Titanium particles inhibit osteoblast adhesion to fibronectin-coated substrates.
To illuminate the effect of titanium particles on osteoblast function, we compared the adhesion force of neonatal rat calvarial osteoblasts on fibronectin-coated glass after incubation with titanium particles (80% had diameters of less than 5 microm). The cells were incubated with the particles for 1.5-72 hours. Using a micropipette single-cell manipulation system, we showed that the adhesion force of the osteoblasts to fibronectin-coated glass (1.0 microg/ml) was significantly affected by the presence of particulate debris. The adhesion force of the cells incubated with titanium particles for less than 4 hours was not significantly affected by exposure to the particles; after 4 hours, however, it was significantly reduced relative to that of controls. Aspiration of particle-challenged osteoblasts into the micropipette demonstrated that the particles were not stripped from the cell surface and therefore confirmed that the osteoblasts had ingested them. During aspiration, the particles traveled through the cytoplasm rather than on the cell surface. When the osteoblasts were exposed to the particles and cytochalasin D, they exhibited much lower adhesion forces than did the controls or the cells exposed to titanium particles only; this indicates an important role of actin filaments in the osteoblastic response to particles. Staining for F-actin also indicated an influence of internalized titanium particulate on cytoskeletal arrangement and cell spreading. Furthermore, with standard Northern blotting techniques, levels of mRNA for collagen type I and fibronectin were significantly reduced as early as 4 hours after exposure to particles compared with levels in controls, and this effect continued to 72 hours. These data indicate that direct exposure of osteoblasts to titanium particles, which we propose to be ingested by the osteoblasts, can significantly decrease osteoblast adhesion force; this may lead to decreased cellular activity and gene expression of fibronectin and collagen type I in the presence of titanium wear debris.


Electromechanical coupling constant extraction of thin-film piezoelectric materials using a bulk acoustic wave resonator.
Thin-film piezoelectric materials such as ZnO and AlN have great potential for on-chip devices such as filters, actuators and sensors. The electromechanical coupling constant is an important material parameter which determines the piezoelectric response of these films. This paper presents a technique based on the Butterworth Van-Dyke (BVD) model which, together with a simple one-mask over-moded resonator, can be used to extract the bulk, one-dimensional electromechanical coupling constant K(2) of any piezoelectrically active thin-film. The BVD model is used to explicitly define the series resonance, parallel resonance, and quality factor Q of any given resonating mode. Common methods of defining the series resonance, parallel resonance, and Q are shown to be inaccurate for low coupling, lossy resonators such as the over-moded resonator. Specifically, an electromechanical coupling constant K(2) of (2.6+/-0.1)% was measured for an (002) c-axis textured AlN film with an X-ray diffraction rocking curve of 7.5 degrees using the BVD based extraction technique.


Global protein expression analysis in apicomplexan parasites: current status.
Members of the phylum Apicomplexa are important protozoan parasites that cause some of the most serious, and in some cases, deadly diseases in humans and animals. They include species from the genus Plasmodium, Toxoplasma, Eimeria, Neospora, Cryptosporidium, Babesia and Theileria. The medical, veterinary and economic impact of these pathogens on a global scale is enormous. Although chemo- and immuno-prophylactic strategies are available to control some of these parasites, they are inadequate. Currently, there is an urgent need to design new vaccines or chemotherapeutics for apicomplexan diseases. High-throughput global protein expression analyses using gel or non-gel based protein separation technologies coupled with mass spectrometry and bioinformatics provide a means to identify new drug and vaccine targets in these pathogens. Protein identification based proteomic projects in apicomplexan parasites is currently underway, with the most significant progress made in the malaria parasite, Plasmodium falciparum. More recently, preliminary two-dimensional gel electrophoresis maps of Toxoplasma gondii and Neospora caninum tachyzoites and Eimeria tenella sporozoites, have been produced, as well as for micronemes in E. tenella. In this review, the status of proteomics in the analysis of global protein expression in apicomplexan parasites will be compared and the challenges associated with these investigations discussed.


Elucidating the role of blood metabolites on pancreatic cancer risk using two-sample Mendelian randomization analysis.
Pancreatic ductal adenocarcinoma (PDAC) is an uncommon but highly fatal malignancy. Identifying causal metabolite biomarkers offers an opportunity to facilitate effective risk assessment strategies for PDAC. In this study, we performed a two-sample Mendelian randomization (MR) study to characterize the potential causal effects of metabolites in plasma on PDAC risk. Genetic instruments were determined for a total of 506 metabolites from one set of comprehensive genome-wide association studies (GWAS) involving 913 individuals of European ancestry from the INTERVAL/EPIC-Norfolk cohorts. Another set of genetic instruments was developed for 483 metabolites from an independent GWAS conducted with 8299 individuals of European ancestry from the Canadian Longitudinal Study on Aging (CLSA) cohort. We analyzed GWAS data of the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), comprising 8275 PDAC cases and 6723 controls of European ancestry. The association of metabolites with PDAC risk was assessed using the inverse-variance weighted (IVW) method, and complemented with sensitivity analyses of MR-Egger and MR-PRESSO tests. Potential side effects of targeting the identified metabolites for PDAC intervention were further evaluated by a phenome-wide MR (Phe-MR) analysis. Forty-four unique metabolites were identified to be significantly associated with PDAC risk, of which four top-ranking metabolites (X: 12798, X: 11787, X: 11308 and X: 19141) showed replication evidence when using instruments developed from both two cohorts. Our results highlight novel blood metabolites related to PDAC risk, which may help prioritize metabolic features for PDAC mechanistic research and further evaluation of their potential role in PDAC risk assessment.


Prevention of diarrhoea in young children in developing countries.
An updated review of nonvaccine interventions for the prevention of childhood diarrhoea in developing countries is presented. The importance of various key preventive strategies (breast-feeding, water supply and sanitation improvements) is confirmed and certain aspects of others (promotion of personal and domestic hygiene, weaning education/food hygiene) are refined. Evidence is also presented to suggest that, subject to cost-effectiveness examination, two other strategies-vitamin A supplementation and the prevention of low birth weight-should be promoted to the first category of interventions, as classified by Feachem, i.e. those which are considered to have high effectiveness and strong feasibility.


[The condition of the system "peroxide oxidation of lipids-antioxidant defense" in mixed saliva of patients with chronic generalized periodontitis].
The comparative analysis was made concerning conditions of the system "Peroxide oxidation of lipids-antioxidant defenses in mixed saliva of patients with chronic disseminated periodontitis of light (n = 45), mean (n = 36) and severe (n = 18) degrees. The control group consisted of 25 clinically healthy persons with intact periodontium. The study revealed that in comparison with control group, in patients with chronic disseminated periodontitis occurred an increasing of content of heptane-soluble diene conjugates, isopropanol-soluble ketodienes and conjugated trienes, ceruloplasmin and a decreasing of level of alpha-tocopherol, especially under severe degree of disease. The study also established a non-linear U-dependence between indicators of the system "Peroxide oxidation of lipids-antioxidant defenses" in mixed saliva and severity of affection of tissues of periodontium in patients with chronic disseminated dermatosis.


What do we gain from the sixth stool guaiac?
The six sequential stool guaiac protocol has been advocated for screening of colonic cancer. Analysis of the expenditures involved in such a program shows that the cost of detecting cancer rises exponentially so that the marginal cost of the sixth test may be 20,000 times the average cost. The marginal cost is decreased with lower test sensitivity and increased with lower prevalence of colonic cancer. This result shows that even an inexpensive test can become quite costly in terms of cases detected. The marginal cost per case detected depends on the prevalence of the condition in the population screened and the sensitivity of the test applied.


Epigenetic control of alternative mRNA processing at the imprinted Herc3/Nap1l5 locus.
Alternative polyadenylation increases transcriptome diversity by generating multiple transcript isoforms from a single gene. It is thought that this process can be subject to epigenetic regulation, but few specific examples of this have been reported. We previously showed that the Mcts2/H13 locus is subject to genomic imprinting and that alternative polyadenylation of H13 transcripts occurs in an allele-specific manner, regulated by epigenetic mechanisms. Here, we demonstrate that allele-specific polyadenylation occurs at another imprinted locus with similar features. Nap1l5 is a retrogene expressed from the paternally inherited allele, is situated within an intron of a 'host' gene Herc3, and overlaps a CpG island that is differentially methylated between the parental alleles. In mouse brain, internal Herc3 polyadenylation sites upstream of Nap1l5 are used on the paternally derived chromosome, from which Nap1l5 is expressed, whereas a downstream site is used more frequently on the maternally derived chromosome. Ablating DNA methylation on the maternal allele at the Nap1l5 promoter increases the use of an internal Herc3 polyadenylation site and alters exon splicing. These changes demonstrate the influence of epigenetic mechanisms in regulating Herc3 alternative mRNA processing. Internal Herc3 polyadenylation correlates with expression levels of Nap1l5, suggesting a possible role for transcriptional interference. Similar mechanisms may regulate alternative polyadenylation elsewhere in the genome.


Comparison of students' encountered diseases and available diseases at clerkship sites by exploratory multivariate analysis: Are encountered diseases predictable?
Students in clerkship are expected to gain clinical expertise by interacting with real patients in clinical situations. Monitoring and predicting the students' encounter diseases (EDs) is important for providing an optimal experience. EDs should be compared with the available diseases (ADs) at the clerkship site and with the required diseases described in some guidelines for the clinical curriculum. To explore the differences in ADs as learning resources among different types of clerkship sites and to investigate discrepancies between EDs and ADs. A retrospective observational study used secondary data from government statistics to compare ADs of various types of observable clerkship sites by biplot analyses, which allowed multivariate comparisons. EDs collected from logbooks during clerkships at a university hospital were also compared with ADs across sites. The distributions of ADs differed according to institutional type, and EDs at Kyushu University Hospital were similar to the ADs for the category of hospitals in which it was placed. EDs at a clerkship site may be predictable to some extent by analysing the site's distribution of ADs, but further study is needed. Biplot is useful for visualising these types of statistical similarity.


Time-resolved ellipsometry for studies of heat transfer at liquid/solid and gas/solid interfaces.
We describe a sensitive method for measuring time-dependent changes in refractive index within approximately 5 microm of an interface using off-null time-resolved ellipsometry and a dual-cavity femtosecond laser. The sensitivity to changes in refractive index is two orders of magnitude higher than conventional picosecond interferometry. A thin metal film on a sapphire substrate is heated by approximately 10 K using an ultrafast optical pump pulse; the subsequent changes of the phase difference deltaDelta between p and s polarized reflectivity are tracked using off-null ellipsometry using a time-delayed probe pulse. We demonstrate a sensitivity of deltaDelta approximately = 3x10(-7) deg/square root(Hz) using interfaces between Au and water, and Au and various gases including R134a, a common refrigerant. Our data for the damping rate of approximately 200 MHz frequency acoustic waves in O(2), N(2), and Ar at atmospheric pressure agree well with prior results obtained at much lower pressures and frequencies.


