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Negative Findings (negative + finding)
Selected AbstractsCognitive,behavioral treatment for alcohol dependence: a review of evidence for its hypothesized mechanisms of actionADDICTION, Issue 10 2000Jon Morgenstern Objective. This review examined support for the hypothesis that cognitive-behavioral treatment (CBT) for alcohol dependence works through increasing cognitive and behavioral coping skills. Method. Ten studies were identified that examined the hypothesized mechanisms of action of CBT. These studies involved random assignment (or its near equivalent) of participants to CBT and at least one comparison condition. Results. Although numerous analyses of the possible causal links have been conducted to evaluate whether CBT works through increasing coping, the results indicate little support for the hypothesized mechanisms of action of CBT. Conclusions. Research has not yet established why CBT is an effective treatment for alcohol dependence. Negative findings may reflect methodological flaws of prior studies. Alternatively, findings may indicate one or more conceptual assumptions underlying CBT require revision. [source] ORIGINAL RESEARCH,ERECTILE DYSFUNCTION: Independent Determinants of Coronary Artery Disease in Erectile Dysfunction PatientsTHE JOURNAL OF SEXUAL MEDICINE, Issue 4pt1 2010Shih-Tai Chang MD ABSTRACT Introduction., There is growing evidence of a link between erectile dysfunction (ED) and coronary artery disease (CAD). Aims., The purpose of this study was to explore the independent determinants of CAD in ED outpatients. Methods., This study enrolled 243 patients, ranging in age from 21 to 81 years old, suffering from ED as diagnosed by the International Index of Erectile Function (IIEF) scores. All patients underwent exercise stress tests or thallium-201 single-photon emission computed tomography perfusion imagings. Based on examination results, patients were divided into study (22 patients with a positive finding) and control groups (221 patients with a negative finding). Main Outcome Measures., The differences of demographic characteristics, biochemical profiles, pro-inflammatory and inflammatory markers, and echocardiographic characteristics between study and control group were compared. Results., The age, presence of DM and current smoking status were significant high in the study group. A significant lower high-density lipoprotein (HDL) cholesterol level, a higher percentage of HDL cholesterol level < 40 mg/dL, and a higher apo-lipoprotein B/A1, high sensitive C-reactive protein (hs-CRP) and homocysteine found in the study group. The Framingham cardiac risk scores, the ratio of mitral inflow velocity to early diastolic velocity in the annulus derived by tissue Doppler imaging (E/Et), the ratio of E/Et , 15, the value of carotid intima-media thickness (IMT), and IMT , 1 mm were higher in study group than in the control group. In stepwise multiple logistic regression analysis, a high waist-to-hip ratio (WHR), high IMT, high E/Et, hs-CRP levels, LDL cholesterol , 130 mg/dL, smoking status, and the presence of DM and metabolic syndrome (MS) were independent determinants of CAD in ED patients. Conclusions., This study first shows the independent determinants of CAD in ED outpatients. This novel finding may improve the screening of low-risk ED patients for CAD. Chang S-T, Chu C-M, Hsu J-T, Hsiao J-F, Chung C-M, Ho C, Peng Y-S, Chen P-Y, and Shee J-J. Independent determinants of coronary artery disease in erectile dysfunction patients. J Sex Med 2010;7:1478,1487. [source] Correction for QT/RR Hysteresis in the Assessment of Drug-Induced QTc Changes,Cardiac Safety of GadobutrolANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2009M.D., Marek Malik Ph.D. Background: The so-called thorough QT/QTc (TQT) studies required for every new pharmaceutical compound are negative if upper single-sided 95% confidence interval (CI) of placebo and baseline corrected QTc prolongation is <10 ms. This tight requirement has many methodological implications. If the investigated drug has a fast action and ECGs cannot be obtained at stable heart rates, QT/RR hysteresis correction is needed. Methods: This was used in a TQT study of gadobutrol. The TQT study was a randomized double-blind five-times crossover study of three doses of gadobutrol (0.1, 0.3, and 0.5 mmol/kg) that was placebo and positive effect controlled (moxifloxacin 400 mg). The study enrolled 50 healthy subjects with data of all periods. QT/RR hysteresis was assessed from prestudy exercise test ECGs. Among others, comparisons were made between population heart rate correction without hysteresis considerations and combined population heart rate and hysteresis correction. Results: The highest heart rate increase (placebo and baseline controlled) of 13.1 beats per minute (90% CI 9.9,16.4) occurred 1 minute after the administration of the highest dose of gadobutrol. Without hysteresis consideration, the highest ,,QTc were 9.91 ms (90% CI 8.01,11.81) while with hysteresis