Congenital heart disease-associated liver disease: a narrative review.
Congenital heart diseases (CHD) can be associated with liver dysfunction. The cause for liver impairment can result out of a wide spectrum of different causes, including liver congestion, hypoxemia or low cardiac output. Fortunately, most CHD show a good long-term outcome from a cardiac perspective, but great attention should be paid on non-cardiac health problems that develop frequently in patients suffering from CHD. The treatment of liver dysfunction in CHD requires a close multidisciplinary management in a vulnerable patient collective. Unfortunately, structured recommendations on the management of liver dysfunction in patients with CHD are scarce. The objective of this review is to provide insights on the pathophysiology and etiologies of liver dysfunction as one of the most relevant non-cardiac problems related to CHD. Furthermore, we advise here on the management of liver disease in CHD with special attention on assessment of liver dysfunction, management of portal hypertension as well as on surveillance and management of hepatocellular carcinoma (HCC). A multidisciplinary perspective may help to optimize morbidity and mortality in the long-term course in these patients. However, as evidence is low in many aspects, we encourage the scientific community to perform prospective studies to gain more insights in the treatment of liver dysfunction in patients with CHD.


Pyk2 overexpression in postsynaptic neurons blocks amyloid β1-42-induced synaptotoxicity in microfluidic co-cultures.
Recent meta-analyses of genome-wide association studies identified a number of genetic risk factors of Alzheimer's disease; however, little is known about the mechanisms by which they contribute to the pathological process. As synapse loss is observed at the earliest stage of Alzheimer's disease, deciphering the impact of Alzheimer's risk genes on synapse formation and maintenance is of great interest. In this article, we report a microfluidic co-culture device that physically isolates synapses from pre- and postsynaptic neurons and chronically exposes them to toxic amyloid β peptides secreted by model cell lines overexpressing wild-type or mutated (V717I) amyloid precursor protein. Co-culture with cells overexpressing mutated amyloid precursor protein exposed the synapses of primary hippocampal neurons to amyloid β1-42 molecules at nanomolar concentrations and induced a significant decrease in synaptic connectivity, as evidenced by distance-based assignment of postsynaptic puncta to presynaptic puncta. Treating the cells with antibodies that target different forms of amyloid β suggested that low molecular weight oligomers are the likely culprit. As proof of concept, we demonstrate that overexpression of protein tyrosine kinase 2 beta-an Alzheimer's disease genetic risk factor involved in synaptic plasticity and shown to decrease in Alzheimer's disease brains at gene expression and protein levels-selectively in postsynaptic neurons is protective against amyloid β1-42-induced synaptotoxicity. In summary, our lab-on-a-chip device provides a physiologically relevant model of Alzheimer's disease-related synaptotoxicity, optimal for assessing the impact of risk genes in pre- and postsynaptic compartments.


Predicting dairy herd resilience on farms with conventional milking systems.
This research paper addresses the problem that, thus far, there is no method available to predict herd resilience for farms that do not use automated milking systems (AMS). Recently, a methodology was developed to estimate both individual cow as well as herd resilience using daily milk yield observations at individual cow level from farms with AMS. This AMS-based method, however, is not suitable on farms that use conventional milking systems (CMS) where such individual cow milk yield observations are lacking. Therefore, this research aimed at predicting herd resilience using herd performance data that is commonly available on CMS farms. To do so, data consisting of 585 Dutch AMS farms where herd resilience estimates using the AMS-based method were available was examined. To predict herd resilience with herd performance data, only those data that are also commonly available on CMS farms were used in a 5-fold cross validation Random Forest model. These herd resilience estimates were subsequently compared with the AMS-based herd resilience estimates. Results showed that it is possible to predict with a 69.9% probability whether a herd performs with above or below average herd resilience using only variables available on CMS farms. Especially, the proportion of cows with an indication of rumen acidosis, proportion of cows with an elevated somatic cell count and the fluctuation in herd size over the years are good predictors of herd resilience. Since herd management decisions appear to affect herd resilience, a lower predicted herd resilience could be taken as a general indication that tactical or strategic management changes could be taken to improve the herd resilience.


An Improved Direct Injection Technique With Flowable Composites. A Digital Workflow Case Report.
This article presents a clinical technique based on a case report for restoring the contours and shape of the upper teeth involved in the smile display of a young patient. After planning the treatment for the patient using digital tools (Digital pictures, Digital Smile Design, digital waxup, three-dimensional [3D] printed models, mockup), the upper teeth were restored using an improved injection technique. This improved technique involves the direct injection of flowable composite resin using clear polyvinyl siloxane molds made from 3D-printed models of the patient. The details and benefits of this new technique are described in the article.


Low-impact laparoscopy in colorectal resection-A multicentric randomised trial comparing low-pressure pneumoperitoneum plus microsurgery versus low-pressure pneumoperitoneum alone: The PAROS II trial.
Low-pressure pneumoperitoneum (LLP) in laparoscopy colorectal surgery (CS) has resulted in reduced hospital stay and lower analgesic consumption. Microsurgery (MS) in CS is a technique that has a significant impact with respect to postoperative pain. The combination of MS plus LLP, known as low-impact laparoscopy (LIL), has never been applied in CS. Therefore, this trial will assess the efficacy of LLP plus MS versus LLP alone in terms of decreasing postoperative pain 24 h after surgery, without taking opioids. PAROS II will be a prospective, multicentre, outcome assessor-blinded, randomised controlled phase III clinical trial that compares LLP plus MS versus LLP alone in patients undergoing laparoscopic surgery for colonic or upper rectal cancer or benign pathology. The primary outcome will be the number of patients with postoperative pain 24 h after the surgery, as defined by a visual analogue scale rating ≤3 and without taking opioids. Overall, PAROS II aims to recruit 148 patients for 50% of patients to reach the primary outcome in the LLP plus MS arm, with 80% power and an 5% alpha risk. The PAROS II trial will be the first phase III trial to investigate the impact of LIL, including LLP plus MS, in laparoscopic CS. The results may improve the postoperative recovery experience and decrease opioid consumption after laparoscopic CS.


Potency of HIV-2-specific antibodies increase in direct association with loss of memory B cells.
: Potent HIV-neutralizing antibodies are critical for vaccination and viral reservoir control. High levels of neutralizing antibodies characterize HIV-2 infection, a naturally occurring model of attenuated HIV disease with low-to-undectable viremia. We found that HIV-2-specific antibody potency increased in direct association with the loss of both switched and unswitched memory B cells in untreated HIV-2 infection. Thus, HIV antibody affinity maturation is linked to memory B-cell exhaustion even in reduced viremia settings.


Phosphatidylinositol 3-kinase is required for the induction of ornithine decarboxylase in leukemia cells stimulated to growth.
The involvement of phosphatidylinositol 3-kinase (PI3K) in the induction of ornithine decarboxylase (ODC) was investigated by using specific PI3K inhibitors. In difluoromethylornithine-resistant L1210 cells stimulated to growth from quiescence, treatment with LY294002 inhibited cell growth and provoked a complete block of the induction of ODC activity (IC50 approximately 2 microM) and ODC protein. Some reduction in the accumulation of ODC mRNA was also observed, whereas ODC turnover was not affected significantly. Wortmannin, another specific inhibitor of PI3K, structurally unrelated to LY294002, also inhibited ODC induction with an IC50 of about 10 nM. These results indicate that PI3K activity is required for the induction of ODC, possibly affecting both ODC mRNA level and translation. Since p70 S6 kinase (p70S6K) is considered an important mediator of PI3K action in several experimental systems, the effect of rapamycin, which can lead to selective inhibition of p70S6K, was also investigated. Rapamycin inhibited p70S6K activity and produced ODC inhibiting effects similar to those elicited by LY294002. However, LY294002 and wortmannin at concentrations which inhibited almost completely PI3K activity did not decrease p70S6K activity, suggesting that p70S6K does not mediate the PI3K effects on ODC, but may lie on a separate pathway in this experimental model.


Simulated real-ear measurements of benefit from digital feedback suppression.
Digital feedback suppression (DFS) enables users of hearing instruments (HI) to benefit from amplification levels that normally would provoke whistling or poor sound quality. A standardized test for the measurement of DFS benefit is not available. This paper proposes and evaluates an objective method for assessment of extra feedback-free amplification (headroom) provided by a given DFS. It is shown that the whistle-free loop gain can be calculated from data obtained with simulated real-ear measurements with the modified pressure method. Test-retest trials were carried out to assess the reliability of the proposed method. Also, a method was developed for defining an appropriate gain level at which the proposed measurement should be carried out. It is concluded that the proposed method needs to be modified to provide useful information.


New-onset and relapsed liver diseases following COVID-19 vaccination: a systematic review.
Liver diseases post-COVID-19 vaccination is extremely rare but can occur. A growing body of evidence has indicated that portal vein thrombosis, autoimmune hepatitis, raised liver enzymes and liver injuries, etc., may be potential consequence of COVID-19 vaccines. To describe the results of a systematic review for new-onset and relapsed liver disease following COVID-19 vaccination. For this systematic review, we searched Proquest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses PRISMA guideline for studies on the incidence of new onset or relapsed liver diseases post-COVID-19 vaccination, published from December 1, 2020 to July 31, 2022, with English language restriction. Two hundred seventy-five cases from one hundred and eighteen articles were included in the qualitative synthesis of this systematic review. Autoimmune hepatitis (138 cases) was the most frequent pathology observed post-COVID-19 vaccination, followed by portal vein thrombosis (52 cases), raised liver enzymes (26 cases) and liver injury (21 cases). Other cases include splanchnic vein thrombosis, acute cellular rejection of the liver, jaundice, hepatomegaly, acute hepatic failure and hepatic porphyria. Mortality was reported in any of the included cases for acute hepatic failure (n = 4, 50%), portal vein thrombosis (n = 25, 48.1%), splanchnic vein thrombosis (n = 6, 42.8%), jaundice (n = 1, 12.5%), raised liver enzymes (n = 2, 7.7%), and autoimmune hepatitis (n = 3, 2.2%). Most patients were easily treated without any serious complications, recovered and did not require long-term hepatic therapy. Reported evidence of liver diseases post-COIVD-19 vaccination should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively very small in relation to the hundreds of millions of vaccinations that have occurred and the protective benefits offered by COVID-19 vaccination far outweigh the risks.


Effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus. European Paediatric Hepatitis C Virus Network.
To investigate the effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus. Pooled retrospective analysis of prospectively collected data. Data on hepatitis C virus seropositive mothers and their children identified around delivery were sent from 24 centres of the European Paediatric Hepatitis C Virus Network. Hepatitis C virus infection status of children born to hepatitis C virus infected women. A total of 1,474 hepatitis C virus infected women were identified, of whom 503 (35%) were co-infected with HIV. Co-infected women were more than twice as likely to transmit hepatitis C virus to their children than women with hepatitis C virus infection alone. Overall 9.2% (136/1,474) of children were hepatitis C virus infected. Among the women with hepatitis C virus infection-only, multivariate analyses did not show a significant effect of mode of delivery and breastfeeding: caesarean section vs vaginal delivery OR = 1.17, P = 0.66; breastfed versus non-breastfed OR = 1.07, P = 0.83. However, HIV co-infected women delivered by caesarean section were 60% less likely to have an infected child than those delivered vaginally (OR = 0.36, P = 0.01) and those who breastfed were about four times more likely to infect their children than those who did not (OR = 6.41, P = 0.03). HIV infected children were three to four times more likely also to be hepatitis C virus infected than children without HIV infection (crude OR = 3.76, 95% CI 1.89-7.41). These results do not support a recommendation of elective caesarean section or avoidance of breastfeeding for women with hepatitis C virus infection only, but the case for HIV infected women undergoing caesarean section delivery and avoiding breastfeeding is strengthened if they are also hepatitis C virus infected.


Location of major antibody binding domains on alpha-subunit of dog kidney Na+-K+-ATPase.
The locations of binding sites on the alpha-subunit of dog kidney Na+-K+-ATPase for both monoclonal antibodies and antibodies from polyclonal antisera have been determined. Three distinct regions of the alpha-subunit, all located within the amino terminal half of the polypeptide, were recognized by the antibodies: a region near the amino terminus of the polypeptide and two regions that are separated by a site for trypsin cleavage of the ATPase in KCl. No significant binding of antibodies to the carboxy terminal region of the alpha-subunit was detected. The binding sites for the antibodies are located within regions of the polypeptide predicted to be exposed within the cytoplasm of the cell (P. L. Jorgensen, S. J. D. Karlish, and C. Gitler, J. Biol. Chem. 257: 7435-7442, 1982). This prediction was verified by the demonstration that the antibodies did not react with Na+-K+-ATPase in tight right-side-out vesicles but would bind to the protein after the vesicles had been disrupted with detergent. A model for the folding of the alpha-subunit through the membrane, based on these data, is presented.


Demoralisation, depression and desire for death: problems with the Dutch guidelines for euthanasia of the mentally ill.
Given the recent publication of Dutch guidelines for euthanasia of the mentally ill, our aim in this paper is to review the clinical role of the psychiatrist in assessing patients who seek euthanasia or physician-assisted suicide. Three areas are examined that are informative of the role of the psychiatrist in assessing patients who desire death: recent surveys of psychiatrists' attitudes, empirical and clinical studies, and treatment issues. Demoralisation and depression emerge as pertinent clinical issues worthy of psychiatric intervention. The role of the psychiatrist is complex and includes issues of assessment, systems, countertransference and treatment. Dutch guidelines for physician-assisted suicide in the mentally ill generate serious concern given the uncertainty of prognosis, potential range and variability of outcome of treatments of suicidality and the boundary violations that are involved for the psychiatrist. The guidelines have the potential to dangerously alter the practice of psychiatry and should be condemned.


Maternal and child health nurses' self-perceived confidence in dealing with child behaviour problems.
Addressing behaviour problems in children is increasingly becoming part of routine care. The question therefore arises as to which workforce members are best suited to deliver structured interventions and what skill sets they might need apart from knowledge of the specific parenting programme offered. To assess maternal and child health (MCH) nurses' self-perceived confidence in dealing with child behaviour problems. Cross-sectional questionnaire study. Data collection occurred prior to cluster randomization in the Families in Mind trial. MCH clinics in nine local government areas in greater Melbourne, in 2010. All MCH nurses in the nine areas were invited to participate, 153 (79%) completed the survey. Nurses' comfort, competency, attitudes and perceived difficulties in dealing with child behaviour problems. The majority of nurses (63%) viewed it as their role to deal with, rather than refer, child behaviour problems and felt that the task was rewarding (86%). They believed that parenting advice should be offered universally, rather than only to families with severe problems (94%). Nurses felt rather comfortable and competent to broach and discuss child behaviour problems without need for prior parental request, but somewhat less comfortable and competent to manage child behaviour problems or to make a difference. Experienced nurses (>10 years in practice) felt more comfortable and competent. Nurses described that the major challenge in their dealing with child behaviour problems was parental denial or resistance (60%). MCH nurses are at the frontline of preventive medical services for families with young children where behaviour problems are a common concern. Because managing young children's behaviour problems primarily occurs through adult behaviour change, techniques addressing parent denial and non-compliance, such as motivational interviewing and empowerment should be a part of MCH nurses' skill sets.


DNA Damage, DNA Repair, and Cancer: Second Edition.
Following our first Special Issue, we are pleased to present this Special Issue in the International Journal of Molecular Sciences, titled 'DNA Damage, DNA Repair, and Cancer: Second Edition' [...].


Pituitary gonadotropin-releasing hormone receptors during the rat estrous cycle.
The binding of [6-alanine]gonadotropin-releasing hormone to pituitary plasma membranes increased threefold between metestrus and early proestrus in female rats. Receptor numbers fell rapidly on the afternoon of proestrus coincident with the preovulatory gonadotropin surge. The numbers of receptors for gonadotropin-releasing hormone were positively correlated with concentrations of estradiol in serum; this pattern may be a necessary component of increased pituitary sensitivty to gonadotropin-releasing hormone observed during proestrus.


Natriuretic Peptide Expression and Function in GH3 Somatolactotropes and Feline Somatotrope Pituitary Tumours.
Patients harbouring mutations in genes encoding C-type natriuretic peptide (CNP; NPPC) or its receptor guanylyl cyclase B (GC-B, NPR2) suffer from severe growth phenotypes; loss-of-function mutations cause achondroplasia, whereas gain-of-function mutations cause skeletal overgrowth. Although most of the effects of CNP/GC-B on growth are mediated directly on bone, evidence suggests the natriuretic peptides may also affect anterior pituitary control of growth. Our previous studies described the expression of NPPC and NPR2 in a range of human pituitary tumours, normal human pituitary, and normal fetal human pituitary. However, the natriuretic peptide system in somatotropes has not been extensively explored. Here, we examine the expression and function of the CNP/GC-B system in rat GH3 somatolactotrope cell line and pituitary tumours from a cohort of feline hypersomatotropism (HST; acromegaly) patients. Using multiplex RT-qPCR, all three natriuretic peptides and their receptors were detected in GH3 cells. The expression of Nppc was significantly enhanced following treatment with either 100 nM TRH or 10 µM forskolin, yet only Npr1 expression was sensitive to forskolin stimulation; the effects of forskolin and TRH on Nppc expression were PKA- and MAPK-dependent, respectively. CNP stimulation of GH3 somatolactotropes significantly inhibited Esr1, Insr and Lepr expression, but dramatically enhanced cFos expression at the same time point. Oestrogen treatment significantly enhanced expression of Nppa, Nppc, Npr1, and Npr2 in GH3 somatolactotropes, but inhibited CNP-stimulated cGMP accumulation. Finally, transcripts for all three natriuretic peptides and receptors were expressed in feline pituitary tumours from patients with HST. NPPC expression was negatively correlated with pituitary tumour volume and SSTR5 expression, but positively correlated with D2R and GHR expression. Collectively, these data provide mechanisms that control expression and function of CNP in somatolactotrope cells, and identify putative transcriptional targets for CNP action in somatotropes.


Relationships between preference ratings, sensory profiles, and acoustical measurements in concert halls.
Preferences of concert hall acoustics are explored with preference mapping. The investigation is performed on previously gathered data from individual vocabulary profiling of nine concert halls and three pieces of symphonic music, namely, excerpts of compositions by Beethoven, Bruckner, and Mozart. Individual preferences are regressed onto a latent three-dimensional sensory space obtained by multiple factor analysis of descriptive sensory data. Overlaying individually estimated preference surfaces onto one another produces preference maps which illustrates both the overall preference of the stimuli as well as differences between individual listeners. A comparison of the maps between music motifs illustrates how each music signal affects the weighting of different acoustical qualities in preference judgments. Differences in preferences between individuals are pronounced in the excerpts of Beethoven and Bruckner, while the responses are more homogeneous for Mozart music motif. Overall, proximity is identified as the main aspect associated with preference, but also loudness, envelopment, and bass are important. A correlation analysis of objective parameters and subjective perceptions substantiates the importance of lateral sound energy for good concert hall acoustics. Particularly, the lateral early energy fraction at high frequencies is found to be associated with the perception of proximity, and hence, also with preference.


[The carcinogenic activity of spirobromine].
The carcinogenic activity of spyrobromin was studied during the chronic experiment on 1.5-2-month-old rats and mice of both sexes. The drug was administered intragastrically and intraperitoneally once a week in the maximally tolerant dose for 24 months. Under the given experimental conditions spyrobromin can diminish the latent period of the development of tumours in the experimental rats at intraperitoneal administration. At intragastric administration of the drug no decrease was noted in the latent period and no increase of tumours was observed in the experimental groups of the animals as compared with control. Spyrobromin is considered to be a weak carcinogen. The oral route of administration is the most safe with respect to the oncogenic risk.


