bluuebunny/crossref_metadata_2025 huggingface dataset:
The Vα14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode
Authors: Li Yali , Girardi Enrico , Wang Jing , Yu Esther Dawen , Painter Gavin F. , Kronenberg Mitchell , Zajonc Dirk M.
Published: October 2010

Invariant natural killer T cells (iNKT cells) rapidly produce effector cytokines. In this study, we report the first crystal structures of the iNKT cell T cell receptor (TCR) bound to two natural, microbial glycolipids presented by CD1d. Binding of the TCR induced CDR3-α–dependent structural changes in the F′ roof of CD1d; these changes resemble those occurring in the absence of TCR engagement when the highly potent synthetic antigen α-galactosylceramide (α-GalCer) binds CD1d. Furthermore, in the Borrelia burgdorferi α–galactosyl diacylglycerol–CD1d complex, TCR binding caused a marked repositioning of the galactose sugar into an orientation that closely resembles α-GalCer. The TCR-dependent reorientation of the sugar, together with the induced CD1d fit, may explain the weaker potency of the microbial antigens compared with α-GalCer. We propose that the TCR of iNKT cells binds with a conserved footprint onto CD1d, regardless of the bound glycolipid antigen, and that for microbial antigens this unique binding mode requires TCR-initiated conformational changes.
A novel subset of CD4+ TH2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma
Authors: Wang Yui-Hsi , Voo Kui Shin , Liu Bo , Chen Chun-Yu , Uygungil Burcin , Spoede William , Bernstein Jonathan A. , Huston David P. , Liu Yong-Jun
Published: October 2010

The inflammatory cytokine interleukin (IL)-17 is involved in the pathogenesis of allergic diseases. However, the identity and functions of IL-17–producing T cells during the pathogenesis of allergic diseases remain unclear. Here, we report a novel subset of TH2 memory/effector cells that coexpress the transcription factors GATA3 and RORγt and coproduce TH17 and TH2 cytokines. Classical TH2 memory/effector cells had the potential to produce IL-17 after stimulation with proinflammatory cytokines IL-1β, IL-6, and IL-21. The number of IL-17-TH2 cells was significantly increased in blood of patients with atopic asthma. In a mouse model of allergic lung diseases, IL-17–producing CD4+ TH2 cells were induced in the inflamed lung and persisted as the dominant IL-17–producing T cell population during the chronic stage of asthma. Treating cultured bronchial epithelial cells with IL-17 plus TH2 cytokines induced strong up-regulation of chemokine eotaxin-3, Il8, Mip1b, and Groa gene expression. Compared with classical TH17 and TH2 cells, antigen-specific IL-17–producing TH2 cells induced a profound influx of heterogeneous inflammatory leukocytes and exacerbated asthma. Our findings highlight the plasticity of TH2 memory cells and suggest that IL-17–producing TH2 cells may represent the key pathogenic TH2 cells promoting the exacerbation of allergic asthma.
The Economic Effect of Screening Orthopedic Surgery Patients Preoperatively for Methicillin-ResistantStaphylococcus aureus
Authors: Lee Bruce Y. , Wiringa Ann E. , Bailey Rachel R. , Goyal Vishal , Tsui Becky , Lewis G. Jonathan , Muder Robert R. , Harrison Lee M.
Published: October 2010

Background and Objective.

Patients undergoing orthopedic surgery are susceptible to methicillin-resistantStaphylococcus aureus(MRSA) infections, which can result in increased morbidity, hospital lengths of stay, and medical costs. We sought to estimate the economic value of routine preoperative MRSA screening and decolonization of orthopedic surgery patients.

Methods.

A stochastic decision-analytic computer simulation model was used to evaluate the economic value of implementing this strategy (compared with no preoperative screening or decolonization) among orthopedic surgery patients from both the third-party payer and hospital perspectives. Sensitivity analyses explored the effects of varying MRSA colonization prevalence, the cost of screening and decolonization, and the probability of decolonization success.

Results.

Preoperative MRSA screening and decolonization was strongly cost-effective (incremental cost-effectiveness ratio less than $6,000 per quality-adjusted life year) from the third-party payer perspective even when MRSA prevalence was as low as 1%, decolonization success was as low as 25%, and decolonization costs were as high as $300 per patient. In most scenarios this strategy was economically dominant (ie, less costly and more effective than no screening). From the hospital perspective, preoperative MRSA screening and decolonization was the economically dominant strategy for all scenarios explored.

Conclusions.

Routine preoperative screening and decolonization of orthopedic surgery patients may under many circumstances save hospitals and third-party payers money while providing health benefits.
The Use of Antimicrobial Agents after Diagnosis of Viral Respiratory Tract Infections in Hospitalized Adults: Antibiotics or Anxiolytics?
Authors: Shiley Kevin T. , Lautenbach Ebbing , Lee Ingi
Published: October 2010

Objective.

Because extensive antibiotic use by inpatients has been associated with the development of multidrug-resistant organisms, we aimed to determine which variables were associated with the use of antibiotics after viral respiratory tract infection diagnosis among adult patients admitted to the hospital with respiratory symptoms.

Methods.