correction, these values were 7.62 ms (90% CI 6.37,8.87), thus turning a marginally positive TQT study into a negative finding. Conclusion: Hence, omitting hysteresis correction from episodes of fast heart rate changes may lead to incorrect conclusions. Despite substantial rate acceleration, accurate hysteresis correction confirms that gadobutrol does not have any effects on cardiac repolarization that would be within the limits of regulatory relevance. [source] The effect of GSM and TETRA mobile handset signals on blood pressure, catechol levels and heart rate variability ,BIOELECTROMAGNETICS, Issue 6 2007Anthony T. Barker Abstract An acute rise in blood pressure has been reported in normal volunteers during exposure to signals from a mobile phone handset. To investigate this finding further we carried out a double blind study in 120 healthy volunteers (43 men, 77 women) in whom we measured mean arterial pressure (MAP) during each of six exposure sessions. At each session subjects were exposed to one of six different radio frequency signals simulating both GSM and TETRA handsets in different transmission modes. Blood catechols before and after exposure, heart rate variability during exposure, and post exposure 24 h ambulatory blood pressure were also studied. Despite having the power to detect changes in MAP of less than 1 mmHg none of our measurements showed any effect which we could attribute to radio frequency exposure. We found a single statistically significant decrease of 0.7 mmHg (95% CI 0.3,1.2 mmHg, P,=,.04) with exposure to GSM handsets in sham mode. This may be due to a slight increase in operating temperature of the handsets when in this mode. Hence our results have not confirmed the original findings of an acute rise in blood pressure due to exposure to mobile phone handset signals. In light of this negative finding from a large study, coupled with two smaller GSM studies which have also proved negative, we are of the view that further studies of acute changes in blood pressure due to GSM and TETRA handsets are not required. Bioelectromagnetics 28:433,438, 2007. © 2007 Wiley-Liss, Inc. [source] Assessment of cardiovascular risk in waiting-listed renal transplant patients: a single center experience in 558 casesCLINICAL TRANSPLANTATION, Issue 5 2009G. Leonardi Abstract:, Cardiac screening is recommended to prevent cardiovascular death after renal transplantation. This retrospective observational study illustrates the results of application of a cardiac assessment algorithm in a series of 558 renal transplant candidates at a single center in Turin, Italy. A dipyridamole-stress sestamibi myocardial scintiscan (DMS) performed in 302/558 (54.1%) cases was positive in 52 (17.2%), negative in 200 (66.2%), borderline in 16 (5.3%), and with signs of previous necrosis in 34 (11.4%). Coronary lesions detected by angiography in 48.1% of the 52 positives were treated medically (13.5%) or by percutaneous/surgical procedure (34.6%). Coronary lesions were detected in 14.1% of asymptomatic population subgroup. The minor and major cardiovascular event rates and the cardiovascular death rate were 1.9%, 0%, and 0%, respectively, in positive DMS group (high-cardiological risk) vs. 10%, 4.5%, and 3.5% in the negatives (p > 0.5; n.s.). It is suggested that not increased cardiovascular event or deaths rates in the high-risk group reflect early coronary lesion detection and correction. Since 55.9% of cardiovascular events or deaths occurred in the negative group more than 24 months after the DMS, its mandatory repetition every two yr after a negative finding is recommended. [source] Comparisons of overground endoscopy and treadmill endoscopy in UK Thoroughbred racehorsesEQUINE VETERINARY JOURNAL, Issue 3 2010K. J. ALLEN Summary Reasons for performing study: To date there is no information on the comparison of the more recently documented technique of performing endoscopy during ridden exercise in the field, with the more traditional method of endoscopy during high-speed treadmill exercise. Objectives: To compare the results of upper respiratory tract endoscopy in UK Thoroughbred racehorses performed during ridden exercise in the field with those obtained during exercise on the treadmill. Methods: A direct comparison was undertaken in 4 horses whereby both procedures were performed in the same horse within 10 days of each other. An indirect comparison was also undertaken whereby the results of overground endoscopy performed in 50 racehorses was compared to the results obtained during treadmill endoscopy in a further 50 racehorses. Horses were matched for age, gender, use (National Hunt vs. Flat) and presenting complaint (abnormal respiratory noise vs. poor performance). Results: Dorsal displacement of the soft palate was diagnosed less frequently during overground endoscopy than during treadmill endoscopy. There was no significant difference in the diagnosis of dynamic laryngeal collapse between the 2 techniques. The treadmill exercise test was performed over longer distances at higher