Reliability of gingival blood sample to screen diabetes in dental hospital.
Early detection and treatment of diabetes mellitus may reduce the burden of diabetes and its complications. Screening of undiagnosed diabetes with gingival blood sample in patients attending to the dental hospital and to check the reliability with standard method. Five hundred and fifty new patients age ranged from 30 to 50 years were randomly selected. Of 550 patients examined, gingival blood samples of 454 patients were collected from bleeding site and analyzed with self-monitoring device. Blood glucose values were recorded. In addition, all the patients were advised for the second visit with overnight fasting for fasting Blood glucose assessment. Among them, 442 patients returned for fasting blood glucose assessment in laboratory with blood glucose analyzer. In the total of 454 patients gingival blood glucose assessment with self-monitoring device, 64 patients showed ≥200 mg/dL, which indicates diabetes, and the other 390 patients showed ≤200 mg/dL, which indicates patients are not diabetic. Whereas, the results of the laboratory blood glucose analysis, 24 (5.43%) patients showed ≥126 mg/dL, 36 (8.14%) patients showed 100-125 mg/dL and the other 382 patients are not diabetic. Comparison of blood glucose measurements by two methods showed sensitivity 96.66% and specificity 99.47%. The results of the present study showed blood obtained from periodontal pocket probing is a reliable sample to screen diabetes in periodontal disease population. Early diagnosis of diabetes in the dental hospitals can help improve the patient's oral health and overall health status by helping patients avoid or reduce complications from diabetes.


Cortisol titre increases with novelty of academic oral examinations.
In the present study we evaluated whether intensity and novelty of oral academic examinations are reflected in saliva cortisol titre. 91 pupils completed questionnaires on sensation seeking according to Zuckerman as well as on stress coping strategies and rated their individual stress intensity upon minor oral examinations. 26 of these students donated saliva samples before as well as ten and 30 minutes after the examination to quantify cortisol using an immuno assay. Oral examinations during the school year, where students may re-adjust their grade on subsequent examinations, were regarded as minor oral examinations, whereas school exit examinations, where students do not have the chance to correct their grade anymore and may even risk a delay of several months in their academic career when they fail, were regarded as major examinations. Minor oral examinations revealed either a moderate, but significant, increase in saliva cortisol titre by 1.1 fold or did not have a significant impact on cortisol titre. In contrast, school exit exams elevated cortisol titre 5.2 fold. In minor oral examinations, moderate correlations between cortisol titre and subsets in sensation seeking and coping strategies, respectively, were identified. Intensity and novelty of an academic examination is significantly correlated to cortisol titre. Minor oral examinations, with little consequences on academic career, only have a minor impact on cortisol titre, whereas school exit examinations, which are novel to students and may have major consequences on the academic career, elicit a major increase in cortisol titre.


Physical activity and relaxation during and after work are independently associated with the need for recovery.
Research is needed to better understand the associations between during-work and after-work-hours physical activity and relaxation and need for recovery (NFR), so a study of these variables in office workers at a financial service provider was undertaken. Self-reported baseline data of 412 employees (mean age = 41.3 y; 39.6% women) were used. Linear regression analyses were performed to test associations of physical activity, relaxation, detachment, and breaks at work with NFR. A lower NFR was significantly positively associated with standing, stair climbing, active lunch break, relaxation at work, detachment at work, physical detachment at work, relaxation at home, and detachment at home. In the multiple model, a lower NFR was independently positively associated with frequency of stair climbing, minutes spent in leisure activities, detachment at work, physical detachment at work, and relaxation and detachment at home (P < .05). Significant effect modification indicated that the positive association between relaxation at home and NFR was stronger with high job demands. Although prospective evidence is necessary to confirm the causal relationships, our findings suggest that engaging in stair climbing, leisure activities, (physical) detachment at work, relaxation and detachment after work is associated with a lower NFR. For future work site health promotion initiatives, interventions might be targeted at improving physical activity and relaxation.


Bilateral vertical ridge augmentation with block grafts and guided bone regeneration in the posterior mandible: a case report.
The aim is to describe bilateral vertical ridge augmentation with intraoral block grafts and guided bone regeneration in the posterior mandible in preparation for implant placement. A 61-year-old woman, edentulous in the posterior mandible, presented for implant rehabilitation. The radiographic study showed 3 to 6 mm of bone height from the ridge to the mandibular canal. Autogenous bone block grafts from the chin and the mandibular ramus, harvested with ultrasonics, were used to augment the alveolar ridge. To reduce resorption, the grafts were covered with particulate alloplastic material and a collagen membrane. Delayed implants were placed 6 months after vertical augmentation, and 3 months later implants were loaded with a fixed prosthesis. A temporary sensory complication occurred, but 12 months after implant loading, there were no failures. In this case report block bone grafting was a feasible option to vertically augment the alveolar ridge in the posterior mandible.


A transgenic mouse model of sickle cell disorder.
A single base-pair mutation (beta s) in codon 6 of the human beta-globin gene, causing a single amino-acid substitution, is the cause of sickle cell anaemia. The mutant haemoglobin molecule, HbS, polymerizes when deoxygenated and causes deformation of the erythrocytes to a characteristic 'sickled' shape. Sickling of cells in small vessels causes painful crises and other life-threatening complications. Although the molecular basis for sickle cell anaemia has been known for 30 years, no definitive treatment is available. An animal model of sickle cell anaemia would not only allow a detailed analysis of the factors that initiate erythrocyte sickling in vivo and of the pathophysiology of the disease, but would also permit the development of novel approaches to the treatment of the disease. By using the dominant control region sequences from the human beta-globin locus, together with human alpha- and beta s-globin genes, we have obtained three transgenic mice with HbS levels ranging from 10 to 80% of total haemoglobin in their red cells. As observed in homozygous and heterozygous Hbs patients, the erythrocytes of this mouse sickle readily on deoxygenation. Irreversibly sickled cells, which are characteristic of sickle-cell patients homozygous for beta s, are also observed in the peripheral blood of the mouse with high levels of HbS.


Translational autoregulation of ermC 23S rRNA methyltransferase expression in Bacillus subtilis.
ermC specifies an rRNA methyltransferase that confers resistance to erythromycin. The expression of this determinant is induced by the addition of erythromycin. The induction mechanism has been shown to operate posttranscriptionally, and its mechanism has been elucidated. We now show that synthesis of the ermC gene product in Bacillus subtilis is also autoregulated by a mechanism operating on the level of translation. The synthesis of methyltransferase was shown to be gene dosage compensated by Western blot analysis. Several mutants were analyzed that specify altered ermC gene products and are deregulated. Analysis of mutants and of the wild-type strain by Northern blotting demonstrated that autoregulation is posttranscriptional. We suggest a translational repression model in which the ermC methyltransferase binds to its own mRNA, at a region that resembles the methylation target site on 23S rRNA. The overall control of ermC expression is discussed in light of these multiple regulatory mechanisms.


Serological analysis of human deoxyribonucleic acid polymerases. Preparation and properties of antiserum to deoxyribonucleic acid polymerase I from human lymphoid cells.
The preparation and properties of an antiserum to human DNA polymerase I (6 to 8 S) are described. Care was taken in the purification of the antigen to remove certain other DNA polymerases found in human cells. An incubation of antigen and antiserum lasting about 48 hours is necessary to achieve maximal inhibition. About 1 mug of the antipolymerase immunoglobulin G, prepared in rats, neutralizes 60% of the activity present in 54 ng of the enzyme. Tritrations varying both antiserum and enzyme demonstrate clear regions of antigen and antibody excess. Inhibition of enzyme activity is about the same whether the templateprimer is (dA)n-(dT)12-18, or partially digested DNA. An assay was developed which measures the remaining activity in the supernatant after precipitation of enzyme-antibody complexes with goat anti-rat immunoglobulin G. In this assay, 2.2 mug of the antipolymerase immunoglobulin G quantitatively bind 33 ng of DNA polymerase I. With use of the direct neutralization assay and the immuno-precipitation test, we found little, if any, antigenic relationship between DNA polymerase I and DNA polymerase II (3.4 S). Similarly, little, if any, relationship was found to the DNA polymerases from five RNA tumor viruses. The activities of RNA-directed DNA polymerases from the blood leukocytes of two patients with acute myelogenous leukemia and from the placentas of rhesus monkeys were not inhibited in neutralization assays which were shortened because these enzymes were thermolabile. In identically shortened neutralization assays, the antipolymerase immunoglobulin G neutralized up to 76% of the activity of DNA polymerase I. In addition to its utility in distinguishing cellular DNA polymerases, the rat antiserum should be useful reagent for testing of novel DNA polymerases isolated in small quantities from human tumors for contamination with DNA polymerase I. This enzyme is present in abundance in proliferating tissue and often confuses the biochemical characterization of these novel enzymes.


Reactivity with TdT in Merkel cell carcinoma: a potential diagnostic pitfall.
Merkel cell carcinoma (MCC) is a high-grade neuroendocrine carcinoma of skin characterized by cells with a "blastic" appearance, scant cytoplasm, and fine, evenly distributed chromatin. Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase present in thymic T cells, lymphoblastic lymphoma/leukemia, and some cases of acute myeloid leukemia. After observing TdT immunoreactivity in a case of MCC, we analyzed 26 tumors by immunohistochemical analysis to determine their spectrum of reactivity with TdT and identified TdT in 19 (73%) of 26 MCCs. Staining intensity was variable but was often moderate to strong and present in a significant percentage of cells. Because MCC has cytomorphologic features similar to those of lymphoblastic lymphoma and may manifest as metastatic disease, reactivity with TdT in MCC could represent a diagnostic pitfall in the differential diagnosis with lymphoblastic lymphoma, particularly because the latter may lack CD45 and/or CD20, yet both neoplasms may express PAX-5, a B-cell-associated marker.


