Broken bodies, healing spirits: road trauma survivor's perceptions of pastoral care during inpatient orthopaedic rehabilitation.
The aim of this article is to present findings from an Australian study that explored road trauma survivors' perceptions of spirituality and of a hospital-based pastoral care service throughout their inpatient rehabilitation. All participants had experienced severe orthopaedic injury. A mixed-method research design was used. The survey method elicited demographic, pastoral care contact and hospitalisation data. It included the Posttraumatic Growth Inventory (PTGI; Tedeschi and Calhoun 1996) and an adapted World Health Organisation Pastoral Intervention (WHO 2002) coding schema (Constitution of the World Health Organisation, basic documents, supplement. 45 ed.). An interview method was used to elicit information about participants' prior and current experiences of faith and spirituality, expectations, and experiences of the pastoral care service, and perceptions of the role of pastoral care in their rehabilitation. A thematic analysis of both quantitative and qualitative data identified nine core themes of supportive pastoral care. Pastoral care was seen as a valued and supportive intervention. Participants who completed the PTGI reported at least some degree of posttraumatic growth. Further research is recommended to examine the role and efficacy of pastoral care that is integral to road trauma recovery support.


Nanoparticles as Nonfluorescent Analogues of Fluorophores for Optical Nanoscopy.
Optical microscopy modalities that achieve spatial resolution beyond the resolution limit have opened up new opportunities in the biomedical sciences to reveal the structure and kinetics of biological processes on the nanoscale. These methods are, however, mostly restricted to fluorescence as contrast mechanism, which limits the ultimate spatial resolution and observation time that can be achieved by photobleaching of the fluorescent probes. Here, we demonstrate that Raman scattering provides a valuable contrast mechanism for optical nanoscopy in the form of super-resolution structured illumination microscopy. We find that nanotags, i.e., gold and silver nanoparticles that are capable of surface-enhanced Raman scattering (SERS), can be imaged with a spatial resolution beyond the diffraction limit in four dimensions alongside and with similar excitation power as fluorescent probes. The highly polarized nature of super-resolution structured illumination microscopy renders these nanotags elliptical in the reconstructed super-resolved images, which enables us to determine their orientation within the sample. The robustness of nanotags against photobleaching allows us to image these particles for unlimited periods of time. We demonstrate this by imaging isolated nanotags in a dense layer of fluorophores, as well as on the surface of and after internalization by osteosarcoma cells, always in the presence of fluorescent probes. Our results show that SERS nanotags have the potential to become highly multiplexed and chemically sensitive optical probes for optical nanoscopy that can replace fluorophores in applications where fluorescence photobleaching is prohibitive for following the evolution of biological processes for extended times.


Effect of maternal chronic disease on obstetric complications in twin pregnancies in a United States cohort.
To evaluate the effect of maternal chronic disease on obstetric complications among twin pregnancies. Multicenter, retrospective, observational study. Clinical centers (19 hospitals). Twin pregnancies (n = 4,821) delivered ≥ 23 weeks of gestation and classified by maternal chronic disease (either none or any of the following: asthma, depression, hypertension, diabetes, and heart, thyroid, gastrointestinal or renal disease). None. Gestational age at delivery, gestational hypertension, pre-eclampsia, gestational diabetes, placental abruption, placenta previa, hemorrhage, chorioamnionitis, maternal postpartum fever, premature rupture of membranes, labor onset (spontaneous vs. nonspontaneous), route of delivery, and maternal admission to intensive care unit. Women with chronic disease delivered earlier (mean gestational length, 34.1 vs. 34.6 weeks) and were less likely to have term birth (risk ratio 0.80; 95% confidence interval 0.70-0.90). Cesarean delivery after spontaneous labor (risk ratio 1.20; 95% confidence interval 1.05-1.37) was also increased with chronic disease. No statistically significant effects were observed for other complications studied. Women who used assisted reproductive technology were more likely to hemorrhage, independent of chronic disease, but other findings were generally similar to the non-assisted reproductive technology sample. Chronic disease was associated with additional risk of earlier delivery and cesarean section after spontaneous labor in a nationwide sample of US twin pregnancies.


Quality of life and communication in orthognathic treatment.
The primary aim was to determine what, if any, relationships exist between communication and quality of life in patients receiving orthognathic treatment since this has not been explored. A secondary aim was to compare the Quality of Life (QoL) of a pre-treatment sample with those at 2 years post-surgery. A cross-sectional questionnaire method was used. Outpatient clinics providing orthognathic treatment at four UK hospital sites. Two separate samples of pre-treatment (n = 73) and 2-year post-surgery (n = 78) patients participated in the study. At clinic appointments, all eligible patients were invited to complete the Orthognathic Quality of Life Questionnaire (OQLQ), a previously validated condition-specific quality of life measure. At the same time, participants at the 2-year post-surgery stage also completed a second short questionnaire, the Communication Assessment Tool-Team (CAT-T), where they rated the quality of communication they had received during treatment. One hundred and fifty-one complete responses were received. The average age was 24.5 years (S.D. 9.77) and the majority (67%) were female in both groups. Statistically significant associations were found between QoL and quality of communication in the treated sample. Findings also showed a comparatively poorer QoL for the pre-treatment participants. This reduced QoL was more pronounced in females than males for all aspects except dentofacial appearance. There was an improvement in QoL for patients at 2 years post-surgery compared to pre-treatment. There is an association between QoL and quality of communication as reported by participants at 2 years post-surgery. These novel findings are similar to outcomes in other patient settings such as oncology, but further investigation is required to establish the direction of cause and effect.


Fixation of periprosthetic or osteoporotic distal femoral fractures with locking plates: a pilot randomised controlled trial.
We hypothesised that the use of a polyaxial locking plate design offers the same clinical benefits as a monoaxial locking plate system following distal femoral osteoporotic/periprosthetic fracture fixation. A multicentre prospective randomised pilot trial was conducted. Inclusion criteria were patients over 60 years with a displaced osteoporotic or periprosthetic distal femoral fracture. Details documented included time to union, complications, reinterventions and functional outcomes according to the Oxford knee score and EuroQol EQ-5D. Analysis of factors influencing an early fracture healing response was performed between those with clear features of radiological callus formation at three months. Statistical analysis was performed using a logistic regression model with multiple covariates assessed for each plate system (1:1 ratio) over a follow-up period of one year. Forty patients (34 females) with a mean age of 77 (60-99) were recruited. Four patients deceased within the first six months. Twenty-five patients united by the six month follow-up. Six more patients progressed to union between six and nine months. Five patients developed non-union (two patients had implant failure; one in each group) and all underwent revision surgery. Malunion was evident in two cases, one with 15° of valgus (monoaxial plate), and one with 12° of recurvatum (polyaxial plate). Between the two plate systems, statistical analysis revealed no significant differences in most of the recorded parameters. Radiological features of early bone healing were present when the surgical approach was smaller (p = 0.015), and when a greater working length of the bridging plate was present (p = 0.016). Both plate systems demonstrated good union rates and limited implant related complications. Good reduction, mechanically sound construct and respect of the local fracture biology was more important than the particular plate design characteristics.


Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height.
Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10(-8)). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10(-11)). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.


The Potato MAP3K StVIK Is Required for the Phytophthora infestans RXLR Effector Pi17316 to Promote Disease.
Plant pathogens deliver effectors to manipulate processes in their hosts, creating a suitable environment for invasion and proliferation. Yet, little is known about the host proteins that are targeted by effectors from filamentous pathogens. Here, we show that stable transgenic expression in potato (Solanum tuberosum) and transient expression in Nicotiana benthamiana of the arginine-any amino acid-leucine-arginine effector Pi17316 enhances leaf colonization by the late blight pathogen Phytophthora infestans Expression of Pi17316 also attenuates cell death triggered by the pathogen-associated molecular pattern Infestin1 (INF1), indicating that the effector suppresses pattern-triggered immunity. However, this effector does not attenuate cell death triggered by a range of resistance proteins, showing that it specifically suppresses INF1-triggered cell death (ICD). In yeast two-hybrid assays, Pi17316 interacts directly with the potato ortholog of VASCULAR HIGHWAY1-interacting kinase (StVIK), encoding a predicted MEK kinase (MAP3K). Interaction in planta was confirmed by coimmunoprecipitation and occurs at the plant plasma membrane. Virus-induced gene silencing of VIK in N. benthamiana attenuated P. infestans colonization, whereas transient overexpression of StVIK enhanced colonization, indicating that this host protein acts as a susceptibility factor. Moreover, VIK overexpression specifically attenuated ICD, indicating that it is a negative regulator of immunity. The abilities of Pi17316 to enhance P. infestans colonization or suppress ICD were compromised significantly in NbVIK-silenced plants, demonstrating that the effector activity of Pi17316 is mediated by this MAP3K. Thus, StVIK is exploited by P. infestans as a susceptibility factor to promote late blight disease.


How do microRNAs regulate gene expression?
Several thousand human genes, amounting to about one-third of the whole genome, are potential targets for regulation by the several hundred microRNAs (miRNAs) encoded in the genome. The regulation occurs posttranscriptionally and involves the approximately 21-nucleotide miRNA interacting with a target site in the mRNA that generally has imperfect complementarity to the miRNA. The target sites are almost invariably in the 3'-untranslated region of the messenger RNA (mRNA), often in multiple copies. Metazoan miRNAs were previously thought to down-regulate protein expression by inhibiting target mRNA translation at some stage after the translation initiation step, without much effect on mRNA abundance. However, recent studies have questioned these suppositions. With some targets, an increase in the rate of mRNA degradation by the normal decay pathway contributes to the decrease in protein expression. miRNAs can also inhibit translation initiation, specifically the function of the cap-binding initiation factor, eIF4E. Repressed target mRNAs as well as miRNAs themselves accumulate in cytoplasmic foci known as P-bodies, where many enzymes involved in mRNA degradation are concentrated. However, P-bodies may also serve as repositories for the temporary and reversible storage of untranslated mRNA, and reducing the expression (knockdown) of several distinct P-body protein components can alleviate miRNA-mediated repression of gene expression.


