abstract: OBJECTIVES: To describe fetal spectrum and echocardiographic characteristics of @entity4 ( @entity4 , cardinal veins) without other structural @entity3 (isolated @entity4 ), evaluate associated extracardiac and @entity1 and review neonatal outcome. METHODS: From 2003 to 2009, 369 consecutive fetuses were diagnosed with @entity3 , including 27 cases with an isolated @entity4 . The following variables were collected: type of @entity4 , @entity2 , karyotype and short-term outcome. RESULTS: The most common forms of @entity4 were persistent @entity5 ( @entity7 ) (n = 15) and interrupted @entity6 ( @entity6 ) (n = 6). The other @entity4 types were a persistent left @entity7 without a right @entity7 (n = 4), bilateral agenesis of the @entity7 with cephalic venous drainage toward the @entity6 through the azygos system (n = 1) and total @entity4 to the coronary sinus (n = 1). @entity1 were confirmed in five cases, all with a persistent left @entity7 , with @entity2 present in four of them. Ten other @entity0 had @entity2 detected prenatally or postnatally. When available, @entity4 diagnosis was confirmed postnatally in all cases. CONCLUSION: Isolated ASVRs can be accurately diagnosed prenatally and are frequently associated with extracardiac and @entity1 . A detailed morphological ultrasound and fetal karyotype should be suggested. Neonatal outcome was mainly related to the associated anomalies.

title: Prenatal diagnosis of abnormal cardinal systemic venous return without other XXXX : a case series.

answer: @entity3


abstract: @entity5 ( @entity5 ), which results from progressive hepatobiliary @entity1 , is an important cause of morbidity and mortality, but it is difficult to identify before @entity2 ( @entity2 ) ensues. Clinical signs, serum @entity4 aminotransferase (ALT) levels, and ultrasound (US) are widely applied, but their value in predicting the presence of @entity1 , the development of @entity2 , or adverse outcomes is undetermined. The potential gold standard, liver biopsy, is not standard practice and, notwithstanding sampling error considerations, has not been systematically evaluated. Forty @entity0 with @entity6 (median age = 10.6 years) with abnormal clinical, biochemical, and US findings were subjected to dual-pass percutaneous liver biopsy. Clinical outcomes were recorded over 12 years of follow-up (median = 9.5 years for survivors). Logistic regression and receiver operating characteristic analyses were applied to predict @entity5 (which was assessed by @entity1 staging and quantitative immunohistochemistry) and the occurrence of @entity2 . @entity2 occurred in 17 of 40 @entity0 (42%), including 6 of 7 (17%) who died during follow-up. Clinical examination, serum ALT levels, and US findings failed to predict either the presence of liver @entity1 or the development of @entity2 . @entity1 staging on liver biopsy, where the accuracy was improved by dual passes (P = 0.002, nonconcordance = 38%), predicted the development of @entity2 (P < 0.001), which occurred more frequently and at a younger age in those with severe @entity1 . CONCLUSION: Clinical modalities currently employed to evaluate suspected @entity5 help to identify a cohort of @entity0 at risk for @entity3 and adverse outcomes but do not predict an individual's risk of liver @entity1 or @entity2 development. Liver @entity1 on biopsy predicts the development of clinically significant @entity3 . Dual passes help to address sampling concerns. Liver biopsy has a relevant role in the management of @entity0 with suspected @entity5 and deserves more widespread application.

title: Importance of @entity5 in XXXX and the predictive value of liver biopsy.

answer: @entity6


abstract: @entity5 ( @entity5 ), which results from progressive hepatobiliary @entity1 , is an important cause of morbidity and mortality, but it is difficult to identify before @entity2 ( @entity2 ) ensues. Clinical signs, serum @entity4 aminotransferase (ALT) levels, and ultrasound (US) are widely applied, but their value in predicting the presence of @entity1 , the development of @entity2 , or adverse outcomes is undetermined. The potential gold standard, liver biopsy, is not standard practice and, notwithstanding sampling error considerations, has not been systematically evaluated. Forty @entity0 with @entity6 (median age = 10.6 years) with abnormal clinical, biochemical, and US findings were subjected to dual-pass percutaneous liver biopsy. Clinical outcomes were recorded over 12 years of follow-up (median = 9.5 years for survivors). Logistic regression and receiver operating characteristic analyses were applied to predict @entity5 (which was assessed by @entity1 staging and quantitative immunohistochemistry) and the occurrence of @entity2 . @entity2 occurred in 17 of 40 @entity0 (42%), including 6 of 7 (17%) who died during follow-up. Clinical examination, serum ALT levels, and US findings failed to predict either the presence of liver @entity1 or the development of @entity2 . @entity1 staging on liver biopsy, where the accuracy was improved by dual passes (P = 0.002, nonconcordance = 38%), predicted the development of @entity2 (P < 0.001), which occurred more frequently and at a younger age in those with severe @entity1 . CONCLUSION: Clinical modalities currently employed to evaluate suspected @entity5 help to identify a cohort of @entity0 at risk for @entity3 and adverse outcomes but do not predict an individual's risk of liver @entity1 or @entity2 development. Liver @entity1 on biopsy predicts the development of clinically significant @entity3 . Dual passes help to address sampling concerns. Liver biopsy has a relevant role in the management of @entity0 with suspected @entity5 and deserves more widespread application.

title: Importance of XXXX in @entity6 and the predictive value of liver biopsy.

answer: @entity5


abstract: BACKGROUND: The incidence rate of acute @entity1 has been reported as having increased during recent decades in Western countries. Reported mortality lies around 10% and has improved during the past 20 years. The incidence rate and 30-day case fatality rate of acute @entity1 in North Jutland County, Denmark were examined for the period 1981 to 2000. METHODS: Data were collected from the Hospital Discharge Registry of North Jutland County for the period 1981-2000. Sex- and age-standardized incidence rates and 30-day case fatality rate of a first attack of acute @entity1 were calculated. Data on endoscopic procedures were assessed for the period 1992 to 2000 and on certain drugs for 1991 to 1999. RESULTS: The incidence rate of acute @entity1 in @entity0 increased from 17.1 per 100,000 @entity0 -years in 1981 (95% confidence interval (CI), 12.6-23.2) to 37.8 per 100,000 @entity0 -years in 2000 (95% CI, 31.0-46.1). The corresponding increase in @entity0 was from 18 per 100,000 @entity0 -years in 1981 (95% CI, 13.3-24.2) to 27.1 per 100,000 @entity0 -years in 2000 (95% CI, 21.5-34.3). The incidence rate of acute @entity1 increased with age in both sexes. The overall 30-day case fatality rate was 7.5% (95% CI, 6.5-8.7) increasing with age, adjusted @entity2 (95% CI, 3.5-11.6) and decreased with time, adjusted OR = 0.7 (95% CI, 0.4-1.0). CONCLUSION: The incidence of acute @entity1 has increased, and in @entity0 surpassed that in @entity0 in 1999 and 2000. Short-term prognosis has improved.

title: Secular trends in incidence and 30-day case fatality of acute XXXX in North Jutland County, Denmark: a register-based study from 1981-2000.

answer: @entity1


abstract: BACKGROUND: @entity4 associated with aging in males may improve with anabolic/androgenic @entity1 therapy. The efficacy and safety of @entity2 therapy in the treatment of @entity4 in elderly hypogonadal males is inconclusive. The following study identifies a subgroup of elderly depressed males who may benefit from @entity2 therapy. METHOD: @entity0 included 16 elderly eugonadal males with @entity4 (DSM-IV criteria) and a Hamilton Rating Scale for @entity4 (HAM-D) score > 18. Following a single-blind 2-week placebo lead-in, @entity0 were randomly assigned to treatment with either a physiologic dose of @entity6 (TC), 100 mg/week, or supraphysiologic dose of 200 mg/week IM for 6 weeks. Psychometric testing was carried out at entry into the study, at the TC injection baseline, and every 2 weeks thereafter. Tests included an objective measurement, the HAM-D, and the Buss-Durkee Hostility Inventory. RESULTS: One @entity0 meeting inclusion criteria responded during the placebo lead-in; thus, 15 @entity0 were randomly assigned to treatment (100 mg/week, N = 8; 200 mg/week, N = 7). There was a 42% decrease in the mean HAM-D scores from 20.1 to 11.9 (p <.0001). However, the majority of the change was due to improvement in the 10 late-onset (< or = 45 years old) @entity4 @entity0 , whose mean HAM-D score decreased from 19.8 to 9.3 (53%), versus the 5 early-onset @entity4 @entity0 , whose mean HAM-D score decreased from 20.8 to 17.0 (18%) (p =.0110). The TC dose did not affect the response. Similar HAM-D decreases of 43% and 41% occurred for the respective 100- and 200-mg/week doses. The HAM-D responder analysis found that none of 5 early-onset @entity0 had HAM-D response, whereas 6 (60%) of 10 late-onset @entity0 responded (p =.025). Similarly, none of the early-onset @entity0 experienced a remission whereas 5 (50%) of the late-onset @entity0 were categorized as remitters (p =.053). Correlations between the peak and mean total @entity2 concentrations and HAM-D change scores suggested that only minimal TC doses were required to produce an antidepressant effect. CONCLUSION: These data suggest that @entity2 therapy would best be limited to @entity0 with late-onset @entity4 . The findings suggest that short-term therapy with TC is safe. Long-term treatment safety is unknown. Psychiatrists using @entity2 therapy should ascertain that @entity0 have been recently valuated for @entity3 . If @entity2 therapy is initiated, serial serum @entity5 sampling should be used for monitoring @entity0 ' prostate status.

title: XXXX therapy in late-life major @entity4 in males.

answer: @entity2


abstract: BACKGROUND: @entity4 associated with aging in males may improve with anabolic/androgenic @entity1 therapy. The efficacy and safety of @entity2 therapy in the treatment of @entity4 in elderly hypogonadal males is inconclusive. The following study identifies a subgroup of elderly depressed males who may benefit from @entity2 therapy. METHOD: @entity0 included 16 elderly eugonadal males with @entity4 (DSM-IV criteria) and a Hamilton Rating Scale for @entity4 (HAM-D) score > 18. Following a single-blind 2-week placebo lead-in, @entity0 were randomly assigned to treatment with either a physiologic dose of @entity6 (TC), 100 mg/week, or supraphysiologic dose of 200 mg/week IM for 6 weeks. Psychometric testing was carried out at entry into the study, at the TC injection baseline, and every 2 weeks thereafter. Tests included an objective measurement, the HAM-D, and the Buss-Durkee Hostility Inventory. RESULTS: One @entity0 meeting inclusion criteria responded during the placebo lead-in; thus, 15 @entity0 were randomly assigned to treatment (100 mg/week, N = 8; 200 mg/week, N = 7). There was a 42% decrease in the mean HAM-D scores from 20.1 to 11.9 (p <.0001). However, the majority of the change was due to improvement in the 10 late-onset (< or = 45 years old) @entity4 @entity0 , whose mean HAM-D score decreased from 19.8 to 9.3 (53%), versus the 5 early-onset @entity4 @entity0 , whose mean HAM-D score decreased from 20.8 to 17.0 (18%) (p =.0110). The TC dose did not affect the response. Similar HAM-D decreases of 43% and 41% occurred for the respective 100- and 200-mg/week doses. The HAM-D responder analysis found that none of 5 early-onset @entity0 had HAM-D response, whereas 6 (60%) of 10 late-onset @entity0 responded (p =.025). Similarly, none of the early-onset @entity0 experienced a remission whereas 5 (50%) of the late-onset @entity0 were categorized as remitters (p =.053). Correlations between the peak and mean total @entity2 concentrations and HAM-D change scores suggested that only minimal TC doses were required to produce an antidepressant effect. CONCLUSION: These data suggest that @entity2 therapy would best be limited to @entity0 with late-onset @entity4 . The findings suggest that short-term therapy with TC is safe. Long-term treatment safety is unknown. Psychiatrists using @entity2 therapy should ascertain that @entity0 have been recently valuated for @entity3 . If @entity2 therapy is initiated, serial serum @entity5 sampling should be used for monitoring @entity0 ' prostate status.