Immune responses associated with perioperative exposure and reexposure to topical bovine thrombin do not impair hemostasis.
Topical bovine thrombin has been associated with immune responses and anecdotal reports of coagulopathy. This open-label study assessed the impact on clinical hemostasis of human antibodies to bovine thrombin (aBT) or factor V/Va (aBV/Va) in response to topical bovine thrombin (THROMBIN-JMI) in patients both with and without preexisting anti-bovine antibodies. Noninferiority analysis assessed primary endpoint for mean shift from baseline activated partial thromboplastin time (aPTT) at 48 hours postsurgery; secondary endpoints included changes from baseline antibodies/titers and coagulation parameters through 8 weeks postsurgery. A total of 550 patients underwent surgery with THROMBIN-JMI utilized at investigator's discretion. Adjusted mean aPTT change in (+)aBT/(+)THROMBIN-JMI cohort was greater than (-)aBT/(-)THROMBIN-JMI cohort; 4.67-second upper confidence bound exceeded 4.5-second margin (based on assumed mean aPTT of 30 seconds) and noninferiority was not met. Post hoc analysis indicated noninferiority would have been met had noninferiority margin been set prior at relative 15% of actual baseline aPTT. Antibodies/titers were unchanged by THROMBIN-JMI exposure 48 hours postsurgery and unrelated to postsurgical changes in coagulation. Thus, THROMBIN-JMI exposure in patients with/without preexisting aBT or aBV/Va does not alter hemostasis.


The hybridoma revolution: an offshoot of basic research.
In this narrative, I describe how my interest in the nature and origin of antibody diversity led me to tackle the problem by using somatic cell genetic techniques. The first hybridoma (an immortal antibody-secreting cell line derived by fusion of a short-lived lymphocyte and a myeloma cell line) was an offshoot of this approach. Although not intended for such purposes, it soon became obvious that this invention had widespread potential in basic research and industry. Indeed, the technique opened new inroads into the study of complex biological substances and became the method of choice to define new differentiation markers. Hybridomas also allowed us to dissect the immune response to a simple antigen and to demonstrate the critical role of somatic mutations in the generation of high affinity antibodies. Now, monoclonal antibodies can be derived and manipulated in vitro, leading to important new developments in therapeutic applications. BioEssays 1999;21:966-973.


Bone Grafts in Dental Implant Management: A Narrative Review.
Successful implant dentistry can be directly related to the quality and quantity of bone at the recipient site of the implant. Over the years, bone grafts have been used for the treatment of various osseous defects. Due to the widespread acceptance of dental implants, interest in bone reconstruction for the oral cavity has increased dramatically over the past decade. Many patients who request implant rehabilitation require ancillary procedures to increase the quantity and quality of the recipient's bone. The internal architecture of the bone is generally described in terms of quality of the bone, which in turn reflects the strength (degree of compactness) of the bone. This is considered a crucial factor about the available bone at the edentulous site while planing about the design of the planned implant, surgical approach, healing time, and the initial progressive bone loading during the prosthetic reconstruction. Atrophy of the alveolar processes is expressed as a reduction of height and width. Databases were electronically searched up to April 2019 to identify human bone graft studies to provide contemporary and comprehensive information about the various bone grafts used in dental implant management.


Circulation long non-coding RNAs act as biomarkers for predicting tumorigenesis and metastasis in hepatocellular carcinoma.
Alpha Fetal Protein (AFP) was one of the traditional biomarker for diagnosis of Hepatocellular carcinoma (HCC) clinically, however, with the low specificity of AFP, the early diagnosis or the metastasis prediction of HCC is inferior. A new, minimally invasive and more specificity biomarker for the diagnosis or metastasis prediction of HCC are necessary. In this study, we applied an lncRNA microarray to screen the potential biomarker for HCC. The multi-stage validation and risk score formula detection was used for validation. We discovered three lncRNA, RP11-160H22.5, XLOC_014172 and LOC149086, which were up-regulated in HCC comparing with the cancer-free controls with the merged area under curve (AUC) in training set and validation set of 0.999 and 0.896. Furthermore, XLOC_014172 and LOC149086 was confirmed highly increased in metastasis HCC patients with the merged AUC in training set and validation set of 0.900 and 0.934. Besides, most patients presented a decreased level of the three lncRNAs after operation, while the patients with secondary increased level might be associated with tumor hematogenous metastasis. RP11-160H22.5, XLOC_014172 and LOC149086 might be the potential biomarker for the tumorigenesis prediction and XLOC_014172 and LOC149086 for metastasis prediction in the future.


Phosphine-alkene ligands as mechanistic probes in the Pauson-Khand reaction.
An alkyne tetracarbonyl dicobalt complex with a chelated phosphine-alkene ligand, in which the phosphorus atom and the alkene from the ligand are attached to the same cobalt atom has been prepared, isolated, and characterized by X-ray crystallography. The complex serves as a mechanistic model for an intermediate of the Pauson-Khand (PK) reaction. Although the alkene fragment is located in an equatorial coordination site with an appropriate orientation, and, therefore, should undergo insertion, it failed to give the PK product upon either thermal or N-methylmorpholine N-oxide activation. However, a phosphine-alkene complex that contains a terminal alkene readily provided the corresponding PK product. We attribute this change in reactivity to the different ability of each olefin to undergo 1,2-insertion. These results provide further insights into the factors that govern a crucial step in the PK reaction, the olefin insertion.


Understanding GaN/InGaN core-shell growth towards high quality factor whispering gallery modes from non-polar InGaN quantum wells on GaN rods.
GaN microrods are used as a basis for subsequent InGaN quantum well (QW) and quantum dot deposition by metal-organic vapor phase epitaxy. The coverage of the shell along the sidewall of rods is dependent on the rod growth time and a complete coverage is obtained for shorter rod growth times. Transmission electron microscopy measurements are performed to reveal the structural properties of the InGaN layer on the sidewall facet and on the top facet. The presence of layers in the microrod and on the microrod surface will be discussed with respect to GaN and InGaN growth. A detailed model will be presented explaining the formation of multiple SiN layers and the partial and full coverage of the shell around the core. Cathodoluminescence measurements are performed to analyze the InGaN emission properties along the microrod and to study the microresonator properties of such hexagonal core-shell structures. High quality factor whispering gallery modes with [Formula: see text] are reported for the first time in a GaN microrod/InGaN non-polar QW core-shell geometry. The GaN/InGaN core-shell microrods are expected to be promising building blocks for low-threshold laser diodes and ultra-sensitive optical sensors.


Integrating competing dimensional models of personality: linking the SNAP, TCI, and NEO using Item Response Theory.
Mounting evidence suggests that several inventories assessing both normal personality and personality disorders measure common dimensional personality traits (i.e., Antagonism, Constraint, Emotional Instability, Extraversion, and Unconventionality), albeit providing unique information along the underlying trait continuum. We used Widiger and Simonsen's (2005) pantheoretical integrative model of dimensional personality assessment as a guide to create item pools. We then used Item Response Theory (IRT) to compare the assessment of these five personality traits across three established dimensional measures of personality: the Schedule for Nonadaptive and Adaptive Personality (SNAP), the Temperament and Character Inventory (TCI), and the Revised NEO Personality Inventory (NEO PI-R). We found that items from each inventory map onto these five common personality traits in predictable ways. The IRT analyses, however, documented considerable variability in the item and test information derived from each inventory. Our findings support the notion that the integration of multiple perspectives will provide greater information about personality while minimizing the weaknesses of any single instrument.


Controlling the extent of spin exchange coupling in 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) biradicals via molecular recognition with cucurbit[n]uril hosts.
The binding interactions between two paramagnetic cobaltocenium guests and the hosts cucurbit[7]uril (CB7) and cucurbit[8]uril (CB8) were investigated using a combination of electronic absorption, NMR, and electron paramagnetic resonance (EPR) spectroscopies, mass spectrometry, and X-ray crystallography. Guest 1, (4-amido-2,2,6,6-tetramethylpiperidine-1-oxyl)cobaltocenium, forms very stable inclusion complexes with CB7 and CB8. However, CB7 interacts with 1 by including the organometallic cobaltocenium unit, while CB8 engulfs the TEMPO residue. The corresponding equilibrium association constant (K) values are 2.8 ± 0.3 × 10(6) M(-1) for CB7•1 and 2.1 ± 1.0 × 10(8) M(-1) for CB8•1. Biradical guest 2, 1,1'-bis(4-amido-2,2,6,6-tetramethylpiperidine-1-oxyl)cobaltocenium, forms a very stable ternary complex with two CB8 hosts, in which each 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) residue is encircled by a host molecule. The structure of this ternary complex was confirmed in the solid state using single-crystal X-ray diffraction. Binding of the TEMPO side arms by the CB8 hosts gradually decreases the observed level of spin exchange coupling between the two nitroxide groups. In the final 2:1 complex, no spin exchange coupling was observed, but the initial levels of spin exchange coupling could be regenerated in a reversible fashion by adding a competing guest, adamantyltrimethylammonium (AdTMA), to the solution. The binding interactions between 2 and CB7 are similar but the stabilities of the 1:1 and 2:1 complexes are much lower than those of the corresponding CB8 complexes.


Multiprofessional intervention to improve adherence to medication in stroke patients: a study protocol for a randomised controlled trial (ADMED AVC study).
Adherence to secondary preventive medications is often suboptimal in patients with stroke, exposing them to an increased risk of recurrent cerebral and/or cardiovascular events. Effective actions in the long term to improve adherence to medication are needed. The study will evaluate the efficacy of a collaborative multiprofessional patient-centred intervention conducted by a pharmacist on adherence to secondary preventive medication in stroke survivors. This is a multicentre cluster-randomised controlled trial. Two groups of 91 patients (intervention vs standard care) will be recruited. The clinical pharmacist intervention targeting secondary preventive medication will consist of three parts over 1 year: (1) an individual semi-structured interview at hospital discharge; (2) follow-up telephone interviews at 3, 6 and 9 months after discharge; and (3) a final individual semi-structured interview 1 year after discharge. Information on patient follow-up will be shared with the general practitioner and the community pharmacist by sending a report of each interview. The primary outcome is adherence to medication during the 12 months after hospital discharge, assessed using a composite endpoint: the medication possession ratio associated with a self-administered questionnaire. The local ethics committee, the national committee for use of personal data in medical research and the national data protection agency approved the study. The sponsor has no role in study design; collection, analysis and interpretation of data; or report writing. This pharmacist-led educational programme has the potential to significantly improve adherence to medication in stroke survivors which could lead to a decrease in recurrent cerebral and/or cardiovascular events. NCT02611440.


