Primary postpartum haemorrhage (PPH) was reported in 34% of pregnancies and secondary PPH in 24%. PPH was frequently severe and occurred up to 20 days after delivery. There was a wide variation in approach to prevention and Metformin datasheet treatment of PPH but most women received platelet transfusion, sometimes with additional recombinant FVIIa and anti-fibrinolytics. Maternal alloimmunization against platelet antigens was reported in 73% of pregnancies and was associated with four neonatal deaths. These data emphasize the need for multidisciplinary management of pregnancy in women with GT. Delivery plans should recognize the need for prevention and aggressive treatment of PPH and should

minimize foetal bleeding risk in pregnancies complicated by alloimmunization. “
“Although many people with haemophilia discontinue prophylaxis in their late teens or early adulthood, the consequences of this decision are largely not known. This 18-month, observational, case-controlled, multicentre study

evaluated long-term prophylaxis and the consequences of switching from prophylaxis Natural Product Library in vivo to on-demand treatment in late teens and young adults with severe haemophilia A. Participants with haemophilia (aged 14–29 years) on prophylaxis ≥60% of the time for the 5 years before study entry were enrolled into 1 of 2 prospective or 1 retrospective group. Group 1 was prophylaxis, group 2 had voluntarily discontinued prophylaxis ≤12 months before study entry and group 3 had voluntarily discontinued prophylaxis

selleck chemicals llc ≥13 months before study entry. Assessments included bleeding frequency (primary endpoint), Haemo-QoL-A health-related quality of life (HRQoL) scores, Gilbert score, development of target joints, Haemophilia Activities List, Godin Leisure-Time, treatment satisfaction and State-Trait Anxiety Inventory (secondary and exploratory endpoints). Descriptive statistics were provided for all variables. Thirty-eight participants (group 1, n = 22; group 2, n = 5; group 3, n = 11; median age, 19.5 years) were enrolled. The median annualized number of bleeding events was 0, 4.8 and 24 in groups 1, 2 and 3 respectively. HRQoL was lower in participants who discontinued prophylaxis vs. those who remained on prophylaxis. Changes in the remaining secondary and exploratory variables were small, but were generally worse in participants who discontinued prophylaxis. Following a switch from prophylaxis to on-demand therapy, the number of bleeding events increased and HRQoL worsened in late teens and young adults with severe haemophilia A. “
“Joint damage from bleeding episodes leads to physical or functional limitations in people with haemophilia. Various factors may influence the frequency and severity of joint damage. This study examined whether age, prophylaxis, history of high-titre inhibitors (HTI) and bleeding events influenced the Haemophilia Joint Health Score (HJHS) in children.

After 1 hour, the wells were washed four times with PBST, and the substrate (o-phenylenediamine dihydrochloride and H2O2) was added. The reaction was stopped after 30 minutes by adding 50 μL 2 N HCl. Color development was measured in an ELISA plate reader

at 490 nm. Mean optical densities (OD) from triplicate wells containing either peptide E1, E2A, or E2B, and the mean OD of the control wells (NHS) were calculated. Serum samples from each patient were all processed on the same day, and each plate contained a positive control serum sample. The recognition cutoff for each peptide was calculated as the mean value obtained with at least three NHS + 3 standard deviations (SD). To this end, the anti-E1E2A,B ELISA test was carried Raf inhibitor out either in the absence of peptide (no peptide) or with the three biotinylated peptides E1, E2A,

and E2B added together at the final concentration of 5 μg/mL each on the same well. The test was also performed by direct coating of nonbiotinylated peptides on the solid phase. For testing the specificity of detection, two irrelevant biotinylated peptides, peptide-1× (Bio-RSFKSWTGQTPGEFRESRRRDNP LG-amide; 25 aa) and peptide-2× (Bio-SCARRGCIR RRPGHAG-amide; 16 aa) were used in comparison with E1, E2A, and E2B peptides. The peptides 1× and 2× showed from 7%-20% of sequence homology with the D32.10 epitope sequences E1, E2A, and E2B. Peptide-1× did not contain any cysteine residue whereas peptide-2× contained two cysteine residues. Indeed, the critical residues for the D32.10 mAb recognition were identified as Cys306 (E1),

