abstract: UNASSIGNED: Nanoscience is a field that has stood out in recent years. The accurate long-term health and environmental risks associated with these emerging materials are unknown. Therefore, this work investigated how to eliminate @entity1 nanoparticles (AgNPs) from synthetic effluents by electrocoagulation (EC) due to the widespread use of this type of nanoparticle (NP) in industry and its potential inhibition power over microorganisms responsible for biological treatment in effluent treatment plants. Synthesized AgNPs were studied via four different routes by chemical reduction in aqueous solutions to simulate the chemical variations of a hypothetical industrial effluent, and efficiency conditions of the EC treatment were determined. All routes used @entity4 as the source of @entity1 ions, and two synthesis routes were studied with @entity3 as a stabilizer. In route I, @entity3 functioned simultaneously as the reducing agent and stabilizing agent, whereas route II used @entity5 as a reducing agent. Route III used @entity0 as the reducing agent and @entity6 as the stabilizer; route IV used @entity6 as the stabilizing agent and @entity5 as the reducing agent. The efficiency of the EC process of the different synthesized solutions was studied. For route I, after 85  min of treatment, a significant decrease in the plasmon resonance peak of the sample was observed, which reflects the efficiency in the mass reduction of AgNPs in the solution by 98.6%. In route II, after 12  min of EC, the absorbance results reached the detection limit of the measurement instrument, which indicates a minimum reduction of 99.9% of AgNPs in the solution. During the 4  min of treatment in route III, the absorbance intensities again reached the detection limit, which indicates a minimum reduction of 99.8%. In route IV, after 10  min of treatment, a minimum AgNP reduction of 99.9% was observed. Based on these results, it was possible to verify that the solutions containing @entity2 considerably increased the necessary times required to eliminate AgNPs from the synthesized effluent, whereas solutions free of this reagent showed better results on floc formation and, therefore, are best for the treatment. The elimination of AgNPs from effluents by EC proved effective for the studied routes.

title: Synthetic wastewaters treatment by electrocoagulation to remove XXXX nanoparticles produced by different routes.

answer: @entity1


abstract: PURPOSE: Previously, studies examining correlates of @entity1 have been limited by small sample size, restricted geographic area, and little socio-cultural variability. Further, few studies have examined correlates of total @entity2 ( @entity2 ) and screen time (ST) in the same population. This study aimed to investigate correlates of @entity2 and ST in @entity0 around the world. METHODS: The sample included 5,844 @entity0 (45.6% @entity0 , mean age = 10.4 years) from study sites in Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal, South Africa, the United Kingdom, and the United States. @entity0 - and parent-reported behavioral, household, and neighborhood characteristics and directly measured anthropometric and accelerometer data were obtained. Twenty-one potential correlates of @entity2 and ST were examined using multilevel models, adjusting for sex, age, and highest parental education, with school and study site as random effects. Variables that were moderately associated with @entity2 and/or ST in univariate analyses (p<0.10) were included in the final models. Variables that remained significant in the final models (p<0.05) were considered correlates of @entity2 and/or ST. RESULTS: @entity0 averaged 8.6 hours of daily @entity2 , and 54.2% of @entity0 failed to meet ST guidelines. In all study sites, @entity0 reported higher ST, were less likely to meet ST guidelines, and had higher BMI z-scores than @entity0 . In 9 of 12 sites, @entity0 engaged in significantly more @entity2 than @entity0 . Common correlates of higher @entity2 and ST included poor weight status, not meeting physical activity guidelines, and having a TV or a computer in the bedroom. CONCLUSIONS: In this global sample many common correlates of @entity2 and ST were identified, some of which are easily modifiable (e.g., removing TV from the bedroom), and others that may require more intense behavioral interventions (e.g., increasing physical activity). Future work should incorporate these findings into the development of culturally meaningful public health messages.

title: Correlates of Total Sedentary Time and Screen Time in 9-11 Year-Old XXXX around the World: The International Study of Childhood Obesity, Lifestyle and the Environment.

answer: @entity0


abstract: UNASSIGNED: Limited data exist on the efficacy of long-term therapies for @entity2 . In osteoporotic postmenopausal @entity0 receiving denosumab for 7  years, nonvertebral fracture rates significantly decreased in years 4-7 versus years 1-3. This is the first demonstration of a further benefit on fracture outcomes with long-term therapy for @entity2 . INTRODUCTION: This study aimed to evaluate whether denosumab treatment continued beyond 3  years is associated with a further reduction in nonvertebral fracture rates. METHODS: @entity0 who completed the 3-year placebo-controlled @entity3 REduction Evaluation of Denosumab in @entity2 every 6 Months (FREEDOM) study were invited to participate in an open-label extension. The present analysis includes 4,074 postmenopausal @entity0 with @entity2 (n   =   2,343 long-term; n   =   1,731 cross-over) who enrolled in the extension, missed  <=1 dose during their first 3  years of denosumab treatment, and continued into the fourth year of treatment. Comparison of nonvertebral fracture rates during years 1-3 of denosumab with that of the fourth year and with the rate during years 4-7 was evaluated. RESULTS: For the combined group, the nonvertebral fracture rate per 100 @entity0 -years was 2.15 for the first 3  years of denosumab treatment (referent) and 1.36 in the fourth year (rate ratio [RR]   =   0.64; 95  % confidence interval (CI)   =   0.48 to 0.85, p   =   0.003). Comparable findings were observed in the groups separately and when nonvertebral fracture rates during years 1-3 were compared to years 4-7 in the long-term group (RR   =   0.79; 95  % CI   =   0.62 to 1.00, p   =   0.046). @entity3 rate reductions in year 4 were most prominent in subjects with persisting low hip @entity1 ( @entity1 ). CONCLUSIONS: Denosumab treatment beyond 3  years was associated with a further reduction in nonvertebral fracture rate that persisted through 7  years of continuous denosumab administration. The degree to which denosumab further reduces nonvertebral fracture risk appears influenced by the hip bone density achieved with initial therapy.

title: Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip XXXX after 3  years.

answer: @entity1


abstract: PURPOSE: @entity8 , which occurs in immunocompromised states such as @entity3 , has rarely been studied in @entity0 with @entity1 ( @entity1 ) on immunosuppressive therapy. MATERIALS AND METHODS: Three hundred and twenty-four consecutive @entity1 recipients on immunosuppressive treatment and 170 healthy subjects were evaluated for @entity8 and other parasites by modified trichrome staining, wet mount using normal saline, @entity4 and polymerase chain reaction (PCR). Clinical, demographic and laboratory parameters associated with occurrence of @entity8 were studied using univariate and multivariate analysis. The species of microsporidia were studied using PCR-restriction fragment length polymorphism (RFLP). @entity0 were treated with @entity5 (400 mg twice daily for 2 weeks). RESULTS: Of 324 @entity1 recipients initially screened, 52 were excluded from final analysis due to incomplete data. @entity0 with @entity1 [n = 272, age 42    12.54 years, 222 (81.6%) male] more often had @entity8 than healthy subjects by modified trichrome stain and PCR [n = 170, age 33.8    6.7 years, 123 (72.3%) male] [16/272 (5.8%) vs. 0/170 (0%), P < 0.001]. @entity0 with @entity8 were younger (33.9    8.3 years vs. 42.3    12.6 years; P = 0.009), had @entity2 more often (13/16, 81% vs. 123/256, 48%; P = 0.02), which was longer in duration (60, 32.5-105 days vs. 12, 6.2-18 days; P < 0.001) and had associated @entity6 (2/16, 12.5% vs. 2/256, 0.8%; P = 0.018). Younger age, presence of @entity2 and associated @entity6 were significant on multivariate analysis. @entity7 was detected in 15/16 (93%) @entity0 with @entity8 . CONCLUSION: @entity8 occurs frequently in @entity0 with @entity1 on immunosuppressive treatment, particularly among younger @entity0 with @entity2 and associated @entity6 . @entity7 is the major species identified among these @entity0 .

title: XXXX in renal transplant recipients: Prevalence, predictors of occurrence and genetic characterization.

answer: @entity8


abstract: BACKGROUND: Animal studies showed that the use of metformin after @entity2 (MI) resulted in a protective effect on cardiac myocytes. In this study, we examined the effect of metformin in @entity0 with @entity1 (DM) on left ventricular ejection fraction (LVEF) and post-MI mortality. METHODS: We reviewed charts of @entity0 with MI admitted to the UAMS medical center. Baseline characteristics and 12-month follow up data were collected. @entity0 were classified into three groups: Control group- no DM (n = 464), Metformin group- DM + MI (n = 88) and No-Metformin group- DM + MI (n = 168). First, we compared Metformin and No-Metformin groups to the Control group. Second, we performed propensity-score matching in @entity0 with DM, and compared Metformin to No-Metformin groups. RESULTS: All-cause 30-day and 12-month mortality was significantly higher in the No-Metformin group compared to controls (13.5 vs 9.3% p = 0.03 at 30 days, 23.7 vs 15.9 % p = 0.03 at 12 months). However, all-cause 30-day and 12-month mortality were similar in the Controls and Metformin group (9.3 vs 6.8 % p = 0.93 at 30 days, 15.9 vs 11.4 % p = 0.97 at 12 months). Mean LVEF on presentation (45 % in the three groups) and at follow up (47.84, 46.38 and 43.62 % in Control, Metformin, and No-Metformin groups, respectively) were not statistically different. There were no significant differences in regard to re-hospitalization, re-intervention, new stroke, CHF development, new MI, or identifiable arrhythmias. Metformin was an independent predictor of lower 30-day and 12-month all-cause mortality in @entity0 with DM (HR 0.25, p = 0.02 and HR 0.32, p = 0.01, respectively). In the matched analysis, 30-day all-cause mortality was significantly higher in the No-Metformin compared to the Metformin group (21.1 vs 8.8 %, p = 0.05). However the difference in 12-month all-cause mortality did not reach statistical significance (24.6 vs 15.8 %, p = 0.15). CONCLUSION: This proof-of-concept study shows that use of metformin in @entity0 with DM is associated with lower 30-day all-cause mortality and tendency for a lower 12-month all-cause mortality following MI without discernible improvement in LVEF.

title: The Effect of Metformin Use on Left Ventricular Ejection Fraction and Mortality Post- XXXX .