'Doing the "right" thing': how parents experience and manage decision-making for children's 'normalising' surgeries.
Using cleft lip and palate as an exemplar, this article examines parents' decision-making for children in the context of elective treatments which aim to 'normalise' a child's function, appearance, communication or identity. Using purposive and theoretical sampling, 35 parents with children from infancy to young adulthood were recruited through a specialist cleft centre in England. Parents were interviewed in-depth between 2006 and 2008 about their beliefs and motivations in relation to treatment decision-making in this context. A grounded theory approach was used to analyse the data. Findings revealed a core category, 'doing the "right" thing', that encapsulated parents' main concern in relation to their children's treatment and highlighted several emotional, social and cultural considerations underpinning their decision-making stance. Parents fulfilled a perceived 'moral' obligation to be 'good' parents by pursuing the 'normalising' treatments, particularly surgeries, made available to their children. Such treatments were viewed as a way of facilitating their child's social inclusion and helping them reach their full potential. In order to enable their continued pursuit of treatments over the long-term, parents also constructed specialist practitioners as highly competent and particularly trustworthy. This article captures the complexities involved in parents' decision-making for children's elective 'normalising' treatments, where both functional and appearance-related concerns are involved. It suggests that social norms about parenting, physical appearance and healthcare practitioner power may significantly shape decision-making in this context, so that such choices may be viewed primarily as 'moral' rather than social. Services could support parents with such challenges, by gauging their needs for information about surgery and its likely outcomes and providing emotional/decisional support to consider all available options.


Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain.
Post-ischemic inflammation is an essential step in the progression of brain ischemia-reperfusion injury. However, the mechanism that activates infiltrating macrophages in the ischemic brain remains to be clarified. Here we demonstrate that peroxiredoxin (Prx) family proteins released extracellularly from necrotic brain cells induce expression of inflammatory cytokines including interleukin-23 in macrophages through activation of Toll-like receptor 2 (TLR2) and TLR4, thereby promoting neural cell death, even though intracellular Prxs have been shown to be neuroprotective. The extracellular release of Prxs in the ischemic core occurred 12 h after stroke onset, and neutralization of extracellular Prxs with antibodies suppressed inflammatory cytokine expression and infarct volume growth. In contrast, high mobility group box 1 (HMGB1), a well-known damage-associated molecular pattern molecule, was released before Prx and had a limited role in post-ischemic macrophage activation. We thus propose that extracellular Prxs are previously unknown danger signals in the ischemic brain and that its blocking agents are potent neuroprotective tools.


Repression of flagellar genes in exponential phase by CsgD and CpxR, two crucial modulators of Escherichia coli biofilm formation.
Escherichia coli adapts its lifestyle to the variations of environmental growth conditions, swapping between swimming motility or biofilm formation. The stationary-phase sigma factor RpoS is an important regulator of this switch, since it stimulates adhesion and represses flagellar biosynthesis. By measuring the dynamics of gene expression, we show that RpoS inhibits the transcription of the flagellar sigma factor, FliA, in exponential growth phase. RpoS also partially controls the expression of CsgD and CpxR, two transcription factors important for bacterial adhesion. We demonstrate that these two regulators repress the transcription of fliA, flgM, and tar and that this regulation is dependent on the growth medium. CsgD binds to the flgM and fliA promoters around their -10 promoter element, strongly suggesting direct repression. We show that CsgD and CpxR also affect the expression of other known modulators of cell motility. We propose an updated structure of the regulatory network controlling the choice between adhesion and motility.


Polyphenol-Rich Extract from Propolis Reduces the Expression and Activity of Streptococcus mutans Glucosyltransferases at Subinhibitory Concentrations.
Tooth decay is an infectious disease, whose main causative agent identified is Streptococcus mutans (S. mutans). Diverse treatments have been used to eradicate this microorganism, including propolis. To date, it has been shown that polyphenols from Chilean propolis inhibit S. mutans growth and biofilm formation. However, the molecular mechanisms underlying this process are unclear. In the present study, we assessed the effect of Chilean propolis on the expression and activity of the glycosyltransferases enzymes and their related genes. Polyphenol-rich extract from propolis inhibited gene expression of glycosyltransferases (GtfB, GtfC, and GtfD) and their related regulatory genes, for example, VicK, VicR, and CcpA. Moreover, the treatment inhibited glucosyltransferases activity measured by the formation of sucrose-derived glucans. Additionally, an inhibitory effect was observed in the expression of SpaP involved in sucrose-independent virulence of S. mutans. In summary, our results suggest that Chilean propolis has a dose-dependent effect on the inhibition of genes involved in S. mutans virulence and adherence through the inhibition of glucosyltransferases, showing an anticariogenic potential of polyphenols from propolis beyond S. mutans growth inhibition.


N-acetylcysteine amide decreases oxidative stress but not cell death induced by doxorubicin in H9c2 cardiomyocytes.
While doxorubicin (DOX) is widely used in cancer chemotherapy, long-term severe cardiotoxicity limits its use. This is the first report of the chemoprotective efficacy of a relatively new thiol antioxidant, N-acetylcysteine amide (NACA), on DOX-induced cell death in cardiomyocytes. We hypothesized that NACA would protect H9c2 cardiomyocytes from DOX-induced toxicity by reducing oxidative stress. Accordingly, we determined the ability of NACA to mitigate the cytotoxicity of DOX in H9c2 cells and correlated these effects with the production of indicators of oxidative stress. DOX at 5 microM induced cardiotoxicity while 1) increasing the generation of reactive oxygen species (ROS), 2) decreasing levels and activities of antioxidants and antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase) and 3) increasing lipid peroxidation. NACA at 750 microM substantially reduced the levels of ROS and lipid peroxidation, as well as increased both GSH level and GSH/GSSG ratio. However, treating H9c2 cells with NACA did little to protect H9c2 cells from DOX-induced cell death. Although NACA effectively reduced oxidative stress in DOX-treated H9c2 cells, it had minimal effects on DOX-induced cell death. NACA prevented oxidative stress by elevation of GSH and CYS, reduction of ROS and lipid peroxidation, and restoration of antioxidant enzyme activities. Further studies to identify oxidative stress-independent pathways that lead to DOX-induced cell death in H9c2 are warranted.


Randomized clinical trial of the effect of prenatal fluoride supplements in preventing dental caries.
This randomized, double-blind study tested the caries-preventive efficacy of prenatal fluoride supplementation in 798 children followed until age 5. Initially, 1,400 women in the first trimester of pregnancy residing in communities served by fluoride-deficient drinking water were randomly assigned to one of two groups. During the last 6 months of pregnancy the treatment group received 1 mg fluoride daily in the form of a tablet and the control group received a placebo. Both treatment and control subjects were encouraged to use postnatal dietary fluoride supplements. Caries was measured in children at age 3 and 5 while fluorosis was assessed at age 5. Caries activity was very low in both study groups: 92% of children remained caries-free in the treatment group and 91% remained caries-free in the placebo group. Fluorosis was observed in 26 subjects, all classified as very mild. Overall, there were no statistically significant differences in the study groups with respect to caries and fluorosis in deciduous teeth. The study had sufficient power to detect an absolute risk reduction of 5.1% while only a 1.5% reduction was observed. These findings do not support the hypothesis that prenatal fluoride has a strong caries-preventive effect.


Interactions between ventrolateral prefrontal and anterior cingulate cortex during learning and behavioural change.
Hypotheses and beliefs guide credit assignment - the process of determining which previous events or actions caused an outcome. Adaptive hypothesis formation and testing are crucial in uncertain and changing environments in which associations and meanings are volatile. Despite primates' abilities to form and test hypotheses, establishing what is causally responsible for the occurrence of particular outcomes remains a fundamental challenge for credit assignment and learning. Hypotheses about what surprises are due to stochasticity inherent in an environment as opposed to real, systematic changes are necessary for identifying the environment's predictive features, but are often hard to test. We review evidence that two highly interconnected frontal cortical regions, anterior cingulate cortex and ventrolateral prefrontal area 47/12o, provide a biological substrate for linking two crucial components of hypothesis-formation and testing: the control of information seeking and credit assignment. Neuroimaging, targeted disruptions, and neurophysiological studies link an anterior cingulate - 47/12o circuit to generation of exploratory behaviour, non-instrumental information seeking, and interpretation of subsequent feedback in the service of credit assignment. Our observations support the idea that information seeking and credit assignment are linked at the level of neural circuits and explain why this circuit is important for ensuring behaviour is flexible and adaptive.


Effective coverage and budget implications of skill-mix change to improve neonatal nursing care: an explorative simulation study in Kenya.
Neonatal mortality is an urgent policy priority to improve global population health and reduce health inequality. As health systems in Kenya and elsewhere seek to tackle increased neonatal mortality by improving the quality of care, one option is to train and employ neonatal healthcare assistants (NHCAs) to support professional nurses by taking up low-skill tasks. Monte-Carlo simulation was performed to estimate the potential impact of introducing NHCAs in neonatal nursing care in four public hospitals in Nairobi on effectively treated newborns and staff costs over a period of 10 years. The simulation was informed by data from 3 workshops with >10 stakeholders each, hospital records and scientific literature. Two univariate sensitivity analyses were performed to further address uncertainty. Stakeholders perceived that 49% of a nurse full-time equivalent could be safely delegated to NHCAs in standard care, 31% in intermediate care and 20% in intensive care. A skill-mix with nurses and NHCAs would require ~2.6 billionKenyan Shillings (KES) (US$26 million) to provide quality care to 58% of all newborns in need (ie, current level of coverage in Nairobi) over a period of 10 years. This skill-mix configuration would require ~6 billion KES (US$61 million) to provide quality of care to almost all newborns in need over 10 years. Changing skill-mix in hospital care by introducing NHCAs may be an affordable way to reduce neonatal mortality in low/middle-income countries. This option should be considered in ongoing policy discussions and supported by further evidence.


