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Studies Suggesting (studies + suggesting)
Kinds of Studies Suggesting Selected AbstractsPROPOSITION 8 AND CRIME RATES IN CALIFORNIA: THE CASE OF THE DISAPPEARING DETERRENTCRIMINOLOGY AND PUBLIC POLICY, Issue 3 2006CHERYL MARIE WEBSTER Research Summary: In 1999, Daniel Kessler and Steven Levitt published an article that purported to provide support for the marginal deterrent effects of harsher sanctions on levels of crime. Specifically, they concluded that sentence enhancements that came into effect in California in June 1982 as a result of Proposition 8 were responsible for a subsequent drop in serious crime in this state. Our article examines the analyses and findings of this article and suggests that their conclusion of a deterrent impact fails to withstand scrutiny when more complete and more detailed crime data are used and the comparability of "control" groups is carefully examined. In particular, the addition of annual crime levels for all years (versus only the odd-numbered years that Kessler and Levitt examine) calls into question the prima facie support for a deterrent effect presented by Kessler and Levitt. Specifically, it demonstrates not only that the crime drop in California began before, rather than after, the passing into law of the sentence enhancements in 1982 but also that the downward slope did not accelerate after the change in law. Furthermore, the comparability of the two "control" groups with the "treatment" group is challenged, rendering suspect any findings based on these comparisons. Policy Implications: Case studies suggesting that crime decreased after the imposition of harsh sentencing policies are often cited as evidence of marginal general deterrence. As has been demonstrated in other contexts, the question that needs to be asked is "Compared with what?" Kessler and Levitt's (1999) article demonstrates that those interested in sentencing policy need to be sensitive not only to the appropriateness of the comparisons that are made, but also to the choice of data that are presented. [source] Childhood trauma in obsessive-compulsive disorder, trichotillomania, and controlsDEPRESSION AND ANXIETY, Issue 2 2002Christine Lochner M.A. Abstract There is relatively little data on the link between childhood trauma and obsessive-compulsive/putative obsessive-compulsive spectrum disorders. The revised Childhood Trauma Questionnaire (CTQ), which assesses physical, emotional, and sexual abuse as well as physical and emotional neglect, was administered to female patients with obsessive-compulsive disorder (OCD; n = 74; age: 36.1 ± 16.3), TTM (n = 36; age: 31.8 ± 12.3), and a group of normal controls (n = 31; age: 21.5 ± 1.0). The findings showed a significantly greater severity of childhood trauma in general, and emotional neglect specifically, in the patient groups compared to the controls. Although various factors may play a role in the etiology of both OCD and trichotillomania (TTM), this study is consistent with some evidence from previous studies suggesting that childhood trauma may play a role in the development of these disorders. Depression and Anxiety 15:66,68, 2002. © 2002 Wiley-Liss, Inc. [source] Trends in Pediatric Melanoma Mortality in the United States, 1968 through 2004DERMATOLOGIC SURGERY, Issue 2 2008KEVAN G. LEWIS MD BACKGROUND AND OBJECTIVE Mortality from melanoma in children is a poorly understood and controversial problem in dermatology. There is paucity of research into this important public health dilemma. The purpose of this study was to characterize pediatric melanoma mortality in the United States and to evaluate trends over time. METHODS AND MATERIALS Deaths were derived from a database of more than 75 million records of the U.S. Center for National Health Statistics based on routine death certification. Information on age, race, gender, and geographic location was available for years 1968 through 2004. RESULTS During the 37-year period, there were 643 deaths attributed to melanoma in children under 20 years of age in the United States, an average of 18 per year. The overall age-adjusted mortality rate for melanoma in children was 2.25 deaths per year (per 10 million at-risk individuals). Mortality rates were strongly associated with age. In the oldest age group (age 15,19 years) the mortality rate was approximately an order of magnitude 8,18 times higher compared to younger age groups. Mortality among males was 25% higher than females. Mortality rates for white children were more than twice as high as black children. Overall mortality from melanoma in children declined steadily from 1968 to 2004. The highest mortality rates were observed in Idaho, Nevada, Arizona, and New Mexico. CONCLUSIONS Although mortality from melanoma among children in the United State is low, the magnitude of the public health burden from this preventable cause of death is substantial. In contrast to results of studies suggesting that the incidence of melanoma may be rising in children and adolescents, the data