bluuebunny/crossref_metadata_2025_split huggingface dataset:
WHO systematic review of maternal morbidity and mortality: the prevalence of severe acute maternal morbidity (near miss)
Authors: Say Lale , Pattinson Robert C , Gülmezoglu A Metin 
Published: August 2004

Abstract
Aim
To determine the prevalence of severe acute maternal morbidity (SAMM) worldwide (near miss).

Method
Systematic review of all available data. The methodology followed a pre-defined protocol, an extensive search strategy of 10 electronic databases as well as other sources. Articles were evaluated according to specified inclusion criteria. Data were extracted using data extraction instrument which collects additional information on the quality of reporting including definitions and identification of cases. Data were entered into a specially constructed database and tabulated using SAS statistical management and analysis software.

Results
A total of 30 studies are included in the systematic review. Designs are mainly cross-sectional and 24 were conducted in hospital settings, mostly teaching hospitals. Fourteen studies report on a defined SAMM condition while the remainder use a response to an event such as admission to intensive care unit as a proxy for SAMM. Criteria for identification of cases vary widely across studies. Prevalences vary between 0.80% – 8.23% in studies that use disease-specific criteria while the range is 0.38% – 1.09% in the group that use organ-system based criteria and included unselected group of women. Rates are within the range of 0.01% and 2.99% in studies using management-based criteria. It is not possible to pool data together to provide summary estimates or comparisons between different settings due to variations in case-identification criteria. Nevertheless, there seems to be an inverse trend in prevalence with development status of a country.

Conclusion
There is a clear need to set uniform criteria to classify patients as SAMM. This standardisation could be made for similar settings separately. An organ-system dysfunction/failure approach is the most epidemiologically sound as it is least open to bias, and thus could permit developing summary estimates.
What is Nutrition & Metabolism?
Authors: Feinman Richard D , Hussain M Mahmood 
Published: August 2004

AbstractA new Open Access journal, Nutrition & Metabolism (N&M) will publish articles that integrate nutrition with biochemistry and molecular biology. The open access process is chosen to provide rapid and accessible dissemination of new results and perspectives in a field that is of great current interest. Manuscripts in all areas of nutritional biochemistry will be considered but three areas of particular interest are lipoprotein metabolism, amino acids as metabolic signals, and the effect of macronutrient composition of diet on health. The need for the journal is identified in the epidemic of obesity, diabetes, dyslipidemias and related diseases, and a sudden increase in popular diets, as well as renewed interest in intermediary metabolism.
Ketogenic diets and physical performance
Authors: Phinney Stephen D 
Published: August 2004

AbstractImpaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis.
Amino acids as regulators of gene expression
Authors: Kimball Scot R , Jefferson Leonard S 
Published: August 2004

AbstractThe role of amino acids as substrates for protein synthesis is well documented. However, a function for amino acids in modulating the signal transduction pathways that regulate mRNA translation has only recently been described. Interesting, some of the signaling pathways regulated by amino acids overlap with those classically associated with the cellular response to hormones such as insulin and insulin-like growth factors. The focus of this review is on the signaling pathways regulated by amino acids, with a particular emphasis on the branched-chain amino acid leucine, and the steps in mRNA translation controlled by the signaling pathways.
β3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and adipose tissue phospholipids induced by a cafeteria diet
Authors: Darimont Christian , Turini Marco , Epitaux Micheline , Zbinden Irène , Richelle Myriam , Montell Eulàlia , Ferrer-Martinez Andreu , Macé Katherine 
Published: August 2004

Abstract
Background
Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3-adrenoceptor (β3-AR) agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114) could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet.

Methods
Male Sprague-Dawley rats fed a cafeteria diet were treated orally with either the β3-AR agonist ZD7114 (1 mg/kg per day) or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study.

Results
In addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG) and diacylglycerol (DAG) accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet.

Conclusions
These results show that activation of the β3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with β3-AR activation.
Diet induced thermogenesis
Authors: Westerterp Klaas R 
Published: August 2004

Abstract
Objective
Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet.

Methods
Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition.

Results
Most studies measure diet-induced thermogenesis as the increase in energy expenditure above basal metabolic rate. Generally, the hierarchy in macronutrient oxidation in the postprandial state is reflected similarly in diet-induced thermogenesis, with the sequence alcohol, protein, carbohydrate, and fat. A mixed diet consumed at energy balance results in a diet induced energy expenditure of 5 to 15 % of daily energy expenditure. Values are higher at a relatively high protein and alcohol consumption and lower at a high fat consumption. Protein induced thermogenesis has an important effect on satiety.
In conclusion, the main determinants of diet-induced thermogenesis are the energy content and the protein- and alcohol fraction of the diet. Protein plays a key role in body weight regulation through satiety related to diet-induced thermogenesis.
A randomized trial of recruitment methods for older African American men in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial
Authors: Ford Marvella E , Havstad Suzanne L , Davis Shawna D 
Published: August 2004

