bluuebunny/crossref_metadata_2025 huggingface dataset:
MiR‐195, miR‐196b, miR‐181c, miR‐21 expression levels and O‐6‐methylguanine‐DNA methyltransferase methylation status are associated with clinical outcome in glioblastoma patients
Authors: Lakomy Radek , Sana Jiri , Hankeova Simona , Fadrus Pavel , Kren Leos , Lzicarova Eva , Svoboda Marek , Dolezelova Hana , Smrcka Martin , Vyzula Rostislav , Michalek Jaroslav , Hajduch Marian , Slaby Ondrej
Published: September 2011

Glioblastoma multiforme (GBM) is the most frequently occurring primary malignant brain tumor; patients with GBM often have a very poor prognosis and differing responses to treatment. Therefore, it is very important to find new biomarkers that can predict clinical outcomes and help in treatment decisions. MicroRNAs are small, non‐coding RNAs that function as post‐transcriptional regulators of gene expression and play a key role in the pathogenesis of GBM. In a group of 38 patients with primary GBM, we analyzed the expression of eight microRNAs (miR‐21, miR‐128a, miR‐181c, miR‐195, miR‐196a, miR‐196b, miR‐221, and miR‐222). In addition, we examined the methylation status of O‐6‐methylguanine‐DNA methyltransferase (MGMT) promoter by high‐resolution melting analysis, as this has been shown to be a predictive marker in GBM. MGMT methylation status correlated with progression‐free survival (P = 0.0201; log–rank test) as well as with overall survival (P = 0.0054; log–rank test). MiR‐195 (P = 0.0124; log–rank test) and miR‐196b (P = 0.0492; log–rank test) positively correlated with overall survival. Evaluation of miR‐181c in combination with miR‐21 predicted time to progression within 6 months of diagnosis with 92% sensitivity and 81% specificity (P < 0.0001). Our data confirmed that the methylation status of MGMT but also miR‐21, miR‐181c, miR‐195, and miR‐196b to be associated with survival of GBM patients. Above all, we suggest that the combination of miR‐181c and miR‐21 could be a very sensitive and specific test to identify patients at high risk of early progression after surgery. (Cancer Sci 2011; 102: 2186–2190)
Genetically engineered humanized anti‐ganglioside GM2 antibody against multiple organ metastasis produced by GM2‐expressing small‐cell lung cancer cells
Authors: Yamada Tadaaki , Bando Hideaki , Takeuchi Shinji , Kita Kenji , Li Qi , Wang Wei , Akinaga Shiro , Nishioka Yasuhiko , Sone Saburo , Yano Seiji
Published: September 2011

Small‐cell lung cancer (SCLC) grows rapidly and metastasizes to multiple organs. We examined the antimetastatic effects of the humanized anti‐ganglioside GM2 (GM2) antibodies, BIW‐8962 and KM8927, compared with the chimeric antibody KM966, in a SCID mouse model of multiple organ metastases induced by GM2‐expressing SCLC cells. BIW‐8962 and KM8927 induced higher antibody‐dependent cellular cytotoxicity and complement‐dependent cytotoxicity than KM966 against the GM2‐expressing SCLC cell line SBC‐3 in vitro. These humanized antibodies inhibited the production of multiple organ metastases, increased the number of apoptotic cells, and prolonged the survival of the SCID mice. Histological analyses using clinical specimens showed that SCLC cells expressed GM2. These findings suggest that humanized anti‐GM2 antibodies could be therapeutically useful for controlling multiple organ metastases of GM2‐expressing SCLC. (Cancer Sci 2011; 102: 2157–2163)
Detection of four diabetes specific autoantibodies in a single radioimmunoassay: an innovative high-throughput approach for autoimmune diabetes screening
Authors: Tiberti C , Yu L , Lucantoni F , Panimolle F , Spagnuolo I , Lenzi A , Eisenbarth G S , Dotta F
Published: September 2011

Highly sensitive and specific radioimmunoassays have been validated for autoantibodies reacting with the four major autoantigens identified so far in autoimmune diabetes. However, the analysis of this large number of autoantigens has increased the costs and time necessary for complete autoantibody screenings. Our aim was to demonstrate that it is possible to detect the immunoreactivity against a combination of four different autoantigens by a single assay, this representing a rapid, low-cost first approach to evaluate humoral autoimmunity in diabetes. By using this novel multi-autoantigen radioimmunoassay (MAA), in subsequent steps we analysed 830 sera, 476 of known and 354 of unknown diabetes-specific immunoreactivity, collected from various groups of individuals including type 1 and type 2 diabetes patients, autoantibody-positive patients with a clinical diagnosis of type 2 diabetes (LADA), prediabetic subjects, individuals at risk to develop autoimmune diabetes, siblings of type 1 diabetic patients, coeliac patients and healthy control subjects. All sera reacting with one or more of the four autoantigens by single assays also resulted positive with MAA, as well as eight of 24 type 1 diabetic patients classified initially as autoantibody-negative at disease onset based on single autoantibody assays. In addition, MAA showed 92% sensitivity and 99% specificity by analysing 140 blinded sera from type 1 diabetic patients and control subjects provided in the 2010 Diabetes Autoantibody Standardization Program. MAA is the first combined method also able to evaluate, in addition to glutamic acid decarboxylase (GAD) and tyrosine phosphatase (IA)-2, insulin and islet beta-cell zinc cation efflux transporter (ZnT8) autoantibodies. It appears to be particularly appropriate as a first-line approach for large-scale population-based screenings of anti-islet autoimmunity.
Effects of an invasive crayfish on trophic relationships in north‐temperate lake food webs
Authors: NILSSON E. , SOLOMON C. T. , WILSON K. A. , WILLIS T. V. , LARGET B. , VANDER ZANDEN M. J.
Published: September 2011

1. The introduction of invasive species is one of the main threats to global biodiversity, ecosystem structure and ecosystem processes. In freshwaters, invasive crayfish alter macroinvertebrate community structure and destroy macrophyte beds. There is limited knowledge on how such invasive species‐driven changes affect consumers at higher trophic levels.

