Children's perspective on their right to participate in decision-making according to the United Nations Convention on the Rights of the Child article 12.
ABSTRACT Aims: According to the United Nations Convention on the Rights of the Child article 12, children have a right to express their views. However, knowledge on how children with a disability perceive this right and the extent to which they would like to access this right is unclear. The aim of this study was to describe and capture the meaning of children's perspective on their right to participate in decision-making together with the children's lived experiences in pediatric rehabilitation. Methods: A phenomenological hermeneutical research design was applied for gathering the thoughts and lived experiences of seven children with different disabilities through individual interviews and observations. Results: The children expressed satisfaction with participation being limited to less important decisions. This may be understood as lack of experience with participation in decision-making or an inherent wish of becoming like peers and therefore viewing therapists as experts of a normalization process. Conclusions: Health care professionals should consider informing the child of the possibility of decision-making and for negotiating power-sharing and responsibility concerning decisions in pediatric rehabilitation.


Serum exosomes and cytokines promote a T-helper cell type 2 environment in the peripheral blood of glioblastoma patients.
Glioblastoma (GBM) is an aggressive infiltrative brain tumor with a particularly poor prognosis that is characterized by microvascular proliferation, necrotic tissue, and significant infiltration of M2-like monocytes. Compromised barrier function in tumor vasculature might be expected to permit communication between the tumor microenvironment and peripheral blood. To ascertain whether tumor-derived vesicles and/or factors might reach the bloodstream and what effects these molecules have on the peripheral compartment, we analyzed blood samples collected from primary GBM patients. Notably, a significant number of patient sera samples contained tumor exosome-reactive immunoglobulin (Ig)G2 and IgG4 antibody isotypes, which are consistent with Th2 immunity. M2-like monocytes expressing CD14+ and CD163+, another indicator of Th2 bias, are elevated in GBM patient blood and associated with high serum concentrations of colony-stimulating factor 2 and 3, as well as interleukin-2, -4, and -13, the latter 2 cytokines being hallmarks of Th2 immunity. GBM patient sera samples induce high levels of CD163 expression when added to normal monocytes, providing mechanistic evidence of a basis for Th2 bias. Fractionation of GBM patient sera into samples enriched for exosomes or soluble factors proved that both fractions are capable of inducing CD163 expression in normal monocytes. The results of the current study indicate a Th2 bias in the periphery of GBM patients, likely as a result of products elaborated by the tumor. Consequentially, through immune modulation these brain tumors exert systemic effects beyond the confines of the CNS.


Identification of a New Antimicrobial, Desertomycin H, Utilizing a Modified Crowded Plate Technique.
The antibiotic-resistant bacteria-associated infections are a major global healthcare threat. New classes of antimicrobial compounds are urgently needed as the frequency of infections caused by multidrug-resistant microbes continues to rise. Recent metagenomic data have demonstrated that there is still biosynthetic potential encoded in but transcriptionally silent in cultivatable bacterial genomes. However, the culture conditions required to identify and express silent biosynthetic gene clusters that yield natural products with antimicrobial activity are largely unknown. Here, we describe a new antibiotic discovery scheme, dubbed the modified crowded plate technique (mCPT), that utilizes complex microbial interactions to elicit antimicrobial production from otherwise silent biosynthetic gene clusters. Using the mCPT as part of the antibiotic crowdsourcing educational program Tiny EarthTM, we isolated over 1400 antibiotic-producing microbes, including 62 showing activity against multidrug-resistant pathogens. The natural product extracts generated from six microbial isolates showed potent activity against vancomycin-intermediate resistant Staphylococcus aureus. We utilized a targeted approach that coupled mass spectrometry data with bioactivity, yielding a new macrolactone class of metabolite, desertomycin H. In this study, we successfully demonstrate a concept that significantly increased our ability to quickly and efficiently identify microbes capable of the silent antibiotic production.


Moscow Health Survey 2004--social surveying under difficult circumstances.
The aim of this paper is to present the Moscow Health Survey 2004, which was designed to examine health inequalities in Moscow. In particular we want to discuss social survey problems, such as non-response, in Moscow and Russia. Interviews, covering social and economic circumstances, health and social trust, of a stratified random sample of the greater Moscow population, aged 18+. Reasons for nonresponse were noted down with great care. Odds ratios (ORs) for self-rated health by gender and by six social dimensions were estimated separately for districts with low and high response rates. Bias due to non-response is discussed. About one in two (53.1%) of approached individuals could not be interviewed, resulting in 1190 completed interviews. Non-response in most Russian surveys, but perhaps particularly in Moscow, is large, partly due to fear of strangers and distrust of authorities. ORs for poor health vary significantly by gender, occupational class, education and economic hardship. We find no significant differences in these ORs when comparing districts with low and high response rates. Non-response may be a problem when estimating prevalence rates or population means, but much less so when estimating odds ratios in multivariate analyses.


