Success of an alternative for interim management of irreversible pulpitis.
Extraction and endodontic therapy are treatment options for irreversible pulpitis. Extraction often is chosen for financial reasons. The authors conducted a study to investigate an alternative interim therapy. The authors recruited patients (N = 73) with irreversible pulpitis and whose teeth were restorable but who opted for extraction owing to financial reasons. After undergoing pulpotomy, the teeth were restored by random assignment with one of two intermediate restorative materials: Caulk IRM (Dentsply Caulk, Milford, Del.) (Group I, n = 38) or an IRM base with glass ionomer core (Fuji IX GP, GC America, Alsip, Ill.) (Group II, n = 35). The authors monitored the teeth over six and 12 months for pain, integrity of restoration and radiographic periapical status by densitometric analysis. By six months, 10 percent of subjects remaining in the study (Group I, n = 27; Group II, n = 25) reported pain; by 12 months, 22 percent (Group I, n = 22; Group II, n = 18) reported pain. A two-tailed Fisher exact test showed no significant difference (P > or = .05) between groups at either time interval. No apical radiographic change was noted in 49 percent of teeth at six months (Group I, n = 18; Group II, n = 19) and 42 percent at 12 months (Group I, n = 16; Group II, n = 15). Chi2 analysis demonstrated no significant differences (P > or = .05) between groups. Seven of 22 restorations in Group I and four of 18 in Group II required repair at 12 months with no statistical difference (chi2 analysis, P > or = .05). The interim treatment of eugenol pulpotomy using either restorative material reliably prevented pain for six months. For longer periods, both restorations may require repair. This option should preserve the integrity of the arch and extend the use of the tooth while the patient finds the means to finance complete endodontic treatment.


Quantitation of metalloproteinase gene expression in rheumatoid and psoriatic arthritis synovial tissue distal and proximal to the cartilage-pannus junction.
The distinct and different patterns of radiological damage in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) may be a product of the relative balance of proteolytic enzyme and inhibitor gene expression in synovial tissue. This study compared metalloproteinase gene expression in synovium located proximal to the cartilage-pannus junction (CPJ) and distal to the CPJ (non-CPJ) in patients with PsA and RA. Synovial biopsies were obtained from CPJ and non-CPJ sites under direct vision at arthroscopy of an inflamed knee in patients with PsA (n = 12) and RA (n = 12) who were not under disease modifying antirheumatic drug treatment. A competitive, quantitative RT-PCR technique was established for synovial RNA using a polycompetitor construct containing mRNA-specific primer sites for collagenase (MMP-1), stromelysin (MMP-3), tissue inhibitor of metalloproteinase-1 (TIMP-1), and GAPDH. cDNA products were separated and quantified by ethidium bromide stained gel electrophoresis and mRNA values were normalized relative to GAPDH expression. MMP-1, MMP-3, and TIMP-1 mRNA were upregulated in RA and PsA synovium with a prodestructive (MMP-1 + MMP-3)/TIMP-1 balance in both diseases. Similar levels of MMP mRNA expression were observed in PsA and RA despite the presence of less radiological erosion in the PsA group. No difference was observed in the degree of upregulation of MMP-1, MMP-3, or TIMP-1 mRNA in paired biopsies from CPJ and non-CPJ sites in either PsA (n = 8) or RA (n = 10). The ratio of TIMP-1 expression in CPJ compared to non-CPJ biopsies was higher in patients with nonerosive disease (10.1 +/- 27.8) than in erosive patients (0.75 +/- 0.27; p = 0.07). PsA and RA have similar levels of MMP-1, MMP-3, and TIMP-1 mRNA expression in synovium. There is no evidence of increased metalloproteinase mRNA expression at the CPJ in RA or PsA. The different patterns of radiological progression seen in RA and PsA were not explained by differences in synovial mRNA expression of MMP-1, MMP-3, or TIMP-1.


Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters.
miR-17 approximately 92, miR-106b approximately 25, and miR-106a approximately 363 belong to a family of highly conserved miRNA clusters. Amplification and overexpression of miR-1792 is observed in human cancers, and its oncogenic properties have been confirmed in a mouse model of B cell lymphoma. Here we show that mice deficient for miR-17 approximately 92 die shortly after birth with lung hypoplasia and a ventricular septal defect. The miR-17 approximately 92 cluster is also essential for B cell development. Absence of miR-17 approximately 92 leads to increased levels of the proapoptotic protein Bim and inhibits B cell development at the pro-B to pre-B transition. Furthermore, while ablation of miR-106b approximately 25 or miR-106a approximately 363 has no obvious phenotypic consequences, compound mutant embryos lacking both miR-106b approximately 25 and miR-17 approximately 92 die at midgestation. These results provide key insights into the physiologic functions of this family of microRNAs and suggest a link between the oncogenic properties of miR-17 approximately 92 and its functions during B lymphopoiesis and lung development.


A non-verbal Turing test: differentiating mind from machine in gaze-based social interaction.
In social interaction, gaze behavior provides important signals that have a significant impact on our perception of others. Previous investigations, however, have relied on paradigms in which participants are passive observers of other persons' gazes and do not adjust their gaze behavior as is the case in real-life social encounters. We used an interactive eye-tracking paradigm that allows participants to interact with an anthropomorphic virtual character whose gaze behavior is responsive to where the participant looks on the stimulus screen in real time. The character's gaze reactions were systematically varied along a continuum from a maximal probability of gaze aversion to a maximal probability of gaze-following during brief interactions, thereby varying contingency and congruency of the reactions. We investigated how these variations influenced whether participants believed that the character was controlled by another person (i.e., a confederate) or a computer program. In a series of experiments, the human confederate was either introduced as naïve to the task, cooperative, or competitive. Results demonstrate that the ascription of humanness increases with higher congruency of gaze reactions when participants are interacting with a naïve partner. In contrast, humanness ascription is driven by the degree of contingency irrespective of congruency when the confederate was introduced as cooperative. Conversely, during interaction with a competitive confederate, judgments were neither based on congruency nor on contingency. These results offer important insights into what renders the experience of an interaction truly social: Humans appear to have a default expectation of reciprocation that can be influenced drastically by the presumed disposition of the interactor to either cooperate or compete.


Does Conventional Lateral Long Bone Radiography Present Sagittal Axes Accurately? A Comparison with Direct Lateral Long Bone Radiography.
To investigate the sagittal alignment, proper and consistent radiographic evaluation is needed. We sought to use an alternative method of obtaining the same view, a direct lateral view and compare it with the conventional method. Conventional lateral long bone radiography and direct lateral long bone radiography were undertaken by 74 consecutive patients undergoing total knee arthroplasty (TKA), preoperatively and postoperatively. Angles between sagittal axes and the mechanical axis (MA), and the visible hip joint area were measured. Postoperative angles between the MA and femoral implant were also significantly different between the two radiologic methods of conventional and direct lateral long bone radiography (92.1 ± 2.1 degrees vs. 94.4 ± 2.6 degrees, p = 0.034). Hip joint visibility was significantly inferior using the direct lateral method (p < 0.001). The angles on the sagittal axes on conventional radiography of the lower extremities were different from those on direct lateral long bone radiography. The direct lateral long bone radiographs show the true lateral view, and surgeons may consider using the direct lateral method when evaluating relevant alignments before and after TKAs. For obese patients, however, conventional or combined methods should be considered because of inferior visibility of the hip joint using the direct method.


Gene regulatory divergence between locally adapted ecotypes in their native habitats.
Local adaptation is a key driver of ecological specialization and the formation of new species. Despite its importance, the evolution of gene regulatory divergence among locally adapted populations is poorly understood, especially how that divergence manifests in nature. Here, we evaluate gene expression divergence and allele-specific gene expression responses for locally adapted coastal perennial and inland annual accessions of the yellow monkeyflower, Mimulus guttatus, in a field reciprocal transplant experiment. Overall, 6765 (73%) of surveyed genes were differentially expressed between coastal and inland habitats, while 7213 (77%) were differentially expressed between the coastal perennial and inland annual accessions. Cis-regulatory variation was pervasive, affecting 79% (5532) of differentially expressed genes. We detected trans effects for 52% (3611) of differentially expressed genes. Expression plasticity of alleles across habitats (G × E interactions) appears to be relatively common (affecting 18% of transcripts) and could minimize fitness trade-offs at loci that contribute to local adaptation. We also found evidence that at least one chromosomal inversion may act as supergene by holding together haplotypes of differentially expressed genes, but this pattern depends on habitat context. Our results highlight multiple key patterns regarding the relationship between gene expression and the evolution of locally adapted populations.


Predominant and secondary pollen botanical origins influence the carotenoid and fatty acid profile in fresh honeybee-collected pollen.
Total and individual carotenoids, fatty acid composition of total lipids, and main lipid classes of 16 fresh bee-collected pollen samples from Romania were determined by high-performance liquid chromatography with photodiode array detection and capillary gas chromatography with mass detection. Analyzed samples were found rich in lutein, whereas β-criptoxanthin and β-carotene were present in a wide range of amounts correlated with predominant botanical origin of the samples. High amounts of lutein were correlated with the presence of Callendula officinalis, Taraxacum officinale and Anthylis sp. The highest amount of total lipids was found in samples where pollen from Brassica sp. was predominant. Lipid classes were dominated by polyunsaturated fatty acids. Saturated fatty acids were determined in variable amounts. Lipid and carotenoid contents present great variability, explained by the various botanical species present in the samples.


Human CD3 transgenic mice: preclinical testing of antibodies promoting immune tolerance.
Monoclonal antibodies have proven to be potent agents to promote immunological tolerance in animal models of autoimmune disease and transplantation. However, optimal clinical application and pharmaceutical development have been limited by the species specificity of therapeutic antibodies, as well exemplified in the case of anti-CD3 antibodies. Compelling evidence in the nonobese diabetic (NOD) mouse, recently translated to clinical autoimmune insulin-dependent diabetes, demonstrates that a short CD3 antibody treatment effectively and durably controls disease progression. We established transgenic mice expressing the human ε chain of the CD3 complex bred onto the NOD background. These mice developed a high incidence of spontaneous autoimmune diabetes and harbored T cells sensitive both in vitro and in vivo to anti-human CD3 antibodies. Treatment of diabetic transgenic mice with otelixizumab, an anti-human CD3 antibody that has proven effective in the clinic, resulted in durable disease remission dependent on transferable T cell-mediated tolerance. This model should enable the evaluation of anti-human CD3 antibodies to determine their potential clinical utility.