Cys494 Enzalutamide (E2A), and Cys620 (E2B).12 Serum IgG fraction was purified using protein G–sepharose 4-fast flow selleckchem (Pharmacia France, Montigny-le-Bretonneux, France). Two hundred μL of heat-inactivated serum diluted by one-half in PBS was mixed with 200 μL of protein G–sepharose immunobeads for 30 minutes at 25°C and then centrifuged for 90 seconds at 3800g. The supernatant was discarded and the immunobeads were then washed three times with Immunopure IgG binding buffer (Pierce Protein, Perbio Science France SAS) by centrifugation for 90 seconds at 5000g each time. Immunopure IgG elution buffer (400 μL; Pierce Protein, Perbio Science France SAS) was added to the immunobeads, which were mixed thoroughly and then centrifuged for 90 seconds at 5000g. The supernatant was neutralized with 35 μL 1 M Tris-HCl (pH 8.0). The IgG concentration was determined using a micro BCA assay (Bio-Rad Laboratories, Marnes-la-Coquette, France). Purified IgGs were stored at −80°C. The protein mean concentration for four serums from NHS was 1.29 ± 0.13 mg/mL, for 12 serums from cured (C) patients was 2.09 ± 0.46 mg/mL, and for 14 serums from NT patients was 3.19 ± 0.27 mg/mL. Statistical comparison between two groups of patients was performed with a t test, and P values were calculated using the GraphPad Prism 4 software. P value < 0.

Thus, further declines in GC mortality rates may require more intensive efforts for the prevention and control

of H. pylori infection and other risk factors, including tobacco and diet, as well as exposures associated with cancer of the cardia, such as reflux disease and obesity. Moreover, there is still the need for intervention to improve early diagnosis and management in high risk countries. Prevention of cardia cancers has become a priority Venetoclax in several regions. Apart from H. pylori infection, which is confirmed and widely accepted as the principal trigger of gastric carcinogenesis, diet plays an indisputable role in gastric carcinogenesis as well. High intake of salted, pickled or smoked foods, as well as dried fish and meat and refined carbohydrates significantly

increase the risk of developing GC, while fibers, fresh vegetables, and fruit are inversely associated with GC risk. A recent Cobimetinib meta-analysis, including eight epidemiologic studies, with a total of 53,729 subjects, confirmed an increased risk of GC with a “western/unhealthy” diet, rich in starchy foods, meat, and fats, in respect of a “prudent/healthy” diet, rich in fruits and vegetables (OR 1.51; 95% CI 1.21–1.89) [7]. Whether autoimmune gastritis is etiologically linked to H. pylori infection is a matter of discussion. In a large population-based study pepsinogen I and II, antibodies against H. pylori in general, the cytotoxin-associated gene A protein (CagA) and parietal cells were measured by ELISA in 9684 subjects aged 50–74 years [8]. Pepsinogen I < 70 ng/mL this website and pepsinogen I/II <3 were indicative of the presence of chronic atrophic gastritis (CAG). Antigastric parietal cell antibody (APCA) prevalence was examined in the overall population and according to sex, age, and H. pylori serological

status. APCA prevalence (19.5%) was strongly associated with CAG, and the association was highest with increasing severity of CAG. Furthermore, the association between APCA and CAG was stronger among H. pylori-negative subjects (OR = 11.3; 95% CI: 7.5–17.1) than among H. pylori-positive subjects (OR = 2.6; 95% CI: 2.1–3.3). Interestingly, the association between APCA prevalence and CAG was much stronger among subjects with a CagA-negative infection compared with subjects with a CagA-positive infection. These results suggest that H. pylori infection and APCA-mediated autoimmune response might, for the most part, be independent, distinct pathways, rather than causally related pathways leading to CAG. Assessment of APCA might be a useful complement to established markers (such as pepsinogens and H. pylori antibodies) in screening for CAG. Previous studies have reported that H. pylori eradication after endoscopic resection for early GC may prevent metachronous GC, while other studies are not in agreement [9, 10].