Sequence requirements for transcriptional arrest in exon 1 of the murine adenosine deaminase gene.
We have previously shown that a transcription arrest site near the 5' end of the murine adenosine deaminase (ADA) gene is significantly involved in the regulation of ADA gene expression. To facilitate the analysis of this transcription arrest site, we have analyzed the transcription products from cloned ADA gene fragments injected into Xenopus laevis oocytes. When genomic fragments spanning the 5' end of the ADA gene were injected into oocytes, a 96-nucleotide (nt) ADA RNA was the major transcription product. The 5' end of this RNA mapped to the transcription initiation site for the ADA gene, and its 3' terminus mapped 7 nt downstream of the translation initiation codon within exon 1. A 300-base-pair fragment of genomic DNA spanning the 5' end of the ADA gene was sufficient to generate the 96-nt transcript which accounted for approximately one-half of the transcription products from injected templates. Deletion of a segment of approximately 65 base pairs, located immediately downstream of the 3' terminus of the 96-nt transcript, resulted in a substantial reduction in the synthesis of the 96-nt transcript and a corresponding increase in the production of larger transcripts. These studies show that the transcriptional apparatus of X. laevis oocytes responds to the transcription arrest site associated with exon 1 of the murine ADA gene and that oocyte injections provide a convenient functional assay for additional mechanistic studies.


Controlled-Release Oxycodone vs. Placebo in the Treatment of Chronic Breathlessness-A Multisite Randomized Placebo Controlled Trial.
Chronic breathlessness is a clinical syndrome that results in significant distress and disability. Morphine can reduce chronic breathlessness when the contributing etiologies are optimally treated. Does oxycodone reduce chronic breathlessness compared with placebo? A multisite, randomized, placebo-controlled, double-blind, parallel-arm, fixed-dose trial of oral controlled-release oxycodone 15 mg (5 mg, eight hourly) or placebo (ACTRN12609000806268 at www.anzctr.org.au). As-needed immediate-release morphine (2.5 mg per dose; six and less doses/day) was available for both arms as required by one ethics committee overseeing the trial. Recruitment occurred from 2010 to 2014 in 14 inpatient and outpatient respiratory, cardiology, and palliative care services across Australia. Participants were adults, with chronic breathlessness (modified Medical Research Council Scale 3 or 4), who were opioid naive. The primary end point was the proportion of people with greater than 15% reduction from baseline in the intensity of breathlessness now (0-100 mm visual analogue scale) comparing arms Days 5-7. Secondary end points were average and worst breathlessness, quality of life, function, and harms. Of 157 participants randomized, 155 were included (74 oxycodone and 81 placebo), but the study did not reach target recruitment. There was difference in neither between groups for the primary outcome (P = 0.489) nor any of the prespecified secondary outcomes. Placebo participants used more as-needed morphine (mean 7.0 vs. 4.2 doses; P ≤ 0.001). Oxycodone participants reported more nausea (P < 0.001). There was no signal of benefit from oxycodone over placebo. Future research should focus on investigating the existence of an opioid class effect on the reduction of chronic breathlessness.


Role of sarcoplasmic reticulum in inhibitory junction potentials and hyperpolarizations by nitric oxide donors in opossum oesophagus.
1. Previous patch clamp studies of oesophageal circular muscle cells showed that nitric oxide (NO) modulated the opening of Ca2(+)-activated K+ channels involved in mediating the inhibitory junction potentials (i.j.ps). This study clarified the role of Ca2+ release from the superficial sarcoplasmic reticulum (SR) in the mechanism of i.j.ps or hyperpolarizing responses to NO-releasing compounds. Electrical and mechanical activities were simultaneously recorded by intracellular microelectrode or double sucrose gap techniques. 2. The NO-donors, sydnonimine (SIN-1) and sodium nitroprusside, each at 500 microM, hyperpolarized oesophageal circular muscle cells by 15-20 mV, like i.j.ps. 3. The selective inhibitors of SR Ca2(+)-ATPase (cyclopiazonic acid 10-30 microM and thapsigargin 5 microM) and the SR Ca2+ release channel activator (ryanodine 30 microM) caused depolarization and spontaneous contractions which were diminished after prolonged (> 30 min) incubation with these agents in Ca2(+)-containing medium. Moreover, these agents inhibited both the i.j.p. and NO-donor hyperpolarizations, suggesting that a functional SR Ca2+ uptake is necessary for the response to endogenous or exogenous NO. 4. These results, along with our previous findings of the dependence of i.j.ps and NO-donor hyperpolarizations on K+ channel activation and cyclic GMP elevation, support the hypothesis that subplasmalemmal (Ca2+)i elevation, via vectorial Ca2+ release from superficial SR toward the plasmalemma, may be an important mechanism by which NO, from NO-liberating compounds or released from inhibitory neurones induces relaxation and i.j.ps in opossum oesophagus.