title: @entity2 therapy in late-life major XXXX in males.

answer: @entity4


abstract: Aim of this study was to provide clinico-experimental basis of application of biodegradable implants in surgical treatment of @entity3 . Experimental investigations were performed on non-pedigree female @entity2 with body weight of 200-250 grams. 10 animals were used, 20 sciatic nerves were operated. Morphological examinations were done on 21st and 101st days after surgery. Clinical part of the study was performed after finishing of experimental block and included 20 @entity0 with @entity3 . Information about @entity0 included: sex, age, type and localization of lesion, preoperative @entity1 , data of electrophysiological and ultrasonographic studies and MRI. Follow-up period varied between 3 and 12 months. The series included 13 male and 7 female @entity0 , age was 20-63 years. Injection of "Sphero(r)Gel" in the area of nerve suture enables more effective regeneration of axons and their growth through the injury site. Application of "ElastoPOB(r)" membrane favors demarcation of peripheral nerve from surrounding scar tissues in the wound. Acquired data demonstrate decreased influence of scarring process on the nerve trunk in the postoperative period according to neurological examination, electroneuromyography, ultrasonography and MRI.

title: [Clinico-experimental basis of application of biodegradable implants in surgical treatment of XXXX ].

answer: @entity3


abstract: Recognition of bacterial constituents by mast cells (MCs) is dependent on the presence of pattern recognition receptors, such as Toll-like receptors (TLRs). The final cellular response, however, depends on the influence of multiple environmental factors. In the current study we tested the hypothesis that the PI3K-activating ligands insulin-like growth factor-1 ( @entity7 ), insulin, antigen, and @entity9 (SF) are able to modulate the @entity5 -mediated production of proinflammatory cytokines in @entity0 MCs. Costimulation with any of these ligands caused increased @entity1 -triggered secretion of @entity4 and @entity3 , but attenuated the production of @entity2 , though all three cytokines were produced in an NFkB-dependent manner. The pan-specific PI3K-inhibitor @entity6 reverted the altered production of these cytokines. In agreement, MCs deficient for @entity10 , a negative regulator of the PI3K pathway, showed augmented secretion of @entity4 / @entity3 and reduced production of @entity2 in response to @entity1 alone. The differential effects of @entity7 on @entity5 -mediated cytokine production were also observed in the context of @entity8 and @entity12 receptor-mediated MC activation. Importantly, these effects were seen in both bone marrow-derived and peritoneal MCs, suggesting general relevance for MCs. Using pharmacological and genetic tools, we could show that the @entity11   isoform of PI3K is strongly implicated in SF-triggered suppression of @entity1 -induced @entity2 production. Costimulation with antigen was affected to a lesser extent. In conclusion, NFkB-dependent production of proinflammatory cytokines in MCs is differentially controlled by PI3K-activating ligand/receptor systems.

title: Activation of the PI3K pathway increases TLR-induced @entity3 and XXXX but reduces @entity2 production in mast cells.

answer: @entity4


abstract: Recognition of bacterial constituents by mast cells (MCs) is dependent on the presence of pattern recognition receptors, such as Toll-like receptors (TLRs). The final cellular response, however, depends on the influence of multiple environmental factors. In the current study we tested the hypothesis that the PI3K-activating ligands insulin-like growth factor-1 ( @entity7 ), insulin, antigen, and @entity9 (SF) are able to modulate the @entity5 -mediated production of proinflammatory cytokines in @entity0 MCs. Costimulation with any of these ligands caused increased @entity1 -triggered secretion of @entity4 and @entity3 , but attenuated the production of @entity2 , though all three cytokines were produced in an NFkB-dependent manner. The pan-specific PI3K-inhibitor @entity6 reverted the altered production of these cytokines. In agreement, MCs deficient for @entity10 , a negative regulator of the PI3K pathway, showed augmented secretion of @entity4 / @entity3 and reduced production of @entity2 in response to @entity1 alone. The differential effects of @entity7 on @entity5 -mediated cytokine production were also observed in the context of @entity8 and @entity12 receptor-mediated MC activation. Importantly, these effects were seen in both bone marrow-derived and peritoneal MCs, suggesting general relevance for MCs. Using pharmacological and genetic tools, we could show that the @entity11   isoform of PI3K is strongly implicated in SF-triggered suppression of @entity1 -induced @entity2 production. Costimulation with antigen was affected to a lesser extent. In conclusion, NFkB-dependent production of proinflammatory cytokines in MCs is differentially controlled by PI3K-activating ligand/receptor systems.

title: Activation of the PI3K pathway increases TLR-induced @entity3 and @entity4 but reduces XXXX production in mast cells.

answer: @entity2


abstract: Recognition of bacterial constituents by mast cells (MCs) is dependent on the presence of pattern recognition receptors, such as Toll-like receptors (TLRs). The final cellular response, however, depends on the influence of multiple environmental factors. In the current study we tested the hypothesis that the PI3K-activating ligands insulin-like growth factor-1 ( @entity7 ), insulin, antigen, and @entity9 (SF) are able to modulate the @entity5 -mediated production of proinflammatory cytokines in @entity0 MCs. Costimulation with any of these ligands caused increased @entity1 -triggered secretion of @entity4 and @entity3 , but attenuated the production of @entity2 , though all three cytokines were produced in an NFkB-dependent manner. The pan-specific PI3K-inhibitor @entity6 reverted the altered production of these cytokines. In agreement, MCs deficient for @entity10 , a negative regulator of the PI3K pathway, showed augmented secretion of @entity4 / @entity3 and reduced production of @entity2 in response to @entity1 alone. The differential effects of @entity7 on @entity5 -mediated cytokine production were also observed in the context of @entity8 and @entity12 receptor-mediated MC activation. Importantly, these effects were seen in both bone marrow-derived and peritoneal MCs, suggesting general relevance for MCs. Using pharmacological and genetic tools, we could show that the @entity11   isoform of PI3K is strongly implicated in SF-triggered suppression of @entity1 -induced @entity2 production. Costimulation with antigen was affected to a lesser extent. In conclusion, NFkB-dependent production of proinflammatory cytokines in MCs is differentially controlled by PI3K-activating ligand/receptor systems.

title: Activation of the PI3K pathway increases TLR-induced XXXX and @entity4 but reduces @entity2 production in mast cells.

answer: @entity3


abstract: STUDY DESIGN: A prospective study. OBJECTIVES: To assess the outcome of @entity0 with a single thoracolumbar burst @entity3 treated with circumferential short-segment fusion consisting of posterior reduction, short-segment fusion, and delayed staged mini-open anterior short-segment fusion. SUMMARY OF BACKGROUND DATA: The surgical treatment of thoracolumbar @entity3 remains controversial. In attempting to combine the advantages of posterior procedures, including initial correction of @entity4 and early decompression, and those of anterior procedures, including direct decompression and restoration of anterior column support, a combined posterior and delayed staged anterior procedure seems to be a reasonable choice. However, conventional combined procedures are invasive. METHODS: We prospectively selected 28 consecutive @entity0 with single thoracolumbar burst @entity3 for circumferential short-segment fusion consisting of posterior reduction, short-segment fusion, and delayed staged mini-open anterior short-segment fusion. The pedicle screw systems were removed after confirmation of posterior bony fusion to preserve as many motion segments as possible in those @entity0 who could be treated with circumferential monosegmental fusion. Radiographic and clinical assessment of 28 @entity0 who received this treatment was carried out. RESULTS: The mean loss of correction of @entity4 between the time of the combined procedure and final follow-up was 3.7 degrees (range, 0 to 10.2 degrees). Bony fusion was eventually achieved in all @entity0 . There were 15 cases with monosegmental and 13 cases with bisegmental circumferential fusion. All 10 @entity0 with initial @entity1 improved by at least 1 Frankel grade: 3 improved by 1 grade, 5 improved by 2 grades, and 2 improved by 3 grades. In total, 27 @entity0 , who were P1 or P2 on the @entity2 scale, were considered to have obtained clinically satisfactory results. CONCLUSIONS: This combined procedure is less invasive than the conventional combined one, and finally achieves shorter stabilization, resulting in preservation of motion segments. It thus seems to be a reasonable treatment option for thoracolumbar @entity3 .

title: Combined posterior and delayed staged mini-open anterior short-segment fusion for thoracolumbar XXXX .

answer: @entity3


abstract: OBJECTIVE AND STUDY DESIGN: Several noninvasive adjunctive methods have been proposed for identification of potentially @entity1 . The VELscope is an optical device for detecting spatial changes in mucosa autofluorescence caused by @entity3 in conjunction with an intraoral exam. The aim of our prospective study was to correlate loss of autofluorescence from undiagnosed mucosa lesions with histology. RESULTS: In total 64 @entity0 considered at risk for @entity4 (20 had previous OSCC) were included in the study. Regions with fluorescence visualization loss were considered as malignant or @entity7 . All @entity0 underwent biopsy after VELscope examination. In 22 @entity0 (34.4%) a loss of autofluorescence indicating a @entity5 ( @entity5 ) or @entity6 was detected. The sensitivity of identification of malignant and @entity7 areas with the VELscope was 100% and the specificity was 80.8%, respectively, compared with histology as gold standard. The positive predictive value was 54.5% and the negative predictive value was 100% respectively. CONCLUSION: Evaluation of autofluorescence imaging with VELscope can assist in the identification of malignant and potentially malignant oral lesions from normal mucosa in high-risk @entity0 but does not help discriminating benign lesions from malignant or @entity2 .

title: Autofluorescence imaging of potentially XXXX .