Prenatal exposure to nicotine via maternal infusions: effects on development of catecholamine systems.
The effects of a continuous 16-day gestational exposure to nicotine on development of central and peripheral catecholaminergic pathways were examined in the offspring of dams who received a minipump implant on the 4th day of gestation. Prenatal nicotine exposure resulted in a selective suppression of maturational increases in norepinephrine and dopamine levels and utilization rates in the cerebral cortex and also reduced transmitter levels in sympathetic pathways to the lung and kidney. The regional selectivity of the effect, combined with measurements of synaptosomal uptake of [3H]norepinephrine and of tyrosine hydroxylase activity, all suggested that the alterations in transmitter disposition reflected reduced neural activity as opposed to actions on general cellular development or synaptogenesis. Although the lag in development was largely made up by weaning, deficits in norepinephrine utilization reappeared in young adulthood in the cerebral cortex and midbrain + brainstem, suggesting that lasting functional alterations may occur as a consequence of prenatal nicotine exposure. Comparisons with the results obtained with maternal nicotine injections (which produce largely stimulatory effects on norepinephrine levels and turnover) suggest that the hypoxia/ischemia associated with injected nicotine causes a reactive hyperinnervation; the adverse actions of nicotine on neurotransmitter development are thus highly dependent upon the route of drug administration.


Understanding the nurse's role in smoking cessation.
Guidelines from the National Institute for Health and Clinical Excellence (NICE) recommend that every nurse should consult their patients about giving up smoking. This is an important public health role but in order to fulfil it, nurses need to have an understanding of the motivations and barriers that underpin smoking cessation. Furthermore, nurses need to know the options available to support the patient. This review provides an overview of the stages and motivations behind smokers' intentions. It aims to increase the knowledge of nurses and provide them with a greater understanding of the issues which smokers face. This review identified smoking cessation as a continuum. Nurses play an important role in raising the issue of smoking cessation with patients and they can offer a balanced perspective on the challenges they might face. They can then sign-post patients to the most appropriate smoking cessation options.


A review of the determination of persistent organic pollutants for environmental forensics investigations.
The field of environmental forensics emerged in the 1980s as a consequence of legislative frameworks enacted to enable parties, either states or individuals, to seek compensation with regard to contamination or injury due to damage to the environment. This legal environment requires stringent record keeping and defendable data therefore analysis can sometimes be confined to data to be obtained from certified laboratories using a standard accredited analytical method. Many of these methods were developed to target specific compounds for risk assessment purposes and not for environmental forensics applications such as source identification or age dating which often require larger data sets. The determination of persistent organic pollutants (POPs) for environmental forensic applications requires methods that are selective but also cover a wide range of target analytes which can be identified and quantified without bias. POPs are used in a wide variety of applications such as flame retardants, fire suppressants, heat transfer agents, surfactants and pesticides mainly because of their chemical inertness and stability. They also include compounds such as dioxins that can be unintentionally produced from industrial activities. POPs are persistent in the environment, bioaccumulative and/or toxic and therefore require analytical methods that are sensitive enough to meet the low detection limits needed for the protection of the environment and human health. A variety of techniques, procedures and instruments can be used which are well suited for different scenarios. Optimised methods are important to ensure that analytes are quantitatively extracted, matrix coextractables and interferences are removed and instruments are used most effectively and efficiently. This can require deviation from standard methods which can open the data up to further scrutiny in the courtroom. However, when argued effectively and strict QA/QC procedures are followed the development and optimization of methods based on investigation specific scenarios has the potential to generate better quality and more useful data.


Upregulation of PTEN in glioma cells by cord blood mesenchymal stem cells inhibits migration via downregulation of the PI3K/Akt pathway.
PTEN (phosphatase and tensin homologue deleted on chromosome ten) is a tumor suppressor gene implicated in a wide variety of human cancers, including glioblastoma. PTEN is a major negative regulator of the PI3K/Akt signaling pathway. Most human gliomas show high levels of activated Akt, whereas less than half of these tumors carry PTEN mutations or homozygous deletions. The unique ability of mesenchymal stem cells to track down tumor cells makes them as potential therapeutic agents. Based on this capability, new therapeutic approaches have been developed using mesenchymal stem cells to cure glioblastoma. However, molecular mechanisms of interactions between glioma cells and stem cells are still unknown. In order to study the mechanisms by which migration of glioma cells can be inhibited by the upregulation of the PTEN gene, we studied two glioma cell lines (SNB19 and U251) and two glioma xenograft cell lines (4910 and 5310) alone and in co-culture with human umbilical cord blood-derived mesenchymal stem cells (hUCBSC). Co-cultures of glioma cells showed increased expression of PTEN as evaluated by immunofluorescence and immunoblotting assays. Upregulation of PTEN gene is correlated with the downregulation of many genes including Akt, JUN, MAPK14, PDK2, PI3K, PTK2, RAS and RAF1 as revealed by cDNA microarray analysis. These results have been confirmed by reverse-transcription based PCR analysis of PTEN and Akt genes. Upregulation of PTEN resulted in the inhibition of migration capability of glioma cells under in vitro conditions. Also, wound healing capability of glioma cells was significantly inhibited in co-culture with hUCBSC. Under in vivo conditions, intracranial tumor growth was inhibited by hUCBSC in nude mice. Further, hUCBSC upregulated PTEN and decreased the levels of XIAP and Akt, which are responsible for the inhibition of tumor growth in the mouse brain. Our studies indicated that upregulation of PTEN by hUCBSC in glioma cells and in the nude mice tumors downregulated Akt and PI3K signaling pathway molecules. This resulted in the inhibition of migration as well as wound healing property of the glioma cells. Taken together, our results suggest hUCBSC as a therapeutic agent in treating malignant gliomas.


IL-8 induces a specific transcriptional profile in human neutrophils: synergism with LPS for IL-1 production.
IL-8 is an inflammatory CXC chemokine involved in neutrophil recruitment and activation in various inflammatory conditions. The transcriptional profile induced by IL-8 in human neutrophils was analyzed using high-density oligonucleotide arrays and compared with that of the prototypic phagocyte activator LPS. As expected, LPS induced a major effect on the cell transcriptome, upregulating 116 (0.93%) and downregulating 70 (0.56%) of the transcripts. IL-8 induced a less profound modulation of the cell transcriptome, with upregulation of 30 (0.25%) and downregulation of 6 (0.04%) of the transcripts. Although the two proinflammatory mediators induced partially overlapping transcriptional profiles (50.0% of IL-8-responsive genes were concordantly regulated by LPS), IL-8 also modulated a significant number of genes unresponsive to LPS, including soluble mediators, membrane receptors, signaling molecules, and regulators of transcription and translation. A set of IL-8-inducible genes was related to cell motility, possibly a strategy to prepare for migration into tissues. Analysis of the IL-8-responsive gene IL-1beta at the protein level revealed that transcript induction was not followed by protein production. Neutrophils stimulated with IL-8, however, showed a significant increase in IL-1beta secretion after subsequent exposure to LPS. Thus, the effect of IL-8 at the transcriptional level could provide a synergistic effect with microbial products for neutrophil activation.


Protection against group B meningococcal disease. II. Infection and resulting immunity in a guinea pig model.
A guinea pig subcutaneous chamber model was used to evaluate the specificity of the immune response resulting from Neisseria meningitidis infection. Small numbers of meningococci easily infected the chambers. The infections persisted for 6-8 days with relatively high levels of organisms (10(5)-10(6)/milliliter) in the chambers, and were then rapidly eliminated and no organisms could be cultured beyond day 14. Clearance of infection correlated with appearance of circulating antibody. Antibody against both the protein serotype antigen and the capsular polysaccharide were induced as a result of meningococcal infection. The group-specific polysaccharide response peaked 2-3 wk after the animals were inoculated, while the type-specific protein response peaked at 5-6 wk. The animals were quite resistant to reinfection with either the homologous serogroup or serotype.


Using semi-automated segmentation of computed tomography datasets for three-dimensional visualization and volume measurements of equine paranasal sinuses.
The system of the paranasal sinuses morphologically represents one of the most complex parts of the equine body. A clear understanding of spatial relationships is needed for correct diagnosis and treatment. The purpose of this study was to describe the anatomy and volume of equine paranasal sinuses using three-dimensional (3D) reformatted renderings of computed tomography (CT) slices. Heads of 18 cadaver horses, aged 2-25 years, were analyzed by the use of separate semi-automated segmentation of the following bilateral paranasal sinus compartments: rostral maxillary sinus (Sinus maxillaris rostralis), ventral conchal sinus (Sinus conchae ventralis), caudal maxillary sinus (Sinus maxillaris caudalis), dorsal conchal sinus (Sinus conchae dorsalis), frontal sinus (Sinus frontalis), sphenopalatine sinus (Sinus sphenopalatinus), and middle conchal sinus (Sinus conchae mediae). Reconstructed structures were displayed separately, grouped, or altogether as transparent or solid elements to visualize individual paranasal sinus morphology. The paranasal sinuses appeared to be divided into two systems by the maxillary septum (Septum sinuum maxillarium). The first or rostral system included the rostral maxillary and ventral conchal sinus. The second or caudal system included the caudal maxillary, dorsal conchal, frontal, sphenopalatine, and middle conchal sinuses. These two systems overlapped and were interlocked due to the oblique orientation of the maxillary septum. Total volumes of the paranasal sinuses ranged from 911.50 to 1502.00 ml (mean ± SD, 1151.00 ± 186.30 ml). 3D renderings of equine paranasal sinuses by use of semi-automated segmentation of CT-datasets improved understanding of this anatomically challenging region.


Deep PPG: Large-Scale Heart Rate Estimation with Convolutional Neural Networks.
Photoplethysmography (PPG)-based continuous heart rate monitoring is essential in a number of domains, e.g., for healthcare or fitness applications. Recently, methods based on time-frequency spectra emerged to address the challenges of motion artefact compensation. However, existing approaches are highly parametrised and optimised for specific scenarios of small, public datasets. We address this fragmentation by contributing research into the robustness and generalisation capabilities of PPG-based heart rate estimation approaches. First, we introduce a novel large-scale dataset (called PPG-DaLiA), including a wide range of activities performed under close to real-life conditions. Second, we extend a state-of-the-art algorithm, significantly improving its performance on several datasets. Third, we introduce deep learning to this domain, and investigate various convolutional neural network architectures. Our end-to-end learning approach takes the time-frequency spectra of synchronised PPG- and accelerometer-signals as input, and provides the estimated heart rate as output. Finally, we compare the novel deep learning approach to classical methods, performing evaluation on four public datasets. We show that on large datasets the deep learning model significantly outperforms other methods: The mean absolute error could be reduced by 31 % on the new dataset PPG-DaLiA, and by 21 % on the dataset WESAD.