Infection with Batrachochytrium dendrobatidis is common in tropical lowland habitats: Implications for amphibian conservation.
Numerous species of amphibians declined in Central America during the 1980s and 1990s. These declines mostly affected highland stream amphibians and have been primarily linked to chytridiomycosis, a deadly disease caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd). Since then, the majority of field studies on Bd in the Tropics have been conducted in midland and highland environments (>800 m) mainly because the environmental conditions of mountain ranges match the range of ideal abiotic conditions for Bd in the laboratory. This unbalanced sampling has led researchers to largely overlook host-pathogen dynamics in lowlands, where other amphibian species declined during the same period. We conducted a survey testing for Bd in 47 species (n = 348) in four lowland sites in Costa Rica to identify local host-pathogen dynamics and to describe the abiotic environment of these sites. We detected Bd in three sampling sites and 70% of the surveyed species. We found evidence that lowland study sites exhibit enzootic dynamics with low infection intensity and moderate to high prevalence (55% overall prevalence). Additionally, we found evidence that every study site represents an independent climatic zone, where local climatic differences may explain variations in Bd disease dynamics. We recommend more detection surveys across lowlands and other sites that have been historically considered unsuitable for Bd occurrence. These data can be used to identify sites for potential disease outbreaks and amphibian rediscoveries.


Effects of perioperative tight glycemic control on postoperative outcomes: a meta-analysis.
Background The optimal glycemic target during the perioperative period is still controversial. We aimed to explore the effects of tight glycemic control (TGC) on surgical mortality and morbidity. Methods PubMed, EMBASE and CENTRAL were searched from January 1, 1946 to February 28, 2018. Appropriate trails comparing the postoperative outcomes (mortality, hypoglycemic events, acute kidney injury, etc.) between different levels of TGC and liberal glycemic control were identified. Quality assessments were performed with the Jadad scale combined with the allocation concealment evaluation. Pooled relative risk (RR) and 95% CI were calculated using random effects models. Heterogeneity was detected by the I2 test. Results Twenty-six trials involving a total of 9315 patients were included in the final analysis. The overall mortality did not differ between tight and liberal glycemic control (RR, 0.92; 95% CI, 0.78-1.07; I 2 = 20.1%). Among subgroup analyses, obvious decreased risks of mortality were found in the short-term mortality, non-diabetic conditions, cardiac surgery conditions and compared to the very liberal glycemic target. Furthermore, TGC was associated with decreased risks for acute kidney injury, sepsis, surgical site infection, atrial fibrillation and increased risks of hypoglycemia and severe hypoglycemia. Conclusions Compared to liberal control, perioperative TGC (the upper level of glucose goal ≤150 mg/dL) was associated with significant reduction of short-term mortality, cardic surgery mortality, non-diabetic patients mortality and some postoperative complications. In spite of increased risks of hypoglycemic events, perioperative TGC will benefits patients when it is done carefully.


Improving Medication Adherence with Two-way Short Message Service Reminders in Sickle Cell Disease and Asthma. A feasibility randomized controlled trial.
Sickle cell disease (SCD) is a childhood and adult disease that primarily affects African Americans, characterized by life threatening sequelae mitigated by medications. One-way and two-way short message service (SMS) medication reminders have differing efficacy in chronic diseases. There is limited literature about SMS medication reminders in SCD. The goal of this study was to test the feasibility, defined by recruitment/acceptance, retention/attrition, and technology utilization, of two-way SMS medication reminders in individuals with SCD with and without asthma. Participants were randomly allocated to standard care or reminders. Two-way SMS reminders were automated using Research Electronic Data Capture (REDCap) for hydroxyurea, fluticasone, budesonide and montelukast. Adherence was measured using the Morisky Medication Adherence Scale-8 (MMAS-8). Asthma control was assessed using the Childhood and Adult-Asthma Control Tests (ACT). Participants were enrolled 28 to 60 days with a common termination date. The recruitment rate was 95% (47/49) and 82.9% completed the study. Among the 47 study participants enrolled, 51.1% were male, 61.7% were adults, median age was 20 (range: 3 to 59), and 98% were African Americans. Of the 26 participants receiving messages, 20% responded on over 95% of the days and usage varied with an average response rate of 33%, ranging from 21% to 46%. Medication adherence scores improved significantly in the intervention group (3.42 before, 5.46 after; p=0.002), but not in the control group (3.90 before, 4.75 after; p=0.080). Childhood-ACT scores improved in the intervention group (19.20 before, 24.25 after). Adult-ACT scores within the intervention arm were unchanged (21.0 before, 22.0 after. ACT scores did not improve significantly. This study demonstrated the feasibility for two-way SMS medication reminders to improve medication adherence in a high-risk population where daily medication adherence is critical to health outcomes and quality of life.