A retrospective cohort study was conducted at 2 affiliated urban hospitals in Pennsylvania. We identified all adult patients admitted to the hospital during the period from November 1, 2005, through August 1, 2007, with a viral assay positive for influenza A or B, parainfluenza, adenovirus, or respiratory syncytial virus. Among these patients, we identified those who received antibiotics after the diagnosis of viral RTL Data on demographics; comorbidities; and physical examination, laboratory, and radiographic findings were ascertained to identify risk factors for antimicrobial use among these patients.

Results.

A total of 196 hospitalized patients with positive viral assay results were included; 125 of 131 patients administered antibiotics continued to receive them after viral RTI diagnosis. Among 52 patients with an abnormal chest radiograph, 46 continued antibiotic therapy. An abnormal chest radiograph was independently associated with continued antibiotic use (adjusted odds ratio, 4.28 [95% confidence interval, 1.71-10.77]; P = .002). However, the majority of patients (79 of 125 [63%]) who continued antibiotic therapy had normal chest imaging findings. Eight patients (6%) who continued antibiotic therapy and no patients who stopped developed C. difficile infection (95% CI, 1.5-00; p = .05), but there was no significant difference in length of stay or mortality.

Conclusions.

Antibiotics are commonly used to treat hospitalized patients with known acute viral RTIs. Continued use is strongly associated with abnormal radiograph findings at admission. However, the reasons for continuation of antibiotics in the treatment of the majority of patients with normal radiographs are unclear and may represent inappropriate use.
Microbiologic and Clinical Epidemiologic Characteristics of the Chicago Subset of a Multistate Outbreak ofSerratia marcescensBacteremia
Authors: Sikka Monica K. , Hayden Mary K. , Pur Stacy , Segreti John , Harris Alan A. , Weinstein Robert A. , Trenholme Gordon
Published: October 2010

We describe 22 patients from a multistate outbreak ofSerraría marcescensbacteremia that was linked to contaminated prefilled syringes of heparin and saline supplied by 1 manufacturer. Contents of unused syringes were cultured in pools samples from 25 (5.3%) of 472 syringes grewS. marcescens. Despite good clinical outcomes overall, patients had substantial morbidity.
The N-Terminal Domain of PMTV TGB1 Movement Protein Is Required for Nucleolar Localization, Microtubule Association, and Long-Distance Movement
Authors: Wright Kathryn M. , Cowan Graham H. , Lukhovitskaya Nina I. , Tilsner Jens , Roberts Alison G. , Savenkov Eugene I. , Torrance Lesley
Published: October 2010

The triple-gene-block (TGB)1 protein of Potato mop-top virus (PMTV) was fused to fluorescent proteins and expressed in epidermal cells of Nicotiana benthamiana under the control of the 35S promoter. TGB1 fluorescence was observed in the cytoplasm, nucleus, and nucleolus and occasionally associated with microtubules. When expressed from a modified virus (PMTV.YFP-TGB1) which formed local lesions but was not competent for systemic movement, yellow fluorescent protein (YFP)-TGB1 labeled plasmodesmata in cells at the leading edge of the lesion and plasmodesmata, microtubules, nuclei, and nucleoli in cells immediately behind the leading edge. Deletion of 84 amino acids from the N-terminus of unlabeled TGB1 within the PMTV genome abolished movement of viral RNA to noninoculated leaves. When the same deletion was introduced into PMTV.YFP-TGB1, labeling of microtubules and nucleoli was abolished. The N-terminal 84 amino acids of TGB1 were fused to green fluorescent protein (GFP) and expressed in epidermal cells where GFP localized strongly to the nucleolus (not seen with unfused GFP), indicating that these amino acids contain a nucleolar localization signal; the fusion protein did not label microtubules. This is the first report of nucleolar and microtubule association of a TGB movement protein. The results suggest that PMTV TGB1 requires interaction with nuclear components and, possibly, microtubules for long-distance movement of viral RNA.
A Four-Partner Plant–Virus Interaction: Enemies Can Also Come from Within
Authors: Iskra-Caruana Marie-Line , Baurens Franc-Christophe , Gayral Philippe , Chabannes Matthieu
Published: October 2010

Plant viruses are disseminated by either vertical (vegetative multiplication or sexual reproduction) or horizontal (vector-mediated) propagation. Plant pararetroviruses—members of the Caulimoviridae family—have developed an alternative strategy for vertical propagation via integration within the host plant genome, although integration is not required for viral replication. Integrated endogenous pararetrovirus (EPRV) sequences have undergone extensive viral genome rearrangements and contain more than one copy of the viral genome. Furthermore, EPRV can become infectious upon spontaneous escape of active virus following stresses such as wounding, tissue culture, or interspecific crosses. Such infectious EPRV are of great importance, not only in terms of their ability to precipitate epidemic outbreaks but also because of their effect on breeding of numerous plant genomes in temperate and tropical crops. This is especially true for banana, a crop susceptible to banana streak viruses, the causative agents of banana streak disease. Thus, the classical three-component banana–Banana streak virus (BSV)–mealybug pathosystem can be expanded to include endogenous BSV as an alternative source of active virions. The BSV-banana pathosystem is one of only three pathosystems known to date to harbor this remarkable feature, and the present review focuses exclusively on it to illustrate this four-partner interaction.
Genetic Analysis of Streptomycin-Resistant (SmR) Strains of Erwinia amylovora Suggests that Dissemination of Two Genotypes Is Responsible for the Current Distribution of SmR E. amylovora in Michigan
Authors: McGhee Gayle C. , Guasco Jesse , Bellomo Lisa M. , Blumer-Schuette Sara E. , Shane William W. , Irish-Brown Amy , Sundin George W.
Published: October 2010