Suppression of eNOS-derived superoxide by caveolin-1: a biopterin-dependent mechanism.
In the vasculature, nitric oxide (NO) is generated by endothelial NO synthase (eNOS) in a calcium/calmodulin-dependent reaction. In the absence of the requisite eNOS cofactor tetrahydrobiopterin (BH(4)), NADPH oxidation is uncoupled from NO generation, leading to the production of superoxide. Although this phenomenon is apparent with purified enzyme, cellular studies suggest that formation of the BH(4) oxidation product, dihydrobiopterin, is the molecular trigger for eNOS uncoupling rather than BH(4) depletion alone. In the current study, we investigated the effects of both BH(4) depletion and oxidation on eNOS-derived superoxide production in endothelial cells in an attempt to elucidate the molecular mechanisms regulating eNOS oxidase activity. Results demonstrated that pharmacological depletion of endothelial BH(4) does not result in eNOS oxidase activity, whereas BH(4) oxidation gave rise to significant eNOS-oxidase activity. These findings suggest that the endothelium possesses regulatory mechanisms, which prevent eNOS oxidase activity from pterin-free eNOS. Using a combination of gene silencing and pharmacological approaches, we demonstrate that eNOS-caveolin-1 association is increased under conditions of reduced pterin bioavailability and that this sequestration serves to suppress eNOS uncoupling. Using small interfering RNA approaches, we demonstrate that caveolin-1 gene silencing increases eNOS oxidase activity to 85% of that observed under conditions of BH(4) oxidation. Moreover, when caveolin-1 silencing was combined with a pharmacological inhibitor of AKT, BH(4) depletion increased eNOS-derived superoxide to 165% of that observed with BH(4) oxidation. This study identifies a critical role of caveolin-1 in the regulation of eNOS uncoupling and provides new insight into the mechanisms through which disease-associated changes in caveolin-1 expression may contribute to endothelial dysfunction.


[Pregnancy after Breast Cancer: State of the Art].
Breast cancer survivors have given rise to several issues of major relevance from a clinical and scientific point of view. In fact, breast cancer is the most prevalent malignancy in women of reproductive age. The effect of pregnancy on overall survival and in the recurrence after treatment of breast cancer, as well as the questions related to heredity continue to be matter of the highest timeliness and scientific interest. Most recent studies seem to agree in admitting that pregnancy after breast cancer appears to be potentially safe to both the women and her offspring, although this issue remains complex. Heredity and genetics seem to play an important role in this subject, but the conclusions lack absolute and unequivocal consistency. There is a need for meta-analysis, cohort and case-control studies, translational and prospective studies extended in time, in order to obtain greater safety in the establishment of strategies and guidelines for clinicians and adequate objective information for young breast cancer patients.


Enhanced xylitol production using non-detoxified xylose rich pre-hydrolysate from sugarcane bagasse by newly isolated Pichia fermentans.
Integrated management of hemicellulosic fraction and its economical transformation to value-added products is the key driver towards sustainable lignocellulosic biorefineries. In this aspect, microbial cell factories are harnessed for the sustainable production of commercially viable biochemicals by valorising C5 and C6 sugars generated from agro-industrial waste. However, in the terrestrial ecosystem, microbial systems can efficiently consume glucose. On the contrary, pentose sugars are less preferred carbon source as most of the microbes lack metabolic pathway for their utilization. The effective utilization of both pentose and hexose sugars is key for economical biorefinery. Bioprospecting the food waste and selective enrichment on xylose-rich medium led to screening and isolation of yeast which was phylogenetically identified as Pichia fermentans. The newly isolated xylose assimilating yeast was explored for xylitol production. The wild type strain robustly grew on xylose and produced xylitol with > 40% conversion yield. Chemical mutagenesis of isolated yeast with ethyl methanesulphonate (EMS) yielded seven mutants. The mutant obtained after 15 min EMS exposure, exhibited best xylose bioconversion efficiency. This mutant under shake flask conditions produced maximum xylitol titer and yield of 34.0 g/L and 0.68 g/g, respectively. However, under the same conditions, the control wild type strain accumulated 27.0 g/L xylitol with a conversion yield of 0.45 g/g. Improved performance of the mutant was attributed to 34.6% activity enhancement in xylose reductase with simultaneous reduction of xylitol dehydrogenase activity by 22.9%. Later, the culture medium was optimized using statistical design and validated at shake flask and bioreactor level. Bioreactor studies affirmed the competence of the mutant for xylitol accumulation. The xylitol titer and yield obtained with pure xylose were 98.9 g/L and 0.67 g/g, respectively. In comparison, xylitol produced using non-detoxified xylose rich pre-hydrolysate from sugarcane bagasse was 79.0 g/L with an overall yield of 0.54 g/g. This study demonstrates the potential of newly isolated P. fermentans in successfully valorising the hemicellulosic fraction for the sustainable xylitol production.


Impact damage and repair in shells of the limpet Patella vulgata.
Experiments and observations were carried out to investigate the response of the Patella vulgata limpet shell to impact. Dropped-weight impact tests created damage that usually took the form of a hole in the shell's apex. Similar damage was found to occur naturally, presumably as a result of stones propelled by the sea during storms. Apex holes were usually fatal, but small holes were sometimes repaired, and the repaired shell was as strong as the original, undamaged shell. The impact strength (energy to failure) of shells tested in situ was found to be 3.4-times higher than that of empty shells found on the beach. Surprisingly, strength was not affected by removing the shell from its home location, or by removing the limpet from the shell and allowing the shell to dry out. Sand abrasion, which removes material from the apex, was found to have a strong effect. Shells were also subjected to repeated impacts, which caused failure after 2-120 repetitions. In situ shells performed poorly in this test. It is proposed that the apex acts as a kind of sacrificial feature, which confers increased resistance but only for a small number of impacts. Microscopy showed that damage initiates internally as delamination cracks on low-energy interfaces, leading to loss of material by spalling. This mode of failure is a consequence of the layered structure of the shell, which makes it vulnerable to the tensile and shear stresses in the impact shock wave.


Physical conditioning programs for improving work outcomes among workers with back pain.
The aim of this review was to assess the effect of physical conditioning programs, compared to no or alternative interventions, in reducing time lost from work among patients with back pain. We conducted a systematic review with meta-analysis and meta-regression of randomized controlled trials (RCT) of physical conditioning programs for workers with back-pain-related work disability. We included 23 RCT with 3676 participants, with 13 studies having a low risk of bias. In 14 studies, physical conditioning programs were compared to "usual care". Among workers with acute back pain, there was no effect on sickness absence. For workers with subacute back pain, we found conflicting results. Among workers with chronic back pain, pooled results of five studies showed a small effect on sickness absence at one year follow-up [standardized mean difference (SMD) -0.18, 95% confidence interval (95% CI) -0.37-0.00] but this effect disappeared at longer follow-up times. Six studies compared physical conditioning programs to exercise only with conflicting results. The addition of cognitive behavioral therapy to physical conditioning programs did not change the effectiveness. The meta-regression showed no significant effect of program intensity, inclusion of a workplace visit, occupation, setting of the intervention, the type of comparison, or the follow up time. The effectiveness of physical conditioning programs in reducing sick leave for workers with back pain remains uncertain. For acute back pain, these programs probably have no effect; for subacute back pain, the effect is unclear, and for chronic back pain there is a small effect at one year follow-up that does not last in the long run. Remaining heterogeneity could not be explained by meta-regression. A better understanding of the mechanism behind physical conditioning programs and return to work is needed to develop more effective interventions.


Dependence on p75 for innervation of some sympathetic targets.
The low-affinity neurotrophin receptor p75 binds all neurotrophins with similar affinity. For elucidation of its function, mice bearing a null mutation in the p75 locus were generated. Examination of sympathetic innervation of target tissues revealed that pineal glands lacked innervation and sweat gland innervation was absent or reduced in particular footpads. The absence of adult innervation reflects the failure of axons to reach these targets during development rather than a target deficit. These results indicate that p75 facilitates development of specific populations of sympathetic neurons, for which it may support axon growth.


Campylobacter jejuni-associated hemolytic-uremic syndrome in a mother and daughter.
A mother and daughter with Campylobacter jejuni-associated hemolytic-uremic syndrome (HUS) are discussed. The mother was hospitalized with bloody diarrhea and HUS; C jejuni was isolated from her stool. The 2-year-old daughter had been admitted five days prior to her mother with HUS following a three-day prodrome of vomiting and diarrhea. Multiple stool cultures were negative for enteric pathogens; however, cultures were not obtained until the eighth hospital day and after antibiotic therapy. Extensive investigation failed to identify another cause for the diarrheal illness or HUS in our patients. Indirect immunofluorescent antibody titers for C jejuni were 1:32 and 1:16 for the mother and daughter, respectively. An asymptomatic 9-month-old son had C jejuni isolated from his stool and had an immunofluorescent antibody titer of 1:64. Three other family members were asymptomatic, stool-culture negative, and had immunofluorescent antibody titers less than or equal to 1:4. The susceptibility to develop HUS following an enteric antigenic stimulus is illustrated by the patients presented. The need for systematic investigation of all HUS cases for potential susceptibility markers, as well as an exhaustive etiologic search, is emphasized.


Evidence-based assessment of acute pain in older adults: current nursing practices and perceived barriers.
To report data on current nurse practice behaviors related to evidence-based assessment of acute pain in older adults, perceived stage of adoption of pain assessment practices, and perceptions of barriers to optimal assessment in this population. Medical records from 709 older adult patients hospitalized with hip fractures from 12 acute care settings were abstracted for nurse assessment practices during the first 72 hours after admission. Questionnaires sent to nurses on study units regarding perceived stage of adoption and barriers to assessment in older adults. Data revealed several areas in which pain assessment practices were not optimal. Pain was not routinely assessed every 4 hours, and pain location was assessed even less frequently. Pain behaviors were assessed more in patients with a diagnosis of dementia compared to those without dementia, but the frequency of pain behavior assessments was low. Pain was not routinely assessed within 60 minutes of administering an analgesic. Nurses reported not using optimal pain assessment practices even when they were aware of and persuaded that those practices were desirable. In addition, nurses reported that difficulty communicating with patients created the greatest challenge in managing pain. Our data suggest that pain is not being assessed and reassessed in a manner that is consistent with current practice recommendations in older adult patients with pathologic processes that highly suggest the presence of acute pain.


Optimization of informed consent for umbilical cord blood banking.
The purpose of this project was to evaluate the informed consent process for donation to a public umbilical cord blood bank. Telephone interviews were conducted with 170 women who had given consent to donate their newborn infants' umbilical cord blood. Of the 170 women who were contacted, 96.8% of the women reported that all their questions had been answered. Nevertheless, approximately one third of the respondents did not consider themselves to be in research, and almost one quarter of the respondents did not know how to contact the umbilical cord blood bank if they or their infant became seriously ill. Further, a substantial proportion of the respondents did not understand the full range of alternatives to donation and incorrectly endorsed potential benefits. Informed consent could be optimized by (1) having those personnel who obtain consent emphasize that banking involves research and to explain the true benefits of donation, (2) ensuring that parents know how and when to contact the umbilical cord blood bank after donation, and (3) using phone surveys to continue assessments and to monitor changes in the process.