Novel monolithic integration scheme for high-speed electroabsorption modulators and semiconductor optical amplifiers using cascaded structure.
A new monolithic integration scheme, namely cascaded-integration (CI), for improving high-speed optical modulation is proposed and demonstrated. High-speed electroabsorption modulators (EAMs) and semiconductor optical amplifiers (SOAs) are taken as the integrated elements of CI. This structure is based on an optical waveguide defined by cascading segmented EAMs with segmented SOAs, while high-impedance transmission lines (HITLs) are used for periodically interconnecting EAMs, forming a distributive optical re-amplification and re-modulation. Therefore, not only the optical modulation can be beneficial from SOA gain, but also high electrical reflection due to EAM low characteristic impedance can be greatly reduced. Two integration schemes, CI and conventional single-section (SS), with same total EAM- and SOA- lengths are fabricated and compared to examine the concept. Same modulation-depth against with EAM bias (up to 5V) as well as SOA injection current (up to 60mA) is found in both structures. In comparison with SS, a < 1dB extra optical-propagation loss in CI is measured due to multi-sections of electrical-isolation regions between EAMs and SOAs, suggesting no significant deterioration in CI on DC optical modulation efficiency. Lower than -12dB of electrical reflection from D.C. to 30GHz is observed in CI, better than -5dB reflection in SS for frequency of above 5GHz. Superior high-speed electrical properties in CI structure can thus lead to higher speed of electrical-to-optical (EO) response, where -3dB bandwidths are >30GHz and 13GHz for CI and SS respectively. Simulation results on electrical and EO response are quite consistent with measurement, confirming that CI can lower the driving power at high-speed regime, while the optical loss is still kept the same level. Taking such distributive advantage (CI) with optical gain, not only higher-speed modulation with high output optical power can be attained, but also the trade-off issue due to impedance mismatch can be released to reduce the driving power of modulator. Such kind of monolithic integration scheme also has potential for the applications of other high-speed optoelectronics devices.


Targeting PP2A and proteasome activity ameliorates features of allergic airway disease in mice.
Asthma is an allergic airway disease (AAD) caused by aberrant immune responses to allergens. Protein phosphatase-2A (PP2A) is an abundant serine/threonine phosphatase with anti-inflammatory activity. The ubiquitin proteasome system (UPS) controls many cellular processes, including the initiation of inflammatory responses by protein degradation. We assessed whether enhancing PP2A activity with fingolimod (FTY720) or 2-amino-4-(4-(heptyloxy) phenyl)-2-methylbutan-1-ol (AAL(S) ), or inhibiting proteasome activity with bortezomib (BORT), could suppress experimental AAD. Acute AAD was induced in C57BL/6 mice by intraperitoneal sensitization with ovalbumin (OVA) in combination with intranasal (i.n) exposure to OVA. Chronic AAD was induced in mice with prolonged i.n exposure to crude house dust mite (HDM) extract. Mice were treated with vehicle, FTY720, AAL(S) , BORT or AAL(S) +BORT and hallmark features of AAD assessed. AAL(S) reduced the severity of acute AAD by suppressing tissue eosinophils and inflammation, mucus-secreting cell (MSC) numbers, type 2-associated cytokines (interleukin (IL)-33, thymic stromal lymphopoietin, IL-5 and IL-13), serum immunoglobulin (Ig)E and airway hyper-responsiveness (AHR). FTY720 only suppressed tissue inflammation and IgE. BORT reduced bronchoalveolar lavage fluid (BALF) and tissue eosinophils and inflammation, IL-5, IL-13 and AHR. Combined treatment with AAL(S) +BORT had complementary effects and suppressed BALF and tissue eosinophils and inflammation, MSC numbers, reduced the production of type 2 cytokines and AHR. AAL(S) , BORT and AAL(S) +BORT also reduced airway remodelling in chronic AAD. These findings highlight the potential of combination therapies that enhance PP2A and inhibit proteasome activity as novel therapeutic strategies for asthma.


Cost-effectiveness of easy-access, risk-informed oral pre-exposure prophylaxis in HIV epidemics in sub-Saharan Africa: a modelling study.
Approaches that allow easy access to pre-exposure prophylaxis (PrEP), such as over-the-counter provision at pharmacies, could facilitate risk-informed PrEP use and lead to lower HIV incidence, but their cost-effectiveness is unknown. We aimed to evaluate conditions under which risk-informed PrEP use is cost-effective. We applied a mathematical model of HIV transmission to simulate 3000 setting-scenarios reflecting a range of epidemiological characteristics of communities in sub-Saharan Africa. The prevalence of HIV viral load greater than 1000 copies per mL among all adults (HIV positive and negative) varied from 1·1% to 7·4% (90% range). We hypothesised that if PrEP was made easily available without restriction and with education regarding its use, women and men would use PrEP, with sufficient daily adherence, during so-called seasons of risk (ie, periods in which individuals are at risk of acquiring infection). We refer to this as risk-informed PrEP. For each setting-scenario, we considered the situation in mid-2021 and performed a pairwise comparison of the outcomes of two policies: immediate PrEP scale-up and then continuation for 50 years, and no PrEP. We estimated the relationship between epidemic and programme characteristics and cost-effectiveness of PrEP availability to all during seasons of risk. For our base-case analysis, we assumed a 3-monthly PrEP cost of US$29 (drug $11, HIV test $4, and $14 for additional costs necessary to facilitate education and access), a cost-effectiveness threshold of $500 per disability-adjusted life-year (DALY) averted, an annual discount rate of 3%, and a time horizon of 50 years. In sensitivity analyses, we considered a cost-effectiveness threshold of $100 per DALY averted, a discount rate of 7% per annum, the use of PrEP outside of seasons of risk, and reduced uptake of risk-informed PrEP. In the context of PrEP scale-up such that 66% (90% range across setting-scenarios 46-81) of HIV-negative people with at least one non-primary condomless sex partner take PrEP in any given period, resulting in 2·6% (0·9-6·0) of all HIV negative adults taking PrEP at any given time, risk-informed PrEP was predicted to reduce HIV incidence by 49% (23-78) over 50 years compared with no PrEP. PrEP was cost-effective in 71% of all setting-scenarios, and cost-effective in 76% of setting-scenarios with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%. In sensitivity analyses with a $100 per DALY averted cost-effectiveness threshold, a 7% per year discount rate, or with PrEP use that was less well risk-informed than in our base case, PrEP was less likely to be cost-effective, but generally remained cost-effective if the prevalence of HIV viral load greater than 1000 copies per mL among all adults was higher than 3%. In sensitivity analyses based on additional setting-scenarios in which risk-informed PrEP was less extensively used, the HIV incidence reduction was smaller, but the cost-effectiveness of risk-informed PrEP was undiminished. Under the assumption that making PrEP easily accessible for all adults in sub-Saharan Africa in the context of community education leads to risk-informed use, PrEP is likely to be cost-effective in settings with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%, suggesting the need for implementation of such approaches, with ongoing evaluation. US Agency for International Development, US President's Emergency Plan for AIDS Relief, and Bill & Melinda Gates Foundation.


Nephrotoxicity of HAART.
Highly active antiretroviral therapy (HAART) and other medical therapies for HIV-related infections have been associated with toxicities. Antiretroviral therapy can contribute to renal dysfunction directly by inducing acute tubular necrosis, acute interstitial nephritis, crystal nephropathy, and renal tubular disorders or indirectly via drug interactions. With the increase in HAART use, clinicians must screen patients for the development of kidney disease especially if the regimen employed increases risk of kidney injury. It is also important that patients with chronic kidney disease (CKD) are not denied the best combinations, especially since most drugs can be adjusted based on the estimated GFR. Early detection of risk factors, systematic screening for chronic causes of CKD, and appropriate referrals for kidney disease management should be advocated for improved patient care. The interaction between immunosuppressive therapy and HAART in patients with kidney transplants and the recent endorsement of tenofovir/emtricitabine by the Centers for Disease Control (CDC) for preexposure prophylaxis bring a new dimension for nephrotoxicity vigilance. This paper summarizes the common antiretroviral drugs associated with nephrotoxicity with particular emphasis on tenofovir and protease inhibitors, their risk factors, and management as well as prevention strategies.


Genetic organization of the O7-specific lipopolysaccharide biosynthesis cluster of Escherichia coli VW187 (O7:K1).
In previous studies the authors cloned and characterized the DNA sequence of the regions at both ends of the O7-specific lipopolysaccharide (LPS) biosynthesis cluster of Escherichia coli VW187 (O7:K1), and identified the biosynthetic genes for dTDP-rhamnose and GDP-mannose, as well as one of the candidate glycosyltransferases. In this work the complete DNA sequence of a 6.9 kb intervening region is presented. Seven new ORFs were identified. All the functions required for the synthesis and transfer of the O7 LPS were assigned on the basis of complementation experiments of transposon insertion mutants, and amino acid sequence homology to proteins involved in LPS synthesis of other bacteria. Of the seven ORFs, two encoded membrane proteins that were homologous to the O-antigen translocase (Wzx) and polymerase (Wxy), two were involved in the biosynthesis of dTDP-N-acetylviosamine, and the remaining three showed homologies to sugar transferases. The O antigen chain length regulator gene wzz was also identified in the vicinity of the O7 polysaccharide cluster. O7-specific DNA primers were designed and tested for serotyping of O7 E. coli strains.


[The accidental detection of apical periodontitis].
Accidental detection of an asymptomatic apical periodontitis raises the question whether this lesion should be treated or not. Arguments favouring treatment are that the inflammation may cause pain in the future, may enlarge or may negatively affect the host's resistance. Reasons for not treating may be that treatment weakens the tooth, may cause iatrogenic damage and that treatment is expensive and burdensome for the patient and does not lead in all cases to complete healing. Scientific evidence supporting either choice, whether treating the lesion or not, is lacking. In making such decisions, therefore, personal judgments by the patient and the dentist concerning the impact on the quality of life of the patient play an important role.