inclines, albeit at lower speeds than the overground test. In contrast to the treadmill test, the overground test was frequently performed in intervals. Conclusions: The results of both the direct and indirect comparisons suggest that dorsal displacement of the soft palate is diagnosed less often during overground endoscopy than during treadmill endoscopy. Strenuous exercise tests may be more easily performed on a treadmill than by performing multiple exercise intervals in the field. Potential relevance: Care should be taken in interpreting negative findings during both procedures, but particularly during overground endoscopy if racing conditions have not been appropriately replicated. [source] Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2005C. Kornblum The purpose of our randomized, double-blind, placebo-controlled crossover study in 15 patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns,Sayre syndrome (KSS) because of single large-scale mitochondrial (mt) DNA deletions was to determine whether oral creatine (Cr) monohydrate can improve skeletal muscle energy metabolism in vivo. Each treatment phase with Cr in a dosage of 150 mg/kg body weight/day or placebo lasted 6 weeks. The effect of Cr was estimated by phosphorus-31 magnetic resonance spectroscopy (31P-MRS), clinical and laboratory tests. 31P-MRS analysis prior to treatment showed clear evidence of severe mitochondrial dysfunction. However, there were no relevant changes in 31P-MRS parameters under Cr. In particular, phosphocreatine (PCr)/ATP at rest did not increase, and there was no facilitation of post-exercise PCr recovery. Clinical scores and laboratory tests did not alter significantly under Cr, which was tolerated without major side-effects in all patients. Cr supplementation did not improve skeletal muscle oxidative phosphorylation in our series of patients. However, one explanation for our negative findings may be the short study duration or the limited number of patients included. [source] Employment of People with Disabilities Following the ADAINDUSTRIAL RELATIONS, Issue 1 2003Douglas Kruse Studies finding a negative effect of the Americans with Disabilities Act (ADA) on the employment of people with disabilities have used the work disability measure, which has several potential problems in measuring employment trends. Using Survey of Income and Program Participation (SIPP) data that permit alternative measures of disability, this study finds decreased employment among those reporting work disabilities in the first few years after the ADA was passed but increased employment when using a more probably appropriate measure of ADA coverage (functional and activity limitations that do not prevent work). State-by-state variation in labor market tightness is used to find that people with disabilities may have especially procyclical employment, but the contrary results in overall employment trends remain after accounting for labor market tightness. Given the problems in measuring who is covered by the ADA, there is reason to be cautious of both positive and negative findings. [source] Clinical application of wireless capsule endoscopyJOURNAL OF DIGESTIVE DISEASES, Issue 2 2003Zhi Zheng GE BACKGROUND: Diagnostic modalities for identifying lesions within the small bowel have been quite limited. Wireless capsule endoscopy (WCE) is a new, innovative technique that can detect very small mucosal lesions in the entire small bowel and can be used in the outpatient setting. The present study explored the diagnostic value, tolerance and safety of WCE in the identification of small bowel pathology that was not detected with conventional small bowel imaging studies. METHODS: From May through September 2002, 15 patients with suspected small bowel diseases were prospectively examined, Of them, 12 presented with persistent obscure gastrointestinal bleeding and negative findings on upper endoscopy, colonoscopy, small bowel radiography, and bleeding-scan scintig-raphy or mesenteric angiography. RESULTS: Wireless capsule endoscopy identified pathologic small bowel findings in 11 of the 15 patients (73%): angioectasias, Dieulafoy's lesion, polypoid lesion, submucosal mass, Crohn's disease, carcinoid tumor, lipoma, aphthous ulcer, and hemorrhagic gastritis; four of the patients had two lesions. The images displayed were considered to be good. The capsule endoscopes remained in the stomach for an average of 82 min (range 6,311 min) and the mean transit time in the small bowel was 248 min (range 104,396 min). The mean time of recording was 7 h 29 min (from 5 h to 8 h 30 min). The mean time to reach the cecum was 336 min (180,470 min). The average number of the images transmitted by the capsule was 57 919 and the average time the physician took to review the images transmitted by the capsule was 82 min (range 30,120 min). The average time of elimination of the capsule was 33 h (range 24,48 h). All 15 patients reported that the capsule was easy to swallow, painless, and preferable to conventional endoscopy. No complications