Syndromes, disorders and maternal risk factors associated with neural tube defects (VII).

PubMed

Chen, Chih-Ping

2008-09-01

Neural tube defects (NTDs) may be associated with syndromes, disorders and maternal risk factors. This article provides a comprehensive review of the syndromes, disorders and maternal risk factors associated with NTDs, including DK phocomelia syndrome (von Voss-Cherstvoy syndrome), Siegel-Bartlet syndrome, fetal warfarin syndrome, craniotelencephalic dysplasia, Czeizel-Losonci syndrome, maternal cocaine abuse, Weissenbacher- Zweymller syndrome, parietal foramina (cranium bifidum), Apert syndrome, craniomicromelic syndrome, XXagonadism with multiple dysraphic lesions including omphalocele and NTDs, Fryns microphthalmia syndrome, Gershoni-Baruch syndrome, PHAVER syndrome, periconceptional vitamin B6 deficiency, and autosomal dominant Dandy-Walker malformation with occipital cephalocele. NTDs associated with these syndromes, disorders and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders and maternal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.

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.

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

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

Delayed bleeding and hemorrhage of mucosal defects after gastric endoscopic submucosal dissection on second-look endoscopy.

PubMed

Ono, Shoko; Ono, Masayoshi; Nakagawa, Manabu; Shimizu, Yuichi; Kato, Mototsugu; Sakamoto, Naoya

2016-04-01

Although second-look endoscopy is performed within several days after gastric endoscopic submucosal dissection (ESD), there has been no evidence supporting the usefulness of the intervention. We investigated the relationship between delayed bleeding and hemorrhage of mucosal defects after ESD on second-look endoscopy and analyzed risk factors of active bleeding on second-look endoscopy. A total of 441 consecutive ESD cases with gastric cancer or adenoma were retrospectively analyzed. Second-look endoscopy was performed in the morning after the day of ESD. Bleeding of mucosal defects on second-look endoscopy was classified according to the Forrest classification, and active bleeding was defined as Forrest Ia or Ib. Delayed bleeding was defined as hematemesis or melena after second-look endoscopy. A total of 406 second-look endoscopies were performed, and delayed bleeding occurred in 11 patients. The incidence rate of delayed bleeding after second-look endoscopy in patients with Forrest Ia or Ib was significantly higher than that in patients with Forrest IIa, IIb or III (7.69 vs. 2.02 %, p < 0.05). Complication of a histological ulcer, large size of the resected specimen and long ESD procedure time were shown to be risk factors for hemorrhage of mucosal defects after ESD on second-look endoscopy by univariate analysis. Multivariate analysis indicated that only large size of the resected specimen was a risk factor. In a specimen size of >35 mm, the odds ratio of active bleeding on second-look endoscopy was 1.9. Active bleeding of mucosal defects on second-look endoscopy is a risk factor for delayed bleeding.

Birth defects related to bendectin use in pregnancy. I. Oral clefts and cardiac defects.

PubMed

Mitchell, A A; Rosenberg, L; Shapiro, S; Slone, D

1981-06-12

The risk of birth defects previously associated with Bendectin use in early pregnancy were evaluated in a case-control study of malformed infants whose mothers were interviewed in three regional centers; 98 infants with isolated cleft palate (CP), 221 with cleft lip with or without cleft palate (CL +/- CP), and 122 with selected heart defects (HD) were compared with 970 other malformed infants who served as controls. Relative risk estimates (with their 95% confidence limits) for first-trimester exposure to Bendectin were as follows: CP, 0.9 (0.5 to 1.5); CL +/- CP, 0.6 (0.4 to 0.8); and HD, 1.0 (0.6 to 1.6). Allowance for a large number of potentially confounding factors did not materially influence the risk estimates. These findings suggest that early in utero exposure to Bendectin does not appreciably increase the risk of oral clefts or selected cardiac defects.

Biobehavioral Risk Factors in Children of Schizophrenic Parents.

ERIC Educational Resources Information Center

Erlenmeyer-Kimling, L.; Cornblatt, Barbara

1984-01-01

Research on risk factors for schizophrenia is reviewed with emphasis on children of schizophrenic parents. Four areas of biobehavioral functioning that have been examined in high-risk research are discussed. Three of these are considered compatible with hypothesis neurointegrative defect underlying schizophrenic-proneness. (Author/CL)

Cement Leakage in Percutaneous Vertebral Augmentation for Osteoporotic Vertebral Compression Fractures: Analysis of Risk Factors.

PubMed

Xie, Weixing; Jin, Daxiang; Ma, Hui; Ding, Jinyong; Xu, Jixi; Zhang, Shuncong; Liang, De

2016-05-01

The risk factors for cement leakage were retrospectively reviewed in 192 patients who underwent percutaneous vertebral augmentation (PVA). To discuss the factors related to the cement leakage in PVA procedure for the treatment of osteoporotic vertebral compression fractures. PVA is widely applied for the treatment of osteoporotic vertebral fractures. Cement leakage is a major complication of this procedure. The risk factors for cement leakage were controversial. A retrospective review of 192 patients who underwent PVA was conducted. The following data were recorded: age, sex, bone density, number of fractured vertebrae before surgery, number of treated vertebrae, severity of the treated vertebrae, operative approach, volume of injected bone cement, preoperative vertebral compression ratio, preoperative local kyphosis angle, intraosseous clefts, preoperative vertebral cortical bone defect, and ratio and type of cement leakage. To study the correlation between each factor and cement leakage ratio, bivariate regression analysis was employed to perform univariate analysis, whereas multivariate linear regression analysis was employed to perform multivariate analysis. The study included 192 patients (282 treated vertebrae), and cement leakage occurred in 100 vertebrae (35.46%). The vertebrae with preoperative cortical bone defects generally exhibited higher cement leakage ratio, and the leakage is typically type C. Vertebrae with intact cortical bones before the procedure tend to experience type S leakage. Univariate analysis showed that patient age, bone density, number of fractured vertebrae before surgery, and vertebral cortical bone were associated with cement leakage ratio (P<0.05). Multivariate analysis showed that the main factors influencing bone cement leakage are bone density and vertebral cortical bone defect, with standardized partial regression coefficients of -0.085 and 0.144, respectively. High bone density and vertebral cortical bone defect are independent risk factors associated with bone cement leakage.

[Risk factors for teeth aplasia and hypoplasia in cleft lip and palate children].

PubMed

Korolenkova, M V; Starikova, N V; Ageeva, L V

2016-01-01

The aim of the study was to assess the significance of environmental risk factors for teeth aplasia and hypoplasia in cleft lip and palate children. Two hundred and forty-seven cleft lip and palate (CLP) children were enrolled in the study including 105 (42.5%) with bilateral CLP and 57.5% with unilateral CLP. The mean age was 11.2±4.9 years. Teeth condition was assessed clinically and radiologically. The impact of risk factors for teeth anomalies was analyzed by retrospective data obtained from computer database (absence of preoperative orthopedic treatment, palatal defects after primary palatoplasty and type of primary procedures). Surgical trauma by early periosteoplasty (at the age of 3-4 months), excessive scarring and tissue traction due to absence of early orthopedic treatment and palatal defect were associated with significantly higher incidence of incisors hypoplasia (both developmental enamel defects and microdentia) and aplasia of central incisors not seen in the other study subgroups. Incisors aplasia and hypoplasia in CLP patients do not always have disembryogenic origin but may depend on external environmental factors, including surgical trauma.

The effect of patient selection and surgical technique on the results of Conserve® Plus hip resurfacing--3.5- to 14-year follow-up.

PubMed

Amstutz, Harlan C; Takamura, Karren M; Le Duff, Michel J

2011-04-01

The results of metal-on-metal hip Conserve® Plus resurfacings with up to 14 years of follow-up with and without risk factors of small component size and/or large femoral defects were compared as performed with either first- or second-generation surgical techniques. There was a 99.7% survivorship at ten years for ideal hips (large components and small defects) and a 95.3% survivorship for hips with risk factors optimized technique has measurably improved durability in patients with risk factors at the 8-year mark. The lessons learned can help offset the observed learning curve of resurfacing. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Maternal obesity and congenital heart defects: a population-based study123

PubMed Central

Mills, James L; Troendle, James; Conley, Mary R; Carter, Tonia; Druschel, Charlotte M

2010-01-01

Background: Obesity affects almost one-third of pregnant women and causes many complications, including neural tube defects. It is not clear whether the risk of congenital heart defects, the most common malformations, is also increased. Objective: This study was conducted to determine whether obesity is associated with an increased risk of congenital heart defects. Design: A population-based, nested, case-control study was conducted in infants born with congenital heart defects and unaffected controls from the cohort of all births (n = 1,536,828) between 1993 and 2003 in New York State, excluding New York City. The type of congenital heart defect, maternal body mass index (BMI; in kg/m2), and other risk factors were obtained from the Congenital Malformations Registry and vital records. Mothers of 7392 congenital heart defect cases and 56,304 unaffected controls were studied. Results: All obese women (BMI ≥ 30) were significantly more likely than normal-weight women (BMI: 19–24.9) to have children with a congenital heart defect [odds ratio (OR): 1.15; 95% CI: 1.07, 1.23; P < 0.0001]. Overweight women were not at increased risk (OR: 1.00; 95% CI: 0.94, 1.06). The risk in morbidly obese women (BMI ≥ 40) was higher (OR: 1.33; 95% CI: 1.15, 1.54; P = 0.0001) than that in obese women with a BMI of 30–39.9 (OR: 1.11; 95% CI: 1.04, 1.20; P = 0.004). There was a highly significant trend of increasing OR for congenital heart defects with increasing maternal obesity (P < 0.0001). The offspring of obese women had significantly higher ORs for atrial septal defects, hypoplastic left heart syndrome, aortic stenosis, pulmonic stenosis, and tetralogy of Fallot. Conclusions: Obese, but not overweight, women are at significantly increased risk of bearing children with a range of congenital heart defects, and the risk increases with increasing BMI. Weight reduction as a way to reduce risk should be investigated. PMID:20375192

Current diagnosis and treatments for critical congenital heart defects

PubMed Central

ZENG, ZHANDONG; ZHANG, HONGWEI; LIU, FENGLI; ZHANG, NING

2016-01-01

Congenital heart defects (CHD) affect approximately 7% of infants, and account for 3% of all infant deaths. CHD is most often caused by the defects associated with ductus arteriosus, which is a vessel that usually closes shortly after birth. The types of CHD include tetralogy of fallot, hypoplastic left heart syndrome, pulmonary atresia, total anomalous pulmonary venous return, transposition of great arteries, tricuspid atresia and truncus arteriosus. There are some risk factors that can increase the chance of a fetus developing CHD such as prematurity, an existing CHD in a first-degree relative, genetic syndromes, infections in utero, maternal drug consumptions and disorders. CHD is diagnosed is through different techniques including pulse oximetry, echocardiograms and physical exams. In this review, we examined the current incidence of CHD, the risk factors associated with CHD, the current methods of diagnosis and surgical options used to repair the defects. PMID:27168772

Possible association of first and high birth order of pregnant women with the risk of isolated congenital abnormalities in Hungary - a population-based case-matched control study.

PubMed

Csermely, Gyula; Susánszky, Éva; Czeizel, Andrew E; Veszprémi, Béla

2014-08-01

In epidemiological studies at the estimation of risk factors in the origin of specified congenital abnormalities in general birth order (parity) is considered as confounder. The aim of this study was to analyze the possible association of first and high (four or more) birth order with the risk of congenital abnormalities in a population-based case-matched control data set. The large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities included 21,494 cases with different isolated congenital abnormality and their 34,311 matched controls. First the distribution of birth order was compared of 24 congenital abnormality groups and their matched controls. In the second step the possible association of first and high birth order with the risk of congenital abnormalities was estimated. Finally some subgroups of neural-tube defects, congenital heart defects and abdominal wall's defects were evaluated separately. A higher risk of spina bifida aperta/cystica, esophageal atresia/stenosis and clubfoot was observed in the offspring of primiparous mothers. Of 24 congenital abnormality groups, 14 had mothers with larger proportion of high birth order. Ear defects, congenital heart defects, cleft lip± palate and obstructive defects of urinary tract had a linear trend from a lower proportion of first born cases to the larger proportion of high birth order. Birth order showed U-shaped distribution of neural-tube defects and clubfoot, i.e. both first and high birth order had a larger proportion in cases than in their matched controls. Birth order is a contributing factor in the origin of some isolated congenital abnormalities. The higher risk of certain congenital abnormalities in pregnant women with first or high birth order is worth considering in the clinical practice, e.g. ultrasound scanning. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Racial/ethnic variations in the prevalence of selected major birth defects, metropolitan Atlanta, 1994-2005.

PubMed

Kucik, James E; Alverson, Clinton J; Gilboa, Suzanne M; Correa, Adolfo

2012-01-01

Birth defects are the leading cause of infant mortality and are responsible for substantial child and adult morbidity. Documenting the variation in prevalence of birth defects among racial/ethnic subpopulations is critical for assessing possible variations in diagnosis, case ascertainment, or risk factors among such groups. We used data from the Metropolitan Atlanta Congenital Defects Program, a population-based birth defects registry with active case ascertainment. We estimated the racial/ethnic variation in prevalence of 46 selected major birth defects among live births, stillbirths, and pregnancy terminations at >20 weeks gestation among mothers residing in the five central counties of metropolitan Atlanta between 1994 and 2005, adjusting for infant sex, maternal age, gravidity, and socioeconomic status (SES). We also explored SES as a potential effect measure modifier. Compared with births to non-Hispanic white women, births to non-Hispanic black women had a significantly higher prevalence of five birth defects and a significantly lower prevalence of 10 birth defects, while births to Hispanic women had a significantly higher prevalence of four birth defects and a significantly lower prevalence of six birth defects. The racial/ethnic disparities in the prevalence of some defects varied by SES, but no clear pattern emerged. Racial/ethnic disparities were suggested in 57% of included birth defects. Disparities in the prevalence of birth defects may result from different underlying genetic susceptibilities; exposure to risk factors; or variability in case diagnosis, ascertainment, or reporting among the subpopulations examined. Policies that improve early diagnosis of birth defects could reduce associated morbidity and mortality.

Success rate and risk factors of failure of the induced membrane technique in children: a systematic review.

PubMed

Aurégan, Jean-Charles; Bégué, Thierry; Rigoulot, Guillaume; Glorion, Christophe; Pannier, Stéphanie

2016-12-01

The induced membrane technique was designed by Masquelet et al. to address segmental bone defects of critical size in adults. It has been used after bone defects of traumatic, infectious and tumoral origin with satisfactory results. Recently, it has been used in children but, after an initial enthusiasm, several cases of failure have been reported. The purpose of this study was to assess the success rate and the risk factors of failure of the induced membrane for children. We conducted a systematic review of all the studies reporting the results of the induced membrane technique to address bone defects of critical size in children. Our primary outcome was the success rate of the technique defined as a bone union before any iterative surgery. Our secondary outcomes were the complications and the risk factors of failure. We searched Medline via Pubmed, EMBASE and the Cochrane Library. Twelve studies, including 69 patients, met the inclusion criteria. There were 41 boys and 28 girls. Mean age at surgery was 10 years. Mean size of resection was 12.38 cm and the mean time between the two stages was 5.86 months. Mean rate of bone union after the two stages of the induced membrane technique was 58% (40/69) but this rate increased to 87% after revision surgeries (60/69). Main complications were non-unions (19/69), lysis of the graft (6/69) and fractures of the bone graft (6/69). Only 1/69 deep infection was reported. Other non specific complications were regularly reported such limb length discrepancies, joint stiffness and protruding wires. Risk factor of failure that could be suspected comprised the resection of a malignant tumour, a bone defect located at the femur, a wide resection, a long time between the two stages, an unstable osteosynthesis and a bone graft associating autograft to other graft materials. The induced membrane technique is suitable for bone defects of critical size in children. It is a reliable technique with no need of micro vascular surgery. However, we found several risk factors of failure for the use of the induced membrane technique to address segmental bone defect of critical size in children. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gene variants in the folate-mediated one-carbon metabolism (FOCM) pathway as risk factors for conotruncal heart defects.

PubMed

Zhu, Huiping; Yang, Wei; Lu, Wei; Etheredge, Analee J; Lammer, Edward J; Finnell, Richard H; Carmichael, Suzan L; Shaw, Gary M

2012-05-01

We evaluated 35 variants among four folate-mediated one-carbon metabolism pathway genes, MTHFD1, SHMT1, MTHFR, and DHFR as risk factors for conotruncal heart defects. Cases with a diagnosis of single gene disorders or chromosomal aneusomies were excluded. Controls were randomly selected from area hospitals in proportion to their contribution to the total population of live-born infants. Odds ratios (OR) and the 95% confidence intervals (CI) were computed for each genotype (homozygous variant or heterozygote, vs. homozygous wildtype) and for increase of each less common allele (log-additive model). Interactions between each variant and three folate intake variables (maternal multivitamin use, maternal dietary folate intake, and combined maternal folate intake) were also evaluated under the log-additive model. In general, we did not identify notable associations. The A allele of MTHFD1 rs11627387 was associated with a 1.7-fold increase in conotruncal defects risk in both Hispanic mothers (OR = 1.7, 95% CI = 1.1-2.5) and Hispanic infants (OR = 1.7, 95% CI = 1.2-2.3). The T allele of MTHFR rs1801133 was associated with a 2.8-fold increase of risk among Hispanic women whose dietary folate intake was ≤ 25th centile. The C allele of MTHFR rs1801131 was associated with a two-fold increase of risk (OR = 2.0, 95% CI = 1.0-3.9) only among those whose dietary folate intake was >25th centile. Our study suggested that MTHFD1 rs11627387 may be associated with risk of conotruncal defects through both maternal and offspring genotype effect among the Hispanics. Maternal functional variants in MTHFR gene may interact with dietary folate intake and modify the conotruncal defects risk in the offspring. Copyright © 2012 Wiley Periodicals, Inc.

Dental enamel defects predict adolescent health indicators: A cohort study among the Tsimane' of Bolivia.

PubMed

Masterson, Erin E; Fitzpatrick, Annette L; Enquobahrie, Daniel A; Mancl, Lloyd A; Eisenberg, Dan T A; Conde, Esther; Hujoel, Philippe P

2018-05-01

Bioarchaeological findings have linked defective enamel formation in preadulthood with adult mortality. We investigated how defective enamel formation in infancy and childhood is associated with risk factors for adult morbidity and mortality in adolescents. This cohort study of 349 Amerindian adolescents (10-17 years of age) related extent of enamel defects on the central maxillary incisors (none, less than 1/3, 1/3 to 2/3, more than 2/3) to adolescent anthropometrics (height, weight) and biomarkers (hemoglobin, glycated hemoglobin, white blood cell count, and blood pressure). Risk differences and 95% confidence intervals were estimated using multiple linear regression. Enamel defects and stunted growth were compared in their ability to predict adolescent health indicators using log-binomial regression and receiver operating characteristics (ROCs). Greater extent of defective enamel formation on the tooth surface was associated with shorter height (-1.35 cm, 95% CI: -2.17, -0.53), lower weight (-0.98 kg, 95% CI: -1.70, -0.26), lower hemoglobin (-0.36 g/dL, 95% CI: -0.59, -0.13), lower glycated hemoglobin (-0.04 %A 1c , 95% CI: -0.08, -0.00008), and higher white blood cell count (0.74 10 9 /L, 95% CI: 0.35, 1.14) in adolescence. Extent of enamel defects and stunted growth independently performed similarly as risk factors for adverse adolescent outcomes, including anemia, prediabetes/type II diabetes, elevated WBC count, prehypertension/hypertension, and metabolic health. Defective enamel formation in infancy and childhood predicted adolescent health outcomes and may be primarily associated with infection. Extent of enamel defects and stunted growth may be equally predictive of adverse adolescent health outcomes. © 2018 Wiley Periodicals, Inc.

Fumonisins

USDA-ARS?s Scientific Manuscript database

Fumonisins are fungal toxins found in corn and in foods made from corn. Fumonisins are toxic to animals but their impact on human health is uncertain. Epidemiological evidence suggests that fumonisins may be risk factors for birth defects known as neural tube defects (NTDs) and for growth retardat...

Factors associated with delayed bleeding after resection of large nonpedunculated colorectal polyps.

PubMed

Elliott, Timothy R; Tsiamoulos, Zacharias P; Thomas-Gibson, Siwan; Suzuki, Noriko; Bourikas, Leonidas A; Hart, Ailsa; Bassett, Paul; Saunders, Brian P

2018-04-06

 Delayed bleeding is the most common significant complication after piecemeal endoscopic mucosal resection (p-EMR) of large nonpedunculated colorectal polyps (NPCPs). Risk factors for delayed bleeding are incompletely defined. We aimed to determine risk factors for delayed bleeding following p-EMR.  Data were analyzed from a prospective tertiary center audit of patients with NPCPs ≥ 20 mm who underwent p-EMR between 2010 and 2012. Patient, polyp, and procedure-related data were collected. Four post p-EMR defect factors were evaluated for interobserver agreement and included in analysis. Delayed bleeding severity was reported in accordance with guidelines. Predictors of bleeding were identified.  Delayed bleeding requiring hospitalization occurred after 22 of 330 procedures (6.7 %). A total of 11 patients required blood transfusion; of these, 4 underwent urgent colonoscopy, 1 underwent radiological embolization, and 1 required surgery. Interobserver agreement for identification of the four post p-EMR defect factors was moderate (kappa range 0.52 - 0.57). Factors associated with delayed bleeding were visible muscle fibers ( P  = 0.03) and the presence of a "cherry red spot" ( P  = 0.05) in the post p-EMR defect. Factors not associated with delayed bleeding were American Association of Anesthesiologists class, aspirin use, polyp size, site, and use of argon plasma coagulation.  Visible muscle fibers and the presence of a "cherry red spot" in the resection defect were associated with delayed bleeding after p-EMR. These findings suggest evaluation and photodocumentation of the post p-EMR defect is important and, when considered alongside other patient and procedural factors, may help to reduce the incidence and severity of delayed bleeding. © Georg Thieme Verlag KG Stuttgart · New York.

A Systematic Review and Meta-Analysis of Perforator-Pedicled Propeller Flaps in Lower Extremity Defects: Identification of Risk Factors for Complications.

PubMed

Bekara, Farid; Herlin, Christian; Mojallal, Ali; Sinna, Raphael; Ayestaray, Benoit; Letois, Flavie; Chavoin, Jean Pierre; Garrido, Ignacio; Grolleau, Jean Louis; Chaput, Benoit

2016-01-01

Currently, increased interest in the perforator-pedicled propeller flap should not obscure the fact that it is, in reality, a complex procedure requiring experience and monitoring similar to free flaps. Through a meta-analysis, the authors aimed to identify the risk factors of perforator-pedicled propeller flap failure in lower extremity defects. The MEDLINE, PubMed Central, Embase, and Cochrane databases were searched from 1991 to May of 2014 for articles describing perforator-pedicled propeller flaps in the lower extremity. The study selection met the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Fixed-effects models were used. Forty articles complied with the inclusion criteria, representing 428 perforator-pedicled propeller flaps. The most common cause was posttraumatic (55.2 percent). Most of the defects were at the distal third of the lower leg (45.6 percent). The arc of rotation was 180 degrees for 34.3 percent. Complications were found in 25.2 percent, including partial necrosis (10.2 percent) and complete necrosis (3.5 percent). Complete flap survival was found in 84.3 percent. The authors identified three significant risk factors: age older than 60 years (relative risk, 1.61; p = 0.03), diabetes (relative risk, 2.00; p = 0.02), and arteriopathy (relative risk, 3.12; p = 0.01). No significant results were found regarding smoking status other than a tendency (p = 0.06), acute cause (p = 0.59), posttraumatic cause (p = 0.97), distal third of the lower leg (p = 0.66), fascia inclusion (p = 0.70), and pedicle rotation greater than 120 degrees (p = 0.41). Age older than 60 years, diabetes, and arteriopathy are significant risk factors of perforator-pedicled propeller flap complications in the lower extremity. Risk, IV.

Critical congenital heart defects and abnormal levels of routinely collected first- and second-trimester biomarkers.

PubMed

Borelli, Melissa; Baer, Rebecca J; Chambers, Christina D; Smith, Tyler C; Jelliffe-Pawlowski, Laura L

2017-02-01

We examined the association between maternal characteristics, routinely collected first- and second-trimester biomarkers and the risk of having an infant with a critical congenital heart defect (CCHD). Included were women who participated in the California Prenatal Screening Program who had nuchal translucency (NT) measurement and first- and second-trimester serum screening. All pregnancies ended in a live birth of an infant without aneuploidy or a neural tube defect. Poisson regression analyses were used to estimate the relative risk and 95% confidence interval of a CCHD by maternal characteristics, first- and second-trimester serum biomarkers or NT measurements. The sample included 118,194 mother-infant pairs; 284 infants had a CCHD. Women with preexisting diabetes were three-times as likely to have an infant with a CCHD. After adjusting for preexisting diabetes, women with first-trimester human chorionic gonatotropin (hCG) measurement <10th centile were 1.6-times as likely to have an infant with a CCHD (P = 0.011). Women with a NT measurement ≥95th centile were at two- to threefold higher risk of having an infant with a CCHD (P's = 0.004-0.007). Pregnancies with two risk factors for an infant with a CCHD were 5.6-times more likely to have an infant with a CCHD than women with no identified risk factors (P < 0.001). Despite the increased risk, performance testing demonstrated low sensitivity and specificity for screening use of these risk factors. Of the women with an infant with a CCHD, only 21.8% had an identified risk factor. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic Acid fortification.

PubMed

Molloy, Anne M; Kirke, Peadar N; Troendle, James F; Burke, Helen; Sutton, Marie; Brody, Lawrence C; Scott, John M; Mills, James L

2009-03-01

Folic acid fortification has reduced neural tube defect prevalence by 50% to 70%. It is unlikely that fortification levels will be increased to reduce neural tube defect prevalence further. Therefore, it is important to identify other modifiable risk factors. Vitamin B(12) is metabolically related to folate; moreover, previous studies have found low B(12) status in mothers of children affected by neural tube defect. Our objective was to quantify the effect of low B(12) status on neural tube defect risk in a high-prevalence, unfortified population. We assessed pregnancy vitamin B(12) status concentrations in blood samples taken at an average of 15 weeks' gestation from 3 independent nested case-control groups of Irish women within population-based cohorts, at a time when vitamin supplementation or food fortification was rare. Group 1 blood samples were from 95 women during a neural tube defect-affected pregnancy and 265 control subjects. Group 2 included blood samples from 107 women who had a previous neural tube defect birth but whose current pregnancy was not affected and 414 control subjects. Group 3 samples were from 76 women during an affected pregnancy and 222 control subjects. Mothers of children affected by neural tube defect had significantly lower B(12) status. In all 3 groups those in the lowest B(12) quartiles, compared with the highest, had between two and threefold higher adjusted odds ratios for being the mother of a child affected by neural tube defect. Pregnancy blood B(12) concentrations of <250 ng/L were associated with the highest risks. Deficient or inadequate maternal vitamin B(12) status is associated with a significantly increased risk for neural tube defects. We suggest that women have vitamin B(12) levels of >300 ng/L (221 pmol/L) before becoming pregnant. Improving B(12) status beyond this level may afford a further reduction in risk, but this is uncertain.

Application of data screening to drug exposure in large risk factor studies of birth defects.

PubMed

Louik, Carol; Werler, Martha; Anderka, Marlene; Mitchell, Allen A

2015-08-01

Birth defects are the leading cause of infant death. While causes of most are unknown, those that might be due to medication use are among the most preventable. This study describes an approach to identifying those medications that most warrant attention by using a "screen" program that calculates odds ratios for pairs of exposures and specific birth defects. We discuss the development of this tool and illustrate its application to two large risk factor studies, the Slone Epidemiology Center's Birth Defects Study and the Centers for Disease Control and Prevention's National Birth Defects Prevention Study, ideal settings for the systematic study of risks and relative safety of drugs in relation to birth defects while recognizing the inherent limitations of such an approach. Suggestions for establishing criteria for exposures and outcomes that balance the need for specific details with the practical considerations of sample size and volume of output are presented. Selection of appropriate exposure reference categories and control groups is also discussed, as well as the need to address potential confounding. An example that motivated a detailed investigation of possible associations between a medication (butalbital) and selected specific birth defects is provided. While screening programs such as the one described can be a valuable tool for exploring potential associations in large data bases, they must be applied with caution. The issue of multiple testing and chance findings is a major concern. While statistics are a necessary component, human judgment must be an integral part of the process. © 2015 Wiley Periodicals, Inc.

Presence of the 5,10-methylenetetrahydrofolate reductase C677T mutation in Puerto Rican patients with neural tube defects.

PubMed

García-Fragoso, Lourdes; García-García, Inés; de la Vega, Alberto; Renta, Jessicca; Cadilla, Carmen L

2002-01-01

Folic acid supplementation can reduce the incidence of neural tube defects. The first reported genetic risk factor for neural tube defects is a C677T mutation in the 5,10-methylenetetrahydrofolate reductase gene, resulting in decreased activity of the enzyme. We examined the enzyme mutation role of methylenetetrahydrofolate reductase in the etiology of neural tube defects in our population. The study group consisted of 204 Puerto Rican individuals including 37 pregnant females with a prenatal diagnosis of neural tube defects in their fetuses, 31 newborns, 36 fathers, and 100 healthy adults. The prevalence of the C677T mutation was examined. Homozygosity for the alanine to valine substitution (TT) was observed in 9% of the controls and 19% of the mothers with children with neural tube defects. Our results indicate that the presence of the T allele at the methylenetetrahydrofolate reductase 677 position may increase the risk of giving birth to an infant with a neural tube defect.

Safety of inadvertent anthrax vaccination during pregnancy: An analysis of birth defects in the U.S. military population, 2003-2010.

PubMed

Conlin, Ava Marie S; Sevick, Carter J; Gumbs, Gia R; Khodr, Zeina G; Bukowinski, Anna T

2017-08-03

Anthrax vaccine adsorbed (AVA) vaccination is compulsory for United States military servicemembers with operational indicators. As the number of female military servicemembers has increased, so has the chance of inadvertent AVA vaccination during pregnancy. Building upon past analyses assessing AVA vaccination during pregnancy and birth defects risk, this study sought to determine if inadvertent AVA vaccination during pregnancy is significantly associated with risk of birth defects after adjusting for other potential risk factors. The study population included 126,839 liveborn infants in the Department of Defense Birth and Infant Health Registry (2003-2010). Mothers were categorized by AVA vaccination exposure timing in relation to pregnancy. Infant medical records were assessed for birth defect diagnoses within the first year of life. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Infants of first trimester AVA vaccinated mothers versus receipt at any other time point (OR, 1.10; 95% CI, 0.93-1.29) were not at higher odds of birth defects in adjusted models. Infants of mothers vaccinated prepregnancy versus postpregnancy had a 1.11 (95% CI, 1.01-1.22) higher odds of having a birth defect. Vaccination postpregnancy versus never vaccinated revealed a 10% lower odds of birth defects (OR, 0.90; 95% CI, 0.83-0.99). No strong associations between inadvertent AVA vaccination during pregnancy and birth defects risk were observed. Marginal associations between prepregnancy vaccination or never vaccinated women and birth defects risk was observed when compared to postpregnancy vaccination. These findings may be due to self-selection and/or reverse causation bias when assessing comparisons with postpregnancy vaccination, and a "healthy worker" effect when assessing comparisons with women never vaccinated. Copyright © 2017 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...

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

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

Pharmacological stress, rest perfusion and delayed enhancement cardiac magnetic resonance identifies very early cardiac involvement in systemic sclerosis patients of recent onset.

PubMed

Giacomelli, Roberto; Di Cesare, Ernesto; Cipriani, Paola; Ruscitti, Piero; Di Sibio, Alessandra; Liakouli, Vasiliki; Gennarelli, Antonio; Carubbi, Francesco; Splendiani, Alessandra; Berardicurti, Onorina; Di Benedetto, Paola; Ciccia, Francesco; Guggino, Giuliana; Radchenko, Ganna; Triolo, Giovanni; Masciocchi, Carlo

2017-09-01

To evaluate occult cardiac involvement in asymptomatic systemic sclerosis (SSc) patients by pharmacological stress, rest perfusion and delayed enhancement cardiac magnetic resonance (CMR), for a very early identification of patients at higher risk of cardiac-related mortality. Sixteen consecutive patients with definite SSc, fulfilling the American College of Rheumatology/European League Against Rheumatism 2013 classification criteria in less than 1 year from the onset of Raynaud's phenomenon, underwent pharmacological stress, rest perfusion and delayed enhancement CMR. At enrollment, no patient showed signs and/or symptoms suggestive for cardiac involvement. No patient showed traditional cardiovascular risk factors. Both the 12-lead electrocardiogram examination and echocardiographic evaluation did not show any alterations in our cohort. Stress perfusion defects of left ventricle were detected in six out of 16 (37.5%) patients and these defects did not match with the coronary flow distribution. The results showed the presence of two different patterns of stress perfusion defects: sub-endocardial and/or a midmyocardial. The presence of stress perfusion defects did not correlate with any clinical feature of enrolled patients. Myocardial stress perfusion defects may be detected early by pharmacological stress perfusion CMR, a reliable and sensitive technique for the noninvasive evaluation of SSc heart disease, in patients with SSc of recent onset. These defects seem to be independent from traditional risk factors and associated comorbidities, suggesting they are a specific hallmark of the disease. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

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

Risk of thromboembolic complications in adult congenital heart disease: A literature review.

PubMed

Karsenty, Clement; Zhao, Alexandre; Marijon, Eloi; Ladouceur, Magalie

2018-05-30

Adult congenital heart disease (ACHD) is a constantly expanding population with challenging issues. Initial medical and surgical treatments are seldom curative, and the majority of patients still experience late sequelae and complications, especially thromboembolic events. These common and potentially life-threating adverse events are probably dramatically underdiagnosed. Better identification and understanding of thromboembolic risk factors are essential to prevent long-term related morbidities. In addition to specific situations associated with a high risk of thromboembolic events (Fontan circulation, cyanotic congenital heart disease), atrial arrhythmia has been recognized as an important risk factor for thromboembolic events in ACHD. Unlike in patients without ACHD, thromboembolic risk stratification scores, such as the CHA 2 DS 2 -VASc score, may not be applicable in ACHD. Overall, after a review of the scientific data published so far, it is clear that the complexity of the underlying congenital heart disease represents a major risk factor for thromboembolic events. As a consequence, prophylactic anticoagulation is indicated in patients with complex congenital heart disease and atrial arrhythmia, regardless of the other risk factors, as opposed to simple heart defects. The landscape of ACHD is an ongoing evolving process, and specific thromboembolic risk scores are needed, especially in the setting of simple heart defects; these should be coupled with specific trials or long-term follow-up of multicentre cohorts. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Reduction of Fumonisin Toxicity by Extrusion and Nixtamalization (Alkaline Cooking)

USDA-ARS?s Scientific Manuscript database

Fumonisins are found in corn. The most common, fumonisin FB1 (FB1) is toxic to animals, disrupts sphingolipid metabolism, and is a suspected risk factor for neural tube defects (NTDs; serious birth defect) and cancer in humans that consume contaminated corn as a diet staple. FB1 levels in foods an...

Efficacy of caesarean scar defect repair in improving postmenstrual bleeding and factors associated with poor effect.

PubMed

Xu, He-Yang; Yang, Meng-Yi; Zhang, Xuyin; Wang, Qing; Yi, Xiao-Fang; Ding, Jing-Xin; Hua, Ke-Qin

2017-11-01

Caesarean scar defect (CSD) can cause postmenstrual bleeding. Defect repair is an effective technique to improve this symptom, but there are still a few patients getting little improvement. This retrospective study evaluates the efficacy of scar repair and explores the factors associated with poor effect. In total, 123 patients were involved in the final analysis. All of them complained about menstruation period >7 days due to postmenstrual bleeding. Before surgery, 87.8% of patients had a menstruation period more than 10 days and 20.3% had a period more than 15 days. After surgery, a normal menstruation period (< =7 days) was achieved in 46.3% (95%CI 37.3%-55.6%) of patients and a menstruation period lasting no more than 10 days was achieved in 74.8% (95%CI 66.2%-82.2%). Through multivariate logistic analysis, four factors were found dependently associated with poor effect (defined as menstruation period >10 days after surgery): repeated caesarean section (OR 9.75, 95%CI 2.30-41.36, 0.002) was a risk factor, while defect volume >600 mm 3 (OR 0.14, 95%CI 0.03-0.56, 0.006), interval from caesarean section to symptom emerging >3 months (OR 0.25, 95%CI 0.07-0.94, 0.041) and straight or retroflexed uterus (OR 0.19, 95%CI 0.05-0.79, 0.022) were protective factors. Impact statement What is already known on this subject? Caesarean scar defect can cause postmenstrual bleeding. Defect repair can improve this symptom, but there are still a few patients getting little improvement after surgery. What do the results of this study add? Defect volume >600 mm 3 , interval from caesarean section to symptom emerging >3 months and straight or retroflexed uterus are protective factors of poor effect (defined as menstruation period >10 days after surgery), and repeated caesarean section is a risk factor. What are the implications of these findings for clinical practice and/or further research? These findings may help in counselling the patients and in medical decision. Further researches are needed to explore other factors associated with surgical effect and build prediction models.

Maternal Exposure to Traffic-Related Air Pollution and Birth Defects in Massachusetts

PubMed Central

Girguis, Mariam S.; Strickland, Matthew J.; Hu, Xuefei; Liu, Yang; Bartell, Scott M.; Vieira, Verónica M.

2015-01-01

Exposures to particulate matter with diameter of 2.5 µm or less (PM2.5) may influence risk of birth defects. We estimated associations between maternal exposure to prenatal traffic-related air pollution and risk of cardiac, orofacial, and neural tube defects among Massachusetts births conceived 2001 through 2008. Our analyses included 2,729 cardiac, 255 neural tube, and 729 orofacial defects. We used satellite remote sensing, meteorological and land use data to assess PM2.5 and traffic-related exposures (distance to roads and traffic density) at geocoded birth addresses. We calculated adjusted odds ratios (OR) and confidence intervals (CI) using logistic regression models. Generalized additive models were used to assess spatial patterns of birth defect risk. There were positive but non-significant associations for a 10µg/m3 increase in PM2.5 and perimembranous ventricular septal defects (OR = 1.34, 95% CI: 0.98, 1.83), patent foramen ovale (OR = 1.19, 95% CI: 0.92, 1.54) and patent ductus arteriosus (OR = 1.20, 95% CI: 0.95, 1.62). There was a non-significant inverse association between PM2.5 and cleft lip with or without palate (OR = 0.76, 95% CI: 0.50, 1.10), cleft palate only (OR= 0.89, 95% CI: 0.54, 1.46) and neural tube defects (OR= 0.77, 95% CI: 0.46, 1.05). Results for traffic related exposure were similar. Only ostium secundum atrial septal defects displayed significant spatial variation after accounting for known risk factors. PMID:26705853

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

[Difficulties of the methods for studying environmental exposure and neural tube defects].

PubMed

Borja-Aburto, V H; Bermúdez-Castro, O; Lacasaña-Navarro, M; Kuri, P; Bustamante-Montes, P; Torres-Meza, V

1999-01-01

To discuss the attitudes in the assessment of environmental exposures as risk factors associated with neural tube defects, and to present the main risk factors studied to date. Environmental exposures have been suggested to have a roll in the genesis of birth defects. However, studies conducted in human populations have found difficulties in the design and conduction to show such an association for neural tube defects (anencephaly, espina bifida and encephalocele) because of problems raised from: a) the frequency measures used to compare time trends and communities, b) the classification of heterogeneous malformations, c) the inclusion of maternal, paternal and fetal factors as an integrated process and, d) the assessment of environmental exposures. Hypothetically both maternal and paternal environmental exposures can produce damage before and after conception by direct action on the embryo and the fetus-placenta complex. Therefore, in the assessment of environmental exposures we need to take into account: a) both paternal and maternal exposures; b) the critical exposure period, three months before conception for paternal exposures and one month around the conceptional period for maternal exposures; c) quantitatively evaluate environmental exposures when possible, avoiding a dichotomous classification; d) the use of biological markers of exposure is highly recommended as well as markers of genetic susceptibility.

Impact of anatomic characteristics and initial biventricular surgical strategy on outcomes in various forms of double-outlet right ventricle.

PubMed

Villemain, Olivier; Belli, Emre; Ladouceur, Magalie; Houyel, Lucile; Jalal, Zakaria; Lambert, Virginie; Ly, Mohamed; Vouhé, Pascal; Bonnet, Damien

2016-09-01

Surgical management of various forms of double-outlet right ventricle uses a variety of approaches depending on the underlying anatomic form. In this study, we sought to determine the risk factors of mortality and reoperation in those with double-outlet right ventricle undergoing biventricular repair, according to anatomic characteristics and initial surgical strategy. Between 1992 and 2013, 433 patients were included in the study. Double-outlet right ventricle was classified as double-outlet right ventricle with subaortic ventricular septal defect associated with subpulmonary obstruction in 33% of patients (n = 141), with subaortic ventricular septal defect without subpulmonary obstruction in 30% of patients (n = 130), with subpulmonary ventricular septal defect in 32% of patients (n = 139), and with noncommitted ventricular septal defect in 5% of patients (n = 23). Three types of repairs were performed: (1) intraventricular baffle repair, n = 149 (34%); (2) intraventricular baffle repair with right ventricular outflow tract reconstruction, n = 163 (38%); and (3) intraventricular baffle repair with arterial switch operation, n = 121 (28%). Thirty-day overall mortality was 7.4%. Early reoperation was needed in 6% of the cases. Early mortality was higher in the intraventricular baffle repair with arterial switch operation group (P = .01). Survival at 10 years was 86.2%, and freedom from reoperation at 10 years was 61.4%. At last follow-up (median, 5.7 years; 95% confidence interval, 4.5-6.6), mortality and reoperation rates were similar in the different surgical strategy groups. Late reoperation and late mortality were significantly higher in the double-outlet right ventricle with noncommitted ventricular septal defect group (P < .01). In multivariate analyses, risk factors for reoperation were concomitant surgical procedures (P = .03) and duration of cardiopulmonary bypass (P < .01). Risk factors for mortality were restrictive ventricular septal defect (P = .01), mitral cleft (P < .01), and associated coronary artery anomalies (P = .01). Those with the anatomic type of double-outlet right ventricle with noncommitted ventricular septal defect were at higher risk for reoperation and mortality. Intraventricular baffle repair with arterial switch operation was the surgical strategy in patients at higher risk of early death. Initial surgical strategy did not influence the late outcomes. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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

High-risk single ventricle palliation in children with Down syndrome: single institution experience.

PubMed

Ooi, Yinn K; Sinha, Pranava; Gierdalski, Marcin; Harahsheh, Ashraf

2015-03-01

Of the children with Down syndrome 40-50% have cardiac defects and the majority of these cardiac defects are amenable to biventricular repair. The outcome of single ventricle palliation is improving; nonetheless, there are limited data on Down syndrome patients with associated high-risk factors undergoing single ventricle palliation. Our aim was to study the outcomes of children with Down syndrome and high-risk factors on the single ventricle palliation pathway. A retrospective study on all patients with Down syndrome on the single ventricle palliation pathway from 2005 until 2011 was conducted. Operative, clinical, echocardiographic, haemodynamic data, and follow-up data were reviewed. A total of 310 patients underwent at least one single ventricle surgical intervention. Of those, eight patients had Down syndrome, five of which had associated risk factors - low birth weight, high pulmonary vascular resistance, pulmonary vein stenosis, significant atrioventricular valve regurgitation, and extracardiac anomalies. Mortality in the high-risk group was 80% (4/5), compared with 33% (1/3) in the non-high-risk patients. Overall, after a median follow-up period of 138 days (8-576 days), only 37.5% (3/8) of patients were alive. Despite many improvements in the care of single ventricle patients, the fate of those with Down syndrome and associated high-risk factors remains poor. Further multicentre longer-term studies are needed to validate and quantify the cumulative effects of negative prognostic factors in this complex group of patients.

Factors affecting maternal participation in the genetic component of the National Birth Defects Prevention Study-United States, 1997-2007.

PubMed

Glidewell, Jill; Reefhuis, Jennita; Rasmussen, Sonja A; Woomert, Alison; Hobbs, Charlotte; Romitti, Paul A; Crider, Krista S

2014-04-01

As epidemiological studies expand to examine gene-environment interaction effects, it is important to identify factors associated with participation in genetic studies. The National Birth Defects Prevention Study is a multisite case-control study designed to investigate environmental and genetic risk factors for major birth defects. The National Birth Defects Prevention Study includes maternal telephone interviews and mailed buccal cell self-collection kits. Because subjects can participate in the interview, independent of buccal cell collection, detailed analysis of factors associated with participation in buccal cell collection was possible. Multivariable logistic regression models were used to identify the factors associated with participation in the genetic component of the study. Buccal cell participation rates varied by race/ethnicity (non-Hispanic whites, 66.9%; Hispanics, 60.4%; and non-Hispanic blacks, 47.3%) and study site (50.2-74.2%). Additional monetary incentive following return of buccal cell kit and shorter interval between infant's estimated date of delivery and interview were associated with increased participation across all racial/ethnic groups. Higher education and delivering an infant with a birth defect were associated with increased participation among non-Hispanic whites and Hispanics. Factors associated with participation varied by race/ethnicity. Improved understanding of factors associated with participation may facilitate strategies to increase participation, thereby improving generalizability of study findings.

Nongenetic risk factors for holoprosencephaly: An updated review of the epidemiologic literature.

PubMed

Summers, April D; Reefhuis, Jennita; Taliano, Joanna; Rasmussen, Sonja A

2018-05-15

Holoprosencephaly (HPE) is a major structural birth defect of the brain that occurs in approximately 1 in 10,000 live births. Although some genetic causes of HPE are known, a substantial proportion of cases have an unknown etiology. Due to the low birth prevalence and rarity of exposure to many potential risk factors for HPE, few epidemiologic studies have had sufficient sample size to examine risk factors. A 2010 review of the literature identified several risk factors that had been consistently identified as occurring more frequently among cases of HPE, including maternal diabetes, twinning, and a predominance of females, while also identifying a number of potential risk factors that had been less widely studied. In this article, we summarize a systematic literature review conducted to update the evidence for nongenetic risk factors for HPE. © 2018 Wiley Periodicals, Inc.

Periconceptional Folic Acid Supplementation and Infant Risk of Congenital Heart Defects in Norway 1999-2009.

PubMed

Leirgul, Elisabeth; Gildestad, Trude; Nilsen, Roy Miodini; Fomina, Tatiana; Brodwall, Kristoffer; Greve, Gottfried; Vollset, Stein Emil; Holmstrøm, Henrik; Tell, Grethe S; Øyen, Nina

2015-09-01

The birth prevalence of congenital heart defects (CHDs) has decreased in Canada and Europe. Recommended intake of folic acid in pregnancy is a suggestive risk-reducing factor for CHDs. We investigated the association between periconceptional intake of folic acid supplements and infant risk of CHDs. Information on maternal intake of folic acid supplements before and during pregnancy in the Medical Birth Registry of Norway 1999-2009 was updated with information on CHD diagnoses from national health registers and the Cardiovascular Diseases in Norway Project. The association between folic acid intake and infant risk of CHD was estimated as relative risk (RR) with binomial log linear regression. Among 517 784 non-chromosomal singleton births, 6200 children were identified with CHD and 1153 with severe CHD. For all births, 18.4% of the mothers initiated folic acid supplements before pregnancy and 31.6% during pregnancy. The adjusted RR for severe CHD was 0.99 [95% confidence interval [CI] 0.86, 1.13] comparing periconceptional intake of folic acid with no intake. Specifically, RR for conotruncal defects was 0.99 [95% CI 0.80, 1.22], atrioventricular septal defects 1.19 [95% CI 0.78, 1.81], left ventricular outflow tract obstructions 1.02 [95% CI 0.78, 1.32], and right ventricular outflow tract obstructions 0.97 [95% CI 0.72, 1.29]. Birth prevalence of septal defects was higher in the group exposed to folic acid supplements with RR 1.19 [95% CI 1.10, 1.30]. Periconceptional folic acid supplement use showed no association with severe CHDs in the newborn. An unexpected association with an increased risk of septal defects warrants further investigation. © 2015 The Authors. Paediatric and Perinatal Epidemiology Published by John Wiley & Sons Ltd.

Factors associated with coronary artery disease and stroke in adults with congenital heart disease.

PubMed

Bokma, Jouke P; Zegstroo, Ineke; Kuijpers, Joey M; Konings, Thelma C; van Kimmenade, Roland R J; van Melle, Joost P; Kiès, Philippine; Mulder, Barbara J M; Bouma, Berto J

2018-04-01

To determine factors associated with coronary artery disease (CAD) and ischaemic stroke in ageing adult congenital heart disease (ACHD) patients. We performed a multicentre case-control study, using data from the national CONgenital CORvitia (CONCOR) registry to identify ACHD patients within five participating centres. Patients with CAD were matched (1:2 ratio) with ACHD patients without CAD on age, CHD defect group and gender. Patients with ischaemic stroke (or transient ischaemic attack) were matched similarly. Medical charts were reviewed and a standardised questionnaire was used to determine presence of risk factors. Of 6904 ACHD patients, a total of 55 cases with CAD (80% male, mean age 55.1±12.4 years) and 56 cases with stroke (46% male, mean age 46.9±15.2) were included and matched with control patients. In multivariable logistic regression analysis, traditional atherosclerotic risk factors (hypertension (OR 2.45; 95% CI 1.15 to 5.23), hypercholesterolaemia (OR 3.99; 95% CI 1.62 to 9.83) and smoking (OR 2.25; 95% CI 1.09 to 4.66)) were associated with CAD. In contrast, these risk factors were not associated with ischaemic stroke. In multivariable analysis, stroke was associated with previous shunt operations (OR 4.20; 95% CI 1.36 to 12.9), residual/unclosed septal defects (OR 2.38; 95% CI 1.03 to 5.51) and left-sided mechanical valves (OR 2.67; 95% CI 1.09 to 6.50). Traditional atherosclerotic risk factors were associated with CAD in ACHD patients. In contrast, ischaemic stroke was related to factors (previous shunts, septal defects, mechanical valves) suggesting a cardioembolic aetiology. These findings may inform surveillance and prevention strategies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Identification of Genetic Co-Modifiers in Shwachman-Diamond Syndrome

DTIC Science & Technology

2013-03-01

abnormalities, pancreatic insufficient, and bone marrow failure.5 Neutropenia characterizes the primary defect in SDS, however, the degree of... neutropenia can fluctuate and panctyopenia commonly occurs. Skeletal defects (e.g. metaphyseal dysplasia or polydactyly) are associated with lower numbers of...Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia . Experience of the

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

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

Animal models used for testing hydrogels in cartilage regeneration.

PubMed

Zhu, Chuntie; Wu, Qiong; Zhang, Xu; Chen, Fubo; Liu, Xiyang; Yang, Qixiang; Zhu, Lei

2018-05-14

Focal cartilage or osteochondral lesions can be painful and detrimental. Besides pain and limited function of joints, cartilage defect is considered as one of the leading extrinsic risk factors for osteoarthritis (OA). Thus, clinicians and scientists have paid great attention to regenerative therapeutic methods for the early treatment of cartilaginous defects. Regenerative medicine, showing great hope for regenerating cartilage tissue, rely on the combination of biodegradable scaffolds and specific biological cues, such as growth factors, adhesive factors and genetic materials. Among all biomaterials, hydrogels have emerged as promising cartilage tissue engineering scaffolds for simultaneous cell growth and drug delivery. A wide range of animal models have been applied in testing repair with hydrogels in cartilage defects. This review summarized the current animal models used to test hydrogels technologies for the regeneration of cartilage. Advantages and disadvantages in the establishment of the cartilage defect animal models among different species were emphasized, as well as feasibility of replication of diseases in animals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Implications of Parental Consanguinity on the Care of Neonates.

PubMed

Ng, Diana

2016-08-01

Approximately 6% of births worldwide, 7.9 million children, are born with a serious genetic congenital abnormality each year. A factor thought to increase the prevalence of birth defects is parental consanguinity, which is a social custom practiced in at least 20% of the world's population. The purpose of this article is to explore the relationship between consanguinity and congenital defects. This article also aims to enhance neonatal healthcare practitioners' comprehension of its implications for practice and research. A review of literature was compiled from a search of the online databases Cumulative Index of Nursing and Allied Health (CINAHL), PubMed, EBSCO MegaFILE, and Google Scholar. Literature pertinent to this topic primarily consists of research studies that examine the inbreeding depression phenomenon through comparison of the prevalence of birth defects among the offspring of consanguineous and nonconsanguineous couples. Current studies indicate that the progeny of consanguineous couples are at an increased risk of congenital defects compared with those of nonconsanguineous couples. Consanguinity is one risk factor among many that can lead to a major birth defect. Relationships between consanguineous populations and neonatal healthcare practitioners such as registered nurses, advanced practice nurses, and physicians could significantly alter neonatal health outcomes. Specific recommendations such as genetic counseling and therapeutic communication are discussed. Further studies need to investigate the connection between consanguinity and birth defects while controlling for nongenetic variables. Moreover, a focus on consanguineous communities in the United States would prove beneficial.

Maternal hypertension and risk for hypospadias in offspring.

PubMed

Agopian, A J; Hoang, Thanh T; Mitchell, Laura E; Morrison, Alanna C; Tu, Duong; Nassar, Natasha; Canfield, Mark A

2016-12-01

Hypospadias is one of the most common birth defects in male infants. Maternal hypertension is a suspected risk factor; however, few previous studies have addressed the possibility of reporting bias, and several previous studies have not accounted for hypospadias severity. We analyzed data from the Texas Birth Defects Registry for 10,924 nonsyndromic cases and statewide vital records for deliveries during 1999-2009, using Poisson regression. After adjustment for potential confounders, hypospadias was associated with maternal hypertension (adjusted prevalence ratio: 1.5, 95% confidence interval: 1.4-1.7). Similar associations were observed with gestational and pregestational hypertension, including separate analyses restricted to the subset of cases with severe (second- or third-degree) hypospadias. All of these associations were also similar among the subset of cases with isolated hypospadias (without additional birth defects). To evaluate the potential for bias due to potential hypertension misclassification, we repeated our analyses using logistic regression, comparing the cases to controls with other birth defects. In these analyses, the associations with gestational hypertension were similar, but adjusted associations with pregestational hypertension were no longer observed. Our findings support an association between gestational hypertension and hypospadias in offspring, but also suggest that previously observed associations with pregestational hypertension may have been inflated due to differential misclassification of hypertension (e.g., reporting bias). As gestational hypertension is recognized after hypospadias development, more research is needed to determine if this association reflects an increase in gestational hypertension risk secondary to hypospadias or if both conditions have shared risk factors (e.g., precursors of gestational hypertension). © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Outerbridge Grade IV Cartilage Lesions in the Hip Identified at Arthroscopy.

PubMed

Bhatia, Sanjeev; Nowak, Douglas D; Briggs, Karen K; Patterson, Diana C; Philippon, Marc J

2016-05-01

To determine factors associated with grade IV cartilage defects in the hip in patients undergoing hip arthroscopy with joint pain. Data from consecutive patients who underwent hip arthroscopy performed by a single surgeon over a period of 4 years were included in this study. The study group included 1,097 patients (491 women and 606 men; mean age, 37 years) who underwent hip arthroscopy for pain, had no prior hip surgery, and were aged 18 years or older. Preoperative radiographs, patient demographic characteristics, and operative details were used to identify risk factors for cartilage defects. Grade IV chondral defects were present in 308 of 1,097 hips (28%). Isolated chondral lesions were more frequently observed on the acetabulum (76%) than on the femoral head (24%). Defects of the acetabulum were more commonly anterosuperior (94.7%) and less commonly posterolateral (5.3%). Patients with less than 2 mm of joint space on preoperative radiographs were 8 times more likely to have a grade IV lesion than those with more than 2 mm. Men were more likely than women to have grade IV lesions (35% v 19%, P = .0001); patients with grade IV lesions were older than those without (42 years v 34 years, P = .0001). Hips with grade IV lesions had significantly higher alpha angles than those without (74° v 70°, P = .0001). Patients with grade IV defects reported a longer duration of symptoms than those without (37 months v 27 months, P = .007). Independent risk factors for the presence of grade IV chondral defects were less than 2 mm of joint space, male gender, increasing age, larger alpha angle, and longer duration of symptoms. Grade IV chondral defects in patients undergoing hip arthroscopy were associated with decreased joint space, increased time from symptom onset to arthroscopy, male gender, and larger alpha angles associated with femoroacetabular impingement. Level IV, prognostic case series. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Descriptive epidemiology of anophthalmia and microphthalmia, Hawaii, 1986-2001.

PubMed

Forrester, Mathias B; Merz, Ruth D

2006-03-01

Population-based epidemiologic data on anophthalmia and microphthalmia in the United States are limited and have come mainly from only a few states. The intent of this study was to report on the epidemiology of these eye defects. Cases were derived from a population-based birth defects registry in Hawaii and comprised all infants and fetuses with anophthalmia and microphthalmia who were delivered during 1986-2001. Anophthalmia and microphthalmia rates per 10,000 births were determined for selected factors, and comparisons were made by calculating the rate ratios and 95% confidence intervals (CIs). Ninety-six cases of anophthalmia and microphthalmia were identified, with a rate of 3.21 per 10,000 live births. The eye defects were isolated in 5 cases (5.2%), and 24 cases (25.0%) had confirmed chromosomal abnormalities. The risk of anophthalmia and microphthalmia varied over time and was significantly higher for live-born infants with low birth weights and gestational ages. The anophthalmia and microphthalmia rates also varied by maternal race/ethnicity, sex, and plurality, although these differences were not statistically significant. Anophthalmia and microphthalmia frequently occurred with other birth defects, and the rate was consistent with that found in the literature. The risk of defects differed significantly with time period, birth weight, and gestational age. The impact of many factors on anophthalmia and microphthalmia in Hawaii was frequently consistent with that reported elsewhere. Copyright 2006 Wiley-Liss, Inc.

Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair

PubMed Central

Agarwal, Rachit; García, Andrés J.

2015-01-01

Bone tissue has a remarkable ability to regenerate and heal itself. However, large bone defects and complex fractures still present a significant challenge to the medical community. Current treatments center on metal implants for structural and mechanical support and auto- or allo-grafts to substitute long bone defects. Metal implants are associated with several complications such as implant loosening and infections. Bone grafts suffer from donor site morbidity, reduced bioactivity, and risk of pathogen transmission. Surgical implants can be modified to provide vital biological cues, growth factors and cells in order to improve osseointegration and repair of bone defects. Here we review strategies and technologies to engineer metal surfaces to promote osseointegration with the host tissue. We also discuss strategies for modifying implants for cell adhesion and bone growth via integrin signaling and growth factor and cytokine delivery for bone defect repair. PMID:25861724

Risk of limb birth defects and mother's home proximity to cornfields.

PubMed

Ochoa-Acuña, Hugo; Carbajo, Cristina

2009-07-15

Although previous studies have linked proximity to crops and birth defects, they lacked individual-level exposure data and none was based on using planted area instead of linear proximity to crops as the exposure metric. We studied birth defects in relation to the area of corn or soybeans within 500 m of the mother's residence. We selected all singleton births from rural areas conceived during the 2000-2004 spring-summer months (n=48,216). We determined whether the area with corn or soybeans around the home was associated with birth defects using multiple unconditional logistic regression. We found that limb birth defects (ICD-9-CM 754.5, 755) increased in relation to cornfields (Adjusted OR=1.22; 95 % CI=1.01, 1.47 per additional 10 ha planted with corn within 500 m). None of the birth defect types studied was associated with soybeans. In the Midwest, a significant and expanding proportion of the population is now living in close proximity to cornfields. Our results suggest that additional studies should be conducted to identify which factor(s) associated with cornfields are behind the observed increase in limb birth defects.

Improving the Method of Roof Fall Susceptibility Assessment based on Fuzzy Approach

NASA Astrophysics Data System (ADS)

Ghasemi, Ebrahim; Ataei, Mohammad; Shahriar, Kourosh

2017-03-01

Retreat mining is always accompanied by a great amount of accidents and most of them are due to roof fall. Therefore, development of methodologies to evaluate the roof fall susceptibility (RFS) seems essential. Ghasemi et al. (2012) proposed a systematic methodology to assess the roof fall risk during retreat mining based on risk assessment classic approach. The main defect of this method is ignorance of subjective uncertainties due to linguistic input value of some factors, low resolution, fixed weighting, sharp class boundaries, etc. To remove this defection and improve the mentioned method, in this paper, a novel methodology is presented to assess the RFS using fuzzy approach. The application of fuzzy approach provides an effective tool to handle the subjective uncertainties. Furthermore, fuzzy analytical hierarchy process (AHP) is used to structure and prioritize various risk factors and sub-factors during development of this method. This methodology is applied to identify the susceptibility of roof fall occurrence in main panel of Tabas Central Mine (TCM), Iran. The results indicate that this methodology is effective and efficient in assessing RFS.

Triple-negative breast cancer risk in women is defined by the defect of estrogen signaling: preventive and therapeutic implications

PubMed Central

Suba, Zsuzsanna

2014-01-01

Epidemiologic studies strongly support that triple-negative breast cancers (TNBCs) may be distinct entities as compared with estrogen receptor (ER)+ tumors, suggesting that the etiologic factors, clinical characteristics, and therapeutic possibilities may vary by molecular subtypes. Many investigations propose that reproductive factors and exogenous hormone use differently or even quite inversely affect the risk of TNBCs and ER+ cancers. Controversies concerning the exact role of even the same risk factor in TNBC development justify that the biological mechanisms behind the initiation of both TNBCs and non-TNBCs are completely obscure. To arrive at a comprehensive understanding of the etiology of different breast cancer subtypes, we should also reconsider our traditional concepts and beliefs regarding cancer risk factors. Malignancies are multicausal, but the disturbance of proper estrogen signaling seems to be a crucial risk factor for the development of mammary cancers. The grade of defect in metabolic and hormonal equilibrium is directly associated with TNBC risk for women during their whole life. Inverse impact of menopausal status or parity on the development of ER+ and ER− breast cancers may not be possible; these controversial results derive from the misinterpretation of percentage-based statistical evaluations. Exogenous or parity-associated excessive estrogen supply is suppressive against breast cancer, though the lower the ER expression of tumors, the weaker the anticancer capacity. In women, the most important preventive strategy against breast cancers – included TNBCs – is the strict control and maintenance of hormonal equilibrium from early adolescence through the whole lifetime, particularly during the periods of great hormonal changes. PMID:24482576

Maternal reproductive history and the risk of isolated congenital malformations.

PubMed

Materna-Kiryluk, A; Więckowska, B; Wiśniewska, K; Borszewska-Kornacka, M K; Godula-Stuglik, U; Limon, J; Rusin, J; Sawulicka-Oleszczuk, H; Szwałkiewicz-Warowicka, E; Walczak, M

2011-03-01

We examined the relationship between maternal reproductive history and the newborn's risk of isolated congenital malformations in a large case-control cohort from the Polish Registry of Congenital Malformations. Congenital malformations were classified into four categories: isolated congenital heart defects (n=1673), isolated cleft palate (n=255), cleft lip with or without cleft palate (n=448) and renal agenesis (n=103). The case groups were compared with a shared group of 2068 controls recruited in the same time period and geographic area. Multivariable logistic regression was used to assess the risk associated with maternal gravidity and of previous miscarriages after accounting for maternal age and other potential risk factors. In unadjusted analyses, maternal gravidity was significantly associated with increased risk of all four classes of congenital malformations. After adjustment, a significant association persisted for congenital heart defects [odds ratio (OR)=1.22, [95% confidence interval (CI) 1.09, 1.36], P=0.0007] and cleft lip with or without cleft palate (OR=1.21, [95% CI 1.09, 1.36], P=0.0005). A similar trend existed for isolated cleft palate (OR=1.18, [95% CI 1.02, 1.37], P=0.03). There was no appreciable increase in the risk of congenital malformations associated with a maternal history of miscarriages, but a trend for a protective effect on the occurrence of cleft lip with or without cleft palate was observed (OR=0.72, [95% CI 0.52, 0.99], P=0.045). Based on our data, maternal gravidity represents a significant risk factor for congenital heart defects and cleft lip with or without cleft palate in the newborn infant. Our data do not support an increase in risk because of past history of miscarriages. © 2011 Blackwell Publishing 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.

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

Evaluation of prenatal risk factors for prediction of outcome in right heart lesions: CVP score in fetal right heart defects.

PubMed

Neves, Ana Luisa; Mathias, Leigh; Wilhm, Marilyn; Leshko, Jennifer; Linask, Kersti K; Henriques-Coelho, Tiago; Areias, José C; Huhta, James C

2014-09-01

To determine the prenatal variables predicting the risk of perinatal death in congenital right heart defects. Retrospective analysis of 28 fetuses with right heart defects was performed. Logistic regression analyses were performed to obtain odds ratios (OR) for the relationship between the risk of death and echocardiographic parameters. The parameters that correlated with the outcome were incorporated in an attempt to devise a disease-specific cardiovascular profile score. Fetal echocardiograms (143) from 28 patients were analyzed. The cardiovascular profile score predicted the risk of death. A lower right ventricle (RV) pressure was associated with mortality (OR 0.959; 95% confidence intervals (CI) 0.940-0.978). Higher peak aortic velocity through the aortic valve (OR 0.104; 95% CI 0.020-0.529) was associated with a better outcome. These cardiac function parameters were incorporated in a modified disease-specific CVP Score. Patients with a mean modified cardiovascular profile score of ≤ 6 were over 3.7 times more likely to die than those with scores of 7-10. The original Cardiovascular Profile Score predicted the risk of death in right heart defects. The modified score was not validated as a good prediction tool by this study. Fetal RV pressure estimate and peak aortic velocity can be used as independent prognostic predictors.

Association of young and advanced age of pregnant women with the risk of isolated congenital abnormalities in Hungary - a population-based case-matched control study.

PubMed

Csermely, Gyula; Susánszky, Éva; Czeizel, Andrew E

2015-03-01

To analyze the possible association of maternal age with the risk of all congenital abnormalities (CAs) in a population-based large case-matched control data set. The Hungarian Case-Control Surveillance of Congenital Abnormalities included 21,494 cases with isolated CA and their 34,311 matched controls. First the distribution of maternal age groups in 24 CA-groups and their matched controls was compared. In the second step, young (19 years or less) and advanced (35 years or more) age groups were compared. Finally, the subgroups of neural-tube defects, congenital heart defects and abdominal wall's CA were evaluated separately. A higher risk of gastroschisis, congenital heart defects, particularly left-sided obstructive defects, undescended testis and clubfoot was found in the youngest age group (19 years or less) of cases. The higher proportion of pregnant women with advanced age (i.e. 35 years or more) showed only a borderline excess in cases with clubfoot. The so-called U-shaped risk of maternal age distribution was found in cases with clubfoot and in the total group of isolated CAs. The maternal age is a contributing factor to the origin of some isolated CAs mainly in young pregnant women.

Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects.

PubMed

Bauters, Marijke; Frints, Suzanna G; Van Esch, Hilde; Spruijt, Liesbeth; Baldewijns, Marcella M; de Die-Smulders, Christine E M; Fryns, Jean-Pierre; Marynen, Peter; Froyen, Guy

2014-08-01

Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X;22)(q27;q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects. © 2014 Wiley Periodicals, Inc.

Air Pollution, Neighbourhood Socioeconomic Factors and Neural Tube Defects in the San Joaquin Valley of California

PubMed Central

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

2015-01-01

Background Environmental pollutants and neighbourhood socioeconomic factors have been associated with neural tube defects, but the potential impact of interaction between ambient air pollution and neighbourhood socioeconomic factors on the risks of neural tube defects is not well understood. Methods We used data from the California Center of the National Birth Defects Study and the Children’s Health and Air Pollution Study to investigate whether associations between air pollutant exposure in early gestation and neural tube defects were modified by neighbourhood socioeconomic factors in the San Joaquin Valley of California, 1997–2006. Five pollutant exposures, three outcomes and 9 neighbourhood socioeconomic factors were included for a total of 135 investigated associations. Estimates were adjusted for maternal race-ethnicity, education and multivitamin use. Results We present below odds ratios that exclude 1 and a chi-square test of homogeneity p-value of <0.05. We observed increased odds of spina bifida comparing the highest to lowest quartile of particulate matter <10 micrometres (PM10) among those living in a neighbourhood with: a) median household income of less than $30,000 per year (OR 5.1, 95% CI 1.7, 15.3); b) more than 20% living below the federal poverty level (OR 2.6, 95% CI 1.1, 6.0); and c) more than 30% with less than or equal to a high school education (OR 3.2, 95% CI 1.4, 7.4). The ORs were not statistically significant among those higher SES neighbourhoods. Conclusions Our results demonstrate effect modification by neighbourhood socioeconomic factors in the association of particulate matter and neural tube defects in California. PMID:26443985

Air Pollution, Neighbourhood Socioeconomic Factors, and Neural Tube Defects in the San Joaquin Valley of California.

PubMed

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

2015-11-01

Environmental pollutants and neighbourhood socioeconomic factors have been associated with neural tube defects, but the potential impact of interaction between ambient air pollution and neighbourhood socioeconomic factors on the risks of neural tube defects is not well understood. We used data from the California Center of the National Birth Defects Study and the Children's Health and Air Pollution Study to investigate whether associations between air pollutant exposure in early gestation and neural tube defects were modified by neighbourhood socioeconomic factors in the San Joaquin Valley of California, 1997-2006. There were 5 pollutant exposures, 3 outcomes, and 9 neighbourhood socioeconomic factors included for a total of 135 investigated associations. Estimates were adjusted for maternal race-ethnicity, education, and multivitamin use. We present below odds ratios (ORs) that exclude 1 and a chi-square test of homogeneity P-value of <0.05. We observed increased odds of spina bifida comparing the highest to lowest quartile of particulate matter <10 μm (PM10 ) among those living in a neighbourhood with: (i) median household income of less than $30 000 per year [OR 5.1, 95% confidence interval (CI) 1.7, 15.3]; (ii) more than 20% living below the federal poverty level (OR 2.6, 95% CI 1.1, 6.0); and (iii) more than 30% with less than or equal to a high school education (OR 3.2, 95% CI 1.4, 7.4). The ORs were not statistically significant among those higher socioeconomic status (SES) neighbourhoods. Our results demonstrate effect modification by neighbourhood socioeconomic factors in the association of particulate matter and neural tube defects in California. © 2015 John Wiley & Sons Ltd.

Assisted Reproductive Technology and Birth Defects Among Liveborn Infants in Florida, Massachusetts, and Michigan, 2000-2010.

PubMed

Boulet, Sheree L; Kirby, Russell S; Reefhuis, Jennita; Zhang, Yujia; Sunderam, Saswati; Cohen, Bruce; Bernson, Dana; Copeland, Glenn; Bailey, Marie A; Jamieson, Denise J; Kissin, Dmitry M

2016-06-06

Use of assisted reproductive technology (ART) has been associated with increased risks for birth defects. Variations in birth defect risks according to type of ART procedure have been noted, but findings are inconsistent. To examine the prevalence of birth defects among liveborn infants conceived with and without ART and to evaluate risks associated with certain ART procedures among ART-conceived infants. Used linked ART surveillance, birth certificates, and birth defects registry data for 3 states (Florida, Massachusetts, and Michigan). Methods for ascertaining birth defect cases varied by state. Resident live births during 2000 to 2010 were included, and the analysis was conducted between Feburary 2015 and August 2015. Use of ART among all live births and use of certain ART procedures among ART births. Prevalence of selected chromosomal and nonchromosomal birth defects that are usually diagnosed at or immediately after birth. Of the 4 618 076 liveborn infants between 2000 and 2010, 64 861 (1.4%) were conceived using ART. Overall, the prevalence of 1 or more of the selected nonchromosomal defects was 58.59 per 10 000 for ART infants (n = 389) vs 47.50 per 10 000 for non-ART infants (n = 22 036). The association remained significant after adjusting for maternal characteristics and year of birth (adjusted risk ratio [aRR], 1.28; 95% CI, 1.15-1.42). Similar differences were observed for singleton ART births vs their non-ART counterparts (63.69 per 10 000 [n = 218] vs 47.17 per 10 000 [n = 21 251]; aRR, 1.38; 95% CI, 1.21-1.59). Among multiple births, the prevalence of rectal and large intestinal atresia/stenosis was higher for ART births compared with non-ART births (aRR, 2.39; 95% CI, 1.38-4.12). Among ART births conceived after fresh embryo transfer, infants born to mothers with ovulation disorders had a higher prevalence of nonchromosomal birth defects (aRR, 1.53; 95% CI, 1.13-2.06) than those born to mothers without the diagnosis, and use of assisted hatching was associated with birth defects among singleton births (aRR, 1.55; 95% CI, 1.10-2.19). Multiplicity-adjusted P values for these associations were greater than .05. Infants conceived after ART had a higher prevalence of certain birth defects. Assisted hatching and diagnosis of ovulation disorder were marginally associated with increased risks for nonchromosomal birth defects; however, these associations may be caused by other underlying factors.

Tibial tunnel defect size as a risk factor in growth arrest following paediatric transphyseal anterior cruciate ligament reconstruction: an anatomical study.

PubMed

Pananwala, Hasitha; Jabbar, Yaser; Mills, Leonora; Symes, Michael; Nandapalan, Haren; Sefton, Andrew; Delungahawatte, Lasitha; Dao, Quang

2016-09-01

There is ongoing controversy regarding growth disturbances in younger patients undergoing anterior cruciate ligament reconstructions. Animal models have shown that an injury of 7-9% of the physeal area is a risk factor for growth disturbances. A total of 39 magnetic resonance imaging studies of the knee were examined. The proximal tibial physeal area was determined using a calibrated 'region of interest' ligature encompassing the tibial physis in the axial plane. The potential defect left by commonly used drill sizes was calculated as a percentage of the physeal area. A 7-mm drill leaves a mean defect of 1.45% physeal area (range: 1.11-1.89%, SD: 0.28, 95% CI: ±0.09), 8-mm drill leaves a 1.84% mean defect (range: 1.43-2.49%, SD: 0.38, 95% CI: ±0.12) and a 9-mm drill leaves a 2.30% mean defect (range: 1.83-3.19%, SD: 0.58, 95% CI: ±0.17). At 55°, 7-mm drill leaves a mean defect of 1.96% (range: 1.32-2.28%, SD: 0.37, 95% CI: ±0.12), 8-mm drill leaves a mean defect of 2.19% (range: 1.71-2.95%, SD: 0.46, 95% CI: ±0.14) and a 9-mm drill leaves a mean defect of 2.76% (range: 2.16-3.73%, SD: 0.58, 95% CI: ±0.18). There was a statistically significant difference in the tunnel area with a change of drill angle (7-mm drill P = 0.005, 8-mm drill P = 0.001, 9-mm drill P = 0.001). On the basis of this study in the context of animal model and observational evidence, the area of physeal injury using drill tunnels for anterior cruciate ligament reconstruction would not appear to contribute to potential growth disturbances. © 2016 Royal Australasian College of Surgeons.