Background Incidence rates for many types of cancer are higher among African American men than in the general population, yet African American men are less likely to participate in cancer screening trials. This paper describes the outcomes of a randomized trial (the AAMEN Project) designed to recruit African American men aged 55–74 years to a prostate, lung and colorectal cancer screening trial. Methods The recruitment interventions address four types of barriers to clinical trial participation: sociocultural barriers, economic barriers, individual barriers and barriers inherent in study design. Subjects were randomized to a control group or one of three increasingly intensive intervention arms, which used different combinations of mail, phone and in person church-based recruitment. Results Of the 39 432 African American men residing in the geographically defined study population (southeastern Michigan and northern Ohio), 17 770 men (45%) could be contacted, and 12 400 (31% of 39 432) were found to be eligible to participate. No statistically significant differences in age, education or income level were found among participants in the four study arms. A significantly greater enrollment yield (3.9%) was seen in the most intensive, church-based intervention arm, compared to the enrollment yields in the other two intervention arms (2.5 and 2.8%) or the control group (2.9%) (P, 0.01). Conclusions The intervention that involved the highest rate of face-to-face contact with the study participants produced the highest enrollment yield, but several strategies that were thought could improve yield had no effect. These findings, which are consistent with current literature on population-based recruitment, should facilitate the development of future recruitment efforts involving older African American men.
Are missing outcome data adequately handled? A review of published randomized controlled trials in major medical journals
Authors: Wood Angela M , White Ian R , Thompson Simon G 
Published: August 2004

Background Randomized controlled trials almost always have some individuals with missing outcomes. Inadequate handling of these missing data in the analysis can cause substantial bias in the treatment effect estimates. We examine how missing outcome data are handled in randomized controlled trials in order to assess whether adequate steps have been taken to reduce nonresponse bias and to identify ways to improve procedures for missing data. Methods We reviewed all randomized trials published between July and December 2001 in BMJ, JAMA, Lancet and New England Journal of Medicine, excluding trials in which the primary outcome was described as a time-to-event. We focused on trial designs, how missing outcome data were described and the statistical methods used to deal with the missing outcome data, including sensitivity analyses. Results We identified 71 trials of which 63 (89%) reported having partly missing outcome data: 13 trials had more than 20% of patients with missing outcomes. In 26 trials that measured the outcome at a single time point, 92% performed a complete case analysis and 8% imputed the missing outcomes using baseline values or the worst case value. In 37 trials with repeated measures of the outcome, 46% performed complete case analyses, potentially excluding individuals with some follow-up data, while 14% performed a repeated measures analysis, 19% used the last observation carried forward, 11% imputed with the worst case value and 2% imputed using regression predictions. Thirteen (21%) of trials with missing data reported a sensitivity analysis. Conclusions Our review shows that missing outcome data are a common problem in randomized controlled trials, and are often inadequately handled in the statistical analysis in the top tier medical journals. Authors should explicitly state the assumptions underlying the handling of the missing outcomes and justify them through data descriptions and sensitivity analyses.
Optimizing clinical trial supply requirements: simulation of computer-controlled supply chain management
Authors: Peterson Magnus , Byrom Bill , Dowlman Nikki , McEntegart Damian 
Published: August 2004

Background Computer-controlled systems are commonly used in clinical trials to control dispensing and manage site inventories of trial supplies. Typically such systems are used with an interactive telephone or web system that provide an interface with the study site. Realizing the maximum savings in medication associated with this approach has, in the past, been problematic as it has been difficult to fully estimate medication requirements due to the complexities of these algorithms and the inherent variation in the clinical trial recruitment process. Methods We describe the traditional and automated methods of supplying sites. We detail a simulation approach that models the automated system. We design a number of simulation experiments using this model to investigate the supply strategy properties that influence medication overage and other strategy performance metrics. Results The computer-controlled medication system gave superior performance to the traditional method. In one example, a 75% overage of wasted medication in the traditional system was associated with higher supply failure than an automated system strategy with an overage of 47%. In a further example, we demonstrate that the impact of using a country stratified as opposed to site stratified scheme affects the number of deliveries and probability of supply failures more than the amount of drug wasted with respective increases of 20, 2300 and 4%. Medication savings with automated systems are particularly significant in repeat dispensing designs. We show that the number of packs required can fall by as much as 50% if one uses a predictive medication algorithm. Conclusions We conclude that a computer-controlled supply chain enables medication savings to be realized and that it is possible to quantify the distribution of these savings using a simulation model. The simulation model can be used to optimize the prestudy medication supply strategy and for midstudy monitoring using real-time data contained in the study database.
Up-Regulation of Basal Transcriptional Activity of the Cytochrome P450 Cholesterol Side-Chain Cleavage (CYP11A) Gene by Isoform-Specific Calcium-Calmodulin-Dependent Protein Kinase in Primary Cultures of Ovarian Granulosa Cells
Authors: Seals Richard C. , Urban Randall J. , Sekar Natesampillai , Veldhuis Johannes D. 
Published: August 2004

