Nutritional influence on serum ammonia in young patients receiving sodium valproate.
Hyperammonemia is a common side effect of valproic acid (VPA) therapy. This study was designed to investigate a potential nutritional influence on serum ammonia levels during VPA therapy. In 10 VPA-treated young patients (5 receiving monotherapy, 5 receiving VPA-primidone polytherapy), venous serum ammonia, triglycerides, and cholesterol were measured on 3 consecutive days as follows: (a) after a 13-h overnight fast; (b) 2 h after an oral fat load with butter (1.2 g fat/kg body weight); and (c) 2 h after an oral protein load with fresh cheese (1 g protein/kg body weight). Ten young adults served as controls. After protein load VPA patients had significantly higher serum ammonia levels than controls (mean: 194 vs. 75 micrograms/dl in controls; p less than 0.006). Ammonia values were higher after protein load than after fat load or after fasting (p less than 0.0001). Patients receiving polytherapy had higher ammonia levels than patients receiving monotherapy (not significant). There was no correlation to the height of serum VPA levels. Clinical symptoms attributable to hyperammonemia (vomiting, apathy) were found in only one patient, and her serum ammonia was as high as 426 micrograms/dl. Triglycerides and cholesterol did not show any VPA-induced differences. We assume that VPA alters the short-term regulation of ureasynthesis. We recommend the avoidance of high protein intake in patients receiving VPA therapy, especially in young patients receiving polytherapy or comedication, or in risk situations like serious infections.


A comprehensive computerized patient record with automated linkage to QMR.
The author has developed comprehensive computerized charting software, Dr. Welford's Chart Notes Program, that interprets each portion of a patient record for the 4,653 QMR Findings and exports the identified Findings to a file that can be imported by QMR for immediate case analysis. The QMR Link utilizes a hierarchical Vocabulary System composed of approximately 20,000 terms and a "fuzzy logic" that identifies similar and implicit concepts as well as exact matches to QMR Findings. This system thereby makes it much quicker and easier to utilize QMR in evaluating a patient's illness.


Omega-3 fatty acids for intermittent claudication.
Omega-3 fatty acids are established as being effective in the treatment and prevention of coronary artery disease. It is possible that they may also benefit people with peripheral arterial disease, since the pathogenesis of the two conditions is similar. To determine the effects of omega-3 supplementation in people with intermittent claudication. Trials were identified from the Cochrane Peripheral Vascular Diseases Group trials register (last searched April 2004), and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 1, 2004). In addition, literature from pharmaceutical companies (Roche Pharmaceuticals and Seven Seas), manufacturers of omega-3 rich foods (Columbus Eggs) and web sites of nutritional organisations dedicated to omega-3 fatty acids (Omega-3 information and the Fish Foundation) were searched. Randomised controlled trials of omega-3 fatty acids versus placebo or non-omega-3 fatty acids in people with intermittent claudication. One reviewer (TS) identified potential trials, assessed study quality and extracted data. The other reviewer (WH) assessed study quality and checked data extraction. Four studies were included involving a total of 203 participants. The overall methodological quality of studies was good. All studies compared omega-3 fatty acid supplementation with placebo. Two studies used an omega-6 fatty acid as the placebo preparation, one used a monounsaturated fatty acid and one used a combination of omega-6 and monounsaturated fatty acids.Omega-3 fatty acid supplementation reduced triglyceride levels (weighted mean difference (WMD) -0.66 mmol/litre; 95% confidence interval (CI) -1.24 to -0.09) and diastolic blood pressure (WMD -1.94 mmHg; 95% CI -3.58 to -0.29) in the treatment group, but increased total cholesterol levels (WMD 0.41 mmol/litre; 95% CI 0.03 to 0.80) and LDL cholesterol levels (WMD 0.43 mmol/litre; 95% CI 0.12 to 0.74). Gastrointestinal side-effects were observed in one study. No significant changes were observed in pain-free walking distance (WMD -17 m; 95% CI -51 to 17 m), maximal walking distance (WMD -21 m; 95% CI -59 to 17 m) or ankle brachial pressure index (WMD -0.03; 95% CI -0.1 to 0.04). Omega-3 fatty acids appear to have some beneficial biochemical and haemodynamic effects in people with intermittent claudication but there is no evidence of improved clinical outcomes. It should be noted that no consistent effect on primary outcome measures was detected. Further research is needed in this area, to evaluate short- and long-term effects on more clinically relevant outcomes.


Highly stable plasminogen activator inhibitor type one (VLHL PAI-1) protects fibrin clots from tissue plasminogen activator-mediated fibrinolysis.
Plasminogen activator inhibitor-1 (PAI-1) is the major specific inhibitor of tissue-type plasminogen activator (tPA) which mediates fibrin clot lysis through activation of plasminogen. Wild-type-PAI-1 (wPAI-1) is rapidly converted to the latent form (half-life of approximately 2 h) and loses its ability to inhibit tPA. We developed a very long half-life PAI-1 (VLHL PAI-1), a recombinant protein with a half-life >700 h compared with wPAI-1. In this study, VLHL PAI-1 was assessed for its ability to inhibit clot lysis in vitro. Clot formation was initiated in normal plasma supplemented with tPA by the addition of either tissue factor or human recombinant FVIIa. Clot lysis time, monitored turbidimetrically in a microtiter plate reader, was determined at various concentrations of wPAI-1 and VLHL PAI-1. Both wPAI-1 and VLHL PAI-1 caused a significant increase in clot lysis time, although the latter was somewhat less effective at lower concentrations. The VLHL PAI-1, but not wPAI-1, maintained its anti-fibrinolytic activity after preincubation overnight at 37 degrees. These studies demonstrate that VLHL PAI-1 is an effective inhibitor of fibrin clot degradation. Due to the high stability of VLHL PAI-1 compared with wPAI-1, this novel inhibitor of tPA-mediated fibrinolysis may have therapeutic applications for treating surgical and trauma patients when used directly or in conjunction with the procoagulant recombinant FVIIa.


Diketopyrrolopyrrole Columnar Liquid-Crystalline Assembly Directed by Quadruple Hydrogen Bonds.
A diketopyrrolopyrrole (DPP) dye self-assembles via a unique hydrogen-bonding motif into an unprecedented columnar liquid-crystalline (LC) structure. X-ray and polarized FTIR experiments reveal that the DPPs organize into a one-dimensional assembly with the chromophores oriented parallel to the columnar axis. This columnar structure is composed of two π-π-stacked DPP dimers with mirror-image configurations that stack alternately through quadruple hydrogen bonding by 90° rotation. This exotic packing is dictated by the complementarity between H-bonds and the steric demands of the wedge-shaped groups attached at the core. This novel LC supramolecular material opens a new avenue of research on DPP dye assemblies with photofunctional properties tailored by H-bonding networks.


Technology and the future of cochlear implants.
Cochlear implants are one of the dramatic success stories of the bioengineering enterprise. Although these prostheses are used extensively, they still can be improved substantially. We suggest that high-density electrode designs will permit field shaping and field steering to an extent not presently possible with the arrays that are used today. Those opportunities will make it possible to make use of the phase information that is richly available to normal listeners. Although this information makes possible more precise location of sound sources in the auditory environment, and will likely improve the recognition of intelligent sound in noise, it will require the consumption of additional power in future cochlear prostheses. Those opportunities and trade-offs provide the designers of cochlear implants with exciting goals for the future.


Pyruvate decarboxylase catalyzes decarboxylation of branched-chain 2-oxo acids but is not essential for fusel alcohol production by Saccharomyces cerevisiae.
The fusel alcohols 3-methyl-1-butanol, 2-methyl-1-butanol, and 2-methyl-propanol are important flavor compounds in yeast-derived food products and beverages. The formation of these compounds from branched-chain amino acids is generally assumed to occur via the Ehrlich pathway, which involves the concerted action of a branched-chain transaminase, a decarboxylase, and an alcohol dehydrogenase. Partially purified preparations of pyruvate decarboxylase (EC 22.214.171.124) have been reported to catalyze the decarboxylation of the branched-chain 2-oxo acids formed upon transamination of leucine, isoleucine, and valine. Indeed, in a coupled enzymatic assay with horse liver alcohol dehydrogenase, cell extracts of a wild-type Saccharomyces cerevisiae strain exhibited significant decarboxylation rates with these branched-chain 2-oxo acids. Decarboxylation of branched-chain 2-oxo acids was not detectable in cell extracts of an isogenic strain in which all three PDC genes had been disrupted. Experiments with cell extracts from S. cerevisiae mutants expressing a single PDC gene demonstrated that both PDC1- and PDC5-encoded isoenzymes can decarboxylate branched-chain 2-oxo acids. To investigate whether pyruvate decarboxylase is essential for fusel alcohol production by whole cells, wild-type S. cerevisiae and an isogenic pyruvate decarboxylase-negative strain were grown on ethanol with a mixture of leucine, isoleucine, and valine as the nitrogen source. Surprisingly, the three corresponding fusel alcohols were produced in both strains. This result proves that decarboxylation of branched-chain 2-oxo acids via pyruvate decarboxylase is not an essential step in fusel alcohol production.


Translocation of 15N indicates nitrogen recycling in the mat-forming lichen Cladonia portentosa.
Nitrogen translocation was measured in Cladonia portentosa during 2 yr growth in Scottish heathland. Translocation was predicted to occur if N is resorbed from senescent basal tissue and recycled within the thallus. (15)N was introduced into either the lower (TU thalli) or upper (TD thalli) 25 mm of 50-mm-long thalli as (15)N-NH(4) (+), (15)N-NO(3) (-) or (15)N-glycine. Labelled thalli were placed within intact lichen cushions, either upright (TU) or inverted (TD). Vertical distribution of label was quantified immediately following labelling and after 1 and 2 yr. Independently of the form of introduced label, (15)N migrated upwards in TU thalli, with new growth being a strong sink. Sink regions for (15)N during year 1 (including new growth) became sources of (15)N translocated to new growth in year 2. Upward migration into inverted bases was minimal in TD thalli, but was again marked in new growth that developed from inverted apices. Relocation of N to regions of growth could facilitate internal N recycling, a process postulated to explain the ecological success of mat-forming lichens.