Long-term neurodevelopmental outcome and exercise capacity after corrective surgery for tetralogy of Fallot or ventricular septal defect in infancy.

PubMed

Hövels-Gürich, Hedwig H; Konrad, Kerstin; Skorzenski, Daniela; Nacken, Claudia; Minkenberg, Ralf; Messmer, Bruno J; Seghaye, Marie-Christine

2006-03-01

The purpose of this prospective study was to assess whether neurodevelopmental status and exercise capacity of children 5 to 10 years after corrective surgery for tetralogy of Fallot or ventricular septal defect in infancy was different compared with normal children and influenced by the preoperative condition of hypoxemia or cardiac insufficiency. Forty unselected children, 20 with tetralogy of Fallot and hypoxemia and 20 with ventricular septal defect and cardiac insufficiency, operated on with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass at a mean age of 0.7 +/- 0.3 years (mean +/- SD), underwent, at mean age 7.4 +/- 1.6 years, standardized evaluation of neurologic status, gross motor function, intelligence, academic achievement, language, and exercise capacity. Results were compared between the groups and related to preoperative, perioperative, and postoperative status and management. Rate of mild neurologic dysfunction was increased compared with normal children, but not different between the groups. Exercise capacity and socioeconomic status were not different compared with normal children and between the groups. Compared with the normal population, motor function, formal intelligence, academic achievement, and expressive and receptive language were significantly reduced (p < 0.01 to p < 0.001) in the whole group and in the subgroups, except for normal intelligence in ventricular septal defect patients. Motor dysfunction was significantly higher in the Fallot group compared with the ventricular septal defect group (p < 0.01) and correlated with neurologic dysfunction, lower intelligence, and reduced expressive language (p < 0.05 each). Reduced New York Heart Association functional class was correlated with lower exercise capacity and longer duration of cardiopulmonary bypass (p < 0.05 each). Reduced socioeconomic status significantly influenced dysfunction in formal intelligence (p < 0.01) and academic achievement (p < 0.05). Preoperative risk factors such as prenatal hypoxia, perinatal asphyxia, and preterm birth, factors of perioperative management such as cardiac arrest, lowest nasopharyngeal temperature, and age at surgery, and postoperative risk factors as postoperative cardiocirculatory insufficiency and duration of mechanical ventilation were not different between the groups and had no influence on outcome. Degree of hypoxemia in Fallot patients and degree of cardiac insufficiency in ventricular septal defect patients did not influence the outcome within the subgroups. Children with preoperative hypoxemia in infancy are at higher risk for motor dysfunction than children with cardiac insufficiency. Corrective surgery in infancy for tetralogy of Fallot or ventricular septal defect with combined circulatory arrest and low flow bypass is associated with reduced neurodevelopmental outcome, but not with reduced exercise capacity in childhood. In our experience, the general risk of long-term neurodevelopmental impairment is related to unfavorable effects of the global perioperative management. Socioeconomic status influences cognitive capabilities.

Reconstructed bone chip detachment is a risk factor for sinusitis after transsphenoidal surgery.

PubMed

Hsu, Yao-Wen; Ho, Ching-Yin; Yen, Yu-Shu

2014-01-01

Sphenoid sinusitis is a complication associated with endoscopic transsphenoidal pituitary surgery. Studies that address the relationship between methods of sellar defect reconstruction and postoperative sinusitis are rare. The purpose of this study was to investigate the incidence, the possible risk factors, and the causative pathogens of sphenoid sinusitis after endoscopic transsphenoidal pituitary surgery. Prospective cohort study. We performed a prospective analysis of 182 patients with benign pituitary tumor who underwent endoscopic transsphenoidal pituitary surgery and sellar defect reconstruction with bone chip, from July 2008 through July 2011. All patients were followed up with nasal endoscopy for at least 6 weeks. Fifty-seven (31.3%) patients developed postoperative sphenoid sinusitis. Comparing the sinusitis and nonsinusitis groups, we found that bone chip detachment was a significant risk factor for postoperative sinusitis, with a relative risk of 2.86 (64.1% vs. 22.4%). The most common pathogens present in cases of postoperative sinusitis were methicillin-sensitive Staphylococcus aureus, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. Regular follow-up with nasal endoscopy can prevent delayed diagnosis of postoperative sphenoid sinusitis. Culture-directed antibiotics with aggressive endoscopic debridement are an effective treatment for these patients. An optimal reconstruction strategy should be further developed to reduce bone chip detachment and secondary sinusitis. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

[Association between illness and mental status in pregnant women and birth defects].

PubMed

Zhao, D D; Dai, Y X; Guo, L Q; Liu, R; Wang, H L; Mi, B B; Dang, S N; Yan, H

2017-11-10

Objective: To understand the prevalence of birth defects, related diseases and mental status of women during pregnancy in Shaanxi province and to analyse the major risk factors on birth defects and congenital heart disease. Possible association between maternal diseases or mental status and the risk of birth defects, was also explored. Methods: A cross-sectional design was used in this study and stratified multistage random sampling method was used. The whole survey was from Jury 2013 to November 2013. Logistic regression method was used to analyze the association between maternal diseases, mental status during pregnancy and birth defects. Results: The overall prevalence of birth defects was 195.04 per 10 000 in Shaanxi. Among the 29 121 mothers participating in this study, 51.1% developed illness and 6.8% "changed their mental status during pregnancy. After adjusting all the confounding factors, results showed that, histories of cold" , fever, and intrahepatic cholestasis were ( OR =1.33, 95 %CI : 1.10-1.61, OR =1.54, 95 %CI : 1.09-2.16, and OR =32.77, 95 %CI :4.08-263.04) respectively, during pregnancy that related to birth defects. Self-reported unstable mental status ( OR =1.60, 95 %CI : 1.19-2.15) and family friction ( OR =2.07, 95 %CI : 1.12-3.79) were both related to the birth rates. Histories of cold and fever ( OR =1.59, 95 %CI : 1.28-1.98; OR =1.43, 95 %CI : 1.48-4.00), during early pregnancy, unstable mental status during mid-pregnant period ( OR =1.52, 95 %CI : 1.05-2.19), unstable mental status during late-pregnant period ( OR =1.63, 95 %CI : 1.05-2.19) and family friction during late-pregnant period ( OR =2.89, 95 %CI : 1.16-7.20) were found to be related to birth defects. Compared with those without history of cold, those with the history of cold during first ( OR =1.24, 95 %CI : 1.02-1.52) and second stages ( OR =2.06, 95 %CI : 1.30-3.26) of pregnancy were more likely to bear fetus with birth defects. Compared with those without these histories, those with histories of fever ( OR =1.49, 95 %CI : 1.04-2.13), emotional problem ( OR =1.71, 95 %CI : 1.19-2.45) and related diseases ( OR =2.67, 95 %CI : 1.32-5.39) during the first period of pregnancy were more likely to bear fetus with birth defects. Conclusion: The incidence of birth defects in Shaanxi was high. Histories of cold, fever, unstable mental status and family friction during pregnancy, seemed to have increased the risks of bearing child with birth defects.

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

[Neurological and psychomotor development of foetuses and children with congenital heart disease--causes and prevalence of disorders and long-term prognosis].

PubMed

Herberg, U; Hövels-Gürich, H

2012-06-01

Children with severe congenital heart defects (CHD) requiring open heart surgery in the first year of life are at high risk for developing neurological and psychomotor abnormalities. Depending on the type and severity of the CHD, between 15 and over 50% of these children have deficits, which are usually confined to distinct domains of development, although formal intelligence tends to be normal. Children with mild CHD, who comprise the majority of congenital heart defects, have a far better developmental prognosis than those with complex CHD. This review concentrates on the impact of severe CHD on the developing brain of the foetus and infant. It also provides a summary of recent clinical and neuroimaging studies, and an overview of the long-term neurological prognosis. Advanced neuroimaging modalities indicate that, related to altered cerebral blood flow and oxygenation, foetuses with severe CHD show delayed third trimester brain maturation and increased vulnerability for hypoxic injury. Morphological and neurological abnormalities are present before surgery, commonly affecting the white matter. In the long-term, impaired neurological and developmental outcomes are related to the combination of prenatal, perinatal and additional perioperative risk factors. Therefore, new therapeutic approaches aim to optimise the intra- and perinatal management of foetuses and newborns with congenital heart defects. Identification and avoidance of risk factors, early neurodevelopmental assessment and therapy may optimise the long-term outcome in this high-risk population. © Georg Thieme Verlag KG Stuttgart · New York.

Maternal DNA hypomethylation and congenital heart defects

PubMed Central

Chowdhury, Shimul; Cleves, Mario A.; MacLeod, Stewart L.; James, S. Jill; Zhao, Weizhi; Hobbs, Charlotte A.

2011-01-01

Background Congenital heart defects (CHDs) are among the most prevalent and serious of birth defects. Multiple maternal factors are thought to contribute to CHD development including folate intake. Maternal DNA methylation, which is dependent on folate metabolism, may impact the risk of CHDs. Objective Our study was designed to determine whether maternal long interspersed nucleotide elements-1 (LINE-1) DNA hypomethylation is associated with increased occurrence of non-syndromic CHDs and whether maternal folate-dependent metabolites are correlated with DNA methylation status. Design Using a case-control study design, we measured global DNA methylation status among mothers whose pregnancies were affected by non-syndromic CHDs (n=180) and mothers of unaffected pregnancies (n=187). Methylation of LINE-1 was used as a surrogate marker of global DNA methylation status. The association between DNA methylation and CHD risk was determined while adjusting for selected lifestyle factors. Results LINE-1 DNA methylation was significantly lower in cases compared with controls (p=0.049). After covariate adjustments, a significant difference between cases and controls remained (p=0.010). Among women with LINE-1 methylation in the lowest decile of DNA methylation, the estimated risk of having a CHD-affected pregnancy was almost twice that of women in all other deciles (OR=1.91; 95% CI: 1.03, 3.58). Conclusions Our findings indicate that maternal LINE-1 DNA hypomethylation is associated with an increased risk of CHDs. Future studies investigating the association between maternal DNA methylation patterns and CHDs should be pursued. PMID:21254366

Possible Common Aetiology behind Maternal Preeclampsia and Congenital Heart Defects in the Child: a Cardiovascular Diseases in Norway Project Study.

PubMed

Brodwall, Kristoffer; Leirgul, Elisabeth; Greve, Gottfried; Vollset, Stein Emil; Holmstrøm, Henrik; Tell, Grethe S; Øyen, Nina

2016-01-01

The aetiology of congenital heart defects (CHD) is mostly unknown, but maternal factors may modify the infant risk of CHD. We investigated the association between maternal preeclampsia and offspring risk of severe CHD in a nation-wide cohort study. Information on all births registered in the Medical Birth Registry of Norway, 1994-2009, was completed with information on CHD diagnoses from national health registries and the Cardiovascular Diseases in Norway Project (CVDNOR). Among 914 703 singleton births without chromosomal abnormalities, 32 864 (3.6%) were born after a pregnancy with preeclampsia. The preeclampsia was diagnosed before the 34th week of pregnancy (early-onset preeclampsia) in 2618 (8.0% of preeclamptic pregnancies). CHDs were diagnosed in 10 691 infants; of these, 2473 had severe CHD. The risk of severe CHD was compared between births with and without maternal preeclampsia and estimated with binomial log-linear regression. When adjusting for year of birth, maternal age, parity, and pregestational diabetes, the risk ratio (RR) for severe CHD in offspring of mothers with any preeclampsia was 1.3 [95% confidence interval (CI) 1.1, 1.5], and in pregnancies with early-onset preeclampsia, the RR was 2.8 (95% CI 1.8, 4.4). The association between early-onset preeclampsia and specific types of severe CHD was stronger for atrioventricular septal defects (AVSD), with adjusted RR 13.5 (95% CI 6.8, 26.8). Early-onset preeclampsia was strongly associated with infant risk of severe CHD, specifically; the risk of AVSD was 15-fold higher if the mother was diagnosed with early-onset preeclampsia, suggesting common aetiological factors for early-onset preeclampsia and erroneous fetal heart development. © 2015 John Wiley & Sons Ltd.

White Paper: A Defect Prioritization Method Based on the Risk Priority Number

DTIC Science & Technology

2013-11-01

adapted The Failure Modes and Effects Analysis ( FMEA ) method employs a measurement technique called Risk Priority Number (RPN) to quantify the...Up to an hour 16-60 1.5 Brief Interrupt 0-15 1 Table 1 – Time Scaling Factors In the FMEA formulation, RPN is a product of the three categories

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.

The Advanced Glaucoma Intervention Study (AGIS): 12. Baseline risk factors for sustained loss of visual field and visual acuity in patients with advanced glaucoma.

PubMed

2002-10-01

To examine the relationships between baseline risk factors and sustained decrease of visual field (SDVF) and sustained decrease of visual acuity (SDVA). Cohort study of participants in the Advanced Glaucoma Intervention Study (AGIS). This multicenter study enrolled patients between 1988 and 1992 and followed them until 2001; 789 eyes of 591 patients with advanced glaucoma were randomly assigned to one of two surgical sequences, argon laser trabeculoplasty (ALT)-trabeculectomy-trabeculectomy (ATT) or trabeculectomy-ALT-trabeculectomy (TAT). This report is based on data from 747 eyes. Eyes were offered the next intervention in the sequence upon failure of the previous intervention. Failure was based on recurrent intraocular pressure elevation, visual field defect, and disk rim criteria. Study visits occurred every 6 months; potential follow-up ranged from 8 to 13 years. For each intervention sequence, Cox multiple regression analyses were used to examine the baseline characteristics for association with two vision outcomes: SDVF and SDVA. The magnitude of the association is measured by the hazard ratio (HR), where HR for binary variables is the relative change in the hazard (or risk) of the outcome in eyes with the factor divided by the hazard in eyes without the factor, and HR for continuous variables is the relative change in the hazard (or risk) of the outcome in eyes with a unit increase in the factor. Characteristics associated with increased SDVF risk in the ATT sequence are: less baseline visual field defect (hazard ratio [HR] = 0.86, P <.001, 95% CI = 0.82-0.90), male gender (HR = 2.23, P <.001, 1.54-3.23), and worse baseline visual acuity (HR = 0.96, P =.001, 0.94-0.98); in the TAT sequence: less baseline visual field defect (HR = 0.93, P =.001, 0.89-0.97) and diabetes (HR = 1.87, P =.007, 1.18-2.97). Characteristics associated with increased SDVA risk in both treatment sequences are better baseline acuity (ATT: HR = 1.05, P <.001, 1.02-1.09; TAT: HR = 1.06, P <.001, 1.03-1.08), older age (ATT: HR = 1.05, P =.001, 1.02-1.08; TAT: HR = 1.04, P =.002, 1.01-1.06), and less formal education (ATT: HR = 1.92, P =.001, 1.29-2.88; TAT: HR = 1.77, P =.002, 1.22-2.54). For SDVF, risk factors were better baseline visual field in both treatment sequences, male gender, and worse baseline visual acuity in the ATT sequence, and diabetes in the TAT sequence. For SDVA, risk factors in both treatment sequences were better baseline visual acuity, older age, and less formal education.

Assisted Reproductive Technology and Birth Defects Among Liveborn Infants in Florida, Massachusetts, and Michigan, 2000–2010

PubMed Central

Boulet, Sheree L.; Kirby, Russell S.; Reefhuis, Jennita; Zhang, Yujia; Sunderam, Saswati; Cohen, Bruce; Bernson, Dana; Copeland, Glenn; Bailey, Marie A.; Jamieson, Denise J.; Kissin, Dmitry M.

2016-01-01

IMPORTANCE Use of assisted reproductive technology (ART) has been associated with increased risks for birth defects. Variations in birth defect risks according to type of ART procedure have been noted, but findings are inconsistent. OBJECTIVES To examine the prevalence of birth defects among liveborn infants conceived with and without ART and to evaluate risks associated with certain ART procedures among ART-conceived infants. DESIGN, SETTING, AND PARTICIPANTS Used linked ART surveillance, birth certificates, and birth defects registry data for 3 states (Florida, Massachusetts, and Michigan). Methods for ascertaining birth defect cases varied by state. Resident live births during 2000 to 2010 were included, and the analysis was conducted between Feburary 2015 and August 2015. EXPOSURES Use of ART among all live births and use of certain ART procedures among ART births. MAIN OUTCOME AND MEASURES Prevalence of selected chromosomal and nonchromosomal birth defects that are usually diagnosed at or immediately after birth. RESULTS Of the 4 618 076 liveborn infants between 2000 and 2010, 64 861 (1.4%) were conceived using ART. Overall, the prevalence of 1 or more of the selected nonchromosomal defects was 58.59 per 10 000 for ART infants (n = 389) vs 47.50 per 10 000 for non-ART infants (n = 22 036). The association remained significant after adjusting for maternal characteristics and year of birth (adjusted risk ratio [aRR], 1.28; 95%CI, 1.15–1.42). Similar differences were observed for singleton ART births vs their non-ART counterparts (63.69 per 10 000 [n = 218] vs 47.17 per 10 000 [n = 21 251]; aRR, 1.38; 95%CI, 1.21–1.59). Among multiple births, the prevalence of rectal and large intestinal atresia/stenosis was higher for ART births compared with non-ART births (aRR, 2.39; 95%CI, 1.38–4.12). Among ART births conceived after fresh embryo transfer, infants born to mothers with ovulation disorders had a higher prevalence of nonchromosomal birth defects (aRR, 1.53; 95%CI, 1.13–2.06) than those born to mothers without the diagnosis, and use of assisted hatching was associated with birth defects among singleton births (aRR, 1.55; 95%CI, 1.10–2.19). Multiplicity-adjusted P values for these associations were greater than .05. CONCLUSIONS AND RELEVANCE Infants conceived after ART had a higher prevalence of certain birth defects. Assisted hatching and diagnosis of ovulation disorder were marginally associated with increased risks for nonchromosomal birth defects; however, these associations may be caused by other underlying factors. PMID:27043648

Recurrent candidiasis and early-onset gastric cancer in a patient with a genetically defined partial MYD88 defect.

PubMed

Vogelaar, Ingrid P; Ligtenberg, Marjolijn J L; van der Post, Rachel S; de Voer, Richarda M; Kets, C Marleen; Jansen, Trees J G; Jacobs, Liesbeth; Schreibelt, Gerty; de Vries, I Jolanda M; Netea, Mihai G; Hoogerbrugge, Nicoline

2016-04-01

Gastric cancer is caused by both genetic and environmental factors. A woman who suffered from recurrent candidiasis throughout her life developed diffuse-type gastric cancer at the age of 23 years. Using whole-exome sequencing we identified a germline homozygous missense variant in MYD88. Immunological assays on peripheral blood mononuclear cells revealed an impaired immune response upon stimulation with Candida albicans, characterized by a defective production of the cytokine interleukin-17. Our data suggest that a genetic defect in MYD88 results in an impaired immune response and may increase gastric cancer risk.

Risk factors in limb reduction defects.

PubMed

Stoll, C; Alembik, Y; Dott, B; Roth, M P

1992-07-01

Risk factors were studied in 123 children with limb reduction defects (LRD) from 118,265 consecutive births of known outcome during the period from 1979 to 1987 in the area which is covered by our registry of congenital malformations. For each case a control was studied. The LRD was localised and classified according to the EUROCAT guide for the description and classification of limb defects. The prevalence of LRD was 1.04 per thousand: 82.9% of the babies were liveborn, 13.0% were late spontaneous abortion or stillborn and termination was performed in 4.0% of the cases. The proportion of males was 0.55. The most common malformations in the 51.2% of children who had at least one other anomaly than LRD were associated cardiac, digestive and renal anomalies. The pregnancy with limb anomalies was more often complicated by oligohydramnios, polyhydramnios and threatened abortion but there were no differences in parental characteristics. However, 9.7% of marriages were consanguineous (P less than 0.01) and the incidence of LRD in first-degree relatives of the children with LRD was high. First-degree relatives also had more non-limb malformations than did those of controls.

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.

The association between major birth defects and preterm birth.

PubMed

Honein, Margaret A; Kirby, Russell S; Meyer, Robert E; Xing, Jian; Skerrette, Nyasha I; Yuskiv, Nataliya; Marengo, Lisa; Petrini, Joann R; Davidoff, Michael J; Mai, Cara T; Druschel, Charlotte M; Viner-Brown, Samara; Sever, Lowell E

2009-03-01

To evaluate the association between preterm birth and major birth defects by maternal and infant characteristics and specific types of birth defects. We pooled data for 1995-2000 from 13 states with population-based birth defects surveillance systems, representing about 30% of all U.S. births. Analyses were limited to singleton, live births from 24-44 weeks gestational age. Overall, birth defects were more than twice as common among preterm births (24-36 weeks) compared with term births (37-41 weeks gestation) (prevalence ratio [PR] = 2.65, 95% confidence interval [CI] 2.62-2.68), and approximately 8% of preterm births had a birth defect. Birth defects were over five times more likely among very preterm births (24-31 weeks gestation) compared with term births (PR = 5.25, 95% CI 5.15-5.35), with about 16% of very preterm births having a birth defect. Defects most strongly associated with very preterm birth included central nervous system defects (PR = 16.23, 95% CI 15.49-17.00) and cardiovascular defects (PR = 9.29, 95% CI 9.03-9.56). Birth defects contribute to the occurrence of preterm birth. Research to identify shared causal pathways and risk factors could suggest appropriate interventions to reduce both preterm birth and birth defects.

Silent myocardial ischemia in patients with symptomatic intracranial atherosclerosis: associated factors.

PubMed

Arenillas, Juan F; Candell-Riera, Jaume; Romero-Farina, Guillermo; Molina, Carlos A; Chacón, Pilar; Aguadé-Bruix, Santiago; Montaner, Joan; de León, Gustavo; Castell-Conesa, Joan; Alvarez-Sabín, José

2005-06-01

Optimization of coronary risk evaluation in stroke patients has been encouraged. The relationship between symptomatic intracranial atherosclerosis and occult coronary artery disease (CAD) has not been evaluated sufficiently. We aimed to investigate the prevalence of silent myocardial ischemia in patients with symptomatic intracranial atherosclerosis and to identify factors associated with its presence. From 186 first-ever transient ischemic attack or ischemic stroke patients with intracranial stenoses, 65 fulfilled selection criteria, including angiographic confirmation of a symptomatic atherosclerotic stenosis and absence of known CAD. All patients underwent a maximal-stress myocardial perfusion single-photon emission computed tomography (SPECT). Lipoprotein(a) [Lp(a)], C-reactive protein, and homocysteine (Hcy) levels were determined before SPECT. Stress-rest SPECT detected reversible myocardial perfusion defects in 34 (52%) patients. Vascular risk factors associated with a pathologic SPECT were hypercholesterolemia (P=0.045), presence of >2 risk factors (P=0.004) and high Lp(a) (P=0.023) and Hcy levels (P=0.018). Ninety percent of patients with high Lp(a) and Hcy levels had a positive SPECT. Existence of a stenosed intracranial internal carotid artery (ICA; odds ratio [OR], 7.22, 2.07 to 25.23; P=0.002) and location of the symptomatic stenosis in vertebrobasilar arteries (OR, 4.89, 1.19 to 20.12; P=0.027) were independently associated with silent myocardial ischemia after adjustment by age, sex, and risk factors. More than 50% of the patients with symptomatic intracranial atherosclerosis and not overt CAD show myocardial perfusion defects on stress-rest SPECT. Stenosed intracranial ICA, symptomatic vertebrobasilar stenosis and presence of high Lp(a) and Hcy levels may characterize the patients at a higher risk for occult CAD.

Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments.

PubMed

Sun, RongRong; Liu, Min; Lu, Lei; Zheng, Yi; Zhang, Peiying

2015-07-01

The congenital heart disease includes abnormalities in heart structure that occur before birth. Such defects occur in the fetus while it is developing in the uterus during pregnancy. About 500,000 adults have congenital heart disease in USA (WebMD, Congenital heart defects medications, www.WebMD.com/heart-disease/tc/congenital-heart-defects-medications , 2014). 1 in every 100 children has defects in their heart due to genetic or chromosomal abnormalities, such as Down syndrome. The excessive alcohol consumption during pregnancy and use of medications, maternal viral infection, such as Rubella virus, measles (German), in the first trimester of pregnancy, all these are risk factors for congenital heart disease in children, and the risk increases if parent or sibling has a congenital heart defect. These are heart valves defects, atrial and ventricular septa defects, stenosis, the heart muscle abnormalities, and a hole inside wall of the heart which causes defect in blood circulation, heart failure, and eventual death. There are no particular symptoms of congenital heart disease, but shortness of breath and limited ability to do exercise, fatigue, abnormal sound of heart as heart murmur, which is diagnosed by a physician while listening to the heart beats. The echocardiogram or transesophageal echocardiogram, electrocardiogram, chest X-ray, cardiac catheterization, and MRI methods are used to detect congenital heart disease. Several medications are given depending on the severity of this disease, and catheter method and surgery are required for serious cases to repair heart valves or heart transplantation as in endocarditis. For genetic study, first DNA is extracted from blood followed by DNA sequence analysis and any defect in nucleotide sequence of DNA is determined. For congenital heart disease, genes in chromosome 1 show some defects in nucleotide sequence. In this review the causes, diagnosis, symptoms, and treatments of congenital heart disease are described.

Relative susceptibilities of male germ cells to genetic defects induced by cancer chemotherapies

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

Wyrobek, A J; Schmid, T E; Marchetti, F

Some chemotherapy regimens include agents that are mutagenic or clastogenic in model systems. This raises concerns that cancer survivors, who were treated before or during their reproductive years, may be at increased risks for abnormal reproductive outcomes. However, the available data from offspring of cancer survivors are limited, representing diverse cancers, therapies, time-to-pregnancies, and reproductive outcomes. Rodent breeding data after paternal exposures to individual chemotherapeutic agents illustrate the complexity of factors that influence the risk for transmitted genetic damage including agent, dose, endpoint, and the germ-cell susceptibility profiles that vary across agents. Direct measurements of chromosomal abnormalities in sperm ofmore » mice and humans by sperm FISH have corroborated the differences in germ-cell susceptibilities. The available evidence suggests that the risk of producing chromosomally defective sperm is highest during the first few weeks after the end of chemotherapy, and decays with time. Thus, sperm samples provided immediately after the initiation of cancer therapies may contain treatment-induced genetic defects that will jeopardize the genetic health of offspring.« less

Risk factors for congenital diaphragmatic hernia in the Bogota birth defects surveillance and follow-up program, Colombia.

PubMed

García, Ana M; Machicado, S; Gracia, G; Zarante, I M

2016-03-01

The mortality rate for congenital diaphragmatic hernia (CDH) remains high and prevention efforts are limited by the lack of known risk factors. The aim of this study was to determine prevalence, risk factors, and neonatal results associated with CDH on a surveillance system hospital-based in Bogotá, Colombia. The data used in this study were obtained from The Bogota Birth Defects Surveillance and Follow-up Program (BBDSFP), between January 2001 and December 2013. With 386,419 births, there were 81 cases of CDH. A case-control methodology was conducted with 48 of the total cases of CDH and 192 controls for association analysis. The prevalence of CDH was 2.1 per 10,000 births. In the case-control analysis, risk factors found were maternal age ≥35 years (OR, 33.53; 95 % CI, 7.02-160.11), infants with CDH were more likely to be born before 37 weeks of gestation (OR, 5.57; 95 % CI, 2.05-15.14), to weigh less than 2500 g at birth (OR, 9.05; 95 % CI, 3.51-23.32), and be small for gestational age (OR, 5.72; 95 % CI, 2.18-14.99) with a high rate of death before hospital discharge in the CDH population (CDH: 38 % vs BBDSFP: <1 %; p < 0.001). The prevalence of CDH calculated was similar to the one reported in the literature. CDH is strongly associated with a high rate of death before hospital discharge and the risk factors found were maternal age ≥35 years, preterm birth, be small for gestational age, and have low weight at birth. These neonatal characteristics in developing countries would help to identify early CDH. Prevention efforts have been limited by the lack of known risk factors and established epidemiological profiles, especially in developing countries.

Airport noise and teratogenesis.

PubMed

Edmonds, L D; Layde, P M; Erickson, J D

1979-01-01

It has been suggested that exposures to high-noise levels near major airports may cause increased incidence of birth defects in the offspring of parents residing near these airports. Using data gathered in Metropolitan Atlanta during 1970 to 1972, we compared the rates of seventeen categories of defects in high- and low-noise census tracts. No significant differences were observed. However, when we subdivided the category of central nervous system defects into several subcategories of specific defects, we noted a significantly increased incidence of spina bifida without hydrocephalus in the high-noise areas. Because the small number of cases associated with this finding we did a matched case-control study using all cases of central nervous system defects born during the years 1968 to 1976. No significantly increased risk for residents in the high-noise areas was noted in this study. It is our opinion that noise or other factors associated with residence near airports are unlikely to be important environmental teratogens.

[Risk factors in the results of the colour vision test Roth 28-hue (E) desaturated in glaucoma patients].

PubMed

Jass, C M; Böhringer, D; Erb, C; Jordan, J F

2013-11-01

Glaucoma is an ocular disease with typical progressive damage of the optic nerve. In the past it was postulated that glaucoma induces acquired colour vision disorders. Until now all studies about glaucoma and colour vision disorders did not include vascular risk factors. In the present study we determined several vascular risk factors concerning the results of the colour vision test Roth 28-hue (E) desaturated in glaucoma patients. On the basis of an analysis of variance (ANOVA) we determined the influence of several risk factors, such as arteriosclerotic and vasospastic risk factors, on the results of the colour vision test Roth 28-hue (E) desaturated in glaucoma patients. 353 glaucoma patients were included in this study. We detected a strong influence of age and mean defect in perimetry and an additional effect of arteriosclerotic and vasospastic risk factors on the results of the colour vision test Roth 28-hue (E) desaturated in glaucoma patients. We suspect that arteriosclerotic and vasospastic risk factors independently to glaucoma have an influence on colour vision. In the future attention additionally has to be given to vascular risk factors in the colour vision testing of glaucoma patients. Georg Thieme Verlag KG Stuttgart · New York.

Parental risk factors for oral clefts among Central Africans, Southeast Asians, and Central Americans

PubMed Central

Ly, Stephanie; Magee, Kathleen S.; Ihenacho, Ugonna; Baurley, James W.; Sanchez‐Lara, Pedro A.; Brindopke, Frederick; Nguyen, Thi‐Hai‐Duc; Nguyen, Viet; Tangco, Maria Irene; Giron, Melissa; Abrahams, Tamlin; Jang, Grace; Vu, Annie; Zolfaghari, Emily; Yao, Caroline A.; Foong, Athena; DeClerk, Yves A.; Samet, Jonathan M.; Magee, William

2015-01-01

Background Several lifestyle and environmental exposures have been suspected as risk factors for oral clefts, although few have been convincingly demonstrated. Studies across global diverse populations could offer additional insight given varying types and levels of exposures. Methods We performed an international case–control study in the Democratic Republic of the Congo (133 cases, 301 controls), Vietnam (75 cases, 158 controls), the Philippines (102 cases, 152 controls), and Honduras (120 cases, 143 controls). Mothers were recruited from hospitals and their exposures were collected from interviewer‐administered questionnaires. We used logistic regression modeling to estimate odds ratios (OR) and 95% confidence intervals (CI). Results Family history of clefts was strongly associated with increased risk (maternal: OR = 4.7; 95% CI, 3.0–7.2; paternal: OR = 10.5; 95% CI, 5.9–18.8; siblings: OR = 5.3; 95% CI, 1.4–19.9). Advanced maternal age (5 year OR = 1.2; 95% CI, 1.0–1.3), pregestational hypertension (OR = 2.6; 95% CI, 1.3–5.1), and gestational seizures (OR = 2.9; 95% CI, 1.1–7.4) were statistically significant risk factors. Lower maternal (secondary school OR = 1.6; 95% CI, 1.2–2.2; primary school OR = 2.4, 95% CI, 1.6–2.8) and paternal education (OR = 1.9; 95% CI, 1.4–2.5; and OR = 1.8; 95% CI, 1.1–2.9, respectively) and paternal tobacco smoking (OR = 1.5, 95% CI, 1.1–1.9) were associated with an increased risk. No other significant associations between maternal and paternal factors were found; some environmental factors including rural residency, indoor cooking with wood, chemicals and water source appeared to be associated with an increased risk in adjusted models. Conclusion Our study represents one of the first international studies investigating risk factors for clefts among multiethnic underserved populations. Our findings suggest a multifactorial etiology including both maternal and paternal factors. Birth Defects Research (Part A) 103:863–879, 2015. © 2015 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc. PMID:26466527

Mental health status of North Korean refugees in South Korea and risk and protective factors: a 10-year review of the literature

PubMed Central

Lee, Yeeun; Lee, Minji; Park, Subin

2017-01-01

ABSTRACT Background: North Korean refugees (NKRs) are often exposed to traumatic events in North Korea and during their defection. Furthermore, they face sociocultural barriers in adapting to the new society to which they have defected. Objective: To integrate previous findings on this mentally vulnerable population, we systematically reviewed articles on the mental health of NKRs in South Korea. Method: We searched for empirical studies conducted in the last 10 years in six online databases (international journals: Embase, PubMed, Scopus, Web of Science; Korean journals: DBPIA, KMbase) through June 2017. Only quantitative studies using new empirical data on the mental health of NKRs were included. We summarized the 56 studies ultimately selected in terms of NKRs’ mental health status and three domains of associated factors: pre- and post-settlement factors and personal factors. Results: NKRs had a high prevalence and severity of psychiatric symptoms, particularly post-traumatic stress disorder and depression. We identified nine risk factors consistently found in previous studies, including traumatic experience, longer stay periods in third country, forced repatriation, acculturative stress, low income, older age, poor physical health, and female and male sex, as well as four protective factors, including educational level in North Korea, social support, family relationship quality, and resilience. Conclusions: We suggest that future studies focus on the causal interactions between different risk and protective factors and mental health outcomes among NKRs from a longitudinal perspective. Furthermore, comprehensive policies for NKRs’ psychological adaptation are needed, particularly the development of evidence-based mental health interventions. PMID:29038687

Mental health status of North Korean refugees in South Korea and risk and protective factors: a 10-year review of the literature.

PubMed

Lee, Yeeun; Lee, Minji; Park, Subin

2017-01-01

Background : North Korean refugees (NKRs) are often exposed to traumatic events in North Korea and during their defection. Furthermore, they face sociocultural barriers in adapting to the new society to which they have defected. Objective : To integrate previous findings on this mentally vulnerable population, we systematically reviewed articles on the mental health of NKRs in South Korea. Method : We searched for empirical studies conducted in the last 10 years in six online databases (international journals: Embase, PubMed, Scopus, Web of Science; Korean journals: DBPIA, KMbase) through June 2017. Only quantitative studies using new empirical data on the mental health of NKRs were included. We summarized the 56 studies ultimately selected in terms of NKRs' mental health status and three domains of associated factors: pre- and post-settlement factors and personal factors. Results : NKRs had a high prevalence and severity of psychiatric symptoms, particularly post-traumatic stress disorder and depression. We identified nine risk factors consistently found in previous studies, including traumatic experience, longer stay periods in third country, forced repatriation, acculturative stress, low income, older age, poor physical health, and female and male sex, as well as four protective factors, including educational level in North Korea, social support, family relationship quality, and resilience. Conclusions : We suggest that future studies focus on the causal interactions between different risk and protective factors and mental health outcomes among NKRs from a longitudinal perspective. Furthermore, comprehensive policies for NKRs' psychological adaptation are needed, particularly the development of evidence-based mental health interventions.

An Introduction to Risk with a Focus on Design Diversity in the Stockpile

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

Noone, Bailey C

2012-08-13

The maintenance and security of nuclear weapons in the stockpile involves decisions based on risk analysis and quantitative measures of risk. Risk is a factor in all decisions, a particularly important factor in decisions of a large scale. One example of high-risk decisions we will discuss is the risk involved in design diversity within the stockpile of nuclear weapons arsenal. Risk is defined as 'possibility of loss or injury' and the 'degree of probability of such loss' (Kaplan and Garrick 12). To introduce the risk involved with maintaining the weapons stockpile we will draw a parallel to the design andmore » maintenance of Southwest Airlines fleet of Boeing 737 planes. The clear benefits for cost savings in maintenance of having a uniform fleet are what historically drove Southwest to have only Boeing 737s in their fleet. Less money and resources are need for maintenance, training, and materials. Naturally, risk accompanies those benefits. A defect in a part of the plane indicates a potential defect in that same part in all the planes of the fleet. As a result, safety, business, and credibility are at risk. How much variety or diversity does the fleet need to mitigate that risk? With that question in mind, a balance is needed to accommodate the different risks and benefits of the situation. In a similar way, risk is analyzed for the design and maintenance of nuclear weapons in the stockpile. In conclusion, risk must be as low as possible when it comes to the nuclear weapons stockpile. Design and care to keep the stockpile healthy involves all aspects of risk management. Design diversity is a method that helps to mitigate risk, and to help balance options in stockpile stewardship.« less

Understand Your Risk for Heart Failure

MedlinePlus

... Heart.org Arrhythmia About Arrhythmia Why Arrhythmia Matters Understand Your Risk for Arrhythmia Symptoms, Diagnosis & Monitoring of ... Heart Defects The Impact of Congenital Heart Defects Understand Your Risk for Congenital Heart Defects Symptoms & Diagnosis ...

Impact of patient-specific factors, irradiated left ventricular volume, and treatment set-up errors on the development of myocardial perfusion defects after radiation therapy for left-sided breast cancer

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

Evans, Elizabeth S.; Prosnitz, Robert G.; Yu Xiaoli

2006-11-15

Purpose: The aim of this study was to assess the impact of patient-specific factors, left ventricle (LV) volume, and treatment set-up errors on the rate of perfusion defects 6 to 60 months post-radiation therapy (RT) in patients receiving tangential RT for left-sided breast cancer. Methods and Materials: Between 1998 and 2005, a total of 153 patients were enrolled onto an institutional review board-approved prospective study and had pre- and serial post-RT (6-60 months) cardiac perfusion scans to assess for perfusion defects. Of the patients, 108 had normal pre-RT perfusion scans and available follow-up data. The impact of patient-specific factors onmore » the rate of perfusion defects was assessed at various time points using univariate and multivariate analysis. The impact of set-up errors on the rate of perfusion defects was also analyzed using a one-tailed Fisher's Exact test. Results: Consistent with our prior results, the volume of LV in the RT field was the most significant predictor of perfusion defects on both univariate (p = 0.0005 to 0.0058) and multivariate analysis (p = 0.0026 to 0.0029). Body mass index (BMI) was the only significant patient-specific factor on both univariate (p = 0.0005 to 0.022) and multivariate analysis (p = 0.0091 to 0.05). In patients with very small volumes of LV in the planned RT fields, the rate of perfusion defects was significantly higher when the fields set-up 'too deep' (83% vs. 30%, p = 0.059). The frequency of deep set-up errors was significantly higher among patients with BMI {>=}25 kg/m{sup 2} compared with patients of normal weight (47% vs. 28%, p = 0.068). Conclusions: BMI {>=}25 kg/m{sup 2} may be a significant risk factor for cardiac toxicity after RT for left-sided breast cancer, possibly because of more frequent deep set-up errors resulting in the inclusion of additional heart in the RT fields. Further study is necessary to better understand the impact of patient-specific factors and set-up errors on the development of RT-induced perfusion defects.« less

Color vision abnormalities in type II diabetes: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study II report no 2

PubMed Central

Gella, Laxmi; Raman, Rajiv; Kulothungan, Vaitheeswaran; Pal, Swakshyar Saumya; Ganesan, Suganeswari; Srinivasan, Sangeetha; Sharma, Tarun

2017-01-01

Purpose: The purpose of this study is to assess color vision abnormalities in a cohort of subjects with type II diabetes and elucidate associated risk factors. Methods: Subjects were recruited from follow-up cohort of Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study I. Six hundred and seventy-three eyes of 343 subjects were included from this population-based study. All subjects underwent detailed ophthalmic evaluation, including the Farnsworth-Munsell 100 hue test. Results: The prevalence of impaired color vision (ICV) was 43% (CI: 39.2–46.7). Risk factors for ICV were higher heart rate (odds ratio [OR]: 1.043, [1.023–1.064]) and a higher intraocular pressure (IOP) (OR: 1.086, [1.012–1.165]). Subjects with clinically significant macular edema (CSME) had three times higher chance of having ICV. C1, C2, and C3 are the commonly found Early Treatment Diabetic Retinopathy Study (ETDRS) patterns. The moment of inertia method showed that the angle did not reveal any specific pattern of color vision defect. Although the major and minor radii were high in those with ICV, we did not observe polarity. Confusion index was high in subjects with ICV, indicating a severe color vision defect. Conclusions: The prevalence of ICV was 43% among subjects with type II diabetes. The most commonly observed patterns were increasing severities of the blue–yellow defect on ETDRS patterns, but no specific pattern was observed at the moment of inertia analysis. The presence of CSME, a higher heart rate, and IOP was significant risk factors for ICV. This functional impairment in color vision could significantly contribute to morbidity among subjects with diabetes. PMID:29044066

Color vision abnormalities in type II diabetes: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study II report no 2.

PubMed

Gella, Laxmi; Raman, Rajiv; Kulothungan, Vaitheeswaran; Pal, Swakshyar Saumya; Ganesan, Suganeswari; Srinivasan, Sangeetha; Sharma, Tarun

2017-10-01

The purpose of this study is to assess color vision abnormalities in a cohort of subjects with type II diabetes and elucidate associated risk factors. Subjects were recruited from follow-up cohort of Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study I. Six hundred and seventy-three eyes of 343 subjects were included from this population-based study. All subjects underwent detailed ophthalmic evaluation, including the Farnsworth-Munsell 100 hue test. The prevalence of impaired color vision (ICV) was 43% (CI: 39.2-46.7). Risk factors for ICV were higher heart rate (odds ratio [OR]: 1.043, [1.023-1.064]) and a higher intraocular pressure (IOP) (OR: 1.086, [1.012-1.165]). Subjects with clinically significant macular edema (CSME) had three times higher chance of having ICV. C1, C2, and C3 are the commonly found Early Treatment Diabetic Retinopathy Study (ETDRS) patterns. The moment of inertia method showed that the angle did not reveal any specific pattern of color vision defect. Although the major and minor radii were high in those with ICV, we did not observe polarity. Confusion index was high in subjects with ICV, indicating a severe color vision defect. The prevalence of ICV was 43% among subjects with type II diabetes. The most commonly observed patterns were increasing severities of the blue-yellow defect on ETDRS patterns, but no specific pattern was observed at the moment of inertia analysis. The presence of CSME, a higher heart rate, and IOP was significant risk factors for ICV. This functional impairment in color vision could significantly contribute to morbidity among subjects with diabetes.

Cerebrovascular accidents in sickle cell disease. Risk factors and blood transfusion influence. French Study Group on Sickle Cell Disease.

PubMed

de Montalembert, M; Beauvais, P; Bachir, D; Galacteros, F; Girot, R

1993-03-01

This study presents a series of 34 sickle cell patients with one or more cerebrovascular accidents (CVA). Risk factors were studied in a subgroup of 19 patients whose clinical and biological characteristics were compared to those of a group of 444 sickle cell patients without CVA. The only risk factor discovered was a past history of purulent meningitis, which was significantly more frequent in sickle cell patients than in those without CVA (P < 0.0001). No biological or radiological factor affecting the risk of recurrence was found. The risk of recurrence, neurological defects or death after subsequent CVA justify long-term transfusion treatment in patients presenting with a second CVA. However our study shows that 10 patients who were not transfused after their first CVA had no recurrences, (median follow up = 7.9 years; 2-18 years), providing a basis for discussion on the indications of long-term transfusion therapy for sickle cell patients presenting with their first CVA.

[Genetic obesity: new diagnostic options].

PubMed

de Vries, T I; Alsters, S I M; Kleinendorst, L; van Haaften, G; van der Zwaag, B; Van Haelst, M M

2017-01-01

- Obesity is an important risk factor for morbidity and premature death, as well as a contributing factor to psychosocial problems. The incidence of obesity has increased dramatically over the last few decades.- Obesity is considered to be a multifactorial condition in which both environmental factors and genetic factors play a part.- In approximately 5% of patients with morbid obesity, a monogenic cause can be identified. Mutations in the MC4R gene are the most frequently occurring monogenic cause of obesity.- The department of Genetics at the VU University Medical Center Amsterdam offers morbidly obese patients a diagnostic analysis of 50 obesity-associated genes. - An underlying obesity-associated genetic defect can influence patient response to certain treatments. Therefore, if the gene defect is known, it can be taken into account when considering treatment options.- The understanding of the genetics of obesity will significantly contribute to research into the development of personalized treatment options.

Risk factors for esophageal stenosis after entire circumferential endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

PubMed

Miwata, Tomohiro; Oka, Shiro; Tanaka, Shinji; Kagemoto, Kenichi; Sanomura, Yoji; Urabe, Yuji; Hiyama, Toru; Chayama, Kazuaki

2016-09-01

Endoscopic submucosal dissection (ESD) is used to perform en block resection for esophageal squamous cell carcinoma, but it is strongly associated with postoperative stenosis, especially during entire circumferential resection. This study aimed to clarify the risk factors for refractory postoperative stenosis after entire circumferential esophageal ESD. Nineteen patients who underwent entire circumferential esophageal ESD from February 2006 to December 2013 at Hiroshima University Hospital were divided into two groups: refractory postoperative stenosis [≥6 endoscopic balloon dilation (EBD) procedures, 12 lesions in 12 patients] and non-refractory postoperative stenosis (≤5 EBD procedures, 7 lesions in 7 patients). We retrospectively examined the patient factors (age, sex, alcohol consumption, smoking index, and chemoradiation therapy history), tumor factors (location, macroscopic type, fibrosis, and depth), and treatment factors (mean procedure time, entire circumferential resection diameter, muscle layer damage, and steroid administration method) between the two groups. Muscle layer damage (p = 0.019) and ≥5 cm of longitudinal mucosal defect length after entire circumferential esophageal ESD (p = 0.010) were significant factors associated with the refractory group. Regarding the patient and tumor factors, there were no significant differences between the two groups. Our data suggest that refractory post-ESD stenosis occurs after entire circumferential esophageal ESD with muscle layer damage and ≥5 cm of longitudinal mucosal defect length.

Visual field defects may not affect safe driving.

PubMed

Dow, Jamie

2011-10-01

In Quebec a driver whose acquired visual field defect renders them ineligible for a driver's permit renewal may request an exemption from the visual field standard by demonstrating safe driving despite the defect. For safety reasons it was decided to attempt to identify predictors of failure on the road test in order to avoid placing driving evaluators in potentially dangerous situations when evaluating drivers with visual field defects. During a 4-month period in 2009 all requests for exemptions from the visual field standard were collected and analyzed. All available medical and visual field data were collated for 103 individuals, of whom 91 successfully completed the evaluation process and obtained a waiver. The collated data included age, sex, type of visual field defect, visual field characteristics, and concomitant medical problems. No single factor, or combination of factors, could predict failure of the road test. All 5 failures of the road test had cognitive problems but 6 of the successful drivers also had known cognitive problems. Thus, cognitive problems influence the risk of failure but do not predict certain failure. Most of the applicants for an exemption were able to complete the evaluation process successfully, thereby demonstrating safe driving despite their handicap. Consequently, jurisdictions that have visual field standards for their driving permit should implement procedures to evaluate drivers with visual field defects that render them unable to meet the standard but who wish to continue driving.

Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

PubMed

Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W J; Payan-Gomez, Cesar; van IJcken, Wilfred F J; Rijksen, Yvonne M A; Nigg, Alex L; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H J; Mastroberardino, Pier G

2016-05-31

The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

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.

[Association of folate metabolism genes MTRR and MTHFR with complex congenital abnormalities among Chinese population in Shanxi Province, China].

PubMed

Zhang, Qin; Bai, Bao-Ling; Liu, Xiao-Zhen; Miao, Chun-Yue; Li, Hui-Li

2014-08-01

To explore the association of polymorphisms in folate metabolism genes, methionine synthase reductase (MTRR) gene and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, with complex congenital abnormalities and to further investigate its association with complex congenital abnormalities derived from three germ layers. A total of 250 cases of birth defects (with complex congenital abnormalities including congenital heart disease, neural tube defects, and craniofacial anomalies) in Shanxi Province, China were included in the study. MTRR single nucleotide polymorphism (SNP) (rs1801394) and MTHFR SNP (rs1801133) were genotyped by the SNaPshot method, and the genotyping results were compared with those of controls (n=420). SNPs rs1801394 and rs1801133 were associated with multiple birth defects. For the recessive model, individuals with GG genotype at rs1801394 and CC genotype at rs1801133 had a relatively low risk of developing birth defects, so the two genotypes were protective factors against birth defects. The homozygous recessive genotype at rs1801133, which served as a protective factor, was associated with ectoderm- or endoderm-derived complex congenital abnormalities, while the homozygous recessive genotype at rs1801394, which served as a protective factor, was associated with ectoderm-, mesoderm- or endoderm-derived complex congenital abnormalities. Among the Chinese population in Shanxi Province, the SNPs in folate metabolism genes (MTRR and MTHFR) are associated with complex congenital abnormalities and related to ectoderm, mesoderm or endoderm development.

Genetics of human neural tube defects

PubMed Central

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

2009-01-01

Neural tube defects (NTDs) are common, severe congenital malformations whose causation involves multiple genes and environmental factors. Although more than 200 genes are known to cause NTDs in mice, there has been rather limited progress in delineating the molecular basis underlying most human NTDs. Numerous genetic studies have been carried out to investigate candidate genes in cohorts of patients, with particular reference to those that participate in folate one-carbon metabolism. Although the homocysteine remethylation gene MTHFR has emerged as a risk factor in some human populations, few other consistent findings have resulted from this approach. Similarly, attention focused on the human homologues of mouse NTD genes has contributed only limited positive findings to date, although an emerging association between genes of the non-canonical Wnt (planar cell polarity) pathway and NTDs provides candidates for future studies. Priorities for the next phase of this research include: (i) larger studies that are sufficiently powered to detect significant associations with relatively minor risk factors; (ii) analysis of multiple candidate genes in groups of well-genotyped individuals to detect possible gene–gene interactions; (iii) use of high throughput genomic technology to evaluate the role of copy number variants and to detect ‘private’ and regulatory mutations, neither of which have been studied to date; (iv) detailed analysis of patient samples stratified by phenotype to enable, for example, hypothesis-driven testing of candidates genes in groups of NTDs with specific defects of folate metabolism, or in groups of fetuses with well-defined phenotypes such as craniorachischisis. PMID:19808787

Playing wind instruments as a potential aetiologic cofactor in external cervical resorption: two case reports.

PubMed

Gunst, V; Huybrechts, B; De Almeida Neves, A; Bergmans, L; Van Meerbeek, B; Lambrechts, P

2011-03-01

To present two cases of external cervical resorption (ECR) on maxillary incisors, in which the primary aetiologic factor is suggested to be pressure trauma by frequently playing wind instruments. The exact aetiological spectrum of ECR is still poorly understood. For resorption to occur, a defect in the cementum layer (trigger) is a likely prerequisite. Whilst the mechanism for continuation (stimulus) is still unclear, knowledge of potential predisposing factors is important in assessing patients at risk. Pressure generated by playing wind instruments could present an aetiological factor in ECR because it affects the cervical region of the root surface. The cases that are presented may confirm this hypothesis and the extent of resorption defects is shown by cone-beam computer tomography (CT) and micro-focus CT imaging techniques. © 2010 International Endodontic Journal.

Preoperative Detailed Coagulation Tests Are Required in Patients With Noonan Syndrome.

PubMed

Morice, Anne; Harroche, Annie; Cairet, Pascale; Khonsari, Roman H

2017-12-29

Patients with Noonan syndrome often require surgery at young ages. They are at high risk of perioperative bleeding from coagulation defects that might not have been detected by routine screening. These risks are rarely described in the oral and maxillofacial surgery (OMS) literature. The aim of this study was to evaluate the perioperative bleeding risks associated with Noonan syndrome and to propose preoperative guidelines. This report describes a retrospective case series of patients with Noonan syndrome who underwent OMS procedures during a continuous observational period (2013 through 2016) in the authors' center. Clinical data, blood screening test results, and perioperative bleeding were analyzed. Five patients (age, 4 to 20 yr) with Noonan syndrome who underwent OMS procedures were included in this study. One patient presented a spontaneous bleeding tendency (epistaxis requiring cauterization). Blood screening showed clotting defects in 3 patients. One patient presented abnormal perioperative bleeding owing to a mild defect in factor XI. Patients with Noonan syndrome must be referred to a hematologist for specific preoperative investigations and for adapted perioperative management. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Association of neural tube defects in children of mothers with MTHFR 677TT genotype and abnormal carbohydrate metabolism risk: a case-control study.

PubMed

Cadenas-Benitez, N M; Yanes-Sosa, F; Gonzalez-Meneses, A; Cerrillos, L; Acosta, D; Praena-Fernandez, J M; Neth, O; Gomez de Terreros, I; Ybot-González, P

2014-03-26

Abnormalities in maternal folate and carbohydrate metabolism have both been shown to induce neural tube defects (NTD) in humans and animal models. However, the relationship between these two factors in the development of NTDs remains unclear. Data from mothers of children with spina bifida seen at the Unidad de Espina Bífida del Hospital Infantil Virgen del Rocío (case group) were compared to mothers of healthy children with no NTD (control group) who were randomly selected from patients seen at the outpatient ward in the same hospital. There were 25 individuals in the case group and 41 in the control group. Analysis of genotypes for the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism in women with or without risk factors for abnormal carbohydrate metabolism revealed that mothers who were homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism were more likely to have offspring with spina bifida and high levels of homocysteine, compared to the control group. The increased incidence of NTDs in mothers homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism stresses the need for careful metabolic screening in pregnant women, and, if necessary, determination of the MTHFR 677CT genotype in those mothers at risk of developing abnormal carbohydrate metabolism.

Later Competence and Adaptation in Infants Who Survive Severe Heart Defects.

ERIC Educational Resources Information Center

O'Dougherty, Margaret; And Others

1983-01-01

Describes a model of risk potential for developmental outcome that was based on cardiac, medical, surgical, and family stress factors in 31 children with transposition of the great arteries. All children had undergone reparative open heart surgery utilizing cardiopulmonary bypass during infancy. (Author/RH)

Infant abusive head trauma in a military cohort.

PubMed

Gumbs, Gia R; Keenan, Heather T; Sevick, Carter J; Conlin, Ava Marie S; Lloyd, David W; Runyan, Desmond K; Ryan, Margaret A K; Smith, Tyler C

2013-10-01

Evaluate the rate of, and risk factors for, abusive head trauma (AHT) among infants born to military families and compare with civilian population rates. Electronic International Classification of Diseases data from the US Department of Defense (DoD) Birth and Infant Health Registry were used to identify infants born to military families from 1998 through 2005 (N = 676 827) who met the study definition for AHT. DoD Family Advocacy Program data were used to identify infants with substantiated reports of abuse. Rates within the military were compared with civilian population rates by applying an alternate AHT case definition used in a civilian study. Applying the study definition, the estimated rate of substantiated military AHT was 34.0 cases in the first year of life per 100 000 live births. Using the alternate case definition, the estimated AHT rate was 25.6 cases per 100 000 live births. Infant risk factors for AHT included male sex, premature birth, and a diagnosed major birth defect. Parental risk factors included young maternal age (<21 years), lower sponsor rank or pay grade, and current maternal military service. This is the first large database study of AHT with the ability to link investigative results to cases. Overall rates of AHT were consistent with civilian populations when using the same case definition codes. Infants most at risk, warranting special attention from military family support programs, include infants with parents in lower military pay grades, infants with military mothers, and infants born premature or with birth defects.

Early detection of glaucoma by means of a novel 3D computer‐automated visual field test

PubMed Central

Nazemi, Paul P; Fink, Wolfgang; Sadun, Alfredo A; Francis, Brian; Minckler, Donald

2007-01-01

Purpose A recently devised 3D computer‐automated threshold Amsler grid test was used to identify early and distinctive defects in people with suspected glaucoma. Further, the location, shape and depth of these field defects were characterised. Finally, the visual fields were compared with those obtained by standard automated perimetry. Patients and methods Glaucoma suspects were defined as those having elevated intraocular pressure (>21 mm Hg) or cup‐to‐disc ratio of >0.5. 33 patients and 66 eyes with risk factors for glaucoma were examined. 15 patients and 23 eyes with no risk factors were tested as controls. The recently developed 3D computer‐automated threshold Amsler grid test was used. The test exhibits a grid on a computer screen at a preselected greyscale and angular resolution, and allows patients to trace those areas on the grid that are missing in their visual field using a touch screen. The 5‐minute test required that the patients repeatedly outline scotomas on a touch screen with varied displays of contrast while maintaining their gaze on a central fixation marker. A 3D depiction of the visual field defects was then obtained that was further characterised by the location, shape and depth of the scotomas. The exam was repeated three times per eye. The results were compared to Humphrey visual field tests (ie, achromatic standard or SITA standard 30‐2 or 24‐2). Results In this pilot study 79% of the eyes tested in the glaucoma‐suspect group repeatedly demonstrated visual field loss with the 3D perimetry. The 3D depictions of visual field loss associated with these risk factors were all characteristic of or compatible with glaucoma. 71% of the eyes demonstrated arcuate defects or a nasal step. Constricted visual fields were shown in 29% of the eyes. No visual field changes were detected in the control group. Conclusions The 3D computer‐automated threshold Amsler grid test may demonstrate visual field abnormalities characteristic of glaucoma in glaucoma suspects with normal achromatic Humphrey visual field testing. This test may be used as a screening tool for the early detection of glaucoma. PMID:17504855

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.

Maternal risk factors in fetal alcohol syndrome: provocative and permissive influences.

PubMed

Abel, E L; Hannigan, J H

1995-01-01

We present an hypothesis integrating epidemiological, clinical case, and basic biomedical research to explain why only relatively few women who drink alcohol during pregnancy give birth to children with alcohol-related birth defects (ARBDs), in particular, Fetal Alcohol Syndrome (FAS). We argue that specific sociobehavioral risk factors, e.g., low socioeconomic status, are permissive for FAS in that they provide the context for increased vulnerability. We illustrate how these permissive factors are related to biological factors, e.g., decreased antioxidant status, which in conjunction with alcohol, provoke FAS/ARBDs in vulnerable fetuses. We propose an integrative heuristic model hypothesizing that these permissive and provocative factors increase the likelihood of FAS/ARBDs because they potentiate two related mechanisms of alcohol-induced teratogenesis, specifically, maternal/fetal hypoxia and free radical formation.

Understanding the increased risk of neural tube defect-affected pregnancies among Mexico-born women in California: immigration and anthropometric factors.

PubMed

Velie, Ellen M; Shaw, Gary M; Malcoe, Lorraine H; Schaffer, Donna M; Samuels, Steven J; Todoroff, Karen; Block, Gladys

2006-05-01

Mexico-born women in the United States have an unexplained twofold increased risk of neural tube defect (NTD)-affected pregnancies. We examined whether immigration characteristics were associated with the NTD risk and whether anthropometric factors contributed to the increased risk among Mexico-born women. Data were derived from a large population-based case-control study in California. In-person interviews were conducted with mothers of 538 (88% of eligible) NTD-affected fetuses/infants and mothers of 539 (88%) randomly selected non-malformed control infants. The crude odds ratio (OR) for NTDs among all Mexico-born women, women residing <2 years in the US, and women >16 years old at immigration compared with non-Hispanic white women was 2.4 [95% confidence interval (CI) = 1.8, 3.3], 7.2 [95% CI = 3.7, 14.0] and 3.0 [95% CI = 2.0, 4.4], respectively. Risk for second- or third-generation Mexican-Americans was similar to that of white women. The crude OR for all Mexico-born women was reduced from 2.4 to 2.0 [95% CI = 1.3, 3.0] and for those residing <2 years in the US from 8.4 to 7.1 [95% CI = 3.2, 15.3] after adjustment for maternal body mass index (BMI), height, compromised diet, diabetes, and other known risk factors. In term pregnancies, additional adjustment for pregnancy weight gain reduced the OR in all Mexico-born women and recent immigrants by 16% and 25%, respectively. Low pregnancy weight gain (<10 vs. 10-14 kg) was particularly associated with increased NTD risk among Mexico-born women (OR(ADJ) = 5.8; 95% CI = 2.1, 15.8). Findings indicate that recent Mexican immigrants have a sevenfold increased risk for NTDs. Maternal BMI and height contributed very little, and inadequate weight gain contributed modestly to the NTD risk disparity for Mexican immigrants.

Should Cesarean Scar Defect Be Treated Laparoscopically? A Case Report and Review of the Literature.

PubMed

Api, Murat; Boza, Aysen; Gorgen, Husnu; Api, Olus

2015-01-01

Several obstetric complications due to inappropriately healed cesarean scar such as placenta accreta, scar dehiscence, and ectopic scar pregnancy are increasingly reported along with rising cesarean rates. Furthermore, many gynecologic conditions, including abnormal uterine bleeding, pelvic pain and infertility, are imputed to deficient cesarean scar healing. Hysteroscopy is the most commonly reported approach for the revision of cesarean scar defects (CSDs). Nevertheless, existing evidence is inadequate to conclude that either hysteroscopy or laparoscopy is effective or superior to each other. Although several management options have been suggested recently, the laparoscopic approach has not been thoroughly scrutinized. We present a case and reviewed the data related to the laparoscopic repair of CSDs and compared the hysteroscopic and laparoscopic management options based on the data from previously published articles. As a result of our analyses, the laparoscopic approach increases uterine wall thickness when compared with the hysteroscopic approach, and both surgical techniques seem to be effective for the resolution of gynecologic symptoms. Hysteroscopic treatment most likely corrects the scar defect but does not strengthen the uterine wall; thus, the potential risk of dehiscence or rupture in subsequent pregnancies does not seem to be improved. Because large uterine defects are known risk factors for scar dehiscence, the repair of the defect to reinforce the myometrial endurance seems to be an appropriate method of treatment. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

RISK FACTORS FOR NEURAL TUBE DEFECTS: ASSOCIATIONS BETWEEN UNCOUPLING PROTEIN 2 POLYMORPHISMS AND SPINA BIFIDA. (R828292)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Nixtamalization Reduces Fumonisin Toxicity

USDA-ARS?s Scientific Manuscript database

Fumonisin B1 is a fungal toxin found in corn and corn-based foods. It causes diseases in animals, and is a suspected risk factor for birth defects in humans depending on contaminated corn as a diet staple. Tortillas, snacks and other foods are made from corn by the alkaline cooking process known as ...

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

Violence against Women and Gastroschisis: A Case-Control Study

PubMed Central

Ortega-García, Juan Antonio; Soldin, Offie P.; Sánchez-Sauco, Miguel Felipe; Cánovas-Conesa, Alicia; Gomaríz-Peñalver, Virtudes; Jaimes-Vega, Diana Carolina; Perales, Joseph E.; Cárceles-Alvarez, Alberto; Martínez-Ros, Maria Teresa; Ruiz, Daniel

2013-01-01

Background: Gastroschisis, a birth defect characterized by herniated fetal abdominal wall, occurs more commonly in infants born to teenage and young mothers. Ischemia of the vascular vitelline vessels is the likely mechanism of pathogenesis. Given that chronic stress and violence against women are risk factors for cardiovascular disease we explored whether these may represent risk factors for gastroschisis, when they occur during pregnancy. A case-control study was conducted, with 15 incident cases of children born with gastroschisis in the Region of Murcia, Spain, from December 2007 to June 2013. Forty concurrent controls were recruited at gestation weeks 20–24 or post-partum. All mothers of cases and controls completed a comprehensive, in-person, ‘green sheet’ questionnaire on environmental exposures. Results: Mothers of children with gastroschisis were younger, smoked more cigarettes per week relative to controls, were exposed to higher amounts of illegal drugs, and suffered from domestic violence more frequently than the controls. Multivariable logistic regression analysis highlights periconceptional ‘gender-related violence’ (OR: 16.6, 95% CI 2.7 to 101.7) and younger maternal age (OR 1.1, 95% CI 1.0–1.3). Conclusions: Violence against pregnant women is associated with birth defects, and should be studied in more depth as a cause-effect teratogenic. Psychosocial risk factors, including gender-based violence, are important for insuring the health and safety of the pregnant mother and the fetus. PMID:24142184

Association between developmental defects of enamel and dental caries: A systematic review and meta-analysis.

PubMed

Vargas-Ferreira, F; Salas, M M S; Nascimento, G G; Tarquinio, S B C; Faggion, C M; Peres, M A; Thomson, W M; Demarco, F F

2015-06-01

Dental caries is the main problem oral health and it is not well established in the literature if the enamel defects are a risk factor for its development. Studies have reported a potential association between developmental defects enamel (DDE) and dental caries occurrence. We investigated the association between DDE and caries in permanent dentition of children and teenagers. A systematic review was carried out using four databases (Pubmed, Web of Science, Embase, and Science Direct), which were searched from their earliest records until December 31, 2014. Population-based studies assessing differences in dental caries experience according to the presence of enamel defects (and their types) were included. PRISMA guidelines for reporting systematic reviews were followed. Meta-analysis was performed to assess the pooled effect, and meta-regression was carried out to identify heterogeneity sources. From the 2558 initially identified papers, nine studies fulfilled all inclusion criteria after checking the titles, abstracts, references, and complete reading. Seven of them were included in the meta-analysis with random model. A positive association between enamel defects and dental caries was identified; meta-analysis showed that individuals with DDE had higher pooled odds of having dental caries experience [OR 2.21 (95% CI 1.3; 3.54)]. Meta-regression analysis demonstrated that adjustment for sociodemographic factors, countries' socioeconomic status, and bias (quality of studies) explained the high heterogeneity observed. A higher chance of dental caries should be expected among individuals with enamel defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pathogenetic role of Factor VII deficiency and thrombosis in cross-reactive material positive patients.

PubMed

Girolami, A; Sambado, L; Bonamigo, E; Ferrari, S; Lombardi, A M

2013-12-01

Congenital Factor VII (FVII) deficiency can be divided into two groups: cases of "true" deficiency, or cross-reactive material (CRM) negative and variants that are cross-reactive material positive.The first form is commonly recognized as Type I condition whereas the second one is known as Type II. FVII deficiency has been occasionally associated with thrombotic events, mainly venous. The reasons underlying this peculiar manifestation are unknown even though in the majority of associated patients thrombotic risk factors are present. The purpose of the present study was to investigate if a thrombotic event was more frequent in Type I or in Type II defect.The majority of patients with FVII deficiency and thrombosis belong to Type II defects. In the following paper we discuss the possible role of the dysfunctional FVII cross-reaction material as a contributory cause for the occurrence of thrombosis.

APOL1–Mediated Cell Injury Involves Disruption of Conserved Trafficking Processes

PubMed Central

Kruzel-Davila, Etty; Shemer, Revital; Ofir, Ayala; Bavli-Kertselli, Ira; Darlyuk-Saadon, Ilona; Oren-Giladi, Pazit; Wasser, Walter G.; Magen, Daniella; Zaknoun, Eid; Schuldiner, Maya; Salzberg, Adi; Kornitzer, Daniel; Marelja, Zvonimir; Simons, Matias

2017-01-01

APOL1 harbors C–terminal sequence variants (G1 and G2), which account for much of the increased risk for kidney disease in sub–Saharan African ancestry populations. Expression of the risk variants has also been shown to cause injury to podocytes and other cell types, but the underlying mechanisms are not understood. We used Drosophila melanogaster and Saccharomyces cerevisiae to help clarify these mechanisms. Ubiquitous expression of the human APOL1 G1 and G2 disease risk alleles caused near-complete lethality in D. melanogaster, with no effect of the G0 nonrisk APOL1 allele, corresponding to the pattern of human disease risk. We also observed a congruent pattern of cellular damage with tissue-specific expression of APOL1. In particular, expression of APOL1 risk variants in D. melanogaster nephrocytes caused cell-autonomous accumulation of the endocytic tracer atrial natriuretic factor-red fluorescent protein at early stages and nephrocyte loss at later stages. We also observed differential toxicity of the APOL1 risk variants compared with the APOL1 nonrisk variants in S. cerevisiae, including impairment of vacuole acidification. Yeast strains defective in endosomal trafficking or organelle acidification but not those defective in autophagy displayed augmented APOL1 toxicity with all isoforms. This pattern of differential injury by the APOL1 risk alleles compared with the nonrisk alleles across evolutionarily divergent species is consistent with an impairment of conserved core intracellular endosomal trafficking processes. This finding should facilitate the identification of cell injury pathways and corresponding therapeutic targets of interest in these amenable experimental platforms. PMID:27864431

Birth defects and congenital health risks in children conceived through assisted reproduction technology (ART): a meeting report.

PubMed

2014-08-01

Assisted Reproduction Treatment (ART) is here to stay. This review addresses the parental background of birth defects, before, during and after conception and focuses both on the underlying subfertility and on the question whether ART as a treatment is an additional contributing factor. Searches were performed in Medline and other databases. Summaries were discussed in a Delphi panel set-up by the European Society of Human Reproduction and Embryology (ESHRE). Several birth defects and adult diseases arise during the earliest stages of ovarian development and oocyte differentiation: this is the case of cleft palate disorders in offspring from female rat exposed to Dioxin during fetal life or the polycystic ovary diseases in female offspring (primates) exposed to elevated androgen concentration during fetal life. Human oocytes and embryos often fail to stop the propagation of aneuploid cells but maintain their ability to repair DNA damages including those introduced by the fertilizing sperm. There is a 29 % increased risk of birth defects in the newborns spontaneously conceived by subfertile couples and the risk is further increased (34 %) when conception is achieved by treating infertlity with ART (Danish IVF Registry). Periconceptional conditions are critical for ART babies: their birth weight is in general smaller (Norvegian Registry) but a more prolonged culture time doubled the number of large babies (Finnish Registry). The long-term developmental effects of ART on child and subsequent health as an adult remains a subject worthy of futher monitoring and investigation.

Comparison of matrix frequency-doubling technology perimetry and standard automated perimetry in monitoring the development of visual field defects for glaucoma suspect eyes.

PubMed

Hu, Rongrong; Wang, Chenkun; Racette, Lyne

2017-01-01

Perimetry is indispensable for the clinical management of glaucoma suspects. Our goal is to compare the performance of standard automated perimetry (SAP) and Matrix frequency-doubling technology (FDT) perimetry in monitoring the development of visual field (VF) defects in glaucoma suspect eyes. Longitudinal data of paired SAP and FDT from 221 eyes of 155 glaucoma suspects enrolled in the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study were included. All eyes had glaucomatous optic neuropathy or ocular hypertension, but normal SAP and FDT results at baseline. The development of glaucomatous VF defects was defined as the presence of a cluster of ≥ 3 (less conservative) or ≥ 4 (more conservative) locations confirmed on ≥ 2 additional consecutive tests. Risk factors for the development of VF defects were analyzed by COX proportional hazard models. After conversion into common logarithmic units, the rates of change of global VF indices were fitted with linear mixed models. FDT detected more eyes that developed VF defects than SAP using the less conservative criterion, and no significant difference was observed using the more conservative criterion. For those eyes detected by both SAP and FDT, FDT detected the development of VF defects either earlier than SAP or simultaneously in most cases. Baseline structural measurements were not significantly associated with an increased risk for the development of glaucomatous VF defects on either SAP or FDT. Older age was significantly associated with the development of VF defects on FDT but not on SAP. Both SAP and FDT detected a progressing worsening trend of pattern standard deviation over time with a similar rate of change between these test types. Matrix FDT would be useful to monitor the onset of VF defects in glaucoma suspects and may outperform SAP in the early stage of glaucomatous VF damage.

Frequency Optimization for Enhancement of Surface Defect Classification Using the Eddy Current Technique

PubMed Central

Fan, Mengbao; Wang, Qi; Cao, Binghua; Ye, Bo; Sunny, Ali Imam; Tian, Guiyun

2016-01-01

Eddy current testing is quite a popular non-contact and cost-effective method for nondestructive evaluation of product quality and structural integrity. Excitation frequency is one of the key performance factors for defect characterization. In the literature, there are many interesting papers dealing with wide spectral content and optimal frequency in terms of detection sensitivity. However, research activity on frequency optimization with respect to characterization performances is lacking. In this paper, an investigation into optimum excitation frequency has been conducted to enhance surface defect classification performance. The influences of excitation frequency for a group of defects were revealed in terms of detection sensitivity, contrast between defect features, and classification accuracy using kernel principal component analysis (KPCA) and a support vector machine (SVM). It is observed that probe signals are the most sensitive on the whole for a group of defects when excitation frequency is set near the frequency at which maximum probe signals are retrieved for the largest defect. After the use of KPCA, the margins between the defect features are optimum from the perspective of the SVM, which adopts optimal hyperplanes for structure risk minimization. As a result, the best classification accuracy is obtained. The main contribution is that the influences of excitation frequency on defect characterization are interpreted, and experiment-based procedures are proposed to determine the optimal excitation frequency for a group of defects rather than a single defect with respect to optimal characterization performances. PMID:27164112

Frequency Optimization for Enhancement of Surface Defect Classification Using the Eddy Current Technique.