Serum Level of CD48 and Its Expression on Blood Leukocytes in Persistent Asthmatic Patients.
CD48 is a surface receptor (mCD48) expressed on most hematopoietic cells, as well as in a soluble form (sCD48). It seems to play a major role in asthma through the interactions of mast cells with eosinophils via its ligand CD244. Hence, this study was done to evaluate the role of CD48, in its membrane and soluble forms, as a novel biomarker in asthma with various degrees of severity. One hundred participants were enrolled in this study and divided into 4 equal groups matched in age and sex; mild asthma, moderate asthma, severe asthma and apparently healthy controls. All were investigated for blood leukocytes mCD48 expression using flow cytometry and sCD48 in serum using ELISA. Our results revealed that the sCD48 was significantly elevated in patients with mild asthma compared with the controls (P<0.001) while significantly decreased in severe asthma than mild asthma (P<0.001) and moderate asthma (P=0.002) patient groups. Expression of mCD48 on eosinophils in moderate asthma group was significantly elevated compared with the control and the mild asthmatic groups (P<0.001). However, it was significantly decreased in severe asthma compared with moderate and mild asthma (P<0.001 and P=0.03, respectively). While it was significantly upregulated in severe asthmatic group compared to controls, patients with mild and moderate asthma on T-cell, B cells, Monocytes and NK cells (P<0.001 for all). In conclusion, CD48 may play a role in asthma and its level varies with severity of the disease being a useful marker in mild asthma.


Essential and long-chain polyunsaturated fatty acid status and fatty acid composition of breast milk of lactating adolescents.
The aims of the present study were to evaluate essential fatty acids (EFA) and long-chain PUFA (LCPUFA) status in lactating adolescents and its association with breast milk composition. Healthy nursing adolescents from Rio de Janeiro, Brazil (n 30; 14-19 years; 30-120 d postpartum), exclusively or predominantly breast-feeding, participated in this study. Breast milk and blood samples were collected after overnight fasting. Fatty acid composition of breast milk, erythrocyte membrane (EM) and plasma NEFA were determined by GC. Indices of fatty acid status (mean melting point (MMP); EFA status index; DHA status indices, 22 : 5n-6:22 : 4n-6 and 22 : 6n-3:22 : 5n-6 ratios) were calculated from EM fatty acid composition. Dietary intake of n-3 fatty acids was low when compared with current recommendations for lactating women. MMP was associated with indices of DHA status, some individual fatty acids in EM and years post-menarche and weeks postpartum, suggesting the use of erythrocyte MMP as a possible comprehensive biochemical marker of LCPUFA status in this physiological condition. The DHA status of lactating adolescents and their milk DHA concentrations were similar to the values of Brazilian lactating adults, but lower compared with the values of lactating adults from other countries. Therefore, these lactating adolescents were apparently not disadvantaged, as compared with the Brazilian adults, when EM and breast milk fatty acid composition were considered. In general, PUFA in milk from adolescents presented few associations with their concentrations in plasma NEFA and with maternal status. However, milk DHA was associated with maternal LCPUFA and DHA states.


Evaluation of free radical formation associated with diagnostic ultrasound.
Our objective was to evaluate kidney antioxidant status in rats subjected to an ultrasound examination. Thirty rats were divided into five groups for injection of saline (S) or anesthetic (A), and application of ultrasound using different modes, B mode, pulsed wave Doppler, and continuous wave Doppler, under anesthesia. Ultrasound was performed on days 1, 3, and 5 relative to the initiation of the experiment. Rats were then scarified on day 6. The kidney tissue thiobarbituric acid reactive substance (TBARS) level and superoxide dismutase (SOD) activity were measured. Both TBARS level and SOD activity increased, 21% and 38%, respectively, due to anesthesia (P < 0.04 for both). SOD activity increased further by a factor of 1.2 in response to ultrasound examination (P < 0.05), whereas TBARS level was not affected by Doppler and continuous wave Doppler compared to anesthesia. Increases in the level of TBARS (P < 0.03) and SOD activity (P < 0.01) were greatest when B-mode ultrasound was employed. These substances did not increase further when continuous wave Doppler was employed. The peak-negative acoustic pressure (9.16 vs. 9.74 MPa) and frequency (3.57 vs. 6.95 MHz) for B mode and pulsed wave Doppler were greater than those for continuous wave Doppler (0.22 MPa and 1.96 MHz). The estimated mechanical indexes were 4.87, 3.70, and 0.15 for B mode, pulsed wave Doppler, and continuous wave Doppler, respectively. In conclusion, anesthesia may cause tissue damage as reflected by elevated lipid peroxidation and free radical formation and ultrasound examination may amplify tissue damage through mechanical effects caused by ultrasound absorption.


Effect of posture on deglutitive biomechanics in healthy individuals.
The purpose of this study was to assess displacement of oropharyngeal structures, particularly the hyoid bone and velum, and variations in timing of the pharyngeal stage of swallowing in the upright versus the supine position. Twelve Caucasian adult subjects between 19 and 27 years of age participated. Subjects were recorded swallowing 7 cc of liquid barium in the upright and supine positions. The hyoid bone had a significantly greater amount of anterior displacement while in the supine position compared to that of the upright position (p < 0.01). While in the upright position, the velum comes to a fully elevated position at nearly the same time as the initiation of the pharyngeal swallow (within an average of 27 ms of each other), whereas in the supine position the velum continues to elevate on average 115 ms after the initiation of the pharyngeal swallow. Results indicated a significant difference (p < 0.05) in the amount of velar movement from rest to the fully elevated position between the upright and supine positions for female subjects. The results from the study demonstrate variations in hyoid displacement, velar movement, and bolus movement through the pharynx with respect to the two body positions and the subjects' gender.


South African mothers' coping with an unplanned Caesarean section.
In this study, researchers explored mothers' coping strategies in dealing with birth by unplanned Caesarean section. Mothers' experiences of a traumatic birth could be influenced by perceived strengths when coping with the stress related to the incident. Coping strategies resulted in reassessment of the birth process and were associated with a more positive and memorable experience. In-depth interviews with 10 women explored their lived experiences of childbirth. Data were analyzed thematically. Phenomenological theory served as a framework for the structuring, organizing, and categorizing of data. Mothers described several factors and coping strategies that they perceived to be effective in reducing the impact of their traumatic birth experiences.


Effects of Microwave 10 GHz Radiation Exposure in the Skin of Rats: An Insight on Molecular Responses.
Microwave (MW) radiation poses the risk of potential hazards on human health. The present study investigated the effects of MW 10 GHz exposure for 3 h/day for 30 days at power densities of 5.23 ± 0.25 and 10.01 ± 0.15 mW/cm2 in the skin of rats. The animals exposed to 10 mW/cm2 (corresponded to twice the ICNIRP-2020 occupational reference level of MW exposure for humans) exhibited significant biophysical, biochemical, molecular and histological alterations compared to sham-irradiated animals. Infrared thermography revealed an increase in average skin surface temperature by 1.8°C and standard deviation of 0.3°C after 30 days of 10 mW/cm2 MW exposure compared to the sham-irradiated animals. MW exposure also led to oxidative stress (ROS, 4-HNE, LPO, AOPP), inflammatory responses (NFkB, iNOS/NOS2, COX-2) and metabolic alterations [hexokinase (HK), lactate dehydrogenase (LDH), citrate synthase (CS) and glucose-6-phospahte dehydrogenase (G6PD)] in 10 mW/cm2 irradiated rat skin. A significant alteration in expression of markers associated with cell survival (Akt/PKB) and HSP27/p38MAPK-related stress-response signaling cascade was observed in 10 mW/cm2 irradiated rat skin compared to sham-irradiated rat skin. However, MW-irradiated groups did not show apoptosis, evident by unchanged caspase-3 levels. Histopathological analysis revealed a mild cytoarchitectural alteration in epidermal layer and slight aggregation of leukocytes in 10 mW/cm2 irradiated rat skin. Altogether, the present findings demonstrated that 10 GHz exposure in continuous-wave mode at 10 mW/cm2 (3 h/day, 30 days) led to significant alterations in molecular markers associated with adaptive stress-response in rat skin. Furthermore, systematic scientific studies on more prevalent pulsed-mode of MW-radiation exposure for prolonged duration are warranted.


Inflammatory bowel disease at the korle bu teaching hospital, accra.
SummaryCase files of patients with Inflammatory Bowel Disease (IBD) managed by the author in the Medical Department over the period 1997 - 2004 have been reviewed to identify some features of the disease that may aid improved diagnosis and management. The findings indicate that IBD may not be rare in the country and that there is usually a long delay in establishing the diagnosis. It appears that, in Ghana, more males than females are affected and that most are fifty years of age or below. Malignant colonic change is uncommon but there is a high default rate among the patients. Five patients (29%) died. Cases managed in an Arab country, between 1987 and 1996, have been compared. In that group more female than male patients were affected but the commonest age group affected was similar. The diagnosis was similarly delayed but no deaths were recorded as opposed to the Ghana patients. Since Inflammatory Bowel Disease (IBD) is a potentially treatable condition medical practitioners need increased awareness to avoid undue delay in diagnosis.


Pediatric intractable epilepsy: the role of presurgical evaluation and seizure outcome.
Surgical experience with long-term follow-up is limited in childhood intractable epilepsy, compared with adult epilepsy. To assess the role of each presurgical evaluation modality and to identify prognostic factors for favorable seizure control after epilepsy surgery, 38 children with intractable epilepsy who underwent surgery were retrospectively reviewed. Among the available preoperative evaluation modalities, PET and neuropsychological testing showed the highest rates of positive results, whereas MRI was the most concordant with EEG findings. During a follow-up period of at least 12 months, 26 of the 38 patients showed favorable seizure control (Engel classifications I and II). The best seizure control was achieved in patients with a temporal resection and discrete lesion on magnetic resonance imaging. In spite of the invasive study, the less satisfactory results followed an extratemporal resection. We conclude that epilepsy surgery benefits children with intractable epilepsy and that the role of invasive study should be reestablished according to the area of resection and presence of discrete lesion on MRI.