Prognostic significance of autoimmunity during treatment of melanoma with interferon.
Immunotherapy for advanced melanoma induces serologic and clinical manifestations of autoimmunity. We assessed the prognostic significance of autoimmunity in patients with stage IIB, IIC, or III melanoma who were treated with high-dose adjuvant interferon alfa-2b. We enrolled 200 patients in a substudy of a larger, ongoing randomized trial. Blood was obtained before the initiation of intravenous interferon therapy, after 1 month of therapy, and at 3, 6, 9, and 12 months. Serum was tested for antithyroid, antinuclear, anti-DNA, and anticardiolipin autoantibodies, and patients were examined for vitiligo. The median duration of follow-up was 45.6 months. Relapse occurred in 115 patients, and 82 patients died. The median relapse-free survival was 28.0 months, and the median overall survival was 58.7 months. Autoantibodies and clinical manifestations of autoimmunity were detected in 52 patients (26 percent). The median relapse-free survival was 16.0 months among patients without autoimmunity (108 of 148 had a relapse) and was not reached among patients with autoimmunity (7 of 52 had a relapse). The median survival was 37.6 months among patients without autoimmunity (80 of 148 died) and was not reached among patients with autoimmunity (2 of 52 died). In univariate and multivariate regression analyses, autoimmunity was an independent prognostic marker for improved relapse-free survival and overall survival (P<0.001). The appearance of autoantibodies or clinical manifestations of autoimmunity during treatment with interferon alfa-2b is associated with statistically significant improvements in relapse-free survival and overall survival in patients with melanoma.


UTP and ATP induce different membrane voltage responses in rat mesangial cells.
UTP and ATP induce different membrane voltage responses in rat mesangial cells. Recent studies have indicated that UTP and ATP might modulate mesangial cell function in a different manner. Here we compared the effect of UTP and ATP on membrane voltage (Vm) and ion currents in mesangial cells in primary culture, and we examined whether different nucleotide receptors are involved. In patch-clamp experiments in the fast whole cell configuration, UTP (in contrast to ATP) caused a sustained and concentration-dependent depolarization (half-maximal effective dose, 10(-5) M), but ATP caused only a transient depolarization. During the depolarization, UTP induced a sustained increase of the whole cell conductance (Gm), whereas ATP induced only a transient increase of Gm. When cells were dialyzed with Cs2SO4 and extracellular Cl- was replaced by 145 mM sodium gluconate, addition of UTP or ATP (both 10(-4) M) did not significantly increase Gm. Addition of ATP in the presence of UTP caused an additional depolarization by 5 mV, which was followed by a hyperpolarization by 21 mV. Repetitive application of ATP led to an attenuation of the ATP-induced depolarization. Then, in the presence of ATP, UTP still induced a significant depolarization by 10 mV. Suramine and reactive blue 2 did not inhibit the depolarization induced by UTP, but these inhibited the Vm response to ATP. In microfluorescence experiments, UTP and ATP caused a concentration-dependent increase of the intracellular calcium activity ([Ca2+]i) in mesangial cells. Application of both UTP and ATP had no additive effect on [Ca2+]i. The results suggest that mesangial cells possess, in addition to P2y purinoceptors, separate nucleotide receptors for UTP.


Structural domains of interleukin-2 receptor beta critical for signal transduction: kinase association and nuclear complex-formation.
The structural domains of interleukin-2 receptor beta (IL-2R beta) were examined, characterizing the protein domains, associated phosphoproteins and nuclear complexes of IL-2-induced signal transduction. A series of IL-2R beta cytoplasmic deletion mutants were constructed and transfected into a murine pre-B-cell line, Ba/F3. The proliferative response of characterized clones was determined. A minimal linear cytoplasmic sequence required for proliferation and a sequence motif (PQPLXP) needed along with Box1-Box2 for IL-2-induced proliferation were identified. Anti-phosphotyrosine Western-blot analysis of a stimulated biologically active clone showed several IL-2-induced tyrosylphosphorylated proteins with molecular masses ranging from 45 to 116 kDa. In vitro kinase studies of biologically active clone-receptor complexes showed a 116 kDa protein (p116) to be the major tyrosine-phosphorylated component. The presence of the p116 kinase in the receptor complex correlates with IL-2-induced proliferation. An IL-2-inducible p116 kinase has recently been characterized as a Jak kinase family member and named Jak3. Nuclear complexes were formed with the GRR oligomer only when the IL-2R beta mutant supported proliferation. This led us to conclude that Box1-Box2 and PQPLXP motifs associate with Jak3 and that this association is an essential element in the IL-2 signal-transduction pathway culminating in the formation of a nuclear complex.


Mapping haplotype-haplotype interactions with adaptive LASSO.
The genetic etiology of complex diseases in human has been commonly viewed as a complex process involving both genetic and environmental factors functioning in a complicated manner. Quite often the interactions among genetic variants play major roles in determining the susceptibility of an individual to a particular disease. Statistical methods for modeling interactions underlying complex diseases between single genetic variants (e.g. single nucleotide polymorphisms or SNPs) have been extensively studied. Recently, haplotype-based analysis has gained its popularity among genetic association studies. When multiple sequence or haplotype interactions are involved in determining an individual's susceptibility to a disease, it presents daunting challenges in statistical modeling and testing of the interaction effects, largely due to the complicated higher order epistatic complexity. In this article, we propose a new strategy in modeling haplotype-haplotype interactions under the penalized logistic regression framework with adaptive L1-penalty. We consider interactions of sequence variants between haplotype blocks. The adaptive L1-penalty allows simultaneous effect estimation and variable selection in a single model. We propose a new parameter estimation method which estimates and selects parameters by the modified Gauss-Seidel method nested within the EM algorithm. Simulation studies show that it has low false positive rate and reasonable power in detecting haplotype interactions. The method is applied to test haplotype interactions involved in mother and offspring genome in a small for gestational age (SGA) neonates data set, and significant interactions between different genomes are detected. As demonstrated by the simulation studies and real data analysis, the approach developed provides an efficient tool for the modeling and testing of haplotype interactions. The implementation of the method in R codes can be freely downloaded from http://www.stt.msu.edu/~cui/software.html.


Diabetes mellitus and hypertension.
Diabetes mellitus and hypertension are common diseases that coexist at a greater frequency than chance alone would predict. Hypertension in the diabetic individual markedly increases the risk and accelerates the course of cardiac disease, peripheral vascular disease, stroke, retinopathy, and nephropathy. Our understanding of the factors that markedly increase the frequency of hypertension in the diabetic individual remains incomplete. Diabetic nephropathy is an important factor involved in the development of hypertension in diabetics, particularly type I patients. However, the etiology of hypertension in the majority of diabetic patients cannot be explained by underlying renal disease and remains "essential" in nature. The hallmark of hypertension in type I and type II diabetics appears to be increased peripheral vascular resistance. Increased exchangeable sodium may also play a role in the pathogenesis of blood pressure in diabetics. There is increasing evidence that insulin resistance/hyperinsulinemia may play a key role in the pathogenesis of hypertension in both subtle and overt abnormalities of carbohydrate metabolism. Population studies suggest that elevated insulin levels, which often occurs in type II diabetes mellitus, is an independent risk factor for cardiovascular disease. Other cardiovascular risk factors in diabetic individuals include abnormalities of lipid metabolism, platelet function, and clotting factors. The goal of antihypertensive therapy in the patient with coexistent diabetes is to reduce the inordinate cardiovascular risk as well as lowering blood pressure.


Arytenoid mucosal injury in young Thoroughbred horses--investigation of a proposed aetiology and clinical significance.
To determine whether trauma to the larynx caused by nasotracheal intubation induced mucosal ulceration of the arytenoid cartilages of adult horses, and to determine the incidence of such ulceration in yearling Thoroughbred horses and its effect on athletic performance. Laryngeal trauma was induced in a group of 21 adult horses by introduction of a nasogastric tube into the trachea three times within 5 min. Injury to the arytenoid cartilages or vocal cords was subjectively assessed immediately after intubation, and thereafter at weekly intervals for 10 weeks. The outcome and athletic performance of 33 Thoroughbred yearling horses with idiopathic disease of the arytenoid cartilages, diagnosed at the yearling sales, were evaluated and compared to those of control horses of the same gender and age, from the same sale. Mucosal injury was noted immediately after intubation in every horse. Evidence of injury to the vocal or corniculate processes of the arytenoid cartilages or vocal cords was still apparent in 10/21 (48%) horses 1 week after intubation, five of which developed persistent lesions that remained present and unchanged from 28 days following intubation until the end of the 10-week observation period. All persistent lesions were nodules or focal swellings of the vocal cords or arytenoid cartilages, and there was no evidence of mucosal ulceration, infection or discharge. Mucosal ulceration of the vocal processes was the most common abnormality detected in the yearlings, affecting 16/33 (48%) that were diagnosed with idiopathic arytenoid disease at the yearling sales. Five of the 33 (15%) horses were diagnosed with arytenoid chondritis at the time of sale and were excluded from the performance outcome analysis. Of the 28 horses diagnosed with arytenoid abnormalities excluding chondritis, 19 (68%) raced with no history of respiratory-related problems, two (7%) were subsequently diagnosed with laryngeal hemiplegia, and seven (25%) were lost to follow-up. The case animals were 2.7 times more likely to race than control horses, but there was no difference between cases and controls in the likelihood of starting more than three times. This study showed that nasotracheal intubation in adult horses could result in immediate mucosal trauma, persistent swelling, and focal scarring of the arytenoid cartilages, but this did not mimic mucosal ulceration or chondritis of the arytenoid cartilages observed in yearling Thoroughbred horses. The population studied, however, may not accurately represent the population in which idiopathic disease occurs. In this study, arytenoid mucosal ulceration detected at sale did not commonly progress to arytenoid chondritis. However, a study of a larger population of horses with untreated, naturally occurring disease is required to confirm these findings. It is unlikely that trauma from nasogastric intubation caused arytenoid mucosal ulceration, therefore this procedure should not necessarily be discouraged. This study did not find evidence that horses diagnosed with arytenoid mucosal ulceration at yearling sales had a reduced performance history, therefore it is reasonable to continue to pass horses with uncomplicated arytenoid mucosal ulceration during post-sale endoscopic examination. However, monitoring of the lesions and treatment, if required, may be indicated in the post-sale period.