answer: @entity1


abstract: BACKGROUND: @entity7 is a characteristic feature of chronic @entity3 and is thought to result from a change in the balance between synthesis and degradation of extracellular matrix (ECM) proteins. Recent studies suggest that activated pancreatic stellate cells (PSCs) play a central role in pancreatic fibrogenesis via increased synthesis of ECM proteins. However, the role of these cells in ECM protein degradation has not been fully elucidated. AIMS: To determine: (i) whether PSCs secrete matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) and, if so (ii) whether MMP and @entity12 secretion by PSCs is altered in response to known @entity4 activating factors such as @entity0 factor alpha ( @entity6 ), @entity8 ( @entity8 ), @entity2 ( @entity2 ), @entity5 , and @entity10 . METHODS: Cultured @entity1 PSCs (n=3-5 separate cell preparations) were incubated at 37 degrees C for 24 hours with serum free culture medium containing @entity6 (5-25 U/ml), @entity8 (0.5-1 ng/ml), @entity2 (0.001-10 ng/ml), @entity5 (10-50 mM), or @entity10 (150-200 micro M), or no additions (controls). Medium from control cells was examined for the presence of MMPs by zymography using a 10% @entity9 -0.1% gelatin gel. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine gene expression of @entity11 and the tissue inhibitors of metalloproteinases @entity12 and @entity14 . Western blotting was used to identify a specific MMP, @entity13 (a gelatinase that digests basement membrane collagen and the dominant MMP observed on zymography) and a specific @entity12 , @entity14 . Reverse zymography was used to examine functional TIMPs in @entity4 secretions. The effect of @entity6 , @entity8 , and @entity2 on @entity13 secretion was assessed by densitometry of western blots. The effect of @entity5 and @entity10 on @entity13 and @entity14 secretion was also assessed by this method. RESULTS: Zymography revealed that PSCs secrete a number of MMPs including proteinases with molecular weights consistent with @entity13 , @entity11 , and @entity15 . RT-PCR demonstrated the presence of mRNA for metalloproteinase inhibitors @entity12 and @entity14 in PSCs while reverse zymography revealed the presence of functional @entity14 in @entity4 secretions. @entity13 secretion by PSCs was significantly increased by @entity8 and @entity2 , but was not affected by @entity6 . @entity5 and @entity10 induced secretion of both @entity13 and @entity14 by PSCs. CONCLUSIONS: Pancreatic stellate cells have the capacity to synthesise a number of matrix metalloproteinases, including @entity13 , @entity11 , and @entity15 and their inhibitors @entity12 and @entity14 . @entity13 secretion by PSCs is significantly increased on exposure to the proinflammatory cytokines @entity8 and @entity2 . Both @entity5 and its metabolite @entity10 increase @entity13 as well as @entity14 secretion by PSCs. IMPLICATION: The role of pancreatic stellate cells in extracellular matrix formation and fibrogenesis may be related to their capacity to regulate the degradation as well as the synthesis of extracellular matrix proteins.

title: XXXX pancreatic stellate cells secrete matrix metalloproteinases: implications for extracellular matrix turnover.

answer: @entity1


abstract: OBJECTIVE: To calculate and discuss the percentage of imbalance for selected @entity1 predisposition genes in @entity0 referred for routine diagnostic array comparative genomic hybridisation (CGH). DESIGN: Audit of findings from application of array CGH for @entity0 referred for @entity2 , @entity4 and @entity3 in 4805 @entity0 referred to Guy's and St Thomas' NHS Foundation Trust for cytogenetic investigation from South East London, Kent and East Sussex and other genetic centres across the UK. RESULTS: 29 of 4805 (0.6%) @entity0 examined by array CGH had genomic imbalance of <5 Mb involving @entity1 predisposition genes. Six @entity0 were referred for syndromes involving @entity1 predisposition genes; none of the other 23 @entity0 with array CGH findings in @entity1 predisposition genes had any symptoms/family history stated on their referral form suggestive for the respective syndrome. Twelve whole gene deletions, two partial deletions, 12 duplications, two partial duplications, and one mosaic duplication were observed. In 17/29 @entity0 (59%), inheritance could not be established, eight imbalances were de novo, and four inherited. CONCLUSIONS: This new technology raises the possibility of unexpected findings in @entity1 predisposition genes. Therefore, the possibility of such findings has to be addressed in pre-test and post-test counselling by genetically trained healthcare professionals. As many of these findings have not been described previously, their clinical significance is unknown and @entity0 need long-term follow-up to determine their clinical relevance. This will enable genetic healthcare professionals to advise such @entity0 about their @entity1 risks and appropriate @entity1 risk management options.

title: Unexpected findings in XXXX predisposition genes detected by array comparative genomic hybridisation: what are the issues?

answer: @entity1


abstract: BACKGROUND: Adults born at a very low birth weight (VLBW) (< 1500 g), compared with those born at term, bear risk factors for @entity1 , including higher blood pressure and insulin resistance. OBJECTIVE: We studied, in young adults born at a VLBW, early signs of an accelerated atherosclerotic process and the relationship of these signs with postnatal growth. METHODS: We compared 92 with a VLBW with 68 who were born at term. At age 18 to 27, we measured stiffness and @entity2 ( @entity2 ) of the right carotid artery and @entity3 ( @entity3 ) of the right brachial artery. RESULTS: Those with a VLBW had 1.1% units higher @entity3 (95% confidence interval [CI]: 0.0-2.2) (P = .06) and 0.5% units higher @entity2 relative to lumen size (95% CI: 0.1-0.9). @entity2 or @entity3 , when analyzed as the absolute change in millimeters, and carotid stiffness in the groups were similar. Among those with a VLBW, each 100-g-greater @entity5 during the first 2 postnatal weeks predicted 1.1% units higher @entity3 (95% CI: 0.2-2.0) in adulthood. CONCLUSIONS: Although young adults born at VLBWs, compared with those born at term, have higher levels of risk factors for @entity1 , we found no clear evidence for elevated early markers of @entity4 . However, in relation to artery lumen diameter, @entity2 in the @entity0 who had a VLBW was higher than in those who were born at term. In our study, @entity5 during the first postnatal weeks had no harmful effect on the arteries in young adulthood.

title: Intima-media thickness and XXXX in the Helsinki study of very low birth weight adults.

answer: @entity3


abstract: CONTEXT AND OBJECTIVE: The magnitude of weight loss-induced high-density lipoprotein @entity1 (HDL-C) changes may depend on genetic factors. We examined the associations of eight candidate genes, identified by genome-wide association studies, with HDL-C at baseline and 10 yr after bariatric surgery in the Swedish Obese Subjects study. METHODS: Single-nucleotide polymorphisms (SNP) (n = 60) in the following gene loci were genotyped: @entity6 , @entity7 , @entity9 , @entity10 , @entity4 , @entity8 , @entity3 , and @entity2 / @entity5 . Cross-sectional associations were tested before (n = 1771) and 2 yr (n = 1583) and 10 yr (n = 1196) after surgery. Changes in HDL-C were tested between baseline and yr 2 (n = 1518) and yr 2 and 10 (n = 1149). A multiple testing corrected threshold of P = 0.00125 was used for statistical significance. RESULTS: In adjusted multivariate models, @entity9 SNP @entity11 explained from 3.2-4.2% (P < 10(-14)) of the variation in HDL-C at all three time points, whereas @entity9 SNP @entity12 contributed an additional 0.6 and 0.9% at baseline and yr 2, respectively. @entity4 SNP @entity13 showed consistent associations across all time points (R(2) = 0.4-1.1%; 3.8   10(-6) < P < 3   10(-3)), whereas @entity3 SNP @entity14 contributed approximately 0.5% (5   10(-4) < P < 0.0012) at yr 2 and 10. In aggregate, four SNP in three genes explained 4.2, 6.8, and 5.6% of the HDL-C variance at baseline, yr 2, and yr 10, respectively. None of the SNP was significantly associated with weight loss-related changes in HDL-C. CONCLUSIONS: SNP in the @entity9 , @entity4 , and @entity3 loci contribute significantly to plasma HDL-C levels in @entity0 individuals, and the associations persist even after considerable weight loss due to bariatric surgery. However, they are not associated with surgery-induced changes in HDL-C levels.

title: Association of GWAS-based candidate genes with HDL- @entity1 levels before and after bariatric surgery in the Swedish XXXX subjects study.

answer: @entity0


abstract: CONTEXT AND OBJECTIVE: The magnitude of weight loss-induced high-density lipoprotein @entity1 (HDL-C) changes may depend on genetic factors. We examined the associations of eight candidate genes, identified by genome-wide association studies, with HDL-C at baseline and 10 yr after bariatric surgery in the Swedish Obese Subjects study. METHODS: Single-nucleotide polymorphisms (SNP) (n = 60) in the following gene loci were genotyped: @entity6 , @entity7 , @entity9 , @entity10 , @entity4 , @entity8 , @entity3 , and @entity2 / @entity5 . Cross-sectional associations were tested before (n = 1771) and 2 yr (n = 1583) and 10 yr (n = 1196) after surgery. Changes in HDL-C were tested between baseline and yr 2 (n = 1518) and yr 2 and 10 (n = 1149). A multiple testing corrected threshold of P = 0.00125 was used for statistical significance. RESULTS: In adjusted multivariate models, @entity9 SNP @entity11 explained from 3.2-4.2% (P < 10(-14)) of the variation in HDL-C at all three time points, whereas @entity9 SNP @entity12 contributed an additional 0.6 and 0.9% at baseline and yr 2, respectively. @entity4 SNP @entity13 showed consistent associations across all time points (R(2) = 0.4-1.1%; 3.8   10(-6) < P < 3   10(-3)), whereas @entity3 SNP @entity14 contributed approximately 0.5% (5   10(-4) < P < 0.0012) at yr 2 and 10. In aggregate, four SNP in three genes explained 4.2, 6.8, and 5.6% of the HDL-C variance at baseline, yr 2, and yr 10, respectively. None of the SNP was significantly associated with weight loss-related changes in HDL-C. CONCLUSIONS: SNP in the @entity9 , @entity4 , and @entity3 loci contribute significantly to plasma HDL-C levels in @entity0 individuals, and the associations persist even after considerable weight loss due to bariatric surgery. However, they are not associated with surgery-induced changes in HDL-C levels.

title: Association of GWAS-based candidate genes with HDL- XXXX levels before and after bariatric surgery in the Swedish @entity0 subjects study.

answer: @entity1


abstract: OBJECTIVE: To compare the cost per responder of ustekinumab with etanercept based on data from the active comparator ACCEPT trial. METHODS: In ACCEPT, @entity0 received ustekinumab 45 mg (n = 209) or 90 mg (n = 347) at weeks 0 and 4 or etanercept 50 mg (n = 347) twice weekly for 12 weeks. The proportions of @entity0 achieving >= 75% improvement in the Psoriasis Area and Severity Index [PASI 75] were determined at week 12. The cost per PASI 75 responder was determined for week 16, a time coinciding with treatment coverage of both drugs and accounting for the different dosing intervals. Costs for 16 weeks of therapy were based on the Wholesale Acquisition Cost (WAC) in the United States. The analysis used weight-based efficacy results for ustekinumab (45 mg for @entity0  <= 100 kg; 90 mg for @entity0 > 100 kg) and overall efficacy for etanercept, consistent with the approved dosages. RESULTS: A total of 28% of @entity0 weighed > 100 kg. The PASI 75 response rates at week 12 were 72.2% for the ustekinumab 45 mg group in @entity0  <= 100 kg, 65.0% for the ustekinumab 90 mg group in @entity0 > 100 kg, and 56.8% for the etanercept group. At week 16, the cost per responder was  17,842 for ustekinumab and  20,077 for etanercept. CONCLUSION: The cost per responder was lower for ustekinumab than for etanercept through 16 weeks in @entity1 @entity0 .

title: Cost per responder analysis of ustekinumab and etanercept for moderate to severe XXXX .