suggest that mortality in these groups may be falling. Additional study is warranted to further characterize and ultimately reduce mortality from childhood melanoma. [source] Extinction in the developing rat: An examination of renewal effectsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 6 2007Carol S.L. Yap Abstract In the present series of experiments the context-specificity of extinction was examined from a developmental perspective. For postnatal day (PN) 23 rats, renewal of freezing to an aversive odor conditioned stimulus (CS) was observed when rats were conditioned in Context A, extinguished in Context B, and tested in Context A (i.e., ABA renewal). This effect was not observed in PN16 rats, which is consistent with previous studies suggesting that rats <,PN20 are impaired in encoding contextual information [i.e., Carew and Rudy [1991]. Developmental Psychobiology, 24, 191,209]. Subsequent experiments demonstrated that for rats conditioned at PN16 and tested at PN23, contextual regulation of extinction performance depended on the age at which extinction occurred. Specifically, ABA renewal was observed in rats given extinction training at PN22 but not in rats given extinction training at PN17. These latter results show that whether or not context regulates the expression of an ambiguous memory is determined by the animal's age when the memory becomes ambiguous. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 565-575, 2007. [source] The transferability of distribution models across regions: an amphibian case studyDIVERSITY AND DISTRIBUTIONS, Issue 3 2009Flavio Zanini ABSTRACT Aim, Predicting species distribution is of fundamental importance for ecology and conservation. However, distribution models are usually established for only one region and it is unknown whether they can be transferred to other geographical regions. We studied the distribution of six amphibian species in five regions to address the question of whether the effect of landscape variables varied among regions. We analysed the effect of 10 variables extracted in six concentric buffers (from 100 m to 3 km) describing landscape composition around breeding ponds at different spatial scales. We used data on the occurrence of amphibian species in a total of 655 breeding ponds. We accounted for proximity to neighbouring populations by including a connectivity index to our models. We used logistic regression and information-theoretic model selection to evaluate candidate models for each species. Location, Switzerland. Results, The explained deviance of each species' best models varied between 5% and 32%. Models that included interactions between a region and a landscape variable were always included in the most parsimonious models. For all species, models including region-by-landscape interactions had similar support (Akaike weights) as models that did not include interaction terms. The spatial scale at which landscape variables affected species distribution varied from 100 m to 1000 m, which was in agreement with several recent studies suggesting that land use far away from the ponds can affect pond occupancy. Main conclusions, Different species are affected by different landscape variables at different spatial scales and these effects may vary geographically, resulting in a generally low transferability of distribution models across regions. We also found that connectivity seems generally more important than landscape variables. This suggests that metapopulation processes may play a more important role in species distribution than habitat characteristics. [source] Homologous desensitization of guanylyl cyclase A, the receptor for atrial natriuretic peptide, is associated with a complex phosphorylation patternFEBS JOURNAL, Issue 11 2010Juliane Schröter Atrial natriuretic peptide (ANP), via its guanylyl cyclase A (GC-A) receptor and intracellular guanosine 3,,5,-cyclic monophosphate production, is critically involved in the regulation of blood pressure. In patients with chronic heart failure, the plasma levels of ANP are increased, but the cardiovascular actions are severely blunted, indicating a receptor or postreceptor defect. Studies on metabolically labelled GC-A-overexpressing cells have indicated that GC-A is extensively phosphorylated, and that ANP-induced homologous desensitization of GC-A correlates with receptor dephosphorylation, a mechanism which might contribute to a loss of function in vivo. In this study, tandem MS analysis of the GC-A receptor, expressed in the human embryonic kidney cell line HEK293, revealed unambiguously that the intracellular domain of the receptor is phosphorylated at multiple residues: Ser487, Ser497, Thr500, Ser502, Ser506, Ser510 and Thr513. MS quantification based on multiple reaction monitoring demonstrated that ANP-provoked desensitization was accompanied by a complex pattern of receptor phosphorylation and dephosphorylation. The population of completely phosphorylated GC-A was diminished. However, intriguingly, the phosphorylation of GC-A at Ser487 was selectively