answer: @entity2


abstract: UNASSIGNED: microRNA (miRNA) dysregulation is involved in the development and progression of various @entity0 @entity1 , including @entity2 ( @entity2 ). However, how to identify the miRNAs targeting specific mRNA in cells is a significant challenge because of the interaction complexity and the limited knowledge of rules governing these processes. Some miRNAs are not predictable by current computer algorithms available. Here, using @entity3 mRNA as target, we established a new method, called miRNA in vivo precipitation (miRIP), to identify which kind of miRNAs can actually bind to the specific mRNA in cells. Several unpredictable miRNAs that bound @entity3 mRNA in HepG2 and PC-3 cells were identified by the miRIP method. Among these miRNAs identified by miRIP, miR-92a was found and confirmed to interact robustly with @entity3 mRNA, both in HepG2 and PC-3 cells. miR-92a was found to be remarkably increased in @entity2 tissues, and higher expression of miR-92a significantly correlated with lower expression of @entity3 , which is related to poor survival of @entity2 @entity0 . Moreover, inhibition of miR-92a could significantly suppress @entity2 growth in vitro and in vivo by upregulating @entity3 . Together, miR-92a, which is identified by miRIP, is functionally shown to be associated with @entity2 growth as an oncogenic miRNA by inhibiting expression of targeting gene @entity3 . In addition, several unpredictable miRNAs that target @entity4 mRNA were also identified by the miRIP method in HepG2 cells. Our results demonstrated that the miRIP approach can effectively identify the unpredictable but intracellular existing miRNAs that target specific mRNA in vivo. @entity1 Res; 75(14); 1-11.   2015 AACR.

title: An In Vivo Method to Identify microRNA Targets Not Predicted by Computation Algorithms: XXXX Targeting by miR-92a in @entity1 .

answer: @entity3


abstract: UNASSIGNED: microRNA (miRNA) dysregulation is involved in the development and progression of various @entity0 @entity1 , including @entity2 ( @entity2 ). However, how to identify the miRNAs targeting specific mRNA in cells is a significant challenge because of the interaction complexity and the limited knowledge of rules governing these processes. Some miRNAs are not predictable by current computer algorithms available. Here, using @entity3 mRNA as target, we established a new method, called miRNA in vivo precipitation (miRIP), to identify which kind of miRNAs can actually bind to the specific mRNA in cells. Several unpredictable miRNAs that bound @entity3 mRNA in HepG2 and PC-3 cells were identified by the miRIP method. Among these miRNAs identified by miRIP, miR-92a was found and confirmed to interact robustly with @entity3 mRNA, both in HepG2 and PC-3 cells. miR-92a was found to be remarkably increased in @entity2 tissues, and higher expression of miR-92a significantly correlated with lower expression of @entity3 , which is related to poor survival of @entity2 @entity0 . Moreover, inhibition of miR-92a could significantly suppress @entity2 growth in vitro and in vivo by upregulating @entity3 . Together, miR-92a, which is identified by miRIP, is functionally shown to be associated with @entity2 growth as an oncogenic miRNA by inhibiting expression of targeting gene @entity3 . In addition, several unpredictable miRNAs that target @entity4 mRNA were also identified by the miRIP method in HepG2 cells. Our results demonstrated that the miRIP approach can effectively identify the unpredictable but intracellular existing miRNAs that target specific mRNA in vivo. @entity1 Res; 75(14); 1-11.   2015 AACR.

title: An In Vivo Method to Identify microRNA Targets Not Predicted by Computation Algorithms: @entity3 Targeting by miR-92a in XXXX .

answer: @entity1


abstract: BACKGROUND: In @entity0 with @entity1 , liver transplantation is the only available curative treatment. Although the outcome and quality of life in the @entity0 have improved over the past decades, primary dys- or nonfunction ( @entity3 /PNF) can occur. Early detection of @entity3 is crucial and could lead to individual therapies. This study was designed to identify early markers of @entity2 and @entity3 in liver biopsies taken during the first hour after reperfusion. METHODS: Biopsies from donor livers were prospectively taken as a routine during the first hour after reperfusion. Recipient data, transaminases and outcome were routinely monitored. In total, 10 biopsy specimens taken from @entity0 with 90-day mortality and @entity3 , and @entity0 with long-term survival but without @entity3 were used for DNA microarrays. Markers that were significantly up- or down-regulated in the microarray were verified using quantitative real-time PCR. RESULTS: Age, indications and labMELD score were similar in both groups. Peak-transaminases during the first week after transplantation were significantly different in the two groups. In total, 20 differentially regulated markers that correlated to @entity3 were identified using microarray analysis and verified with quantitative real-time PCR. CONCLUSIONS: The markers identified in this study could predict @entity3 at a very early time point and might point to interventions that ameliorate @entity2 and thus prevent @entity3 . Identification of @entity0 and organs at risk might lead to individualized therapies and could ultimately improve outcome.

title: Early markers of XXXX after liver transplantation: association with primary dysfunction.

answer: @entity2


abstract: Two-pore channels (TPCs) localize to the endolysosomal system and have recently emerged as targets for the @entity1 -mobilizing messenger, @entity3 ( @entity3 ). However, their membrane topology is unknown. Using fluorescence protease protection assays, we show that @entity0 @entity2 and @entity4 possess cytosolic N and C termini and therefore an even number of transmembrane regions. Fluorophores placed at position 225 or 347 in @entity2 , or 339 in @entity4 were also cytosolic, whereas a fluorophore at position 628 in @entity2 was luminal. These data together with sequence similarity to voltage-gated @entity1 and Na(+) channels, and unbiased in silico predictions are consistent with a topology in which two homologous domains are present, each comprising 6 transmembrane regions and a re-entrant pore loop. Immunocytochemical analysis of selectively permeabilized cells using antipeptide antibodies confirmed that the C-terminal tails of recombinant TPCs are cytosolic and that residues 240-254 of @entity4 prior to putative pore 1 are luminal. Both @entity2 and @entity4 are N-glycosylated with residues 599, 611, and 616 contributing to glycosylation of @entity2 . This confirms the luminal position of these residues, which immediately precede the putative pore loop of the second domain. Mutation of all three glycosylation sites in @entity2 enhances @entity3 -evoked cytosolic @entity1 signals. Our data establish essential features of the topology of two-pore channels.

title: Membrane topology of XXXX -sensitive two-pore channels and their regulation by N-linked glycosylation.

answer: @entity3


abstract: @entity1 ( @entity1 ) is the most frequent form of chronic @entity2 . During the progress of this disease, phases of aggravation of pulmonary function (exacerbations) can occur, which reduce the quality of life. Clinical experience shows that single investigations are insufficient. Therefore a prolonged monitoring is required to recognize an exacerbation early. This home monitoring will involve a quick respiratory test and a related application for Android, iOS and Windows phones. This rapid test transmits the relevant pulmonary parameters, converted in an Extensible Markup Language file to the smartphone. The application will analyze the incoming data to evaluate the current health status of the @entity0 . Additionally the data will be transferred to the virtual control point (server) and stored in a database. If critical values are detected, the server will send a notification to prior defined relatives and doctors. A connection to a Hospital Information System will be possible through an included Health Level 7 interface. This offers an improved site-independent @entity0 care. The project is planned to be in development until 2016.

title: Supporting Prolonged XXXX Monitoring Using an Application for Mobile Devices.

answer: @entity1


abstract: OBJECTIVES: to describe the clinicopathologic features of @entity2 in @entity0 who develop locoregional recurrence of disease, to identify factors that predict prognosis in the subset of @entity0 treated with salvage surgery, and to determine the adjusted effect of time to recurrence. DESIGN: cohort study. SETTING: a @entity1 institute in Sydney, New South Wales, Australia. @entity0 : a total of 77 @entity0 who underwent salvage surgery for @entity2 that had been treated initially by surgery, radiotherapy, or surgery with postoperative radiotherapy. MAIN OUTCOME MEASURES: univariable and multivariable analysis of clinical and pathologic risk factors. RESULTS: median time to recurrence from initial treatment was 7.5 months (range, 0.9-143.9 mo), with 86% of recurrences occurring within the first 24 months. Surgical salvage was attempted in 77 @entity0 who had experienced recurrence at the primary site (n = 39), @entity1 (n = 27), and contralateral neck (n = 11). Time to recurrence, initial treatment modality, and site of failure were independent prognostic variables. CONCLUSIONS: the relationship of these prognostic variables displays a dynamic interaction. Initial combined-modality treatment and shorter time to recurrence were associated with worse outcome, while the effect of site of recurrence (local vs regional) was dependent on an interaction with the time to recurrence. The result of this interaction was that local recurrence was worse for those who experienced it early (eg, <6 mo after the initial treatment) and nodal recurrence was worse for those who experienced it late (eg, >=  6 mo after the intial treatment).

title: Predicting the prognosis of XXXX after first recurrence.

answer: @entity2


abstract: This paper presents @entity3 ( @entity3 ) observations made on the collagen, mineral and ground substance components comprising @entity0 cortical bone, which to a very large extent have been made possible by a sample preparation technique which takes advantage of the @entity1 propagation behavior inherent to the mature, highly heterogeneous, lamellar cortical bone tissue. By varying the extent to which bone samples are decalcified, it is possible to study certain morphological aspects of all these three main components of bone. Collagen features observable at fairly low magnification (approximately 1000x) include collagen bundle orientations with respect to the long axis of bone or of the osteon samples and collagen bundle morphological interrelationships. Much higher magnifications (approximately 20,000x) reveal spherical structures attached to the collagen fibrils which comprise the fiber bundle. Ground substance, yet to be identified biochemically, was noted in so-called interlamellar regions of osteons and of periosteal and endosteal tissue as well as in resting lines, cement lines and hypercalcified rings. It was observed to contain @entity2 and to be trypsin soluble, providing evidence for the presence of a noncollagenous protein and of chondroitin sulfate which may be biochemically related in a protein polysaccharide complex. Such conclusion does not, however, preclude the presence of other ground substance components in this observed material. Large concentrations of mineral were noted in the interlamellar region of osteons and of periosteal and endosteal bone. This mineral does not seem to be directly associated with collagen. This study involves the use of @entity3 in both the secondary and back-scattered electron detection modes and energy dispersive x-ray microanalysis (XMA).

title: Scanning electron microscopy studies of collagen, mineral and ground substance in XXXX cortical bone.

answer: @entity0


abstract: @entity4 is a diffuse @entity1 arising in the pleura, peritoneum, or other serosal surface and is closely associated with @entity2 exposure. An estimated 2,500 to 3,000 cases are diagnosed each year in the United States. Although there are individual case reports and small series detailing the clinical aspects of @entity3 , few studies examine a large series of @entity0 with @entity4 from the clinical perspective. This study reports on the findings of 238 cases of @entity4 from a private consultative medical practice. Most cases had a history of occupational @entity2 exposure. The mean latency was 48.5 yr, with @entity0 having a longer latency than @entity0 . The mean age at diagnosis was 70. Survival overall was poor (mean 8.8 months), but treatment was beneficial (mean 11.3 versus 6.4 months). Epithelioid histology conferred a survival advantage over sarcomatoid and responded better to treatment. Our data support an inverse relationship between @entity2 dose and latency.

title: XXXX : a clinical study of 238 cases.