Transcranial direct current stimulation in the male mouse to promote recovery after stroke.
Transcranial direct current stimulation (tDCS) constitutes a promising approach for promoting recovery of function after stroke, although the underlying neurobiological mechanisms are unclear. To conduct translational research in animal models, stimulation parameters should not lead to neuronal lesions. Liebetanz et al. recommend charge densities for cathodal stimulation in rats, but parameters for mice are not established. We established tDCS in the wild-type mouse, enabling studies with genetically-engineered mice (GEM). tDCS equipment was adapted to fit the mouse skull. Using different polarities and charge densities, tDCS was safe to apply in the mouse where the charge density was below 198 kC/m(2) for single or repeated stimulations. These findings are crucial for future investigations of the neurobiological mechanisms underlying tDCS using GEM.


An electrochemical redox couple activitated by microelectrodes for confined chemical patterning of surfaces.
Microelectrodes, printed as an array on the surface of a silicon chip, generate chemically active species in a solution of electrolyte held between the electrode array and a glass plate. The active species induce chemical change in molecules coupled to the surface of the glass plate, which is separated from the electrode array by a gap of several micrometers. This paper explores the nature and pattern of the induced chemical change. The patterning is discussed with respect to the electrolyte composition and the magnitude and duration of current applied to the microelectrodes. We show that under suitable conditions the active species is confined to micrometer-sized features and diffusion does not obscure the surface pattern produced.


Googling children's health: reliability of medical advice on the internet.
To assess the reliability and accuracy of medical advice, over a range of types of websites, found using the Google search engine, thus simulating a patient's experience. Advice was sought for five common paediatric questions using the Google search engine. The first 100 results of each question were classified as either being consistent or inconsistent with current recommendations or as 'no answer given'. Record of the type of site and its visibility was noted. 39% of the 500 sites searched gave correct information; 11% were incorrect and 49% failed to answer the question. Where an answer was available, 78% of sites gave the correct information. The accuracy of information varied depending on the topic and ranged from 51% (mumps, measles and rubella and autism) to 100% (breast feeding with mastitis/the sleeping position of a baby). Governmental sites gave uniformly accurate advice. News sites gave correct advice in 55% of cases. No sponsored sites were encountered that gave the correct advice. The authors have shown that the advice on the internet is very variable. Patients are known to use the internet for their own research and as such the authors encourage healthcare workers to recommend government or NHS websites.


The putative alpha helix 2 of human immunodeficiency virus type 1 Vpr contains a determinant which is responsible for the nuclear translocation of proviral DNA in growth-arrested cells.
Several viral determinants were shown to play a role in the ability of human immunodeficiency virus type 1 (HIV-1) to infect nondividing cells. In particular, Vpr and Gag matrix (MA) were recognized to be involved in the nuclear transport of the viral preintegration complex. The goal of the present study was to evaluate the ability of isogenic HIV-1 viruses harboring different vpr and gag genes to infect nondividing cells. Surprisingly, our results reveal that the introduction of mutations in the MA nuclear localization signal marginally affected the ability of proviruses to establish infection in growth-arrested HeLa or MT4 cells. In contrast, we show that in our experimental system, the absence of Vpr expression leads to a reduction in viral infectivity and production which correlates with a decrease in the synthesis and nuclear transport of proviral DNA as determined by PCR analysis. Moreover, our data demonstrate that this reduction of viral replication is also observed with proviruses containing different mutated Vpr alleles. In particular, the Vpr Q65E mutant, which contains a substitution in the second predicted amphipathic alpha-helical structure located in the central region of the protein, is associated with an impairment of the protein nuclear localization and a concomitant reduction of the nuclear transport of proviral DNA. The results of this study provide evidence that a putative amphipathic alpha-helical structure in the central region of Vpr contains a determinant involved in the nuclear translocation of the preintegration complex in nondividing cells.


Role of glutathione in cisplatin resistance in osteosarcoma cell lines.
This study was designed to examine whether and how glutathione and catalase increase the resistance of osteosarcoma cells to the toxicity of cisplatin. Eight osteosarcoma cell lines were exposed to varying concentrations of cisplatin, and a [3H]thymidine incorporation study then estimated their drug sensitivity. Cells were pretreated with aminotriazole and buthionine sulfoximine to depress catalase and glutathione activities and then entered into the same protocol to assess their sensitivity to cisplatin. Intracytoplasmic levels of catalase and glutathione were measured before and after the treatments. Cisplatin-glutathione conjugates were created to examine how glutathione might depress the toxicity of cisplatin. Although the cell lines differed in the magnitude of their response to cisplatin, there was a statistical correlation between intrinsic glutathione content and cisplatin resistance. Pretreatment with aminotriazole reduced catalase activity by 84% but did not change the sensitivity to cisplatin. Depletion of glutathione activity by 70% increased the sensitivity of the cells to the cytotoxicity of cisplatin. In addition, cisplatin was detoxified following conjugation with glutathione. The increased sensitization to cisplatin toxicity caused by the depletion of glutathione and cisplatin detoxification after the in vitro reaction of glutathione to cisplatin indicated that the formation of the glutathione-cisplatin conjugate was an important mechanism in the cellular resistance to cisplatin. These data also demonstrated that catalase activity did not contribute to resistance to cisplatin and suggested that H2O2-induced oxidative stress did not significantly contribute to the cytotoxicity of cisplatin in osteosarcoma cells.


Establishing a Geriatric Psychiatric Consultation in a VA Medical Center.
The authors describe the establishment of a Geriatric Psychiatry Consultation-Liaison Team (GPCLT) at a Veterans Administration Medical Center (VAMC) that previously had no organized geriatric psychiatric service. Geriatric psychiatric consultation was required by three intermediate-care units treating older, chronically medically ill veterans with psychiatric symptoms or disorders. The GPCLT comprised a black, female geriatric psychiatrist and a white, male social worker. This combination of disciplines maximized skills, and the ethnic-gender differences of team members addressed questions of racial tension and gender issues between patients and VAMC staff members. The compliance with recommendations of the GPCLT, ranging from 89% to 98% across the three units, its selection as a clinical site for a university-affiliated Geriatric Psychiatry Fellowship Program, and the increase in the total hours of social work time assigned to the GPCLT documented the positive perception of the team by both the VAMC and the affiliated university. Specific recommendations are presented for consideration by other, similar settings.


Genome Sequence of Pseudomonas plecoglossicida Strain NZBD9.
Pseudomonas plecoglossicida NZBD9 is the causative agent of white nodules in cultured large yellow croaker in Fujian Province, China. We sequenced the genome of NZBD9 to gain a better understanding of the etiological agent. The genome sequence of the bacterium consists of 5.44 million bp, with a G+C content of 61.9%.


[Intake of fermented milk containing Lactobacillus casei DN-114 001 and its effect on gut flora].
To study the gut flora in infants who received fermented milk containing Lactobacillus casei and Streptococcus termophilus and its effect on secretory immunoglobulin levels. An experimental, randomized, prospective, parallel group study was carried out. Thirty-five infants were included (18 in the treatment group and 17 in the control group) with a mean age of 2 years (SD: 0.6 years; range: 1-3 years). The experimental group received both fermented milk (0.5 l/day) containing L. casei and S. termophilus for 6 weeks and standard cow's milk for the following 6 weeks. The control group received standard cow's milk (0.5 l/day) for 12 weeks. Secretory IgA levels in saliva were evaluated in the experimental group at the start of the study (baseline levels) and 6 weeks later. In both groups, stools were collected to study gut flora at 0, 6 and 12 week. Secretory IgA levels significantly increased (p =0.0063) from a mean baseline value of 2.5 mg/dl to a mean of 3.4 mg/dl at 6 weeks. Gram-negative aerobic flora were decreased in the experimental group after 6 weeks compared with the control group (p =0.0203). The number of infants with Lactobacillus spp in their gut flora was greater in the experimental group than in the control group at week 6 and this difference was statistically significant (p =0.028) at week 12. Conclusion The present study provides evidence of L. casei survival in the gastrointestinal tract and of its effect of increasing secretory IgA.


Preliminary validation of a consumer-oriented colorectal cancer risk assessment tool compatible with the US Surgeon General's My Family Health Portrait.
This study examines the analytic validity of a software tool designed to provide individuals with risk assessments for colorectal cancer based on personal health and family history information. The software is compatible with the US Surgeon General's My Family Health Portrait (MFHP). An algorithm for risk assessment was created using accepted colorectal risk assessment guidelines and programmed into a software tool (MFHP). Risk assessments derived from 150 pedigrees using the MFHP tool were compared with "gold standard" risk assessments developed by three expert cancer genetic counselors. Genetic counselor risk assessments showed substantial, but not perfect, agreement. MFHP risk assessments for colorectal cancer yielded a sensitivity for colorectal cancer risk of 81% (95% confidence interval: 54-96%) and specificity of 90% (95% confidence interval: 83-94%), as compared with genetic counselor pedigree review. The positive predictive value for risk for MFHP was 48% (95% confidence interval: 29-68%), whereas the negative predictive value was 98% (95% confidence interval: 93-99%). Agreement between MFHP and genetic counselor pedigree review was moderate (κ = 0.54). The analytic validity of the MFHP colorectal cancer risk assessment software is similar to those of other types of screening tools used in primary care. Future investigations should explore the clinical validity and utility of the software in diverse population groups.Genet Med 17 9, 753-756.


The role of personality and coping style in relation to awareness of current functioning in early-stage dementia.
This study investigated the role of psychological factors in unawareness in early-stage dementia, focusing on personality and coping strategies. Forty-nine individuals with a 'non-frontal' dementia and their partners completed standardized self-report questionnaires. Multiple regression analyses indicated that personality factors, in particular negative attitudes towards emotional expression, were related to avoidant coping in managing the threat of dementia. Neither negative attitudes towards emotional expression nor avoidant behavioural coping related to unawareness after controlling for relevant disease-related and emotional variables. However, a relationship was found between conscientiousness and unawareness. The findings were interpreted with reference to literature on processes of denial and a distinction between conscious behavioural avoidance and unconscious defensive denial was made. Implications for clinical practice were considered.