2. In this study, we explore how the invasive rusty crayfish Orconectes rusticus, a benthic omnivore, affects benthic macroinvertebrates, as well as the broader consequences for ecosystem‐level trophic flows in terms of fish benthivory and trophic position (TP). We expected crayfish to decrease abundance of benthic macroinvertebrates, making most fish species less reliant on benthic resources. We expected crayfish specialists (e.g. Lepomis sp. and Micropterus sp.) to increase their benthic dependence.

3. In 10 northern Wisconsin lakes, we measured rusty crayfish relative abundance (catch per unit effort, CPUE), macroinvertebrate abundance, and C and N stable isotope ratios of 11 littoral fish species. We used stable isotope data and mixing models to characterise the trophic pathways supporting each fish species, and related trophic structure to crayfish relative abundance, fish body size and abiotic predictors using hierarchical Bayesian models.

4. Benthic invertebrate abundance was negatively correlated with rusty crayfish relative abundance. Fish benthivory increased with crayfish CPUE for all 11 fish species; posterior probabilities of a positive effect were >95%. TP also increased slightly with crayfish CPUE for some species, particularly smallmouth bass, largemouth bass, rock bass and Johnny darter. Moreover, both fish body size and lake abiotic variables explained variation in TP, while their effects on benthivory were small.

5. Rusty crayfish abundance explained relatively little of the overall variation in fish benthivory and TP. Although rusty crayfish appear to have strong effects on abundances of benthic macroinvertebrates, energy flow pathways and trophic niches of lentic fishes were not strongly influenced by invasive rusty crayfish.
Invasion hotspots for non‐native plants in Australia under current and future climates
Authors: O'Donnell Jessica , Gallagher Rachael V. , Wilson Peter D. , Downey Paul O. , Hughes Lesley , Leishman Michelle R.
Published: September 2011

We apply the concept of biodiversity hotspot analysis (the identification of biogeographical regions of high species diversity) to identify invasion hotspots – areas of potentially suitable climate for multiple non‐native plant species – in Australia under current and future climates. We used the species distribution model Maxent to model climate suitability surfaces for 72 taxa, recognized as ‘Weeds of National Significance’ (WoNS) in Australia, under current and projected climate for 2020 and 2050. Current climate suitability layers were summed across all 72 species, and we observed two regions of high climatic suitability corresponding to the top 25th percentile of combined climatic suitability values across Australia. We defined these as potential invasion hotspots. Areas of climatic suitability equivalent to the hotspot regions were identified in the composite maps for 2020 and 2050, to track spatial changes in the hotspots over the two time steps. Two potential invasion hotspot regions were identified under current and projected climates: the south west corner of Western Australia (SW), and south eastern Australia (SE). Herbarium data confirmed the presence of 73% and 99% of those species predicted to be in each hotspot respectively, suggesting that the SE has greater invasion potential. The area of both hotspots was predicted to retract southward and towards the coast under future climate scenarios, reducing in size by 81% (SW) and 71% (SE) by 2050. This reduction was driven by the dominance of southern temperate invasive plant species in the WoNS list (47 of the 72), of which 44 were predicted to experience reductions in their bioclimatic range by 2050. While climate is likely to become less suitable for the majority of WoNS in the future, potential invasion hotspots based on climate suitability are likely to remain in the far south of eastern Australia, and in the far south west of Western Australia by 2050.
The responses of grassland plants to experimentally simulated climate change depend on land use and region
Authors: Bütof Astrid , von Riedmatten Lars R. , Dormann Carsten F. , Scherer‐Lorenzen Michael , Welk Erik , Bruelheide Helge
Published: September 2011

Macroclimatic niche properties derived from species distribution ranges are fundamental for projections of climate change impacts on biodiversity. However, it has been recognized that changes in regional or local distribution patterns also depend on interactions with land use. The reliability and transferability of large scale geographic predictions to small scale plant performance need to be tested experimentally. Thus, we asked how grassland plant species pairs with different macroclimatic niche properties respond to increased spring temperature and decrease summer precipitation in three different land‐use types. An experiment was carried out in the framework of the German Biodiversity Exploratories simulating climate change in 45 experimental plots in three geographical regions (Schorfheide‐Chorin, Hainich‐Dün, Schwäbische Alb) and three grassland management types (meadow, pasture, mown pasture). We planted six plant species as phytometers, each two of them representing congeneric species with contrasting macroclimatic niches and recorded plant survival and growth over 1 year. To quantify the species macroclimatic niches with respect to drought tolerance, the species’ distribution ranges were mapped and combined with global climate data. The simulated climate change had a general negative effect on plant survival and plant growth, irrespective of the macroclimatic niche characteristics of the species. Against expectation, species with ranges extending into drier regions did not generally perform better under drier conditions. Growth performance and survival was best in mown pastures, representing a quite intensive type of land use in all study regions. Species with higher macroclimatic drought tolerance were generally characterized by lower growth rates and higher survival rates in land‐use types with regular mowing regimes, probably because of reduced competition in the growing season. In conclusion, plant species with similar climatic niche characteristics cannot be expected to respond consistently over different regions owing to complex interactions of climate change with land use practices.
Warming, eutrophication, and predator loss amplify subsidies between aquatic and terrestrial ecosystems
Authors: Greig Hamish S. , Kratina Pavel , Thompson Patrick L. , Palen Wendy J. , Richardson John S. , Shurin Jonathan B.
Published: September 2011