answer: @entity4


abstract: UNASSIGNED: Transcription of @entity0 cytomegalovirus ( @entity5 ) @entity4 ie1 and ie3 is controlled by the major @entity4 promoter/enhancer (MIEP) and requires differential splicing. Based on complete loss of genome replication of an @entity5 mutant carrying a deletion of the ie3-specific exon 5, the multifunctional IE3 protein (611 @entity3 , pIE611) is considered essential for viral replication. Our analysis of ie3 transcription resulted in the identification of novel ie3 isoforms derived from alternatively spliced ie3 transcripts. Construction of an IE3-HA virus by insertion of an in-frame HA-epitope sequence allowed detection of the @entity0 isoforms in infected cells, verifying that the newly identified transcripts are coding for proteins. This prompted the construction of an @entity5 mutant lacking ie611, but retaining the coding capacity for the newly identified isoforms ie453 and ie310. Using   ie611 @entity5 , we demonstrate the dispensability of the canonical ie3 gene product pIE611 for viral replication. To determine the role of pIE611 for viral gene expression during @entity5 infection in an unbiased global approach, we used label-free quantitative mass-spectrometry to delineate pIE611-dependent changes of the @entity5 proteome. Interestingly, further analysis revealed transcriptional as well as post-transcriptional regulation of @entity5 gene products by pIE611. IMPORTANCE: Cytomegaloviruses are pathogenic b-herpesviruses persisting in a lifelong latency from which reactivation can occur under conditions of immuno-suppression, immuno- @entity2 or @entity1 . The switch from latency to reactivation requires expression of @entity4 genes. Therefore, understanding of @entity4 gene regulation might add insights into viral pathogenesis. The @entity0 cytomegalovirus ( @entity5 ) @entity4 (ie) 3 protein (611 @entity3 , pIE611) is considered essential for viral replication. The identification of novel protein isoforms derived from alternatively spliced ie3 transcripts prompted the construction of an @entity5 mutant lacking ie611, but retaining the coding capacity for the newly identified isoforms ie453 and ie310. Using   ie611 @entity5 , we demonstrate the dispensability of the canonical ie3 gene product pIE611 for viral replication and delineated pIE611-dependent changes of the @entity5 proteome. Our findings have fundamental implications for the interpretation of earlier studies on 'pIE3' functions and highlight the complex orchestration of @entity5 gene regulation.

title: The Canonical XXXX 3 Gene Product pIE611 of @entity0 Cytomegalovirus Is Dispensable for Viral Replication, but Mediates Transcriptional and Post-transcriptional Regulation of Viral Gene Products.

answer: @entity4


abstract: UNASSIGNED: Transcription of @entity0 cytomegalovirus ( @entity5 ) @entity4 ie1 and ie3 is controlled by the major @entity4 promoter/enhancer (MIEP) and requires differential splicing. Based on complete loss of genome replication of an @entity5 mutant carrying a deletion of the ie3-specific exon 5, the multifunctional IE3 protein (611 @entity3 , pIE611) is considered essential for viral replication. Our analysis of ie3 transcription resulted in the identification of novel ie3 isoforms derived from alternatively spliced ie3 transcripts. Construction of an IE3-HA virus by insertion of an in-frame HA-epitope sequence allowed detection of the @entity0 isoforms in infected cells, verifying that the newly identified transcripts are coding for proteins. This prompted the construction of an @entity5 mutant lacking ie611, but retaining the coding capacity for the newly identified isoforms ie453 and ie310. Using   ie611 @entity5 , we demonstrate the dispensability of the canonical ie3 gene product pIE611 for viral replication. To determine the role of pIE611 for viral gene expression during @entity5 infection in an unbiased global approach, we used label-free quantitative mass-spectrometry to delineate pIE611-dependent changes of the @entity5 proteome. Interestingly, further analysis revealed transcriptional as well as post-transcriptional regulation of @entity5 gene products by pIE611. IMPORTANCE: Cytomegaloviruses are pathogenic b-herpesviruses persisting in a lifelong latency from which reactivation can occur under conditions of immuno-suppression, immuno- @entity2 or @entity1 . The switch from latency to reactivation requires expression of @entity4 genes. Therefore, understanding of @entity4 gene regulation might add insights into viral pathogenesis. The @entity0 cytomegalovirus ( @entity5 ) @entity4 (ie) 3 protein (611 @entity3 , pIE611) is considered essential for viral replication. The identification of novel protein isoforms derived from alternatively spliced ie3 transcripts prompted the construction of an @entity5 mutant lacking ie611, but retaining the coding capacity for the newly identified isoforms ie453 and ie310. Using   ie611 @entity5 , we demonstrate the dispensability of the canonical ie3 gene product pIE611 for viral replication and delineated pIE611-dependent changes of the @entity5 proteome. Our findings have fundamental implications for the interpretation of earlier studies on 'pIE3' functions and highlight the complex orchestration of @entity5 gene regulation.

title: The Canonical @entity4 3 Gene Product pIE611 of XXXX Cytomegalovirus Is Dispensable for Viral Replication, but Mediates Transcriptional and Post-transcriptional Regulation of Viral Gene Products.

answer: @entity0


abstract: We investigated the inhibitory effects of b   - or b   -adrenoceptor (AR) antagonists on salivary amylase secretion produced by various emetic agents, such as @entity2 , @entity8 , and @entity11 ( @entity9 ), or the non-emetic agent b(  )-AR agonist @entity7 in @entity0 . We also determined the inhibitory effect of @entity5 , a @entity3 D   -receptor antagonist, on increases in the salivary amylase activity induced by @entity8 or @entity10 , a 5-HT(3)-receptor antagonist, on @entity9 -induced increased salivary amylase activity. @entity7 (0.01 mg/kg, s.c.) produced an increase in salivary amylase and the increase was inhibited by the b(  )-AR antagonist @entity4 (5 mg/kg, s.c.) and b   -AR antagonist @entity6 (2 mg/kg, s.c.) but not by the b   -AR antagonist @entity12 (8 mg/kg, s.c.). The increased amylase activity induced by @entity2 (15 mg/kg, i.v.), @entity8 (3 mg/kg, s.c.), or @entity9 (120 mg/kg, i.p.) was inhibited significantly by @entity6 (2 mg/kg, s.c.) but not by @entity12 (8 mg/kg, s.c.). In addition, increases in amylase activities induced by @entity8 and @entity9 were inhibited significantly by @entity5 (10 mg/kg, i.v.) and @entity10 (3 mg/kg, i.v.), respectively. These results suggest that salivary amylase secretion induced by various emetogens is involved in b   -adrenoceptor activity and that salivary amylase activity is useful to detect emetogens with no direct b   -AR activation in @entity0 , a species that does not exhibit @entity1 .

title: Possible involvement of b    receptors in various emetogen-induced increases in salivary amylase activity in XXXX .

answer: @entity0


abstract: Proliferative @entity11 is the most severe form of @entity11 . Outcomes of this disease are affected by ethnicity, clinical characteristics, irreversible damage on renal biopsy, initial response to treatment and future disease course (for example, the occurrence of @entity1 ). Initial intensive (induction) treatment of proliferative @entity11 is aimed at achieving remission, but optimal duration and intensity are not well defined. A combination of intravenous @entity10 and @entity6 have been shown to decrease the risk of @entity7 , but are associated with substantial acute toxic effects (such as @entity5 ) and chronic toxic effects (such as @entity12 ). In white populations, low-dose @entity10 is a reasonable alternative to high-dose @entity10 as it is similarly effective and associated with less @entity3 . @entity13 mofetil is as effective as high-dose intravenous @entity10 in terms of inducing remission and similar in terms of safety. Although most @entity0 respond to induction treatment, remission is often only achieved after @entity0 are switched to maintenance treatment. As maintenance treatment, @entity9 is superior to @entity8 and @entity8 is similarly effective to @entity4 in terms of prevention or reducing the risk of relapse. Rituximab should be reserved for @entity0 with @entity2 . Treatment of @entity11 should be individually tailored to @entity0 , with more aggressive therapy reserved for @entity0 at high risk of @entity1 and progression of @entity1 .

title: Treatment of proliferative XXXX : a slowly changing landscape.

answer: @entity11


abstract: UNASSIGNED: Discrepancies between @entity2 RNA results assayed by different FDA-approved platforms have been reported. Plasma samples collected from 332 randomly selected clinical trial @entity0 during second year of antiretroviral treatment were assayed with 3 FDA-approved platforms: UltraSensitive Roche Amplicor Monitor, @entity3 [Monitor], Abbott RealTime @entity2 Test/m2000 [Abbott] and Roche TaqMan @entity2 Test, v2.0 [TaqMan]. Samples from 61 additional @entity0 with confirmed @entity2 RNA >50 c/mL during trial follow-up were also included. Endpoints were @entity2 RNA quantification  <= vs. >50 c/mL at an individual sample level (primary) and determination of confirmed @entity1 ( @entity1 ) from longitudinal samples. 389 @entity0 had results obtained from all assays on at least one sample (median=6). Proportions of results >50 c/mL were 19% [Monitor], 22% [TaqMan] and 25% [Abbott]. Despite indication of strong agreement (Cohen's kappa: 0.76-0.82), Abbott was more likely to detect @entity2 RNA >50 c/mL than Monitor (matched pair odds ratio [mOR]=4.2; modified Obuchowski p<0.001) and TaqMan ( @entity4 ; p<0.001); TaqMan was more likely than Monitor (mOR=2.6; p<0.001). Although strong agreement in classifying @entity1 across assay comparisons (kappa: 0.75-0.92), at a 50 c/mL threshold, differences in the probability of @entity1 classification (in the same direction as primary) were apparent (all McNemar's p<0.007). At a 200 c/mL @entity1 threshold, no differences between assays were apparent (all p>0.13). Despite strong agreement among assays, significant differences were observed with respect to detecting @entity2 RNA >50 c/mL and identifying @entity1 at the 50 c/mL threshold. This has important implications for the definition of @entity1 in clinical trials and clinical practice.

title: Comparison of Three Different FDA-Approved Plasma XXXX RNA Assay Platforms Confirm the Virologic Failure Endpoint of 200 copies/mL Despite Improved Assay Sensitivity.

answer: @entity2


abstract: BACKGROUND: Previously, when a conventional neck exploration (CNE) without preceding diagnostic imaging was the surgical treatment for @entity0 with @entity2 ( @entity2 ) solitary @entity3 were observed in 69-88% of @entity0 . The advent of @entity1 ( @entity1 ), aiming at a preoperatively identified @entity6 may be associated with a different incidence of solitary and multiglandular @entity6 . MATERIALS AND METHODS: In a cohort of 467 @entity0 with sporadic @entity2 who preferentially underwent @entity1 in four hospitals in the same geographical region, the incidence of solitary @entity3 , multiple @entity3 , and @entity4 ( @entity4 ) was evaluated. RESULTS: A total of 367 @entity0 were scheduled for @entity1 ; 100 @entity0 underwent a planned CNE. The overall surgical success rate of the first operation was 93%, and the cumulative success rate, including a second operative procedure, was 99%. Normocalcemia resulted from removing 1 abnormal PG in 426 @entity0 (91%) and more than one abnormal gland in 35 @entity0 (8%). A @entity5 was diagnosed in four of the 426 @entity0 with a single abnormal gland. @entity4 was observed in 1 @entity0 . In hospitals where diagnostic workup usually consisted of ultrasound (US) and computed tomography (CT) the incidence of solitary @entity3 was 88%, compared with 96% in hospitals where MIBI, US, and CT were used preoperatively (P  =  0.007). CONCLUSIONS: A higher frequency of solitary @entity3 was observed than historically reported. The extent of the preoperative workup influences the number of observed solitary @entity3 .