Effect of fibrinogen degradation products and lung ground substance on surfactant function.
Acute lung injury syndromes have many characteristics including protein-rich alveolar edema, hyaline membranes, and abnormal surface tension at the alveolar air-liquid interface. Increased surface tension can occur because of a relative surfactant deficiency and/or dysfunction. It has been previously demonstrated that surfactant dysfunction occurs when plasma protein inhibitors leak into the alveolar space during the induction of the lung injury and edema formation. The present study investigated whether inhibitors that would be generated during the stage of repair from lung injury could impair surfactant function. We determined whether fibrinogen degradation products (FDP) which would be released during lysis of the fibrin(ogen)-containing alveolar exudate and hyaline membranes, and components of the lungs' ground substance could inhibit the in vitro function of a lipid extract surfactant preparation. FDP were prepared by incubating human fibrinogen with plasmin or neutrophil elastase for 4 min to 60 h and were characterized by SDS-PAGE. Early (fragment X and Y) and late (fragment D and E) plasmin-derived FDP (MW greater than 40,000) inhibited surfactant function as assessed by a bubble surfactometer. The early elastase-derived FDP also inhibited surfactant, but the later and much smaller fragments (MW less than 15,000) did not affect surfactant function. Laminin also inhibited surfactant in a dose-dependent manner. Neither hyaluronic acid nor heparan sulfate affected surfactant performance in vitro. We conclude that plasmin-induced lysis of intraalveolar fibrinogen and hyaline membranes will result in prolonged generation (i.e. days) of surfactant inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)


Colonization and genetic diversification processes of Leishmania infantum in the Americas.
Leishmania infantum causes visceral leishmaniasis, a deadly vector-borne disease introduced to the Americas during the colonial era. This non-native trypanosomatid parasite has since established widespread transmission cycles using alternative vectors, and human infection has become a significant concern to public health, especially in Brazil. A multi-kilobase deletion was recently detected in Brazilian L. infantum genomes and is suggested to reduce susceptibility to the anti-leishmanial drug miltefosine. We show that deletion-carrying strains occur in at least 15 Brazilian states and describe diversity patterns suggesting that these derive from common ancestral mutants rather than from recurrent independent mutation events. We also show that the deleted locus and associated enzymatic activity is restored by hybridization with non-deletion type strains. Genetic exchange appears common in areas of secondary contact but also among closely related parasites. We examine demographic and ecological scenarios underlying this complex L. infantum population structure and discuss implications for disease control.


Effect of an anti-inflammatory dose of prednisone on thyroid hormone monitoring in hypothyroid dogs.
It is not uncommon for a hypothyroid dog to be receiving concurrent corticosteroids. As hypothyroid dogs receiving thyroid supplement need periodic monitoring, knowledge of whether prednisone alters thyroid hormone concentrations would be useful to determine whether testing can or should be done while the dog is receiving therapy and whether dose adjustments are appropriate. In this study, the effect of short-term anti-inflammatory prednisone was determined in dogs with naturally occurring hypothyroidism. Eight adult dogs were given prednisone (1.0 mg/kg, orally) daily for 7 days and then on alternate days for 14 days. Serum total thyroxine (T(4) ), free T(4) (fT(4) ), and thyroid-stimulating hormone (TSH) were measured on days 7, 21 and 28 and compared with baseline data. Total T(4) concentrations were significantly decreased after 7 days of anti-inflammatory prednisone, but were not significantly altered from baseline on days 21 or 28. Free T(4) and TSH concentrations were not significantly altered from baseline at any point during the study. Two dogs had decreased total T(4) concentrations on day 7, which may have resulted in an alteration in thyroid supplementation. Results showed that administration of prednisone at a dosage of 1 mg/kg, orally, once daily for 7 days decreased total T(4) , while fT(4) was unchanged, suggesting that fT(4) may be less affected by daily prednisone administration. Anti-inflammatory doses of prednisone administered every other day did not interfere with thyroid hormone monitoring.


Effects of Different Dietary Interventions on Blood Pressure: Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Previous studies have shown beneficial effects of individual dietary approaches for blood pressure (BP) control, but their relative effectiveness is not well established. We performed a systematic review of published dietary pattern interventions and estimated the aggregate BP effects through meta-analysis. PubMed, EMBASE, and Web of Science databases were searched to identify studies published between January 1, 1990 and March 1, 2015. Studies meeting specific inclusion and exclusion criteria were selected. Data were pooled using random effects meta-analysis models. Twenty-four trials with 23 858 total participants were included. The overall pooled net effect of dietary intervention on systolic BP and diastolic BP was -3.07 mm Hg (95% confidence interval, -3.85 to -2.30) and -1.81 mm Hg (95% confidence interval, -2.24 to -1.38), respectively. The Dietary Approaches to Stop Hypertension diet had the largest net effect (systolic BP, -7.62 mm Hg [95% confidence interval, -9.95 to -5.29] and diastolic BP, -4.22 mm Hg [95% confidence interval, -5.87 to -2.57]). Low-sodium; low-sodium, high-potassium; low-sodium, low-calorie; and low-calorie diets also led to significant systolic and diastolic BP reductions, whereas Mediterranean diet participants experienced a significant incremental reduction in diastolic but not systolic BP. Subgroup analysis also showed important variations in effectiveness based on duration, size, and participant demographics. In conclusion, dietary modifications are associated with clinically meaningful, though variable, reductions in BP. Some diets are more effective than others and under different circumstances, which has important implications from both clinical and public health perspectives.


caBIG VISDA: modeling, visualization, and discovery for cluster analysis of genomic data.
The main limitations of most existing clustering methods used in genomic data analysis include heuristic or random algorithm initialization, the potential of finding poor local optima, the lack of cluster number detection, an inability to incorporate prior/expert knowledge, black-box and non-adaptive designs, in addition to the curse of dimensionality and the discernment of uninformative, uninteresting cluster structure associated with confounding variables. In an effort to partially address these limitations, we develop the VIsual Statistical Data Analyzer (VISDA) for cluster modeling, visualization, and discovery in genomic data. VISDA performs progressive, coarse-to-fine (divisive) hierarchical clustering and visualization, supported by hierarchical mixture modeling, supervised/unsupervised informative gene selection, supervised/unsupervised data visualization, and user/prior knowledge guidance, to discover hidden clusters within complex, high-dimensional genomic data. The hierarchical visualization and clustering scheme of VISDA uses multiple local visualization subspaces (one at each node of the hierarchy) and consequent subspace data modeling to reveal both global and local cluster structures in a "divide and conquer" scenario. Multiple projection methods, each sensitive to a distinct type of clustering tendency, are used for data visualization, which increases the likelihood that cluster structures of interest are revealed. Initialization of the full dimensional model is based on first learning models with user/prior knowledge guidance on data projected into the low-dimensional visualization spaces. Model order selection for the high dimensional data is accomplished by Bayesian theoretic criteria and user justification applied via the hierarchy of low-dimensional visualization subspaces. Based on its complementary building blocks and flexible functionality, VISDA is generally applicable for gene clustering, sample clustering, and phenotype clustering (wherein phenotype labels for samples are known), albeit with minor algorithm modifications customized to each of these tasks. VISDA achieved robust and superior clustering accuracy, compared with several benchmark clustering schemes. The model order selection scheme in VISDA was shown to be effective for high dimensional genomic data clustering. On muscular dystrophy data and muscle regeneration data, VISDA identified biologically relevant co-expressed gene clusters. VISDA also captured the pathological relationships among different phenotypes revealed at the molecular level, through phenotype clustering on muscular dystrophy data and multi-category cancer data.


Oxidized BAL fluid proteins in patients with interstitial lung diseases.
Oxygen-derived free radicals, released by phagocytic cells, have been postulated to contribute to lung tissue damage. We therefore investigated oxidative damage to proteins from bronchoalveolar lavage fluid (BALF) as an indicator of oxidative stress and to assess antioxidant defences in the lungs. We examined BAL fluids from patients with interstitial lung diseases, such as idiopathic pulmonary fibrosis (IPF, nonsmokers (NS) and smokers (S)), sarcoidosis (SARC, nonsmokers), and asbestosis (ASB, ex-smokers (EXS)). The oxidation of BALF proteins is accompanied by the introduction of carbonyl groups into their amino acid side-chains and can be quantitated by labeling these groups with tritiated borohydride. The total lung content of oxidized proteins recovered by bronchoalveolar lavage (BAL) was 0.3 +/- 0.07 nmol carbonyl.mL-1 BALF (mean +/- SEM) in the NS control group (n = 9) and tended to be increased, in the asymptomatic S group (n = 8; 0.59 +/- 0.14 nmol.mL-1). This parameter was significantly elevated both in IPF-NS (n = 14; 0.84 +/- 0.2 nmol carbonyl.mL-1 BALF) and SARC-NS (n = 15; 0.73 +/- 0.16 nmol.mL-1) as compared with the NS control. On the contrary, in smoking patients with IPF (n = 6; 0.41 +/- 0.1 nmol carbonyl.mL-1 BALF) and also in ASB-EXS (n = 6; 0.37 +/- 0.06 nmol.mL-1) it was not different from NS controls. The total amount of oxidized proteins correlated positively with the absolute number of eosinophils (EOS) in IPF-NS, IPF-S and SARC, and also with absolute polymorphonuclear neutrophil (PMN) numbers in IPF-NS and IPF-S. In conclusion, oxidative damage of BALF proteins occurred in nonsmoking patients with IPF and SARC. The amount of oxidized bronchoalveolar lavage fluid protein may provide a quantitative assessment of oxygen burden, a balance between oxidant stress and antioxidant defences.