AbstractIntracellular calcium ions (Ca2+) regulate steroidogenesis in the placenta, adrenal gland, testis, and ovary. Earlier data indicate that Ca2+/calmodulin-dependent protein kinase (CamK) may mediate Ca2+-dependent up-regulation of CYP11A (cholesterol side-chain cleavage). To examine this notion further, we assessed the expression and actions of isotype-specific CamK on in vitro transcription of the swine CYP11A gene promoter in primary cultures of ovarian granulosa-luteal cells. RT-PCR and oligodeoxynucleotide sequencing identified gene transcripts encoding CamKII and IV in granulosa and theca cells and corpora lutea. DNA sequence homology with the cognate human and rat genes was 97 and 94% (CamKII) and 96 and 88% (CamKIV), respectively. SDS-PAGE and isoform-specific immunoblotting corroborated expression of CamKII (∼52 kDa) and CamKIV (∼60 kDa) proteins. To monitor transcriptional control, granulosa-luteal cells were transfected transiently with a putative 5′-upstream regulatory region of the homologous CYP11A gene −2320 to +23 bp from the transcriptional start site driving luciferase (CYP11A/luc). Coexpression of constitutively active CamKIV elevated basal transcription by 3.5 ± 0.2-fold (P &lt; 0.001), whereas inactive mutant CamKIV and native CamKII had no effect. Forskolin, an activator of adenylyl cyclase, stimulated expression of CYP11A/luciferase by 4.5 ± 0.9-fold (P &lt; 0.001) and did not enhance transcriptional drive by exogenous CamKIV. Preliminary promoter-deletional analyses showed that a proximal 5′-fragment −100 to +23 bp, but not −50/+23 bp, retained full responsiveness to CamKIV (4.5 ± 0.4-fold; P &lt; 0.001). Threefold cotransfection of −100/+23 bp CYP11A/luciferase, active CamKIV, and a dominant-negative mutant of the cAMP-responsive element binding protein (10, 100, and 250 ng) inhibited CamKIV-stimulated transcriptional activity by 17, 47, and 48% (pooled sem± 2%) [P &lt; 0.01]. The dominant-negative mutant of the cAMP-responsive element binding protein also repressed forskolin’s stimulation of −100/+23 CYP11A/luciferase by 12, 38, and 52% (P &lt; 0.01). Based on these ensemble outcomes, we postulate that endogenous CamKIV may serve as a Ca2+-dependent effector mechanism to maintain basal CYP11A gene expression in ovarian granulosa-luteal cells.
Nuclear Factor of Activated T Cells (NFAT) Is Involved in the Depolarization-Induced Activation of Growth Hormone-Releasing Hormone Gene Transcription in Vitro
Authors: Asai Masato , Iwasaki Yasumasa , Yoshida Masanori , Mutsuga-Nakayama Noriko , Arima Hiroshi , Ito Masafumi , Takano Koji , Oiso Yutaka 
Published: August 2004

AbstractGHRH plays a pivotal role in the regulation of both synthesis and secretion of GH in the anterior pituitary. In this study, we examined the molecular mechanism of depolarization-induced GHRH gene transcription using the hypothalamus cell line, Gsh+/+, revealing the involvement of the transcription factor called nuclear factor of activated T cells (NFAT). GHRH, NFAT1, NFAT4, and related genes were endogenously expressed in Gsh+/+ cells and the rat arcuate nucleus, where NFAT1 and GHRH were colocalized. Cellular excitation with high potassium potently stimulated endogenous GHRH gene 5′-promoter activity as well as the NFAT-mediated gene transcription, the former being further enhanced by coexpression of NFAT. On the other hand, cyclosporin A (a calcineurin-NFAT inhibitor) or EGTA (a calcium chelator) significantly blocked the depolarization-induced GHRH gene transcription. EMSA and site-directed mutagenesis experiments showed the direct binding of NFAT at five sites of the GHRH promoter, among which the relative importance of three distal sites (−417/−403, −402/−387, −317/−301) was suggested. Finally, elimination of all five sites completely abolished the NFAT-induced GHRH gene up-regulation. Altogether, our results suggest that the transcription factor NFAT is involved in the depolarization-induced transcriptional activation of GHRH gene in the neuronal cells.
Endothelin B receptor Ca2+ signaling in shark vascular smooth muscle: participation of inositol trisphosphate and ryanodine receptors
Authors: Fellner Susan K. , Parker Laurel A. 
Published: August 2004