Advancing surgical simulation in gynecologic oncology: robotic dissection of a novel pelvic lymphadenectomy model.
Pelvic lymphadenectomy is a key component of the surgical treatment of several gynecologic cancers and involves mastery of complex anatomic relationships. Our aim was to demonstrate that the anatomy relevant to robotic pelvic lymphadenectomy can be modeled using low-cost techniques, thereby enabling simulation focused on surgical dissection, a task that integrates technical skills and anatomic knowledge. A model of pelvic lymphadenectomy was constructed through experimentation with several different materials and a number of prototypes. In the final version, blood vessels were simulated by rubber tubing stented with wire and lymph nodes by cotton balls. Adipose and areolar tissue were simulated by a gelatin solution poured into the model and then allowed to cool and semisolidify. Three gynecologic oncologists and 2 gynecologic oncology fellows dissected the model using the surgical robot (da Vinci Surgical System) and completed a structured questionnaire. Five additional gynecologic oncologists assessed the model at a national conference. The model received high ratings for face and content validity. Median ratings were almost all 4 of 5 or higher (range, 3-5). Participants who dissected the model (n = 5) unanimously rated it as "useful for training throughout residency and fellowship." A novel low-cost inanimate model of pelvic lymphadenectomy has been developed and rated highly for face and content validity. This model may permit more regular simulation sessions compared with alternatives such as cadaveric dissection and animal laboratories, thereby complementing them and facilitating distributed practice.


Agglutinins and cardiac surgery: a web based survey of cardiac anaesthetic practice; questions raised and possible solutions.
Cardiac surgery involves cardiopulmonary bypass during which the core temperature is generally lowered to hypothermic levels. Patients presenting for cardiac surgery are sometimes reported to have cold or warm autoantibodies at the time of blood screening. It is known that cold agglutinins may cause potentially life-threatening haemolysis, intracoronary haemagglutination leading to inadequate cardioplegia distribution, thrombosis, embolism, ischaemia or infarction. The risk (if any) posed by warm autoantibodies is less clear. Because of the absence of hospital policies and of clear UK guidelines that explain how to manage such cases, we decided to conduct a web-based survey regarding standard anaesthesia practice in patients with both cold and warm autoantibodies presenting for cardiac surgery. We devised a short electronic survey asking for responses to 8 questions on cold auto-antibodies and 2 on warm auto-antibodies. This was sent to all members of the Association of Cardiothoracic Anaesthetists. Responses were collated and expressed as percentages. Free text responses were analysed for trend or reported verbatim. The results of our survey demonstrate that there is no consensus on the appropriate management of such patients, with responses ranging from cancelling surgery to proceeding without additional precautions. In collaboration with haematologists and taking into account the available evidence, our institution has now developed a management strategy for cardiac patients with cold autoantibodies. Further studies will be required to determine the usefulness of our algorithm in daily practice.


An Inferred Ancestral CotA Laccase with Improved Expression and Kinetic Efficiency.
Laccases are widely used in industrial production due to their broad substrate availability and environmentally friendly nature. However, the pursuit of laccases with superior stability and increased heterogeneous expression to meet industry demands appears to be an ongoing challenge. To address this challenge, we resurrected five ancestral sequences of laccase BsCotA and their homologues. All five variants were successfully expressed in soluble and functional forms with improved expression levels in Escherichia coli. Among the five variants, three exhibited higher catalytic rates, thermal stabilities, and acidic stabilities. Notably, AncCotA2, the best-performing variant, displayed a kcat/KM of 7.5 × 105 M-1·s-1, 5.2-fold higher than that of the wild-type BsCotA, an improved thermo- and acidic stability, and better dye decolorization ability. This study provides a laccase variant with high application potential and presents a new starting point for future enzyme engineering.


[Personal experiences of immunotherapy using the transfer factor].
Six subjects, four suffering from chronic mucocutaneous candidosis, one from ataxiatelangiectasia and one from partial combined immunological deficiency with ongoing pulmonary tuberculosis, were treated with transfer factor. The deficient immunological situation normalized in all subjects after treatment. Clinically, all showed improvement excepting one candidosis case.


Computational detection of cis -regulatory modules.
The transcriptional regulation of a metazoan gene depends on the cooperative action of multiple transcription factors that bind to cis-regulatory modules (CRMs) located in the neighborhood of the gene. By integrating multiple signals, CRMs confer an organism specific spatial and temporal rate of transcription. Based on the hypothesis that genes that are needed in exactly the same conditions might share similar regulatory switches, we have developed a novel methodology to find CRMs in a set of coexpressed or coregulated genes. The ModuleSearcher algorithm finds for a given gene set the best scoring combination of transcription factor binding sites within a sequence window using an A(*)procedure for tree searching. To keep the level of noise low, we use DNA sequences that are most likely to contain functional cis-regulatory information, namely conserved regions between human and mouse orthologous genes. The ModuleScanner performs genomic searches with a predicted CRM or with a user-defined CRM known from the literature to find possible target genes. The validity of a set of putative targets is checked using Gene Ontology annotations. We demonstrate the use and effectiveness of the ModuleSearcher and ModuleScanner algorithms and test their specificity and sensitivity on semi-artificial data. Next, we search for a module in a cluster of gene expression profiles of human cell cycle genes. The ModuleSearcher is available as a web service within the TOUCAN workbench for regulatory sequence analysis, which can be downloaded from http://www.esat.kuleuven.ac.be/~dna/BioI.


Prognostic factors including Ki-67 and p53 in Bacillus Calmette-Guérin-treated non-muscle-invasive bladder cancer: a prospective study.
To prospectively evaluate the prognostic utility of the traditional prognostic factors and molecular markers p53 and Ki-67 in a homogeneous series of patients with non-muscle-invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG). 192 intermediate- and high-risk NMIBC cases were enrolled. The variables in study were age, stage, grade, focality, tumour size, presence of associated carcinoma in situ, recurrence rate before BCG, maintenance for BCG, Ki-67 and p53. The endpoints considered were recurrence-free survival, progression-free survival, cancer-specific survival (CSS) and overall survival (OS). T stage resulted in being associated with CSS, whereas age with OS. BCG maintenance was a significantly favourable independent predictor of OS, CSS, recurrence and progression. In univariate analysis, the labelling index of Ki-67 was significantly associated with OS, CSS and progression. Multivariate analysis, however, confirmed this association only for OS. On the contrary, the labelling index of p53 was a significant predictor of recurrence, both in uni- and multivariate analyses, but with a HR inferior to 1. Ki-67 was an independent predictor of survival. p53 overexpression showed a significant yet inverse correlation with recurrence, thus showing little clinical utility. Age, stage and maintenance were confirmed as independent predictors of BCG response.


Foundations of infants' social group evaluations.
Previous research has suggested that infants exhibit a preference for familiar over unfamiliar social groups (e.g., preferring individuals from their own language group over individuals from a foreign language group). However, because past studies often employ forced-choice procedures, it is not clear whether infants' intergroup preferences are driven by positivity toward members of familiar groups, negativity toward members of unfamiliar groups, or both. Across six experiments, we implemented a habituation procedure to independently measure infants' positive and negative evaluations of speakers of familiar and unfamiliar languages. We report that by 1 year of age, infants positively evaluate individuals who speak a familiar language, but do not negatively evaluate individuals who speak an unfamiliar language (Experiments 1 and 2). Several experiments rule out lower-level explanations (Experiments 3-6). Together these data suggest that children's early social group preferences may be shaped by positive evaluations of familiar group(s), rather than negative evaluations of unfamiliar groups.


Differences in renal ammonia metabolism in male and female kidney.
Renal ammonia metabolism has a major role in the maintenance of acid-base homeostasis. Sex differences are well recognized as an important biological variable in many aspects of renal function, including fluid and electrolyte metabolism. However, sex differences in renal ammonia metabolism have not been previously reported. Therefore, the purpose of the current study was to investigate sex differences in renal ammonia metabolism. We studied 4-mo-old wild-type C57BL/6 mice fed a normal diet. Despite similar levels of food intake, and, thus, protein intake, which is the primary determinant of endogenous acid production, female mice excreted greater amounts of ammonia, but not titratable acids, than did male mice. This difference in ammonia metabolism was associated with fundamental structural differences between the female and male kidney. In the female mouse kidney, proximal tubules account for a lower percentage of the renal cortical parenchyma compared with the male kidney, whereas collecting ducts account for a greater percentage of the renal parenchyma than in male kidneys. To further investigate the mechanism(s) behind the greater ammonia excretion in female mice, we examined differences in the expression of proteins involved in renal ammonia metabolism and transport. Greater basal ammonia excretion in females was associated with greater expression of PEPCK, glutamine synthetase, NKCC2, Rhbg, and Rhcg than was observed in male mice. We conclude that there are sex differences in basal ammonia metabolism that involve both renal structural differences and differences in expression of proteins involved in ammonia metabolism.


Folate status in women of childbearing age with obesity: a review.
Several studies have described a positive association between elevated BMI and birth defects risk. Data on plasma concentration of folate in pregnant women with obesity have shown values far below those recommended, regardless of diet, while folate levels should increase before pregnancy to reduce neural tube defects. We report a descriptive review of the most recent studies (from 2005 to 2015) to evaluate folate status through a population of women of childbearing age affected by obesity. The literature contains few studies, which present conflicting results regarding folate status in non-pregnant women of childbearing age affected by obesity, and it appears that there is a modification in folate metabolism, with a reduction in plasma folate levels and an increase in erythrocyte folate uptake. In conclusion, the folate status in women of childbearing age should be assessed by both plasma and erythrocyte levels to start a personalised and more adequate supplementation before conception. Further studies need to be conducted in a larger population, which take into account variables that can affect folate metabolism, such as dietary intake, lifestyle and genetic factors, oral contraceptives or other drug use, previous weight-loss programmes, or a history of bariatric surgery.