Primary familial brain calcification linked to deletion of 5' noncoding region of SLC20A2.
Primary familial brain calcification (PFBC) is a rare neurological disease often inherited as a dominant trait. Mutations in four genes (SLC20A2, PDGFB, PDGFRB, and XPR1) have been reported in patients with PFBC. Of these, point mutations or small deletions in SLC20A2 are most common. Thus far, only one large deletion covering entire SLC20A2 and several smaller, exonic deletions of SLC20A2 have been reported. The aim of this study was to identify the causative gene defect in a Finnish PFBC family with three affected patients. A Finnish family with three PFBC patients and five unaffected subjects was studied. Sanger sequencing was used to exclude mutations in the coding and splice site regions of SLC20A2, PDGFRB, and PDGFB. Whole-exome (WES) and whole-genome sequencing (WGS) were performed to identify the causative mutation. A SNP array was used in segregation analysis. Copy number analysis of the WGS data revealed a heterozygous deletion of ~578 kb on chromosome 8. The deletion removes the 5' UTR region, the noncoding exon 1 and the putative promoter region of SLC20A2 as well as the coding regions of six other genes. Our results support haploinsufficiency of SLC20A2 as a pathogenetic mechanism in PFBC. Analysis of copy number variations (CNVs) is emerging as a crucial step in the molecular genetic diagnostics of PFBC, and it should not be limited to coding regions, as causative variants may reside in the noncoding parts of known disease-associated genes.


Genome-wide identification of significant aberrations in cancer genome.
Somatic Copy Number Alterations (CNAs) in human genomes are present in almost all human cancers. Systematic efforts to characterize such structural variants must effectively distinguish significant consensus events from random background aberrations. Here we introduce Significant Aberration in Cancer (SAIC), a new method for characterizing and assessing the statistical significance of recurrent CNA units. Three main features of SAIC include: (1) exploiting the intrinsic correlation among consecutive probes to assign a score to each CNA unit instead of single probes; (2) performing permutations on CNA units that preserve correlations inherent in the copy number data; and (3) iteratively detecting Significant Copy Number Aberrations (SCAs) and estimating an unbiased null distribution by applying an SCA-exclusive permutation scheme. We test and compare the performance of SAIC against four peer methods (GISTIC, STAC, KC-SMART, CMDS) on a large number of simulation datasets. Experimental results show that SAIC outperforms peer methods in terms of larger area under the Receiver Operating Characteristics curve and increased detection power. We then apply SAIC to analyze structural genomic aberrations acquired in four real cancer genome-wide copy number data sets (ovarian cancer, metastatic prostate cancer, lung adenocarcinoma, glioblastoma). When compared with previously reported results, SAIC successfully identifies most SCAs known to be of biological significance and associated with oncogenes (e.g., KRAS, CCNE1, and MYC) or tumor suppressor genes (e.g., CDKN2A/B). Furthermore, SAIC identifies a number of novel SCAs in these copy number data that encompass tumor related genes and may warrant further studies. Supported by a well-grounded theoretical framework, SAIC has been developed and used to identify SCAs in various cancer copy number data sets, providing useful information to study the landscape of cancer genomes. Open-source and platform-independent SAIC software is implemented using C++, together with R scripts for data formatting and Perl scripts for user interfacing, and it is easy to install and efficient to use. The source code and documentation are freely available at http://www.cbil.ece.vt.edu/software.htm.


Avoiding transfusions in children undergoing cardiac surgery: a meta-analysis of randomized trials of aprotinin.
Aprotinin, a potent antifibrinolytic drug, reduces the proportion of adults who receive blood transfusions during cardiac surgery, although the effect in children remains unclear. We performed a systematic review of the literature to identify all English language, randomized controlled trials of aprotinin involving children undergoing corrective or palliative cardiac surgery with cardiopulmonary bypass. All studies were assessed for methodological quality, and sources of heterogeneity were examined. We measured the effect of aprotinin on the proportion of children transfused, the volume of blood transfused, and the volume of chest tube drainage. Twelve trials enrolling 626 eligible children met the inclusion criteria. Aprotinin reduced the proportion of children who received red blood cell or whole blood transfusions during cardiac surgery by 33% (relative risk = 0.67; 95% confidence interval, 0.51 to 0.89). Aprotinin did not have a significant effect on the volume of blood transfused or on the amount of postoperative chest tube drainage. Most of the studies were of poor methodological quality and predefined transfusion triggers were infrequently used. Overall, aprotinin reduced the proportion of children who received blood transfusion during cardiac surgery with cardiopulmonary bypass. Further high-quality trials with clinically important outcomes may be warranted before aprotinin can be routinely recommended in this population.


Effects of moisture on soil microorganisms and nematodes: A field experiment.
The effects of soil moisture changes on bacteria, fungi, protozoa, and nematodes and changes in oxygen consumption were studied in a field experiment. In one plot the soil was drip-irrigated daily for 10 days, while an adjacent plot experienced one rainfall and was then allowed to dry out. Oxygen consumption was the parameter measured which responded most rapidly to changes in soil moisture content. Lengths of fluorescein diacetate-active hyphae paralleled oxygen consumption in both plots. Total hyphal length was not affected by one rainfall but increased from 700 mg(-1) dry weight soil to more than 1,600 m in less than 10 days in the irrigated plot. In the rain plot, bacterial numbers doubled within 3 days and declined during the following period of drought. In the irrigated plot, numbers increased by 50% and then remained constant over the duration of the study. Only small changes in protozoan numbers were observed, with the exception of the last sampling date in the irrigated plot when large numbers of naked amoebae were recorded 2 days after a large natural rainfall. Nematode numbers, especially obligate root feeders, increased in both treatments. The increases were caused by decoiling rather than growth. The results indicate that fungal respiration was dominating, while bacteria, lacking a suitable source of energy, were less active, except for the first days.


DN2 Thymocytes Activate a Specific Robust DNA Damage Response to Ionizing Radiation-Induced DNA Double-Strand Breaks.
For successful bone marrow transplantation (BMT), a preconditioning regime involving chemo and radiotherapy is used that results in DNA damage to both hematopoietic and stromal elements. Following radiation exposure, it is well recognized that a single wave of host-derived thymocytes reconstitutes the irradiated thymus, with donor-derived thymocytes appearing about 7 days post BMT. Our previous studies have demonstrated that, in the presence of donor hematopoietic cells lacking T lineage potential, these host-derived thymocytes are able to generate a polyclonal cohort of functionally mature peripheral T cells numerically comprising ~25% of the peripheral T cell pool of euthymic mice. Importantly, we demonstrated that radioresistant CD44+ CD25+ CD117+ DN2 progenitors were responsible for this thymic auto-reconstitution. Until recently, the mechanisms underlying the radioresistance of DN2 progenitors were unknown. Herein, we have used the in vitro "Plastic Thymus" culture system to perform a detailed investigation of the mechanisms responsible for the high radioresistance of DN2 cells compared with radiosensitive hematopoietic stem cells. Our results indicate that several aspects of DN2 biology, such as (i) rapid DNA damage response (DDR) activation in response to ionizing radiation-induced DNA damage, (ii) efficient repair of DNA double-strand breaks, and (iii) induction of a protective G1/S checkpoint contribute to promoting DN2 cell survival post-irradiation. We have previously shown that hypoxia increases the radioresistance of bone marrow stromal cells in vitro, at least in part by enhancing their DNA double-strand break (DNA DSB) repair capacity. Since the thymus is also a hypoxic environment, we investigated the potential effects of hypoxia on the DDR of DN2 thymocytes. Finally, we demonstrate for the first time that de novo DN2 thymocytes are able to rapidly repair DNA DSBs following thymic irradiation in vivo.


Is occupation a good predictor of self-rated health in China?
China's rapidly changing economic landscape has led to widening social inequalities. Occupational status in terms of occupational type and prestige may reflect these socio-structural shifts of social position and be more predictive of self-rated health status than income and education, which may only reflect more gradual acquisitions of social status over time. The goals of this study were to understand the role of occupational status in predicting self-rated health, which is well known to be associated with long-term mortality, as well as compare the occupational status to the other major socioeconomic indicators of income and education. Data from the 2010 baseline surveys of the China Family Panel Studies, which utilized multi-stage probability sampling with implicit stratification was used. Logistic regression was used to examine the relationship of various socioeconomic indicators (i.e. occupational status, income, and education) with self-rated health as the primary outcome of interest. A series of models considered the associations of occupational category or occupational prestige with self-rated health. The final sample consisted of 14,367 employed adults aged 18-60, which was nationally representative of working adults in China. We found that occupation was not a major predictor of self-rated health in China when age, ethnicity, location, marital status, physical and mental health status were controlled for, with the exception of women working in lower grade management and professional jobs (OR = 1.82, 95% CI: 1.03-3.22). In comparison, income followed by education exhibited greater association with self-rated health. The highest income group had the least probability to report poor health (In men: OR = 0.30, 95% CI: 0.21-0.43. In women: OR = 0.44, 95% CI: 0.26-0.73). People educated with junior high school had better self-rated health than those with primary and below education level (In men: OR = 0.62, 95% CI: 0.50-0.75. In women: OR = 0.53, 95% CI: 0.42-0.68). Income, education and occupation were correlated with each other. Within the context of rapid societal changes in China, income and its implications for greater healthcare access and benefits had the greatest association with self-rated health followed by education. Occupational status was not associated. Occupational categories and prestige should be better adapted to reflect China's unique sociopolitical and historical context.


Hip arthroscopy in osteoarthritis consequent to FAI.
Femoral Acetabular Impingement (FAI) means a set of alterations involving the acetabulum, proximal femur, or both of these components that can results in osteoarthritis. Arthroscopy is a choice for the treatment of initial stages of osteoarthritis (OA) in order to reduce evolution of the degenerative processes; advanced degrees of osteoarthritis are absolute contraindications. 40 patients affected by osteoarthritis in FAI underwent hip arthroscopy between May 2010 and March 2015. In all 40 cases OA secondary to FAI was diagnosed. All patients were clinically and instrumentally analyzed pre-operatively and then post-operatively after 3, 6, and 12 months. We evaluated the degree of OA using the Tonnis classification; our study included only patients affected by Tonnis grade 0-2 osteoarthritis. The mean modified Harris Hip Score showed an evolution from 54.7 points to an average value of 89,1 points after 12 months. The Lower Extremities Functional Scale evolved by 43 points to an average value of 65,28 points. Based on the data of this study, supported by the concordance with recent literature reviews, in degrees Tonnis 0 and 1 an arthroscopic treatment is recommended. Instead the therapeutic algorithm in Tonnis grade 2 is still being discussed. We detect a significant response to arthroscopic intervention which leads us to suggest that validation of this method needs further confirmatory studies.