“
“Grindelia robusta, a perennial herb, contains an essential oil that is used as an antitussive, sedative, and analgesic agent. During the spring of 2007, ‘Candidatus Phytoplasma asteris’-related phytoplasmas were identified in plants showing virescence and phyllody symptoms. The qualitative and quantitative composition of the oil of healthy

and infected plants was compared by gas chromatography/mass spectrometry. Samples from six symptomatic and five asymptomatic plants tested by nested PCR followed by RFLP analyses confirmed the presence of ‘Ca. P. asteris’ in all symptomatic samples. The oils from healthy and infected plants, obtained by steam distillation, contained 42 components; that of healthy plants contained a higher concentration of monoterpenes, especially limonene and bornyl acetate, which were nearly 50% higher. “
“Plants respond to many stress factors, including infections Selleck SCH727965 caused by root pathogens, with reductions in photosynthesis and growth. We studied the response of mature cucumber plants after a weak inoculation of the roots with Pythium aphanidermatum. The epidemiology of the disease was recorded using an indirect ELISA. Although mycelium was detected in the roots, photosynthesis was not affected over a period of five weeks. Nevertheless, plant growth was significantly reduced by the pathogen. Possible modes of action are

discussed. “
“Fusarium langsethiae is a toxigenic fungus that was formally described as a new species in 2004. This fungus was first detailed in the 1990s but was initially referred to as ‘powdery Fusarium poae’ having a spore morphology similar to F. poae RAD001 manufacturer but a mycotoxin profile like that of Fusarium sporotrichioides. The species has been isolated from infected oat, wheat this website and barley grains but has been reported as more problematic in the former crop rather than the latter two. Whilst the epidemiology of F. langsethiae remains unclear, the fungus has been shown to produce high levels of type-A trichothecenes HT-2 and T-2 toxins in small-grain cereals. HT-2 and T-2 toxins are two of the most potent trichothecenes capable of inhibiting protein synthesis in eukaryotes.

In this regard, mycotoxin contamination caused by F. langsethiae is clearly a food and feed safety hazard. With the European Commission considering legislation of HT-2 and T-2 toxins, more information is required not only on the producer and conditions favouring mycotoxin production, but also on reliable methods of pathogen detection and reduction of cereal contamination. This review describes recent research concerning the known epidemiology of F. langsethiae and suggestions of what needs to be known about the fungus in order to be able to understand and employ measures for preventing its infection and contamination of cereals with HT-2 and T-2 toxins. “
“Sunflower rust caused by Puccinia helianthi is considered to be a major disease of sunflower because it causes significant yield losses.

01) but did not reach statistical significance compared to the water group. Conclusion: The use of simethicone given before endoscopy provided better mucosal visibility requiring lesser selleck chemical volume of water flushes and shorter procedure time. Key Word(s): 1. Simethicone; 2. mucosal visibility; 3. endoscopy Presenting Author: OSAMU DOHI Additional Authors: ATSUSHI MAJIMA,

YURIKO ONOZAWA, TOMOKO KITAICHI, YUSUKE HORII, KENTARO SUZUKI, AKIRA TOMIE, KAZUHIRO KAMADA, NOBUAKI YAGI, YUJI NAITO, YOSHITO ITOH Corresponding Author: OSAMU DOHI Affiliations: Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Murakami Memorial Hospital Asahi University, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine Objective: Blue LASER Imaging (BLI) is a new image-enhanced endoscopy with a laser light source developed for narrow-band light observation. The aim of this study is to evaluate the usefulness of BLI for the diagnosis of early gastric cancer. Methods: We prospectively analyzed 110

gastric lesions that were examined with both the conventional endoscopy with white-light image (C-WLI) observation and magnifying endoscopy with BLI (M-BLI) observation at Kyoto selleck chemicals llc Prefectural University of Medicine between November 2012 and May 2014. The diagnostic criteria of gastric cancer using C-WLI were both an irregular margin and an irregular mucosal area. The diagnostic criteria of gastric cancer using ME-BLI were an irregular microvascular (MV) pattern and/or irregular microsurface (MS) learn more pattern with the demarcation line evaluated by VS classification system. The lesions were taken biopsies after M-BLI observation following C-WLI observation. We evaluated the correlations between

the diagnosis of M-BLI and that of histopathology, compared with the correlations between the diagnosis of C-WLI and that of histopathology. Results: We analyzed 110 detected lesions (23 cancers and 87 noncancers). The accuracy, sensitivity and specificity of high confidence M-BLI diagnoses were 93.6, 91.3 and 94.3%, respectively. Most of the false positive cases were depressed mucosal lesions with the histopathological diagnosis of regenerative gland in pyloric/fundic mucosa with inflammatory cell infiltration. On the other hand, the accuracy, sensitivity and specificity of C-WLI diagnoses were 88.1, 56.5 and 96.6%, respectively. Conclusion: M-BLI was useful for the diagnostic accuracy and sensitivity of early gastric cancer compared with C-WLI. Key Word(s): 1. BLI; 2. VS classification; 3.