PubMed

Fan, Mengbao; Wang, Qi; Cao, Binghua; Ye, Bo; Sunny, Ali Imam; Tian, Guiyun

2016-05-07

Eddy current testing is quite a popular non-contact and cost-effective method for nondestructive evaluation of product quality and structural integrity. Excitation frequency is one of the key performance factors for defect characterization. In the literature, there are many interesting papers dealing with wide spectral content and optimal frequency in terms of detection sensitivity. However, research activity on frequency optimization with respect to characterization performances is lacking. In this paper, an investigation into optimum excitation frequency has been conducted to enhance surface defect classification performance. The influences of excitation frequency for a group of defects were revealed in terms of detection sensitivity, contrast between defect features, and classification accuracy using kernel principal component analysis (KPCA) and a support vector machine (SVM). It is observed that probe signals are the most sensitive on the whole for a group of defects when excitation frequency is set near the frequency at which maximum probe signals are retrieved for the largest defect. After the use of KPCA, the margins between the defect features are optimum from the perspective of the SVM, which adopts optimal hyperplanes for structure risk minimization. As a result, the best classification accuracy is obtained. The main contribution is that the influences of excitation frequency on defect characterization are interpreted, and experiment-based procedures are proposed to determine the optimal excitation frequency for a group of defects rather than a single defect with respect to optimal characterization performances.

Risk of Congenital Heart Defects after Ambient Heat Exposure Early in Pregnancy.

PubMed

Auger, Nathalie; Fraser, William D; Sauve, Reg; Bilodeau-Bertrand, Marianne; Kosatsky, Tom

2017-01-01

Congenital heart defects may be environmentally related, but the association with elevated ambient temperature has received little attention. We studied the relationship between outdoor heat during the first trimester of pregnancy and risk of congenital heart defects. We carried out a retrospective cohort study of 704,209 fetuses between 2 and 8 weeks postconception from April to September in Quebec, Canada, 1988-2012. We calculated the prevalence of congenital heart defects at birth according to the number of days women were exposed to maximum temperature ≥ 30°C. In log-binomial regression models, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) for the relationship of temperature with seven critical and eight noncritical heart defects, adjusted for pregnancy characteristics. Prevalence of congenital heart defects was 979.5 per 100,000 for 10 days or more of temperature ≥ 30°C compared with 878.9 per 100,000 for 0 days of exposure. Temperature was more precisely associated with noncritical than critical defects, which had lower prevalence. Fetuses exposed to 15 days of temperature ≥ 30°C between 2 and 8 weeks postconception had 1.06 times the risk of critical defects (95% CI: 0.67, 1.67) and 1.12 times the risk of noncritical defects (95% CI: 0.98, 1.29) relative to 0 days. Associations were higher for atrial septal defects (PR 1.37, 95% CI: 1.10, 1.70) than for other noncritical defects. For atrial septal defects, associations with elevated temperatures began the 3rd week postconception. Extreme heat exposure during the first trimester may be associated with noncritical heart defects, especially of the atrial septum. Citation: Auger N, Fraser WD, Sauve R, Bilodeau-Bertrand M, Kosatsky T. 2017. Risk of congenital heart defects after ambient heat exposure early in pregnancy. Environ Health Perspect 125:8-14; http://dx.doi.org/10.1289/EHP171.

Predictive factors for red blood cell transfusion in children undergoing noncomplex cardiac surgery.

PubMed

Mulaj, Muj; Faraoni, David; Willems, Ariane; Sanchez Torres, Cristel; Van der Linden, Philippe

2014-08-01

Red blood cell (RBC) transfusion is frequently required in pediatric cardiac surgery and is associated with altered outcome and increased costs. Determining which factors predict transfusion in this context will enable clinicians to adopt strategies that will reduce the risk of RBC transfusion. This study aimed to assess predictive factors associated with RBC transfusion in children undergoing low-risk cardiac surgery with cardiopulmonary bypass (CPB). Children undergoing surgery to repair ventricular septal defect or atrioventricular septal defect from 2006 to 2011 were included in this retrospective study. Demography, preoperative laboratory testing, intraoperative data, and RBC transfusion were reviewed. Univariate and multivariate logistic regression analysis were used to define factors that were able to predict RBC transfusion. Then, we employed receiver operating characteristic analysis to design a predictive score. Among the 334 children included, 261 (78%) were transfused. Age (<18 months), priming volume of the CPB (>43 mL/kg), type of oxygenator used, minimal temperature reached during CPB (<32°C), and preoperative hematocrit (<34%) were independently associated with RBC transfusion in the studied population. A predictive score 2 or greater was the best predictor of RBC transfusion. The present study identified several factors that were significantly associated with perioperative RBC transfusion. Based on these factors, we designed a predictive score that can be used to develop a patient-based blood management program with the aim of reducing the incidence of RBC transfusion. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

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.

Cleft extension and risks of other birth defects in children with isolated cleft palate.

PubMed

Chetpakdeechit, Woranuch; Mohlin, Bengt; Persson, Christina; Hagberg, Catharina

2010-03-01

To study the risks of having other birth defects in children born with an isolated cleft palate (iCP) when the length of the cleft was taken into account. The hypothesis was that a newborn with an extensive cleft lesion may have an increased risk of other birth defects compared to a child with a less extensive cleft of the palate. All Caucasian children with iCP born between 1975 and 2005 in the southwestern region of Sweden were included. Data were collected from standardized medical records and the length of the cleft was checked on the pre-surgical dental cast for each child. A total of 343 children were born with an iCP. The incidence was 0.64/1000 live births. Thirty-four percent of children with either a total or partial iCP had other birth defects. The risk was 1.7 times higher for a total compared to a partial iCP. The two most common birth defects were congenital heart disease and intellectual disability. Ear problems related to infections were registered in 43% of cases. Fifteen percent of the children had the Pierre Robin sequence, which was analyzed as a separate variable and not included as a birth defect. The length of the iCP was found to influence the risk of having another birth defect as the total palatal clefts were more often combined with other birth defects compared to partial clefts. Careful medical check-ups are important for newborns with iCP since they have increased risks of other birth defects.

A novel profit-allocation strategy for SDN enterprises

NASA Astrophysics Data System (ADS)

Hu, Wei; Hou, Ye; Tian, Longwei; Li, Yuan

2017-01-01

Aiming to solve the problem of profit allocation for supply and demand network (SDN) enterprises that ignores risk factors and generates low satisfaction, a novel profit-allocation model based on cooperative game theory and TOPSIS is proposed. This new model avoids the defect of the single-profit allocation model by introducing risk factors, compromise coefficients and high negotiation points. By measuring the Euclidean distance between the ideal solution vector and the negative ideal solution vector, every node's satisfaction problem for the SDN was resolved, and the mess phenomenon was avoided. Finally, the rationality and effectiveness of the proposed model was verified using a numerical example.

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.

Spectrum and management of complement immunodeficiencies (excluding hereditary angioedema) across Europe.

PubMed

Turley, A J; Gathmann, B; Bangs, C; Bradbury, M; Seneviratne, S; Gonzalez-Granado, L I; Hackett, S; Kutukculer, N; Alachkar, H; Hambleton, S; Ritterbusch, H; Kralickova, P; Marodi, L; Seidel, M G; Dueckers, G; Roesler, J; Huissoon, A; Baxendale, H; Litzman, J; Arkwright, P D

2015-02-01

Complement immunodeficiencies (excluding hereditary angioedema and mannose binding lectin deficiency) are rare. Published literature consists largely of case reports and small series. We collated data from 18 cities across Europe to provide an overview of primarily homozygous, rather than partial genotypes and their impact and management. Patients were recruited through the ESID registry. Clinical and laboratory information was collected onto standardized forms and analyzed using SPSS software. Seventy-seven patients aged 1 to 68 years were identified. 44 % presented in their first decade of life. 29 % had C2 deficiency, defects in 11 other complement factors were found. 50 (65 %) had serious invasive infections. 61 % of Neisseria meningitidis infections occurred in patients with terminal pathway defects, while 74 % of Streptococcus pneumoniae infections occurred in patients with classical pathway defects (p < 0.001). Physicians in the UK were more likely to prescribe antibiotic prophylaxis than colleagues on the Continent for patients with classical pathway defects. After diagnosis, 16 % of patients suffered serious bacterial infections. Age of the patient and use of prophylactic antibiotics were not associated with subsequent infection risk. Inflammatory/autoimmune diseases were not seen in patients with terminal pathway, but in one third of patients classical and alternative pathway defects. The clinical phenotypes of specific complement immunodeficiencies vary considerably both in terms of the predominant bacterial pathogen, and the risk and type of auto-inflammatory disease. Appreciation of these phenotypic differences should help both immunologists and other specialists in their diagnosis and management of these rare and complex patients.

Post-Liver Transplantation Diabetes Mellitus: A Review of Relevance and Approach to Treatment.

PubMed

Peláez-Jaramillo, Maria J; Cárdenas-Mojica, Allison A; Gaete, Paula V; Mendivil, Carlos O

2018-04-01

Post-liver transplantation diabetes mellitus (PLTDM) develops in up to 30% of liver transplant recipients and is associated with increased risk of mortality and multiple morbid outcomes. PLTDM is a multicausal disorder, but the main risk factor is the use of immunosuppressive agents of the calcineurin inhibitor (CNI) family (tacrolimus and cyclosporine). Additional factors, such as pre-transplant overweight, nonalcoholic steatohepatitis and hepatitis C virus infection, may further increase risk of developing PLTDM. A diagnosis of PLTDM should be established only after doses of CNI and steroids are stable and the post-operative stress has been overcome. The predominant defect induced by CNI is insulin secretory dysfunction. Plasma glucose control must start immediately after the transplant procedure in order to improve long-term results for both patient and transplant. Among the better known antidiabetics, metformin and DPP-4 inhibitors have a particularly benign profile in the PLTDM context and are the preferred oral agents for long-term management. Insulin therapy is also an effective approach that addresses the prevailing pathophysiological defect of the disorder. There is still insufficient evidence about the impact of newer families of antidiabetics (GLP-1 agonists, SGLT-2 inhibitors) on PLTDM. In this review, we summarize current knowledge on the epidemiology, pathogenesis, course of disease and medical management of PLTDM.

Rate of progression of total, upper, and lower visual field defects in patients with open-angle glaucoma and high myopia.

PubMed

Yoshino, Takaiko; Fukuchi, Takeo; Togano, Tetsuya; Sakaue, Yuta; Seki, Masaaki; Tanaka, Takayuki; Ueda, Jun

2016-03-01

We evaluated the rate of progression of total, upper, and lower visual field defects in patients with treated primary open-angle glaucoma (POAG) with high myopia (HM). Seventy eyes of 70 POAG patients with HM [≤-8 diopters (D)] were examined. The mean deviation (MD) slope and the upper and lower total deviation (upper TD, lower TD) slopes of the Humphrey Field Analyzer were calculated in patients with high-tension glaucoma (HTG) (>21 mmHg) versus normal-tension glaucoma (NTG) (≤21 mmHg). The mean age of all the patients (29 eyes with HTG and 41 eyes with NTG) was 48.5 ± 9.6 years. The MD slope, and upper and lower TD slopes of the HM group were compared to those of the non-HM group (NHM) (>-8 D) selected from 544 eyes in 325 age-matched POAG patients. In all, 70 eyes with HM and NHM were examined. The mean MD slope was -0.33 ± 0.33 dB/year in the HM, and -0.38 ± 0.49 dB/year in the NHM. There were no statistical differences between the HM and NHM (p = 0.9565). In the comparison of HTG versus NTG patients in both groups, the MD slope, and upper and lower TD slopes were similar. The rate of progression of total, upper, and lower visual field defects was similar among patients with HM and NHM. Although HM is a risk factor for the onset of glaucoma, HM may not be a risk factor for progression of visual field defects as assessed by the progression rate under treatment.

Levels of Polycyclic Aromatic Hydrocarbons in Maternal Serum and Risk of Neural Tube Defects in Offspring

PubMed Central

2015-01-01

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants, and have been reported to be a risk factor for human neural tube defects (NTDs). We investigated the relationship between PAH concentrations in maternal serum and NTD risk in offspring using a case-control study design, and explored the link between PAH concentrations to household energy usage characteristics and life styles. One hundred and seventeen women who had NTD-affected pregnancies (cases) and 121 women who delivered healthy infants (controls) were recruited in Northern China. Maternal blood samples were collected at pregnancy termination or at delivery. Twenty-seven PAHs were measured by gas chromatography–mass spectrometry. The concentrations of 13 individual PAHs detected were significantly higher in the cases than in the controls. Clear dose–response relationships between concentrations of most individual PAHs and the risk of total NTDs or subtypes were observed, even when potential covariates were adjusted for. High-molecular-weight PAHs (H-PAHs) showed higher risk than low-molecular-weight PAHs (L-PAHs). No associations between PAH concentrations and indoor life styles and energy usage characteristics were observed. It was concluded that maternal exposure to PAHs was associated with an increased risk of NTDs, and H-PAHs overall posed a higher risk for NTDs than L-PAHs. PMID:25488567

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.

Prevalence and Patient-Level Risk Factors for 30-Day Readmissions Following Free Tissue Transfer for Head and Neck Cancer.

PubMed

Offodile, Anaeze C; Pathak, Abraham; Wenger, Julia; Orgill, Dennis P; Guo, Lifei

2015-09-01

Hospital readmissions are a marker of surgical care delivery and quality that are progressively more scrutinized. To provide a comprehensive analysis of 30-day readmissions for patients with head and neck cancer who underwent free flap reconstruction to highlight the rate, causes, and associated patient risk factors. Retrospective cohort study at a single tertiary care academic institution. The study consisted of 249 patients who underwent microvascular reconstruction of a presumed head and neck oncologic defect from January 1, 2000, through June 30, 2014. Follow-up continued through July 30, 2014. Microvascular reconstruction of an oncologic head and neck defect. Incidence of 30-day all-cause readmissions, patient risk factors, and readmission indications. Regression analyses were conducted to discern patient-level risk factors related to 30-day readmissions. Among the 249 patients, the 30-day all-cause readmission rate was 14.5%, while the unplanned readmission rate was 11.6%. The most common reason for readmission was neck wound complications. Predictors of readmission following multivariable analysis were T4 pathologic stage (odds ratio [OR], 11.68; 95% CI, 1.37-99.81; P = .02) and having a tumor located in the oropharynx (OR, 4.64; 95% CI, 1.89-11.38; P = .001), hypopharynx (OR, 8.30; 95% CI, 1.52-45.24; P = .01), or larynx (OR, 10.97; 95% CI, 2.27-52.98; P = .003). Patients who were readmitted were more likely to experience neck wound complications (OR, 5.07; 95% CI, 1.31-19.57; P = .02) and undergo reoperation (OR, 47.20; 95% CI, 8.33-267.33; P < .001). In this study, advanced pathologic tumor staging and tumor location were associated with 30-day readmissions in patients with head and neck cancer who receive free flaps. Our results provide a benchmark for risk stratification that can be used in system-based practice improvements, health care cost savings, and postoperative patient counseling.

Take a byte out of MEEF: VAMPIRE: Vehicle for Advanced Mask Pattern Inspection Readiness Evaluations

NASA Astrophysics Data System (ADS)

Badger, Karen D.; Rankin, Jed; Turley, Christina; Seki, Kazunori; Dechene, Dan J.; Abdelghany, Hesham

2016-09-01

MEEF, or Mask Error Enhancement Factor, is simply defined as the ratio of the change in printed wafer feature width to the change in mask feature width scaled to wafer level. It is important in chip manufacturing that leads to the amplification of mask errors, creating challenges with both achieving dimensional control tolerances and ensuring defect free masks, as measured by on-wafer image quality. As lithographic imaging continues to be stressed, using lower and lower k1 factor resolution enhancement techniques, the high MEEF areas present on advanced optical masks creates an environment where the need for increased mask defect sensitivity in high-MEEF areas becomes more and more critical. There are multiple approaches to mask inspection that may or may not provide enough sensitivity to detect all wafer-printable defects; the challenge in the application of these techniques is simultaneously maintaining an acceptable level of mask inspectability. The higher the MEEF, the harder the challenge will be to achieve and appropriate level of sensitivity while maintaining inspectability…and to do so on the geometries that matter. The predominant photomask fabrication inspection approach in use today compares the features on the reticle directly with the design database using high-NA optics. This approach has the ability to detect small defects, however, when inspecting aggressive OPC, it can lead to the over-detection of inconsequential, or nuisance defects. To minimize these nuisance detections, changing the sensitivity of the inspection can improve the inspectability of a mask inspected in high-NA mode, however, it leads to the inability to detect subtle, yet wafer-printable defects in High-MEEF geometry, due to the fact that this `desense' must be applied globally. There are also `lithography-emulating' approaches to inspection that use various means to provide high defect sensitivity and the ability to tolerate inconsequential, non-printing defects by using scanner-like conditions to determine which defects are wafer printable. This inspection technique is commonly referred to as being `lithography plane' or `litho plane,' since it's assessing the mask quality based on how the mask appears to the imaging optics during use, as proposed to traditional `reticle plane' inspection which is comparing the mask only with its target design. Regardless of how the defects are detected, the real question is when should they be detected? For larger technology nodes, defects are considered `statistical risks'…i.e., first they have to occur, and then they have to fall in high-MEEF areas in order to be of concern, and be below the detection limits of traditional reticle-plane inspection. In short, the `perfect storm' has to happen in order to miss printable defects using well-optimized traditional inspection approaches. The introduction of lithographic inspection techniques has revealed this statistical game is a much higher risk than originally estimated, in that very subtle waferprintable CD errors typically fall into the desense band for traditional reticle plane inspection. Because printability is largely influenced by MEEF, designs with high-MEEF values are at greater risk of traditional inspection missing printable CD errors. The question is… how high is high… and at what MEEF is optical inspection at the reticle plane sufficient? This paper will provide evaluation results for both reticle-plane and litho-plane inspections as they pertain to varying degrees of MEEF. A newly designed high-MEEF programmed defect test mask, named VAMPIRE, will be introduced. This test mask is based on 7 nm node technology and contains intentionally varying degrees of MEEF as well as a variety of programmed defects in high-MEEF environments…all of which have been verified for defect lithographic significance on a Zeiss AIMS system.

Risk factors associated with neural tube defects in infants referred to western Iranian obstetrical centers; 2013–2014

PubMed Central

Zaheri, Farzaneh; Ranaie, Fariba; Shahoei, Roonak; Hasheminasab, Leila; Roshani, Daem

2017-01-01

Background Neural tubes defects (NTDs) are known to be the second most prevalent congenital disorder worldwide whose risk factors have not been explicitly addressed yet. Aim To determine the risk factors affecting NTDs among infants who referred to obstetrical centers in Kurdistan, a western province of Iran. Methods This prospective case-control study was conducted in the form of prospective case-control. Sample population included all women (27,153 cases) who referred to obstetrical centers in Kurdistan for either delivery or abortion during 2013 and 2014. Inclusion criterion was the presence of a known NTD in infants, and exclusion criterion was the reluctance of patients to participate in the study. Accordingly, 46 cases participated in the study as the case group, and 138 cases (three times higher than case group) were selected to be the control group. Case and control groups were matched in terms of the number of pregnancies and place of birth. The variables investigated in the present study were as follows: age, occupation, BMI, abortion history, family relation with husband, fetus’ sex, number of twins, history of previous children with NTD, receiving prenatal surveillance, consumption of folic acid and multivitamins, smoking, alcohol drinking, passive smoking, and suffering from such diseases as epilepsy and diabetes. Data were analyzed using various statistical tests, including chi-square, Fishers’ exact test, multiple logistic regression analysis using SPSS version 20. In the study group, inclusion criteria included all women who had an infant with tube defects that their total number was 46 individuals. In the control group inclusion criteria included mothers with healthy infants who were similar to the study group in terms of birth place and frequency of pregnancy. Results The results of the present study demonstrated that prenatal surveillance (p<0.002), multivitamin consumption (p<0.001), history of having a child with NTD (p<0.001), alcohol drinking (p<0.014), and passive smoking were related to NTDs (p<0.001). Conclusion Before fertilization and during pregnancy, mothers should be examined in terms of exposure to harmful agents, diet, and nutritional status in order to identify possible risk factors and find opportunities to prevent NTDs in infants. PMID:28848641

Resorption of Autogenous Bone Graft in Cranioplasty: Resorption and Reintegration Failure

PubMed Central

Lee, Si Hoon; Lee, Uhn; Park, Cheol Wan; Lee, Sang Gu; Kim, Woo Kyung

2014-01-01

Objective Re-implantation of autologous skull bone has been known to be difficult because of its propensity for resorption. Moreover, the structural characteristics of the area of the defect cannot tolerate physiologic loading, which is an important factor for graft healing. This paper describes our experiences and results with cranioplasty following decompressive craniectomy using autologous bone flaps. Methods In an institutional review, the authors identified 18 patients (11 male and 7 female) in whom autologous cranioplasty was performed after decompressive craniectomy from January 2008 to December 2011. We examined the age, reasons for craniectomy, size of the skull defect, presence of bony resorption, and postoperative complications. Results Postoperative bone resorption occurred in eight cases (44.4%). Among them, two experienced symptomatic breakdown of the autologous bone graft that required a second operation to reconstruct the skull contour using porous polyethylene implant (Medpor®). The incidence of bone resorption was more common in the pediatric group and in those with large cranial defects (>120 cm2). No significant correlation was found with sex, reasons for craniectomy, and cryopreservation period. Conclusion The use of autologous bone flap for reconstruction of a skull defect after decompressive craniectomy is a quick and cost-effective method. But, the resorption rate was greater in children and in patients with large skull defects. As a result, we suggest compressive force of the tightened scalp, young age, large skull defect, the gap between bone flap and bone edge and heat sterilization of autologous bone as risk factors for bone resorption. PMID:27169026

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.

Critical evaluation of lowering the recommended dietary intake of folate.

PubMed

Obeid, Rima; Koletzko, Berthold; Pietrzik, Klaus

2014-04-01

We evaluated the recommendation of the Austrian, German, and Swiss Societies for Nutrition of lowering dietary folate intake from 400 to 300 μg dietary folate equivalents/d. A dose-response relation exists between folate intake or plasma level and disease risk within the normal range. Improving folate status can prevent between 30% and 75% of neural tube defects. A prepregnancy plasma folate of >18.0 nmol/L (mean 26.1 nmol/L) is associated with low total homocysteine (tHcy) (<10.0 μmol/L) and optimal prevention of birth defects. Because the closure of the neural tube occurs in the first 8 weeks after conception, women with low prepregnancy folate intake cannot achieve maximal risk reduction. The Austrian, German, and Swiss Societies for Nutrition recommend that young women should additionally supplement with 400 μg folic acid at least 4 weeks before conception. This short time window is not sufficient to achieve optimal plasma folate and tHcy levels in the majority of women. Factors affecting the relation between folate intake and blood biomarkers are total folate intake, baseline plasma folate, time available for supplement use, dose and form (folic acid or methyl folate), genetic polymorphisms, physiological and lifestyle factors. Lowering the recommended dietary folate intake may have important public health consequences. Elderly people and young women are at risk for diseases related to folate shortage. Reducing birth defects through supplementation of folic acid remains a poor option, as <20% of young women (i.e., in Germany) supplement with the vitamin. Recommending adequate food folate intake is crucial for reaching the target protective plasma folate levels in the population. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Antibiotic Use after Free Tissue Reconstruction of Head and Neck Defects: Short Course vs. Long Course

PubMed Central

Le, Bin; Pierce, Brendan H.G.; Isaksson Vogel, Rachel; Chipman, Jeffrey G.

2016-01-01

Abstract Background: Free tissue reconstruction has become the standard of care for most major defects in the head and neck. Surgical site infection (SSI) can lead to vessel thrombosis and eventual flap loss. The use of antibiotics after free tissue reconstruction has not been studied in the current environment of heightened bacterial antibiotic resistance. We compared the use of short-term and longer-term antibiotics in a series of patients receiving free tissue reconstructions. Methods: A retrospective review was performed of 147 patients receiving 149 free flaps who were treated with either short-course (≤2 d; n = 149 [43%]) or long-course (>2 d; n = 85 [57%])) post-operative antibiotics from 2009 to 2014. The outcomes examined were infection, return to the operating room, length of hospital stay, and patient death up to six weeks post-surgery. In addition, risk factors associated with SSI were explored. Results: Surgical site infection, flap dehiscence, flap loss, and length of stay were not different in the two groups. However, those receiving long-course antibiotics had a significantly higher rate of pneumonia (24.7% vs. 10.9%; p = 0.03), although they had a lower rate of urinary tract infection (0.0% vs 9.4%, respectively; p = 0.01). Body mass index remained a statistically significant risk factor in the multivariable analysis (p = 0.005). Conclusion: Prolonged antibiotic use after free flap reconstruction of head and neck defects does not appear to prevent SSI better than short-course treatment in this population. Moreover, long-course antibiotic use was associated with a higher risk of pneumonia. PMID:26501794

PubMed Central

DE MATOS, L.L.; BELLI, M.; KULCSAR, M.A.V.; CERNEA, C.R.; GARCIA BRANDÃO, L.; PINTO, F.R.

2014-01-01

SUMMARY The pectoralis major myocutaneous flap (PMMF) is a safe and versatile flap used widely for head and neck cancer reconstructions, but one of the major and most feared complications is oro- or pharyngocutaneous fistula. Herein, we attempt to establish risk factors for fistula formation in reconstructions of mucosal defects in the head and neck using PMMF through retrospective analysis of PMMF performed during 3 years at a single institution, with a total of 84 procedures. There were 69 men and 15 women, with a mean age of 59.5 years. There were 15 cases of partial flap loss, two total flap losses and 31 fistulas. The independent risk factors for fistula formation were preoperative serum hemoglobin < 13 g/dl, preoperative serum albumin < 3.4 g/dl and hypopharynx reconstruction. The PMMF is still a very useful flap and this is the first multivariate analysis analysing risk factors for fistula formation. These findings are helpful in selecting patients with elevated risk of fistula formation, and therefore preventive measures can be undertaken to avoid potentially serious complications. PMID:25762830

Prevention of type 2 diabetes mellitus in women with previous gestational diabetes mellitus

PubMed Central

Moon, Joon Ho; Kwak, Soo Heon; Jang, Hak C.

2017-01-01

Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with onset or first recognition during pregnancy, is characterized by underlying maternal defects in the β-cell response to insulin during pregnancy. Women with a previous history of GDM have a greater than 7-fold higher risk of developing postpartum diabetes compared with women without GDM. Various risk factors for postpartum diabetes have been identified, including maternal age, glucose levels in pregnancy, family history of diabetes, pre-pregnancy and postpartum body mass index, dietary patterns, physical activity, and breastfeeding. Genetic studies revealed that GDM shares common genetic variants with type 2 diabetes. A number of lifestyle interventional trials that aimed to ameliorate modifiable risk factors, including diet, exercise, and breastfeeding, succeeded in reducing the incidence of postpartum diabetes, weight retention, and other obesity-related morbidities. The present review summarizes the findings of previous studies on the incidence and risk factors of postpartum diabetes and discusses recent lifestyle interventional trials that attempted to prevent postpartum diabetes. PMID:28049284

Prevention of type 2 diabetes mellitus in women with previous gestational diabetes mellitus.

PubMed

Moon, Joon Ho; Kwak, Soo Heon; Jang, Hak C

2017-01-01

Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with onset or first recognition during pregnancy, is characterized by underlying maternal defects in the β-cell response to insulin during pregnancy. Women with a previous history of GDM have a greater than 7-fold higher risk of developing postpartum diabetes compared with women without GDM. Various risk factors for postpartum diabetes have been identified, including maternal age, glucose levels in pregnancy, family history of diabetes, pre-pregnancy and postpartum body mass index, dietary patterns, physical activity, and breastfeeding. Genetic studies revealed that GDM shares common genetic variants with type 2 diabetes. A number of lifestyle interventional trials that aimed to ameliorate modifiable risk factors, including diet, exercise, and breastfeeding, succeeded in reducing the incidence of postpartum diabetes, weight retention, and other obesity-related morbidities. The present review summarizes the findings of previous studies on the incidence and risk factors of postpartum diabetes and discusses recent lifestyle interventional trials that attempted to prevent postpartum diabetes.

Cerebral Venous Sinus Thrombosis in a Patient with Undiagnosed Factor VII Deficiency.

PubMed

Qadir, Hira; Rashid, Anila; Adil, Salman Naseem

2017-09-01

Factor VII (FVII) deficiency is one of the rare inherited bleeding disorders. Thrombosis has been occasionally described in inherited FVII deficiency. Here, we report a young female with undiagnosed FVII deficiency who presented with cerebral venous sinus thrombosis (CVST). Oral contraceptive pill was found to be prothrombotic risk factor. The CVSToccurred in spite of the congenital FVII deficiency indicating that no definitive antithrombotic protection is assured by this defect. Low molecular weight heparin and anti-Xa assay were found to be safe choice of anticoagulation and monitoring, respectively, in this patient.

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

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.

Segmental bone defects: from cellular and molecular pathways to the development of novel biological treatments

PubMed Central

Pneumaticos, Spyros G; Triantafyllopoulos, Georgios K; Basdra, Efthimia K; Papavassiliou, Athanasios G

2010-01-01

Abstract Several conditions in clinical orthopaedic practice can lead to the development of a diaphyseal segmental bone defect, which cannot heal without intervention. Segmental bone defects have been traditionally treated with bone grafting and/or distraction osteogenesis, methods that have many advantages, but also major drawbacks, such as limited availability, risk of disease transmission and prolonged treatment. In order to overcome such limitations, biological treatments have been developed based on specific pathways of bone physiology and healing. Bone tissue engineering is a dynamic field of research, combining osteogenic cells, osteoinductive factors, such as bone morphogenetic proteins, and scaffolds with osteoconductive and osteoinductive attributes, to produce constructs that could be used as bone graft substitutes for the treatment of segmental bone defects. Scaffolds are usually made of ceramic or polymeric biomaterials, or combinations of both in composite materials. The purpose of the present review is to discuss in detail the molecular and cellular basis for the development of bone tissue engineering constructs. PMID:20345845

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

The Co-Occurrence of Autism and Birth Defects: Prevalence and Risk in a Population-Based Cohort

ERIC Educational Resources Information Center

Schendel, Diana E.; Autry, Andrew; Wines, Roberta; Moore, Cynthia

2009-01-01

Aim: To estimate the prevalence of major birth defects among children with autism, the prevalence of autism in children with birth defects, and the risk for autism associated with having birth defects. Method: Retrospective cohort including all children born in Atlanta, GA, USA, 1986 to 1993, who survived to age 3 years and were identified through…

Quantitative analysis of visible surface defect risk in tablets during film coating using terahertz pulsed imaging.

PubMed

Niwa, Masahiro; Hiraishi, Yasuhiro

2014-01-30

Tablets are the most common form of solid oral dosage produced by pharmaceutical industries. There are several challenges to successful and consistent tablet manufacturing. One well-known quality issue is visible surface defects, which generally occur due to insufficient physical strength, causing breakage or abrasion during processing, packaging, or shipping. Techniques that allow quantitative evaluation of surface strength and the risk of surface defect would greatly aid in quality control. Here terahertz pulsed imaging (TPI) was employed to evaluate the surface properties of core tablets with visible surface defects of varying severity after film coating. Other analytical methods, such as tensile strength measurements, friability testing, and scanning electron microscopy (SEM), were used to validate TPI results. Tensile strength and friability provided no information on visible surface defect risk, whereas the TPI-derived unique parameter terahertz electric field peak strength (TEFPS) provided spatial distribution of surface density/roughness information on core tablets, which helped in estimating tablet abrasion risk prior to film coating and predicting the location of the defects. TPI also revealed the relationship between surface strength and blending condition and is a nondestructive, quantitative approach to aid formulation development and quality control that can reduce visible surface defect risk in tablets. Copyright © 2013 Elsevier B.V. All rights reserved.

In vivo formation of N-acyl-fumonisin B1

USDA-ARS?s Scientific Manuscript database

Fumonisins are fungal toxins found in corn and in corn-based foods. Fumonisin B1 (FB1) is the most common and is toxic to animals, causes cancer in rodents, and is a suspected risk factor for cancer and birth defects in humans. The hydrolyzed form of FB1 (HFB1) also occurs in foods and is metabolize...

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

Prevalence of birth defects among American-Indian births in California, 1983-2010.

PubMed

Aggarwal, Deepa; Warmerdam, Barbara; Wyatt, Katrina; Ahmad, Shabbir; Shaw, Gary M

2015-02-01

Approximately 6.3 million live births and fetal deaths occurred during the ascertainment period in the California Birth Defects Monitoring Program registry. American-Indian and non-Hispanic white women delivered 40,268 and 2,044,118 births, respectively. While much information has been published about non-Hispanic white infants, little is known regarding the risks of birth defects among infants born to American-Indian women. This study used data from the California Birth Defects Monitoring Program to explore risks of selected birth defects in offspring of American-Indian relative to non-Hispanic white women in California. The study population included all live births and fetal deaths 20 weeks or greater from 1983 to 2010. Prevalence ratios and corresponding 95% confidence intervals (CI) were computed using Poisson regression for 51 groupings of birth defects. Prevalence ratios were estimated for 51 groupings of birth defects. Of the 51, nine had statistically precise results ranging from 0.78 to 1.85. The eight groups with elevated risks for American-Indian births were reduction deformities of brain, anomalies of anterior segments, specified anomalies of ear, ostium secundum type atrial septal defect, specified anomalies of heart, anomalies of the aorta, anomalies of great veins, and cleft lip with cleft palate. Our results suggest that American-Indian women having babies in California may be at higher risk for eight birth defect phenotypes compared with non-Hispanic whites. Further research is needed to determine whether these risks are observed among other populations of American-Indian women or when adjusted for potential covariates. © 2015 Wiley Periodicals, Inc.

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

Magnitude of Neural Tube Defects and Associated Risk Factors at Three Teaching Hospitals in Addis Ababa, Ethiopia.

PubMed

Gedefaw, Abel; Teklu, Sisay; Tadesse, Birkneh Tilahun

2018-01-01

There is scarcity of data on prevalence of neural tube defects (NTDs) in lower-income countries. Local data are important to understand the real burden of the problem and explore risk factors to design and implement preventive approaches. This study aimed to determine prevalence and risk factors of NTDs. A hospital-based cross-sectional and unmatched case-control study was conducted at three teaching hospitals of Addis Ababa University. NTDs were defined as cases of anencephaly, spina bifida, and encephalocele based on ICD-10 criteria. The prevalence of NTDs was calculated per 10,000 births for both birth and total prevalence. During seven months, we observed 55 cases of NTDs out of 8677 births after 28 weeks of gestation-birth prevalence of 63.4 per 10,000 births (95% confidence interval (CI), 51-77). A total of 115 cases were medically terminated after 12 weeks of gestation. Fifty-six of these terminations (48.7%) were due to NTDs. Thus, total prevalence of NTDs after 12 weeks' gestation is 126 per 10,000 births (95% CI, 100-150). Planned pregnancy (adjusted odds ratio (aOR), 0.47; 95% CI, 0.24-0.92), male sex (aOR, 0.56; 95% CI, 0.33-0.94), normal or underweight body mass index (aOR, 0.49; 95%, 0.29-0.95), and taking folic acid or multivitamins during first trimester (aOR, 0.47; 95%, 0.23-0.95) were protective of NTDs. However, annual cash family income less than $1,300 USD (aOR, 2.5; 95%, 1.2-5.5), $1,300-1,800 USD (aOR, 2.8; 95%, 1.3-5.8), and $1,801-2,700 USD (aOR, 2.6; 95%, 1.2-5.8) was found to be risk factors compared to income greater than $2,700 USD. The prevalence of NTDs was found to be high in this setting. Comprehensive preventive strategies focused on identified risk factors should be urgently established. More studies on prevention strategies, including folic acid supplementations, should be conducted in the setting.

Pre and post-natal risk and determination of factors for child obesity.

PubMed

Trandafir, L M; Temneanu, O R

2016-01-01

Obesity is considered a condition presenting a complex, multi-factorial etiology that implies genetic and non-genetic factors. The way the available information should be efficiently and strategically used in the obesity and overweight prohylaxisprogrammes for children all over the world is still unclear for most of the risk factors. Mothers' pre-conception weight and weight gain during pregnancy are two of the most important prenatal determinants of childhood obesity. Maternal obesity and gestational weight gain are associated with foetal macrosomia and childhood obesity, and this effect extends into adulthood. Obesity and the metabolic syndrome in children originate in intrauterine life. The current obesity epidemic is probably the result of our evolutive inheritance associated with the consumption of highly processed food with an increased calorific value. The determination of risk factors involved in child obesity are: genetic predisposition, diet, sedentary behaviors, socioeconomic position, ethnic origin, microbiota, iatrogenic, endocrine diseases, congenital and acquired hypothalamic defects, usage of medications affecting appetite. However, the vast majority of patients will not have any of these identifiable conditions. Regardless of the aetiology, all the patients should be considered for modifiable lifestyle risk factors and screened for the complications of obesity.

Factor V Leiden 1691G/A and prothrombin gene 20210G/A polymorphisms as prothrombotic markers in adult Egyptian acute leukemia patients.

PubMed

El Sissy, Azza Hamdy; El Sissy, Maha H; Elmoamly, Shereef

2014-11-01

Factor V Leiden 1691G/A and prothrombin gene 20210G/A mutations are the most common genetic defects leading to thrombosis. This work aimed to study the FV Leiden and the prothrombin gene polymorphism in adult Egyptian patients with acute leukemia and their importance in thrombophilia screening. The study included 76 patients with acute leukemia and 100 healthy controls. Genotyping was done by real-time polymerase chain reaction technique. For factor V Leiden, the frequency of G/A mutation conferred more than 2.5-fold of increased risk of (OR 2.639 95 % CI 1.045-6.669). The frequency of factor V Leiden combined (G/A + A/A) genotypes conferred 2.83-fold of increased risk (OR 2.828, CI 1.13-7.075), The A allele conferred almost threefold increased risk (OR 2.824, 95 % CI 1.175-6.785). Despite higher frequency in patients compared to controls, there was no risk of association between prothrombin gene mutation and acute leukemia in adult Egyptians nor was there between combined genotypes of prothrombin gene mutation and factor V Leiden.

Bacterial Pneumonia in Patients with Cancer: Novel Risk Factors and Management.

PubMed

Wong, Justin L; Evans, Scott E

2017-06-01

Bacterial pneumonias exact unacceptable morbidity on patients with cancer. Although the risk is often most pronounced among patients with treatment-induced cytopenias, the numerous contributors to life-threatening pneumonias in cancer populations range from derangements of lung architecture and swallow function to complex immune defects associated with cytotoxic therapies and graft-versus-host disease. These structural and immunologic abnormalities often make the diagnosis of pneumonia challenging in patients with cancer and impact the composition and duration of therapy. This article addresses host factors that contribute to pneumonia susceptibility, summarizes diagnostic recommendations, and reviews current guidelines for management of bacterial pneumonia in patients with cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Cardiometabolic features of polycystic ovary syndrome.

PubMed

Hoffman, Leslie K; Ehrmann, David A

2008-04-01

Polycystic ovary syndrome (PCOS) is a complex disorder comprising both hormonal and metabolic abnormalities that include impaired glucose tolerance, type 2 diabetes, vascular disease, dyslipidemia, and obstructive sleep apnea. Insulin resistance is a central pathogenetic factor in PCOS that seems to result from a post-receptor-binding defect in insulin action. Insulin resistance and the consequent development of hyperinsulinemia contribute to the constellation of cardiometabolic abnormalities noted above. Although there is a paucity of data in regard to cardiovascular event rates and mortality in PCOS, an increased prevalence of cardiovascular risk factors has been well documented. Attention to the metabolic risks associated with PCOS, starting as early as adolescence, is essential to the medical care of these patients.

Risk of selected structural abnormalities in infants after increased nuchal translucency measurement.

PubMed

Baer, Rebecca J; Norton, Mary E; Shaw, Gary M; Flessel, Monica C; Goldman, Sara; Currier, Robert J; Jelliffe-Pawlowski, Laura L

2014-12-01

We sought to examine the association between increased first-trimester fetal nuchal translucency (NT) measurement and major noncardiac structural birth defects in euploid infants. Included were 75,899 singleton infants without aneuploidy or critical congenital heart defects born in California in 2009 through 2010 with NT measured between 11-14 weeks of gestation. Logistic binomial regression was employed to estimate relative risks (RRs) and 95% confidence intervals (CIs) for occurrence of birth defects in infants with an increased NT measurement (by percentile at crown-rump length [CRL] and by ≥3.5 mm compared to those with measurements <90th percentile for CRL). When considered by CRL adjusted percentile and by measurement ≥3.5 mm, infants with a NT ≥95th percentile were at risk of having ≥1 major structural birth defects (any defect, RR, 1.6; 95% CI, 1.3-1.9; multiple defects, RR, 2.1; 95% CI, 1.3-3.4). Infants with a NT measurement ≥95th percentile were at particularly high risk for pulmonary, gastrointestinal, genitourinary, and musculoskeletal anomalies (RR, 1.6-2.7; 95% CI, 1.1-5.4). Our findings demonstrate that risks of major pulmonary, gastrointestinal, genitourinary, and musculoskeletal structural birth defects exist for NT measurements ≥95th percentile. The ≥3-fold risks were observed for congenital hydrocephalus; agenesis, hypoplasia, and dysplasia of the lung; atresia and stenosis of the small intestine; osteodystrophies; and diaphragm anomalies. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Air pollution, neighborhood acculturation factors, and neural tube defects among Hispanic women in California.

PubMed

Padula, Amy M; Yang, Wei; Carmichael, Suzan L; Lurmann, Frederick; Balmes, John; Hammond, S Katharine; Shaw, Gary M

2017-04-03

Neural tube defects (NTDs) are one of the most common types of birth defects. Environmental pollutants and acculturation have been associated with NTDs independently. The potential effect modification of acculturation in the relationship between ambient air pollution and risks of NTDs is not well understood. We investigated whether associations between traffic-related air pollutant exposure in early gestation and NTDs, and more specifically spina bifida, were modified by individual and neighborhood acculturation factors among 139 cases and 466 controls born in the San Joaquin Valley of California, 1997 to 2006. Five criteria pollutant exposures in tertiles, two outcomes, and seven neighborhood acculturation factors from the U.S. Census at the block group level were included for a total of 280 investigated associations. Estimates were adjusted for maternal education and multivitamin use in the first 2 months of pregnancy. Additional analyses were stratified by nativity. Increased odds of NTDs were observed for individuals who had high exposures to carbon monoxide, nitrogen oxide, or nitrogen dioxide and lived in neighborhoods that were more acculturated. Conversely, there were increased odds of NTDs for those who had high prenatal exposure to PM 10 and lived in neighborhoods that were less acculturated. The results of spina bifida alone were generally stronger in magnitude. When stratified by individual nativity (U.S.- vs. foreign-born), carbon monoxide, nitrogen oxide, and nitrogen dioxide were more strongly associated with NTDs among U.S.-born Hispanic mothers. Neighborhood acculturation factors were modifiers of the relationship between air pollution and NTDs in California, though not in a consistent direction for all pollutants. Birth Defects Research 109:403-422, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

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.

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.

Pathophysiology, risk factors, and screening methods for prediabetes in women with polycystic ovary syndrome

PubMed Central

Gourgari, Evgenia; Spanakis, Elias; Dobs, Adrian Sandra

2016-01-01

Polycystic ovary syndrome (PCOS) is a syndrome associated with insulin resistance (IR), obesity, infertility, and increased cardiometabolic risk. This is a descriptive review of several mechanisms that can explain the IR among women with PCOS, other risk factors for the development of diabetes, and the screening methods used for the detection of glucose intolerance in women with PCOS. Few mechanisms can explain IR in women with PCOS such as obesity, insulin receptor signaling defects, and inhibition of insulin-mediated glucose uptake in adipocytes. Women with PCOS have additional risk factors for the development of glucose intolerance such as family history of diabetes, use of oral contraceptives, anovulation, and age. The Androgen Society in 2007 and the Endocrine Society in 2013 recommended using oral glucose tolerance test as a screening tool for abnormal glucose tolerance in all women with PCOS. The approach to detection of glucose intolerance among women with PCOS varies among health care providers. Large prospective studies are still needed for the development of guidelines with strong evidence. When assessing risk of future diabetes in women with PCOS, it is important to take into account the method used for screening as well as other risk factors that these women might have. PMID:27570464

Pathophysiology, risk factors, and screening methods for prediabetes in women with polycystic ovary syndrome.

PubMed

Gourgari, Evgenia; Spanakis, Elias; Dobs, Adrian Sandra

2016-01-01

Polycystic ovary syndrome (PCOS) is a syndrome associated with insulin resistance (IR), obesity, infertility, and increased cardiometabolic risk. This is a descriptive review of several mechanisms that can explain the IR among women with PCOS, other risk factors for the development of diabetes, and the screening methods used for the detection of glucose intolerance in women with PCOS. Few mechanisms can explain IR in women with PCOS such as obesity, insulin receptor signaling defects, and inhibition of insulin-mediated glucose uptake in adipocytes. Women with PCOS have additional risk factors for the development of glucose intolerance such as family history of diabetes, use of oral contraceptives, anovulation, and age. The Androgen Society in 2007 and the Endocrine Society in 2013 recommended using oral glucose tolerance test as a screening tool for abnormal glucose tolerance in all women with PCOS. The approach to detection of glucose intolerance among women with PCOS varies among health care providers. Large prospective studies are still needed for the development of guidelines with strong evidence. When assessing risk of future diabetes in women with PCOS, it is important to take into account the method used for screening as well as other risk factors that these women might have.

Panorama of Reconstruction of Skull Base Defects: From Traditional Open to Endonasal Endoscopic Approaches, from Free Grafts to Microvascular Flaps

PubMed Central

Reyes, Camilo; Mason, Eric; Solares, C. Arturo

2014-01-01

Introduction A substantial body of literature has been devoted to the distinct characteristics and surgical options to repair the skull base. However, the skull base is an anatomically challenging location that requires a three-dimensional reconstruction approach. Furthermore, advances in endoscopic skull base surgery encompass a wide range of surgical pathology, from benign tumors to sinonasal cancer. This has resulted in the creation of wide defects that yield a new challenge in skull base reconstruction. Progress in technology and imaging has made this approach an internationally accepted method to repair these defects. Objectives Discuss historical developments and flaps available for skull base reconstruction. Data Synthesis Free grafts in skull base reconstruction are a viable option in small defects and low-flow leaks. Vascularized flaps pose a distinct advantage in large defects and high-flow leaks. When open techniques are used, free flap reconstruction techniques are often necessary to repair large entry wound defects. Conclusions Reconstruction of skull base defects requires a thorough knowledge of surgical anatomy, disease, and patient risk factors associated with high-flow cerebrospinal fluid leaks. Various reconstruction techniques are available, from free tissue grafting to vascularized flaps. Possible complications that can befall after these procedures need to be considered. Although endonasal techniques are being used with increasing frequency, open techniques are still necessary in selected cases. PMID:25992142

Glaucoma and quality of life: fall and driving risk.

PubMed

Montana, Cynthia L; Bhorade, Anjali M

2018-03-01

Numerous population-based studies suggest that glaucoma is an independent risk factor for falling and motor vehicle collisions, particularly for older adults. These adverse events lead to increased healthcare expenditures and decreased quality of life. Current research priorities, therefore, include identifying factors that predispose glaucoma patients to falling and unsafe driving, and developing screening strategies and targeted rehabilitation. The purpose of this article is to review recent studies that address these priorities. Studies continue to support that glaucoma patients, particularly those with advanced disease, have an increased risk of falling or unsafe driving. Risk factors, however, remain variable and include severity and location of visual field defects, contrast sensitivity, and performance on divided attention tasks. Such variability is likely because of the multifactorial nature of ambulating and driving and compensatory strategies used by patients. Falls and unsafe driving remain a serious public health issue for older adults with glaucoma. Ambulation and driving are complex tasks and there is no consensus yet, regarding the best methods for risk stratification and targeted interventions to increase safety. Therefore, comprehensive and individualized assessments are recommended to most effectively evaluate a patient's risk for falling or unsafe driving.

Defective Insulin Signalling, Mediated by Inflammation, Connects Obesity to Alzheimer Disease; Relevant Pharmacological Therapies and Preventive Dietary Interventions.

PubMed

Rodriguez-Casado, Arantxa; Toledano-Díaz, Adolfo; Toledano, Adolfo

2017-01-01

Recent evidence suggests that obesity, besides being a risk factor for cardiovascular events, also increases the risk of Alzheimer's disease. Insulin resistance is common in all cases of obesity and appears to be the linkage between both diseases. Obesity, often associated with excessive fat and sugar intake, represents a preclinical stage toward insulin resistance during which nutrition intervention is likely to have maximum effect. In this way, healthy lifestyles lifetime to prevent obesity-related modifiable risk factors such as inflammation, oxidative stress and metabolic disorders could be simultaneously beneficial for preserving cognition and controlling the Alzheimer's disease. This review relates extensive research literature on facts linking nutrients and dietary patterns to obesity and Alzheimer's disease. In addition briefly presents molecular mechanisms involved in obesity- induced insulin resistance and the contribution of peripheral inflammatory and defective insulin signalling pathways, as well as ectopic lipids accumulation to Alzheimer's development through brain inflammation, neuronal insulin resistance, and cognitive dysfunction seen in Alzheimer's disease. The work relates current and emerging pharmacological and non-pharmacological therapies for the management of obesity, insulin resistance and Alzheimer's considering them as disorders with common molecular features. The findings of this review validate the importance of some nutritional interventions as possible approach to prevent or delay simultaneously progression of Alzheimer's disease and obesity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Prognostic factors in Acanthamoeba keratitis.

PubMed

Kaiserman, Igor; Bahar, Irit; McAllum, Penny; Srinivasan, Sathish; Elbaz, Uri; Slomovic, Allan R; Rootman, David S

2012-06-01

To assess the prognostic factors influencing visual prognosis and length of treatment after acanthamoeba keratitis (AK). Forty-two AK eyes of 41 patients treated between 1999 and 2006 were included. A diagnosis of AK was made on the basis of culture results with a corresponding clinical presentation. We calculated the prognostic effect of the various factors on final visual acuity and the length of treatment. Multivariate regression analysis was used to adjust for the simultaneous effects of the various prognostic factors. Mean follow-up was 19.7 ± 21.0 months. Sixty-four percent of cases had > 1 identified risk factor for AK, the most common risk factor being contact lens wear (92.9% of eyes). At presentation, median best spectacle corrected visual acuity (BCVA) was 20/200 (20/30 to Hand Motion [HM]) that improved after treatment to 20/50 (20/20 to Counting Fingers [CF]). Infection acquired by swimming or related to contact lenses had significantly better final BCVA (p = 0.03 and p = 0.007, respectively). Neuritis and pseudodendrites were also associated with better final BCVA (p = 0.04 and p = 0.05, respectively). Having had an epithelial defect on presentation and having been treated with topical steroid were associated with worse final best spectacle corrected visual acuity (BSCVA) (p = 0.0006 and p = 0.04). Multivariate regression analysis found a good initial visual acuity (p = 0.002), infections related to swimming (p = 0.01), the absence of an epithelial defect (p = 0.03), having been treated with chlorhexidine (p = 0.05), and not having receive steroids (p = 0.003) to significantly forecast a good final BCVA. We identified several prognostic factors that can help clinicians evaluate the expected visual damage of the AK infection and thus tailor treatment accordingly. Copyright © 2012 Canadian Ophthalmological Society. All rights reserved.

Risk factors for Dandy-Walker malformation: a population-based assessment.

PubMed

Reeder, Matthew R; Botto, Lorenzo D; Keppler-Noreuil, Kim M; Carey, John C; Byrne, Janice L B; Feldkamp, Marcia L

2015-09-01

Dandy-Walker malformation (DWM) is the most common congenital malformation of the cerebellum, but its causes are largely unknown. An increasing number of genes associated with congenital cerebellar malformations have been identified; however, few studies have examined the potential role of non-genetic, potentially modifiable risk factors. From the National Birth Defects Prevention Study, we examined maternal, paternal, and infant characteristics and maternal conditions and periconceptional exposures (from 1 month before to 3 months after conception) among infants with DWM (n = 160) and unaffected controls (n = 10,200), delivered between 1997 and 2009. Odds ratios, crude (cOR) and adjusted (aOR) were computed using logistic regression. Maternal factors associated with DWM included non-Hispanic black race/ethnicity (aOR = 2.0, 95%CI: 1.3-3.2). Among maternal conditions, a history of infertility increased the risk for DWM (all: aOR = 2.4, 95%CI: 1.3-4.6; multiple: aOR = 3.9, 95%CI: 1.7-8.9). The lack of association with many maternal exposures supports the hypothesis of a major contribution of genetic factors to the risk for DWM; however, the observed associations with maternal non-Hispanic black race/ethnicity and maternal history of infertility indicate that further research into factors underlying these characteristics may uncover potentially modifiable risk factors, acting alone or as a component of gene-environment interactions. © 2015 Wiley Periodicals, Inc.

Novel Tenascin-C Haplotype Modifies the Risk for a Failure to Heal After Rotator Cuff Repair.

PubMed

Kluger, Rainer; Huber, Klaus R; Seely, Philipp G; Berger, Christian E; Frommlet, Florian

2017-11-01

Several single-nucleotide polymorphisms (SNPs) in the TNC gene have recently been found to be associated with degenerative rotator cuff tears. Exonic SNPs in the TNC gene are related to the risk for a failure to heal after rotator cuff repair. Case-control study; Level of evidence, 3. A total of 302 patients from the Vienna area and European Caucasian ancestry underwent mini-open rotator cuff repair for a full-thickness superior or posterosuperior tear and were assessed for the integrity of the repair 1 year postoperatively with a real-time 7.5- to 10-MHz ultrasound linear array transducer. Outcomes were classified as intact (complete footprint coverage), small (<200 mm 2 ), or large (≥200 mm 2 ) recurrent defect. Patients were genotyped for 15 previously identified risk SNPs within a 49-kbp segment of the TNC gene with the KASP genotyping technology or the Ion-Torrent Personal Genome Machine System. All recurrent defects were atraumatic failures, and the overall failure rate was 39.7%. Of the traditional risk factors, only the initial tear size was significantly associated with a failure to heal. In a multinomial logistic regression model, the T allele at rs1138545 [C>T] was protective for a large recurrent defect (odds ratio = 0.16; 95% CI, 0.09-0.31). The role of rs1138545 was further backed by haplotype analysis, which showed that the combination of the C allele at rs1138545 [C>T], the A allele at rs2104772 [A>T], and the G allele at rs10759752 [A>G] formed the risk-related haplotype [CAG]. The CAG haplotype was associated with large recurrent defects ( P < .0001; haplotype frequency, 0.394; haplotype score, 4.518). Exonic marker rs1138545 transcribed into all isoforms of the TNC protein, whereas exonic marker rs2104772, which has been associated with Achilles tendinopathy before, transcribed only into large isoforms of the TNC protein. Recurrent defects after rotator cuff repairs are clinically relevant, and a heritable component of the disorder is plausible on the basis of a genetic association with 8 TNC variants. Characterization of TNC sequences that favor tendon healing will help engineer new products in regenerative medicine.

High Prevalence of Pulmonary Hypertension Complicates the Care of Infants with Omphalocele.

PubMed

Hutson, Shandee; Baerg, Joanne; Deming, Douglas; St Peter, Shawn D; Hopper, Andrew; Goff, Donna A

2017-01-01

Omphalocele is one of the most common abdominal wall defects. Many newborn infants born with omphalocele present with significant respiratory distress at birth, requiring mechanical ventilatory support, and have clinical evidence of pulmonary hypertension. Little information exists on the prevalence of and risk factors associated with pulmonary hypertension in this cohort of infants. To describe the prevalence of and risk factors associated with pulmonary hypertension among infants with omphalocele. This is a multicenter retrospective chart review of demographic data and clinical characteristics of infants with omphalocele admitted to the neonatal intensive care units of Loma Linda University Children's Hospital and Children's Mercy Hospital between 1994 and 2011. Echocardiogram images were reviewed for pulmonary hypertension, and statistical analyses were performed to identify risk factors associated with the presence of pulmonary hypertension. Pulmonary hypertension was diagnosed in 32/56 (57%) infants with omphalocele. Compared to infants without pulmonary hypertension, infants with pulmonary hypertension were more likely to have a liver-containing defect (16/32 [50%] vs. 5/24 [21%], p = 0.03), require intubation at birth (18/32 [56%] vs. 6/24 [17%], p = 0.03), and die during initial hospitalization (12/32 [38%] vs. 2/24 [8%], p = 0.01). The majority of infants with omphalocele have evidence of pulmonary hypertension which is associated with increased mortality. Echocardiograms to screen for pulmonary hypertension should be obtained at ≥2 days of life in infants with omphalocele, especially in those with liver within the omphalocele sac and/or in those infants who require intubation at birth to screen for pulmonary hypertension. © 2017 S. Karger AG, Basel.

Single Ventricle Defects

MedlinePlus

... Your Risk • Symptoms & Diagnosis • Care & Treatment • Tools & Resources Web Booklets on Congenital Heart Defects These online publications ... to you or your child’s defect and concerns. Web Booklet: Adults With Congenital Heart Defects Web Booklet: ...

Cigarette smoking and pulmonary diffusion defects in rheumatoid arthritis.

PubMed

Westedt, M L; Hazes, J M; Breedveld, F C; Sterk, P J; Dijkman, J H

1998-01-01

The pathogenesis of lung disease in rheumatoid arthritis (RA) has still to be defined. Risk factors associated with lung involvement in RA were investigated by means of pulmonary function studies in 40 RA patients without apparent lung disease. A decreased carbon monoxide (CO) diffusion capacity indicative of interstitial lung disease (ILD) was the main pulmonary function defect found in the first 20 patients. The occurrence was associated with current cigarette smoking. This association was confirmed in a case control study performed subsequently. These data suggest that ILD in RA is stimulated by smoking and provide an additional argument that modification of smoking behaviour in RA patients might lead to less severe complications.

A geographic analysis of individual and environmental risk factors for hypospadias births

PubMed Central

Winston, Jennifer J; Meyer, Robert E; Emch, Michael E

2014-01-01

Background Hypospadias is a relatively common birth defect affecting the male urinary tract. We explored the etiology of hypospadias by examining its spatial distribution in North Carolina and the spatial clustering of residuals from individual and environmental risk factors. Methods We used data collected by the North Carolina Birth Defects Monitoring Program from 2003-2005 to estimate local Moran's I statistics to identify geographic clustering of overall and severe hypospadias, using 995 overall cases and 16,013 controls. We conducted logistic regression and local Moran's I statistics on standardized residuals to consider the contribution of individual variables (maternal age, maternal race/ethnicity, maternal education, smoking, parity, and diabetes) and environmental variables (block group land cover) to this clustering. Results Local Moran's I statistics indicated significant clustering of overall and severe hypospadias in eastern central North Carolina. Spatial clustering of hypospadias persisted when controlling for individual factors, but diminished somewhat when controlling for environmental factors. In adjusted models, maternal residence in a block group with more than 5% crop cover was associated with overall hypospadias (OR = 1.22; 95% CI = 1.04 – 1.43); that is living in a block group with greater than 5% crop cover was associated with a 22% increase in the odds of having a baby with hypospadias. Land cover was not associated with severe hypospadias. Conclusions This study illustrates the potential contribution of mapping in generating hypotheses about disease etiology. Results suggest that environmental factors including proximity to agriculture may play some role in the spatial distribution of hypospadias. PMID:25196538

First Trimester Influenza Vaccination and Risks for Major Structural Birth Defects in Offspring.

PubMed

Kharbanda, Elyse Olshen; Vazquez-Benitez, Gabriela; Romitti, Paul A; Naleway, Allison L; Cheetham, T Craig; Lipkind, Heather S; Klein, Nicola P; Lee, Grace; Jackson, Michael L; Hambidge, Simon J; McCarthy, Natalie; DeStefano, Frank; Nordin, James D

2017-08-01

To examine risks for major structural birth defects in infants after first trimester inactivated influenza vaccine (IIV) exposures. In this observational study, we used electronic health data from 7 Vaccine Safety Datalink sites to examine risks for selected major structural defects in infants after maternal IIV exposure. Vaccine exposures for women with continuous insurance enrollment through pregnancy who delivered singleton live births between 2004 and 2013 were identified from standardized files. Infants with continuous insurance enrollment were followed to 1 year of age. We excluded mother-infant pairs with other exposures that potentially increased their background risk for birth defects. Selected cardiac, orofacial or respiratory, neurologic, ophthalmologic or otologic, gastrointestinal, genitourinary and muscular or limb defects were identified from diagnostic codes in infant medical records using validated algorithms. Propensity score adjusted generalized estimating equations were used to estimate prevalence ratios (PRs). We identified 52 856 infants with maternal first trimester IIV exposure and 373 088 infants whose mothers were unexposed to IIV during first trimester. Prevalence (per 100 live births) for selected major structural birth defects was 1.6 among first trimester IIV exposed versus 1.5 among unexposed mothers. The adjusted PR was 1.02 (95% CI 0.94-1.10). Organ system-specific PRs were similar to the overall PR. First trimester maternal IIV exposure was not associated with an increased risk for selected major structural birth defects in this large cohort of singleton live births. Copyright © 2017 Elsevier Inc. All rights reserved.

Risk factors for dental problems: Recommendations for oral health in infancy.

PubMed

Wagner, Yvonne; Heinrich-Weltzien, Roswitha

2017-11-01

Primary care providers, gynaecologists and paediatricians have to be aware of the importance of oral health in infancy and possible consequences for child's development, growth, health and quality of life. Oral diseases, particularly dental caries, developmental defects of the dental tissues and periodontal or orthodontic issues have a complex and interrelated aetiology with common, primarily behavioral based risk factors. A sugar-rich diet is the key risk factor with detrimental consequences for general and oral health, particularly in combination with an insufficient oral hygiene. Therefore, daily tooth brushing with fluoride toothpaste and reducing of sugar intake are the key pillars to prevent oral diseases, including a positive effect on numerous chronic diseases. Future preventive approaches should focus on pregnant women and mothers of infants with a common vision of health and a shared responsibility for children's oral health care to promote healthy lifestyles and self-care practices in families. Copyright © 2017 Elsevier B.V. All rights reserved.

Residual defects of the external anal sphincter following primary repair: an observational study using transperineal ultrasound.

PubMed

Shek, K L; Guzman-Rojas, R; Dietz, H P

2014-12-01

Obstetric anal sphincter tears are common and an important factor in the etiology of anal incontinence. The objective of the study was to evaluate the prevalence of residual defects of the external anal sphincter (EAS) after primary repair of obstetric anal sphincter injury using four-dimensional (4D) transperineal ultrasound and to correlate sonographic findings of residual defects and levator avulsion with significant symptoms of anal incontinence, defined as St Mark's fecal incontinence score (SMIS) of ≥ 5. This was a retrospective observational study. One-hundred and forty women were seen after primary repair of obstetric anal sphincter tears in a dedicated perineal clinic at a tertiary hospital in Australia. They all underwent a standardized interview, and physical and 4D transperineal ultrasound examination. Mean follow-up interval was 1.9 months after delivery. Eighty-nine (64%) women had a 3a/3b tear, 28 (20%) a 3c/4(th) degree tear and 23 (16%) an unclassified 3(rd) degree tear. Thirty-five (25%) patients reported symptoms of anal incontinence. Nine had an SMIS of ≥ 5. A residual defect was found in 56 (40%) cases and levator avulsion in 27 (19%). On multivariate logistic regression, residual defects (P = 0.03; odds ratio (OR) = 6.38; 95% CI, 1.23-33.0) and levator avulsion (P = 0.047; OR = 4.38; 95% CI, 1.02-18.77) were found to be independent risk factors for anal incontinence. Residual defects of the EAS were found on transperineal ultrasound in 40% of women after primary repair of obstetric anal sphincter injuries. Although most were asymptomatic, residual anal sphincter defects and levator avulsion were associated with significant symptoms of anal incontinence as quantified using the SMIS. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Spatial analysis of gastroschisis in Massachusetts and Texas

PubMed Central

Yazdy, Mahsa M.; Werler, Martha M.; Anderka, Marlene; Langlois, Peter H.; Vieira, Veronica M.

2014-01-01

Purpose Previous research has suggested gastroschisis, a congenital malformation, may be linked to environmental or infectious factors and cases can occur in clusters. The objective of this study was to identify geographic areas of elevated gastroschisis risk. Methods Cases of gastroschisis were identified from birth defect registries in Massachusetts and Texas. Random samples of live births were selected as controls. Generalized additive models were used to create a continuous map surface of odds ratios (OR) by smoothing over latitude and longitude. Maternal age, race/ethnicity, education, cigarette smoking, and insurance status (MA only) were assessed for confounding. We used permutation tests to identify statistically significant areas of increased risk. Results An area of increased risk was identified in north-central Massachusetts, but was not significant after adjustment (p-value=0.07; OR=2.0). In Texas, two statistically significant areas of increased risk were identified after adjustment (p-value=0.02; OR=1.3 and 1.2). Texas had sufficient data to assess the combination of space and time, which identified an increased risk in 2003 and 2004. Conclusion This study suggests there were areas of elevated gastroschisis risk in Massachusetts and Texas that cannot be explained by the risk factors we assessed. Additional exploration of underlying artifactual, environmental, infectious, or behavioral factors may further our understanding of gastroschisis. PMID:25454289

Cardiac risk stratification in renal transplantation using a form of artificial intelligence.

PubMed

Heston, T F; Norman, D J; Barry, J M; Bennett, W M; Wilson, R A

1997-02-15

The purpose of this study was to determine if an expert network, a form of artificial intelligence, could effectively stratify cardiac risk in candidates for renal transplant. Input into the expert network consisted of clinical risk factors and thallium-201 stress test data. Clinical risk factor screening alone identified 95 of 189 patients as high risk. These 95 patients underwent thallium-201 stress testing, and 53 had either reversible or fixed defects. The other 42 patients were classified as low risk. This algorithm made up the "expert system," and during the 4-year follow-up period had a sensitivity of 82%, specificity of 77%, and accuracy of 78%. An artificial neural network was added to the expert system, creating an expert network. Input into the neural network consisted of both clinical variables and thallium-201 stress test data. There were 5 hidden nodes and the output (end point) was cardiac death. The expert network increased the specificity of the expert system alone from 77% to 90% (p < 0.001), the accuracy from 78% to 89% (p < 0.005), and maintained the overall sensitivity at 88%. An expert network based on clinical risk factor screening and thallium-201 stress testing had an accuracy of 89% in predicting the 4-year cardiac mortality among 189 renal transplant candidates.

Puberty as a risk factor for less favorable visual outcome in idiopathic intracranial hypertension.

PubMed

Stiebel-Kalish, Hadas; Kalish, Yuval; Lusky, Moshe; Gaton, Dan D; Ehrlich, Rita; Shuper, Avinoam

2006-08-01

To test the hypothesis that puberty is a risk factor for poorer visual outcome in idiopathic intracranial hypertension (IIH). Retrospective chart review case series. Tertiary referral center, neuro-ophthalmology unit. Ninety-six patients with IIH followed for a minimum of one year. Age (grouped into prepubertal, pubertal, teenage, or adult), obesity, initial intracranial pressure (ICP), measurements and presence of hypertension, anemia, or renal failure were correlated with final visual outcome using chi(2), stepwise logistic regression, and model-selection log linear analyses. Visual outcome was graded into "excellent" -- no evidence of an optic neuropathy or any permanent visual field defect in either eye, "moderate"-- evidence of an optic neuropathy and/or a mild (nasal constriction) visual field defect, or "poor outcome" (peripheral constriction) -- permanent visual field defect. Outcome data were complete for 96 patients. Moderate to poor visual outcome, as opposed to excellent, was significantly associated with puberty (P = .007 using the gender-specific definition of puberty, .0002 using the broad definition). Moderate-poor visual outcome occurred in none of seven IIH patients of prepubertal age (<9 years), in 15 of 26 patients presenting between nine to 16 years, in two of six patients aged 17 to 22 years, and in seven of 57 adult patients over the age of 23 years. In this series of 96 patients with IIH, visual outcome was less favorable in pubertal patients than in prepubertal, teenage, and adult patients. We recommend that clinicians maintain a high index of awareness when caring for pubescent children with IIH.

Advances in molecular genetics for pulmonary atresia.

PubMed

Gao, Manchen; He, Xiaomin; Zheng, Jinghao

2017-03-01

Genetic and environmental factors may be similar in certain CHD. It has been widely accepted that it is the cumulative effect of these risk factors that results in disease. Pulmonary atresia is a rare type of complex cyanotic CHD with a poor prognosis. Understanding the molecular mechanism of pulmonary atresia is essential for future diagnosis, prevention, and therapeutic approaches. In this article, we reviewed several related copy number variants and related genetic mutations, which were identified in patients with pulmonary atresia, including pulmonary atresia with ventricular septal defect and pulmonary atresia with intact ventricular septum.

Using birth defects registry data to evaluate infant and childhood mortality associated with birth defects: an alternative to traditional mortality assessment using underlying cause of death statistics.

PubMed

Copeland, Glenn E; Kirby, Russell S

2007-11-01

Although birth defects are a leading cause of death in infancy and early childhood, the proportion of all deaths to children with clinically diagnosed birth defects is not well documented. The study is intended to measure the proportion of all deaths to infants and children under age 10 occurring to children with birth defects and how and why this proportion differs from the proportion of deaths due to an underlying cause of congenital anomalies using standard mortality statistics. A linked file of Michigan livebirths and deaths was combined with data from a comprehensive multisource birth defects registry of Michigan livebirths born during the years 1992 through 2000. The data were analyzed to determine the mortality rate for infants and children with birth defects and for children with no reported birth defect. Mortality risk ratios were calculated. The underlying causes of death for children with birth defects were also categorized and compared to cause- specific mortality rates for the general population. Congenital anomalies were the underlying cause of death for 17.8% of all infant deaths while infants with birth defects were 33.7% of all infant deaths in the study. Almost half of all Michigan deaths to children aged 1 to 2 were within the birth defects registry, though only 15.0% had an underlying cause of death of a congenital anomaly based upon standard mortality statistics. The mortality experience among children with birth defects was significantly higher than other children throughout the first 9 years of life, ranging from 4.6 for 5 year olds to 12.8 for children 1 to 2. Mortality risk ratios examined by cause of death for infants with birth defects were highest for other endocrine (28.1), other CNS (28.1), and heart (21.9) conditions. For children 1 through 9, the highest differential risk was seen for other perinatal conditions (39.0), other endocrine (29.7), other CNS (24.5), and heart (21.4). Childhood mortality analyses that incorporate birth defects registry data provide a more comprehensive picture of the full burden of birth defects on mortality in infant and children and can provide an effective mechanism for monitoring the survival and mortality risks of children with selected birth defects on a population basis.

Does maternal environmental tobacco smoke interact with social-demographics and environmental factors on congenital heart defects?

PubMed

Liu, Xiaoqing; Nie, Zhiqiang; Chen, Jimei; Guo, Xiaoling; Ou, Yanqiu; Chen, Guanchun; Mai, Jinzhuang; Gong, Wei; Wu, Yong; Gao, Xiangmin; Qu, Yanji; Bell, Erin M; Lin, Shao; Zhuang, Jian

2018-03-01

Congenital heart defects (CHDs) are a major cause of death in infancy and childhood. Major risk factors for most CHDs, particularly those resulting from the combination of environmental exposures with social determinants and behaviors, are still unknown. This study evaluated the main effect of maternal environmental tobacco smoke (ETS), and its interaction with social-demographics and environmental factors on CHDs in China. A population-based, matched case-control study of 9452 live-born infants and stillborn fetuses was conducted using the Guangdong Registry of Congenital Heart Disease data (2004-2014). The CHDs were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia tomography/catheterization. Controls were randomly chosen from singleton newborns without any malformation, born in the same hospital as the cases and 1:1 matched by infant sex, time of conception, and parental residence (same city and town to ensure sufficient geographical distribution for analyses). Face-to-face interviews were conducted to collect information on demographics, behavior patterns, maternal disease/medication, and environmental exposures. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals of ETS exposure on CHDs while controlling for all risk factors. Interactive effects were evaluated using a multivariate delta method for maternal demographics, behavior, and environmental exposures on the ETS-CHD relationship. Mothers exposed to ETS during the first trimester of pregnancy were more likely to have infants with CHD than mothers who did not (aOR = 1.44, 95% CI 1.25-1.66). We also observed a significant dose-response relationship when mothers were exposed to ETS and an increasing number of risk factors and CHDs. There were greater than additive interactions for maternal ETS and migrant status, low household income and paternal alcohol consumption on CHDs. Maternal low education also modified the ETS-CHD association on the multiplicative scale. These findings may help to identify high-risk populations for CHD, providing an opportunity for targeted preventive interventions. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Pharmacogenetic aspects of drug-induced torsade de pointes: potential tool for improving clinical drug development and prescribing.

PubMed

Shah, Rashmi R

2004-01-01

Drug-induced torsade de pointes (TdP) has proved to be a significant iatro-genic cause of morbidity and mortality and a major reason for the withdrawal of a number of drugs from the market in recent times. Enzymes that metabolise many of these drugs and the potassium channels that are responsible for cardiac repolarisation display genetic polymorphisms. Anecdotal reports have suggested that in many cases of drug-induced TdP, there may be a concealed genetic defect of either these enzymes or the potassium channels, giving rise to either high plasma drug concentrations or diminished cardiac repolarisation reserve, respectively. The presence of either of these genetic defects may predispose a patient to TdP, a potentially fatal adverse reaction, even at therapeutic dosages of QT-prolonging drugs and in the absence of other risk factors. Advances in pharmacogenetics of drug metabolising enzymes and pharmacological targets, together with the prospects of rapid and inexpensive genotyping procedures, promise to individualise and improve the benefit/risk ratio of therapy with drugs that have the potential to cause TdP. The qualitative and the quantitative contributions of these genetic defects in clinical cases of TdP are unclear because not all of the patients with TdP are routinely genotyped and some relevant genetic mutations still remain to be discovered. There are regulatory guidelines that recommend strategies aimed at uncovering the risk of TdP associated with new chemical entities during their development. There are also a number of guidelines that recommend integrating pharmacogenetics in this process. This paper proposes a strategy for integrating pharmacogenetics into drug development programmes to optimise association studies correlating genetic traits and endpoints of clinical interest, namely failure of efficacy or development of repolarisation abnormalities. Until pharmacogenetics is carefully integrated into all phases of development of QT-prolonging drugs and large-scale studies are undertaken during their post-marketing use to determine the genetic components involved in induction of TdP, routine genotyping of patients remains unrealistic. Even without this pharmacogenetic data, the clinical risk of TdP can already be greatly minimised. Clinically, a substantial proportion of cases of TdP are due to the use of either high or usual dosages of drugs with potential to cause TdP in the presence of factors that inhibit drug metabolism. Therefore, choosing the lowest effective dose and identifying patients with these non-genetic risk factors are important means of minimising the risk of TdP. In view of the common secondary pharmacology shared by these drugs, a standard set of contraindications and warnings have evolved over the last decade. These include factors responsible for pharmacokinetic or pharmacodynamic drug interactions. Among the latter, the more important ones are bradycardia, electrolyte imbalance, cardiac disease and co-administration of two or more QT-prolonging drugs. In principle, if large scale prospective studies can demonstrate a substantial genetic component, pharmacogenetically driven prescribing ought to reduce the risk further. However, any potential benefits of pharmacogenetics will be squandered without any reduction in the clinical risk of TdP if physicians do not follow prescribing and monitoring recommendations.