enhanced after exposure to ANP. The functional relevance of this observation was analysed by site-directed mutagenesis. The substitution of Ser487 by glutamate (which mimics phosphorylation) blunted the activation of the GC-A receptor by ANP, but prevented further desensitization. Our data corroborate previous studies suggesting that the responsiveness of GC-A to ANP is regulated by phosphorylation. However, in addition to the dephosphorylation of the previously postulated sites (Ser497, Thr500, Ser502, Ser506, Ser510), homologous desensitization seems to involve the phosphorylation of GC-A at Ser487, a newly identified site of phosphorylation. The identification and further characterization of the specific mechanisms involved in the downregulation of GC-A responsiveness to ANP may have important pathophysiological implications. Structured digital abstract ,,MINT-7713870, MINT-7713887: PMCA (uniprotkb:P20020) and GC-A (uniprotkb:P18910) colocalize (MI:0403) by fluorescence microscopy (MI:0416) [source] Effects of body mass, climate, geography, and census area on population density of terrestrial mammalsGLOBAL ECOLOGY, Issue 5 2001Marina Silva Abstract Aim The aim of this study was to investigate the effects of climate, geography, census area and the distribution of body mass on the mass : density relationship in terrestrial mammal populations. Location The areas covered include most major terrestrial biomes including the tropics, savannas, and temperate forests. Method Data on population density and body mass from 827 populations belonging to 330 different terrestrial mammal species were derived from a review of the literature. Results LOWESS and polynomial regression analysis indicated that the overall mass : density relationship on log-log scales was not linear and that the slope of this relationship behaves differently across the range of body mass. Body mass explained between 37 and 67% of the variability in population density depending upon the dietary category or the biome group. We also developed two multivariate models that can explain up to 65% of the variability in population density in terrestrial mammals. We also tested for a confounding effect of census area on the mass : density relationship on log-log scales in terrestrial mammals. Conclusions Our findings support previous studies suggesting that body mass is a major predictor of the variance in population density in terrestrial mammals. We suggest that the non-linearity of the mass : density relationship may result from the fact that the overall distribution of body mass is a mixture of distributions across dietary groups and biomes. In contrast to body mass, our results indicate that climatic and geographical factors have a minor effect on population density. Although census area was closely correlated with body mass, body mass was generally a better predictor of population density than was census area. [source] Haplotype Analysis Confirms the Association Between the HCRTR2 Gene and Cluster HeadacheHEADACHE, Issue 7 2008Innocenzo Rainero MD Background., Several studies suggested that genetic factors play a role in cluster headache (CH) susceptibility. We found a significant association between the 1246 G>A polymorphism of the hypocretin receptor-2 (HCRTR2) gene and the disease. This association was confirmed in a large study from Germany but was not replicated in a dataset of CH patients from Northern Europe. Objective., The purpose of this study was to further evaluate the association between CH and the HCRTR2 gene using new polymorphisms, estimating the frequency of different gene haplotypes, searching for gene mutations, and evaluating the effects of the examined polymorphisms on hypocretin binding sites. Methods., We genotyped 109 CH patients and 211 healthy controls for 5 new polymorphisms of the HCRTR2 gene and we inferred different gene haplotypes. Complete HCRTR2 sequencing was undertaken for 11 independent CH patients, 5 of whom had a positive family history. The effects of the 1246 G>A polymorphism on the hypocretin binding sites were evaluated using different computer-assisted analyses. Results., Three new polymorphisms of the HCRTR2 gene resulted significantly associated with CH. The GTAAGG haplotype resulted more frequent in cases than in controls (OR: 3.68; 95% CI: 1.85-7.67). No point mutation of the HCRTR2 gene was found. Binding analyses showed that the 1246 G>A polymorphism (substitution of valine at position 308 by isoleucine) has no effect on the hypocretin binding sites but could influence the dimerization process of the receptor. Conclusion., Our data confirm previous studies suggesting that the HCRTR2 gene or a linked locus significantly modulates the risk for CH. In addition, we suggest that the V308I substitution of the HCRTR2 may interfere with the dimerization process of the receptor, thereby influencing its functional activity. [source] Isolation and molecular characterization of Musca domestica delta-9 desaturase sequencesINSECT MOLECULAR BIOLOGY, Issue 6 2002A. L. Eigenheer Abstract