Resource utilization and environmental and spatio-temporal overlap of a hilltopping lycaenid butterfly community in the colombian andes.
Coexistence by a great number of species could reflect niche segregation at several resource axes. Differences in the use of a hilltop as mating site for a Eumaeini (Lycaenidae) community were measured to test whether niche segregation exists within this group. Specimens were collected throughout 21 samplings between July-October of 2004 and July-October of 2005. Two environmental variables and three temporal-spacial variables were analyzed utilizing null models with three randomization algorithms. Significant differences were found among the species with respect to utilization of vertical space, horizontal space, temporary distribution and environmental temperature. The species did not show significant differences with respect to light intensity. For all samplings, the niche overlap observed in the two environmental variables were higher or significantly higher than expected by chance, suggesting that niche segregation does not exist due to competition within these variables. Similar results were observed for temporal distribution. Some evidence of niche segregation was found in vertical space and horizontal space variables where some samples presented lower overlap than expected by chance. The results pointed out that community's assemblage could be mainly shaped in two ways. The first is that species with determined habitat requirements fit into unoccupied niche spaces. The second is by niche segregation in the vertical space distribution variable.


Is postprandial hypertriglyceridaemia in relatives of type 2 diabetic subjects a consequence of insulin resistance?
Higher postprandial triglyceride responses reported in first degree relatives of people with type 2 diabetes (REL) were postulated to be the result of an early, possibly intrinsic, defect in oral lipid handling. The postprandial triglyceride response to high fat meals (HFM) in normal subjects is reduced by the insulin response to dietary carbohydrate (CHO) in the meal. The aims of this study were to examine whether (1) insulin resistance is associated with an intrinsic defect in triglyceride handling in insulin-resistant REL and (2) insulin resistance is associated with altered triglyceride handling after HFM with high CHO content. Postprandial responses to a HFM in normolipidaemic, normoglycaemic REL were compared with subjects without a family history of diabetes mellitus (CON). Over 6 h, the insulin, glucose, triglyceride and nonesterified fatty acid (NEFA) responses after a high fat (80 g fat), low CHO (HFM-LC; 20 g CHO, 4250 kJ) meal and a high fat, high CHO (HFM-HC; 100 g CHO, 5450 kJ) meal were examined. The 10 (7F/3M) REL were significantly more insulin-resistant, determined by glucose infusion during a hyperinsulinaemic euglycaemic clamp than the 10 (5F/5M) CON (glucose infusion rate 44.6 +/- 4.9 vs. 60.0 +/- 4.8 micromol min(-1) kg FFM(-1), P = 0.037). Subjects were similar for age and body mass index (BMI). The triglyceride increments after the HFM-LC were similar in both, peaking at 180-240 min (Delta0.77 +/- 0.11 mmol L(-1)), demonstrating no postprandial defect in REL, despite insulin resistance. There was a significantly lower postprandial triglyceride response in CON following the HFM-HC compared with the HFM-LC, but not in REL. In contrast, the higher insulin level during the HFM-HC was associated with significantly greater NEFA level suppression than in the HFM-LC (2.13 +/- 0.51 vs. 0.70 +/- 0.35 mmol L(-1), P = 0.03), only in the REL. These results are inconsistent with a primary aetiological role for postprandial hypertriglyceridaemia in already insulin resistant type 2 diabetic REL, but raise the possibility that this potentially atherogenic manifestation is secondary to insulin resistance lessening VLDL production and/or release from the liver.


Mesenteric cavernous hemangioma involving small bowel and appendix: a rare presentation of a vascular tumor.
We report on a case of cavernous hemangioma of the small bowel mesentery. Fewer than five cases of large mesenteric cavernous hemangioma have been reported in the English literature. Cavernous hemangioma of the small bowel mesentery is extremely rare. A 32-year-old black male presented with 1 week of abdominal pain, nausea, vomiting, and anorexia. He had recently undergone computed tomographic guided biopsy of a pelvic mass at another facility. Repeat CT guided biopsy was nondiagnostic, mesenteric angiography was inconclusive, and magnetic resonance imaging was performed as well. Complete workup was performed to localize primary source of abdominal mass and eventual open biopsy was planned resulting in en bloc resection of the mass, which had invaded the terminal ileum and appendix. Final pathologic diagnosis was cavernous mesenteric hemangioma. The patient experienced a prolonged postoperative ileus and was eventually discharged in stable condition, tolerating a regular diet with adequate bowel and urinary function. Diagnosis of cavernous mesenteric hemangioma is difficult and multiple imaging modalities can prove inconclusive. Adequate biopsy can be difficult to obtain even in patients with small body habitus. Standard of care is resection of entire mass en bloc.


A Non-Human Primate Model of Severe Pneumococcal Pneumonia.
Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and infectious death in adults worldwide. A non-human primate model is needed to study the molecular mechanisms that underlie the development of severe pneumonia, identify diagnostic tools, explore potential therapeutic targets, and test clinical interventions during pneumococcal pneumonia. To develop a non-human primate model of pneumococcal pneumonia. Seven adult baboons (Papio cynocephalus) were surgically tethered to a continuous monitoring system that recorded heart rate, temperature, and electrocardiography. Animals were inoculated with 109 colony-forming units of S. pneumoniae using bronchoscopy. Three baboons were rescued with intravenous ampicillin therapy. Pneumonia was diagnosed using lung ultrasonography and ex vivo confirmation by histopathology and immunodetection of pneumococcal capsule. Organ failure, using serum biomarkers and quantification of bacteremia, was assessed daily. Challenged animals developed signs and symptoms of pneumonia 4 days after infection. Infection was characterized by the presence of cough, tachypnea, dyspnea, tachycardia and fever. All animals developed leukocytosis and bacteremia 24 hours after infection. A severe inflammatory reaction was detected by elevation of serum cytokines, including Interleukin (IL)1Ra, IL-6, and IL-8, after infection. Lung ultrasonography precisely detected the lobes with pneumonia that were later confirmed by pathological analysis. Lung pathology positively correlated with disease severity. Antimicrobial therapy rapidly reversed symptomology and reduced serum cytokines. We have developed a novel animal model for severe pneumococcal pneumonia that mimics the clinical presentation, inflammatory response, and infection kinetics seen in humans. This is a novel model to test vaccines and treatments, measure biomarkers to diagnose pneumonia, and predict outcomes.


Plasmon-free SERS detection of environmental CO2 on TiO2 surfaces.
SiO2/TiO2 core/shell beads (T-rex) were designed, fabricated and tested for Raman detection of environmental CO2 under real-working conditions, as those encountered, for example, in solar-to-fuel conversion reactions. The exploitation of light trapping and morphology dependent resonances was crucial for extending the limit of detection of CO2 adsorbed on TiO2 surfaces. T-rex beads allowed for achieving surface enhanced Raman scattering (SERS) without using plasmonic metals showing high-efficiency, fast response and reproducibility in CO2 detection in both air and solvents. The dependence of SERS activity on Mie-type resonances was investigated through a systematic comparison of experimental data and numerical simulations, demonstrating that T-rex beads can be tailored for the detection of gaseous environmental pollutants on the basis of simple, Mie-scattering based calculations. Three-dimensional T-rex colloidal crystals were also successfully tested in precise, in situ, real time detection of CO2 as a function of different temperature-sweep cycles.


Pronounced cancer resistance in a subterranean rodent, the blind mole-rat, Spalax: in vivo and in vitro evidence.
Subterranean blind mole rats (Spalax) are hypoxia tolerant (down to 3% O2), long lived (>20 years) rodents showing no clear signs of aging or aging related disorders. In 50 years of Spalax research, spontaneous tumors have never been recorded among thousands of individuals. Here we addressed the questions of (1) whether Spalax is resistant to chemically-induced tumorigenesis, and (2) whether normal fibroblasts isolated from Spalax possess tumor-suppressive activity. Treating animals with 3-Methylcholantrene (3MCA) and 7,12-Dimethylbenz(a) anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA), two potent carcinogens, confirmed Spalax high resistance to chemically induced cancers. While all mice and rats developed the expected tumors following treatment with both carcinogens, among Spalax no tumors were observed after DMBA/TPA treatment, while 3MCA induced benign fibroblastic proliferation in 2 Spalax individuals out of12, and only a single animal from the advanced age group developed malignancy 18 months post-treatment. The remaining animals are still healthy 30 months post-treatment. In vitro experiments showed an extraordinary ability of normal Spalax cultured fibroblasts to restrict malignant behavior in a broad spectrum of human-derived and in newly isolated Spalax 3MCA-induced cancer cell lines. Growth of cancer cells was inhibited by either direct interaction with Spalax fibroblasts or with soluble factors released into culture media and soft agar. This was accompanied by decreased cancer cell viability, reduced colony formation in soft agar, disturbed cell cycle progression, chromatin condensation and mitochondrial fragmentation. Cells from another cancer resistant subterranean mammal, the naked mole rat, were also tested for direct effect on cancer cells and, similar to Spalax, demonstrated anti-cancer activity. No effect on cancer cells was observed using fibroblasts from mouse, rat or Acomys. Spalax fibroblast conditioned media had no effect on proliferation of noncancerous cells. This report provides pioneering evidence that Spalax is not only resistant to spontaneous cancer but also to experimentally induced cancer, and shows the unique ability of Spalax normal fibroblasts to inhibit growth and kill cancer cells, but not normal cells, either through direct fibroblast-cancer cell interaction or via soluble factors. Obviously, along with adaptation to hypoxia, Spalax has evolved efficient anti-cancer mechanisms yet to be elucidated. Exploring the molecular mechanisms allowing Spalax to survive in extreme environments and to escape cancer as well as to kill homologous and heterologous cancer cells may hold the key for understanding the molecular nature of host resistance to cancer and identify new anti-cancer strategies for treating humans.


