics with low herniation risk, suggesting further evaluation for disc repair may be warranted. PMID:26577987

Hyperspectral range imaging for transportation systems evaluation

NASA Astrophysics Data System (ADS)

Bridgelall, Raj; Rafert, J. B.; Atwood, Don; Tolliver, Denver D.

2016-04-01

Transportation agencies expend significant resources to inspect critical infrastructure such as roadways, railways, and pipelines. Regular inspections identify important defects and generate data to forecast maintenance needs. However, cost and practical limitations prevent the scaling of current inspection methods beyond relatively small portions of the network. Consequently, existing approaches fail to discover many high-risk defect formations. Remote sensing techniques offer the potential for more rapid and extensive non-destructive evaluations of the multimodal transportation infrastructure. However, optical occlusions and limitations in the spatial resolution of typical airborne and space-borne platforms limit their applicability. This research proposes hyperspectral image classification to isolate transportation infrastructure targets for high-resolution photogrammetric analysis. A plenoptic swarm of unmanned aircraft systems will capture images with centimeter-scale spatial resolution, large swaths, and polarization diversity. The light field solution will incorporate structure-from-motion techniques to reconstruct three-dimensional details of the isolated targets from sequences of two-dimensional images. A comparative analysis of existing low-power wireless communications standards suggests an application dependent tradeoff in selecting the best-suited link to coordinate swarming operations. This study further produced a taxonomy of specific roadway and railway defects, distress symptoms, and other anomalies that the proposed plenoptic swarm sensing system would identify and characterize to estimate risk levels.

Advances in mucogingival surgery.

PubMed

Prato, G P

2000-01-01

The term Mucogingival Surgery was proposed by Friedman in 1957 to indicate any surgery "designed to preserve attached gingiva, to remove frena or muscle attachment, and to increase the depth of the vestibule". The aim of this type of surgery was to maintain an adequate amount of attached gingiva and to prevent continuous loss of attachment. This philosophy was supported by many horizontal observations in humans that confirmed the need for a certain band of attached gingiva to maintain periodontal tissue in a healthy state. Subsequently, clinical and experimental studies by Wennström and Lindhe (1983) demonstrated that as long as plaque buildup is kept under careful control there is no minimum width of keratinised gingiva necessary to prevent the development of periodontal disease. These observations reduce the importance of Mucogingival Surgery. Surgical techniques are used mostly to solve aesthetic problems, since the term "Periodontal Plastic Surgery" has been suggested to indicate surgical procedures performed to correct or eliminate anatomical, developmental or traumatic deformities of the gingiva or alveolar mucosa. More recently the Consensus Report of the American Academy of Periodontology (1996) defines Mucogingival Therapy as "non surgical and surgical correction of the defects in morphology, position and/or amount of soft tissue and underlying bone". This assigns importance to non-surgical therapy and to the bone condition because of its influence on the morphology of the defects. In this respect the Mucogingival Therapy includes: Root coverage procedures, Gingival augmentation, Augmentation of the edentulous ridge, Removing of the aberrant frenulum, Prevention of ridge collapse associated with tooth extraction, Crown lengthening, Teeth that are not likely to erupt, Loss of interdental papilla which presents an aesthetic and/or phonetic problem.

Clinical Presentation and Natural History of Hypertrophic Cardiomyopathy in RASopathies.

PubMed

Calcagni, Giulio; Adorisio, Rachele; Martinelli, Simone; Grutter, Giorgia; Baban, Anwar; Versacci, Paolo; Digilio, Maria Cristina; Drago, Fabrizio; Gelb, Bruce D; Tartaglia, Marco; Marino, Bruno

2018-04-01

RASopathies are a heterogeneous group of genetic syndromes characterized by mutations in genes that regulate cellular processes, including proliferation, differentiation, survival, migration, and metabolism. Excluding congenital heart defects, hypertrophic cardiomyopathy is the most frequent cardiovascular defect in patients affected by RASopathies. A worse outcome (in terms of surgical risk and/or mortality) has been described in a specific subset of Rasopathy patients with early onset, severe hypertrophic cardiomyopathy presenting with heart failure. New short-term therapy with a mammalian target of rapamycin inhibitor has recently been used to prevent heart failure in these patients with a severe form of hypertrophic cardiomyopathy. Copyright © 2017 Elsevier Inc. All rights reserved.

Folate and epigenetic mechanisms in neural tube development and defects.

PubMed

Meethal, Sivan Vadakkadath; Hogan, Kirk J; Mayanil, Chandra S; Iskandar, Bermans J

2013-09-01

Multiple genetic and epigenetic factors involved in central nervous system (CNS) development influence the incidence of neural tube defects (NTDs). The beneficial effect of periconceptional folic acid on NTD prevention denotes a vital role for the single-carbon biochemical pathway in NTD genesis. Indeed, NTDs are associated with polymorphisms in a diversity of genes that encode folate pathway enzymes. Recent evidence suggests that CNS development and function, and consequently NTDs, are also associated with epigenetic mechanisms, many of which participate in the folate cycle and its input and output pathways. We provide an overview with select examples drawn from the authors' research.

Prenatal folic acid use associated with decreased risk of myelomeningocele: A case-control study offers further support for folic acid fortification in Bangladesh.

PubMed

Kancherla, Vijaya; Ibne Hasan, Md Omar Sharif; Hamid, Rezina; Paul, Ligi; Selhub, Jacob; Oakley, Godfrey; Quamruzzaman, Quazi; Mazumdar, Maitreyi

2017-01-01

Neural tube defects contribute to severe morbidity and mortality in children and adults; however, they are largely preventable through maternal intake of folic acid before and during early pregnancy. We examined the association between maternal prenatal folic acid supplement intake and risk of myelomeningocele (a severe and common type of neural tube defect) in the offspring. We performed secondary analysis using data from a case-control study conducted at Dhaka Community Hospital, Bangladesh between April and November of 2013. Cases and controls included children with and without myelomeningocele, respectively, and their mothers. Cases were identified from local hospitals and rural health clinics served by Dhaka Community Hospital. Controls were selected from pregnancy registries located in the same region as the cases, and matched (1:1) to cases by age and sex. Myelomeningocele in the offspring was confirmed by a pediatrician with expertise in classifying neural tube defects. Maternal prenatal folic acid supplement intake was the main exposure of interest. We estimated crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression analysis. There were 53 pairs of matched cases and controls in our study. Overall, 51% of case mothers reported using folic acid supplements during pregnancy compared to 72% of control mothers (p = 0.03). Median plasma folate concentrations at the time of study visit were 2.79 ng/mL and 2.86 ng/mL among case and control mothers, respectively (p = 0.85). Maternal prenatal folic acid use significantly decreased the odds of myelomeningocele in the offspring (unadjusted OR = 0.42, 95% CI = 0.18-0.96). The association was slightly attenuated after adjusting for maternal age at the time of pregnancy (adjusted OR = 0.43, 95% CI = 0.18-1.02). Our study confirms the protective association between maternal prenatal folic acid supplement use and myelomeningocele among children born in Bangladesh. Our findings point to an overall low folic acid supplement use and low plasma folate concentrations among women of reproductive age in Bangladesh. Mandatory fortification of staple foods with folic acid can address low folate status among women of child-bearing age, and prevent child morbidity and mortality associated with myelomeningocele in Bangladesh.

Prevention of infection in children and adolescents with primary immunodeficiency disorders.