Assessment of Irrigation Physics in a Land Surface Modeling Framework using Non-Traditional and Human-Practice Datasets.
Irrigation increases soil moisture, which in turn controls water and energy fluxes from the land surface to the planetary boundary layer and determines plant stress and productivity. Therefore, developing a realistic representation of irrigation is critical to understanding land-atmosphere interactions in agricultural areas. Irrigation parameterizations are becoming more common in land surface models and are growing in sophistication, but there is difficulty in assessing the realism of these schemes, due to limited observations (e.g., soil moisture, evapotranspiration) and scant reporting of irrigation timing and quantity. This study uses the Noah land surface model run at high resolution within NASA's Land Information System to assess the physics of a sprinkler irrigation simulation scheme and model sensitivity to choice of irrigation intensity and greenness fraction datasets over a small, high resolution domain in Nebraska. Differences between experiments are small at the interannual scale but become more apparent at seasonal and daily time scales. In addition, this study uses point and gridded soil moisture observations from fixed and roving Cosmic Ray Neutron Probes and co-located human practice data to evaluate the realism of irrigation amounts and soil moisture impacts simulated by the model. Results show that field-scale heterogeneity resulting from the individual actions of farmers is not captured by the model and the amount of irrigation applied by the model exceeds that applied at the two irrigated fields. However, the seasonal timing of irrigation and soil moisture contrasts between irrigated and non-irrigated areas are simulated well by the model. Overall, the results underscore the necessity of both high-quality meteorological forcing data and proper representation of irrigation for accurate simulation of water and energy states and fluxes over cropland.


Abortion surveillance - United States, 2010.
Since 1969, CDC has conducted abortion surveillance to document the number and characteristics of women obtaining legal induced abortions in the United States. 2010. Each year, CDC requests abortion data from the central health agencies of 52 reporting areas (the 50 states, the District of Columbia, and New York City). The reporting areas provide this information voluntarily. For 2010, data were received from 49 reporting areas. For the purpose of trend analysis, abortion data were evaluated from the 46 areas that reported data every year during 2001-2010. Census and natality data, respectively, were used to calculate abortion rates (number of abortions per 1,000 women) and ratios (number of abortions per 1,000 live births). A total of 765,651 abortions were reported to CDC for 2010. Of these abortions, 753,065 (98.4%) were from the 46 reporting areas that provided data every year during 2001-2010. Among these same 46 reporting areas, the abortion rate for 2010 was 14.6 abortions per 1,000 women aged 15-44 years, and the abortion ratio was 228 abortions per 1,000 live births. Compared with 2009, the total number and rate of reported abortions for 2010 decreased 3% and reached the lowest levels for the entire period of analysis (2001-2010); the abortion ratio was stable, changing only 0.4%. From 2001 to 2010, the total number, rate, and ratio of reported abortions decreased 9%, 10%, and 8%, respectively. Given the 3% decrease from 2009 to 2010 in the total number and rate of reported abortions, in combination with the 5% decrease that had occurred in the previous year from 2008 to 2009, the overall decrease for both measures was greater during 2006-2010 than during 2001-2005, despite the annual variations that resulted in no net decrease during 2006-2008. In 2010 and throughout the period of analysis, women in their 20s accounted for the majority of abortions and had the highest abortion rates, whereas women in their 30s and older accounted for a much smaller percentage of abortions and had lower abortion rates. In 2010, women aged 20-24 and 25-29 years accounted for 32.9% and 24.5% of all abortions, respectively, and had abortion rates of 26.7 and 20.2 abortions per 1,000 women aged 20-24 and 25-29 years, respectively. In contrast, women aged 30-34, 35-39, and ≥40 years accounted for 15.3%, 8.9%, and 3.4% of all abortions, respectively, and had abortion rates of 13.2, 7.6, and 2.8 abortions per 1,000 women aged 30-34 years, 35-39 years, ≥40 years, respectively. Throughout the period of analysis, abortion rates decreased among women aged 20-24 and 25-29 years, whereas they increased among women aged ≥40 years. In 2010, adolescents aged 15-19 years accounted for 14.6% of all abortions and had an abortion rate of 11.7 abortions per 1,000 adolescents aged 15-19 years. Throughout the period of analysis, the percentage of all abortions accounted for by adolescents and the adolescent abortion rate decreased. In contrast to the percentage distribution of abortions and abortion rates by age, abortion ratios in 2010 and throughout the entire period of analysis were highest among adolescents and lowest among women aged 30-39 years. Abortion ratios decreased from 2001 to 2010 for women in all age groups except for those aged <15 years, for whom they increased. In 2010, most (65.9%) abortions were performed at ≤8 weeks' gestation, and 91.9% were performed at ≤13 weeks' gestation. Few abortions (6.9%) were performed at 14-20 weeks' gestation, and even fewer (1.2%) were performed at ≥21 weeks' gestation. From 2001 to 2010, the percentage of all abortions performed at ≤8 weeks' gestation increased 10%, whereas the percentage performed at >13 weeks' decreased 10%. Moreover, among abortions performed at ≤13 weeks' gestation, the distribution shifted toward earlier gestational ages, with the percentage of these abortions performed at ≤6 weeks' gestation increasing 36%. In 2010, a total of 72.4% of abortions were performed by curettage at ≤13 weeks' gestation, 17.7% were performed by early medical abortion (a nonsurgical abortion at ≤8 weeks' gestation), and 8.3% were performed by curettage at >13 weeks' gestation. Among abortions that were performed at ≤8 weeks' gestation, and thus were eligible for early medical abortion on the basis of gestational age, 26.5% were completed by this method. From 2009 to 2010, the use of early medical abortion increased 13%. Deaths of women associated with complications from abortions for 2010 are being investigated under CDC's Pregnancy Mortality Surveillance System. In 2009, the most recent year for which data were available, eight women were identified to have died as a result of complications from known legal induced abortions. No reported deaths were associated with illegal induced abortions. Among the 46 areas that reported data every year during 2001-2010, the gradual decrease that had occurred during previous decades in the total number and rate of reported abortions continued through 2005, whereas year-to-year variation from 2006 to 2008 resulted in no net change during this later period. However, the large decreases that occurred both from 2008 to 2009 and from 2009 to 2010 resulted in a greater overall decrease during 2006-2010 as compared with 2001-2005 and the lowest number and rate of reported abortions for the entire period of analysis. Unintended pregnancy is the major contributor to abortion. Because unintended pregnancies are rare among women who use the most effective methods of reversible contraception, increasing access to and use of these methods can help further reduce the number of abortions performed in the United States. The data in this report can help program planners and policy makers identify groups of women at greatest risk for unintended pregnancy and help guide and evaluate prevention efforts.


Mixed venous oxygen saturation and oxygen partial pressure as predictors of cardiac index after coronary artery bypass grafting.
To determine the relationship between the mixed venous oxygen saturation (SvO2) and the cardiac index (CI) in individuals during the first 8 hours after coronary artery bypass grafting. Descriptive with a correlational design. Cardiac intensive care unit at a university medical center in the midwestern United States. Twenty-one subjects (16 men and 5 women) undergoing coronary artery bypass grafting. SvO2, thermodilution cardiac output and CI measured every 2 hours during the first 8 hours after surgery. Elective coronary artery bypass grafting. Significant (p < 0.05) but moderate correlations between SvO2 and CI were found only at 6 and 8 hours after surgery (r = 0.66, p = 0.001; r = 0.44, p = 0.47). Secondary analysis determined that in subjects without lung disease, mixed venous oxygen tension (PvO2) had significant correlation with CI at all data collection times (r = 0.54 to 0.72; p = 0.003 to 0.02). The results of this study indicate that immediately after coronary artery bypass grafting, SvO2 cannot reliably predict CI. Although statistically significant results were found for the correlation between PvO2 and CI at all data collection times, the correlations were too low to support the use of the PvO2 as a reliable clinical predictor of CI without further study.


Functional Connectivity of EEG Signals Under Laser Stimulation in Migraine.
In previous studies, migraine patients showed abnormalities in pain-related evoked responses, as reduced habituation to repetitive stimulation. In this study, we aimed to apply a novel analysis of EEG bands synchronization and directed dynamical influences under painful stimuli in migraine patients compared to non-migraine healthy volunteers. Thirty-one migraine without aura outpatients (MIGR) were evaluated and compared to 19 controls (CONT). The right hand was stimulated by means of 30 consecutive CO2 laser stimuli. EEG signal was examined by means of Morlet wavelet, synchronization entropy (SE), and Granger causality (GC), and the statistically validated results were mapped on the corresponding scalp locations. The vertex complex of averaged laser-evoked responses (LEPs) showed reduced habituation compared to CONT. In the prestimulus phase, enhanced SE in the 0, 5-30 Hz range was present in MIGR and CONT between the bilateral temporal-parietal and the frontal regions around the midline. Migraine patients showed an anticipation of EEG changes preceding the painful stimulation compared to CONT. In the poststimulus phase, the same cortical areas were more connected in MIGR vs CONT. In both groups of patients and CONT, the habituation index was negatively correlated with the GC scores. A different pattern of cortical activation after painful stimulation was present in migraine. The increase in cortical connections during repetitive painful stimulation may subtend the phenomenon of LEPs reduced habituation. Brain network analysis may give an aid in understanding subtle changes of pain processing under laser stimuli in migraine patients.