Depletion of cartilage collagen fibrils in mice carrying a dominant negative Col2a1 transgene affects chondrocyte differentiation.
We have generated transgenic mice harboring the deletion of exon 48 in the mouse alpha1(II) procollagen gene (Col2a1). This was the first dominant negative mutation identified in the human alpha1(II) procollagen gene (COL2A1). Patients carrying a single allele with this mutation suffer from a severe skeletal disorder called spondyloepiphyseal dysplasia congenita (SED). Transgenic mice phenotype was neonatally lethal with severe respiratory failure, short bones, and cleft palate. Transgene mRNA was expressed at high levels. Growth plate cartilage of transgenic mice presented morphological abnormalities and reduced number of collagen type II fibrils. Chondrocytes carrying the mutation showed altered expression of several differentiation markers, like fibroblast growth factor receptor 3 (Fgfr3), Indian hedgehog (Ihh), runx2, cyclin-dependent kinase inhibitor P21CIP/WAF (Cdkn1a), and collagen type X (Col10a1), suggesting that a defective extracellular matrix (ECM) depleted of collagen fibrils affects chondrocytes differentiation and that this defect participates in the reduced endochondral bone growth observed in chondrodysplasias caused by mutations in COL2A1.


Fishing for foreign bodies.
A guide to the radiological detection of fish bones for the sporting physician is presented. By radiologically examining fish bones superimposed on the neck, it was found that most bones are detectable, thus lending support to the use of plain neck films in screening for impacted fish bones.


Process efficiency and ventilation requirement in black soldier fly larvae composting of substrates with high water content.
In order to transition from a linear to a circular economy in the organic waste management sector, more of the elements in waste need to be recycled. Use of black soldier fly (Hermetia illucens L.; Diptera: Stratiomyidae) larvae (BSFL) for organic waste treatment has potential to harvest more complex molecules than conventional methods. Many organic waste substrates have high water content (>80%), but the impact on BSFL treatment efficiency of substrate water contents >80% is not known. This study evaluated the impact of high water content food waste on BSFL composting efficiency in terms of waste-to-biomass conversion ratio, material reduction, larval survival and the ventilation required for enabling dry separation of larvae from residue. In total, six water contents ranging from 76% to 97.5% were evaluated in two experimental trials. It was found that increasing water content reduced biomass conversion ratio and survival rate of the larvae, from 33.4% of volatile solids (VS) and 97.2% survival in 76% water to 17.5% of VS and 19.3% survival in 97.5% water. Furthermore, we found that the ventilation requirement for achieving dry separation of larvae from residue could be modelled by estimating the amount of water that would need to be removed, taking into account the water bound in the larvae, and knowing the specifics of the ventilation set-up of the modelled system. The findings could have implications on the waste management sector interested in implementing BSFL treatment, as the findings demonstrate that it is possible to treat wet substrates (such as fruit and vegetable wastes) without any pre-treatment other than grinding and attain an adequately dry residue for enabling dry separation of the larvae from the residue.


Influence of the precision of spectral backscatter measurements on the estimation of scatterers size in cancellous bone.
The goal of this study is to propose a model for the ultrasonic frequency-dependent backscatter coefficient in femoral cancellous bone. This model has been developed with success to predict backscatter in human calcaneal bone [Jenson, Ultr. Med. Biol. 2003]. A weak scattering model is used and the backscatter coefficient is expressed in terms of a Gaussian autocorrelation function of the medium. The backscatter coefficient is computed and comparison is made with experimental data for 37 specimens and for frequency ranging from 0.4 to 1.2 MHz. An excellent agreement between experimental data and predictions is found for both the magnitude and the frequency-dependence of the backscatter coefficient. Then, a nonlinear regression is performed for each specimen, and the mean trabecular thickness is estimated. Experimental data and theoretical predictions are averaged over the 37 specimens. We also find a close agreement between theoretical predictions obtained using the Gaussian autocorrelation function (scatterer size=134+/-15 microm) and the mean trabecular thickness (Tb.Th=132+/-12 microm) derived from the analysis of bone 3-D micro-architecture using high-resolution micro-tomography. However, the correlation between individual experimental and estimated Tb.Th values is moderate (R(2)=0.44). The performance of the estimator are limited mainly by two factors: interference noise due to random positioning of the scatterers and attenuation. We show that the fundamental limitation of our estimator due to the speckle noise is around 5 microm for trabecular thickness estimation. This limitation is lower than the observed biological variability which is around 30 microm and should not be a limiting factor for individual prediction. A second limitation is the tremendous attenuation encountered in highly scattering media such as cancellous bone, which results in highly damped backscatter signals. The compensation for attenuation is difficult to perform, and it may be a critical point that limits the precision of the estimator.


Peritumoural MRI radiomics signature of brain metastases can predict epidermal growth factor receptor mutation status in lung adenocarcinoma.
To investigate whether magnetic resonance imaging (MRI) radiomics features of brain metastases (BMs) can predict epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma. Between June 2014 and December 2022, 58 histopathologically confirmed lung adenocarcinoma patients (27 with EGFR wild-type, 31 with EGFR mutation) who underwent gadobenate dimeglumine-enhanced brain MRI were recruited retrospectively. A total of 123 metastatic brain lesions were allocated randomly into the training cohort (n=86) and test cohort (n=37) at a ratio of 7:3. Radiomics models based on multi-sequence MRI images in different regions such as volume of interest (VOI)enhancing tumour, VOIwholetumour, VOIperitumour 1mm, VOIperitumour 3mm, and VOIperitumour 5mm were built. The optimal radiomics model was integrated into the clinical or radiological indicators to construct a fusion model through multivariable logistic regression analysis. The optimal radiomics model based on the VOIperitumour 1mm, a combination of nine features selected from the fluid-attenuated inversion recovery (FLAIR) sequence, yielded areas under the curves (AUCs) of >0.75 in the training and test cohorts. The prediction of the fusion model with integration of clinical factors (age) and radiomics score (the optimal radiomics model) was not better than that of the optimal radiomics model alone in the test cohort (AUC: 0.808 and 0.785, respectively, p=0.525). The FLAIR radiomics model based on VOIperitumour 1mm as an effective biomarker helps predict EGFR mutation status in lung adenocarcinoma patients with BMs and then assists clinicians in selecting optimal treatment strategies.


In vitro DNA synthesis in the macronuclear replication band of Euplotes eurystomus.
Isolated macronuclei from the hypotrichous ciliated protozoan Euplotes eurystomus incorporate biotinylated dUTP specifically into the replication band (RB) as detected with immunofluorescence, using rabbit anti-biotin antibodies followed by fluorescein-conjugated goat anti-rabbit IgG. When gold-conjugated goat anti-rabbit IgG was used in a preembedded reaction, subsequent immunoelectron microscopic analysis demonstrated that the biotinylated nucleotide appeared more concentrated in the rear zone of the RB, with almost no labeling in the forward zone. It was possible to use the immunofluorescent assay to establish that incorporation of biotinylated dUTP is inhibited by simultaneous addition of N-ethyl maleimide or aphidicolin, and by omission of any one of the other unlabeled dNTPs. In addition, prolonged heat shock of the intact cells, before lysis and in vitro assay, yielded markedly reduced incorporation. Comparison with published data on the in vivo incorporation of [3H]thymidine into Euplotes eurystomus RBs indicates the fidelity of the in vitro reaction.


Cannibalism and predation behaviour of the blowfly, Chrysomyia albiceps (Wiedemann) larvae (Diptera: Calliphoridae).
Chrysomyia albiceps is considered as a carrion inhabitant and is essentially scavenger. It is among the first species to arrive at carrion and lays its eggs on it almost immediately under favourable conditions. Field studies in Giza area showed that although other flies arrive at the carrion shortly following Chrysomyia, as decomposition progresses, its larvae are the major component predominate, and the common fly emerging from carrion is its adults. First instar larvae is entirely necrophagous, but the 2nd and early 3rd instar larvae may be facultatively predaceous on other dipteran larvae (Muscina and Parasarcophaga) as an alternative food source under crowded or starved conditions. Cannibalism, second and early 3rd instars preying on the 1st instar larvae and on themselves has also been found. Considering the predation behaviour, C. albiceps may be considered as beneficial biological control agent to help in reducing populations of carrion flies which are of medical and veterinary importance owing to their significant role in causing the different kind of myiasis of man and animals. The second instar is less inclined than the early 3rd instar to serve as a predator. The numerous heavily sclerotized spines and fleshy processes of the robust and powerful preyer early 3rd instar larvae help in subduing the prey while their strong mouthhooks are used to penetrate the bodies of the other larvae for fluid extraction.


EVERREST prospective study: a 6-year prospective study to define the clinical and biological characteristics of pregnancies affected by severe early onset fetal growth restriction.
Fetal growth restriction (FGR) is a serious obstetric condition for which there is currently no treatment. The EVERREST Prospective Study has been designed to characterise the natural history of pregnancies affected by severe early onset FGR and establish a well phenotyped bio-bank. The findings will provide up-to-date information for clinicians and patients and inform the design and conduct of the EVERREST Clinical Trial: a phase I/IIa trial to assess the safety and efficacy of maternal vascular endothelial growth factor (VEGF) gene therapy in severe early onset FGR. Data and samples from the EVERREST Prospective Study will be used to identify ultrasound and/or biochemical markers of prognosis in pregnancies with an estimated fetal weight (EFW) <3rd centile between 20+0 and 26+6 weeks of gestation. This is a 6 year European multicentre prospective cohort study, recruiting women with a singleton pregnancy where the EFW is <3rd centile for gestational age and <600 g at 20+0 to 26+6 weeks of gestation. Detailed data are collected on: maternal history; antenatal, peripartum, and postnatal maternal complications; health economic impact; psychological impact; neonatal condition, progress and complications; and infant growth and neurodevelopment to 2 years of corrected age in surviving infants. Standardised longitudinal ultrasound measurements are performed, including: fetal biometry; uterine artery, umbilical artery, middle cerebral artery, and ductus venosus Doppler velocimetry; and uterine artery and umbilical vein volume blood flow. Samples of maternal blood and urine, amniotic fluid (if amniocentesis performed), placenta, umbilical cord blood, and placental bed (if caesarean delivery performed) are collected for bio-banking. An initial analysis of maternal blood samples at enrolment is planned to identify biochemical markers that are predictors for fetal or neonatal death. The findings of the EVERREST Prospective Study will support the development of a novel therapy for severe early onset FGR by describing in detail the natural history of the disease and by identifying women whose pregnancies have the poorest outcomes, in whom a therapy might be most advantageous. The findings will also enable better counselling of couples with affected pregnancies, and provide a valuable resource for future research into the causes of FGR. NCT02097667 registered 31st October 2013.