were observed. CONCLUSIONS: Wireless capsule endoscopy is safe, well tolerated, and useful for identifying occult lesions of the small bowel, especially in patients who present with obscure gastrointestinal bleeding. [source] Review article: a critical view on impaired accommodation as therapeutic target for functional dyspepsiaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2006B. D. J. VAN DEN ELZEN Summary Several important pathophysiological mechanisms have been identified in functional dyspepsia, however a complete understanding of these mechanisms and beneficial therapeutic strategies are still lacking. Based on the currently available literature we aimed at providing a critical view on one of these pathophysiological mechanisms, impaired accommodation. Although impaired gastric accommodation is identified as a major pathophysiological mechanism, the clinical evidence supporting its role as an important therapeutic target is currently still lacking. Treatment with fundic relaxant drugs has shown conflicting results and has been rather disappointing in general. These negative findings could be explained by the fact that impaired fundic accommodation is part of a more complex disorder involving other regions of the proximal gut or by the increasing insight that central mechanisms may play an important role. Future studies of impaired accommodation should take these considerations into account. [source] vCJD , predicting the future?NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 5 2000D. A. Hilton The recent emergence of variant Creutzfeldt,Jakob disease (vCJD) in the UK, and demonstration that vCJD is caused by the same prion strain that causes bovine spongiform encephalopathy, have led to concerns about the possibility of a human epidemic. Although only 79 cases of vCJD have occurred to date, it is likely that hundreds of thousands of infected cattle entered the human food chain in the late 1980s and early 1990s, and the average incubation period of vCJD is unknown. Mathematical models have not yet been able to give useful predictions of future numbers of cases, and in the absence of a blood test for vCJD, current attempts to reduce uncertainties about future numbers of cases are based on the accumulation of PrPSc in lymphoreticular tissues. Extensive lymphoreticular PrPSc accumulation has been seen in all cases of symptomatic vCJD so far examined, and in one case 8 months prior to the onset of symptoms. Animal models of prion disease suggest that lymphoreticular involvement occurs early in the incubation period and reliably predicts future neurological disease. Based on these data, large scale anonymous studies looking for PrP accumulation in surgically removed tonsillectomy and appendicectomy specimens are underway. Examination of the first 3000 specimens has not revealed any positive samples, but at the moment the significance of negative findings is uncertain. It is anticipated that by the time these studies are complete more data will be available on how early PrP can be demonstrated in lymphoreticular tissue in vCJD, which together with the results from examination of further samples, will allow some comment as to the likelihood of a large human vCJD epidemic. [source] A cognitive aid for neonatal resuscitation: a randomized controlled trialPEDIATRIC ANESTHESIA, Issue 7 2009M.D. Bould Introduction:, Anaesthetists are among several health care practitioners responsible for neonatal resuscitation in Canada. The Neonatal resuscitation program (NRP) courses are the North American educational standard. NRP has been shown to be an effective way of learning skills and knowledge but retention has been found to be problematic [1]. The use of cognitive aids is mandatory in industries such as aviation, to avoid dependence on memory when decision making in critical situations. Visual cognitive aids have been studied retrospectively in resuscitation and performance was found to correlate to the frequency of use of the aid [2]. Cognitive aids have been found to be of benefit in an unblinded prospective study [3]. We aimed to conduct the first blinded study on the effect of a cognitive aid on the performance of simulated resuscitation. Methods:, We conducted a single-blind randomized controlled trial to investigate whether the presence of a cognitive aid improved performance in a simulated neonatal resuscitation. After ethics board approval we recruited 32 anaesthesia residents who had previously passed the NRP. Subjects were randomized to an intervention group that had a poster detailing the NRP algorithm and a control group without the poster. The cognitive aid was positioned so that it could not be seen on the video recordings of the simulation that was used to assess performance. The scenario was piloted to confirm adequate blinding. Both groups had their performance in a simulated neonatal resuscitation recorded and subsequently analyzed by a peer, an expert anaesthetist and an expert neonatologist, using a previously validated checklist. A further rater observed