title: Shifting incidence of solitary XXXX in the era of @entity1 . A multi-institutional study.

answer: @entity3


abstract: BACKGROUND: Previously, when a conventional neck exploration (CNE) without preceding diagnostic imaging was the surgical treatment for @entity0 with @entity2 ( @entity2 ) solitary @entity3 were observed in 69-88% of @entity0 . The advent of @entity1 ( @entity1 ), aiming at a preoperatively identified @entity6 may be associated with a different incidence of solitary and multiglandular @entity6 . MATERIALS AND METHODS: In a cohort of 467 @entity0 with sporadic @entity2 who preferentially underwent @entity1 in four hospitals in the same geographical region, the incidence of solitary @entity3 , multiple @entity3 , and @entity4 ( @entity4 ) was evaluated. RESULTS: A total of 367 @entity0 were scheduled for @entity1 ; 100 @entity0 underwent a planned CNE. The overall surgical success rate of the first operation was 93%, and the cumulative success rate, including a second operative procedure, was 99%. Normocalcemia resulted from removing 1 abnormal PG in 426 @entity0 (91%) and more than one abnormal gland in 35 @entity0 (8%). A @entity5 was diagnosed in four of the 426 @entity0 with a single abnormal gland. @entity4 was observed in 1 @entity0 . In hospitals where diagnostic workup usually consisted of ultrasound (US) and computed tomography (CT) the incidence of solitary @entity3 was 88%, compared with 96% in hospitals where MIBI, US, and CT were used preoperatively (P  =  0.007). CONCLUSIONS: A higher frequency of solitary @entity3 was observed than historically reported. The extent of the preoperative workup influences the number of observed solitary @entity3 .

title: Shifting incidence of solitary @entity3 in the era of XXXX . A multi-institutional study.

answer: @entity1


abstract: OBJECTIVE: To investigate the early diagnosis and treatment of @entity2 ( @entity2 ) complicated by testicular @entity8 (TART). METHODS: We retrospectively analyzed the clinical data of 1 case of late-onset @entity2 complicated by TART diagnosed and treated in Xiamen @entity0 and @entity0 Health Care Hospital. RESULTS: The @entity0 was a 15 years old @entity0 , short statured and dark skinned, with skin pigmentation in the gum and external genital, secondary sex characteristics of the adult and irregular tubercles palpable in the bilateral testes. Laboratory examinations showed obviously increased levels of ACTH, 17-KS, @entity6 -S and @entity4 and evidently decreased levels of FSH, LH and CO. The low-dose @entity1 suppression test reduced ACTH and @entity6 -S to normal. Imaging examinations revealed soft tissue density in the bilateral adrenal glands, especially on the right, and irregularly increased volume of the bilateral testes, particularly on the left, with heterogeneous signals and septas and surrounded by the fluid signals. Histopathological examinations showed the eosinophilic cytoplasm to be polygon- or round-shaped, interstitium-like cells arranged in line, and lipopigment in the endochylema. Immunohistochemical results were negative for @entity7 . The clinical signs of the @entity0 were improved after 3 months of @entity1 treatment, the hyperplastic nodules in the left @entity3 decreased obviously and those in the right @entity3 disappeared after 6 months, and the hyperplastic nodules in the adrenal glands vanished after 9 months. CONCLUSION: Based on the clinical manifestations and the results of auxiliary examinations, this case was diagnosed as late-onset @entity2 complicated by TART, which was attributed to the continued surge of ACTH induced by @entity5 . Sufficient @entity1 treatment could make the TART decrease or disappear and the @entity2 vanish; it could also improve the clinical symptoms and bring the laboratory results to normal.

title: [ @entity2 complicated by testicular XXXX : one-case clinical analysis].

answer: @entity8


abstract: OBJECTIVE: To investigate the early diagnosis and treatment of @entity2 ( @entity2 ) complicated by testicular @entity8 (TART). METHODS: We retrospectively analyzed the clinical data of 1 case of late-onset @entity2 complicated by TART diagnosed and treated in Xiamen @entity0 and @entity0 Health Care Hospital. RESULTS: The @entity0 was a 15 years old @entity0 , short statured and dark skinned, with skin pigmentation in the gum and external genital, secondary sex characteristics of the adult and irregular tubercles palpable in the bilateral testes. Laboratory examinations showed obviously increased levels of ACTH, 17-KS, @entity6 -S and @entity4 and evidently decreased levels of FSH, LH and CO. The low-dose @entity1 suppression test reduced ACTH and @entity6 -S to normal. Imaging examinations revealed soft tissue density in the bilateral adrenal glands, especially on the right, and irregularly increased volume of the bilateral testes, particularly on the left, with heterogeneous signals and septas and surrounded by the fluid signals. Histopathological examinations showed the eosinophilic cytoplasm to be polygon- or round-shaped, interstitium-like cells arranged in line, and lipopigment in the endochylema. Immunohistochemical results were negative for @entity7 . The clinical signs of the @entity0 were improved after 3 months of @entity1 treatment, the hyperplastic nodules in the left @entity3 decreased obviously and those in the right @entity3 disappeared after 6 months, and the hyperplastic nodules in the adrenal glands vanished after 9 months. CONCLUSION: Based on the clinical manifestations and the results of auxiliary examinations, this case was diagnosed as late-onset @entity2 complicated by TART, which was attributed to the continued surge of ACTH induced by @entity5 . Sufficient @entity1 treatment could make the TART decrease or disappear and the @entity2 vanish; it could also improve the clinical symptoms and bring the laboratory results to normal.

title: [ XXXX complicated by testicular @entity8 : one-case clinical analysis].

answer: @entity2


abstract: To investigate the cellular mechanisms of pressure-overload @entity3 transition to @entity2 , we observed time course of changes in morphology and contractile function of cardiomyocytes in transverse abdominal aortic constriction (TAC) @entity0 . Since TAC @entity0 suffered higher stress, body weight had a slower growth rate compared with that of synchronous control @entity0 . Therefore, the left ventricular to body weight ratio produced experimental bias to evaluate the degree of @entity3 . Length and width of collagenase-isolated cardiomyocyte were directly measured. Length, width and calculated surface area of cardiomyocyte showed a progressive increase in 8-, 16-, and 20-week TAC @entity0 . The increasing rate of surface area in cardiomyocytes was higher at the middle stage of TAC (from the eighth to sixteenth week). Due to the constraint of @entity1 formation, the increasing rate of surface area in cardiomyocytes was slower at the late stage of @entity4 (from the sixteenth to twentieth week). The sarcomere length of cardiomyocytes was unchanged, whereas sarcomere numbers were significantly increased in 8-, 16-, and 20-week TAC @entity0 . Shortening amplitude of unloaded contraction in single cardiomyocyte was significantly enhanced in 1-week TAC @entity0 , but not altered in 8-week TAC @entity0 compared with that in the synchronous control @entity0 . On the contrary, unloaded shortening amplitude of single cardiomyocyte was significantly reduced in 16- and 20-week TAC @entity0 . The above results suggest that the reduced shortening amplitude may be associated with intrinsic molecular alterations in hypertrophied cardiomyocytes.

title: [ XXXX and changes in contractile function of cardiomyocyte].

answer: @entity3


abstract: Severe @entity5 is associated with significant @entity2 . We therefore investigated the effects of systemic therapy on the cardiovascular risk of @entity5 @entity0 . Thirteen consecutive @entity0 receiving @entity6 esters were included and followed for 24  weeks both clinically and by means of laboratory monitoring, 10 completed the study. Eight of ten @entity0 showed a PASI-50 response. Two of three @entity0 with clinical insulin resistance (Homeostasis Model Assessment of insulin resistance >2.5) showed normal insulin responsiveness at the end of the study. Clinical improvement was paralleled by a reduction of high-sensitive CRP serum levels (median -25%). There was a trend toward reduced serum levels for the @entity1 (median -10%) and resistin (median -4%), while the potentially cardio-protective @entity4 showed a trend toward increased serum levels under therapy (median +19%). Systemic endothelial function assessed by venous occlusion plethysmography revealed an improvement of endothelial vasodilator function after 24  weeks of treatment (p  <  0.02). This is the first prospective study documenting an amelioration of endothelial cell function in @entity0 with moderate-to-severe @entity5 under effective continuous systemic therapy. Future studies need to compare the cardioprotective effects of different treatment modalities, based on hard end points such as the rate of @entity3 .

title: Systemic therapy of XXXX ameliorates endothelial cell function: results of a prospective longitudinal pilot trial.

answer: @entity5


abstract: We have previously reported (Samelson, L.E., Patel, M.D., Weissman, A.M., Harford, J.B., and Klausner, R.D. (1986) Cell 46, 1083-1090) that T cell activation by antigen is associated with activation of two biochemical pathways. In this scheme two protein kinases are activated by stimulation of the @entity5 ( @entity5 ). These kinases phosphorylate two different chains of the @entity5 complex. Protein kinase C is responsible for the phosphorylation of the gamma, and, to a lesser extent, the epsilon chains of the receptor on @entity1 residues while the activation of an unidentified @entity2 kinase leads to phosphorylation of the p21 subunit of the receptor on @entity2 residues. In addition to activation by specific antigens, T cells can be functionally activated in vitro by the addition of antibodies that bind either the antigen receptor or the @entity4 molecule, an entity independent of the receptor. We have used antibodies directed against these molecules and show that they result in the same dual kinase activation observed with antigen stimulation. In addition we have compared the three ligands, antigen, and antibodies directed against the epsilon chain of the @entity5 or against @entity4 , in terms of how they couple to the two kinase pathways. Activation of @entity3 breakdown and @entity5 phosphorylation on @entity1 by all three stimuli are sensitive to @entity0 inhibition. In contrast, only antigen-stimulated @entity2 kinase activation is sensitive to @entity0 while the two antibody reagents activate the @entity2 kinase in a manner that is entirely insensitive to @entity0 inhibition.

title: T cell receptor XXXX phosphorylation. Variable coupling for different activating ligands.

answer: @entity2


abstract: PURPOSE: To evaluate the antiurolithiatic activity of Pinus eldarica fruit on induced @entity3 @entity2 in @entity0 . MATERIALS AND METHODS: @entity3 @entity2 in @entity0 was induced by administering @entity4 1% for 30 days via drinking water. The prophylactic and therapeutic groups received P. eldarica fruit extract (500 and 1000 mg/kg/day) as well for 30 days and from the 14th day through the end of the experiment, respectively. The following variables were assessed; urine volume, urinary @entity1 excretion, and crystalluria. Finally, @entity0 ' kidneys were histopathologically examined. RESULTS: The aqueous extract prophylactic treatment (500 mg/kg/day) increased urinary @entity1 excretion. Qualitative analysis of crystalluria and histopathologic examination showed that the administered dose of extract prevented stone formation in the kidneys significantly. The prophylactic treatment did not increase urine volume in comparison with @entity4 . Stone formation did not decrease in the treatment group. CONCLUSION: This study indicates that P. eldarica fruit extract prevents @entity3 deposition, without producing diuresis.