Early evolution of the LIM homeobox gene family.
LIM homeobox (Lhx) transcription factors are unique to the animal lineage and have patterning roles during embryonic development in flies, nematodes and vertebrates, with a conserved role in specifying neuronal identity. Though genes of this family have been reported in a sponge and a cnidarian, the expression patterns and functions of the Lhx family during development in non-bilaterian phyla are not known. We identified Lhx genes in two cnidarians and a placozoan and report the expression of Lhx genes during embryonic development in Nematostella and the demosponge Amphimedon. Members of the six major LIM homeobox subfamilies are represented in the genomes of the starlet sea anemone, Nematostella vectensis, and the placozoan Trichoplax adhaerens. The hydrozoan cnidarian, Hydra magnipapillata, has retained four of the six Lhx subfamilies, but apparently lost two others. Only three subfamilies are represented in the haplosclerid demosponge Amphimedon queenslandica. A tandem cluster of three Lhx genes of different subfamilies and a gene containing two LIM domains in the genome of T. adhaerens (an animal without any neurons) indicates that Lhx subfamilies were generated by tandem duplication. This tandem cluster in Trichoplax is likely a remnant of the original chromosomal context in which Lhx subfamilies first appeared. Three of the six Trichoplax Lhx genes are expressed in animals in laboratory culture, as are all Lhx genes in Hydra. Expression patterns of Nematostella Lhx genes correlate with neural territories in larval and juvenile polyp stages. In the aneural demosponge, A. queenslandica, the three Lhx genes are expressed widely during development, including in cells that are associated with the larval photosensory ring. The Lhx family expanded and diversified early in animal evolution, with all six subfamilies already diverged prior to the cnidarian-placozoan-bilaterian last common ancestor. In Nematostella, Lhx gene expression is correlated with neural territories in larval and juvenile polyp stages. This pattern is consistent with a possible role in patterning the Nematostella nervous system. We propose a scenario in which Lhx genes play a homologous role in neural patterning across eumetazoans.


Coherent noise suppression in digital holography based on flat fielding with apodized apertures.
Great number of approaches has been carried out in digital holography (DH) in order to overcome the problem of coherent noise in the reconstruction process. In this paper, we describe a new method that can be used to suppress the coherent noise in phase-contrast image. The proposed method is a combination of the flat fielding method and the apodized apertures technique. The proposed method is applied to a sample of 200 μm step height. The quality of the phase-contrast image of the sample is refined and the coherent noise level is reduced drastically by the order of 65%. The proposed method can also applicable to noise reduction of intensity imaging.


Ribavirin: the need for exposure precautions.
Ribavirin is used in the treatment of respiratory syncytial virus (RSV) in high-risk patients, including patients who have undergone hematopoietic stem cell transplantation, to reduce mortality from RSV pneumonia. It is classified as a hazardous drug with potential for carcinogenicity and teratogenicity. Very few recent studies have examined the risk of exposure, and recommendations for exposure precautions are lacking. Administration should include the use of personal protective equipment and terminal cleaning of the patient room after each administration. This article examines ribavirin use among patients who have undergone hematopoietic stem cell transplantation and have RSV-related pneumonia and explores safety considerations for staff. Nursing leaders on a hematopoietic stem cell transplantation unit addressed gaps in knowledge about ribavirin therapy, and completed a review of the hospital's ribavirin policy, which led to policy revisions, increased knowledge about the safe administration of ribavirin, and improvements in staff and patient education.


Privacy Preserving k-Nearest Neighbor for Medical Diagnosis in e-Health Cloud.
Cloud computing is highly suitable for medical diagnosis in e-health services where strong computing ability is required. However, in spite of the huge benefits of adopting the cloud computing, the medical diagnosis field is not yet ready to adopt the cloud computing because it contains sensitive data and hence using the cloud computing might cause a great concern in privacy infringement. For instance, a compromised e-health cloud server might expose the medical dataset outsourced from multiple medical data owners or infringe on the privacy of a patient inquirer by leaking his/her symptom or diagnosis result. In this paper, we propose a medical diagnosis system using e-health cloud servers in a privacy preserving manner when medical datasets are owned by multiple data owners. The proposed system is the first one that achieves the privacy of medical dataset, symptoms, and diagnosis results and hides the data access pattern even from e-health cloud servers performing computations using the data while it is still robust against collusion of the entities. As a building block of the proposed diagnosis system, we design a novel privacy preserving protocol for finding the k data with the highest similarity (PE-FTK) to a given symptom. The protocol reduces the average running time by 35% compared to that of a previous work in the literature. Moreover, the result of the previous work is probabilistic, i.e., the result can contain some error, while the result of our PE-FTK is deterministic, i.e., the result is correct without any error probability.


Ontological labels for automated location of anatomical shape differences.
A method for automated location of shape differences in diseased anatomical structures via high resolution biomedical atlases annotated with labels from formal ontologies is described. In particular, a high resolution magnetic resonance image of the myocardium of the human left ventricle was segmented and annotated with structural terms from an extracted subset of the Foundational Model of Anatomy ontology. The atlas was registered to the end systole template of a previous study of left ventricular remodeling in cardiomyopathy using a diffeomorphic registration algorithm. The previous study used thresholding and visual inspection to locate a region of statistical significance which distinguished patients with ischemic cardiomyopathy from those with nonischemic cardiomyopathy. Using semantic technologies and the deformed annotated atlas, this location was more precisely found. Although this study used only a cardiac atlas, it provides a proof-of-concept that ontologically labeled biomedical atlases of any anatomical structure can be used to automate location-based inferences.


An incomplete periacetabular osteotomy for treatment of neuromuscular hip dysplasia.
Standard innominate osteotomies that are recommended for treatment of the typical form of developmental dysplasia of the hip are not recommended for dysplasia associated with neuromuscular disorders. A periacetabular osteotomy that permitted accurate correction of the posterolateral acetabular deficiency was done on 40 patients (50 hips). The purpose of this study was to present the surgical technique, to evaluate whether it can improve acetablular dysplasia, and to provide stable hips. The patients had a mean age of 9.5 years at the time of surgery. The medial cortex of the ilium was left intact, whereas the supraacetabular and retroacetabular cancellous bone, and posterolateral cortical bone were cut. The posterior cut extended down to the triradiate cartilage, or through its former site, respectively. Forty-one hips were evaluated at a mean followup of 5.3 years (range, 2-11.7 years) after surgery. The mean acetabular index improved from 32 degrees preoperatively to 12 degrees at followup. The mean migration percentage improved from 77% to 13%. A redislocation or unstable hip occurred in two patients. According to caregivers, surgery improved personal care, positioning, and comfort. This osteotomy decreases the radius of the elongated acetabulum, provides coverage by articular cartilage particularly at the posterolateral aspect of the acetabulum, and preserves the entire medial wall of the ilium.


Specific targeting of human caspases using designed ankyrin repeat proteins.
Abstract Caspases play important roles in cell death, differentiation, and proliferation. Due to their high homology, especially of the active site, specific targeting of a particular caspase using substrate analogues is very difficult. Although commercially available small molecules based on peptides are lacking high specificity due to overlapping cleavage motives between different caspases, they are often used as specific tools. We have selected designed ankyrin repeat proteins (DARPins) against human caspases 1-9 and identified high-affinity binders for the targeted caspases, except for caspase 4. Besides previously reported caspase-specific DARPins, we generated novel DARPins (D1.73, D5.15, D6.11, D8.1, D8.4, and D9.2) and confirmed specificity for caspases 1, 5, 6, and 8 using a subset of caspase family members. In addition, we solved the crystal structure of caspase 8 in complex with DARPin D8.4. This binder interacts with non-conserved residues on the large subunit, thereby explaining its specificity. Structural analysis of this and other previously published crystal structures of caspase/DARPin complexes depicts two general binding areas either involving active site forming loops or a surface area laterally at the large subunit of the enzyme. Both surface areas involve non-conserved surface residues of caspases.


The Role of Temporal Trends in Growing Networks.
The rich get richer principle, manifested by the Preferential attachment (PA) mechanism, is widely considered one of the major factors in the growth of real-world networks. PA stipulates that popular nodes are bound to be more attractive than less popular nodes; for example, highly cited papers are more likely to garner further citations. However, it overlooks the transient nature of popularity, which is often governed by trends. Here, we show that in a wide range of real-world networks the recent popularity of a node, i.e., the extent by which it accumulated links recently, significantly influences its attractiveness and ability to accumulate further links. We proceed to model this observation with a natural extension to PA, named Trending Preferential Attachment (TPA), in which edges become less influential as they age. TPA quantitatively parametrizes a fundamental network property, namely the network's tendency to trends. Through TPA, we find that real-world networks tend to be moderately to highly trendy. Networks are characterized by different susceptibilities to trends, which determine their structure to a large extent. Trendy networks display complex structural traits, such as modular community structure and degree-assortativity, occurring regularly in real-world networks. In summary, this work addresses an inherent trait of complex networks, which greatly affects their growth and structure, and develops a unified model to address its interaction with preferential attachment.


Effects of wind-energy facilities on breeding grassland bird distributions.
The contribution of renewable energy to meet worldwide demand continues to grow. Wind energy is one of the fastest growing renewable sectors, but new wind facilities are often placed in prime wildlife habitat. Long-term studies that incorporate a rigorous statistical design to evaluate the effects of wind facilities on wildlife are rare. We conducted a before-after-control-impact (BACI) assessment to determine if wind facilities placed in native mixed-grass prairies displaced breeding grassland birds. During 2003-2012, we monitored changes in bird density in 3 study areas in North Dakota and South Dakota (U.S.A.). We examined whether displacement or attraction occurred 1 year after construction (immediate effect) and the average displacement or attraction 2-5 years after construction (delayed effect). We tested for these effects overall and within distance bands of 100, 200, 300, and >300 m from turbines. We observed displacement for 7 of 9 species. One species was unaffected by wind facilities and one species exhibited attraction. Displacement and attraction generally occurred within 100 m and often extended up to 300 m. In a few instances, displacement extended beyond 300 m. Displacement and attraction occurred 1 year after construction and persisted at least 5 years. Our research provides a framework for applying a BACI design to displacement studies and highlights the erroneous conclusions that can be made without the benefit of adopting such a design. More broadly, species-specific behaviors can be used to inform management decisions about turbine placement and the potential impact to individual species. Additionally, the avoidance distance metrics we estimated can facilitate future development of models evaluating impacts of wind facilities under differing land-use scenarios.