The exchange of organisms and energy among ecosystems has major impacts on food web structure and dynamics, yet little is known about how climate warming combines with other pervasive anthropogenic perturbations to affect such exchanges. We used an outdoor freshwater mesocosm experiment to investigate the interactive effects of warming, eutrophication, and changes in top predators on the flux of biomass between aquatic and terrestrial ecosystems. We demonstrated that predatory fish decoupled aquatic and terrestrial ecosystems by reducing the emergence of aquatic organisms and suppressing the decomposition of terrestrial plant detritus. In contrast, warming and nutrients enhanced cross‐ecosystem exchanges by increasing emergence and decomposition, and these effects were strongest in the absence of predators. Furthermore, we found that warming advanced while predators delayed the phenology of insect emergence. Our results demonstrate that anthropogenic perturbations may extend well beyond ecosystem boundaries by influencing cross‐ecosystem subsidies. We find that these changes are sufficient to substantially impact recipient communities and potentially alter the carbon balance between aquatic and terrestrial ecosystems and the atmosphere.
Population vulnerability to climate change linked to timing of breeding in boreal ducks
Authors: Drever Mark C. , Clark Robert G. , Derksen Chris , Slattery Stuart M. , Toose Peter , Nudds Thomas D.
Published: September 2011

Identifying and understanding why traits make species vulnerable to changing climatic conditions remain central problems in evolutionary and applied ecology. We used spring snow cover duration as a proxy for phenological timing of wetland ecosystems, and examined how snow cover duration during spring and during the entire snow season affected population dynamics of duck species breeding in the western boreal forest of North America, 1973–2007. We predicted that population level responses would differ among duck species, such that late‐nesting species with reduced flexibility in their timing of breeding, i.e. scaup (Aythya spp.) and scoter (Melanitta spp.), would be more strongly affected by changing snow cover conditions relative to species better able to adjust timing of breeding to seasonal phenology, i.e. mallard (Anas platyrhynchos) and American wigeon (Anas americana). Population growth rates of scaup and scoter were positively linked to spring snow cover duration; after accounting for effects of density dependence, larger populations resulted after springs with long snow cover duration than after springs with short snow cover duration. In contrast, population growth rates of mallard and wigeon were either negatively or only weakly associated with snow cover duration. Duck population models were then incorporated with snow cover duration derived from climate model simulations under the A2 emission scenario, and these predictions suggested that late‐nesting duck species will experience the most severe population declines. Results are consistent with a hypothesis that the gradual climatic warming observed in the western boreal forest of North America has contributed to and may continue to exacerbate population declines of scaup and scoter.
Push‐out bond strength of two new calcium silicate‐based endodontic sealers to root canal dentine
Authors: Sagsen B. , Ustün Y. , Demirbuga S. , Pala K.
Published: September 2011

Sagsen B, Ustün Y, Demirbuga S, Pala K. Push‐out bond strength of two new calcium silicate‐based endodontic sealers to root canal dentine. International Endodontic Journal, 44, 1088–1091, 2011.

Aim  To assess the push‐out bond strength of two new calcium silicate‐based endodontic sealers in the root canals of extracted teeth.

Methodology  Thirty extracted single‐rooted central incisors of similar sizes were selected randomly and distributed to three groups (n = 10). All canals were instrumented using ProTaper rotary instruments to achieve tapered canal walls. Irrigation was performed using 5 mL 2.5% NaOCl between each instrument, and the smear layer was removed using 5 mL 17% EDTA. The canals were filled with three different sealers using a cold lateral compaction technique: group 1: AH Plus + gutta‐percha, group 2: I Root SP + gutta‐percha and group 3: MTA Fillapex + gutta‐percha. Three horizontal sections were prepared at a thickness of 1 mm ±0.1 in the apical, middle and coronal parts of each root. The test specimens were subjected to the push‐out test method using a Universal Test Machine (Instron, Canton, MA, USA) that carried 1‐mm, 0.5‐mm and 0.3‐mm plungers for coronal, middle and apical specimens, respectively. The loading speed was 1 mm min−1. The push‐out data were analysed by two‐way analysis of variance (anova) and the post hoc Holm–Sidak test, with significance set at P < 0.05.

Results  In the coronal specimens, there was no significant difference between the sealers. In the middle and apical segments, there was no significant difference between I Root SP and AH Plus groups. However, the I Root SP and AH Plus had significantly higher bond strength values than the MTA Fillapex (P < 0.05). In terms of root segments, the bond strengths in the middle specimens and the apical specimens were higher compared with the bond strengths in the coronal specimens (P < 0.05). There were no significant differences between the bond strengths in the middle and apical specimens.

Conclusion  MTA Fillapex had the lowest push‐out bond values to root dentine compared with other sealers.
Diagnostic accuracy of limited‐volume cone‐beam computed tomography in the detection of periapical bone loss: 360° scans versus 180° scans
Authors: Lennon S. , Patel S. , Foschi F. , Wilson R. , Davies J. , Mannocci F.
Published: September 2011

Lennon S, Patel S, Foschi F, Wilson R, Davies J, Mannocci F. Diagnostic accuracy of limited‐volume cone‐beam computed tomography in the detection of periapical bone loss: 360° scans versus 180° scans. International Endodontic Journal, 44, 1118–1127, 2011.