Evaluation of two fully automated immunoassay based tests for the measurement of 1α,25-dihydroxyvitamin D in human serum and comparison with LC-MS/MS.
1α,25-Dihydroxyvitamin D [1,25(OH)2 vitD] is the bioactive form of vitamin D. Due to the very low concentrations of 1,25(OH)2 vitD in the blood and its lipophilic character, measurement of this parameter is analytically challenging. Requiring preceding manual extraction steps before analysis, previous assays have been laborious. In the presented study, we evaluated the performance of two immunoassays from DiaSorin and from Immunodiagnostic Systems (IDS) which combine fully automated extraction and measurement of 1,25(OH)2 vitD. Imprecision and linearity were verified according to Clinical and Laboratory Standards Institute EP15-A3 and EP6-A guidelines, respectively. Ninety-three patient serum samples sent to our institute for determination of 1,25(OH)2 vitD, as well as 20 Vitamin D External Quality Assessment Scheme (DEQAS) samples, were used to evaluate correlation and agreement of 1,25(OH)2 vitD measurements between the two immunoassays and with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Total imprecision was 5.2% or less for the DiaSorin test but reached 20.1% for the IDS iSYS test. 1,25(OH)2 vitD concentrations measured with the DiaSorin assay showed a strong correlation with 1,25(OH)2 vitD levels measured by LC-MS/MS and a good agreement with method specific means of DEQAS samples. By contrast, the IDS iSYS test overestimated 1,25(OH)2 vitD concentrations in human serum, particularly at higher concentrations. Due to its high sensitivity, low imprecision, broad measurement range, and good agreement with 1,25(OH)2 vitD concentrations measured by LC-MS/MS, the DiaSorin test is a valuable analytical option for the determination of 1,25(OH)2 vitD.


Propofol induces impairment of mitochondrial biogenesis through inhibiting the expression of peroxisome proliferator-activated receptor-γ coactivator-1α.
Propofol is a commonly used general anesthetic in patient care. Recent studies have shown that propofol has neurological side effects especially in young children, which raises a concern regarding the safety of its use. We explored the effects of the molecular mechanism of propofol on neuronal mitochondrial function in SH-SY5Y cells. Our results demonstrate that clinically relevant doses of propofol reduce the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in a dose- and time-dependent manner. At a concentration of 2%, propofol suppresses the mitochondrial regulator nuclear respiratory factor 1 and mitochondrial transcription factor A and impairs neuronal mitochondrial biogenesis. These impairments involve reduction of mitochondrial mass and reduction of the ratio of mitochondrial to nuclear DNA as well as reduction of cytochrome C oxidase activity. Propofol treatment reduces intracellular adenosine triphosphate (ATP) production, the mitochondrial respiratory rate, and increases mitochondrial reactive oxygen species production, implying that it disturbs neuronal mitochondrial function. Overexpression of PGC-1α rescued propofol-induced reduced mitochondrial mass, ATP production, and respiratory rate, indicating that PGC-1α is the mediator of the effect of propofol on mitochondrial function. Finally, we demonstrate that propofol suppresses PGC-1α by inhibiting cAMP-response element binding protein (CREB) activation and promoting PKA RI expression, and the addition of cyclic adenosine monophosphate rescues propofol-mediated reduced PGC-1α. In conclusion, PGC-1α is the central mediator of propofol-induced impairment of mitochondrial biogenesis and neuronal mitochondrial dysfunction. Our study demonstrates the molecular mechanism behind propofol-induced neurotoxicity and provides valuable information regarding its side effects in clinical practice.


Free water elimination and mapping from diffusion MRI.
Relating brain tissue properties to diffusion tensor imaging (DTI) is limited when an image voxel contains partial volume of brain tissue with free water, such as cerebrospinal fluid or edema, rendering the DTI indices no longer useful for describing the underlying tissue properties. We propose here a method for separating diffusion properties of brain tissue from surrounding free water while mapping the free water volume. This is achieved by fitting a bi-tensor model for which a mathematical framework is introduced to stabilize the fitting. Applying the method on datasets from a healthy subject and a patient with edema yielded corrected DTI indices and a more complete tract reconstruction that passed next to the ventricles and through the edema. We were able to segment the edema into areas according to the condition of the underlying tissue. In addition, the volume of free water is suggested as a new quantitative contrast of diffusion MRI. The findings suggest that free water is not limited to the borders of the brain parenchyma; it therefore contributes to the architecture surrounding neuronal bundles and may indicate specific anatomical processes. The analysis requires a conventional DTI acquisition and can be easily merged with existing DTI pipelines.


Immune Landscape of Invasive Ductal Carcinoma Tumor Microenvironment Identifies a Prognostic and Immunotherapeutically Relevant Gene Signature.
Background: Invasive ductal carcinoma (IDC) is a clinically and molecularly distinct disease. Tumor microenvironment (TME) immune phenotypes play crucial roles in predicting clinical outcomes and therapeutic efficacy. Method: In this study, we depict the immune landscape of IDC by using transcriptome profiling and clinical characteristics retrieved from The Cancer Genome Atlas (TCGA) data portal. Immune cell infiltration was evaluated via single-sample gene set enrichment (ssGSEA) analysis and systematically correlated with genomic characteristics and clinicopathological features of IDC patients. Furthermore, an immune signature was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm. A random forest algorithm was applied to identify the most important somatic gene mutations associated with the constructed immune signature. A nomogram that integrated clinicopathological features with the immune signature to predict survival probability was constructed by multivariate Cox regression. Results: The IDC were clustered into low immune infiltration, intermediate immune infiltration, and high immune infiltration by the immune landscape. The high infiltration group had a favorable survival probability compared with that of the low infiltration group. The low-risk score subtype identified by the immune signature was characterized by T cell-mediated immune activation. Additionally, activation of the interferon-α response, interferon-γ response, and TNF-α signaling via the NFκB pathway was observed in the low-risk score subtype, which indicated T cell activation and may be responsible for significantly favorable outcomes in IDC patients. A random forest algorithm identified the most important somatic gene mutations associated with the constructed immune signature. Furthermore, a nomogram that integrated clinicopathological features with the immune signature to predict survival probability was constructed, revealing that the immune signature was an independent prognostic biomarker. Finally, the relationship of VEGFA, PD1, PDL-1, and CTLA-4 expression with the immune infiltration landscape and the immune signature was analyzed to interpret the responses of IDC patients to immunotherapy. Conclusion: Taken together, we performed a comprehensive evaluation of the immune landscape of IDC and constructed an immune signature related to the immune landscape. This analysis of TME immune infiltration landscape has shed light on how IDC respond to immunotherapy and may guide the development of novel drug combination strategies.


Risk Prediction of Prostate Cancer with Single Nucleotide Polymorphisms and Prostate Specific Antigen.
Combined information on single nucleotide polymorphisms and prostate specific antigen offers opportunities to improve the performance of screening by risk stratification. We aimed to predict the risk of prostate cancer based on prostate specific antigen together with single nucleotide polymorphism information. We performed a prospective study of 20,575 men with prostate specific antigen testing and 4,967 with a polygenic risk score for prostate cancer based on 66 single nucleotide polymorphisms from the Finnish population based screening trial of prostate cancer and 5,269 samples of 7 single nucleotide polymorphisms from the Finnish prostate cancer DNA study. A Bayesian predictive model was built to estimate the risk of prostate cancer by sequentially combining genetic information with prostate specific antigen compared with prostate specific antigen alone in study subjects limited to those with prostate specific antigen 4 ng/ml or above. The posterior odds of prostate cancer based on 7 single nucleotide polymorphisms together with the prostate specific antigen level ranged from 3.7 at 4 ng/ml, 14.2 at 6 and 40.7 at 8 to 98.2 at 10 ng/ml. The ROC AUC was elevated to 88.8% (95% CI 88.6-89.1) for prostate specific antigen combined with the risk score based on 7 single nucleotide polymorphisms compared with 70.1% (95% CI 69.6-70.7) for prostate specific antigen alone. It was further escalated to 96.7% (95% CI 96.5-96.9) when all prostate cancer susceptibility polygenes were combined. Expedient use of multiple genetic variants together with information on prostate specific antigen levels better predicts the risk of prostate cancer than prostate specific antigen alone and allows for higher prostate specific antigen cutoffs. Combined information also provides a basis for risk stratification which can be used to optimize the performance of prostate cancer screening.


Antioxidant Effect and Functional Properties of Hydrolysates Derived from Egg-White Protein.
This study utilized commercially available proteolytic enzymes to prepare egg-white protein hydrolysates (EPHs) with different degrees of hydrolysis. The antioxidant effect and functionalities of the resultant products were then investigated. Treatment with Neutrase yielded the most α-amino groups (6.52 mg/mL). Alcalase, Flavourzyme, Protamex, and Ficin showed similar degrees of α-amino group liberation (3.19-3.62 mg/mL). Neutrase treatment also resulted in the highest degree of hydrolysis (23.4%). Alcalase and Ficin treatment resulted in similar degrees of hydrolysis. All hydrolysates, except for the Flavourzyme hydrolysate, had greater radical scavenging activity than the control. The Neutrase hydrolysate showed the highest 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity (IC50=3.6mg/mL). Therefore, Neutrase was identified as the optimal enzyme for hydrolyzing egg-white protein to yield antioxidant peptides. During Neutrase hydrolysis, the reaction rate was rapid over the first 4 h, and then subsequently declined. The IC50 value was lowest after the first hour (2.99 mg/mL). The emulsifying activity index (EAI) of EPH treated with Neutrase decreased, as the pH decreased. The EPH foaming capacity was maximal at pH 3.6, and decreased at an alkaline pH. Digestion resulted in significantly higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ABTS radical scavenging activity. The active peptides released from egg-white protein showed antioxidative activities on ABTS and DHHP radical. Thus, this approach may be useful for the preparation of potent antioxidant products.


Consequences of asymmetric competition between resident and invasive defoliators: a novel empirically based modelling approach.
Invasive species can have profound effects on a resident community via indirect interactions among community members. While long periodic cycles in population dynamics can make the experimental observation of the indirect effects difficult, modelling the possible effects on an evolutionary time scale may provide the much needed information on the potential threats of the invasive species on the ecosystem. Using empirical data from a recent invasion in northernmost Fennoscandia, we applied adaptive dynamics theory and modelled the long term consequences of the invasion by the winter moth into the resident community. Specifically, we investigated the outcome of the observed short-term asymmetric preferences of generalist predators and specialist parasitoids on the long term population dynamics of the invasive winter moth and resident autumnal moth sharing these natural enemies. Our results indicate that coexistence after the invasion is possible. However, the outcome of the indirect interaction on the population dynamics of the moth species was variable and the dynamics might not be persistent on an evolutionary time scale. In addition, the indirect interactions between the two moth species via shared natural enemies were able to cause asynchrony in the population cycles corresponding to field observations from previous sympatric outbreak areas. Therefore, the invasion may cause drastic changes in the resident community, for example by prolonging outbreak periods of birch-feeding moths, increasing the average population densities of the moths or, alternatively, leading to extinction of the resident moth species or to equilibrium densities of the two, formerly cyclic, herbivores.