the scenario in real time to examine frequency of use of the cognitive aid. Results:, The inter-rater reliability of the checklist was excellent with an intraclass correlation coefficient of 0.88. Consequently the mean of the scores assigned by all three raters was used for analysis. The median checklist score in the control group 18.2 [15.0,20.5 (10.7,25.3)] was not significantly different from that in the intervention group 20.3 [18.3,21.3 (15.0,24.3)] (P = 0.08). Retention of NRP skills and knowledge of was poor: when evaluated by the neonatologist none of the subjects correctly performed all life-saving interventions necessary to pass the checklist. Although only one subject in the intervention group did not use the aid at all, only 26.7% used the aid frequently and none used it extensively. Discussion:, Retention of skills after NRP training was poor. Our study confirms previous findings of poor retention of skills after NRP training: Kaczorowski et al. investigated family medicine trainees and found that none of 44 residents that were retested 6,8 months after an NRP course would have passed the course due to errors in life-saving interventions [1]. Previous research has shown that the presence of a cognitive aid can improve performance in the simulated management of a rare, high stakes scenario: malignant hyperthermia [3]. Our negative findings contrast with this and another previous study [2]. A potential reason for this discrepancy is that the raters in the previous studies were not blinded to group allocation, nor were the rating scales used validated. The infrequent use of the cognitive aid may be the reason that it did not improve performance in. Further research is required to investigate whether cognitive aids can be useful if their use is incorporated into NRP training. Conclusion:, A randomized single-blinded trial found that a cognitive aid did not improve performance at simulated resuscitation, in contrast to previous retrospective and unblended studies. Retention of skills and knowledge after resuscitation training remains an ongoing challenge for medical educators. [source] Norepinephrine transporter and ,2c adrenoceptor allelic variants and personality factors,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 6 2002Shih-Jen Tsai Abstract It has been suggested that reward dependence, as measured by the Tridimensional Personality Questionnaire (TPQ), is related to central noradrenergic activity, a proposition supported by two studies of urinary norepinephrine metabolite. In the current investigation, 190 normal young Han Chinese were examined, with genetic polymorphisms determined for the norepinephrine transporter (1287G/A) and the ,2c -adrenoceptor (Del322,325) to test the association with TPQ personality traits. No significant association was demonstrated for these two polymorphisms and any of the TPQ personality-factor scores, including reward dependence and its subscales. Our negative findings suggest that the investigated polymorphisms of the norepinephrine transporter and the ,2c adrenoceptor do not play a major role in the reward-dependence personality trait as assessed by TPQ. © 2002 Wiley-Liss, Inc. [source] Development of Rotary Blood Pump Technology: Past, Present, and FutureARTIFICIAL ORGANS, Issue 6 2000Yukihiko Nosé Abstract: Even though clinical acceptance of a nonpulsatile blood flow was demonstrated almost 45 years ago, the development of a nonpulsatile blood pump was completely ignored until 20 years ago. In 1979, the first author's group demonstrated that completely pulseless animals did not exhibit any abnormal physiology if 20% higher blood flows were provided to them. However, during the next 10 years (1979,1988), minimum efforts were provided for the development of a nonpulsatile, permanently implantable cardiac prosthesis. In 1989, the first author and his team at Baylor College of Medicine initiated a developmental strategy of various types of nonpulsatile rotary blood pumps, including a 2-day rotary blood pump for cardiopulmonary bypass application, a 2 week pump for ECMO and short-term circulatory assistance, a 2 year pump as a bridge to transplantation, and a permanently implantable cardiac prosthesis. Following the design and developmental strategy established in 1989, successful development of a 2-day pump (the Nikkiso-Fairway cardiopulmonary bypass pump) in 4 years (1989,1993), a 2 week pump (Kyocera gyro G1E3 pump) in 6 years (1992,1998), and a bridge to transplant pump (DeBakey LVAD,an axial flow blood pump) in 10 years (1988,1998) was made. Currently, a permanently implantable centrifugal blood pump development program is successfully completing its initial Phase 1 program of 5 years (1995,2000). Implantation exceeded 9 months without any negative findings. An additional 5 year Phase II program (2000,2005) is expected to complete such a device that will be clinically available. [source] Satisfaction and Use of Prenatal Care: Their Relationship Among African-American Women in a Large Managed Care OrganizationBIRTH, Issue 