answer: @entity1


abstract: OBJECTIVE: Exercise training partially corrects @entity2 in @entity0 with @entity3 ( @entity3 ). Growth factors like @entity1 ( @entity1 ) as well as @entity6 ( @entity6 ) are known to modulate the bioavailability of @entity4 and, thereby, contribute to the maintenance of a normal vascular tone. The aim of the present study was to determine the impact of 4 weeks of exercise training on circulating growth factors and to elucidate their involvement in the training-induced changes in vasomotion in @entity0 with @entity3 . METHODS AND RESULTS: A total of 39 @entity0 were enrolled (training group: n   =   20; control group: n   =   19). At start of study and after 4 weeks, average peak flow velocity (APV) of the left internal mammary artery (LIMA) in response to @entity5 was measured invasively in the treatment and control groups. Serum concentrations of @entity1 and @entity6 were determined by enzyme-linked immunosorbent assay. After exercise training, LIMA APV in response to @entity5 was increased by 93% (from 69        17% at start of study to 133        16% at 4 weeks, p   <   0.01 vs. start of study and control). At start of study, there was no association between any of the vascular growth factors and endothelial function. However, after exercise training a close correlation was apparent between the @entity5 -induced change in APV and @entity6 (r   =   0.69, p   <   0.01) and @entity1 (r   =   0.76, p   <   0.01) serum concentrations. In the control group, these correlations were not evident and there was no change in endothelial function either. CONCLUSION: Exercise training improves agonist-mediated endothelium-dependent vasodilatation in @entity3 , partially through a restoration of the endothelial response to @entity6 and @entity1 .

title: Exercise training restores the endothelial response to vascular growth factors in @entity0 with stable XXXX .

answer: @entity3


abstract: OBJECTIVE: Exercise training partially corrects @entity2 in @entity0 with @entity3 ( @entity3 ). Growth factors like @entity1 ( @entity1 ) as well as @entity6 ( @entity6 ) are known to modulate the bioavailability of @entity4 and, thereby, contribute to the maintenance of a normal vascular tone. The aim of the present study was to determine the impact of 4 weeks of exercise training on circulating growth factors and to elucidate their involvement in the training-induced changes in vasomotion in @entity0 with @entity3 . METHODS AND RESULTS: A total of 39 @entity0 were enrolled (training group: n   =   20; control group: n   =   19). At start of study and after 4 weeks, average peak flow velocity (APV) of the left internal mammary artery (LIMA) in response to @entity5 was measured invasively in the treatment and control groups. Serum concentrations of @entity1 and @entity6 were determined by enzyme-linked immunosorbent assay. After exercise training, LIMA APV in response to @entity5 was increased by 93% (from 69        17% at start of study to 133        16% at 4 weeks, p   <   0.01 vs. start of study and control). At start of study, there was no association between any of the vascular growth factors and endothelial function. However, after exercise training a close correlation was apparent between the @entity5 -induced change in APV and @entity6 (r   =   0.69, p   <   0.01) and @entity1 (r   =   0.76, p   <   0.01) serum concentrations. In the control group, these correlations were not evident and there was no change in endothelial function either. CONCLUSION: Exercise training improves agonist-mediated endothelium-dependent vasodilatation in @entity3 , partially through a restoration of the endothelial response to @entity6 and @entity1 .

title: Exercise training restores the endothelial response to vascular growth factors in XXXX with stable @entity3 .

answer: @entity0


abstract: BACKGROUND: @entity2 , @entity4 and @entity6 may not be independent risk factors for @entity1 ; however they may contribute via their relationship with unhealthy lifestyle behaviours. This study aimed to examine the association between @entity4 , risk behaviours and @entity0 demographic characteristics in a sample of general practice @entity0 aged 40-65 years with at least one risk factor for @entity1 . DESIGN: Cross-sectional analytic study. METHODS: @entity0 , randomly selected from general practice records, completed a questionnaire about their behavioural risk factors and psychological health as part of a cluster randomized controlled trial of a general practice based intervention to prevent @entity3 . The Kessler Psychological Distress Score ( @entity7 ) was the main outcome measure for the multilevel, multivariate analysis. RESULTS: Single-level bi-variate analysis demonstrated a significant association between higher @entity7 and middle age (p   =   0.001), high @entity5 (p   =   0), current smoking (p   =   0), physical inactivity (p   =   0.003) and low fruit and vegetable consumption (p   =   0.008). Socioeconomic (SES) indicators of deprivation (employment and accommodation status) were also significantly associated with higher @entity7 (p   =   0). No individual behavioural risk factor was associated with @entity7 on multilevel multivariate analysis; however indicators of low SES remained significant (p   <   0.001). CONCLUSIONS: When all factors were considered, @entity4 was not associated with behavioural risk factors for @entity1 . Other underlying factors, such as @entity6 type and socioeconomic status, may be associated with both the behaviours and the distress.

title: Socio-demographic factors, behaviour and @entity6 : associations with XXXX .

answer: @entity4


abstract: BACKGROUND: @entity2 , @entity4 and @entity6 may not be independent risk factors for @entity1 ; however they may contribute via their relationship with unhealthy lifestyle behaviours. This study aimed to examine the association between @entity4 , risk behaviours and @entity0 demographic characteristics in a sample of general practice @entity0 aged 40-65 years with at least one risk factor for @entity1 . DESIGN: Cross-sectional analytic study. METHODS: @entity0 , randomly selected from general practice records, completed a questionnaire about their behavioural risk factors and psychological health as part of a cluster randomized controlled trial of a general practice based intervention to prevent @entity3 . The Kessler Psychological Distress Score ( @entity7 ) was the main outcome measure for the multilevel, multivariate analysis. RESULTS: Single-level bi-variate analysis demonstrated a significant association between higher @entity7 and middle age (p   =   0.001), high @entity5 (p   =   0), current smoking (p   =   0), physical inactivity (p   =   0.003) and low fruit and vegetable consumption (p   =   0.008). Socioeconomic (SES) indicators of deprivation (employment and accommodation status) were also significantly associated with higher @entity7 (p   =   0). No individual behavioural risk factor was associated with @entity7 on multilevel multivariate analysis; however indicators of low SES remained significant (p   <   0.001). CONCLUSIONS: When all factors were considered, @entity4 was not associated with behavioural risk factors for @entity1 . Other underlying factors, such as @entity6 type and socioeconomic status, may be associated with both the behaviours and the distress.

title: Socio-demographic factors, behaviour and XXXX : associations with @entity4 .

answer: @entity6


abstract: BACKGROUND AND OBJECTIVES: @entity1 distort the body image with possible negative effects on the quality of life and psychosocial health of @entity0 . While @entity4 does not affect the physical well-being, it may be psychologically distressing. The present study was based on the hypothesis that particular factors might be critical regarding the adjustment to the disease. @entity0 AND METHODS: We investigated the @entity4 -related quality of life and @entity2 of 216 @entity0 diagnosed with the disease in relation to @entity3 . For this purpose, we administered the self-completed questionnaires Dermatological Quality of Life Index, General Health Questionnaire, Eysenck Personality Inventory, and Rosenberg Self-Esteem Scale. RESULTS: Statistical analysis revealed a significant positive correlation between @entity0 ' distress and health-related quality of life. Moreover, the impact of @entity4 on the quality of life was significantly associated with disease variables as well as personality traits and gender. On the other hand, @entity2 was significantly associated with personality traits and gender, but not with disease components. CONCLUSIONS: Our results indicate that the psychosocial adjustment to the disease is mainly influenced by subjective factors. This observation could imply the need for targeted support interventions in the treatment of @entity4 .

title: Investigation of factors associated with health-related quality of life and XXXX in @entity4 .

answer: @entity2


abstract: BACKGROUND AND OBJECTIVES: @entity1 distort the body image with possible negative effects on the quality of life and psychosocial health of @entity0 . While @entity4 does not affect the physical well-being, it may be psychologically distressing. The present study was based on the hypothesis that particular factors might be critical regarding the adjustment to the disease. @entity0 AND METHODS: We investigated the @entity4 -related quality of life and @entity2 of 216 @entity0 diagnosed with the disease in relation to @entity3 . For this purpose, we administered the self-completed questionnaires Dermatological Quality of Life Index, General Health Questionnaire, Eysenck Personality Inventory, and Rosenberg Self-Esteem Scale. RESULTS: Statistical analysis revealed a significant positive correlation between @entity0 ' distress and health-related quality of life. Moreover, the impact of @entity4 on the quality of life was significantly associated with disease variables as well as personality traits and gender. On the other hand, @entity2 was significantly associated with personality traits and gender, but not with disease components. CONCLUSIONS: Our results indicate that the psychosocial adjustment to the disease is mainly influenced by subjective factors. This observation could imply the need for targeted support interventions in the treatment of @entity4 .

title: Investigation of factors associated with health-related quality of life and @entity2 in XXXX .

answer: @entity4


abstract: BACKGROUND: @entity6 requires metabolic activation by @entity7 ( @entity7 ). Proton pump inhibitors (PPIs) that inhibit @entity7 are commonly coadministered with @entity6 to reduce the risk of @entity3 . This analysis compares treatment outcomes for @entity0 in the French Registry of Acute ST-Elevation and Non-ST-Elevation @entity5 (FAST-MI) who did or did not receive @entity6 and/or PPIs. METHODS AND RESULTS: The FAST-MI registry included 3670 @entity0 (2744 @entity6 - and PPI-na  ve @entity0 ) presenting with definite MI. @entity0 were categorized according to use of @entity6 and/or PPI within 48 hours after hospital admission. PPI use was not associated with an increased risk for any of the main in-hospital events (in-hospital survival, reinfarction, @entity1 , @entity4 , and transfusion). Likewise, PPI treatment was not an independent predictor of 1-year survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P=0.57) or 1-year MI, @entity1 , or @entity2 (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; P=0.72). No differences were seen when the type of PPI or @entity7 genotype was taken into account. In the propensity-matched cohorts, the odds ratios for major in-hospital events in PPI versus no PPI were 0.29 (95% CI, 0.06 to 1.44) and 1.70 (95% CI, 0.10 to 30.3) for @entity0 with 1 and 2 variant alleles, respectively. Similarly, the hazard ratio for 1-year events in hospital survivors was 0.68 (95% CI, 0.26 to 1.79) and 0.55 (95% CI, 0.06 to 5.30), respectively. CONCLUSION: PPI use was not associated with an increased risk of cardiovascular events or mortality in @entity0 administered @entity6 for recent MI, whatever the @entity7 genotype, although harm could not be formally excluded in @entity0 with 2 loss-of-function alleles.

title: Clinical events as a function of proton pump inhibitor use, @entity6 use, and XXXX genotype in a large nationwide cohort of acute @entity5 : results from the French Registry of Acute ST-Elevation and Non-ST-Elevation @entity5 (FAST-MI) registry.

answer: @entity7


abstract: BACKGROUND: @entity6 requires metabolic activation by @entity7 ( @entity7 ). Proton pump inhibitors (PPIs) that inhibit @entity7 are commonly coadministered with @entity6 to reduce the risk of @entity3 . This analysis compares treatment outcomes for @entity0 in the French Registry of Acute ST-Elevation and Non-ST-Elevation @entity5 (FAST-MI) who did or did not receive @entity6 and/or PPIs. METHODS AND RESULTS: The FAST-MI registry included 3670 @entity0 (2744 @entity6 - and PPI-na  ve @entity0 ) presenting with definite MI. @entity0 were categorized according to use of @entity6 and/or PPI within 48 hours after hospital admission. PPI use was not associated with an increased risk for any of the main in-hospital events (in-hospital survival, reinfarction, @entity1 , @entity4 , and transfusion). Likewise, PPI treatment was not an independent predictor of 1-year survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P=0.57) or 1-year MI, @entity1 , or @entity2 (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; P=0.72). No differences were seen when the type of PPI or @entity7 genotype was taken into account. In the propensity-matched cohorts, the odds ratios for major in-hospital events in PPI versus no PPI were 0.29 (95% CI, 0.06 to 1.44) and 1.70 (95% CI, 0.10 to 30.3) for @entity0 with 1 and 2 variant alleles, respectively. Similarly, the hazard ratio for 1-year events in hospital survivors was 0.68 (95% CI, 0.26 to 1.79) and 0.55 (95% CI, 0.06 to 5.30), respectively. CONCLUSION: PPI use was not associated with an increased risk of cardiovascular events or mortality in @entity0 administered @entity6 for recent MI, whatever the @entity7 genotype, although harm could not be formally excluded in @entity0 with 2 loss-of-function alleles.