Psychological outcomes of life story work for community-dwelling seniors: A randomised controlled trial.
Life story work has a long tradition in the caring sciences and has been found to serve a number of psychological functions. The effects of life story work on the psychological well-being of community-dwelling older people were examined in this study. For this randomised controlled trial, 244 community-dwelling participants in 17 social centres run by a non-governmental organisation were recruited. The participants were randomly allocated to intervention (n = 124) and control (n = 120) groups. Each member of the intervention group worked with a volunteer to prepare his/her life storybook, while those in the control group participated in a social program. Data were collected at baseline, immediately postintervention, and at three and six months postintervention. The outcomes included measures of life satisfaction, self-esteem, general mental well-being and depressive symptoms. No significant interaction effect was observed between the groups over time, except for an improvement in the general mental well-being of the control group at three months postintervention. A comparison of the findings in the literature showed that some positive results were reported for LSW studies conducted in nursing homes, whereas in community studies, the results were not always positive. Life story work for seniors in the community did not have the same positive outcomes as previously observed among nursing home residents. It is possible that the intervention had a greater effect on more deprived individuals. Community-dwelling seniors can be encouraged to participate in social activities, which apparently can lead to similar outcomes. Clinicians should not assume that similar interventions can have similar effects when delivered in a different setting. Community-dwelling seniors can be encouraged to participate in social activities, which can also promote psychological wellbeing similar to to the effects of activities related to life story work.


UV-A screening in Cladophora sp. lowers internal UV-A availability and photoreactivation as compared to non-UV screening in Ulva intestinalis.
In the Baltic Sea, two co-occurring green macroalgae Cladophora sp. and Ulva intestinalis grow in the upper eulittoral. Due to regular and high sunlight exposure in their habitat, both species need resistance mechanisms to protect themselves against ultraviolet-B (UV-B)-induced DNA damage. While Cladophora sp. possesses efficient screening of UV-B and ultraviolet-A (UV-A) radiation, U. intestinalis was recently shown to have higher DNA repair by UVA-driven photoreactivation than Cladophora sp. [F. Pescheck and W. Bilger, Mar. Biol., 2018, 165, 132]. In the present study, the hypothesis that the screening of UV-A radiation limits internal UV-A availability for photoreactivation in Cladophora sp. was tested. Both species had identical and much lower fractions of damaged DNA when sampled in situ under direct sunlight as expected based on a photophysical prediction. To quantify the effect of UV-A screening spectrally and physiologically, in vivo UV screening spectra were determined and the UV-A photon flux dependency of photoreactivation was investigated for both species. Identical intrinsic photoreactivation rates were revealed by the applied correction for internal UV-A photon flux density and under irradiation with visible radiation which is not screened by the UV absorbing compounds in Cladophora sp. Natural sunlight was weighted with in vivo action spectra for DNA damage induction and light-dependent repair. The resulting spectrum was further corrected for the apparent UV screening spectra of both species to calculate the species-specific internal ratios of DNA damaging and photoreactivating photons. This photophysical modelling improves the understanding of UV damage and tolerance mechanisms in the two co-occurring green macroalgae under solar irradiation.


The role of vimentin intermediate filaments in cortical and cytoplasmic mechanics.
The mechanical properties of a cell determine many aspects of its behavior, and these mechanics are largely determined by the cytoskeleton. Although the contribution of actin filaments and microtubules to the mechanics of cells has been investigated in great detail, relatively little is known about the contribution of the third major cytoskeletal component, intermediate filaments (IFs). To determine the role of vimentin IF (VIF) in modulating intracellular and cortical mechanics, we carried out studies using mouse embryonic fibroblasts (mEFs) derived from wild-type or vimentin(-/-) mice. The VIFs contribute little to cortical stiffness but are critical for regulating intracellular mechanics. Active microrheology measurements using optical tweezers in living cells reveal that the presence of VIFs doubles the value of the cytoplasmic shear modulus to ∼10 Pa. The higher levels of cytoplasmic stiffness appear to stabilize organelles in the cell, as measured by tracking endogenous vesicle movement. These studies show that VIFs both increase the mechanical integrity of cells and localize intracellular components.


Increased identification of parathyroid glands using near infrared light during thyroid and parathyroid surgery.
Parathyroid gland (PG) identification during thyroid and parathyroid surgery is challenging. Accidental parathyroidectomy increases the rate of postoperative hypocalcaemia. Recently, autofluorescence with near infrared light (NIRL) has been described for PG visualization. The aim of this study is to analyze the increased rate of visualization of PGs with the use of NIRL compared to white light (WL). All patients undergoing thyroid and parathyroid surgery were included in this study. PGs were identified with both NIRL and WL by experienced head and neck surgeons. The number of PGs identified with NIRL and WL were compared. The identification of PGs was correlated to age, sex, and histopathological diagnosis. Seventy-four patients were included in the study. The mean age was 48.4 (SD ±13.5) years old. Mean PG fluorescence intensity (47.60) was significantly higher compared to the thyroid gland (22.32) and background (9.27) (p < 0.0001). The mean number of PGs identified with NIRL and WL were 3.7 and 2.5 PG, respectively (p < 0.001). The difference in the number of PGs identified with NIRL and WL and fluorescence intensity was not related to age, sex, or histopathological diagnosis, with the exception of the diagnosis of thyroiditis, in which there was a significant increase in the number of PGs visualized with NIRL (p = 0.026). The use of NIRL for PG visualization significantly increased the number of PGs identified during thyroid and parathyroid surgery, and the differences in fluorescent intensity among PGs, thyroid glands, and background were not affected by age, sex, and histopathological diagnosis.


Subpontic osseous hyperplasia: a case report.
Subpontic osseous hyperplasia is an ectopic growth of bone occurring on the edentulous ridge beneath a fixed partial denture replacing a mandibular first molar. A 56-year-old woman experienced an enlargement of the hard and soft tissues beneath the pontic region of a fixed partial denture replacing her mandibular left first molar. Following removal of the fixed partial denture, the bony enlargement was surgically removed, and the bony fragments were submitted for histologic analysis, which demonstrated mature lamellar bone and appositional growth. One year postoperatively, there has been no recurrence of the lesion. The possible etiologies and treatment modalities are reviewed and a rationale for treatment is presented.


A polydnavirus-encoded protein of an endoparasitoid wasp is an immune suppressor.
The molecular mechanism by which polydnaviruses of endoparasitoid wasps disrupt cell-mediated encapsulation reactions of host insects is largely unknown. Here we show that a polydnavirus-encoded protein, produced from baculovirus and plasmid expression vectors, prevents cell surface exposure of lectin-binding sites and microparticle formation during immune stimulation of haemocytes. The inactivation of immune-related cellular processes by this protein was analysed using a specific lectin and annexin V and shown to be virtually identical to polydnavirus-mediated effects on haemocytes. Cytochalasin D application has similar effects on haemocytes, suggesting that the immune suppression by the polydnavirus protein is caused by the destabilization of actin filaments. Since the exposure of cell surface glycoproteins and the formation of microparticles are part of an immune response to foreign objects or microorganisms and a prerequisite for cell-mediated encapsulation of microorganisms and parasites, the virus-encoded protein may become an important tool for the inactivation of cellular immune reactions in insects and an essential component in understanding immune suppression in parasitized host insects.


Effects of the aromatase inhibitor letrozole on normal breast epithelial cell proliferation and metabolic indices in postmenopausal women: a pilot study for breast cancer prevention.
The aromatase enzyme converts androgens to estrogens and is the therapeutic target for aromatase inhibitors in postmenopausal patients with estrogen receptor-positive metastatic breast cancer. Third-generation inhibitors such as letrozole are being considered as potential prophylactic agents for breast cancer. The rationale for their preventive application would be aided by knowledge of their effects on the normal breast and on other estrogen-dependent processes such as bone and lipid metabolism. Thirty-two women without active breast disease were recruited to 3-month treatment with letrozole (2.5 mg/day). Core-cut biopsies from the breast and blood samples were collected before and at the end of treatment. Plasma estradiol levels were markedly suppressed in all but two patients, who were excluded from the efficacy assessment. There was no significant change in the proliferation marker Ki67 (mean change, -23%; 95% confidence interval, -50% to +23%) or estrogen receptor in breast epithelial cells with treatment. Similarly, there were no significant changes in plasma levels of insulin-like growth factor I or lipid profiles. However, there was a significant increase (25%) in the levels of the bone resorption marker C-telopeptide crosslinks (CTx). We conclude that any prophylactic effect of letrozole is not likely to be dependent on antiproliferative effects on normal breast. Studies in healthy patients will need to recognize the potential for enhanced bone resorption.


[Treatment of Hemothorax with Bronchial Artery Embolization Combined with Video-assisted Thoracic Surgery Following Hemi-arch Replacement for Stanford Type A Acute Aortic Dissection].
A 51-year-old male arrived at our hospital by ambulance, presenting with a sudden onset of chest pain. Computed tomography (CT) revealed Stanford type A acute aortic dissection. Although emergency hemi-arch replacement was successfully performed, the blood pressure decreased and anemia acutely progressed. As chest X-ray revealed right lung opacity, a chest drain was inserted and 3,000 ml of bloody effusion was drawn over a period of 2 hours. Enhanced CT revealed hemothorax and extravasation of the right lung. Since the preoperative CT showed an abnormally dilated right bronchial artery, the branch vessels of the bronchial artery were considered to be the source of hemorrhage. Bronchial artery coil embolization was first performed, which decreased the bronchial artery flow, stabilizing the hemodynamics. Video-assisted thoracic surgery (VATS) was then performed, and the bleeding site at the surface of the lung was electrocauterized. Finally, the hemorrhage was controlled. This case suggests that the combination of coil embolization and VATS is an effective procedure.