PubMed

Papadopoulou-Alataki, Efimia; Hassan, Amel; Davies, E Graham

2012-12-01

Primary Immunodeficiency diseases (PIDs) are a heterogenous group of inherited disorders that may involve one or multiple components of the immune system. PIDs are uncommon, chronic and severe disorders, in which patients cannot mount a sufficiently protective immune response, leading to an increased susceptibility to infections. This review addresses the current practices for the prevention of infection in children and adolescents with PIDs, particular covering immunisations and antimicrobial prophylaxis. Over recent years, there have been major advances in molecular and cellular understanding in the field of PIDs. Many different disorders are recognised with variable spectra of infection susceptibility depending on the particular aspects of the immune response that are affected. Immunoglobulin prophylaxis is the mainstay of treatment for PIDs and provides passive protection. Prophylactic antimicrobials are efficacious in children and adolescents with predominant defects in primary T cell immunodeficiency diseases and phagocytic disorders, and also with predominant defects in antibody production. Prophylactic antibiotics are suggested for patients with antibody deficiency diseases if recurrent infections exceed three per year, if severe infections occur despite adequate immunoglobulin replacement and in hypogammaglobulinaemic patients who have bronchiectasis. Certain immunisations are effective in antibody deficiencies, T cell deficiencies, complement deficiencies and phagocytic disorders. There are remarkably few published data relating to clinical management aimed at preventing infectious complications in children and adolescents with PIDs. The cornerstones of the prevention of infection in most PID patients are: antimicrobial prophylaxis, appropriate vaccination, immunoglobulin replacement, for the more severe cases, and regular ongoing follow-up.

Topological defects in epithelia govern cell death and extrusion

NASA Astrophysics Data System (ADS)

Saw, Thuan Beng; Doostmohammadi, Amin; Nier, Vincent; Kocgozlu, Leyla; Thampi, Sumesh; Toyama, Yusuke; Marcq, Philippe; Lim, Chwee Teck; Yeomans, Julia M.; Ladoux, Benoit

2017-04-01

Epithelial tissues (epithelia) remove excess cells through extrusion, preventing the accumulation of unnecessary or pathological cells. The extrusion process can be triggered by apoptotic signalling, oncogenic transformation and overcrowding of cells. Despite the important linkage of cell extrusion to developmental, homeostatic and pathological processes such as cancer metastasis, its underlying mechanism and connections to the intrinsic mechanics of the epithelium are largely unexplored. We approach this problem by modelling the epithelium as an active nematic liquid crystal (that has a long range directional order), and comparing numerical simulations to strain rate and stress measurements within monolayers of MDCK (Madin Darby canine kidney) cells. Here we show that apoptotic cell extrusion is provoked by singularities in cell alignments in the form of comet-shaped topological defects. We find a universal correlation between extrusion sites and positions of nematic defects in the cell orientation field in different epithelium types. The results confirm the active nematic nature of epithelia, and demonstrate that defect-induced isotropic stresses are the primary precursors of mechanotransductive responses in cells, including YAP (Yes-associated protein) transcription factor activity, caspase-3-mediated cell death, and extrusions. Importantly, the defect-driven extrusion mechanism depends on intercellular junctions, because the weakening of cell-cell interactions in an α-catenin knockdown monolayer reduces the defect size and increases both the number of defects and extrusion rates, as is also predicted by our model. We further demonstrate the ability to control extrusion hotspots by geometrically inducing defects through microcontact printing of patterned monolayers. On the basis of these results, we propose a mechanism for apoptotic cell extrusion: spontaneously formed topological defects in epithelia govern cell fate. This will be important in predicting extrusion hotspots and dynamics in vivo, with potential applications to tissue regeneration and the suppression of metastasis. Moreover, we anticipate that the analogy between the epithelium and active nematic liquid crystals will trigger further investigations of the link between cellular processes and the material properties of epithelia.

MOCVD growth of gallium nitride with indium surfactant

NASA Astrophysics Data System (ADS)

Won, Dong Jin

In this thesis research, the effect of indium surfactant on Ga-polar and N-polar GaN films grown at 950 °C by MOCVD on various substrates such as Si-face SiC, bulk GaN, Si(111), and C-face SiC was studied to investigate the stress relaxation mechanism, structural, and optical properties of GaN films which were modified by the indium surfactant. The effect of indium surfactant on GaN films grown on SiC was studied first. In the 1.8 microm thick Ga-polar GaN films grown on lattice-mismatched Si-face SiC substrates utilizing indium surfactant at 950 °C, inverted hexagonal pyramid surface defects, so-called V-defects which consist of six (1011) planes, formed at threading dislocations on the GaN surface, which gave rise to the relaxation of compressive misfit stress in an elastic way. Simultaneously, enhanced surface mobility of Ga and N adatoms with indium surfactant lead to improved 2D growth, which may be contradictory to the formation of surface defects like V-defects. In order to find the driving force for V-defect formation in the presence of indium, a nucleation and growth model was developed, taking into consideration the strain, surface, and dislocation energies modified by indium surfactant. This model found that the V-defect formation can be energetically preferred since indium reduces the surface energy of the (1011) plane, which gives rise to the V-defect formation and growth that can overcome the energy barrier at the critical radius of the V-defect. These Ga-polar GaN films were found to be unintentionally doped with Si. Thus, an investigation into the effect of intentional Si doping at a constant TMIn flow rate on GaN films was also performed. Si turned out to be another important factor in the generation of V-defects because Si may be captured at the threading dislocation cores by forming Si -- N bonds, acting as a mask to locally prevent GaN growth. This behavior appeared to assist the initiation of the V-defect which enables V-defects to easily grow beyond the critical radius. Thus, introduction of indium surfactant and Si doping was found to be the most favorable conditions for V-defect formation in Ga-polar GaN films grown on Si-face SiC substrates. The nucleation and growth model predicted that V-defects may not form in homoepitaxy because the energy barrier for V-defect formation approaches infinity due to zero misfit stress. When indium surfactant and Si dopant were introduced simultaneously during the homoepitaxial growth, V-defects did not form in 1.8 microm thick Ga-polar GaN films grown at 950 °C on bulk GaN that had very low threading dislocation density, as predicted by the nucleation and growth model. Ga-polar GaN films grown on Si(111) substrates using indium surfactant showed that additional tensile stress was induced by indium with respect to the reference GaN. Since cracking is known to be a stress relaxation mechanism for tension, the In-induced additional tensile stress is thus detrimental to the GaN films which experience the tensile thermal stress associated with the difference in coefficient of thermal expansion between GaN and the substrate during cooling after growth. The generation of tensile stress by indium seemed correlated with a reduction of V-defects since a high density of V-defects formed under the initial compressive stress at the GaN nucleation stage and then V-defect density decreased as the film grew. Even though the initial misfit stress of the GaN film grown on Si(111) was lower than that of GaN grown on SiC, a high density of V-defects were created under the initial compressive stress. Therefore, the high density of threading dislocations was believed to strongly drive the V-defect formation under In-rich conditions. Consequently, without using high quality bulk GaN substrates, V-defects could not be avoided in Ga-polar GaN films grown on foreign substrates such as Si-face SiC and Si(111) in the presence of indium surfactant and Si dopants during growth. Thus, N-polar GaN films were investigated using vicinal C-face SiC substrates because a theoretical study utilizing first-principles calculations predicted that V-defects are not energetically favored on the N-face GaN. When indium surfactant and Si doping were used during N-polar GaN growth, V-defects did not form, as predicted by theory. This observation suggests that V-defect free N-polar InGaN alloys also can be achieved, which may enable stable green laser diodes with long lifetime to be fabricated using the high indium composition N-polar InGaN films. (Abstract shortened by UMI.)

The effect of sputter temperature on vacancy island behavior on Ni(111) measured by photoemission of adsorbed xenon

NASA Astrophysics Data System (ADS)

Malafsky, Geoffrey P.