Air toxics and birth defects: a Bayesian hierarchical approach to evaluate multiple pollutants and spina bifida.

PubMed

Swartz, Michael D; Cai, Yi; Chan, Wenyaw; Symanski, Elaine; Mitchell, Laura E; Danysh, Heather E; Langlois, Peter H; Lupo, Philip J

2015-02-09

While there is evidence that maternal exposure to benzene is associated with spina bifida in offspring, to our knowledge there have been no assessments to evaluate the role of multiple hazardous air pollutants (HAPs) simultaneously on the risk of this relatively common birth defect. In the current study, we evaluated the association between maternal exposure to HAPs identified by the United States Environmental Protection Agency (U.S. EPA) and spina bifida in offspring using hierarchical Bayesian modeling that includes Stochastic Search Variable Selection (SSVS). The Texas Birth Defects Registry provided data on spina bifida cases delivered between 1999 and 2004. The control group was a random sample of unaffected live births, frequency matched to cases on year of birth. Census tract-level estimates of annual HAP levels were obtained from the U.S. EPA's 1999 Assessment System for Population Exposure Nationwide. Using the distribution among controls, exposure was categorized as high exposure (>95(th) percentile), medium exposure (5(th)-95(th) percentile), and low exposure (<5(th) percentile, reference). We used hierarchical Bayesian logistic regression models with SSVS to evaluate the association between HAPs and spina bifida by computing an odds ratio (OR) for each HAP using the posterior mean, and a 95% credible interval (CI) using the 2.5(th) and 97.5(th) quantiles of the posterior samples. Based on previous assessments, any pollutant with a Bayes factor greater than 1 was selected for inclusion in a final model. Twenty-five HAPs were selected in the final analysis to represent "bins" of highly correlated HAPs (ρ > 0.80). We identified two out of 25 HAPs with a Bayes factor greater than 1: quinoline (ORhigh = 2.06, 95% CI: 1.11-3.87, Bayes factor = 1.01) and trichloroethylene (ORmedium = 2.00, 95% CI: 1.14-3.61, Bayes factor = 3.79). Overall there is evidence that quinoline and trichloroethylene may be significant contributors to the risk of spina bifida. Additionally, the use of Bayesian hierarchical models with SSVS is an alternative approach in the evaluation of multiple environmental pollutants on disease risk. This approach can be easily extended to environmental exposures, where novel approaches are needed in the context of multi-pollutant modeling.

Right-sided infective endocarditis: recent epidemiologic changes

PubMed Central

Yuan, Shi-Min

2014-01-01

Background: Infective endocarditis (IE) has been increasingly reported, however, little is available regarding recent development of right-sided IE. Methods: Right-sided IE was comprehensively analyzed based on recent 5⅓-year literature. Results: Portal of entry, implanted foreign material, and repaired congenital heart defects were the main predisposing risk factors. Vegetation size on the right-sided valves was much smaller than those beyond the valves. Multiple logistic regression analysis revealed that predisposing risk factors, and vegetation size and locations were independent predictive risks of patients’ survival. Conclusions: Changes of right-sided IE in the past 5⅓ years included younger patient age, and increased vegetation size, but still prominent Staphylococcus aureus infections. Complication spectrum has changed into more valve insufficiency, more embolic events, reduced abscess formation, and considerably decreased valve perforations. With effective antibiotic regimens, prognoses of the patients seemed to be better than before. PMID:24482708

Risk assessment and causal preventive measures.

PubMed

Lussi, Adrian; Hellwig, Elmar

2014-01-01

A prerequisite for preventive measures is to diagnose erosive tooth wear and to evaluate the different etiological factors in order to identify persons at risk. No diagnostic device is available for the assessment of erosive defects. Thus, they can only be detected clinically. Consequently, erosion not diagnosed at an early stage may render timely preventive measures difficult. In order to assess the risk factors, patients should record their dietary intake for a distinct period of time. Then a dentist can determine the erosive potential of the diet. A table with common beverages and foodstuffs is presented for judging the erosive potential. Particularly, patients with more than 4 dietary acid intakes have a higher risk for erosion when other risk factors are present. Regurgitation of gastric acids is a further important risk factor for the development of erosion which has to be taken into account. Based on these analyses, an individually tailored preventive program may be suggested to the patients. It may comprise dietary advice, use of calcium-enriched beverages, optimization of prophylactic regimes, stimulation of salivary flow rate, use of buffering medicaments and particular motivation for nondestructive toothbrushing habits with an erosive-protecting toothpaste as well as rinsing solutions. Since erosion and abrasion often occur simultaneously, all of the causative components must be taken into consideration when planning preventive strategies but only those important and feasible for an individual should be communicated to the patient. © 2014 S. Karger AG, Basel.

Reconstruction of the Foot and Ankle Using Pedicled or Free Flaps: Perioperative Flap Survival Analysis

PubMed Central

Li, Xiucun; Cui, Jianli; Maharjan, Suraj; Lu, Laijin; Gong, Xu

2016-01-01

Objective The purpose of this study is to determine the correlation between non-technical risk factors and the perioperative flap survival rate and to evaluate the choice of skin flap for the reconstruction of foot and ankle. Methods This was a clinical retrospective study. Nine variables were identified. The Kaplan-Meier method coupled with a log-rank test and a Cox regression model was used to predict the risk factors that influence the perioperative flap survival rate. The relationship between postoperative wound infection and risk factors was also analyzed using a logistic regression model. Results The overall flap survival rate was 85.42%. The necrosis rates of free flaps and pedicled flaps were 5.26% and 20.69%, respectively. According to the Cox regression model, flap type (hazard ratio [HR] = 2.592; 95% confidence interval [CI] (1.606, 4.184); P < 0.001) and postoperative wound infection (HR = 0.266; 95% CI (0.134, 0.529); P < 0.001) were found to be statistically significant risk factors associated with flap necrosis. Based on the logistic regression model, preoperative wound bed inflammation (odds ratio [OR] = 11.371,95% CI (3.117, 41.478), P < 0.001) was a statistically significant risk factor for postoperative wound infection. Conclusion Flap type and postoperative wound infection were both independent risk factors influencing the flap survival rate in the foot and ankle. However, postoperative wound infection was a risk factor for the pedicled flap but not for the free flap. Microvascular anastomosis is a major cause of free flap necrosis. To reconstruct complex or wide soft tissue defects of the foot or ankle, free flaps are safer and more reliable than pedicled flaps and should thus be the primary choice. PMID:27930679

Impact of preterm birth on infant mortality for newborns with congenital heart defects: The EPICARD population-based cohort study.

PubMed

Laas, Enora; Lelong, Nathalie; Ancel, Pierre-Yves; Bonnet, Damien; Houyel, Lucile; Magny, Jean-François; Andrieu, Thibaut; Goffinet, François; Khoshnood, Babak

2017-05-15

Congenital heart defects (CHD) and preterm birth (PTB) are major causes of infant mortality. However, limited data exist on risk of mortality associated with PTB for newborns with CHD. Our objective was to assess impact of PTB on risk of infant mortality for newborns with CHD, while taking into account the role of associated anomalies and other potentially confounding factors. We used data on 2172 live births from a prospective population-based cohort study of CHD (the EPICARD Study) and compared neonatal, post-neonatal and overall infant mortality for infants born at <32, 32-34 and 35-36 weeks vs. those born at term (37-41 weeks). Preterm newborns had a 3.8-fold higher risk of infant death (17.9%) than term newborns (4.7%), RR 3.8, 95%CI 2.7-5.2; the risk associated with PTB was more than four-fold higher for neonatal (RR 4.3, 95% CI 2.9-6.6) and three-fold higher for post-neonatal deaths (RR 3.0, 95% CI 1.7-5.2). Survival analysis showed that newborns <35 weeks had a higher risk of mortality, which decreased but persisted after exclusion of associated anomalies and adjustment for potential confounders. Preterm birth is associated with an approximately four-fold higher risk of infant mortality for newborns with CHD. This excess risk appears to be mostly limited to newborns <35 weeks of gestation and is disproportionately due to early deaths.

Mapping disease at an approximated individual level using aggregate data: a case study of mapping New Hampshire birth defects.

PubMed

Shi, Xun; Miller, Stephanie; Mwenda, Kevin; Onda, Akikazu; Reese, Judy; Onega, Tracy; Gui, Jiang; Karagas, Margret; Demidenko, Eugene; Moeschler, John

2013-09-06

Limited by data availability, most disease maps in the literature are for relatively large and subjectively-defined areal units, which are subject to problems associated with polygon maps. High resolution maps based on objective spatial units are needed to more precisely detect associations between disease and environmental factors. We propose to use a Restricted and Controlled Monte Carlo (RCMC) process to disaggregate polygon-level location data to achieve mapping aggregate data at an approximated individual level. RCMC assigns a random point location to a polygon-level location, in which the randomization is restricted by the polygon and controlled by the background (e.g., population at risk). RCMC allows analytical processes designed for individual data to be applied, and generates high-resolution raster maps. We applied RCMC to the town-level birth defect data for New Hampshire and generated raster maps at the resolution of 100 m. Besides the map of significance of birth defect risk represented by p-value, the output also includes a map of spatial uncertainty and a map of hot spots. RCMC is an effective method to disaggregate aggregate data. An RCMC-based disease mapping maximizes the use of available spatial information, and explicitly estimates the spatial uncertainty resulting from aggregation.

Cesarean scar defects: an underrecognized cause of abnormal uterine bleeding and other gynecologic complications.

PubMed

Tower, Amanda M; Frishman, Gary N

2013-01-01

The gynecologic sequelae due to deficient uterine scar healing after cesarean section are only recently being identified and described. These include conditions such as abnormal bleeding, pelvic pain, infertility, and cesarean scar ectopic pregnancy, as well as a potentially higher risk of complications and difficulties during gynecologic procedures such as uterine evacuation, hysterectomy, endometrial ablation, and insertion of an intrauterine device. The proposed mechanism of abnormal uterine bleeding is a pouch or "isthmocele" in the lower uterine segment that causes delayed menstrual bleeding. The prevalence of symptomatic or clinically relevant cesarean scar defects (CSDs) ranges from 19.4% to 88%. Possible risk factors for CSD include number of cesarean sections, uterine position, labor before cesarean section, and surgical technique used to close the uterine incision. There are no accepted guidelines for the diagnostic criteria of CSD. We propose that a CSD be defined on transvaginal ultrasound or saline infusion sonohysterography as a triangular hypoechoic defect in the myometrium at the site of the previous hysterotomy. We also propose a classification system to aid in standardized classification for future research. Surgical techniques for repair of CSD include laparoscopic excision, resectoscopic treatment, vaginal revision, and endometrial ablation. Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.

Effect of vaginal delivery on anal sphincter function in Asian primigravida: a prospective study.

PubMed

Wickramasinghe, Dakshitha Praneeth; Senaratne, Supun; Senanayake, Hemantha; Samarasekera, Dharmabandhu Nandadeva

2016-09-01

The true incidence of obstetric anal sphincter injuries (OASI) among Asian primigravida is not known. This study aimed to evaluate OASI in Sri Lankan primigravida. One hundred and one consecutive primigravida in their last trimester were recruited from antenatal clinics at a tertiary care centre in Sri Lanka and followed up 6 weeks and 6 months after delivery. They were assessed using anorectal manometry (3D-ARM) and endoanal ultrasound (3D-EAUS) on both occasions. Seventy-three (75.3 %) had vaginal delivery without instrumentation, whereas 3 (3.1 %) each delivered using forceps or vacuum. Twelve (12.4 %) had emergency caesarean sections and 6 (6.2 %) had elective caesarean sections. None had clinically identified anal sphincter injuries. EAUS identified IAS defects in 3 (5.1 %) and EAS defects in 28 (47.5 %). Both resting (p = 0.3) and squeeze (p = 0.001) pressures had decreased following childbirth. Multivariate analysis identified antepartum RP and postpartum EAS defects to be associated with RP reduction (χ(2)(4)=17.825, p < 0.0005) and antepartum SP and postpartum EAS defects to be associated with SP reduction (χ(2)(5)=31.517, p < 0.0005). Episiotomy was protective, whereas delivering after 40 weeks' gestation and delivering a baby with a longer length increased the risk of SP reduction. EAS defects (χ(2) (6)=23.502, p = .001) were more common in mothers who had labour augmented by oxytocin and in those who delivered a baby with a larger head circumference. Labour induction and delivering a longer baby were protective for EAS defects. Several risk and protective factors for the structural and functional damage of sphincters were identified. These findings will help to formulate a policy to minimize future obstetric anal sphincter injuries.

Maternal report of fever from cold or flu during early pregnancy and the risk for noncardiac birth defects, National Birth Defects Prevention Study, 1997-2011.

PubMed

Waller, Dorothy Kim; Hashmi, Syed Shahrukh; Hoyt, Adrienne T; Duong, Hao T; Tinker, Sarah C; Gallaway, Michael Shayne; Olney, Richard S; Finnell, Richard H; Hecht, Jacqueline Tauber; Canfield, Mark A

2018-03-01

As maternal fever affects approximately 6-8% of early pregnancies, it is important to expand upon previous observations of an association between maternal fever and birth defects. We analyzed data from the National Birth Defects Prevention Study, a multistate, case-control study of major structural birth defects. Telephone interviews were completed by mothers of cases (n = 17,162) and controls (n = 10,127). Using multivariable logistic regression, we assessed the association between maternal self-report of cold or flu with fever and cold or flu without fever during early pregnancy and 30 categories of non-cardiac birth defects. Maternal report of cold or flu with fever was significantly associated with 8 birth defects (anencephaly, spina bifida, encephalocele, cleft lip with or without cleft palate, colonic atresia/stenosis, bilateral renal agenesis/hypoplasia, limb reduction defects, and gastroschisis) with elevated adjusted odds ratios ranging from 1.2 to 3.7. Maternal report of cold or flu without fever was not associated with any of the birth defects studied. This study adds to the evidence that maternal fever during early pregnancy is associated with an increased risk for selected birth defects. Elevated associations were limited to mothers who reported a fever, suggesting that it is fever that contributes to the excess risk rather than illnesses associated with it. However, fever may also serve as a marker for more severe infections. © 2017 Wiley Periodicals, Inc.

Risk factors for accelerated polyethylene wear and osteolysis in ABG I total hip arthroplasty

PubMed Central

Havranek, Vitezslav; Zapletalova, Jana

2009-01-01

We analysed data from 155 revisions of identical cementless hip prostheses to determine the influence of patient-, implant- and surgery-related factors on the polyethylene wear rate and size of periprosthetic osteolysis (OL). This was calculated by logistic regression analysis. Factors associated with an increased/decreased wear rate included position of the cup relative to Kohler’s line, increase in abduction angle of the cup, traumatic and inflammatory arthritis as a primary diagnosis, and patient height. Severe acetabular bone defects were predicted by an increased wear rate (odds ratio, OR = 5.782 for wear rate above 200 mm3/y), and increased height of the patient (OR = 0.905 per each centimetre). Predictors of severe bone defects in the femur were the increased wear rate (OR = 3.479 for wear rate above 200 mm3/y) and placement of the cup outside of the true acetabulum (OR = 3.292). Variables related to surgical technique were the most predictive of polyethylene wear rate. PMID:19214506

Thymidylate synthase repeat polymorphisms and risk of neural tube defects in a population from the northern United Kingdom.

PubMed

Wilding, Craig S; Relton, Caroline L; Sutton, Matthew J; Jonas, Pat A; Lynch, Sally-Ann; Tawn, E Janet; Burn, John

2004-07-01

A 28-bp repeat polymorphism in the 5'UTR of the thymidylate synthase (TYMS) gene represents a candidate risk factor for neural tube defects (NTDs) due to involvement in folate-dependent homocysteine metabolism. Non-Hispanic, white, U.S. citizens carrying at least one 2x 28-bp repeat allele have recently been shown to be at a four-fold increased risk of spina bifida (SB). We investigated the association between this polymorphism and risk of NTD in families affected by NTDs and controls from the northern United Kingdom (UK). PCR was performed on genomic DNA extracted from blood or mouth swabs of family members affected by NTDs (mothers, fathers, and cases), and unaffected controls (mothers and infants) to determine the number of 28-bp repeat units within the promoter region of TYMS. Case-control and TDT analyses of the influence of TYMS genotype on risk of NTD, or NTD pregnancy, were conducted. Odds ratio (OR) analysis indicated that individuals carrying the 2x 28-bp repeat allele either in homozygous or heterozygous form, are not at increased risk of NTDs, or of having an NTD affected pregnancy. Control population allele frequencies are seen to be markedly different between the U.S. controls and those in this study. TYMS polymorphism appears to be not universally associated with NTD risk across Caucasian samples. The elevated risk of spina bifida in U.S. samples appears to be driven by an unusually low risk allele (2x 28 bp) frequency in control samples. Family based (TDT) testing of U.S. samples is therefore advocated.

A scoping review of biopsychosocial risk factors and co-morbidities for common spinal disorders.

PubMed

Green, Bart N; Johnson, Claire D; Haldeman, Scott; Griffith, Erin; Clay, Michael B; Kane, Edward J; Castellote, Juan M; Rajasekaran, Shanmuganathan; Smuck, Matthew; Hurwitz, Eric L; Randhawa, Kristi; Yu, Hainan; Nordin, Margareta

2018-01-01

The purpose of this review was to identify risk factors, prognostic factors, and comorbidities associated with common spinal disorders. A scoping review of the literature of common spinal disorders was performed through September 2016. To identify search terms, we developed 3 terminology groups for case definitions: 1) spinal pain of unknown origin, 2) spinal syndromes, and 3) spinal pathology. We used a comprehensive strategy to search PubMed for meta-analyses and systematic reviews of case-control studies, cohort studies, and randomized controlled trials for risk and prognostic factors and cross-sectional studies describing associations and comorbidities. Of 3,453 candidate papers, 145 met study criteria and were included in this review. Risk factors were reported for group 1: non-specific low back pain (smoking, overweight/obesity, negative recovery expectations), non-specific neck pain (high job demands, monotonous work); group 2: degenerative spinal disease (workers' compensation claim, degenerative scoliosis), and group 3: spinal tuberculosis (age, imprisonment, previous history of tuberculosis), spinal cord injury (age, accidental injury), vertebral fracture from osteoporosis (type 1 diabetes, certain medications, smoking), and neural tube defects (folic acid deficit, anti-convulsant medications, chlorine, influenza, maternal obesity). A range of comorbidities was identified for spinal disorders. Many associated factors for common spinal disorders identified in this study are modifiable. The most common spinal disorders are co-morbid with general health conditions, but there is a lack of clarity in the literature differentiating which conditions are merely comorbid versus ones that are risk factors. Modifiable risk factors present opportunities for policy, research, and public health prevention efforts on both the individual patient and community levels. Further research into prevention interventions for spinal disorders is needed to address this gap in the literature.

A scoping review of biopsychosocial risk factors and co-morbidities for common spinal disorders

PubMed Central

Smuck, Matthew; Hurwitz, Eric L.; Randhawa, Kristi; Yu, Hainan; Nordin, Margareta

2018-01-01

Objective The purpose of this review was to identify risk factors, prognostic factors, and comorbidities associated with common spinal disorders. Methods A scoping review of the literature of common spinal disorders was performed through September 2016. To identify search terms, we developed 3 terminology groups for case definitions: 1) spinal pain of unknown origin, 2) spinal syndromes, and 3) spinal pathology. We used a comprehensive strategy to search PubMed for meta-analyses and systematic reviews of case-control studies, cohort studies, and randomized controlled trials for risk and prognostic factors and cross-sectional studies describing associations and comorbidities. Results Of 3,453 candidate papers, 145 met study criteria and were included in this review. Risk factors were reported for group 1: non-specific low back pain (smoking, overweight/obesity, negative recovery expectations), non-specific neck pain (high job demands, monotonous work); group 2: degenerative spinal disease (workers’ compensation claim, degenerative scoliosis), and group 3: spinal tuberculosis (age, imprisonment, previous history of tuberculosis), spinal cord injury (age, accidental injury), vertebral fracture from osteoporosis (type 1 diabetes, certain medications, smoking), and neural tube defects (folic acid deficit, anti-convulsant medications, chlorine, influenza, maternal obesity). A range of comorbidities was identified for spinal disorders. Conclusion Many associated factors for common spinal disorders identified in this study are modifiable. The most common spinal disorders are co-morbid with general health conditions, but there is a lack of clarity in the literature differentiating which conditions are merely comorbid versus ones that are risk factors. Modifiable risk factors present opportunities for policy, research, and public health prevention efforts on both the individual patient and community levels. Further research into prevention interventions for spinal disorders is needed to address this gap in the literature. PMID:29856783

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.

Nutritional status and eating disorders: neglected risks factor for nontuberculous mycobacterial lung disease?

PubMed

Portillo, Karina; Morera, Josep

2012-01-01

Nontuberculous mycobacterial lung disease (NTMLD) in immunocompetent patients is an increasingly important epidemiologic concern. However, risk factors associated with susceptibility to NTMLD are not completely known. A prevalence of NTMLD appears to be rising, mainly in some populations such as middle-aged or elderly thin women, (a group including those with Lady Windermere syndrome) with neither remarkable history of respiratory disease nor smoking habit. Right middle lobe (RML) and lingula are often involved. Various predisposing factors and genetic defects have been described as possible causes of development of NTMLD, namely: voluntary suppression of cough, RML anatomical factors, menopause and mutations in cystic fibrosis transmembrane conductance regulator (CFTR). Malnutrition is also an important and common risk factor associated with other mycobacterial disease like tuberculosis (TB) and its probable association with NTMLD as have been pointed out for some authors. However, a real description of all nutritional aspects and eating habits of patients prior to NTMLD diagnosis is lacking. We hypothesized that malnutrition and eating disorders like anorexia nervosa could be risk factors that may promoting NTMLD. From a clinical viewpoint, if this hypothesis proves to be correct, eating habits and nutritional aspects should be taken into account in the diagnosis process of suspected NTMLD, since they are easily identifiable and treatable conditions. Copyright © 2011 Elsevier Ltd. All rights reserved.

The role of folate metabolism in orofacial development and clefting

PubMed Central

Wahl, Stacey E.; Kennedy, Allyson E.; Wyatt, Brent H.; Moore, Alexander D.; Pridgen, Deborah E.; Cherry, Amanda M.; Mavila, Catherine B.; Dickinson, Amanda J.G.

2015-01-01

Folate deficiency has been associated with numerous diseases and birth defects including orofacial defects. However, whether folate has a role in the face during early orofacial development has been unclear. The present study reveals that pharmacological and antisense oligonucleotide mediated inhibition of DHFR, an integral enzyme in the folate pathway, results in specific changes in the size and shape of the midface and embryonic mouth. Such defects are accompanied by a severe reduction in the muscle and cartilage jaw elements without significant change in neural crest pattern or global levels of methylation. We propose that the orofacial defects associated with DHFR deficient function are the result of decreased cell proliferation and increased cell death via DNA damage. In particular, localized apoptosis may also be depleting the cells of the face that express crucial genes for the differentiation of the jaw structures. Folate supplementation is widely known to reduce human risk for orofacial clefts. In the present study, we show that activating folate metabolism can reduce median oral clefts in the primary palate by increasing cell survival. Moreover, we demonstrate that a minor decrease in DHFR function exacerbates median facial clefts caused by RAR inhibition. This work suggests that folate deficiencies could be a major contributing factor to multifactorial orofacial defects. PMID:26144049

Epidemiology, Etiology, and Treatment of Isolated Cleft Palate

PubMed Central

Burg, Madeleine L.; Chai, Yang; Yao, Caroline A.; Magee, William; Figueiredo, Jane C.

2016-01-01

Isolated cleft palate (CPO) is the rarest form of oral clefting. The incidence of CPO varies substantially by geography from 1.3 to 25.3 per 10,000 live births, with the highest rates in British Columbia, Canada and the lowest rates in Nigeria, Africa. Stratified by ethnicity/race, the highest rates of CPO are observed in non-Hispanic Whites and the lowest in Africans; nevertheless, rates of CPO are consistently higher in females compared to males. Approximately fifty percent of cases born with cleft palate occur as part of a known genetic syndrome or with another malformation (e.g., congenital heart defects) and the other half occur as solitary defects, referred to often as non-syndromic clefts. The etiology of CPO is multifactorial involving genetic and environmental risk factors. Several animal models have yielded insight into the molecular pathways responsible for proper closure of the palate, including the BMP, TGF-β, and SHH signaling pathways. In terms of environmental exposures, only maternal tobacco smoke has been found to be strongly associated with CPO. Some studies have suggested that maternal glucocorticoid exposure may also be important. Clearly, there is a need for larger epidemiologic studies to further investigate both genetic and environmental risk factors and gene-environment interactions. In terms of treatment, there is a need for long-term comprehensive care including surgical, dental and speech pathology. Overall, five main themes emerge as critical in advancing research: (1) monitoring of the occurrence of CPO (capacity building); (2) detailed phenotyping of the severity (biology); (3) understanding of the genetic and environmental risk factors (primary prevention); (4) access to early detection and multidisciplinary treatment (clinical services); and (5) understanding predictors of recurrence and possible interventions among families with a child with CPO (secondary prevention). PMID:26973535

[Screening for cutaneous carcinoma].

PubMed

Beani, J C

1996-09-01

Skin carcinoma is the most frequent of all cancers. The main risk factor is represented by solar exposition and, so, individuals with special risk are xeroderma pigmento sum (enzymatic defect of DNA repair), light phototype person, sun-seekers, outdoor-workers and patients treated with high doses of PUVA. X-rays, mineral oils, tar and arsenic are also known skin carcinogens. HPV can also participate to skin carcinogenis alone or associated with UV particularly in immunosupressed sujets. Subjects with predisposition for skin carcinoma can be pointed out and cautioned. Detection of preepitheliomatous lesions is easy; actinic keratosis are the main signs.

Transforming The Munitions And Missile Maintenance Officer Career Field

DTIC Science & Technology

2016-04-01

is a United States Air Force Officer currently attending Air and Space Command College at Maxwell Air Force Base , AL. Maj Edington was previously...INTRODUCTION Since the unauthorized transportation of nuclear warheads from Minot Air Force Base (MAFB) to Barksdale Air Force Base (BAFB) and the mistaken... base .66 These factors coupled with risk-aversion for anything but perfect results during inspections (i.e. zero defects), and the well-established

Congenital heart defects and extracardiac malformations.

PubMed

Rosa, Rosana Cardoso M; Rosa, Rafael Fabiano M; Zen, Paulo Ricardo G; Paskulin, Giorgio Adriano

2013-06-01

To review the association between congenital heart defects and extracardiac malformations. Scientific articles were searched in the Medline, Lilacs, and SciELO databases, using the descriptors "congenital heart disease," "congenital heart defects," "congenital cardiac malformations," "extracardiac defects," and "extracardiac malformations." All case series that specifically explored the association between congenital heart defects and extracardiac malformations were included. Congenital heart diseases are responsible for about 40% of birth defects, being one of the most common and severe malformations. Extracardiac malformations are observed in 7 to 50% of the patients with congenital heart disease, bringing a greater risk of comorbidity and mortality and increasing the risks related to heart surgery. Different studies have attempted to assess the presence of extracardiac abnormalities in patients with congenital heart disease. Among the changes described, those of the urinary tract are more often reported. However, no study has evaluated all patients in the same way. Extracardiac abnormalities are frequent among patients with congenital heart disease, and patients with these alterations may present an increased risk of morbimortality. Therefore, some authors have been discussing the importance and cost-effectiveness of screening these children for other malformations by complementary exams.

Effects of oxidative stress on hyperglycaemia-induced brain malformations in a diabetes mouse model

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

Jin, Ya; Wang, Guang; Han, Sha-Sha

Pregestational diabetes mellitus (PGDM) enhances the risk of fetal neurodevelopmental defects. However, the mechanism of hyperglycaemia-induced neurodevelopmental defects is not fully understood. In this study, several typical neurodevelopmental defects were identified in the streptozotocin-induced diabetes mouse model. The neuron-specific class III beta-tubulin/forkhead box P1-labelled neuronal differentiation was suppressed and glial fibrillary acidic protein-labelled glial cell lineage differentiation was slightly promoted in pregestational diabetes mellitus (PGDM) mice. Various concentrations of glucose did not change the U87 cell viability, but glial cell line-derived neurotrophic factor expression was altered with varying glucose concentrations. Mouse maternal hyperglycaemia significantly increased Tunel{sup +} apoptosis but didmore » not dramatically affect PCNA{sup +} cell proliferation in the process. To determine the cause of increased apoptosis, we determined the SOD activity, the expression of Nrf2 as well as its downstream anti-oxidative factors NQO1 and HO1, and found that all of them significantly increased in PGDM fetal brains compared with controls. However, Nrf2 expression in U87 cells was not significantly changed by different glucose concentrations. In mouse telencephalon, we observed the co-localization of Tuj-1 and Nrf2 expression in neurons, and down-regulating of Nrf2 in SH-SY5Y cells altered the viability of SH-SY5Y cells exposed to high glucose concentrations. Taken together, the data suggest that Nrf2-modulated antioxidant stress plays a crucial role in maternal hyperglycaemia-induced neurodevelopmental defects. - Highlights: • Typical neurodevelopmental defects could be observed in STZ-treated mouse fetuses. • Nrf2 played a crucial role in hyperglycaemia-induced brain malformations. • The effects of hyperglycaemia on neurons and glia cells were not same.« less

DNA methylation analysis of Homeobox genes implicates HOXB7 hypomethylation as risk factor for neural tube defects

PubMed Central

Rochtus, Anne; Izzi, Benedetta; Vangeel, Elise; Louwette, Sophie; Wittevrongel, Christine; Lambrechts, Diether; Moreau, Yves; Winand, Raf; Verpoorten, Carla; Jansen, Katrien; Van Geet, Chris; Freson, Kathleen

2015-01-01

Neural tube defects (NTDs) are common birth defects of complex etiology. Though family- and population-based studies have confirmed a genetic component, the responsible genes for NTDs are still largely unknown. Based on the hypothesis that folic acid prevents NTDs by stimulating methylation reactions, epigenetic factors, such as DNA methylation, are predicted to be involved in NTDs. Homeobox (HOX) genes play a role in spinal cord development and are tightly regulated in a spatiotemporal and collinear manner, partly by epigenetic modifications. We have quantified DNA methylation for the different HOX genes by subtracting values from a genome-wide methylation analysis using leukocyte DNA from 10 myelomeningocele (MMC) patients and 6 healthy controls. From the 1575 CpGs profiled for the 4 HOX clusters, 26 CpGs were differentially methylated (P-value < 0.05; β-difference > 0.05) between MMC patients and controls. Seventy-seven percent of these CpGs were located in the HOXA and HOXB clusters, with the most profound difference for 3 CpGs within the HOXB7 gene body. A validation case-control study including 83 MMC patients and 30 unrelated healthy controls confirmed a significant association between MMC and HOXB7 hypomethylation (-14.4%; 95% CI: 11.9–16.9%; P-value < 0.0001) independent of the MTHFR 667C>T genotype. Significant HOXB7 hypomethylation was also present in 12 unaffected siblings, each related to a MMC patient, suggestive of an epigenetic change induced by the mother. The inclusion of a neural tube formation model using zebrafish showed that Hoxb7a overexpression but not depletion resulted in deformed body axes with dysmorphic neural tube formation. Our results implicate HOXB7 hypomethylation as risk factor for NTDs and highlight the importance for future genome-wide DNA methylation analyses without preselecting candidate pathways. PMID:25565354

New developments in the epidemiology and genetics of gout.

PubMed

Zaka, Raihana; Williams, Charlene J

2006-06-01

The prevalence of gout appears to be rapidly increasing worldwide and is no longer a disorder suffered primarily by over-fed alcohol consumers. Emerging risk factors include longevity, metabolic syndrome, and new classes of pharmacologic agents. In some ethnic populations, no obvious risk factors can explain the high incidence of hyperuricemia and gout, suggesting a genetic liability. Studies to identify genes associated with gout have included families with defects in purine metabolism, as well as families in whom the occurrence of gout is secondary to renal disorders such as juvenile hyperuricemic nephropathy and medullary cystic kidney disease. Case-control studies of isolated aboriginal cohorts suffering from primary gout have revealed several chromosomal loci that may harbor genes that are important to the development and/or progression of gout.

Caudal dysgenesis in islet-1 transgenic mice

PubMed Central

Muller, Yunhua Li; Yueh, Yir Gloria; Yaworsky, Paul J.; Salbaum, J. Michael; Kappen, Claudia

2014-01-01

Maternal diabetes during pregnancy is responsible for the occurrence of diabetic embryopathy, a spectrum of birth defects that includes heart abnormalities, neural tube defects, and caudal dysgenesis syndromes. Here, we report that mice transgenic for the homeodomain transcription factor Isl-1 develop profound caudal growth defects that resemble human sacral/caudal agenesis. Isl-1 is normally expressed in the pancreas and is required for pancreas development and endocrine cell differentiation. Aberrant regulation of this pancreatic transcription factor causes increased mesodermal cell death, and the severity of defects is dependent on transgene dosage. Together with the finding that mutation of the pancreatic transcription factor HLXB9 causes sacral agenesis, our results implicate pancreatic transcription factors in the pathogenesis of birth defects associated with diabetes. PMID:12738808

[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.

Birth Defects

MedlinePlus

... both. Some birth defects like cleft lip or neural tube defects are structural problems that can be ... during pregnancy is a key factor in causing neural tube defects. For most birth defects, the cause ...

Genetics, gene expression and bioinformatics of the pituitary gland.

PubMed

Davis, Shannon W; Potok, Mary Anne; Brinkmeier, Michelle L; Carninci, Piero; Lyons, Robert H; MacDonald, James W; Fleming, Michelle T; Mortensen, Amanda H; Egashira, Noboru; Ghosh, Debashis; Steel, Karen P; Osamura, Robert Y; Hayashizaki, Yoshihide; Camper, Sally A

2009-04-01

Genetic cases of congenital pituitary hormone deficiency are common and many are caused by transcription factor defects. Mouse models with orthologous mutations are invaluable for uncovering the molecular mechanisms that lead to problems in organ development and typical patient characteristics. We are using mutant mice defective in the transcription factors PROP1 and POU1F1 for gene expression profiling to identify target genes for these critical transcription factors and candidates for cases of pituitary hormone deficiency of unknown aetiology. These studies reveal critical roles for Wnt signalling pathways, including the TCF/LEF transcription factors and interacting proteins of the groucho family, bone morphogenetic protein antagonists and targets of notch signalling. Current studies are investigating the roles of novel homeobox genes and pathways that regulate the transition from proliferation to differentiation, cell adhesion and cell migration. Pituitary adenomas are a common human health problem, yet most cases are sporadic, necessitating alternative approaches to traditional Mendelian genetic studies. Mouse models of adenoma formation offer the opportunity for gene expression profiling during progressive stages of hyperplasia, adenoma and tumorigenesis. This approach holds promise for the identification of relevant pathways and candidate genes as risk factors for adenoma formation, understanding mechanisms of progression, and identifying drug targets and clinically relevant biomarkers. Copyright 2009 S. Karger AG, Basel.

Genetics, Gene Expression and Bioinformatics of the Pituitary Gland

PubMed Central

Davis, Shannon W; Potok, Mary Anne; Brinkmeier, Michelle L; Carninci, Piero; Lyons, Robert H; MacDonald, James W.; Fleming, Michelle T; Mortensen, Amanda H; Egashira, Noboru; Ghosh, Debashis; Steel, Karen P.; Osamura, Robert Y; Hayashizaki, Yoshihide; Camper, Sally A

2011-01-01

Genetic cases of congenital pituitary hormone deficiency are common and many are caused by transcription factor defects. Mouse models with orthologous mutations are invaluable for uncovering the molecular mechanisms that lead to problems in organ development and typical patient characteristics. We are using mutant mice defective in the transcription factors PROP1 and POU1F1 for gene expression profiling to identify target genes for these critical transcription factors and candidates for cases of pituitary hormone deficiency of unknown etiology. These studies reveal critical roles for Wnt signalling pathways including the TCF/LEF transcription factors and interacting proteins of the groucho family, bone morphogenetic proteins antagonists, and targets of notch signalling. Current studies are investigating roles of novel homeobox genes and pathways that regulate the transition from proliferation to differentiation, cell adhesion and cell migration. Pituitary adenomas are a common human health problem, yet most cases are sporadic, necessitating alternative approaches to traditional Mendelian genetic studies. Mouse models of adenoma formation offer the opportunity for gene expression profiling during progressive stages of hyperplasia, adenoma and tumorigenesis. This approach holds promise for identification of relevant pathways and candidate genes as risk factors for adenoma formation, understanding mechanisms of progression, and identifying drug targets and clinically relevant biomarkers. PMID:19407506

Luteal phase support for in vitro fertilization-embryo transfer--present and future methods to improve successful implantation.

PubMed

Check, J H

2012-01-01

To present reasons for luteal phase deficiency when taking controlled ovarian hyperstimulation (COH) for purposes of inducing multiple oocytes for in vitro fertilization (IVF), and to suggest strategies to overcome the defect. Treatment options presented include luteal phase support with human chorionic gonadotropin (hCG) injection, progesterone, estradiol, gonadotropin releasing hormone agonists, cytokines, e.g., granulocyte colony stimulating factor, and lymphocyte immunotherapy. hCG and progesterone produce the best results and are comparable or at best a slight edge to hCG but the latter is associated with too high a risk for ovarian hyperstimulation syndrome. Vaginal progesterone is the most efficacious with the least side-effects. Better methods are needed to adequately assess full correction of the luteal phase defect. In some cases the luteal phase defect associated with COH is not correctable and FSH stimulation should be reduced or all embryos frozen and defer transfer to an artificial estrogen progesterone or natural cycle.

Developmental sub-chronic exposure to chlorpyrifos reduces anxiety-related behavior in zebrafish larvae

PubMed Central

Richendrfer, Holly; Pelkowski, Sean D.; Colwill, Ruth M.; Créton, Robbert

2013-01-01

Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders. PMID:22579535

Emergent risk factors associated with eyeball loss and ambulatory vision loss after globe injuries.

PubMed

Hyun Lee, Seung; Ahn, Jae Kyoun

2010-07-01

The objective of this study was to evaluate risk factors associated with eyeball loss and ambulatory vision loss on emergent examination of patients with ocular trauma. We reviewed the medical records of 1,875 patients hospitalized in a single tertiary referral center between January 2003 and December 2007. Emergent examinations included a history of trauma, elapsed time between injury and hospital arrival, visible intraocular tissues, and initial visual acuity (VA) using a penlight. The main outcome measures were ocular survival and ambulatory vision survival (>20/200) at 1 year after trauma using univariate and multivariate regression analysis. The ocular trauma scores were significantly higher in open globe injuries than in closed globe injuries (p < 0.01). In open globe injuries, initial VA less than light perception (LP) and a history of golf ball injury were the significant risk factors associated with eyeball loss. Elapsed time more than 12 hours and visible intraocular tissues were the significant risk factors associated with ambulatory vision loss. The most powerful predictor of eyeball loss and ambulatory vision loss was eyeball rupture. In closed globe injuries, there were no significant risk factors of eyeball loss, whereas initial vision less than LP and the presence of relative afferent pupillary defect were the significant risk factors associated with ambulatory vision loss. An initial VA less than LP using a penlight, a history of golf ball injury, and elapsed time more than 12 hours between ocular trauma and hospital arrival were associated with eyeball loss and ambulatory vision loss. Physicians should bear these factors in mind so that they can more effectively counsel patients with such injuries.

Risk factors for neural tube defects in Riyadh City, Saudi Arabia: Case-control study.

PubMed

Salih, Mustafa A M; Murshid, Waleed R; Mohamed, Ashry Gad; Ignacio, Lena C; de Jesus, Julie E; Baabbad, Rubana; El Bushra, Hassan M

2014-01-01

Both genetic and non-genetic environmental factors are involved in the etiology of neural tube defects (NTD) which affect 0.5-2/1000 pregnancies worldwide. This study aimed to explore the risk factors for the development of NTD in Saudi population, and highlight identifiable and preventable causes. Similar studies are scarce in similar populations ofthe Arabian Peninsula and North Africa. This is an unmatched concurrent case-control study including NTD cases born at King Khalid University Hospital, Riyadh during a 4-year period (2002-2006). The case-control study included 25 cases and 125 controls (case: control ratio of 1:5). Years of formal education, employment, household environment (including availability of air conditioning) and rate of parental consanguinity did not differ between mothers of cases and controls. Significantly higher proportion of mothers of cases had history of stillbirth compared to control mothers (16% vs 4.1%, P=0.02). Also family history of hydrocephalus and congenital anomalies were more prevalent in cases than controls (P values=0.0000 and 0.003, respectively). There was significant protective effect of periconceptional folic acid consumption both prior to conception (OR 0.02, 95% CI 0.00-0.07) and during the first 6 weeks of conception (OR 0.13, 95% CI 0.04-0.39). Further research, including a larger cohort, is required to enable ascertainment of gene-nutrient and gene environment interactions associated with NTD in Saudi Arabia.

Predicting adverse neonatal outcomes in fetuses with abdominal wall defects using prenatal risk factors.

PubMed

Nicholas, Sara S; Stamilio, David M; Dicke, Jeffery M; Gray, Diana L; Macones, George A; Odibo, Anthony O

2009-10-01

The aim of this study was to determine whether prenatal variables can predict adverse neonatal outcomes in fetuses with abdominal wall defects. A retrospective cohort study that used ultrasound and neonatal records for all cases of gastroschisis and omphalocele seen over a 16-year period. Cases with adverse neonatal outcomes were compared with noncases for multiple candidate predictive factors. Univariable and multivariable statistical methods were used to develop the prediction models, and effectiveness was evaluated using the area under the receiver operating characteristic curve. Of 80 fetuses with gastroschisis, 29 (36%) had the composite adverse outcome, compared with 15 of 33 (47%) live neonates with omphalocele. Intrauterine growth restriction was the only significant variable in gastroschisis, whereas exteriorized liver was the only predictor in omphalocele. The areas under the curve for the prediction models with gastroschisis and omphalocele are 0.67 and 0.74, respectively. Intrauterine growth restriction and exteriorization of the liver are significant predictors of adverse neonatal outcome with gastroschisis and omphalocele.

Otoacoustic Emissions in Rural Nicaragua: Cost Analysis and Implications for Newborn Hearing Screening.

PubMed

Wong, Lye-Yeng; Espinoza, Francisca; Alvarez, Karen Mojica; Molter, Dave; Saunders, James E

2017-05-01

Objective (1) Determine the incidence and risk factors for congenital hearing loss. (2) Perform cost analysis of screening programs. Study Design Proportionally distributed cross-sectional survey. Setting Jinotega, Nicaragua. Subjects and Methods Otoacoustic emissions (OAEs) were used to screen 640 infants <6 months of age from neonatal intensive care unit, institutional, and home birth settings. Data on 15 risk factors were analyzed. Cost of 4 implementation strategies was studied: universal screening, screening at the regional health center (RHC), targeted screening, and screening at the RHC plus targeted screening. Cost-effectiveness analysis over 10 years was based on disability-adjusted life year estimates, with the World Health Organization standard of cost-effectiveness ratio (CER) / gross domestic product (GDP) <3, with GDP set at $4884.15. Results Thirty-eight infants failed the initial OAE (5.94%). In terms of births, 325 (50.8%) were in the RHC, 69 (10.8%) in the neonatal intensive care unit, and 29 (4.5%) at home. Family history and birth defect were significant in univariate analysis; birth defect was significant in multivariate analysis. Cost-effectiveness analysis demonstrated that OAE screening is cost-effective without treatment (CER/GDP = 0.06-2.00) and with treatment (CER/GDP = 0.58-2.52). Conclusions Our rate of OAE failures was comparable to those of developed countries and lower than hearing loss rates noted among Nicaraguan schoolchildren, suggesting acquired or progressive etiology in the latter. Birth defects and familial hearing loss correlated with OAE failure. OAE screening of infants is feasible and cost-effective in rural Nicaragua, although highly influenced by estimated hearing loss severity in identified infants and the high travel costs incurred in a targeted screening strategy.

Complement C4 deficiency--a plausible risk factor for non-tuberculous mycobacteria (NTM) infection in apparently immunocompetent patients.

PubMed

Kotilainen, Hannele; Lokki, Marja-Liisa; Paakkanen, Riitta; Seppänen, Mikko; Tukiainen, Pentti; Meri, Seppo; Poussa, Tuija; Eskola, Jussi; Valtonen, Ville; Järvinen, Asko

2014-01-01

Non-tuberculous mycobacteria (NTM) are ubiquitous in the environment and they infect mainly persons with underlying pulmonary diseases but also previously healthy elderly women. Defects in host resistance that lead to pulmonary infections by NTM are relatively unknown. A few genetic defects have been associated with both pulmonary and disseminated mycobacterial infections. Rare disseminated NTM infections have been associated with genetic defects in T-cell mediated immunity and in cytokine signaling in families. We investigated whether there was an association between NTM infections and deficiencies of complement components C4A or C4B that are encoded by major histocompatibility complex (MHC). 50 adult patients with a positive NTM culture with symptoms and findings of a NTM disease were recruited. Patients' clinical history was collected and symptoms and clinical findings were categorized according to 2007 diagnostic criteria of The American Thoracic Society (ATS). To investigate the deficiencies of complement, C4A and C4B gene copy numbers and phenotype frequencies of the C4 allotypes were analyzed. Unselected, healthy, 149 Finnish adults were used as controls. NTM patients had more often C4 deficiencies (C4A or C4B) than controls (36/50 [72%] vs 83/149 [56%], OR = 2.05, 95%CI = 1.019-4.105, p = 0.042). C4 deficiencies for female NTM patients were more common than for controls (29/36 [81%] vs 55/100 [55%], OR = 3.39, 95% CI = 1.358-8.460, p = 0.007). C4 deficiences seemed not to be related to any specific underlying disease or C4 phenotype. C4 deficiency may be a risk factor for NTM infection in especially elderly female patients.

Enhancements and Extensions of Formal Models for Risk Assessment in Software Projects

DTIC Science & Technology

2002-09-01

the five defect categories. Cosmetic Defects. The name that corresponds to QSM®’s cosmetic defects. Cosmetic defects can be described as deferred...California. June 2002. (Fent00) Fenton , N. E. and Neil, M., Software Metrics: Roadmap. Proceedings of the Conference on the Future of Software

Maternal choline concentrations during pregnancy and choline-related genetic variants as risk factors for neural tube defects.

PubMed

Mills, James L; Fan, Ruzong; Brody, Lawrence C; Liu, Aiyi; Ueland, Per M; Wang, Yifan; Kirke, Peadar N; Shane, Barry; Molloy, Anne M

2014-10-01

Low maternal choline intake and blood concentration may be risk factors for having a child with a neural tube defect (NTD); however, the data are inconsistent. This is an important question to resolve because choline, if taken periconceptionally, might add to the protective effect currently being achieved by folic acid. We examined the relation between NTDs, choline status, and genetic polymorphisms reported to influence de novo choline synthesis to investigate claims that taking choline periconceptionally could reduce NTD rates. Two study groups of pregnant women were investigated: women who had a current NTD-affected pregnancy (AP; n = 71) and unaffected controls (n = 214) and women who had an NTD in another pregnancy but not in the current pregnancy [nonaffected pregnancy (NAP); n = 98] and unaffected controls (n = 386). Blood samples to measure betaine and total choline concentrations and single nucleotide polymorphisms related to choline metabolism were collected at their first prenatal visit. Mean (±SD) plasma total choline concentrations in the AP (2.8 ± 1.0 mmol/L) and control (2.9 ± 0.9 mmol/L) groups did not differ significantly. Betaine concentrations were not significantly different between the 2 groups. Total choline and betaine in the NAP group did not differ from controls. Cases were significantly more likely to have the G allele of phosphatidylethanolamine-N-methyltransferase (PEMT; V175M, +5465 G>A) rs7946 (P = 0.02). Our results indicate that maternal betaine and choline concentrations are not strongly associated with NTD risk. The association between PEMT rs7946 and NTDs requires confirmation. The addition of choline to folic acid supplements may not further reduce NTD risk. © 2014 American Society for Nutrition.

Maternal choline concentrations during pregnancy and choline-related genetic variants as risk factors for neural tube defects123

PubMed Central

Mills, James L; Fan, Ruzong; Brody, Lawrence C; Liu, Aiyi; Ueland, Per M; Wang, Yifan; Kirke, Peadar N; Shane, Barry; Molloy, Anne M

2014-01-01

Background: Low maternal choline intake and blood concentration may be risk factors for having a child with a neural tube defect (NTD); however, the data are inconsistent. This is an important question to resolve because choline, if taken periconceptionally, might add to the protective effect currently being achieved by folic acid. Objective: We examined the relation between NTDs, choline status, and genetic polymorphisms reported to influence de novo choline synthesis to investigate claims that taking choline periconceptionally could reduce NTD rates. Design: Two study groups of pregnant women were investigated: women who had a current NTD-affected pregnancy (AP; n = 71) and unaffected controls (n = 214) and women who had an NTD in another pregnancy but not in the current pregnancy [nonaffected pregnancy (NAP); n = 98] and unaffected controls (n = 386). Blood samples to measure betaine and total choline concentrations and single nucleotide polymorphisms related to choline metabolism were collected at their first prenatal visit. Results: Mean (±SD) plasma total choline concentrations in the AP (2.8 ± 1.0 mmol/L) and control (2.9 ± 0.9 mmol/L) groups did not differ significantly. Betaine concentrations were not significantly different between the 2 groups. Total choline and betaine in the NAP group did not differ from controls. Cases were significantly more likely to have the G allele of phosphatidylethanolamine-N-methyltransferase (PEMT; V175M, +5465 G>A) rs7946 (P = 0.02). Conclusions: Our results indicate that maternal betaine and choline concentrations are not strongly associated with NTD risk. The association between PEMT rs7946 and NTDs requires confirmation. The addition of choline to folic acid supplements may not further reduce NTD risk. PMID:25240073

Antidepressant use during pregnancy and the risk of major congenital malformations in a cohort of depressed pregnant women: an updated analysis of the Quebec Pregnancy Cohort

PubMed Central

Bérard, Anick; Zhao, Jin-Ping; Sheehy, Odile

2017-01-01

Objective Antidepressant use during gestation has been associated with risk of major congenital malformations but estimates can lack statistical power or be confounded by maternal depression. We aimed to determine the association between first-trimester exposure to antidepressants and the risk of major congenital malformations in a cohort of depressed/anxious women. Setting and participants Data were obtained from the Quebec Pregnancy Cohort (QPC). All pregnancies with a diagnosis of depression or anxiety, or exposed to antidepressants in the 12 months before pregnancy, and ending with a live-born singleton were included. Outcome measures Antidepressant classes (selective serotonin reuptake inhibitors (SSRI), serotonin–norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA) and other antidepressants) and types were individually compared with non-exposure during the first trimester (depressed untreated). Major congenital malformations overall and organ-specific malformations in the first year of life were identified. Results 18 487 pregnant women were included. When looking at the specific types of antidepressant used during the first trimester, only citalopram was increasing the risk of major congenital malformations (adjusted OR, (aOR) 1.36, 95% CI 1.08 to 1.73; 88 exposed cases), although there was a trend towards increased risk for the most frequently used antidepressants. Antidepressants with serotonin reuptake inhibition effect (SSRI, SNRI, amitriptyline (the most used TCA)) increased the risk of certain organ-specific defects: paroxetine increased the risk of cardiac defects (aOR 1.45, 95% CI 1.12 to 1.88), and ventricular/atrial septal defects (aOR 1.39, 95% CI 1.00 to 1.93); citalopram increased the risk of musculoskeletal defects (aOR 1.92, 95% CI 1.40 to 2.62), and craniosynostosis (aOR 3.95, 95% CI 2.08 to 7.52); TCA was associated with eye, ear, face and neck defects (aOR 2.45, 95% CI 1.05 to 5.72), and digestive defects (aOR 2.55, 95% CI 1.40 to 4.66); and venlafaxine was associated with respiratory defects (aOR 2.17, 95% CI 1.07 to 4.38). Conclusions Antidepressants with effects on serotonin reuptake during embryogenesis increased the risk of some organ-specific malformations in a cohort of pregnant women with depression. PMID:28082367

Association of birth defects with the mode of assisted reproductive technology in a Chinese data-linkage cohort.

PubMed

Yu, Hui-Ting; Yang, Qing; Sun, Xiao-Xi; Chen, Guo-Wu; Qian, Nai-Si; Cai, Ren-Zhi; Guo, Han-Bing; Wang, Chun-Fang

2018-05-01

To evaluate the impact of assisted reproductive technology (ART) on the offspring of Chinese population. Retrospective, data-linkage cohort. Not applicable. Live births resulting from ART or natural conception. None. Birth defects coded according to ICD-10. Births after ART were more likely to be female and multiple births, especially after intracytoplasmic sperm injection (ICSI). ART was associated with a significantly increased risk of birth defects, especially, among singleton births, a significantly increased risk in fresh-embryo cycles after in vitro fertilization (IVF) and frozen-embryo cycles after ICSI. Associations between ART and multiple defects, between ART and gastrointestinal malformation, genital organs malformation, and musculoskeletal malformation among singleton births, and between ART and cardiac septa malformation among multiple births were observed. This study suggests that ART increases the risk of birth defects. Subgroup analyses indicate higher risk for both fresh and frozen embryos, although nonsignificantly for frozen embryos after IVF and for fresh embryos were presented with low power. Larger sample size research is needed to clarify effects from fresh- or frozen-embryo cycles after IVF and ICSI. Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Recent advances in recurrent urinary tract infection from pathogenesis and biomarkers to prevention.

PubMed

Jhang, Jia-Fong; Kuo, Hann-Chorng

2017-01-01

Recurrent urinary tract infection (UTI) might be one of the most common problems in urological clinics. Recent research has revealed novel evidence about recurrent UTI and it should be considered a different disease from the first infection. The pathogenesis of recurrent UTI might include two mechanisms, bacterial factors and deficiencies in host defense. Bacterial survival in the urinary bladder after antibiotic treatment and progression to form intracellular bacterial communities might be the most important bacterial factors. In host defense deficiency, a defect in pathogen recognition and urothelial barrier function impairment play the most important roles. Immunodeficiency and urogenital tract anatomical abnormalities have been considered the essential risk factors for recurrent UTI. In healthy women, voiding dysfunction and behavioral factors also increase the risk of recurrent UTI. Sexual intercourse and estrogen deficiency in postmenopausal women might have the strongest association with recurrent UTI. Traditional lifestyle factors such as fluid intake and diet are not considered independent risk factors now. Serum and urine biomarkers to predict recurrent UTI from the first infection have also attracted a wide attention recently. Current clinical evidence suggests that serum macrophage colony-stimulating factor and urinary nerve growth factor have potential predictive value for recurrent UTI. Clinical trials have proven the efficacy of the oral immunoactive agent OM-89 for the prevention of UTI. Vaccines for recurrent UTI are recommended by the latest guidelines and are available on the market.

Degenerative Changes in the Knee 2 Years After Anterior Cruciate Ligament Rupture and Related Risk Factors: A Prospective Observational Follow-up Study.

PubMed

van Meer, Belle L; Oei, Edwin H G; Meuffels, Duncan E; van Arkel, Ewoud R A; Verhaar, Jan A N; Bierma-Zeinstra, Sita M A; Reijman, Max

2016-06-01

Anterior cruciate ligament (ACL) rupture is a well-known risk factor for development of knee osteoarthritis. Early identification of those patients at risk and early identification of the process of ACL rupture leading to osteoarthritis may aid in preventing the onset or progression of osteoarthritis. To identify early degenerative changes as assessed on magnetic resonance imaging (MRI) after 2-year follow-up in patients with a recent ACL rupture and to evaluate which determinants are related to these changes. Cohort study; Level of evidence, 2. Included in this study were 154 adults aged between 18 and 45 years with acute ACL rupture diagnosed by physical examination and MRI, without previous knee trauma or surgery, and without osteoarthritic changes on radiographs. A total of 143 patients completed the 2-year follow-up, and the results in this study apply to these 143 patients. All patients were treated according to the Dutch guideline on ACL injury. Of the 143 patients, 50 patients were treated nonoperatively during the 2-year follow-up period. Main outcome was early degenerative changes assessed on MRI defined as progression of cartilage defects and osteophytes in tibiofemoral and patellofemoral compartments. Patient characteristics, activity level, functional instability, treatment type, and trauma-related variables were evaluated as determinants. The median time between MRI at baseline and MRI at 2-year follow-up was 25.9 months (interquartile range, 24.7-26.9 months). Progression of cartilage defects in the medial and lateral tibiofemoral compartments was present in 12% and 27% of patients, and progression of osteophytes in tibiofemoral and patellofemoral compartments was present in 10% and 8% of patients, respectively. The following determinants were positively significantly associated with early degenerative changes: male sex (odds ratio [OR], 4.43; 95% CI, 1.43-13.66; P = .010), cartilage defect in the medial tibiofemoral compartment at baseline (OR, 3.66; 95% CI, 1.04-12.95; P = .044), presence of bone marrow lesions in the medial tibiofemoral compartment 1 year after trauma (OR, 5.19; 95% CI, 1.56-17.25; P = .007), joint effusion 1 year after trauma (OR, 4.19; 95% CI, 1.05-16.72; P = .042), and presence of meniscal tears (OR, 6.37; 95% CI, 1.94-20.88; P = .002). When the patients were categorized into 3 treatment groups (nonoperative, reconstruction <6 months after ACL rupture, and reconstruction ≥6 months after ACL rupture), there was no significant relationship between the treatment options and the development of early degenerative changes. Two years after ACL rupture, early degenerative changes were assessed on MRI. Concomitant medial cartilage defect and meniscal injury, male sex, persistent bone marrow lesions in the medial tibiofemoral compartment, and joint effusion are risk factors for degenerative changes. © 2016 The Author(s).

Human Factors Implications and Issues in Network Enabled Operations

DTIC Science & Technology

2006-08-28

même par des soldats individuels. L’armée de mer, quant à elle, évolue dans un environnement de complexité moyenne comparativement aux forces...approach found in most of the derivatives of NCW because the FORCEnet paper states that in the design of this new approach to warfare and other...defects mentality, risk aversion, poorly designed war fighting experiments, and widespread contentment with current performance, expectations for NCW will

Thoracic aortic dissection and rupture in conotruncal cardiac defects: A population-based study.

PubMed

Frischhertz, Benjamin P; Shamszad, Pirouz; Pedroza, Claudia; Milewicz, Dianna M; Morris, Shaine A

2015-04-01

Although the risk of thoracic aortic dissection and rupture (TAD) is well-known in bicuspid aortic valve (BAV), the risk of TAD in other congenital heart diseases (CHD), particularly conotruncal lesions like tetralogy of Fallot (TOF), truncus arteriosus, D-transposition of the great arteries (D-TGA), and double outlet right ventricle is currently unknown. The primary purpose of this study was to describe TAD in conotruncal CHD, and the secondary purpose was to explore whether an association exists between TAD and conotruncal CHD. Using the Texas Inpatient Public Use Data File, an administrative database of all Texas hospitalizations, including >37.9 million hospitalizations from January 1999 through June 2012, 12,016 cases of TAD and 214 cases of TAD in CHD were identified. The most common lesions were BAV (42%), atrial septal defect (21%), aortic coarctation (7%), ventricular septal defect (6%), and patent ductus arteriosus (4%). Three patients with TOF, 2 with D-TGA, and 1 with truncus arteriosus were admitted with TAD. An exploratory case-control study in patients older than 1 year using multilevel logistic regression models to evaluate the association between CHD and TAD that controlled for known TAD risk factors demonstrated a significant association between TAD and BAV (OR 10, 95% CI 8.2-13) but not coarctation of the aorta or any conotruncal lesion. TAD in conotruncal CHD is exquisitely rare. In our hospitalized population, there was no increased occurrence of TAD in conotruncal CHD above what would be expected in the rest of the hospitalized population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Update on Early Childhood Caries since the Surgeon General's Report

PubMed Central

Tinanoff, Norman; Reisine, Susan

2009-01-01

The 2000 Surgeon General's Report on Oral Health (SGROH) included a limited discussion of the condition known as Early Childhood Caries (ECC). Because of its high prevalence, its impact on young children's quality of life and potential for increasing their risk of caries in the permanent dentition, ECC is arguably one of the most serious and costly health conditions among young children. A necessary first step in preventing dental caries in preschool children is understanding and evaluating the child's caries risk factors. Previous caries experience and white spot lesions should automatically classify a preschool child as high risk for caries. Microbial factors, such as presence of visible plaque and tests that identify a child as having high levels of mutans streptococci also predict caries in young children. Frequency of sugar consumption, enamel developmental defects, social factors such as socioeconomic status, psychosocial factors, and being an ethnic minority also have shown to be relevant in determining caries risk. Based on this knowledge of specific risk factors for an individual, different preventive strategies as well as different intensities of preventive therapies can be employed. Caries preventive strategies in preschool children include fluoride therapy, such as supervised tooth brushing with fluoridated dentifrice, systemic fluoride supplement to children living in a non-fluoridated area that are at risk for caries, and professional topical fluoride with fluoride varnish. There is emerging evidence that intensive patient counseling or motivational interviews with parents to change specific behaviors may reduce caries prevalence in their children. Findings regarding antimicrobial interventions, efforts to modify diets, and traditional dental health education are less consistent. PMID:19945074

Risk factors associated with deforming oral habits in children aged 5 to 11: a case-control study.

PubMed

Reyes Romagosa, Daniel Enrique; Paneque Gamboa, María Rosa; Almeida Muñiz, Yamilka; Quesada Oliva, Leticia María; Escalona Oliva, Damiana; Torres Naranjo, Sonia

2014-03-31

Dental and maxillofacial anomalies have multiple and complex causes. Most frequent among these are poor oral habits. A large number of children present with oral malocclusions, most of which are caused by deforming oral habits. It is important to learn about risk factors for this condition in order to institute preventive measures, early detection and treatment, and identification of low- and high-risk groups. To identify risk factors associated with deforming oral habits, which, if maintained over time, are responsible for occlusion defects, speech disorders, and can affect physical and emotional child development. A case-control study of children presenting with deforming oral habits in the municipality of Manzanillo in Granma province was conducted between January and August 2013. 540 children aged 5 to 11 were included of which 180 had deforming oral habits and were asked to fill out a survey to identify specific type of habits leading to malocclusion. The case group was composed of children with deforming habits, and the remaining 360 children without poor oral habits were the control group. Each case was randomly matched to two control cases. The children mothers were also surveyed to gather supplemental information. Children with deforming oral habits were mostly female. At age 10, onychophagia was the predominant oral deforming habit. Risk factors detected for these habits were sociobiological maternal and child variables such as low and high birth weight, maternal breastfeeding inexperience, and discord in the family. The study identified likely risk factors associated with deforming oral habits. These are discord in the family, birth weight, and lack of breastfeeding experience.

Current outcomes and risk factors for the Norwood procedure.

PubMed

Stasik, Chad N; Gelehrter, S; Goldberg, Caren S; Bove, Edward L; Devaney, Eric J; Ohye, Richard G

2006-02-01

Tremendous strides have been made in the outcomes for hypoplastic left heart syndrome and other functional single-ventricle malformations over the past 25 years. This progress relates primarily to improvements in survival for patients undergoing the Norwood procedure. Previous reports on risk factors have been on smaller groups of patients or collected over relatively long periods of time, during which management has evolved. We analyzed our current results for the Norwood procedure with attention to risk factors for poor outcome. A single-institution review of all patients undergoing a Norwood procedure for a single-ventricle malformation from May 1, 2001, through April 30, 2003, was performed. Patient demographics, anatomy, clinical condition, associated anomalies, operative details, and outcomes were recorded. Of the 111 patients, there were 23 (21%) hospital deaths. Univariate analysis revealed noncardiac abnormalities (genetic or significant extracardiac diagnosis, P = .0018), gestational age (P = .03), diagnosis of unbalanced atrioventricular septal defect (P = .017), and weight of less than 2.5 kg (P = .0072) to be related to hospital death. On multivariate analysis, only weight of less than 2.5 kg and noncardiac abnormalities were found to be independent risk factors. Patients with either of these characteristics had a hospital survival of 52% (12/23), whereas those at standard risk had a survival of 86% (76/88). Although improvements in management might have lessened the effect of some of the traditionally reported risk factors related to variations in the cardiovascular anatomy, noncardiac abnormalities and low birth weight remain as a future challenge for the physician caring for the patient with single-ventricle physiology.

Cerebrovascular defects in Foxc1 mutants correlate with aberrant WNT and VEGF-A pathways downstream of retinoic acid from the meninges

PubMed Central

Mishra, Swati; Choe, Youngshik; Pleasure, Samuel J.; Siegenthaler, Julie A.

2016-01-01

Growth and maturation of the cerebrovasculature is a vital event in neocortical development however mechanisms that control cerebrovascular development remain poorly understood. Mutations in or deletions that include the FOXC1 gene are associated with congenital cerebrovascular anomalies and increased stroke risk in patients. Foxc1 mutant mice display severe cerebrovascular hemorrhage at late gestational ages. While these data demonstrate Foxc1 is required for cerebrovascular development, its broad expression in the brain vasculature combined with Foxc1 mutant’s complex developmental defects have made it difficult to pinpoint its function(s). Using global and conditional Foxc1 mutants, we find 1) significant cerebrovascular growth defects precede cerebral hemorrhage and 2) expression of Foxc1 in neural crest-derived meninges and brain pericytes, though not endothelial cells, is required for normal cerebrovascular development. We provide evidence that reduced levels of meninges-derived retinoic acid (RA), caused by defects in meninges formation in Foxc1 mutants, is a major contributing factor to the cerebrovascular growth defects in Foxc1 mutants. We provide data that suggests that meninges-derived RA ensures adequate growth of the neocortical vasculature via regulating expression of WNT pathway proteins and neural progenitor derived-VEGF-A. Our findings offer the first evidence for a role of the meninges in brain vascular development and provide new insight into potential causes of cerebrovascular defects in patients with FOXC1 mutations. PMID:27671872

Cerebrovascular defects in Foxc1 mutants correlate with aberrant WNT and VEGF-A pathways downstream of retinoic acid from the meninges.

PubMed

Mishra, Swati; Choe, Youngshik; Pleasure, Samuel J; Siegenthaler, Julie A

2016-12-01

Growth and maturation of the cerebrovasculature is a vital event in neocortical development however mechanisms that control cerebrovascular development remain poorly understood. Mutations in or deletions that include the FOXC1 gene are associated with congenital cerebrovascular anomalies and increased stroke risk in patients. Foxc1 mutant mice display severe cerebrovascular hemorrhage at late gestational ages. While these data demonstrate Foxc1 is required for cerebrovascular development, its broad expression in the brain vasculature combined with Foxc1 mutant's complex developmental defects have made it difficult to pinpoint its function(s). Using global and conditional Foxc1 mutants, we find 1) significant cerebrovascular growth defects precede cerebral hemorrhage and 2) expression of Foxc1 in neural crest-derived meninges and brain pericytes, though not endothelial cells, is required for normal cerebrovascular development. We provide evidence that reduced levels of meninges-derived retinoic acid (RA), caused by defects in meninges formation in Foxc1 mutants, is a major contributing factor to the cerebrovascular growth defects in Foxc1 mutants. We provide data that suggests that meninges-derived RA ensures adequate growth of the neocortical vasculature via regulating expression of WNT pathway proteins and neural progenitor derived-VEGF-A. Our findings offer the first evidence for a role of the meninges in brain vascular development and provide new insight into potential causes of cerebrovascular defects in patients with FOXC1 mutations. Copyright © 2016 Elsevier Inc. All rights reserved.

Modelling survival and mortality risk to 15 years of age for a national cohort of children with serious congenital heart defects diagnosed in infancy.

PubMed

Knowles, Rachel L; Bull, Catherine; Wren, Christopher; Wade, Angela; Goldstein, Harvey; Dezateux, Carol

2014-01-01

Congenital heart defects (CHDs) are a significant cause of death in infancy. Although contemporary management ensures that 80% of affected children reach adulthood, post-infant mortality and factors associated with death during childhood are not well-characterised. Using data from a UK-wide multicentre birth cohort of children with serious CHDs, we observed survival and investigated independent predictors of mortality up to age 15 years. Data were extracted retrospectively from hospital records and death certificates of 3,897 children (57% boys) in a prospectively identified cohort, born 1992-1995 with CHDs requiring intervention or resulting in death before age one year. A discrete-time survival model accounted for time-varying predictors; hazards ratios were estimated for mortality. Incomplete data were addressed through multilevel multiple imputation. By age 15 years, 932 children had died; 144 died without any procedure. Survival to one year was 79.8% (95% confidence intervals [CI] 78.5, 81.1%) and to 15 years was 71.7% (63.9, 73.4%), with variation by cardiac diagnosis. Importantly, 20% of cohort deaths occurred after age one year. Models using imputed data (including all children from birth) demonstrated higher mortality risk as independently associated with cardiac diagnosis, female sex, preterm birth, having additional cardiac defects or non-cardiac malformations. In models excluding children who had no procedure, additional predictors of higher mortality were younger age at first procedure, lower weight or height, longer cardiopulmonary bypass or circulatory arrest duration, and peri-procedural complications; non-cardiac malformations were no longer significant. We confirm the high mortality risk associated with CHDs in the first year of life and demonstrate an important persisting risk of death throughout childhood. Late mortality may be underestimated by procedure-based audit focusing on shorter-term surgical outcomes. National monitoring systems should emphasise the importance of routinely capturing longer-term survival and exploring the mechanisms of mortality risk in children with serious CHDs.

Does maternal exposure to benzene and PM10 during pregnancy increase the risk of congenital anomalies? A population-based case-control study

PubMed Central

Vinceti, Marco; Malagoli, Carlotta; Malavolti, Marcella; Cherubini, Andrea; Maffeis, Giuseppe; Rodolfi, Rossella; Heck, Julia E.; Astolfi, Gianni; Calzolari, Elisa; Nicolini, Fausto

2015-01-01

A few studies have suggested an association between maternal exposure to ambient air pollution from vehicular traffic and risk of congenital anomalies in the offspring, but epidemiologic evidence is neither strong nor entirely consistent. In a population-based case-control study in a Northern Italy community encompassing 228 cases of birth defects and 228 referent newborns, we investigated if maternal exposure to PM10 and benzene from vehicular traffic during early pregnancy, as estimated through a dispersion model, was associated with excess teratogenic risk. In conditional logistic regression analysis, and with adjustment for the other pollutant, we found that higher exposure to PM10 but not benzene was associated with increased risk of birth defects overall. Anomaly categories showing the strongest dose-response relation with PM10 exposure were musculoskeletal and chromosomal abnormalities but not cardiovascular defects, with Down syndrome being among the specific abnormalities showing the strongest association, though risk estimates particularly for the less frequent defects were statistically very unstable. Further adjustment in the regression model for potential confounders did not considerably alter the results. All the associations were stronger for average levels of PM10 than for their maximal level. Findings of this study give some support for an excess teratogenic risk following maternal exposure during pregnancy to PM10, but not benzene. Such association appears to be limited to some birth defect categories. PMID:26410719

Total Anomalous Pulmonary Venous Connection (TAPVC)

MedlinePlus

... Your Risk • Symptoms & Diagnosis • Care & Treatment • Tools & Resources Web Booklets on Congenital Heart Defects These online publications ... to you or your child’s defect and concerns. Web Booklet: Adults With Congenital Heart Defects Web Booklet: ...

Nephrolithiasis in renal tubular acidosis.

PubMed

Buckalew, V M

1989-03-01

Renal tubular acidosis is a term applied to several conditions in which metabolic acidosis is caused by specific defects in renal tubular hydrogen ion secretion. Three types of renal tubular acidosis generally are recognized based on the nature of the tubular defect. Nephrolithiasis occurs only in type I renal tubular acidosis, a condition marked by an abnormality in the generation and maintenance of a hydrogen ion gradient by the distal tubule. A forme fruste of type I renal tubular acidosis has been described in which the characteristic defect in distal hydrogen ion secretion occurs in the absence of metabolic acidosis (incomplete renal tubular acidosis). Type I renal tubular acidosis is a heterogeneous disorder that may be hereditary, idiopathic or secondary to a variety of conditions. Secondary type I renal tubular acidosis in sporadic cases is associated most commonly with autoimmune diseases, such as Sjögren's syndrome and systemic lupus erythematosus, and it occurs more frequently in women than men. Nephrolithiasis, which may occur in any of the subsets of type I renal tubular acidosis, accounts for most of the morbidity in adults and adolescents. Major risk factors for nephrolithiasis include alkaline urine, hypercalciuria and hypocitraturia. In addition, we found hyperuricosuria in 21 per cent of the patients with type I renal tubular acidosis with nephrolithiasis. The most frequently occurring risk factor, hypocitraturia, is due to decreased filtered load and/or to increased tubular reabsorption of filtered citrate. While increased tubular reabsorption may be due to systemic acidosis, hypocitraturia occurs in incomplete renal tubular acidosis. Furthermore, alkali therapy (either bicarbonate or citrate salts) increases citrate excretion in complete and incomplete type I renal tubular acidosis. These data suggest that hypocitraturia in type I renal tubular acidosis may be due to a defect in proximal tubule function. Hypercalciuria appears to have 2 causes. It may be due to metabolic acidosis, usually in children with a hereditary defect in urine acidification. In other cases familial idiopathic hypercalciuria causes nephrocalcinosis and nephrolithiasis resulting in distal tubular damage and type I renal tubular acidosis. In these latter cases hypercalciuria is present in complete and incomplete type I renal tubular acidosis. Potassium citrate appears to reduce calcium excretion in both types of hypercalciuric type I renal tubular acidosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Heterogeneous Contribution of Insulin Sensitivity and Secretion Defects to Gestational Diabetes Mellitus

PubMed Central

Powe, Camille E.; Allard, Catherine; Battista, Marie-Claude; Doyon, Myriam; Bouchard, Luigi; Ecker, Jeffrey L.; Perron, Patrice; Florez, Jose C.; Thadhani, Ravi

2016-01-01

OBJECTIVE To characterize physiologic subtypes of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS Insulin sensitivity and secretion were estimated in 809 women at 24–30 weeks' gestation, using oral glucose tolerance test–based indices. In women with GDM (8.3%), defects in insulin sensitivity or secretion were defined below the 25th percentile in women with normal glucose tolerance (NGT). GDM subtypes were defined based on the defect(s) present. RESULTS Relative to women with NGT, women with predominant insulin sensitivity defects (51% of GDM) had higher BMI and fasting glucose, larger infants (birth weight z score 0.57 [−0.01 to 1.37] vs. 0.03 [−0.53 to 0.52], P = 0.001), and greater risk of GDM-associated adverse outcomes (57.6 vs. 28.2%, P = 0.003); differences were independent of BMI. Women with predominant insulin secretion defects (30% of GDM) had BMI, fasting glucose, infant birth weights, and risk of adverse outcomes similar to those in women with NGT. CONCLUSIONS Heterogeneity of physiologic processes underlying hyperglycemia exists among women with GDM. GDM with impaired insulin sensitivity confers a greater risk of adverse outcomes. PMID:27208340

21 CFR 101.79 - Health claims: Folate and neural tube defects.

Code of Federal Regulations, 2013 CFR

2013-04-01

... result in infant mortality or serious disability. The birth defects anencephaly and spina bifida are the... development. Because the neural tube forms and closes during early pregnancy, the defect may occur before a... pregnancy had a reduced risk of having a child with a neural tube defect. (Products containing this level of...