The GmFAD7 gene family from soybean: identification of novel genes and tissue-specific conformations of the FAD7 enzyme involved in desaturase activity.
The FAD7 gene encodes a omega3 fatty acid desaturase which catalyses the production of trienoic fatty acids (TAs) in plant chloroplasts. A novel GmFAD7 gene (named GmFAD7-2) has been identified in soybean, with high homology to the previously annotated GmFAD7 gene. Genomic sequencing analysis together with searches at the soybean genome database further confirmed that both GmFAD7 genes were located in two different loci within the soybean genome, suggesting that the soybean omega3 plastidial desaturase FAD7 is encoded by two different paralogous genes. Both GmFAD7-1 and GmFAD7-2 genes were expressed in all soybean tissues examined, displaying their highest mRNA accumulation in leaves. This expression profile contrasted with GmFAD3A and GmFAD3B mRNA accumulation, which was very low in this tissue. These results suggested a concerted control of plastidial and reticular omega3 desaturase gene expression in soybean mature leaves. Analysis of GmFAD7 protein distribution in different soybean tissues showed that, in mature leaves, two bands were detected, coincident with the higher expression level of both GmFAD7 genes and the highest 18:3 fatty acid accumulation. By contrast, in seeds, where FAD7 activity is low, specific GmFAD7 protein conformations were observed. These GmFAD7 protein conformations were affected in vitro by changes in the redox conditions of thiol groups and iron availability. These results suggest the existence of tissue-specific post-translational regulatory mechanisms affecting the distribution and conformation of the FAD7 enzymes related with the control of its activity.


Etiology of out-of-hospital cardiac arrest in psychiatric patients: Chart review.
Although sudden cardiac deaths are more common in psychiatric patients than the general population, data on their causes are very limited. The aim of this study was to investigate initial rhythms and causes of out-of-hospital cardiac arrest (OHCA) in patients with psychiatric disorders. We conducted a systematic chart review of patients resuscitated after OHCA and hospitalized in the Tertiary Emergency Medical Center of Tokyo Metropolitan Bokutoh Hospital in Japan between January 2010 and December 2017. The initial rhythms and causes of OHCA were compared between psychiatric patients and non-psychiatric patients. Parameters of interest were compared using chi-squared test, Fisher's exact test, or the Mann-Whitney U-test, as appropriate. A total of 49 psychiatric and 600 non-psychiatric patients were eligible for this study. Fatal but shockable arrhythmias (i.e. ventricular fibrillation and ventricular tachycardia) were less frequently observed as initial rhythms in patients with psychiatric disorders than the others (22.4% vs 49.7%, P < 0.001). Cardiac origin was less common as the cause of OHCA (26.5% vs 58.5%, P < 0.01), while airway obstruction and pulmonary embolism were more frequent in psychiatric versus non-psychiatric patients (24.5% vs 6.5%, P < 0.01; and 12.2% vs 1.5%, P < 0.01, respectively). The results were similar when psychiatric patients were compared with sex- and age-matched controls selected from the non-psychiatric patient group. Although fatal arrhythmias may be less common, non-cardiac causes such as pulmonary embolism and airway obstruction need to be treated with high clinical suspicion in an event of sudden cardiac arrest in psychiatric patients.


Non-specific urethritis. A placebo-controlled trial of minocycline in conjunction with laboratory investigations.
The results of a double-blind therapeutic trial on 81 men suffering from non-specific urethritis (NSU) show that minocycline was more effective than a placebo. Before treatment Chlamydia trachomatis was isolated from 31 per cent. of the men, ureaplasmas from 58 per cent., and Mycoplasma hominis from 7-5 per cent. There is evidence that chlamydiae are a cause of urethritis. However, after minocycline therapy improvement in the clinical response of patients from whom only ureaplasmas were isolated was less significant, so that the evidence that these organisms are pathogenic is less convincing. Possible reasons for this are discussed, as are the implications of finding minocycline-resistant ureaplasmas in at least 6 per cent. of the patients who harboured these organisms. The symptoms and signs of patients from whom micro-organisms were not isolated also improved after minocycline therapy, implying that the aetiological agents in this group of patients are antibiotic-sensitive. However, the results do not exclude the possibility that a minocycline-resistant agent is the cause of urethritis in a minority of patients.


The role of duck LGP2 in innate immune response of host anti-tembusu virus.
Laboratory of Genetics and Physiology 2 (LGP2), along with Retinoic Acid Induced Gene-I (RIG-I) and Melanoma Differentiation Associated Gene 5, are members of the retinoic acid-inducible gene-I-like receptors (RLRs) in pattern recognition receptors, playing an important role in the host's innate immunity. Due to lacking a caspase activation and recruitment domain, LGP2 is controversially regarded as a positive or negative regulator in the antiviral response. This study aimed to explore how duck LGP2 (duLGP2) participates in duck innate immunity and its role in countering the duck Tembusu virus (DTMUV). In duck embryo fibroblast cells, the overexpression of duLGP2 significantly reduced the cell's antiviral capacity by inhibiting type I interferon (IFN) production and the expression of downstream IFN-stimulated genes. Conversely, duLGP2 knockdown had the opposite effect. For the first time, we introduced the LGP2 gene fragment into duck embryos using a lentiviral vector to ensure persistent expression and generated gene-edited ducks with LGP2 overexpression. We demonstrated that duLGP2 facilitates DTMUV replication in both in vitro and in vivo experiments, leading to robust inflammatory and antiviral responses. Interestingly, the repressive effects of duLGP2 on type I IFN production were only observed in the early stage of DTMUV infection, with type I IFN responses becoming enhanced as the viral load increased. These results indicate that duLGP2 acts as a negative regulator during the resting state and early stages of DTMUV infection. This study provides a theoretical basis for further research on duck RLRs and developing new anti-DTMUV drugs or vaccine adjuvants.


Closure of Persistent, Small, Posterior Elbow Soft Tissue Defects Using a Rotation Flap: A Retrospective Study.
Treating soft tissue defects occurring over the posterior elbow is challenging. This study aimed to evaluate the long-term outcomes of using rotation flaps for soft tissue defects over the posterior elbow. A retrospective study was conducted among patients who had sustained posterior elbow defects and underwent rotation flap under local anesthesia between January 2, 2011, and December 31, 2014. Patient inclusion criteria stipulated the soft tissue defect had to be small (<12 cm2), was the result of wound dehiscence following posterior approach surgery immediately following trauma, and had failed to heal using nonsurgical treatment or primary closure. Patients with an active infection, malignancies, a defect of any etiology other than trauma, or incomplete operative data were excluded. Patient demographics, medical history, operative reports, and outcomes were abstracted. Flap failure and surgical complications were monitored for a minimum of 2 years after surgery. Range of motion (ROM; 0˚ to normal 130˚) and Mayo Elbow Performance Scores (MEPS) were evaluated and recorded before surgery and after 2 years' follow-up and included evaluating pain, ROM, stability, and daily function. Patient, wound, surgical, and wound healing variables were compared between the flap survival and flap failure/complication groups using Mann-Whitney U and chi-squared tests. The Wilcoxon signed-rank test was used to compare pre- and postoperative MEPS and elbow ROM. Thirty (30) patients (13 male, 17 female; mean age 55 ± 15.6 [range 19-74] years) had complete records. Eighteen (18) flaps were created using the transolecranon approach, and 12 rotation flaps involved an olecranon fracture; 24 flaps survived and 6 patients experienced flap failure/complications (wound dehiscence or infection). Mean procedure duration was 25.6 ± 10.1 minutes. All defects were located over the olecranon with exposed bone or hardware. Mean defect size was 7.4 cm2 ± 2.9 cm2, the average defect duration was 60.4 (range 31-89) days, average time to wound healing was 21.9 ± 11.5 days, and mean follow-up time was 29.4 (range 24-56) months. All flaps successfully survived without recurrence. Mean pre- and postoperative MEPS were significantly different (56.4 vs. 90.2 points; P <.001). ROM did not differ significantly between mean preoperative range (extension 9.8˚ ± 3.2˚ and flexion 116.7˚ ± 10.2˚) and mean final follow-up range (extension 9.6˚ ± 2.6˚ and flexion 118.5˚ ± 11.3˚; P = .459). Rotation flap surgery performed under local anesthesia may offer a simple and safe option in the treatment of small (<12 cm2) trauma-related defects over the posterior elbow. More research is needed to develop evidence-based guidelines for optimal approaches to posterior elbow soft tissue defect closure techniques.


When the mental number line involves a delay: the writing of numbers by children of different arithmetical abilities.
Our study focused on number transcoding in children. It investigated how 9-year-olds with and without arithmetical disabilities wrote Arabic digits after they had heard them as number words. Planning time before writing each digit was registered. Analyses revealed that the two groups differed not only in arithmetical abilities but also in verbal and reading abilities. Children with arithmetical disabilities were overall slower in planning Arabic digits than were control children with normal arithmetical abilities. In addition, they showed a number size effect for numbers smaller than 10, suggesting a semantically mediated route in number processing. Control children did not need more planning time for large numbers (e.g., 8) than for small numbers (e.g., 3), suggesting a direct nonsemantic route. For both two- and three-digit numbers, both groups of children showed a number size effect, although the effect was smaller each time for control children. The presence of the stronger number size effect for children with arithmetical disabilities was seen as a delay in the development of quick and direct transcoding. The relation between transcoding problems and arithmetical disabilities is discussed. A defect in the linking of numerical symbols to analog numerical representations is proposed as an explanation for the transcoding problems found in some children.


Resistance-factors in the hospital and non-hospital environment.
The enteric flora of a group of antibiotic-treated patients and two groups of non-antibiotic-treated individuals were studied for antibiotic resistance patterns and presence of transferable R-factors. The former group consisted of 100 hospitalised patients, the latter two groups consisted of 200 hospitalised patients and 200 individuals from rural communities in Jamaica. The occurrence of multiple-resistant organisms with transferable R-factors was significantly higher in the antibiotic-treated group. R-factors were also more common in the hospitalised, non-treated group than in the non-hospitalised, non-treated group. Follow-up studies on hospitalised patients showed a tendency to increased occurrence of R-factors with duration of hospitalisation, whether the patients were treated with antibiotics or not. These studies have shown that both antibiotic treatment and hospitalisation promote the occurrence of R-factors.


Effects of Postprandial Blood Pressure on Gait Parameters in Older People.
Postprandial hypotension (PPH), a fall in systolic blood pressure (SBP) within 2 h of a meal, may detrimentally affect gait parameters and increase the falls risk in older people. We aimed to determine the effects of postprandial SBP on heart rate (HR), gait speed, and stride length, double-support time and swing time variability in older subjects with and without PPH. Twenty-nine subjects were studied on three days: glucose ("G"), water and walk ("WW"), glucose and walk ("GW"). Subjects consumed a glucose drink on "G" and "GW" and water on "WW". The "G" day determined which subjects had PPH. On "WW" and "GW" gait was analyzed. Sixteen subjects demonstrated PPH. In this group, there were significant changes in gait speed (p = 0.040) on "WW" and double-support time variability (p = 0.027) on "GW". The area under the curve for the change in gait parameters from baseline was not significant on any study day. Among subjects without PPH, SBP increased on "WW" (p < 0.005) and all gait parameters remained unchanged on all study days. These findings suggest that by changing gait parameters, PPH may contribute to an increased falls risk in the older person with PPH.