Aim  To investigate the effect of reducing limited‐volume cone‐beam computed tomographs arc of rotation from 360° to 180° on the ability to diagnose small, artificially created apical lesions.

Methodology  Small, artificial apical bone lesions were prepared with a bur in the apical region of the distal root of ten mandibular first molars, in human dry mandibles. The jaws were scanned in a fixed position with limited‐volume CBCT making a 360° and 180° arc of rotation, before and after each periapical lesion had been created. A 4 × 4 cm field of view was used at 90 kV, with a current of 4 mA. Ten examiners blinded to the scan parameters and controls scored the presence/absence of bone lesions. Intra‐examiner reliability was determined after 2 weeks, reviewing half the data set. Statistical analyses with paired t‐tests determined the diagnostic accuracy of the two modalities (360° vs. 180°) in terms of sensitivity, specificity, receiver operating characteristic area under the curve, positive predictive values and negative predictive values.

Results  The mean values for sensitivity of the 360° and 180° scans were 0.91 and 0.89, respectively; their mean specificities were 0.73. No significant differences were reflected in the statistical analyses.

Conclusions  Both 360° and 180° cone‐beam computed tomography scans yielded similar accuracy in the detection of artificial bone lesions. The use of 180° scans might be advisable to reduce the radiation dose to the patient in line with the ICRP guidance to use as low a dosage as reasonably achievable.
Medico‐legal aspects of vertical root fractures in root filled teeth
Authors: Rosen E. , Tsesis I. , Tamse A. , Bjørndal L. , Taschieri S. , Givol N.
Published: September 2011

Rosen E, Tsesis I, Tamse A, Bjørndal L, Taschieri S, Givol N. Medico‐legal aspects of vertical root fractures in root filled teeth. International Endodontic Journal, 45, 7–11, 2012.

Aim  To analyse the medico‐legal aspects of vertical root fracture (VRF) following root canal treatment (RCT).

Methodology  A comprehensive search in a professional liability insurance database was conducted to retrospectively identify cases of VRF following RCT. The complaints were categorized as either financial risk bearing or financial nonrisk bearing, and related demographic, prosthetic and endodontic variables were analysed.

Results  Seventy‐seven legal cases of patients with VRFs following RCT were identified. Most of the cases were either in premolars or in mandibular molar teeth (P < 0.05). Poor‐quality root filling was associated with an extended delay of diagnosis (P < 0.05). The presence of a post significantly increased the financial risk assessment (P < 0.05).

Conclusions  Poor quality root fillings complicate the diagnosis of VRF, which in turn extends the time for achieving an accurate diagnosis and increasing the medico‐legal risk. Premolar and mandibular molar teeth were more prone to medico‐legal claims related to VRF following RCT. Post should be placed only when essential for additional core support to avoid medico‐legal risk.
Determining non‐invasiveness in ornamental plants to build green lists
Authors: Dehnen‐Schmutz Katharina
Published: September 2011

1. Ornamental horticulture is the most important pathway for plant invasions world‐wide. Large numbers of non‐native plants are used as ornamentals, and current policies fail to effectively address the continued escape of species from cultivation. Legislative measures are often limited to the listing of few high‐risk species banned from sale or planting. This approach, however, may give the impression that non‐listed species are not considered to be a risk and are therefore safe to use. The continued widespread use of species not yet identified as having the risk to become invasive may create a problem in the future.

2. This article argues that knowledge gained from studies designed to identify invasive traits of species and factors contributing to their invasion success can also be used to identify species with a low invasion risk that can be recommended to the horticultural trade, landscaping sector and gardeners for safer use.

3. The criteria identified for non‐invading species to be listed in a green list include sufficiently long residence time, high propagule pressure, no records of invasive occurrences elsewhere and an indication of some robustness to climate change. An example is provided for a random sample of ornamental species used in Britain.

4. 
Synthesis and application. There is a pressing need to prevent further plant invasions resulting from ornamental horticulture. A green list of non‐native ornamental species that have been assessed as having a low risk of escaping cultivation will contribute to the prevention of plant invasions. Species not yet assessed which may have the potential to become invasive in the future can then be more easily avoided. This list would be particularly useful in large‐scale plantings and landscaping projects. Currently, policies often focus on (i) species that are already introduced and recognized as invasive and (ii) the prevention of potential further invasions from new introductions. This study suggests that attention to non‐invasive species already present in the country and widely used in horticulture can help to advance policies for dealing with invasive ornamental species.
Effect of potassium silicate on epidemic components of powdery mildew on melon
Authors: Dallagnol L. J. , Rodrigues F. A. , Tanaka F. A. O. , Amorim L. , Camargo L. E. A.
Published: September 2011

The effects of silicon (Si) supplied in the form of potassium silicate (PS) were evaluated on epidemic components of powdery mildew of melon under greenhouse conditions. The PS was applied to the roots or to leaves. In the first experiment, epidemic components were evaluated after inoculation with Podosphaera xanthii. In the second experiment, the disease progress rate was evaluated on plants subjected to natural infection. The area under the disease progress curve was reduced by 65% and 73% in the foliar and root treatments, respectively, compared to control plants, as a consequence of reductions in infection efficiency, colony expansion rate, colony area, conidial production and disease progress rate. However, root application of PS was more effective than foliar application in reducing most of the epidemic components, except for infection efficiency. This can be explained by the high Si concentration in leaf tissues with root application, in contrast to the foliar treatment where Si was only deposited on the external leaf surfaces. The effects of PS reported in this study demonstrated that powdery mildew of melon can be controlled, and that the best results can be achieved when PS is supplied to the roots.
A peroxisomal carrier delivers NAD+ and contributes to optimal fatty acid degradation during storage oil mobilization
Authors: Bernhardt Kristin , Wilkinson Sabrina , Weber Andreas P. M. , Linka Nicole
Published: September 2011