The Effect of Childhood Household Dysfunction on Future HIV Risk among Probationers.
Adverse childhood events (ACE) can lead to numerous health risks in adulthood. ACEs coupled with increased risk-taking behaviors can lead to increased risk for HIV infection, particularly in vulnerable populations. The purpose of this study was to determine if mental health symptom severity mediates the relationship between childhood household dysfunction and adult HIV risk among a group of probationers. T-tests were used to evaluate associations between demographic characteristics and cumulative engagement in sexual risk behaviors in 282 drug-involved probationers. A mediation analysis was conducted to determine the direct and indirect effect of cumulative household dysfunction and high-risk sexual behaviors through mental health symptom severity. We found significant differences in the occurrence of different childhood household dysfunction problems by probationer gender, race, and criminal risk level. Mental health symptom severity demonstrated a significant indirect mediation effect of household dysfunction adverse events and engagement in sexual risky behaviors, b = .03, 95% BCa CI [.007, .057]. Given the high prevalence of childhood trauma in probationers and the direct associations with mental illness and sexual risk-taking behaviors, the need for offenders to have access to and receive mental health treatment while under community supervision is evident. Mental health and substance abuse treatment services can not only reduce risks for recidivism but also HIV infection and transmission within this population.


Large-area semi-transparent light-sensitive nanocrystal skins.
We report a large-area, semi-transparent, light-sensitive nanocrystal skin (LS-NS) platform consisting of single monolayer colloidal nanocrystals. LS-NS devices, which were fabricated over areas up to 48 cm(2) using spray-coating and several cm-squares using dip-coating, are operated on the principle of photogenerated potential buildup, unlike the conventional charge collection. Implementing proof-of-concept devices using CdTe nanocrystals with ligand removal, we observed a substantial sensitivity enhancement factor of ~73%, accompanied with a 3-fold faster response time (<100 ms). With fully sealed nanocrystal monolayers, LS-NS is found to be highly stable under ambient conditions, promising for low-cost large-area UV/visible sensing in windows and facades of smart buildings.


Changes in angiotensinogen messenger RNA in differentiating 3T3-F442A adipocytes.
Angiotensinogen messenger RNA (mRNA) has been identified in both brown and white adipose tissue. Recently we have shown that when 3T3-L1 cells were treated with isobutylmethylxanthine (IBMX) to accelerate differentiation, angiotensinogen mRNA increased markedly in adipocytes as compared with preadipocytes. To determine if a correlation existed between the regulatory events associated with the differentiation process, we compared the change in angiotensinogen mRNA in spontaneously differentiating 3T3-F442A cells with two established parameters of differentiation in adipocyte cell lines. Differentiation was assessed by visual examination of cells for lipid droplets, fluorescent staining of the F-actin fibers, and increases in glycerol phosphate dehydrogenase mRNA. F-actin fibers were highly structured in preadipocytes, becoming disassembled and very disorganized as cells differentiated into adipocytes. The quantity of angiotensinogen mRNA increased as the number of lipid-containing cells increased within a culture. Glycerol phosphate dehydrogenase mRNA accumulated in differentiated adipocytes to about the same extent as angiotensinogen mRNA. Thus, increases in angiotensinogen mRNA were associated with the morphological and biochemical changes that occur during the phenotypic modulation of 3T3-F442A cells.


Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology, Practice Parameters Committee.
Guidelines for clinical practice are intended to indicate preferred approaches to medical problems as established by scientifically valid research. Double-blind placebo-controlled studies are preferable, but compassionate use reports and expert review articles are utilized in a thorough review of the literature conducted through Medline with the National Library of Medicine. When only data that will not withstand objective scrutiny are available, a recommendation is identified as a consensus of experts. Guidelines are applicable to all physicians who address the subject without regard to the specialty training or interests and are intended to indicate the preferable but not necessarily the only acceptable approach to a specific problem. Guidelines are intended to be flexible and must be distinguished from standards of care, which are inflexible and rarely violated. Given the wide range of specifics in any health-care problem, the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision. Guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees. Each has been extensively reviewed and revised by the Committee, other experts in the field, physicians who will use them, and specialists in the science of decision of analysis. The recommendations of each guideline are therefore considered valid at the time of their production based on the data available. New developments in medical research and practice pertinent to each guideline will be reviewed at a time established and indicated at the publication in order to assure continued validity.


Expression and role of serum and glucocorticoid-regulated kinase 2 in the regulation of Na+/H+ exchanger 3 in the mammalian kidney.
Serum and glucocorticoid-regulated kinase 2 (sgk2) is 80% identical to the kinase domain of sgk1, an important mediator of mineralocorticoid-regulated sodium (Na(+)) transport in the distal nephron of the kidney. The expression pattern and role in renal function of sgk2 are virtually uncharacterized. In situ hybridization and immunohistochemistry of rodent kidney coupled with real-time RT-PCR of microdissected rat kidney tubules showed robust sgk2 expression in the proximal straight tubule and thick ascending limb of the loop of Henle. Sgk2 expression was minimal in distal tubule cells with aquaporin-2 immunostaining but significant in proximal tubule cells with Na(+)/H(+) exchanger 3 (NHE3) immunostaining. To ascertain whether mineralocorticoids regulate expression of sgk2 in a manner similar to sgk1, we examined sgk2 mRNA expression in the kidneys of adrenalectomized rats treated with physiological doses of aldosterone together with the glucocorticoid receptor antagonist RU486. Northern blot analysis and in situ hybridization showed that, unlike sgk1, sgk2 expression in the kidney was not altered by aldosterone treatment. Based on the observation that sgk2 is expressed in proximal tubule cells that also express NHE3, we asked whether sgk2 regulates NHE3 activity. We heterologously expressed sgk2 in opossum kidney (OKP) cells and measured Na(+)/H(+) exchange activity by Na(+)-dependent cell pH recovery. Constitutively active sgk2, but not sgk1, stimulated Na(+)/H(+) exchange activity by >30%. Moreover, the sgk2-mediated increase in Na(+)/H(+) exchange activity correlated with an increase in cell surface expression of NHE3. Together, these results suggest that the pattern of expression, regulation, and role of sgk2 within the mammalian kidney are distinct from sgk1 and that sgk2 may play a previously unrecognized role in the control of transtubular Na(+) transport through NHE3 in the proximal tubule.


Alcohol abuse and illegal drug use among Los Angeles County trauma patients: prevalence and evaluation of single item screener.
The misuse of alcohol and illicit drugs is implicated with injury and repeat injury. Admission to a trauma center provides an opportunity to identify patients with substance use problems and initiate intervention and prevention strategies. To facilitate the identification of trauma patients with substance use problems, we studied alcohol abuse and illegal substance use patterns in a large cohort of urban trauma patients, identified correlates of alcohol abuse, and assessed the utility of a single item binge-drinking screener for identifying patients with past 12-month substance use problems. Between February 2004 and August 2006, 677 patients from four large trauma centers in Los Angeles County were interviewed. The sample was broadly representative of the entire Los Angeles County trauma center patient population. Twenty-four percent of patients met criteria for alcohol abuse and 15% reported using an illegal drug other than marijuana in the past 12 months. Male gender, assaultive injury, peritrauma substance use, and history of binge drinking were prominent risk factors. A single item binge drinking screen correctly identified alcohol abuse status in 76% of all patients; the screen also performed moderately well in discriminating between those who had or had not used illegal drugs in the past 12 months, with sensitivity estimates reaching 0.79 and specificity estimates reaching 0.74. A large proportion of urban trauma patients abuse alcohol and use illegal drugs. Distinct sociodemographic and substance use history may indicate underlying risky behaviors. Interventions and injury prevention programs need to address these causal behaviors to reduce injury morbidity and recidivism. In the busy trauma care setting, a one-item screener could be helpful in identifying patients who would benefit from more thorough assessment and possible brief intervention.


The role of human MBF1 as a transcriptional coactivator.
Multiprotein bridging factor 1 (MBF1) is a coactivator which mediates transcriptional activation by interconnecting the general transcription factor TATA element-binding protein and gene-specific activators such as the Drosophila nuclear receptor FTZ-F1 or the yeast basic leucine zipper protein GCN4. The human homolog of MBF1 (hMBF1) has been identified but its function, especially in transcription, remains unclear. Here we report the cDNA cloning and functional analysis of hMBF1. Two isoforms, which we term hMBF1alpha and hMBF1beta, have been identified. hMBF1alpha mRNA was detected in a number of tissues, whereas hMBF1beta exhibited tissue-specific expression. Both isoforms bound to TBP and Ad4BP/SF-1, a mammalian counterpart of FTZ-F1, and mediated Ad4BP/SF-1-dependent transcriptional activation. While hMBF1 was detected in the cytoplasm by immunostaining, coexpression of the nuclear protein Ad4BP/SF-1 with hMBF1 induced accumulation of hMBF1 in the nucleus, suggesting that hMBF1 is localized in the nucleus through its binding to Ad4BP/SF-1. hMBF1 also bound to ATF1, a member of the basic leucine zipper protein family, and mediated its activity as a transcriptional activator. These data establish that the coactivator MBF1 is functionally conserved in eukaryotes.


Risk factors for bulimia nervosa. A community-based case-control study.
Many apparently disparate risk factors have been implicated as causes of eating disorders. This study was designed to test the hypothesis that 2 broad classes of risk factors exist for bulimia nervosa: those that increase the risk for development of a psychiatric disorder in general and those that increase the risk of dieting. It was predicted that the latter are especially common among persons with bulimia nervosa. A case-control design was used involving 2 integrated comparisons. First, 102 subjects with bulimia nervosa were compared with 204 healthy control subjects without an eating disorder. Second, the same 102 subjects with bulimia nervosa were compared with 102 subjects with other psychiatric disorders. To reduce sampling bias, the subjects were recruited directly from the community. A broad range of putative risk factors was assessed. The subjects with bulimia nervosa and the healthy control subjects differed in their rates of exposure to most of the putative risk factors. Far fewer differences were evident between the subjects with bulimia nervosa and the control subjects with other psychiatric disorders, although exposure to factors that were likely to increase the risk of dieting and to negative self-evaluation and certain parental problems (including alcohol use disorder) were substantially more common among those with bulimia nervosa. The findings support the hypothesis that bulimia nervosa is the result of exposure to general risk factors for psychiatric disorder and risk factors for dieting. An unexpected finding was the particularly high rates of premorbid negative self-evaluation and certain parental problems among those with bulimia nervosa.