1 2003Arden Handler DrPH ABSTRACT:Background: Although many more mothers of almost all ethnic groups began prenatal care in the first trimester during the last decade, a significant number of low-income and minority women still fail to obtain adequate care in the United States,a failure that may be related to their dissatisfaction with the prenatal care experience. This study sought to examine the relationship between satisfaction with care and subsequent prenatal care utilization among African-American women using prospective methods. Methods: A sample of 125 Medicaid and 275 non-Medicaid African-American adult women seeking care through a large Midwest managed care organization were interviewed before or at 28 weeks' gestation at one of two prenatal care sites. Women were interviewed about personal characteristics, prenatal care experience, and ratings of care (satisfaction). Information about subsequent use of prenatal care was obtained through retrospective medical record review after delivery. Univariate and multivariable analyses examining the relationship between women's satisfaction and prenatal care use were conducted using a dichotomous measure of satisfaction and a continuous measure of utilization. Results: Women were highly satisfied with prenatal care, with an overall mean satisfaction score of 80.3. Non-Medicaid women were significantly (p < 0.05) less satisfied with their prenatal care (mean score, 79.1) than Medicaid women (mean score, 82.8), and the latter had significantly fewer visits on average than the former subsequent to the interview. Analyses showed no significant difference in subsequent utilization according to whether a woman had a high versus low level of satisfaction at the prenatal care interview. Conclusions: This study challenges the assumption that improving a woman's satisfaction with care will lead to an increase in the adequacy of her prenatal care utilization. Since this study was limited to African-American women and is the first prospective study of women's satisfaction with care and prenatal care utilization, the negative findings do not yet settle this area of inquiry. Monitoring women's satisfaction with prenatal care in both managed care and fee-for-service settings and working to improve those aspects of care associated with decreased satisfaction is warranted. (BIRTH 30:1 March 2003) [source] Can Young Infants Add and Subtract?CHILD DEVELOPMENT, Issue 6 2000Ann Wakeley Three experiments (N= 68), using Wynn's procedure, tested 5-month-old infants' looking time reactions to correct and incorrect results of simple addition and subtraction transformations. The aim was to investigate both the robustness and the parameters of infants' arithmetic competence. Experiments 1 and 2 (N= 44) were replications of Wynn's first two experiments in which infants were shown addition (1 + 1 = 1 or 2) and subtraction (2 , 1 = 1 or 2) requiring imprecise calculation. Experiment 3 (N= 24) was a subtraction counterpart (3 , 1 = 1 or 2) to Wynn's third experiment requiring precise calculation of addition (1 + 1 = 2 or 3). Unlike Wynn, we found no systematic evidence of either imprecise or precise adding and subtracting in young infants. Our results, together with the mix of both positive and negative findings from other studies of infant arithmetic, suggest that infants' reactions to displays of adding and subtracting are variable and, therefore, that infants' numerical competencies are not robust. This conclusion is consistent with previous findings indicating that simple adding and subtracting develops gradually and continuously throughout infancy and early childhood. [source] Toward understanding the genetic basis of neural tube defectsCLINICAL GENETICS, Issue 4 2007Z Kibar Neural tube defects (NTDs) represent a common group of severe congenital malformations that result from failure of neural tube closure during early development. Their etiology is quite complex involving environmental and genetic factors and their underlying molecular and cellular pathogenic mechanisms remain poorly understood. Animal studies have recently demonstrated an essential role for the planar cell polarity pathway (PCP) in mediating a morphogenetic process called convergent extension during neural tube formation. Alterations in members of this pathway lead to NTDs in vertebrate models, representing novel and exciting candidates for human NTDs. Genetic studies in NTDs have focused mainly on folate-related genes based on the finding that perinatal folic acid supplementation reduces the risk of NTDs by 60,70%. A few variants in these genes have been found to be significantly associated with an increased risk for NTDs. The candidate gene approach investigating genes involved in neurulation has failed to identify major causative genes in the etiology of NTDs. Despite this history of generally negative findings, we are achieving a rapid and impressive progress in understanding the genetic basis of NTDs, based mainly on the powerful tool of animal models. [source] | |||||||||||||