21 CFR 101.79 - Health claims: Folate and neural tube defects.

Code of Federal Regulations, 2014 CFR

2014-04-01

... result in infant mortality or serious disability. The birth defects anencephaly and spina bifida are the... development. Because the neural tube forms and closes during early pregnancy, the defect may occur before a... pregnancy had a reduced risk of having a child with a neural tube defect. (Products containing this level of...

21 CFR 101.79 - Health claims: Folate and neural tube defects.

Code of Federal Regulations, 2012 CFR

2012-04-01

... result in infant mortality or serious disability. The birth defects anencephaly and spina bifida are the... development. Because the neural tube forms and closes during early pregnancy, the defect may occur before a... pregnancy had a reduced risk of having a child with a neural tube defect. (Products containing this level of...

Identifying diversion of inferior vena cava after repair of atrial septal defect.

PubMed

Lee, Yi Wei; Lee, Wei Chieh; Chua, Sarah

2015-10-01

Inadvertent IVC diversion into left atrium is a rare morbidity following ASD repair. Reported risk factors included a large secundum, or low-lying ASD, or inferior sinus venosus defect, and anomalous pulmonary connection into the RA. In our case, transesophageal echocardiogram showed abnormal connection of IVC to LA, but could not be identified owing to limited window. Cardiac CT could offer better anatomic clarification. On contrast transesophageal echocardiogram with agitated saline injected via right femoral vein, an abnormal right-to-left shunt was demonstrated by transit of microbubbles from IVC into LA, while majority of rest entered into the RA. Therefore, we confirm the IVC diversion into LA. Detection of such unusual condition is a challenge due to the fact that special echocardiographic windows are often needed.

BIRTH DEFECTS RISK ASSOCIATED WITH MATERNAL SPORT FISH CONSUMPTION: POTENTIAL EFFECT MODIFICATION BY SEX OF OFFSPRING

EPA Science Inventory

Contaminated sport fish consumption may result in exposure to various reproductive and developmental toxicants, including pesticides and other suspected endocrine disruptors. We investigated the relation between maternal sport fish meals and risk of major birth defects among infa...

Rail flaw sizing using conventional and phased array ultrasonic testing.

DOT National Transportation Integrated Search

2012-12-01

An approach to detecting and characterizing internal defects in rail through the use of phased array ultrasonic testing has shown the potential to reduce the risk of missed defects and improve transverse defect characterization. : Transportation Tech...

Correlation between morphological defects, electron beam-induced current imaging, and the electrical properties of 4H-SiC Schottky diodes

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

Wang, Y.; Ali, G.N.; Mikhov, M.K.

2005-01-01

Defects in SiC degrade the electrical properties and yield of devices made from this material. This article examines morphological defects in 4H-SiC and defects visible in electron beam-induced current (EBIC) images and their effects on the electrical characteristics of Schottky diodes. Optical Nomarski microscopy and atomic force microscopy were used to observe the morphological defects, which are classified into 26 types based on appearance alone. Forward and reverse current-voltage characteristics were used to extract barrier heights, ideality factors, and breakdown voltages. Barrier heights decrease about linearly with increasing ideality factor, which is explained by discrete patches of low barrier heightmore » within the main contact. Barrier height, ideality, and breakdown voltage all degrade with increasing device diameter, suggesting that discrete defects are responsible. Electroluminescence was observed under reverse bias from microplasmas associated with defects containing micropipes. EBIC measurements reveal several types of features corresponding to recombination centers. The density of dark spots observed by EBIC correlates strongly with ideality factor and barrier height. Most morphological defects do not affect the reverse characteristics when no micropipes are present, but lower the barrier height and worsen the ideality factor. However, certain multiple-tailed defects, irregularly shaped defects and triangular defects with 3C inclusions substantially degrade both breakdown voltage and barrier height, and account for most of the bad devices that do not contain micropipes. Micropipes in these wafers are also frequently found to be of Type II, which do not run parallel to the c axis.« less

Correlation Between Morphological Defects, Electron Beam Induced Current Imaging, and the Electrical Properties of 4H-SiC Schottky Diodes

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

Wang,Y.; Ali, G.; Mikhov, M.

2005-01-01

Defects in SiC degrade the electrical properties and yield of devices made from this material. This article examines morphological defects in 4H-SiC and defects visible in electron beam-induced current (EBIC) images and their effects on the electrical characteristics of Schottky diodes. Optical Nomarski microscopy and atomic force microscopy were used to observe the morphological defects, which are classified into 26 types based on appearance alone. Forward and reverse current-voltage characteristics were used to extract barrier heights, ideality factors, and breakdown voltages. Barrier heights decrease about linearly with increasing ideality factor, which is explained by discrete patches of low barrier heightmore » within the main contact. Barrier height, ideality, and breakdown voltage all degrade with increasing device diameter, suggesting that discrete defects are responsible. Electroluminescence was observed under reverse bias from microplasmas associated with defects containing micropipes. EBIC measurements reveal several types of features corresponding to recombination centers. The density of dark spots observed by EBIC correlates strongly with ideality factor and barrier height. Most morphological defects do not affect the reverse characteristics when no micropipes are present, but lower the barrier height and worsen the ideality factor. However, certain multiple-tailed defects, irregularly shaped defects and triangular defects with 3C inclusions substantially degrade both breakdown voltage and barrier height, and account for most of the bad devices that do not contain micropipes. Micropipes in these wafers are also frequently found to be of Type II, which do not run parallel to the c axis.« less

Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA.

PubMed Central

Garry, Vincent F; Harkins, Mary E; Erickson, Leanna L; Long-Simpson, Leslie K; Holland, Seth E; Burroughs, Barbara L

2002-01-01

We previously demonstrated that the frequency of birth defects among children of residents of the Red River Valley (RRV), Minnesota, USA, was significantly higher than in other major agricultural regions of the state during the years 1989-1991, with children born to male pesticide applicators having the highest risk. The present, smaller cross-sectional study of 695 families and 1,532 children, conducted during 1997-1998, provides a more detailed examination of reproductive health outcomes in farm families ascertained from parent-reported birth defects. In the present study, in the first year of life, the birth defect rate was 31.3 births per 1,000, with 83% of the total reported birth defects confirmed by medical records. Inclusion of children identified with birth or developmental disorders within the first 3 years of life and later led to a rate of 47.0 per 1,000 (72 children from 1,532 live births). Conceptions in spring resulted in significantly more children with birth defects than found in any other season (7.6 vs. 3.7%). Twelve families had more than one child with a birth defect (n = 28 children). Forty-two percent of the children from families with recurrent birth defects were conceived in spring, a significantly higher rate than that for any other season. Three families in the kinships defined contributed a first-degree relative other than a sibling with the same or similar birth defect, consistent with a Mendelian inheritance pattern. The remaining nine families did not follow a Mendelian inheritance pattern. The sex ratio of children with birth defects born to applicator families shows a male predominance (1.75 to 1) across specific pesticide class use and exposure categories exclusive of fungicides. In the fungicide exposure category, normal female births significantly exceed male births (1.25 to 1). Similarly, the proportion of male to female children with birth defects is significantly lower (0.57 to 1; p = 0.02). Adverse neurologic and neurobehavioral developmental effects clustered among the children born to applicators of the fumigant phosphine (odds ratio [OR] = 2.48; confidence interval [CI], 1.2-5.1). Use of the herbicide glyphosate yielded an OR of 3.6 (CI, 1.3-9.6) in the neurobehavioral category. Finally, these studies point out that (a) herbicides applied in the spring may be a factor in the birth defects observed and (b) fungicides can be a significant factor in the determination of sex of the children of the families of the RRV. Thus, two distinct classes of pesticides seem to have adverse effects on different reproductive outcomes. Biologically based confirmatory studies are needed. PMID:12060842

Urinary pH as a Risk Factor for Stone Type

NASA Astrophysics Data System (ADS)

Sakhaee, Khashayar

2007-04-01

A high urinary pH is main risk factor for the calcium phosphate stone formation; however, its pathophysiologic mechanism has not been fully understood. The introduction of Topiramate in the treatment of various neurological disorders has been complicated by metabolic acidosis, significant hypocitraturia, elevated urinary pH, and calcium phosphate stone formation. This model provides a probe to investigate the pathophysiologic mechanism of calcium phosphate stone formation and perhaps to develop appropriate countermeasures in the future. On the other hand an unduly acidic urine predisposes one to uric acid nephrolithiasis. Our recent investigation linking low urinary pH, and defective renal ammoniagenesis to insulin resistance provides new knowledge to unfold the pathophysiology of uric acid nephrolithiasis. The metabolic profile leading to uric acid stone may emerge as one of the components of metabolic syndrome.

Risks and Benefits of Exercise Training in Adults With Congenital Heart Disease.

PubMed

Chaix, Marie-A; Marcotte, François; Dore, Annie; Mongeon, François-Pierre; Mondésert, Blandine; Mercier, Lise-Andrée; Khairy, Paul

2016-04-01

Exercise capacity in adults with various forms of congenital heart disease is substantially lower than that of the general population. Although the underlying congenital heart defect, and its sequelae, certainly contribute to observed exercise limitations, there is evidence suggesting that deconditioning and a sedentary lifestyle are important implicated factors. The prevalence of acquired cardiovascular comorbidities is on the increase in the aging population with congenital heart disease, such that obesity and a sedentary lifestyle confer increased risk. Health fears and misconceptions are common barriers to regular physical activity in adults with congenital heart disease, despite evidence linking lower functional capacity to poor outcomes, and data supporting the safety and efficacy of exercise in bestowing numerous physical and psychosocial rewards. With few exceptions, adults with congenital heart disease should be counselled to exercise regularly. In this contemporary review, we provide a practical approach to assessing adults with congenital heart disease before exercise training. We examine available evidence supporting the safety and benefits of exercise training. Risks associated with exercise training in adults with congenital heart disease are discussed, particularly with regard to sudden cardiac death. Finally, recommendations for exercise training are provided, with consideration for the type of congenital heart disease, the nature (ie, static vs dynamic) and intensity (ie, low, medium, high) of the physical activity, and associated factors such as systemic ventricular dysfunction and residual defects. Further research is required to determine optimal exercise regimens and to identify effective strategies to implement exercise training as a key determinant of healthy living. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Effects of oxidative stress on hyperglycaemia-induced brain malformations in a diabetes mouse model.

PubMed

Jin, Ya; Wang, Guang; Han, Sha-Sha; He, Mei-Yao; Cheng, Xin; Ma, Zheng-Lai; Wu, Xia; Yang, Xuesong; Liu, Guo-Sheng

2016-09-10

Pregestational diabetes mellitus (PGDM) enhances the risk of fetal neurodevelopmental defects. However, the mechanism of hyperglycaemia-induced neurodevelopmental defects is not fully understood. In this study, several typical neurodevelopmental defects were identified in the streptozotocin-induced diabetes mouse model. The neuron-specific class III beta-tubulin/forkhead box P1-labelled neuronal differentiation was suppressed and glial fibrillary acidic protein-labelled glial cell lineage differentiation was slightly promoted in pregestational diabetes mellitus (PGDM) mice. Various concentrations of glucose did not change the U87 cell viability, but glial cell line-derived neurotrophic factor expression was altered with varying glucose concentrations. Mouse maternal hyperglycaemia significantly increased Tunel(+) apoptosis but did not dramatically affect PCNA(+) cell proliferation in the process. To determine the cause of increased apoptosis, we determined the SOD activity, the expression of Nrf2 as well as its downstream anti-oxidative factors NQO1 and HO1, and found that all of them significantly increased in PGDM fetal brains compared with controls. However, Nrf2 expression in U87 cells was not significantly changed by different glucose concentrations. In mouse telencephalon, we observed the co-localization of Tuj-1 and Nrf2 expression in neurons, and down-regulating of Nrf2 in SH-SY5Y cells altered the viability of SH-SY5Y cells exposed to high glucose concentrations. Taken together, the data suggest that Nrf2-modulated antioxidant stress plays a crucial role in maternal hyperglycaemia-induced neurodevelopmental defects. Copyright © 2016 Elsevier Inc. All rights reserved.

Further thoughts on the utility of risk matrices.

PubMed

Ball, David J; Watt, John

2013-11-01

Risk matrices are commonly encountered devices for rating hazards in numerous areas of risk management. Part of their popularity is predicated on their apparent simplicity and transparency. Recent research, however, has identified serious mathematical defects and inconsistencies. This article further examines the reliability and utility of risk matrices for ranking hazards, specifically in the context of public leisure activities including travel. We find that (1) different risk assessors may assign vastly different ratings to the same hazard, (2) even following lengthy reflection and learning scatter remains high, and (3) the underlying drivers of disparate ratings relate to fundamentally different worldviews, beliefs, and a panoply of psychosocial factors that are seldom explicitly acknowledged. It appears that risk matrices when used in this context may be creating no more than an artificial and even untrustworthy picture of the relative importance of hazards, which may be of little or no benefit to those trying to manage risk effectively and rationally. © 2013 Society for Risk Analysis.

Magnitude of Myocutaneous Flaps and Factors Associated With Loss of Volume in Oral Cancer Reconstructive Surgery.

PubMed

Sakamoto, Yuki; Yanamoto, Souichi; Ota, Yoshihide; Furudoi, Shungo; Komori, Takahide; Umeda, Masahiro

2016-03-01

Myocutaneous flaps are often used to repair oral and maxillofacial defects after surgery for oral cancer; however, their volume decreases during the postoperative period. To facilitate treatment planning, the authors measured the extent of such postoperative flap volume loss and identified associated factors in patients who underwent oral reconstruction with myocutaneous flaps. The authors designed and performed a retrospective observational study of patients who underwent reconstructive procedures involving rectus abdominal myocutaneous (RAM) or pectoralis major myocutaneous (PMMC) flaps at Tokai University Hospital, Kobe University Hospital, or Nagasaki University Hospital from April 2009 through March 2013. Flap type and other clinical variables were examined as potential predictors of flap loss. The primary outcome was flap loss at 6 months postoperatively. Correlations between each potential predictor and the primary outcome were examined using multiple regression analysis. The subjects were 75 patients whose oral defects were reconstructed with RAM flaps (n = 57) or PMMC flaps (n = 18). RAM flaps exhibited a mean volume shrinkage of 22% at 6 months postoperatively, which was less than the 27.5% displayed by the PMMC flaps, but the difference was not important. Renal failure, previous surgery of the oral region, postoperative radiotherapy, and postoperative serum albumin level were found to be meaningful risk factors for postoperative flap volume loss. The results of this study suggest that larger flaps should be used in patients who possess these risk factors or are scheduled to undergo postoperative radiotherapy. Future studies should examine the utility of postoperative nutritional management for preventing flap volume loss. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Drug insight: Anti-tumor necrosis factor therapy for inflammatory arthropathies during reproduction, pregnancy and lactation.

PubMed

Skomsvoll, Johan F; Wallenius, Marianne; Koksvik, Hege S; Rødevand, Erik; Salvesen, Kjell A; Spigset, Olav; Kvien, Tore K

2007-03-01

Tumor necrosis factor (TNF) antagonists are widely used to reduce disease activity and joint damage, and to improve health-related quality of life in patients suffering from rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis. To date, no increased risk of embryotoxicity or teratogenicity, or adverse pregnancy outcome (such as birth defects, premature birth, and low birth weight) has been reported in patients with inflammatory arthropathies treated with anti-TNF therapy, compared with the general population. However, the available data are limited, and methotrexate, which is commonly used in combination with anti-TNF drugs, is teratogenic. Until more data are available, no firm conclusions can be reached regarding the safety of anti-TNF therapy in pregnancy. Nevertheless, in selected cases where there is high disease activity, anti-TNF therapy might be recommended, depending on the results of individual risk-benefit analyses. Fully informed consent from the mother is needed in such cases. Anti-TNF agents are not usually used during lactation, although the risk of toxicity is probably negligible.

5,10 Methylenetetrahydrofolate reductase genetic polymorphism as a risk factor for neural tube defects

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

Ou, C.Y.; Brown, V.K.; Khoury, M.J.

1996-06-28

Persons with a thermolabile form of the enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) have reduced enzyme activity and increased plasma homocysteine which can be lowered by supplemental folic acid. Thermolability of the enzyme has recently been shown to be caused by a common mutation (677C{sup {r_arrow}}T) in the MTHFR gene. We studied 41 fibroblast cultures from NTD-affected fetuses and compared their genotypes with those of 109 blood specimens from individuals in the general population. 677C{sup {r_arrow}}T homozygosity was associated with a 7.2 fold increased risk for NTDs (95% confidence interval: 1.8-30.3; p value: 0.001). These preliminary data suggest that the 677C{supmore » {r_arrow}}T polymorphism of the MTHFR gene is a risk factor for spina bifida and anencephaly that may provide a partial biologic explanation for why folic acid prevents these types of NTD. 13 refs., 1 fig., 1 tab.« less

Metabolic dysfunction in obstructive sleep apnea: A critical examination of underlying mechanisms

PubMed Central

MESARWI, Omar A.; SHARMA, Ellora V.; JUN, Jonathan C.; POLOTSKY, Vsevolod Y.

2015-01-01

It has recently become clear that obstructive sleep apnea (OSA) is an independent risk factor for the development of metabolic syndrome, a disorder of defective energy storage and use. Several mechanisms have been proposed to explain this finding, drawing upon the characteristics that define OSA. In particular, intermittent hypoxia, sleep fragmentation, elevated sympathetic tone, and oxidative stress – all consequences of OSA – have been implicated in the progression of poor metabolic outcomes in OSA. In this review we examine the evidence to support each of these disease manifestations of OSA as a unique risk for metabolic dysfunction. Tissue hypoxia and sleep fragmentation are each directly connected to insulin resistance and hypertension, and each of these also may increase sympathetic tone, resulting in defective glucose homeostasis, excessive lipolysis, and elevated blood pressure. Oxidative stress further worsens insulin resistance and in turn, metabolic dysfunction also increases oxidative stress. However, despite many studies linking each of these individual components of OSA to the development of metabolic syndrome, there are very few reports that actually provide a coherent narrative about the mechanism underlying metabolic dysfunction in OSA. PMID:26412981

Infections in myelodysplastic syndromes

PubMed Central

Toma, Andréa; Fenaux, Pierre; Dreyfus, François; Cordonnier, Catherine

2012-01-01

Myelodysplastic syndromes are associated with a risk of severe infections. While neutropenia is likely to be the main predisposing factor, several other immune defects have been reported, including impaired neutrophil function, B-, T- and NK-cell defects and the possible consequences of iron overload due to red blood cell transfusions. The advanced age of most patients, their frequent comorbidities, and the fact that drugs such as hypomethylating agents and lenalidomide, which are effective in myelodysplastic syndromes but can transiently worsen neutropenia, may increase the risk of infection and their severity in this context. The majority of infections in myelodysplastic syndromes are bacterial, while the incidence of fungal infections is not well known and viral infections seem to be rare. No prophylactic measures against infections have demonstrated efficacy in myelodysplastic syndromes. However, pending more data, we propose here some recommendations for the management of patients with myelodysplastic syndromes. In the future, an important contribution can be made by prospective trials testing the efficacy of prophylactic and therapeutic approaches to infection in these patients, especially in the context of the new drugs available for myelodysplastic syndromes. PMID:22733024

Does Atrial Septal Defect Increase the Risk of Stroke Following Total Hip and Knee Arthroplasty?

PubMed

Chughtai, Morad; Perfetti, Dean C; Khlopas, Anton; Sultan, Assem A; Sodhi, Nipun; Newman, Jared M; Gwam, Chukwuweike U; Maheshwari, Aditya V; Mont, Michael A

2017-12-22

Atrial septal defect (ASD) is a common asymptomatic congenital heart condition that predisposes patients to paradoxical emboli in the cerebral vasculature. In this study, we evaluated the prevalence of ASD and risk of stroke for patients with ASD undergoing primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). We used the New York Statewide Planning and Research Cooperative System to identify 258,911 elective primary THA/TKA between 2005 and 2014, including 140 patients with ASD. Logistic regression models calculated odds ratios (OR) and 95% confidence intervals (CI) and controlled for demographic and medical risk factors for stroke. The prevalence of ASD was 54 per 100,000 patients undergoing THA/TKA. The rate of stroke within 30 days of surgery was 5.7% (95% CI: 2.5%, 11.0%) for patients with ASD, and 0.1% (95% CI: 0.1%, 0.1%) for all other patients. In regression models, the risk of stroke was 70 times greater (OR: 70.0, 95% CI: 32.9, 148.9) for patients with ASD compared to patients without this condition (p<0.001). Patients with ASD undergoing THA and TKA are predisposed to stroke in the postoperative period. Orthopaedic surgeons indicating patients for surgery and internists performing preoperative medical clearance should be aware of these risks and discuss them prior to surgery. The efficacy of pharmacological and surgical measures to reduce postoperative stroke within this patient population should be topics of future investigation.

Maternal occupation and the risk of neural tube defects in offspring.

PubMed

Kim, Jihye; Langlois, Peter H; Mitchell, Laura E; Agopian, A J

2017-07-19

We evaluated the association between maternal occupation and the risk of neural tube defects (NTDs) in offspring. Data for 491 nonsyndromic cases were obtained from the Texas Birth Defects Registry for deliveries between 1999 and 2009. We randomly selected 2,291 controls among all live births in Texas during this time. Maternal occupations were classified using automated software and manual assignment. Multivariable logistic regression analyses were used to examine the relationship between maternal occupation and risk for any NTD, adjusting for maternal race/ethnicity, any diabetes, and maternal body mass index. These analyses were repeated for spina bifida specifically. Some maternal occupations, particularly those related to business/finance, health care practice, and cleaning/maintenance, were significantly associated with increased risk of spina bifida and/or any NTD. Further research is needed to identify the specific occupational exposures related to NTD risk.

Bendectin and birth defects: I. A meta-analysis of the epidemiologic studies.

PubMed

McKeigue, P M; Lamm, S H; Linn, S; Kutcher, J S

1994-07-01

"Bendectin" (Doxylamine/Dicyclomine/Pyridoxine) was widely used for the treatment of nausea and vomiting of pregnancy until 1983, when production was discontinued in the face of lawsuits alleging that the drug caused congenital malformations. We have conducted a meta-analysis of the 16 cohort and 11 case-control studies that report birth defects from Bendectin-exposed pregnancies. This meta-analysis provides an estimate of the relative risk of malformation at birth in association with Bendectin exposure. The pooled estimate of the relative risk of any malformation at birth in association with exposure to Bendectin in the first trimester was 0.95 (95% Cl 0.88 to 1.04). Separate analyses were undertaken for cardiac defects, central nervous system defects, neural tube defects, limb reductions, oral clefts, and genital tract malformations. In these categories, the pooled estimates of relative risk ranged from 0.81 for oral clefts to 1.11 for limb reductions, with all 95% confidence intervals enclosing unity. With the exception of studies for oral clefts and for pyloric stenosis, tests for heterogeneity of association indicated for each table that all studies were estimating the same odds ratio. These studies, as a group, showed no difference in the risk of birth defects between those infants whose mothers had taken Bendectin during the first trimester of pregnancy and those infants whose mothers had not. It is unlikely that Bendectin exposure contributed to the prevalence of congenital malformations in the population.

Air Pollution, Neighborhood Acculturation Factors, and Neural Tube Defects Among Hispanic Women in California

PubMed Central

Padula, Amy M.; Yang, Wei; Carmichael, Suzan L.; Lurmann, Frederick; Balmes, John; Hammond, S. Katharine; Shaw, Gary M.

2017-01-01

Background Neural tube defects (NTDs) are one of the most common types of birth defects. Environmental pollutants and acculturation have been associated with NTDs independently. The potential effect modification of acculturation in the relationship between ambient air pollution and risks of NTDs is not well understood. Methods We investigated whether associations between traffic-related air pollutant exposure in early gestation and NTDs, and more specifically spina bifida, were modified by individual and neighborhood acculturation factors among 139 cases and 466 controls born in the San Joaquin Valley of California, 1997 to 2006. Five criteria pollutant exposures in tertiles, two outcomes, and seven neighborhood acculturation factors from the U.S. Census at the block group level were included for a total of 280 investigated associations. Estimates were adjusted for maternal education and multivitamin use in the first 2 months of pregnancy. Additional analyses were stratified by nativity. Results Increased odds of NTDs were observed for individuals who had high exposures to carbon monoxide, nitrogen oxide, or nitrogen dioxide and lived in neighborhoods that were more acculturated. Conversely, there were increased odds of NTDs for those who had high prenatal exposure to PM10 and lived in neighborhoods that were less acculturated. The results of spina bifida alone were generally stronger in magnitude. When stratified by individual nativity (U.S.- vs. foreign-born), carbon monoxide, nitrogen oxide, and nitrogen dioxide were more strongly associated with NTDs among U.S.-born Hispanic mothers. Conclusion Neighborhood acculturation factors were modifiers of the relationship between air pollution and NTDs in California, though not in a consistent direction for all pollutants. PMID:28398703

The genetics of folate metabolism and maternal risk of birth of a child with Down syndrome and associated congenital heart defects

PubMed Central

Coppedè, Fabio

2015-01-01

Almost 15 years ago it was hypothesized that polymorphisms of genes encoding enzymes involved in folate metabolism could lead to aberrant methylation of peri-centromeric regions of chromosome 21, favoring its abnormal segregation during maternal meiosis. Subsequently, more than 50 small case-control studies investigated whether or not maternal polymorphisms of folate pathway genes could be risk factors for the birth of a child with Down syndrome (DS), yielding conflicting and inconclusive results. However, recent meta-analyses of those studies suggest that at least three of those polymorphisms, namely MTHFR 677C>T, MTRR 66A>G, and RFC1 80G>A, are likely to act as maternal risk factors for the birth of a child with trisomy 21, revealing also complex gene-nutrient interactions. A large-cohort study also revealed that lack of maternal folic acid supplementation at peri-conception resulted in increased risk for a DS birth due to errors occurred at maternal meiosis II in the aging oocyte, and it was shown that the methylation status of chromosome 21 peri-centromeric regions could favor recombination errors during meiosis leading to its malsegregation. In this regard, two recent case-control studies revealed association of maternal polymorphisms or haplotypes of the DNMT3B gene, coding for an enzyme required for the regulation of DNA methylation at centromeric and peri-centromeric regions of human chromosomes, with risk of having a birth with DS. Furthermore, congenital heart defects (CHD) are found in almost a half of DS births, and increasing evidence points to a possible contribution of lack of folic acid supplementation at peri-conception, maternal polymorphisms of folate pathway genes, and resulting epigenetic modifications of several genes, at the basis of their occurrence. This review summarizes available case-control studies and literature meta-analyses in order to provide a critical and up to date overview of what we currently know in this field. PMID:26161087

Pregnancy outcome of first trimester exposure to the vitamin K antagonist phenprocoumon depends on duration of treatment.

PubMed

Hüttel, Eleanor; Padberg, Stephanie; Meister, Reinhard; Beck, Evelin; Schaefer, Christof

2017-05-03

The aim of this observational cohort study was to specify the risk of the vitamin K antagonist (VKA) phenprocoumon during first trimester of pregnancy, in particular to estimate the risk of birth defects and spontaneous fetal loss. Four hundred eight pregnancies with phenprocoumon exposure were compared to 1,642 pregnancies neither exposed to VKA nor to other major teratogens or fetotoxicants. There was no typical warfarin embryopathy in our exposed cohort. However, the overall rate of major birth defects was significantly increased (7.4 % vs 2.3 %; adjusted odds ratio [OR adj ] 2.14; 95 % confidence interval [CI] 1.4-3.4). With early cessation until five completed gestational weeks the birth defect risk was similar to the comparison cohort (2.4 % vs 2.3 %; OR adj 1.07; 95 % CI 0.2-3.6). With treatment duration exceeding seven gestational weeks the rate of major birth defects increased up to five-fold (10.8 % vs 2.3 %; OR adj 5.18; 95 % CI 2.0-11.6). The overall risk of spontaneous abortion (SAB) was 38.0 % vs 17.5 % in the comparison cohort (adjusted hazard ratio [HR adj ] 2.9; 95 % CI 2.2-3.9). The treatment duration had a significant effect on the hazard of SAB (HR adj 1.12; 95 % CI 1.01-1.25 per each additional exposure week). Phenprocoumon and other VKA carry an embryotoxic risk. This risk seems to be time-dependent with a steep risk increase for birth defects and also for fetal loss after week 5. If maternal disease permits, VKA therapy should be switched to safer alternatives such as heparins immediately after early recognition of pregnancy.

Limb reduction defects in the northern region of England 1985-92.

PubMed Central

Wright, M J; Newell, J N; Charlton, M E; Hey, E N; Donaldson, L J; Burn, J

1995-01-01

STUDY OBJECTIVE--To test the hypothesis that children born to mothers living near the sea are at increased risk of limb reduction defects. DESIGN--Descriptive data analysis. SETTING--The northern health region of England. PATIENTS--All children born between 1 January 1985 and 31 December 1992 in the northern region of England with isolated limb reduction defects. MAIN RESULTS--The birth prevalence of isolated limb reduction defects was not affected by the distance the mother lived from the sea. There was some evidence of space-time clustering, but there was no evidence of statistically significant variation in the occurrence of the condition with sex, time of birth (monthly or yearly), or county of birth. CONCLUSIONS--There is no evidence that children born to mothers living near the sea are at increased risk of limb reduction defects. PMID:7629469

[Incidence and evolution of congenital heart disease in Spain from 2003 until 2012].

PubMed

Pérez-Lescure Picarzo, Javier; Mosquera González, Margarita; Latasa Zamalloa, Pello; Crespo Marcos, David

2018-03-29

Congenital heart disease (CHD) represents the most common congenital malformation. The objective of this study was to analyse the incidence of CHD in Spain, and it is the first nationwide study so far. A retrospective observational study was performed in order to evaluate the incidence of CHD in Spain. The administrative database (minimum basic data set) from 2003 to 2012 was analysed in children less than one year old admitted to hospital with codes of CHD (International Classification of Diseases, 9th Revision, clinical modification). Cumulative incidence, Incidence relative risk, and standardised incidence ratio were calculated to study geographic variations. There were 64,831 infants with CHD among the 4,766,325 births analysed during the period studied, with an incidence of 13.6‰. The incidence excluding atrial septal defect was 7.29 ‰.The most frequent CHD were atrial septal defect (6.31‰), ventricular septal defect (3.48‰), patent ductus arteriosus (2.71‰), coarctation of the aorta (0.55‰), pulmonary stenosis (0.50‰), transposition of the great arteries (0.49‰), atrioventricular septal defect (0.45‰), and tetralogy of Fallot (0.41‰). Castilla and Leon, together with Extremadura, showed the highest risks for severe and very severe CHD, while Madrid and Cantabria showed the lowest. An increase of mild CHD was observed during the period analysed. This could have been influenced by improvements in diagnostic techniques, extended use of echocardiography, and the International Classification of Diseases, 9th Revision, clinical modification coding system, and to a decrease in very severe CHD, which is less influenced by external factors. Significant geographical differences were found in the incidence of severe and very severe CHD. Copyright © 2018. Publicado por Elsevier España, S.L.U.

Planar Cell Polarity Pathway Genes and Risk for Spina Bifida

PubMed Central

Wen, Shu; Zhu, Huiping; Lu, Wei; Mitchell, Laura E.; Shaw, Gary M.; Lammer, Edward J.; Finnell, Richard H.

2009-01-01

Spina bifida, a neural tube closure defect (NTD) involving the posterior portion of what will ultimately give rise to the spinal cord, is one of the most common and serious birth defects. The etiology of spina bifida is thought to be multi-factorial and involve multiple interacting genes and environmental factors. The causes of this congenital malformation remain largely unknown. However, several candidate genes for spina bifida have been identified in lower vertebrates, including the planar cell polarity (PCP) genes. We used data from a case-control study conducted in California to evaluate the association between variation within several key PCP genes and the risk of spina bifida. The PCP genes included in this study were the human homologues of the Xenopus genes Flamingo, Strabismus, Prickle, Dishevelled and Scrib, two of the homologues of Xenopus Wnt genes, WNT5A and WNT11, and two of the homologues of Xenopus Frizzled, FZD3 and FZD6. None of the 172 SNPs that were evaluated were significantly associated with spina bifida in any racial/ethnic group after correction for multiple testing. However, several SNPs in the PRICKLE2 gene had unadjusted p value<0.01. In conclusion our results, though largely negative, suggest that the PRICKLE2 gene may potentially modify the risk of spina bifida and deserves further investigation. PMID:20101694

Inhalation anesthetics and the reproductive risk associated with occupational exposure among women working in veterinary anesthesia.

PubMed

Allweiler, Sandra I; Kogan, Lori R

2013-05-01

To investigate reproductive health issues for women working in veterinary anesthesia compared with those working in veterinary critical care. Reproductive health issues were classified as time to conceive, fertility treatment, miscarriage, and children with birth defects. Questionnaire-based survey. A survey was designed to assess the reproductive health of female personnel working in veterinary anesthesia. To account for other job related factors that might impact reproductive health (i.e. stress, heavy lifting, long working hours and varying schedules), women working in veterinary critical care were used as a comparison group. There were 295 respondents including, (209 faculty and staff working in veterinary anesthesia and 86 in veterinary critical care). There were no statistical differences in length of time to conceive, number of couples receiving fertility treatment, miscarriages, and children with birth defects between the two groups. This study did not show a statistically significant difference in reproductive risk for women working in veterinary anesthesia when compared to women working in veterinary critical care. Overall the incidence for reproductive health problems is similar to the risk for the general population of females in North America. © 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Device closure of secundum atrial septal defect's and the risk of cardiac erosion.

PubMed

Thomson, J D R; Qureshi, S A

2015-12-01

Cardiac erosion related to transcatheter atrial septal defect closure devices is of increasing concern. Erosion is reported to have occurred with most of currently available occluder devices. Perhaps due to the very large number of implants worldwide, the Amplatzer (St Jude) occluder is associated with the majority of cardiac erosion events reported in the literature. Best current estimates of the incidence of erosion with the St Jude device are between one and three cases per 1000 implants. Most events occur early after implantation and it is rare, although not unheard of, for events to occur after a year following device insertion. It is important that those involved with closure programmes are vigilant for the problem, because device-related erosion is associated with a significant mortality risk. Despite considerable debate, the risk factors (either patient or device) for erosion remain unclear and require further investigation. Currently available data sets have focussed largely on erosion cohorts and are unable to place these cases in appropriate context with non-erosion closure cases. What is certain is that programmes implanting these devices must take care to implant appropriately sized devices and have in place plans to ensure that patients are both well informed and can access help and advice in the event of developing symptoms.

Bacterial keratitis: predisposing factors, clinical and microbiological review of 300 cases

PubMed Central

Bourcier, T; Thomas, F; Borderie, V; Chaumeil, C; Laroche, L

2003-01-01

Aim: To identify predisposing factors and to define clinical and microbiological characteristics of bacterial keratitis in current practice. Methods: A retrospective analysis of the hospital records of patients presenting with bacterial keratitis and treated at the Quinze-Vingts National Center of Ophthalmology, Paris, France, was performed during a 20 month period. A bacterial keratitis was defined as a suppurative corneal infiltrate and overlying epithelial defect associated with presence of bacteria on corneal scraping and/or that was cured with antibiotic therapy. Risk factors, clinical and microbiological data were collected. Results: 300 cases (291 patients) of presumed bacterial keratitis were included. Potential predisposing factors, usually multiple, were identified in 90.6% of cases. Contact lens wear was the main risk factor (50.3%). Trauma or a history of keratopathy was found in 15% and 21% of cases, respectively. An organism was identified in 201 eyes (68%). 83% of the infections involved Gram positive bacteria, 17% involved Gram negative bacteria, and 2% were polymicrobial. Gram negative bacteria were associated with severe anterior chamber inflammation (p=0.004), as well as greater surface of infiltrates (p=0.01). 99% of ulcers resolved with treatment, but only 60% of patients had visual acuity better than the level at admission, and 5% had very poor visual outcome. Conclusions: Contact lens wear is the most important risk factor. Most community acquired bacterial ulcers resolve with appropriate treatment. PMID:12812878

The impact of RABL2B gene (rs144944885) on human male infertility in patients with oligoasthenoteratozoospermia and immotile short tail sperm defects.

PubMed

Hosseini, Seyedeh Hanieh; Sadighi Gilani, Mohammad Ali; Meybodi, Anahita Mohseni; Sabbaghian, Marjan

2017-04-01

Male infertility is a multifactorial disorder with impressively genetic basis; besides, sperm abnormalities are the cause of numerous cases of male infertility. In this study, we evaluated the genetic variants in exons 4 and 5 and their intron-exon boundaries in RABL2B gene in infertile men with oligoasthenoteratozoospermia (OAT) and immotile short tail sperm (ISTS) defects to define if there is any association between these variants and human male infertility. To this purpose, DNA was extracted from peripheral blood and after PCR reaction and sequencing, the results of sequenced segments were analyzed. In the present study, 30 infertile men with ISTS defect and 30 oligoasthenoteratozoospermic infertile men were recruited. All men were of Iranian origin and it took 3 years to collect patient's samples with ISTS defect. As a result, the 50776482 delC intronic variant (rs144944885) was identified in five patients with oligoasthenoteratozoospermia defect and one patient with ISTS defect in heterozygote form. This variant was not identified in controls. The allelic frequency of the 50776482 delC variant was significantly statistically higher in oligoasthenoteratozoospermic infertile men (p < 0.05). Bioinformatics studies suggested that the 50776482 delC allele would modify the splicing of RABL2B pre-mRNA. In addition, we identified a new genetic variant in RABL2B gene. According to the present study, 50776482 delC allele in the RABL2B gene could be a risk factor in Iranian infertile men with oligoasthenoteratozoospermia defect, but more genetic studies are required to understand the accurate role of this variant in pathogenesis of human male infertility.

Linking a pharmaceutical claims database with a birth defects registry to investigate birth defect rates of suspected teratogens.

PubMed

Colvin, Lyn; Slack-Smith, Linda; Stanley, Fiona J; Bower, Carol

2010-11-01

Data linkage of population administrative data is being investigated as a tool for pharmacovigilance in pregnancy in Australia. Records of prescriptions of known or suspected teratogens dispensed to pregnant women have been linked to a birth defects registry to determine if defects associated with medicine exposure can be detected. The Pharmaceutical Benefits Scheme is a national claims database that has been linked with population-based data to extract linkages for women with a pregnancy event in Western Australia from 2002 to 2005 (n = 106 074). Records of births to the women who were dispensed medicines in categories D or X of the Australian ADEC pregnancy risk category were linked to the Birth Defects Registry of Western Australia. Population rates of registered birth defects per 1000 births were calculated for each medicine. There were 47 medicines dispensed at least once during pregnancy with 23 associated with a registered birth defect to a woman dispensed the medicine. When the birth defect rate for each medicine was compared with the rate for all other women not dispensed that medicine, most medicines showed an increased risk. Medicines with the higher risks were medroxyprogesterone acetate (OR: 1.8; 95%CI: 1.4-2.3), follitropin alfa (OR: 2.5; 95%CI: 1.2-5.0), carbamazepine (OR: 3.1; 95%CI: 1.7-5.6) and enalapril maleate (OR: 8.1; 95%CI: 1.6-41.7). Many known associations between medicines and birth defects were identified, suggesting that linked administrative data could be an important means of pharmacovigilance in pregnancy in Australia. Copyright © 2010 John Wiley & Sons, Ltd.

Pediatric anemia in rural Ghana: a cross-sectional study of prevalence and risk factors.

PubMed

VanBuskirk, Kelley M; Ofosu, Anthony; Kennedy, Amy; Denno, Donna M

2014-08-01

To assess anemia prevalence and identify associated parameters in children <3 years of age in a rural area of Ghana. Univariate and multivariate logistic regression of cross-sectional survey results from 861 children aged <3 years attending routine immunization services in Berekum district. Anemia prevalence was 73.1%; most were either mildly (31.2%) or moderately (38.7%) affected. Risk factors for anemia (hemoglobin < 11.0 g/dl) in multivariate analysis were malaria parasitemia and male sex; these factors and younger age were associated with anemia severity. A partial defect in glucose-6-phosphate dehydrogenase was associated with decreased severity. Height-for-age, but not weight-for-age, was associated with anemia and its severity. Malaria parasitemia was strongly associated with anemia and its severity, suggesting that malaria control may be the most effective way to reduce the burden of anemia in rural Ghanaian children. © The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis

PubMed Central

Bever, Katherine M.; Masha, Luke I.; Sun, Fangui; Stern, Lauren; Havasi, Andrea; Berk, John L.; Sanchorawala, Vaishali; Seldin, David C.; Sloan, J. Mark

2016-01-01

Patients with immunoglobulin light chain amyloidosis are at risk for both thrombotic and bleeding complications. While the hemostatic defects have been extensively studied, less is known about thrombotic complications in this disease. This retrospective study examined the frequency of venous thromboembolism in 929 patients with immunoglobulin light chain amyloidosis presenting to a single referral center, correlated risk of venous thromboembolism with clinical and laboratory factors, and examined complications of anticoagulation in this population. Sixty-five patients (7%) were documented as having at least one venous thromboembolic event. Eighty percent of these patients had events within one year prior to or following diagnosis. Lower serum albumin was associated with increased risk of VTE, with a hazard ratio of 4.30 (CI 1.60–11.55; P=0.0038) for serum albumin less than 3 g/dL compared to serum albumin greater than 4 g/dL. Severe bleeding complications were observed in 5 out of 57 patients with venous thromboembolism undergoing treatment with anticoagulation. Prospective investigation should be undertaken to better risk stratify these patients and to determine the optimal strategies for prophylaxis against and management of venous thromboembolism. PMID:26452981

Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis.

PubMed

Bever, Katherine M; Masha, Luke I; Sun, Fangui; Stern, Lauren; Havasi, Andrea; Berk, John L; Sanchorawala, Vaishali; Seldin, David C; Sloan, J Mark

2016-01-01

Patients with immunoglobulin light chain amyloidosis are at risk for both thrombotic and bleeding complications. While the hemostatic defects have been extensively studied, less is known about thrombotic complications in this disease. This retrospective study examined the frequency of venous thromboembolism in 929 patients with immunoglobulin light chain amyloidosis presenting to a single referral center, correlated risk of venous thromboembolism with clinical and laboratory factors, and examined complications of anticoagulation in this population. Sixty-five patients (7%) were documented as having at least one venous thromboembolic event. Eighty percent of these patients had events within one year prior to or following diagnosis. Lower serum albumin was associated with increased risk of VTE, with a hazard ratio of 4.30 (CI 1.60-11.55; P=0.0038) for serum albumin less than 3 g/dL compared to serum albumin greater than 4 g/dL. Severe bleeding complications were observed in 5 out of 57 patients with venous thromboembolism undergoing treatment with anticoagulation. Prospective investigation should be undertaken to better risk stratify these patients and to determine the optimal strategies for prophylaxis against and management of venous thromboembolism. Copyright© Ferrata Storti Foundation.

Predictive value of myocardial perfusion single-photon emission computed tomography and the impact of renal function on cardiac death.

PubMed

Hakeem, Abdul; Bhatti, Sabha; Dillie, Kathryn Sullivan; Cook, Jeffrey R; Samad, Zainab; Roth-Cline, Michelle D; Chang, Su Min

2008-12-09

Patients with chronic kidney disease (CKD) have worse cardiovascular outcomes than those without CKD. The prognostic utility of myocardial perfusion single-photon emission CT (MPS) in patients with varying degrees of renal dysfunction and the impact of CKD on cardiac death prediction in patients undergoing MPS have not been investigated. We followed up 1652 consecutive patients who underwent stress MPS (32% exercise, 95% gated) for cardiac death for a mean of 2.15+/-0.8 years. MPS defects were defined with a summed stress score (normal summed stress score <4, abnormal summed stress score>or=4). Ischemia was defined as a summed stress score >or=4 plus a summed difference score >or=2, and scar was defined as a summed difference score <2 plus a summed stress score >or=4. Renal function was calculated with the Modified Diet in Renal Disease equation. CKD (estimated glomerular filtration rate <60 mL . min(-1) . 1.73 m(-2)) was present in 36%. Cardiac death increased with worsening levels of perfusion defects across the entire spectrum of renal function. Presence of ischemia was independently predictive of cardiac death, all-cause mortality, and nonfatal myocardial infarction. Patients with normal MPS and CKD had higher unadjusted cardiac death event rates than those with no CKD and normal MPS (2.7% versus 0.8%, P=0.001). Multivariate Cox proportional hazards models revealed that both perfusion defects (hazard ratio 1.90, 95% CI 1.47 to 2.46) and CKD (hazard ratio 1.96, 95% CI 1.29 to 2.95) were independent predictors of cardiac death after accounting for risk factors, left ventricular dysfunction, pharmacological stress, and symptom status. Both MPS and CKD had incremental power for cardiac death prediction over baseline risk factors and left ventricular dysfunction (global chi(2) 207.5 versus 169.3, P<0.0001). MPS provides effective risk stratification across the entire spectrum of renal function. Renal dysfunction is also an important independent predictor of cardiac death in patients undergoing MPS. Renal function and MPS have additive value in risk stratisfying patients with suspected coronary artery disease. Patients with CKD appear to have a relatively less benign prognosis than those without CKD, even in the presence of a normal scan.

Recent advances in recurrent urinary tract infection from pathogenesis and biomarkers to prevention

PubMed Central

Jhang, Jia-Fong; Kuo, Hann-Chorng

2017-01-01

Recurrent urinary tract infection (UTI) might be one of the most common problems in urological clinics. Recent research has revealed novel evidence about recurrent UTI and it should be considered a different disease from the first infection. The pathogenesis of recurrent UTI might include two mechanisms, bacterial factors and deficiencies in host defense. Bacterial survival in the urinary bladder after antibiotic treatment and progression to form intracellular bacterial communities might be the most important bacterial factors. In host defense deficiency, a defect in pathogen recognition and urothelial barrier function impairment play the most important roles. Immunodeficiency and urogenital tract anatomical abnormalities have been considered the essential risk factors for recurrent UTI. In healthy women, voiding dysfunction and behavioral factors also increase the risk of recurrent UTI. Sexual intercourse and estrogen deficiency in postmenopausal women might have the strongest association with recurrent UTI. Traditional lifestyle factors such as fluid intake and diet are not considered independent risk factors now. Serum and urine biomarkers to predict recurrent UTI from the first infection have also attracted a wide attention recently. Current clinical evidence suggests that serum macrophage colony-stimulating factor and urinary nerve growth factor have potential predictive value for recurrent UTI. Clinical trials have proven the efficacy of the oral immunoactive agent OM-89 for the prevention of UTI. Vaccines for recurrent UTI are recommended by the latest guidelines and are available on the market. PMID:28974905

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

Risk Factors for Prosthetic Pulmonary Valve Failure in Patients With Congenital Heart Disease.

PubMed

Oliver, Jose Maria; Garcia-Hamilton, Diego; Gonzalez, Ana Elvira; Ruiz-Cantador, Jose; Sanchez-Recalde, Angel; Polo, Maria Luz; Aroca, Angel

2015-10-15

The incidence and risk factors for prosthetic pulmonary valve failure (PPVF) should be considered when determining optimal timing for pulmonary valve replacement (PVR) in asymptomatic patients with congenital heart disease (CHD). The cumulative freedom for reintervention due to PPVF after 146 PVR in 114 patients with CHD was analyzed. Six potential risk factors (underlying cardiac defect, history of palliative procedures, number of previous cardiac interventions, hemodynamic indication for PVR, type of intervention, and age at intervention) were analyzed using Cox proportional hazard modeling. Receiver operating characteristic (ROC) curves were used for discrimination. Internal validation in patients with tetralogy of Fallot was also performed. Median age at intervention was 23 years. There were 60 reinterventions due to PPVF (41%). Median event-free survival was 14 years (95% confidence interval [CI] 12 to 16 years). The only independent risk factor was the age at intervention (hazard ratio [HR] 0.93, 95% CI 0.90 to 0.97; p = 0.001; area under the ROC curve 0.95, 95% CI 0.92 to 0.98; p <0.001). The best cut-off point was 20.5 years. Freedom from reintervention for PPVF 15 years after surgery was 70% when it was performed at age >20.5 years compared with 33% when age at intervention was <20.5 years (p = 0.004). Internal validation in 102 PVR in patient cohort with tetralogy of Fallot (ROC area 0.98, 95% CI 0.96 to 1.0; p <0.001) was excellent. In conclusion, age at intervention is the main risk factor of reintervention for PPVF. The risk of reintervention is 2-fold when PVR is performed before the age of 20.5 years. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Holoprosencephaly: signalling interactions between the brain and the face, the environment and the genes, and the phenotypic variability in animal models and humans

PubMed Central

Graf, Daniel; Marcucio, Ralph

2014-01-01

Holoprosencephaly (HPE) is the most common developmental defect of the forebrain characterized by inadequate or absent midline division of the forebrain into cerebral hemispheres, with concomitant midline facial defects in the majority of cases. Understanding the pathogenesis of HPE requires knowledge of the relationship between the developing brain and the facial structures during embryogenesis. A number of signalling pathways control and coordinate the development of the brain and face, including Sonic hedgehog (SHH), Bone Morphogenetic Protein (BMP), Fibroblast Growth Factor (FGF), and Nodal signalling. Mutations in these pathways have been identified in animal models of HPE and human patients. Due to incomplete penetrance and variable expressivity of HPE, patients carrying defined mutations may not manifest the disease at all, or have a spectrum of defects. It is currently unknown what drives manifestation of HPE in genetically at risk individuals, but it has been speculated that other gene mutations and environmental factors may combine as cumulative insults. HPE can be diagnosed in utero by a high-resolution prenatal ultrasound or a fetal magnetic resonance imaging, sometimes in combination with molecular testing from chorionic villi or amniotic fluid sampling. Currently, there are no effective preventive methods for HPE. Better understanding of the mechanisms of gene-environment interactions in HPE would provide avenues for such interventions. PMID:25339593

Mother and child characteristics at birth and early age leukemia: a case-cohort population-based study.

PubMed

Reis, Rejane de Souza; Silva, Neimar de Paula; Santos, Marceli de Oliveira; Oliveira, Julio Fernando Pinto; Thuler, Luiz Claudio Santos; de Camargo, Beatriz; Pombo-de-Oliveira, Maria S

The population-based cancer registries (PBCR) and the Information System on Live Births in Brazil (Sistema de Informações sobre Nascidos Vivos [SINASC]) have information that enables the test for risk factors associated with leukemia at an early age. The aim of this study was to identify maternal and birth characteristics associated with early-age acute leukemia (EAL) in Brazil. A case-cohort study was performed using secondary dataset information of PBCR and SINASC. The risk association variables were grouped into (i) characteristics of the child at birth and (ii) characteristics of maternal exposure during pregnancy. The case-control ratio was 1:4. Linkage was performed using R software; odds ratio (OR) and 95% confidence interval (CI) were calculated by logistic regression models. EAL was associated with maternal occupational exposure to chemicals (agricultural, chemical, and petrochemical industry; adjOR: 2.18, 95% CI: 1.16-4.10) and with birth defects (adjOR: 3.62, 95% CI: 1.19-11.00). The results of this study, with the identification of EAL risk factors in population-based case-cohort study, strengthen the knowledge and improve databases, contributing to investigations on risk factors associated with childhood leukemia worldwide. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Long-term results after the Rastelli repair for transposition of the great arteries.

PubMed

Hörer, Jürgen; Schreiber, Christian; Dworak, Eva; Cleuziou, Julie; Prodan, Zsolt; Vogt, Manfred; Holper, Klaus; Lange, Rüdiger

2007-06-01

This study sought to assess risk factors for late mortality after the Rastelli operation for patients with transposition of the great arteries, ventricular septal defect, and left ventricular outflow tract obstruction. Records of 39 patients who underwent the Rastelli operation between 1977 and 2004 were reviewed. Median age at the time of operation was 5.1 years (2.2 years within the last 5 years). There were no early deaths. During a median follow-up of 8.9 years (range, 0 to 25 years), 2 patients died of sudden death, 1 of pneumonia, 1 during reoperation, and 2 received heart transplantation. Freedom from death or transplantation was 93.8% +/- 4.3% and 57.5% +/- 15.1% at 10 and 20 years, respectively. Freedom from conduit replacement was 48.8% +/- 10.3% and 32.5% +/- 10.3% at 10 and 20 years, respectively. Subvalvular and valvular left ventricular outflow tract obstruction (p = 0.012), stenosis of the peripheral pulmonary arteries (p < 0.001), enlargement of the ventricular septal defect (p = 0.030), and longer ischemic time (p = 0.015) were predictive for death or transplantation. Patients younger than 4 years at the time of the Rastelli operation showed a trend toward a better freedom from death or transplantation (p = 0.068), but needed significantly more conduit replacements (p = 0.038) compared with patients 4 years or older. The Rastelli operation is a low-risk procedure with regard to early mortality. The status of the pulmonary arteries and ventricular septal defect enlargement are predictive for long-term survival. Patients 4 years of age or older at the time of the Rastelli operation require fewer reoperations for conduit exchange. Nevertheless, early Rastelli repair is recommended because patients 4 years or older are at risk for a higher long-term mortality.

Proposal to Develop Enhancements and Extensions of Formal Models for Risk Assessment In Software Projects

DTIC Science & Technology

2002-09-01

seconds per minute that the runtime environment was up and running. Defect Categories. The labels of the 5 defect categories. 78 Cosmetic Defects...The name that corresponds to QSM’s cosmetic defects. Cosmetic defects can be described as deferred, such as errors in format of displays or...2002. [Fent00] Fenton , N. E. and Neil, M. Software Metrics: Roadmap. Proceedings of the Conference on the Future of Software Engineering, 2000, pp

Evaluation and treatment of failed shoulder instability procedures.

PubMed

Ho, Anthony G; Gowda, Ashok L; Michael Wiater, J

2016-09-01

Management of the unstable shoulder after a failed stabilization procedure can be difficult and challenging. Detailed understanding of the native shoulder anatomy, including its static and dynamic restraints, is necessary for determining the patient's primary pathology. In addition, evaluation of the patient's history, physical exam, and imaging is important for identifying the cause for failure after the initial procedure. Common mistakes include under-appreciation of bony defects, failure to recognize capsular laxity, technical errors, and missed associated pathology. Many potential treatment options exist for revision surgery, including open or arthroscopic Bankart repair, bony augmentation procedures, and management of Hill Sachs defects. The aim of this narrative review is to discuss in-depth the common risk factors for post-surgical failure, components for appropriate evaluation, and the different surgical options available for revision stabilization. Level of evidence Level V.

Risk of major congenital malformations in relation to maternal overweight and obesity severity: cohort study of 1.2 million singletons

PubMed Central

Cnattingius, Sven; Villamor, Eduardo; Söderling, Jonas; Pasternak, Björn; Stephansson, Olof; Neovius, Martin

2017-01-01

Objective To estimate the risks of major congenital malformations in the offspring of mothers who are underweight (body mass index (BMI) <18.5), overweight (BMI 25 to <30), or in obesity classes I (BMI 30 to <35), II (35 to <40), or III (≥40) compared with offspring of normal weight mothers (BMI 18.5 to <25) in early pregnancy. Design Population based cohort study. Setting Nationwide Swedish registries. Participants 1 243 957 liveborn singleton infants from 2001 to 2014 in Sweden. Data on maternal and pregnancy characteristics were obtained by individual record linkages. Exposure Maternal BMI at the first prenatal visit. Main outcome measures Offspring with any major congenital malformation, and subgroups of organ specific malformations diagnosed during the first year of life. Risk ratios were estimated using generalised linear models adjusted for maternal factors, sex of offspring, and birth year. Results A total of 43 550 (3.5%) offspring had any major congenital malformation, and the most common subgroup was for congenital heart defects (n=20 074; 1.6%). Compared with offspring of normal weight mothers (risk of malformations 3.4%), the proportions and adjusted risk ratios of any major congenital malformation among the offspring of mothers with higher BMI were: overweight, 3.5% and 1.05 (95% confidence interval 1.02 to 1.07); obesity class I, 3.8% and 1.12 (1.08 to 1.15), obesity class II, 4.2% and 1.23 (1.17 to 1.30), and obesity class III, 4.7% and 1.37 (1.26 to 1.49). The risks of congenital heart defects, malformations of the nervous system, and limb defects also progressively increased with BMI from overweight to obesity class III. The largest organ specific relative risks related to maternal overweight and increasing obesity were observed for malformations of the nervous system. Malformations of the genital and digestive systems were also increased in offspring of obese mothers. Conclusions Risks of any major congenital malformation and several subgroups of organ specific malformations progressively increased with maternal overweight and increasing severity of obesity. For women who are planning pregnancy, efforts should be encouraged to reduce adiposity in those with a BMI above the normal range. PMID:28615173

Abnormalities of peptide metabolism in Alzheimer disease.

PubMed

Panchal, Maï; Rholam, Mohamed; Brakch, Noureddine

2004-10-01

The steady-state level of peptide hormones represents a balance between their biosynthesis and proteolytic processing by convertases and their catabolism by proteolytic enzymes. Low levels of neuropeptide Y, somatostatin and corticotropin-releasing factor, described in Alzheimer disease (AD), were related to a defect in proteolytic processing of their protein precursors. In contrast the abundance of beta-amyloid peptides, the major protein constituents of senile plaques is likely related to inefficient catabolism. Therefore, attention is mainly focused on convertases that generate active peptides and counter-regulatory proteases that are involved in their catabolism. Some well-described proteases such as NEP are thought to be involved in beta-amyloid catabolism. The search of other possible candidates represents a primary effort in the field. A variety of vascular risk factors such as diabetes, hypertension and arteriosclerosis suggest that the functional vascular defect contributes to AD pathology. It has also been described that beta-amyloid peptides potentiate endothelin-1 induced vasoconstriction. In this review, we will critically evaluate evidence relating proteases implicated in amyloid protein precursor proteolytic processing and beta-amyloid catabolism.

Bendectin (Debendox) as a risk factor for pyloric stenosis.

PubMed

Eskenazi, B; Bracken, M B

1982-12-15

The maternal use of Bendectin (Debendox) in the first trimester of pregnancy was examined in a case-control (n = 1,427 and 3,001, respectively) study of malformed infants whose mothers were interviewed between 1974 and 1976. Mothers of infants with congenital malformation showed an increased likelihood (odds ratio = 1.40) of having used Bendectin, with a stronger association of Bendectin with birth defects for mothers who also smoked (odds ratio = 2.91). A significant association was observed between the occurrence of pyloric stenosis in the infant and exposure to Bendectin in utero (odds ratio = 4.33). When maternal sociodemographic factors, including smoking, and smoking alone, were controlled, the association between Bendectin and pyloric stenosis was further increased (odds ratio = 4.63 and 5.24, respectively). Except for a possible association of Bendectin with heart valve anomalies (odds ratio = 2.99), we were unable to document other significantly increased risks for congenital malformations.

Surgical Membranes as Directional Delivery Devices to Generate Tissue: Testing in an Ovine Critical Sized Defect Model

PubMed Central

Knothe Tate, Melissa L.; Chang, Hana; Moore, Shannon R.; Knothe, Ulf R.

2011-01-01

Purpose Pluripotent cells residing in the periosteum, a bi-layered membrane enveloping all bones, exhibit a remarkable regenerative capacity to fill in critical sized defects of the ovine femur within two weeks of treatment. Harnessing the regenerative power of the periosteum appears to be limited only by the amount of healthy periosteum available. Here we use a substitute periosteum, a delivery device cum implant, to test the hypothesis that directional delivery of endogenous periosteal factors enhances bone defect healing. Methods Newly adapted surgical protocols were used to create critical sized, middiaphyseal femur defects in four groups of five skeletally mature Swiss alpine sheep. Each group was treated using a periosteum substitute for the controlled addition of periosteal factors including the presence of collagen in the periosteum (Group 1), periosteum derived cells (Group 2), and autogenic periosteal strips (Group 3). Control group animals were treated with an isotropic elastomer membrane alone. We hypothesized that periosteal substitute membranes incorporating the most periosteal factors would show superior defect infilling compared to substitute membranes integrating fewer factors (i.e. Group 3>Group 2>Group 1>Control). Results Based on micro-computed tomography data, bone defects enveloped by substitute periosteum enabling directional delivery of periosteal factors exhibit superior bony bridging compared to those sheathed with isotropic membrane controls (Group 3>Group 2>Group 1, Control). Quantitative histological analysis shows significantly increased de novo tissue generation with delivery of periosteal factors, compared to the substitute periosteum containing a collagen membrane alone (Group 1) as well as compared to the isotropic control membrane. Greatest tissue generation and maximal defect bridging was observed when autologous periosteal transplant strips were included in the periosteum substitute. Conclusion Periosteum-derived cells as well as other factors intrinsic to periosteum play a key role for infilling of critical sized defects. PMID:22174873

A Case Series and Review of Bacillus Cereus Endocarditis from India.

PubMed

Gopinathan, Anusha; Kumar, Anil; Sen, Amitabh C; Sudha, Srisruthy; Varma, Praveen; Gs, Sunil; Eapen, Malini; Dinesh, Kavitha R

2018-01-01

Bacillus cereus is a gram positive bacilli found commonly in the soil and environment. It is a bacteria rarely associated with endocarditis. Intravenous drug abuse, presence of valvular defects, pacemakers, immunodeficiency are some of the known risk factors for B.cereus endocarditis. We present here a case series of two patients with B.cereus endocarditis along with a review of the literature. This is the first report of B.cereus endocarditis from India to the best of our knowledge.

Infections Complicating Orthotopic Liver Transplantation

PubMed Central

Schröter, Gerhard P. J.; Hoelscher, Manfred; Putnam, Charles W.; Porter, Kendrick A.; Hansbrough, John F.; Starzl, Thomas E.

2011-01-01

In 93 recipients of 102 orthotopic liver homografts, the incidence of bacteremia or fungemia exceeded 70%. The graft itself was usually an entry site for systemic infection after both immunologic and nonimmunologic parenchymal injury, especially if there was defective biliary drainage. The role of the homograft itself as the special infectious risk factor has prompted increased use of defunctionalized jejunal Roux limbs to reduce graft contamination. It has also stimulated very aggressive postoperative diagnostic efforts to rule out remedial mechanical complications of the transplant. PMID:793568

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.

Sample Size for Tablet Compression and Capsule Filling Events During Process Validation.

PubMed

Charoo, Naseem Ahmad; Durivage, Mark; Rahman, Ziyaur; Ayad, Mohamad Haitham

2017-12-01

During solid dosage form manufacturing, the uniformity of dosage units (UDU) is ensured by testing samples at 2 stages, that is, blend stage and tablet compression or capsule/powder filling stage. The aim of this work is to propose a sample size selection approach based on quality risk management principles for process performance qualification (PPQ) and continued process verification (CPV) stages by linking UDU to potential formulation and process risk factors. Bayes success run theorem appeared to be the most appropriate approach among various methods considered in this work for computing sample size for PPQ. The sample sizes for high-risk (reliability level of 99%), medium-risk (reliability level of 95%), and low-risk factors (reliability level of 90%) were estimated to be 299, 59, and 29, respectively. Risk-based assignment of reliability levels was supported by the fact that at low defect rate, the confidence to detect out-of-specification units would decrease which must be supplemented with an increase in sample size to enhance the confidence in estimation. Based on level of knowledge acquired during PPQ and the level of knowledge further required to comprehend process, sample size for CPV was calculated using Bayesian statistics to accomplish reduced sampling design for CPV. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

How We Manage Invasive Fungal Disease in Acute Myeloid Leukemia Patients with Glucose 6 Dehydrogenase Deficiency

PubMed Central

Sanna, Marco; Caocci, Giovanni; La Nasa, Giorgio

2017-01-01

Glucose-6-phosphate dehydrogenase (G6PD) represents a common human enzyme defect, particularly prevalent in the Mediterranean, African e Asian area, where malaria was or is still endemic. Recently, we identified G6PD deficiency as a risk factor for developing invasive fungal disease (IFD) and particularly Candida Sepsis in patients undergoing intensive chemotherapy for acute myeloid leukemia (AML), suggesting that there is an urgent need for strategies to properly manage this kind of patients at high risk of invasive mycoses. Here we propose our algorithm for correct identification, prophylaxis, and treatment of IFD in patients with G6PD deficiency undergoing intensive chemotherapy for AML. PMID:28894556

How We Manage Invasive Fungal Disease in Acute Myeloid Leukemia Patients with Glucose 6 Dehydrogenase Deficiency.

PubMed

Sanna, Marco; Caocci, Giovanni; La Nasa, Giorgio

2017-01-01

Glucose-6-phosphate dehydrogenase (G6PD) represents a common human enzyme defect, particularly prevalent in the Mediterranean, African e Asian area, where malaria was or is still endemic. Recently, we identified G6PD deficiency as a risk factor for developing invasive fungal disease (IFD) and particularly Candida Sepsis in patients undergoing intensive chemotherapy for acute myeloid leukemia (AML), suggesting that there is an urgent need for strategies to properly manage this kind of patients at high risk of invasive mycoses. Here we propose our algorithm for correct identification, prophylaxis, and treatment of IFD in patients with G6PD deficiency undergoing intensive chemotherapy for AML.

Conditional Creation and Rescue of Nipbl-Deficiency in Mice Reveals Multiple Determinants of Risk for Congenital Heart Defects

PubMed Central

Jacobs, Russell E.; Lopez-Burks, Martha E.; Choi, Hojae; Wikenheiser, Jamie; Hallgrimsson, Benedikt; Jamniczky, Heather A.; Fraser, Scott E.; Lander, Arthur D.; Calof, Anne L.

2016-01-01

Elucidating the causes of congenital heart defects is made difficult by the complex morphogenesis of the mammalian heart, which takes place early in development, involves contributions from multiple germ layers, and is controlled by many genes. Here, we use a conditional/invertible genetic strategy to identify the cell lineage(s) responsible for the development of heart defects in a Nipbl-deficient mouse model of Cornelia de Lange Syndrome, in which global yet subtle transcriptional dysregulation leads to development of atrial septal defects (ASDs) at high frequency. Using an approach that allows for recombinase-mediated creation or rescue of Nipbl deficiency in different lineages, we uncover complex interactions between the cardiac mesoderm, endoderm, and the rest of the embryo, whereby the risk conferred by genetic abnormality in any one lineage is modified, in a surprisingly non-additive way, by the status of others. We argue that these results are best understood in the context of a model in which the risk of heart defects is associated with the adequacy of early progenitor cell populations relative to the sizes of the structures they must eventually form. PMID:27606604

Crash risk factors for interstate large trucks in North Carolina.

PubMed

Teoh, Eric R; Carter, Daniel L; Smith, Sarah; McCartt, Anne T

2017-09-01

Provide an updated examination of risk factors for large truck involvements in crashes resulting in injury or death. A matched case-control study was conducted in North Carolina of large trucks operated by interstate carriers. Cases were defined as trucks involved in crashes resulting in fatal or non-fatal injury, and one control truck was matched on the basis of location, weekday, time of day, and truck type. The matched-pair odds ratio provided an estimate of the effect of various driver, vehicle, or carrier factors. Out-of-service (OOS) brake violations tripled the risk of crashing; any OOS vehicle defect increased crash risk by 362%. Higher historical crash rates (fatal, injury, or all crashes) of the carrier were associated with increased risk of crashing. Operating on a short-haul exemption increased crash risk by 383%. Antilock braking systems reduced crash risk by 65%. All of these results were statistically significant at the 95% confidence level. Other safety technologies also showed estimated benefits, although not statistically significant. With the exception of the finding that short-haul exemption is associated with increased crash risk, results largely bolster what is currently known about large truck crash risk and reinforce current enforcement practices. Results also suggest vehicle safety technologies can be important in lowering crash risk. This means that as safety technology continues to penetrate the fleet, whether from voluntary usage or government mandates, reductions in large truck crashes may be achieved. Practical application: Results imply that increased enforcement and use of crash avoidance technologies can improve the large truck crash problem. Copyright © 2017 National Safety Council and Elsevier Ltd. All rights reserved.

Oxidative stress and vascular inflammation in aging.

PubMed

El Assar, Mariam; Angulo, Javier; Rodríguez-Mañas, Leocadio

2013-12-01

Vascular aging, a determinant factor for cardiovascular disease and health status in the elderly, is now viewed as a modifiable risk factor. Impaired endothelial vasodilation is a early hallmark of arterial aging that precedes the clinical manifestations of vascular dysfunction, the first step to cardiovascular disease and influencing vascular outcomes in the elderly. Accordingly, the preservation of endothelial function is thought to be an essential determinant of healthy aging. With special attention on the effects of aging on the endothelial function, this review is focused on the two main mechanisms of aging-related endothelial dysfunction: oxidative stress and inflammation. Aging vasculature generates an excess of the reactive oxygen species (ROS), superoxide and hydrogen peroxide, that compromise the vasodilatory activity of nitric oxide (NO) and facilitate the formation of the deleterious radical, peroxynitrite. Main sources of ROS are mitochondrial respiratory chain and NADPH oxidases, although NOS uncoupling could also account for ROS generation. In addition, reduced antioxidant response mediated by erythroid-2-related factor-2 (Nrf2) and downregulation of mitochondrial manganese superoxide dismutase (SOD2) contributes to the establishment of chronic oxidative stress in aged vessels. This is accompanied by a chronic low-grade inflammatory phenotype that participates in defective endothelial vasodilation. The redox-sensitive transcription factor, nuclear factor-κB (NF-κB), is upregulated in vascular cells from old subjects and drives a proinflammatory shift that feedbacks oxidative stress. This chronic NF-κB activation is contributed by increased angiotensin-II signaling and downregulated sirtuins and precludes adequate cellular response to acute ROS generation. Interventions targeted to recover endogenous antioxidant capacity and cellular stress response rather than exogenous antioxidants could reverse oxidative stress-inflammation vicious cycle in vascular aging. Lifestyle attitudes such as caloric restriction and exercise training appear as effective ways to overcome defective antioxidant response and inflammation, favoring successful vascular aging and decreasing the risk for cardiovascular disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Teratology in cultural documents and today.

PubMed

Schumacher, Gert-Horst

2004-12-01

Teratology is the science of congenital malformations. The incidence of birth defects amounts to 2-3%, but it doubles postnatal owing to the fact that many dysfunctions are not discernible at birth. Congenital malformations were already known in ancient cultures, records from Assyrian and Babylonian astrologists as well as from physicians and philosophers of the Hippocratic era are testifying it. In medieval times they were recognized as supernatural phenomenons, terata, from what the term TERATOLOGY derived. In the eyes of the superstitious people affected stillborns were regarded as monster, symbol of devil or miracle. The foundation of anatomy as a science by Vesalius marked the beginning of a reorientation. In the 17th century, when the age of enlightenment began, ideas concerning the origin of birth defects became more objective. Original studies dealing with congenital malformations became common in the 18th century. Fundamental discoveries made by microscopy placed Teratology on a truly scientific basis. Significant impetus was grown to teratological research with the discovery of Gregg (1941) that German measles (rubella virus) of pregnant women caused birth defects in the embryo and the contergan disaster (1959--1962). Congenital malformations originate from genetic factors (single gene defects and chromosomal aberrations) and environmental factors, such as radiation, drugs, chemicals, and infectious agents. The susceptibility of teratogen depends on the period of embryonal development, which is classified into gametogenesis, blastogenesis, embryogenesis and fetogenesis. The Food and Drug Administration of the USA published guidelines for teratogenetic testing (1966). There are in-vivo and in-vitro-test programmes, the latter became of increasing importance owing to the large number of chemicals to be tested and the activities of opponents against animal experiments. Although great advances were made, the problem remained to transfer results from in-vivo and in-vitro tests to the constitution of man without risk.

Maternal Use of Weight Loss Products and the Risk of Neural Tube Defects in Offspring: A Systematic Literature Review.

PubMed

Hoang, Thanh T; Agopian, A J; Mitchell, Laura E

2018-01-15

Several studies have assessed potential associations between use of weight loss products in the periconceptional period and neural tube defects (NTDs). However, the individual studies are inconclusive and there has not been a systematic review of this literature. We conducted a systematic search, using Ovid MEDLINE and PubMed, to identify studies that evaluated the association between products used for weight loss and the risk of NTDs. Because many studies of birth defects only evaluate a composite birth defect outcome, we evaluated studies that defined the outcome as "any major birth defect" or as NTDs. We abstracted data on study design, exposure definition, outcome definition, covariates and effect size estimates from each article that met our inclusion criteria. For studies that evaluated a composite birth defect outcome, we also abstracted the number of NTD cases included in the composite outcome. We used a modified version of the Newcastle-Ottawa Scale to assess the quality of each article. We screened 865 citations and identified nine articles that met our inclusion criteria. The majority of studies reported positive associations between maternal use of weight loss products and birth defects (overall and NTDs). However, there were few significant associations and there was considerable heterogeneity in the specific exposures assessed across the nine studies. Our systematic review of weight loss products and NTDs indicates that the literature on this topic is sparse. Because several studies reported modest, positive associations between risk and use of weight loss products, additional studies are warranted. Birth Defects Research 110:48-55, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Periconceptional nutrient intakes and risks of neural tube defects in California.