Patients' nursing records revealing opportunities for interprofessional workplace learning in primary care: a chart review study.
Working and learning go hand in hand during interprofessional collaborative practice. Patients' nursing records are designed to record patient care and health status. It is not known whether these records are also used to keep track of interprofessional contacts or interprofessional learning between team members. This study explored the usefulness of patients' nursing records in optimising interprofessional workplace learning for general practitioners. We utilized a descriptive retrospective chart review. All palliative home care teams of the Dutch speaking part of Belgium were involved. Throughout the year 2010, a representative sample of patient charts was selected. Characteristics of encounters between general practitioners and palliative care nurses were extracted from the charts. Detailed accounts of interprofessional contacts were found in the charts. Palliative care nurses recorded number and type of contacts, topics discussed during contacts and general practitioner's learning activities. Palliative care nurses are sensitive and open towards the general practitioners' learning needs. Patients' nursing records provide useful information for interprofessional team discussions on workplace learning. Healthcare professionals should be trained to respond to each other's learning needs.


Effect of resistance training on biomarkers of vascular function and oxidative stress in young African-American and Caucasian men.
African Americans (AA) have an earlier onset of hypertension and a different vascular profile than their Caucasian (Cau) peers. Research suggests that biological mediators of vascular inflammation are different among these groups in hypertensive populations. Resistance training (RT) is an important exercise modality that improves the vascular profile of young AA men. We examined the role of RT on biomarkers of vascular function and oxidative stress in body mass index-matched AA and Cau men. RT for 6 weeks elicited significant changes in circulating matrix metalloprotease-9 (MMP-9) and 8-Isoprostane (8-IsoP) in young AA men (n=14, AA; n=18, Cau; 18-35 years). MMP-9 was lower and decreased in AA (pre: P=0.02; post: P<0.001) and a time × group interaction for MMP-9 (F(1, 30)=4.81; P=0.036) and 8-IsoP (F(1, 24)=7.09; P=0.014) was detected. 8-IsoP decreased in AA (P=0.026) but did not change in Cau (P=0.309). Notably, the increase in strength (1-repetition maximum (1-RM)) was correlated with the decrease in MMP-9 (r=-0.398; P=0.022). Furthermore, these adaptations were independent of any improvement in cardiorespiratory fitness. We demonstrate that RT effectively reduces matrix remodeling proteins and oxidative stress in young AA men. Increasing strength may be beneficial for improving vascular health and offsetting novel cardiovascular risk factors of hypertension in young AA men.


Summaries of findings, descriptions of interventions, and information about adverse effects would make reviews more informative.
To describe challenges when extracting and presenting relevant, consistent, and accessible information from systematic reviews. We systematically selected comparisons and outcomes from 18 Cochrane reviews, evaluated the quality of evidence for each outcome using the GRADE system, and developed standardized patient information. We evaluated the information using patient, review author, researcher, and clinician feedback. Challenges included large numbers of comparisons and outcomes; missing information about treatments and adverse effects; and variations in how effect was measured and presented. By selecting comparisons and outcomes based on patient-relevance, quality, and nonredundancy, we halved the number of outcomes. We prepared information about treatments and adverse effects using other sources. We framed outcomes consistently and standardized the presentation of magnitude of effect. The incorporation of summary of findings tables in reviews could address these challenges. Problems could also be reduced if review groups agreed upon standard outcomes; excluded less relevant outcomes; incorporated more information about interventions and adverse effects; and implemented clearer guidelines for the presentation of results.


Functional chromatin features are associated with structural mutations in cancer.
Structural mutations (SMs) play a major role in cancer development. In some cancers, such as breast and ovarian, DNA double-strand breaks (DSBs) occur more frequently in transcribed regions, while in other cancer types such as prostate, there is a consistent depletion of breakpoints in transcribed regions. Despite such regularity, little is understood about the mechanisms driving these effects. A few works have suggested that protein binding may be relevant, e.g. in studies of androgen receptor binding and active chromatin in specific cell types. We hypothesized that this behavior might be general, i.e. that correlation between protein-DNA binding (and open chromatin) and breakpoint locations is common across divergent cancers. We investigated this hypothesis by comprehensively analyzing the relationship among 457 ENCODE protein binding ChIP-seq experiments, 125 DnaseI and 24 FAIRE experiments, and 14,600 SMs from 8 diverse cancer datasets covering 147 samples. In most cancers, including breast and ovarian, we found enrichment of protein binding and open chromatin in the vicinity of SM breakpoints at distances up to 200 kb. Furthermore, for all cancer types we observed an enhanced enrichment in regions distant from genes when compared to regions proximal to genes, suggesting that the SM-induction mechanism is independent from the bias of DSBs to occur near transcribed regions. We also observed a stronger effect for sites with more than one protein bound. Protein binding and open chromatin state are associated with nearby SM breakpoints in many cancer datasets. These observations suggest a consistent mechanism underlying SM locations across different cancers.


Lateral sinus thrombosis in children: a review.
A retrospective study was undertaken to review the clinical presentation, evaluation, management, and outcome of otogenic lateral sinus thrombosis (LST) in children. All pediatric patients with LST seen in our department between 1999 and 2007 were included; there were 9 cases involving 6 boys and 3 girls whose ages ranged from 8 to 12 years. They had all been treated with antibiotics elsewhere prior to admission, and the duration of symptoms before admission ranged from 5 to 18 days. The most common presenting symptoms were ear discharge, headache, otalgia, and fever. Radiologic evaluation included computed tomography and magnetic resonance imaging. All patients underwent radical mastoidectomy with incision of the lateral sinus and removal of its content. There were no deaths. Pseudomonas and Proteus spp were the most commonly identified organisms. Otogenic LST still poses a serious threat that warrants immediate attention and care. It is often associated with other intracranial complications, such as cerebellar abscess. Computed tomography and magnetic resonance imaging play an important role in the management of this disease. Early and aggressive surgical intervention of this otogenic complication can potentially minimize mortality.


Italian Pioneers in Cardionephrology: how some fundamental Italian cardiorenal researches have passed into oblivion.
A historical research was made on papers published by Italian scientists on cardiorenal diseases. The investigated period is between the beginning of the 20th century and the entry of Italy into the Second World War, 1940. 34 papers dealing with the relationship between the kidney and the cardiovascular system were retrieved. All but two articles were published in Italian medical periodicals. The topics covered are varied and range from cardiotoxicity of substances in uremia to the role of renal disease in vascular damage. Some articles are forerunners of later pathophysiological concepts and research technologies. These concern early atherosclerotic vascular damage and the presence of dialyzable cardiotoxic substances in renal insufficiency. Unfortunately, these highly innovative researches have had little diffusion and have fallen into oblivion in Italy and abroad. In conclusion, our research shows that in the first half of the 20th century in Italy there was a lively interest in cardio-renal diseases and that some researchers had produced precursor results of what was confirmed many years later.


Enhancement of lateral resolution and optical sectioning capability of two-photon fluorescence microscopy by combining temporal-focusing with structured illumination.
We demonstrate super-resolution imaging with background fluorescence rejection by interferometric temporal focusing microscopy, in which temporal focusing is combined with structured illumination. The lateral resolution and the optical sectioning capability are simultaneously improved by factors of 1.6 and 1.4, respectively, compared to conventional temporal focusing microscopy. Fluorescent beads (200 nm diameter) that are difficult to distinguish from the background fluorescence in conventional temporal focusing microscopy, are clearly visualized by interferometric temporal focusing microscopy.


Protracted venous infusion 5-fluorouracil with concomitant radiotherapy compared with bolus 5-fluorouracil for unresectable pancreatic cancer.
Radiation therapy (RT) with concurrent 5-fluorouracil (5-FU) administered by protracted venous infusion (PVI) replaced our prior institutional protocol of RT with bolus administration of 5-FU as standard therapy for unresectable pancreatic cancer in 1994. In this article, we compare the treatment intensity, toxicity, and outcome for patients with unresectable pancreatic cancer treated on these sequential protocols. Fifty-four patients, 27 on each protocol, with biopsy-confirmed pancreatic cancer received chemoradiotherapy. The radiotherapy field included the gross tumor volume and regional lymph nodes to a dose of 45 Gy, followed by "boost" to the gross tumor volume to 54 Gy to 60 Gy. From 1987 to 1994, patients received concurrent 5-FU administered by bolus injection, at a dose of 500 mg/m2 on days 1 to 3 and days 29 to 31 of RT. After December 1994, 5-FU was administered by PVI (200-250 mg/m2) beginning on day 1 and continuing until the completion of RT. The chemotherapy treatment intensity was increased in the group receiving 5-FU by PVI, as evidenced by an increased average weekly and cumulative dose of 5-FU (p < 0.01). The radiotherapy treatment intensity was equivalent between the two groups. The incidence of objectively quantified toxicity was not statistically different between treatment groups. Overall survival remained poor in both treatment groups. With a median follow-up of 18 months (range: 3-30 months) for surviving patients, the 6-month, 1-year, and 2-year survivals for the PVI 5-FU-treated group versus the bolus 5-FU-treated group were 56% versus 52%, 34% versus 18%, and 22% versus 13%, respectively (p = 0.9). Radiotherapy with concomitant 5-FU by PVI results in a greater weekly and total dose of chemotherapy. The method of 5-FU administration (bolus versus PVI) did not change the RT treatment intensity, experienced toxicity, or overall survival.