1994-04-01

The temperature dependence of vacancy coalescence on an ion bombarded Ni(111) surface is measured by photoemission of adsorbed xenon (PAX). The Ni(111) crystal is sputtered by a low fluence (0.06 ML incident ions) Ar + ion beam with incident kinetic energies of 500-3000 eV. The Xe coverage decreases rapidly with increasing temperature between 88 and 375 K with little additional change from 375 to 775 K. The PAX spectra are acquired with a Xe chamber pressure of 8 × 10 -10 Torr and at a temperature of 88 K. Under these conditions, the Xe is selectively adsorbed at defect sites which would make the Xe coverage proportional to the surface defect density on simple defect structures but the large size of the Xe atom relative to the Ni atom prevents the direct relationship of Xe coverage to the defect density when complex and varying defect structures are present. The decrease in Xe coverage is not attributed to the loss of defect sites by adatom-vacancy recombination but the changing vacancy island shape and size with temperature which alters the ratio of adsorbed Xe atoms to surface vacancy sites. This ratio decreases with increasing temperature as the vacancy islands progress from small and irregularly shaped islands to larger and hexagonally shaped islands. This transition is seen in Monte Carlo simulations of the kinetically driven atomic diffusion on the sputtered surface.

Imaging atomic-scale effects of high-energy ion irradiation on superconductivity and vortex pinning in Fe(Se,Te)

PubMed Central

Massee, Freek; Sprau, Peter Oliver; Wang, Yong-Lei; Davis, J. C. Séamus; Ghigo, Gianluca; Gu, Genda D.; Kwok, Wai-Kwong

2015-01-01

Maximizing the sustainable supercurrent density, JC, is crucial to high-current applications of superconductivity. To achieve this, preventing dissipative motion of quantized vortices is key. Irradiation of superconductors with high-energy heavy ions can be used to create nanoscale defects that act as deep pinning potentials for vortices. This approach holds unique promise for high-current applications of iron-based superconductors because JC amplification persists to much higher radiation doses than in cuprate superconductors without significantly altering the superconducting critical temperature. However, for these compounds, virtually nothing is known about the atomic-scale interplay of the crystal damage from the high-energy ions, the superconducting order parameter, and the vortex pinning processes. We visualize the atomic-scale effects of irradiating FeSexTe1−x with 249-MeV Au ions and find two distinct effects: compact nanometer-sized regions of crystal disruption or “columnar defects,” plus a higher density of single atomic site “point” defects probably from secondary scattering. We directly show that the superconducting order is virtually annihilated within the former and suppressed by the latter. Simultaneous atomically resolved images of the columnar crystal defects, the superconductivity, and the vortex configurations then reveal how a mixed pinning landscape is created, with the strongest vortex pinning occurring at metallic core columnar defects and secondary pinning at clusters of point-like defects, followed by collective pinning at higher fields. PMID:26601180

Imaging atomic-scale effects of high-energy ion irradiation on superconductivity and vortex pinning in Fe(Se,Te).

PubMed

Massee, Freek; Sprau, Peter Oliver; Wang, Yong-Lei; Davis, J C Séamus; Ghigo, Gianluca; Gu, Genda D; Kwok, Wai-Kwong

2015-05-01

Maximizing the sustainable supercurrent density, J C, is crucial to high-current applications of superconductivity. To achieve this, preventing dissipative motion of quantized vortices is key. Irradiation of superconductors with high-energy heavy ions can be used to create nanoscale defects that act as deep pinning potentials for vortices. This approach holds unique promise for high-current applications of iron-based superconductors because J C amplification persists to much higher radiation doses than in cuprate superconductors without significantly altering the superconducting critical temperature. However, for these compounds, virtually nothing is known about the atomic-scale interplay of the crystal damage from the high-energy ions, the superconducting order parameter, and the vortex pinning processes. We visualize the atomic-scale effects of irradiating FeSe x Te1-x with 249-MeV Au ions and find two distinct effects: compact nanometer-sized regions of crystal disruption or "columnar defects," plus a higher density of single atomic site "point" defects probably from secondary scattering. We directly show that the superconducting order is virtually annihilated within the former and suppressed by the latter. Simultaneous atomically resolved images of the columnar crystal defects, the superconductivity, and the vortex configurations then reveal how a mixed pinning landscape is created, with the strongest vortex pinning occurring at metallic core columnar defects and secondary pinning at clusters of point-like defects, followed by collective pinning at higher fields.

Drugging the Cancers Addicted to DNA Repair.

PubMed

Nickoloff, Jac A; Jones, Dennie; Lee, Suk-Hee; Williamson, Elizabeth A; Hromas, Robert

2017-11-01

Defects in DNA repair can result in oncogenic genomic instability. Cancers occurring from DNA repair defects were once thought to be limited to rare inherited mutations (such as BRCA1 or 2). It now appears that a clinically significant fraction of cancers have acquired DNA repair defects. DNA repair pathways operate in related networks, and cancers arising from loss of one DNA repair component typically become addicted to other repair pathways to survive and proliferate. Drug inhibition of the rescue repair pathway prevents the repair-deficient cancer cell from replicating, causing apoptosis (termed synthetic lethality). However, the selective pressure of inhibiting the rescue repair pathway can generate further mutations that confer resistance to the synthetic lethal drugs. Many such drugs currently in clinical use inhibit PARP1, a repair component to which cancers arising from inherited BRCA1 or 2 mutations become addicted. It is now clear that drugs inducing synthetic lethality may also be therapeutic in cancers with acquired DNA repair defects, which would markedly broaden their applicability beyond treatment of cancers with inherited DNA repair defects. Here we review how each DNA repair pathway can be attacked therapeutically and evaluate DNA repair components as potential drug targets to induce synthetic lethality. Clinical use of drugs targeting DNA repair will markedly increase when functional and genetic loss of repair components are consistently identified. In addition, future therapies will exploit artificial synthetic lethality, where complementary DNA repair pathways are targeted simultaneously in cancers without DNA repair defects. © The Author 2017. Published by Oxford University Press.

Monitoring Welding-Gas Quality

NASA Technical Reports Server (NTRS)

Huddleston, Kevin L.

1988-01-01

System monitors welding gas to ensure characteristics within predetermined values. Responds to changes that might go unnoticed by human operator and acts quickly to prevent weld defects. Electronic pressure controller employs various amounts of gain, equalization, and compensation to respond to changes in gas-supply pressure. Works in conjuction with pressure/oxygen/moisture monitor.

Site-directed Nanotherapeutics to Abrogate RRMS and Promote Remyelination Repair (Rev)

DTIC Science & Technology

2013-03-01

in the labs additionally delayed the onset of the practical work.  Long lasting defect in freeze / dryer prevented a more in depth investigation of...drug content and reduced functionality of the peptides. Freezing of the NP without cryoprotection leads to disassembly; freezing with a cryoprotectant

Tracheal invasion by Thyroid nodule in Thyroidectomy

DTIC Science & Technology

2017-10-20

through the first tracheal ring. The tracheal defect was fixed with a strap muscle flap and surgery concluded uneventfully. Following deep extubation, an...air leak at the surgical site was noted. The patient was reintubated, the incision was re-opened and the tracheal flap was revised to prevent tracheal leaking.

77 FR 19074 - Airworthiness Directives; DASSAULT AVIATION Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-30

... reports of fuel leakage from a defective fuel high-level sensor located in the wing front spar. This AD requires inspecting to determine fuel quantity sensors part numbers and replacing of certain fuel quantity sensors with new fuel quantity sensors. We are issuing this AD to prevent internal fuel leakage with...

School Security and Safety.

ERIC Educational Resources Information Center

Licht, Kenneth F.

The author contends that safety and accident prevention should be given primary consideration in a school system's risk management program. He argues that accidents and losses are symptoms of defects in the management system. Two classes of loss discussed are (1) accidental -- injury/loss resulting from unintended events; and (2) purposeful --…

77 FR 76492 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-28

... and older but are not proficient with diagnosing infants or younger children because children age 5...). Background and Brief Description The Division of Human Development and Disability, located within NCBDDD, promotes the health of babies, children, and adults, with a focus on preventing birth defects and...