title: Clinical events as a function of proton pump inhibitor use, XXXX use, and @entity7 genotype in a large nationwide cohort of acute @entity5 : results from the French Registry of Acute ST-Elevation and Non-ST-Elevation @entity5 (FAST-MI) registry.

answer: @entity6


abstract: BACKGROUND: @entity6 requires metabolic activation by @entity7 ( @entity7 ). Proton pump inhibitors (PPIs) that inhibit @entity7 are commonly coadministered with @entity6 to reduce the risk of @entity3 . This analysis compares treatment outcomes for @entity0 in the French Registry of Acute ST-Elevation and Non-ST-Elevation @entity5 (FAST-MI) who did or did not receive @entity6 and/or PPIs. METHODS AND RESULTS: The FAST-MI registry included 3670 @entity0 (2744 @entity6 - and PPI-na  ve @entity0 ) presenting with definite MI. @entity0 were categorized according to use of @entity6 and/or PPI within 48 hours after hospital admission. PPI use was not associated with an increased risk for any of the main in-hospital events (in-hospital survival, reinfarction, @entity1 , @entity4 , and transfusion). Likewise, PPI treatment was not an independent predictor of 1-year survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P=0.57) or 1-year MI, @entity1 , or @entity2 (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; P=0.72). No differences were seen when the type of PPI or @entity7 genotype was taken into account. In the propensity-matched cohorts, the odds ratios for major in-hospital events in PPI versus no PPI were 0.29 (95% CI, 0.06 to 1.44) and 1.70 (95% CI, 0.10 to 30.3) for @entity0 with 1 and 2 variant alleles, respectively. Similarly, the hazard ratio for 1-year events in hospital survivors was 0.68 (95% CI, 0.26 to 1.79) and 0.55 (95% CI, 0.06 to 5.30), respectively. CONCLUSION: PPI use was not associated with an increased risk of cardiovascular events or mortality in @entity0 administered @entity6 for recent MI, whatever the @entity7 genotype, although harm could not be formally excluded in @entity0 with 2 loss-of-function alleles.

title: Clinical events as a function of proton pump inhibitor use, @entity6 use, and @entity7 genotype in a large nationwide cohort of acute XXXX : results from the French Registry of Acute ST-Elevation and Non-ST-Elevation @entity5 (FAST-MI) registry.

answer: @entity5


abstract: BACKGROUND: @entity6 requires metabolic activation by @entity7 ( @entity7 ). Proton pump inhibitors (PPIs) that inhibit @entity7 are commonly coadministered with @entity6 to reduce the risk of @entity3 . This analysis compares treatment outcomes for @entity0 in the French Registry of Acute ST-Elevation and Non-ST-Elevation @entity5 (FAST-MI) who did or did not receive @entity6 and/or PPIs. METHODS AND RESULTS: The FAST-MI registry included 3670 @entity0 (2744 @entity6 - and PPI-na  ve @entity0 ) presenting with definite MI. @entity0 were categorized according to use of @entity6 and/or PPI within 48 hours after hospital admission. PPI use was not associated with an increased risk for any of the main in-hospital events (in-hospital survival, reinfarction, @entity1 , @entity4 , and transfusion). Likewise, PPI treatment was not an independent predictor of 1-year survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P=0.57) or 1-year MI, @entity1 , or @entity2 (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; P=0.72). No differences were seen when the type of PPI or @entity7 genotype was taken into account. In the propensity-matched cohorts, the odds ratios for major in-hospital events in PPI versus no PPI were 0.29 (95% CI, 0.06 to 1.44) and 1.70 (95% CI, 0.10 to 30.3) for @entity0 with 1 and 2 variant alleles, respectively. Similarly, the hazard ratio for 1-year events in hospital survivors was 0.68 (95% CI, 0.26 to 1.79) and 0.55 (95% CI, 0.06 to 5.30), respectively. CONCLUSION: PPI use was not associated with an increased risk of cardiovascular events or mortality in @entity0 administered @entity6 for recent MI, whatever the @entity7 genotype, although harm could not be formally excluded in @entity0 with 2 loss-of-function alleles.

title: Clinical events as a function of proton pump inhibitor use, @entity6 use, and @entity7 genotype in a large nationwide cohort of acute @entity5 : results from the French Registry of Acute ST-Elevation and Non-ST-Elevation XXXX (FAST-MI) registry.

answer: @entity5


abstract: BACKGROUND: Animal models of @entity0 diseases are essential as they allow analysis of the disease process at the cellular level and can advance therapeutics by serving as a tool for drug screening and target validation. Here we report the development of a complete genetic model of @entity3 ( @entity3 ) in the vertebrate @entity4 to complement existing @entity4 , @entity1 , and invertebrate models and show its utility for testing compounds that alter @entity7 splicing. RESULTS: The @entity0 motoneuron disease @entity3 is caused by low levels, as opposed to a complete absence, of the @entity5 ( @entity5 ). To generate a true model of @entity3 in @entity4 , we have generated a transgenic @entity4 expressing the @entity0 @entity7 gene ( @entity7 ), which produces only a low amount of full-length @entity5 , and crossed this onto the @entity5 -/- background. We show that @entity0 @entity7 is spliced in @entity4 as it is in @entity0 and makes low levels of @entity5 protein. Moreover, we show that an antisense oligonucleotide that enhances correct @entity7 splicing increases full-length hSMN RNA in this model. When we placed this transgene on the @entity5 mutant background it rescued the neuromuscular presynaptic @entity6 defect that occurs in @entity5 mutants and increased their survival. CONCLUSIONS: We have generated a transgenic fish carrying the @entity0 @entity7 gene. This gene is spliced in fish as it is in @entity0 and @entity1 suggesting a conserved splicing mechanism in these vertebrates. Moreover, antisense targeting of an intronic splicing silencer site increased the amount of full length @entity5 generated from this transgene. Having this transgene on the @entity5 mutant fish rescued the presynaptic defect and increased survival. This model of @entity4 @entity3 has all of the components of @entity0 @entity3 and can thus be used to understand @entity2 in @entity3 , can be used as an vivo test for drugs or antisense approaches that increase full-length @entity5 , and can be developed for drug screening.

title: Generation and Characterization of a genetic @entity4 model of XXXX carrying the @entity0 @entity7 gene.

answer: @entity3


abstract: BACKGROUND: Animal models of @entity0 diseases are essential as they allow analysis of the disease process at the cellular level and can advance therapeutics by serving as a tool for drug screening and target validation. Here we report the development of a complete genetic model of @entity3 ( @entity3 ) in the vertebrate @entity4 to complement existing @entity4 , @entity1 , and invertebrate models and show its utility for testing compounds that alter @entity7 splicing. RESULTS: The @entity0 motoneuron disease @entity3 is caused by low levels, as opposed to a complete absence, of the @entity5 ( @entity5 ). To generate a true model of @entity3 in @entity4 , we have generated a transgenic @entity4 expressing the @entity0 @entity7 gene ( @entity7 ), which produces only a low amount of full-length @entity5 , and crossed this onto the @entity5 -/- background. We show that @entity0 @entity7 is spliced in @entity4 as it is in @entity0 and makes low levels of @entity5 protein. Moreover, we show that an antisense oligonucleotide that enhances correct @entity7 splicing increases full-length hSMN RNA in this model. When we placed this transgene on the @entity5 mutant background it rescued the neuromuscular presynaptic @entity6 defect that occurs in @entity5 mutants and increased their survival. CONCLUSIONS: We have generated a transgenic fish carrying the @entity0 @entity7 gene. This gene is spliced in fish as it is in @entity0 and @entity1 suggesting a conserved splicing mechanism in these vertebrates. Moreover, antisense targeting of an intronic splicing silencer site increased the amount of full length @entity5 generated from this transgene. Having this transgene on the @entity5 mutant fish rescued the presynaptic defect and increased survival. This model of @entity4 @entity3 has all of the components of @entity0 @entity3 and can thus be used to understand @entity2 in @entity3 , can be used as an vivo test for drugs or antisense approaches that increase full-length @entity5 , and can be developed for drug screening.

title: Generation and Characterization of a genetic XXXX model of @entity3 carrying the @entity0 @entity7 gene.

answer: @entity4


abstract: BACKGROUND: Animal models of @entity0 diseases are essential as they allow analysis of the disease process at the cellular level and can advance therapeutics by serving as a tool for drug screening and target validation. Here we report the development of a complete genetic model of @entity3 ( @entity3 ) in the vertebrate @entity4 to complement existing @entity4 , @entity1 , and invertebrate models and show its utility for testing compounds that alter @entity7 splicing. RESULTS: The @entity0 motoneuron disease @entity3 is caused by low levels, as opposed to a complete absence, of the @entity5 ( @entity5 ). To generate a true model of @entity3 in @entity4 , we have generated a transgenic @entity4 expressing the @entity0 @entity7 gene ( @entity7 ), which produces only a low amount of full-length @entity5 , and crossed this onto the @entity5 -/- background. We show that @entity0 @entity7 is spliced in @entity4 as it is in @entity0 and makes low levels of @entity5 protein. Moreover, we show that an antisense oligonucleotide that enhances correct @entity7 splicing increases full-length hSMN RNA in this model. When we placed this transgene on the @entity5 mutant background it rescued the neuromuscular presynaptic @entity6 defect that occurs in @entity5 mutants and increased their survival. CONCLUSIONS: We have generated a transgenic fish carrying the @entity0 @entity7 gene. This gene is spliced in fish as it is in @entity0 and @entity1 suggesting a conserved splicing mechanism in these vertebrates. Moreover, antisense targeting of an intronic splicing silencer site increased the amount of full length @entity5 generated from this transgene. Having this transgene on the @entity5 mutant fish rescued the presynaptic defect and increased survival. This model of @entity4 @entity3 has all of the components of @entity0 @entity3 and can thus be used to understand @entity2 in @entity3 , can be used as an vivo test for drugs or antisense approaches that increase full-length @entity5 , and can be developed for drug screening.

title: Generation and Characterization of a genetic @entity4 model of @entity3 carrying the @entity0 XXXX gene.