Oxytocin mitigated the depressive-like behaviors of maternal separation stress through modulating mitochondrial function and neuroinflammation.
Mother-infant contact has a critical role on brain development and behavior. Experiencing early-life adversities (such as maternal separation stress or MS in rodents) results in adaptations of neurotransmission systems, which may subsequently increase the risk of depression symptoms later in life. In this study, we show that Oxytocin (OT) exerted antioxidant and anti-inflammatory properties. Previous studies indicate that neuroinflammation and mitochondrial dysfunction are associated with the pathophysiology of depression. To investigate the antidepressant-like effects of OT, we applied MS paradigm (as a valid animal model of depression) to male mice at postnatal day (PND) 2 to PND 14 (3h daily, 9AM to 12AM) and investigated the depressive-like behaviors of these animals at PND 60 in different groups. Animals in this work were divided into 4 experimental groups: 1) saline-treated, 2) OT-treated, 3) atosiban (OT antagonist)-treated and, 4) OT+ atosiban-treated mice. We used forced swimming test (FST), splash test, sucrose preference test (SPT) and open field test (OFT) for behavioral assessment. Additionally, we used another set of animals to investigate the effects of MS and different treatments on mitochondrial function and the expression of the relevant genes for neuroinflammation. Our results showed that MS provoked depressive- like behaviors in the FST, SPT and splash test. In addition, our molecular findings revealed that MS is capable of inducing abnormal mitochondrial function and immune-inflammatory response in the hippocampus. Further, we observed that treating stressed animals with OT (intracerebroventricular, i.c.v. injection) attenuated the MS-induced depressive-like behaviors through improving mitochondrial function and decreasing the hippocampal expression of immune-inflammatory genes. In conclusion, we showed that MS-induced depressive-like behaviors in adult male mice are associated with abnormal mitochondrial function and immune-inflammatory responses in the hippocampus, and activation of OTergic system has protective effects against negative effects of MS on brain and behavior of animals.


Anterior cingulate activity and level of cognitive conflict: explicit comparisons.
The role of anterior cingulate cortex (ACC) in attention is a matter of debate. One hypothesis suggests that its role is to monitor response-level conflict, but explicit evidence is somewhat lacking. In this study, the activation of ACC was compared in (a) color and number standard Stroop tasks in which response preparation and interference shared modality (response-level conflict) and (b) color and number matching Stroop tasks in which response preparation and interference did not share modality (non-response-level conflict). In the congruent conditions, there was no effect of task type. In the interference conditions, anterior cingulate activity in the matching tasks was less than that in the standard tasks. These results support the hypothesis that ACC specifically mediates generalized modality-independent selection processes invoked by response competition.


GM-CSF produced by recombinant vaccinia virus or in GM-CSF transgenic mice has no effect in vivo on murine cutaneous leishmaniasis.
The hemopoietic growth and differentiation regulators, granulocyte-macrophage colony-stimulating factor (GM-CSF) and the multipotential stimulating factor (multi-CSF) have been shown to have major effects on the effector function of mature macrophages. In this study we have examined the effect of recombinant GM-CSF and multi-CSF expressed transiently from recombinant vaccinia virus, or constitutively in GM-CSF transgenic mice on the development of cutaneous leishmaniasis, caused by Leishmania major in genetically susceptible or resistant mice. We observed no effect on the development of lesions when GM-CSF or multi-CSF were administered before infection, nor on the healing of lesions when they were administered after appearance of lesions. Although only some of the GM-CSF transgenic mice or their normal littermates developed lesions after infection with L. major, there was no difference between the groups in the rate of lesion development or in the size of lesions.


The impact of the withdrawal of Adderall XR (long-acting mixed amphetamine salts) from the Canadian market on paediatric patients and their families.
Adderall XR (Shire BioChem Inc, Canada), a medication used to treat attention deficit hyperactivity disorder, was withdrawn from the Canadian market in February 2005 due to concerns of possible cardiotoxicity and cerebral vascular events among a small number of individuals who had taken the medication. The primary objective of the present study was to investigate the degree to which the physician's relationship with the families of the patients to whom the medication was prescribed was affected by the withdrawal of Adderall XR from the Canadian market. The study sought to explore the perceptions of caregivers of patients who took Adderall XR to the drug recall. As a secondary objective, the study also assessed the differences in perception of caregivers toward physicians compared with their perception of other agencies involved with the recall. Questionnaires were sent to the caregivers of 123 patients who had been taking the drug at the time of the withdrawal. Of the 53 (43%) completed questionnaires, 89% of respondents indicated that they were concerned when informed of the withdrawal, while 58% indicated that they were frightened. Despite the concerns, only a modest degree of anger was expressed. Thirty per cent of respondents reported anger directed at Health Canada, 24% reported anger directed at the manufacturer, while no caregiver reported anger directed at their physician. Only three families (5.7%) indicated a decrease in confidence in the physician following the event. Fifty-eight per cent indicated a willingness to resume taking Adderall XR, if it was deemed safe by Health Canada. These results offer insight into patient and family perspectives following an unexpected medication recall. While caregivers were generally concerned and often frightened by this event, the present data do not suggest that the parent-physician relationship was greatly affected.


[Medical treatment of portal hypertension].
Several agents can reduce portal pressure in patients with portal hypertension. These drugs act in different ways and have different actions. Several hemodynamic investigations have elucidated the effects of beta-blockade on the splanchnic circulation. Propranolol and other non-selective beta-blockers significantly decreased portal pressure in patients with cirrhosis. In some patients, beta-blockers did not decrease portal pressure while cardiac output and azygos blood flow significantly decreased. The cause and severity of cirrhosis do not influence the effects of beta-blockers. The efficacy of beta-blockers in the prevention of the first gastrointestinal bleeding is well established. Meta-analysis showed that among patients receiving beta-blockers, 10 per cent bled 1 year after inclusion as against 30 per cent in the placebo group. A significant difference in survival rate was also observed between the two groups. The efficacy of beta-blockers in the prevention of recurrent gastrointestinal bleeding is variable; 5 trials showed a significant difference while 3 did not show any significant difference between patients receiving beta-blockers and those receiving a placebo. Meta analysis showed a significant difference in the risk of rebleeding but did not show any difference in survival rate. Thus, beta-blockers reduce the degree of portal hypertension in patients with cirrhosis and decrease the risk of gastrointestinal bleeding in compliant patients.


Spatial variation in helminth community structure in the red-legged partridge (Alectoris rufa L.): effects of definitive host density.
Parasite community ecology has recently focused on understanding the forces structuring these communities. There are few surveys, however, designed to study the spatial repeatability and predictability of parasite communities at the local scale in one host. The purpose of our study was to address the relationship between infracommunity and component community richness, and to describe spatial variations on the local scale, of helminth parasite communities in an avian host, the red-legged partridge (Alectoris rufta). We sampled 235 wild partridges from 8 separate localities, with different partridge population densities, in the Ciudad Real and Toledo provinces of central Spain, and we determined their overall and intestinal helminth species. We found that habitat variables (mean temperature and land use) were not significantly associated with any component community. The partridge population abundance index was directly correlated with the prevalence and mean intensity of infection but not with component community species richness. There was a curvilinear relationship between infracommunity and component community species richness, as well as negative interspecific associations, for the helminth species assemblage parasitizing the intestine. A nestedness/anti-nestedness pattern, considered as part of a continuum, was associated with prevalence, mean intensity and partridge population abundance index, but not with component community richness. Increases in the partridge population abundance index and the prevalence and mean intensity of infection were associated with increases in helminth community nestedness. Although negative interactions between helminth species could not be ruled out as forces structuring helminth communities, our results suggest that parasite community structure in the red-legged partridge was primarily determined by the extrinsic influence of parasite habitat heterogeneity and its amplification of the differing probabilities of colonization of parasite species.


A lifting line model to investigate the influence of tip feathers on wing performance.
Bird wings have been studied as prototypes for wing design since the beginning of aviation. Although wing tip slots, i.e. wings with distinct gaps between the tip feathers (primaries), are very common in many birds, only a few studies have been conducted on the benefits of tip feathers on the wing's performance, and the aerodynamics behind tip feathers remains to be understood. Consequently most aircraft do not yet copy this feature. To close this knowledge gap an extended lifting line model was created to calculate the lift distribution and drag of wings with tip feathers. With this model, is was easily possible to combine several lifting surfaces into various different birdwing-like configurations. By including viscous drag effects, good agreement with an experimental tip slotted reference case was achieved. Implemented in C++ this model resulted in computation times of less than one minute per wing configuration on a standard notebook computer. Thus it was possible to analyse the performance of over 100 different wing configurations with and without tip feathers. While generally an increase in wing efficiency was obtained by splitting a wing tip into distinct, feather-like winglets, the best performance was generally found when spreading more feathers over a larger dihedral angle out of the wing plane. However, as the results were very sensitive to the precise geometry of the feather fan (especially feather twist) a careless set-up could just as easily degrade performance. Hence a detailed optimization is recommended to realize the full benefits by simultaneously optimizing feather sweep, twist and dihedral angles.


Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: clinical trial design.
The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the fourth of four papers. Here, we examine the phases of a clinical trial program, the elements, types, and protocols for valid clinical trial design. The most rigorous and valid SCI clinical trial would be a prospective double-blind randomized control trial utilizing appropriate placebo control subjects. However, in specific situations, it is recognized that other trial procedures may have to be considered. We review the strengths and limitations of the various types of clinical trials with specific reference to SCI. It is imperative that the design and conduct of SCI clinical trials should meet appropriate standards of scientific inquiry to insure that meaningful conclusions about efficacy and safety can be achieved and that the interests of trial subjects are protected. We propose these clinical trials guidelines for use by the SCI clinical research community.


Validity and reliability of a pictorial instrument for assessing perceived motor competence in Portuguese children.
It is important to assess young children's perceived Fundamental Movement Skill (FMS) competence in order to examine the role of perceived FMS competence in motivation toward physical activity. Children's perceptions of motor competence may vary according to the culture/country of origin; therefore, it is also important to measure perceptions in different cultural contexts. The purpose was to assess the face validity, internal consistency, test-retest reliability and construct validity of the 12 FMS items in the Pictorial Scale for Perceived Movement Skill Competence for Young Children (PMSC) in a Portuguese sample. Two hundred one Portuguese children (girls, n = 112), 5 to 10 years of age (7.6 ± 1.4), participated. All children completed the PMSC once. Ordinal alpha assessed internal consistency. A random subsamples (n = 47) were reassessed one week later to determine test-retest reliability with Bland-Altman method. Children were asked questions after the second administration to determine face validity. Construct validity was assessed on the whole sample with a Bayesian Structural Equation Modelling (BSEM) approach. The hypothesized theoretical model used the 12 items and two hypothesized factors: object control and locomotor skills. The majority of children correctly identified the skills and could understand most of the pictures. Test-retest reliability analysis was good, with an agreement ration between 0.99 and 1.02. Ordinal alpha values ranged from acceptable (object control 0.73, locomotor 0.68) to good (all FMS 0.81). The hypothesized BSEM model had an adequate fit. The PMSC can be used to investigate perceptions of children's FMS competence. This instrument can also be satisfactorily used among Portuguese children.