Composition modulation by twinning in InAsSb nanowires.
We observe a composition modulated axial heterostructure in zincblende (ZB) InAs0.90Sb0.10 nanowires initiated by pseudo-periodic twin boundaries using scanning tunneling microscopy. The twin boundaries exhibit four planes with reduced Sb concentration due to a lower Sb incorporation during lateral overgrowth of a 4H wurtzite as compared to a ZB stacking sequence. We anticipate that this leads to compositional band offsets in addition to known structural band offsets present between 4H and ZB polytypes, changing the band alignment from type II to type I.


Purification and characterization of protein kinase C from the nematode Caenorhabditis elegans.
Protein kinase C (PKC) of Caenorhabditis elegans was identified by enzymatic activity and [3H]phorbol 12,13-dibutyrate binding after DEAE-Sephacel column chromatography of a crude cytosolic extract. Ca(2+)-dependent activation of nematode PKC was observed in the presence of phosphatidylserine. The enzyme was maximally activated by 1,2-dioleoylglycerol or phorbol 12-myristate 13-acetate in the presence of phosphatidylserine and Ca2+. Hydroxyapatite column chromatography showed only one peak of PKC activity with histone H1 and myelin basic protein as substrates. The enzyme was purified to near homogeneity by sequential chromatography on polylysine-agarose and phosphatidylserine affinity columns. The purified protein showed a molecular mass of 79 kDa on SDS/PAGE. The substrate specificity of the C. elegans enzyme was shown to be different from that of mammalian PKCs. Here we describe some of the properties of the nematode enzyme.


Low cyanobacterial diversity in biotopes of the Transantarctic Mountains and Shackleton Range (80-82°S), Antarctica.
The evolutionary history and geographical isolation of the Antarctic continent have produced a unique environment rich in endemic organisms. In many regions of Antarctica, cyanobacteria are the dominant phototrophs in both aquatic and terrestrial ecosystems. We have used microscopic and molecular approaches to examine the cyanobacterial diversity of biotopes at two inland continental Antarctic sites (80-82°S). These are among the most southerly locations where freshwater-related ecosystems are present. The results showed a low cyanobacterial diversity, with only 3-7 operational taxonomic units (OTUs) per sample obtained by a combination of strain isolations, clone libraries and denaturing gradient gel electrophoresis based on 16S rRNA genes. One OTU was potentially endemic to Antarctica and is present in several regions of the continent. Four OTUs were shared by the samples from Forlidas Pond and the surrounding terrestrial mats. Only one OTU, but no internal transcribed spacer (ITS) sequences, was common to Forlidas Pond and Lundström Lake. The ITS sequences were shown to further discriminate different genotypes within the OTUs. ITS sequences from Antarctic locations appear to be more closely related to each other than to non-Antarctic sequences. Future research in inland continental Antarctica will shed more light on the geographical distribution and evolutionary isolation of cyanobacteria in these extreme habitats.


Phenotype and Progression of Retinal Degeneration Associated With Nullizigosity of ABCA4.
We describe the phenotypes associated with nullizigosity and nine splicing mutations in the ABCA4 gene. The study included 19 patients with biallelic null mutations (Group A, nullizygous), 27 with splicing mutations in the homozygous state or in trans with a null mutation (Group B), and 20 with p.G1961E in trans with a null mutation (Group C, control). Ages at onset and visual acuities were determined from medical histories. Area of decreased autofluorescence within a 30° × 30° fundus autofluorescence (FAF) image was measured with the Region Finder (N = 58). Full-field electroretinography (ERG) was performed incorporating the International Society for Clinical Electrophysiology of Vision (ISCEV) standard (N = 40). For groups A to C, the median ages of onset were 6, 8, and 17, respectively. Kaplan Meier survival analysis estimated that 50% of patients reached visual acuity below 20/400 at the ages of 29, 48, and 66 years, respectively. The area of reduced FAF was estimated to increase by 1.5, 1.2, and 0.03 mm2 per year, respectively, and cone-rod dystrophy was present in 10/12, 13/15, and 0/13 of cases, respectively. Splicing mutation c.5714+5G>A was associated with a significantly milder phenotype in comparison with nullizygous patients for all parameters. Nullizygosity for ABCA4 is associated with early onset cone-rod dysfunction with rapid progression shown by enlargement of central atrophy on FAF, decline of ERG amplitudes with age, and a high risk of reaching legal blindness by the fourth decade. Most studied splicing mutations were associated with a similarly severe phenotype. Estimated rates of progression may facilitate further genotype-phenotype correlations and inform the design of treatment trials.


Phase-amplitude coupling in rat orbitofrontal cortex discriminates between correct and incorrect decisions during associative learning.
Cross-frequency interactions between oscillations in local field potentials (LFPs) are thought to support communication between brain structures by temporally coordinating neural activity. It is unknown, however, whether such interactions differentiate between different levels of performance in decision-making tasks. Here, we investigated theta (4-12 Hz) to gamma (30-100 Hz) phase-amplitude coupling in LFP recordings from rat orbitofrontal cortex. Across subsequent periods of a task in which rats learned to discriminate two odors associated with positive and negative outcomes, theta-to-gamma phase-amplitude coupling (PAC) was highest during the odor-sampling task period that preceded a Go/NoGo decision. This task-dependent modulation could not be explained by changes in oscillatory power and appeared to be time-locked to odor onset, not to the timing of the behavioral response. We found that PAC strength during odor sampling correlated with learning, as indexed by improved performance across trials. Moreover, this increase in PAC magnitude was apparent only on trials with correct Go and NoGo decisions, but not incorrect Go decisions. In addition, we found that PAC preferred coupling phase showed consistency over sessions only for correct, but not incorrect trials. In conclusion, orbitofrontal cortex theta-gamma PAC strength differentiates between different levels of performance in an olfactory decision-making task and may play a role in the generation and utilization of stimulus-based outcome predictions, necessary for adaptive decision-making.


Evaluating prose style transfer with the Bible.
In the prose style transfer task a system, provided with text input and a target prose style, produces output which preserves the meaning of the input text but alters the style. These systems require parallel data for evaluation of results and usually make use of parallel data for training. Currently, there are few publicly available corpora for this task. In this work, we identify a high-quality source of aligned, stylistically distinct text in different versions of the Bible. We provide a standardized split, into training, development and testing data, of the public domain versions in our corpus. This corpus is highly parallel since many Bible versions are included. Sentences are aligned due to the presence of chapter and verse numbers within all versions of the text. In addition to the corpus, we present the results, as measured by the BLEU and PINC metrics, of several models trained on our data which can serve as baselines for future research. While we present these data as a style transfer corpus, we believe that it is of unmatched quality and may be useful for other natural language tasks as well.


Increased bronchial responsiveness to exercise as a risk factor for symptomatic asthma: findings from a longitudinal population study of children and adolescents.
The prevalence of asthma seems to be on the increase and risk factors are not well-established. To investigate the relationship between asymptomatic increased bronchial responsiveness to exercise (BRE) and subsequent development of asthma, we studied a population sample of children and adolescents, aged 7-17 yrs at enrollment, examined twice 6 yrs apart (54 and 68%, respectively, of the original sample participated in the two examinations). Complete information was available for 383 subjects (191 males and 192 females). Case history and questionnaire data were obtained and were used to assess the presence or absence of symptomatic asthma. Exercise testing, performed at enrolment only, consisted of steady running on a 10% sloping treadmill for 6 min in a climate chamber. BRE was recorded as percentage fall in forced expiratory volume in one second (FEV1) from pre-exercise FEV1, within 15 min after exercise. Twenty subjects (5%) had asthma at enrolment, whereas 58 subjects (15%) had current asthma (i.e. symptoms within the preceding 12 months) at the time of follow-up, of whom 40 were asymptomatic at enrolment (new asthma). In general, increased BRE at enrolment was significantly associated with symptomatic asthma at follow-up. Analysing the data for subjects who were asymptomatic at enrolment (n=363), showed that new asthma at follow-up was not predicted by increased BRE at enrolment, whether BRE was evaluated as a continuous (R2=0.06, p=0.13) or dichotomous (cut-off: BRE =10% decline in FEV1; odds ratio (OR) 0.8 (0.4-1.2); p=0.11) variable. However, the data do not exclude the possibility that asymptomatic subjects with BRE >15% have an increased risk for subsequent development of asthma. The findings of the present study suggest that increased bronchial responsiveness to exercise in asymptomatic children and adolescents is not a strong predictor for subsequent development of symptomatic asthma. Further studies, preferably of larger samples, are needed to confirm these findings.


Prescribing at the hospital-general practice interface. I: Hospital outpatient dispensing policies in England.
To describe the outpatient dispensing policies of major acute hospitals in England. Postal questionnaire survey in November 1990. All (278) major acute hospitals in England with more than 250 beds, excluding maternity, paediatric, or psychiatric hospitals; nine hospitals declined. Hospital chief pharmacists. Current dispensing policy and exceptions to it; when the policy was formed; and who was involved in its formation. Completed questionnaires were received from 200 (72%) of the hospitals approached. The quantities of drugs dispensed to outpatients ranged from zero in 12 hospitals to unlimited amounts in nine; nearly half (92) dispensed a 14 days' supply of drugs. The greater the restriction on outpatient dispensing, the more recently the policy had been introduced (chi 2 for trend = 7.15; df = 1; p less than 0.01). Permissible exceptions to the policy included the consultant's specific request (134 hospitals), difficulty in obtaining drugs in the community (102), urgent need for start of treatment (49), and certain types of patients (41) or drugs or their regimens (104). Groups who were neither represented on the hospital committee concerned with policy formation nor consulted before policy changes included regional health authorities in 122 hospitals, district health authorities in 101 hospitals, and general practitioners in 32 hospitals. Outpatient dispensing policies varied considerably among the hospitals surveyed, but they seemed to be moving towards greater restrictions on the supply of drugs given to outpatients.