answer: @entity7


abstract: BACKGROUND: Animal models of @entity0 diseases are essential as they allow analysis of the disease process at the cellular level and can advance therapeutics by serving as a tool for drug screening and target validation. Here we report the development of a complete genetic model of @entity3 ( @entity3 ) in the vertebrate @entity4 to complement existing @entity4 , @entity1 , and invertebrate models and show its utility for testing compounds that alter @entity7 splicing. RESULTS: The @entity0 motoneuron disease @entity3 is caused by low levels, as opposed to a complete absence, of the @entity5 ( @entity5 ). To generate a true model of @entity3 in @entity4 , we have generated a transgenic @entity4 expressing the @entity0 @entity7 gene ( @entity7 ), which produces only a low amount of full-length @entity5 , and crossed this onto the @entity5 -/- background. We show that @entity0 @entity7 is spliced in @entity4 as it is in @entity0 and makes low levels of @entity5 protein. Moreover, we show that an antisense oligonucleotide that enhances correct @entity7 splicing increases full-length hSMN RNA in this model. When we placed this transgene on the @entity5 mutant background it rescued the neuromuscular presynaptic @entity6 defect that occurs in @entity5 mutants and increased their survival. CONCLUSIONS: We have generated a transgenic fish carrying the @entity0 @entity7 gene. This gene is spliced in fish as it is in @entity0 and @entity1 suggesting a conserved splicing mechanism in these vertebrates. Moreover, antisense targeting of an intronic splicing silencer site increased the amount of full length @entity5 generated from this transgene. Having this transgene on the @entity5 mutant fish rescued the presynaptic defect and increased survival. This model of @entity4 @entity3 has all of the components of @entity0 @entity3 and can thus be used to understand @entity2 in @entity3 , can be used as an vivo test for drugs or antisense approaches that increase full-length @entity5 , and can be developed for drug screening.

title: Generation and Characterization of a genetic @entity4 model of @entity3 carrying the XXXX @entity7 gene.

answer: @entity0


abstract: In 8 @entity0 with @entity1 , the cutaneous blood flow (CBF) was measured simultaneously in both involved and uninvolved psoriatic skin before (i.e., on the first day of hospitalization) and on the 3rd, 7th, 14th, and 28th days of treatment with tar. The 133Xe washout method was used after epicutaneous labeling and compared to the laser Doppler velocimetry ( @entity2 ) technique. Control experiments were performed in 10 normal individuals. Before treatment the mean CBF in involved psoriatic skin was 62.6 +/- 18.7 SD ml X (100 g X min)-1, which is significantly higher than CBF of uninvolved skin in psoriatic @entity0 , 9.5 +/- 4.0 SD ml X (100 g X min)-1, (p less than 0.01) and is 13.6 times higher than CBF in the normal individuals (p less than 0.01). Fifty hours following onset of treatment (i.e., after only 2 applications of tar), mean CBF of the involved psoriatic skin had decreased significantly to 35.0 +/- 13.9 SD ml X (100 g X min)-1, (p less than 0.01), which was not statistically different from the CBF on the 7th day. During the following weeks, the CBF in involved psoriatic skin decreased at a more moderate rate than that observed during the first week and was 15.0 +/- 6.1 SD ml X (100 g X min)-1 on the 28th day. This value is not significantly different from the CBF of uninvolved skin in these @entity0 . At the end of treatment, the CBF of the uninvolved skin had decreased significantly (p less than 0.05) in all the @entity0 to values similar to those observed in the skin of normal individuals. A parallel decline was observed in a clinical psoriatic score index; however, it is not known whether the observed decrease in CBF was preceded or succeeded by the clinical improvement. A comparison of the 133Xe measurements and @entity2 measurements in the normal individuals by linear regression analysis yielded a correlation coefficient of -0.24 (N = 20, p greater than 0.05). In the skin of psoriatic @entity0 the correlation coefficient was 0.01, (N = 47, p greater than 0.05) for unaffected skin, and 0.61 (N = 47, p less than 0.001) in the involved psoriatic skin sites. The @entity2 measurements did not reflect changes in the uninvolved skin in psoriatic @entity0 during treatment and resulted in a remarkably high C.V. in the bilateral measurements of skin in normal individuals (43.8%) compared to the C.V. of 133Xe flow measurements (14.8%). It is concluded that while the @entity2 method gives a rough estimate of blood flow in cutaneous tissue with a high capillary perfusion rate, inaccurate measurements are made in skin areas with normal to twice the normal CBF range.

title: The effects of antipsoriatic treatment on cutaneous blood flow in XXXX measured by 133Xe washout method and laser Doppler velocimetry.

answer: @entity1


abstract: @entity8 respond favorably to chemotherapy either at diagnosis or when they recur. Histologically similar @entity2 may arise in the CNS usually in the pineal or suprasellar regions. Although radiation therapy may produce a 5 year disease-free survival in excess of 60% in localized pure @entity9 , @entity8 of other histology tend to recur. We have conducted 14 chemotherapy trials in 8 @entity0 with recurrent @entity8 using 3 different single agent and 2 multi-agent chemotherapy regimens. The histologic diagnoses of the @entity0 were @entity9 (4), @entity7 (2), @entity3 (1), and @entity2 (1). There were 7 males and 1 female with a median age of 13 years. The primary @entity2 arose in the pineal region in 6 and was multicentric in 2. Seven @entity0 had local recurrences and one developed an initial recurrence in the spinal canal. Three @entity0 had CNS @entity1 at relapse and 2 had systemic @entity1 . Objective responses were documented in 7 of 14 trials (50%). Responses were observed with @entity4 (80 mg/kg) in 3 of 4 @entity0 for 2+, 3, and 5 mos, @entity5 (120 mg/m2) in 1 of 2 @entity0 for 2+ mos, and the VAB 6 protocol ( @entity11 , @entity6 , @entity4 , @entity10 -d, @entity5 ) in 3 of 5 @entity0 for 5, 8, and 18 mos. The median duration of response was 5 mos. (2+-18). High doses of single chemotherapy agents such as @entity4 and @entity5 as well as VAB 6 regimen have definite activity in recurrent @entity8 , especially @entity9 . Good palliation may be achieved with chemotherapy alone with acceptable morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

title: Chemotherapy trials in recurrent primary XXXX .

answer: @entity8


abstract: @entity4 were encountered in nine @entity0 , ranging in age from 39 to 76 years, at the University of Michigan Medical Center between 1961 and 1983. @entity2 and @entity7 were etiologic factors in six cases. Four @entity0 were without symptoms, whereas five experienced @entity6 , including one with a @entity8 . Eight @entity0 were subjected to surgical treatment; no @entity1 occurred and symptoms were resolved in all @entity0 . A literature review of 108 celiac @entity4 revealed two distinct subgroups. Among 60 celiac @entity4 encountered before 1950, representing the historic @entity9 , 40% were infectious (usually luetic), 7% were traumatic, and 52% were of undetermined cause. Most were symptomatic, 87% ruptured, and 95% were diagnosed at postmortem examination. The contemporary @entity9 since 1950 consisted of 48 cases, including nine in the Michigan experience. Congenital or developmental medial defects of the arterial wall and @entity7 were the most common causes of @entity5 . Most @entity5 in the contemporary period were either asymptomatic or accompanied by vague abdominal discomfort. @entity3 affected 13% of those @entity5 . Operative therapy was successfully undertaken in 91% of 43 @entity0 during the contemporary @entity9 , including eight in the present series.

title: XXXX : historic (1745-1949) versus contemporary (1950-1984) differences in etiology and clinical importance.

answer: @entity4


abstract: PURPOSE: To describe the prevalence of age-related degeneration ( @entity3 ) in a rural Chinese population and to assess its associations with age, gender, and smoking. DESIGN: Population-based cross-sectional. @entity0 : @entity0 aged 30+ years, recruited between October 2006 and October 2007, from Yongnian County, Handan, Hebei Province, China. METHODS: All @entity0 underwent a standardized interview and comprehensive eye examinations, including digital retinal photography of both eyes. Trained graders assessed the presence and severity of @entity1 following the modified @entity2 ( @entity2 ) used in the Blue Mountains Eye Study (BMES). Direct age standardization to the world population (year 2000) was performed to compare the prevalence across different populations. MAIN OUTCOME MEASURES: @entity3 and @entity2 . RESULTS: Of 6830 participates, fundus photographs were gradable for 6581 @entity0 (96.4%), including 4049 aged 50+ years. Early and late @entity3 prevalence rates were 3.0% and 0.1%, respectively, among @entity0 . The age-standardized prevalence rates among @entity0 aged 50+ years were 4.7% and 0.2%, respectively. After controlling for age, @entity0 had a higher prevalence of early (3.9% vs. 2.3%, odds ratio [OR] 1.7; 95% confidence interval [CI], 1.3-2.2) and late @entity3 (0.1% vs. 0.03%; OR 3.5; CI, 0.4-33.4) compared with @entity0 . Older age (sex-adjusted OR 1.7; CI, 1.3-2.2 per decade of age) and current smoking (age-sex-adjusted OR 1.4; CI, 1.0-2.1) were significantly associated with early @entity3 prevalence. The proportion of current smokers was substantially higher in @entity0 (58.7%) than in @entity0 (0.3%). The attributable risk of early @entity3 from smoking among Chinese @entity0 was 24.2%. After controlling for current smoking, the excess prevalence of early @entity3 in @entity0 compared with @entity0 reduced by 50% (OR 1.4; 95% CI, 0.9-2.0). CONCLUSIONS: The prevalence of early @entity3 in this rural Chinese sample was similar to white @entity0 in the BMES and Asian Malays in the Singapore Malay Eye Study. Late @entity3 prevalence, however, was lower. Higher prevalence rates for early and late @entity3 in @entity0 compared with @entity0 were largely attributed to substantially higher proportions of smokers in rural Chinese @entity0 than in @entity0 .

title: Prevalence of age-related XXXX in a rural Chinese population: the Handan Eye Study.

answer: @entity2


abstract: OBJECTIVE: This study aims to evaluate whether coronary @entity1 scoring (CCS) is also feasible using low-radiation-dose coronary computed tomography angiography (CCTA) in combination with iterative reconstruction. METHODS: Forty-three individuals without known @entity0 underwent both noncontrast CCS (  1 @entity2 ) for reference Agatston scores and low-dose CCTA (  3 @entity2 ). Raw CCTA data were reconstructed with filtered back projection (FBP), hybrid iterative reconstruction (HIR), and model-based iterative reconstruction (MIR). Calcification volumes were derived with thresholds of >351 and >600 Hounsfield units (HU) and converted to proxy Agatston scores with linear regression analysis. RESULTS: Intraclass correlation coefficients for Agatston scores versus CCTA volumes with FBP and iterative reconstruction were excellent (ranges 0.94-0.99 and 0.96-0.99 for >351 HU and >600 HU thresholds, respectively). The >351 HU threshold resulted in higher CCTA volume scores ranging from 65.9 (15.1-347.0) for HIR to 94.8 (42.0-423.0) for MIR (P = 0.001 and <0.001, respectively). The >600 HU threshold scores ranged from 14.1 (0.0-159.3) for HIR to 28.6 (0.0-215.6) for MIR (P = 0.003 and 0.027, respectively). At >351 HU, reclassification occurred in 21 individuals (49%) for FBP and HIR and 25 individuals (58%) for MIR. Reclassifications decreased with >600 HU to 10 (HIR, 23%), 8 (FBP, 19%), and 4 (MIR, 9%). CONCLUSIONS: The CCS is feasible using iteratively reconstructed low-dose CCTA with a @entity1 threshold of >600 HU. Using MIR, only 9% of individuals were reclassified.

title: Assessment of Coronary Artery XXXX on Low-Dose Coronary Computed Tomography Angiography With Iterative Reconstruction.