Within the hyper-arid Atacama Desert, one of the driest parts of the world, 10 sites

with differing altitude and distance to the shore were sampled along a total air-line distance (from south to north) of ~1,100 km. Opaganib supplier Filamentous cyanobacteria belonging to Nostocophycideae and Synechococcophycideae were present. Oscillatoriophycideae exhibited the highest species richness among the subclasses of cyanobacteria, and included mostly filamentous species along with some coccoids (e.g., Chroococcidiopsis). Thirty species-level phylotypes could be recognized using a cut-off of 99% 16S rRNA sequence similarity within the 22 genera defined at 97% 16S rRNA sequence similarity. Eight of the 30 taxa could be detected by both clonal and culture sequences. Five taxa were observed only in cultures, whereas the cloning approach revealed 17 additional taxa, which might be in the collection Selleck BMS-777607 but unsequenced, hard-to-cultivate, or entirely unculturable species using standard cultivation media. The Atacama Desert soils have a high diversity of phylotypes, among which are likely both new genera and new species awaiting characterization and description. “
“Klebsormidium crenulatum (Kütz.) Lokhorst (Klebsormidiophyceae, Streptophyta)

isolated from an alpine soil in Tyrol, Austria, was experimentally exposed to desiccation under various relative air humidities (RH 5, 75, and >95%, ambient air 55%–60%). The effects on the structure and ultrastructure of K. crenulatum after 1, 4, or 7 d of desiccation at 5, 75, and >95% RH were investigated. The cross walls were deformed to an undulated shape, and the cell diameter was reduced to ∼60% of the control. Regardless

of the RH applied, in all cases the cytoplasm appeared denser click here compared to that of liquid-culture-grown cells. Electron-dense particles with diameters of 0.4 μm–0.8 μm were observed in the cytoplasm, likely representing lipid droplets. The chloroplasts of desiccated samples contained a large number of plastoglobules. The number and appearance of mitochondria were not visibly altered, as also verified by 3,3′ dihexyloxacarbocyanine iodine (DIOC6) staining. The amphiphilic styryl dye FM 1-43 resulted in staining of the plasma membrane in cells from liquid culture. In 7 d desiccated samples, a marked fluorescence is seen in ∼40%–50% of the cells, which were dead. Actin microfilaments (MFs) were drastically disrupted after desiccation; only dotlike actin batches remained. These results demonstrate that flexibility of the cell walls and maintenance of the key organelles play a key role in the tolerance of desiccation stress in K. crenulatum.

These cells delivered matrix metalloproteinases-13 and -9, respectively, into the hepatic scar. The effector cell infiltrate was accompanied by increased levels of the antiinflammatory cytokine interleukin 10. A reduction in hepatic myofibroblasts

was followed by reduced fibrosis detected 4 weeks after macrophage infusion. Serum albumin levels were elevated at this time. Up- regulation of the liver progenitor cell mitogen tumor necrosis factor-like weak inducer of apoptosis (TWEAK) preceded expansion of the progenitor cell compartment. Increased expression of colony stimulating factor-1, insulin-like growth factor-1, and vascular endothelial growth factor also followed BMM delivery. In contrast to the effects of differentiated macrophages, liver fibrosis was not significantly altered by the application of macrophage precursors and was exacerbated by whole BM. Conclusion: learn more Macrophage cell therapy improves clinically buy Staurosporine relevant parameters in experimental chronic liver injury.

Paracrine signaling to endogenous cells amplifies the effect. The benefits from this single, defined cell type suggest clinical potential. (HEPATOLOGY 2011;) Chronic liver injury results in scar deposition, hepatocyte loss, and ultimately cirrhosis. The only effective treatment for endstage liver disease is liver transplantation; however, organ demand exceeds available supply. There is, therefore, an urgent need to develop alternative therapies for cirrhosis. BM (bone marrow)-derived cell populations influence the progression and recovery phases of liver fibrosis.1-3 Clinical studies of BM cell therapy for cirrhosis are under way. However, the use of mixed cell populations limits