Subclassifying disordered proteins by the CH-CDF plot method.
Intrinsically disordered proteins (IDPs) are associated with a wide range of functions. We suggest that sequence-based subtypes, which we call flavors, may provide the basis for different biological functions. The problem is to find a method that separates IDPs into different flavor / function groups. Here we discuss one approach, the (Charge-Hydropathy) versus (Cumulative Distribution Function) plot or CH-CDF plot, which is based the combined use of the CH and CDF disorder predictors. These two predictors are based on significantly different inputs and methods. This CH-CDF plot partitions all proteins into 4 groups: structured, mixed, disordered, and rare. Studies of the Protein Data Bank (PDB) entries and homologous show different structural biases for each group classified by the CH-CDF plot. The mixed class has more order-promoting residues and more ordered regions than the disordered class. To test whether this partition accomplishes any functional separation, we performed gene ontology (GO) term analysis on each class. Some functions are indeed found to be related to subtypes of disorder: the disordered class is highly active in mitosis-related processes among others. Meanwhile, the mixed class is highly associated with signaling pathways, where having both ordered and disordered regions could possibly be important.


Differential protein S-thiolation of glyceraldehyde-3-phosphate dehydrogenase isoenzymes influences sensitivity to oxidative stress.
The irreversible oxidation of cysteine residues can be prevented by protein S-thiolation, in which protein -SH groups form mixed disulfides with low-molecular-weight thiols such as glutathione. We report here the identification of glyceraldehyde-3-phosphate dehydrogenase as the major target of protein S-thiolation following treatment with hydrogen peroxide in the yeast Saccharomyces cerevisiae. Our studies reveal that this process is tightly regulated, since, surprisingly, despite a high degree of sequence homology (98% similarity and 96% identity), the Tdh3 but not the Tdh2 isoenzyme was S-thiolated. The glyceraldehyde-3-phosphate dehydrogenase enzyme activity of both the Tdh2 and Tdh3 isoenzymes was decreased following exposure to H2O2, but only Tdh3 activity was restored within a 2-h recovery period. This indicates that the inhibition of the S-thiolated Tdh3 polypeptide was readily reversible. Moreover, mutants lacking TDH3 were sensitive to a challenge with a lethal dose of H2O2, indicating that the S-thiolated Tdh3 polypeptide is required for survival during conditions of oxidative stress. In contrast, a requirement for the nonthiolated Tdh2 polypeptide was found during exposure to continuous low levels of oxidants, conditions where the Tdh3 polypeptide would be S-thiolated and hence inactivated. We propose a model in which both enzymes are required during conditions of oxidative stress but play complementary roles depending on their ability to undergo S-thiolation.


The effect of mixing pharmaceutical and tannery wastewaters on the biodegradation characteristics of the effluents.
This paper evaluated the effect of mixing the effluent of a pharmaceutical plant producing acetylsalicylic acid with tannery wastewater, on the biodegradation of the effluents. The evaluation involved the analysis of the oxygen uptake rate (OUR), profiles of each wastewater and the mixture by respirometry. Model calibration using the experimental OUR data identified major COD fractions and associated process kinetics for all samples analyzed. The tannery sample was a plain-settled effluent having a total COD of around 2200 mg/L with a readily biodegradable fraction of 15%. The same fraction was 57% in the pharmaceutical wastewater sample having a much stronger total COD content of 40,435 mg/L. Consequently, mixing of the pharmaceutical effluent with the tannery wastewater up to 38% of the total COD in the mixture increased the readily biodegradable COD fraction but had an inhibitory effect on the biodegradation kinetics. This effect was relatively lower on growth, but quite significant on the hydrolysis of the slowly biodegradable COD decreasing the maximum hydrolysis rate from 2.0 day(-1) to 1.2 day(-1). Model evaluation of the respirometric data, as performed in this study sets a workable protocol for the assessment of the compatibility of different wastewater mixtures for biological treatability.


Expressional analysis and role of calcium regulated kinases in abiotic stress signaling.
Perception of stimuli and activation of a signaling cascade is an intrinsic characteristic feature of all living organisms. Till date, several signaling pathways have been elucidated that are involved in multiple facets of growth and development of an organism. Exposure to unfavorable stimuli or stress condition activates different signaling cascades in both plants and animal. Being sessile, plants cannot move away from an unfavorable condition, and hence activate the molecular machinery to cope up or adjust against that particular stress condition. In plants, role of calcium as second messenger has been studied in detail in both abiotic and biotic stress signaling. Several calcium sensor proteins such as calmodulin (CaM), calcium dependent protein kinases (CDPK) and calcinuerin B-like (CBL) were discovered to play a crucial role in abiotic stress signaling in plants. Unlike CDPK, CBL and CaM are calcium-binding proteins, which do not have any protein kinase enzyme activity and interact with a target protein kinase termed as CBL-interacting protein kinase (CIPK) and CaM kinases respectively. Genome sequence analysis of Arabidopsis and rice has led to the identification of multigene familes of these calcium signaling protein kinases. Individual and global gene expression analysis of these protein kinase family members has been analyzed under several developmental and different abiotic stress conditions. In this review, we are trying to overview and emphasize the expressional analysis of calcium signaling protein kinases under different abiotic stress and developmental stages, and linking the expression to possible function for these kinases.


A Case-Study of the Molecular Diagnosis of Echinococcus multilocularis in Wild Boar with Comments on its Public Health Significance in Turkey.
Echinococcus multilocularis is a parasite species of zoonotic importance which can be fatal to humans and causes Alveolar Echinococcosis (AE). This report describes the development of a cyst from the liver of a wild boar and molecular confirmation of its identification. The cyst material was obtained from the liver of a wild boar killed by hunters. Genomic DNA was extracted from the germinal layer of the cyst material, and 875 bp mitochondrial cytochrome c oxidase subunit I (COI) gene fragment was amplified by PCR and sequenced. A BLAST search matched 100% with published Echinococcus multilocularis sequences. This study confirms the occurrence of E. multilocularis in a wild boar for the first time in Turkey.


Growth of Secure Messaging Through a Patient Portal as a Form of Outpatient Interaction across Clinical Specialties.
Patient portals are online applications that allow patients to interact with healthcare organizations. Portal adoption is increasing, and secure messaging between patients and healthcare providers is an emerging form of outpatient interaction. Research about portals and messaging has focused on medical specialties. We characterized adoption of secure messaging and the contribution of messaging to outpatient interactions across diverse clinical specialties after broad portal deployment. This retrospective cohort study at Vanderbilt University Medical Center examined use of patient-initiated secure messages and clinic visits in the three years following full deployment of a patient portal across adult and pediatric specialties. We measured the proportion of outpatient interactions (i.e., messages plus clinic visits) conducted through secure messaging by specialty over time. Generalized estimating equations measured the likelihood of message-based versus clinic outpatient interaction across clinical specialties. Over the study period, 2,422,114 clinic visits occurred, and 82,159 unique portal users initiated 948,428 messages to 1,924 recipients. Medicine participated in the most message exchanges (742,454 messages; 78.3% of all messages sent), followed by surgery (84,001; 8.9%) and obstetrics/gynecology (53,424; 5.6%). The proportion of outpatient interaction through messaging increased from 12.9% in 2008 to 33.0% in 2009 and 39.8% in 2010 (p<0.001). Medicine had the highest proportion of outpatient interaction conducted through messaging in 2008 (23.3% of outpatient interactions in medicine). By 2010, this proportion was highest for obstetrics/gynecology (83.4%), dermatology (71.6%), and medicine (56.7%). Growth in likelihood of message-based interaction was greater for anesthesiology, dermatology, obstetrics/gynecology, pediatrics, and psychiatry than for medicine (p<0.001). This study demonstrates rapid adoption of secure messaging across diverse clinical specialties, with messaging interactions exceeding face-to-face clinic visits for some specialties. As patient portal and secure messaging adoption increase beyond medicine and primary care, research is needed to understand the implications for provider workload and patient care.


A novel dominant-negative mutation of the hepatocyte nuclear factor-1alpha gene in Japanese early-onset type 2 diabetes.
We investigated the presence and the function of hepatocyte nuclear factor-1alpha (HNF-1alpha) mutations in 26 Japanese subjects with type 2 diabetes. The subjects were between 20 and 39 years of age on diagnosis and had diabetic first-degree relatives. Two different frameshift mutations were found in 2 subjects (8 %). One novel mutation, T539fsdelC (deletion of C in codon 539 for Thr), is predicted to generate a protein of normal 539 residues at the N-terminus followed by an abnormal 119 amino acid protein. The mutation, P291fsinsC (insertion of C in codon 291 for Pro) should lead to production of a truncated protein of 315 amino acids. Transfection reporter assay using MIN6 and HepG2 cells revealed both mutations to have null function in the transactivation of reporter gene expression. When transfected with wild-type gene, these mutations behaved as dominant-negative regulators in both cells. An equimolar amount of T539fsdelC reduced wild-type activity by approximately 80% in MIN6 cells, while the same concentration of P291fsinsc reduced it by 30%. The sequences responsible for the transactivation activity of HNF-1alpha are confined largely to amino acids 547-628, so that the T539fsdelC mutation, which affects this entire region, replacing amino acids 540-631 with an abnormal 119 amino acid protein, may acquire a potent dominant-negative function.


Nonstationary color tracking for vision-based human-computer interaction.
Skin color offers a strong cue for efficient localization and tracking of human body parts in video sequences for vision-based human-computer interaction. Color-based target localization could be achieved by analyzing segmented skin color regions. However, one of the challenges of color-based target tracking is that color distributions would change in different lighting conditions such that fixed color models would be inadequate to capture nonstationary color distributions over time. Meanwhile, using a fixed skin color model trained by the data of a specific person would probably not work well for other people. Although some work has been done on adaptive color models, this problem still needs further studies. We present our investigation of color-based image segmentation and nonstationary color-based target tracking, by studying two different representations for color distributions. We propose the structure adaptive self-organizing map (SASOM) neural network that serves as a new color model. Our experiments show that such a representation is powerful for efficient image segmentation. Then, we formulate the nonstationary color tracking problem as a model transduction problem, the solution of which offers a way to adapt and transduce color classifiers in nonstationary color distributions. To fulfill model transduction, we propose two algorithms, the SASOM transduction and the discriminant expectation-maximization (EM), based on the SASOM color model and the Gaussian mixture color model, respectively. Our extensive experiments on the task of real-time face/hand localization show that these two algorithms can successfully handle some difficulties in nonstationary color tracking. We also implemented a real-time face/hand localization system based on such algorithms for vision-based human-computer interaction.