Streptomycin-resistant (SmR) strains of the fire blight pathogen Erwinia amylovora were first isolated in southwest Michigan in 1991. Since that time, resistant strains have progressed northward to other apple-producing regions in the state. A total of 98.7% of SmR strains isolated between 2003 and 2009 in Michigan harbored the strA-strB genes on transposon Tn5393. strA and strB encode phosphotransferase enzymes that modify streptomycin to a nonbactericidal form. Mutational resistance to streptomycin, caused by a point mutation-mediated target-site alteration of the ribosomal S12 protein, occurred in 1.3% of E. amylovora strains from Michigan. Tn5393 was originally introduced to E. amylovora on the plasmid pEa34; thus, the first SmR strains isolated contained both pEa34 and the ubiquitous nonconjugative plasmid pEA29. More recently, we have observed SmR strains in which Tn5393 is present on pEA29, suggesting that the transposon has moved via transposition from pEa34 to pEA29. Almost all of the strains containing Tn5393 on pEA29 had lost pEa34. Of 210 pEA29::Tn5393 plasmids examined, the transposon was inserted at either nucleotide position 1,515 or 17,527. Both of these positions were in noncoding regions of pEA29. Comparative sequencing of the housekeeping genes groEL and potentially variable sequences on pEA29 was done in an attempt to genetically distinguish SmR strains from streptomycin-sensitive (SmS) strains isolated in Michigan. Only 1 nucleotide difference within the total 2,660 bp sequenced from each strain was observed in 2 of 29 strains; multiple sequence differences were observed between the Michigan strains and E. amylovora control strains isolated in the western United States or from Rubus spp. Alterations in virulence observable using an immature pear fruit assay were detected in three of eight SmR strains examined. Our current genetic data indicate that only two SmR strain genotypes (strains containing pEA29::Tn5393 with Tn5393 inserted at either nucleotide position 1,515 or 17,527 on the plasmid) are responsible for the dissemination of Tn5393-encoded streptomycin resistance in Michigan, and that the SmR and SmS strains in Michigan compose a homogenous group.
Evaluation of Kasugamycin for Fire Blight Management, Effect on Nontarget Bacteria, and Assessment of Kasugamycin Resistance Potential in Erwinia amylovora
Authors: McGhee Gayle C. , Sundin George W.
Published: October 2010

The emergence and spread of streptomycin-resistant strains of Erwinia amylovora in Michigan has necessitated the evaluation of new compounds effective for fire blight control. The aminoglycoside antibiotic kasugamycin (Ks) targets the bacterial ribosome and is particularly active against E. amylovora. The efficacy of Ks formulated as Kasumin 2L for control of fire blight was evaluated in six experiments conducted over four field seasons in our experimental orchards in East Lansing, MI. Blossom blight control was statistically equivalent to the industry standard streptomycin in all experiments. E. amylovora populations remained constant on apple flower stigmas pretreated with Kasumin and were ≈100-fold lower than on stigmas treated with water. Kasumin applied to apple trees in the field also resulted in a 100-fold reduced total culturable bacterial population compared with trees treated with water. We performed a prospective analysis of the potential for kasugamycin resistance (KsR) development in E. amylovora which focused on spontaneous resistance development and acquisition of a transferrable KsR gene. In replicated lab experiments, the development of spontaneous resistance in E. amylovora to Ks at 250 or 500 ppm was not observed when cells were directly plated on medium containing high concentrations of the antibiotic. However, exposure to increasing concentrations of Ks in media (initial concentration 25 μg ml–1) resulted in the selection of Ks resistance (at 150 μg ml–1) in the E. amylovora strains Ea110, Ea273, and Ea1189. Analysis of mutants indicated that they harbored mutations in the kasugamycin target ksgA gene and that all mutants were impacted in relative fitness observable through a reduced growth rate in vitro and decreased virulence in immature pear fruit. The possible occurrence of a reservoir of KsR genes in orchard environments was also examined. Culturable gram-negative bacteria were surveyed from six experimental apple orchards that had received at least one Kasumin application. In total, 401 KsR isolates (42 different species) were recovered from apple flowers and leaves and orchard soil samples. Although we have not established the presence of a transferrable KsR gene in orchard bacteria, the frequency, number of species, and presence of KsR enterobacterial species in orchard samples suggests the possible role of nontarget bacteria in the future transfer of a KsR gene to E. amylovora. Our data confirm the importance of kasugamycin as an alternate antibiotic for fire blight management and lay the groundwork for the development and incorporation of resistance management strategies.
Impact of Swiss Needle-Cast on Growth of Douglas-Fir
Authors: Kimberley M. O. , Hood I. A. , Knowles R. L.
Published: October 2010