Chromatic confocal microscopy using staircase diffractive surface.
A chromatic confocal microscope (CCM) is a high-dynamic-range noncontact distance measurement sensor; it is based on a hyperchromatic lens. The vast majority of commercial CCMs use refractive-based chromatic dispersion to chromatically code the optical axis. This approach significantly limits the range of applications and performance of the CCM. In order to be a suitable alternative to a laser triangulation gauge and laser encoder, the performance of the CCM must be improved. In this paper, it is shown how hybrid aspheric diffractive (HAD) lenses can bring the CCM to its full potential by increasing the dynamic range by a factor of 2 and the resolution by a factor of 5 while passively athermizing and increasing the light throughput efficiency of the optical head [M. Rayer, U.S. patent 1122052.2 (2011)]. The only commercially suitable manufacturing process is single-point diamond turning. However, the optical power carried by the diffractive side of a hybrid aspheric diffractive lens is limited by the manufacturing process. A theoretical study of manufacturing losses has revealed that the HAD configuration with the highest diffraction efficiency is for a staircase diffractive surface (SDS). SDS lenses have the potential to reduce light losses associated with manufacturing limits by a factor of 5 without increasing surface roughness, allowing scalar diffraction-limited optical design with a diffractive element.


Effect of Clot Stiffness on Recombinant Tissue Plasminogen Activator Lytic Susceptibility in Vitro.
The lytic recombinant tissue plasminogen activator (rt-PA) is the only drug approved by the Food and Drug Administration for treating ischemic stroke. Less than 40% of patients with large vessel occlusions who are treated with rt-PA have improved blood flow. However, up to 6% of all patients receiving rt-PA develop intracerebral hemorrhage. Predicting the efficacy of rt-PA treatment a priori could help guide therapeutic decision making, such that rt-PA is administered only to those individuals who would benefit from this treatment. Clot composition and structure affect the lytic efficacy of rt-PA and have an impact on elasticity. However, the relationship between clot elasticity and rt-PA lytic susceptibility has not been adequately investigated. The goal of this study was to quantify the relationship between clot elasticity and rt-PA susceptibility in vitro. Human and porcine highly retracted and mildly retracted clots were fabricated in glass pipettes. The rt-PA lytic susceptibility was evaluated in vitro using the percent clot mass loss. The Young's moduli of the clots were estimated using ultrasound-based single-track-location shear wave elasticity imaging. The percent mass loss in mildly retracted porcine and human clots (28.9 ± 6.1% and 45.2 ± 7.1%, respectively) was significantly higher (p < 0.05) than in highly retracted porcine and human clots (10.9 ± 2.1% and 25.5 ± 10.0%, respectively). Furthermore, the Young's moduli of highly retracted porcine and human clots (5.33 ± 0.92 and 3.21 ± 1.97 kPa, respectively) were significantly higher (p < 0.05) than those of mildly retracted porcine and human clots (2.66 ± 0.55 and 0.79 ± 0.21 kPa, respectively). The results revealed an inverse relationship between the percent clot mass loss and Young's modulus. These findings motivate continued investigation of ultrasound-based methods to assess clot stiffness in order to predict rt-PA thrombolytic efficacy.


Therapeutic targeting of SPINK1-positive prostate cancer.
Gene fusions involving ETS (erythroblastosis virus E26 transformation-specific) family transcription factors are found in ~50% of prostate cancers and as such can be used as a basis for the molecular subclassification of prostate cancer. Previously, we showed that marked overexpression of SPINK1 (serine peptidase inhibitor, Kazal type 1), which encodes a secreted serine protease inhibitor, defines an aggressive molecular subtype of ETS fusion-negative prostate cancers (SPINK1+/ETS⁻, ~10% of all prostate cancers). Here, we examined the potential of SPINK1 as an extracellular therapeutic target in prostate cancer. Recombinant SPINK1 protein (rSPINK1) stimulated cell proliferation in benign RWPE as well as cancerous prostate cells. Indeed, RWPE cells treated with either rSPINK1 or conditioned medium from 22RV1 prostate cancer cells (SPINK1+/ETS⁻) significantly increased cell invasion and intravasation when compared with untreated cells. In contrast, knockdown of SPINK1 in 22RV1 cells inhibited cell proliferation, cell invasion, and tumor growth in xenograft assays. 22RV1 cell proliferation, invasion, and intravasation were attenuated by a monoclonal antibody (mAb) to SPINK1 as well. We also demonstrated that SPINK1 partially mediated its neoplastic effects through interaction with the epidermal growth factor receptor (EGFR). Administration of antibodies to SPINK1 or EGFR (cetuximab) in mice bearing 22RV1 xenografts attenuated tumor growth by more than 60 and 40%, respectively, or ~75% when combined, without affecting PC3 xenograft (SPINK1⁻/ETS⁻) growth. Thus, this study suggests that SPINK1 may be a therapeutic target in a subset of patients with SPINK1+/ETS⁻ prostate cancer. Our results provide a rationale for both the development of humanized mAbs to SPINK1 and evaluation of EGFR inhibition in SPINK1+/ETS⁻ prostate cancers.


Molecular and genetic mechanisms of obesity: implications for future management.
Obesity has become a worldwide public health problem affecting millions of people. A disruption of the balance between energy intake and energy expenditure is believed to be the major cause of obesity. Substantial progress has been made in deciphering the pathogenesis of energy homeostasis over the past few years. The fact that obesity is under strong genetic control has been well established. Human monogenic obesity is rare in large populations, the most common form of obesity is considered to be a polygenic disorder arising from the interaction of multiple genetic and environmental factors. Here, we attempt to briefly review the most recent understanding of molecular mechanisms involved in energy homeostasis and adipogenesis. We discuss the advantages and disadvantages of various approaches commonly used in search for susceptibility genes for obesity. The main results from these genetic studies are summarized, with comments made on the most striking or representative findings. Finally, the implications of the recent advances in the understanding of molecular genetic mechanisms of body weight regulation on prevention and therapeutic intervention of obesity will be discussed.


(Biphenyl-2-alkyne) derivatives as common precursors for the synthesis of 9-iodo-10-organochalcogen-phenanthrenes and 9-organochalcogen-phenanthrenes.
In this paper, we report our results on the cyclization of (biphenyl-2-alkyne) derivatives to give two different types of phenanthrene derivatives, 9-iodo-10-organochalcogen-phenanthrenes and 9-organochalcogen-phenanthrenes. The strategy for the synthesis was based on the use of electrophilic cyclization for the preparation of 9-iodo-10-organochalcogen-phenanthrenes and iron(iii) chloride/diorganyl diselenide-mediated intramolecular cyclization to prepare 9-organochalcogen-phenanthrenes. The effects of solvent, temperature, reaction time and stoichiometry on the efficiency of cyclization reactions were investigated. The standard reaction conditions were compatible with many functional groups in the substrates, such as methyl, chlorine, fluorine and methoxyl. This protocol was efficient for diorganyl diselenides and disulfides but ineffective for diorganyl ditellurides. The resulting phenanthrenes were further functionalized through Sonogashira reactions followed by the electrophilic cyclization reaction to give the selenophene-fused aromatic compounds.


Cancer genetic health communication in families tested for hereditary breast/ovarian cancer risk: a qualitative investigation of impact on children's genetic health literacy and psychosocial adjustment.
Children's literacy about the genetics of late-onset hereditary breast/ovarian cancer (HBOC) often develops through conversations with parents about BRCA gene testing and adults' cancer diagnoses. These conversations may promote early understanding of HBOC, but the long-term impact on children's psychosocial adjustment remains unclear. We investigated cancer genetic health communication in BRCA-tested families to consider benefits, risks, and moderating influences on children's understanding and well-being. Adolescent and young adult children (ages 12-24) of mothers who underwent BRCA testing 1+ years previously completed qualitative interviews that were transcribed, coded (intercoder K ≥ .70), and content-analyzed (N = 34). Children readily recalled conversations about BRCA testing and HBOC (100%) that they considered important (94%), but implications for children were ambiguous and obfuscated their concerns. Psychosocial impacts were muted, multifaceted, and displayed a range of favorable (82%), neutral (71%), and unfavorable (59%) response-frequently co-occurring within the same child over different aspects (e.g., medical, concern for self and others). Children verbalized active (50%) and avoidant (38%) coping strategies: about 1:5 endorsed transient thoughts about vulnerability to HBOC, 1:3 had not further considered it, and all reported specific actions they had or would undertake to remain healthy (e.g., diet/exercise). A majority (94%) of children had or would consider genetic testing for themselves, usually later in life (59%). Long-term outcomes highlighted benefits (awareness of HBOC, psychological hardiness, healthier lifestyle behaviors), as well as some psychosocial concerns that could be managed through interventions promoting genetic health literacy.


Factors Associated with Primary School Teachers' Attitudes Towards the Inclusion of Students with Disabilities.
Teachers' attitudes toward inclusion are often based on the practical implementation of inclusive education rather than a specific ideology and understanding of inclusiveness. This study aimed to identify the factors associated with primary school teachers' attitudes towards inclusion of students with all disabilities in regular schools. Seventy four primary school teachers participated in a cross-sectional survey conducted in Western Australia. Teachers' attitudes and efficacy toward integration of students with disabilities were measured using the Opinions Relative to Integration of Students with Disabilities scale and Bandura's Teacher Efficacy scale respectively. Four teacher attributes-age, gender, teaching self-efficacy and training collectively explained 42% of the variability in teachers' attitude toward including students with disabilities. The current study further contributes to the accumulation of knowledge that can unpack the complex pattern of factors that should be considered to promote positive attitudes towards inclusive schools.


Screening for Depression in Children and Adolescents: US Preventive Services Task Force Recommendation Statement.
This article describes the update of the 2009 US Preventive Services Task Force (USPSTF) recommendation on screening for major depressive disorder (MDD) in children and adolescents. The USPSTF reviewed the evidence on the benefits and harms of screening, accuracy of primary care-feasible screening tests, and benefits and harms of treatment with psychotherapy, medications, and collaborative care models in patients aged 7 to 18 years. This recommendation applies to children and adolescents aged ≤18 years who do not have an MDD diagnosis. The USPSTF recommends screening for MDD in adolescents aged 12 to 18 years. Screening should be implemented with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up (B recommendation). The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for MDD in children aged ≤11 years (I statement).