title: Antiurolithiatic activity of Pinus eldarica medw: fruits aqueous extract in XXXX .

answer: @entity0


abstract: In the last thirty decade, with the emergence of new trends in molecular biology and advances in high-throughput technologies, much progress has been made in basic renal physiology. Molecular genetics has allowed the identification and elucidation of the structure, function and effects of the mutations of several of the main transporters and ion channels involved in @entity0 . Some @entity0 , such as @entity4 and @entity7 , have been found to be due to mutations in genes @entity10 (type I) (See the section "Molecular biology and genotype-phenotype correlation in @entity3 ") and @entity5 (type II and type III), (See the section "Molecular biology and genotype-phenotype correlation in @entity3 ") and in @entity9 , respectively. @entity6 , a rare cause of @entity2 , is now known to be caused by a mutation in tubular transport, due to a mutation in the @entity8 gene, encoding for a Na+ channel protein (ENaC). Nevertheless, numerous issues remain unsettled and warrant additional research. These important advances and discoveries are not without limitations and challenges as changes in individual gene expression do not always translate into changes in its protein or protein modification. This raises proteomics as the most logical next step in our understanding of biological processes, as proteins from these deregulated genes are the functional agents in the cells. Proteomics takes a global and comprehensive view of a system, involving in many cases some notion of high throughput; but in contrast to genomics, there is no single biochemical method that can be used for the analysis of all proteins. Genomics and proteomics can complement each other in clinical applications by balancing the strengths and weaknesses of each individual technology. Several proteomics approaches have been exploited to shed more light on the molecular pathophysiology of several @entity1 , such as @entity3 , and have provided important insights into the defective molecular mechanisms underlying these @entity0 . Here we summarize several of the most important discoveries arising from molecular genetic and proteomic studies on @entity1 and show how these results can complement each other to increase our comprehension of these disorders at the molecular level.

title: Proteomics and XXXX .

answer: @entity0


abstract: The results of treatment of @entity1 with a Milwaukee brace were studied in 133 @entity0 (127 @entity0 and six @entity0 ) whose ages ranged from eight years and five months to sixteen years and two months at the beginning of treatment. These 133 @entity0 had 192 separate curves (119 right thoracic, thirty-nine high lumbar, twelve thoracolumbar, and twenty-two high left thoracic). Of these @entity0 , seventy-four with 109 curves were followed for five years or more after the brace was discontinued (average, eight years; range, five to thirteen years); twenty-nine @entity0 were treated surgically because of a poor response to the brace or progression of the curve; and thirty @entity0 were lost to follow-up. More than 80 per cent of the seventy-four @entity0 followed for five years or more showed some increase of their curves after the brace was discontinued. The average correction at follow-up compared with the original curve was 2 degrees for thoracic curves (range, -18 to 24 degrees) and 4 degrees for the thoracolumbar and lumbar curves (range, -11 to 17 degrees). The brace was more effective for curves of less than 40 degrees. More than one-third of the @entity0 with curves of 40 degrees or more eventually required surgical treatment. Age, curve pattern, and status of the iliac and ring epiphyses did not correlate withe response to brace treatment. The best guideline for prediction of the results of brace treatment was the response of the curve to the brace, especially during the first year of treatment. If the curve is reduced in the brace to less than 50 per cent of its initial measurement, there is a good chance of obtaining significant permanent correction.

title: Treatment of XXXX in the Milwaukee brace.

answer: @entity1


abstract: The ontogeny of optic fiber patterns within the @entity1 retina has been studied in @entity0 -stained serial sections and whole mounts. Ganglion cell axons ("pioneers") appear much earlier than previously recognized, at Nieuwkoop-Faber ('56) Stage 28. Fibers fasciculate into bundles as they arise in the retina and reach the chiasma by NF Stage 32. Because the retina grows in rings at its margins, @entity2 cell axons differentiate at the periphery and join the nearest fiber bundles (fascicles) to reach the optical disc. A radial fascicle pattern develops by Stage X (Grant et al., '80) within the optic fiber layer of the retina and acts as a template of pathways that lead all later appearing fibers out of the retina. Since the retina grows asymmetrically along its dorso-ventral axis, the fascicle pattern develops asymmetrically, with dorsal quadrant fascicles forming an arcuate pattern in contrast to shorter, thicker ventral quadrant fascicles. The growth pattern of the retina and the "principle" of fiber following suggest that "positional information" is acquired by @entity2 cells according to a system of polar coordinates (MacDonald, '77). A radial distance "r" from the center is determined temporarily by @entity2 cell birthday and an angular value "theta" is given by the angular position of the fascicle followed by its axons to the optical disc. Wedges of @entity2 cells send their axons into a common fascicle which retains its integrity as it leaves the retina at the optic disc. This pattern of optic fiber development suggests a model for retino-topic ordering of the optic fiber projection in @entity1 , with the fascicle acting as the "pattern-forming unit of connectivity."

title: Ontogeny of the retina and optic nerve in XXXX . II. Ontogeny of the optic fiber pattern in the retina.

answer: @entity1


abstract: The neutral proteinase elastase is released from polymorphonuclear (PMN) leukocytes in various physiological and pathological conditions. Aim of the present study was to gain further insight into the mechanisms which govern the liberation of this proteinase. Therefore, the effects of the @entity1 ionophore @entity4 and of the protein kinase C activator @entity5 ( @entity6 ) on neutrophils were investigated in @entity0 whole-blood samples. Furthermore, the inhibitory effects of the @entity1 channel blocker @entity3 and of the calmodulin blocker @entity7 were followed. @entity4 induced a release of elastase from neutrophils in a dose- and time-dependent manner. Complexation of extracellular @entity1 by @entity8 ( @entity2 ) completely abolished the stimulatory effect of @entity4 . In a concentration of 10(-4) M @entity3 was capable of attenuating (-49%) the @entity4 -induced secretion of @entity9 . Besides the increase in intracellular @entity1 concentration, the activation of protein kinase C by @entity6 did also cause a release of neutrophil elastase. This release was strictly depending on the concentration of @entity6 and the time of incubation. In contrast to the stimulatory effect of @entity4 , the @entity6 -induced liberation of neutrophil elastase was attenuated, but not completely abolished, by complexation of extracellular @entity1 with @entity2 . Both 10(-4) M @entity3 (-43%) and 10(-5) M @entity7 (-42%) were able to reduce the @entity6 -induced release of neutrophil elastase. Based upon these data, we conclude that both the translocation of @entity1 intracellularly by @entity4 and the activation of protein kinase C by @entity6 stimulate the release of neutrophil elastase. @entity3 and @entity7 were capable of suppressing the stimulation of elastase release.

title: Stimulation and inhibition of elastase release from @entity0 neutrophil-dependence on the XXXX messenger system.

answer: @entity1


abstract: The neutral proteinase elastase is released from polymorphonuclear (PMN) leukocytes in various physiological and pathological conditions. Aim of the present study was to gain further insight into the mechanisms which govern the liberation of this proteinase. Therefore, the effects of the @entity1 ionophore @entity4 and of the protein kinase C activator @entity5 ( @entity6 ) on neutrophils were investigated in @entity0 whole-blood samples. Furthermore, the inhibitory effects of the @entity1 channel blocker @entity3 and of the calmodulin blocker @entity7 were followed. @entity4 induced a release of elastase from neutrophils in a dose- and time-dependent manner. Complexation of extracellular @entity1 by @entity8 ( @entity2 ) completely abolished the stimulatory effect of @entity4 . In a concentration of 10(-4) M @entity3 was capable of attenuating (-49%) the @entity4 -induced secretion of @entity9 . Besides the increase in intracellular @entity1 concentration, the activation of protein kinase C by @entity6 did also cause a release of neutrophil elastase. This release was strictly depending on the concentration of @entity6 and the time of incubation. In contrast to the stimulatory effect of @entity4 , the @entity6 -induced liberation of neutrophil elastase was attenuated, but not completely abolished, by complexation of extracellular @entity1 with @entity2 . Both 10(-4) M @entity3 (-43%) and 10(-5) M @entity7 (-42%) were able to reduce the @entity6 -induced release of neutrophil elastase. Based upon these data, we conclude that both the translocation of @entity1 intracellularly by @entity4 and the activation of protein kinase C by @entity6 stimulate the release of neutrophil elastase. @entity3 and @entity7 were capable of suppressing the stimulation of elastase release.

title: Stimulation and inhibition of elastase release from XXXX neutrophil-dependence on the @entity1 messenger system.

answer: @entity0


abstract: AIM: To investigate the effect of @entity5 ( @entity4 ) on expression of Fas/ @entity0 mRNA during @entity1 /reperfusion injury (PI/RI) in the @entity2 . METHODS: Single @entity1 /reperfusion animal model was used in this study. The @entity2 were randomly divided into three groups (n = 30, in each): sham operated group (Sham), I/R group (I/R) and I/R + @entity4 group (I/R + @entity4 ). Changes of several parameters which included apoptotic index (AI), wet to dry ratio of lung tissue weight (W/D) and index of quantitative assessment of histologic @entity3 (IQA) were measured at 1h, 3h, 5h after reperfusion in lung tissue. Meanwhile the location and expression of Fas/ @entity0 mRNA were observed. Lung tissue was prepared for light microscopic and electron microscopic ob servation at 1 h, 3 h, 5 h after reperfusion. RESULTS: As compared with group I/R, Fas/ @entity0 mRNA slightly expressed in intima and extima of small pulmonary artery, alveoli, and bronchiole epithelia in group @entity4 . The values of AI, W/D and IQA showed significantly lower in group I/R + @entity4 than that in group I/R at 1 h, 3 h, 5 h after reperfusion in lung tissue (P < 0.01 and P < 0.05). Meanwhile, abnormal changes of the lung tissue in morphologically were lessen markedly in group I/R + @entity4 . CONCLUSION: @entity5 has notable protective effects on PI/RI in @entity2 by inhibiting Fas/ @entity0 mRNA express in lung tissue and decreasing apoptosis.

title: [Effect of @entity5 on expression of Fas/ XXXX in @entity3 induced by @entity1 /reperfusion in @entity2 ].