77 FR 37050 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-20

... proficient with diagnosing infants or younger children because children age 5 and younger require a different... Division of Human Development and Disability, located within NCBDDD, promotes the health of babies, children, and adults, with a focus on preventing birth defects and developmental disabilities and...

A Process for Making On-Going Improvements for Dispensing Medication: Using a TQM Approach

DTIC Science & Technology

1991-06-01

Technical, February 1991. 5. " Poka - Yoke , Improving Product Quality by Preventing Defects," English Trans-ation, 1988, Productivity, Inc., Edited by NKS...Source Inspection and the Poka - Yoke System, English Translation, Productiv- ity, Inc., p. v (preface), 1986. 58 INITIAL DISTRIBUTION LIST No. of

78 FR 23458 - Airworthiness Directives; Dassault Aviation Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-19

... aircraft flight manual (AFM); performing operational tests of the oxygen mask oxygen assembly; and... prompted by failure of the flight crew oxygen supply due to a potentially defective flight crew mask oxygen assembly. We are issuing this AD to prevent failure to supply oxygen upon demand to the flight crew in...

76 FR 27325 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... Enhanced Implementation of the ``Learn the Signs. Act Early.'' Campaign in 4 Target Sites,--New--National Center on Birth Defects and Developmental Disabilities (NCBDDD), Centers for Disease Control and Prevention (CDC). Background and Brief Description CDC's ``Learn the Signs Act Early'' campaign is a health...

Coulomb spin liquid in anion-disordered pyrochlore Tb 2Hf 2O 7

DOE PAGES

Sibille, Romain; Lhotel, Elsa; Hatnean, Monica Ciomaga; ...

2017-10-12

Here, the charge ordered structure of ions and vacancies characterizing rare-earth pyrochlore oxides serves as a model for the study of geometrically frustrated magnetism. The organization of magnetic ions into networks of corner-sharing tetrahedra gives rise to highly correlated magnetic phases with strong fluctuations, including spin liquids and spin ices. It is an open question how these ground states governed by local rules are affected by disorder. Here we demonstrate in the pyrochlore Tb 2Hf 2O 7, that the vicinity of the disordering transition towards a defective fluorite structure translates into a tunable density of anion Frenkel disorder while cationsmore » remain ordered. Quenched random crystal fields and disordered exchange interactions can therefore be introduced into otherwise perfect pyrochlore lattices of magnetic ions. We show that disorder can play a crucial role in preventing long-range magnetic order at low temperatures, and instead induces a strongly fluctuating Coulomb spin liquid with defect-induced frozen magnetic degrees of freedom.« less

Automated detection of retinal nerve fiber layer defects on fundus images: false positive reduction based on vessel likelihood

NASA Astrophysics Data System (ADS)

Muramatsu, Chisako; Ishida, Kyoko; Sawada, Akira; Hatanaka, Yuji; Yamamoto, Tetsuya; Fujita, Hiroshi

2016-03-01

Early detection of glaucoma is important to slow down or cease progression of the disease and for preventing total blindness. We have previously proposed an automated scheme for detection of retinal nerve fiber layer defect (NFLD), which is one of the early signs of glaucoma observed on retinal fundus images. In this study, a new multi-step detection scheme was included to improve detection of subtle and narrow NFLDs. In addition, new features were added to distinguish between NFLDs and blood vessels, which are frequent sites of false positives (FPs). The result was evaluated with a new test dataset consisted of 261 cases, including 130 cases with NFLDs. Using the proposed method, the initial detection rate was improved from 82% to 98%. At the sensitivity of 80%, the number of FPs per image was reduced from 4.25 to 1.36. The result indicates the potential usefulness of the proposed method for early detection of glaucoma.

Xeroderma pigmentosum neurological abnormalities correlate with colony-forming ability after ultraviolet radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrews, A.D.; Barrett, S.F.; Robbins, J.H.

1978-04-01

Xeroderma pigmentosum is an autosomal recessive disease in which DNA repair processes are defective. All xeroderma pigmentosum patients develop premature aging of sun exposed skin, and some develop neurological abnormalities due to premature death of nerve cells. Sensitivity to ultraviolet radiation of 24 xeroderma pigmentosum fibroblast strains was studied in vitro by measuring each strain's ability to divide and form colonies after irradiation. The most sensitive strains were derived from patients who had an early onset of neurological abnormalities; less sensitive strains were from patients with a later onset; and the most resistant strains were from patients without neurological abnormalities.more » The uv sensitivities of strains from each member of a sibling pair with xeroderma pigmentosum were identical, indicating that uv sensitivity of xeroderma pigmentosum strains is determined by the patient's inherited DNA repair defect. The results suggest that effective DNA repair is required to maintain the functional integrity of the human nervous system by preventing premature death of neurons.« less

PREFACE: The International Workshop on Positron Studies of Defects 2014

NASA Astrophysics Data System (ADS)

Sugita, Kazuki; Shirai, Yasuharu

2016-01-01

The International Workshop on Positron Studies of Defects 2014 (PSD-14) was held in Kyoto, Japan from 14-19 September, 2014. The PSD Workshop brought together positron scientists interested in studying defects to an international platform for presenting and discussing recent results and achievements, including new experimental and theoretical methods in the field. The workshop topics can be characterized as follows: • Positron studies of defects in semiconductors and oxides • Positron studies of defects in metals • New experimental methods and equipment • Theoretical calculations and simulations of momentum distributions, positron lifetimes and other characteristics for defects • Positron studies of defects in combination with complementary methods • Positron beam studies of defects at surfaces, interfaces, in sub-surface regions and thin films • Nanostructures and amorphous materials

Defect reduction for semiconductor memory applications using jet and flash imprint lithography

NASA Astrophysics Data System (ADS)

Ye, Zhengmao; Luo, Kang; Lu, Xiaoming; Fletcher, Brian; Liu, Weijun; Xu, Frank; LaBrake, Dwayne; Resnick, Douglas J.; Sreenivasan, S. V.

2012-07-01

Acceptance of imprint lithography for manufacturing will require demonstration that it can attain defect levels commensurate with the defect specifications of high-end memory devices. Defects occurring during imprinting can generally be broken into two categories; random defects and repeating defects. Examples of random defects include fluid phase imprint defects, such as bubbles, and solid phase imprint defects, such as line collapse. Examples of repeater defects include mask fabrication defects and particle induced defects. Previous studies indicated that soft particles cause nonrepeating defects. Hard particles, on the other hand, can cause either permanent resist plugging or mask damage. In a previous study, two specific defect types were examined; random nonfill defects occurring during the resist filling process and repeater defects caused by interactions with particles on the substrate. We attempted to identify the different types of imprint defect types using a mask with line/space patterns at dimensions as small as 26 nm. An Imprio 500 twenty-wafer per hour development tool was used to study the various defect types. The imprint defect density was reduced nearly four orders of magnitude, down to ˜4/cm2 in a period of two years following the availability of low defect imprint masks at 26-nm half-pitch. This reduction was achieved by identifying the root cause of various defects and then taking the appropriate corrective action.

Ethanol metabolism by alcohol dehydrogenase or cytochrome P450 2E1 differentially impairs hepatic protein trafficking and growth hormone signaling.