Phaeocryptopus gaeumannii, the cause of Swiss needle-cast, is widely distributed in plantations of Douglas-fir in many parts of the world. Nevertheless, information remains limited on its precise effect on stand growth, particularly in relation to regional climate, and on its consequent economic cost. In New Zealand, the spread of P. gaeumannii over a period of ≈30 years following its discovery in 1959 was closely monitored, and the timing of its arrival in different forests is known. This information was coupled with data from permanent sample plots in order to quantify the associated historical growth increment loss. Analyses revealed a steady decline in growth rate over the period from the first appearance of P. gaeumannii to a point when it stabilized at a lower increment level 14 to 20 years later. The cumulative mean reduction was 25% for mean top height, 27% for basal area, and 32% for stem volume. Volume growth rate decline was greater in the North Island (35%) than the South Island (23%) of New Zealand. These reductions in volume growth are estimated to equate to a loss in net present value of $NZ2,620 ha–1and $NZ1,470 ha–1for the North and South Islands, respectively, using a discount rate of 6%. Mortality did not increase as a result of infection by P. gaeumannii. The disease had less effect on cooler sites, especially those with low spring minimum temperatures (P < 0.001). Negligible growth decline occurred on sites with daily minimum October temperatures averaging <3.2°C.
Conservation of an RNA regulatory map between Drosophila and mammals
Authors: Brooks Angela N. , Yang Li , Duff Michael O. , Hansen Kasper D. , Park Jung W. , Dudoit Sandrine , Brenner Steven E. , Graveley Brenton R.
Published: October 2010

Alternative splicing is generally controlled by proteins that bind directly to regulatory sequence elements and either activate or repress splicing of adjacent splice sites in a target pre-mRNA. Here, we have combined RNAi and mRNA-seq to identify exons that are regulated by Pasilla (PS), the Drosophila melanogaster ortholog of mammalian NOVA1 and NOVA2. We identified 405 splicing events in 323 genes that are significantly affected upon depletion of ps, many of which were annotated as being constitutively spliced. The sequence regions upstream and within PS-repressed exons and downstream from PS-activated exons are enriched for YCAY repeats, and these are consistent with the location of these motifs near NOVA-regulated exons in mammals. Thus, the RNA regulatory map of PS and NOVA1/2 is highly conserved between insects and mammals despite the fact that the target gene orthologs regulated by PS and NOVA1/2 are almost entirely nonoverlapping. This observation suggests that the regulatory codes of individual RNA binding proteins may be nearly immutable, yet the regulatory modules controlled by these proteins are highly evolvable.
The Arabidopsis Botrytis Susceptible1 Interactor Defines a Subclass of RING E3 Ligases That Regulate Pathogen and Stress Responses
Authors: Luo Hongli , Laluk Kristin , Lai Zhibing , Veronese Paola , Song Fengming , Mengiste Tesfaye
Published: October 2010

We studied the function of Arabidopsis (Arabidopsis thaliana) Botrytis Susceptible1 Interactor (BOI) in plant responses to pathogen infection and abiotic stress. BOI physically interacts with and ubiquitinates Arabidopsis BOS1, an R2R3MYB transcription factor previously implicated in stress and pathogen responses. In transgenic plants expressing the BOS1-β-glucuronidase transgene, β-glucuronidase activity could be detected only after inhibition of the proteosome, suggesting that BOS1 is a target of ubiquitin-mediated degradation by the proteosome. Plants with reduced BOI transcript levels generated through RNA interference (BOI RNAi) were more susceptible to the necrotrophic fungus Botrytis cinerea and less tolerant to salt stress. In addition, BOI RNAi plants exhibited increased cell death induced by the phytotoxin α-picolinic acid and by a virulent strain of the bacterial pathogen Pseudomonas syringae, coincident with peak disease symptoms. However, the hypersensitive cell death associated with different race-specific resistance genes was unaffected by changes in the level of BOI transcript. BOI expression was enhanced by B. cinerea and salt stress but repressed by the plant hormone gibberellin, indicating a complex regulation of BOI gene expression. Interestingly, BOI RNAi plants exhibit reduced growth responsiveness to gibberellin. We also present data revealing the function of three Arabidopsis BOI-RELATED GENES (BRGs), which contribute to B. cinerea resistance and the suppression of disease-associated cell death. In sum, BOI and BRGs represent a subclass of RING E3 ligases that contribute to plant disease resistance and abiotic stress tolerance through the suppression of pathogen-induced as well as stress-induced cell death.
Predicted effects of climate warming on the distribution of 50 stream fishes in Wisconsin, U.S.A.
Authors: Lyons J. , Stewart J. S. , Mitro M.
Published: October 2010

Summer air and stream water temperatures are expected to rise in the state of Wisconsin, U.S.A., over the next 50 years. To assess potential climate warming effects on stream fishes, predictive models were developed for 50 common fish species using classification‐tree analysis of 69 environmental variables in a geographic information system. Model accuracy was 56·0–93·5% in validation tests. Models were applied to all 86 898 km of stream in the state under four different climate scenarios: current conditions, limited climate warming (summer air temperatures increase 1° C and water 0·8° C), moderate warming (air 3° C and water 2·4° C) and major warming (air 5° C and water 4° C). With climate warming, 23 fishes were predicted to decline in distribution (three to extirpation under the major warming scenario), 23 to increase and four to have no change. Overall, declining species lost substantially more stream length than increasing species gained. All three cold‐water and 16 cool‐water fishes and four of 31 warm‐water fishes were predicted to decline, four warm‐water fishes to remain the same and 23 warm‐water fishes to increase in distribution. Species changes were predicted to be most dramatic in small streams in northern Wisconsin that currently have cold to cool summer water temperatures and are dominated by cold‐water and cool‐water fishes, and least in larger and warmer streams and rivers in southern Wisconsin that are currently dominated by warm‐water fishes. Results of this study suggest that even small increases in summer air and water temperatures owing to climate warming will have major effects on the distribution of stream fishes in Wisconsin.
A prospective study into the aetiology of lymphocytic duodenosis
Authors: Aziz I. , Evans K. E. , Hopper A. D. , Smillie D. M. , Sanders D. S.
Published: October 2010