Registered nurses transitioning from acute care to primary healthcare employment: A qualitative insight into nurses' experiences.
To describe the experiences of acute care registered nurses transitioning to primary healthcare settings. The worldwide increasing demand for primary healthcare services has resulted in skilled acute care nurses transitioning to primary healthcare settings to meet workforce requirements. Little is known about the experiences and challenges associated with the transition. Knowledge of this will enable employers to design appropriate support processes and transitioning nurses can make informed choices. Semistructured interviews were conducted with nurses who had transitioned into primary healthcare employment in the last 5 years. Data analysis was undertaken using Braun and Clarke's (2006) thematic analysis approach. Thirteen nurses were interviewed, and two themes identified-role learning: the new environment, and role socialisation: transition validation. Role learning was influenced according to the quality of orientation programmes, previous experience, clinical knowledge and professional support. Support and professional respect from mentors and/or employers greatly assisted with role socialisation and the transition experience. Transitioning to primary healthcare employment provides unique challenges which must be considered by employers if they are to attract and retain experienced acute care registered nurses. Understanding the experiences of nurses who transition from acute to primary healthcare employment can inform the design of orientation programmes and ongoing professional supports to address barriers and challenges. Targeted orientation and support has the potential to enhance recruitment and retention of experienced nurses in primary health care.


Effects of low concentrations of cis- and trans-urocanic acid on cytokine elaboration by keratinocytes.
The urocanic acid cis isomer (cis-UCA) is a possible cutaneous photoreceptor for the immunomodulatory phenomena that follow ultraviolet B irradiation. Several experiments in animals show an inhibitory action of cis-UCA on cellular immunity. However, the action of cis-UCA on the synthesis of cytokines in keratinocytes remains unknown. Long-term cultures of normal human keratiocytes were prepared in a serum-free medium, and stimulated with 1 microgram/ml of phorbol 12-myristate 13-acetate (TPA) and UCA or UVB-UCA (10-100 micrograms/ml). Synthesis of the following cytokines was measured using ELISA and Northern blot techniques: TNF-alpha, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TGF-beta 1. TPA increased TNF-alpha protein levels in culture supernatants. No changes in Il-1 alpha and IL-1 beta protein levels were detected in basal culture supernatant after TPA stimulus. TPA augmented RNA expression for TNF-alpha, IL-1 alpha, IL-1 beta and TGF-beta 1. UCA isomers did not induce cytokine changes in protein synthesis. Expression of IL-1 alpha and IL-1 beta genes was increased after exposure to 100 micrograms/ml UVB-UCA (70 micrograms/ml cis-UCA). A slight increase in TNF-alpha RNA expression was detected when the dose of UVB-UCA reached 100 micrograms/ml. No effects on cytokine synthesis were found after UCA stimulus. These results suggest that low doses of cis-UCA do not effect cytokine synthesis by keratinocytes.


Machine Learning-Assisted Network Inference Approach to Identify a New Class of Genes that Coordinate the Functionality of Cancer Networks.
Emerging evidence indicates the existence of a new class of cancer genes that act as "signal linkers" coordinating oncogenic signals between mutated and differentially expressed genes. While frequently mutated oncogenes and differentially expressed genes, which we term Class I cancer genes, are readily detected by most analytical tools, the new class of cancer-related genes, i.e., Class II, escape detection because they are neither mutated nor differentially expressed. Given this hypothesis, we developed a Machine Learning-Assisted Network Inference (MALANI) algorithm, which assesses all genes regardless of expression or mutational status in the context of cancer etiology. We used 8807 expression arrays, corresponding to 9 cancer types, to build more than 2 × 108 Support Vector Machine (SVM) models for reconstructing a cancer network. We found that ~3% of ~19,000 not differentially expressed genes are Class II cancer gene candidates. Some Class II genes that we found, such as SLC19A1 and ATAD3B, have been recently reported to associate with cancer outcomes. To our knowledge, this is the first study that utilizes both machine learning and network biology approaches to uncover Class II cancer genes in coordinating functionality in cancer networks and will illuminate our understanding of how genes are modulated in a tissue-specific network contribute to tumorigenesis and therapy development.


Fission-track dating of haughton astrobleme and included biota, devon island, Canada.
Haughton Astrobleme is a major extraterrestrial impact structure located on Devon Island in the Canadian Arctic Archipelago, Northwest Territories. Apatite grains separated from shocked Precambrian gneiss contained in a polymict breccia from the center of the astrobleme yielded a fission-track date of 22.4 million +/- 1.4 million years before the present or early Miocene (Aquitanian). This provides a date for the impact event and an upper limit on the age of crater-filling lake sediments and a flora and vertebrate fauna occurring in them. A geologically precise date for these fossils provides an important biostratigraphic reference point for interpreting the biotic evolution of the Arctic.