PubMed

Doody, Erin E; Groebner, Jennifer L; Walker, Jetta R; Frizol, Brittnee M; Tuma, Dean J; Fernandez, David J; Tuma, Pamela L

2017-12-01

The liver metabolizes alcohol using alcohol dehydrogenase (ADH) and cytochrome P 450 2E1 (CYP2E1). Both enzymes metabolize ethanol into acetaldehyde, but CYP2E1 activity also results in the production of reactive oxygen species (ROS) that promote oxidative stress. We have previously shown that microtubules are hyperacetylated in ethanol-treated polarized, hepatic WIF-B cells and livers from ethanol-fed rats. We have also shown that enhanced protein acetylation correlates with impaired clathrin-mediated endocytosis, constitutive secretion, and nuclear translocation and that the defects are likely mediated by acetaldehyde. However, the roles of CYP2E1-generated metabolites and ROS in microtubule acetylation and these alcohol-induced impairments have not been examined. To determine if CYP2E1-mediated alcohol metabolism is required for enhanced acetylation and the trafficking defects, we coincubated cells with ethanol and diallyl sulfide (DAS; a CYP2E1 inhibitor) or N -acetyl cysteine (NAC; an antioxidant). Both agents failed to prevent microtubule hyperacetylation in ethanol-treated cells and also failed to prevent impaired secretion or clathrin-mediated endocytosis. Somewhat surprisingly, both DAS and NAC prevented impaired STAT5B nuclear translocation. Further examination of microtubule-independent steps of the pathway revealed that Jak2/STAT5B activation by growth hormone was prevented by DAS and NAC. These results were confirmed in ethanol-exposed HepG2 cells expressing only ADH or CYP2E1. Using quantitative RT-PCR, we further determined that ethanol exposure led to blunted growth hormone-mediated gene expression. In conclusion, we determined that alcohol-induced microtubule acetylation and associated defects in microtubule-dependent trafficking are mediated by ADH metabolism whereas impaired microtubule-independent Jak2/STAT5B activation is mediated by CYP2E1 activity. NEW & NOTEWORTHY Impaired growth hormone-mediated signaling is observed in ethanol-exposed hepatocytes and is explained by differential effects of alcohol dehydrogenase (ADH)- and cytochrome P 450 2E1 (CYP2E1)-mediated ethanol metabolism on the Jak2/STAT5B pathway. Copyright © 2017 the American Physiological Society.

Effects of artificial tracheal fixation on tracheal epithelial regeneration and prevention of tracheal stenosis.

PubMed

Nakaegawa, Yuta; Nakamura, Ryosuke; Tada, Yasuhiro; Suzuki, Ryo; Takezawa, Toshiaki; Nakamura, Tatsuo; Omori, Koichi

2017-06-01

Tight fixation of the artificial trachea is important for epithelialization and tracheal stenosis. The authors have developed an artificial trachea and have used it for tracheal reconstruction. Although various studies on tracheal reconstruction have been conducted, no studies have examined the effect of artificial tracheal fixation on tracheal stenosis and regeneration. Therefore, the purpose of the present study was to evaluate the effect of artificial tracheal fixation. Preliminary animal experiment. Artificial tracheae were implanted into rabbits with partial tracheal defects. Tracheal stenosis and regeneration of the tracheal epithelium on the artificial tracheae were evaluated by endoscopic examination, scanning electron microscopic analysis, and histological examination. The artificial tracheae fixed to the tracheal defects were classified into three groups (0-point, 4-point, and 8-point) by the number of fixation points. At 14 and 28 days post-implantation, the luminal surface of the implantation area was mostly covered with epithelium in all fixation groups. However, a small amount of granulation tissue was observed in the 0-point fixation group at 14 days post-implantation. Moreover, tracheal stenosis did not occur in the 8-point fixation group, but stenosis was detected in the other groups.

Labor market productivity costs for caregivers of children with spina bifida: a population-based analysis.

PubMed

Tilford, John M; Grosse, Scott D; Goodman, Allen C; Li, Kemeng

2009-01-01

Caregiver productivity costs are an important component of the overall cost of care for individuals with birth defects and developmental disabilities, yet few studies provide estimates for use in economic evaluations. This study estimates labor market productivity costs for caregivers of children and adolescents with spina bifida. Case families were recruited from a state birth defects registry in Arkansas. Primary caregivers of children with spina bifida (N = 98) reported their employment status in the past year and demographic characteristics. Controls were abstracted from the Current Population Survey covering the state of Arkansas for the same time period (N = 416). Estimates from regression analyses of labor market outcomes were used to calculate differences in hours worked per week and lifetime costs. Caregivers of children with spina bifida worked an annual average of 7.5 to 11.3 hours less per week depending on the disability severity. Differences in work hours by caregivers of children with spina bifida translated into lifetime costs of $133,755 in 2002 dollars using a 3% discount rate and an age- and sex-adjusted earnings profile. Including caregivers' labor market productivity costs in prevention effectiveness estimates raises the net cost savings per averted case of spina bifida by 48% over the medical care costs alone. Information on labor market productivity costs for caregivers can be used to better inform economic evaluations of prevention and treatment strategies for spina bifida. Cost-effectiveness calculations that omit caregiver productivity costs substantially overstate the net costs of the intervention and underestimate societal value.

Defect of Fe-S cluster binding by DNA polymerase δ in yeast suppresses UV-induced mutagenesis, but enhances DNA polymerase ζ - dependent spontaneous mutagenesis.

PubMed

Stepchenkova, E I; Tarakhovskaya, E R; Siebler, H M; Pavlov, Y I

2017-01-01

Eukaryotic genomes are duplicated by a complex machinery, utilizing high fidelity replicative B-family DNA polymerases (pols) α, δ and ε. Specialized error-prone pol ζ, the fourth B-family member, is recruited when DNA synthesis by the accurate trio is impeded by replication stress or DNA damage. The damage tolerance mechanism dependent on pol ζ prevents DNA/genome instability and cell death at the expense of increased mutation rates. The pol switches occurring during this specialized replication are not fully understood. The loss of pol ζ results in the absence of induced mutagenesis and suppression of spontaneous mutagenesis. Disruption of the Fe-S cluster motif that abolish the interaction of the C-terminal domain (CTD) of the catalytic subunit of pol ζ with its accessory subunits, which are shared with pol δ, leads to a similar defect in induced mutagenesis. Intriguingly, the pol3-13 mutation that affects the Fe-S cluster in the CTD of the catalytic subunit of pol δ also leads to defective induced mutagenesis, suggesting the possibility that Fe-S clusters are essential for the pol switches during replication of damaged DNA. We confirmed that yeast strains with the pol3-13 mutation are UV-sensitive and defective in UV-induced mutagenesis. However, they have increased spontaneous mutation rates. We found that this increase is dependent on functional pol ζ. In the pol3-13 mutant strain with defective pol δ, there is a sharp increase in transversions and complex mutations, which require functional pol ζ, and an increase in the occurrence of large deletions, whose size is controlled by pol ζ. Therefore, the pol3-13 mutation abrogates pol ζ-dependent induced mutagenesis, but allows for pol ζ recruitment for the generation of spontaneous mutations and prevention of larger deletions. These results reveal differential control of the two major types of pol ζ-dependent mutagenesis by the Fe-S cluster present in replicative pol δ. Copyright © 2016 Elsevier B.V. All rights reserved.