We have isolated fatty acyl-CoA desaturase cDNA (Mdomd9) and genomic sequences from the housefly, Musca domestica. Two ,1.66 kb cDNAs were recovered. They had identical coding regions and 3, untranslated regions (UTRs), but differed in their 5, UTRs. The open reading frame encodes a 380 amino acid (aa) protein with 82% identity to Drosophila melanogaster desat1, and significant (> 50%) identity with other insect delta-9 desaturases. Functional analyses in a yeast expression system confirmed the cDNA encodes a ,9 desaturase. Northern analysis indicated two transcripts of 1.7 and 2.9 kb that hybridized specifically to the open reading frame. PCR amplification of genomic templates revealed three intron sites that are conserved among other insect species. Southern analysis of genomic DNA indicated at least two desaturase gene copies per haploid genome. There is a high degree of polymorphism, most of which appears to be due to variable intron sequences; curiously, individual flies had varying morphs of intron II and intron III. Together, the data suggest that there are more ,9 desaturase alleles within the population studied than there are loci within the genome, and support other studies suggesting that insect fatty acyl-CoA desaturases are a dynamically evolving gene family. [source] Soluble protein oligomers as emerging toxins in alzheimer's and other amyloid diseasesIUBMB LIFE, Issue 4-5 2007Sergio T. Ferreira Abstract Amyloid diseases are a group of degenerative disorders characterized by cell/tissue damage caused by toxic protein aggregates. Abnormal production, processing and/or clearance of misfolded proteins or peptides may lead to their accumulation and to the formation of amyloid aggregates. Early histopathological investigation of affected organs in different amyloid diseases revealed the ubiquitous presence of fibrillar protein aggregates forming large deposits known as amyloid plaques. Further in vitro biochemical and cell biology studies, as well as studies using transgenic animal models, provided strong support to what initially seemed to be a solid concept, namely that amyloid fibrils played crucial roles in amyloid pathogenesis. However, recent studies describing tissue-specific accumulation of soluble protein oligomers and their strong impact on cell function have challenged the fibril hypothesis and led to the emergence of a new view: Fibrils are not the only toxins derived from amyloidogenic proteins and, quite possibly, not the most important ones with respect to disease etiology. Here, we review some of the recent findings and concepts in this rapidly developing field, with emphasis on the involvement of soluble oligomers of the amyloid-, peptide in the pathogenesis of Alzheimer's disease. Recent studies suggesting that soluble oligomers from different proteins may share common mechanisms of cytotoxicity are also discussed. Increased understanding of the cellular toxic mechanisms triggered by protein oligomers may lead to the development of rational, effective treatments for amyloid disorders. IUBMB Life, 59: 332-345, 2007 [source] Root competition: beyond resource depletionJOURNAL OF ECOLOGY, Issue 4 2006H. JOCHEN SCHENK Summary 1Root competition is defined as a reduction in the availability of a soil resource to roots that is caused by other roots. Resource availability to competitors can be affected through resource depletion (scramble competition) and by mechanisms that inhibit access of other roots to resources (contest competition, such as allelopathy). 2It has been proposed that soil heterogeneity can cause size-asymmetric root competition. Support for this hypothesis is limited and contradictory, possibly because resource uptake is affected more by the amount and spatial distribution of resource-acquiring organs, relative to the spatial distribution of resources, than by root system size per se. 3Root competition intensity between individual plants generally decreases as resource availability (but not necessarily habitat productivity) increases, but the importance of root competition relative to other factors that structure communities may increase with resource availability. 4Soil organisms play important, and often species-specific, roles in root interactions. 5The findings that some roots can detect other roots, or inert objects, before they are contacted and can distinguish between self and non-self roots create experimental challenges for those attempting to untangle the effects of self/non-self root recognition, self-inhibition and root segregation or proliferation in response to competition. Recent studies suggesting that root competition may represent a ,tragedy-of-the-commons' may have failed to account for this complexity. 6Theories about potential effects of root competition on plant diversity (and vice versa) appear to be ahead of the experimental evidence, with only one study documenting different effects of root competition on plant diversity under different levels of resource availability. 