[Longitudinal study on osteoarthritis and bone metabolism].
The relationship between Osteoarthritis (OA) and Osteoporosis (OP) is not well defined due to lacking in longitudinal data, mainly regarding correlations between biochemical factors and OA incidence. Aim of this paper was to investigate the predictive value for OA incidence of bone mass variations and of selected biochemical markers in healthy women participating in a population-based longitudinal study carried out in Naples (Italy). High completion rate (85.2%) and statistically adequate sample size were obtained: 139 women (45 to 79 years of age) were examined and follow up visit was performed after two years (24+/-2 months), following the same protocol. Patients underwent medical examination, questionnaire, anthropometric measurements, blood sampling and urine collection. Bone mineral density (BMD) measurement was performed by dual energy X-ray absorptiometry (DEXA) at the lumbar spine (L1-L4) and femoral neck. Radiographs of dorsal and lumbar spine in lateral view were performed at basal and at 24 months visits; a team of three experts scored radiographs using Kellgren and Lawrence grading. The score was calculated for two individual radiographic features (narrowing of the joint space, presence of osteophytes) and as a global score. Results show a relevant percentage, 23% up, of subjects presenting both OA and OP. In the cross-sectional study the presence of osteophytosis correlates with anthropometric variables and PTH levels. In the longitudinal study results show a correlation between serum vitamin D and delta score for osteophytosis (beta=0.02 p<0.05). Data obtained outline the importance of further studies on the pathogenetic link between OA and bone metabolism.


A Bifunctional Anti-Amyloid Blocks Oxidative Stress and the Accumulation of Intraneuronal Amyloid-Beta.
There is growing recognition regarding the role of intracellular amyloid beta (Aβ) in the Alzheimer's disease process, which has been linked with aberrant signaling and the disruption of protein degradation mechanisms. Most notably, intraneuronal Aβ likely underlies the oxidative stress and mitochondrial dysfunction that have been identified as key elements of disease progression. In this study, we employed fluorescence imaging to explore the ability of a bifunctional small molecule to reduce aggregates of intracellular Aβ and attenuate oxidative stress. Structurally, this small molecule is comprised of a nitroxide spin label linked to an amyloidophilic fluorene and is known as spin-labeled fluorene (SLF). The effect of the SLF on intracellular Aβ accumulation and oxidative stress was measured in MC65 cells, a human neuronal cell line with inducible expression of the amyloid precursor protein and in the N2a neuronal cell line treated with exogenous Aβ. Super-resolution microscopy imaging showed SLF decreases the accumulation of intracellular Aβ. Confocal microscopy imaging of MC65 cells treated with a reactive oxygen species (ROS)-sensitive dye demonstrated SLF significantly reduces the intracellular Aβ-induced ROS signal. In order to determine the contributions of the separate SLF moieties to these protective activities, experiments were also carried out on cells with nitroxides lacking the Aβ targeting domain or fluorene derivatives lacking the nitroxide functionality. The findings support a synergistic effect of SLF in counteracting both the conformational toxicity of both endogenous and exogenous Aβ, its promotion of ROS, and Aβ metabolism. Furthermore, these studies demonstrate an intimate link between ROS production and Aβ oligomer formation.


Bluetongue, Schmallenberg - what is next? Culicoides-borne viral diseases in the 21st Century.
In the past decade, two pathogens transmitted by Culicoides biting midges (Diptera: Ceratopogonidae), bluetongue virus and Schmallenberg virus, have caused serious economic losses to the European livestock industry, most notably affecting sheep and cattle. These outbreaks of arboviral disease have highlighted large knowledge gaps on the biology and ecology of indigenous Culicoides species. With these research gaps in mind, and as a means of assessing what potential disease outbreaks to expect in the future, an international workshop was held in May 2013 at Wageningen University, The Netherlands. It brought together research groups from Belgium, France, Germany, Spain, Switzerland, United Kingdom and The Netherlands, with diverse backgrounds in vector ecology, epidemiology, entomology, virology, animal health, modelling, and genetics. Here, we report on the key findings of this workshop.


Low dose methotrexate in the first trimester of pregnancy: results of a French collaborative study.
To assess the risk of major malformations in pregnant women with chronic inflammatory disorders treated with low dose methotrexate (MTX) during the first trimester of pregnancy. Secondary outcomes included the rate of miscarriage, birth weight, and gestational age at delivery. Data from the French network of 31 pharmacovigilance centers and 2 teratology information services were analyzed. The outcome of pregnancy was prospectively assessed in women exposed during the first trimester of pregnancy. Data on maternal history and drug exposure were collected at the initial inquiry, and on the outcome of pregnancy at followup. Twenty-eight cases were available for analysis. MTX exposure ended before 8 weeks of gestation in 26 patients. Miscarriages occurred in 4 patients and 5 had elective termination of pregnancy. There were 19 live births, among whom 3 were premature. Birth weights in full-term children were within the expected range. One child exposed until 8.5 weeks of gestation had only minor anomalies (metatarsus varus and eyelid angioma). Although no definitive conclusion can be drawn, our results and the analysis of the literature support the conclusion that no strong teratogenic risk is associated with low dose MTX provided that the drug is discontinued as early as possible in pregnant women.


Catalytic Performance and Near-Surface X-ray Characterization of Titanium Hydride Electrodes for the Electrochemical Nitrate Reduction Reaction.
The electrochemical nitrate reduction reaction (NO3RR) on titanium introduces significant surface reconstruction and forms titanium hydride (TiHx, 0 < x ≤ 2). With ex situ grazing-incidence X-ray diffraction (GIXRD) and X-ray absorption spectroscopy (XAS), we demonstrated near-surface TiH2 enrichment with increasing NO3RR applied potential and duration. This quantitative relationship facilitated electrochemical treatment of Ti to form TiH2/Ti electrodes for use in NO3RR, thereby decoupling hydride formation from NO3RR performance. A wide range of NO3RR activity and selectivity on TiH2/Ti electrodes between -0.4 and -1.0 VRHE was observed and analyzed with density functional theory (DFT) calculations on TiH2(111). This work underscores the importance of relating NO3RR performance with near-surface electrode structure to advance catalyst design and operation.


Exposure to low level chronic radiation leads to adaptation to a subsequent acute X-ray dose and communication of modified acute X-ray induced bystander signals in medaka (Japanese rice fish, Oryzias latipes).
To determine the effect of acute high dose X-rays on the direct and bystander response of chronically exposed medaka in vivo using the fish communication model. Medaka were obtained from the Low Dose Rate Irradiation Facility (LoDIF) located at the Savannah River Ecology Laboratory (SREL), University of Georgia, Aiken, South Carolina, USA where they had been exposed over 264 days to cumulative total doses of 0, 0.03, 0.66 and 5.88 Gy. They were exposed to the acute dose at McMaster University and then allowed to swim with unexposed medaka. All groups were sacrificed and fins were cultured as explants and assayed using an established technique and reporter assay. Directly irradiated medaka with no chronic exposure showed a classic in vivo bystander response. Chronic pre-exposure resulted in a chronic dose-dependent increase in reporter cell survival in directly exposed fish. A 'pro-survival' response was also seen in the bystander fish. The proteins bcl-2 (b cell lymphoma 2) and c-Myc (myelocytomatosis oncogene cellular) in tissue explants were good predictors of pro-life or pro-death signals. Environmentally relevant chronic exposure to medaka in vivo results in adaptive responses in fish subsequently irradiated with high acute doses and in communication of protective signals to fish swimming with exposed fish. The data have implications for interpretation of radiation effects in biota.


Epigallocatechin-3-gallate inhibits growth of activated hepatic stellate cells by enhancing the capacity of glutathione synthesis.
Activation of hepatic stellate cells (HSC), the key effectors in hepatic fibrogenesis, is characterized by enhanced cell proliferation and overproduction of extracellular matrix. Oxidative stress promotes HSC activation. Glutathione (GSH) is the most important intracellular antioxidant, whose synthesis is mainly regulated by glutamate-cysteine ligase (GCL). We reported previously that (-)-epigallocatechin-3-gallate (EGCG), the major and most active component in green tea extracts, inhibited HSC activation. The aim of this study is to elucidate the underlying mechanisms. We hypothesize that this inhibitory effect of EGCG might mainly result from its antioxidant capability by increasing de novo synthesis of GSH. In this report, we observe that EGCG enhances the levels of cytoplasmic and mitochondrial GSH and increases GCL activity by inducing gene expression of the catalytic subunit GCLc, leading to de novo synthesis of GSH. Real-time polymerase chain reaction and Western blotting analyses show that de novo synthesis of GSH is required for EGCG to regulate the expression of genes relevant to apoptosis and to cell proliferation. Additional experiments demonstrate that exogenous transforming growth factor (TGF)-beta1 suppresses GCLc gene expression and reduces the level of GSH in cultured HSC. Transient transfection assays and Western blotting analyses further display that EGCG interrupts TGF-beta signaling by reducing gene expression of TGF-beta receptors and Smad4, leading to increased expression of GCLc. These results support our hypothesis and collectively demonstrate that EGCG increases the level of cellular GSH in HSC by stimulating gene expression of GCLc, leading to the inhibition of cell proliferation of activated HSC in vitro.


dRecQ4 is required for DNA synthesis and essential for cell proliferation in Drosophila.
The family of RecQ DNA helicases plays an important role in the maintenance of genomic integrity. Mutations in three of the five known RecQ family members in humans, BLM, WRN and RecQ4, lead to disorders that are characterized by predisposition to cancer and premature aging. To address the in vivo functions of Drosophila RecQ4 (dRecQ4), we generated mutant alleles of dRecQ4 using the targeted gene knock-out technique. Our data show that dRecQ4 mutants are homozygous lethal with defects in DNA replication, cell cycle progression and cell proliferation. Two sets of experiments suggest that dRecQ4 also plays a role in DNA double strand break repair. First, mutant animals exhibit sensitivity to gamma irradiation. Second, the efficiency of DsRed reconstitution via single strand annealing repair is significantly reduced in the dRecQ4 mutant animals. Rescue experiments further show that both the N-terminal domain and the helicase domain are essential to dRecQ4 function in vivo. The N-terminal domain is sufficient for the DNA repair function of dRecQ4. Together, our results show that dRecQ4 is an essential gene that plays an important role in not only DNA replication but also DNA repair and cell cycle progression in vivo.


Torsion sensitivity in NMR of aligned molecules: study on various substituted biphenyls.
To estimate the torsion sensitivity of dipolar coupling, biphenylic molecules were chosen as probes due to their relatively simple structure and the surprisingly high ambiguity of the only flexible parameter-the interring torsion angle. Solution structures of 4,4'-dibromobiphenyl and 4,4'-diiodobiphenyl are reported for the first time in two liquid crystals I52 and ZLI 1695. The comparison of NMR structures of various para-substituted biphenyls (BPs), calculated by the additive potential maximum entropy (APME) approach, shows that the small spread of torsion angle values in case of different solvents and para-substituents is in good agreement with theoretical expectations from hybrid density functional theory (DFT) methods. Furthermore, the real structural changes of interring torsion and the prevalence of solvent effects over para-halosubstitution can be correctly revealed from these small fluctuations.