Outcomes and reoperations after total correction of complete atrio-ventricular septal defect.
Surgical correction of complete atrio-ventricular septal defect (AVSD) achieves satisfactory results with low morbidity and mortality, but may require reoperation. Our recent operative results at mid-term were followed-up. From June 2000 to December 2007, 81 patients (Down syndrome; n=60), median age 4.0 months (range 0.7-118.6) and weight 4.7kg (range 2.2-33), underwent complete AVSD correction. Patch closure for the ventricular septal defect (VSD; n=69) and atrial septal defect (ASD; n=42) was performed with left atrio-ventricular valve (LAVV) cleft closure (n=76) and right atrio-ventricular valve (RAVV) repair (n=57). Mortality, morbidity, and indications for reoperation were retrospectively studied; the end point 'time to reoperation' was analyzed using Kaplan-Meier curves. Follow-up was complete except in two patients and spanned a median of 28 months (range 0.4-6.1 years). In-hospital mortality was 3.7% (n=3) and one late death occurred. Reoperation was required in 7/79 patients (8.9%) for LAVV insufficiency (n=4), for a residual ASD (n=1), for right atrio-ventricular valve insufficiency (n=1), and for subaortic stenosis (n=1). At last follow-up, no or only mild LAVV and RAVV insufficiency was present in 81.3% and 92.1% of patients, respectively, and 2/3 of patients were medication-free. Risk factors for reoperation were younger age (<3 months; p=0.001) and lower weight (<4kg; p=0.003), and a trend towards less and later reoperations in Down syndrome (p<0.2). Surgical correction of AVSD can be achieved with low mortality and need for reoperation, regardless of Down syndrome or not. Immediate postoperative moderate or more residual atrio-ventricular valve insufficiency will eventually require a reoperation, and could be anticipated in patients younger than 3 months and weighing <4kg.


Vowel Formants in Normal and Loud Speech.
Purpose This study evaluated how 1st and 2nd vowel formant frequencies (F1, F2) differ between normal and loud speech in multiple speaking tasks to assess claims that loudness leads to exaggerated vowel articulation. Method Eleven healthy German-speaking women produced normal and loud speech in 3 tasks that varied in the degree of spontaneity: reading sentences that contained isolated /i: a: u:/, responding to questions that included target words with controlled consonantal contexts but varying vowel qualities, and a recipe recall task. Loudness variation was elicited naturalistically by changing interlocutor distance. First and 2nd formant frequencies and average sound pressure level were obtained from the stressed vowels in the target words, and vowel space area was calculated from /i: a: u:/. Results Comparisons across many vowels indicated that high, tense vowels showed limited formant variation as a function of loudness. Analysis of /i: a: u:/ across speech tasks revealed vowel space reduction in the recipe retell task compared to the other 2. Loudness changes for F1 were consistent in direction but variable in extent, with few significant results for high tense vowels. Results for F2 were quite varied and frequently not significant. Speakers differed in how loudness and task affected formant values. Finally, correlations between sound pressure level and F1 were generally positive but varied in magnitude across vowels, with the high tense vowels showing very flat slopes. Discussion These data indicate that naturalistically elicited loud speech in typical speakers does not always lead to changes in vowel formant frequencies and call into question the notion that increasing loudness is necessarily an automatic method of expanding the vowel space. Supplemental Material https://doi.org/10.23641/asha.8061740.


The vertical heights of maxillary and mandibular bones in panoramic radiographs of dentate and edentulous subjects.
The purposes of this study were to determine the variation in maxillary and mandibular vertical measurements made from panoramic radiographs and to assess differences in measurements between dentate and edentulous jaws. A total of 192 alveolar ridges (96 dentate and 96 edentulous) were examined. The mean ages of the dentate and edentulous groups were 51.05 and 59.98 years, respectively. Measurements were made from reference lines drawn from anatomic landmarks on standardized panoramic radiographs. In the dentate group, there was no statistically significant difference between men and women in the height of the maxilla. However, the height of the mandible was significantly greater in men than in women. In the edentulous group, the heights of the maxilla at the anterior and first premolar regions were significantly greater in men than in women. In the same group, mandibular heights were also significantly greater in men than in women. Reductions in the height of the edentulous mandible and maxilla were significantly more pronounced in women than in men. The decrease in the vertical height of the maxilla was not statistically significant in men. There are differences between the sexes in alveolar ridge resorption after tooth loss.


Improving cognitive treatments for delusions.
A clear challenge for schizophrenia research is to improve markedly the efficacy of psychological treatments for delusional beliefs. Effect sizes for the first generation of cognitive approaches are weak to moderate. These therapies now lag behind the transformation over the past ten years in understanding the causes of delusions. This paper advocates an interventionist-causal model approach: to focus on one putative causal factor at a time, show that an intervention can change it, and examine the subsequent effects on the delusional beliefs. A number of new studies that illustrate this approach with patients with schizophrenia spectrum disorders who have not responded to previous treatment are reviewed. These early stage studies show great promise in terms of efficacy, although remain to be subjected to methodologically rigorous evaluation. The advantages and difficulties of the interventionist approach applied to psychosis are considered, and future studies are highlighted. The importance for clinical services of cognitive approaches to psychosis will increase further if the theoretical advances can be translated into treatment.


High-efficiency beam bending using graded photonic crystals.
We explore beam-bending properties of graded index (GRIN) waveguide with hyperbolic secant profile. The transmission efficiency and bandwidth features are extracted for GRIN photonic crystal (PC) media composed of dielectric rods. Light guiding performance of the GRIN PC medium is analyzed for 90° and 180° waveguide bends. The finite-difference time-domain method is deployed to investigate the performance of the designed GRIN waveguides. By the help of proposed photonic configuration, bending of light is achieved with a high efficiency within a broad bandwidth, which promotes the use of GRIN PC structures for efficient light-bending purposes.


Speckle-reduced three-dimensional volume holographic display by use of integral imaging.
We propose a method to implement a speckle-reduced coherent three-dimensional (3D) display system by a combination of integral imaging and photorefractive volume holographic storage. The 3D real object is imaged through the microlens array and stored in the photorefractive crystal. During the reconstruction process a phase conjugate reading beam is used to minimize aberration, and a rotating diffuser located on the imaging plane of the lens array is employed to reduce the speckle noise. The speckle-reduced 3D image with a wide viewing angle can be reconstructed by use of the proposed system. Experimental results are presented and optical parameters of the proposed system are discussed in detail.


The quartz crystal microbalance: a new tool for the investigation of the bioadhesion of diatoms to surfaces of differing surface energies.
Diatoms are a major component of the biofoul layer found on modern low-surface-energy, 'foul release' coatings. While diatoms adhere more strongly to hydrophobic, as opposed to hydrophilic, surfaces, surprisingly little is known of the chemical composition of their adhesives. Even less is known about the underlying processes that characterize the interaction between the adhesive and a given surface, including those of differing wettability. Using the quartz crystal microbalance with dissipation monitoring (QCM-D), we examined differences in the viscoelastic properties of the extracellular adhesives produced by the marine diatoms Amphora coffeaeformis Cleve and Craspedostauros australis Cox interacting with surfaces of differing wettability; 11-mercaptoundecanoic acid (MUA) that is hydrophilic and 1-undecanethiol (UDT) that is hydrophobic. While the overall delta f/delta D ratios were slightly different, the trends were the same for both diatom species, with the layer secreted upon UDT to be more viscoelastic and far more consistent over several experiments, compared to that on MUA which was less viscoelastic and demonstrated far more variability between experiments. While the nature of the parameter shifts for C. australis were the same for both surfaces, A. coffeaeformis cells settling upon UDT illustrated significant positive f and D shifts during the initial stages of cell settlement and adhesion to the surface. Further experiments revealed the parameter shifts to occur only during the initial adhesion of cells upon the pristine virgin UDT surface. The mechanism behind these parameter responses was isolated to the actin-myosin/adhesion complex (AC), using the myosin inhibitor 2,3-butanedione 2-monoxime (BDM) to remove the cells ability to 'pull' on adhesive strands emanating from the cell raphe. The observations made herein have revealed that adhesives secreted by fouling diatoms differ significantly in their interaction with surfaces depending on their wettability, as well as illustrating the unique mechanics behind the adhesion of A. coffeaeformis upon hydrophobic surfaces, a mechanism that may contribute significantly to the cells success in colonizing hydrophobic surfaces.


Noise contributions for imaging spectrometers.
In the past decade imaging spectrometers for observation of the Earth were developed to use the complete information of a spectrum as a major tool in the study of physical and biological processes of the Earth. Instead of a few relatively broad spectral bands (line detector), this imager concept provides for the detection of many contiguous narrow spectral bands by applying the technology of matrix detectors. The change from one-dimensional to two-dimensional solid-state imagers makes it necessary to carry out the specific signal-to-noise ratio (SNR) analysis of such detectors. A simulation of maximum and minimum radiances for typical spectral signatures of the Earth (water, vegetation) and the verification of these radiances with modular optoelectronic scanner data provide the means for calculation of electrons generated at the matrix detector. For a hypothetical sensor, water-minimum and vegetation-maximum signals are calculated, and the degradation of the SNR caused by image smear of two-dimensional solid-state imagers is demonstrated.