Tobacco Use as a Risk Factor.
Tobacco, particularly tobacco smoking, has a substantial influence on periodontal health and disease. It is associated with an increased disease rate in terms of periodontal bone loss, periodontal attachment loss, as well as periodontal pocket formation. In addition, it exerts a masking effect on gingival symptoms of inflammation. Risk assessment based on an increasing body of investigations over the past few years suggests that the tobacco attributable risk is considerable, estimated odds ratios being of the order 2.5 to 6.0 or even greater. Although the mechanisms by which tobacco exerts its influence are obscure, information available to date does not support the view that its action simply relates to other environmental factors such as the dental plaque or some specific microflora. It seems more likely that it primarily has a systemic influence affecting host response or susceptibility. The chief novelty of the present report is that current data suggest that, although the overall disease prevalence is decreasing, the proportion of periodontal disease attributed to tobacco is stable or even increasing. This seems to be analogous to what has been observed for other smoking-associated chronic diseases. This, in turn, indicates that periodontal disease behaves like several other chronic diseases and, further, that tobacco should be considered a major risk factor for chronic periodontal disease. J Petiodontol 1994;65:545-550.


Smoking and Parkinson's disease: systematic review of prospective studies.
We estimated the pooled risk of tobacco smoking for Parkinson's disease (PD). Inclusion criteria included systematic searches of MedLine, PsycLIT, Embase, Current Contents, previously published reviews, examination of cited reference sources, and personal contact and discussion with several investigators expert in the field. Published prospective studies on PD and cigarette smoking. When two or more studies were based on an identical study, the study that principally investigated the relationship or the study that was published last was used. Seven prospective studies were carried out between 1959 and 1997, of which six reported risk estimates. Four cohorts were based on standardised mortality rates, which were exclusively of male. Only one study included risk estimates for both males and females separately. The risk of ever smoker was 0.51 (95% confidence interval, 0.43 to 0.61). There was an obvious protective effect of current smoking in the pooled estimate (relative risk, 0.35; 95% CI, 0.26-0.47). Former smokers had lower risk compared with never smokers (relative risk, 0.66; 95% CI, 0.49-0.88). Although our pooled estimates show that smoking is inversely associated with the risk of PD, the four prospective studies that were based on follow-up of mortality of smokers had many limitations. Further studies evaluating the association between smoking and PD in women are strongly needed.


Effects of animal source food and micronutrient fortification in complementary food products on body composition, iron status, and linear growth: a randomized trial in Cambodia.
Poor nutritional quality of complementary foods often limits growth. Animal source foods, such as milk or meat, are often unaffordable. Local affordable alternatives are needed. We evaluate the efficacy of 2 newly developed, rice-based complementary food products: WinFood (WF) with small fish and edible spiders and WinFood-Lite (WF-L) fortified with small fish, against 2 existing fortified corn-soy blend products, CSB+ (purely plant based) and CSB++ (8% dried skimmed milk). In total, 419 infants aged 6 mo were enrolled in this randomized, single-blinded study for 9 mo, designed primarily to assess increments in fat-free mass by a deuterium dilution technique and change in plasma ferritin and soluble transferrin receptor. Secondary endpoints were changes in anthropometric variables, including knee-heel length. Data were analyzed by the intention-to-treat approach. There was no difference in fat-free mass increment in WF or WF-L compared with CSB+ [WF: +0.04 kg (95% CI: -0.20, 0.28 kg); WF-L: +0.14 kg (95% CI: -0.10, 0.38 kg)] or CSB++ [WF: -0.03 kg (95% CI: -0.27, 0.21 kg); WF-L: +0.07 kg (95% CI: -0.18, 0.31 kg)] and no effect on iron status. The 1.7-mm (95% CI: -0.1, 3.5 mm) greater increase in knee-heel length in WF-L than in CSB+ was not significant. No difference was found between the locally produced products (WF and WF-L) and the CSBs. Micronutrient fortification may be necessary, and small fish may be an affordable alternative to milk to improve complementary foods. The dietary role of edible spiders needs to be further explored. This trial was registered at controlled-trials.com as ISRCTN19918531.


The Los Angeles County Community Disaster Resilience Project - a community-level, public health initiative to build community disaster resilience.
Public health officials need evidence-based methods for improving community disaster resilience and strategies for measuring results. This methods paper describes how one public health department is addressing this problem. This paper provides a detailed description of the theoretical rationale, intervention design and novel evaluation of the Los Angeles County Community Disaster Resilience Project (LACCDR), a public health program for increasing community disaster resilience. The LACCDR Project utilizes a pretest-posttest method with control group design. Sixteen communities in Los Angeles County were selected and randomly assigned to the experimental community resilience group or the comparison group. Community coalitions in the experimental group receive training from a public health nurse trained in community resilience in a toolkit developed for the project. The toolkit is grounded in theory and uses multiple components to address education, community engagement, community and individual self-sufficiency, and partnerships among community organizations and governmental agencies. The comparison communities receive training in traditional disaster preparedness topics of disaster supplies and emergency communication plans. Outcome indicators include longitudinal changes in inter-organizational linkages among community organizations, community member responses in table-top exercises, and changes in household level community resilience behaviors and attitudes. The LACCDR Project is a significant opportunity and effort to operationalize and meaningfully measure factors and strategies to increase community resilience. This paper is intended to provide public health and academic researchers with new tools to conduct their community resilience programs and evaluation research. Results are not yet available and will be presented in future reports.


Fine needle aspiration diagnosis of extracranial glioblastoma multiforme: Case report and review of the literature.
Hitherto uncommon, the incidence of extracranial metastases of primary brain malignancies may increase, with improved treatment methods and longer patient survival. Fine needle aspiration biopsy is a simple, safe and reliable method to diagnose metastatic malignancy. It has definite advantages over tissue biopsy, which is more invasive and is of higher risk to the patient. Ours is a case of glioblastoma multiforme, which metastasized to the scalp and was diagnosed on fine needle aspiration biopsy. Only a few articles document the cytological features of extracranial glioblastoma multiforme, diagnosed by fine needle aspiration biopsy. We report the case of an elderly female who presented with focal neurological symptoms. She was diagnosed radiologically with an intracranial lesion in the left temporal region, which was subsequently resected. Histology revealed a glioblastoma multiforme confirmed by immunohistochemistry. The tumor recurred subsequently and the patient was treated with chemotherapy, intraoperatively. At a later stage, she presented with a scalp mass on which fine needle aspiration biopsy was performed. The cytomorphological features aided by immunohistochemistry supported a diagnosis of metastatic glioblastoma multiforme. The mass was later resected and histology confirmed the fine needle aspiration diagnosis of glioblastoma multiforme. Reports of extracranial metastases of primary brain tumors are few. When they do occur, the primary cause is implantation during surgery or biopsy. However, spontaneous metastases to other organs do occur rarely. We believe fine needle aspiration biopsy to be very useful in the diagnosis of metastatic glioblastoma multiforme. The ability to use a cellblock for immunohistochemical studies is greatly advantageous and helpful in differentiating this tumor, from other malignancies that can occur in the scalp. A detailed discussion of the material obtained from fine needle aspiration biopsy of metastatic glioblastoma multiforme is presented, as well as a review of previous accounts in the literature.


Muscadine grape products intake, diet and blood constituents of non-diabetic and type 2 diabetic subjects.
Red wines and grape juices contain polyphenolics with antioxidant and antiplatelet properties that may be protective against oxidative stress leading to hypertension, insulin resistance, and type 2 diabetes (T2D). This study evaluated the effects of supplementing meals of subjects with 150 mL of muscadine grape juice (MJ), muscadine grape wine (MW), and dealcoholized muscadine grape wine (Dz-W) on glycemic indices, blood constituents, lipid profile, anthropometric, and nutrient intakes of healthy and T2D subjects over a 28-d period. Subjects with T2D were assigned to take MJ, MW, or Dz-W. Non-diabetics consumed MJ and controls were given no test drinks. Several metabolic indicators associated with diabetic conditions were measured at baseline and repeated after 28 d. Diabetics given MW and Dz-W showed lower levels of blood glucose, insulin, and glycated hemoglobin, indicating better glycemic control. Elevated dietary vitamin C and E levels were observed in diabetics given Dz-W, indicating improved antioxidant status. Decreased red blood cell membrane saturated fatty acids and increased mono- and polyunsaturated fatty acids for subjects with T2D given MW suggested improved membrane fluidity. Lower sodium and chloride values for subjects T2D given MW suggested lower risk for developing hypertension. Improved hepatic conditions were noted by decreases in alanine aminotransferase and aspartate aminotransferase among subjects with T2D given MW, indicating better insulin sensitivity and decreased tendency toward impaired liver function. Daily intake of 150 mL of MW or Dz-W with meals improved several metabolic responses among diabetics compared with diabetics given MJ.


Do Cryptic Reservoirs Threaten Gambiense-Sleeping Sickness Elimination?
Trypanosoma brucei gambiense causes human African trypanosomiasis (HAT). Between 1990 and 2015, almost 440000 cases were reported. Large-scale screening of populations at risk, drug donations, and efforts by national and international stakeholders have brought the epidemic under control with <2200 cases in 2016. The World Health Organization (WHO) has set the goals of gambiense-HAT elimination as a public health problem for 2020, and of interruption of transmission to humans for 2030. Latent human infections and possible animal reservoirs may challenge these goals. It remains largely unknown whether, and to what extend, they have an impact on gambiense-HAT transmission. We argue that a better understanding of the contribution of human and putative animal reservoirs to gambiense-HAT epidemiology is mandatory to inform elimination strategies.