Quantum Hall states observed in thin films of Dirac semimetal Cd3As2.
A well known semiconductor Cd3As2 has reentered the spotlight due to its unique electronic structure and quantum transport phenomena as a topological Dirac semimetal. For elucidating and controlling its topological quantum state, high-quality Cd3As2 thin films have been highly desired. Here we report the development of an elaborate growth technique of high-crystallinity and high-mobility Cd3As2 films with controlled thicknesses and the observation of quantum Hall effect dependent on the film thickness. With decreasing the film thickness to 10 nm, the quantum Hall states exhibit variations such as a change in the spin degeneracy reflecting the Dirac dispersion with a large Fermi velocity. Details of the electronic structure including subband splitting and gap opening are identified from the quantum transport depending on the confinement thickness, suggesting the presence of a two-dimensional topological insulating phase. The demonstration of quantum Hall states in our high-quality Cd3As2 films paves a road to study quantum transport and device application in topological Dirac semimetal and its derivative phases.


BAC TransgeneOmics: a high-throughput method for exploration of protein function in mammals.
The interpretation of genome sequences requires reliable and standardized methods to assess protein function at high throughput. Here we describe a fast and reliable pipeline to study protein function in mammalian cells based on protein tagging in bacterial artificial chromosomes (BACs). The large size of the BAC transgenes ensures the presence of most, if not all, regulatory elements and results in expression that closely matches that of the endogenous gene. We show that BAC transgenes can be rapidly and reliably generated using 96-well-format recombineering. After stable transfection of these transgenes into human tissue culture cells or mouse embryonic stem cells, the localization, protein-protein and/or protein-DNA interactions of the tagged protein are studied using generic, tag-based assays. The same high-throughput approach will be generally applicable to other model systems.


Allergic rhinitis in South Africa: 2012 guidelines.
Allergic rhinitis (AR) is an important disease in South Africa. The South African Allergic Rhinitis Working Group (SAARWG) has published previous guidelines for AR diagnosis and management. Areas of concern have arisen that require additional information, including the management of AR in infancy, appropriate and inappropriate allergy testing, cost of AR management, diagnosis and distinguishing the condition from sinusitis, use of over-the-counter medications, and the concept of the 'united airway'. Clinicians should consider the possibility of AR in infants with recurrent nasal symptoms. Allergy testing should be used wisely and based on local allergens. Total IgE testing is not routinely required to prove allergy. Acute and chronic sinusitis should be considered in conjunction with AR; treatment of rhinitis will improve these conditions. Over-the-counter medications should be used sparingly and with caution. Concern for long-term use of topical decongestants must be noted. Asthma should always be considered in AR diagnosis. Immunotherapy is available in SA and may be extremely useful in selected AR patients. The SAARWG proposed an algorithm for the diagnosis and management of rhinitis in South Africa. AR is common, important and troubling to patients; therefore, every effort should be made to target therapy correctly. Patient education is important in the management of AR.


Effects of vitamin A and D receptor gene polymorphisms/haplotypes on immune responses to measles vaccine.
Vitamins A and D, and their receptors, are important regulators of the immune system, including vaccine immune response. We assessed the association between polymorphisms in the vitamin A receptors [retinoic acid receptor α, retinoic acid receptor β (RARB), and retinoic acid receptor γ] and vitamin D receptor (VDR)/retinoid X receptor α (RXRA) genes and interindividual variations in immune responses after two doses of measles vaccine in 745 children. Using a tag single nucleotide polymorphism (SNP) approach, we genotyped 745 healthy children for the 391 polymorphisms in vitamin A receptor and VDR genes. The RARB haplotype (rs6800566/rs6550976/rs9834818) was significantly associated with variations in both measles antibody (global, P=0.013) and cytokine secretion levels, such as interleukin (IL)-10 (global, P=0.006), interferon (IFN)-α (global, P=0.008), and tumor necrosis factor-α (global, P=0.039) in the Caucasian subgroup. Specifically, the RARB haplotype, AAC, was associated with higher (t-statistic: 3.27, P=0.001) measles antibody levels. At the other end of the spectrum, haplotype GG for rs6550978/rs6777544 was associated with lower antibody levels (t-statistic: -2.32, P=0.020) in the Caucasian subgroup. In a sensitivity analysis, the RARB haplotype, CTGGGCAA, remained marginally significant (P<0.02) when the single SNP rs12630816 was included in the model for IL-10 secretion levels. A significant association was found between lower measles-specific IFN-γ Enzyme-linked immunosorbent spot responses and haplotypes rs11102986/rs11103473/rs11103482/rs10776909/rs12004589/rs35780541/rs2266677/rs875444 (global, P=0.004) and rs6537944/rs3118571 (global, P<0.001) in the RXRA gene for Caucasians. We also found associations between multiple RARB, VDR, and RXRA SNPs/haplotypes and measles-specific IL-2, IL-6, IL-10, IFN-α, IFN-γ, IFNλ-1, and TNF-α cytokine secretions. Our results suggest that specific allelic variations and haplotypes in the vitamin A receptor and VDR genes may influence adaptive immune responses to measles vaccine.


First Report of Powdery Mildew on Euphorbia pekinensis Caused by Podosphaera euphorbiae-helioscopiae in China.
Euphorbia pekinensis Rupr, the Peking spurge, is a perennial grass that is planted throughout northeast China. Its roots can be used as a Chinese medicine for diuretic or purgative purposes. Some diterpenoids isolated from Euphorbia spp. show strong antitumor, antivirus, skin-irritating, and tumor-promoting activities. Some species contain chemicals that can be used as pesticides. In September and October 2009, spurge plants were seriously infected by powdery mildew fungi in Changchun Agri-Expon, Jilin Province, China. White mildew colonies appeared in early autumn and initial colonies coalesced to cover the entire upper sides of leaves, stems, and petals 3 to 4 weeks after the disease was noticed. Until late October, chasmothecia were observed on leaves and stems and the infected areas also became dark brown. Mycelium was amphigenous, in patches, white, and persistent. Conidia with distinct fibrosin bodies were ellipsoid-cylindrical, 21.6 to 33.8 × 12 to 15.6 μm, and produced in chains. Germ tubes arose near a pole of the conidia and terminated in simple, unlobed apices. Conidiophores were 59.8 to 139.9 μm; foot cells were straight to slightly flexuous, followed by one to three cells, and 24 to 48 × 8.4 to 10.8 μm. Hyphal appressoria were papillate. Chasmothecia were 70 to 95 μm in diameter, averaging 79.4 μm, and were immersed in mycelia. Mycelioid appendages (5 to 12) occurred in the lower part of the chasmothecia and were flexuous, curved, thick walled, and strongly undulate. Appendages were long (349-) 490 to 1,000 (-1,300) μm, averaging 759.4 μm. They were often densely crowded around the chasmothecia. Asci were single, sessile or short stalked, 60 to 80 × 45 to 70 μm, and eight spored. Ascospores were ellipsoid-ovoid and 16.8 to 28.8 × 10.8 to 18 μm. The fungus was identified as Podosphaera euphorbiae-helioscopiae on the basis of morphological characteristics of the anamorphic and teleomorphic stages. An herbarium specimen was deposited in the Herbarium of Mycology of Jilin Agriculture University (CJLCC100). Genomic DNA was extracted from the chasmothecia, and the internal transcribed spacer region (ITS) and the D1/D2 domains of the 28S rDNA were amplified and sequenced (GenBank Nos. JF795490 and JF795491). The ITS sequence has 98% identity with those of Podosphaera lini, P. macularis, and P. spiraeae, and the D1-D2 sequence of 28S rDNA has 99% identity with those of P. negeri and P. spiraeae, which indicated that this fungus belongs to the genus Podosphaera, even though there is no direct sequence evidence that it is P. euphorbiae-helioscopiae. P. euphorbiae-helioscopiae has only been previously reported in Japan (2), occurring on Euphorbia helioscopia. This species is unique because of the long and curved, thick-walled appendages, and there is no comparable species (1). P. euphorbiae-hirtae and P. euphorbiae are reported to infect Euphorbiaceae plants. Both species differ from P. euphorbiae-helioscopiae in their conspicuously shorter appendages (1,3). To our knowledge, this is the first reported occurrence of powdery mildew on E. pekinensis, and P. euphorbiae-helioscopiae is new to China. This is also the first description of the anamorph of the fungus since there is no record in the Erysiphales Database. References: (1) U. Braun. Nova Hedwigia 89:1, 1987. (2) Y. Nomura. Taxonomical Study of Erysiphaceae of Japan. Yokendo LTD, Tokyo, 1997. (3) R. Y. Zheng and Y. N. Yu. Flora Fungorum Sinicorum. Vol. 1. Erysiphales. Science Press, Beijing, 1987.


Staged partial hepatectomy versus transarterial chemoembolization for the treatment of spontaneous hepatocellular carcinoma rupture: a multicenter analysis in Korea.
The aim of this study was to identify the prognostic factors and compare the long-term outcomes of staged hepatectomy and transarterial chemoembolization (TACE) for patients with spontaneous rupture of hepatocellular carcinoma (HCC). This study is a multicenter, retrospective analysis of patients with newly diagnosed ruptured HCC. To compare overall survival between staged hepatectomy group and TACE alone group, we performed propensity score-matching to adjust for significant differences in patient characteristics. To identify prognostic factors, the clinical characteristics at the time of diagnosis of tumor rupture were investigated using Cox-regression analysis. From 2000 to 2014, 172 consecutive patients with newly diagnosed ruptured HCC were treated in 6 Korean centers. One hundred seventeen patients with Child-Pugh class A disease were identified; of which 112 were initially treated with transcatheter arterial embolization (TAE) for hemostasis and five underwent emergency surgery for bleeder ligation. Of the 112 patients treated with TAE, 44 underwent staged hepatectomy, 61 received TACE alone, and 7 received conservative treatment after TAE. Those that underwent staged hepatectomy had significantly higher overall survival than those that underwent TACE alone before matching (P < 0.001) and after propensity score-matching (P = 0.006). Multivariate analysis showed that type of treatment, presence of portal vein thrombosis, pretreatment transfusion >1,200 mL, and tumor size >5 cm were associated with poor overall survival. Staged hepatectomy may offer better long-term survival than TACE alone for spontaneous rupture of HCC. Staged hepatectomy should be considered in spontaneous rupture of HCC with resectable tumor and preserved liver function.