An epidemic of silicosis among former denim sandblasters.
Sandblasting denim using silica has emerged as a new cause of silicosis in Turkey. Following the discovery of several cases of silicosis in (young) workers who used this process, the frequency and main occupational risk factors of silicosis among former denim sandblasters in the region of Erzurum (Turkey) were evaluated. Demographic characteristics and information on working conditions were obtained by questionnaire and interview. In addition, spirometry testing was performed and chest radiographs were evaluated according to International Labour Office (ILO) classification of pneumoconioses in 157 former denim sandblasters. All subjects were male, with a mean (range) age of 23 (15-44) yrs. They had worked for a mean (range) of 36 (1-120) months, starting employment at a 17 (10-38) yrs of age. Most subjects (83%) had respiratory symptoms, especially dyspnoea (52%) but also chest pain (46%). Radiological evidence of silicosis (ILO score 1/0 or higher) was present in 77 (53%) out of 145 subjects with interpretable chest radiographs. These subjects had lower forced expiratory volume in one second and forced vital capacity. The risk of silicosis correlated with seniority (i.e. working as a foreman), exposure duration and number of places of work. Considering the high prevalence rate of silicosis in such workplaces, further problems are inevitable in the future unless effective measures are taken.


Simulation on flow field and gas hold-up of a pilot-scale oxidation ditch by using liquid-gas CFD model.
A liquid-gas two-phase computational fluid dynamics (CFD) model was developed to simulate flow field and gas hold-up in a pilot-scale oxidation ditch (OD). The volume of fluid (VOF) model and the mass flow inlet boundary condition for gas injection were introduced in this model. The simulated values of the flow velocities and the gas hold-up were verified by experimental measurements in the pilot-scale OD. The results showed that the gas hold-up at test-site 3, immediately downstream of the surface aerator, was the highest among all three test-sites. Most of the gas existed in the upper portion of the ditch and was close to the inner side of the channel. Based on the liquid-gas two-phase CFD model, three operating conditions with different setting height ratios of the submerged impellers were simulated. The simulated results suggested that the setting heights of the submerged impellers have significant impacts on the flow velocity distribution. Lowering the setting height could increase the flow velocity in the pilot-scale OD. An optimal setting height ratio of 0.273 was proposed, which would be beneficial for minimizing sludge sedimentation, especially near the inner side of the curve bend.


Reduced ventricular proarrhythmic potential of the novel combined ion-channel blocker AZD1305 versus dofetilide in dogs with remodeled hearts.
AZD1305 is an investigational antiarrhythmic agent for management of atrial fibrillation. It blocks various cardiac ion currents at different potencies and has atrial-predominant electrophysiological effects. We investigated the electrophysiological and proarrhythmic effects of AZD1305 versus dofetilide in dogs with chronic complete atrioventricular block and myocardial hypertrophic remodeling. AZD1305 was administered to anesthetized mongrel dogs before and >2 weeks after the induction of atrioventricular block and ventricular and atrial electrophysiological parameters were assessed. In all dogs, the selective I(Kr) blocker dofetilide was used to examine susceptibility to acquired torsades de pointes in chronic atrioventricular block and for comparison. At normal sinus rhythm, AZD1305 increased QT and RR intervals from 290±7 to 397±15 ms (+37%, P<0.0001) and from 603±22 to 778±32 ms (+29%, P=0.002), respectively. In the same animals at chronic atrioventricular block, AZD1305 increased the QT interval from 535±28 to 747±36 ms (+40%, P<0.0001), similar to the QT prolongation by dofetilide (511±22 to 703±45 ms [+38%, P<0.0001]). AZD1305 slightly slowed the idioventricular rhythm. Whereas all (n=14) chronic atrioventricular block animals exhibited torsades de pointes on dofetilide, the arrhythmia was induced in only 4 of 11 dogs after AZD1305. Beat-to-beat variability of left-ventricular monophasic-action-potential duration increased after dofetilide (2.3±0.2 to 6.3±0.7 ms; P<0.0001) but not after AZD1305 (2.8±0.3 to 3.7±0.3 ms; P=0.20) despite similar left-ventricular monophasic-action-potential duration prolongations. Despite causing similar degrees of repolarization delay as the selective I(Kr) blocker dofetilide, the combined ion-channel blocker AZD1305 induces less repolarization instability and has a lower ventricular proarrhythmic potential in the remodeled dog heart.