Prospectives for Gene Therapy of Retinal Degenerations

PubMed Central

Thumann, Gabriele

2012-01-01

Retinal degenerations encompass a large number of diseases in which the retina and associated retinal pigment epithelial (RPE) cells progressively degenerate leading to severe visual disorders or blindness. Retinal degenerations can be divided into two groups, a group in which the defect has been linked to a specific gene and a second group that has a complex etiology that includes environmental and genetic influences. The first group encompasses a number of relatively rare diseases with the most prevalent being Retinitis pigmentosa that affects approximately 1 million individuals worldwide. Attempts have been made to correct the defective gene by transfecting the appropriate cells with the wild-type gene and while these attempts have been successful in animal models, human gene therapy for these inherited retinal degenerations has only begun recently and the results are promising. To the second group belong glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR). These retinal degenerations have a genetic component since they occur more often in families with affected probands but they are also linked to environmental factors, specifically elevated intraocular pressure, age and high blood sugar levels respectively. The economic and medical impact of these three diseases can be assessed by the number of individuals affected; AMD affects over 30 million, DR over 40 million and glaucoma over 65 million individuals worldwide. The basic defect in these diseases appears to be the relative lack of a neurogenic environment; the neovascularization that often accompanies these diseases has suggested that a decrease in pigment epithelium-derived factor (PEDF), at least in part, may be responsible for the neurodegeneration since PEDF is not only an effective neurogenic and neuroprotective agent but also a potent inhibitor of neovascularization. In the last few years inhibitors of vascularization, especially antibodies against vascular endothelial cell growth factors (VEGF), have been used to prevent the neovascularization that accompanies AMD and DR resulting in the amelioration of vision in a significant number of patients. In animal models it has been shown that transfection of RPE cells with the gene for PEDF and other growth factors can prevent or slow degeneration. A limited number of studies in humans have also shown that transfection of RPE cells in vivo with the gene for PEDF is effective in preventing degeneration and restore vision. Most of these studies have used virally mediated gene delivery with all its accompanying side effects and have not been widely used. New techniques using non-viral protocols that allow efficient delivery and permanent integration of the transgene into the host cell genome offer novel opportunities for effective treatment of retinal degenerations. PMID:23372421

Magnifying narrow-band imaging of gastric mucosal morphology predicts the H. pylori-related epigenetic field defect.

PubMed

Tahara, Tomomitsu; Yamazaki, Jumpei; Tahara, Sayumi; Okubo, Masaaki; Kawamura, Tomohiko; Horiguchi, Noriyuki; Ishizuka, Takamitsu; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Shibata, Tomoyuki; Kuroda, Makoto; Ohmiya, Naoki

2017-06-08

DNA methylation is associated with "field defect" in the gastric mucosa. To characterize "field defect" morphologically, we examined DNA methylation of non-neoplastic gastric mucosa in relation to their morphology seen by narrow-band imaging (NBI) with magnifying endoscopy. Magnifying NBI of non-neoplastic gastric body was classified as follows: normal-small and round pits with uniform subepithelial capillary networks; type 1-a little enlarged round pits with indistinct subepithelial capillary networks; type 2-remarkably enlarged pits with irregular vessels; and type 3-clearly demarcated oval or tubulovillous pits with bulky coiled or wavy vessels. Methylation of nine candidate genes (MYOD1, SLC16A12, GDNF, IGF2, MIR 124A1, CDH1, PRDM5, RORA and MLF1) were determined by bisulfite pyrosequencing. Infinium HumanMethylation450 array was used to characterize the methylation of >450,000 CpG sites. Mean Z score methylation of nine genes positively correlated with the changes of mucosal patterns from normal to types 1, 2, and 3 (P < 0.0001). Genome-wide analysis showed that development of mucosal patterns correlated with methylation accumulation especially at CpG islands. Genes with promoter CpG islands that were gradually methylated with the development of mucosal patterns significantly enriched the genes involved in zinc-related pathways. The results indicates that gastric mucosal morphology predicts a "field defect" in this tissue type. Accumulation of DNA methylation is associated with "field defect" in the non-neoplastic gastric mucosa. Endoscopic identification of "field defect" has important implications for preventing gastric cancer. Our results suggest that magnifying NBI of gastric mucosal morphology predicts a "field defect" in the gastric mucosa.

Preventing light-induced degradation in multicrystalline silicon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lindroos, J., E-mail: jeanette.lindroos@aalto.fi; Boulfrad, Y.; Yli-Koski, M.

2014-04-21

Multicrystalline silicon (mc-Si) is currently dominating the silicon solar cell market due to low ingot costs, but its efficiency is limited by transition metals, extended defects, and light-induced degradation (LID). LID is traditionally associated with a boron-oxygen complex, but the origin of the degradation in the top of the commercial mc-Si brick is revealed to be interstitial copper. We demonstrate that both a large negative corona charge and an aluminum oxide thin film with a built-in negative charge decrease the interstitial copper concentration in the bulk, preventing LID in mc-Si.

Preventing light-induced degradation in multicrystalline silicon

NASA Astrophysics Data System (ADS)

Lindroos, J.; Boulfrad, Y.; Yli-Koski, M.; Savin, H.

2014-04-01

Multicrystalline silicon (mc-Si) is currently dominating the silicon solar cell market due to low ingot costs, but its efficiency is limited by transition metals, extended defects, and light-induced degradation (LID). LID is traditionally associated with a boron-oxygen complex, but the origin of the degradation in the top of the commercial mc-Si brick is revealed to be interstitial copper. We demonstrate that both a large negative corona charge and an aluminum oxide thin film with a built-in negative charge decrease the interstitial copper concentration in the bulk, preventing LID in mc-Si.

Awareness, knowledge, and use of folic acid among non-pregnant Korean women of childbearing age

PubMed Central

Kim, Min Ji; Kim, Jihyun; Hwang, Eun Joung; Song, YoonJu; Kim, Heon

2018-01-01

BACKGROUND/OBJECTIVES Folic acid supplementation before pregnancy is known to reduce the risk of neural tube defects. The purposes of this study were to investigate the awareness, knowledge, and use of folic acid supplements along with their associated factors among non-pregnant Korean women of childbearing age. SUBJECTS/METHODS From August 2012 to March 2013, 704 women aged 19–45 years completed a self-administered questionnaire regarding their awareness, knowledge, and use of folic acid as well as questions to identify risk of inadequate folate intake. RESULTS Approximately 67% of women reported that they had heard of folic acid, and 23.7% had knowledge of both the role of folic acid in preventing birth defects and appropriate time for taking folic acid supplements to prevent birth defects. However, only 9.4% of women took folic acid supplements at the time of the survey. Women aged 19–24 years, unmarried women, and women who had never been pregnant were less likely to be aware and knowledgeable of folic acid or take folic acid supplements. In addition, women at high risk of inadequate folate intake were less likely to take folic acid supplements. In a multivariate analysis, women aged 19–24 years, women with a high school diploma or lower education level, and unmarried women were less likely to be aware and have knowledge of folic acid. The percentage of women taking folic acid supplements was significantly higher among knowledgeable women than among unknowledgeable women. CONCLUSIONS These results support our hypothesis that women with knowledge of folic acid are more likely to take folic acid supplements. Therefore, educational programs or campaigns to improve knowledge regarding the importance of folic acid and to promote consumption of folic acid supplements as well as folate-rich foods are needed to target young, less educated, and unmarried women. PMID:29399300

Fibrin sealant for mesh fixation in laparoscopic umbilical hernia repair: 1-year results of a randomized controlled double-blinded study.

PubMed

Eriksen, J R; Bisgaard, T; Assaadzadeh, S; Jorgensen, L N; Rosenberg, J

2013-08-01

Fibrin sealant for mesh fixation has significant positive effects on early outcome after laparoscopic ventral hernia repair (LVHR) compared with titanium tacks. Whether fibrin sealant fixation also results in better long-term outcome is unknown. We performed a randomized controlled trial including patients with umbilical hernia defects from 1.5 to 5 cm at three Danish hernia centres. We used a 12 cm circular mesh. Participants were randomized to fibrin sealant or titanium tack fixation. Patients were seen in the outpatient clinic at 1 and 12 months follow-up. Forty patients were included of whom 34 were available for intention to treat analysis after 1 year. There were no significant differences in pain, discomfort, fatigue, satisfaction or quality of life between the two groups at the 1-year follow-up. Five patients (26 %) in the fibrin sealant group and one (6 %) in the tack group were diagnosed with a recurrence at the 1-year follow-up (p = 0.182) (overall recurrence rate 17 %). Hernia defects in patients with recurrence were significantly larger than in those without recurrence (median 4.0 vs. 2.8 cm, p = 0.009). Patients with larger hernia defects and fibrin sealant mesh fixation had higher recurrence rates than expected, although the study was not powered for assessment of recurrence. There was no significant difference between groups in any parameters after the 1-year follow-up. The beneficial effects of mesh fixation with fibrin sealant on early outcome warrant further studies on optimization of the surgical technique to prevent recurrence.