The existence of a transport protein that imports cytosolic NAD+ into peroxisomes has been controversially discussed for decades. Nevertheless, the biosynthesis of NAD+ in the cytosol necessitates the import of NAD+ into peroxisomes for numerous reduction/oxidation (redox) reactions. However, a gene encoding such a transport system has not yet been identified in any eukaryotic organism. Here, we describe the peroxisomal NAD+ carrier in Arabidopsis. Our candidate gene At2g39970 encodes for a member of the mitochondrial carrier family. We confirmed its peroxisomal localization using fluorescence microscopy. For a long time At2g39970 was assumed to represent the peroxisomal ATP transporter. In this study, we could show that the recombinant protein mediated the transport of NAD+. Hence, At2g39970 was named PXN for peroxisomal NAD+ carrier. The loss of PXN in Arabidopsis causes defects in NAD+‐dependent β‐oxidation during seedling establishment. The breakdown of fatty acid released from storage oil was delayed, which led to the retention of oil bodies in pxn mutant seedlings. Based on our results, we propose that PXN delivers NAD+ for optimal fatty acid degradation during storage oil mobilization.
Fresh blood for transfusion in adults with beta thalassaemia
Authors: Priddee N. R. , Pendry K. , Ryan K. E.
Published: September 2011

Background: Patients with beta‐thalassaemia major require life‐long blood transfusion with the aim of achieving normal growth and development whilst minimising iron overload. A pre‐transfusion Hb between 9·5 and 10 g/dL is thought to achieve this balance. UK consensus is that fresh blood (less than 14 days) is better at maintaining this target pre‐transfusion Hb but there is no firm stipulation in place and no robust evidence supporting this.

Methods: After introduction of a universal fresh blood policy for adult beta‐thalassaemics in 2010, we reviewed locally transfused adult patients to determine if there was any significant difference in pre‐transfusion Hb using fresh blood. Nine adult thalassaemic patients were analysed for two consecutive 6‐month periods in 2009 and 2010 (periods 1 and 2).

Results: Mean pre‐transfusion Hb was significantly higher by an average of 0·5 g/dL in period 2 than period 1 (P < 0·05). The average unit age was 18 vs 9·5 days for periods 1 and 2 respectively (P < 0·05). There were no significant differences in potential confounders such as transfusion volume (P = 0·06), number of units transfused, ferritin or transfusion interval.

Discussion: Use of fresh blood produced significantly higher pre‐transfusion Hb, giving credence to UK consensus. Lesser volumes of fresh blood appeared to achieve the target pre‐transfusion Hb, which may translate to reduced iron overload and chelation costs. Whether the assumption that the use of blood less than 7 days old in these patients would result in greater benefit requires further study.
Audiological findings in 100 USH2 patients
Authors: Abadie C , Blanchet C , Baux D , Larrieu L , Besnard T , Ravel P , Biboulet R , Hamel C , Malcolm S , Mondain M , Claustres M , Roux A‐F
Published: September 2011

Abadie C, Blanchet C, Baux D, Larrieu L, Besnard T, Ravel P, Biboulet R, Hamel C, Malcolm S, Mondain M, Claustres M, Roux A‐F. Audiological findings in 100 USH2 patients.

Bilateral sensorineural hearing loss (HL), classically described as mild to severe with a typically down‐sloping audiometric configuration, is the earliest symptom occurring in Usher syndrome type II (USH2).

Audiological findings were analyzed in a total of 100 USH2 patients (92 families) divided into three groups according to the gene involved: 88 USH2A, 10 GPR98 and 2 DFNB31 patients. A fine analysis of audiograms was performed (pure tone average, degree of severity, configuration).

The median age of HL diagnosis was 5 years (range 8 months–31 years) although the median age at USH2 diagnosis was 34.5 (range 8–76). Moderate HL was predominant (76%) and a gently down‐sloping configuration characterized most audiograms (66%). No statistically significant difference was found between USH2A and GPR98 patients but a tendency was clearly noted for more GPR98 patients to present with severe hearing loss. It is not possible to predict the mutated gene from audiograms.
BRCA1 and BRCA2 mutations among familial breast cancer patients from Costa Rica
Authors: Gutiérrez Espeleta GA , Llacuachaqui M , García‐Jiménez L , Aguilar Herrera M , Loáiciga Vega K , Ortiz A , Royer R , Li S , Narod SA
Published: September 2011

Gutiérrez Espeleta GA, Llacuachaqui M, García‐Jiménez L, Aguilar Herrera M, Loáiciga Vega K, Ortiz A, Royer R, Li S, Narod SA. BRCA1 and BRCA2 mutations among familial breast cancer patients from Costa Rica.