7Roots can interact with their biotic and abiotic environments using a large variety of often species-specific mechanisms, far beyond the traditional view that plants interact mainly through resource depletion. Research on root interactions between exotic invasives and native species holds great promise for a better understanding of the way in which root competition may affect community structure and plant diversity, and may create new insights into coevolution of plants, their competitors and the soil community. [source] N,3 polyunsaturated fatty acids impair lifespan but have no role for metabolismAGING CELL, Issue 1 2007Teresa G. Valencak Summary Although generally considered as beneficial components of dietary fats, polyunsaturated fatty acids (PUFA) have been suspected to compromise maximum lifespan (MLSP) in mammals. Specifically, high amounts of phospholipid PUFAs are thought to impair lifespan due to an increase in the susceptibility of membranes to lipid peroxidation and its damaging effect on cellular molecules. Also, there is evidence from in vitro studies suggesting that highly unsaturated PUFAs elevate basal metabolic rate (BMR). Previous comparative studies in this context were based on small sample sizes, however, and, except for one study, failed to address possible confounding influences of body weight and taxonomic relations between species. Therefore, we determined phospholipid membrane composition in skeletal muscle from 42 mammalian species to test for a relation with published data on MLSP, and with literature data on BMR (30 species). Using statistical models that adjust for the effects of body weight and phylogeny, we found that among mammals, MLSP indeed decreases as the ratio of n,3 to n,6 PUFAs increases. In contrast to previous studies, we found, however, no relation between MLSP and either membrane unsaturation (i.e. PUFA content or number of double bonds) or to the very long-chain, highly unsaturated docosahexaenoic acid (DHA). Similarly, our data set gave no evidence for any notable relation between muscle phospholipid fatty acid composition and BMR, or MLSP and BMR in mammals. These results contradict the ,membrane pacemaker theory of aging', that is, the concept of a direct link between high amounts of membrane PUFAs, elevated BMR, and thus, impaired longevity. [source] HIGH PREVALENCE OF EXTENDED-SPECTRUM ,-LACTAMASES ESCHERICHIA COLI AND VANCOMYCIN-RESISTANT ENTEROCOCCI ISOLATES FROM CHICKEN PRODUCTS.JOURNAL OF FOOD SAFETY, Issue 1 2010A PROBLEM OF PUBLIC HEALTH ABSTRACT Twenty-nine chicken products were acquired from different supermarkets in Portugal during September to December 2007 and were analyzed for extended-spectrum ,-lactamases (ESBL) Escherichia coli and vancomycin-resistant enterococci (VRE). Cefotaxime-resistant E. coli isolates were recovered in 27 of 29 chicken samples representing 93% of the analyzed samples. The highest percentages of resistance (more than 50% of the isolates) were detected for ampicillin, nalidixic acid and tetracycline. VRE isolates were detected in 17 of 29 samples of chicken origin (59%) and were identified as Enterococcus durans (n = 15) and E. faecium (n = 2) with the highest percentages of resistance being detected for erythromycin, tetracycline, ampicillin and ciprofloxacin. Seven E. durans and the two E. faecium isolates recovered from chicken wings, gizzard and skin show gelatinase activity. The high rate of colonization of chicken products by these bacteria supports other studies suggesting that the food chain could be a source of ESBL and VRE colonization in humans representing a public health problem. PRACTICAL APPLICATIONS The data indicate that chicken products may be contaminated with a high prevalence of extended-spectrum ,-lactamases Escherichia coli and vancomycin-resistant enterococci (VRE). It is important to mention that the isolates present a diversity of phenotypes of antimicrobial resistance, and half of the VRE isolates show also gelatinase activity, indicating that these animals may be a reservoir of bacteria showing virulence and increased resistance to antimicrobial agents, raising special concerns about their transmission to humans through the food chain. [source] Population-based type-specific prevalence of high-risk human papillomavirus infection in middle-aged Swedish WomenJOURNAL OF MEDICAL VIROLOGY, Issue 4 2002Ola Forslund Abstract Human papillomavirus (HPV) DNA testing can be used to identify women at risk of the development of cervical cancer. The cost-effectiveness of HPV screening is dependent on the type-specific HPV prevalence in the general population. The present study describes the prevalence and spectrum of high-risk HPV types found in a large real-life population-based HPV screening trial undertaken entirely within the cervical screening program offered to middle-aged Swedish women. Cervical brush samples from 6,123 women aged 32,38 years were analyzed using a general HPV primer (GP5+/6+) polymerase chain reaction-enzyme immunoassay (PCR-EIA) combined with reverse dot-blot hybridization for confirmation and HPV typing