answer: @entity1


abstract: OBJECTIVE: Despite the fact that rituximab depletes B cells in all treated @entity0 with @entity1 , not all @entity0 show a favourable clinical response. The goal of this study was to provide insight into pharmacological changes in peripheral blood that are associated with clinical response to rituximab. METHODS: Gene expression profiling was performed on peripheral blood RNA of 13 @entity0 with @entity1 (test group) using Illumina HumanHT beadchip microarrays. An independent group of nine @entity0 was used for validation using TaqMan quantitative PCR. Clinical responder status was determined after 6 months using change in 28-joint Disease Activity Score (/\DAS28) and European League Against @entity2 (EULAR) response criteria. Significance analysis of microarrays and ontology analysis were used for data analysis and interpretation. RESULTS: Pharmacogenomic analyses demonstrated marked interindividual differences in the pharmacological responses at 3 and 6 months after start of treatment with rituximab. Interestingly, only differences in the regulation of type I interferon (IFN)-response genes after 3 months correlated with the /\DAS28 response. Good responders (DAS>1.2; n=7) exhibited a selective increase in the expression of type I IFN-response genes, whereas this activity was unchanged or hardly changed in non-responders (DAS<1.2; n=6) (p=0.0040 at a cut-off of 1.1-fold induction). Similar results were obtained using EULAR response criteria. These results were validated in an independent cohort of nine @entity0 (five non-responders and four responders, p=0.0317). CONCLUSIONS: A good clinical response to rituximab in @entity1 is associated with a selective drug-induced increase in type I IFN-response activity in @entity0 with @entity1 . This finding may provide insight in the biological mechanism underlying the therapeutic response to rituximab.

title: Pharmacological induction of interferon type I activity following treatment with rituximab determines clinical response in XXXX .

answer: @entity1


abstract: OBJECTIVE: to estimate and visualise the efficacy of treatment with etanercept (Enbrel) in @entity0 with @entity2 ( @entity2 ) using colour Doppler and spectral Doppler ultrasonography to determine the possible changes in synovial perfusion during a one year observation period. METHODS: Eleven @entity0 from the European multicentre trial of the efficacy and safety of etanercept were included in this study when transferred into the open label, long term safety, and efficacy study. Before a scheduled dosage increase to 50 mg/week they were examined clinically, serologically, and by ultrasonography using the colour Doppler pixels and the spectral Doppler resistance index (RI) as indicators of @entity1 . The @entity0 were re-examined at two weeks and at one year follow up RESULTS: The clinical activity decreased significantly from baseline to week 2, but no significant changes were seen from baseline to one year. The number of coloured pixels in each region of interest decreased from baseline to week 2 with a median reduction of 60% (p=0.005). This effect on the perfusion in the synovium could not be found after one year of treatment. During the initial treatment we detected an increase in synovial RI by spectral Doppler. The median increase in peripheral resistance from baseline to week 2 as estimated by the mean RI was 22.6% (p=0.005). The increase in peripheral resistance was maintained to some extent after one year (mean RI increased by 18.8% p=0.074). CONCLUSION: Ultrasonography seems to be a promising tool for the detection of treatment response using spectral Doppler and pixel estimation.

title: Effects of treatment with etanercept (Enbrel, TNRF:Fc) on XXXX evaluated by Doppler ultrasonography.

answer: @entity2


abstract: @entity15 , a new @entity14 , was given to fifty @entity0 (28 male and 22 female) aged 15 to 86 years with @entity2 of the urinary tract or prostate. @entity3 , i.e. @entity9 in 20 cases and @entity10 in 21, were usually chronic and associated with @entity12 . Nine @entity0 had @entity2 of the prostate. Pathogens recovered from the urine were 26 @entity5 , 8 @entity11 , 16 Serratia, 5 @entity13 or @entity1 -positive Proteus, 1 Providencia, and 4 Pseudomonas. Minimal inhibitory concentrations of @entity15 ranged from 0.015 to 64 micrograms/ml (mean MIC: 0.12 micrograms/ml). @entity15 was given as single drug therapy in all @entity0 but one, in a daily dosage of 2 g divided into two intramuscular injections, for 3 to 28 days (average 22 days). Follow-up after discontinuation of treatment was four weeks. Therapeutic results were as follows: 13 successes and 7 failures by relapse for the 20 @entity9 @entity0 , 13 successes and 7 failures by relapse for the 20 interpretable cases of @entity10 , and 4 successes and 5 failures by relapse for the 9 @entity0 with @entity6 . Local tolerance was excellent. @entity8 in 2 @entity0 and @entity4 in 1 required withdrawal of the drug. Three other @entity0 with @entity4 were able to continue treatment. Intolerance to ingestion of alcoholic beverages was reported by 10 @entity0 . @entity7 was recorded in 2 cases and a transient mononucleosic reaction in one. No renal of hepatic side effects were documented.

title: [Clinical evaluation of @entity15 in urinary tract and XXXX ].

answer: @entity6


abstract: @entity15 , a new @entity14 , was given to fifty @entity0 (28 male and 22 female) aged 15 to 86 years with @entity2 of the urinary tract or prostate. @entity3 , i.e. @entity9 in 20 cases and @entity10 in 21, were usually chronic and associated with @entity12 . Nine @entity0 had @entity2 of the prostate. Pathogens recovered from the urine were 26 @entity5 , 8 @entity11 , 16 Serratia, 5 @entity13 or @entity1 -positive Proteus, 1 Providencia, and 4 Pseudomonas. Minimal inhibitory concentrations of @entity15 ranged from 0.015 to 64 micrograms/ml (mean MIC: 0.12 micrograms/ml). @entity15 was given as single drug therapy in all @entity0 but one, in a daily dosage of 2 g divided into two intramuscular injections, for 3 to 28 days (average 22 days). Follow-up after discontinuation of treatment was four weeks. Therapeutic results were as follows: 13 successes and 7 failures by relapse for the 20 @entity9 @entity0 , 13 successes and 7 failures by relapse for the 20 interpretable cases of @entity10 , and 4 successes and 5 failures by relapse for the 9 @entity0 with @entity6 . Local tolerance was excellent. @entity8 in 2 @entity0 and @entity4 in 1 required withdrawal of the drug. Three other @entity0 with @entity4 were able to continue treatment. Intolerance to ingestion of alcoholic beverages was reported by 10 @entity0 . @entity7 was recorded in 2 cases and a transient mononucleosic reaction in one. No renal of hepatic side effects were documented.

title: [Clinical evaluation of XXXX in urinary tract and @entity6 ].

answer: @entity15


abstract: @entity1 ( @entity1 ) is a classification given to a group of nonpathogenic, single-stranded DNA viruses known to reside latently in primates. During latency in @entity0 , @entity1 type 2 ( @entity3 ) preferentially integrates at a site on chromosome 19q13.3ter by targeting a sequence composed of an @entity1 Rep binding element (RBE), a spacer, and a nicking site. Here, we report the DNA sequence of an @entity2 @entity1 integration site isolated from CV-1 cells. Overall, it has 98% homology to the analogous @entity0 site, including identical spacer and nicking sequences. However, the simian RBE is expanded, having five perfect directly repeated GAGC tetramers. We carried out a number of in vitro and in vivo assays to determine the effect of this expanded RBE sequence on the Rep-RBE interaction and @entity1 targeted integration. Using electromobility shift assays it was demonstrated that @entity5 Rep68 bound the expanded RBE with a sixfold-greater affinity than the @entity0 RBE. To determine the basis for the affinity increase, DNase I protection and methylation interference (MI) assays were performed. Comparison of footprints on both the @entity0 and simian RBEs revealed nearly identical protection; however, MI analysis suggested greater interaction with the @entity4 of the expanded RBE, thus providing a biochemical basis for the increased binding activity. In vivo, integration targeted to the simian RBE was demonstrated by PCR analysis of latently infected Cos-7 cells. Interestingly, the frequency of site-specific integration was twofold greater in Cos-7 cells than in HeLa cells. Overall, these experiments establish that the simian RBE, identified in CV-1 cells, functions analogously to the @entity0 RBE and provide further evidence for a developing model that proposes individual roles for the RBE and the spacer and nicking site elements.

title: Identification and characterization of an adeno-associated virus integration site in CV-1 cells from the XXXX .

answer: @entity2


abstract: BACKGROUND: @entity6 ( @entity6 ) @entity2 is a heterogeneous group of @entity3 . The authors recently mapped an autosomal dominant demyelinating form of @entity6 type 1 ( @entity7 ) to chromosome 16p13.1-p12.3. OBJECTIVE: To find the gene mutations underlying @entity7 . METHODS: The authors used a combination of standard positional cloning and candidate gene approaches to identify the causal gene for @entity7 . Western blot analysis was used to determine relative protein levels in @entity0 and control lymphocyte extracts. Northern blotting was used to characterize gene expression in 1) multiple tissues; 2) developing sciatic nerve; and 3) nerve-crush and nerve-transection experiments. RESULTS: The authors identified missense mutations ( @entity8 , @entity9 , W116G) in the LITAFgene (lipopolysaccharide-induced @entity1 necrosis factor-alpha factor) in three @entity7 pedigrees. @entity5 , which is also referred to as SIMPLE, is a widely expressed gene encoding a 161-amino acid protein that may play a role in protein degradation pathways. The mutations associated with @entity7 were found to cluster, defining a domain of the @entity5 protein having a critical role in peripheral nerve function. Western blot analysis suggested that the @entity9 and W116G mutations do not alter the level of @entity5 protein in peripheral blood lymphocytes. The @entity5 transcript is expressed in sciatic nerve, but its level of expression is not altered during development or in response to @entity4 . This finding is in stark contrast to that seen for other known genes that cause @entity7 . CONCLUSIONS: Mutations in @entity5 may account for a significant proportion of @entity7 @entity0 with previously unknown molecular diagnosis and may define a new mechanism of peripheral nerve perturbation leading to demyelinating @entity2 .

title: Mutation of a putative protein degradation gene @entity5 /SIMPLE in XXXX 1C.

answer: @entity6


abstract: BACKGROUND: @entity6 ( @entity6 ) @entity2 is a heterogeneous group of @entity3 . The authors recently mapped an autosomal dominant demyelinating form of @entity6 type 1 ( @entity7 ) to chromosome 16p13.1-p12.3. OBJECTIVE: To find the gene mutations underlying @entity7 . METHODS: The authors used a combination of standard positional cloning and candidate gene approaches to identify the causal gene for @entity7 . Western blot analysis was used to determine relative protein levels in @entity0 and control lymphocyte extracts. Northern blotting was used to characterize gene expression in 1) multiple tissues; 2) developing sciatic nerve; and 3) nerve-crush and nerve-transection experiments. RESULTS: The authors identified missense mutations ( @entity8 , @entity9 , W116G) in the LITAFgene (lipopolysaccharide-induced @entity1 necrosis factor-alpha factor) in three @entity7 pedigrees. @entity5 , which is also referred to as SIMPLE, is a widely expressed gene encoding a 161-amino acid protein that may play a role in protein degradation pathways. The mutations associated with @entity7 were found to cluster, defining a domain of the @entity5 protein having a critical role in peripheral nerve function. Western blot analysis suggested that the @entity9 and W116G mutations do not alter the level of @entity5 protein in peripheral blood lymphocytes. The @entity5 transcript is expressed in sciatic nerve, but its level of expression is not altered during development or in response to @entity4 . This finding is in stark contrast to that seen for other known genes that cause @entity7 . CONCLUSIONS: Mutations in @entity5 may account for a significant proportion of @entity7 @entity0 with previously unknown molecular diagnosis and may define a new mechanism of peripheral nerve perturbation leading to demyelinating @entity2 .