The role of nitrates in the prevention of preeclampsia: an update.

PubMed

Kalidindi, Madhavi; Velauthar, Luxmi; Khan, Khalid; Aquilina, Joseph

2012-12-01

Defective nitric oxide synthesis and nitric oxide-mediated vasodilatation is widely documented in the pathophysiology of preeclampsia, a leading cause of maternal and perinatal morbidity and mortality worldwide. Several studies demonstrated the beneficial role of nitric oxide agents, especially glyceryl trinitrate and L-arginine in reducing the blood pressure and improving the uteroplacental blood flow velocities. However, there is insufficient evidence on the efficacy and safety of these agents in the prevention of preeclampsia and its complications, as there are very few randomized controlled trials with small number of women. The aim of this review is to summarize and evaluate the role of nitrates in the prevention of preeclampsia based on the available evidence in the literature till date and suggestions for future research. Supplementation with L-arginine and antioxidant vitamins reduced the incidence of preeclampsia in women at high risk of preeclampsia [P < 0.001, absolute risk reduction 0.17 (confidence interval 0.12-0.21)]. On the basis of the recent evidence, nitric oxide agents may be beneficial in the prevention of preeclampsia. Randomized controlled trials initiated in the first trimester and using long-acting nitrates are needed in high-risk women to validate these findings.

Xylitol prevents NEFA-induced insulin resistance in rats

PubMed Central

Kishore, P.; Kehlenbrink, S.; Hu, M.; Zhang, K.; Gutierrez-Juarez, R.; Koppaka, S.; El-Maghrabi, M. R.

2013-01-01

Aims/hypothesis Increased NEFA levels, characteristic of type 2 diabetes mellitus, contribute to skeletal muscle insulin resistance. While NEFA-induced insulin resistance was formerly attributed to decreased glycolysis, it is likely that glucose transport is the rate-limiting defect. Recently, the plant-derived sugar alcohol xylitol has been shown to have favourable metabolic effects in various animal models. Furthermore, its derivative xylulose 5-phosphate may prevent NEFA-induced suppression of glycolysis. We therefore examined whether and how xylitol might prevent NEFA-induced insulin resistance. Methods We examined the ability of xylitol to prevent NEFA-induced insulin resistance. Sustained ~1.5-fold elevations in NEFA levels were induced with Intralipid/heparin infusions during 5 h euglycaemic–hyperinsulinaemic clamp studies in 24 conscious non-diabetic Sprague-Dawley rats, with or without infusion of xylitol. Results Intralipid infusion reduced peripheral glucose uptake by ~25%, predominantly through suppression of glycogen synthesis. Co-infusion of xylitol prevented the NEFA-induced decreases in both glucose uptake and glycogen synthesis. Although glycolysis was increased by xylitol infusion alone, there was minimal NEFA-induced suppression of glycolysis, which was not affected by co-infusion of xylitol. Conclusions/interpretation We conclude that xylitol prevented NEFA-induced insulin resistance, with favourable effects on glycogen synthesis accompanying the improved insulin-mediated glucose uptake. This suggests that this pentose sweetener has beneficial insulin-sensitising effects. PMID:22460760

ANN based Performance Evaluation of BDI for Condition Monitoring of Induction Motor Bearings

NASA Astrophysics Data System (ADS)

Patel, Raj Kumar; Giri, V. K.

2017-06-01

One of the critical parts in rotating machines is bearings and most of the failure arises from the defective bearings. Bearing failure leads to failure of a machine and the unpredicted productivity loss in the performance. Therefore, bearing fault detection and prognosis is an integral part of the preventive maintenance procedures. In this paper vibration signal for four conditions of a deep groove ball bearing; normal (N), inner race defect (IRD), ball defect (BD) and outer race defect (ORD) were acquired from a customized bearing test rig, under four different conditions and three different fault sizes. Two approaches have been opted for statistical feature extraction from the vibration signal. In the first approach, raw signal is used for statistical feature extraction and in the second approach statistical features extracted are based on bearing damage index (BDI). The proposed BDI technique uses wavelet packet node energy coefficients analysis method. Both the features are used as inputs to an ANN classifier to evaluate its performance. A comparison of ANN performance is made based on raw vibration data and data chosen by using BDI. The ANN performance has been found to be fairly higher when BDI based signals were used as inputs to the classifier.

Poly(ADP-ribose) polymerase-dependent energy depletion occurs through inhibition of glycolysis.

PubMed

Andrabi, Shaida A; Umanah, George K E; Chang, Calvin; Stevens, Daniel A; Karuppagounder, Senthilkumar S; Gagné, Jean-Philippe; Poirier, Guy G; Dawson, Valina L; Dawson, Ted M

2014-07-15

Excessive poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) activation kills cells via a cell-death process designated "parthanatos" in which PAR induces the mitochondrial release and nuclear translocation of apoptosis-inducing factor to initiate chromatinolysis and cell death. Accompanying the formation of PAR are the reduction of cellular NAD(+) and energetic collapse, which have been thought to be caused by the consumption of cellular NAD(+) by PARP-1. Here we show that the bioenergetic collapse following PARP-1 activation is not dependent on NAD(+) depletion. Instead PARP-1 activation initiates glycolytic defects via PAR-dependent inhibition of hexokinase, which precedes the NAD(+) depletion in N-methyl-N-nitroso-N-nitroguanidine (MNNG)-treated cortical neurons. Mitochondrial defects are observed shortly after PARP-1 activation and are mediated largely through defective glycolysis, because supplementation of the mitochondrial substrates pyruvate and glutamine reverse the PARP-1-mediated mitochondrial dysfunction. Depleting neurons of NAD(+) with FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, does not alter glycolysis or mitochondrial function. Hexokinase, the first regulatory enzyme to initiate glycolysis by converting glucose to glucose-6-phosphate, contains a strong PAR-binding motif. PAR binds to hexokinase and inhibits hexokinase activity in MNNG-treated cortical neurons. Preventing PAR formation with PAR glycohydrolase prevents the PAR-dependent inhibition of hexokinase. These results indicate that bioenergetic collapse induced by overactivation of PARP-1 is caused by PAR-dependent inhibition of glycolysis through inhibition of hexokinase.