The Avon Longitudinal Study of Parents and Children (ALSPAC): a resource for genetic epidemiology.
The Avon Longitudinal Study of Parents and Children (ALSPAC) has collected detailed phenotypic and environmental information from pregnancy onwards on approximately 14 000 babies born in 1991-1992. A DNA bank on over 10 000 mothers and children has been established with generic consent for (undisclosed) genetic analysis, and cell lines on both children and parents are planned. As a multigenerational population cohort unselected by disease, trait or exposure, ALSPAC is uniquely placed to explore the genetic and environmental determinants of adverse developmental responses and common disease. Added value for genetic epidemiology generally is the ability to detect distortion of the expected Mendelian 50:50 transmission of alleles to study subjects (e.g. due to differential loss of embryos of one genotype) or to test for heterosis, i.e. whether heterozygotes have a greater or lesser effect than either homozygote. Finally, phenome scans (a fixed format analysis of the associations between a genotype of interest and thousands of outcome variables from the cohort database) could be used as a screening tool to test whether certain classes of genetic variation have more impact than others on human health and development.


The influence of hapten-conjugated isologous mouse gamma-globulin as a tolerogen on H-2 restricted cytotoxic effector cells.
Hapten-conjugated isologous mouse gamma-globulin (TNP-MGG) can induce specific unresponsiveness in spleen populations for primary antibody responses in vitro to both T-dependent (TNP-KLH) and T-independent (TNP-LPS) antigens. This was also tested simultaneously for its influence on spleen populations in the generation of cytotoxic effector cell populations to hapten-modified self. Unlike its effect on primary antibody responses (tolerogenic), TNP-MGG does not inhibit the generation of cytotoxic T cells against TNBS-treated syngeneic spleen cells. TNP-MGG was also unable to act as an immunogen in generating cytotoxic effectors against TNBS-treated spleen cells. These data show that although TNP-MGG has a tolerogenic effect on B lymphocytes (and possibly helper T lymphocytes) it does not block the generation of killer T lymphocytes directed against the hapten-modified spleen cells. A different mechanism of tolerance induction for TNP-MGG compared to hapten-modified syngeneic murine spleen is therefore suggested.


A novel scale-down cell culture and imaging design for the mechanistic insight of cell colonisation within porous substrate.
At the core of translational challenges in tissue engineering is the mechanistic understanding of the underpinning biological processes and the complex relationships among components at different levels, which is a challenging task due to the limitations of current tissue culture and assessment methodologies. Therefore, we proposed a novel scale-down strategy to deconstruct complex biomatrices into elementary building blocks, which were resembled by thin modular substrate and then evaluated separately in miniaturised bioreactors using various conventional microscopes. In order to investigate cell colonisation within porous substrate in this proof-of-concept study, TEM specimen supporters (10-30 μm thick) with fine controlled open pores (100∼600 μm) were selected as the modular porous substrate and suspended in 3D printed bioreactor systems. Noninvasive imaging of human dermal fibroblasts cultured on these free-standing substrate using optical microscopes illustrated the complicated dynamic processes used by both individual and coordinated cells to bridge and segment porous structures. Further in situ analysis via SEM and TEM provided high-quality micrographs of cell-cell and cell-scaffold interactions at microscale, depicted cytoskeletal structures in stretched and relaxed areas at nanoscale. Thus this novel scaled-down design was able to improve our mechanistic understanding of tissue formation not only at single- and multiple-cell levels, but also at micro- and nanoscales, which could be difficult to obtain using other methods.


[Diagnostic strategy for a solitary thyroid nodule. Example of development of recommendations for a practice guideline].
The solitary thyroid nodule is frequently observed and many strategies are proposed for the diagnosis of the etiology and for the choice of treatment. Despite many discussions no clear consensus has been so far reached. The french groups concerned by this problem set up a Clinical Practice Guide line with the methodological help of Agence Nationale pour le Développement de l'Evaluation Médicale. Based upon the critical review of the literature a consensus was obtained concerning the natural history of the nodules and the diagnosis value of the complementary explorations. The clinical approach alone completed by a TSH determination gives the therapeutical choice in about 30% of the patient without any other explorations. In the remaining cases 3 methods (isotope scan, echography, cytopuncture) can be used alone or in a combined sequence. So far no strategy can be privilegiated. It is necessary to set up a systematic comparison between the possible strategies and this will be made by the french thyroid specialists after this first step of delimitation of a clinical practise guide line.


3D Laser Micro- and Nanoprinting: Challenges for Chemistry.
3D printing is a powerful emerging technology for the tailored fabrication of advanced functional materials. This Review summarizes the state-of-the art with regard to 3D laser micro- and nanoprinting and explores the chemical challenges limiting its full exploitation: from the development of advanced functional materials for applications in cell biology and electronics to the chemical barriers that need to be overcome to enable fast writing velocities with resolution below the diffraction limit. We further explore chemical means to enable direct laser writing of multiple materials in one resist by highly wavelength selective (λ-orthogonal) photochemical processes. Finally, chemical processes to construct adaptive 3D written structures that are able to respond to external stimuli, such as light, heat, pH value, or specific molecules, are highlighted, and advanced concepts for degradable scaffolds are explored.


Increased release of serotonin from rat ileum due to dexfenfluramine.
Plasma levels of serotonin are elevated in primary pulmonary hypertension even after bilateral lung transplantation, suggesting a possible etiologic role. Serotonin is released primarily from the small intestine. Anorectic agents, such as dexfenfluramine, which can cause pulmonary hypertension, are known to inhibit potassium channels in vascular smooth muscle cells. We examined the hypothesis that dexfenfluramine may stimulate release of serotonin from the ileum by inhibition of K+ channels. In an isolated loop of rat ileum perfused with a physiological salt solution, the administration of dexfenfluramine, its major metabolite D-norfenfluramine, the potassium channel blocker 4-aminopyridine (5 mM), and caffeine (30 mM) increased serotonin levels in the venous effluent. Potassium chloride (60 mM) tended to increase serotonin levels. In genetically susceptible individuals, dexfenfluramine may induce pulmonary hypertension by increasing cytosolic calcium in enterochromaffin cells of the small intestine, thus releasing serotonin and causing vasoconstriction. This work indicates that dexfenfluramine and its major metabolite d-norfenfluramine can increase serotonin release from the small intestine.


Cognitive Reappraisal and Depression in Children with a Parent History of Depression.
Although decades of research have documented that children whose parents have a history of Major Depressive Disorder (MDD) are at a higher risk of developing depression themselves, not all of these children go on to develop depression themselves, thus highlighting the need to understand potential moderators of risk. The current study examined whether child emotion regulation, specifically, the use of cognitive reappraisal and suppression, moderated the link between parent and child depression. We recruited 458 parents and their children between the ages of 7-11 from the community. The majority of children were Caucasian (74.2%) and approximately half were girls (46.1%). Among children with a parent history of MDD, those who reported using cognitive reappraisal more frequently were less likely to have a history of depressive diagnoses themselves and had higher current levels of positive affect. Although children's use of suppression was not associated with their levels of depressive symptoms among children with a parent history of MDD, higher levels of suppression were related to higher levels of depressive symptoms among children with no parent history of MDD. These findings suggest that, among children with a history of parent depression, children's use of cognitive reappraisal may influence their own risk for developing depression and highlights the potential utility of early interventions that focus on improving the use of emotion regulation strategies like cognitive reappraisal among children of depressed parents.


Generalized monotonically convergent algorithms for solving quantum optimal control problems.
A wide range of cost functionals that describe the criteria for designing optimal pulses can be reduced to two basic functionals by the introduction of product spaces. We extend previous monotonically convergent algorithms to solve the generalized pulse design equations derived from those basic functionals. The new algorithms are proved to exhibit monotonic convergence. Numerical tests are implemented in four-level model systems employing stationary and/or nonstationary targets in the absence and/or presence of relaxation. Trajectory plots that conveniently present the global nature of the convergence behavior show that slow convergence may often be attributed to "trapping" and that relaxation processes may remove such unfavorable behavior.


Association between Non-Competitive Physical Exercise and Menstrual Disorders.
Menstrual disorders are highly prevalent and generate discomfort, anxiety, and more gynecological visits. There has been an increase in the practice of physical exercise among the general population. This study determined the association between physical exercise and menstrual disorders. An observational analytical study was conducted during 2016 in women of reproductive age from southeast Spain. Information was collected on sociodemographic, gynecological, and nutritional status variables, and the International Physical Activity Questionnaire (IPAQ) was used to gather data on physical exercise. Quantitative/qualitative variables were compared using the non- parametric Mann-Whitney U test and categorical variables with the chi-square (χ2) or Fisher's exact test, followed by multivariate logistic regression analysis. The study included 122 women; physical exercise was practiced by 50%; menstrual disorders were reported by 53.28 %. The practice of physical exercise, h/week of physical exercise, body type, level of physical exercise, and marital status were associated with the presence of menstrual cycle disorders (p˂0.05). This association persisted (p=0.042) after adjustment of the analysis for impaired nutritional status, medication consumption, the presence of disease, age, marital status, age at menarche, and number of children. A high physical activity not related to the practice of sport is associated with menstrual disorders.