the understanding of mechanisms of action.4 The identification of defined single cell types with beneficial effects will enable rational and predictable therapy. Macrophages have a broad repertoire of context-dependent immune, inflammatory, trophic, and regulatory actions.5 selleck chemicals llc We have previously shown that upon cessation of chronic liver injury, endogenous macrophages mediate hepatic scar remodeling through local matrix metalloproteinase (MMP) expression.2, 6 BM precursors differentiate into macrophages under the control of colony stimulating factor-1 (CSF-1) via its receptor (CSF-1R). CSF-1 also regulates macrophage proliferation, viability, and phenotypic fate.7 Furthermore, exogenous CSF-1 stimulates macrophage infiltration, improving fibrosis and function in models of renal8 and cardiac9 injury. Developing therapy using cells from the monocyte-macrophage lineage therefore holds promise. In chronic liver injury, hepatocyte proliferation is impaired and liver progenitor cells (LPCs) become activated to supply hepatocytes.10 LPCs are not of BM origin11, 12; however, their activation is influenced by a number of paracrine signals that represent potential targets for BM-derived cell therapy.

Interestingly, many of the genes up-regulated are involved in cell cycle control and cancer (Table 2). IPA-mediated functional analysis reveals that the major classes of genes changed following HNF4α deletion are in the cancer and cell proliferation category. The up-regulation of promitogenic genes explains the significant increase in proliferation within the liver of HNF4α-KO mice. This observation also raises questions

regarding the mechanism by which HNF4α is regulating promitogenic genes. Whereas beyond the scope of this study, a closer look at the up-regulated genes in HNF4α-KO mice raises the possibility that HNF4α inhibits hepatocyte proliferation by way of both direct and GS-1101 datasheet indirect inhibition for select subpopulations of genes. Bonzo et al.17 first reported the observation that deletion of HNF4α results in an increase in hepatocyte proliferation due to an increase in promitogenic gene expression. The data obtained in this study further confirmed that HNF4α inhibits proliferation through the inhibition of genes involved in cell cycle control. Analysis within the Bonzo et al. study was performed 19 days following initial TAM exposure. Our study strengthens their findings by showing that hepatocyte proliferation and changes in promitogenic gene expression occur as early as 7 days after HNF4α deletion. This suggests that the increased promitogenic gene expression and hepatocyte proliferation

may be due directly to the loss of HNF4α as opposed to another factor that HNF4α may regulate. We have recently made similar observation using an adeno-associated Selleck EX-527 virus 8-mediated Cre system.19 Our analysis revealed that a large number of the genes up-regulated after

HNF4α deletion are regulated by c-Myc. The RNA-Seq data showed a 3.8-fold increase in c-Myc gene expression, corroborating these results. Previous studies have indicated that HNF4α competes with c-Myc for binding on the promoter of cell cycle inhibitor p21/WAF1.27 Further analysis revealed that several genes up-regulated in the c-Myc gene network are involved in stimulation of cell proliferation and cancer selleck chemicals llc pathogenesis including the set oncoprotein, fus, ccnb1, and ccnb2. These data indicate that HNF4α may indirectly down-regulate these genes by way of suppressing c-Myc activation in normal adult hepatocytes. It has been speculated that deletion of HNF4α will result in rapid liver failure, making it difficult to directly study its role in the pathogenesis of HCC.17 Whether HNF4α deletion itself can result in hepatocarcinogenesis is not known and may be difficult to study due to limitations of the model system; therefore, we decided to investigate whether HNF4α deletion can promote existing tumors in the liver and can be tested using the two-stage DEN-induced chemical carcinogenesis model. Our studies indicate that HNF4α deletion during the late stage of HCC progression can substantially promote DEN-induced hepatic tumor formation.

Silencing of the SR gene induces a decrease in the basal proliferative capacity of large cholangiocytes compared with large

mock-transfected cholangiocytes. In our evaluation of SR expression, we found a time-dependent increase in the expression of SR in large cholangiocytes during BDL compared with normal large cholangiocytes. This finding was consistent with previous studies showing that: (1) in the rodent liver SR is only expressed by large cholangiocytes,1, 4, 5, 9, 12 (2) SR expression is up-regulated following BDL ligation in large cholangiocytes,14, 17 and (3) the extent of secretin effects on cholangiocyte functions parallel with the duration of BDL.16 This finding parallels recent findings that mouse cholangiocytes share a similar heterogeneous LY294002 profile