Clinics in diagnostic imaging (175). Corpus callosum glioblastoma multiforme (GBM): butterfly glioma.
A 54-year-old man presented with change in behaviour, nocturnal enuresis, abnormal limb movement and headache of one week's duration. The diagnosis of butterfly glioma (glioblastoma multiforme) was made based on imaging characteristics and was further confirmed by biopsy findings. As the corpus callosum is usually resistant to infiltration by tumours, a mass that involves and crosses the corpus callosum is suggestive of an aggressive neoplasm. Other neoplastic and non-neoplastic conditions that may involve the corpus callosum and mimic a butterfly glioma, as well as associated imaging features, are discussed.


Thoracic Splenosis - A necessary differential diagnosis for pleural based nodules with history of thoracoabdominal trauma.
Thoracic Splenosis (TS) is a rare medical condition, where there is auto-transplantation of the splenic tissue in the thoracic cavity, often leading to pleural based nodules. Our patient is the first ever case of this condition in Pakistan, and underwent extensive diagnostic procedures as well as medical treatments, before receiving the diagnosis of TS. He underwent HRCT for chronic cough that revealed pleural and mediastinal nodules. This coupled with a vague mass in the testes led to the provisional diagnosis of metastasized testicular tumour, and later a diagnosis of pulmonary tuberculosis was made. However, eventually a 99mTc denatured red blood cell scan confirmed the diagnosis of TS. TS is a benign condition, whereas other causes of pleural nodules are relatively malignant, hence its diagnosis is essential in ruling out malignancies. Among the multiple invasive and non-invasive diagnostic modalities, the gold standard remains 99mTc denatured red blood cell scan, which is a sensitive test that provides an accurate diagnosis and bars the need of multiple invasive procedures.


Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants (the SToP-BPD study): statistical analysis plan.
Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth with short-term and long-term adverse consequences. Although the glucocorticoid dexamethasone has been proven to be beneficial for the prevention of BPD, there are concerns about an increased risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. The aim of the Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants (SToP-BPD) trial is to assess the efficacy and safety of postnatal hydrocortisone administration for the reduction of death or BPD in ventilator-dependent preterm infants. The SToP-BPD study is a multicentre, double-blind, placebo-controlled hydrocortisone trial in preterm infants at risk for BPD. After parental informed consent is obtained, ventilator-dependent infants are randomly allocated to hydrocortisone or placebo treatment during a 22-day period. The primary outcome measure is the composite outcome of death or BPD at 36 weeks postmenstrual age. Secondary outcomes are short-term effects on pulmonary condition and long-term neurodevelopmental sequelae assessed at 2 years corrected age. Complications of treatment, other serious adverse events and suspected unexpected serious adverse reactions are reported as safety outcomes. This pre-specified statistical analysis plan was written and submitted without knowledge of the unblinded data. Netherlands Trial Register, NTR2768 . Registered on 17 February 2011. EudraCT, 2010-023777-19. Registered on 2 November 2010.


[Mental disorders and participation in the labor market: a multicenter national study in Brazil].
The objective was to explore the relationship between labor market participation and patient characteristics in a representative sample of 2,475 adults admitted to 26 Brazilian mental health institutions (15 Centers for Psychosocial Care and 11 hospitals). Socio-demographic, clinical, and behavioral characteristics were obtained with structured interviews. Multinomial regression was used. Increased likelihood of temporary absence from the work market was associated with female gender, single, divorced, or widowed conjugal status, lack of stable housing, and history of first admission or treatment before the age of 18. Increased likelihood of permanent absence from the labor market was associated with older age. Temporary or permanent leave from work was directly associated with low schooling, lifetime hospitalizations, and diagnosis of severe mental disorder and inversely associated with alcohol and drug use. The occupational vulnerabilities identified in the study raise the debate on specific policies for the mental health sector.


User-Centric Approach to Specifying Technical Attributes of Drug Delivery Devices: Empirical Study of Autoinjector-Cap Removal Forces.
The subcutaneous delivery of biologics using pre-filled autoinjector devices continues to attract broad scholarly interests. However, research still lacks a detailed understanding of user perceptions as the basis for specifying the clinically relevant technical attributes of a device, such as the cap-removal force. Therefore, this article studies the ability of users to remove the autoinjector cap, as well as the effects of the cap-removal force and user characteristics on the perceived ease of decapping. Forty-two participants among patients, caregivers, and healthcare professionals removed the protective cap using non-functional devices with different target cap-removal forces between 25 N and 55 N. Data were collected on the ability of the users to effectively decap the device and their perceived ease of decapping. Linear regression was then applied to quantify the impact of the decapping force and patient characteristics on the perceived ease of decapping. The participants of the study effectively decapped all autoinjector devices irrespective of age, sex, and dexterity impairments. Moreover, the study reveals that the perceived ease of decapping decreases significantly with increasing decapping force and participants' dexterity impairments. The study provides initial empirical evidence on the ability of users to decap autoinjector devices and shows how increasing the cap-removal force and dexterity impairments reduce the perceived ease of decapping.


Trace element biomonitoring in hair and blood of occupationally unexposed population residing in polluted areas of East Kazakhstan and Pavlodar regions.
Eastern and North-Eastern regions of Kazakhstan are considered to be environmentally disadvantaged due to industrial pollution and activity of the former Semipalatinsk Nuclear Test Site. Ferrous metallurgy is represented by the world's largest ferroalloy plant located in Aksu. In addition to a ferroalloy plant, Aksu is the home for the largest thermal power plant in Kazakhstan. Biomonitoring of 31 hair and blood trace elements (Ag, Ba, Be, Bi, Cs, Co, Ce, Cr, Cu, Eu, Gd, Hf, In, La, Li, Mn, Mo, Nb, Nd, Pb, Sc, Sn, Tl, Th, U, V, W, Y, Yb, Zn, and Zr) in non-occupationally exposed population residing in polluted areas of East Kazakhstan and Pavlodar regions. Five case groups, residing in the vicinity to the former Semipalatinsk Nuclear Test Site (Akzhar, Borodulikha, and Karaul) or in proximity to industrial plants (Aksu and Ust-Kamenogorsk) have been assessed vs. controls from a rural settlement in Kurchum. In total, 204 hair and blood samples were analyzed by inductively coupled plasma mass spectrometry. The observed blood concentrations of trace elements were in agreement with earlier studies on residents of industrially polluted areas. Elevated levels of blood Ba, Mn, Pb, V, and Zn were detected in residents of Aksu and Ust-Kamenogorsk. The elemental composition of head hair was characterized by greater stability between the study sites. Residency near the former Semipalatinsk Test Site could be considered as safe, while the environmental status of industrial settlements appears to be rather adverse.


Metabolism of Mycobacterium leprae in macrophages.
The incorporation of 14C-labeled palmitic acid ( [U-14C]PA) into the phenolic glycolipid-I (PGL-I) fraction of Mycobacterium leprae was studied in a murine macrophage system in vitro. Peritoneal macrophages from Swiss Webster mice were infected with fresh viable or Formalin-killed M. leprae harvested from infected footpads of nu/nu mice, and [U-14C]PA was added to the culture medium. Labeled glycolipid synthesized by live M. leprae was fractionated on a Florisil-silicic acid column and identified as PGL-I by using thin-layer chromatography and localization on a polysulfone membrane with an anti-PGL-I monoclonal antibody. Increased incorporation of [U-14C]PA into the PGL-I fraction was observed in macrophages infected with only live M. leprae. Treatment of the infected macrophages with rifampin caused a significant reduction in the incorporation of palmitic acid into PGL-I. These preliminary studies suggest that PGL-I synthesis can be used to quantitate the metabolism of M. leprae in macrophages in vitro.


Carbon nitride used as a reactive template to prepare mesoporous molybdenum sulfide and nitride.
Carbon nitride C3N4 has been used as a sacrificial template to prepare inorganic materials with hierarchical pore structure. C3N4 impregnated with ammonium heptamolybdate was treated in reactive gas mixtures (H2S/H2 or NH3/H2). This approach allowed mesoporous molybdenum sulfide and molybdenum nitride materials to be obtained that replicate the morphology of the C3N4 template. Advantageous catalytic properties have been demonstrated in the thiophene hydrodesulfurization (HDS) and electrochemical hydrogen evolution reaction (HER). The highest rates in both reactions were observed for partially sulfidized Mo2N solid.


Management of severe asthma in childhood--state of the art and novel perspectives.
The majority of children with asthma have mild or moderate disease and can obtain adequate control of symptoms through avoidance of triggering factors and/or with the help of medications. There is still a group of children with severe asthma in whom symptom control is poor depending either on identifiable aggravating factors or on true therapy resistance. These children have a poor quality of life and are limited by the severity of their disease. There is a need for a staged approach to the assessment and treatment of this small but vulnerable and resource-consuming group. The current review will provide an overview of a possible standardized approach to characterize this heterogeneous group of severely sick children including some newly developed ways of assessing asthma severity and potentialities of new asthma therapies. Furthermore, the umbrella term 'problematic severe asthma' is described. The term encompasses children whose severe asthma is due to identifiable exacerbating factors, as well as children who are resistant to any conventional therapeutic approach. Characteristics of these two groups of children are described, as are possible biomarkers and current and emerging diagnostic tools for allergy evaluation. Some recent advances and future possibilities for treatment of severe asthma are also presented in this review.


Ploidy-, gender-, and dose-dependent alteration of selected biomarkers in Clarias gariepinus treated with benzo[a]pyrene.
Naturally-occurring and artificially-induced polyploids have been documented in various fish species but to date no comparison has been reported of the impacts of ploidy on fish biomarker responses to organic pollutants. This study describes effects of ploidy, gender, and dose on biliary fluorescent aromatic compound (FAC) concentrations, hepatic ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST) activities in one of the most commonly cultured warm-water species, the African catfish Clarias gariepinus. Recently matured male and female diploid and triploid fish were intraperitoneally (i.p.) injected with 0, 5 or 25mg/kg benzo[a]pyrene (BaP) and liver and gallbladder were sampled 48hr later. No significant differences were found between ploidies in bile concentrations of 7,8 dihydrodiolbenzo[a]pyrene (7,8D BaP), 1-hydroxybenzo[a]pyrene (1-OH BaP) or 3-hydroxybenzo[a]pyrene (3-OH BaP). However, concentrations of the biliary FACs did differ between males and females at different dose of injection with generally higher concentrations in females at the low dose of BaP and higher concentrations in males at the higher BaP concentration. Hepatic EROD activity did not exhibit gender-dependent difference, whereas it was significantly higher in triploids than diploids. GST activities were not significantly influenced by any of the tested factors. This work advanced our understanding of the role of ploidy, gender, and dose in biotransformation of pollutants in fish.