Integration of a recombinant chitinase into Bacillus thuringiensis parasporal insecticidal crystal.
Chitinases have been successfully used in combination with Bacillus thuringiensis delta-endotoxins forming crystals in order to enhance their insecticidal activities. In this context, we opted for promoting the chitinase integration into these crystals. Thus, we engineered, for the first time, a fusion protein (CDF) consisting of the chitinase Chi255 and the carboxy-terminal half of Cry1Ac, both from B. thuringiensis subsp. kurstaki. The constructed transcriptional fusion (chi255Δsp-CTcry1Ac) was cloned into a shuttle vector (Escherichia coli/B. thuringiensis) downstream the sporulation-dependent promoters BtI-BtII and upstream the cry1Ac transcription terminator. The resulting plasmid, named pF, was transferred by electroporation to crystalliferous B. thuringiensis strain BNS3 and acrystalliferous strain BNS3Cry-. The functionality of the chimerical chitinase was demonstrated by an improvement of the relative chitinolytic activity of the recombinant strain BNS3/pF by 2.5 folds. Western blot analyses showed that, despite of the instability of CDF when expressed in the acrystalliferous strain, the C-terminal half of Cry1Ac succeeded to allow the integration of the chimerical chitinase into the crystal of BNS3. The recombinant strain BNS3/pF (LC(50) = 144.06 μg g(-1)) was 1.5 times more active against Ephestia kuehniella larvae than the wild strain (LC(50) = 212.10 μg g(-1)).


Imaging properties of high aspect ratio absorption gratings for use in preclinical x-ray grating interferometry.
X-ray grating interferometry is one among various methods that allow extracting the so-called phase and visibility contrasts in addition to the well-known transmission images. Crucial to achieving a high image quality are the absorption gratings employed. Here, we present an in-depth analysis of how the grating type and lamella heights influence the final images. Benchmarking gratings of two different designs, we show that a frequently used proxy for image quality, a grating's so-called visibility, is insufficient to predict contrast-to-noise ratios (CNRs). Presenting scans from an excised rat lung, we demonstrate that the CNRs obtained for transmission and visibility images anti-correlate. This is explained by the stronger attenuation implied by gratings that are engineered to provide high visibilities by means of an increased lamella height. We show that even the visibility contrast can suffer from this effect when the associated reduced photon flux on the detector is not outweighed by a corresponding gain in visibility. Resulting in an inevitable trade-off between the quality of the two contrasts, the question of how an optimal grating should be designed can hence only be answered in terms of Pareto optimality.


Psychopathy, self-identified race/ethnicity, and nonviolent recidivism: A longitudinal study.
Psychopathy has long been noted to play an important role in the prediction of criminal behavior and offending. Although many studies have demonstrated that psychopathic traits are predictive of violent recidivism among offenders, relatively few studies have examined the predictive validity of psychopathic traits for nonviolent recidivism and very few have examined this issue in a sample of offenders in the United States. To address this issue, we examined the predictive validity of psychopathy for both nonviolent and general recidivism using the Psychopathy Checklist-Revised (PCL-R) in a sample of 422 county jail inmates. We also examined whether ratings on Factors 1 and 2 differentially predicted nonviolent and general recidivism and whether predictive validity varied among European American, African American, and Latino American male offenders. Psychopathic traits were modestly predictive of nonviolent and general (total) recidivism. Factor 2 ratings were not more predictive of nonviolent recidivism than Factor 1 ratings in this sample, but the two factor scores also predicted nonviolent recidivism interactively. Psychopathic traits were also predictive of both outcomes in subsamples of European American and African American offenders, but not among Latino American offenders. Findings are consistent in magnitude and pattern with prior studies addressing the prediction of violence, and they show that the relationship between psychopathy and criminal conduct generalizes to the prediction of nonviolent crime in a United States offender sample. Results suggest potential differences between the predictive validity of psychopathy among Latino American offenders and other racial/ethnic groups, which suggest the need for additional research. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Synergistic Reactivation of Latent HIV Expression by Ingenol-3-Angelate, PEP005, Targeted NF-kB Signaling in Combination with JQ1 Induced p-TEFb Activation.
Although anti-retroviral therapy (ART) is highly effective in suppressing HIV replication, it fails to eradicate the virus from HIV-infected individuals. Stable latent HIV reservoirs are rapidly established early after HIV infection. Therefore, effective strategies for eradication of the HIV reservoirs are urgently needed. We report that ingenol-3-angelate (PEP005), the only active component in a previously FDA approved drug (PICATO) for the topical treatment of precancerous actinic keratosis, can effectively reactivate latent HIV in vitro and ex vivo with relatively low cellular toxicity. Biochemical analysis showed that PEP005 reactivated latent HIV through the induction of the pS643/S676-PKCδ/θ-IκBα/ε-NF-κB signaling pathway. Importantly, PEP005 alone was sufficient to induce expression of fully elongated and processed HIV RNAs in primary CD4+ T cells from HIV infected individuals receiving suppressive ART. Furthermore, PEP005 and the P-TEFb agonist, JQ1, exhibited synergism in reactivation of latent HIV with a combined effect that is 7.5-fold higher than the effect of PEP005 alone. Conversely, PEP005 suppressed HIV infection of primary CD4+ T cells through down-modulation of cell surface expression of HIV co-receptors. This anti-cancer compound is a potential candidate for advancing HIV eradication strategies.


Defining 'signal' and its subtypes in pharmacovigilance based on a systematic review of previous definitions.
Having surveyed the etymology and previous definitions of the pharmacovigilance term 'signal', we propose a definition that embraces all the surveyed ideas, reflects real-world pharmacovigilance processes, and accommodates signals of both harmful and beneficial effects. The essential definitional features of a pharmacovigilance signal are (i) that it is based on one or more reports of an association between an intervention or interventions and an event or set of related events (e.g. a syndrome), including any type of evidence (clinical or experimental); (ii) that it represents an association that is new and important and has not been previously investigated and refuted; (iii) that it incites to action (verification and remedial action); (iv) that it does not encompass intervention-event associations that are not related to causality or risk with a specified degree of likelihood and scientific plausibility. Based on these features, we propose this definition of a signal of suspected causality: "information that arises from one or multiple sources (including observations and experiments), which suggests a new potentially causal association, or a new aspect of a known association, between an intervention and an event or set of related events, either adverse or beneficial, which would command regulatory, societal or clinical attention, and is judged to be of sufficient likelihood to justify verifiable and, when necessary, remedial actions." This defines an unverified signal; we have also defined term-- indeterminate, verified, and refuted signals--that qualify it in relation to verification. This definition and its accompanying flowchart should inform decision making in considering benefits and harms caused by pharmacological and nonpharmacological interventions.


Calcium infusion suggests a "set-point" abnormality of parathyroid gland function in familial benign hypercalcemia and more complex disturbances in primary hyperparathyroidism.
PTH clearly plays a role in maintaining the hypercalcemia of familial benign hypercalcemia (FBH or familial hypocalciuric hypocalcemia). To better define the abnormalities of parathyroid function in FBH and primary hyperparathyroidism (1 degree HPT), we used a two-site immunochemiluminometric assay for intact PTH to examine PTH suppressibility in normal individuals and patients having FBH or 1 degree HPT. Twelve normal, 11 FBH, and 7 1 degree HPT subjects were given calcium (Ca) iv with frequent sampling for ionized Ca and intact PTH. In normal and FBH subjects, plasma PTH levels decreased essentially identically in response to iv Ca. In the 1 degree HPT group, PTH was not normally suppressible. However, there was a spectrum of responsiveness in 1 degree HPT patients, with a significant correlation between tumor mass and degree of PTH nonsuppressibility (r = 0.87, P = 0.01). Analysis of the relationship between plasma PTH and ionized Ca values in the three groups demonstrated a shift to the right in the FBH curve, with no difference of slope, consistent with the notion of a simple "set-point" error in FBH. In contrast, the curve in 1 degree HPT was not only shifted to the right but also differed from normal in slope (normal, -8.92; 1 degree HPT, -3.92, P = 0.04). Thus, we propose that the parathyroid functional abnormality in FBH represents a simple set-point error, whereas the defect in 1 degree HPT consists of a set-point error combined with varying degrees of Ca nonsuppressible PTH secretion that may be related to tumor mass.


On first looking into Kutcher's "Contested Medicine": ethical tensions in clinical research.
Contested Medicine examines the experiments done at the University of Cincinnati by Eugene Saenger and his colleagues during the 1960s, a time of great fear that the Cold War between the United States and the Soviet Union would become a hot war using nuclear weapons. These studies were to provide the Department of Defense information relevant to the consequences of exposure of military personnel to ionizing radiation in such circumstances. Kutcher, a radiation physicist turned historian of science, is especially well prepared to put these studies into the context of the evolving bioethics of the time. He reviews the essential ethical reviews, beginning with the Nuremberg Code and extending to those of the Advisory Committee on Human Radiation Experiments appointed by President Clinton. These evolving ethical standards provide a cautionary note to today's methods of clinical experimentation in search of proper evidence-based medicine. There has been an ascendance of the priority of patient rights over societal good except in increasingly limited special circumstances. Some of what was considered good and necessary science in the 1960s and 1970s is no longer considered proper. Similarly, future ethical norms may well find current trial methodology to be flawed.


Role of doctors in the prevention of suicide: the final consultation.
It is generally assumed that people committing suicide see their doctor shortly before their death, and consequently that enhancing doctors' psychiatric knowledge and interview skills might help prevent some suicides. A study was undertaken to determine the nature and timing of final contacts with medical practitioners by people committing suicide. Adults dying by suicide in Scotland during 1988-89 were identified by the General Register Office for Scotland and their primary care case notes studied. Within this national sample, medical contact near to the time of the suicidal act was rare, except for those individuals who had a previous psychiatric history. These data suggest that medical practitioners, particularly those working in primary care, are not failing to detect and intervene in significant numbers of preventable suicides. Consequently, the likelihood of implementing successful suicide prevention strategies based within primary care is open to question. Greater awareness of the risk of eventual suicide in those with a previous history of psychiatric disorder may contribute to any future reduction in suicide rates.


Regulatory and clinical considerations for biosimilar oncology drugs.
Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar agents-molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs-provide opportunities both to improve health-care access and outcomes, and to reduce costs. Several international regulatory pathways have been developed to expedite entry of biosimilars into global marketplaces. The first wave of oncology biosimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, and in Australia, Japan, China, Russia, India, and South Korea. Their use is emerging worldwide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approval exist. In this Review, we discuss oncology biosimilars and summarise their regulatory frameworks, clinical experiences, and safety concerns.