The Limiting Dynamics of SGD: Modified Loss, Phase-Space Oscillations, and Anomalous Diffusion.
In this work, we explore the limiting dynamics of deep neural networks trained with stochastic gradient descent (SGD). As observed previously, long after performance has converged, networks continue to move through parameter space by a process of anomalous diffusion in which distance traveled grows as a power law in the number of gradient updates with a nontrivial exponent. We reveal an intricate interaction among the hyperparameters of optimization, the structure in the gradient noise, and the Hessian matrix at the end of training that explains this anomalous diffusion. To build this understanding, we first derive a continuous-time model for SGD with finite learning rates and batch sizes as an underdamped Langevin equation. We study this equation in the setting of linear regression, where we can derive exact, analytic expressions for the phase-space dynamics of the parameters and their instantaneous velocities from initialization to stationarity. Using the Fokker-Planck equation, we show that the key ingredient driving these dynamics is not the original training loss but rather the combination of a modified loss, which implicitly regularizes the velocity, and probability currents that cause oscillations in phase space. We identify qualitative and quantitative predictions of this theory in the dynamics of a ResNet-18 model trained on ImageNet. Through the lens of statistical physics, we uncover a mechanistic origin for the anomalous limiting dynamics of deep neural networks trained with SGD. Understanding the limiting dynamics of SGD, and its dependence on various important hyperparameters like batch size, learning rate, and momentum, can serve as a basis for future work that can turn these insights into algorithmic gains.


Aortic distensibility and arterial-ventricular coupling in early chronic kidney disease: a pattern resembling heart failure with preserved ejection fraction.
To examine arterial and left ventricular function and their interaction in patients with early-stage chronic kidney disease (CKD). Cross-sectional observational study in a university teaching hospital. 117 patients with stage 2 (60-89 ml/min/1.73 m(2)) or stage 3 (30-59 ml/min/1.73 m(2)) non-diabetic CKD, without overt cardiovascular disease were compared with 40 controls. Aortic distensibility and left ventricular mass were assessed using cardiac magnetic resonance imaging. Systolic and diastolic ventricular function and arterial-ventricular elastance (stiffness) were assessed by transthoracic echocardiography. Arterial stiffness as measured by aortic distensibility and arterial elastance. Left ventricular mass, left ventricular systolic and diastolic function, including end-diastolic and end-systolic elastance and their relationship with arterial elastance. Compared with controls, patients with CKD 2 and CKD 3 had reduced aortic distensibility (4.12 (1.3) vs 2.94 (1.8) vs 2.18 (1.8)x10(-3) mm Hg, p<0.01), increased arterial elastance (1.4 (1.3) vs 1.65 (0.40) vs 1.74 0.48) mm Hg, p<0.05) and increased end-systolic (1.88 (0.48) vs 2.43 (0.83) vs 2.42(0.78) mm Hg/ml, p<0.05) and end diastolic elastances (0.07 (0.04) vs 0.11 (0.04) vs 0.12 (0.04, p<0.01). Aortic distensibility was positively correlated with estimated glomerular filtration rate (r = 0.349, p<0.01) and indices of elastance were inversely correlated (r = 0.284, p<0.05). Systolic function was not impaired in patients with early CKD compared with controls but diastolic filling velocities (Em) were reduced (8.1 (0.9) vs 7.9 (0.6) vs 7.5 (0.7) cm/s, p<0.01) while mean left atrial pressure (E/Em) was increased (5.6 (1.1), vs 7.4 (1.8) vs 8.0 (2.4), p<0.01) and end-diastolic elastance was increased. Early-stage CKD is characterised by reduced aortic distensibility and increases in arterial, ventricular systolic and diastolic stiffness; arterial-ventricular coupling is preserved. This pattern of pathophysiological abnormalities resembles that seen in heart failure with preserved ejection fraction and may account for the high levels of cardiovascular morbidity and mortality in patients at all stages of CKD. NCT00291720.


5-aminolaevulinic acid-based photodynamic therapy inhibits ultraviolet B-induced skin photodamage.
To evaluate the photoprotective effect of 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT) on ultraviolet B (UVB)-induced skin photodamage. In vivo experiments, the dorsal skin of hairless mice were treated with ALA-PDT or saline-PDT, and then exposed to 180 mJ/m2 UVB. Results showed that the number of sunburn cells and apoptotic cells in the epidermis of ALA-PDT-treated groups at 24 h after UVB irradiation were significantly decreased compared with those in the UVB groups. And the removal rate of CPDs was obviously higher in ALA-PDT-treated groups. At 48 h, the number of Ki67 positive nuclei in ALA-PDT-UVB group was significantly fewer than that in UVB group. Further in vitro experiments, human keratinocyte cell line (HaCaT) cells of two groups (one treated with ALA-PDT, the other untreated), were exposed to 60 mJ/m2 UVB irradiation. We found 0.5 mmol/L of ALA and 3 J/cm2 of red light did not affect the vitality of cells, and could reduce UVB induced apoptosis, accelerate the clearance of CPDs, inhibit proliferation and activate p53. Thus, our data demonstrate that ALA-PDT pretreatment can induce a protective DNA damage response that protects skin cells from UVB-induced photodamages.