Maintenance of activity and eating change after a clinical trial of tailored newsletters with older rural women.
In the Wellness for Women Project, a randomized-by-site 1-year controlled clinical trial, the efficacy of generic newsletters and newsletters tailored on Health Promotion Model behavior-specific cognitions, eating behavior, and activity behavior were compared among 225 women aged 50 to 69 years. The purpose of this study was to compare the maintenance of change in healthy eating and physical activity over the 12 months following the tailored versus generic mailed newsletter intervention. Outcomes at 18 and 24 months included behavioral markers and biomarkers of physical activity and eating. Data were analyzed using the multivariate approach to repeated measures analysis of variance and generalized estimating equations (alpha <.05). At 18 months, the tailored group maintained levels of all eating and activity behaviors, whereas the generic group maintained levels of fruit and vegetable servings, a moderate or greater activity, stretching exercise, lower body strength and flexibility but increased saturated fat intake and declined in weekly strength exercise and cardiorespiratory fitness. At 24 months, both groups maintained or returned to 12-month levels of all eating behaviors,moderate or greater activity, stretching exercise, and flexibility but declined in cardiorespiratory fitness; the tailored group maintained levels of strength exercise and lower body strength, whereas the generic group decreased in both. A greater proportion of women who received tailored newsletters continued to achieve most Healthy People 2010 criteria for eating and activity. Mailed tailored print newsletters were more efficacious than generic newsletters in facilitating maintenance of change in eating and activity for 6 months postintervention. Both tailored and generic newsletters facilitated the maintenance of change in eating behaviors and in moderate or greater physical activity and stretching exercise, whereas tailored newsletters were more efficacious in maintaining change in strength exercise for 12 months postintervention.


[Possible role of immune-phenomena in the pathogenesis of rheumatoid arthritis (author's transl)].
The R.A. is accompanied by a variety of different immune-phenomena. These are not restricted to the well known and diagnostically exploited IgM-rheumatoid factors in serum, but involve also rheumatoid factors of the Ig-classes G and A, which, at least partially are produced by lymphoid cells, which infiltrate the synovial membranes. These cellular infiltrations consist of macrophages, B and T lymphocytes, the latter being in excess. There is now good evidence that locally deposited, complement activating immune-complexes participate in the inflammatory lesions of the R.A.-joints by inducing the release of hydrolases from phagocytic cells. This event is also mediated by lymphokines and complement factors. Is is suggested that the pathogenicity of the immunoreactions occuring within the synovial tissue and fluid is a quantitative rather than a qualitative problem. In contrast to other tissues, the anatomy of the joint may favour the local accumulation of the immune-complexes. Moreover abundant immuno-reactions may be provided by a defective T-cell mediated control. Thus there is strong indication that immune-phenomena play an important role in the pathogenesis of R.A. This does not exclude the significance of metaboltic disturbances of the connective tissues for this disease.


Setting Directions: Anisotropy in Hierarchically Organized Porous Silica.
Structural hierarchy, porosity, and isotropy/anisotropy are highly relevant factors for mechanical properties and thereby the functionality of porous materials. However, even though anisotropic and hierarchically organized, porous materials are well known in nature, such as bone or wood, producing the synthetic counterparts in the laboratory is difficult. We report for the first time a straightforward combination of sol-gel processing and shear-induced alignment to create hierarchical silica monoliths exhibiting anisotropy on the levels of both, meso- and macropores. The resulting material consists of an anisotropic macroporous network of struts comprising 2D hexagonally organized cylindrical mesopores. While the anisotropy of the mesopores is an inherent feature of the pores formed by liquid crystal templating, the anisotropy of the macropores is induced by shearing of the network. Scanning electron microscopy and small-angle X-ray scattering show that the majority of network forming struts is oriented towards the shearing direction; a quantitative analysis of scattering data confirms that roughly 40% of the strut volume exhibits a preferred orientation. The anisotropy of the material's macroporosity is also reflected in its mechanical properties; i.e., the Young's modulus differs by nearly a factor of 2 between the directions of shear application and perpendicular to it. Unexpectedly, the adsorption-induced strain of the material exhibits little to no anisotropy.


Finding scientific topics.
A first step in identifying the content of a document is determining which topics that document addresses. We describe a generative model for documents, introduced by Blei, Ng, and Jordan [Blei, D. M., Ng, A. Y. & Jordan, M. I. (2003) J. Machine Learn. Res. 3, 993-1022], in which each document is generated by choosing a distribution over topics and then choosing each word in the document from a topic selected according to this distribution. We then present a Markov chain Monte Carlo algorithm for inference in this model. We use this algorithm to analyze abstracts from PNAS by using Bayesian model selection to establish the number of topics. We show that the extracted topics capture meaningful structure in the data, consistent with the class designations provided by the authors of the articles, and outline further applications of this analysis, including identifying "hot topics" by examining temporal dynamics and tagging abstracts to illustrate semantic content.


Identification of mutans streptococci by restriction fragment length polymorphism analysis of polymerase chain reaction-amplified 16S ribosomal RNA genes.
Mutans streptococci are frequently isolated from dental plaque and carious lesions. These bacteria have been identified by conventional methods such as biochemical and serologic tests followed by the isolation of colonies on the mitis-salivarius agar, which are sometimes inconsistent. Recently, species-specific polymerase chain reaction (PCR) has been reported to rapidly identify Streptococcus mutans and Streptococcus sobrinus. However, in the case of identification and classification into several species, e.g. within the group of mutans streptococci consisting of seven species, the identification using species-specific PCR seems somewhat inefficient because of need for the development and preparation of specific primers for each species. Therefore, in this study we developed a simple method using restriction fragment length polymorphism analysis of PCR-amplified 16S ribosomal RNA genes (16S rRNA genes PCR-RFLP) for the identification of seven different species included in the group of mutans streptococci. We amplified 16S rRNA gene sequences from genomic DNA samples by PCR using universal primers and digested the PCR products with the restriction endonucleases, HpaII and HaeIII. HpaII produced six RFLP patterns for eight reference strains, since the patterns for S. sobrinus, Streptococcus downei and Streptococcus ferus were similar. RFLP patterns produced with HaeIII could separate these three species. Furthermore, the RFLP patterns predicted from the 16S rRNA gene sequences in the GenBank database agreed with the actual RFLP patterns produced in the present study. The 16S rRNA sequence comparisons can be used to identify oral mutans streptococci; however, the identification by sequencing is sometimes difficult in large-scale studies and for small laboratories. Therefore, 16S rRNA genes PCR-RFLP, using HpaII and HaeIII, could be an alternative method for the identification of mutans streptococci, and may be applicable for large-scale studies on the cariogenicity of mutans streptococci.


Suppressing role of transforming growth factor-beta 1 on cathepsin activity in cultured kidney tubule cells.
Elevated expression and activity of transforming growth factor-beta 1 (TGF-beta 1) have been indicated in various renal diseases, implicating the potential involvement of this growth factor in the accumulation of extracellular matrix. To assess its potential role on protein turnover in tubule cells, we investigated in LLC-PK1 cells the effects of TGF-beta 1 on the activities of lysosomal cysteine proteinases cathepsins B, H, and L + B, which play a major role in the degradation of both cellular protein and extracellular matrix. The results show that 1-10 ng/ml TGF-beta 1 exerted inhibitory effects on cathepsin B and L + B activities, when applied to either the basolateral or apical membrane of these cells (basolateral side: B -23.2%, L + B -19.9%; apical side: B -28.2%, L + B -22.6%). Application of TGF-beta 1 to both sides enhanced suppression of the enzyme activities (B -37.8%, L + B -37.4%). This suppression of cathepsin activities was accompanied by a reduction of cellular protein degradation rate by 20.0% after 24 h and 51.7% after 48 h. Furthermore, TGF-beta 1 stimulated cellular protein synthesis by 50.0% after 48 h. The combined effects on protein turnover resulted in cellular hypertrophy: increases of both protein content and cell size after 48 h. Concerning the underlying mechanism, TGF-beta 1 did not induce a rise in intracellular Ca2+ concentration nor did Ca2+ channel blocker verapamil (10(-6) M) ameliorate the TGF-beta 1-induced inhibition of cathepsin activities. However, TGF-beta 1 raised the pH in lysosomes, which obviously impaired the acidic cysteine proteinases. In conclusion, the TGF-beta 1-induced cellular hypertrophy is caused by both enhanced protein synthesis and reduced protein breakdown. Suppression of cathepsin B and L + B activities mediated probably by an alkalinization in lysosomes is involved in the decreased protein degradation.


[Tools for brief intervention--the national norms charts of alcohol consumption (for adult men and women)--, report No1].
We made out two ranking tables of alcohol consumption norms for Japanese adult men and women based on National Health and Nutrition Survey Japan. 2005. and Nationalwide Survey of Alcohol Drinking and Alcoholism among Japanese adults. From the tables, we drew Ranking Lists, which rank subjects out of 100 Japanese men or women in the frequency and quantity of drinking, and visually indicate heavier drinkers as higher and less degree. In the UK or US, such tables and charts already have been made out from their norms, and carried on the websites and used in the PROJECT MATCH by NIAAA. So we attempt- ed to make them out from Japanese norms, and intend to use these charts for brief intervention at medical examinations in the workplace and at medical institutions, in order to motivate heavy drinkers to receive treatment and modify their drinking behavior according to self-regulation model by Agostinelli, G. et al., as well as to encourage them to recognize their danger of overdrinking objectively.