Aliment Pharmacol Ther 2010; 32: 1392–1397

Background  Lymphocytic duodenosis is defined by normal villous architecture and intraepithelial lymphocytes (IELs) >25 per 100 enterocytes. Such patients should not be diagnosed with coeliac disease, solely by histology, as previous retrospective studies have suggested other associations with lymphocytic duodenosis.

Aim  To study prospectively the aetiology of lymphocytic duodenosis.

Methods  One hundred patients with lymphocytic duodenosis were investigated rigorously for coeliac disease and other known associations for lymphocytic duodenosis by initial investigations of coeliac serology, and exclusion of infection. Of 34 with no explanation for lymphocytic duodenosis, 29 underwent repeat duodenal biopsies following a gluten challenge.

Results  Coeliac disease was present in 16% of patients with lymphocytic duodenosis. In the absence of a positive coeliac diagnosis, lymphocytic duodenosis was most commonly associated with drugs (21%), infection (19%), immune dysregulation (4%), inflammatory bowel disease (2%), microscopic colitis (2%), sarcoidosis (1%) and IgA deficiency (1%). Of 34 with no known associations, 18 had symptoms of irritable bowel syndrome (IBS), and in 29 patients investigated with repeat duodenal biopsies, the IEL count returned to normal in 22.

Conclusions  In 66% of cases of lymphocytic duodenosis, a known association can be found by further investigations; importantly, 16% will have coeliac disease. In those with no apparent cause, there may be an association with IBS and the IEL count becomes normal on repeat biopsy in 76%.
Association of functional polymorphisms related to the transcriptional level of FOXP3 with prognosis of autoimmune thyroid diseases
Authors: Inoue N , Watanabe M , Morita M , Tomizawa R , Akamizu T , Tatsumi K , Hidaka Y , Iwatani Y
Published: October 2010

The severity of Hashimoto's disease (HD) and intractability (or inducibility to remission) of Graves' disease (GD) varies among patients. Forkhead box P3 (FoxP3) is a crucial regulatory factor for the development and function of regulatory T (Treg) cells, and deficiency of the FoxP3 gene (FOXP3) suppresses the regulatory function of Treg cells. To clarify the association of the functional polymorphisms of the FOXP3 with the prognosis of GD and HD, we genotyped −3499A/G, −3279C/A and −2383C/T polymorphisms in FOXP3 gene obtained from 38 patients with severe HD, 40 patients with mild HD, 65 patients with intractable GD, in whom remission was difficult to induce, 44 patients with GD in remission and 71 healthy volunteers. The −3279CA genotype was more frequent in patients with GD in remission than in patients with intractable GD, and the −3279AA genotype, which correlates to defective transcription of FOXP3, was absent in patients with GD in remission. The −2383CC genotype was more frequent in patients with severe HD than in those with mild HD. In conclusion, the −3279A/C polymorphism is related to the development and intractability of GD and the −2383CC genotype to the severity of HD.
The value of detectable thyroglobulin in patients with differentiated thyroid cancer after initial 131I therapy
Authors: van Dijk D. , Plukker J. T. M. , van der Horst‐Schrivers A. N. A. , Jansen L. , Brouwers A. H. , Muller‐Kobold A. , Sluiter W. J. , Links T. P.
Published: October 2010

Objective  To assess the prognostic value of detectable thyroglobulin (Tg) after initial surgery and radioactive iodine (131I) therapy by comparing patients with a negative post‐therapeutic whole body scan (WBS) with either detectable or undetectable Tg.

Background  Differentiated thyroid cancer has a good prognosis. However, recurrences can occur up to 30 years after initial treatment. Because life‐long follow‐up is necessary, it is important to explore possible risk factors associated with recurrence and mortality.

Design, patients and measurements  We studied 539 patients who were treated between 1980 and 2007. After the last therapeutic dosage of 5550 MBq 131I, 72 patients had negative post‐therapeutic WBS and positive Tg levels (Tg+ group) and 399 patients had negative post‐therapeutic WBS and negative Tg (Tg‐ group). The 68 remaining patients had proven residual macroscopic disease. We investigated recurrences and overall mortality in the Tg+ and Tg‐ group compared with the Dutch population.

Results  In the Tg+ group, detectable recurrences occurred significantly earlier and more frequently than in the Tg‐ group (19%vs 13%, P = 0·024). Survival between these groups was comparable, but shorter than the general Dutch population [Standardised Mortality Rate (SMR) 1·38 (95% CI 1·12;1·63) (P = 0·003)]. Disease‐free survival in the Tg groups was comparable and not significantly different from the Dutch population [SMR = 1·09 (95% CI 0·81;1·34) (P = 0·569)].