as rat cholangiocytes5 and freshly isolated and immortalized large mouse cholangiocytes are the only cell types to express the SR.5, 8, 14 In human, SR expression is present in the biliary tract in Selleckchem RXDX-106 normal bile ducts and ductules and the majority of cholangiocarcinomas, but is not present in hepatocytes or hepatocellular carcinoma.26, 27 Consistent with animal models of cholestasis, SR expression was up-regulated in ductular reactions in liver cirrhosis.27 In our in vivo model, the level of the reduction of cholangiocyte proliferation is consistent with the paradigm that cholangiocyte proliferation is regulated in autocrine and paracrine mechanisms by a number of stimulatory neurohormonal factors.18, 20, 28 In a knockout mouse model for α-calcitonin gene-related peptide, the lack of circulating α-calcitonin gene-related peptide also reduces biliary proliferation during BDL to a similar degree as the lack of SR,20 which indicates that the regulation of biliary

proliferation during extrahepatic cholestasis is multifactorial and a complex regulatory system.18, 20, 28 The trophic effects of secretin were dependent upon the activation of the cAMP/PKA/ERK1/2 signaling. The second messenger system, cAMP, is a key factor for the function of large cholangiocytes.1, 4, 7, 9, 13 Secretin stimulates bicarbonate secretion of large bile ducts through activation of cAMP-dependent CFTRCl−/HCO3− anion exchanger 2.1, 4, 7, 9, 13 Also, the activation of the cAMP/PKA/ERK1/2 check details pathway modulates cholangiocyte proliferation.12, 15, 18, 29 In fact, the direct stimulation of adenylyl cyclase activity by the chronic administration of forskolin stimulates normal cholangiocyte proliferation both in vivo and in vitro, which is associated with activation of the PKA/Src/MEK/ERK1/2 pathway.29 Maintenance of cAMP levels by forskolin administration prevents the impairment of cholangiocyte proliferation and enhancement of biliary apoptosis induced by vagotomy.30 Furthermore, Banales et al. have shown31 that cAMP stimulates cholangiocyte proliferation through two downstream effectors (i.e., PKA and Epacs) in an animal model of autosomal recessive polycystic kidney disease.

Confounding by indication is not supported as an explanation for the associations we observed with CHDs in our main analysis unless the types and severity of headaches for which butalbital is prescribed differ from those treated with triptans (eg, if butalbital was prescribed for more severe migraine headaches). However, in the exploratory analysis of smaller case groups, elevated ORs were observed for single ventricle among both butalbital and triptans users. Although it was a criterion for exclusion from analysis, maternal pregestational diabetes Opaganib was much more common among infants with single ventricle compared with control infants and compared with infants with other types

of birth defects. The relationship between diabetes and migraines is not well understood; however, there is evidence of an association between insulin-resistance and migraine headaches.[19] It is possible that untreated/undiagnosed insulin resistance is a confounding factor in the analysis of migraine medications and single

ventricle. Given the small number of infants with single ventricle exposed to either butalbital or triptans, our findings may also be explained by chance. We did not find evidence that the other active ingredients in EPZ015666 butalbital products are responsible for the associations observed for butalbital-containing products. Other ingredients in butalbital products (in combination products also used for migraine and tension headaches) were associated with 1 noncardiac defect and with left ventricular outflow tract obstruction defects but not with any other type of CHD whereas butalbital products were associated with various conotruncal, right ventricular outflow tract obstruction, and septal defects as well as single ventricle, and with nonsignificant elevations for certain left ventricular outflow tract obstruction defects. An NBDPS analysis by Feldkamp et al of single-ingredient-acetaminophen click here use and a range of birth defects observed patterns of associations that are not similar to those we observed for butalbital. No significant associations were observed with CHDs; all ORs for CHDs were less

than 1.5.[20] Similarly, an NBDPS analysis of maternal caffeine consumption and CHDs found only a few nonsignificant positive associations and no association with pulmonary valve stenosis.[21] If our results were due to coexposures to other migraine medications, we would have expected that exclusion of infants whose mothers reported those medications would have caused most of the positive ORs to move closer to the null. The ORs became more unstable but did not change in a predictable way, suggesting that coexposures are not responsible for our findings. The strengths of our study include the clinically well-characterized case groups resulting from clinical geneticists’ classification of case infants using pathogenetically uniform case definitions.