Increased excretion of nitric oxide in exhaled air of patients with chronic renal failure.
Nitric oxide exerts multiple effects on renal function. It remains unclear whether endogenous nitric oxide production is increased or decreased in patients with chronic renal failure. To evaluate endogenous nitric oxide production in these patients we studied exhaled nitric oxide output by an ozone chemiluminescence method and plasma NO2(-)/NO3(-) levels by the Griess method in 40 patients with end-stage chronic renal failure who underwent regular continuous ambulatory peritoneal dialysis (n=30) or haemodialysis (n=10), and in 28 healthy subjects. Patients with chronic renal failure had a higher exhaled nitric oxide concentration [39+/-3 versus 19+/-1 parts per billion, (mean+/-S.E.M.), P<0.0001], a greater nitric oxide output (177+/-11 versus 96+/-7 nl.min-1.m-2, P<0.001) and a higher plasma NO2(-)/NO3(-) concentration (96+/-14 versus 33+/-4 micromol, P<0.01) than controls. These values did not differ between patients on haemodialysis and those on continuous ambulatory peritoneal dialysis. Patients with chronic renal failure had significantly higher plasma concentrations of both interleukin-1beta and interferon-gamma than controls. The exhaled nitric oxide output did not correlate with plasma NO2(-)/NO3(-) or with peritoneal dialysate NO2(-)/NO3(-), but plasma NO2(-)/NO3(-) correlated with dialysate NO2(-)/NO3(-) in patients who underwent continuous ambulatory peritoneal dialysis (r=0.77, P<0.01). Haemodialysis for 4 h acutely decreased plasma NO2(-)/NO3(-) (92+/-17 versus 50+/-8 micromol, P<0.05) and cGMP concentration (16.5+/-4.3 versus 5.1+/-1. 7 pmol/ml, P<0.01), but did not decrease exhaled nitric oxide output. The increase in exhaled nitric oxide with the simultaneous increase in circulating cytokines suggests that nitric oxide synthase seems to be induced significantly in patients with chronic renal failure. Increased endogenous nitric oxide production may have a pathophysiological role in patients with uraemia.


High-Dose Astaxanthin Supplementation Suppresses Antioxidant Enzyme Activity during Moderate-Intensity Swimming Training in Mice.
Exercise-induced reactive oxygen and nitrogen species are increasingly considered as beneficial health promotion. Astaxanthin (ASX) has been recognized as a potent antioxidant suitable for human ingestion. We investigated whether ASX administration suppressed antioxidant enzyme activity in moderate-intensity exercise. Seven-week-old male C57BL/6 mice (n = 8/group) were treated with ASX (5, 15, and 30 mg/kg BW) combined with 45 min/day moderate-intensity swimming training for four weeks. Results showed that the mice administrated with 15 and 30 mg/kg of ASX decreased glutathione peroxidase, catalase, malondialdehyde, and creatine kinase levels in plasma or muscle, compared with the swimming control group. Beyond that, these two (15 and 30 mg/kg BW) dosages of ASX downregulated gastrocnemius muscle erythroid 2p45 (NF-E2)-related factor 2 (Nrf2). Meanwhile, mRNA of Nrf2 and Nrf2-dependent enzymes in mice heart were also downregulated in the ASX-treated groups. However, the mice treated with 15 or 30 mg/kg ASX had increased constitutive nitric oxidase synthase and superoxide dismutase activity, compared with the swimming and sedentary control groups. Our findings indicate that high-dose administration of astaxanthin can blunt antioxidant enzyme activity and downregulate transcription of Nrf2 and Nrf2-dependent enzymes along with attenuating plasma and muscle MDA.


Endoscopic miniprobe ultrasonography in diagnosis of carcinomas and submucosal tumors of large intestine.
To assess the value of endoscopic miniprobe ultrasonography in the diagnosis of carcinomas and submucosal tumors of the large intestine. A total of 96 patients with carcinomas and submucosal tumors of the large intestine were given colonoscopic ultrasonography with a miniprobe (Olympus UM-2R, 12 MHz; UM-3R, 20 MHz) from December, 2000 to January, 2002. Carcinomas of the large intestine of 81 patients appeared as a hypoechoic mass under endoscopic ultrasonography, by which 67 patients (82.7%) were accurately diagnosed as having infiltrated colorectal carcinomas. The sensitivity of endoscopic ultrasonography in the diagnosis of lymph node metastasis was 55.4%, while the specificity was 68.8%. The positive predictive value and the negative predictive value were 0.88 and 0.28, respectively. All 15 cases with submucosal tumors were diagnosed correctly under endoscopic ultrasonography except for one leiomyoma, which was misdiagnosed as leiomyosarcoma. Endoscopic miniprobe ultrasonography has a high accuracy in determining the invasion depth of carcinomas of the large intestine and the diagnosis of submucosal tumors. The pre-operative endoscopic ultrasonography may provide valuable information and influence the choice of therapy for carcinomas and submucosal tumors of the large intestine.


Examining the Relationships Among Cognitive Acceptance, Behavioral Commitment, Autonomous Extrinsic Motivation, and Physical Activity.
This study examined the relationships among cognitive acceptance, behavioral commitment, psychological need satisfaction, autonomous extrinsic motivation (EM) for physical activity (PA), and PA behavior. Participants (N = 456, M age = 40.7 years) completed online measures of these variables, and data were analyzed using structural equation modeling. Results indicated a direct pathway from behavioral commitment to autonomous EM, plus indirect effects via autonomy, competence, and relatedness. There was no direct pathway from cognitive acceptance to autonomous EM, but there were indirect effects via competence and autonomy satisfaction. There was a direct pathway from cognitive acceptance to self-reported PA plus indirect effects via autonomous EM. There was no direct pathway from behavioral commitment to self-reported PA, but there were indirect effects via autonomous EM. Cognitive acceptance and behavioral commitment potentially support the development of autonomous EM for PA. Future research using longitudinal and intervention-based research designs is required to determine the causal relationships among these variables.


Role of secondary hyperparathyroidism in the genesis of hypertriglyceridemia and VLDL receptor deficiency in chronic renal failure.
Recent studies have revealed marked down-regulation of hepatic lipase (HL), lipoprotein lipase (LPL) and very low density lipoprotein-receptor (VLDL-R) expressions in animals with chronic renal failure (CRF). Acquired deficiency of these proteins, which together play an important role in catabolism of triglyceride-rich lipoproteins, is involved in the pathogenesis of CRF hypertriglyceridemia. Down-regulation of HL and LPL expressions in CRF can be completely reversed by parathyroidectomy (PTx), suggesting the role of excess parathormone (PTH). However, the role of hyperparathyroidism in the pathogenesis of CRF-induced VLDL-R deficiency has not been investigated before, and was studied here. To this end, VLDL-R mRNA (Northern analysis) and VLDL-R protein (Western analysis) of the fat pad and soleus muscle were compared in CRF (5/6 nephrectomized) rats, CRF animals with PTx (CRF-PTx) and sham-operated control animals. The CRF animals exhibited marked hypertriglyceridemia coupled with significant reductions in skeletal muscle and adipose tissue VLDL-R mRNA abundance and protein mass. Parathyroidectomy resulted in a significant, but partial, amelioration of CRF hypertriglyceridemia. However, in contrast to its effect on HL and LPL expressions, PTx did not improve VLDL-R expression, suggesting a PTH-independent mechanism for the latter abnormality. The differential effect of PTx on HL and LPL on the one hand and VLDL-R on the other can, in part, account for partial as opposed to complete correction of the associated hypertriglyceridemia with PTx in the CRF animals.


[Device and method for neuro-psychic relaxation].
A pattern model of a device for tranquilization a relaxation--a photo-acoustic relaxator--was constructed and procedures for its application elaborated. Unlike psychotherapy, hypnosis, autogenic training and pharmacological agents in this method natural factors of actions, such as light and sound are used. The relaxation achieved by rhythmic photoacoustic effects with the help of the device pre-supposes the regulation of the patient's respiration. The effect produced by the relaxation sittings is shown to depend on the temperament of the examined. The use of the device is particularly effective in persons displaying a high degree of suggestibility and emotional susceptibility.


[Chloroma (granulocytic sarcoma, myeloblastoma). Clinical aspects and radiological diagnosis].
Six cases of granulocytic sarcoma are presented. A mediastinal chloroma and a tumor of the submandibular gland were observed with two patients as single sign of acute myeloic leukaemia. In one patient a chloroma appeared as first manifestation of acute myeloic leukaemia. Two patients exhibited the tumor as first symptom of a blastic crisis of chronic myelogenous leukaemia (femoral bone, lumbar spine). The sixth patient with a myelodyplastic syndrome showed a chloroma of the breast. Various radiological procedures were applied including plain radiography, MRT, CT and mammography. The results are compared with literature. Principles of therapy were supplemented.


The role of excessive versus acute administration of erythropoietin in attenuating hepatic ischemia-reperfusion injury.
Ischemia-reperfusion injury (I/R) is the main cause of primary graft nonfunction. Our aim was to evaluate the effect of excessive versus acute administration of erythropoietin (EPO) in attenuating the hepatic injury induced by I/R in mice. The effect of segmental (70%) hepatic ischemia was evaluated in a transgenic mouse line with constitutive overexpression of human EPO cDNA and in wild-type (WT) mice. Mice were randomly allocated to 5 main experimental groups: (i) WT-sham, (ii) WT ischemia, (iii) WT ischemia + recombinant human erythropoietin (rhEPO), (iv) transgenic-sham, and (v) transgenic ischemia. The EPO-pretreated mice showed a significant reduction in liver enzyme levels and intrahepatic caspase-3 activity and fewer apoptotic hepatocytes (p < 0.05 for all) compared with the WT untreated I/R group. EPO decreased c-Jun N-terminal kinase (JNK) phosphorylation and nuclear factor-κB (NF-κB) expression during I/R. In transgenic I/R livers, baseline histology showed diffused hepatic injury, and no significant beneficial effect was noted between the WT untreated and the transgenic I/R mice. In conclusion, acute pretreatment with EPO in WT mice attenuated in vivo I/R liver injury. However, in excessive EPO overexpression, the initial liver injury abolished the beneficial effect of EPO. These findings have important implications for the potential use of acute EPO in I/R injury during liver transplantation.