Conclusion  Patients with detectable Tg during the last 131I treatment and a negative post‐therapeutic WBS have significant earlier and more recurrences than patients without detectable Tg. Survival in both groups is comparable. After initial therapy, the combination of a negative high dose post‐therapeutic WBS with detectable Tg is a valuable predictor for earlier and more recurrences, but is not associated with survival.
Elevated anti‐Müllerian hormone (AMH) and inhibin B levels in prepubertal girls with type 1 diabetes mellitus
Authors: Codner Ethel , Iñiguez Germán , Hernández Isabel M. , Lopez Patricia , Rhumie Hana K. , Villarroel Claudio , Rey Rodolfo A.
Published: October 2010

Objective  Elevated anti‐Müllerian hormone (AMH) and adrenal androgen levels have been observed during childhood in girls at risk of developing polycystic ovarian syndrome (PCOS). The aim of this study was to evaluate ovarian function and adrenal steroid levels in prepubertal girls with type 1 diabetes mellitus (T1D).

Design  Cross‐sectional study.

Patients/Measurements  We evaluated hormonal and ultrasonographic characteristics in girls with T1D (N = 73) and compared them to characteristics found in a control group of healthy girls (N = 86). Data are reported as geometric means (95% CI).

Results  Prepubertal girls with T1D had higher levels of AMH (29·1 pmol/l (23·2–36·3) vs 20·9 pmol/l (16·6–26·1), P = 0·038), inhibin B (arithmetic mean: 16·7 pg/ml (11·6–21·7) vs 11·7 pg/ml (10·0–13·5), P = 0·044) and dehydroepiandrosterone sulphate (DHEAS) (0·3 nmol/l (0·2–0·6) vs 0·2 nmol/l (0·1–0·3)) than controls (P = 0·045). During puberty, decreasing AMH levels were observed in girls with T1D only (P < 0·0001). Girls with T1D in Tanner stages 4–5 had lower AMH levels than their paired healthy controls (10·1 pmol/l (7·4–13·9) vs 15·7 pmol/l (11·6–21·3), respectively, P = 0·047).

Conclusions  Our observations indicate that prepubertal girls with T1D may exhibit similar endocrine findings to those of other girls at risk of developing PCOS. The elevated levels of AMH and inhibin B suggest that higher numbers of follicles are present in the ovary during childhood in these patients and that insulin treatment may act as a local growth factor. In addition, AMH levels differed in prepubertal and pubertal girls, suggesting that the effect of T1D on ovarian folliculogenesis changes once gonadotrophin levels rise during puberty.
Phenological responses to extreme droughts in a Mediterranean forest
Authors: MISSON LAURENT , DEGUELDRE DAVID , COLLIN CHRISTIAN , RODRIGUEZ RAQUEL , ROCHETEAU ALAIN , OURCIVAL JEAN‐MARC , RAMBAL SERGE
Published: October 2010

Mediterranean regions are projected to experience more frequent, prolonged and severe drought as a consequence of climate change. We used a retractable rainfall shelter, to investigate the impact of extreme droughts on the development of Quercus ilex leaves, flowers and fruit. In 2008, 97% of rainfall was excluded from a forest plot during the autumn, representing 50% of the 1127 mm of rain that fell during the year. In 2009, 87% of rainfall was excluded during the spring, representing 58% of the 749 mm that fell during the year. The rainfall shelter did not impact neither incident radiation nor air temperature. Autumn rainfall exclusion did not significantly affect leaf, flowers or fruit development. Spring rainfall exclusion resulted in larger and more sustained depression of leaf water potential during the key phases of foliar and floral development. Consequently, only half of the sampled trees (6) reached the shoot lengthening stage which leads to functionally mature leaves (phenophase 4), with one abandoning leaf development at budburst (phenophase 3) and the other two at the bud swelling stage (phenophase 2). All trees of the control plot passed phenophase 4, with most reaching complete leaf development. The impact of extreme droughts on flower development differed between the sexes. The spring exclusion had no effect on male flower, but only one of six trees completed female fruit maturation, compared with four in the control plot. The difference between the male and female drought impacts is likely attributable to the occurrence of male floral development before the period of lowest leaf water potential, and to the lower resource allocation requirements of male flowers. The information provided by our experimental approach may constitute a crucial step to evaluate the impact of increasing drought due to climate change on the most dominant Mediterranean tree species and to help drawing a full picture of the ecological consequences of the decline in water resource on forest dynamics under changing conditions.
Nonlinear nitrous oxide (N2O) response to nitrogen fertilizer in on‐farm corn crops of the US Midwest
Authors: HOBEN J. P. , GEHL R. J. , MILLAR N. , GRACE P. R. , ROBERTSON G. P.
Published: October 2010