title: Mutation of a putative protein degradation gene XXXX /SIMPLE in @entity6 1C.

answer: @entity5


abstract: PURPOSE OF REVIEW: @entity3 ( @entity3 ) causes significant morbidity and mortality, mainly due to complications [ @entity2 , @entity5 , @entity11 ( @entity11 ) and esophageal @entity4 (EVH)]. Studies of the complications, management and outcomes in @entity0 with @entity3 over the last 18 months are reviewed. RECENT FINDINGS: Predictors of response to @entity13 therapy in @entity2 have been reported, along with the effect of minimal @entity2 on driving. @entity8 was found to lead to better maintenance of remission and decreased readmission rates in @entity0 with @entity1 and @entity2 . Satavaptan (a vasopressin receptor antagonist) was investigated for treatment of refractory @entity5 and appeared to be effective, but this compound is not currently approved by the US Food and Drug Administration (FDA). @entity0 with refractory @entity5 taking @entity6 were found to have poorer outcomes than those not taking @entity6 . @entity12 currently appears to be the best medical therapy available for @entity0 with type 1 @entity11 ; the addition with albumin to @entity12 appeared to decrease mortality in @entity0 with type 1 @entity11 . In primary prophylaxis of EVH, @entity7 was found to reduce the rate of initial @entity4 compared with band ligation. Early transjugular intrahepatic portosystemic shunts placed in highly selected @entity0 with acute EVH and a high risk of endoscopic failure decreased long-term mortality. In @entity0 with @entity9 , primary prophylaxis with @entity10 may decrease the probability of gastric @entity4 compared with nonselective beta-blockers. SUMMARY: Refinement in clinical management strategies for @entity0 with @entity1 and its complications appear to continue to contribute to improved @entity0 outcomes.

title: Complications and outcomes in XXXX .

answer: @entity3


abstract: OBJECTIVE: The purpose of this study is to evaluate the efficacy of a customized acoustical stimulus (Neuromonics) system in the treatment of chronic @entity2 . STUDY DESIGN: Multi-institutional prospective. SETTING: Nine U.S. Tertiary Otological referral centers; ambulatory. @entity0 : Fifty-two adults with chronic @entity2 for a minimum of 6 months, with poor or no response to previous treatments, and not undergoing concomitant therapies were enrolled. INTERVENTIONS: Treatment was delivered in 2 stages: Stage 1 consisted of stimulation with the @entity0 -customized musical tracks and white noise masking of the @entity2 for 2 months, 2 to 4 hours a day. Stage 2 consisted of listening to the same tracks, with no @entity2 masking for 4 months. Both phases included education, cognitive therapy, and periodic follow-up. MAIN OUTCOME MEASURES: Treatment response was measured through validated psychometric testing: the Tinnitus Reaction Questionnaire and the Tinnitus Handicap Inventory. Other measures included the @entity1 Scale and loudness discomfort levels. RESULTS: @entity0 ' responses were recorded from 38 @entity0 at 6 months, 28 @entity0 at 12 months, and 12 @entity0 at 24 months after initiation of treatment. A total of 14 @entity0 withdrew or were lost to follow-up, and the rest had not reached the 12- or 24-month testing interval. The Tinnitus Reaction Questionnaire score was significantly reduced in 74% of @entity0 at 12 months and 84% of @entity0 at 24 months. Tinnitus Handicap Inventory scores were significantly reduced in 77% of @entity0 at 12 months and 50% at 24 months. CONCLUSION: The customized acoustical stimulus system offers a safe and effective means of @entity2 management for @entity0 with chronic @entity2 .

title: Evaluation of a customized acoustical stimulus system in the treatment of chronic XXXX .

answer: @entity2


abstract: The aim of this study was to evaluate myofibrillar @entity2 kinase (CK) activity and to quantify the substrate channelling of @entity0 between CK and myosin ATPase under different pH conditions within the integrity of myofibrils. A pure myofibrillar fraction was prepared using differential centrifugation. The homogeneity of the preparation and the purity of the fraction were confirmed microscopically and by enzymatic assays for contaminant enzyme activities. The specific activity of myofibrillar CK reached 584 +/- 33 nmol PCr min(-1) mg(-1) at pH 6.75. Two methods were used to detect CK activity: (1) measurement of direct @entity0 production, and (2) measurement of PCr consumption. This method of evaluation has been tested in experiments with isolated @entity2 kinase. No discrepancy in CK activity between the methods was observed in the pH range tested (6.0-7.5). However, the same procedures resulted in a significant discrepancy between the amounts of reacted PCr and produced @entity0 within the pure myofibrillar fraction. This discrepancy represents the portion of @entity0 produced by the CK reaction, which is preferentially channelled to the myosin ATPase before diffusing into the bulk solution. The maximum evaluated difference reached 42.3 % at pH 6.95. The substrate channelling between myofibrillar-bound CK and myosin ATPase was evaluated under various pH levels within the physiological range and it reached a maximum value in a slightly acidic environment. These results suggest that @entity0 / @entity1 flux control by the CK system is more important at lower pH, corresponding to the physiological state of muscle fatigue.

title: Substrate channelling in a XXXX kinase system of rat skeletal muscle under various pH conditions.

answer: @entity2


abstract: When aggregates of HM-1 @entity0 ( @entity0 ) cells were exposed to 10(-6) M @entity1 for 2 days and cultured in medium lacking @entity1 , they differentiated to nerve cells, endoderm cells, and myoblasts. Cells 2 days after initial exposure to @entity1 were not significantly different from the parental @entity0 cells, as judged by cell-surface architecture and by reactivity to lectins. On the fourth day, the surface of the aggregates was covered with two kinds of cells distinguishable from the parental cells. The round cells with short villi seemed to be precursors to endoderm cells. Receptors for Dolichos biflorus agglutinin (DBA) newly appeared and receptors for peanut agglutinin (PNA) were still expressed on their surfaces. The other cells, which were round cells with a few processes, might be precursors to nerve cells. PNA receptors had disappeared from their surfaces, and @entity2 receptors were not expressed. On the sixth day of differentiation, possible precursors to myoblasts were detected; they were flat cells with smooth surfaces. These cells lacked cell-surface receptors for the two lectins, while the precursor cells and the myoblasts excreted intercellular fibers reacting with PNA. HM-1 cells synthesized much embryoglycan, the structure of which was similar to that of the glycan isolated from quasinullipotent F9 cells. The only difference was that the glycan from HM-1 cells lacked DBA binding sites. Synthesis of fucosylated embryoglycan mainly decreased between the second and fourth day of differentiation. As above, cell-surface changes occurred mainly between the second and fourth day. The period seems to be important in determining the fate of the cells, since endoderm cells were scarcely seen among differentiated cells which had been continuously exposed to 10(-6) M @entity1 during the period.

title: Cell-surface changes during in vitro differentiation of pluripotent XXXX cells.

answer: @entity0


abstract: The purpose of this study was to evaluate the safety and effectiveness of percutaneous transluminal angioplasty for @entity3 associated with @entity6 . Eleven @entity0 (10 @entity0 , 1 @entity0 ; ages 35-82 years) with the diagnosis of @entity6 of the large vessels underwent interventional treatment during intraarterial angiography. The causes included @entity1 (n = 8) and @entity8 (n = 3). Thirty-three @entity3 (including brachiocephalic and renal arteries, and arteries of upper and lower extremities) were treated with balloon angioplasty and/or stent placement. Follow-up included clinical examination, angiography, and color duplex ultrasound. Technical success was 100% (25/25) for stenoses and 50% (4/8) for @entity3 , representing all lesions combined from different anatomic locations. Dissection (n = 3) and @entity2 with retroperitoneal @entity7 (n = 1) was found in three @entity0 . During follow-up (mean 12 months), restenoses (n = 8) and re-restenoses (n = 1) occurred in 8 vascular areas. Three of these lesions were treated with repeated @entity4 (n = 4). The cumulative primary clinical success rate was 67.6%, cumulative secondary success rate 74.4%, and cumulative tertiary success rate 75.9%. Interventional therapy in systemic @entity6 provides promising results in technical success rates and followup. Angioplasty may result in @entity5 , but the rate of complications is low.

title: Percutaneous management of @entity3 associated with XXXX : a single center experience.

answer: @entity6


abstract: The purpose of this study was to evaluate the safety and effectiveness of percutaneous transluminal angioplasty for @entity3 associated with @entity6 . Eleven @entity0 (10 @entity0 , 1 @entity0 ; ages 35-82 years) with the diagnosis of @entity6 of the large vessels underwent interventional treatment during intraarterial angiography. The causes included @entity1 (n = 8) and @entity8 (n = 3). Thirty-three @entity3 (including brachiocephalic and renal arteries, and arteries of upper and lower extremities) were treated with balloon angioplasty and/or stent placement. Follow-up included clinical examination, angiography, and color duplex ultrasound. Technical success was 100% (25/25) for stenoses and 50% (4/8) for @entity3 , representing all lesions combined from different anatomic locations. Dissection (n = 3) and @entity2 with retroperitoneal @entity7 (n = 1) was found in three @entity0 . During follow-up (mean 12 months), restenoses (n = 8) and re-restenoses (n = 1) occurred in 8 vascular areas. Three of these lesions were treated with repeated @entity4 (n = 4). The cumulative primary clinical success rate was 67.6%, cumulative secondary success rate 74.4%, and cumulative tertiary success rate 75.9%. Interventional therapy in systemic @entity6 provides promising results in technical success rates and followup. Angioplasty may result in @entity5 , but the rate of complications is low.

title: Percutaneous management of XXXX associated with @entity6 : a single center experience.

answer: @entity3


abstract: Determination of glycemic differences between groups treated with continuous subcutaneous insulin infusion (CSII) or @entity3 ( @entity3 ) was central to the major objective of the study. Assessment of glycemia was based on 24-h inhospital profiles of plasma @entity1 ; pre- and postprandial and bedtime (seven time points) diurnal profiles performed monthly on outpatient samples; and glycosylated hemoglobin ( @entity2 ) measured bimonthly at each center. The correlation between plasma @entity1 determinations in the central laboratory and in local laboratories was 0.988. Significance of differences between treatments was by analysis of variance and least-squares regression. At baseline, mean inhospital plasma @entity1 and @entity2 concentrations and insulin dosages were identical in the groups randomized to CSII or @entity3 . A prompt decrement of indices of glycemic control during CSII was observed such that mean decrements sustained over the 8-mo treatment period in home and in hospital plasma @entity1 profiles and @entity2 relative to values obtained during @entity3 (P less than 0.0001). The likelihood of CSII-treated @entity0 achieving glycemic indices within the normal range was increased. The standardization of the mean and the M-value calculated from inhospital @entity1 profiles during CSII and @entity3 at 4 and 8 mo indicated that there was less plasma @entity1 fluctuation during CSII. The method of pooling standardized local @entity2 measurements from the six centers appeared to be an adequate substitute for centrally performed @entity2 determinations. Advantages of inhospital plasma @entity1 measurements in terms of accuracy and ability to obtain nocturnal samples contrasted with the likelihood of increased realism and superior correlation with @entity2 in home-obtained samples.(ABSTRACT TRUNCATED AT 250 WORDS)

title: Observations on control of glycemia with XXXX or continuous subcutaneous insulin infusion.

answer: @entity3