Communication and cultural interaction in health promotion strategies to migrant populations in Italy: the cross-cultural phone counselling experience.
In the last 10 years migration processes have progressively increased worldwide and in Italy about 5 millions of residing migrants are estimated. To meet health needs of these new residents, effective relational and communication tools, which allow a reciprocal intercultural interaction within health care structures, are therefore necessary. This article faces the main features of the relational-communication processes associated with health promotion and care in the migrant population in Italy to the aim of identifying the key and critical points within the interaction between different cultures, focusing on the role of specific professional figures, including cultural mediators and health educators. Within the activity of HIV phone counselling operated by Psycho-sociobehavioural, Communication and Training Operating Unit of National Institute of Health in Italy, an intercultural approach was successfully experienced in a project targeted to migrants (2007-2008). Specifically, the presence of cultural mediators answering in the languages of main migrants' groups allowed the increase of calls from migrant people and of the information provided.


[Screening of sera from the adult populations of some USSR regions for antibodies to the human T-cell leukemia virus type I (HTLV-I)].
The results of serologic survey of 4118 residents of the USSR Far East from 16 to 82 years of age and 1037 blood donors for antibody to HTLV-I by the method of passive agglutination of gelatin particles coated with viral proteins are summarized. The portion of HTLV-1 seropositive subjects in the Khabarovsk Territory was 1.79% (25 out of 1391), in the Maritime Territory 2.2% (18 out of 801), in the Sakhalin Island 1.6% (26 out of 1557), and in Kamchatka 1.6% (6 out of 369). A discrete area of a higher number of positive cases was found among Nivkhi national group in the village of Nogliki in the Sakhalin Island: 6.4% (10 out of 155). In women, antibody to HTLV-1 was found twice as frequently as in men. Seropositives to HTLV-1 among blood donors in Moscow, the town of Komsomol'sk-na-Amure, and the town of Yuzhno-Sakhalinsk comprised 1.4%, 1.6%, and 5.45%, respectively. The occurrence of HTLV-1 infection among the normal population of the Far East and especially among blood donors attests to the expedience of wider seroepidemiological surveys of the population and especially donors for HTLV-I infection in other regions of the USSR as well.


An open study of vitamin D3 treatment in psoriasis vulgaris.
Active forms of vitamin D3, 1 alpha-hydroxyvitamin D3 and 1 alpha,25-dihydroxyvitamin D3, were administered in an open-design study to 40 patients with psoriasis vulgaris in three ways: to 17 patients 1 alpha-hydroxyvitamin D3 was given orally at a dose of 1.0 micrograms/day for 6 months, to four patients 1 alpha,25-dihydroxyvitamin D3 was given orally at a dose of 0.5 microgram/day for 6 months, and 19 patients were given 1 alpha,25-dihydroxyvitamin D3 applied topically at concentration of 0.5 microgram/g of base for 8 weeks. Improvement was observed at the end of the individual study periods in 13 (76%) patients in Group 1 with a mean period of treatment (+/- SD) of 2.7 +/- 0.6 months, in one patient in Group 2 at 3 months after the start of treatment, and in 16 (84%) patients in Group 3 when the chemical was applied for 3.3 +/- 1.2 weeks. No side-effects were observed in any of these trials. These data suggest that psoriasis may respond to active metabolites of vitamin D3 and that abnormalities in vitamin D metabolism or in responsiveness of the skin cells to active metabolites of vitamin D may be involved in the pathogenesis of this skin disease.


The treatment of cerebral aneurysms. A report on 51 cases.
The treatment of 51 patients with proven cerebral aneurysms is reviewed. The management is discussed and the relative safety of the microneurosurgical operation is stressed.


A characterization of anxiolytic-like actions induced by the novel NMDA/glycine site antagonist, L-701,324.
The effects of the NMDA/glycine site antagonist, 7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(1H)-quinolone (L-701,324), and the benzodiazepine receptor agonist, diazepam, were examined in the elevated plus-maze and in the Vogel's conflict test. Oral administration of L-701,324 caused a dose-dependent increase (2.5 and 5.0 mg/kg, -30 min) in the percent time spent in the open arms with no change in the total number of arm entries or in the percent entries into the open arms of the plus-maze. The same doses of L-701,324 increased punished responding in the Vogel's conflict test in a dose-dependent fashion, with no influence on unpunished drinking behavior. The anxiolytic-like effects of L-701,324 were obtained at doses which by themselves had no influence on the locomotor activity of the animals. Diazepam (2 mg/kg, i.p., -30 min) was slightly more effective than L-701,324 in the plus-maze situation, whereas the increase in punished drinking in the Vogel's test was of the same magnitude for both compounds. Our present results suggest that inhibition of NMDA receptor activity via a blockade of the NMDA/glycine-sensitive site at the NMDA receptor is accompanied by a reduction of anxiety-like behavior in both non-conditioned and conditioned conflict behavior situations.