Inherited mutations in the helicase RTEL1 cause telomere dysfunction and Hoyeraal–Hreidarsson syndrome

PubMed Central

Deng, Zhong; Glousker, Galina; Molczan, Aliah; Fox, Alan J.; Lamm, Noa; Dheekollu, Jayaraju; Weizman, Orr-El; Schertzer, Michael; Wang, Zhuo; Vladimirova, Olga; Schug, Jonathan; Aker, Memet; Londoño-Vallejo, Arturo; Kaestner, Klaus H.; Lieberman, Paul M.; Tzfati, Yehuda

2013-01-01

Telomeres repress the DNA damage response at the natural chromosome ends to prevent cell-cycle arrest and maintain genome stability. Telomeres are elongated by telomerase in a tightly regulated manner to ensure a sufficient number of cell divisions throughout life, yet prevent unlimited cell division and cancer development. Hoyeraal–Hreidarsson syndrome (HHS) is characterized by accelerated telomere shortening and a broad range of pathologies, including bone marrow failure, immunodeficiency, and developmental defects. HHS-causing mutations have previously been found in telomerase and the shelterin component telomeric repeat binding factor 1 (TRF1)-interacting nuclear factor 2 (TIN2). We identified by whole-genome exome sequencing compound heterozygous mutations in four siblings affected with HHS, in the gene encoding the regulator of telomere elongation helicase 1 (RTEL1). Rtel1 was identified in mouse by its genetic association with telomere length. However, its mechanism of action and whether it regulates telomere length in human remained unknown. Lymphoblastoid cell lines obtained from a patient and from the healthy parents carrying heterozygous RTEL1 mutations displayed telomere shortening, fragility and fusion, and growth defects in culture. Ectopic expression of WT RTEL1 suppressed the telomere shortening and growth defect, confirming the causal role of the RTEL1 mutations in HHS and demonstrating the essential function of human RTEL1 in telomere protection and elongation. Finally, we show that human RTEL1 interacts with the shelterin protein TRF1, providing a potential recruitment mechanism of RTEL1 to telomeres. PMID:23959892

Inherited mutations in the helicase RTEL1 cause telomere dysfunction and Hoyeraal-Hreidarsson syndrome.

PubMed

Deng, Zhong; Glousker, Galina; Molczan, Aliah; Fox, Alan J; Lamm, Noa; Dheekollu, Jayaraju; Weizman, Orr-El; Schertzer, Michael; Wang, Zhuo; Vladimirova, Olga; Schug, Jonathan; Aker, Memet; Londoño-Vallejo, Arturo; Kaestner, Klaus H; Lieberman, Paul M; Tzfati, Yehuda

2013-09-03

Telomeres repress the DNA damage response at the natural chromosome ends to prevent cell-cycle arrest and maintain genome stability. Telomeres are elongated by telomerase in a tightly regulated manner to ensure a sufficient number of cell divisions throughout life, yet prevent unlimited cell division and cancer development. Hoyeraal-Hreidarsson syndrome (HHS) is characterized by accelerated telomere shortening and a broad range of pathologies, including bone marrow failure, immunodeficiency, and developmental defects. HHS-causing mutations have previously been found in telomerase and the shelterin component telomeric repeat binding factor 1 (TRF1)-interacting nuclear factor 2 (TIN2). We identified by whole-genome exome sequencing compound heterozygous mutations in four siblings affected with HHS, in the gene encoding the regulator of telomere elongation helicase 1 (RTEL1). Rtel1 was identified in mouse by its genetic association with telomere length. However, its mechanism of action and whether it regulates telomere length in human remained unknown. Lymphoblastoid cell lines obtained from a patient and from the healthy parents carrying heterozygous RTEL1 mutations displayed telomere shortening, fragility and fusion, and growth defects in culture. Ectopic expression of WT RTEL1 suppressed the telomere shortening and growth defect, confirming the causal role of the RTEL1 mutations in HHS and demonstrating the essential function of human RTEL1 in telomere protection and elongation. Finally, we show that human RTEL1 interacts with the shelterin protein TRF1, providing a potential recruitment mechanism of RTEL1 to telomeres.

Molecular Targeted Intervention for Pancreatic Cancer

PubMed Central

Mohammed, Altaf; Janakiram, Naveena B.; Pant, Shubham; Rao, Chinthalapally V.

2015-01-01

Pancreatic cancer (PC) remains one of the worst cancers, with almost uniform lethality. PC risk is associated with westernized diet, tobacco, alcohol, obesity, chronic pancreatitis, and family history of pancreatic cancer. New targeted agents and the use of various therapeutic combinations have yet to provide adequate treatments for patients with advanced cancer. To design better preventive and/or treatment strategies against PC, knowledge of PC pathogenesis at the molecular level is vital. With the advent of genetically modified animals, significant advances have been made in understanding the molecular biology and pathogenesis of PC. Currently, several clinical trials and preclinical evaluations are underway to investigate novel agents that target signaling defects in PC. An important consideration in evaluating novel drugs is determining whether an agent can reach the target in concentrations effective to treat the disease. Recently, we have reported evidence for chemoprevention of PC. Here, we provide a comprehensive review of current updates on molecularly targeted interventions, as well as dietary, phytochemical, immunoregulatory, and microenvironment-based approaches for the development of novel therapeutic and preventive regimens. Special attention is given to prevention and treatment in preclinical genetically engineered mouse studies and human clinical studies. PMID:26266422

3D printing of biomaterials with mussel-inspired nanostructures for tumor therapy and tissue regeneration.

PubMed

Ma, Hongshi; Luo, Jian; Sun, Zhe; Xia, Lunguo; Shi, Mengchao; Liu, Mingyao; Chang, Jiang; Wu, Chengtie

2016-12-01

Primary bone cancer brings patients great sufferings. To deal with the bone defects resulted from cancer surgery, biomaterials with good bone-forming ability are necessary to repair bone defects. Meanwhile, in order to prevent possible tumor recurrence, it is essential that the remaining tumor cells around bone defects are completely killed. However, there are few biomaterials with the ability of both cancer therapy and bone regeneration until now. Here, we fabricated a 3D-printed bioceramic scaffold with a uniformly self-assembled Ca-P/polydopamine nanolayer surface. Taking advantage of biocompatibility, biodegradability and the excellent photothermal effect of polydopamine, the bifunctional scaffolds with mussel-inspired nanostructures could be used as a satisfactory and controllable photothermal agent, which effectively induced tumor cell death in vitro, and significantly inhibited tumor growth in mice. In addition, owing to the nanostructured surface, the prepared polydopamine-modified bioceramic scaffolds could support the attachment and proliferation of rabbit bone mesenchymal stem cells (rBMSCs), and significantly promoted the formation of new bone tissues in rabbit bone defects even under photothermal treatment. Therefore, the mussel-inspired nanostructures in 3D-printed bioceramic exhibited a remarkable capability for both cancer therapy and bone regeneration, offering a promising strategy to construct bifunctional biomaterials which could be widely used for therapy of tumor-induced tissue defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

A computer-guided bone block harvesting procedure: a proof-of-principle case report and technical notes.

PubMed

De Stavola, Luca; Fincato, Andrea; Albiero, Alberto Maria

2015-01-01

During autogenous mandibular bone harvesting, there is a risk of damage to anatomical structures, as the surgeon has no three-dimensional control of the osteotomy planes. The aim of this proof-of-principle case report is to describe a procedure for harvesting a mandibular bone block that applies a computer-guided surgery concept. A partially dentate patient who presented with two vertical defects (one in the maxilla and one in the mandible) was selected for an autogenous mandibular bone block graft. The bone block was planned using a computer-aided design process, with ideal bone osteotomy planes defined beforehand to prevent damage to anatomical structures (nerves, dental roots, etc) and to generate a surgical guide, which defined the working directions in three dimensions for the bone-cutting instrument. Bone block dimensions were planned so that both defects could be repaired. The projected bone block was 37.5 mm in length, 10 mm in height, and 5.7 mm in thickness, and it was grafted in two vertical bone augmentations: an 8 × 21-mm mandibular defect and a 6.5 × 18-mm defect in the maxilla. Supraimposition of the preoperative and postoperative computed tomographic images revealed a procedure accuracy of 0.25 mm. This computer-guided bone harvesting technique enables clinicians to obtain sufficient autogenous bone to manage multiple defects safely.

Software risk estimation and management techniques at JPL

NASA Technical Reports Server (NTRS)

Hihn, J.; Lum, K.

2002-01-01

In this talk we will discuss how uncertainty has been incorporated into the JPL software model, probabilistic-based estimates, and how risk is addressed, how cost risk is currently being explored via a variety of approaches, from traditional risk lists, to detailed WBS-based risk estimates to the Defect Detection and Prevention (DDP) tool.