answer: @entity0


abstract: AIM: To investigate the effect of @entity5 ( @entity4 ) on expression of Fas/ @entity0 mRNA during @entity1 /reperfusion injury (PI/RI) in the @entity2 . METHODS: Single @entity1 /reperfusion animal model was used in this study. The @entity2 were randomly divided into three groups (n = 30, in each): sham operated group (Sham), I/R group (I/R) and I/R + @entity4 group (I/R + @entity4 ). Changes of several parameters which included apoptotic index (AI), wet to dry ratio of lung tissue weight (W/D) and index of quantitative assessment of histologic @entity3 (IQA) were measured at 1h, 3h, 5h after reperfusion in lung tissue. Meanwhile the location and expression of Fas/ @entity0 mRNA were observed. Lung tissue was prepared for light microscopic and electron microscopic ob servation at 1 h, 3 h, 5 h after reperfusion. RESULTS: As compared with group I/R, Fas/ @entity0 mRNA slightly expressed in intima and extima of small pulmonary artery, alveoli, and bronchiole epithelia in group @entity4 . The values of AI, W/D and IQA showed significantly lower in group I/R + @entity4 than that in group I/R at 1 h, 3 h, 5 h after reperfusion in lung tissue (P < 0.01 and P < 0.05). Meanwhile, abnormal changes of the lung tissue in morphologically were lessen markedly in group I/R + @entity4 . CONCLUSION: @entity5 has notable protective effects on PI/RI in @entity2 by inhibiting Fas/ @entity0 mRNA express in lung tissue and decreasing apoptosis.

title: [Effect of @entity5 on expression of Fas/ @entity0 in @entity3 induced by @entity1 /reperfusion in XXXX ].

answer: @entity2


abstract: AIM: To investigate the effect of @entity5 ( @entity4 ) on expression of Fas/ @entity0 mRNA during @entity1 /reperfusion injury (PI/RI) in the @entity2 . METHODS: Single @entity1 /reperfusion animal model was used in this study. The @entity2 were randomly divided into three groups (n = 30, in each): sham operated group (Sham), I/R group (I/R) and I/R + @entity4 group (I/R + @entity4 ). Changes of several parameters which included apoptotic index (AI), wet to dry ratio of lung tissue weight (W/D) and index of quantitative assessment of histologic @entity3 (IQA) were measured at 1h, 3h, 5h after reperfusion in lung tissue. Meanwhile the location and expression of Fas/ @entity0 mRNA were observed. Lung tissue was prepared for light microscopic and electron microscopic ob servation at 1 h, 3 h, 5 h after reperfusion. RESULTS: As compared with group I/R, Fas/ @entity0 mRNA slightly expressed in intima and extima of small pulmonary artery, alveoli, and bronchiole epithelia in group @entity4 . The values of AI, W/D and IQA showed significantly lower in group I/R + @entity4 than that in group I/R at 1 h, 3 h, 5 h after reperfusion in lung tissue (P < 0.01 and P < 0.05). Meanwhile, abnormal changes of the lung tissue in morphologically were lessen markedly in group I/R + @entity4 . CONCLUSION: @entity5 has notable protective effects on PI/RI in @entity2 by inhibiting Fas/ @entity0 mRNA express in lung tissue and decreasing apoptosis.

title: [Effect of @entity5 on expression of Fas/ @entity0 in XXXX induced by @entity1 /reperfusion in @entity2 ].

answer: @entity3


abstract: AIM: To investigate the effect of @entity5 ( @entity4 ) on expression of Fas/ @entity0 mRNA during @entity1 /reperfusion injury (PI/RI) in the @entity2 . METHODS: Single @entity1 /reperfusion animal model was used in this study. The @entity2 were randomly divided into three groups (n = 30, in each): sham operated group (Sham), I/R group (I/R) and I/R + @entity4 group (I/R + @entity4 ). Changes of several parameters which included apoptotic index (AI), wet to dry ratio of lung tissue weight (W/D) and index of quantitative assessment of histologic @entity3 (IQA) were measured at 1h, 3h, 5h after reperfusion in lung tissue. Meanwhile the location and expression of Fas/ @entity0 mRNA were observed. Lung tissue was prepared for light microscopic and electron microscopic ob servation at 1 h, 3 h, 5 h after reperfusion. RESULTS: As compared with group I/R, Fas/ @entity0 mRNA slightly expressed in intima and extima of small pulmonary artery, alveoli, and bronchiole epithelia in group @entity4 . The values of AI, W/D and IQA showed significantly lower in group I/R + @entity4 than that in group I/R at 1 h, 3 h, 5 h after reperfusion in lung tissue (P < 0.01 and P < 0.05). Meanwhile, abnormal changes of the lung tissue in morphologically were lessen markedly in group I/R + @entity4 . CONCLUSION: @entity5 has notable protective effects on PI/RI in @entity2 by inhibiting Fas/ @entity0 mRNA express in lung tissue and decreasing apoptosis.

title: [Effect of XXXX on expression of Fas/ @entity0 in @entity3 induced by @entity1 /reperfusion in @entity2 ].

answer: @entity5


abstract: AIM: To investigate the effect of @entity5 ( @entity4 ) on expression of Fas/ @entity0 mRNA during @entity1 /reperfusion injury (PI/RI) in the @entity2 . METHODS: Single @entity1 /reperfusion animal model was used in this study. The @entity2 were randomly divided into three groups (n = 30, in each): sham operated group (Sham), I/R group (I/R) and I/R + @entity4 group (I/R + @entity4 ). Changes of several parameters which included apoptotic index (AI), wet to dry ratio of lung tissue weight (W/D) and index of quantitative assessment of histologic @entity3 (IQA) were measured at 1h, 3h, 5h after reperfusion in lung tissue. Meanwhile the location and expression of Fas/ @entity0 mRNA were observed. Lung tissue was prepared for light microscopic and electron microscopic ob servation at 1 h, 3 h, 5 h after reperfusion. RESULTS: As compared with group I/R, Fas/ @entity0 mRNA slightly expressed in intima and extima of small pulmonary artery, alveoli, and bronchiole epithelia in group @entity4 . The values of AI, W/D and IQA showed significantly lower in group I/R + @entity4 than that in group I/R at 1 h, 3 h, 5 h after reperfusion in lung tissue (P < 0.01 and P < 0.05). Meanwhile, abnormal changes of the lung tissue in morphologically were lessen markedly in group I/R + @entity4 . CONCLUSION: @entity5 has notable protective effects on PI/RI in @entity2 by inhibiting Fas/ @entity0 mRNA express in lung tissue and decreasing apoptosis.

title: [Effect of @entity5 on expression of Fas/ @entity0 in @entity3 induced by XXXX /reperfusion in @entity2 ].

answer: @entity1


abstract: OBJECTIVES: We systematically reviewed the literature on surgical and nonsurgical treatments for @entity0 and @entity0 with @entity3 and @entity3 with concomitant lip-tie. DATA SOURCES: We searched MEDLINE(  ) (PubMed(  )), PsycINFO(  ), Cumulative Index of Nursing and Allied Health Literature (CINAHL(  )) and Embase (Excerpta Medica Database), as well as the reference lists of included studies and recent systematic reviews. We conducted the searches between September 2013 and August 2014. REVIEW METHODS: We included studies of interventions for @entity3 published in English. Two investigators independently screened studies against predetermined inclusion criteria and independently rated the quality of included studies. We extracted data into evidence tables and summarized them qualitatively. RESULTS: We included 58 unique studies comprising 6 randomized controlled trials (RCTs) (3 good, 1 fair, 2 poor quality), 3 cohort studies (all poor quality), 33 case series, 15 case reports, and 1 unpublished thesis. Most studies assessed the effects of frenotomy (a procedure in which the lingual frenulum is divided) on breastfeeding-related outcomes. Four RCTs reported improvements in breastfeeding efficacy using either maternally reported or observer ratings, while two RCTs using observer ratings found no improvement. Mothers consistently reported improved breastfeeding effectiveness after frenotomy, but outcome measures were heterogeneous and short term. Future studies could provide additional data to confirm or change the measure of effectiveness; thus, we consider the strength of evidence (SOE; confidence in the estimate of effect) to be low at this time. Furthermore, this literature is characterized by (1) a lack of details about the surgical procedure, (2) cointerventions allowed variably in control groups, and (3) diversity of provider settings. @entity1 outcomes improved for mothers of frenotomized @entity0 compared with control in one study of 6-day old @entity0 but not in studies of @entity0 a few weeks older. Given these inconsistencies and the small number of comparative studies and @entity0 , the SOE is low for an immediate reduction in @entity1 . Three studies with significant limitations reported improvements in other feeding outcomes with frenotomy, and four poor-quality studies reported some improvements in speech articulation but mixed results related to overall speech sound production. Three poor-quality comparative studies noted some improvements in social concerns and gains in tongue mobility in treated @entity0 . SOE for all of these outcomes is insufficient. SOE is moderate for minor and short-term @entity2 following surgery and insufficient for other harms (reoperation, @entity1 ). CONCLUSIONS: A small body of evidence suggests that frenotomy may be associated with improvements in breastfeeding as reported by mothers, and potentially in @entity1 , but with small short-term studies, inconsistently conducted, SOE is generally low to insufficient. Comparative studies reported improvements in some measures of speech, but assessment of outcomes was inconsistent. Few studies addressed tongue mobility and self-esteem issues. Research is lacking on nonsurgical interventions, as well as on outcomes other than breastfeeding.

title: Treatments for @entity3 and XXXX With Concomitant Lip-Tie

answer: @entity3


abstract: OBJECTIVES: We systematically reviewed the literature on surgical and nonsurgical treatments for @entity0 and @entity0 with @entity3 and @entity3 with concomitant lip-tie. DATA SOURCES: We searched MEDLINE(  ) (PubMed(  )), PsycINFO(  ), Cumulative Index of Nursing and Allied Health Literature (CINAHL(  )) and Embase (Excerpta Medica Database), as well as the reference lists of included studies and recent systematic reviews. We conducted the searches between September 2013 and August 2014. REVIEW METHODS: We included studies of interventions for @entity3 published in English. Two investigators independently screened studies against predetermined inclusion criteria and independently rated the quality of included studies. We extracted data into evidence tables and summarized them qualitatively. RESULTS: We included 58 unique studies comprising 6 randomized controlled trials (RCTs) (3 good, 1 fair, 2 poor quality), 3 cohort studies (all poor quality), 33 case series, 15 case reports, and 1 unpublished thesis. Most studies assessed the effects of frenotomy (a procedure in which the lingual frenulum is divided) on breastfeeding-related outcomes. Four RCTs reported improvements in breastfeeding efficacy using either maternally reported or observer ratings, while two RCTs using observer ratings found no improvement. Mothers consistently reported improved breastfeeding effectiveness after frenotomy, but outcome measures were heterogeneous and short term. Future studies could provide additional data to confirm or change the measure of effectiveness; thus, we consider the strength of evidence (SOE; confidence in the estimate of effect) to be low at this time. Furthermore, this literature is characterized by (1) a lack of details about the surgical procedure, (2) cointerventions allowed variably in control groups, and (3) diversity of provider settings. @entity1 outcomes improved for mothers of frenotomized @entity0 compared with control in one study of 6-day old @entity0 but not in studies of @entity0 a few weeks older. Given these inconsistencies and the small number of comparative studies and @entity0 , the SOE is low for an immediate reduction in @entity1 . Three studies with significant limitations reported improvements in other feeding outcomes with frenotomy, and four poor-quality studies reported some improvements in speech articulation but mixed results related to overall speech sound production. Three poor-quality comparative studies noted some improvements in social concerns and gains in tongue mobility in treated @entity0 . SOE for all of these outcomes is insufficient. SOE is moderate for minor and short-term @entity2 following surgery and insufficient for other harms (reoperation, @entity1 ). CONCLUSIONS: A small body of evidence suggests that frenotomy may be associated with improvements in breastfeeding as reported by mothers, and potentially in @entity1 , but with small short-term studies, inconsistently conducted, SOE is generally low to insufficient. Comparative studies reported improvements in some measures of speech, but assessment of outcomes was inconsistent. Few studies addressed tongue mobility and self-esteem issues. Research is lacking on nonsurgical interventions, as well as on outcomes other than breastfeeding.