Row‐crop agriculture is a major source of nitrous oxide (N2O) globally, and results from recent field experiments suggest that significant decreases in N2O emissions may be possible by decreasing nitrogen (N) fertilizer inputs without affecting economic return from grain yield. We tested this hypothesis on five commercially farmed fields in Michigan, USA planted with corn in 2007 and 2008. Six rates of N fertilizer (0–225 kg N ha−1) were broadcast and incorporated before planting, as per local practice. Across all sites and years, increases in N2O flux were best described by a nonlinear, exponentially increasing response to increasing N rate. N2O emission factors per unit of N applied ranged from 0.6% to 1.5% and increased with increasing N application across all sites and years, especially at N rates above those required for maximum crop yield. At the two N fertilizer rates above those recommended for maximum economic return (135 kg N ha−1), average N2O fluxes were 43% (18 g N2O–N ha−1 day−1) and 115% (26 g N2O–N ha−1 day−1) higher than were fluxes at the recommended rate, respectively. The maximum return to nitrogen rate of 154 kg N ha−1yielded an average 8.3 Mg grain ha−1. Our study shows the potential to lower agricultural N2O fluxes within a range of N fertilization that does not affect economic return from grain yield.
Effect of combined hormonal and insulin therapy on the steroid hormone receptors and growth factors signalling in diabetic mice prostate
Authors: Fávaro Wagner J. , Cagnon Valéria H. A.
Published: October 2010

Diabetes causes harmful effects on prostatic morphology and function. However, there still are doubts about the occurrence of various diseases in the prostate, as well as abnormal angiogenesis in relation to diabetes. Thus, the aim of this study was to correlate and quantify the level of the steroid hormone receptors and the angiogenic and antiangiogenic factors in non‐obese diabetic mice (Nod) after combined hormonal and insulin therapy. Sixty mice were divided into six groups after 20 days of diabetes: the control group received 0.9% NaCl, as did the diabetic group. The diabetic‐insulin group received insulin, the diabetic‐testosterone group received testosterone cypionate, the diabetic‐oestrogen group received 17β‐oestradiol, and the diabetic‐insulin–testosterone–oestrogen group received insulin, testosterone and oestrogen simultaneously. After 20 days, the ventral lobe was processed for immunocytochemical and hormonal analyses. The results showed that the lowest serum testosterone and androgen receptor levels were found in the diabetic group and the highest testosterone and androgen receptor levels in the diabetic‐insulin–testosterone–oestrogen group. The serum oestrogen level and its receptor showed changes opposite to those of testosterone and its receptor. The endostatin reactivity was mainly decreased in diabetic mice. The greatest IGFR‐1 and VEGF reactivities occurred in diabetic mice. Thus, diabetes led to the prostatic hormonal imbalance, affecting molecular dynamics and angiogenesis in this organ. Combined insulin and steroid hormone therapy partially restored the hormonal and angiogenic imbalance caused by diabetes.
Modelling pulsed releases for sterile insect techniques: fitness costs of sterile and transgenic males and the effects on mosquito dynamics
Authors: White Steven M. , Rohani Pejman , Sait Steven M.
Published: October 2010

1. The development of transgenic technologies, coupled with sterile insect techniques (SIT), is being explored in relation to new approaches for the biological control of insect pests. Recent studies have shown that there are often fitness costs associated with transgenic insect strains, but the impact of these costs on their potential use in pest control is poorly understood.

2. In this paper, we explore the impact of an insect fitness cost on two control strategies (classical SIT and transgenic late‐acting bisex lethality) using a stage‐structured mathematical model, which is parameterized for the mosquito Aedes aegypti. Counter to the majority of studies, we use realistic pulsed release strategies and incorporate a fitness cost, which is manifested as a reduction in male mating competitiveness.

3. For both models we show that the level of control of a pest mosquito population is highly sensitive to the rate at which the transgenic or sterile males are released. Population control is more effective when smaller numbers of sterile/transgenic males are released more frequently than larger and less frequent releases.

4. If the wild‐type mosquito population exhibits cycles of peaks and troughs in abundance, as is the case for many insect species, then high frequency releases of transgenic males not only reduce mosquito abundance, but they may dampen future pest outbreaks, whereas the use of SIT alone may have an adverse effect, causing an increase in mosquito abundance. Additionally, the timing of sterile/transgenic male release during the mosquito population cycle is critical in reducing pest outbreak levels.

5. In all cases, the reduced fitness of the sterile/transgenic males causes reductions in control, thus requiring more frequent or greater magnitude releases.

6. Synthesis and applications. The sterile insect technique is considered to be a valuable non‐chemical tool for pest management. With the potential application of recent genetic developments to enhance the technique, it is becoming increasingly important to consider the wider ecological implications of this biological control strategy. Predicting the most efficient release strategies will be important in combating pest and vector insects as well as for limiting potential broader ecological effects. Although the focus of our models are based on the mosquito, A. aegypti, which can spread yellow fever, dengue fever and Chikungunya disease, our modelling approach and results can be applied more broadly to other species.
Couples’ thoughts about and expectations of their future life after the patient’s hospital discharge following acute myocardial infarction
Authors: Eriksson Monica , Asplund Kenneth , Svedlund Marianne
Published: October 2010

Aim.  To describe and interpret couples’ thoughts and expectations about their future life after the patient’s discharge following acute myocardial infarction.

Background.  An acute myocardial infarction is a challenge for both the patient and his/her partner, as it can disrupt family functioning and dynamics. Earlier research has generally focused on either the patient or the partner, and few studies have explored the experiences of the couple.

Design.  Qualitative descriptive and interpretative.

Methods.  Fifteen couples took part in individual interviews, 4–8 weeks after discharge. Data were analysed in two phases using qualitative content analysis.