The contribution of mutations in BRCA1 and BRCA2 genes to the burden of breast cancer in Costa Rica has not been studied. We estimated the frequency of BRCA mutations among 111 Costa Rican women with breast cancer and a family history of breast cancer. These women were mainly from the metropolitan area of San José. A detailed family history was obtained from each patient and a blood sample was processed for DNA extraction. Mutations in BRCA1 and BRCA2 were sought using a combination of techniques and all mutations were confirmed by direct sequencing. Four different mutations were identified in five patients (four in BRCA2 and one in BRCA1) representing 4.5% of the total. Two unrelated patients were found to have a BRCA2 5531delTT mutation. Other BRCA2 mutations included C5507G and 6174delT. Only one BRCA1 mutation was found (C3522T). The family with the BRCA1 mutation had five cases of gastric cancer. Families with BRCA2 mutations were also reported to have cases of gastric and prostate cancers; however, the full range of cancers associated with BRCA1 and BRCA2 mutations in Costa Rica has not yet been established.
Detection of chromosomal aneuploidies in fetal cells isolated from maternal blood using single‐chromosome dual‐probe FISH analysis
Authors: Calabrese G , Baldi M , Fantasia D , Teresa Sessa M , Kalantar M , Holzhauer C , Alunni‐Fabbroni M , Palka G , Sitar G
Published: September 2011

Calabrese G, Baldi M, Fantasia D, Teresa Sessa M, Kalantar M, Holzhauer C, Alunni‐Fabbroni M, Palka G, Sitar G. Detection of chromosomal aneuploidies in fetal cells isolated from maternal blood using single‐chromosome dual‐probe FISH analysis.

Detection of chromosomal aneuploidies using fetal cells isolated from maternal blood, for prenatal non‐invasive genetic investigation, has been a long‐sought goal of clinical genetics to replace amniocentesis and chorionic villous sampling to avoid any risk to the fetus. The purpose of this study was to develop a sensitive and specific new assay for diagnosing aneuploidy with circulating fetal cells isolated from maternal blood as previously reported using two novel approaches: (i) simultaneous immunocytochemistry (ICC) evaluation using a monoclonal antibody for i‐antigen, followed by fluorescence in situ hybridization (FISH); (ii) dual‐probe FISH analysis of interphase nuclei using two differently labeled probes, specific for different loci of chromosomes 21 and 18; in addition, short tandem repeats (STR) analysis on single cells isolated by micromanipulation was applied to confirm the presence of fetal cells in the cell sample enriched from maternal blood. Blood samples were obtained from women carrying trisomic fetuses, and from non‐pregnant women and men as controls. Using ICC–FISH approach, a large heterogeneity in immunostaining pattern was observed, which is a source of very subjective signal interpretation. Differently, dual‐probe FISH analysis provided for a correct diagnosis of all pregnancies: the mean percentage of trisomic cells was 0.5% (range, 0.36–0.76%), while the mean percentage of trisomic cells in the control group (normal pregnancies or non‐pregnant women) was ≤0.20%. The application of the dual‐probe FISH protocol on fetal cells isolated from maternal blood enables accurate molecular detection of fetal aneuploidy, thus providing a foundation for development of non‐invasive prenatal diagnostic testing.
Isolated and syndromic forms of congenital anosmia
Authors: Karstensen HG , Tommerup N
Published: September 2011

Karstensen HG, Tommerup N. Isolated and syndromic forms of congenital anosmia.

Loss of smell (anosmia) is common in the general population and the frequency increases with age. A much smaller group have no memory of ever being able to smell and are classified as having isolated congenital anosmia (ICA). Families are rare, and tend to present in a dominant inheritance pattern. Despite a strong degree of heritability, no human disease‐causing mutations have been identified. Anosmia is part of the clinical spectrum in various diseases, as seen in Kallmann syndrome, various ciliopathies and congenital insensitivity to pain. This review will focus on ICA through already published families and cases as well as syndromes where anosmia is part of the clinical disease spectrum. Furthermore, olfactory signal transduction pathway genes and animal models may shed light on potential candidate genes and pathways involved in ICA.
Low bone mineral density and nutritional vitamin D deficiency in pediatric renal transplant recipients: Assessment of risk factors and response to oral vitamin D therapy
Authors: Sgambat Kristen , Tuchman Shamir , Ryan Leticia , Wood Rachel , Moudgil Asha
Published: September 2011

Sgambat K, Tuchman S, Ryan L, Wood R, Moudgil A. Low bone mineral density and nutritional vitamin D deficiency in pediatric renal transplant recipients: Assessment of risk factors and response to oral vitamin D therapy.  Pediatr Transplantation 2011: 15: 790–797. © 2011 John Wiley & Sons A/S.

Abstract:  VitD deficiency and bone disease are common after Tx. Prevalence and risk factors for low VitD and BMD and response to VitD therapy were investigated in pediatric renal Tx recipients. 25‐hydroxy VitD levels of 71 Tx were compared to 54 healthy AA children. DXA of 44 Tx were compared to 47 AA controls. Of Tx, 59% were AA. Majority (59.1%) of Tx were VitD deficient (23.9%) or insufficient (35.2%). Prevalence of low VitD levels was double in AA (73.9%) vs. non‐AA Tx (37.7%), (p = 0.003). Low VitD among Tx was associated with AA ethnicity (p < 0.01), winter (p < 0.05), older age (p < 0.05), males (p < 0.05) and time <6 months post Tx (p < 0.05). Tx with low VitD were treated with oral ergocalciferol or cholecalciferol (23 each); 13% treated with ergocalciferol vs. 82.6% treated with cholecalciferol achieved repletion (p < 0.0001). Of 36 Tx with whole body DXA, 19.5% had BMD (z < −1) after height adjustment. AA Tx had 3.4‐fold higher risk of low BMD vs. controls (p < 0.05). Low VitD and BMD are prevalent in children after renal Tx. Better repletion of VitD is achieved with cholecalciferol.
The second mini‐transplant for unstable mixed chimerism within the first 100 days after hematopoietic stem cell transplant in severe thalassemia
Authors: Choeyprasert Worawut , Pakakasama Samart , Anurathapan Usanarat , Songdej Duantida , Sirachainun Nongnuch , Sirireung Somtawin , Panthangkool Wanpen , Hongeng Suradej
Published: September 2011

Choeyprasert W, Pakakasama S, Anurathapan U, Songdej D, Sirachainun N, Sirireung S, Panthangkool W, Hongeng S. The second mini‐transplant for unstable mixed chimerism within the first 100 days after hematopoietic stem cell transplant in severe thalassemia. Pediatr Transplantation 2011. © 2011 John Wiley & Sons A/S.