PubMed

Carmichael, Suzan L; Yang, Wei; Shaw, Gary M

2010-08-01

This study investigated the association of neural tube defects (NTDs) with maternal periconceptional intake of folic acid-containing supplements and dietary nutrients, including folate, among deliveries that occurred after folic acid fortification in selected California counties. The population-based case-control study included fetuses and live born infants with spina bifida (189) or anencephaly (141) and 625 nonmalformed, live born controls delivered from 1999 to 2003. Mothers reported supplement use during telephone interviews, which included a 107-item food frequency questionnaire. For dietary nutrients, intakes <25th, 25th to <75th (reference), and > or =75th percentile were compared, based on control distributions. After adjustment for potential confounders, any versus no supplement intake resulted in ORs of 0.8 (95% CI, 0.5-1.3) for anencephaly and 0.8 (95% CI, 0.6-1.2) for spina bifida. After stratification by maternal intake of vitamin supplements, most factors in the glycemic pathway were not associated with either NTD, with the exception of low levels of fructose and glucose that were significantly associated with anencephaly. Some nutrients that contribute to one-carbon metabolism showed lowered risks (folate, riboflavin, vitamins B(6) and B(12)); others did not (choline, methionine, zinc). Antioxidant nutrients tended to be associated with lowered risks (vitamins C, E, A, beta-carotene, lutein). Mothers' intake of vitamin supplements was modestly if at all associated with a lowered risk of NTDs. Dietary intake of several nutrients contributing to one-carbon metabolism and oxidative stress were associated with reduced NTD risk.

Neural Tube Defects and Maternal Folate Intake Among Pregnancies Conceived After Folic Acid Fortification in the United States

PubMed Central

Mosley, Bridget S.; Cleves, Mario A.; Siega-Riz, Anna Maria; Shaw, Gary M.; Canfield, Mark A.; Waller, D. Kim; Werler, Martha M.

2009-01-01

Rates of neural tube defects have decreased since folic acid fortification of the food supply in the United States. The authors’ objective was to evaluate the associations between neural tube defects and maternal folic acid intake among pregnancies conceived after fortification. This is a multicenter, case-control study that uses data from the National Birth Defects Prevention Study, 1998–2003. Logistic regression was used to compute crude and adjusted odds ratios between cases and controls assessing maternal periconceptional use of folic acid and intake of dietary folic acid. Among 180 anencephalic cases, 385 spina bifida cases, and 3, 963 controls, 21.1%, 25.2%, and 26.1%, respectively, reported periconceptional use of folic acid supplements. Periconceptional supplement use did not reduce the risk of having a pregnancy affected by a neural tube defect. Maternal intake of dietary folate was not significantly associated with neural tube defects. In this study conducted among pregnancies conceived after mandatory folic acid fortification, the authors found little evidence of an association between neural tube defects and maternal folic acid intake. A possible explanation is that folic acid fortification reduced the occurrence of folic acid-sensitive neural tube defects. Further investigation is warranted to possibly identify women who remain at increased risk of preventable neural tube defects. PMID:18953063

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.

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.

Survival and Morbidity Outcomes of Very Low Birth Weight Infants with Down Syndrome

PubMed Central

Boghossian, Nansi S.; Hansen, Nellie I.; Bell, Edward F.; Stoll, Barbara J.; Murray, Jeffrey C.; Laptook, Abbot R.; Shankaran, Seetha; Walsh, Michele C.; Das, Abhik; Higgins, Rosemary D.

2010-01-01

OBJECTIVE Individuals with Down syndrome (DS) are at increased risk of several morbidities with lifelong health consequences. Little is known about mortality or morbidity risks in early infancy among very-low-birth-weight (VLBW) infants with DS. Our objective was to compare survival and neonatal morbidities between VLBW infants with DS and VLBW infants with other non-DS chromosomal anomalies, other non-chromosomal birth defects, and VLBW infants without major birth defects. METHODS Data were collected prospectively for infants weighing 401-1500 grams born and/or cared for at one of the study centers participating in the NICHD Neonatal Research Network from 1994 through 2008. Risk of death and morbidities including patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD), were compared between VLBW infants with DS and infants in the other groups. RESULTS Infants with DS were at increased risk of death (adjusted relative risk [RR] 2.47, 95% confidence interval [CI] 2.00-3.07), PDA, NEC, LOS, and BPD relative to infants with no birth defects. Decreased risk of death (RR 0.40, 95% CI 0.31-0.52) and increased risks of NEC and LOS were observed when comparing infants with DS to infants with other non-DS chromosomal anomalies. Relative to infants with non-chromosomal birth defects, infants with DS were at increased risk of PDA and NEC. CONCLUSION The increased risk of morbidities among VLBW infants with DS provides useful information for counseling parents and for caretakers in anticipating the need for enhanced surveillance for prevention of these morbidities. PMID:21098157

Blood folate concentrations among women of childbearing age by race/ethnicity and acculturation, NHANES 2001-2010.

PubMed

Marchetta, Claire M; Hamner, Heather C

2016-01-01

Hispanic women have higher rates of neural tube defects and report lower total folic acid intakes than non-Hispanic white (NHW) women. Total folic acid intake, which is associated with neural tube defect risk reduction, has been found to vary by acculturation factors (i.e. language preference, country of origin, or time spent in the United States) among Hispanic women. It is unknown whether this same association is present for blood folate status. The objective of this research was to assess the differences in serum and red blood cell (RBC) folate concentrations between NHW women and Mexican American (MA) women and among MA women by acculturation factors. Cross-sectional data from the 2001-2010 National Health and Nutrition Examination Survey (NHANES) were used to investigate how blood folate concentrations differ among NHW or MA women of childbearing age. The impact of folic acid supplement use on blood folate concentrations was also examined. MA women with lower acculturation factors had lower serum and RBC folate concentrations compared with NHW women and to their more acculturated MA counterparts. Consuming a folic acid supplement can minimize these disparities, but MA women, especially lower acculturated MA women, were less likely to report using supplements. Public health efforts to increase blood folate concentrations among MA women should consider acculturation factors when identifying appropriate interventions. © 2014 John Wiley & Sons Ltd.

Effect of maternal age and cardiac disease severity on outcome of pregnancy in women with congenital heart disease.

PubMed

Furenäs, Eva; Eriksson, Peter; Wennerholm, Ulla-Britt; Dellborg, Mikael

2017-09-15

There is an increasing prevalence of women with congenital heart defects reaching childbearing age. In western countries women tend to give birth at a higher age compared to some decades ago. We evaluated the CARdiac disease in PREGnancy (CARPREG) and modified World Health Organization (mWHO) risk classifications for cardiac complications during pregnancies in women with congenital heart defects and analyzed the impact of age on risk of obstetric and fetal outcome. A single-center observational study of cardiac, obstetric, and neonatal complications with data from cardiac and obstetric records of pregnancies in women with congenital heart disease. Outcomes of 496 pregnancies in 232 women, including induced abortion, miscarriage, stillbirth, and live birth were analyzed regarding complications, maternal age, mode of delivery, and two risk classifications: CARPREG and mWHO. There were 28 induced abortions, 59 fetal loss, 409 deliveries with 412 neonates. Cardiac (14%), obstetric (14%), and neonatal (15%) complications were noted, including one maternal death and five stillbirths. The rate of cesarean section was 19%. Age above 35years was of borderline importance for cardiac complications (p=0.054) and was not a significant additional risk factor for obstetric or neonatal complications. Both risk classifications had moderate clinical utility, with area under the curve (AUC) 0.71 for CARPREG and 0.65 for mWHO on cardiac complications. Pregnancy complications in women with congenital heart disease are common but severe complications are rare. Advanced maternal age does not seem to affect complication rate. Existing risk classification systems are insufficient in predicting complications. Copyright © 2017 Elsevier B.V. All rights reserved.

Interaction between the SLC19A1 gene and maternal first trimester fever on offspring neural tube defects.

PubMed

Pei, Lijun; Zhu, Huiping; Ye, Rongwei; Wu, Jilei; Liu, Jianmeng; Ren, Aiguo; Li, Zhiwen; Zheng, Xiaoying

2015-01-01

Many studies have indicated that the reduced folate carrier gene (SLC19A1) is associated with an increased risk of neural tube defects (NTDs). However, the interaction between the SLC19A1 gene variant and maternal fever exposure and NTD risk remains unknown. The aim of this study was to investigate whether the risk for NTDs was influenced by the interactions between the SLC19A1 (rs1051266) variant and maternal first trimester fever. We investigated the potential interaction between maternal first trimester fever and maternal or offspring SLC19A1 polymorphism through a population-based case-control study. One hundred and four nuclear families with NTDs and 100 control families with nonmal newborns were included in the study. SLC19A1 polymorphism was determined using polymerase chain reaction-restricted fragment length polymorphism. Mothers who had the GG/GA genotype and first trimester fever had an elevated risk of NTDs (adjusted odds ratio, 11.73; 95% confidence interval, 3.02-45.58) as compared to absence of maternal first trimester fever and AA genotype after adjusting for maternal education, paternal education, and age, and had a significant interactive coefficient (γ = 3.17) between maternal GG/GA genotype and first trimester fever. However, there was no interaction between offspring's GG/GA genotype and maternal first trimester fever (the interactive coefficient γ = 0.97) after adjusting for confounding factors. Our findings suggested that the risk of NTDs was potentially influenced by a gene-environment interaction between maternal SLC19A1 rs1051266 GG/GA genotype and first trimester fever. Maternal GG/GA genotype may strengthen the effect of maternal fever exposure on NTD risk in this Chinese population. © 2014 Wiley Periodicals, Inc.

Birth defects in relation to Bendectin use in pregnancy. II. Pyloric stenosis.

PubMed

Mitchell, A A; Schwingl, P J; Rosenberg, L; Louik, C; Shapiro, S

1983-12-01

To test the hypothesis that the use of Bendectin in pregnancy increases the risk of pyloric stenosis, we determined rates of antenatal Bendectin exposure among 325 infants with pyloric stenosis and among two control groups comprising infants with other defects; one consisted of 3,153 infants with other conditions, and the other, a subset of that group, consisted of 724 infants with defects that may have had their origins at any time in pregnancy. Comparisons between the cases and the two control series yielded estimated relative risks of 0.9 (95% confidence interval, 0.6 to 1.2) and 1.0 (0.7 to 1.4), respectively. The findings from this large case-control study suggest that Bendectin does not increase the risk of pyloric stenosis.

Active Learning in Neuroscience: A Manipulative to Simulate Visual Field Defects

ERIC Educational Resources Information Center

Li, Andrew Yue-Lin; Carvalho, Helena

2016-01-01

Prevalent in 20-57% of stroke patients, visual field defects have been shown to impact quality of life. Studies have shown increased risk of falling, ambulatory difficulties, impaired reading ability, and feelings of panic in crowded or unfamiliar places in patients with visual field defects. Rehabilitation, independence, and mental health may…

Maternal Residential Exposure to Agricultural Pesticides and Birth Defects in a 2003 to 2005 North Carolina Birth Cohort

EPA Science Inventory

Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects. We conducted a case-control study to estimate the associations between a residence-based metric of agr...

Ceramic Defects in Metal-Ceramic Fixed Dental Prostheses Made from Co-Cr and Au-Pt Alloys: A Retrospective Study.

PubMed

Mikeli, Aikaterini; Boening, Klaus W; Lißke, Benjamin

2015-01-01

Ceramic defects in porcelain-fused-to-metal (PFM) restorations may depend on framework alloy type. This study assessed ceramic defects on cobalt-chromium- (Co-Cr-) and gold-platinum- (Au-Pt-) based PFM restorations. In this study, 147 Co-Cr-based and 168 Au-Pt-based PFM restorations inserted between 1998 and 2010 (139 patients) were examined for ceramic defects. Detected defects were assigned to three groups according to clinical defect relevance. Ceramic defect rates (Co-Cr-based: 12.9%; Au-Pt-based: 7.2%) revealed no significant difference but a strong statistical trend (U test, P = .082). Most defects were of little clinical relevance. Co-Cr PFM restorations may be at higher risk for ceramic defects compared to Au-Pt-based restorations.

A discriminant analysis prediction model of non-syndromic cleft lip with or without cleft palate based on risk factors.

PubMed

Li, Huixia; Luo, Miyang; Luo, Jiayou; Zheng, Jianfei; Zeng, Rong; Du, Qiyun; Fang, Junqun; Ouyang, Na

2016-11-23

A risk prediction model of non-syndromic cleft lip with or without cleft palate (NSCL/P) was established by a discriminant analysis to predict the individual risk of NSCL/P in pregnant women. A hospital-based case-control study was conducted with 113 cases of NSCL/P and 226 controls without NSCL/P. The cases and the controls were obtained from 52 birth defects' surveillance hospitals in Hunan Province, China. A questionnaire was administered in person to collect the variables relevant to NSCL/P by face to face interviews. Logistic regression models were used to analyze the influencing factors of NSCL/P, and a stepwise Fisher discriminant analysis was subsequently used to construct the prediction model. In the univariate analysis, 13 influencing factors were related to NSCL/P, of which the following 8 influencing factors as predictors determined the discriminant prediction model: family income, maternal occupational hazards exposure, premarital medical examination, housing renovation, milk/soymilk intake in the first trimester of pregnancy, paternal occupational hazards exposure, paternal strong tea drinking, and family history of NSCL/P. The model had statistical significance (lambda = 0.772, chi-square = 86.044, df = 8, P < 0.001). Self-verification showed that 83.8 % of the participants were correctly predicted to be NSCL/P cases or controls with a sensitivity of 74.3 % and a specificity of 88.5 %. The area under the receiver operating characteristic curve (AUC) was 0.846. The prediction model that was established using the risk factors of NSCL/P can be useful for predicting the risk of NSCL/P. Further research is needed to improve the model, and confirm the validity and reliability of the model.

Genetic Determinants of Parkinson's Disease: Can They Help to Stratify the Patients Based on the Underlying Molecular Defect?

PubMed Central

Redenšek, Sara; Trošt, Maja; Dolžan, Vita

2017-01-01

Parkinson's disease (PD) is a sporadic progressive neurodegenerative brain disorder with a relatively strong genetic background. We have reviewed the current literature about the genetic factors that could be indicative of pathophysiological pathways of PD and their applications in everyday clinical practice. Information on novel risk genes is coming from several genome-wide association studies (GWASs) and their meta-analyses. GWASs that have been performed so far enabled the identification of 24 loci as PD risk factors. These loci take part in numerous cellular processes that may contribute to PD pathology: protein aggregation, protein, and membrane trafficking, lysosomal autophagy, immune response, synaptic function, endocytosis, inflammation, and metabolic pathways are among the most important ones. The identified single nucleotide polymorphisms are usually located in the non-coding regions and their functionality remains to be determined, although they presumably influence gene expression. It is important to be aware of a very low contribution of a single genetic risk factor to PD development; therefore, novel prognostic indices need to account for the cumulative nature of genetic risk factors. A better understanding of PD pathophysiology and its genetic background will help to elucidate the underlying pathological processes. Such knowledge may help physicians to recognize subjects with the highest risk for the development of PD, and provide an opportunity for the identification of novel potential targets for neuroprotective treatment. Moreover, it may enable stratification of the PD patients according to their genetic fingerprint to properly personalize their treatment as well as supportive measures. PMID:28239348

Ovarian Failure and Reproductive Outcomes After Childhood Cancer Treatment: Results From the Childhood Cancer Survivor Study

PubMed Central

Green, Daniel M.; Sklar, Charles A.; Boice, John D.; Mulvihill, John J.; Whitton, John A.; Stovall, Marilyn; Yasui, Yutaka

2009-01-01

These studies were undertaken to determine the effect, if any, of treatment for cancer diagnosed during childhood or adolescence on ovarian function and reproductive outcomes. We reviewed the frequency of acute ovarian failure, premature menopause, live birth, stillbirth, spontaneous and therapeutic abortion and birth defects in the participants in the Childhood Cancer Survivor Study (CCSS). Acute ovarian failure (AOF) occurred in 6.3% of eligible survivors. Exposure of the ovaries to high-dose radiation (especially over 10 Gy), alkylating agents and procarbazine, at older ages, were significant risk factors for AOF. Premature nonsurgical menopause (PM) occurred in 8% of participants versus 0.8% of siblings (rate ratio = 13.21; 95% CI, 3.26 to 53.51; P < .001). Risk factors for PM included attained age, exposure to increasing doses of radiation to the ovaries, increasing alkylating agent score, and a diagnosis of Hodgkin's lymphoma. One thousand two hundred twenty-seven male survivors reported they sired 2,323 pregnancies, and 1,915 female survivors reported 4,029 pregnancies. Offspring of women who received uterine radiation doses of more than 5 Gy were more likely to be small for gestational age (birthweight < 10 percentile for gestational age; 18.2% v 7.8%; odds ratio = 4.0; 95% CI, 1.6 to 9.8; P = .003). There were no differences in the proportion of offspring with simple malformations, cytogenetic syndromes, or single-gene defects. These studies demonstrated that women treated with pelvic irradiation and/or increasing alkylating agent doses were at risk for acute ovarian failure, premature menopause, and small-for-gestational-age offspring. There was no evidence for an increased risk of congenital malformations. Survivors should be generally reassured although some women have to consider their potentially shortened fertile life span in making educational and career choices. PMID:19364956

The XRCC1 Arg194Trp polymorphism is significantly associated with lung adenocarcinoma: a case-control study in an Eastern European Caucasian group

PubMed Central

Cătană, Andreea; Pop, Monica; Hincu, Bianca Domokos; Pop, Ioan V; Petrişor, Felicia M; Porojan, Mihai D; Popp, Radu A

2015-01-01

DNA repair plays an important role in maintaining the integrity of the genome by repairing DNA damage induced by carcinogens. Certain genetic polymorphisms that occur in DNA-repair genes may affect the ability to repair DNA defects, and may represent a risk factor in carcinogenesis. The gene XRCC1 is involved in DNA repair. The purpose of our study was to investigate the association between XRCC1 Arg194Trp and Arg399Gln polymorphisms and the risk of lung cancer in a Romanian population. We recruited 222 healthy controls and 102 patients with lung cancer. Genotypes were determined by multiplex polymerase chain-reaction restriction fragment-length polymorphism. Statistical analysis (odds ratio, recessive model) revealed an increased risk for lung cancer for the homozygous 194Trp genotype (χ2=0.186, odds ratio 10.667, 95% confidence interval 1.309–86.933; P=0.007). Also, we found an association between the 194Trp allele and women with lung adenocarcinoma. In conclusion, the results of the study place the XRCC1 Arg194Trp polymorphism among independent risk factors for developing lung cancer. PMID:26664136

The XRCC1 Arg194Trp polymorphism is significantly associated with lung adenocarcinoma: a case-control study in an Eastern European Caucasian group.

PubMed

Cătană, Andreea; Pop, Monica; Hincu, Bianca Domokos; Pop, Ioan V; Petrişor, Felicia M; Porojan, Mihai D; Popp, Radu A

2015-01-01

DNA repair plays an important role in maintaining the integrity of the genome by repairing DNA damage induced by carcinogens. Certain genetic polymorphisms that occur in DNA-repair genes may affect the ability to repair DNA defects, and may represent a risk factor in carcinogenesis. The gene XRCC1 is involved in DNA repair. The purpose of our study was to investigate the association between XRCC1 Arg194Trp and Arg399Gln polymorphisms and the risk of lung cancer in a Romanian population. We recruited 222 healthy controls and 102 patients with lung cancer. Genotypes were determined by multiplex polymerase chain-reaction restriction fragment-length polymorphism. Statistical analysis (odds ratio, recessive model) revealed an increased risk for lung cancer for the homozygous 194Trp genotype (χ (2)=0.186, odds ratio 10.667, 95% confidence interval 1.309-86.933; P=0.007). Also, we found an association between the 194Trp allele and women with lung adenocarcinoma. In conclusion, the results of the study place the XRCC1 Arg194Trp polymorphism among independent risk factors for developing lung cancer.

Liability for Personal Injury Caused by Defective Medical Computer Programs

PubMed Central

Brannigan, Vincent M.

1980-01-01

Defective medical computer programs can cause personal injury. Financial responsibility for the injury under tort law will turn on several factors: whether the program is a product or a service, what types of defect exist in the product, and who produced the program. The factors involved in making these decisions are complex, but knowledge of the relevant issues can assist computer personnel in avoiding liability.

Haplotype-based gene-gene interaction of bone morphogenetic protein 4 and interferon regulatory factor 6 in the etiology of non-syndromic cleft lip with or without cleft palate in a Chilean population.

PubMed

Blanco, Rafael; Colombo, Alicia; Pardo, Rosa; Suazo, José

2017-04-01

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans, the etiology of which can be dependent on the interactions of multiple genes. We previously reported haplotype associations for polymorphic variants of interferon regulatory factor 6 (IRF6), msh homeobox 1 (MSX1), bone morphogenetic protein 4 (BMP4), and transforming growth factor beta 3 (TGFB3) in Chile. Here, we analyzed the haplotype-based gene-gene interaction for markers of these genes and NSCL/P risk in the Chilean population. We genotyped 15 single nucleoptide polymorphisms (SNPs) in 152 Chilean patients and 164 controls. Linkage disequilibrium (LD) blocks were determined using the Haploview software, and phase reconstruction was performed by the Phase program. Haplotype-based interactions were evaluated using the multifactor dimensionality reduction (MDR) method. We detected two LD blocks composed of two SNPs from BMP4 (Block 1) and three SNPs from IRF6 (Block 2). Although MDR showed no statistical significance for the global interaction model involving these blocks, we found four combinations conferring a statistically significantly increased NSCL/P risk (Block 1-Block 2): T-T/T-G C-G-T/G-A-T; T-T/T-G C-G-C/C-G-C; T-T/T-G G-A-T/G-A-T; and T-T/C-G G-A-T/G-A-T. These findings may reflect the presence of a genomic region containing potential causal variants interacting in the etiology of NSCL/P and may contribute to disentangling the complex etiology of this birth defect. © 2017 Eur J Oral Sci.

Cats, frogs, and snakes: early concepts of neural tube defects.

PubMed

Obladen, Michael

2011-11-01

Disturbed neurulation fascinated scientists of all times. In Egypt, anencephalic infants were venerated as animal-headed gods. Roman law required them to be killed. The medieval world held the mother responsible, either because of assumed imagination or "miswatching," or because of suspected intercourse with animals or devils. Modern embryology and teratology began with the use of the microscope by Malpighi in 1672. Details of neural tube closure were described by Koelliker in 1861 and by His in 1874. From 1822, genetic disease and familial recurrence due to insufficient nutrition were discerned and lower social class identified as a risk factor. It took a century to define the malnutrition as insufficient folate intake. The mandatory supplementation of folate in staple foods successfully reduced the incidence of neural tube defects in the United States, Australia, Canada, and Chile, but it was not adopted by most European countries.

[NUTRITIONAL STATUS ASSESSMENT IN PATIENTS WITH CYSTIC FIBROSIS].

PubMed

Lambe, Cécile; Mallet, Pascale; Bailly, Céline; Sermet-Gaudelus, Isabelle

2015-10-01

Prognosis of cystic fibrosis has been largely modified over the past 30 years. Optimization of nutrition is one of the most important contributing factors of this improvement. Nutritional defect result from the conjunction of loss of calories, maldigestion, hypercatabolism and insufficient intake. Pancreatic opotherapy and ADEK vitamin administration is mandatory in pancreatic insufficient patients. Nutritional status must be evaluated at each clinics to detect nutritional defect as early as possible. Nutritional intake must be hypercaloric, normalipidic and adapted to the tastes of the patient. The clinician must be aware of at risk nutritional period: first year of life, puberty, infectious exacerbation, respiratory worsening and diabetes, In neonatal screened babies, recovery of birth weight percentile must be targeted at 6 months, and for the height must be in accordance to genetic height at 2 years. In all cases it is mandatory to treat denutrition by oral supplementation and if necessay enteral nutrition.

Environmental insults: critical triggers for amyotrophic lateral sclerosis.

PubMed

Yu, Bing; Pamphlett, Roger

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by a rapid loss of lower and upper motor neurons. As a complex disease, the ageing process and complicated gene-environment interactions are involved in the majority of cases. Significant advances have been made in unravelling the genetic susceptibility to ALS with massively parallel sequencing technologies, while environmental insults remain a suspected but largely unexplored source of risk. Several studies applying the strategy of Mendelian randomisation have strengthened the link between environmental insults and ALS, but none so far has proved conclusive. We propose a new ALS model which links the current knowledge of genetic factors, ageing and environmental insults. This model provides a mechanism as to how ALS is initiated, with environmental insults playing a critical role. The available evidence has suggested that inherited defect(s) could cause mitochondrial dysfunction, which would establish the primary susceptibility to ALS. Further study of the underlying mechanism may shed light on ALS pathogenesis. Environmental insults are a critical trigger for ALS, particularly in the aged individuals with other toxicant susceptible genes. The identification of ALS triggers could lead to preventive strategies for those individuals at risk.

Instability of total hip replacement: A clinical study and determination of its risk factors.

PubMed

Ezquerra-Herrando, L; Seral-García, B; Quilez, M P; Pérez, M A; Albareda-Albareda, J

2015-01-01

To determine the risk factors associated with prosthetic dislocation and simulate a finite element model to determine the safe range of movement of various inclination and anteversion cup positions. Retrospective Case Control study with 46 dislocated patients from 1994 to 2011. 83 randomly selected patients. Dislocation risk factors described in the literature were collected. A prosthetic model was simulated using finite elements with 28, 32, 36 mm heads, and a 52 mm cup. Acetabular position was 25°, 40°, and 60° tilt and with 0°, 15° and 25° anteversion. In extension of 0° and flexion of 90°, internal and external rotation was applied to analyze the range of movement, maximum resisting moment, and stress distribution in the acetabulum to impingement and dislocation. There was greater dislocation in older patients (p=0.002). Higher dislocation in fractures than in osteoarthritis (p=0.001). Less anteversion in dislocated patients (p=0.043). Longer femoral neck in dislocated patients (p=0.002). Finite element model: lower dislocation when there is more anteversion, tilt and bigger femoral heads. Advanced age and fractures are the major risk factors for dislocation. "Safe zone" of movement for dislocation avoidance is 40°-60° tilt and 15°-25° anteversion. Both the defect and excess of soft tissue tension predispose to dislocation. Bigger femoral heads are more stable. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

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 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.

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.

Antihistamine Use in Early Pregnancy and Risk of Birth Defects

PubMed Central

Li, Qian; Mitchell, Allen A.; Werler, Martha M.; Yau, Wai-Ping; Hernández-Díaz, Sonia

2014-01-01

Background Several studies have reported an association between use of specific antihistamines in early pregnancy and certain specific birth defects. Objective To test 16 previously-hypothesized associations between specific antihistamines and specific birth defects, and identify possible new associations. Methods We used 1998-2010 data from the Slone Epidemiology Center Birth Defects Study, a multicenter case-control surveillance program of birth defects in North America. Mothers were interviewed within six months of delivery about demographic, reproductive, medical, and behavioral factors, and details on use of prescription and non-prescription medications. We compared 1st trimester exposure to specific antihistamines between 13,213 infants with specific malformations and 6,982 non-malformed controls, using conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for potential confounders, including indication for use. Results Overall, 13.7% of controls were exposed to antihistamines during the 1st trimester. The most commonly-used medications were diphenhydramine (4.2%), loratadine (3.1%), doxylamine (1.9%), and chlorpheniramine (1.7%). Where estimates were stable, none supported the previously-hypothesized associations. Among over 100 exploratory comparisons of other specific antihistamine/defect pairs, 14 had ORs ≥1.5 of which 6 had 95% CI bounds excluding 1.0 before but not after adjustment for multiple comparisons. Conclusion Our findings do not provide meaningful support for previously-posited associations between antihistamines and major congenital anomalies; at the same time, we identified associations that had not been previously suggested. We suspect that previous associations may be chance findings in the context of multiple comparisons, a situation which may also apply to our new findings. PMID:24565715

Sex prevalence of major congenital anomalies in the United Kingdom: a national population-based study and international comparison meta-analysis.

PubMed

Sokal, Rachel; Tata, Laila J; Fleming, Kate M

2014-02-01

The aim of this study was to assess sex differences in major congenital anomaly (CA) diagnoses within a national population sample; to examine the influence of sociodemographic and maternal factors on these risks; and to conduct a meta-analysis using estimates from other population-based studies. We conducted a population-based study in a United Kingdom research database of prospectively collected primary care data (The Health Improvement Network) including children born 1990 to 2009 (n = 794,169) and identified major CA diagnoses using EUROCAT (European Surveillance of Congenital Anomalies) classification. Prevalence ratios (PR) were used to estimate the risk of CA in males compared with females for any CA, system-specific subgroups and specific CA diagnoses. In a subpopulation of children whose medical records were linked to their mothers', we assessed the effect of adjusting for sociodemographic and maternal factors on sex odds ratios. PRs were pooled with measures from previously published studies. The prevalence of any CA was 307/10,000 in males (95% CI, 302-313) and 243/10,000 in females (95% CI, 238-248). Overall the risk of any CA was 26% greater in males (PR (male: female) 1.26, 95% CI, 1.23-1.30) however there was considerable variation across specific diagnoses. The magnitude and direction of risk did not change for any specific CA upon adjustment for sociodemographic and maternal factors. Our PRs were highly consistent with those from previous studies. The overall risk of CA is greater in males than females, although this masked substantial variation by specific diagnoses. Sociodemographic and maternal factors do not appear to affect these risks. Copyright © 2014 The Authors. Birth Defects Research (Part A) published by Wiley Periodicals, Inc.

Beta-glucans in the treatment of diabetes and associated cardiovascular risks

PubMed Central

Chen, Jiezhong; Raymond, Kenneth

2008-01-01

Diabetes mellitus is characterized by high blood glucose level with typical manifestations of thirst, polyuria, polydipsia, and weight loss. It is caused by defects in insulin-mediated signal pathways, resulting in decreased glucose transportation from blood into muscle and fat cells. The major risk is vascular injury leading to heart disease, which is accelerated by increased lipid levels and hypertension. Management of diabetes includes: control of blood glucose level and lipids; and reduction of hypertension. Dietary intake of beta-glucans has been shown to reduce all these risk factors to benefit the treatment of diabetes and associated complications. In addition, beta-glucans also promote wound healing and alleviate ischemic heart injury. However, the mechanisms behind the effect of beta-glucans on diabetes and associated complications need to be further studied using pure beta-glucan. PMID:19337540

Cardiovascular risk in Turner syndrome.

PubMed

Donato, Beatriz; Ferreira, Maria João

2018-06-01

Turner syndrome is a relatively common genetic disorder of female development, characterized by partial or complete absence of an X chromosome, with a variable clinical presentation. Congenital or acquired cardiovascular disease is highly prevalent and a major cause of early death in this syndrome. The most feared complication is aortic dissection, which can occur at a very young age and requires careful assessment of its risk factors. A systematic literature search identified sixty relevant publications. These were reviewed with regard to the increased risk of cardiovascular disease in women with Turner syndrome, especially in pregnancy. The most common congenital cardiovascular defects are presented and illustrated with appropriate iconography. The current recommendations regarding the screening and monitoring of cardiovascular disease in these patients are discussed. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Scanning electron microscopy fractography analysis of fractured hollow implants.

PubMed

Sbordone, Ludovico; Traini, Tonino; Caputi, Sergio; Scarano, Antonio; Bortolaia, Claudia; Piattelli, Adriano

2010-01-01

Fracture of the implant is one of the possible complications affecting dental implants; it is a rare event but of great clinical relevance. The aim of the present study was to perform a scanning electron microscopy (SEM) fractography evaluation of 7 International Team for oral Implantology (ITI) hollow implants removed because of fracture. The most common clinical risk factors, such as malocclusion, bruxism, and cantilevers on the prosthesis, were absent. Seven fractured ITI hollow implants were retrieved from 5 patients and were analyzed with the use of SEM. SEM analysis showed typical signs of a cleavage-type fracture. Fractures could be due to an association of multiple factors such as fatigue, inner defects, material electrochemical problems, and tensocorrosion.

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…

Recurrence of breech presentation in consecutive pregnancies

PubMed Central

Ford, JB; Roberts, CL; Nassar, N; Giles, W; Morris, JM

2010-01-01

Objective To investigate the recurrence risk of breech presentation at term, and to assess the risk factors that contribute to its recurrence. Design Cohort study. Setting New South Wales, Australia. Population Women with their first two (n = 113 854) and first three (n = 21 690) consecutive singleton term pregnancies, in the period 1994–2002. Methods Descriptive statistics including rates, relative risks and adjusted relative risks, as determined from logistic regression and Poisson analyses. Main outcome measures Rates and risks of occurrence and recurrence of breech presentation at birth in each pregnancy, and maternal and infant risk factors associated with breech recurrence. Results First-time breech presentation at term occurred in 4.2% of first pregnancy deliveries, 2.2% of second pregnancies and 1.9% of third pregnancies. The rate of breech recurrence in a second consecutive pregnancy was 9.9%, and in a third consecutive pregnancy (after two prior breech deliveries) was 27.5%. The relative risk of breech recurrence in a second pregnancy was 3.2 (95% CI 2.8–3.6), and in a third consecutive breech pregnancy was 13.9 (95% CI 8.8–22.1). First pregnancy factors associated with recurrence included placenta praevia [adjusted relative risk (aRR) 2.2; 95% CI 1.3–3.7], maternal diabetes (aRR 1.4; 95% CI 1.0–2.1) and a maternal age of ≥35 years (aRR 1.2; 95% CI 0.9–1.6). Second pregnancy factors included birth defects (aRR 2.5; 95% CI 1.4–4.2), placenta praevia (aRR 2.5; 95% CI 1.5–4.1) and a female infant (aRR 1.2; 95% CI 1.0–1.5). Conclusions The increased recurrence risk of breech presentations suggests that women with a history of breech delivery should be closely monitored in the latter stages of pregnancy. PMID:20482538

Collagen implants equipped with 'fish scale'-like nanoreservoirs of growth factors for bone regeneration.

PubMed

Eap, Sandy; Ferrand, Alice; Schiavi, Jessica; Keller, Laetitia; Kokten, Tunay; Fioretti, Florence; Mainard, Didier; Ladam, Guy; Benkirane-Jessel, Nadia

2014-01-01

Implants triggering rapid, robust and durable tissue regeneration are needed to shorten recovery times and decrease risks of postoperative complications for patients. Here, we describe active living collagen implants with highly promising bone regenerative properties. Bioactivity of the implants is obtained through the protective and stabilizing layer-by-layer immobilization of a protein growth factor in association with a polysaccharide (chitosan), within the form of nanocontainers decorating the collagen nanofibers. All components of the implants are US FDA approved. From both in vitro and in vivo evaluations, the sophisticated strategy described here should enhance, at a reduced cost, the safety and efficacy of the therapeutic implants in terms of large bone defects repair compared with current simplistic approaches based on the soaking of the implants with protein growth factor.

Planar cell polarity pathway genes and risk for spina bifida.

PubMed

Wen, Shu; Zhu, Huiping; Lu, Wei; Mitchell, Laura E; Shaw, Gary M; Lammer, Edward J; Finnell, Richard H

2010-02-01

Spina bifida, a neural tube closure defect (NTD) involving the posterior portion of what will ultimately give rise to the spinal cord, is one of the most common and serious birth defects. The etiology of spina bifida is thought to be multi-factorial and involve multiple interacting genes and environmental factors. The causes of this congenital malformation remain largely unknown. However, several candidate genes for spina bifida have been identified in lower vertebrates, including the planar cell polarity (PCP) genes. We used data from a case-control study conducted in California to evaluate the association between variation within several key PCP genes and the risk of spina bifida. The PCP genes included in this study were the human homologs of the Xenopus genes Flamingo, Strabismus, Prickle, Dishevelled, and Scrib, two of the homologs of Xenopus Wnt genes, WNT5A and WNT11, and two of the homologs of Xenopus Frizzled, FZD3 and FZD6. None of the 172 SNPs that were evaluated were significantly associated with spina bifida in any racial/ethnic group after correction for multiple testing. However, several SNPs in the PRICKLE2 gene had unadjusted P-value <0.01. In conclusion, our results, though largely negative, suggest that the PRICKLE2 gene may potentially modify the risk of spina bifida and deserves further investigation. Copyright 2010 Wiley-Liss, Inc.

[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.

[Health consequences of passive smoking].

PubMed

Haustein, K O

2000-01-01

Environmental tobacco smoking (ETS) represents a main risk factor for the generation of diseases of the respiratory tract and of the cardiovascular system in spite of opposite assertions. ETS enhances the risk of lung cancer by a factor of 2-3. New born and small children (< 2 years of life) are at high risk if they live within this period of time in a household together with a maternal more than fraternal smoking. Endothelial cells of the blood vessels were already damaged during the first month of life of passive smoking children, and these defects can be measured during the first decade of life. ETS over a period of more than ten years changes the intima/media ratio by enhancing the thickness of the vessel wall. In addition, poor health behaviour is seen in households of smokers because the behaviour of the parents is transferred to that of their children, and this behaviour is the starting point of further health risks and damages. The represented data should firstly lead to enhancing primary smoking prevention among children and young people, and secondly to organizing programs against ETS at the workplace and in public buildings and at last also in the private home. More than up to date, the non-smoker must be informed about the risks and damages of ETS.

Parental risk factors for oral clefts among Central Africans, Southeast Asians, and Central Americans.

PubMed

Figueiredo, Jane C; Ly, Stephanie; Magee, Kathleen S; Ihenacho, Ugonna; Baurley, James W; Sanchez-Lara, Pedro A; Brindopke, Frederick; Nguyen, Thi-Hai-Duc; Nguyen, Viet; Tangco, Maria Irene; Giron, Melissa; Abrahams, Tamlin; Jang, Grace; Vu, Annie; Zolfaghari, Emily; Yao, Caroline A; Foong, Athena; DeClerk, Yves A; Samet, Jonathan M; Magee, William

2015-10-01

Several lifestyle and environmental exposures have been suspected as risk factors for oral clefts, although few have been convincingly demonstrated. Studies across global diverse populations could offer additional insight given varying types and levels of exposures. We performed an international case-control study in the Democratic Republic of the Congo (133 cases, 301 controls), Vietnam (75 cases, 158 controls), the Philippines (102 cases, 152 controls), and Honduras (120 cases, 143 controls). Mothers were recruited from hospitals and their exposures were collected from interviewer-administered questionnaires. We used logistic regression modeling to estimate odds ratios (OR) and 95% confidence intervals (CI). Family history of clefts was strongly associated with increased risk (maternal: OR = 4.7; 95% CI, 3.0-7.2; paternal: OR = 10.5; 95% CI, 5.9-18.8; siblings: OR = 5.3; 95% CI, 1.4-19.9). Advanced maternal age (5 year OR = 1.2; 95% CI, 1.0-1.3), pregestational hypertension (OR = 2.6; 95% CI, 1.3-5.1), and gestational seizures (OR = 2.9; 95% CI, 1.1-7.4) were statistically significant risk factors. Lower maternal (secondary school OR = 1.6; 95% CI, 1.2-2.2; primary school OR = 2.4, 95% CI, 1.6-2.8) and paternal education (OR = 1.9; 95% CI, 1.4-2.5; and OR = 1.8; 95% CI, 1.1-2.9, respectively) and paternal tobacco smoking (OR = 1.5, 95% CI, 1.1-1.9) were associated with an increased risk. No other significant associations between maternal and paternal factors were found; some environmental factors including rural residency, indoor cooking with wood, chemicals and water source appeared to be associated with an increased risk in adjusted models. Our study represents one of the first international studies investigating risk factors for clefts among multiethnic underserved populations. Our findings suggest a multifactorial etiology including both maternal and paternal factors. © 2015 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc.

The effect of adhesive failure and defects on the stress distribution in all-ceramic crowns.

PubMed

Liu, Yonggang; Xu, Yuanzhi; Su, Bo; Arola, Dwayne; Zhang, Dongsheng

2018-05-29

To explore the effect of adhesive failure and defects between the crown and cement on the stress distribution within all-ceramic crowns and the corresponding risk of failure. An IPS e.max crown of lithium disilicate produced by CAD/CAM for a first mandibular molar was modeled using finite element analysis based on X-ray micro-CT scanned images. Predefined debonding states and interfacial defects between the crown and cement were simulated using the model. The first principal stress distribution of the crown and cement was analyzed under a vertical occlusal load of 600 N. A concept of failure risk was proposed to evaluate the crown. Stress concentrations in the crown were identified on the occlusal surface surrounding the region of loading, beneath the area of loading and at the margin of the interior surface. Stress concentrations in the cement were also evident at the boundary of the debonded areas. The lower surface of the crown is safe to sustain the 600 N vertical load, but the top surface of the cement would undergo cohesive failure. According to the evaluation of failure risk of the crown, the conditions of highest risk corresponded to the conditions with highest percentage of cement damage. The risk of failure is not only associated with debonding between the crown and cement, but also associated with its distribution. Debonding related defects and cementing defects are more deleterious to the interfacial stress than debonding itself. The axial wall plays a critical role in maintaining the principal tensile stress of the crown at an acceptable level. Copyright © 2018 Elsevier Ltd. All rights reserved.

Security Risks: Management and Mitigation in the Software Life Cycle

NASA Technical Reports Server (NTRS)

Gilliam, David P.

2004-01-01

A formal approach to managing and mitigating security risks in the software life cycle is requisite to developing software that has a higher degree of assurance that it is free of security defects which pose risk to the computing environment and the organization. Due to its criticality, security should be integrated as a formal approach in the software life cycle. Both a software security checklist and assessment tools should be incorporated into this life cycle process and integrated with a security risk assessment and mitigation tool. The current research at JPL addresses these areas through the development of a Sotfware Security Assessment Instrument (SSAI) and integrating it with a Defect Detection and Prevention (DDP) risk management tool.

Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease.

PubMed

Dumanski, Jan P; Lambert, Jean-Charles; Rasi, Chiara; Giedraitis, Vilmantas; Davies, Hanna; Grenier-Boley, Benjamin; Lindgren, Cecilia M; Campion, Dominique; Dufouil, Carole; Pasquier, Florence; Amouyel, Philippe; Lannfelt, Lars; Ingelsson, Martin; Kilander, Lena; Lind, Lars; Forsberg, Lars A

2016-06-02

Men have a shorter life expectancy compared with women but the underlying factor(s) are not clear. Late-onset, sporadic Alzheimer disease (AD) is a common and lethal neurodegenerative disorder and many germline inherited variants have been found to influence the risk of developing AD. Our previous results show that a fundamentally different genetic variant, i.e., lifetime-acquired loss of chromosome Y (LOY) in blood cells, is associated with all-cause mortality and an increased risk of non-hematological tumors and that LOY could be induced by tobacco smoking. We tested here a hypothesis that men with LOY are more susceptible to AD and show that LOY is associated with AD in three independent studies of different types. In a case-control study, males with AD diagnosis had higher degree of LOY mosaicism (adjusted odds ratio = 2.80, p = 0.0184, AD events = 606). Furthermore, in two prospective studies, men with LOY at blood sampling had greater risk for incident AD diagnosis during follow-up time (hazard ratio [HR] = 6.80, 95% confidence interval [95% CI] = 2.16-21.43, AD events = 140, p = 0.0011). Thus, LOY in blood is associated with risks of both AD and cancer, suggesting a role of LOY in blood cells on disease processes in other tissues, possibly via defective immunosurveillance. As a male-specific risk factor, LOY might explain why males on average live shorter lives than females. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

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.

Defective plastic infection-control barriers and faulty technique may cause PSP plate contamination used in digital intraoral radiography.

PubMed

Kuperstein, Arthur S

2012-09-01

Fifty-two disinfected photostimulable phosphor (PSP) plates in plastic barrier envelopes were evaluated for contamination following placement in 30 study participants. Forty-four plates were acceptable for use in the study. The risk factor was the abundant oropharyngeal microbial flora and its ability to breach infection-control barrier sheaths. The presence of bacterial colonies on an agar plate was used to determine bacterial contamination and the presence of any growth indicated failure of the barrier envelope. Before clinical placement of the plates, quality review of the PSP plates revealed defects in the integrity of 4 barrier envelopes most likely caused by forceps-related damage or failure to achieve a uniform seal during manufacturing. These defects allowed substantial contamination. Contamination also occurred as a result of failure to extract the PSP plate from the barrier envelope cleanly. Of the 44 barriers with no obvious signs of a defect, 3 produced bacterial growth following culture. The authors concluded that digital sensor sheathed in barrier envelopes remain a potential source of contamination. PSP plates must be disinfected between removal from a contaminated barrier envelope (used in a patient) and placement in a new barrier envelope. In addition, placement into the barrier envelope should ideally be carried out under aseptic conditions. Finally, the integrity of each sealed barrier envelope must be verified visually. Copyright © 2012. Published by Mosby, Inc. All rights reserved.

Birth Defects Research and Tracking

MedlinePlus

... least one month before getting pregnant and during early pregnancy lowers the risk of having a baby with ... 2017) Key Findings: Use of Pain Medicine During Early Pregnancy May Be Related To Birth Defects A study ...

Prevalence and risk factors for neurological disorders in children aged 6 months to 2 years in northern India.

PubMed

Kumar, Rashmi; Bhave, Anupama; Bhargava, Roli; Agarwal, Girdhar G

2013-04-01

To study prevalence and risk factors for neurological disorders--epilepsy, global developmental delay, and motor, vision, and hearing defects--in children aged 6 months to 2 years in northern India. A two-stage community survey for neurological disorders was conducted in rural and urban areas of Lucknow. After initial screening with a new instrument, the Lucknow Neurodevelopment Screen, screen positives and a random proportion of screen negatives were validated using predefined criteria. Prevalence was calculated by weighted estimates. Demographic, socio-economic, and medical risk factors were compared between validated children who were positive and negative for neurological disorders by univariate and logistic regression analysis. Of 4801 children screened (mean age [SD] 15.32mo [5.96]; 2542 males, 2259 females), 196 were positive; 190 screen positives and 269 screen negatives were validated. Prevalence of neurological disorders was 27.92 per 1000 (weighted 95% confidence interval 12.24-43.60). Significant risk factors (p≤0.01) for neurological disorders were higher age in months (p=0.010), lower mean number of appliances in the household (p=0.001), consanguineous marriage of parents (p=0.010), family history of neurological disorder (p=0.001), and infants born exceptionally small (parental description; p=0.009). On logistic regression, the final model included age (p=0.0193), number of appliances (p=0.0161), delayed cry at birth (p=0.0270), postneonatal meningoencephalitis (p=0.0549), and consanguinity (p=0.0801). Perinatal factors, lower socio-economic status, and consanguinity emerged as predictors of neurological disorders. These factors are largely modifiable. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.

Paroxysmal Nocturnal Hemoglobinuria is rare cause for thrombosis of the intra-abdominal veins in the ethnic Indian population - results from FLAER-based flowcytometry screening.

PubMed

Ahluwalia, Jasmina; Naseem, Shano; Sachdeva, Man Updesh Singh; Bose, Parveen; Bose, Sunil Kumar; Kumar, Narender; Thapa, Babu Ram; Varma, Neelam; Chawla, Yogesh Kumar

2014-01-01

Paroxysmal nocturnal hemoglobinuria (PNH) may present as cytopenia, hemolysis, or thrombosis at unusual sites including splanchnic vessels. Thrombosis of the portal veins and hepatic veins are associated with thrombophilic risk factors: deficiencies of protein C, protein S, and antithrombin, positivity for antiphospholipid antibodies, and factor V Leiden mutation. There is limited information regarding PNH presenting primarily as a thrombotic event. We prospectively screened 142 consecutive patients with intrabdominal thrombosis and 106 controls with fluorescently labeled inactive toxin aerolysin (FLAER)-based flowcytometry to assess the frequency of PNH as a thrombophilic risk factor in patients with intra-abdominal thrombosis. Granulocytes of patients and controls were screened with CD 24 and FLAER and monocytes with CD 14 and FLAER. Dual negativity of >1% events in both lineages was interpreted as a positive PNH clone. Screening for thrombophilia risk factors was carried out. Two (1.4%) cases had large PNH clones. RBC also demonstrated the PNH defect. Thrombophilia risk factors were as follows: deficiency of protein S, protein C, and antithrombin in 13.4%, 4.9%, and 2.1%, respectively, and positivity for anti-beta-2 glycoprotein 1, anticardiolipin antibodies, and lupus anticoagulant in 9.2%, 1.4%, and 0.7%, respectively. Factor V Leiden mutation was seen in 1.4% patients. PNH was uncommon in patients with intra-abdominal thrombosis in the ethnic Indian population. Despite low positivity, screening by flowcytometry for PNH is of value in this group of patients because it provides an opportunity to rapidly establish the diagnosis of this treatable disorder, which might otherwise be missed if the initial presentation is only thrombotic. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

7 CFR 52.808 - Freedom from defects.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Freedom from defects. 52.808 Section 52.808... Quality § 52.808 Freedom from defects. (a) General. The factor of freedom from defects refers to the degree of freedom from harmless extraneous material, mutilated cherries, and cherries blemished by scab...

Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors

PubMed Central

Kalaria, Raj N; Maestre, Gladys E; Arizaga, Raul; Friedland, Robert P; Galasko, Doug; Hall, Kathleen; Luchsinger, José A; Ogunniyi, Adesola; Perry, Elaine K; Potocnik, Felix; Prince, Martin; Stewart, Robert; Wimo, Anders; Zhang, Zhen-Xin; Antuono, Piero

2010-01-01

Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (≥5%) in certain Asian and Latin American countries, but consistently low (1–3%) in India and sub-Saharan Africa; Alzheimer's disease accounts for 60% whereas vascular dementia accounts for ∼30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE ε4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions. PMID:18667359

[Progress of Masquelet technique to repair bone defect].

PubMed

Yin, Qudong; Sun, Zhenzhong; Gu, Sanjun

2013-10-01

To summarize the progress of Masquelet technique to repair bone defect. The recent literature concerning the application of Masquelet technique to repair bone defect was extensively reviewed and summarized. Masquelet technique involves a two-step procedure. First, bone cement is used to fill the bone defect after a thorough debridement, and an induced membrane structure surrounding the spacer formed; then the bone cement is removed after 6-8 weeks, and rich cancellous bone is implanted into the induced membrane. Massive cortical bone defect is repaired by new bone forming and consolidation. Experiments show that the induced membrane has vascular system and is also rich in vascular endothelial growth factor, transforming growth factor beta1, bone morphogenetic protein 2, and bone progenitor cells, so it has osteoinductive property; satisfactory results have been achieved in clinical application of almost all parts of defects, various types of bone defect and massive defect up to 25 cm long. Compared with other repair methods, Masquelet technique has the advantages of reliable effect, easy to operate, few complications, low requirements for recipient site, and wide application. Masquelet technique is an effective method to repair bone defect and is suitable for various types of bone defect, especially for bone defects caused by infection and tumor resection.

[CLINICAL CHARACTERISTICS OF CONGENITAL HEART DISEASES ASSOCIATED WITH CONNECTIVE TISSUE DISPLASIA AT CHILDREN LIVING IN EAST REGION OF KAZAKHSTAN].

PubMed

Madiyeva, M; Rymbayeva, T

2017-11-01

The frequency of the combination of congenital heart defects (CHD) and connective tissue dysplasia remains poorly understood. And connective tissue dysplasia enhance severity the clinical of CHD. The aim of the study was to conduct a clinical and laboratory analysis of combinations of congenital heart defects and connective tissue dysplasia in children of Semey and to determine the risk for the development of these pathologies. The object of the study is the children of Semey (East Kazakhstan) aged 1-14 with congenital heart defects (CHD), with connective tissue dysplasia, healthy children and their mothers. Definition complex clinical and laboratory studies in children with CHD and connective tissue dysplasia, and their mothers. In children with CHD, the frequency of external and visceral signs of dysplasia was high. In 88.1% of cases in children with CHD was diagnosed 2-3 degrees of dysplasia. Was found difference in the microelement composition of blood serum and of hemostasis in children with CHD were expressed by hypofibrinogenemia, hypocalcemia, hypomagnesemia. Excess of the frequency of signs of dysplasia in mothers over the control group to consider dysplasia as a factor that influences the clinical of CHD.

Air pollution and limb defects: a matched-pairs case-control study in Taiwan.

PubMed

Lin, Yu-Ting; Lee, Yungling Leo; Jung, Chau-Ren; Jaakkola, Jouni J K; Hwang, Bing-Fang

2014-07-01

Air pollution influences the development of limb defects in animals. There is little epidemiologic evidence on the effect of prenatal air pollution exposure on the risk of limb defects. To assess the relations between exposure to ambient air pollutants and the risk of limb defects. We conducted a matched-pairs case-control study in Taiwan from 2001 through 2007. The case group consisted of 1687 limb defects and the control group was density-sampling matched one to ten based on the month and year of conception from 1510,064 live singleton newborns in 2001-2007. Adjusted conditional logistic regression models were used to estimate odds ratios per 10 ppb change for O3, NO2, 1 ppb change for SO2, 10 µg/m(3) change for PM10, and 100 ppb change for CO during the first trimester and first three gestational months. Of the specific limb defects, reduction deformities of limbs (adjusted OR=1.024, 95% CI: 1.000, 1.048) was associated with a 1 ppb increase in SO2 during weeks of 9-12 of gestation as well as the first trimester. Reduction deformities of limbs was also associated with a 10 ppb increase in O3 during weeks of 1-4 of gestation (adjusted OR=1.391, 95% CI: 1.064, 1.818) among preterm births. The present study provides evidence that exposure to outdoor air SO2 during the first trimester of pregnancy may increase the risk of limb defects. Exposure to O3 was associated with reduction deformities of limbs among preterm births. Similar levels of SO2 and O3 are encountered globally by large numbers of pregnant women. Copyright © 2014 Elsevier Inc. All rights reserved.

N-Acetylcysteine prevents congenital heart defects induced by pregestational diabetes

PubMed Central

2014-01-01

Background Pregestational diabetes is a major risk factor of congenital heart defects (CHDs). Glutathione is depleted and reactive oxygen species (ROS) production is elevated in diabetes. In the present study, we aimed to examine whether treatment with N-acetylcysteine (NAC), which increases glutathione synthesis and inhibits ROS production, prevents CHDs induced by pregestational diabetes. Methods Female mice were treated with streptozotocin (STZ) to induce pregestational diabetes prior to breeding with normal males to produce offspring. Some diabetic mice were treated with N-acetylcysteine (NAC) in drinking water from E0.5 to the end of gestation or harvesting of the embryos. CHDs were identified by histology. ROS levels, cell proliferation and gene expression in the fetal heart were analyzed. Results Our data show that pregestational diabetes resulted in CHDs in 58% of the offspring, including ventricular septal defect (VSD), atrial septal defect (ASD), atrioventricular septal defects (AVSD), transposition of great arteries (TGA), double outlet right ventricle (DORV) and tetralogy of Fallot (TOF). Treatment with NAC in drinking water in pregestational diabetic mice completely eliminated the incidence of AVSD, TGA, TOF and significantly diminished the incidence of ASD and VSD. Furthermore, pregestational diabetes increased ROS, impaired cell proliferation, and altered Gata4, Gata5 and Vegf-a expression in the fetal heart of diabetic offspring, which were all prevented by NAC treatment. Conclusions Treatment with NAC increases GSH levels, decreases ROS levels in the fetal heart and prevents the development of CHDs in the offspring of pregestational diabetes. Our study suggests that NAC may have therapeutic potential in the prevention of CHDs induced by pregestational diabetes. PMID:24533448

UDP-glucose Dehydrogenase Polymorphisms from Patients with Congenital Heart Valve Defects Disrupt Enzyme Stability and Quaternary Assembly*

PubMed Central

Hyde, Annastasia S.; Farmer, Erin L.; Easley, Katherine E.; van Lammeren, Kristy; Christoffels, Vincent M.; Barycki, Joseph J.; Bakkers, Jeroen; Simpson, Melanie A.

2012-01-01

Cardiac valve defects are a common congenital heart malformation and a significant clinical problem. Defining molecular factors in cardiac valve development has facilitated identification of underlying causes of valve malformation. Gene disruption in zebrafish revealed a critical role for UDP-glucose dehydrogenase (UGDH) in valve development, so this gene was screened for polymorphisms in a patient population suffering from cardiac valve defects. Two genetic substitutions were identified and predicted to encode missense mutations of arginine 141 to cysteine and glutamate 416 to aspartate, respectively. Using a zebrafish model of defective heart valve formation caused by morpholino oligonucleotide knockdown of UGDH, transcripts encoding the UGDH R141C or E416D mutant enzymes were unable to restore cardiac valve formation and could only partially rescue cardiac edema. Characterization of the mutant recombinant enzymes purified from Escherichia coli revealed modest alterations in the enzymatic activity of the mutants and a significant reduction in the half-life of enzyme activity at 37 °C. This reduction in activity could be propagated to the wild-type enzyme in a 1:1 mixed reaction. Furthermore, the quaternary structure of both mutants, normally hexameric, was destabilized to favor the dimeric species, and the intrinsic thermal stability of the R141C mutant was highly compromised. The results are consistent with the reduced function of both missense mutations significantly reducing the ability of UGDH to provide precursors for cardiac cushion formation, which is essential to subsequent valve formation. The identification of these polymorphisms in patient populations will help identify families genetically at risk for valve defects. PMID:22815472

Levels of PAH-DNA adducts in cord blood and cord tissue and the risk of fetal neural tube defects in a Chinese population.

PubMed

Yi, Deqing; Yuan, Yue; Jin, Lei; Zhou, Guodong; Zhu, Huiping; Finnell, Richard H; Ren, Aiguo

2015-01-01

Maternal exposure to polycyclic aromatic hydrocarbons (PAHs) has been shown to be associated with an elevated risk for neural tube defects (NTDs). In the human body, PAHs are bioactivated and the resultant reactive epoxides can covalently bind to DNA to form PAH-DNA adducts, which may, in turn, cause transcription errors, changes in gene expression or altered patterns of apoptosis. During critical developmental phases, these changes can result in abnormal morphogenesis. We aimed to examine the relationship between the levels of PAH-DNA adducts in cord blood and cord tissue and the risk of NTDs. From 2010 to 2012, 60 NTD cases and 60 healthy controls were recruited from a population-based birth defects surveillance system in five counties of Shanxi Province in Northern China, where the emission of PAHs remains one of the highest in the country and PAHs exposure is highly prevalent. PAH-DNA adducts in cord blood of 15 NTD cases and 15 control infants, and in cord tissue of 60 NTD cases and 60 control infants were measured using the (32)P-postlabeling method. PAH-DNA adduct levels in cord blood tend to be higher in the NTD group (28.5 per 10(8) nucleotides) compared with controls (19.7 per 10(8) nucleotides), although the difference was not statistically significant (P=0.377). PAH-DNA adducts in cord tissue were significantly higher in the NTD group (24.6 per 10(6) nucleotides) than in the control group (15.3 per 10(6) nucleotides), P=0.010. A positive dose-response relationship was found between levels of PAH-DNA adducts in cord tissue and the risk of NTDs (P=0.009). When the lowest tertile was used as the referent and potential confounding factors were adjusted for, a 1.03-fold (95% CI, 0.37-2.89) and 2.96-fold (95% CI, 1.16-7.58) increase in the risk of NTDs was observed for fetuses whose cord tissue PAH-DNA adduct levels were in the second and highest tertile, respectively. High levels of PAH-DNA adducts in fetal tissues were associated with increased risks of NTDs. Copyright © 2014 Elsevier Inc. All rights reserved.

Prenatal care in your first trimester

MedlinePlus

... for birth defects and genetic problems, such as Down syndrome or brain and spinal column defects. If your ... if the baby is at risk for having Down syndrome. If a test called a quadruple screen is ...

The relevance of echocardiography heart measures for breeding against the risk of subaortic and pulmonic stenosis in Boxer dogs.

PubMed

Menegazzo, L; Bussadori, C; Chiavegato, D; Quintavalla, C; Bonfatti, V; Guglielmini, C; Sturaro, E; Gallo, L; Carnier, P

2012-02-01

The aims of this study were to investigate the role and relative importance of auscultation and echocardiography traits as risk factors for the diagnosis of subaortic (SubAS) and pulmonic (PS) stenosis and to estimate the heritability (h(2)) of cardiac measurements taken through echocardiography for a random sample of Italian Boxer dogs. The data were cardiovascular examination results of 1,283 Italian Boxer dogs (686 females and 597 males) enrolled in the national screening program for heart defects arranged by the Italian Boxer Club. Examinations were performed during a 6-yr period by a group of 7 veterinary cardiologists following a standard protocol. Occurrence and severity of SubAS and PS were diagnosed, taking into account clinical and echocardiography findings such as the grade of cardiac murmur, direct ultrasound imaging of the anatomic obstructive lesions, and values of aortic or pulmonary blood flow velocities. A Bayesian logistic regression analysis was performed to identify clinical and echocardiography variables related to SubAS and PS diagnosis. Estimation of variance components for clinical and echocardiography traits was performed using a mixed linear animal model, Bayesian procedures, and the Gibbs sampler. Prevalence of SubAS (PS) was 8.4% (2.2) and 10.7% (6.4) for female and male dogs, respectively. Cardiac murmur, peak velocities, and annulus areas behaved as risk factors for SubAS and PS. The risk of a positive diagnosis for SubAS was 3 times greater for dogs with aortic annulus area <2.1 cm(2) relative to dogs with areas >2.37 cm(2), 84 times greater for dogs showing aortic peak velocities >2.19 m/s relative to dogs with peak velocities <1.97 m/s, and 41 times greater for dogs with moderate to severe murmur grades relative to dogs with absent murmur. Similar results were obtained for PS. The estimated h(2) for the occurrence of cardiac defects was 23.3% for SubAS and 8.6% for PS. Echocardiography and cardiac murmur grades exhibited moderate h(2) estimates and exploitable additive genetic variation. The estimated h(2) was 36, 24, and 20% for aortic annulus area, aortic peak velocity, and cardiac murmur score, respectively. For the area of the pulmonary annulus and peak pulmonary velocity, the estimated h(2) were smaller, ranging from 9.5 to 12.8%. These measures are candidate indicator traits that might be effectively used in dog breeding to reduce the prevalence and severity of cardiac defects.

Risk of major congenital malformations in relation to maternal overweight and obesity severity: cohort study of 1.2 million singletons.

PubMed

Persson, Martina; Cnattingius, Sven; Villamor, Eduardo; Söderling, Jonas; Pasternak, Björn; Stephansson, Olof; Neovius, Martin

2017-06-14

Objective  To estimate the risks of major congenital malformations in the offspring of mothers who are underweight (body mass index (BMI) <18.5), overweight (BMI 25 to <30), or in obesity classes I (BMI 30 to <35), II (35 to <40), or III (≥40) compared with offspring of normal weight mothers (BMI 18.5 to <25) in early pregnancy. Design  Population based cohort study. Setting  Nationwide Swedish registries. Participants  1 243 957 liveborn singleton infants from 2001 to 2014 in Sweden. Data on maternal and pregnancy characteristics were obtained by individual record linkages. Exposure  Maternal BMI at the first prenatal visit. Main outcome measures  Offspring with any major congenital malformation, and subgroups of organ specific malformations diagnosed during the first year of life. Risk ratios were estimated using generalised linear models adjusted for maternal factors, sex of offspring, and birth year. Results  A total of 43 550 (3.5%) offspring had any major congenital malformation, and the most common subgroup was for congenital heart defects (n=20 074; 1.6%). Compared with offspring of normal weight mothers (risk of malformations 3.4%), the proportions and adjusted risk ratios of any major congenital malformation among the offspring of mothers with higher BMI were: overweight, 3.5% and 1.05 (95% confidence interval 1.02 to 1.07); obesity class I, 3.8% and 1.12 (1.08 to 1.15), obesity class II, 4.2% and 1.23 (1.17 to 1.30), and obesity class III, 4.7% and 1.37 (1.26 to 1.49). The risks of congenital heart defects, malformations of the nervous system, and limb defects also progressively increased with BMI from overweight to obesity class III. The largest organ specific relative risks related to maternal overweight and increasing obesity were observed for malformations of the nervous system. Malformations of the genital and digestive systems were also increased in offspring of obese mothers. Conclusions  Risks of any major congenital malformation and several subgroups of organ specific malformations progressively increased with maternal overweight and increasing severity of obesity. For women who are planning pregnancy, efforts should be encouraged to reduce adiposity in those with a BMI above the normal range. 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.

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.

Research on Operation Assessment Method for Energy Meter

NASA Astrophysics Data System (ADS)

Chen, Xiangqun; Huang, Rui; Shen, Liman; chen, Hao; Xiong, Dezhi; Xiao, Xiangqi; Liu, Mouhai; Xu, Renheng

2018-03-01

The existing electric energy meter rotation maintenance strategy regularly checks the electric energy meter and evaluates the state. It only considers the influence of time factors, neglects the influence of other factors, leads to the inaccuracy of the evaluation, and causes the waste of resources. In order to evaluate the running state of the electric energy meter in time, a method of the operation evaluation of the electric energy meter is proposed. The method is based on extracting the existing data acquisition system, marketing business system and metrology production scheduling platform that affect the state of energy meters, and classified into error stability, operational reliability, potential risks and other factors according to the influencing factors, based on the above basic test score, inspecting score, monitoring score, score of family defect detection. Then, according to the evaluation model according to the scoring, we evaluate electric energy meter operating state, and finally put forward the corresponding maintenance strategy of rotation.

A Method of Evaluating Operation of Electric Energy Meter

NASA Astrophysics Data System (ADS)

Chen, Xiangqun; Li, Tianyang; Cao, Fei; Chu, Pengfei; Zhao, Xinwang; Huang, Rui; Liu, Liping; Zhang, Chenglin

2018-05-01

The existing electric energy meter rotation maintenance strategy regularly checks the electric energy meter and evaluates the state. It only considers the influence of time factors, neglects the influence of other factors, leads to the inaccuracy of the evaluation, and causes the waste of resources. In order to evaluate the running state of the electric energy meter in time, a method of the operation evaluation of the electric energy meter is proposed. The method is based on extracting the existing data acquisition system, marketing business system and metrology production scheduling platform that affect the state of energy meters, and classified into error stability, operational reliability, potential risks and other factors according to the influencing factors, based on the above basic test score, inspecting score, monitoring score, score of family defect detection. Then, according to the evaluation model according to the scoring, we evaluate electric energy meter operating state, and finally put forward the corresponding maintenance strategy of rotation.

Pre-mRNA Splicing in Plants: In Vivo Functions of RNA-Binding Proteins Implicated in the Splicing Process

PubMed Central

Meyer, Katja; Koester, Tino; Staiger, Dorothee

2015-01-01

Alternative pre-messenger RNA splicing in higher plants emerges as an important layer of regulation upon exposure to exogenous and endogenous cues. Accordingly, mutants defective in RNA-binding proteins predicted to function in the splicing process show severe phenotypic alterations. Among those are developmental defects, impaired responses to pathogen threat or abiotic stress factors, and misregulation of the circadian timing system. A suite of splicing factors has been identified in the model plant Arabidopsis thaliana. Here we summarize recent insights on how defects in these splicing factors impair plant performance. PMID:26213982

A Scoring System to Determine Risk of Delayed Bleeding After Endoscopic Mucosal Resection of Large Colorectal Lesions.

PubMed

Albéniz, Eduardo; Fraile, María; Ibáñez, Berta; Alonso-Aguirre, Pedro; Martínez-Ares, David; Soto, Santiago; Gargallo, Carla Jerusalén; Ramos Zabala, Felipe; Álvarez, Marco Antonio; Rodríguez-Sánchez, Joaquín; Múgica, Fernando; Nogales, Óscar; Herreros de Tejada, Alberto; Redondo, Eduardo; Guarner-Argente, Carlos; Pin, Noel; León-Brito, Helena; Pardeiro, Remedios; López-Roses, Leopoldo; Rodríguez-Téllez, Manuel; Jiménez, Alejandra; Martínez-Alcalá, Felipe; García, Orlando; de la Peña, Joaquín; Ono, Akiko; Alberca de Las Parras, Fernando; Pellisé, María; Rivero, Liseth; Saperas, Esteban; Pérez-Roldán, Francisco; Pueyo Royo, Antonio; Eguaras Ros, Javier; Zúñiga Ripa, Alba; Concepción-Martín, Mar; Huelin-Álvarez, Patricia; Colán-Hernández, Juan; Cubiella, Joaquín; Remedios, David; Bessa I Caserras, Xavier; López-Viedma, Bartolomé; Cobian, Julyssa; González-Haba, Mariano; Santiago, José; Martínez-Cara, Juan Gabriel; Valdivielso, Eduardo

2016-08-01

After endoscopic mucosal resection (EMR) of colorectal lesions, delayed bleeding is the most common serious complication, but there are no guidelines for its prevention. We aimed to identify risk factors associated with delayed bleeding that required medical attention after discharge until day 15 and develop a scoring system to identify patients at risk. We performed a prospective study of 1214 consecutive patients with nonpedunculated colorectal lesions 20 mm or larger treated by EMR (n = 1255) at 23 hospitals in Spain, from February 2013 through February 2015. Patients were examined 15 days after the procedure, and medical data were collected. We used the data to create a delayed bleeding scoring system, and assigned a weight to each risk factor based on the β parameter from multivariate logistic regression analysis. Patients were classified as being at low, average, or high risk for delayed bleeding. Delayed bleeding occurred in 46 cases (3.7%, 95% confidence interval, 2.7%-4.9%). In multivariate analysis, factors associated with delayed bleeding included age ≥75 years (odds ratio [OR], 2.36; P < .01), American Society of Anesthesiologist classification scores of III or IV (OR, 1.90; P ≤ .05), aspirin use during EMR (OR, 3.16; P < .05), right-sided lesions (OR, 4.86; P < .01), lesion size ≥40 mm (OR, 1.91; P ≤ .05), and a mucosal gap not closed by hemoclips (OR, 3.63; P ≤ .01). We developed a risk scoring system based on these 6 variables that assigned patients to the low-risk (score, 0-3), average-risk (score, 4-7), or high-risk (score, 8-10) categories with a receiver operating characteristic curve of 0.77 (95% confidence interval, 0.70-0.83). In these groups, the probabilities of delayed bleeding were 0.6%, 5.5%, and 40%, respectively. The risk of delayed bleeding after EMR of large colorectal lesions is 3.7%. We developed a risk scoring system based on 6 factors that determined the risk for delayed bleeding (receiver operating characteristic curve, 0.77). The factors most strongly associated with delayed bleeding were right-sided lesions, aspirin use, and mucosal defects not closed by hemoclips. Patients considered to be high risk (score, 8-10) had a 40% probability of delayed bleeding. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Early pregnancy exposure to antihistamines and risk of congenital heart defects: results of two case-control studies.

PubMed

Smedts, Huberdina P M; de Jonge, Linda; Bandola, Sarah J G; Baardman, Marlies E; Bakker, Marian K; Stricker, Bruno H C; Steegers-Theunissen, Régine P M

2014-09-01

We aimed to study the association between use of antihistamines in early pregnancy and congenital heart defects (CHD) in the offspring. Two case-control studies. HAVEN study, Erasmus MC, University Medical Centre, Rotterdam, and Eurocat Northern Netherlands (NNL), University Medical Center Groningen, Groningen, the Netherlands. We studied 361 children with CHD and 410 controls without congenital malformations from the HAVEN study and replicated the analyses in 445 children with CHD and 530 controls from the Eurocat NNL registry. Information about antihistamine use in early pregnancy and potential confounders was obtained from questionnaires postpartum. We calculated the association between antihistamines and CHD risk by multivariable logistic regression analysis. Odds ratios (OR) with 95% confidence intervals (CI). In the HAVEN study, 25 of 771 mothers used antihistamines that were associated with an increased CHD risk (OR 3.0, 95% CI 1.2-7.3), particularly atrioventricular septal defects (AVSD) (OR 5.1, 95 % CI 1.3-20.5) and perimembranous ventricular septal defects (pVSD) (OR 5.1, 95% CI 1.8-14.4). Mothers with severe nausea who did not use antihistamines had a reduced risk (OR 0.7, 95% CI 0.5-0.98), whereas nauseous mothers using antihistamines showed an almost fivefold increased risk of pVSD (OR 4.8, 95% CI 1.1-21.8). The association between antihistamines and AVSD was confirmed in the Eurocat cohort (OR 3.5, 95% CI 1.4-8.7), but we could not replicate the association with overall CHD risk. We found a positive association between antihistamine use in early pregnancy and CHD risk, particularly AVSD, which seemed to be independent of nausea/vomiting.

Effective scheme to determine accurate defect formation energies and charge transition levels of point defects in semiconductors

NASA Astrophysics Data System (ADS)

Yao, Cang Lang; Li, Jian Chen; Gao, Wang; Tkatchenko, Alexandre; Jiang, Qing

2017-12-01

We propose an effective method to accurately determine the defect formation energy Ef and charge transition level ɛ of the point defects using exclusively cohesive energy Ecoh and the fundamental band gap Eg of pristine host materials. We find that Ef of the point defects can be effectively separated into geometric and electronic contributions with a functional form: Ef=χ Ecoh+λ Eg , where χ and λ are dictated by the geometric and electronic factors of the point defects (χ and λ are defect dependent). Such a linear combination of Ecoh and Eg reproduces Ef with an accuracy better than 5% for electronic structure methods ranging from hybrid density-functional theory (DFT) to many-body random-phase approximation (RPA) and experiments. Accordingly, ɛ is also determined by Ecoh/Eg and the defect geometric/electronic factors. The identified correlation is rather general for monovacancies and interstitials, which holds in a wide variety of semiconductors covering Si, Ge, phosphorenes, ZnO, GaAs, and InP, and enables one to obtain reliable values of Ef and ɛ of the point defects for RPA and experiments based on semilocal DFT calculations.

Evaluation of the cranial base in amnion rupture sequence involving the anterior neural tube: implications regarding recurrence risk.