GREB1: An evolutionarily conserved protein with a glycosyltransferase domain links ERα glycosylation and stability to cancer.
What covalent modifications control the temporal ubiquitination of ERα and hence the duration of its transcriptional activity remain poorly understood. We show that GREB1, an ERα-inducible enzyme, catalyzes O-GlcNAcylation of ERα at residues T553/S554, which stabilizes ERα protein by inhibiting association with the ubiquitin ligase ZNF598. Loss of GREB1-mediated glycosylation of ERα results in reduced cellular ERα levels and insensitivity to estrogen. Higher GREB1 expression in ERα+ve breast cancer is associated with greater survival in response to tamoxifen, an ERα agonist. Mice lacking Greb1 exhibit growth and fertility defects reminiscent of phenotypes in ERα-null mice. In summary, this study identifies GREB1, a protein with an evolutionarily conserved domain related to DNA-modifying glycosyltransferases of bacteriophages and kinetoplastids, as the first inducible and the only other (apart from OGT) O-GlcNAc glycosyltransferase in mammalian cytoplasm and ERα as its first substrate.


Correlation between clinical and radiographic findings on the occurrence of furcation involvement in patients with periodontitis.
Aim : The aim of the present study was to determine the occurrence of furcation involvement in the molars of patients with chronic periodontitis and correlate clinical and radiographic findings. Seventy subjects aged 35-69 years enrolled for treatment at a periodontics specialization program in Pernambuco, Brazil (EAP-SCDP-ABO/PE) participated in the study, comprising a total of 350 molars examined. The clinical diagnosis of furcation involvement was performed with a horizontal Nabers probe, whereas the radiographic examination was performed with periapical and bite-wing radiographs. The images were analyzed with an X-ray viewer at 3× magnification. The Chi-square test was used, with the level of significance set at 5%. A total of 64.5% individuals presented with furcation involvement, 43.1% of whom had degree II furcation. A significant association (P = 0.0060) was found between tooth type and frequency of furcation involvement. The first lower and upper molars were affected in 64.5 and 58.5% of cases, respectively. Adequate agreement (0.65) was observed between the clinical and radiographic findings. Taking into consideration the method employed and the results obtained, it may be concluded that the clinical and radiographic examinations performed are effective tools for diagnosing furcation involvement in teeth affected with periodontal disease.


Varying the counterions at a charged interface.
The influence of different counterions on the adsorption behavior of the ionic soluble surfactant dodecyl-dimethylammonium-pyridimium bromide is investigated. The addition of potassium halogenides to aqueous solutions of the surfactant modifies the surface activity of the amphiphile and has a profound influence on the surface tension isotherms. The measured critical micelle concentration follows the order of the periodic table of elements which is in strong contrast to the surface excess. The number density of the adsorbed surfactants at the cmc does not depend on the amount of counterions in the solution but on the nature of the counterion. Furthermore, evidence is provided that the surface region is depleted on fluoride ions. Surface second harmonic generation and ellipsometry have been used to gain direct structural information which complement the thermodynamic considerations. The combination of both optical techniques yields the number density of the condensed counterions within the compact layer. A strategy to retrieve selected parameters of the ion binding model of Radke et al. is presented. The analysis of the optical data reveal the existence of a phase transition towards a surface condensed state with increasing salt condensation.


Fungal infections: correlation with previous treatment and use of antimycogram.
From July 1987 to November 1988, 427 strains of mycetes (2.3% out of all microbiological samples) were isolated; 280 of these strains (146 from 84 in-patients, 134 from out-patients) were clinically relevant, and the cause of serious or systemic infections in 47 in-patients. Candida sp. (albicans and non-albicans) were the most frequently isolated (62% in-patients, 72% out-patients): Torulopsis sp., more frequent among in-patients (28% against 16%), were responsible for a limited hospital epidemic. 108 antimycograms were done; 7 patients had antimycotic treatment. In our hands antimycograms were useful in tracing hospital fungal infections. Before mycoses were detected, 78% of in-patients were on antibiotic treatment: 54 on 3rd generation cephalosporins, which seem to foster the outburst of fungi. The authors discuss the phenomenon and suggest some interpretation.


Cortical Morphometry and Its Relationship with Cognitive Functions in Children after non-CNS Cancer.
Background: Childhood cancer survivors (Ccs) are at risk for cognitive late-effects, which might result from cortical alterations, even if cancer does not affect the brain. The study aimed to examine gray and white matter volume and its relationship to cognition. Methods: Forty-three Ccs of non-central nervous system cancers and 43 healthy controls, aged 7-16 years, were examined. Cognitive functions and fine motor coordination were assessed and T1-weighted images were collected for voxel-based morphometry. Results: Executive functions (p = .024, d = .31) were poorer in Ccs than controls, however still within the normal range. The volume of the amygdala (p = .011, ŋ2 = .117) and the striatum (p = .03, ŋ2 = .102) was reduced in Ccs. No significant structure-function correlations were found, neither in patients nor controls. Conclusion: Non-CNS childhood cancer and its treatment impacts on brain structures relevant to emotion processing.


Technical note: validation of data loggers for recording lying behavior in dairy goats.
Changes in standing and lying behavior are frequently used in farm animals as indictors of comfort and health. In dairy goats, these behaviors have primarily been measured using labor-intensive video and live observation methodologies. The aim of this study was to validate accelerometer-based data loggers for use in goats. Two commercial dairy goat farms in Ontario were enrolled; goats were fitted with data loggers on their rear left legs and the pens were equipped with video. Data loggers compared well with video in identifying lying and standing events on both farms (farm 1 and 2, respectively: sensitivity=99.7 and 99.8%, specificity=99.5 and 99.4%, false readings=0.43 and 0.36%). The loggers were also able to record if the goat was lying on her left or right side (farm 1 only: sensitivity=99.9%, specificity=99.3%, false readings=0.38%), but these measures were only accurate if the loggers were attached with sufficient tension to prevent logger rotation. The mature does enrolled on farm 1 spent 14.5±1.0h/d lying down and frequently changed lying side even within a single lying bout (24±5 shifts/d between left and right sides and 16±5 lying bouts/d). The young goats on the second farm averaged just 8.5±3.2h/d in lying time, and spread this time over 8±4 bouts/d. Data loggers accurately measured lying time and lying bouts in mature does and younger goats on both farms, and lying laterality (e.g., left and right lying sides) in mature does on farm 1.


Photoallergy to benzophenone.
Incorrect diagnosis of photoallergy to sunscreen products represents a unique clinical dilemma. Increasing sunscreen usage for suspected idiopathic photosensitivity or a change to a sunscreen containing the same photoallergen only worsens the problem. While photoallergy to p-aminobenzoic acid and its esters is well known by dermatologists and the lay public, benzophenone photoallergy is not well appreciated. We report herein the cases of four individuals with photoallergy to oxybenzone in sunscreens. It is likely that such reactions will become more commonplace since oxybenzone is by far the most frequently used agent in modern, high sun protection factor sunscreens (greater than 8 sun protection factor) being marketed today.


Endocytosis of apolipoprotein A-V by members of the low density lipoprotein receptor and the VPS10p domain receptor families.
Apolipoprotein A-V (apoA-V) is present in low amounts in plasma and has been found to modulate triacylglycerol levels in humans and in animal models. ApoA-V displays affinity for members of the low density lipoprotein receptor (LDL-R) gene family, known as the classical lipoprotein receptors, including LRP1 and SorLA/LR11. In addition to LDL-A binding repeats, the mosaic receptor SorLA/LR11 also possesses a Vps10p domain. Here we show that apoA-V also binds to sortilin, a receptor from the Vsp10p domain gene family that lacks LDL-A repeats. Binding of apoA-V to sortilin was competed by neurotensin, a ligand that binds specifically to the Vps10p domain. To investigate the biological fate of receptor-bound apoA-V, binding experiments were conducted with cultured human embryonic kidney cells transfected with either SorLA/LR11 or sortilin. Compared with nontransfected cells, apoA-V binding to SorLA/LR11- and sortilin-expressing cells was markedly enhanced. Internalization experiments, live imaging studies, and fluorescence resonance energy transfer analyses demonstrated that labeled apoA-V was rapidly internalized, co-localized with receptors in early endosomes, and followed the receptors through endosomes to the trans-Golgi network. The observed decrease of fluorescence signal intensity as a function of time during live imaging experiments suggested ligand uncoupling in endosomes with subsequent delivery to lysosomes for degradation. This interpretation was supported by experiments with (125)I-labeled apoA-V, demonstrating clear differences in degradation between transfected and nontransfected cells. We conclude that apoA-V binds to receptors possessing LDL-A repeats and Vsp10p domains and that apoA-V is internalized into cells via these receptors. This could be a mechanism by which apoA-V modulates lipoprotein metabolism in vivo.


Acute osteomyelitis as cause of late sepsis in a nigerian neonate.
Neonatal osteomyelitis (NO) is said to be rare and uncommonly reported in the sub-region. Although this may be true, either because the cases are under-diagnosed, unreported or under-reported. The diagnosis is clinical and supported with blood culture or the aspiration of pus with radiological findings. We report a case of a neonate with acute osteomyelitis of the right femur, diagnosed at 10(th) day of life, which was confirmed with blood culture and radiogram findings of the right upper thigh of the baby. To the best of our knowledge, this is the first documented reported case of NO from the south-eastern Nigeria. It is imperative to recognize the clinical presentation necessary to raise the suspicion of NO and other focal infection in the newborn. With thorough examination and selected investigation the focus of infection in the neonate can be detected.


Correlation between severity of thyroid dysfunction and renal function.
Renal function is profoundly influenced by thyroid status; however, this has not been studied in detail in human subjects. The purpose of the present study was to determine the relationship between renal function and thyroid status before and after treatment for hypothyroidism and hyperthyroidism, respectively. In 37 consecutive hypothyroid and 14 hyperthyroid patients renal function as measured by plasma creatinine and glomerular filtration rate (GFR) [based on the modification of diet in renal disease (MDRD) formula] was determined before treatment and after regaining euthyroidism. Renal function improved significantly during treatment of hypothyroidism and decreased during treatment of hyperthyroidism. There was a strong correlation between the change in thyroid status determined as the ratio log(10)(fT4 post-treatment/fT4 pretreatment) and the change in renal function as a result of therapy expressed as serum creatinine (r(2) = 0.81, P < 0.0001) and estimated GFR (0.69, P < 0.0001). The kidney is an important target of thyroid hormone action.