Abstract:  Allogeneic HSCT is the only curative treatment for severe thalassemia disease. MC occurs in one‐third of these patients within the first two months after HSCT; this is a major risk factor of graft rejection, especially when RHCs are more than 25%. There is still no consensus for the management of MC, especially in the early phase of HSCT. The DLI has also been described in the treatment of MC following HSCT for hemoglobinopathies, but its success is still not guaranteed. The second HSCT has been an approach used in an attempt to cure patients who reject their graft. Concern about toxicity of conditioning regimen, the second HSCT is usually delayed for at least a year after the first HSCT. We would like to demonstrate the successful use of the second mini‐allogeneic HSCT in hemoglobin E/β‐thalassemia with evidence of unstable MC in the first 100 days after allogeneic HSCT to prevent further graft loss after allogeneic HSCT.
Comparison of real‐time florescence quantitative PCR measurements of VAD1 mRNA with three conventional methods in diagnosis and follow‐up treatment of Cryptococcus neoformans infection
Authors: Qishui Ou , Ling Jiang , Ni Lin , Bin Yang , Wen Li
Published: September 2011

This study was to develop a real‐time florescence quantitative PCR (RT‐FQ‐PCR) assay to measure virulence‐associated DEAD‐box RNA helicase (VAD1) mRNA from Cryptococcus neoformans and evaluate its potential use in diagnosis and follow‐up treatment of C. neoformans meningitis (CNM). Cryptococcus neoformans was detected using RT‐FQ‐PCR, ink staining, fungal culturing and C. neoformans antigen detection in CNM compared with a normal control. VAD1 mRNA was measured in both acute and stable CNM patients. The sensitivity of RT‐FQ‐PCR (96%) is higher than ink staining (72%) and culture culturing (64%) (P < 0.05, P < 0.05 respectively), but its sensitivity is the same as antigen detection (96%, P > 0.05). The levels of VAD1 mRNA in the acute and stable phase of a C. neoformans infection are 3.042 ± 0.906 and 2.187 ± 0.665 respectively (P < 0.01). The levels of VAD1 mRNA are correlated to the numbers of C. neoformans, intracranial pressure and glucose concentration in cerebrospinal fluid (CSF; P < 0.01, P < 0.01 and P < 0.05 respectively). The levels of expression of VAD1 mRNA in the group of patients who received an AmB/5‐FC/FZC drug regimen decreased more than in patients taking a 5‐FC/AmB or 5‐FC/FCZ drug combination. Quantitative measurements of VAD1 mRNA are valuable and reliable in diagnosing C. neoformans infection and evaluating a therapy response.
Use of Dermasilk briefs in recurrent vulvovaginal candidosis: safety and effectiveness
Authors: D’Antuono A. , Baldi E. , Bellavista S. , Banzola N. , Zauli S. , Patrizi A.
Published: September 2011

Despite the generally excellent results achieved with fluconazole 150 mg weekly in recurrent vulvovaginal candidosis (RVVC), some patients with a long history of disease do not achieve complete resolution of symptoms following antimycotic treatment. It is thought that use of tight synthetic fabric underwear could be a significant factor in causing recurrence. We decided to compare underwear made of Dermasilk®, a pure fibroin fabric impregnated with a permanent antimicrobial protection, with a cotton placebo to see whether it could be a useful adjunctive tool in the management of RVVC. We recruited 96 women who had a long‐term history of RVVC and had not responded to oral antimycotics with complete satisfaction. The patients were randomly divided into two groups and instructed to use either white cotton placebo briefs or Dermasilk® briefs. Both groups were treated with fluconazole 150 mg once weekly for 6 months. After 6 months, the Dermasilk group showed a statistically significant greater decrease of itching, burning, erythema and a smaller number of recurrences than the cotton group. Our work suggests that Dermasilk® briefs could be a useful adjunctive tool in addition to antimycotic treatment to help relieve the discomfort of recurrent vulvovaginitis.
Sporogenic and vegetative tissues of Saccharina latissima (Laminariales, Phaeophyceae) exhibit distinctive sensitivity to experimentally enhanced ultraviolet radiation : photosynthetically active radiation ratio
Authors: Holzinger Andreas , Di Piazza Lavinia , Lütz Cornelius , Roleda Michael Y.
Published: September 2011