title: Treatments for XXXX and @entity3 With Concomitant Lip-Tie

answer: @entity3


abstract: Interferons (IFNs) have been shown to suppress the proliferation of @entity0 pluripotent hematopoietic progenitor cells, CFU-GEMM, and committed erythroid (BFU-E, CFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. However, no information is yet available concerning the effect of IFNs on @entity0 megakaryocytic progenitor cells CFU-Mk. Furthermore the mechanisms underlying the inhibitory activity of IFNs are still controversial. Therefore highly purified recombinant IFN preparations, rIFN-alpha and @entity1 , were assessed for their influence on in vitro growth of @entity0 bone marrow-derived CFU-Mk as well as CFU-GEMM. In addition, the role of hematopoietic accessory cells, that is, adherent cells and T lymphocytes, in the mediation of the suppressive effect of rIFNs was examined. When added to unseparated bone marrow cells, both rIFN preparations significantly inhibited colony formation with 50% inhibition of CFU-Mk occurring at 22 U/mL for rIFN-alpha and 59 U/mL for @entity1 , while 50% inhibition of CFU-GEMM occurred at 59 U/mL for rIFN-alpha and 101 U/mL for @entity1 . The suppressive effect of rIFN-alpha and @entity1 was selectively abolished by monoclonal antibodies (MoAbs) against rIFN-alpha and @entity1 , thus confirming that the inhibitory activity was due to the rIFN preparations used. The antiproliferative effect of rIFN-alpha and @entity1 on CFU-GEMM growth was not associated with a decrease in the percentage of mixed colonies containing megakaryocytic cells as assessed by use of the MoAb C17.28 against platelet glycoprotein IIIa. Removal of adherent cells and T lymphocytes from the target bone marrow cells had no influence on the suppressive effect of rIFN-alpha, whereas it significantly reduced the inhibitory effect of @entity1 on the growth of megakaryocytic colonies and the other hematopoietic progenitors. The data indicate that (1) @entity0 megakaryocytopoiesis is markedly inhibited by rIFN-alpha and @entity1 , and (2) the inhibitory effect of rIFN-alpha is due to a direct action on hematopoietic progenitor cells, whereas the effect of @entity1 is mediated to a significant degree through accessory cell populations.

title: Effect of recombinant interferons alpha and gamma on XXXX bone marrow-derived megakaryocytic progenitor cells.

answer: @entity0


abstract: BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is currently considered the gold standard treatment for morbid @entity1 . The learning curve for this procedure is about 100 cases, and it is considered the most important factor in decreasing complications and mortality. We present our experience and learning curve with LRYGB. METHODS: The data was collected prospectively. All @entity0 with primary LRYGB between March 2006 and April 2014 were included. Only @entity0 with full data on demographics, length of stay, operating time, and complications were included in the study. RESULTS: Five hundred and eleven @entity0 underwent a LRYGB. Ninety five of them underwent a redo RYGB (conversion), and were excluded. Of the remaining 416 @entity0 , full data was available for 326 and the statistical analysis refers to this group. The complication rate was available for all @entity0 who were included in the study. The mean age and body mass index were 43 years (14-76 years) and 42.8 kg/m2 (34-76) respectively. The mean duration of surgery was 86 minutes (40-420). In the first 100 @entity0 , operating time was 148 min, while in the last 125 @entity0 it was 75 min. The major perioperative complication rate was 7.7%. Of 4 leaks (0.95%, 3 were encountered in the first 100 operations, and one in the following 316 (3% and 0.3% respectively). The mean length of stay was 2.2 days (1-46). None of the @entity0 stayed in the intensive care unit. There was no mortality. CONCLUSIONS: LRYGB is very safe. We confirm that the learning curve for this procedure is more than 100 cases. Appropriate training is crucial.

title: [Learning curve in laparoscopic Roux-en-Y gastric bypass for the treatment of morbid XXXX ].

answer: @entity1


abstract: OBJECTIVES: It is known that infections with @entity2 ) types 6, 11, 16, and 18, cause @entity0 ( @entity0 ), cervical intraepithelial neoplastic lesions (types 1 to 3; CIN 1-3), and genital warts (GW). Together with equivocal cytological abnormalities (ECA), these place a considerable burden on society, but the costs and resource usage are not easily estimated. Therefore, we undertook this study to estimate the burden and costs associated with @entity1 . METHODS: We used Finnish registry-based data for @entity0 , CIN 1-3 and ECA. Data on GW were estimated from associated procedures and medications. The annual burden of disease was estimated from hospitalizations, visits to specialists and primary level care, and pharmaceutical use. The evaluation of costs included health care and screening costs, and productivity lost (separately). Due to the data obtained being fragmented, 2 cost scenarios were constructed. RESULTS: The follow-up of ECA appears to be the most important cost driver. GW should not be underestimated as they affect both genders at an early age. CONCLUSIONS: @entity3 are a burden to society, not only as a result of @entity0 , but also costs related to other diseases and indirect costs in the form of lost productivity.

title: The annual costs associated with XXXX types 6, 11, 16, and 18 infections in Finland.

answer: @entity2


abstract: BACKGROUND: Endophtalmitis post @entity0 surgery is one of most feared and devastating complications resulting in serious consequences and an uncertain visual prognosis. Antimicrobial prophylaxis against endophtalmitis must be based on the best knowledge of conjuntival microbiota. OBJECTIVE: To establish microbiological basis for the best antibiotic prophylaxis to prevent @entity6 in @entity0 surgery. MATERIALS AND METHODS: A descriptive, cross-sectional, prospective study. A preoperative conjunctival sample was taken from the lower fornix of 118 pacients, sowing it immediately in culture media. Identification of growing colonies and susceptibility testing were performed by manual or automated methods. RESULTS: 106 (89.8%) of 118 preoperative cultures were positive. 159 bacteria were isolated in single or mixed flora, with 95% of Gram positive organisms. Staphylococci represented 76.1% of isolated bacteria, with 82.6% of coagulase-negative staphylococci (SCN) and 17.4% of @entity2 . Forty two percent of SCN and 38% of @entity2 were @entity7 resistan; both groups showed high susceptibility to @entity5 and fourth-generation @entity4 . CONCLUSIONS: we recommend the use of topical @entity5 as pre-operative antimicrobial prophylaxis associated with @entity8 antisepsis. A fourth-generation @entity3 is recommended when there is risk of @entity1 .

title: [Microbial flora isolated from patient's conjunctiva previous to XXXX surgery].

answer: @entity0


abstract: Several promising anticancer drug candidates have been sidelined owing to their poor physicochemical properties or unfavorable pharmacokinetics, resulting in high overall cost of drug discovery and development. Use of alternative formulation strategies that alleviate these issues can help advance new molecules to the clinic at a significantly lower cost. @entity5 is a natural product with potent anticancer activity. Its clinical trial was discontinued following the @entity3 . To improve the safety and potency of @entity5 , we formulated the drug in polymeric nanoparticles targeted to the @entity4 ( @entity4 ) overexpressed on several types of @entity1 . Through in vitro studies in different @entity1 cell lines, we found that @entity4 targeted nanoparticles were significantly more effective in killing @entity1 cells than the free drug. In vivo pharmacokinetic studies revealed that encapsulation in nanoparticles resulted in lower brain penetration and enhanced @entity1 accumulation of the drug. Further, targeted nanoparticles were characterized by significantly enhanced @entity1 growth inhibitory activity in a @entity2 xenograft model of @entity1 . These results suggest that the therapeutic index of drugs that were previously considered unusable could be significantly improved by reformulation. Application of novel formulation strategies to previously abandoned drugs provides an opportunity to advance new molecules to the clinic at a lower cost. This can significantly increase the repertoire of treatment options available to @entity1 @entity0 .

title: Reformulating XXXX in @entity4 Targeted Polymeric Nanoparticles Improves Its Therapeutic Index.

answer: @entity5


abstract: Several promising anticancer drug candidates have been sidelined owing to their poor physicochemical properties or unfavorable pharmacokinetics, resulting in high overall cost of drug discovery and development. Use of alternative formulation strategies that alleviate these issues can help advance new molecules to the clinic at a significantly lower cost. @entity5 is a natural product with potent anticancer activity. Its clinical trial was discontinued following the @entity3 . To improve the safety and potency of @entity5 , we formulated the drug in polymeric nanoparticles targeted to the @entity4 ( @entity4 ) overexpressed on several types of @entity1 . Through in vitro studies in different @entity1 cell lines, we found that @entity4 targeted nanoparticles were significantly more effective in killing @entity1 cells than the free drug. In vivo pharmacokinetic studies revealed that encapsulation in nanoparticles resulted in lower brain penetration and enhanced @entity1 accumulation of the drug. Further, targeted nanoparticles were characterized by significantly enhanced @entity1 growth inhibitory activity in a @entity2 xenograft model of @entity1 . These results suggest that the therapeutic index of drugs that were previously considered unusable could be significantly improved by reformulation. Application of novel formulation strategies to previously abandoned drugs provides an opportunity to advance new molecules to the clinic at a lower cost. This can significantly increase the repertoire of treatment options available to @entity1 @entity0 .

title: Reformulating @entity5 in XXXX Targeted Polymeric Nanoparticles Improves Its Therapeutic Index.

answer: @entity4


abstract: By means of a sentence-picture matching task, 22 Broca-aphasics, 22 @entity1 , 16 @entity0 with damage to the right hemisphere and 16 neurologically normal subjects were tested for their ability to understand the actor-object-relation within a sentence. The 4 groups were approximately matched for sex, education, age and general severeness of disease. The stimulus sentences were constructed in such a way that the actor-object-relations were unambiguously clear by morphological means as e.g. case endings; thus, no error should be made by a subject operating on a purely algorithmic grammatical basis. One half of the sentences were irreversible, the other half reversible, i.e. the identification of the actor-object-relation was helped by a semantic cue in one half of the sentences, in the other half not. Crossed with this semantic factor was the syntatic factor "constituent order": one half of the sentences were presented in the normal order "actor-action-object", the other half in the topicalized form "object-action-actor" which is quite possible in German because of its free word order. Overall, the Broca-aphasics made less errors than the Wernicke- @entity0 . The error pattern of the aphasics suggests that both aphasic groups remain responsive to semantic constraints as well as to constituent order: both groups made more errors in reversible than in irreversible sentences and both groups made more errors in topicalized than in normal sentences. There were no significant group differences in these two respects. The only group difference was that Broca-aphasics tended to neglect the syntactic aspect of constituent order if a semantic cue was given, while the @entity1 continued to take the constituent order into account even in sentences where a semantic cue was present. In the light of the findings of the experiment, the hypothesis that @entity2 is characterized by a supramodal blockade of syntax is disputed.