by a single assay. In this study, 6.8% (95% CI 6.2,7.5) (417/6,123) were confirmed as high-risk HPV positive. Infections with 13 different high-risk HPV types were detected, of which HPV 16 was the most prevalent type (2.1%; 128/6,123), followed by HPV 31 (1.1%; 67/6,123). Any one of the HPV types 18, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 66 was detected in 3.6% (223/6,123) of the women. Infection with two, three, and five types simultaneously was identified in 32, 5, and 1 women, respectively. The combination of PCR-EIA as a screening test and reverse dot-blot hybridization as a confirmatory test, was found to be readily applicable to a real-life population-based cervical screening. The type-specific HPV prevalence found support in previous modeling studies suggesting that HPV screening may be a favorable cervical screening strategy. J. Med. Virol. 66:535,541, 2002. © 2002 Wiley-Liss, Inc. [source] Using the h -index to rank influential British researchers in information science and librarianshipJOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE AND TECHNOLOGY, Issue 2 2007Charles Oppenheim The recently developed h -index has been applied to the literature produced by senior British-based academics in librarianship and information science. The majority of those evaluated currently hold senior positions in UK information science and librarianship departments; however, a small number of staff in other departments and retired "founding fathers" were analyzed as well. The analysis was carried out using the Web of Science (Thomson Scientific, Philadelphia, PA) for the years from 1992 to October 2005, and included both second-authored papers and self-citations. The top-ranking British information scientist, Peter Willett, has an h -index of 31. However, it was found that Eugene Garfield, the founder of modern citation studies, has an even higher h -index of 36. These results support other studies suggesting that the h -index is a useful tool in the armory of bibliometrics. [source] Risk reduction and real estate portfolio sizeMANAGERIAL AND DECISION ECONOMICS, Issue 7 2001Peter J. Byrne There is remarkably little empirical evidence of the advantages of increased size on risk levels in real estate portfolios based on actual portfolios. This paper improves this by examining the portfolio risk of a large sample of actual real estate data in the UK over the period from 1981 to 1996. The results show that real estate portfolios of larger sizes tend, on average, to have lower risks than smaller sized portfolios and, more importantly, that portfolios with only a few assets can have very high or very low risk. For fund managers to be confident that their portfolio will have a risk level like the average, they need to hold portfolios of a considerably greater size than they might expect, or can sensibly acquire. Previous studies suggesting that only 20,40 properties are needed to reduce the risk of a property portfolio down to the market level are a significant underestimate. The actual figure is likely to be 400,500 properties, well above that of even the largest fund in the UK. Size alone does not necessarily lead to a reduction in portfolio risk. Other factors are of greater importance. Copyright © 2001 John Wiley & Sons, Ltd. [source] Review Article: Is it time to embrace haemodiafiltration for centre-based haemodialysis? (Review Article)NEPHROLOGY, Issue 4 2008JAMES JB PETRIE SUMMARY: Improvements in survival in dialysis patients over the past few decades have been disappointing. Recent prospective trials such the haemodialysis study have not shown conclusive improvements. Two recent observational studies have found a striking survival advantage for haemodiafiltration (HDF). This review covers the differences between HDF and conventional haemodialysis (HD) and the history of the technological advances in the HDF technique. In addition, it explores the putative benefits of HDF over HD. While the observational studies provide a basis for optimism that HDF will provide benefit to dialysis patients, definitive conclusions cannot be drawn until the results of randomized controlled trials are available. While the evidence in favour of HDF at this stage is observational only, there are no studies suggesting that the treatment is detrimental. The use of HDF should probably be increased, particularly in centres where an increase in the frequency and duration of dialysis cannot be readily achieved. [source] Cystic fibrosis lung disease starts in the small airways: Can we treat it more effectively?PEDIATRIC PULMONOLOGY, Issue 2 2010Harm A.W.M. Tiddens MD Abstract The aims of this article are to summarize existing knowledge regarding the pathophysiology of small airways disease in cystic fibrosis (CF), to speculate about additional mechanisms that might play a role, and to consider the available or potential options to treat it. In the first section, we review the evidence provided by pathologic, physiologic, and imaging studies suggesting that obstruction of small airways begins