SUMMARYIn mammals, endothelin receptors are sub-classified into ETAreceptors (ETAR), which are purely constrictive in vascular smooth muscle (VSM), and ETBR, which may produce constriction in VSM or dilatation by stimulating the production of nitric oxide (NO) from endothelial cells. In contrast, previous studies suggested that shark VSM is stimulated exclusively by ETBR. The Ca2+ signaling pathways utilized by shark VSM in response to stimulation by endothelin-1 (ET-1) have not previously been investigated. We measured cytosolic Ca2+concentration ([Ca2+]i) in fura-2-loaded VSM of anterior mesenteric artery of Squalus acanthias and show that the ETBR agonists IRL 1620 and sarafotoxin S6c (SRX) increase[Ca2+]i in VSM to the same extent as ET-1 and ETBR appears to be the only ETR subtype in sharks. To investigate the participation of the inositol trisphosphate (IP3) receptors(IP3R), we utilized two inhibitors of the mammalian IP3R, TMB-8 and 2-APB. In Ca2+-free Ringer, these agents inhibit the response to ETBR agonist stimulation by 71%. The ryanodine-sensitive receptor (RyR) may be activated by low concentrations of ryanodine, by abrupt local increases of [Ca2+]i,(calcium-induced calcium release) or by cyclic adeninediphosphate ribose(cADPR). We employed three inhibitors of activation of the RyR, Ruthenium Red,8-Br cADPR and high concentrations of ryanodine; these agents blocked the[Ca2+]i response to ETBR agonist stimulation by a mean of 39%. These data show for the first time that in VSM of the shark,ETBR activation stimulates both IP3R and RyR, and that cADPR is involved in RyR activation.
Evidence that thyroid hormone induces olfactory cellular proliferation in salmon during a sensitive period for imprinting
Authors: Lema Sean C. , Nevitt Gabrielle A. 
Published: August 2004

SUMMARY
Salmon have long been known to imprint and home to natal stream odors, yet the mechanisms driving olfactory imprinting remain obscure. The timing of imprinting is associated with elevations in plasma thyroid hormone levels,with possible effects on growth and proliferation of the peripheral olfactory system. Here, we begin to test this idea by determining whether experimentally elevated plasma levels of 3,5,3′-triiodothyronine (T3)influence cell proliferation as detected by the 5-bromo-2′-deoxyuridine(BrdU) cell birth-dating technique in the olfactory epithelium of juvenile coho salmon (Oncorhynchus kisutch). We also explore how natural fluctuations in thyroxine (T4) relate to proliferation in the epithelium during the parr-smolt transformation. In both studies, we found that BrdU labeled both single and clusters of mitotic cells. The total number of BrdU-labeled cells in the olfactory epithelium was significantly greater in fish with artificially elevated T3 compared with placebo controls. This difference in proliferation was restricted to the basal region of the olfactory epithelium, where multipotent progenitor cells differentiate into olfactory receptor neurons. The distributions of mitotic cluster sizes differed significantly from a Poisson distribution for both T3 and placebo treatments, suggesting that proliferation tends to be non-random. Over the course of the parr-smolt transformation, changes in the density of BrdU cells showed a positive relationship with natural fluctuations in plasma T4. This relationship suggests that even small changes in thyroid activity can stimulate the proliferation of neural progenitor cells in the salmon epithelium. Taken together, our results establish a link between the thyroid hormone axis and measurable anatomical changes in the peripheral olfactory system.
Phenotypic deconstruction reveals involvement of manganese transportermalvolioin honey bee division of labor
Authors: Ben-Shahar Yehuda , Dudek Nichole L. , Robinson Gene E. 
Published: August 2004

SUMMARYMolecular analysis of a complex behavioral phenotype is facilitated by dissecting it into simpler behavioral components. Using this approach, we present evidence implicating increased manganese transport by the malvolio (mvl) gene into brain cells as one factor that influences age-related division of labor in honey bee colonies. We studied mvl because manganese affects sucrose responsiveness in Drosophila melanogaster, and sucrose responsiveness is related to division of labor in honey bee colonies. Honey bee foragers are more responsive to sucrose in the laboratory than are younger nurse bees, and pollen foragers are more responsive to sucrose than nectar foragers. Levels of mvl mRNA in the brain and manganese in the head were higher in pollen foragers compared with nurses, with nectar foragers intermediate. Manganese treatment increased honey bee sucrose responsiveness and caused precocious foraging. Manganese levels showed a similar pattern to mvl mRNA but manganese treatment did not increase pollen foraging. These results suggest that, while there are molecular pathways common to sucrose responsiveness and division of labor, linkages between a complex behavior and some of its simpler behavioral components are not obligatory. Together with previous findings,these results support the idea that some feeding-related genes in Drosophila have been used in social evolution to regulate division of labor.