Melatonin improves periodontitis-induced kidney damage by decreasing inflammatory stress and apoptosis in rats.
Two main aims of this animal study were to inspect the possible effects of periodontitis on the structure and functions of the kidneys and the therapeutic effectiveness of melatonin. Twenty-four male Sprague-Dawley rats were randomly divided into three groups: control, experimental periodontitis (Ep), and Ep-melatonin (Ep-Mel). Periodontitis was induced by placing 3.0-silk sutures sub-paramarginally around the cervix of right-left mandibular first molars and maintaining the sutures for 5 weeks. Then melatonin (10 mg/kg body weight/day, 14 days), and the vehicle was administered intraperitonally. Mandibular and kidney tissue samples were obtained following the euthanasia. Periodontal bone loss was measured via histological and microcomputed tomographic slices. On right kidney histopathological and immunohistochemical, and on the left kidney biochemical (malonyl-aldehyde [MDA], glutathione, oxidative stress [OSI], tumor necrosis factor [TNF]-α, interleukin [IL]-1β, matrix metalloproteinase [MMP]-8, MMP-9, and cathepsin D levels) evaluations were performed. Renal functional status was analyzed by levels of serum creatinine, urea, cystatin-C, and urea creatinine. Melatonin significantly restricted ligature-induced periodontal bone loss (P <0 .01) and suppressed the levels of proinflammatory cytokines (TNF-α and IL-1β), oxidative stress (MDA and OSI), and proteases (MMP-8, MMP-9, and CtD) that was significantly higher in the kidneys of the rats with periodontitis (P <0.05). In addition, periodontitis-related histological damages and apoptotic activity were also significantly lower in the Ep-Mel group (P <0.05). However, the markers of renal function of the Ep group were detected slightly impaired in comparison with the control group (P >0.05); and the therapeutic activity of melatonin was limited (P >0.05). Melatonin restricts the periodontitis-induced inflammatory stress, apoptosis, and structural but not functional impairments.


Formalizing mappings to optimize automated schema alignment: application to rare diseases.
In the era of data sharing and systems interoperability, the automation of data schema alignment has become a priority. Discovering data mappings is the aim of many alignment approaches that have been described in the literature and the effectiveness of which depends on data specifications. In this context, we propose a method for mappings formalization that allows automated data integration processes optimization. This method, involving both data element level and value element level, allows an automated inference of mappings expressed by rules. In this paper, we start by describing the methods used to achieve this mappings formalization. Then, we explain how it has been validated by characterizing data from two use cases. We end up by discussing the objectives of the proposed formalization.


Gene Tagging with the CRISPR-Cas9 System to Facilitate Macromolecular Complex Purification.
The need to generate modified cell lines that express tagged proteins of interest has become increasingly important. Here, we describe a detailed protocol for facile CRISPR/Cas9-mediated gene tagging and isolation of modified cells. In this protocol, we combine two previously published strategies that promote CRISPR/Cas9-mediated gene tagging: using chemically modified single-stranded oligonucleotides as donor templates and a co-selection strategy targeting the ATP1A1 gene at the same time as the gene of interest. Altogether, the protocol proposed here is both easier and saves time compared to other approaches for generating cells that express tagged proteins of interest, which is crucial to purify native complex from human cells.


Brain death, the pediatric patient, and the nurse.
The term "brain death" has ties to medical, legal, ethical, and philosophical discourse, and is therefore a complicated and potentially ambiguous term. Some state that with brain death a person no longer has a "master regulating" organ integrating his or her organism as a whole, and the proponents of this view equate this loss of integration with clinical death. Others believe this is not a tenable reason to deem an individual who is brain dead as clinically dead; thus, controversy exists surrounding this issue, and nurses are not resistant to this debate. Whether one supports the definition of brain death as clinical death or not appears to depend on one's view of the mind-body relationship. Pediatric nurses are involved in this controversy because of the care they provide to both the affected child and family in this troubling time.


Blood-filled spaces with and without deproteinized bone grafts in guided bone regeneration. A histomorphometric study of the rabbit skull using non-resorbable membrane.
This experimental study evaluated the effects of deproteinized bone grafts on guided bone regeneration (GBR). A groove was made in the bone marrow of the external cortical plate of the skull. A dome of non-resorbable membrane was placed on the groove and secured with titanium pins. The secluded graft space was filled with autogenous blood clots (control group) and deproteinized bone particles (experimental group). The rabbits were sacrificed 2, 4, 8 and 12 weeks after the operation. Decalcified and paraffin-embedded, transverse 3-mum-thick sections were made and stained with hematoxylin and eosin. The proportions of newly formed bone and newly formed bone-graft particle contact surfaces were histomorphometrically measured in the basal, central, and peripheral areas from the cortical plate to the top of the dome. In the control group, the basal area showed a significant increase at 4 weeks (P<0.01) and a significant decrease at 8 weeks (P<0.01). The central and peripheral areas showed gradual increases in the proportion of newly formed bone. The experimental group showed significant increase at 4 weeks in the basal area and at 8 weeks in central and peripheral area (P<0.01). There were significant differences between both groups in basal and central area (P<0.01). The proportion of newly formed bone-graft particle contact length showed significant increases at 4 weeks (P<0.01) and no significant decreases at 8 and 12 weeks in three areas. The present study showed that deproteinized bone grafts maintain newly formed bone in extensive areas for a prolonged period during GBR.


Disrupted actin: a novel player in pathogen attack sensing?
The actin cytoskeleton is widely involved in plant immune responses. The majority of studies show that chemical disruption of the actin cytoskeleton increases plant susceptibility to pathogen infection. Similarly, several pathogens have adopted this as a virulence strategy and produce effectors that affect cytoskeleton integrity. Such effectors either exhibit actin-depolymerizing activity themselves or prevent actin polymerization. Is it thus possible for plants to recognize the actin's status and launch a counterattack? Recently we showed that chemical depolymerization of actin filaments can trigger resistance to further infection via the specific activation of salicylic acid (SA) signalling. This is accompanied by several defence-related, but SA-independent, effects (e.g. callose deposition, gene expression), relying on vesicular trafficking and phospholipid metabolism. These data suggest that the role of actin in plant-pathogen interactions is more complex than previously believed. It raises the question of whether plants have evolved a mechanism of sensing pathological actin disruption that eventually triggers defence responses. If so, what is the molecular basis of it? Otherwise, why does actin depolymerization specifically influence SA content but not any other phytohormone? Here we propose an updated model of actin's role in plant-microbe interactions and suggest some future directions of research to be conducted in this area.


Changes in age trajectories of smoking experimentation during the California Tobacco Control Program.
We aimed to investigate population-level changes in smoking initiation during California's Tobacco Control (CTC) Program from 1990 to 2005, a period during which tobacco industry marketing practices also changed. We used a discrete time survival analysis of data from the California Tobacco Survey to model changes in age of first smoking experimentation across birth cohorts. Smoking initiation patterns were stable across cohorts aged 9 years or older at the start of the CTC program. For children entering preadolescence since 1990, initiation declined with each more recent cohort. By 2005, the observed decline in experimentation was 80% for male participants and 92% for female participants at age 12 to 14 years; by age 15 to 17 years, 10% of Californian adolescents had experimented in 2005 compared with 45% in preprogram cohorts. However, rates of new experimentation after age 17 years did not change, except for a recent increase in late experimentation (after age 20 years) among young adult men. Our models suggest that the CTC program greatly reduced adolescent smoking initiation among younger adolescents. Late experimentation may have recently increased among young adult men in California, coincident with an increase in tobacco industry marketing aimed at young adults.


Plasma Retinol Concentrations and Dietary Intakes of Mother-Infant Sets in Singleton versus Twin Pregnancy.
Vitamin A (retinol) is essential for normal fetal development, but the recommendation for maternal dietary intake (Retinol Activity Equivalent, RAE) does not differ for singleton vs. twin pregnancy, despite the limited evaluation of retinol status. Therefore, this study aimed to evaluate plasma retinol concentrations and deficiency status in mother-infant sets from singleton vs. twin pregnancies as well as maternal RAE intake. A total of 21 mother-infant sets were included (14 singleton, 7 twin). The HPLC and LC-MS/HS evaluated the plasma retinol concentration, and data were analyzed using the Mann-Whitney U test. Plasma retinol was significantly lower in twin vs. singleton pregnancies in both maternal (192.2 vs. 312.1 vs. mcg/L, p = 0.002) and umbilical cord (UC) samples (102.5 vs. 154.4 vs. mcg/L, p = 0.002). The prevalence of serum-defined vitamin A deficiency (VAD) <200.6 mcg/L was higher in twins vs. singletons for both maternal (57% vs. 7%, p = 0.031) and UC samples (100% vs. 0%, p < 0.001), despite a similar RAE intake (2178 vs. 1862 mcg/day, p = 0.603). Twin pregnancies demonstrated a higher likelihood of vitamin A deficiency in mothers, with an odds ratio of 17.3 (95% CI: 1.4 to 216.6). This study suggests twin pregnancy may be associated with VAD deficiency. Further research is needed to determine optimal maternal dietary recommendations during twin gestation.


GAVeCeLT* consensus statement on the correct use of totally implantable venous access devices for diagnostic radiology procedures.
The use of totally implantable venous access devices in radiology may be associated with complications such as occlusion of the system (because of the high density of some contrast), infection (if the port is not handled in aseptic conditions, using proper barrier protections), and mechanical complications due to the high-pressure administration of contrast by automatic injectors (so-called power injector), including extravasation of contrast media into the soft tissues, subintimal venous or myocardial injection, or serious damage to the device itself (breakage of the external connections, dislocation of the non-coring needle, or breakage of the catheter). The last problem - i.e., the damage of the device from a power injection - is not an unjustified fear, but a reality. A warning by the US Food and Drug Administration of July 2004 reports around 250 complications of this kind, referring to both port and central venous catheters and peripherally inserted central catheter systems, which occurred over a period of several years; in all cases, the damage occurred during the injection of contrast material by means of power injectors for computed tomography or magnetic resonance imaging procedures. Though the risk associated with the use of ports in radiodiagnostics is thus clear, it has been suggested that administration of the contrast material via the port may have some advantage in terms of image quality, increased comfort for the patient, and maybe more accurate reproducibility of the patient's own follow-up exams. This contention needs to be supported by evidence. Also, since many cancer patients who need frequent computed tomography studies already have totally implantable systems, it would seem reasonable to try to define how and when such systems may safely be used. The purpose of this consensus statement is to define recommendations based on the best available evidence, for the safe use of implantable ports in radiodiagnostics.