Cloning and characterization of AtNUDT13, a novel mitochondrial Arabidopsis thaliana Nudix hydrolase specific for long-chain diadenosine polyphosphates.
A cDNA corresponding to the At3g26690 gene, which encodes a Nudix protein (AtNUDT13) with predicted mitochondrial localization, was isolated from an Arabidopsis thaliana library. The 202 amino acid AtNUDT13 polypeptide was overexpressed in Escherichia coli and purified to homogeneity. The preferred substrate for this hydrolase was diadenosine hexaphosphate (Ap(6)A), with K(m) and k(cat)/K(m) values of 0.61 mm and 16.0 x 10(3) m(-)1.s(-1), respectively. Optimal activity was at alkaline pH (8.5) with Mg(2+) (5 mm) as the cofactor. MS analysis revealed that the products of diadenosine hexaphosphate hydrolysis were ADP and adenosine tetraphosphate. Diadenosine pentaphosphate and adenosine tetraphosphate were additional substrates, but diadenosine tetraphosphate and diadenosine triphosphate, adenosine nucleotides, diphosphoinositol polyphosphate and phosphoribosyl pyrophosphate were not hydrolyzed. Chemical crosslinking and size exclusion chromatography demonstrated that the protein exists as a monomer in solution. Subcellular localization studies indicated that the AtNUDT13 protein is targeted to the mitochondria. This is the first description of a plant pyrophosphatase catalyzing the hydrolysis of long-chain diadenosine polyphosphates: molecules with multiple biological activities.


Identification of extremely premature infants at high risk of rehospitalization.
Extremely low birth weight infants often require rehospitalization during infancy. Our objective was to identify at the time of discharge which extremely low birth weight infants are at higher risk for rehospitalization. Data from extremely low birth weight infants in Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers from 2002-2005 were analyzed. The primary outcome was rehospitalization by the 18- to 22-month follow-up, and secondary outcome was rehospitalization for respiratory causes in the first year. Using variables and odds ratios identified by stepwise logistic regression, scoring systems were developed with scores proportional to odds ratios. Classification and regression-tree analysis was performed by recursive partitioning and automatic selection of optimal cutoff points of variables. A total of 3787 infants were evaluated (mean ± SD birth weight: 787 ± 136 g; gestational age: 26 ± 2 weeks; 48% male, 42% black). Forty-five percent of the infants were rehospitalized by 18 to 22 months; 14.7% were rehospitalized for respiratory causes in the first year. Both regression models (area under the curve: 0.63) and classification and regression-tree models (mean misclassification rate: 40%-42%) were moderately accurate. Predictors for the primary outcome by regression were shunt surgery for hydrocephalus, hospital stay of >120 days for pulmonary reasons, necrotizing enterocolitis stage II or higher or spontaneous gastrointestinal perforation, higher fraction of inspired oxygen at 36 weeks, and male gender. By classification and regression-tree analysis, infants with hospital stays of >120 days for pulmonary reasons had a 66% rehospitalization rate compared with 42% without such a stay. The scoring systems and classification and regression-tree analysis models identified infants at higher risk of rehospitalization and might assist planning for care after discharge.


Early awareness and uptake of an effective waiting room video intervention by STD clinics.
Successful diffusion and adoption is critical for the effectiveness and impact of a new intervention. The objective of this research was to evaluate the uptake and implementation of a newly released educational waiting room video in US sexually transmitted diseases (STD) Clinics. A telephone survey was administered to a random sample of 73 clinic directors representing 76 US STD clinics 3 to 5 months following the availability of the intervention. A qualitative analysis was used to categorize survey responses and detect associations among them. Of the 76 clinics, 22% were aware of the intervention and 17% had ordered the intervention kit. The most frequently reported sources for hearing about the video were interpersonal communication/word of mouth, national conferences, and the STDPreventionOnline.org Website. The majority (74%) of clinic directors reported using state or local entities as primary sources of new information; however, reporting these channels was associated with unawareness of the new intervention. Facilitators to adoption included having adequate video/DVD equipment (55%) and a separate, nonshared waiting room for STD services in which to show the video (47%). The data from this sample suggest that making greater use of prominent thought leaders and interpersonal communication, including social networking, and professional groups may improve awareness of new interventions. Some barriers to adoption, such as lack of equipment, have relatively inexpensive solutions yet bureaucratic or technical support issues may still play a role. However, some structural barriers, such as shared waiting areas, will require innovative alternatives to conventional practice.


Development of a Protein Scaffold for Arginine Sensing Generated through the Dissection of the Arginine-Binding Protein from Thermotoga maritima.
Arginine is one of the most important nutrients of living organisms as it plays a major role in important biological pathways. However, the accumulation of arginine as consequence of metabolic defects causes hyperargininemia, an autosomal recessive disorder. Therefore, the efficient detection of the arginine is a field of relevant biomedical/biotechnological interest. Here, we developed protein variants suitable for arginine sensing by mutating and dissecting the multimeric and multidomain structure of Thermotoga maritima arginine-binding protein (TmArgBP). Indeed, previous studies have shown that TmArgBP domain-swapped structure can be manipulated to generate simplified monomeric and single domain scaffolds. On both these stable scaffolds, to measure tryptophan fluorescence variations associated with the arginine binding, a Phe residue of the ligand binding pocket was mutated to Trp. Upon arginine binding, both mutants displayed a clear variation of the Trp fluorescence. Notably, the single domain scaffold variant exhibited a good affinity (~3 µM) for the ligand. Moreover, the arginine binding to this variant could be easily reverted under very mild conditions. Atomic-level data on the recognition process between the scaffold and the arginine were obtained through the determination of the crystal structure of the adduct. Collectively, present data indicate that TmArgBP scaffolds represent promising candidates for developing arginine biosensors.


When Neuroscience 'Touches' Architecture: From Hapticity to a Supramodal Functioning of the Human Brain.
In the last decades, the rapid growth of functional brain imaging methodologies allowed cognitive neuroscience to address open questions in philosophy and social sciences. At the same time, novel insights from cognitive neuroscience research have begun to influence various disciplines, leading to a turn to cognition and emotion in the fields of planning and architectural design. Since 2003, the Academy of Neuroscience for Architecture has been supporting 'neuro-architecture' as a way to connect neuroscience and the study of behavioral responses to the built environment. Among the many topics related to multisensory perceptual integration and embodiment, the concept of hapticity was recently introduced, suggesting a pivotal role of tactile perception and haptic imagery in architectural appraisal. Arguments have thus risen in favor of the existence of shared cognitive foundations between hapticity and the supramodal functional architecture of the human brain. Precisely, supramodality refers to the functional feature of defined brain regions to process and represent specific information content in a more abstract way, independently of the sensory modality conveying such information to the brain. Here, we highlight some commonalities and differences between the concepts of hapticity and supramodality according to the distinctive perspectives of architecture and cognitive neuroscience. This comparison and connection between these two different approaches may lead to novel observations in regard to people-environment relationships, and even provide empirical foundations for a renewed evidence-based design theory.


The identification of response regulator-specific binding sites reveals new roles of two-component systems in Bacillus cereus and closely related low-GC Gram-positives.
In bacteria, environmental challenges are often translated into a transcriptional response via the cognate response regulators (RRs) of specialized two-component systems (TCSs). A phylogenetic footprinting/shadowing approach was designed and used to identify many novel RR-specific operators for species of the Bacillus cereus group and related Gram-positives. Analysis of the operator sequences revealed characteristic traits for each RR subfamily. For instance, operators related to the largest subfamily (OmpR) typically consisted of direct repeats (e.g. TTAAGA-N5-TTAAGA), whereas operators related to the second largest family (NarL) consisted of inverted repeats (e.g. ATGACA-N2-TGTCAT). This difference indicates a fundamentally different organization of the bound RR dimers between the two subfamilies. Moreover, the identification of the specific operator motifs allowed relating several RRs to a minimal regulon and thereby to a characteristic transcriptional response. Mostly, these regulons comprised genes encoding transport systems, suggesting a direct coupling of stimulus perception to the transport of target compounds. New biological roles could be attributed to various TCSs, including roles in cytochrome c biogenesis (HssRS), transport of carbohydrates, peptides and/or amino acids (YkoGH, LytSR), and resistance to toxic ions (LiaSR), antimicrobial peptides (BceRS) and beta-lactam antibiotics (BacRS, YcbLM). As more and more bacterial genome sequences are becoming available, the use of comparative analyses such as the approach applied in this study will further increase our knowledge of bacterial signal transduction mechanisms and provide directions for the assessment of their role in bacterial performance and survival strategies.


Associations between body mass index and the risk of renal events in patients with type 2 diabetes.
We aimed to evaluate the relationship between BMI and the risk of renal disease in patients with type 2 diabetes in the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) study. Participants were divided into six baseline BMI categories: <18.5 (underweight, n = 58); ≥18.5 to <25 (normal, n = 2894); ≥25 to <30 (overweight, n = 4340); ≥30 to <35 (obesity grade 1, n = 2265); ≥35 to <40 (obesity grade 2, n = 744); and ≥40 kg/m2 (obesity grade 3, n = 294); those underweight were excluded. The composite outcome "major renal event" was defined as development of new macroalbuminuria, doubling of creatinine, end stage renal disease, or renal death. These outcomes and development of new microalbuminuria were considered individually as secondary endpoints. During 5-years of follow-up, major renal events occurred in 487 (4.6%) patients. The risk increased with higher BMI. Multivariable-adjusted HRs (95% CIs), compared to normal weight, were: 0.91 (0.72-1.15) for overweight; 1.03 (0.77-1.37) for obesity grade 1; 1.42 (0.98-2.07) for grade 2; and 2.16 (1.34-3.48) for grade 3 (p for trend = 0.006). These findings were similar across subgroups by randomised interventions (intensive versus standard glucose control and perindopril-indapamide versus placebo). Every additional unit of BMI over 25 kg/m2 increased the risk of major renal events by 4 (1-6)%. Comparable results were observed with the risk of secondary endpoints. Higher BMI is an independent predictor of major renal events in patients with type 2 diabetes. Our findings encourage weight loss to improve nephroprotection in these patients.