PubMed

Jones, Kenneth Lyons; Robinson, Luther K; Benirschke, Kurt

2006-09-01

Amniotic bands can cause disruption of the cranial end of the developing fetus, leading in some cases to a neural tube closure defect. Although recurrence for unaffected parents of an affected child with a defect in which the neural tube closed normally but was subsequently disrupted by amniotic bands is negligible; for a primary defect in closure of the neural tube to which amnion has subsequently adhered, recurrence risk is 1.7%. In that primary defects of neural tube closure are characterized by typical abnormalities of the base of the skull, evaluation of the cranial base in such fetuses provides an approach for making a distinction between these 2 mechanisms. This distinction has implications regarding recurrence risk. The skull base of 2 fetuses with amnion rupture sequence involving the cranial end of the neural tube were compared to that of 1 fetus with anencephaly as well as that of a structurally normal fetus. The skulls were cleaned, fixed in 10% formalin, recleaned, and then exposed to 10% KOH solution. After washing and recleaning, the skulls were exposed to hydrogen peroxide for bleaching and photography. Despite involvement of the anterior neural tube in both fetuses with amnion rupture sequence, in Case 3 the cranial base was normal while in Case 4 the cranial base was similar to that seen in anencephaly. This technique provides a method for determining the developmental pathogenesis of anterior neural tube defects in cases of amnion rupture sequence. As such, it provides information that can be used to counsel parents of affected children with respect to recurrence risk.

A central role of eNOS in the protective effect of wine against metabolic syndrome.

PubMed

Leighton, Federico; Miranda-Rottmann, Soledad; Urquiaga, Inés

2006-01-01

The positive health effects derived from moderate wine consumption are pleiotropic. They appear as improvements in cardiovascular risk factors such as plasma lipids, haemostatic mechanisms, endothelial function and antioxidant defences. The active principles would be ethanol and mainly polyphenols. Results from our and other laboratories support the unifying hypothesis that the improvements in risk factors after red wine consumption are mediated by endothelial nitric oxide synthase (eNOS). Many genes are involved, but the participation of eNOS would be a constant feature. The metabolic syndrome is a cluster of metabolic risk factors associated with high risk of cardiovascular disease (CVD). The National Cholesterol Education Programmmes Adult Treatment Panel III (NCEPATP III) clinical definition of the metabolic syndrome requires the presence of at least three risk factors, from among abdominal obesity, high plasma triacylglycerols, low plasma HDL, high blood pressure and high fasting plasma glucose. The molecular mechanisms responsible for the metabolic syndrome are not known. Since metabolic syndrome apparently affects 10-30% of the population in the world, research on its pathogenesis and control is needed. The recent finding that eNOS knockout mice present a cluster of cardiovascular risk factors comparable to those of the metabolic syndrome suggests that defects in eNOS function may cause human metabolic syndrome. These mice are hypertensive, insulin resistant and dyslipidemic. Further support for a pathogenic role of eNOS comes from the finding in humans that eNOS polymorphisms associate with insulin resistance and diabetes, with hypertension, with inflammatory and oxidative stress markers and with albuminuria. So, the data sustain the hypothesis that eNOS enhancement should reduce metabolic syndrome incidence and its consequences. Therefore red wine, since it enhances eNOS function, should be considered as a potential tool for the control of metabolic syndrome. This hypothesis is supported by epidemiological observations and needs experimental validation in human intervention studies. Copyright (c) 2005 John Wiley & Sons, Ltd.

Indications and results of systemic to pulmonary shunts: results from a national database.

PubMed

Dorobantu, Dan Mihai; Pandey, Ragini; Sharabiani, Mansour Taghavi; Mahani, Alireza Shahidzadeh; Angelini, Gianni Davide; Martin, Robin Peter; Stoica, Serban Constantin

2016-06-01

The systemic-to-pulmonary shunt (SPS) remains an important palliative therapy in many congenital heart defects. Unlike other surgical treatments, the mortality after shunt operations has risen. We used an audit dataset to investigate potential reasons for this change and to report national results. A total of 1993 patients classified in 13 diagnoses underwent an SPS procedure between 2000 and 2013. Indication trends by era and also results before repair or next stage are reported. A dynamic hazard model with competing risks and modulated renewal was used to determine predictors of outcomes. The usage of SPS in Tetralogy of Fallot (ToF) has significantly decreased in the last decade, with cases of single ventricle (SV) and pulmonary atresia (PA) with septal communication increasing (P < 0.001 for trends). This is correlated with an increase of early mortality from 5.1% in the first half of the decade to 9.8% in the latter (P = 0.007 for trend). At 1.5 years, 13.9% of patients have died, 17.8% had a shunt reintervention and 68.3% of patients are alive and reintervention-free. Low weight, PA-intact septum, SV and central shunt type are among the factors associated with increased mortality, whereas PA-ventricular septal defect, corrected transposition, isomerism, central shunt and low weight are among those associated with increased reintervention, also having a dynamic effect on the relative risk when compared with ToF patients. Shunt reinterventions are not associated with worse outcomes when adjusted by other covariates, but they do have higher 30-day mortality if occurring earlier than 30 days from the index (P < 0.001). Patients operated in later years were found to have significantly lower survival at a distance from index. The observed historical rise in mortality for shunt operations relates to complex factors including changing practice for repair of ToF and for univentricular palliation. PA and SV patients are the groups of patients at the highest risk of death. Small size, shunt type and underlying anatomical defect are the main determinants of outcomes. Trends in indication and mortality seem to indicate that more severely ill patients benefit from shunting, but with an increase in mortality. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Perioperative outcomes for pediatric neurosurgical procedures: analysis of the National Surgical Quality Improvement Program-Pediatrics.

PubMed

Kuo, Benjamin J; Vissoci, Joao Ricardo N; Egger, Joseph R; Smith, Emily R; Grant, Gerald A; Haglund, Michael M; Rice, Henry E

2017-03-01

OBJECTIVE Existing studies have shown a high overall rate of adverse events (AEs) following pediatric neurosurgical procedures. However, little is known regarding the morbidity of specific procedures or the association with risk factors to help guide quality improvement (QI) initiatives. The goal of this study was to describe the 30-day mortality and AE rates for pediatric neurosurgical procedures by using the American College of Surgeons (ACS) National Surgical Quality Improvement Program-Pediatrics (NSQIP-Peds) database platform. METHODS Data on 9996 pediatric neurosurgical patients were acquired from the 2012-2014 NSQIP-Peds participant user file. Neurosurgical cases were analyzed by the NSQIP-Peds targeted procedure categories, including craniotomy/craniectomy, defect repair, laminectomy, shunts, and implants. The primary outcome measure was 30-day mortality, with secondary outcomes including individual AEs, composite morbidity (all AEs excluding mortality and unplanned reoperation), surgical-site infection, and unplanned reoperation. Univariate analysis was performed between individual AEs and patient characteristics using Fischer's exact test. Associations between individual AEs and continuous variables (duration from admission to operation, work relative value unit, and operation time) were examined using the Student t-test. Patient characteristics and continuous variables associated with any AE by univariate analysis were used to develop category-specific multivariable models through backward stepwise logistic regression. RESULTS The authors analyzed 3383 craniotomy/craniectomy, 242 defect repair, 1811 laminectomy, and 4560 shunt and implant cases and found a composite overall morbidity of 30.2%, 38.8%, 10.2%, and 10.7%, respectively. Unplanned reoperation rates were highest for defect repair (29.8%). The mortality rate ranged from 0.1% to 1.2%. Preoperative ventilator dependence was a significant predictor of any AE for all procedure groups, whereas admission from outside hospital transfer was a significant predictor of any AE for all procedure groups except craniotomy/craniectomy. CONCLUSIONS This analysis of NSQIP-Peds, a large risk-adjusted national data set, confirms low perioperative mortality but high morbidity for pediatric neurosurgical procedures. These data provide a baseline understanding of current expected clinical outcomes for pediatric neurosurgical procedures, identify the need for collecting neurosurgery-specific risk factors and complications, and should support targeted QI programs and clinical management interventions to improve care of children.

Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration.

PubMed

Lee, Christopher Sd; Burnsed, Olivia A; Raghuram, Vineeth; Kalisvaart, Jonathan; Boyan, Barbara D; Schwartz, Zvi

2012-08-24

Adipose stem cells (ASCs) secrete many trophic factors that can stimulate tissue repair, including angiogenic factors, but little is known about how ASCs and their secreted factors influence cartilage regeneration. Therefore, the aim of this study was to determine the effects ASC-secreted factors have in repairing chondral defects. ASCs isolated from male Sprague Dawley rats were cultured in monolayer or alginate microbeads supplemented with growth (GM) or chondrogenic medium (CM). Subsequent co-culture, conditioned media, and in vivo cartilage defect studies were performed. ASC monolayers and microbeads cultured in CM had decreased FGF-2 gene expression and VEGF-A secretion compared to ASCs cultured in GM. Chondrocytes co-cultured with GM-cultured ASCs for 7 days had decreased mRNAs for col2, comp, and runx2. Chondrocytes treated for 12 or 24 hours with conditioned medium from GM-cultured ASCs had reduced sox9, acan, and col2 mRNAs; reduced proliferation and proteoglycan synthesis; and increased apoptosis. ASC-conditioned medium also increased endothelial cell tube lengthening whereas conditioned medium from CM-cultured ASCs had no effect. Treating ASCs with CM reduced or abolished these deleterious effects while adding a neutralizing antibody for VEGF-A eliminated ASC-conditioned medium induced chondrocyte apoptosis and restored proteoglycan synthesis. FGF-2 also mitigated the deleterious effects VEGF-A had on chondrocyte apoptosis and phenotype. When GM-grown ASC pellets were implanted in 1 mm non-critical hyaline cartilage defects in vivo, cartilage regeneration was inhibited as evaluated by radiographic and equilibrium partitioning of an ionic contrast agent via microCT imaging. Histology revealed that defects with GM-cultured ASCs had no tissue ingrowth from the edges of the defect whereas empty defects and defects with CM-grown ASCs had similar amounts of neocartilage formation. ASCs must be treated to reduce the secretion of VEGF-A and other factors that inhibit cartilage regeneration, which can significantly influence how ASCs are used for repairing hyaline cartilage.

Various Stone-Wales defects in phagraphene

NASA Astrophysics Data System (ADS)

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

2016-08-01

Various Stone-Wales defects in phagraphene, which is a graphene allotrope, predicted recently are studied in terms of the nonorthogonal tight-binding model. The energies of the defect formation and the heights of energy barriers preventing the formation and annealing of the defects are found. Corresponding frequency factors in the Arrhenius formula are calculated. The evolution of the defect structure is studied in the real-time mode using the molecular dynamics method.

Role of growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding proteins in the catabolic response to injury and infection.

PubMed

Lang, Charles H; Frost, Robert A

2002-05-01

The erosion of lean body mass resulting from protracted critical illness remains a significant risk factor for increased morbidity and mortality in this patient population. Previous studies have documented the well known impairment in nitrogen balance results from both an increase in muscle protein degradation as well as a decreased rate of both myofibrillar and sacroplasmic protein synthesis. This protein imbalance may be caused by an increased presence or activity of various catabolic agents, such as tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 or glucocorticoids, or may be mediated via a decreased concentration or responsiveness to various anabolic hormones, such as growth hormone or insulin-like growth factor-I. This review focuses on recent developments pertaining to the importance of alterations in the growth hormone-insulin-like growth factor-I axis as a mechanism for the observed defects in muscle protein balance.

Cholesterol Metabolism in CKD

PubMed Central

Reiss, Allison B.; Voloshyna, Iryna; DeLeon, Joshua; Miyawaki, Nobuyuki; Mattana, Joseph

2015-01-01

Patients with chronic kidney disease (CKD) have a substantial risk of developing coronary artery disease. Traditional cardiovascular disease (CVD) risk factors such as hypertension and hyperlipidemia do not adequately explain the high prevalence of CVD in CKD. Both CVD and CKD are inflammatory states and inflammation adversely impacts lipid balance. Dyslipidemia in CKD is characterized by elevated triglycerides and high density lipoprotein that is both decreased and dysfunctional. This dysfunctional high density lipoprotein becomes pro-inflammatory and loses its atheroprotective ability to promote cholesterol efflux from cells, including lipid-overloaded macrophages in the arterial wall. Elevated triglycerides result primarily from defective clearance. The weak association between low density lipoprotein cholesterol level and coronary risk in CKD has led to controversy over the usefulness of statin therapy. This review examines disrupted cholesterol transport in CKD, presenting both clinical and pre-clinical evidence of the impact of the uremic environment on vascular lipid accumulation. Preventative and treatment strategies are explored. PMID:26337134

Risk Factors Associated with Progression to Blindness from Primary Open-Angle Glaucoma in an African-American Population.

PubMed

Pleet, Alexander; Sulewski, Melanie; Salowe, Rebecca J; Fertig, Raymond; Salinas, Julia; Rhodes, Allison; Merritt Iii, William; Natesh, Vikas; Huang, Jiayan; Gudiseva, Harini V; Collins, David W; Chavali, Venkata Ramana Murthy; Tapino, Paul; Lehman, Amanda; Regina-Gigiliotti, Meredith; Miller-Ellis, Eydie; Sankar, Prithvi; Ying, Gui-Shuang; O'Brien, Joan M

2016-08-01

To determine the risk factors associated with progression to blindness from primary open-angle glaucoma (POAG) in an African-American population. This study examined 2119 patients enrolled in the Primary Open-Angle African-American Glaucoma Genetics (POAAGG) study. A total of 59 eyes were identified as legally blind as a result of POAG (cases) and were age-and sex-matched to 59 non-blind eyes with glaucoma (controls). Chart reviews were performed to record known and suspected risk factors. Cases were diagnosed with POAG at an earlier age than controls (p = 0.005). Of the 59 eyes of cases, 16 eyes (27.1%) presented with blindness at diagnosis. Cases had worse visual acuity (VA) at diagnosis (p < 0.0001), with VA worse than 20/40 conferring a 27 times higher risk of progression to blindness (p = 0.0005). Blind eyes also demonstrated more visual field defects (p = 0.01), higher pre-treatment intraocular pressure (IOP; p < 0.0001), and higher cup-to-disc ratio (p = 0.006) at diagnosis. IOP was less controlled in cases, and those with IOP ≥21 mmHg at more than 20% of follow-up visits were 73 times more likely to become blind (p < 0.0001). Cases missed a greater number of appointments per year (p = 0.003) and had non-adherence issues noted in their charts more often than controls (p = 0.03). However, other compliance data did not significantly differ between groups. Access to care, initial VA worse than 20/40, and poor control of IOP were the major risk factors associated with blindness from POAG. Future studies should examine earlier, more effective approaches to glaucoma screening as well as the role of genetics in these significantly younger patients who progress to blindness.

Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study.

PubMed

Wu, O; Robertson, L; Twaddle, S; Lowe, G D O; Clark, P; Greaves, M; Walker, I D; Langhorne, P; Brenkel, I; Regan, L; Greer, I

2006-04-01

To assess the risk of clinical complications associated with thrombophilia in three high-risk patient groups: women using oral oestrogen preparations, women during pregnancy and patients undergoing major orthopaedic surgery. To assess the effectiveness of prophylactic treatments in preventing venous thromboembolism (VTE) and adverse pregnancy outcomes in women with thrombophilia during pregnancy and VTE in patients with thrombophilia, undergoing major orthopaedic surgery. To evaluate the relative cost-effectiveness of universal and selective VTE history-based screening for thrombophilia compared with no screening in the three high-risk patient groups. Electronic databases including MEDLINE, EMBASE, and four other major databases were searched up to June 2003. In order to assess the risk of clinical complications associated with thrombophilia, a systematic review of the literature on VTE and thrombophilia in women using oral oestrogen preparations and patients undergoing major orthopaedic surgery; and studies of VTE and adverse obstetric complications in women with thrombophilia during pregnancy was carried out. Meta-analysis was used to calculate pooled odds ratios (ORs) associated with individual clinical outcomes, stratified by thrombophilia type and were calculated for each patient group. To assess the effectiveness of prophylaxis, a systematic review was carried out on the use of prophylaxis in the prevention of VTE and pregnancy loss in pregnant women with thrombophilic defects and the use of thromboprophylaxis in the prevention of VTE in patients with thrombophilia undergoing major elective orthopaedic surgery. Relevant data were summarised according to the patient groups and stratified according to the types of prophylaxis. A narrative summary was provided; where appropriate, meta-analysis was conducted. An incremental cost-effectiveness analysis was then carried out, from the perspective of the NHS in the UK. A decision analytical model was developed to simulate the clinical consequences of four thrombophilia screening scenarios. Results from the meta-analyses, information from the literature and results of two Delphi studies of clinical management of VTE and adverse pregnancy complications were incorporated into the model. Only direct health service costs were measured and unit costs for all healthcare resources used were obtained from routinely collected data and the literature. Cost-effectiveness was expressed as incremental cost-effectiveness ratios (ICERs); an estimate of the cost per adverse clinical complication prevented, comparing screening with no screening, were calculated for each patient group. In the review of risk of clinical complications, 81 studies were included, nine for oral oestrogen preparations, 72 for pregnancy and eight for orthopaedic surgery. For oral contraceptive use, significant associations of the risk of VTE were found in women with factor V Leiden (FVL); deficiencies of antithrombin, protein C, or protein S, elevated levels of factor VIIIc; and FVL and prothrombin G20210A. For hormone replacement therapy (HRT), a significant association was found in women with FVL. The highest risk in pregnancy was found for FVL and VTE, in particular, homozygous carriers of this mutation are 34 times more likely to develop VTE in pregnancy than non-carriers. Significant risks for individual thrombophilic defects were also established for early, recurrent and late pregnancy loss; preeclampsia; placental abruption; and intrauterine growth restriction. Significant associations were found between FVL and high factor VIIIc and postoperative VTE following elective hip or knee replacement surgery. Prothrombin G20210A was significantly associated with postoperative pulmonary embolism. However, antithrombin deficiency, MTHFR and hyperhomocysteinaemia were not associated with increased risk of postoperative VTE. In the review of the effectiveness of prophylaxis, based on available data from eight studies, low-dose aspirin and heparin was found to be the most effective in preventing pregnancy loss in thrombophilic women during pregnancy, while aspirin alone was the most effective in preventing minor bleeding. All the studies on thrombophilia and major elective orthopaedic surgery included in the review of risk complications were also used in the review of the effectiveness of thromboprophylaxis. However, there were insufficient data to determine the relative effectiveness of different thromboprophylaxis in preventing VTE in this patient group. For the cost-effectiveness analysis, of all the patient groups evaluated, universal screening of women prior to prescribing HRT was the most cost-effective (ICER pound6824). In contrast, universal screening of women prior to prescribing combined oral contraceptives was the least cost-effective strategy (ICER pound202,402). Selective thrombophilia screening based on previous personal and/or family history of VTE was more cost-effective than universal screening in all the patient groups evaluated. Thrombophilia is associated with increased risks of VTE in women taking oral oestrogen preparations and patients undergoing major elective orthopaedic surgery, and of VTE and adverse pregnancy outcomes in women with thrombophilia during pregnancy. There is considerable difference in the magnitude of the risks among different patient groups with different thrombophilic defects. In women who are on combined oral contraceptives, the OR of VTE among those who are carriers of the FVL mutation was 15.62 (95% confidence interval 8.66 to 28.15). However, in view of the prevalence of thrombophilia and the low prevalence of VTE in non-users of combined oral contraceptives, the absolute risk remains low. Significant risks for VTE and adverse pregnancy outcomes have been established with individual thrombophilic defects. Thrombophilic defects including FVL, high plasma factor VIIIc levels and prothrombin G20210A are associated with the occurrence of postoperative VTE in elective hip or knee replacement therapy. These associations are observed in patients who were given preoperative thromboprophylaxis and are, therefore, of clinical significance. Universal thrombophilia screening in women prior to prescribing oral oestrogen preparations, in women during pregnancy and in patients undergoing major orthopaedic surgery is not supported by current evidence. The findings from this study show that selective screening based on prior VTE history is more cost-effective than universal screening. Large prospective studies should be undertaken to refine the risks and establish the associations of thrombophilias with VTE among hormone users and in patients undergoing orthopaedic surgery. The relative value of a thrombophilia screening programme to other healthcare programmes needs to be established.

Diagnosis and treatment of high density lipoprotein deficiency.

PubMed

Schaefer, Ernst J; Anthanont, Pimjai; Diffenderfer, Margaret R; Polisecki, Eliana; Asztalos, Bela F

Low serum high density lipoprotein cholesterol level (HDL-C) <40 mg/dL in men and <50 mg/dL in women is a significant independent risk factor for cardiovascular disease (CVD), and is often observed in patients with hypertriglyceridemia, obesity, insulin resistance, and diabetes. Patients with marked deficiency of HDL-C (<20 mg/dL) in the absence of secondary causes are much less common (<1% of the population). These patients may have homozygous, compound heterozygous, or heterozygous defects involving the apolipoprotein (APO)AI, ABCA1, or lecithin:cholesterol acyl transferase genes, associated with apo A-I deficiency, apoA-I variants, Tangier disease , familial lecithin:cholesteryl ester acyltransferase deficiency, and fish eye disease. There is marked variability in laboratory and clinical presentation, and DNA analysis is necessary for diagnosis. These patients can develop premature CVD, neuropathy, kidney failure, neuropathy, hepatosplenomegaly and anemia. Treatment should be directed at optimizing all non-HDL risk factors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Eleven years of experience with metal-on-metal hybrid hip resurfacing: a review of 1000 conserve plus.

PubMed

Amstutz, Harlan C; Le Duff, Michel J

2008-09-01

Hip resurfacing is currently the fastest growing hip procedure worldwide. We reviewed 1000 hips in 838 patients who received a Conserve Plus (Wright Medical Technology, Inc., Arlington, Tenn) resurfacing at a single institution. The mean age of the patients was 50.0 years with 74.7% male. The hips were resurfaced irrespective of femoral defect size or etiology. The mean follow-up was 5.6 years (range, 1.1-11.0 years). All clinical scores improved significantly (P < .05). There was no acetabular component loosening. Ten were converted to total hip arthroplasty for femoral neck fracture, 20 for femoral loosening, 2 for sepsis, and 1 for recurrent subluxations. The 5-year survivorship was 95.2% with no failures in hips implanted since 2002. Short-term failures can be prevented. First-generation surgical technique and a low body mass index were the most important risk factors for the procedure. Improvements in bone preparation significantly increased prosthetic survival in hips with risk factors for failure.

An update on risk factors for cartilage loss in knee osteoarthritis assessed using MRI-based semiquantitative grading methods.

PubMed

Alizai, Hamza; Roemer, Frank W; Hayashi, Daichi; Crema, Michel D; Felson, David T; Guermazi, Ali

2015-03-01

Arthroscopy-based semiquantitative scoring systems such as Outerbridge and Noyes' scores were the first to be developed for the purpose of grading cartilage defects. As magnetic resonance imaging (MRI) became available for evaluation of the osteoarthritic knee joint, these systems were adapted for use with MRI. Later on, grading methods such as the Whole Organ Magnetic Resonance Score, the Boston-Leeds Osteoarthritis Knee Score and the MRI Osteoarthritis Knee Score were designed specifically for performing whole-organ assessment of the knee joint structures, including cartilage. Cartilage grades on MRI obtained with these scoring systems represent optimal outcome measures for longitudinal studies, and are designed to enhance understanding of the knee osteoarthritis disease process. The purpose of this narrative review is to describe cartilage assessment in knee osteoarthritis using currently available MRI-based semiquantitative whole-organ scoring systems, and to provide an update on the risk factors for cartilage loss in knee osteoarthritis as assessed with these scoring systems.

Image-guided intervention in the coagulopathic patient.

PubMed

Kohli, Marc; Mayo-Smith, William; Zagoria, Ronald; Sandrasegaran, Kumar

2016-04-01

Determining practice parameters for interventional procedures is challenging due to many factors including unreliable laboratory tests to measure bleeding risk, variable usage of standardized terminology for adverse events, poorly defined standards for administration of blood products, and the growing numbers of anticoagulant and antiplatelet medications. We aim to address these and other issues faced by radiologists performing invasive procedures through a review of available literature, and experiential guidance from three academic medical centers. We discuss the significant limitations with respect to using prothrombin-time and international normalized ratio to measure bleeding risk, especially in patients with synthetic defects due to liver function. Factors affecting platelet function including the impact of uremia; recent advances in laboratory testing, including platelet function testing; and thromboelastography are also discussed. A review of the existing literature of fresh-frozen plasma replacement therapy is included. The literature regarding comorbidities affecting coagulation including malignancy, liver failure, and uremia are also reviewed. Finally, the authors present a set of recommendations for laboratory thresholds, corrective transfusions, as well as withholding and restarting medications.

Breast cancer risk associated with genotypic polymorphism of the nonhomologous end-joining genes: a multigenic study on cancer susceptibility.

PubMed

Fu, Yi-Ping; Yu, Jyh-Cherng; Cheng, Ting-Chih; Lou, M Ann; Hsu, Giu-Cheng; Wu, Chia-Yun; Chen, Sou-Tong; Wu, Hurng-Sheng; Wu, Pei-Ei; Shen, Chen-Yang

2003-05-15

The role of the familial breast cancer susceptibility genes, BRCA1 and BRCA2, in the homologous recombination pathway for DNA double-strand break (DSB) repair suggests that the mechanisms involved in DNA DSB repair are of particular etiological importance during breast tumorigenesis. However, there is currently no evidence for an association between breast cancer and the other DSB repair pathway, the nonhomologous end-joining (NHEJ) pathway. It is possible that, because this DNA repair pathway is so crucial for mammalian cells to maintain genomic stability, any severe defects in it would result in serious outcomes, such as genomic instability and cell death, and block subsequent cell outgrowth and tumor formation. Thus, only subtle defects arising from low-penetrance alleles would escape lethality accumulating essential genetic changes and be associated with cancer formation, and the tumorigenic contribution of these alleles would become more obvious if individual putative high-risk genotypes of each NHEJ gene act jointly. Furthermore, this joint effect might be modified by specific environmental factors, and we hypothesized that estrogen exposure might be one such factor because estrogen is suggested to cause DNA DSBs, triggering breast tumorigenesis. Because single nucleotide polymorphisms (SNPs) are the most subtle genetic variation in the genome, to examine these hypotheses, we have genotyped 30 SNPs in all five NHEJ genes (Ku70, Ku80, DNA-PKcs, Ligase IV, and XRCC4) in 254 primary breast cancer patients and 379 healthy controls. Support for these hypotheses came from the observations that (a) two SNPs in Ku70 and XRCC4 were associated with breast cancer risk (P < 0.05); (b) a trend toward increased risk of developing breast cancer was found in women harboring a greater number of putative high-risk genotypes of NHEJ genes (an adjusted odds ratio of 1.46 for having one additional putative high-risk genotype; 95% confidence interval, 1.19-1.80); (c) this association between risk and the number of putative high-risk genotypes was stronger and more significant in women thought to be more susceptible to estrogen, i.e., those with no history of full-term pregnancy; and (d) the protective effect conferred by a history of full-term pregnancy was only significant in women with a lower number of putative high-risk genotypes of NHEJ genes. Based on comprehensive NHEJ gene profiles, this study provides new insights to suggest the role of the NHEJ pathway in breast cancer development and supports the possibility that breast cancer is initiated by estrogen exposure, which causes DNA DSBs.

Morphologic Characteristics and Relating Factors to the Need of Technical Modification in Transcatheter Closure of Large Atrial Septal Defect (≥25 mm)

PubMed Central

Park, Su-Jin; Kim, Nam Kyun; Kim, Jung Ok; Yoo, Byung Won; Sul, Jun Hee

2010-01-01

Background and Objectives The rigid coupling between the delivery wire and the right atrial disk has been occasionally encountered during transcatheter closure of atrial septal defect (ASD). Therefore the device frequently makes a perpendicular angle, and the leading edge of left atrial disk slips through the defect and prolapses into right atrium (RA) before it is properly placed in the septum. The purpose of this study is to investigate relating factors to the need of technical modification in transcatheter closure of large ASD and to evaluate relevant morphologic characteristics of atrial septal rim in this situation. Subjects and Methods From July, 2003 to May, 2007, 312 patients underwent transcatheter occlusion of ASD with Amplatzer Septal Occluder® (ASO, AGA medical corporation, Golden Valley, MN, USA) at Yonsei Cardiovascular Center and among them 109 patients had large ASD (≥25 mm) and these patients were enrolled in our study. Patients were divided into two groups according to the deploying methods of the device (Group I: standard method, Group II: modified methods). Assessments of the defects and its surrounding rims were made by echocardiography. Results There were no differences between 2 groups in age, body weight and height except for balloon-stretched diameter (stop-flow technique) and device size. Group II patients with modified methods showed larger balloon-stretched diameter and device size than group I patients with standard method. The mean length of anterosuperior (AS) rim in group II was significantly shorter than group I (p<0.05). As the size of the device used in procedure increased, there was a trend towards increase in the need of modified methods. Conclusion This study shows that AS rim deficiency and the size of ASD may be the relating factors to the need of technical modification in transcatheter closure of ASD. Therefore, when the initial try with standard method is not successful in large ASD with deficient AS rim, we suggest that changing strategy of implantation may save time and efforts and possibly reduce the risk of complications associated with prolonged procedure. PMID:20421960

The Axolotl Fibula as a Model for the Induction of Regeneration across Large Segment Defects in Long Bones of the Extremities

PubMed Central

Chen, Xiaoping; Song, Fengyu; Jhamb, Deepali; Li, Jiliang; Bottino, Marco C.; Palakal, Mathew J.; Stocum, David L.

2015-01-01

We tested the ability of the axolotl (Ambystoma mexicanum) fibula to regenerate across segment defects of different size in the absence of intervention or after implant of a unique 8-braid pig small intestine submucosa (SIS) scaffold, with or without incorporated growth factor combinations or tissue protein extract. Fractures and defects of 10% and 20% of the total limb length regenerated well without any intervention, but 40% and 50% defects failed to regenerate after either simple removal of bone or implanting SIS scaffold alone. By contrast, scaffold soaked in the growth factor combination BMP-4/HGF or in protein extract of intact limb tissue promoted partial or extensive induction of cartilage and bone across 50% segment defects in 30%-33% of cases. These results show that BMP-4/HGF and intact tissue protein extract can promote the events required to induce cartilage and bone formation across a segment defect larger than critical size and that the long bones of axolotl limbs are an inexpensive model to screen soluble factors and natural and synthetic scaffolds for their efficacy in stimulating this process. PMID:26098852

Maternal folic acid supplementation and dietary folate intake and congenital heart defects

PubMed Central

Mao, Baohong; Qiu, Jie; Zhao, Nan; Shao, Yawen; Dai, Wei; He, Xiaochun; Cui, Hongmei; Lin, Xiaojuan; Lv, Ling; Tang, Zhongfeng; Xu, Sijuan; Huang, Huang; Zhou, Min; Xu, Xiaoying; Qiu, Weitao

2017-01-01

Background It has been reported that folic acid supplementation before and/or during pregnancy could reduce the risk of congenital heart defects (CHDs). However, the results from limited epidemiologic studies have been inconclusive. We investigated the associations between maternal folic acid supplementation, dietary folate intake, and the risk of CHDs. Methods A birth cohort study was conducted in 2010–2012 at the Gansu Provincial Maternity & Child Care Hospital in Lanzhou, China. After exclusion of stillbirths and multiple births, a total of 94 births were identified with congenital heart defects, and 9,993 births without any birth defects. Unconditional logistic regression was used to estimate the associations. Results Compared to non-users, folic acid supplement users before pregnancy had a reduced risk of overall CHDs (OR: 0.42, 95% CI: 0.21–0.86, Ptrend = 0.025) after adjusted for potential confounders. A protective effect was observed for certain subtypes of CHDs (OR: 0.37, 95% CI: 0.16–0.85 for malformation of great arteries; 0.26, 0.10–0.68 for malformation of cardiac septa; 0.34, 0.13–0.93 for Atrial septal defect). A similar protective effect was also seen for multiple CHDs (OR: 0.49, 95% CI: 0.26–0.93, Ptrend = 0.004). Compared with the middle quartiles of dietary folate intake, lower dietary folate intake (<149.88 μg/day) during pregnancy were associated with increased risk of overall CHDs (OR: 1.63, 95% CI: 1.01–2.62) and patent ductus arteriosus (OR: 1.85, 95% CI: 1.03–3.32). Women who were non-user folic acid supplement and lower dietary folate intake have almost 2-fold increased CHDs risk in their offspring. Conclusions Our study suggested that folic acid supplementation before pregnancy was associated with a reduced risk of CHDs, lower dietary folate intake during pregnancy was associated with increased risk. The observed associations varied by CHD subtypes. A synergistic effect of dietary folate intake and folic acid supplementation was also observed. PMID:29145433

Maternal dietary nitrate intake and risk of neural tube defects: A systematic review and dose-response meta-analysis.

PubMed

Kakavandi, Nader Rahimi; Hasanvand, Amin; Ghazi-Khansari, Mahmoud; Sezavar, Ahmad Habibian; Nabizadeh, Hassan; Parohan, Mohammad

2018-05-12

Despite growing evidence for the potential teratogenicity of nitrate, knowledge about the dose-response relationship of dietary nitrate intake and risk of specific birth defects such as neural tube defects (NTDs) is limited. Therefore, the aim of this meta-analysis was to synthesize the knowledge about the dose-response relation between maternal dietary nitrate intake and the risk of NTDs. We conducted a systematic search in PubMed, ISI Web of Science and Scopus up to February 2018 for observational studies. Risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated using a random-effects model for highest versus lowest intake categories. The linear and non-linear relationships between nitrate intake and risk of NTDs were also investigated. Overall, 5 studies were included in the meta-analyses. No association was observed between nitrate intake and NTDs risk in high versus low intake (RR: 1.33; 95% CI: 0.89-1.99, p = 0.158) and linear dose-response (RR: 1.03; 95% CI: 0.99-1.07, p = 0.141) meta-analysis. However, there were positive relationships between nitrate intake and risk of NTDs in non-linear (p non-linearity <0.05) model. Findings from this dose-response meta-analysis indicate that maternal nitrate intake higher than ∼3 mg/day is positively associated with NTDs risk. Copyright © 2018 Elsevier Ltd. All rights reserved.

Leptin signaling and leptin resistance

PubMed Central

Zhou, Yingjiang; Rui, Liangyou

2014-01-01

Leptin is secreted into the bloodstream by adipocytes and is required for the maintenance of energy homeostasis and body weight. Leptin deficiency or genetic defects in the components of the leptin signaling pathways causes obesity. Leptin controls energy balance and body weight primarily by targeting LEPRb-expressing neurons in the brain, particularly in the hypothalamus. These LEPRb-expressing neurons function as the first-order neurons that project to the second-order neurons located within and outside the hypothalamus, forming a neural network that controls the energy homeostasis and body weight. Multiple factors, including inflammation and ER stress, contribute to leptin resistance, and leptin resistance is the key risk factor for obesity. This review is focused on recent advance about leptin action, leptin signaling, and leptin resistance. PMID:23580174

Dandy-Walker malformation: etiologic heterogeneity and empiric recurrence risks.

PubMed

Murray, J C; Johnson, J A; Bird, T D

1985-10-01

The Dandy-Walker malformation (DWM) includes hydrocephalus, incomplete cerebellar vermis and a posterior fossa cyst. Genetic influences and recurrence risks for DWM have not been well characterized. We report a retrospective study of 21 autopsy-proven cases of DWM and review the literature regarding an additional 92 subjects. DWM represents marked genetic and etiologic heterogeneity. Recurrence risk for siblings may be high when DWM is associated with a single gene disorder such as the autosomal recessive Warburg and Meckel-Gruber syndromes. DWM may also result from chromosomal anomalies or environmental factors. When the evidence suggests that DWM has not occurred as part of a Mendelian or chromosomal disorder then the recurrence risk is relatively low (on the order of 1 to 5%). There appears to be an increased frequency of the association of DWM with congenital heart disease, cleft lip/palate and neural tube defects. Based on our study we provide guidelines for the genetic counseling of families having a child with DWM.

Maternal residential proximity to chlorinated solvent emissions and birth defects in offspring: a case-control study.

PubMed

Brender, Jean D; Shinde, Mayura U; Zhan, F Benjamin; Gong, Xi; Langlois, Peter H

2014-11-19

Some studies have noted an association between maternal occupational exposures to chlorinated solvents and birth defects in offspring, but data are lacking on the potential impact of industrial air emissions of these solvents on birth defects. With data from the Texas Birth Defects Registry for births occurring in 1996-2008, we examined the relation between maternal residential proximity to industrial air releases of chlorinated solvents and birth defects in offspring of 60,613 case-mothers and 244,927 control-mothers. Maternal residential exposures to solvent emissions were estimated with metrics that took into account residential distances to industrial sources and annual amounts of chemicals released. Logistic regression was used to generate odds ratios and 95% confidence intervals for the associations between residential proximity to emissions of 14 chlorinated solvents and selected birth defects, including neural tube, oral cleft, limb deficiency, and congenital heart defects. All risk estimates were adjusted for year of delivery and maternal age, education, race/ethnicity, and public health region of residence. Relative to exposure risk values of 0, neural tube defects were associated with maternal residential exposures (exposure risk values >0) to several types of chlorinated solvents, most notably carbon tetrachloride (adjusted odds ratio [aOR] 1.42, 95% confidence interval [CI] 1.09, 1.86); chloroform (aOR 1.40, 95% CI 1.04, 1.87); ethyl chloride (aOR 1.39, 95% CI 1.08, 1.79); 1,1,2-trichloroethane (aOR 1.56, 95% CI 1.11, 2.18); and 1,2,3-trichloropropane (aOR 1.49, 95% CI 1.08, 2.06). Significant associations were also noted between a few chlorinated solvents and oral cleft, limb deficiency, and congenital heart defects. We observed stronger associations between some emissions and neural tube, oral cleft, and heart defects in offspring of mothers 35 years or older, such as spina bifida with carbon tetrachloride (aOR 2.49, 95% CI 1.09, 5.72), cleft palate with 1,2-dichloroethane (aOR 1.93, 95% 1.05, 3.54), cleft lip with or without cleft palate with ethyl chloride (aOR 1.81, 95% CI 1.06, 3.07), and obstructive heart defects with trichloroethylene (aOR 1.43, 95% CI 1.08, 1.88). These findings suggest that maternal residential proximity to industrial emissions of chlorinated solvents might be associated with selected birth defects in offspring, especially among older mothers.

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

Assisted reproductive technologies: a hierarchy of risks for conception, pregnancy outcomes and treatment decisions.

PubMed

Davies, M J; Rumbold, A R; Moore, V M

2017-08-01

The use of assisted reproductive technologies (ART) for the treatment of infertility has grown exponentially over the last 20 years, and now accounts for 4% of all births in Australia, and over 1 m births annually around the globe. There is consistent reporting of increased risk of adverse perinatal outcomes and birth defects following infertility treatment. However, change in practice has been stymied by critical knowledge gaps with regards to (a) the relative contribution of patient and treatment factors to adverse outcomes, (b) the independent contribution of specific contemporary treatments and treatment combinations to outcomes, (c) the impact of innovations in laboratory and clinical practice on treatment success and observed risk and (d) changes over time in patient characteristics. Here we summarize key findings from the South Australian Birth Cohort, which is a whole-of-population cohort of over 300,000 births from 1986 to 2002. Relative to spontaneous conceptions, singletons from assisted conception were more likely to be stillborn [odds ratio (OR)=1.82; 95% confidence interval (CI) 1.34-2.48], while survivors as a group were comprehensively disadvantaged at birth, including lower birth weight (OR=2109 g; 95% CI 2129-289), very low birth weight (OR=2.74; 95% CI 2.19-3.43), very preterm birth (OR=2.30; 95% CI 1.82-2.90) and neonatal death (OR=2.04; 95% CI 1.27-3.26). Major birth defects, including cardiac, urogenital and musculoskeletal defects are doubled after fresh ICSI cycles, which is a particular concern as ICSI now accounts for 70% of all treatment cycles globally. Future study is needed to provide contemporary, precise evidence to inform patient and clinic decision making, and generate knowledge for future innovation in ART laboratory methods and clinical practice, thereby optimizing treatment and health outcomes while reducing adverse events.

Arrhythmias in Adults with Congenital Heart Disease: What Are Risk Factors for Specific Arrhythmias?

PubMed

Loomba, Rohit S; Buelow, Matthew W; Aggarwal, Saurabh; Arora, Rohit R; Kovach, Joshua; Ginde, Salil

2017-04-01

An increasing number of patients with congenital heart disease are now surviving into adulthood. This has also led to the emergence of complications from the underlying congenital heart disease, related surgical interventions, and associated combordities. While the prevalence of particular arrhythmias with specific congenital heart disease has been previously described, a detailed analysis of all lesions and a large number of comorbidities has not been previously published. Admissions with congenital heart disease were identified in the National Inpatient Sample. Associated comorbidities were also identified for these patients. Univariate analysis was done to compare those risk factors associated with specific arrhythmias in the setting of congenital heart disease. Next, regression analysis was done to identify what patient characteristics and comorbidities were associated with increased risk of specific arrhythmias. A total of 52,725,227 admissions were included in the analysis. Of these, 109,168 (0.21%) had congenital heart disease. Of those with congenital heart disease, 27,088 (25%) had an arrhythmia at some point. The most common arrhythmia in those with congenital heart disease was atrial fibrillation, which was noted in 86% of those with arrhythmia followed by atrial flutter which was noted in 20% of those with congenital heart disease. The largest burden of arrhythmia was found to be in those with tricuspid atresia with a 51% prevalence of arrhythmia in this group followed by Ebstein anomaly which had an arrhythmia prevalence of 39%. Increasing age, male gender, double outlet right ventricle, atrioventricular septal defect, heart failure, obstructive sleep apnea, transposition of the great arteries, congenitally corrected transposition, and tetralogy of Fallot were frequently noted to be independent risk factors of specific arrhythmias. Approximately, 25% of adult admissions with congenital heart disease are associated with arrhythmia. The burden of arrhythmia varies by the specific lesion and other risk factors as well. Understanding of these can help in risk stratification and can help devise strategies to lower this risk. © 2016 Wiley Periodicals, Inc.

Prospective study on cranioplasty with individual carbon fiber reinforced polymer (CFRP) implants produced by means of stereolithography.

PubMed

Wurm, Gabriele; Tomancok, Berndt; Holl, Kurt; Trenkler, Johannes

2004-12-01

The aim of this study was to evaluate the value of carbon fiber reinforced polymer (CFRP) cranial implants produced by means of 3-dimensional (3D) stereolithography (SL) and template modeling for reconstructions of complex or extensive cranial defects. A series of 41 cranioplasties with individual CFRP implants was performed in 37 patients between April 1996 and November 2002. Only patients with complex and/or large cranial defects were included, most of them having extended scarring or dural calcification and poor quality of the overlying soft-tissue cover after infection or multiple preceding operations. Involvement of frontal sinus, a known risk factor for complications after cranioplasty, was the case in 21 patients (51.2%). A computer-based 3D model of the skull with the bony defect was generated by means of stereolithography after acquisition, evaluation and transfer of the patient's helical computed tomography (CT) data. A wax template of the defect that was used to design the individual prosthesis-shape was invested in dental stone. Then, the cranial implant was fabricated out of CFRP by loosen mold. Reconstruction of defects measuring up to 17 x 9 cm was performed. The intra-operative fit of the implants was excellent in 36 (87.8%), good in 1 (2.4%), and fair in 4 (9.8%) of the cases. Problems of implant fit occurred because of extended scarring and poor quality of soft-tissue cover. Adverse reactions were observed in 5 patients (1 subdural, 1 subcutaneous hematoma, 2 infections, 1 allergic reaction). Excellent contours and a solid stable reconstruction have been maintained in 30 out of 35 remaining plates (mean follow-up 3.6 years). No adverse effects concerning postoperative imaging, the accuracy of electroencephalograms and radiation therapy have been observed. The authors believe that this relatively new technique represents an advance in the management of complex and large cranial defects, but seems less suitable for simple defects because of cost-intensive techniques. Because of the high mechanical strength, biocompatibility, innovative design, and especially radiolucency, CFRP implants should, however, be considered in smaller defects if further imaging investigations or irradiation therapies are necessary.

EUVL masks: paving the path for commercialization

NASA Astrophysics Data System (ADS)

Mangat, Pawitter J. S.; Hector, Scott D.

2001-09-01

Optical projection lithography has been the principal vehicle of semiconductor manufacturing for more than 20 years and is marching aggressively to satisfy the needs of semiconductor manufacturers for 100nm devices. However, the complexity of optical lithography continues to increase as wavelength reduction continues to 157nm. Extreme Ultraviolet Lithography (EUVL), with wavelength from 13-14 nm, is evolving as a leading next generation lithography option for semiconductor industry to stay on the path laid by Moore's Law. Masks are a critical part of the success of any technology and are considered to be high risk both for optical lithography and NGL technologies for sub-100nm lithography. Two key areas of EUV mask fabrication are reflective multilayer deposition and absorber patterning. In the case of reflective multilayers, delivering defect free multilayers for mask blanks is the biggest challenge. Defect mitigation is being explored as a possible option to smooth the multilayer defects in addition to optimization of the deposition process to reduce defect density. The mask patterning process needs focus on the defect-free absorber stack patterning process, mask cleaning, inspection and repair. In addition, there is considerable effort to understand by simulations, the defect printability, thermal and mechanical distortions, and non-telecentric illumination, to mention a few. To protect the finished mask from defects added during use, a removable pellicle strategy combined with thermophoretic protection during exposure is being developed. Recent migration to square form factor using low thermal expansion material (LTEM) is advantageous as historical developments in optical masks can be applied to EUV mask patterning. This paper addresses recent developments in the EUV mask patterning and highlights critical manufacturing process controls needed to fabricate defect-free full field masks with CD and image placement specifications for sub-70nm node lithography. No technology can be implemented without establishing the commercial infrastructure. The rising cost seems to be a major issue affecting the technology development. With respect to mask fabrication for commercial availability, a virtual mask shop analysis is presented that indicates that the process cost for EUVL masks are comparable to the high end optical mask with a reasonable yield. However, the cost for setting up a new mask facility is considerably high.

Factors associated with developing a fear of falling in subjects with primary open-angle glaucoma.

PubMed

Adachi, Sayaka; Yuki, Kenya; Awano-Tanabe, Sachiko; Ono, Takeshi; Shiba, Daisuke; Murata, Hiroshi; Asaoka, Ryo; Tsubota, Kazuo

2018-02-13

To investigate the relationship between clinical risk factors, including visual field (VF) defects and visual acuity, and a fear of falling, among patients with primary open-angle glaucoma (POAG). All participants answered the following question at a baseline ophthalmic examination: Are you afraid of falling? The same question was then answered every 12 months for 3 years. A binocular integrated visual field was calculated by merging a patient's monocular Humphrey field analyzer VFs, using the 'best sensitivity' method. The means of total deviation values in the whole, superior peripheral, superior central, inferior central, and inferior peripheral VFs were calculated. The relationship between these mean VF measurements, and various clinical factors, against patients' baseline fear of falling and future fear of falling was analyzed using multiple logistic regression. Among 392 POAG subjects, 342 patients (87.2%) responded to the fear of falling question at least twice in the 3 years study period. The optimal regression model for patients' baseline fear of falling included age, gender, mean of total deviation values in the inferior peripheral VF and number of previous falls. The optimal regression equation for future fear of falling included age, gender, mean of total deviation values in the inferior peripheral VF and number of previous falls. Defects in the inferior peripheral VF area are significantly related to the development of a fear of falling.

Pathophysiology of osteoporosis: new mechanistic insights.

PubMed

Armas, Laura A G; Recker, Robert R

2012-09-01

Understanding of the pathophysiology of osteoporosis has evolved to include compromised bone strength and skeletal fragility caused by several factors: (1) defects in microarchitecture of trabeculae, (2) defective intrinsic material properties of bone tissue, (3) defective repair of microdamage from normal daily activities, and (4) excessive bone remodeling rates. These factors occur in the context of age-related bone loss. Clinical studies of estrogen deprivation, antiresorptives, mechanical loading, and disuse have helped further knowledge of the factors affecting bone quality and the mechanisms that underlie them. This progress has led to several new drug targets in the treatment of osteoporosis. Copyright © 2012 Elsevier Inc. All rights reserved.

Mood-Stabilizing Anticonvulsants, Spina Bifida, and Folate Supplementation: Commentary.

PubMed

Patel, Neil; Viguera, Adele C; Baldessarini, Ross J

2018-02-01

High risks of neural tube defects and other teratogenic effects are associated with exposure in early pregnancy to some anticonvulsants, including in women with bipolar disorder. Based on a semistructured review of recent literature, we summarized findings pertaining to this topic. Valproate and carbamazepine are commonly used empirically (off-label) for putative long-term mood-stabilizing effects. Both anticonvulsants have high risks of teratogenic effects during pregnancy. Risks of neural tube defects (especially spina bifida) and other major malformations are especially great with valproate and can arise even before pregnancy is diagnosed. Standard supplementation of folic acid during pregnancy can reduce risk of spontaneous spina bifida, but not that associated with valproate or carbamazepine. In contrast, lamotrigine has regulatory approval for long-term use in bipolar disorder and appears not to have teratogenic effects in humans. Lack of protective effects against anticonvulsant-associated neural tube defects by folic acid supplements in anticipation of and during pregnancy is not widely recognized. This limitation and high risks of neural tube and other major teratogenic effects, especially of valproate, indicate the need for great caution in the use of valproate and carbamazepine to treat bipolar disorder in women of child-bearing age.

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.

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.

Cardiac diseases as a risk factor for stroke in Saudi children.

PubMed

Salih, Mustafa A; Al-Jarallah, Abdullah S; Abdel-Gader, Abdel-Galil M; Al-Jarallah, Ahmed A; Al-Saadi, Muslim M; Kentab, Amal Y; Alorainy, Ibrahim A; Hassan, Hamdy H

2006-03-01

To ascertain the role of cardiac diseases as a risk factor for stroke in a cohort of Saudi children who were evaluated in a retrospective and prospective study. Children with cardiac diseases were identified from within a cohort of 104 Saudi children who presented with stroke. They were seen as inpatients in the Pediatric Wards or evaluated at the Outpatient Clinics of the Division of Pediatric Neurology (DPN), and the Division of Pediatric Cardiology at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia during the periods July 1992 to February 2001 (retrospective study) and February 2001 to March 2003 (prospective study). A comprehensive form for clinical, neuroimaging, neurophysiological and laboratory data retrieval was designed and completed for each patient. Cardiac evaluation included 12-lead ECG and serial echocardiograms. Cardiac catheterization and 24-hour ambulatory ECG (Holter) were conducted on clinical discretion. Cardiac diseases were the underlying risk factor for stroke in 6 (5.8%) of the 104 children (aged one month to 12 years). The patients (4 males and 2 females) were evaluated at the DPN at a mean age of 5.3 years (range = 1-8 years; median 6.5 years). Onset of stroke was at a mean age of 34 months (range = 4 months-8 years; median = 30 months). Five patients had stroke in association with congenital heart disease (CHD), whereas the sixth had restrictive cardiomyopathy. The identified CHD consisted of membranous ventricular septal defect in a 5-year-old boy who had moyamoya syndrome and sickle cell beta(0)-thalassemia, asymptomatic patent ductus arteriosus (PDA) in a 17-month-old girl, atrioventricular canal defect and PDA in an 8-year-old boy who also had Down syndrome, partial anomalous pulmonary venous drainage in a one-year-old boy, and Tetralogy of Fallot in an 8-year-old boy. The latter patient developed hemiparesis secondary to a septic embolus, which evolved into brain abscess involving the right fronto-parietal region. This was successfully managed surgically. The sixth patient was an 8 1/2-year-old girl who had hemiparesis and complex partial seizure in association with restrictive cardiomyopathy. Serial echocardiograms depicted resolution of the cardiac abnormalities within 5 years and subsequent normal findings. Cardiac diseases, as a group, constitute a significant risk factor for stroke in Saudi children. Early diagnosis of these diseases is important to prevent further recurrences of stroke, and because some of them are potentially curable.

Congenital malformations associated with assisted reproductive technology: a California statewide analysis.

PubMed

Kelley-Quon, Lorraine I; Tseng, Chi-Hong; Janzen, Carla; Shew, Stephen B

2013-06-01

Management of congenital malformations comprises a large part of pediatric surgical care. Despite increasing utilization of assisted reproductive technology (ART) and fertility-related services (FRS), associations with birth defects are poorly understood. Infants born after ART or FRS were identified from the California Linked Birth Cohort Dataset from 2006 to 2007 and compared to propensity matched infants conceived naturally. Factors associated with major congenital malformations were evaluated using Firth logistic regression. With a cohort of 4,795 infants born after ART and 46,025 naturally conceived matched controls, major congenital malformations were identified in 3,463 infants. Malformations were increased for ART infants (9.0% vs. 6.6%, p<0.001). After adjusting for infant and maternal factors, ART infants exhibited increased odds of major malformations overall (OR 1.25, 95% CI 1.12-1.39), specifically defects of the eye (OR 1.81, 95% CI 1.04-3.16), head and neck (OR 1.37, 95% CI 1.00-1.86), heart (OR 1.41, 95% CI 1.22-1.64), and genitourinary system (OR 1.40, 95% CI 1.09-1.82). The likelihood of birth defects was increased for multiples (OR 1.35, 95% CI 1.18-1.54) and not singletons. Odds of congenital malformation after FRS alone (n=1,749) were non-significant. ART contributes a significant risk of congenital malformation and may be more pronounced for multiples. Accurate counseling for parents considering ART and multidisciplinary coordination of care prior to delivery are warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

Purification and growth of melanocortin 1 receptor (Mc1r)-defective primary murine melanocytes is dependent on stem cell factor from keratinocyte-conditioned media

PubMed Central

Scott, Timothy L.; Wakamatsu, Kazumasa; Ito, Shosuke; D’Orazio, John A.

2015-01-01

Summary The melanocortin 1 receptor (MC1R) is a transmembrane Gs-coupled surface protein found on melanocytes that binds melanocyte stimulating hormone (MSH) and mediates activation of adenylyl cyclase and generation of the second messenger cAMP. MC1R regulates growth and differentiation of melanocytes and protects against carcinogenesis. Persons with loss-of-function polymorphisms of MC1R tend to be UV-sensitive (fair-skinned and with a poor tanning response) and are at high risk for melanoma. Mechanistic studies of the role of MC1R in melanocytic UV responses, however, have been hindered in part because Mc1r-defective primary murine melanocytes have been difficult to culture in vitro. Until now, effective growth of murine melanocytes has depended on cAMP stimulation with adenylyl cyclase activating or phosphodiesterase inhibiting agents. However, rescuing cAMP in the setting of defective MC1R signaling would be expected to confound experiments directly testing MC1R function on melanocytic UV responses. Here we report a novel method of culturing primary murine melanocytes in the absence of pharmacologic cAMP stimulation by incorporating conditioned supernatants containing stem cell factor (SCF) derived from primary keratinocytes. Importantly, this method seems to permit similar pigment expression by cultured melanocytes as that found in the skin of their parental murine strains. This novel approach will allow mechanistic investigation into MC1R’s role in protection against UV-mediated carcinogenesis and determination of the role of melanin pigment subtypes on UV-mediated melanocyte responses. PMID:19633898

Genetic testing in congenital heart disease: A clinical approach

PubMed Central

Chaix, Marie A; Andelfinger, Gregor; Khairy, Paul

2016-01-01

Congenital heart disease (CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient follow-up. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel. PMID:26981213

Choline and betaine in health and disease.

PubMed

Ueland, Per Magne

2011-02-01

Choline is an essential nutrient, but is also formed by de novo synthesis. Choline and its derivatives serve as components of structural lipoproteins, blood and membrane lipids, and as a precursor of the neurotransmitter acetylcholine. Pre-and postnatal choline availability is important for neurodevelopment in rodents. Choline is oxidized to betaine that serves as an osmoregulator and is a substrate in the betaine-homocysteine methyltransferase reaction, which links choline and betaine to the folate-dependent one-carbon metabolism. Choline and betaine are important sources of one-carbon units, in particular, during folate deficiency. Choline or betaine supplementation in humans reduces concentration of total homocysteine (tHcy), and plasma betaine is a strong predictor of plasma tHcy in individuals with low plasma concentration of folate and other B vitamins (B₂, B₆, and B₁₂) in combination TT genotype of the methylenetetrahydrofolate reductase 677 C->T polymorphism. The link to one-carbon metabolism and the recent availability of food composition data have motivated studies on choline and betaine as risk factors of chronic diseases previously studied in relation to folate and homocysteine status. High intake and plasma level of choline in the mother seems to afford reduced risk of neural tube defects. Intake of choline and betaine shows no consistent relation to cancer or cardiovascular risk or risk factors, whereas an unfavorable cardiovascular risk factor profile was associated with high choline and low betaine concentrations in plasma. Thus, choline and betaine showed opposite relations with key components of metabolic syndrome, suggesting a disruption of mitochondrial choline oxidation to betaine as part of the mitochondrial dysfunction in metabolic syndrome.

Defect Chemistry of Oxides for Energy Applications.

PubMed

Schweke, Danielle; Mordehovitz, Yuval; Halabi, Mahdi; Shelly, Lee; Hayun, Shmuel

2018-05-31

Oxides are widely used for energy applications, as solid electrolytes in various solid oxide fuel cell devices or as catalysts (often associated with noble metal particles) for numerous reactions involving oxidation or reduction. Defects are the major factors governing the efficiency of a given oxide for the above applications. In this paper, the common defects in oxide systems and external factors influencing the defect concentration and distribution are presented, with special emphasis on ceria (CeO 2 ) based materials. It is shown that the behavior of a variety of oxide systems with respect to properties relevant for energy applications (conductivity and catalytic activity) can be rationalized by general considerations about the type and concentration of defects in the specific system. A new method based on transmission electron microscopy (TEM), recently reported by the authors for mapping space charge defects and measuring space charge potentials, is shown to be of potential importance for understanding conductivity mechanisms in oxides. The influence of defects on gas-surface reactions is exemplified on the interaction of CO 2 and H 2 O with ceria, by correlating between the defect distribution in the material and its adsorption capacity or splitting efficiency. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Health consequences of passive smoking].

PubMed

Haustein, K O

2001-06-01

Environmental tobacco smoking (ETS) represents a main risk factor for the generation of diseases of the respiratory tract and of the cardiovascular system in spite of statements to the contrary. ETS enhances the risk of lung cancer by a factor of 2-3. Newborn and small children (< 2 years of life) are at high risk if they live within this period of time in a household exposed to maternal more than fraternal smoking. Endothelial cells of the blood vessels are damaged as early as during the first month of life of passive smoking children, and these defects can be detected during the first decade of life. ETS over a period of more than ten years changes the intima/media ratio by enhancing the thickness of the vessel wall. Additionally, poor health behaviour is seen in households of smokers because the behaviour of the parents is transferred to that of their children, and this behaviour is the starting point of further health risks and damages. The presented data should cause a call for primary smoking prevention preferably among children and young persons on the one hand, and the organisation of programs against ETS at the workplace and in public buildings, as well as in the private house on the other hand. Non-smokers must be informed about the risks and dangers of ETS more than it is the case up to now.

Defects, Entropy, and the Stabilization of Alternative Phase Boundary Orientations in Battery Electrode Particles

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

Heo, Tae Wook; Tang, Ming; Chen, Long-Qing

Using a novel statistical approach that efficiently explores the space of possible defect configurations, our present study investigates the chemomechanical coupling between interfacial structural defects and phase boundary alignments within phase-separating electrode particles. Applied to the battery cathode material Li XFePO 4 as an example, the theoretical analysis reveals that small, defect-induced deviations from an ideal interface can lead to dramatic shifts in the orientations of phase boundaries between Li-rich and Li-lean phases, stabilizing otherwise unfavorable orientations. Significantly, this stabilization arises predominantly from configurational entropic factors associated with the presence of the interfacial defects rather than from absolute energetic considerations.more » The specific entropic factors pertain to the diversity of defect configurations and their contributions to rotational/orientational rigidity of phase boundaries. Comparison of the predictions with experimental observations indicates that the additional entropy contributions indeed play a dominant role under actual cycling conditions, leading to the conclusion that interfacial defects must be considered when analyzing the stability and evolution kinetics of the internal phase microstructure of strongly phase-separating systems. Possible implications for tuning the kinetics of (de)lithiation based on selective defect incorporation are discussed. Ultimately, this understanding can be generalized to the chemomechanics of other defective solid phase boundaries.« less

Defects, Entropy, and the Stabilization of Alternative Phase Boundary Orientations in Battery Electrode Particles

DOE PAGES

Heo, Tae Wook; Tang, Ming; Chen, Long-Qing; ...

2016-01-04

Using a novel statistical approach that efficiently explores the space of possible defect configurations, our present study investigates the chemomechanical coupling between interfacial structural defects and phase boundary alignments within phase-separating electrode particles. Applied to the battery cathode material Li XFePO 4 as an example, the theoretical analysis reveals that small, defect-induced deviations from an ideal interface can lead to dramatic shifts in the orientations of phase boundaries between Li-rich and Li-lean phases, stabilizing otherwise unfavorable orientations. Significantly, this stabilization arises predominantly from configurational entropic factors associated with the presence of the interfacial defects rather than from absolute energetic considerations.more » The specific entropic factors pertain to the diversity of defect configurations and their contributions to rotational/orientational rigidity of phase boundaries. Comparison of the predictions with experimental observations indicates that the additional entropy contributions indeed play a dominant role under actual cycling conditions, leading to the conclusion that interfacial defects must be considered when analyzing the stability and evolution kinetics of the internal phase microstructure of strongly phase-separating systems. Possible implications for tuning the kinetics of (de)lithiation based on selective defect incorporation are discussed. Ultimately, this understanding can be generalized to the chemomechanics of other defective solid phase boundaries.« less

Alkaline Phosphatase Protects Lipopolysaccharide-Induced Early Pregnancy Defects in Mice

PubMed Central

Lei, Wei; Ni, Hua; Herington, Jennifer; Reese, Jeff; Paria, Bibhash C.

2015-01-01

Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial infection during pregnancy leads to pregnancy complications such as early pregnancy defects/loss and preterm birth. Bacterial toxin lipopolysaccharide (LPS), long recognized as a potent proinflammatory mediator, has been identified as a risk factor for pregnancy complications. Alkaline phosphatase (AP) isozymes have been shown to detoxify LPS by dephosphorylation. In this study, we examined the role of alkaline phosphatase (AP) in mitigating LPS-induced early pregnancy complications in mice. We found that 1) the uterus prior to implantation and implantation sites following embryo implantation produce LPS recognition and dephosphorylation molecules TLR4 and tissue non-specific AP (TNAP) isozyme, respectively; 2) uterine TNAP isozyme dephosphorylates LPS at its sites of production; 3) while LPS administration following embryo implantation elicits proinflammatory cytokine mRNA levels at the embryo implantation sites (EISs) and causes early pregnancy loss, dephosphorylated LPS neither triggers proinflammatory cytokine mRNA levels at the EISs nor induces pregnancy complications; 4) AP isozyme supplementation to accelerate LPS detoxification attenuates LPS-induced pregnancy complications following embryo implantation. These findings suggest that a LPS dephosphorylation strategy using AP isozyme may have a unique therapeutic potential to mitigate LPS- or Gram-negative bacteria-induced pregnancy complications in at-risk women. PMID:25910276

Alkaline phosphatase protects lipopolysaccharide-induced early pregnancy defects in mice.

PubMed

Lei, Wei; Ni, Hua; Herington, Jennifer; Reese, Jeff; Paria, Bibhash C

2015-01-01

Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial infection during pregnancy leads to pregnancy complications such as early pregnancy defects/loss and preterm birth. Bacterial toxin lipopolysaccharide (LPS), long recognized as a potent proinflammatory mediator, has been identified as a risk factor for pregnancy complications. Alkaline phosphatase (AP) isozymes have been shown to detoxify LPS by dephosphorylation. In this study, we examined the role of alkaline phosphatase (AP) in mitigating LPS-induced early pregnancy complications in mice. We found that 1) the uterus prior to implantation and implantation sites following embryo implantation produce LPS recognition and dephosphorylation molecules TLR4 and tissue non-specific AP (TNAP) isozyme, respectively; 2) uterine TNAP isozyme dephosphorylates LPS at its sites of production; 3) while LPS administration following embryo implantation elicits proinflammatory cytokine mRNA levels at the embryo implantation sites (EISs) and causes early pregnancy loss, dephosphorylated LPS neither triggers proinflammatory cytokine mRNA levels at the EISs nor induces pregnancy complications; 4) AP isozyme supplementation to accelerate LPS detoxification attenuates LPS-induced pregnancy complications following embryo implantation. These findings suggest that a LPS dephosphorylation strategy using AP isozyme may have a unique therapeutic potential to mitigate LPS- or Gram-negative bacteria-induced pregnancy complications in at-risk women.

The effects of male age on sperm DNA damage in healthy non-smokers

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

Schmid, T; Eskenazi, B; Baumgartner, A

The trend for men to have children at older ages raises concerns that advancing age may increase the production of genetically defective sperm, increasing the risks of transmitting germ-line mutations. We investigated the associations between male age and sperm DNA damage and the influence of several lifestyle factors in a healthy non-clinical group of 80 non-smokers (age: 22-80) with no known fertility problems using the sperm Comet analyses. The average percent of DNA that migrated out of the sperm nucleus under alkaline electrophoresis increased with age (0.18% per year, p=0.006); but there was no age association for damage measured undermore » neutral conditions (p=0.7). Men who consumed >3 cups coffee per day had {approx}20% higher % tail DNA under neutral but not alkaline conditions compared to men who consumed no caffeine (p=0.005). Our findings indicate that (a) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks, and (b) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization increasing the risks for developmental defects and genetic diseases among offspring.« less

Heparan Sulfate Expression in the Neural Crest is Essential for Mouse Cardiogenesis

PubMed Central

Pan, Yi; Carbe, Christian; Pickhinke, Ute; Kupich, Sabine; Ohlig, Stefanie; Frye, Maike; Seelige, Ruth; Pallerla, Srinivas R.; Moon, Anne M.; Lawrence, Roger; Esko, Jeffrey D.; Zhang, Xin; Grobe, Kay

2015-01-01

Impaired heparan sulfate (HS) synthesis in vertebrate development causes complex malformations due to the functional disruption of multiple HS-binding growth factors and morphogens. Here, we report developmental heart defects in mice bearing a targeted disruption of the HS-generating enzyme GlcNAc N-Deacetylase/GlcN N-Sulfotransferase 1 (NDST1), including ventricular septal defects (VSD), persistent truncus arteriosus (PTA), double outlet right ventricle (DORV), and retroesophageal right subclavian artery (RERSC). These defects closely resemble cardiac anomalies observed in mice made deficient in the cardiogenic regulator fibroblast growth factor 8 (FGF8). Consistent with this, we show that HS-dependent FGF8/FGF-receptor2C assembly and FGF8-dependent ERK-phosphorylation are strongly reduced in NDST1−/− embryonic cells and tissues. Moreover, WNT1-Cre/LoxP-mediated conditional targeting of NDST function in neural crest cells (NCCs) revealed that their impaired HS-dependent development contributes strongly to the observed cardiac defects. These findings raise the possibility that defects in HS biosynthesis may contribute to congenital heart defects in humans that represent the most common type of birth defect. PMID:24200809

Genetic variation in biotransformation enzymes, air pollution exposures, and risk of spina bifida.

PubMed

Padula, Amy M; Yang, Wei; Schultz, Kathleen; Lurmann, Fred; Hammond, S Katharine; Shaw, Gary M

2018-05-01

Spina bifida is a birth defect characterized by incomplete closure of the embryonic neural tube. Genetic factors as well as environmental factors have been observed to influence risks for spina bifida. Few studies have investigated possible gene-environment interactions that could contribute to spina bifida risk. The aim of this study is to examine the interaction between gene variants in biotransformation enzyme pathways and ambient air pollution exposures and risk of spina bifida. We evaluated the role of air pollution exposure during pregnancy and gene variants of biotransformation enzymes from bloodspots and buccal cells in a California population-based case-control (86 cases of spina bifida and 208 non-malformed controls) study. We considered race/ethnicity and folic acid vitamin use as potential effect modifiers and adjusted for those factors and smoking. We observed gene-environment interactions between each of the five pollutants and several gene variants: NO (ABCC2), NO 2 (ABCC2, SLC01B1), PM 10 (ABCC2, CYP1A1, CYP2B6, CYP2C19, CYP2D6, NAT2, SLC01B1, SLC01B3), PM 2.5 (CYP1A1 and CYP1A2). These analyses show positive interactions between air pollution exposure during early pregnancy and gene variants associated with metabolizing enzymes. These exploratory results suggest that some individuals based on their genetic background may be more susceptible to the adverse effects of pollution. © 2018 Wiley Periodicals, Inc.

Allergen sensitisation among chronic respiratory diseases in urban and rural areas of the south of Viet Nam.

PubMed

Chu, H T; Godin, I; Phuong, N T; Nguyen, L H; Hiep, T T M; Michel, O

2018-02-01

To evaluate the prevalence of and risk factors for allergen sensitisation among patients with chronic respiratory disease (CRD) in southern Viet Nam. An environmental questionnaire and skin prick tests for airborne and food allergens were administered to patients with CRD, defined as individuals with respiratory symptoms and lung function defects. Of 610 CRD patients, 56% had chronic obstructive pulmonary disease and 31% were asthma patients; 80% were males. The most frequent sensitisers were dust mites (Dermatophagoides farinae 22%, Blomia tropicalis 19%, D. pteronyssinus 18%) and cockroach droppings (13%). Among study participants, 37% were from rural settings and 36% from urban areas, whereas 27% had migrated from rural to urban areas. Compared with people from rural areas, being born in an urban area was a risk factor for sensitisation to mites (OR 1.56, 95%CI 1.11-2.20, P < 0.02). In multivariate analysis, place of birth remained a risk factor for mite sensitisation. Compared with the native urban population, the risk of mite sensitisation was not significantly different among patients born in rural areas and those migrating to urban areas. Dust mites and cockroach droppings were the most frequent allergens among people with CRD in the south of Viet Nam. Compared with the urban population, being native to a rural area was protective against mite sensitisation, but this effect ceased to be significant after migration from rural to urban areas.

Inheritance Analysis of Congenital Left Ventricular Outflow Tract Obstruction Malformations: Segregation, Multiplex Relative Risk, and Heritability

PubMed Central

McBride, Kim L.; Pignatelli, Ricardo; Lewin, Mark; Ho, Trang; Fernbach, Susan; Menesses, Andres; Lam, Wilbur; Leal, Suzanne M.; Kaplan, Norman; Schliekelman, Paul; Towbin, Jeffrey A.; Belmont, John W.

2006-01-01

The left ventricular outflow tract (LVOTO) malformations, aortic valve stenosis (AVS), coarctation of the aorta (COA), and hypoplastic left heart (HLH) constitute a mechanistically defined subgroup of congenital heart defects that have substantial evidence for a genetic component. Evidence from echocardiography studies has shown that bicuspid aortic valve (BAV) is found frequently in relatives of children with LVOTO defects. However, formal inheritance analysis has not been performed. We ascertained 124 families by an index case with AVS, COA, or HLH. A total of 413 relatives were enrolled in the study, of which 351 had detailed echocardiography exams for structural heart defects and measurements of a variety of aortic arch, left ventricle, and valve structures. LVOTO malformations were noted in 30 relatives (18 BAV, 5 HLH, 3 COA, and 3 AVS), along with significant congenital heart defects (CHD) in 2 others (32/413; 7.7%). Relative risk for first-degree relatives in this group was 36.9, with a heritability of 0.71–0.90. Formal segregation analysis suggests that one or more minor loci with rare dominant alleles may be operative in a subset of families. Multiplex relative risk analysis, which estimates number of loci, had the highest maximum likelihood score in a model with 2 loci (range of 1–6 in the lod-1 support interval). Heritability of several aortic arch measurements and aortic valve was significant. These data support a complex but most likely oligogenic pattern of inheritance. A combination of linkage and association study designs is likely to enable LVOTO risk gene identification. This data can also provide families with important information for screening asymptomatic relatives for potentially harmful cardiac defects. PMID:15690347

[Alcohol--woman, pregnancy and a newborn child].

PubMed

Jagielska, Iwona; Kazdepka-Ziemińska, Anita; Stankiewicz, Martyna; Kaźmierczak, Jolanta

2012-01-01

According to the World Health Organization, alcohol is the third most dangerous factor following smoking of tobacco and hypertension of risks impacting health of the population. 50 % of men and 10 % of women suffer from diseases caused by alcohol drinking. Chronic consumption of alcohol damages the nervous system, causes adverse changes in the circulatory system and intestine, increases the risk of cancers. Comparing the impact of alcohol on the health of women and men, in case of women, even similar levels of consumption cause stronger action. Alcohol is the cause of endocrine diseases and among others- reduces fertility. It is the risk factor of premature deliveries, abortions, and placenta- associated pathologies. Disorders of children with prenatal exposure to alcohol are described as fetal alcohol syndrome, alcohol related neurodevelopmental disorders and alcohol related birth defects. It is recommended to impose a total ban on alcohol consumption by pregnant women. Moreover one should emphasize that the minimum safe dose of alcohol for the foetus cannot be specified. In order to resolve alcohol drinking problems a cooperation of representatives of many professions such as: doctors, psychologists, educators and employees of care facilities is necessary. It is also obligatory to obtain support and assistance from the nearest surroundings of the patient.

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.

Growth of left ventricular outflow tract and predictors of future re-intervention after repair for ventricular septal defect and aortic arch obstruction.

PubMed

Jijeh, Abdulraouf; Ismail, Muna; Alhabshan, Fahad

2017-09-01

Ventricular septal defect and aortic arch obstruction are usually associated with a narrow left ventricular outflow tract. The aim of the present study was to analyse the growth and predictors of future obstruction of the left ventricular outflow tract after surgical repair. We carried out a retrospective review of patients who underwent repair for ventricular septal defect and aortic arch obstruction - coarctation or interrupted aortic arch - between July, 2002 and June, 2013. Echocardiographic data were reviewed, and the need for re-intervention was evaluated. A total of 89 patients were included in this study. A significant left ventricular outflow tract growth was noticed after surgical repair. Preoperatively, the mean left ventricular outflow tract Z-score was -1.46±1 (range -5.5 to 1.1) and increased to a mean value of -0.7±1.3 (range -2.7 to 3.2) at last follow-up (p=0.0001), demonstrating relevant growth of the left ventricular outflow tract after repair for ventricular septal defect and aortic arch obstruction. After primary repair, 11 patients (12.3%) required re-intervention with surgical repair for left ventricular outflow tract obstruction after a mean period of 36±21 months. There were no significant differences in age, weight, and indexed aortic valve and left ventricular outflow tract measurements between those who developed obstruction and those who did not. Significant left ventricular outflow tract growth is expected after repair of ventricular septal defect and aortic arch obstruction. Small aortic valve and left ventricular outflow tract at diagnosis are not risk factors to predict the need for surgical re-intervention for left ventricular outflow tract obstruction in future.