early in life and is progressive. In the second section we discuss how the relationships between CF transmembrane conductance regulator (CFTR), ion transport, the volume of the periciliary liquid layer and airway mucus might lead to defective mucociliary clearance in small airways. In addition, we discuss how chronic endobronchial bacterial infection and a chronic neutrophilic inflammatory response increase the viscosity of CF secretions and exacerbate the clearance problem. Next, we discuss how the mechanical properties of small airways could be altered early in the disease process and how remodeling can contribute to small airways disease. In the final section, we discuss how established therapies impact small airways disease and new directions that may lead to improvement in the treatment of small airways disease. We conclude that there are many reasons to believe that small airways play an important role in the pathophysiology of (early) CF lung disease. Therapy should be aimed to target the small airways more efficiently, especially with drugs that can correct the basic defect at an early stage of disease. Pediatr Pulmonol. 2010; 45:107,117. © 2010 Wiley-Liss, Inc. [source] Childhood asthma epidemiology: Insights from comparative studies of rural and urban populations,PEDIATRIC PULMONOLOGY, Issue 2 2008Gary W.K. Wong MD Abstract Asthma is one of the most common chronic respiratory disorders. Many epidemiology studies have suggested an increasing trend of asthma in many different regions of the world but the exact reasons explaining such trend remain unclear. Nevertheless, changing environmental factors are most likely important in explaining the trend of asthma. Studies in the past decade have clearly shown a mark difference in the prevalence between urban and rural regions. The consistent findings of a markedly lower prevalence of asthma in children and adults who have been brought up in a farming environment clearly indicate the importance of environmental influence of asthma development. Although the exact protective environmental factors in the rural region remain to be defined, there have been many studies suggesting that early exposure to microbes or microbial products may play a role in modulating the immune system so as to reduce the future risk of asthma and allergies. Advances in the understanding of the genetic predisposition and how these genetic factors may interact with specific environment factors are of paramount importance for the future development of primary preventive strategies for asthma. Pediatr Pulmonol. 2008; 43:107,116. © 2007 Wiley-Liss, Inc. [source] Alteration of the disulfide-coupled folding pathway of BPTI by circular permutationPROTEIN SCIENCE, Issue 5 2004Grzegorz Bulaj BPTI, bovine pancreatic trypsin inhibitor; cBPTI, a circular form of BPTI generated by forming a peptide bond between the natural termini; cpBPTI, circularly permuted BPTI. Abstract The kinetics of disulfide-coupled folding and unfolding of four circularly permuted forms of bovine pancreatic trypsin inhibitor (BPTI) were studied and compared with previously published results for both wild-type BPTI and a cyclized form. Each of the permuted proteins was found to be less stable than either the wild-type or circular proteins, by 3,8 kcal/mole. These stability differences were used to estimate effective concentrations of the chain termini in the native proteins, which were 1 mM for the wild-type protein and 2.5 to 4000 M for the permuted forms. The circular permutations increased the rates of unfolding and caused a variety of effects on the kinetics of refolding. For two of the proteins, the rates of a direct disulfide-formation pathway were dramatically increased, making this process as fast or faster than the competing disulfide rearrangement mechanism that predominates in the folding of the wild-type protein. These two permutations break the covalent connectivity among the ,-strands of the native protein, and removal of these constraints appears to facilitate direct formation and reduction of nearby disulfides that are buried in the folded structure. The effects on folding kinetics and mechanism do not appear to be correlated with relative contact order, a measure of overall topological complexity. These observations are consistent with the results of other recent experimental and computational studies suggesting that circular permutation may generally influence folding mechanisms by favoring or disfavoring specific interactions that promote alternative pathways, rather than through effects on the overall topology of the native protein. [source] Phasic muscle activity in sleep and clinical features of Parkinson diseaseANNALS OF NEUROLOGY, Issue 3 2010Donald L. Bliwise PhD Objective: The absence of atonia during rapid eye movement (REM) sleep and dream-enactment behavior (REM sleep behavior disorder [RBD]) are common features of sleep in the alpha-synucleinopathies. This study examined this phenomenon quantitatively, using the phasic electromyographic metric (PEM), in relation to