Using run charts for cardiovascular disease risk assessments in general practice.
INTRODUCTION Run charts are quality improvement tools. AIM To investigate the feasibility and acceptability of run charts displaying weekly cardiovascular disease (CVD) risk assessments in general practice and assess their impact on CVD risk assessments. METHODS A controlled non-randomised observational study in nine practices using run charts and nine control practices. We measured the weekly proportion of eligible patients with completed CVD risk assessments for 19 weeks before and after run charts were introduced into intervention practices. A random coefficients model determined changes in CVD risk assessment rates (slope) from pre- to post- intervention by aggregating and comparing intervention and control practices' mean slopes. We interviewed staff in intervention practices about their use of run charts. RESULTS Seven intervention practices used their run chart; six consistently plotting weekly data for >12 weeks and positioning charts in a highly visible place. Staff reported that charts were easy to use, a visual reminder for ongoing team efforts, and useful for measuring progress. There were no significant differences between study groups: the mean difference in pre- to post-run chart slope in the intervention group was 0.03% more CVD risk assessments per week; for the control group the mean difference was 0.07%. The between group difference was 0.04% per week (95% CI: -0.26 to 0.35, P = 0.77). DISCUSSION Run charts are feasible in everyday general practice and support team processes. There were no differences in CVD risk assessment between the two groups, likely due to national targets driving performance at the time of the study.


NephroCheck at 10: addressing unmet needs in AKI diagnosis and risk stratification.
Despite its name, the current diagnosis of acute kidney injury (AKI) still depends on markers of decreased kidney function and not on markers of injury. This results in a delayed diagnosis: AKI is diagnosed based on serum creatinine criteria only when the severity of injury is enough to decrease glomerular filtration rate. Moreover, by the time AKI is diagnosed, the insult may have already ceased, and even appropriate therapy targeted at the specific insult and its associated pathogenic pathways may no longer be effective. Biomarkers of injury are needed that allow the diagnosis of AKI based on injury criteria. At least three commercially available immunoassays assessing urinary or plasma neutrophil gelatinase-associated lipocalin and urinary tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 ([TIMP2]*[IGFBP7]) (NephroCheck®) have generated promising data regarding prediction and early diagnosis of AKI, although their relative performance may depend on clinical context. Recently, a urinary peptidomics classifier (PeptAKI) was reported to predict AKI better than current biomarkers. Focusing on [TIMP2]*[IGFBP7], the cellular origin of urinary TIMP2 and IGFBP7 remains unclear, especially under the most common predisposing condition for AKI, i.e. chronic kidney disease. We now discuss novel data on the kidney cell expression of TIMP2 and IGFBP7 and its clinical implications.


Human monoclonal antibody against a tissue polypeptide antigen-related protein from a patient with a signet-ring cell carcinoma of the stomach.
For a comparative study of the humoral immunity of patients with gastric signet-ring cell carcinoma, lymphocytes from spleen and lymph nodes were fused with the heteromyeloma SPM4-0. Immunoglobulin-producing clones were primarily tested in binding assays on autologous and allogeneic tumor cells and tissues. One of the resulting human monoclonal antibodies, designated 56/16 (IgM, lambda), was found to be suitable for a detailed biochemical characterization. Immunoblotting and comparative two-dimensional gel electrophoresis on cell and tissue extracts as well as on preparations of the cytoskeleton revealed that the main epitope is not an integral membrane molecule but a degradation product of cytokeratin 8, which is a main component of the tumor marker, tissue polypeptide antigen. The Mr 38,000/45,000 antigen could be identified in tumor and normal tissues, with highest expression in secretory cells and organs. Thus, the human monoclonal antibody 56/16 might represent an immune response in the patient against breakdown products of cytokeratin 8, which are released from the tumor cells during cell division, secretion, or cell death. A possible association of the antibody with the secretory activity of signet-ring carcinoma cells is discussed.


Morphometry of human blood leukocyte ultrastructure: its potential value in haematology.
A review of the literature on ultrastructural morphometry of human blood leukocytes has been carried out. It is concluded that: (1) Blood leukocytes are particularly suitable for morphometric study. (2) Morphometric methods have proved valuable in defining differing cytological features of cells in various lymphoid malignancies, and in demonstrating ultrastructural differences (which could not otherwise have been detected) in monocytes and eosinophils corresponding to known functional changes. (3) Appropriate and valid numerical procedures are essential for determining morphometric equations and statistical probabilities; both morphometric measurement and statistical analysis are made easier by the use of computers. (4) Ultrastructural morphometry should ultimately find an important place in clinical haematology.


[Novel function of astrocytes revealed by optogenetics].
Astrocytes respond to neuronal activity. However, whether astrocytic activity has any significance in brain function is unknown. Signaling pathway leading from astrocytes to neurons would be required for astrocytes to participate in neuronal functions and, here, we investigated the presence of such pathway. Optogenetics was used to manipulate astrocytic activity. A light-sensitive protein, channelrhodopsin-2 (ChR2), was selectively expressed in astrocytes. Photostimulation of these astrocytes induced glutamate release which modulated neuronal activity and animal behavior. Such glutamate release was triggered by intracellular acidification produced by ChR2 photoactivation. Astrocytic acidification occurs upon brain ischemia, and we found that another optogenetic tool, archaerhodopsin (ArchT), could counter the acidification and suppress astrocytic glutamate release. Controlling of astrocytic pH may become a therapeutic strategy upon ischemia.


The mandibular permanent second molars and their risk of impaction: a retrospective study.
The aim of this retrospective study is promote a better understanding of the impaction of teeth 37 and 47 by means of clinical and statistical data from the point of view of early interceptive treatment. 478 patients of the Orthodontic School of "La Sapienza" University of Rome (Italy) were studied to assess the eruption of teeth 37 and 47 on at least two good-quality panorex using angular measurements and Nolla's index from January 2008 to December 2013. Data were analysed using ANOVA and Tukey HSD test (P < 0.05). The data obtained on the possible correlations between the examined teeth and the four reference angles show that at t0, the angular variation of teeth 36 or 46 is constant when the teeth are at the end of their eruptive process, while for teeth 37 and 47, this variation is always constant. At t0, the first and the second molars of both quadrants, during eruption showed a similar behaviour. At t1, the four teeth examined in the patients sample showed a model of development analogous to that exhibited at t0. a constant variation (t0-t1) is present among the differences in the development of the 36 and the two angular values, while difference in development of the 37 and that of the angular value is constant only in relationship to the difference in development of the mandibular first molar of the same quadrant. The variations between the difference in development of the 47 and in angular value (t0-t1) are constant only when related to the developing 46. The analytic variance of gradience (vargrad) data confirm peculiar behaviour of the first one, according to both mandibular molars, during their eruptive development. Adoption of universally recognised radiographic predictive methods allows assessment of the case and allows the specialist to plan a suitable treatment to prevent or intercept the molar impaction, with a perspective of a less invasive and shorter therapy. Although rare, impaction of teeth 37 and 47 often requires a complex, multidisciplinary approach.


EMLI-ICC: an ensemble machine learning-based integration algorithm for metastasis prediction and risk stratification in intrahepatic cholangiocarcinoma.
Robust strategies to identify patients at high risk for tumor metastasis, such as those frequently observed in intrahepatic cholangiocarcinoma (ICC), remain limited. While gene/protein expression profiling holds great potential as an approach to cancer diagnosis and prognosis, previously developed protocols using multiple diagnostic signatures for expression-based metastasis prediction have not been widely applied successfully because batch effects and different data types greatly decreased the predictive performance of gene/protein expression profile-based signatures in interlaboratory and data type dependent validation. To address this problem and assist in more precise diagnosis, we performed a genome-wide integrative proteome and transcriptome analysis and developed an ensemble machine learning-based integration algorithm for metastasis prediction (EMLI-Metastasis) and risk stratification (EMLI-Prognosis) in ICC. Based on massive proteome (216) and transcriptome (244) data sets, 132 feature (biomarker) genes were selected and used to train the EMLI-Metastasis algorithm. To accurately detect the metastasis of ICC patients, we developed a weighted ensemble machine learning method based on k-Top Scoring Pairs (k-TSP) method. This approach generates a metastasis classifier for each bootstrap aggregating training data set. Ten binary expression rank-based classifiers were generated for detection of metastasis separately. To further improve the accuracy of the method, the 10 binary metastasis classifiers were combined by weighted voting based on the score from the prediction results of each classifier. The prediction accuracy of the EMLI-Metastasis algorithm achieved 97.1% and 85.0% in proteome and transcriptome datasets, respectively. Among the 132 feature genes, 21 gene-pair signatures were developed to establish a metastasis-related prognosis risk-stratification model in ICC (EMLI-Prognosis). Based on EMLI-Prognosis algorithm, patients in the high-risk group had significantly dismal overall survival relative to the low-risk group in the clinical cohort (P-value < 0.05). Taken together, the EMLI-ICC algorithm provides a powerful and robust means for accurate metastasis prediction and risk stratification across proteome and transcriptome data types that is superior to currently used clinicopathological features in patients with ICC. Our developed algorithm could have profound implications not just in improved clinical care in cancer metastasis risk prediction, but also more broadly in machine-learning-based multi-cohort diagnosis method development. To make the EMLI-ICC algorithm easily accessible for clinical application, we established a web-based server for metastasis risk prediction (http://ibi.zju.edu.cn/EMLI/).