Pyruvate dehydrogenase complex and nicotinamide nucleotide transhydrogenase constitute an energy-consuming redox circuit.
Cellular proteins rely on reversible redox reactions to establish and maintain biological structure and function. How redox catabolic (NAD+/NADH) and anabolic (NADP+/NADPH) processes integrate during metabolism to maintain cellular redox homoeostasis, however, is unknown. The present work identifies a continuously cycling mitochondrial membrane potential (ΔΨm)-dependent redox circuit between the pyruvate dehydrogenase complex (PDHC) and nicotinamide nucleotide transhydrogenase (NNT). PDHC is shown to produce H2O2 in relation to reducing pressure within the complex. The H2O2 produced, however, is effectively masked by a continuously cycling redox circuit that links, via glutathione/thioredoxin, to NNT, which catalyses the regeneration of NADPH from NADH at the expense of ΔΨm. The net effect is an automatic fine-tuning of NNT-mediated energy expenditure to metabolic balance at the level of PDHC. In mitochondria, genetic or pharmacological disruptions in the PDHC-NNT redox circuit negate counterbalance changes in energy expenditure. At the whole animal level, mice lacking functional NNT (C57BL/6J) are characterized by lower energy-expenditure rates, consistent with their well-known susceptibility to diet-induced obesity. These findings suggest the integration of redox sensing of metabolic balance with compensatory changes in energy expenditure provides a potential mechanism by which cellular redox homoeostasis is maintained and body weight is defended during periods of positive and negative energy balance.


Tracking mtDNA heteroplasmy through multiple generations in the North Atlantic right whale (Eubalaena glacialis).
Mitochondrial heteroplasmy has been identified in a variety of species and can result from either paternal leakage, whereby sperm mitochondria enter the ova during fertilization, or more commonly by the "survival" and proliferation of mutant variants within an organism. From an evolutionary perspective, this process represents the generation of new mitochondrial diversity within a species. Although this has been documented in some mammalian species, it has been reported from relatively few wild mammalian populations and in no wild nonhuman population has the transfer and segregation of mitochondrial heteroplasmy been tracked through multiple generations. We report on the first case of the identification and tracking of mitochondrial control region heteroplasmy through 3 generations in the North Atlantic right whale, Eubalaena glacialis. We also identify the full segregation to the mutant variant within a single generation and thus the development of a new haplotype (haplotype G) in a maternal lineage of this endangered species. Witnessed here is the generation of mitochondrial diversity in a genetically depauperate species.


Psychometric Characteristics of the Croatian and the Serbian Versions of the Oral Health Impact Profile for Edentulous Subjects, with a Pilot Study on the Dimensionality.
The aim was to adapt the Croatian and the Serbian versions of the Oral Health Impact Profile for the edentulous population (OHIP-EDENT-CRO and OHIP-EDENT-SRB). The translation and cross-cultural adaptation were carried out in accordance with accepted international standards. A total of 95 and 177 removable denture wearers were recruited in Croatia and Serbia respectively. The reliability was evaluated by calculating Cronbach's alpha coefficient and by test-retest (30 participants in each country). The concurrent validity was determined by calculating the Spearman's rank coefficient between the OHIP-EDENT summary scores and one question related to removable denture satisfaction. Construct validity was determined by exploratory factor analysis (EFA). Responsiveness was determined by comparison of the OHIP-EDENT summary scores before and after dental implant placement to support mandibular overdentures (23 patients in Croatia, 21 in Serbia). Cronbach's alpha coefficient was 0.92 in Croatia and 0.87 in Serbia. The intraclass correlation coefficient was 0.98 in Croatia and 0.94 in Serbia. In Croatia the Spearman's correlation coefficient was -0.71 (p<0.001) and in Serbia -0.74 (p<0.001). Both confirmed concurrent validity. Construct validity was tested by EFA, which extracted four factors in each country, accounting for 66.59% of the variance in Croatia and 59.33% in Serbia. Responsiveness was confirmed in both countries by a significant OHIP-EDENT summary score reduction and a high standardised effect size (3.9 in Croatia, 1.53 in Serbia). The results prove that both instruments, the OHIP-EDENT-CRO and the OHIP-EDENT-SRB, have very good psychometric properties for assessing OHRQoL in the edentulous population.


Predicting Intra-Urban Variation in Air Pollution Concentrations with Complex Spatio-Temporal Dependencies.
We describe a methodology for assigning individual estimates of long-term average air pollution concentrations that accounts for a complex spatio-temporal correlation structure and can accommodate spatio-temporally misaligned observations. This methodology has been developed as part of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air), a prospective cohort study funded by the U.S. EPA to investigate the relationship between chronic exposure to air pollution and cardiovascular disease. Our hierarchical model decomposes the space-time field into a "mean" that includes dependence on covariates and spatially varying seasonal and long-term trends and a "residual" that accounts for spatially correlated deviations from the mean model. The model accommodates complex spatio-temporal patterns by characterizing the temporal trend at each location as a linear combination of empirically derived temporal basis functions, and embedding the spatial fields of coefficients for the basis functions in separate linear regression models with spatially correlated residuals (universal kriging). This approach allows us to implement a scalable single-stage estimation procedure that easily accommodates a significant number of missing observations at some monitoring locations. We apply the model to predict long-term average concentrations of oxides of nitrogen (NOx) from 2005-2007 in the Los Angeles area, based on data from 18 EPA Air Quality System regulatory monitors. The cross-validated R2 is 0.67. The MESA Air study is also collecting additional concentration data as part of a supplementary monitoring campaign. We describe the sampling plan and demonstrate in a simulation study that the additional data will contribute to improved predictions of long-term average concentrations.


Resilience in the face of adversity in adults with an intellectual disability: A literature review.
Persons with an intellectual disability are at a higher risk of experiencing adversities. The concept of resilience offers promising insights into facilitating personal growth after adversity. The current study aims at providing an overview of the current research on resilience and the way this can contribute to quality of life in people with intellectual disability. A literature review was conducted in the databases PsycINFO and Web of Science. To evaluate the quality of the studies, the Mixed Method Appraisal Tool (MMAT) was used. The themes, autonomy, self-acceptance and physical health, were identified as internal sources of resilience. External sources of resilience can be found within the social network and daily activities. The current overview shows promising results to address resilience in adults with intellectual disability. More research is needed to identify the full range of resiliency factors.


The Ktr potassium transport system in Staphylococcus aureus and its role in cell physiology, antimicrobial resistance and pathogenesis.
Potassium (K(+) ) plays a vital role in bacterial physiology, including regulation of cytoplasmic pH, turgor pressure and transmembrane electrical potential. Here, we examine the Staphylococcus aureus Ktr system uniquely comprised of two ion-conducting proteins (KtrB and KtrD) and only one regulator (KtrA). Growth of Ktr system mutants was severely inhibited under K(+) limitation, yet detectable after an extended lag phase, indicating the presence of a secondary K(+) transporter. Disruption of both ktrA and the Kdp-ATPase system, important for K(+) uptake in other organisms, eliminated regrowth in 0.1 mM K(+) , demonstrating a compensatory role for Kdp to the Ktr system. Consistent with K(+) transport mutations, S. aureus devoid of the Ktr system became sensitive to hyperosmotic conditions, exhibited a hyperpolarized plasma membrane, and increased susceptibility to aminoglycoside antibiotics and cationic antimicrobials. In contrast to other organisms, the S. aureus Ktr system was shown to be important for low-K(+) growth under alkaline conditions, but played only a minor role in neutral and acidic conditions. In a mouse competitive index model of bacteraemia, the ktrA mutant was significantly outcompeted by the parental strain. Combined, these results demonstrate a primary mechanism of K(+) uptake in S. aureus and a role for this system in pathogenesis.


Calcium- and Nitric Oxide-Dependent Nuclear Accumulation of Cytosolic Glyceraldehyde-3-Phosphate Dehydrogenase in Response to Long Chain Bases in Tobacco BY-2 Cells.
Sphinganine or dihydrosphingosine (d18:0, DHS), one of the most abundant free sphingoid long chain bases (LCBs) in plants, is known to induce a calcium-dependent programmed cell death (PCD) in plants. In addition, in tobacco BY-2 cells, it has been shown that DHS triggers a rapid production of H2O2 and nitric oxide (NO). Recently, in analogy to what is known in the animal field, plant cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPC), a ubiquitous enzyme involved in glycolysis, has been suggested to fulfill other functions associated with its oxidative post-translational modifications such as S-nitrosylation on cysteine residues. In particular, in mammals, stress signals inducing NO production promote S-nitrosylation of GAPC and its subsequent translocation into the nucleus where the protein participates in the establishment of apoptosis. In the present study, we investigated the behavior of GAPC in tobacco BY-2 cells treated with DHS. We found that upon DHS treatment, an S-nitrosylated form of GAPC accumulated in the nucleus. This accumulation was dependent on NO production. Two genes encoding GAPCs, namely Nt(BY-2)GAPC1 and Nt(BY-2)GAPC2, were cloned. Transient overexpression of Nt(BY-2)GAPC-green fluorescent protein (GFP) chimeric constructs indicated that both proteins localized in the cytoplasm as well as in the nucleus. Mutating into serine the two cysteine residues thought to be S-nitrosylated in response to DHS did not modify the localization of the proteins, suggesting that S-nitrosylation of GAPCs was probably not necessary for their nuclear relocalization. Interestingly, using Förster resonance energy transfer experiments, we showed that Nt(BY-2)GAPCs interact with nucleic acids in the nucleus. When GAPCs were mutated on their cysteine residues, their interaction with nucleic acids was abolished, suggesting a role for GAPCs in the protection of nucleic acids against oxidative stress.


The influence of landscape matrix on isolated patch use by wide-ranging animals: conservation lessons for woodland caribou.
For conservation purposes, it is important to design studies that explicitly quantify responses of focal species to different land management scenarios. Here, we propose an approach that combines the influence of landscape matrices with the intrinsic attributes of remaining habitat patches on the space use behavior of woodland caribou (Rangifer tarandus caribou), a threatened subspecies of Rangifer. We sought to link characteristics of forest remnants and their surrounding environment to caribou use (i.e., occurrence and intensity). We tracked 51 females using GPS telemetry north of the Saguenay River (Québec, Canada) between 2004 and 2010 and documented their use of mature forest remnants ranging between 30 and ∼170 000 ha in a highly managed landscape. Habitat proportion and anthropogenic feature density within incremental buffer zones (from 100 to 7500 m), together with intrinsic residual forest patch characteristics, were linked to caribou GPS location occurrence and density to establish the range of influence of the surrounding matrix. We found that patch size and composition influence caribou occurrence and intensity of use within a patch. Patch size had to reach approximately 270 km(2) to attain 75% probability of use by caribou. We found that small patches (<100 km(2)) induced concentration of caribou activities that were shown to make them more vulnerable to predation and to act as ecological traps. Woodland caribou clearly need large residual forest patches, embedded in a relatively undisturbed matrix, to achieve low densities as an antipredator strategy. Our patch-based methodological approach, using GPS telemetry data, offers a new perspective of space use behavior of wide-ranging species inhabiting fragmented landscapes and allows us to highlight the impacts of large scale management. Furthermore, our study provides insights that might have important implications for effective caribou conservation and forest management.