clinical features of idiopathic Parkinson disease (PD). Based on previous studies suggesting that RBD may be prognostic for the development of later parkinsonism, we hypothesized that clinical indicators of disease severity and more rapid progression would be related to PEM. Methods: A cross-sectional convenience sample of 55 idiopathic PD patients from a movement disorders clinic in a tertiary care medical center underwent overnight polysomnography. PEM, the percentage of 2.5-second intervals containing phasic muscle activity, was quantified separately for REM and non-REM (NREM) sleep from 5 different electrode sites. Results: Higher PEM rates were seen in patients with symmetric disease, as well as in akinetic-rigid versus tremor-predominant patients. Men had higher PEM relative to women. Results occurred in all muscle groups in both REM and NREM sleep. Interpretation: Although our data were cross-sectional, phasic muscle activity during sleep suggests disinhibition of descending motor projections in PD broadly reflective of more advanced and/or progressive disease. Elevated PEM during sleep may represent a functional window into brainstem modulation of spinal cord activity and is broadly consistent with the early pathologic involvement of non-nigral brainstem regions in PD, as described by Braak. ANN NEUROL 2010 [source] Oxidation of carotenoids by heat and tobacco smokeBIOFACTORS, Issue 1 2004John S. Hurst Abstract The stability to autoxidation of the polar carotenoids, lutein and zeaxanthin, was compared to that of the less polar carotenoids, ,-carotene and lycopene at physiologically or pathophysiologically relevant concentrations of 2 and 6 ,M, after exposure to heat or cigarette smoke. Three methodological approaches were used: 1) Carotenoids dissolved in solvents with different polarities were incubated at 37 and 80°C for different times. 2) Human plasma samples were subjected to the same temperature conditions. 3) Methanolic carotenoid solutions and plasma were also exposed to whole tobacco smoke from 1,5 unfiltered cigarettes. The concentrations of individual carotenoids in different solvents were determined spectrophotometrically. Carotenoids from plasma were extracted and analyzed using high performance liquid chromatography. Carotenoids were generally more stable at 37 than at 80°C. In methanol and dichloromethane the thermal degradation of ,-carotene and lycopene was faster than that of lutein and zeaxanthin. However, in tetrahydrofuran ,-carotene and zeaxanthin degraded faster than lycopene and lutein. Plasma carotenoid levels at 37°C did not change, but decreased at 80°C. The decrease of ,-carotene and lycopene levels was higher than those for lutein and zeaxanthin. Also in the tobacco smoke experiments the highest autoxidation rates were found for ,-carotene and lycopene at 2 ,M, but at 6 ,M lutein and zeaxanthin depleted to the same extent as ,-carotene. These data support our previous studies suggesting that oxidative stress degrade ,-carotene and lycopene faster than lutein and zeaxanthin. The only exception was the thermal degradation of carotenoids solubilized in tetrahydrofuran, which favors faster breakdown of ,-carotene and zeaxanthin. [source] Colorectal cancer in U.S. adults younger than 50 years of age, 1998,2001,CANCER, Issue S5 2006Temeika L. Fairley PhD Abstract BACKGROUND. Colorectal cancer (CRC) incidence rates are increasing among persons younger than 50 years of age, a population routinely not screened unless an individual has a high risk of CRC. This population-based study focuses primarily on describing the CRC burden for persons in this age group. METHODS. The data used for this study were derived from the National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) surveillance systems. Age-adjusted incidence rates, rate ratios, and their corresponding 95% confidence intervals were calculated. RESULTS. CRC is ranked among the top 10 cancers occurring in males and females aged 20,49 years regardless of race. Persons younger than 50 years were more likely to present with less localized and more distant disease than do older adults. Among younger adults, age-adjusted incidence rates for poorly differentiated cancers were twice as high as rates for well-differentiated cancers. Incidence rates for poorly differentiated cancers were 60% higher than that for well-differentiated cancers diagnosed in older adults. Rates were significantly higher for blacks and significantly lower for Asians/Pacific Islanders when compared with that for whites for the most demographic and tumor characteristics examined. CONCLUSIONS. This study confirms the findings of previous population-based studies suggesting that younger patients present with more advanced disease than do older patients. This study also identifies racial and ethnic disparities in CRC incidence in this population. These findings suggest the need for additional studies to understand the behavior and etiology of CRC in blacks. Cancer 2006. © 2006 American Cancer Society. [source] | |||||||||||||||||||