Thiazolidinediones Inhibit Mouse Osteoblastic MC3T3-E1 Cell Proliferation in Part Through the Wnt Signaling Pathway.
Peroxisome proliferator-activated receptor γ (PPARγ) and Wnt play different roles in bone homeostasis. Thiazolidinediones are PPARγ agonists that cause bone mineral density loss. This study investigated the relationship between PPARγ and Wnt/β-catenin signaling in mouse osteoblastic MC3T3-E1 cells. MC3T3-E1 cells were treated with either pioglitazone (Pio) or rosiglitazone (Rosi), thiazolidinediones, for 24 hours at 10 to 40-μM concentrations. Recombinant mouse Wnt3a protein (50 ng/mL) for 6 hours was also used to treat the 20-μM Pio and Rosi pretreated cells. Cell proliferation was measured by MTT, and apoptosis with flow cytometry using annexin V/propidium iodide staining; reverse transcriptase-polymerase chain reaction measured mRNA expression levels of LRP5/6 (low-density lipoprotein-related protein 5/6), glycogen synthase kinase 3β (GSK3β), TCF7L2 (transcription factor 7-like 2), PPARγ, and cyclin D1, and Western blots detected β-catenin and p-GSK3β proteins. Pioglitazone and Rosi decreased MC3T3-E1 cell viability by 28.07% and 18.14% at 20 μM, respectively (P < 0.05). Apoptosis increased compared with controls (7.21%), after 20-μM treatment with Pio or Rosi, to 10.45% and 12.10%, respectively (P < 0.05). Both Pio and Rosi decreased β-catenin protein levels and increased p-GSK3β, but the LRP5/6, GSK3β, and TCF7L2 mRNA levels were constant. Upon activation of the Wnt pathway by mouse Wnt3a protein, β-catenin and p-GSK3β protein levels were reversed, accompanied with increased proliferation, but apoptosis remained high. Activation of PPARγ in osteoblasts accompanied Wnt signaling suppression. Activation of Wnt signaling alleviated the PPARγ proliferation decreases but not the apoptosis increases. The thiazolidinedione PPARγ agonists act in part through inhibition of the Wnt signaling pathway, showing there is a relationship between PPARγ and Wnt signaling.


Role in virulence of phospholipases, listeriolysin O and listeriolysin S from epidemic Listeria monocytogenes using the chicken embryo infection model.
Most human listeriosis outbreaks are caused by Listeria monocytogenes evolutionary lineage I strains which possess four exotoxins: a phosphatidylinositol-specific phospholipase C (PlcA), a broad-range phospholipase C (PlcB), listeriolysin O (LLO) and listeriolysin S (LLS). The simultaneous contribution of these molecules to virulence has never been explored. Here, the importance of these four exotoxins of an epidemic lineage I L. monocytogenes strain (F2365) in virulence was assessed in chicken embryos infected in the allantoic cavity. We show that LLS does not play a role in virulence while LLO is required to infect and kill chicken embryos both in wild type transcriptional regulator of virulence PrfA (PrfAWT) and constitutively active PrfA (PrfA*) backgrounds. We demonstrate that PlcA, a toxin previously considered as a minor virulence factor, played a major role in virulence in a PrfA* background. Interestingly, GFP transcriptional fusions show that the plcA promoter is less active than the hly promoter in vitro, explaining why the contribution of PlcA to virulence could be observed more importantly in a PrfA* background. Together, our results suggest that PlcA might play a more important role in the infectious lifecycle of L. monocytogenes than previously thought, explaining why all the strains of L. monocytogenes have conserved an intact copy of plcA in their genomes.


Specific detection of Dehalococcoides species by fluorescence in situ hybridization with 16S rRNA-targeted oligonucleotide probes.
Dehalococcoides ethenogenes is the only known cultivated organism capable of complete dehalogenation of tetrachloroethene (PCE) to ethene. The prevalence of Dehalococcoides species in the environment and their association with complete dehalogenation of chloroethenes suggest that they play an important role in natural attenuation of chloroethenes and are promising candidates for engineered bioremediation of these contaminants. Both natural attenuation and bioremediation require reliable and sensitive methods to monitor the presence, distribution, and fate of the organisms of interest. Here we report the development of 16S rRNA-targeted oligonucleotide probes for Dehalococcoides species. The two designed probes together encompass 28 sequences of 16S rRNA genes retrieved from the public database. Except D. ethenogenes and CBDB1, all the others are environmental clones obtained from sites contaminated with chlorinated ethenes. They are all closely related and form a unique cluster of Dehalococcoides species. In situ hybridization of probe Dhe1259t with D. ethenogenes strain 195 and two enrichment cultures demonstrated the applicability of the probe to monitoring the abundance of active Dehalococcoides species in these enrichment samples.


Cisplatin, etoposide and bleomycin infusion (PEBi regimen) in good-risk patients with germ cell tumors.
Patients with good-risk germ cell tumors have an approximately 85-95% chance of cure with standard chemotherapy. However, acute and late toxicity may be severe and negatively influence the quality of life. In an attempt to reduce toxicity, we evaluated a new schedule including bleomycin administered-as a continuous infusion in patients with low and intermediate volume metastatic disease. Patients were treated as follows: cisplatin, 100 mg/m(2) day 4; etoposide, 100 mg/m(2) days 1 through 5; bleomycin, 15 unit bolus on day 1 followed by 30 mg as a continuous infusion for 72 h, with cycles repeated every 21 days. Between 1992 and 1996, 25 patients entered the study and were assessable for response and side effects. Major patient characteristics were: performance status ECOG 0-1; minimal disease, 13 patients, intermediate disease, 12; median age, 33 years (range 15-50). Twenty-one of 25 patients (84%) achieved a complete remission, 2 patients achieved a partial remission, and 2 patients did not respond to the regimen. At a median follow-up of 24 months, 24/25 patients were alive, 23 were without evidence of disease, and I had persistent disease. Grade III/IV side effects included leuko/neutropenia (8 patients), anemia (3 patients), and nausea/vomiting (3 patients). No drug-related deaths were observed, and no evidence of pulmonary toxicity was registered. In conclusion, the PEBi regimen is an effective and well-tolerated regimen in patients with good-risk germ cell tumors and may be considered as a front-line chemotherapy.


Structural basis for specificity and promiscuity in a carrier protein/enzyme system from the sulfur cycle.
The bacterial Sox (sulfur oxidation) pathway is an important route for the oxidation of inorganic sulfur compounds. Intermediates in the Sox pathway are covalently attached to the heterodimeric carrier protein SoxYZ through conjugation to a cysteine on a protein swinging arm. We have investigated how the carrier protein shuttles intermediates between the enzymes of the Sox pathway using the interaction between SoxYZ and the enzyme SoxB as our model. The carrier protein and enzyme interact only weakly, but we have trapped their complex by using a "suicide enzyme" strategy in which an engineered cysteine in the SoxB active site forms a disulfide bond with the incoming carrier arm cysteine. The structure of this trapped complex, together with calorimetric data, identifies sites of protein-protein interaction both at the entrance to the enzyme active site tunnel and at a second, distal, site. We find that the enzyme distinguishes between the substrate and product forms of the carrier protein through differences in their interaction kinetics and deduce that this behavior arises from substrate-specific stabilization of a conformational change in the enzyme active site. Our analysis also suggests how the carrier arm-bound substrate group is able to outcompete the adjacent C-terminal carboxylate of the carrier arm for binding to the active site metal ions. We infer that similar principles underlie carrier protein interactions with other enzymes of the Sox pathway.


Scene Text Detection and Segmentation based on Cascaded Convolution Neural Networks.
Scene text detection and segmentation are two important and challenging research problems in the field of computer vision. This paper proposes a novel method for scene text detection and segmentation based on cascaded convolution neural networks (CNNs). In this method, a CNN based text-aware candidate text region (CTR) extraction model (named detection network, DNet) is designed and trained using both the edges and the whole regions of text, with which coarse CTRs are detected. A CNN based CTR refinement model (named segmentation network, SNet) is then constructed to precisely segment the coarse CTRs into text to get the refined CTRs. With DNet and SNet, much fewer CTRs are extracted than with traditional approaches while more true text regions are kept. The refined CTRs are finally classified using a CNN based CTR classification model (named classification network, CNet) to get the final text regions. All of these CNN based models are modified from VGGNet-16. Extensive experiments on three benchmark datasets demonstrate that the proposed method achieves state-of-the-art performance and greatly outperforms other scene text detection and segmentation approaches.


Complete Genome Sequence of Streptomyces sp. Strain BSE7F, a Bali Mangrove Sediment Actinobacterium with Antimicrobial Activities.
The strain Streptomyces sp. BSE7F, a novel Streptomyces strain isolated from Indonesian mangrove sediment, displays antimicrobial activities against Gram-positive bacteria, Gram-negative bacteria, and yeast. Bioinformatic analysis of the genome sequence revealed the occurrence of 22 biosynthetic gene clusters disclosing the secondary metabolite capacity of strain BSE7F.


Increased expression of the bifunctional protein PrlF suppresses overproduction lethality associated with exported beta-galactosidase hybrid proteins in Escherichia coli.
We have cloned and determined the nucleotide sequence of the prlF gene. An open reading frame predicting a 111-amino-acid protein (Mr 12,351) with an acidic carboxy terminus was identified. The DNA sequence preceding this open reading frame revealed a putative promoter and a ribosome-binding site. The nucleotide sequence of the prlF1 mutation revealed a 7-base-pair duplication resulting in a slightly smaller predicted gene product of Mr 12,009 that lacked the acidic carboxy terminus. Maxicell analysis of prlF and prlF1 subclones identified peptides of sizes similar to those predicted by the nucleotide sequences. The prlF sequence was shown to be expressed in vivo by both maxicell analysis and construction of a prlF-lacZ fusion. Two kanamycin resistance insertions within the prlF open reading frame were introduced into the chromosome, replacing the wild-type gene. In contrast to the prlF1 mutation, these insertions had no detectable effect on cell growth or on the beta-galactosidase activity or maltose sensitivity (two sensitive indicators of hybrid protein export) conferred by the lamB-lacZ42-1 gene fusion. Overproduction of the wild-type prlF gene product from a plasmid carrying an active hybrid promoter, however, conferred a prlF1 phenotype. In addition, both the prlF1 mutation and both kanamycin resistance insertions increased the beta-galactosidase activity of a prlF-lacZ fusion. These results suggest that prlF is autoregulated and that overproduction of the prlF gene product increases the export efficiency of beta-galactosidase hybrid proteins from the cytoplasm.