Fertile Saccharina latissima sporophytes, collected in the Kongsfjorden, Ny‐Ålesund, Spitsbergen, Norway (78°56.87′ N, 11°51.64′ E) were investigated in relation to its sensitivity to experimentally enhanced ultraviolet radiation : photosynthetically active radiation (UVR : PAR) ratios. Irradiance of UVR were 4.30 W m−2 of UV‐A (320–400 nm) and 0.40 W m−2 of UV‐B (280–320 nm), and PAR (400–700 nm) was ∼4.30 W m−2 (=20 µmol photons m−2 s−1). Excised soral (sporogenic) and non‐soral (vegetative) tissues were separately irradiated for 16 h at 7°C. Transmission electron microscopy showed abundant occurrence of physodes, electron dense particles (∼300–600 nm) in the sorus. Paraphysis cells, with partly crystalline content, large mitochondria and abundant golgi bodies were towering over the sporangia. In soral tissue, cells were not visibly altered by the PAR + UVR irradiation. The chloroplasts, flagella and nucleus of unreleased meiospores inside the sporangial parent cells were visibly intact. Severe changes in the chloroplast structure of vegetative tissue occurred after PAR + UVR irradiation. These changes included wrinkling and dilatation of the thylakoid membranes, and appearance of electron translucent areas inside the chloroplasts. In vegetative cells exposed to PAR + UVR, the total amount of physodes, was slightly higher as in cells exposed to PAR only. Initial values of optimum quantum yield of photosystem II (Fv/Fm) were 0.743 ± 0.04 in non‐soral and 0.633 ± 0.04 in soral tissue. Vegetative tissue was observed to be more sensitive to radiant exposure of PAR and PAR + UVR compared to reproductive tissue. Under PAR, a 20% reduction in Fv/Fm was observed in non‐soral compared to no reduction in soral tissue, whereas under PAR + UVR, 60% and 33% reduction in Fv/Fm was observed in non‐soral and soral tissues, respectively. This can be attributed to the corresponding three times higher antiradical power (ARP) capacity in soral compared to non‐soral tissue.
Valve morphogenesis in an araphid diatom Rhaphoneis amphiceros (Rhaphoneidaceae, Bacillariophyta)
Authors: Sato Shinya , Watanabe Tsuyoshi , Nagumo Tamotsu , Tanaka Jiro
Published: September 2011

The pattern centre in valve morphogenesis is an annulus in centric diatoms or a sternum in pennate diatoms. The genus Rhaphoneis is currently placed within a lineage that diverges at the root of the pennate diatom clade in most molecular phylogenies, and its valves have a unique pattern to their striae, i.e. radiating from both apices, giving the impression that a pattern centre exists at both ends of the valve and virgae (ribs) formation proceeds centripetally. The present study, however, shows that the pattern centre is actually a linear sternum and the formation of virgae proceeds centrifugally, a pattern centre that is commonly found in most araphid diatoms. Thus, the hypothesis that valve morphogenesis based on a linear sternum and perpendicular virgae is a synapomorphy of pennate diatoms is supported. Our study also demonstrates that the pattern of valve formation can be observed by light microscopy with a direct mounting method when the specimen is relatively large, i.e. exceeding approximately 50 µm in valve length. An important advantage of the use of the direct mounting method is that it requires no repeated centrifugation steps for dehydration, steps necessary for observation by a scanning electron microscope, causing the loss and/or collapse of the specimen, particularly with fragile valves in the early stages of development.
Economic burden of injuries in children: Cohort study based on administrative data in a northwestern Italian region
Authors: Petrinco Michele , Di Cuonzo Daniela , Berchialla Paola , Gilardetti Marco , Foltran Francesca , Scarinzi Cecilia , Costa Giuseppe , Gregori Dario
Published: September 2011

Background:  The aims of the present study were to identify which types of injuries are responsible for the major component of the health burden and to estimate the relative costs in a cohort of Italian children.

Methods:  All children (0–14 years) residing in the Piedmont region, who were hospitalized for an injury (ICD‐9‐CM codes 800–995, excluding late effects from injury and allergies) between 1 January 2003 and 31 December 2003, were considered. The cohort was linked by a unique identifier to: all the hospitalizations, all the day‐hospital care, and all the prescribed medicines. Outcome was defined as the difference in health service use in the 12 months following the injury, and was compared to the year preceding the injury occurrence. Total number of hospital admissions for each individual, cumulative length of stay, day‐hospital care, and prescribed medicines were calculated for the two periods. The cost of additional inpatient days and of additional outpatient care was calculated.

Results:  The three most common injury categories were: intracranial injury (27.6%), fracture of upper limb (18.7%); and fracture of lower limb (9.07%); they were responsible for the major part of the additional inpatient days (55%) and outpatient care (70%). The additional expense for the National Health System during the year following an injury is approximately 1700€ for children aged 0–14.

Conclusions:  This is the first Italian study to attempt to quantify the injury economic burden in a cohort of children: the costs imposed on society by injuries, suggest how important it is to commit resources to injury prevention.
Ampicillin versus penicillin in the empiric therapy of extremely low‐birthweight neonates at risk of early onset sepsis
Authors: Metsvaht Tuuli , Ilmoja Mari‐Liis , Parm Ülle , Merila Mirjam , Maipuu Lea , Müürsepp Piia , Julge Kadri , Sepp Epp , Lutsar Irja
Published: September 2011

Background:  There are no comparative data on the impact of different empiric antibiotic regimens on early bowel colonization as well as on clinical efficacy in extremely low‐birthweight (ELBW) neonates at risk of early onset sepsis (EOS).

Methods:  A subgroup analysis was carried out of ELBW neonates recruited into a two‐center, prospective, cluster randomized study comparing ampicillin and penicillin both combined with gentamicin, within the first 72 h of life. A composite primary end‐point (need for change of antibiotics within 72 h and/or 7 day all‐cause mortality) and the rate and duration of colonization by opportunistic aerobic microorganisms were assessed using hierarchical models corrected for study center and period.

Results:  In the ampicillin (n= 36) and penicillin (n= 39) groups change of antibiotics, 7 day mortality and the composite end‐point occurred at similar rates. Neonatal intensive care unit mortality for infants with gestational age <26 weeks was lower in the ampicillin group. Ampicillin treatment was associated with a higher colonization rate by Klebsiella pneumoniae, including ampicillin‐resistant strains.

Conclusion:  Preliminary data indicate an urgent need for adequately powered studies of early antibiotic therapy in the subpopulation of ELBW neonates at risk of EOS.