title: Strategies of decoding actor-object-relations by aphasic XXXX .

answer: @entity0


abstract: The contractile response of vascular smooth muscle is known to consist of fast and slow components of contraction. We investigated the effect of @entity2 and angiotensin-II on these functional properties of vascular smooth muscle in a quantitative fashion by analyzing the velocity of isometric tension development in @entity0 aortic strips as a function of time. Basic premises for contraction velocity analysis are: (1) tension development is proportional to agonist concentration and relates to the amount of @entity1 fixed by the contractile proteins; (2) the rate of tension development (Qt) reflects the rate @entity1 is mobilized; (3) the rate at which @entity1 is made available relates to agonist concentration; (4) @entity1 is available from internal and external sites; (5) the @entity1 source)s) activated are characteristic of the mechanism of action of a particular agonist, and (6) the source of @entity1 activated is identifiable. Aortic strips were contracted maximally with @entity2 and the velocity of contraction found to decrease with time according to the empirical expression Qt = phi 1e-phi 2t + theta 1e-the 2t. Experiments in @entity1 -free medium served to identify the tonic component of @entity2 -induced contraction as the second term while angiotensin demonstrated only one term (phasic) which was independent of extracellular @entity1 . Strips contracted with different concentrations of @entity2 or @entity3 showed dose-dependent actions on these functional properties of vascular smooth muscle as revealed by their effects on the contraction velocity parameters. An expression describing the contribution of each component to total tension developed was derived by integrating the above expression to give Qtot = phi 1 (1--e-phi 2tmax)/phi 2 + theta 1 (1--e-theta 2tmax)/theta 2. The contribution of each component to total tension development was donse-dependent and their sum gave the total tension observed experimentally with @entity2 . For angiotensin, the first term of the preceeding expression gave the observed tension response. It is concluded that contraction velocity analysis affords a new approach for studying the effects of vasoactive agents on the functional properties of vascular smooth muscle.

title: Contraction velocity analysis of XXXX and angiotensin-II activation of vascular smooth muscle.

answer: @entity2


abstract: The spontaneous electrical activities of circular muscle cells of the @entity0 proximal colon were studied with intracellular micro-electrodes. All circular muscle cells exhibited slow waves at frequencies ranging between 2.8 and 7.0 cycles/min. The slow waves consisted of an upstroke phase followed by a plateau phase of variable duration (2-40 s). Many cells displayed a slow diastolic depolarization, or 'pre-potential' between slow waves. Slow waves spontaneously varied in duration and frequency in most preparations, creating distinctive slow wave patterns. @entity3 , 2 X 10(-6) M, decreased the durations of slow waves in many preparations and often changed the pattern to a series of relatively uniform slow waves. A further reduction in mean slow wave duration was produced by additional treatment with @entity2 , 10(-6) M. These results suggested that slow wave duration and pattern were affected by spontaneous discharge from both cholinergic and non-cholinergic excitatory nerves. Transmural nerve stimulation caused a short latency increase in slow wave duration (up to 38 s) that was abolished by @entity3 . In the presence of @entity3 , transmural stimulation evoked inhibitory junction potentials that reduced the amplitude and duration of the subsequent slow wave. The slow wave of reduced amplitude was followed by a slow wave of increased duration. The increase in duration of the slow wave did not appear to be related to the size of the preceding hyperpolarization, suggesting it was mediated by the release from non-cholinergic excitatory nerves. All responses to transmural stimulation were blocked by @entity2 . Microejection of @entity1 on to the muscle adjacent to the micro-electrode also produced an @entity3 -sensitive increase in slow wave duration. Tissues that had been stored in the cold overnight to reduce intrinsic neural activity exhibited regular slow waves of short duration. It is proposed that the basic myogenic pattern of spontaneous slow wave activity consists of regularly occurring slow waves of short duration (2-5 s). Intrinsic cholinergic and non-cholinergic excitatory nerves appear to modulate slow wave activity in vitro, producing distinctive slow wave patterns of variable instantaneous frequency and duration.

title: Enteric neural regulation of slow waves in circular muscle of the XXXX proximal colon.

answer: @entity0


abstract: Simultaneous intracellular staining and electrophysiological recording techniques have been applied to neurones of @entity1 myenteric @entity0 . With micro-electrodes filled with a solution of the fluorescent dye Lucifer Yellow, neurones were first characterized morphologically and electrophysiologically, and subsequently subjected to an indirect immunohistochemical method for the detection of vasoactive intestinal peptide ( @entity2 )-like immunoreactivity. Cross-correlations of morphology, electrophysiology and @entity2 immunoreactivity were successfully achieved in a total of 164 neurones. Sixty-three had the slow after-hyperpolarization characteristic of AH neurones; 101 cells displayed fast excitatory post-synaptic potentials (e.p.s.p.s) in response to transmural or focal stimulation and were therefore, by definition, S neurones. Unequivocal @entity2 immunoreactivity was observed in 25 (25%) S neurones, which, with only one exception, had Dogiel Type I morphology (i.e. many short soma processes and a single long process). In contrast, AH neurones had Dogiel Type II morphology (i.e. smooth soma with several long processes) and none showed @entity2 immunoreactivity. In addition to cholinergic fast e.p.s.p.s., non-cholinergic slow synaptic inputs were evoked in seventeen of the twenty-two @entity2 -immunoreactive S neurones tested. Both the fast and slow e.p.s.p.s could be elicited by stimulation of the preparation, oral or aboral to the site of recording. These observations demonstrate that, in the @entity1 ileum, myenteric plexus neurones showing @entity2 immunoreactivity are of a single electrophysiological type (S neurones) and belong to essentially one morphological class (Dogiel Type I).

title: Electrophysiology and morphology of vasoactive-intestinal-peptide-immunoreactive neurones of the XXXX ileum.

answer: @entity1


abstract: 2 antimicrobial agents, @entity5 , an antibiotic, and a @entity4 , @entity6 , were tested as supplement therapeutic treatment together with rehydration and nursing care in 535 cases of @entity2 in a Guatemalan highland village. All cases were under 5 years of age. 417 cases were bacteriologically tested, and 18% suffered from a recognized bacterial pathogen (Shigella or @entity1 ) and 82% were not. Cases occurred in 2 villages in the period from October 1960-December 1961. In 1 village, @entity0 were treated with the antimicrobial agents in addition to general medical care; in the other, cases were treated with family nursing and folk remedies only. The general death rate from all causes was lower in the village where general medical care was provided. Deaths from @entity2 were relatively few in both villages. An annual mortality from @entity3 of 7.7 per 1000 @entity0 in the treated community and of 17.3 in the untreated community was reported. The difference, however, was attributed mostly to general supportive measure, especially rehydration and nursing care. In vitro, @entity5 was very effective, but it did not prove so clinically. The @entity4 was effective against only 61% of Shigella strains in vitro, and the clinical result was somewhat less.

title: Studies of @entity3 in Central America. VII. Treatment of preschool @entity0 with XXXX and @entity6 under field conditions in a Guatemalan highland village.

answer: @entity5


abstract: 2 antimicrobial agents, @entity5 , an antibiotic, and a @entity4 , @entity6 , were tested as supplement therapeutic treatment together with rehydration and nursing care in 535 cases of @entity2 in a Guatemalan highland village. All cases were under 5 years of age. 417 cases were bacteriologically tested, and 18% suffered from a recognized bacterial pathogen (Shigella or @entity1 ) and 82% were not. Cases occurred in 2 villages in the period from October 1960-December 1961. In 1 village, @entity0 were treated with the antimicrobial agents in addition to general medical care; in the other, cases were treated with family nursing and folk remedies only. The general death rate from all causes was lower in the village where general medical care was provided. Deaths from @entity2 were relatively few in both villages. An annual mortality from @entity3 of 7.7 per 1000 @entity0 in the treated community and of 17.3 in the untreated community was reported. The difference, however, was attributed mostly to general supportive measure, especially rehydration and nursing care. In vitro, @entity5 was very effective, but it did not prove so clinically. The @entity4 was effective against only 61% of Shigella strains in vitro, and the clinical result was somewhat less.

title: Studies of XXXX in Central America. VII. Treatment of preschool @entity0 with @entity5 and @entity6 under field conditions in a Guatemalan highland village.

answer: @entity3


abstract: 2 antimicrobial agents, @entity5 , an antibiotic, and a @entity4 , @entity6 , were tested as supplement therapeutic treatment together with rehydration and nursing care in 535 cases of @entity2 in a Guatemalan highland village. All cases were under 5 years of age. 417 cases were bacteriologically tested, and 18% suffered from a recognized bacterial pathogen (Shigella or @entity1 ) and 82% were not. Cases occurred in 2 villages in the period from October 1960-December 1961. In 1 village, @entity0 were treated with the antimicrobial agents in addition to general medical care; in the other, cases were treated with family nursing and folk remedies only. The general death rate from all causes was lower in the village where general medical care was provided. Deaths from @entity2 were relatively few in both villages. An annual mortality from @entity3 of 7.7 per 1000 @entity0 in the treated community and of 17.3 in the untreated community was reported. The difference, however, was attributed mostly to general supportive measure, especially rehydration and nursing care. In vitro, @entity5 was very effective, but it did not prove so clinically. The @entity4 was effective against only 61% of Shigella strains in vitro, and the clinical result was somewhat less.

title: Studies of @entity3 in Central America. VII. Treatment of preschool @entity0 with @entity5 and XXXX under field conditions in a Guatemalan highland village.

answer: @entity6


abstract: 2 antimicrobial agents, @entity5 , an antibiotic, and a @entity4 , @entity6 , were tested as supplement therapeutic treatment together with rehydration and nursing care in 535 cases of @entity2 in a Guatemalan highland village. All cases were under 5 years of age. 417 cases were bacteriologically tested, and 18% suffered from a recognized bacterial pathogen (Shigella or @entity1 ) and 82% were not. Cases occurred in 2 villages in the period from October 1960-December 1961. In 1 village, @entity0 were treated with the antimicrobial agents in addition to general medical care; in the other, cases were treated with family nursing and folk remedies only. The general death rate from all causes was lower in the village where general medical care was provided. Deaths from @entity2 were relatively few in both villages. An annual mortality from @entity3 of 7.7 per 1000 @entity0 in the treated community and of 17.3 in the untreated community was reported. The difference, however, was attributed mostly to general supportive measure, especially rehydration and nursing care. In vitro, @entity5 was very effective, but it did not prove so clinically. The @entity4 was effective against only 61% of Shigella strains in vitro, and the clinical result was somewhat less.

title: Studies of @entity3 in Central America. VII. Treatment of preschool XXXX with @entity5 and @entity6 under field conditions in a Guatemalan highland village.

answer: @entity0