Results.  The first phase of the analysis revealed two categories: ‘an active approach to the future’ and ‘a wait‐and‐see approach to the future’, both of which described the participants’ thoughts about the future. In the second phase, the couples’ stories were interpreted and grouped into four positions: ‘the life companions’, ‘the tightrope walkers’, ‘the pathfinders’ and ‘the observers’, which illustrated their visions of the future.

Conclusions.  Our results reveal differences in the couples’ thoughts about and expectations of their future life, most of them managed the situation by having a positive attitude to life and their future. The couples discovered their resources and compensated for or balanced each other in the early recovery period.

Relevance to clinical practice.  The results indicate the importance of giving both partners the opportunity to express their views of the situation, as this increases nurses’ understanding of the impact of the illness on their life and relationship. However, the results also highlight the significance of seeing the couple and showing them consideration both as individuals and as a unit.
Acute care management of older people with dementia: a qualitative perspective
Authors: Moyle Wendy , Borbasi Sally , Wallis Marianne , Olorenshaw Rachel , Gracia Natalie
Published: October 2010

Aim and objectives.  This Australian study explored management for older people with dementia in an acute hospital setting.

Background.  As the population ages, increasing numbers of older people with dementia are placed into an acute care hospital to manage a condition other than dementia. These people require special care that takes into account the unique needs of confused older people. Current nursing and medical literature provides some direction in relation to best practice management; however, few studies have examined this management from the perspective of hospital staff.

Design.  A descriptive qualitative approach was used.

Method.  Data were collected using semi‐structured audio‐taped interviews with a cross section of thirteen staff that worked in acute medical or surgical wards in a large South East Queensland, Australia Hospital.

Results.  Analysis of data revealed five subthemes with the overarching theme being paradoxical care, in that an inconsistent approach to care emphasised safety at the expense of well‐being and dignity. A risk management approach was used rather than one that incorporated injury prevention as one facet of an overall strategy.

Conclusion.  Using untrained staff to sit and observe people with dementia as a risk management strategy does not encourage an evidence‐based approach. Staff education and environmental resources may improve the current situation so that people with dementia receive care that takes into account their individual needs and human dignity.

Relevance to clinical practice.  Nurses can assist older people with dementia by encouraging evidence‐based care practices to become the part of hospital policy.
Plant–soil feedbacks contribute to an intransitive competitive network that promotes both genetic and species diversity
Authors: Lankau Richard A. , Wheeler Emily , Bennett Alison E. , Strauss Sharon Y.
Published: October 2010

1. Plant communities are generally thought to follow strict competitive hierarchies, in which species can be linearly ordered according to their ability to compete for a few limiting resources. Such strict hierarchies should lead to reduced diversity, since the single best competitor will eventually exclude the other species. However, more complex dynamics may emerge if different plant species or genotypes compete in different ways, such as through the release of toxic allelochemicals or the alteration of soil microbial communities.

2.
Brassica nigra genotypes and their competitor species show a ‘rock‐paper‐scissors’ like dynamic, in which no one type is competitively superior to all others. This intransitive dynamic can maintain both species diversity and genetic variation in an allelochemical trait of B. nigra.

3. Here we show that feedbacks with soil biota, probably involving arbuscular mycorrhizal fungi, facilitate these dynamics. Brassica nigra genotypes that invest heavily in the allelochemical sinigrin reduce mycorrhizal abundance of surrounding soils, which reduces the growth of heterospecific competitors. Since B. nigra is non‐mycorrhizal, investment in sinigrin does not improve a genotype’s ability to compete with other conspecifics.

4.
Synthesis. These results highlight the importance of complex soil communities for the maintenance of both genetic and species diversity in plant communities.
A review of cost‐effectiveness of varenicline and comparison of cost‐effectiveness of treatments for major smoking‐related morbidities
Authors: Zimovetz Evelina A. , Wilson Koo , Samuel Miny , Beard Stephen M.
Published: October 2010

Rationale This review aims to examine economic evaluations of varenicline, to compare the reported cost‐effectiveness of varenicline with that of treatments for major smoking‐related diseases and to evaluate the findings for decision making.

Methods A literature search was performed to identify published articles in English indexed in MEDLINE and the Cochrane Library (Issue 1, 2009), which includes the Economic Evaluation Database. Additional sources also were searched to identify unpublished varenicline studies, including conference abstracts. The search for varenicline studies was limited from 2006 to October 2009; searches for all other types of studies were limited from 1990 to October 2009.

Results The search yielded a total of 20 relevant economic evaluations of varenicline. In addition, 37 reviews of economic evaluations in chronic obstructive pulmonary disease, non‐small cell lung cancer and cardiovascular disease, as well as studies evaluating the impact of economic rewarding were considered in this review. From these identified economic evaluations, the incremental cost‐effectiveness ratios for varenicline ranged from dominance (more effective and cost saving) to €18 582 per quality‐adjusted life‐year (including indirect costs). These estimates appeared substantially lower when compared with incremental cost‐effectiveness ratios reported for secondary prevention of smoking‐related diseases, which in some cases were as high as €66 218 per quality‐adjusted life‐year.

Conclusions Varenicline appears to be cost‐effective from the perspective of both health care payers and employers, because of reduced health care consumption and costs. The cost‐effectiveness of varenicline also compares favourably to that of interventions recommended for the treatment and prevention of smoking‐related diseases.