Role of positron emission tomography-computed tomography in endometrial cancer.
The efficacy of preoperative 18F-fluoro-D-glucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) in endometrium cancer is controversial. We examined the efficacy of PET-CT and the association between maximum standardized uptake value (SUVmax) and prognostic factors in endometrial cancer. Thirty patients with endometrial cancer underwent preoperative 18F-FDG/PET-CT. The patients were treated with abdominal hysterectomy with bilateral salpingo-oophorectomy, and bilateral systemic pelvic lymphadenectomy was planned for all patients; paraaortic lymphadenectomy was performed in patients with intermediate and high risk. Tumor histology, grade, depth of myometrial invasion, maximum tumor diameter, lymphovascular invasion, nodal status, and ovarian/adnexal metastases were recorded. The mean primary tumor diameter was reported smaller in PET-CT and the effect size of PET-CT was -0.60. The kappa value was 0.06 for myometrial invasion. Pelvic lymph node metastasis was reported in 22.2% of patients in PET-CT. However, 3.7% of patients had pelvic lymph node metastasis. The kappa value for pelvic lymph node metastasis was 0.23, and sensitivity, specificity, and positive and negative predictive values were 100%, 80.7%, 16.6%, and 100%, respectively. Paraaortic lymph node metastasis in PET-CT was suspected in 10%. However, paraaortic lymph node metastasis was found in 6.7% in histopathologic analyses. The kappa value was 0.15. The sensitivity, specificity, and positive and negative predictive values of PET-CT for detecting paraaortic lymph node metastases were 100%, 93.7%, 66.6%, and 100%, respectively. Myometrial invasion and tumor diameter were the only important prognostic factors affecting SUVmax. According to our results, PET-CT has a limited role and diagnostic efficacy in endometrial cancer. The indications of FDG/PET-CT in endometrium cancer should be studied further and revised.


Disclosure of Traditional and Complementary Medicine Use and Its Associated Factors to Medical Doctor in Primary Care Clinics in Kuching Division, Sarawak, Malaysia.
The decision by the patients to disclose traditional and complementary medicine (TCM) use to their doctor is an important area to be explored. This study aimed to determine the disclosure of TCM use and its associated factors to medical doctor among primary care clinic attendees in Kuching Division, Sarawak. It was a cross-sectional study using questionnaire, interviewer administered questionnaire. A total of 1130 patients were screened with 80.2% reporting using TCM. Logistic regression analysis revealed that being female (AOR = 3.219, 95% CI: 1.385, 7.481), perceived benefits that TCM can prevent complication of illness (AOR = 3.999, 95% CI: 1.850, 8.644) and that TCM is more gentle and safer (AOR = 4.537, 95% CI: 2.332, 8.828), perceived barriers of not having enough knowledge about TCM (AOR = 0.530, 95% CI: 0.309, 0.910), patient dissatisfaction towards healthcare providers being too business-like and impersonal (AOR = 0.365, 95% CI: 0.199, 0.669) and paying more for healthcare than one can afford (AOR = 0.413, 95% CI: 0.250, 0.680), and accessibility of doctors (AOR = 3.971, 95% CI: 2.245, 7.023) are the predictors of disclosure of TCM use. An open communication between patients and doctor is important to ensure safe implementation and integration of both TCM and medical treatment.


Long-term outcome after thoracoscopic cardiac sympathectomy for refractory ventricular tachyarrhythmia storm.
A man in his 40s presented with an acute anterior wall myocardial infarction (MI) 6 hours after symptom onset to a non-percutaneous intervention enabled hospital and underwent thrombolysis with tenecteplase. His chest pain resolved post-thrombolysis although ST segment resolution was less than 50%. He had an episode of sustained ventricular tachycardia (VT) 48 hours after MI which was successfully cardioverted with 150 J biphasic shock. A month later he presented with a ventricular tachycardia storm that was refractory to pharmacological management. He underwent radiofrequency ablation of the VT using three-dimensional mapping. Although the patient remained free of VT/ventricular fibrillation (VF) for 48 hours, he had an episode of VF subsequently. A decision for bilateral surgical video assisted thoracoscopic cardiac sympathetic denervation was taken and the patient remained free of ventricular tachyarrhythmias after the procedure until.


A synergistic effect of pretreatment on cell wall structural changes in barley straw (Hordeum vulgare L.) for efficient bioethanol production.
Barley straw (Hordeum vulgare L.) is an attractive lignocellulosic material and one of the most abundant renewable resources for fuel ethanol production. Although it has high cellulose and hemicellulose contents, there are several challenges and limitations in the process of converting it to fuel ethanol. High ash, silica and lignin contents in barley straw make it an inferior feedstock for enzymatic hydrolysis. Therefore pretreatment of barley straw could play an important role in inducing structural and compositional changes that increase the efficiency of enzymatic hydrolysis and make the whole process economically viable. Saccharification was enhanced using various concentrations (0.0, 0.5, 1.0, 2.0 and 3.0% v/v) of a solution of sodium hypochlorite (NaClO) and hydrogen peroxide (H₂O₂) and various reaction times (15, 30 and 45 min) during pretreatment at 121 °C. The highest yield of glucose (447 mg g⁻¹) was achieved by pretreatment with 2.0% NaClO+H₂O₂ solution for 30 min, representing an increase of 65.99% compared with untreated barley straw (152 mg g⁻¹). During fermentation, the highest amount of ethanol (207 mg g⁻¹) was obtained under anaerobic plus 0.4 mmol L⁻¹ benzoic acid conditions, representing an increase of 57.49, 38.16 and 10.14% compared with untreated sample (88 mg g⁻¹), aerobic (128 mg g⁻¹) and anaerobic (186 mg g⁻¹) conditions respectively. The results suggest that pretreatment with 2.0% NaClO+H₂O₂ solution disrupted the recalcitrant structure of barley straw and enhanced the glucose yield and subsequent bioethanol production.


Characteristics of inpatient care and rehabilitation for acute first-ever stroke patients.
The purpose of this study was to analyze the status of inpatient care for acute first-ever stroke at three general hospitals in Korea to provide basic data and useful information on the development of comprehensive and systematic rehabilitation care for stroke patients. This study conducted a retrospective complete enumeration survey of all acute first-ever stroke patients admitted to three distinct general hospitals for 2 years by reviewing medical records. Both ischemic and hemorrhagic strokes were included. Survey items included demographic data, risk factors, stroke type, state of rehabilitation treatment, discharge destination, and functional status at discharge. A total of 2159 patients were reviewed. The mean age was 61.5±14.4 years and the ratio of males to females was 1.23:1. Proportion of ischemic stroke comprised 54.9% and hemorrhagic stroke 45.1%. Early hospital mortality rate was 8.1%. Among these patients, 27.9% received rehabilitation consultation and 22.9% underwent inpatient rehabilitation treatment. The mean period from admission to rehabilitation consultation was 14.5 days. Only 12.9% of patients were transferred to a rehabilitation department and the mean period from onset to transfer was 23.4 days. Improvements in functional status were observed in the patients who had received inpatient rehabilitation treatment after acute stroke management. Our analysis revealed that a relatively small portion of patients who suffered from an acute first-ever stroke received rehabilitation consultation and inpatient rehabilitation treatment. Thus, applying standardized clinical practice guidelines for post-acute rehabilitation care is needed to provide more effective and efficient rehabilitation services to patients with stroke.


Lichen sclerosus et atrophicus in children with phimosis and hypospadias.
This prospective study was designed to evaluate the incidence of lichen sclerosus et atrophicus (LSA) in a pediatric population with hypospadias and phimosis in order to discuss the indications for circumcision and utilization of preputial skin for urethral surgery. All 115 boys, 55 with congenital phimosis, 45 with acquired phimosis, 13 with hypospadias, and 2 with recurrent chronic balanitis, underwent full-thickness biopsies of the foreskin that were examined by a single pathologist. Of the patients with acquired phimosis, 88% showed inflammatory features in the foreskin; 60% had LSA. Of the patients with congenital phimosis, 82% showed inflammatory disease in the prepuce; 30% had LSA. Of the patients operated upon for hypospadias, 61% showed histologic findings of chronic inflammation of the foreskin and LSA was evident in 15%. The high incidence of LSA in the prepuce of patients with phimosis suggests that circumcision should be performed to correct this disease. The frequent presence of chronic inflammation is a possible cause of stenosis when the foreskin is used to perform a urethroplasty in patients with hypospadias.


[Angiogenic activity of mononuclear cells in the peripheral blood of patients with ischemic heart disease].
In the paper the cell-mediated phase of the immune response was assessed in ischaemic heart disease (IHD). The assessment was based on the angiogenesis test in which new capillaries are formed from the already existing vascularization. The process is mediated by mononuclear cells from peripheral blood, and is induced by degradation products appearing as a result of ischaemic injury to the tissues. The test was carried out in 71 patients with IHD and in 65 clinically healthy subjects. A significant fall was demonstrated of the angiogenic activity of mononuclear cells isolated from the peripheral blood of IHD patients as compared with controls (p less than 0.001). No effect was method of disease duration, its form or treatment on angiogenesis. The obtained results may suggest a failure of the immune system competent in this process in IHD. Perhaps this is related to a special form of IHD.


Noninvasively measuring oxygen saturation of human finger-joint vessels by multi-transducer functional photoacoustic tomography.
Imaging small blood vessels and measuring their functional information in finger joint are still challenges for clinical imaging modalities. In this study, we developed a multi-transducer functional photoacoustic tomography (PAT) system and successfully imaged human finger-joint vessels from ∼1 mm to <0.2 mm in diameter. In addition, the oxygen saturation (SO2) values of these vessels were also measured. Our results demonstrate that PAT can provide both anatomical and functional information of individual finger-joint vessels with different sizes, which might help the study of finger-joint diseases, such as rheumatoid arthritis.


Mechanism-based probe for the analysis of cathepsin cysteine proteases in living cells.
Mechanism-based probes are providing new tools to evaluate the enzymatic activities of protein families in complex mixtures and to assign protein function. The application of these chemical probes for the visualization of protein labeling in cells and proteomic analysis is still challenging. As a consequence, imaging and proteomic analysis often require different sets of chemical probes. Here we describe a mechanism-based probe, azido-E-64, that can be used for both imaging and proteomics. Azido-E-64 covalently modifies active Cathepsin (Cat) B in living cells, an abundant cysteine protease involved in microbial infections, apoptosis, and cancer. Furthermore, azido-E-64 contains an azide chemical handle that can be selectively derivatized with phosphine reagents via the Staudinger ligation, which enables the imaging and proteomic analysis of Cat B. We have utilized azido-E-64 to visualize active Cat B during infection of primary macrophages with Salmonella typhimurium , an facultative intracellular bacterial pathogen. These studies demonstrated that active Cat B is specifically excluded from Salmonella -containing vacuoles, which suggests that inhibition of protease activity within bacteria-containing vacuoles may contribute to bacterial virulence.