Bronchial challenges with aerosolized food in asthmatic, food-allergic children.
Allergic asthma is usually considered to be provoked by aeroallergens. However, we have recently recognized a group of children with food allergies who also develop asthma when exposed to the aerosolized form of the food. Between 1997 and 1999 we prospectively identified children with an immunoglobulin (Ig)E-mediated food allergy who develop asthma on inhalational exposure to the relevant food allergen while it is being cooked. Subjects were exposed for 20 min to the aerosolized form of the allergen and the symptoms and the lung function were monitored. Aerosolization was achieved by cooking the food in a small room. Where possible challenges were double-blinded. We identified 12 children with an IgE-mediated food allergy who developed asthma on inhalational exposure to food. The implicated foods were fish, chickpea, milk, egg or buckwheat. Nine out of the 12 children consented to undergo a bronchial food challenge. Five challenges were positive with objective clinical features of asthma. Additionally, two children developed late-phase symptoms with a decrease in lung function. Positive reactions were seen with fish, chickpea and buckwheat. There were no reactions to the seven placebo challenges. We have presented a prospective series of children with food allergy who developed symptoms of asthma with exposure to aerosolized food allergens. Our data demonstrates that, as in the case of other aeroallergens, inhaled food allergens can produce both early- and late-phase asthmatic responses. This highlights the importance of considering foods as aeroallergens in children with coexistent food allergy and allergic asthma. For these children, dietary avoidance alone may not be sufficient and further environmental measures may be required to limit exposure to aerosolized food.


Assessing the performance of docking scoring function, FEP, MM-GBSA, and QM/MM-GBSA approaches on a series of PLK1 inhibitors.
Over-expressed polo-like kinases 1, a key regulator of cell mitosis, is associated with carcinogenesis and poor prognosis. It is very necessary to develop a reliable computational affinity prediction protocol targeting PLK1. In this study, the performance of different docking scoring function, free energy perturbation, MM-GBSA and QM/MM-GBSA were evaluated. The ranking capability of FEP is the best with rs = 0.854. However, the rs obtained from MM-GBSA can reach 0.767, which requires only about one-eighth of the simulation time of FEP. As for the sampling method, single long molecular dynamics (SLMD) surpass the multiple short molecular dynamics (MSMD) in ranking of the 20 congeneric compounds by about 0.1 in rs. In addition, ligands treated by QM can significantly improve the ranking performance. As for the docking scoring functions, a force field-based scoring function is more suitable for ranking congeneric compounds.


Transient junction anisotropies orient annular cell polarization in the Drosophila airway tubes.
In contrast to planes, three-dimensional (3D) structures such as tubes are physically anisotropic. Tubular organs exhibit a striking orientation of landmarks according to the physical anisotropy of the 3D shape, in addition to planar cell polarization. However, the influence of 3D tissue topography on the constituting cells remains underexplored. Here, we identify a regulatory network polarizing cellular biochemistry according to the physical anisotropy of the 3D tube geometry (tube cell polarization) by a genome-wide, tissue-specific RNAi screen. During Drosophila airway remodelling, each apical cellular junction is equipotent to establish perpendicular actomyosin cables, irrespective of the longitudinal or transverse tube axis. A dynamic transverse enrichment of atypical protein kinase C (aPKC) shifts the balance and transiently targets activated small GTPase RhoA, myosin phosphorylation and Rab11 vesicle trafficking to longitudinal junctions. We propose that the PAR complex translates tube physical anisotropy into longitudinal junctional anisotropy, where cell-cell communication aligns the contractile cytoskeleton of neighbouring cells.


The murine DUB-1 gene is specifically induced by the betac subunit of interleukin-3 receptor.
Cytokines regulate cell growth and differentiation by inducing the expression of specific target genes. We have recently isolated a cytokine-inducible, immediate-early cDNA, DUB-1, that encodes a deubiquitinating enzyme. The DUB-1 mRNA was specifically induced by the receptors for interleukin-3, granulocyte-macrophage colony-stimulating factor, and interleukin-5, suggesting a role for the beta common (betac subunit known to be shared by these receptors. In order to identify the mechanism of cytokine induction, we isolated a murine genomic clone for DUB-1 containing a functional promoter region. The DUB-1 gene contains two exons, and the nucleotide sequence of its coding region is identical to the sequence of DUB-1 cDNA. Various regions of the 5' flanking region of the DUB-1 gene were assayed for cytokine-inducible activity. An enhancer region that retains the beta c-specific inducible activity of the DUB-1 gene was identified. Enhancer activity was localized to a 112-bp fragment located 1.4 kb upstream from the ATG start codon. Gel mobility shift assays revealed two specific protein complexes that bound to this minimal enhancer region. One complex was induced by betac signaling, while the other was noninducible. Finally, the membrane-proximal region of human betac was required for DUB-1 induction. In conclusion, DUB-1 is the first example of an immediate-early gene that is induced by a specific subunit of a cytokine receptor. Further analysis of the DUB-1 enhancer element may reveal specific determinants of a betac-specific signaling pathway.


Phosphatase PRL-3 is a direct regulatory target of TGFbeta in colon cancer metastasis.
Metastasis causes most deaths from cancer yet mechanistic understanding and therapeutic options remain limited. Overexpression of the phosphatase PRL-3 (phosphatase of regenerating liver) is associated with metastasis of colon cancer. Here, we show that PRL-3 is a direct target of signaling by TGFβ, which is broadly implicated in progression and metastasis. We found that suppression of PRL-3 expression by TGFβ was mediated by Smad-dependent inhibition of PRL-3 transcription at the level of promoter activity. PRL-3 activation stimulated PI3K/AKT signaling that caused resistance to stress-induced apoptosis. PRL-3 overexpression promoted metastatic colonization in an orthotopic mouse model of colon cancer, whereas PRL-3 knockdown reduced metastatic potential. Altered metastatic phenotypes were not derivative of primary tumor development or local invasion but could be attributed to PRL-3-mediated cell survival. Our findings suggest that inhibiting PRL-3 expression might be an important mechanism through which TGFβ suppresses metastasis in colon cancer. In addition, our findings suggest that loss of TGFβ signaling, which occurs commonly during colon cancer progression, is sufficient to activate a PRL-3-mediated cell survival pathway that can selectively promote metastasis. Therefore, a major implication of our findings is that PRL-3 antagonists may offer significant value for antimetastatic therapy in patients with colon cancer.


Effective catalytic disproportionation of aqueous H2O2 with di- and mono-nuclear manganese(II) complexes containing pyridine alcohol ligands.
The two novel manganese(II) complexes with 2-hydroxymethylpyridine (2-CH2OHpy) {[Mn2(μ-Cl)2(2-CH2OHpy)4]Cl2·2H2O (1)} and 2-hydroxyethylpyridine (2-(CH2)2OHpy) {[Mn(2-(CH2)2OHpy)2(NCS)2] (2)} were synthesized and characterized by means of X-ray diffraction, IR, EPR, HF EPR spectroscopy, magnetic and TG/DTG data. The complexes show catalase-like activity in neutral aqueous solution since they were able to disproportionate H2O2 to harmless H2O and O2. Both complexes act as true catalysts since they reverted to their original form after depleting all the H2O2, as suggested by the operando resonant inelastic X-ray spectroscopy (RIXS) measurements.


Association of postoperative proteinuria with AKI after cardiac surgery among patients at high risk.
Preoperative proteinuria is associated with a higher incidence of postoperative AKI. Whether the same is true for postoperative proteinuria is uncertain. This study tested the hypothesis that increased proteinuria after cardiac surgery is associated with an increased risk for AKI. This prospective cohort study included 1198 adults undergoing cardiac surgery at six hospitals between July 2007 and December 2009. Albuminuria, urine albumin-to-creatinine ratio (ACR), and dipstick proteinuria were measured 0-6 hours after surgery. The primary outcome was AKI, defined as a doubling in serum creatinine or receipt of acute dialysis during the hospital stay. Analyses were adjusted for patient characteristics, including preoperative albuminuria. Compared with the lowest quintile, the highest quintile of albuminuria and highest grouping of dipstick proteinuria were associated with greatest risk for AKI (adjusted relative risks [RRs], 2.97 [95% confidence interval (CI), 1.20-6.91] and 2.46 [95% CI, 1.16-4.97], respectively). Higher ACR was not associated with AKI risk (highest quintile RR, 1.66 [95% CI, 0.68-3.90]). Of the three proteinuria measures, early postoperative albuminuria improved the prediction of AKI to the greatest degree (clinical model area under the curve, 0.75; 0.81 with albuminuria). Similar improvements with albuminuria were seen for net reclassification index (0.55; P<0.001) and integrated discrimination index (0.036; P<0.001). Higher levels of proteinuria after cardiac surgery identify patients at increased risk for AKI during their hospital stay.


Cognitive functions in children at risk for congenital adrenal hyperplasia treated prenatally with dexamethasone.
In Sweden, from 1985 through 1995, 40 fetuses at risk for congenital adrenal hyperplasia (CAH) were treated with dexamethasone (DEX) to prevent virilization of affected females. We report long-term effects on neuropsychological functions and scholastic performance of this controversial treatment. Prenatally treated children, 7 to 17 yr old, were assessed with standardized neuropsychological tests (A Developmental Neuropsychological Assessment and Wechsler Intelligence Scales for Children) and child-completed questionnaires measuring self-perceived scholastic competence (Self-Perception Profile for Children). A parent-completed questionnaire (Child Behavior Checklist/4-18 School Scale) was used to evaluate whether the treatment had any impact on the children's school performance. In addition, a child-completed questionnaire measuring social anxiety (The Social Anxiety Scale for Children-Revised) was completed by the prenatally treated children aged 8 to 17 yr (n = 21) and age- and sex-matched controls (n = 26). Of 40 DEX-treated children, 26 (median age, 11 yr) participated in the study. Thirty-five sex- and age-matched healthy children were controls. There were no between-group differences concerning psychometric intelligence, measures of cerebral lateralization, memory encoding, and long-term memory. Short-term treated, CAH-unaffected children performed poorer than the control group on a test assessing verbal working memory (P = 0.003), and they rated lower on a questionnaire assessing self-perception of scholastic competence (P = 0.003). This group also showed increased self-rated social anxiety assessed by The Social Anxiety Scale for Children-Revised (P = 0.026). Prenatally treated, CAH-affected children performed poorer than controls on tests measuring verbal processing speed, although this difference disappeared when controlling for the child's full-scale IQ. This study indicates that prenatal DEX treatment is associated with previously not described long-term effects on verbal working memory and on certain aspects of self-perception that could be related to poorer verbal working memory. These findings may thus question future DEX treatment of congenital adrenal hyperplasia. Therefore, we encourage additional retrospective studies of larger cohorts to either confirm or challenge the present findings.