Characterization of cartilage defects detected by MRI in Kellgren-Lawrence grade 0 or 1 knees.

PubMed

Taguchi, Kenji; Chiba, Ko; Okazaki, Narihiro; Kido, Yasuo; Miyamoto, Takashi; Yonekura, Akihiko; Tomita, Masato; Uetani, Masataka; Osaki, Makoto

2017-09-01

Osteoarthritis of the knee is generally evaluated by plain X-rays, which are incapable of detecting small cartilage damage. There are some patients who have small cartilage defects on MRI with no abnormal findings on plain X-rays. In this study, the prevalence and regional characteristics of cartilage defects detected by MRI were studied in cases with normal X-ray findings (Kellgren-Lawrence grade 0 and 1). Relationships between the cartilage defects and OA risk factors such as obesity and leg alignment were also investigated. A total of 51 knees of Kellgren-Lawrence grade 0 or 1 without knee joint pain were included. Fat-suppressed spoiled-gradient recalled (SPGR) sagittal images were scanned by 3 T MRI, and the presence of cartilage damage was confirmed. Cartilage damage was visualized three-dimensionally, and its location and morphology were analyzed. On a full length standing radiograph of the lower extremities, leg alignment and other parameters were measured, and their associations with cartilage damage were analyzed. Cartilage defects were detected in 26% of women aged >50 years. Cartilage damage was located on the medial femoral condyle near the intercondylar notch, and was mostly elliptically shaped in the anteroposterior direction. Subjects with damaged cartilage were not obese and did not have abnormal leg alignment. It should be borne in mind that some elderly women may have damaged cartilage on the intercondylar notch side of the medial joint, even though plain X-rays appear normal, and this cannot be predicted by obesity or leg alignment. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Association of compartment defects in anorectal and pelvic floor dysfunction with female outlet obstruction constipation (OOC) by dynamic MR defecography.

PubMed

Li, M; Jiang, T; Peng, P; Yang, X-Q; Wang, W-C

2015-04-01

Chronic constipation affects more than 17% of the global population worldwide, and up to 50% of patients were outlet obstruction constipation (OOC). Women and the elderly are most likely to be affected, due to female-specific risk factors, such as menopause, parity and multiparity. The aim of our study was to investigate the association of compartment defects in anorectal and pelvic floor dysfunction with female outlet obstruction constipation (OOC) by MR defecography. Fifty-six consecutive women diagnosed with outlet obstruction constipation from October 2009 to July 2011 were included. They were categorized into the following groups: anorectal disorder only group (27 patients) and anorectal disorder plus multi-compartment pelvic disorder group (29 patients). Relevant measurements were taken at rest, during squeezing and straining. Anismus was significantly more common in the anorectal disorder group compared to the multi-compartment pelvic disorder group. Conversely, rectocele, rectal prolapse, and descending perineum were significantly more common in the multi-compartment pelvic disorder group compared to the anorectal disorder group. Of the total 56 OOC patients, 34 (60.7%) exhibited anismus and 38 (67.9%) rectocele. Among the anismus patients, there were 8 patients (23.5%) with combined cystocele, and 6 patients (17.6%) with combined vaginal/cervical prolapse. Among the rectocele patients, there were 23 patients (60.5%) with combined cystocele and 18 patients (47.4%) with combined vaginal/cervical prolapse. With respect to anorectal defects, 13 anismus patients (38.2%) were with signal posterior pelvic defects, 4 rectocele patients (10.5%) presented with signal posterior pelvic defects. Inadequate defecatory propulsion due to outlet obstruction constipation is often associated with multi-compartment pelvic floor disorders, whereas not about dyssynergic defecation.

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.

Evaluating Predictive Models of Software Quality

NASA Astrophysics Data System (ADS)

Ciaschini, V.; Canaparo, M.; Ronchieri, E.; Salomoni, D.

2014-06-01

Applications from High Energy Physics scientific community are constantly growing and implemented by a large number of developers. This implies a strong churn on the code and an associated risk of faults, which is unavoidable as long as the software undergoes active evolution. However, the necessities of production systems run counter to this. Stability and predictability are of paramount importance; in addition, a short turn-around time for the defect discovery-correction-deployment cycle is required. A way to reconcile these opposite foci is to use a software quality model to obtain an approximation of the risk before releasing a program to only deliver software with a risk lower than an agreed threshold. In this article we evaluated two quality predictive models to identify the operational risk and the quality of some software products. We applied these models to the development history of several EMI packages with intent to discover the risk factor of each product and compare it with its real history. We attempted to determine if the models reasonably maps reality for the applications under evaluation, and finally we concluded suggesting directions for further studies.

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.

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

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.

Detection of avascular necrosis in adults by single photon emission computed tomography

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

Collier, B.D.; Johnston, R.P.; Carrera, G.

1984-01-01

Twenty-one adult patients with the clinical diagnosis of avascular necrosis (AVN) of the femoral head were examined with planar bone scintigraphy (high resolution collimator) and single photon emission computed tomography (SPECT). The duration of hip pain ranged from 1 day to 18 months. Risk factors (including steroids, renal transplantation, alcoholism, and trauma) were present in 17 cases. A final diagnosis of AVN (20 hips), osteochondral facture, or stress fracture, was established for 17 patients. The 4 remaining patients, who were radiographically normal and did not complain of pain 3 months later, were thought to have no significant bone pathology. SPECTmore » and planar bone scintigraphy were reported as positive for AVN only if a photopenic bony defect could be identified. In particular, uniformly increased activity throughout the femoral head was not considered to be diagnostic of AVN. The authors conclude that by identifying a photopenic defect which is not evident on planar bone scintigraphy, SPECT can contribute to accurate diagnosis of AVN.« less

Inborn oxidative phosphorylation defect as risk factor for propofol infusion syndrome.

PubMed

Vanlander, A V; Jorens, P G; Smet, J; De Paepe, B; Verbrugghe, W; Van den Eynden, G G; Meire, F; Pauwels, P; Van der Aa, N; Seneca, S; Lissens, W; Okun, J G; Van Coster, R

2012-04-01

Propofol is an anesthetic agent widely used for induction and maintenance of anesthesia, and sedation in children. Although generally considered as reliable and safe, administration of propofol can occasionally induce a potentially fatal complication known as propofol infusion syndrome (PRIS). Mitochondrial dysfunction has been implicated in the pathogenesis of PRIS. We report on an adult patient with Leber hereditary optic neuropathy (LHON) who developed PRIS. He was a carrier of the m.3460G>A mutation, one of the major three pathogenic point mutations associated with LHON. The propositus was blind and underwent propofol sedation after severe head injury. Five days after start of propofol infusion, the patient died. The activity of complex I of the oxidative phosphorylation (OXPHOS) system was severely deficient in skeletal muscle. Our observation indicates that fulminate PRIS can occur in an adult patient with an inborn OXPHOS defect and corroborates the hypothesis that PRIS is caused by inhibition of the OXPHOS system. © 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.

Analysis of birth defects among children 3 years after conception through assisted reproductive technology in China.

PubMed

Yin, Li; Hang, Fu; Gu, Long-jie; Xu, Bei; Ma, Ding; Zhu, Gui-jin

2013-11-01

Previous studies inconsistently suggest that assisted reproduction technology (ART) may increase the risk of birth defects in children. Live birth infants, conceived by in vitro fertilization fresh embryo transfer (IVF), intracytoplasmic sperm injection fresh embryo transfer (ICSI), or frozen-thawed embryo transfer (FET) in Reproductive Center of Tongji Hospital (Wuhan, China) between 1997 and 2008, were followed up at birth and after 3 years. Preterm pregnancy, multiple pregnancy, sex ratio (male/female), congenital malformation were compared. A total of 4,236 children were born after ART (IVF 2,543, ICSI 908, FET 785). Compared with IVF, the rate of preterm pregnancy and sex ratio in ICSI were lower (p < 0.05); the rate of multiple pregnancy in ICSI and FET were all lower than IVF (p < 0.05). Congenital defects were comparable in all groups at birth. In total, 2,908 children participated in the second follow-up from 34 months to 60 months with an average of 40 months, and the cases of birth defects had doubled (3 years: 5.16%, birth: 2.22%). The birth defect rate in boys conceived through ICSI was significantly higher than the IVF group after 3-year follow-up (ICSI boys: 8.62%, IVF boys: 5.21% [p < 0.05]), even though there was no significant difference at birth. Compared with IVF, FET may not increase risk of birth defects. Children conceived through ICSI, especially males, had higher rates of congenital malformations that were inapparent at birth. So longitudinal monitoring may provide insights into the risks of ART. Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

Association of childhood adiposity measures with adulthood knee cartilage defects and bone marrow lesions: a 25-year cohort study.

PubMed

Meng, T; Thayer, S; Venn, A; Wu, F; Cicuttini, F; March, L; Dwyer, T; Halliday, A; Cross, M; Laslett, L L; Jones, G; Ding, C; Antony, B

2018-05-25

To describe the associations between childhood adiposity measures and adulthood knee cartilage defects and bone marrow lesions (BMLs) measured 25 years later. 327 participants from the Australian Schools Health and Fitness Survey (ASHFS) of 1985 (aged 7-15 years) were followed up 25 years later (aged 31-41 years). Childhood measures (weight, height and skinfolds) were collected in 1985. Body mass index (BMI), overweight status and fat mass were calculated. Participants underwent 1.5 T knee magnetic resonance imaging (MRI) during 2008-2010, and cartilage defects and BMLs were scored from knee MRI scans. Log binomial regressions were used to examine the associations. Among 327 participants (47.1% females), 21 (6.4%) were overweight in childhood. Childhood adiposity measures were associated with the increased risk of adulthood patellar cartilage defects (Weight relative risk (RR) 1.05/kg, 95% confidence interval (CI) 1.01-1.09; BMI 1.10/kg/m 2 , 1.01-1.19; Overweight 2.22/yes, 1.21-4.08; fat mass 1.11/kg, 1.01-1.22), but not tibiofemoral cartilage defects. Childhood adiposity measures were not significantly associated with adulthood knee BMLs except for the association between childhood overweight status and adulthood patellar BMLs (RR 2.87/yes, 95% CI 1.10-7.53). These significant associations persisted after adjustment for corresponding adulthood adiposity measure. Childhood adiposity measures were associated with the increased risk of adulthood patellar cartilage defects and, to a lesser extent, BMLs, independent of adulthood adiposity measures. These results suggest that adiposity in childhood has long-term effects on patellar structural abnormalities in young adults. Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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.

Chronic acetaminophen ingestion resulting in severe anion gap metabolic acidosis secondary to 5-oxoproline accumulation: an under diagnosed phenomenon.

PubMed

O'Brien, L Morgan Nordstrom; Hooper, Michael; Flemmer, Mark; Marik, Paul Ellis

2012-07-03

Anion gap metabolic acidosis is commonly caused by lactic acidosis, ketoacidosis, and ingestion of methanol, salicylates, ethylene glycol or accumulation of organic/inorganic acids. However, rare causes of metabolic acidosis from enzyme defects, such as disturbances in the γ-glutamyl cycle, are being reported in higher frequencies in the adult population. Such disturbances cause an accumulation of 5-oxoproline and ultimately an anion gap metabolic acidosis. These disturbances are often associated with acetaminophen in the setting of certain risk factors such as sepsis, malnutrition, liver disease, female gender, pregnancy or renal failure.

Learning curves in abdominal wall reconstruction with components separation: one step closer toward improving outcomes and reducing complications.

PubMed

Hultman, Charles Scott; Clayton, John L; Kittinger, Benjamin J; Tong, Winnie M

2014-01-01

Learning curves are characterized by incremental improvement of a process, through repetition and reduction in variability, but can be disrupted with the emergence of new techniques and technologies. Abdominal wall reconstruction continues to evolve, with the introduction of components separation in the 1990s and biologic mesh in the 2000s. As such, attempts at innovation may impact the success of reconstructive outcomes and yield a changing set of complications. The purpose of this project was to describe the paradigm shift that has occurred in abdominal wall reconstruction during the past 10 years, focusing on the incorporation of new materials and methods. We reviewed 150 consecutive patients who underwent abdominal wall reconstruction of midline defects with components separation, from 2000 to 2010. Both univariate and multivariate logistic regression analyses were performed to identify risk factors for complications. Patients were stratified into the following periods: early (2000-2003), middle (2004-2006), and late (2007-2010). From 2000 to 2010, we performed 150 abdominal wall reconstructions with components separation [mean age, 50.2 years; body mass index (BMI), 30.4; size of defect, 357 cm; length of stay, 9.6 days; follow-up, 4.4 years]. Primary fascial closure was performed in 120 patients. Mesh was used in 114 patients in the following locations: overlay (n = 28), inlay (n = 30), underlay (n = 54), and unknown (n = 2). Complications occurred in a bimodal distribution, highest in 2001 (introduction of biologic mesh) and 2008 (conversion from underlay to overlay location). Age, sex, history of smoking, defect size, and length of stay were not associated with incidence of complications. Unadjusted risk factors for seroma (16.8%) were elevated BMI, of previous hernia repairs, use of overlay mesh, and late portion of the learning curve, with logistic regression supporting only late portion of the learning curve [odds ratio (OR), 4.3; 95% confidence interval (CI), 1.0-18.6] and BMI (OR, 1.17; 95% CI, 1.06-1.29). The only unadjusted risk factor for recurrence was location of mesh. Logistic regression, comparing underlay, inlay, and overlay mesh to no mesh, revealed that the use of underlay mesh predicted recurrence (OR, 3.0; 95% CI, 1.04-8.64). All P values were less than 0.05. The overall learning curve for a specific procedure, such as abdominal wall reconstruction, can be quite volatile, especially as innovative techniques and new technologies are introduced and incorporated into the surgeon's practice. Our current practice includes primary repair myofascial flap of the components separation and the use of biologic mesh as an overlay graft, anchored to the external oblique. This process of outcome improvement is not gradual but is often punctuated by periods of failure and redemption.

Factors associated with birth defects in the region of Corpus Christi, Texas

EPA Science Inventory

In recent years, the Birth Defects Epidemiology & Surveillance Branch of the Texas Department of State Health Services (DSHS) has documented a high prevalence of certain birth defects in the Corpus Christi, TX region. We conducted a case-control study to evaluate associations...

Arsenate-induced maternal glucose intolerance and neural tube defects in a mouse model

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

Hill, Denise S.; Wlodarczyk, Bogdan J.; Mitchell, Laura E.

Background: Epidemiological studies have linked environmental arsenic (As) exposure to increased type 2 diabetes risk. Periconceptional hyperglycemia is a significant risk factor for neural tube defects (NTDs), the second most common structural birth defect. A suspected teratogen, arsenic (As) induces NTDs in laboratory animals. Objectives: We investigated whether maternal glucose homeostasis disruption was responsible for arsenate-induced NTDs in a well-established dosing regimen used in studies of arsenic's teratogenicity in early neurodevelopment. Methods: We evaluated maternal intraperitoneal (IP) exposure to As 9.6 mg/kg (as sodium arsenate) in LM/Bc/Fnn mice for teratogenicity and disruption of maternal plasma glucose and insulin levels. Selectedmore » compounds (insulin pellet, sodium selenate (SS), N-acetyl cysteine (NAC), L-methionine (L-Met), N-tert-Butyl-{alpha}-phenylnitrone (PBN)) were investigated for their potential to mitigate arsenate's effects. Results: Arsenate caused significant glucose elevation during an IP glucose tolerance test (IPGTT). Insulin levels were not different between arsenate and control dams before (arsenate, 0.55 ng/dl; control, 0.48 ng/dl) or after glucose challenge (arsenate, 1.09 ng/dl; control, 0.81 ng/dl). HOMA-IR index was higher for arsenate (3.9) vs control (2.5) dams (p = 0.0260). Arsenate caused NTDs (100%, p < 0.0001). Insulin pellet and NAC were the most successful rescue agents, reducing NTD rates to 45% and 35%. Conclusions: IPGTT, insulin assay, and HOMA-IR results suggest a modest failure of glucose stimulated insulin secretion and insulin resistance characteristic of glucose intolerance. Insulin's success in preventing arsenate-induced NTDs provides evidence that these arsenate-induced NTDs are secondary to elevated maternal glucose. The NAC rescue, which did not restore maternal glucose or insulin levels, suggests oxidative disruption plays a role.« less

The Defect in Autophagy Induction by Clinical Isolates of Mycobacterium Tuberculosis Is Correlated with Poor Tuberculosis Outcomes.

PubMed

Li, Furong; Gao, Bo; Xu, Wei; Chen, Ling; Xiong, Sidong

2016-01-01

Tuberculosis (TB) represents a major global health problem. The prognosis of clinically active tuberculosis depends on the complex interactions between Mycobacterium tuberculosis (Mtb) and its host. In recent years, autophagy receives particular attention for its role in host defense against intracellular pathogens, including Mtb. In present study, we aim to investigate the relationship of autophagy induction by clinical isolates of Mtb with the clinical outcomes in patients with TB. We collected 185 clinical isolates of Mtb, and determined the effect of these Mtb isolates on autophagy induction in macrophages. It was found that most of clinical isolates of Mtb were able to induce autophagosome formation in macrophages, however, the autophagy-inducing ability varied significantly among different isolates. Of importance, our results revealed that patients infected by Mtb with poor autophagy-inducing ability displayed more severe radiographic extent of disease (p<0.001), and were more likely to have unfavorable treatment outcomes (p<0.001). No significant association was observed between the extent of Mtb-induced autophagy with some socio-demographic characteristics (such as gender, age and tobacco consumption), and some laboratory tests (such as hemoglobin, leukocyte count and erythrocyte sedimentation rate). Furthermore, results from logistic regression analysis demonstrated that the defect in autophagy induction by clinical isolates of Mtb was an independent risk factor for far-advanced radiographic disease (aOR 4.710 [1.93-11.50]) and unfavorable treatment outcomes (aOR 8.309 [2.22-28.97]) in TB. These data indicated that the defect in autophagy induction by Mtb isolates increased the risk of poor clinical outcomes in TB patients, and detection of clinical isolates-induced autophagosome formation might help evaluate the TB outcomes.

Reduction of Defects in Jewelry Manufacturing

NASA Astrophysics Data System (ADS)

Ayudhya, Phitchaya Phanomwan na; Tangjitsitcharoen, Somkiat

2017-06-01

The aim of this research was to reduce the defects of gem bracelet found during manufacturing process at a jewelry company. It was found that gem bracelet product has the highest rejects compared to the rejects found in ring, earring, and pendant products. Types of defect were classified by using Pareto Diagram consisting of gem falling, seam, unclean casting, impinge, and deformation. The causes of defect were analyzed by Cause and Effect Diagram and applied Failure Mode and Effects Analysis (FMEA) was applied during manufacturing processes. This research found that the improvement of manufacturing process could reduce the Risk Priority Number (RPN) and total of all defects by 48.70% and 48.89%, respectively.

CHKA and PCYT1A gene polymorphisms, choline intake and spina bifida risk in a California population

PubMed Central

Enaw, James O Ebot; Zhu, Huiping; Yang, Wei; Lu, Wei; Shaw, Gary M; Lammer, Edward J; Finnell, Richard H

2006-01-01

Background Neural tube defects (NTDs) are among the most common of all human congenital defects. Over the last two decades, accumulating evidence has made it clear that periconceptional intake of folic acid can significantly reduce the risk of NTD affected pregnancies. This beneficial effect may be related to the ability of folates to donate methyl groups for critical physiological reactions. Choline is an essential nutrient and it is also a methyl donor critical for the maintenance of cell membrane integrity and methyl metabolism. Perturbations in choline metabolism in vitro have been shown to induce NTDs in mouse embryos. Methods This study investigated whether single nucleotide polymorphisms (SNPs) in human choline kinase A (CHKA) gene and CTP:phosphocholine cytidylytransferase (PCYT1A) gene were risk factors for spina bifida. Fluorescence-based allelic discrimination analysis was performed for the two CHKA intronic SNPs hCV1562388 (rs7928739) and hCV1562393, and PCYT1A SNP rs939883 and rs3772109. The study population consisted of 103 infants with spina bifida and 338 non-malformed control infants who were born in selected California counties in the period 1989–1991. Results The CHKA SNP hCV1562388 genotypes with at least one C allele were associated with a reduced risk of spina bifida (odds ratio = 0.60, 95%CI = 0.38–0.94). The PCYT1A SNP rs939883 genotype AA was associated with a twofold increased risk of spina bifida (odds ratio = 1.89, 95% CI = 0.97–3.67). These gene-only effects were not substantially modified by analytic consideration to maternal periconceptional choline intake. Conclusion Our analyses showed genotype effects of CHKA and PCYT1A genes on spina bifida risk, but did not show evidence of gene-nutrient interactions. The underlying mechanisms are yet to be resolved. PMID:17184542

Anal sphincter defects and fecal incontinence 15-24 years after first delivery: a cross-sectional study.

PubMed

Guzmán Rojas, R A; Salvesen, K Å; Volløyhaug, I

2018-05-01

To establish the prevalence of external (EAS) and internal (IAS) anal sphincter defects present 15-24 years after childbirth according to mode of delivery, and their association with development of fecal incontinence (FI). The study additionally aimed to compare the proportion of women with obstetric anal sphincter injuries (OASIS) reported at delivery with the proportion of women with sphincter defect detected on ultrasound 15-24 years later. This was a cross-sectional study including 563 women who delivered their first child between 1990 and 1997. Women responded to a validated questionnaire (Pelvic Floor Distress Inventory) in 2013-2014, from which the proportion of women with FI was recorded. Information about OASIS was obtained from the National Birth Registry. Study participants underwent four-dimensional transperineal ultrasound examination. Defect of EAS or IAS of ≥ 30° in at least four of six slices on tomographic ultrasound was considered a significant defect and was recorded. Four study groups were defined based on mode of delivery of the first child. Women who had delivered only by Cesarean section (CS) constituted the CS group. Women in the normal vaginal delivery (NVD) group had NVD of their first child and subsequent deliveries could be NVD or CS. The forceps delivery (FD) group included women who had FD, NVD or CS after FD of their first born. The vacuum delivery (VD) group included women who had VD, NVD or CS after VD of their first born. Multiple logistic regression was used to calculate adjusted odds ratios (aORs) for comparison of prevalence of an EAS defect following different modes of delivery and to test its association with FI. Fisher's exact test was used to calculate crude odds ratios (ORs) for IAS defects. Defects of EAS and IAS were found after NVD (n = 201) in 10% and 1% of cases, respectively, after FD (n = 144) in 32% and 7% of cases and after VD (n = 120) in 15% and 4% of cases. No defects were found after CS (n = 98). FD was associated with increased risk of EAS defect compared with NVD (aOR = 3.6; 95% CI, 2.0-6.6) and VD (aOR = 3.0; 95% CI, 1.6-5.6) and with increased risk of IAS defect compared with NVD (OR = 7.4; 95% CI, 1.5-70.5). The difference between VD and NVD was not significant for EAS or IAS. FI was reported in 18% of women with an EAS defect, in 29% with an IAS defect and in 8% without a sphincter defect. EAS and IAS defects were associated with increased risk of FI (aOR = 2.5 (95% CI, 1.3-4.9) and OR = 4.2 (95% CI, 1.1-13.5), respectively). Of the ultrasonographic sphincter defects, 80% were not reported as OASIS at first or subsequent deliveries. Anal sphincter defects visualized on transperineal ultrasound 15-24 years after first delivery were associated with FD and development of FI. Ultrasound revealed a high proportion of sphincter defects that were not recorded as OASIS at delivery. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Immune defects in families and patients with xeroderma pigmentosum and trichothiodystrophy.

PubMed Central

Mariani, E; Facchini, A; Honorati, M C; Lalli, E; Berardesca, E; Ghetti, P; Marinoni, S; Nuzzo, F; Astaldi Ricotti, G C; Stefanini, M

1992-01-01

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by photosensitivity, a high incidence of cancer in sun-exposed portions of the skin and a reduced capacity to repair the u.v.-induced DNA damage. One of the XP mutations (XP-D) has also been identified in patients affected by trichothiodystrophy (TTD), a rare autosomal recessive disease characterized by brittle hair, mental and physical retardation, peculiar face and ichthyosis. However, in these patients there is no evidence of increased skin tumour incidence. Since an impairment of cell-mediated immunity has been proposed as a co-factor in the cancer proneness of XP patients, we investigated the involvement of immune defect(s) in five XP patients, five TTD patients, their parents, and 24 TTD relatives. We evaluated the phenotype of circulating lymphocytes, natural killer (NK) cell lytic activity, target cell binding of NK cells at single cell level and the effect of interferons (IFN) alpha and beta on NK cell activity. The relative proportion of CD3+ and CD4+ circulating lymphocytes was reduced in XP but not in TTD patients. NK cell lytic activity was decreased in XP patients and their mothers, but their fathers showed normal lytic activity. NK activity varied among TTD families: four out of five patients and their relatives presented low NK cell activity, and one family was normal. In TTD family members, NK activity increased after incubation with IFN-alpha or IFN-beta, but never reached normal values. In contrast, in XP patients and their mothers, the defect was almost completely corrected after in vitro incubation with IFN-alpha or IFN-beta. Our study indicates impaired NK lytic activity in the majority of TTD and XP patients and that this defect is present also in members of their families. In addition, XP patients present a low number of circulating T cells. These multiple abnormalities, together with DNA repair defects, could be related to the increased cancer risk in XP patients. PMID:1535035

Endoscopic management of gastrointestinal perforations, leaks and fistulas

PubMed Central

Rogalski, Pawel; Daniluk, Jaroslaw; Baniukiewicz, Andrzej; Wroblewski, Eugeniusz; Dabrowski, Andrzej

2015-01-01

Gastrointestinal perforations, leaks and fistulas may be serious and life-threatening. The increasing number of endoscopic procedures with a high risk of perforation and the increasing incidence of leakage associated with bariatric operations call for a minimally invasive treatment for these complications. The therapeutic approach can vary greatly depending on the size, location, and timing of gastrointestinal wall defect recognition. Some asymptomatic patients can be treated conservatively, while patients with septic symptoms or cardio-pulmonary insufficiency may require intensive care and urgent surgical treatment. However, most gastrointestinal wall defects can be satisfactorily treated by endoscopy. Although the initial endoscopic closure rates of chronic fistulas is very high, the long-term results of these treatments remain a clinical problem. The efficacy of endoscopic therapy depends on several factors and the best mode of treatment will depend on a precise localization of the site, the extent of the leak and the endoscopic appearance of the lesion. Many endoscopic tools for effective closure of gastrointestinal wall defects are currently available. In this review, we summarized the basic principles of the management of acute iatrogenic perforations, as well as of postoperative leaks and chronic fistulas of the gastrointestinal tract. We also described the effectiveness of various endoscopic methods based on current research and our experience. PMID:26457014

Short telomeres: from dyskeratosis congenita to sporadic aplastic anemia and malignancy.

PubMed

Gramatges, Maria M; Bertuch, Alison A

2013-12-01

Telomeres are DNA-protein structures that form a protective cap on chromosome ends. As such, they prevent the natural ends of linear chromosomes from being subjected to DNA repair activities that would result in telomere fusion, degradation, or recombination. Both the DNA and protein components of the telomere are required for this essential function, because insufficient telomeric DNA length, loss of the terminal telomeric DNA structure, or deficiency of key telomere-associated factors may elicit a DNA damage response and result in cellular senescence or apoptosis. In the setting of failed checkpoint mechanisms, such DNA-protein defects can also lead to genomic instability through telomere fusions or recombination. Thus, as shown in both model systems and in humans, defects in telomere biology are implicated in cellular and organismal aging as well as in tumorigenesis. Bone marrow failure and malignancy are 2 life-threatening disease manifestations in the inherited telomere biology disorder dyskeratosis congenita. We provide an overview of basic telomere structure and maintenance. We outline the telomere biology defects observed in dyskeratosis congenita, focusing on recent discoveries in this field. Last, we review the evidence of how telomere biology may impact sporadic aplastic anemia and the risk for various cancers. Copyright © 2013 Mosby, Inc. All rights reserved.

Early Childhood Caries: A Review.

PubMed

Alazmah, Abdulfatah

2017-08-01

To review and update the current knowledge about early childhood caries (ECC) and its etiology, prevalence, risk factors, management, and preventive strategies. Early childhood caries is a disease affecting significantly both well-developed and industrial nations. The ECC can significantly affect the child's quality of life, as it may lead to infection, swelling, pain, and other symptoms. The ECC affects children after eruption of primary teeth until age of around 5 years. The ECC affects all parts of the tooth including the smooth surface. Upper anterior teeth and primary molars are usually affected. The lower anterior teeth are less likely affected. The risk factors for ECC are diet, bacteria, and host susceptibility. The additional factors, such as presence of enamel defect and the feeding practices also contribute to the initiation and progress of ECC. Dentists must focus on utilizing existing techniques to distinguish indications of right on time and propelled caries and give guidance on the best way to counteract and control caries in children. Approaches should be directed to preventive caries control strategies among children. Preventing and controlling the development of ECC among children is important to maintain effective eating, speech development, and formation of a positive self-image.

Understanding and determining the etiology of autism.

PubMed

Currenti, Salvatore A

2010-03-01

Worldwide, the rate of autism has been steadily rising. There are several environmental factors in concert with genetic susceptibilities that are contributing to this rise. Impaired methylation and mutations of mecp2 have been associated with autistic spectrum disorders, and related Rett syndrome. Genetic polymorphisms of cytochrome P450 enzymes have also been linked to autism, specifically CYP27B1 that is essential for proper vitamin D metabolism. Vitamin D is important for neuronal growth and neurodevelopment, and defects in metabolism or deficiency have been implicated in autistic individuals. Other factors that have been considered include: maternally derived antibodies, maternal infection, heavy metal exposure, folic acid supplementation, epigenetics, measles, mumps, rubella vaccination, and even electromagnetic radiation. In each case, the consequences, whether direct or indirect, negatively affect the nervous system, neurodevelopment, and environmental responsive genes. The etiology of autism is a topic of controversial debate, while researchers strive to achieve a common objective. The goal is to identify the cause(s) of autism to understand the complex interplay between environment and gene regulation. There is optimism that specific causes and risk factors will be identified. The results of future investigations will facilitate enhanced screening, prevention, and therapy for "at risk" and autistic patients.

Decreased numbers of chemotactic factor receptors in chronic neutropenia with defective chemotaxis: spontaneous recovery from the neutrophil abnormalities during early childhood

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

Yasui, K.; Yamazaki, M.; Miyagawa, Y.

Childhood chronic neutropenia with decreased numbers of chemotactic factor receptors as well as defective chemotaxis was first demonstrated in an 8-month-old girl. Chemotactic factor receptors on neutrophils were assayed using tritiated N-formyl-methionyl-leucyl-phenylalanine (/sup 3/H-FMLP). The patient's neutrophils had decreased numbers of the receptors: numbers of the receptors were 20,000 (less than 3 SD) as compared with those of control cells of 52,000 +/- 6000 (mean +/- SD) (n = 10). The neutropenia disappeared spontaneously by 28 months of age parallel with the improvement of chemotaxis and increase in numbers of chemotactic factor receptors. These results demonstrate a transient decrease ofmore » neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder.« less

Acoustically driven degradation in single crystalline silicon solar cell

NASA Astrophysics Data System (ADS)

Olikh, O. Ya.

2018-05-01

The influence of ultrasound on current-voltage characteristics of crystalline silicon solar sell was investigated experimentally. The transverse and longitudinal acoustic waves were used over a temperature range of 290-340 K. It was found that the ultrasound loading leads to the reversible decrease in the photogenerated current, open-circuit voltage, fill factor, carrier lifetime, and shunt resistance as well as the increase in the ideality factor. The experimental results were described by using the models of coupled defect level recombination, Shockley-Read-Hall recombination, and dislocation-induced impedance. The contribution of the boron-oxygen related defects, iron-boron pairs, and oxide precipitates to both the carrier recombination and acousto-defect interaction was discussed. The experimentally observed phenomena are associated with the increase in the distance between coupled defects as well as the extension of the carrier capture coefficient of complex point defects and dislocations.

Evaluation of human recession defects treated with coronally advanced flaps and either purified recombinant human platelet-derived growth factor-BB with beta tricalcium phosphate or connective tissue: a histologic and microcomputed tomographic examination.

PubMed

McGuire, Michael K; Scheyer, Todd; Nevins, Myron; Schupbach, Peter

2009-02-01

The current study examined the histologic and microcomputed tomographic (micro CT) outcomes of the treatment of gingival recession defects with either a subepithelial connective tissue graft (CTG) or 0.3 mg/mL recombinant human platelet-derived growth factor (rhPDGF-BB) on a beta tricalcium phosphate (beta-TCP) matrix. Gingival recession defects were surgically created in six premolar teeth with no more than 3 mm of keratinized marginal tissue, an osseous crest 2 to 3 mm apical to the newly created gingival margin, and recession depth of at least 3 mm. The defects were left untouched for 2 months; then, four defects were grafted with rhPDGF-BB + beta-TCP + a wound healing dressing, and two defects received CTGs. A coronally advanced flap covered each grafted site. Nine months later, sections were obtained for examination. All four sites treated with rhPDGF-BB + beta-TCP showed connective tissue fibers (Sharpey fibers) perpendicularly inserting into newly formed cementum and alveolar bone. In the two sites treated with CTGs, a long junctional epithelium was seen coronal to the osseous crest and connective tissue fibers ran parallel to the adjacent root surfaces, with no evidence of insertion into cementum or bone. There was no evidence of regeneration of cementum, inserting connective tissue fibers, or supporting alveolar bone. Regeneration of the periodontium in gingival recession defects is possible through growth factor-mediated therapy.

Microbiota-Dependent Marker TMAO Is Elevated in Silent Ischemia but Is Not Associated With First-Time Myocardial Infarction in HIV Infection.

PubMed

Haissman, Judith M; Knudsen, Andreas; Hoel, Hedda; Kjær, Andreas; Kristoffersen, Ulrik S; Berge, Rolf K; Katzenstein, Terese L; Svardal, Asbjørn; Ueland, Thor; Aukrust, Pål; Lebech, Anne-Mette; Nielsen, Susanne D; Trøseid, Marius

2016-02-01

HIV infection is associated with increased risk of coronary heart disease beyond that explained by traditional risk factors, and altered gut microbiota has been proposed as a potential trigger. Trimethylamine-N-oxide (TMAO) is a proatherogenic substance formed in the liver from trimethylamine, exclusively generated by gut microbiota from dietary phosphatidylcholine. We aimed to investigate whether TMAO is associated with subclinical and clinical coronary heart disease in HIV infection. Two previously described cohorts were examined as follows: (1) cross-sectional cohort of HIV-infected persons and uninfected controls with known atherosclerotic plaque burden as assessed by myocardial perfusion scintigraphy, coronary artery calcium score, and intima-media thickness and (2) nested case-control study of HIV-infected persons with first-time myocardial infarction (MI) compared with HIV-infected persons without MI, assessed at 4 time points from before initiation of antiretroviral therapy (ART) to last sample before the case's MI (median: 51, range: 0-239 days). There was no difference in plasma TMAO when comparing HIV-infected persons and uninfected controls. TMAO was elevated in HIV-infected persons with myocardial perfusion defects but was not associated with coronary artery calcium score, intima media thickness, or Framingham risk score. In the nested case control study, plasma TMAO was not associated with first-time MI. However, TMAO increased after ART introduction and was associated with the use of protease inhibitors in both cohorts. TMAO was elevated in HIV-infected persons with myocardial perfusion defects, but was not associated with first-time MI. Our data question TMAO as a useful biomarker of cardiovascular risk in HIV infection, at least in ART-treated individuals.

The aristaless-like homeobox protein Alx3 as an etiopathogenic factor for diabetes mellitus.

PubMed

Vallejo, Mario

2011-01-01

Inactivation of the gene encoding the aristaless-related homeodomain transcription factor Alx3 results in islet cell apoptosis and impaired glucose homeostasis that worsens with age due to the appearance of insulin resistance. Alx3-deficient mice also show extrapancreatic developmental defects with variable penetrance. These include polydactyly, craniofacial midline defects, and neural tube closure defects. In humans, related congenital defects associated with mutations in ALX3 and other aristaless-related genes are being identified. Emerging evidence suggests that normal pancreatic function in humans may require the integrity of aristaless-related genes. Here, the proposal that ALX3 could be considered as a candidate gene for the etiopathogenesis of diabetes or its complications during embryonic or fetal development is discussed.

Molecular concept in human oral cancer.

PubMed

Krishna, Akhilesh; Singh, Shraddha; Kumar, Vijay; Pal, U S

2015-01-01

The incidence of oral cancer remains high in both Asian and Western countries. Several risk factors associated with development of oral cancer are now well-known, including tobacco chewing, smoking, and alcohol consumption. Cancerous risk factors may cause many genetic events through chromosomal alteration or mutations in genetic material and lead to progression and development of oral cancer through histological progress, carcinogenesis. Oral squamous carcinogenesis is a multistep process in which multiple genetic events occur that alter the normal functions of proto-oncogenes/oncogenes and tumor suppressor genes. Furthermore, these gene alterations can deregulate the normal activity such as increase in the production of growth factors (transforming growth factor-α [TGF-α], TGF-β, platelet-derived growth factor, etc.) or numbers of cell surface receptors (epidermal growth factor receptor, G-protein-coupled receptor, etc.), enhanced intracellular messenger signaling and mutated production of transcription factors (ras gene family, c-myc gene) which results disturb to tightly regulated signaling pathways of normal cell. Several oncogenes and tumor suppressor genes have been implicated in oral cancer especially cyclin family, ras, PRAD-1, cyclin-dependent kinase inhibitors, p53 and RB1. Viral infections, particularly with oncogenic human papilloma virus subtype (16 and 18) and Epstein-Barr virus have tumorigenic effect on oral epithelia. Worldwide, this is an urgent need to initiate oral cancer research programs at molecular and genetic level which investigates the causes of genetic and molecular defect, responsible for malignancy. This approach may lead to development of target dependent tumor-specific drugs and appropriate gene therapy.

Molecular concept in human oral cancer

PubMed Central

Krishna, Akhilesh; Singh, Shraddha; Kumar, Vijay; Pal, U. S.

2015-01-01

The incidence of oral cancer remains high in both Asian and Western countries. Several risk factors associated with development of oral cancer are now well-known, including tobacco chewing, smoking, and alcohol consumption. Cancerous risk factors may cause many genetic events through chromosomal alteration or mutations in genetic material and lead to progression and development of oral cancer through histological progress, carcinogenesis. Oral squamous carcinogenesis is a multistep process in which multiple genetic events occur that alter the normal functions of proto-oncogenes/oncogenes and tumor suppressor genes. Furthermore, these gene alterations can deregulate the normal activity such as increase in the production of growth factors (transforming growth factor-α [TGF-α], TGF-β, platelet-derived growth factor, etc.) or numbers of cell surface receptors (epidermal growth factor receptor, G-protein-coupled receptor, etc.), enhanced intracellular messenger signaling and mutated production of transcription factors (ras gene family, c-myc gene) which results disturb to tightly regulated signaling pathways of normal cell. Several oncogenes and tumor suppressor genes have been implicated in oral cancer especially cyclin family, ras, PRAD-1, cyclin-dependent kinase inhibitors, p53 and RB1. Viral infections, particularly with oncogenic human papilloma virus subtype (16 and 18) and Epstein-Barr virus have tumorigenic effect on oral epithelia. Worldwide, this is an urgent need to initiate oral cancer research programs at molecular and genetic level which investigates the causes of genetic and molecular defect, responsible for malignancy. This approach may lead to development of target dependent tumor-specific drugs and appropriate gene therapy. PMID:26668446

A Multicenter Study of 1144 Patients with Cerebral Venous Thrombosis: The VENOST Study.

PubMed

Duman, Taskin; Uluduz, Derya; Midi, Ipek; Bektas, Hesna; Kablan, Yuksel; Goksel, Basak K; Milanlioglu, Aysel; Necioglu Orken, Dilek; Aluclu, Ufuk

2017-08-01

Based on a number of small observational studies, cerebral venous sinus thrombosis has diverse clinical and imaging features, risk factors, and variable outcome. In a large, multicenter cerebral venous thrombosis (VENOST) study, we sought to more precisely characterize the clinical characteristics of Caucasian patients. All data for the VENOST study were collected between the years 2000 and 2015 from the clinical follow-up files. Clinical and radiological characteristics, risk factors, and outcomes were compared in terms of age and sex distribution. Among 1144 patients 68% were women, and in older age group (>50 years) male patients were more prevalent (16.6% versus 27.8%). The most frequent symptoms were headache (89.4%) and visual field defects (28.9%) in men, and headache (86.1%) and epileptic seizures (26.8%) in women. Gynecological factors comprised the largest group in women, in particular puerperium (18.3%). Prothrombotic conditions (26.4%), mainly methylenetetrahydrofolate reductase mutation (6.3%) and Factor V Leiden mutation (5.1%), were the most common etiologies in both genders. 8.1% of patients had infection-associated and 5.2% had malignancy-related etiology that was significantly higher in men and older age group. Parenchymal involvement constitutively hemorrhagic infarcts, malignancy, and older age was associated with higher Rankin score. Epileptic seizures had no effect on prognosis. Clinical and radiological findings were consistent with previous larger studies but predisposing factors were different with a higher incidence of puerperium. Oral contraceptive use was not a prevalent risk factor in our cohort. Malignancy, older age, and hemorrhagic infarcts had worse outcome. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Maternal residential proximity to waste sites and industrial facilities and conotruncal heart defects in offspring.

PubMed

Langlois, Peter H; Brender, Jean D; Suarez, Lucina; Zhan, F Benjamin; Mistry, Jatin H; Scheuerle, Angela; Moody, Karen

2009-07-01

Most studies of the relationship between maternal residential proximity to sources of environmental pollution and congenital cardiovascular malformations have combined heart defects into one group or broad subgroups. The current case-control study examined whether risk of conotruncal heart defects, including subsets of specific defects, was associated with maternal residential proximity to hazardous waste sites and industrial facilities with recorded air emissions. Texas Birth Defects Registry cases were linked to their birth or fetal death certificate. Controls without birth defects were randomly selected from birth certificates. Distances from maternal addresses at delivery to National Priority List (NPL) waste sites, state superfund waste sites, and Toxic Release Inventory (TRI) facilities were determined for 1244 cases (89.5% of those eligible) and 4368 controls (88.0%). Living within 1 mile of a hazardous waste site was not associated with risk of conotruncal heart defects [adjusted odds ratio (aOR) = 0.83, 95% confidence interval (CI) = 0.54, 1.27]. This was true whether looking at most types of defects or waste sites. Only truncus arteriosus showed statistically elevated ORs with any waste site (crude OR: 2.80, 95% CI 1.19, 6.54) and with NPL sites (crude OR: 4.63, 95% CI 1.18, 13.15; aOR 4.99, 95% CI 1.26, 14.51), but the latter was based on only four exposed cases. There was minimal association between conotruncal heart defects and proximity to TRI facilities (aOR = 1.10, 95% CI = 0.91, 1.33). Stratification by maternal age or race/ethnic group made little difference in effect estimates for waste sites or industrial facilities. In this study population, maternal residential proximity to waste sites or industries with reported air emissions was not associated with conotruncal heart defects or its subtypes in offspring, with the exception of truncus arteriosus.

Genetic modifiers of abnormal organelle biogenesis in a Drosophila model of BLOC-1 deficiency

PubMed Central

Cheli, Verónica T.; Daniels, Richard W.; Godoy, Ruth; Hoyle, Diego J.; Kandachar, Vasundhara; Starcevic, Marta; Martinez-Agosto, Julian A.; Poole, Stephen; DiAntonio, Aaron; Lloyd, Vett K.; Chang, Henry C.; Krantz, David E.; Dell'Angelica, Esteban C.

2010-01-01

Biogenesis of lysosome-related organelles complex 1 (BLOC-1) is a protein complex formed by the products of eight distinct genes. Loss-of-function mutations in two of these genes, DTNBP1 and BLOC1S3, cause Hermansky–Pudlak syndrome, a human disorder characterized by defective biogenesis of lysosome-related organelles. In addition, haplotype variants within the same two genes have been postulated to increase the risk of developing schizophrenia. However, the molecular function of BLOC-1 remains unknown. Here, we have generated a fly model of BLOC-1 deficiency. Mutant flies lacking the conserved Blos1 subunit displayed eye pigmentation defects due to abnormal pigment granules, which are lysosome-related organelles, as well as abnormal glutamatergic transmission and behavior. Epistatic analyses revealed that BLOC-1 function in pigment granule biogenesis requires the activities of BLOC-2 and a putative Rab guanine-nucleotide-exchange factor named Claret. The eye pigmentation phenotype was modified by misexpression of proteins involved in intracellular protein trafficking; in particular, the phenotype was partially ameliorated by Rab11 and strongly enhanced by the clathrin-disassembly factor, Auxilin. These observations validate Drosophila melanogaster as a powerful model for the study of BLOC-1 function and its interactions with modifier genes. PMID:20015953

Selective sulfur dioxide adsorption on crystal defect sites on an isoreticular metal organic framework series

PubMed Central

Rodríguez-Albelo, L. Marleny; López-Maya, Elena; Hamad, Said; Ruiz-Salvador, A. Rabdel; Calero, Sofia; Navarro, Jorge A.R.

2017-01-01

The widespread emissions of toxic gases from fossil fuel combustion represent major welfare risks. Here we report the improvement of the selective sulfur dioxide capture from flue gas emissions of isoreticular nickel pyrazolate metal organic frameworks through the sequential introduction of missing-linker defects and extra-framework barium cations. The results and feasibility of the defect pore engineering carried out are quantified through a combination of dynamic adsorption experiments, X-ray diffraction, electron microscopy and density functional theory calculations. The increased sulfur dioxide adsorption capacities and energies as well as the sulfur dioxide/carbon dioxide partition coefficients values of defective materials compared to original non-defective ones are related to the missing linkers enhanced pore accessibility and to the specificity of sulfur dioxide interactions with crystal defect sites. The selective sulfur dioxide adsorption on defects indicates the potential of fine-tuning the functional properties of metal organic frameworks through the deliberate creation of defects. PMID:28198376

Post-tuberculous lung function impairment in a tuberculosis reference clinic in Cameroon.

PubMed

Mbatchou Ngahane, Bertrand Hugo; Nouyep, Junior; Nganda Motto, Malea; Mapoure Njankouo, Yacouba; Wandji, Adeline; Endale, Mireille; Afane Ze, Emmanuel

2016-05-01

After completion of treatment, a proportion of pulmonary TB (pTB) patients experience lung function impairment which can influence their quality of life. This study aimed to determine the prevalence of lung function impairment in patients treated for pTB and investigate its associated factors. A cross-sectional study was conducted in TB clinic of the Douala Laquintinie Hospital in Cameroon. Patients aged 15 and above who were treated for pTB between 2008 and 2012 were included in the study. Demographic data, respiratory symptoms prior TB diagnosis, comorbidities and chest radiography findings prior to TB treatment were collected. All participants underwent spirometric measurements. Airflow obstruction was defined as a post-bronchodilation FEV1/FVC <70% with FVC >80%, restrictive defects as an FEV1/FVC ratio of ≥70% with an FVC <80% predicted, and mixed defects as FVC of <80% predicted and an FEV1/FVC ratio of <70%. Lung function impairment was defined by the presence of at least one of these three abnormalities. Logistic regression analysis was employed to investigate risk factors of lung function impairment. Of a total of 269 participants included in the study, 146 (54.3%) were male. The median age of participants was 33 years. The median duration of symptoms before diagnosis of TB was 4 weeks [interquartile range (IQR) 3-8]. The prevalence of lung function impairment was 45.4% (95% CI 39-51). The multivariate analysis identified duration of symptoms [OR 1.08; 95% CI (1.01-1.15)] and fibrotic pattern [OR 3.54; 95% CI (1.40-8.95)] as independent risk factors for lung function impairment. Post-tuberculous pulmonary function impairment is frequent in Douala. Sensitization of patient with symptoms of pulmonary TB for an earlier visit to healthcare facilities could reduce the impact of pTB on lung function of patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Urinary tract infection caused by community-acquired extended-spectrum β-lactamase-producing bacteria in infants.

PubMed

Kim, Yun Hee; Yang, Eun Mi; Kim, Chan Jong

Urinary tract infection (UTI) caused by resistant strains of bacteria is increasingly prevalent in children. The aim of this study was to investigate the clinical characteristics and risk factors for UTI caused by community-acquired extended-spectrum β-lactamase (CA-ESBL)-producing bacteria in infants. This was a retrospective study performed over 5 years in a single Korean center. Hospitalized infants with febrile UTI were enrolled and divided into two groups (CA-ESBL vs. CA non-ESBL UTI). The yearly prevalence was calculated. Baseline characteristics and clinical course such as fever duration, laboratory and radiological findings were compared between the two groups. Risk factors associated with the CA-ESBL UTI were investigated. Among the enrolled infants (n=185), 31 (17%) had CA-ESBL UTI. The yearly prevalence of ESBL of CA-ESBL UTI increased during the study (0% in 2010, 22.2% in 2015). Infants with CA-ESBL UTI had a longer duration of fever after initiating antibiotics (2.0±1.1 vs. 1.5±0.6 days, p=0.020). Cortical defects on renal scan and early treatment failure were more frequent in CA-ESBL (64.5 vs. 42.2%, p=0.023; 22.6 vs. 4.5%, p=0.001). A logistic regression analysis revealed that urinary tract abnormalities and previous UTI were independent risk factors for CA-EBSL UTI (odds ratio, 2.7; p=0.025; 10.3; p=0.022). The incidence of UTI caused by ESBL-producing bacteria has increased in Korean infants. Recognition of the clinical course and risk factors for ESLB-producing UTI may help to determine appropriate guidelines for its management. Copyright © 2016. Published by Elsevier Editora Ltda.

Impact of facial defect reconstruction on attractiveness and negative facial perception.

PubMed

Dey, Jacob K; Ishii, Masaru; Boahene, Kofi D O; Byrne, Patrick; Ishii, Lisa E

2015-06-01

Measure the impact of facial defect reconstruction on observer-graded attractiveness and negative facial perception. Prospective, randomized, controlled experiment. One hundred twenty casual observers viewed images of faces with defects of varying sizes and locations before and after reconstruction as well as normal comparison faces. Observers rated attractiveness, defect severity, and how disfiguring, bothersome, and important to repair they considered each face. Facial defects decreased attractiveness -2.26 (95% confidence interval [CI]: -2.45, -2.08) on a 10-point scale. Mixed effects linear regression showed this attractiveness penalty varied with defect size and location, with large and central defects generating the greatest penalty. Reconstructive surgery increased attractiveness 1.33 (95% CI: 1.18, 1.47), an improvement dependent upon size and location, restoring some defect categories to near normal ranges of attractiveness. Iterated principal factor analysis indicated the disfiguring, important to repair, bothersome, and severity variables were highly correlated and measured a common domain; thus, they were combined to create the disfigured, important to repair, bothersome, severity (DIBS) factor score, representing negative facial perception. The DIBS regression showed defect faces have a 1.5 standard deviation increase in negative perception (DIBS: 1.69, 95% CI: 1.61, 1.77) compared to normal faces, which decreased by a similar magnitude after surgery (DIBS: -1.44, 95% CI: -1.49, -1.38). These findings varied with defect size and location. Surgical reconstruction of facial defects increased attractiveness and decreased negative social facial perception, an impact that varied with defect size and location. These new social perception data add to the evidence base demonstrating the value of high-quality reconstructive surgery. NA. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Inability to activate Rac1-dependent forgetting contributes to behavioral inflexibility in mutants of multiple autism-risk genes

PubMed Central

Dong, Tao; He, Jing; Wang, Shiqing; Wang, Lianzhang; Cheng, Yuqi; Zhong, Yi

2016-01-01

The etiology of autism is so complicated because it involves the effects of variants of several hundred risk genes along with the contribution of environmental factors. Therefore, it has been challenging to identify the causal paths that lead to the core autistic symptoms such as social deficit, repetitive behaviors, and behavioral inflexibility. As an alternative approach, extensive efforts have been devoted to identifying the convergence of the targets and functions of the autism-risk genes to facilitate mapping out causal paths. In this study, we used a reversal-learning task to measure behavioral flexibility in Drosophila and determined the effects of loss-of-function mutations in multiple autism-risk gene homologs in flies. Mutations of five autism-risk genes with diversified molecular functions all led to a similar phenotype of behavioral inflexibility indicated by impaired reversal-learning. These reversal-learning defects resulted from the inability to forget or rather, specifically, to activate Rac1 (Ras-related C3 botulinum toxin substrate 1)-dependent forgetting. Thus, behavior-evoked activation of Rac1-dependent forgetting has a converging function for autism-risk genes. PMID:27335463

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.

The importance of preoperative oxygen saturation as a predictor of pulmonary arterial hypertension after surgery of atrial septal defects.

PubMed

Park, Han Ki; Shin, Hong Ju; Park, Young Hwan; Ma, Bo Gyoung

2016-09-01

There is no concrete predictor of the change of pulmonary arterial pressure after surgical closure of an atrial septal defect (ASD) in patients with pulmonary arterial hypertension (PAH). The aim of this study was to investigate the role of preoperative room air arterial oxygen saturation (SaO2) (arterial blood gas data) as a predictor of postoperative PAH. The medical records of 36 patients [>20 years, mean pulmonary arterial pressure (mPAP) ≥25 mmHg] who underwent surgical closure of an ASD between March 2004 and January 2014 were retrospectively reviewed. The median age was 47 years (range, 24.6-65.9 years) and mPAP was 38 ± 14 mmHg. The mean pulmonary vascular resistance (Rp) was 3.9 ± 4.2 Wood units, and fenestration was performed in 12 (33%) patients. Only 1 patient received anti-PAH medication preoperatively. The median follow-up period was 4 years (range, 0-10 years). There were two hospital deaths, one of which was related to PAH. At the last follow-up, PAH (estimated tricuspid regurgitation velocity >3 m/s) existed in 7 patients (19%), and 10 patients (28%) were receiving anti-PAH medications (considered as clinical PAH). Univariate analysis for persistent clinical PAH revealed that mPAP, Qp/Qs, Rp, room air arterial oxygen saturation and postoperative functional class were significant risk factors. Only SaO2 remained a significant risk factor in multivariate analysis (P = 0.03). Preoperative room air SaO2 is a useful predictor of persistent PAH in adult patients undergoing surgical closure of an ASD. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

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%.

Increasing reticle inspection efficiency and reducing wafer print-checks using automated defect classification and simulation

NASA Astrophysics Data System (ADS)

Ryu, Sung Jae; Lim, Sung Taek; Vacca, Anthony; Fiekowsky, Peter; Fiekowsky, Dan

2013-09-01

IC fabs inspect critical masks on a regular basis to ensure high wafer yields. These requalification inspections are costly for many reasons including the capital equipment, system maintenance, and labor costs. In addition, masks typically remain in the "requal" phase for extended, non-productive periods of time. The overall "requal" cycle time in which reticles remain non-productive is challenging to control. Shipping schedules can slip when wafer lots are put on hold until the master critical layer reticle is returned to production. Unfortunately, substituting backup critical layer reticles can significantly reduce an otherwise tightly controlled process window adversely affecting wafer yields. One major requal cycle time component is the disposition process of mask inspections containing hundreds of defects. Not only is precious non-productive time extended by reviewing hundreds of potentially yield-limiting detections, each additional classification increases the risk of manual review techniques accidentally passing real yield limiting defects. Even assuming all defects of interest are flagged by operators, how can any person's judgment be confident regarding lithographic impact of such defects? The time reticles spend away from scanners combined with potential yield loss due to lithographic uncertainty presents significant cycle time loss and increased production costs. Fortunately, a software program has been developed which automates defect classification with simulated printability measurement greatly reducing requal cycle time and improving overall disposition accuracy. This product, called ADAS (Auto Defect Analysis System), has been tested in both engineering and high-volume production environments with very successful results. In this paper, data is presented supporting significant reduction for costly wafer print checks, improved inspection area productivity, and minimized risk of misclassified yield limiting defects.

Neighborhood Deprivation and Risk of Congenital Heart Defects, Neural Tube Defects and Orofacial Clefts: A Systematic Review and Meta-Analysis

PubMed Central

Deguen, Séverine; Kihal, Wahida; Jeanjean, Maxime; Padilla, Cindy; Zmirou-Navier, Denis

2016-01-01

Background We conducted this systematic review and meta-analysis to address the open question of a possible association between the socioeconomic level of the neighborhoods in which pregnant women live and the risk of Congenital Heart Defects (CHDs), Neural Tube Defects (NTDs) and OroFacial Clefts (OFCs). Methods We searched MEDLINE from its inception to December 20th, 2015 for case-control, cohort and ecological studies assessing the association between neighborhood socioeconomic level and the risk of CHDs, NTDs and the specific phenotypes Cleft Lip with or without Cleft Palate (CLP) and Cleft Palate (CP). Study-specific risk estimates were pooled according to random-effect and fixed-effect models. Results Out of 245 references, a total of seven case-control studies, two cohort studies and two ecological studies were assessed in the systematic review; all studies were enrolled in the meta-analysis with the exception of the two cohort studies. No significant association has been revealed between CHDs or NTDs and neighborhood deprivation index. For CLP phenotype subgroups, we found a significantly higher rate in deprived neighborhoods (Odds Ratios (OR) = 1.22, 95% CI: 1.10, 1.36) whereas this was not significant for CP phenotype subgroups (OR = 1.20, 95%CI: 0.89, 1.61). Conclusion In spite of the small number of epidemiological studies included in the present literature review, our findings suggest that neighborhood socioeconomic level where mothers live is associated only with an increased risk of CLP phenotype subgroups. This finding has methodological limitations that impede the formulation of firm conclusions, and further investigations should confirm this association. PMID:27783616

COMPARISON OF GEOCODING METHODS USED IN CASE-CONTROL STUDY OF AIR QUALITY AND BIRTH DEFECTS

EPA Science Inventory

Introduction: Accurate geocoding of maternal residence is critical to the success of an ongoing case-control study of exposure to five criteria air pollutants and the risk of selected birth defects in seven Texas counties between 1997 and 2000. The geocoded maternal residence a...

[Metalloproteases, vascular remodeling and atherothrombotic syndromes].

PubMed

Rodríguez, José A; Orbe, Josune; Páramo, José A

2007-09-01

Defects in the synthesis and breakdown of the extracellular matrix (ECM) are now seen as key processes in the development of atherosclerosis and its thrombotic complications. Correlations have been observed between circulating levels of ECM biomarkers and the clinical manifestations of and risk factors for atherosclerosis. Several matrix metalloproteinases (MMPs), endopeptidases that can degrade the ECM, such as MMP-9 and MMP-10, play important roles in the pathophysiology of atherothrombosis and contribute to the expansion of abdominal aortic aneurysms. Moreover, they may also be useful biomarkers of atherosclerotic risk and serve as predictors of coronary and cerebrovascular disease recurrence. Although at present the effect of tissue inhibitors of MMPs (TIMPs) on cardiovascular disease prognosis is still uncertain, the ECM could be a promising therapeutic target in atherothrombotic disease, and several MMP inhibitors are currently undergoing clinical trials.

Thrombophilia screening--at the right time, for the right patient, with a good reason.

PubMed

Stegnar, Mojca

2010-12-01

Thrombophilia can be identified in about half of all patients presenting with venous thromboembolism (VTE). Thrombophilia screening for various indications has increased tremendously, but whether the results of such tests help in the clinical management of patients is uncertain. Here, current recommendations for thrombophilia screening in selected groups of patients, and considerations whether other high-risk subjects should be tested are reviewed. The methods for determination of the most common thrombophilic defects (antithrombin, protein C, protein S deficiencies, Factor V Leiden and prothrombin G20210A) associated with strong to moderate risk of VTE are described, indicating the timing and location of thrombophilia screening. Circumstances when a positive result of thrombophilia screening helps clinicians decide if adjustments of the anticoagulant regime are needed are discussed. Finally, psychological, social and ethical dilemmas associated with thrombophilia screening are indicated.

In Vivo Tracking of Mesechymal Stem Cells Using Fluorescent Nanoparticles in an Osteochondral Repair Model

PubMed Central

Lee, Jong Min; Kim, Byung-Soo; Lee, Haeshin; Im, Gun-Il

2012-01-01

We devised and tested an in vivo system to monitor the migration of mesenchymal stem cells (MSCs) within the marrow cavity. In vitro studies confirmed that platelet-derived growth factor (PDGF)-AA had the most potent chemotactic effect of the tested factors, and possessed the greatest number of receptors in MSCs. MSCs were labeled with fluorescent nanoparticles and injected into the marrow cavity of nude rats through osteochondral defects created in the distal femur. The defects were sealed with HCF (heparin-conjugated fibrin) or PDGF-AA-loaded HCF. In the HCF-only group, the nanoparticle-labeled MSCs dispersed outside the marrow cavity within 3 days after injection. In the PDGF-AA-loaded HCF group, the labeled cells moved time-dependently for 14 days toward the osteochondral defect. HCF-PDGF in low dose (LD; 8.5 ng/µl) was more effective than HCF-PDGF in high dose (HD; 17 ng/µl) in recruiting the MSCs to the osteochondral defect. After 21 days, the defects treated with PDGF and transforming growth factor (TGF)-β1-loaded HCF showed excellent cartilage repair compared with other groups. Further studies confirmed that this in vivo osteochondral MSCs tracking system (IOMTS) worked for other chemoattractants (chemokine (C-C motif) ligand 2 (CCL2) and PDGF-BB). IOMTS can provide a useful tool to examine the effect of growth factors or chemokines on endogenous cartilage repair. PMID:22491215

Chitosan conduits combined with nerve growth factor microspheres repair facial nerve defects

PubMed Central

Liu, Huawei; Wen, Weisheng; Hu, Min; Bi, Wenting; Chen, Lijie; Liu, Sanxia; Chen, Peng; Tan, Xinying

2013-01-01

Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa-line groups than in the nerve growth factor-microspheres and autologous nerve groups. physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation illustrated that the di-ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits. PMID:25206635

Body Dysmorphic Disorder: Easing the Distress of Distortion.

ERIC Educational Resources Information Center

Fore, Cynthia M.

People who suffer from body dysmorphic disorder believe that their body is defected and that this defect makes them ugly. Their distorted body image can be precipitated by many internal and external factors and as a result of their imagined defect, these normal-appearing individuals exhibit self-defeating behaviors. The disorder can lead to the…

The Effect of Brain-Derived Neurotrophic Factor on Periodontal Furcation Defects

PubMed Central

Jimbo, Ryo; Tovar, Nick; Janal, Malvin N.; Mousa, Ramy; Marin, Charles; Yoo, Daniel; Teixeira, Hellen S.; Anchieta, Rodolfo B.; Bonfante, Estevam A.; Konishi, Akihiro; Takeda, Katsuhiro; Kurihara, Hidemi; Coelho, Paulo G.

2014-01-01

This study aimed to observe the regenerative effect of brain-derived neurotrophic factor (BDNF) in a non-human primate furcation defect model. Class II furcation defects were created in the first and second molars of 8 non-human primates to simulate a clinical situation. The defect was filled with either, Group A: BDNF (500 µg/ml) in high-molecular weight-hyaluronic acid (HMW-HA), Group B: BDNF (50 µg/ml) in HMW-HA, Group C: HMW-HA acid only, Group D: empty defect, or Group E: BDNF (500 µg/ml) in saline. The healing status for all groups was observed at different time-points with micro computed tomography. The animals were euthanized after 11 weeks, and the tooth-bone specimens were subjected to histologic processing. The results showed that all groups seemed to successfully regenerate the alveolar buccal bone, however, only Group A regenerated the entire periodontal tissue, i.e., alveolar bone, cementum and periodontal ligament. It is suggested that the use of BDNF in combination with a scaffold such as the hyaluronic acid in periodontal furcation defects may be an effective treatment option. PMID:24454754

SEMATECH produces defect-free EUV mask blanks: defect yield and immediate challenges

NASA Astrophysics Data System (ADS)

Antohe, Alin O.; Balachandran, Dave; He, Long; Kearney, Patrick; Karumuri, Anil; Goodwin, Frank; Cummings, Kevin

2015-03-01

Availability of defect-free reflective mask has been one of the most critical challenges to extreme ultraviolet lithography (EUVL). To mitigate the risk, significant progress has been made on defect detection, pattern shifting, and defect repair. Clearly such mitigation strategies are based on the assumption that defect counts and sizes from incoming mask blanks must be below practical levels depending on mask specifics. The leading industry consensus for early mask product development is that there should be no defects greater than 80 nm in the quality area, 132 mm x 132 mm. In addition less than 10 defects smaller than 80 nm may be mitigable. SEMATECH has been focused on EUV mask blank defect reduction using Veeco Nexus TM IBD platform, the industry standard for mask blank production, and assessing if IBD technology can be evolved to a manufacturing solution. SEMATECH has recently announced a breakthrough reduction of defects in the mask blank deposition process resulting in the production of two defect-free EUV mask blanks at 54 nm inspection sensitivity (SiO2 equivalent). This paper will discuss the dramatic reduction of baseline EUV mask blank defects, review the current deposition process run and compare results with previous process runs. Likely causes of remaining defects will be discussed based on analyses as characterized by their compositions and whether defects are embedded in the multilayer stack or non-embedded.

Hypoxia induced DNA damage in children with isolated septal defect and septal defect with great vessel anomaly of heart.

PubMed

G, Vidya; H Y, Suma; Bhat B, Vishnu; Chand, Parkash; Rao K, Ramachandra

2014-04-01

In Congenital Heart Disease (CHD), shunting of blood occurs through the anatomical defects which lead to mixing of oxygenated and deoxygenated blood. Chronic hypoxia which occurs due to the above said mechanism has the potency to cause DNA damage in children with CHD. In chronic hypoxia, there is a liberation of Reactive Oxygen Species (ROS) due to tissue injury as a result of ischemia and induction of hypoxia inducible factor - 1HIF-1 and p53 which in turn activates pro-apoptotic factors leading to alteration in the regulation of pro-apoptotic gene Blc-2 to be involved in causing the DNA damage. The extent of chronic hypoxia and the DNA damage depends on the nature of the anatomical heart defect. Hence, the present case-control study was conducted to find out the DNA damage in children with isolated septal defect and septal defect with great vessel anomaly of heart and to compare the same. The study group was categorized into those with isolated septal defects and septal defects associated with great vessel anomaly based on echo-cardiogram. Age and sex matched healthy children were taken as controls. Single-cell gel electrophoresis - Comet Assay of Alkaline Version was performed conventionally and the comets were analyzed using comet score software. The comet metrics was found to be statistically significant in children with isolated septal defect and septal defect with great vessel anomaly when compared with that of the controls. In addition, comet metrics also showed significantly increased DNA damage among children with septal defects associated with great vessel anomaly when compared to isolated septal defects. The data strongly suggests a linear correlation of severity of the anomaly involved with the degree of DNA damage as evidenced by lesser extent of DNA damage in isolated septal defect and greater in septal defect with great vessel anomaly.

Information support of monitoring of technical condition of buildings in construction risk area

NASA Astrophysics Data System (ADS)

Skachkova, M. E.; Lepihina, O. Y.; Ignatova, V. V.

2018-05-01

The paper presents the results of the research devoted to the development of a model of information support of monitoring buildings technical condition; these buildings are located in the construction risk area. As a result of the visual and instrumental survey, as well as the analysis of existing approaches and techniques, attributive and cartographic databases have been created. These databases allow monitoring defects and damages of buildings located in a 30-meter risk area from the object under construction. The classification of structures and defects of these buildings under survey is presented. The functional capabilities of the developed model and the field of it practical applications are determined.

Parental cigarette smoking, transforming growth factor-alpha gene variant and the risk of orofacial cleft in Iranian infants

PubMed Central

Ebadifar, Asghar; Hamedi, Roya; KhorramKhorshid, Hamid Reza; Kamali, Koorosh; Moghadam, Fatemeh Aghakhani

2016-01-01

Objective(s): We investigated the influence of genetic variation of the transforming growth-factor alpha (TGFA) locus on the relationship between smoking and oral clefts. Materials and Methods: In this study 105 Iranian infants with non-syndromic cleft lip/palate and 218 controls with non-cleft birth defects were examined to test for associations among maternal exposures, genetic markers, and oral clefts. Maternal and parental smoking histories during pregnancy were obtained through questionnaire. DNA was extracted from newborn screening blood samples, and genotyping of the BamHI polymorphism in the TGFA gene was performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. A number of factors including gender of the newborns, type of oral cleft, consanguinity of the parents, as well as the mother’s age and education were evaluated as potential confounders and effect modifiers. Results: Maternal smoking, in the absence of paternal smoking, was associated with an increased risk for CL/P (OR = 19.2, 95% CI = [(6.2-59.5)]) and cleft palate only (OR =48.7, 95% CI = [(8-29.3)]). If both parents smoked, risks were generally greater (OR = 55.6, 95% CI = [12-20.25]). Analyses for the risk of clefting from maternal smoking, stratified by the presence or absence of the TGFA/BamH1variant, revealed that the risk of clefting among the infants with the TGFA/BamH1 variant when their mothers smoked cigarettes was much greater than the infants who had non-smoker mothers (P=0.001, OR=10.4,95% CI=[3.2,33.6]). Conclusion: The results of this study indicate that first-trimester maternal smoking and infant TGFA locus mutations are both associated with nonsyndromic cleft lip and/or palate (CL/P). PMID:27279979

Congenital anomalies of the kidney and the urinary tract: A murmansk county birth registry study.

PubMed

Postoev, Vitaly A; Grjibovski, Andrej M; Kovalenko, Anton A; Anda, Erik Eik; Nieboer, Evert; Odland, Jon Øyvind

2016-03-01

Congenital anomalies of the kidney and the urinary tract (CAKUTs) are relatively common birth defects. The combined prevalence in Europe was 3.3 per 1000 in 2012. The risk factors for these anomalies are not clearly identified. The aims of our study were to calculate the birth prevalences of urinary malformations in Murmansk County during 2006 to 2011 and to investigate related prenatal risk factors. The Murmansk County Birth Registry was the primary source of information and our study included 50,936 singletons in the examination of structure, prevalence and proportional distribution of CAKUTs. The multivariate analyses of risk factors involved 39,322 newborns. The prevalence of CAKUTs was 4.0 per 1000 newborns (95% confidence interval [CI], 3.4-4.5) and did not change during the study period. The most prevalent malformation was congenital hydronephrosis (14.2% of all cases). Diabetes mellitus or gestational diabetes (odds ratio [OR] = 4.77; 95% CI, 1.16-19.65), acute infections while pregnant (OR = 1.83; 95% CI, 1.14-2.94), the use of medication during pregnancy (OR = 2.03; 95% CI, 1.44-2.82), and conception during the summer (OR = 1.75; 95% CI 1.15-2.66) were significantly associated with higher risk of CAKUTs. The overall fourfold enhancement of the occurrence of urinary malformations in Murmansk County for the 2006 to 2011 period showed little annual dependence. During pregnancy, use of medications, infections, pre-existing diabetes mellitus, or gestational diabetes were associated with increased risk of these anomalies, as was conception during summer. Our findings have direct applications in improving prenatal care in Murmansk County and establishing targets for prenatal screening and women's consultations. © 2016 Wiley Periodicals, Inc.

Bladder calculi in the augmented bladder: a follow-up study of 160 children and adolescents.

PubMed

Kisku, S; Sen, S; Karl, S; Mathai, J; Thomas, R J; Barla, R

2015-04-01

Bladder augmentation (BA) has been used for various congenital and acquired conditions to create a low pressure, continent catheterizable reservoir. The prevalence of calculi within the BA have been reported to be from 3 to 52.5%. The present study reports the prevalence and risk factors of bladder calculi in patients with BA. A retrospective review of 160 patients was performed from January 1997 through December 2012. The various risk factors for the formation of bladder calculi such as the nature of the anatomical defect, presence of preoperative urinary calculi, type of bowel augmentation, addition of a mitrofanoff and/or bladder neck procedure, prevalence of post-operative urinary tract infections (UTIs), need for mitrofanoff revision due to stenosis/difficulty catheterization, postoperative significant hydronephrosis and bladder calculi were recorded for analysis. The children underwent open removal or endoscopic cystolithotripsy. One hundred and eight males and 52 females (average age 6.3 years) were followed up for a median of 70.5 months. All patients performed daily bladder irrigation with tap or drinking water. Post-operative bladder calculi were noted in 14 (8.8%) of 160 patients following BA. Median time to stone formation was 37.5 months (11-120 months). Recurrent febrile UTIs were noted in 16 of the 160 patients following BA. The various risk factors and their outcomes are summarized in table. Eight patients underwent open cystolithotomy and four patients were treated by cystolithotripsy. Post-operative recurrent bladder calculi were noted in 2 patients. Multivariate analysis revealed that exstrophy/epispadias (OR 17.2) and recurrent UTI (OR 55.4) were independent risk factors for developing postoperative calculi in bladder augmentations. All other risk factors did not achieve statistical significance. There seemed to be no difference in the prevalence of calculi in the ileal or colonic augmentations. Mucus secreted by the bowel segment blocks catheters leading to incomplete drainage, stagnation and UTIs. Our protocol consists of daily bladder irrigation till the effluents are clear of mucus. This is probably the key to the low prevalence of postoperative calculi (8.8%) in our patients. Bladder exstrophy/epispadias and UTIs are independent statistically significant risk factors for the formation of bladder calculi in BA patients. Other risk factors such as preoperative calculi, bladder neck procedures and the use of mitrofanoff though not statistically significant, may contribute to the overall risk. The performance of daily bladder irrigation is an important part of our management of mucus. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Defect-engineered graphene chemical sensors with ultrahigh sensitivity.

PubMed

Lee, Geonyeop; Yang, Gwangseok; Cho, Ara; Han, Jeong Woo; Kim, Jihyun

2016-05-25

We report defect-engineered graphene chemical sensors with ultrahigh sensitivity (e.g., 33% improvement in NO2 sensing and 614% improvement in NH3 sensing). A conventional reactive ion etching system was used to introduce the defects in a controlled manner. The sensitivity of graphene-based chemical sensors increased with increasing defect density until the vacancy-dominant region was reached. In addition, the mechanism of gas sensing was systematically investigated via experiments and density functional theory calculations, which indicated that the vacancy defect is a major contributing factor to the enhanced sensitivity. This study revealed that defect engineering in graphene has significant potential for fabricating ultra-sensitive graphene chemical sensors.