Alterations in cell membrane permeability by the lentivirus lytic peptide (LLP-1) of HIV-1 transmembrane protein.
Previously we reported that synthetic peptide homologs of an amphipathic region (designated the lentivirus lytic peptide, or LLP-1) near the carboxy terminus of HIV-1 transmembrane protein (TM) were toxic for both prokaryotic and eukaryotic cells when added exogenously to cell cultures. We postulated that these peptides may exert their toxic effects in much the same manner as natural cytolytic peptides such as magainins, cecropins, and melittin by forming pores through cellular membranes. Here we show the results of 51Cr-release assays and membrane flux measurements of peptide treated cells that support our hypothesis. We have also tested a limited panel of LLP-1 peptide analogs in these assays and found that relatively minor alterations in peptide charge or amphipathicity in the parent HIV LLP-1 sequence resulted in total loss of membrane perturbative properties. These results demonstrate that the peptide homolog of HIV-1 LLP-1 can indeed perturb membranes by forming pores of defined size in cytoplasmic membranes. Furthermore, the analog studies described here reveal that the amphipathy and high positive charge of this protein segment are required for the membrane perturbative properties.


Ethnicity, health and dental care--perspectives among British Asians: 1.
In some areas, Asian communities constitute a sizeable proportion of the population around a general dental practice, yet some have never been to a dentist in the whole of their lives. A significant number of others fail to visit a dentist regularly. This two-part article aims to clarify some of the issues relating to dental care of minority groups, with particular reference to Asian communities. An outline is given of some general and dental health issues which are of particular significance to dental practitioners, as they strive to provide continuous care to the whole population. Part 1 identifies dental health problems characteristic of British Asians, Part 2 will examine some of the barriers to care.


Allylation of intraerythrocytic hemoglobin by raw garlic extracts.
Recent studies have shown that deoxygenated human red blood cells (RBCs) converted garlic-derived polysulfides into hydrogen sulfide, which in turn produced vasorelaxation in aortic ring preparations. The vasoactivity was proposed to occur via glucose- and thiol-dependent acellular reactions. In the present study, we investigated the interaction of garlic extracts with human deoxygenated RBCs and its effect on intracellular hemoglobin molecules. The results showed that garlic extract covalently modified intraerythrocytic deoxygenated hemoglobin. The modification identified consisted of an addition of 71 atomic mass units, suggesting allylation of the cysteine residues. Consistently, purified human deoxyhemoglobin reacted with chemically pure diallyl disulfide, showing the same modification as garlic extracts. Tandem mass spectrometry analysis demonstrated that garlic extract and diallyl disulfide modified hemoglobin's beta-chain at cysteine-93 (beta-93C) or cysteine-112 (beta-112C). These results indicate that garlic-derived organic disulfides as well as pure diallyl disulfide must permeate the RBC membrane and modified deoxyhemoglobin at beta-93C or beta-112C. Although the physiological role of the reported garlic extract-induced allyl modification on human hemoglobin warrants further study, the results indicate that constituents of natural products, such as those from garlic extract, modify intracellular proteins.


The biphasic stimulation of insulin secretion by bombesin involves both cytosolic free calcium and protein kinase C.
Members of the bombesin family of peptides potently stimulate insulin release by HIT-T15 cells, a clonal pancreatic cell line. The response to bombesin consists of a large burst in secretion during the first 30 s, followed by a smaller elevation of the secretory rate, which persists for 90 min. The aim of this study was to identify the intracellular messengers involved in this biphasic secretory response. Addition of 100 nM-bombesin to cells for 20 s increased the cellular accumulation of [3H]diacylglycerol (DAG) by 40% and that of [3H]inositol monophosphate (InsP), bisphosphate (InsP2) and trisphosphate (InsP3) by 40%, 300%, and 800%, respectively. In contrast, cyclic AMP concentrations were unaffected. Bombesin stimulation of [3H]InsP3 formation was detected at 2 s, before the secretory response, which was not measurable until 5 s. Furthermore, the potency of bombesin to stimulate [3H]InsP3 generation (ED50 = 14 +/- 9 nM) agreed with its potency to stimulate insulin release (ED50 = 6 +/- 2 nM). Consistent with its effects on [3H]InsP3 formation, bombesin raised the intracellular free Ca2+ concentration [( Ca2+]i) from a basal value of 0.28 +/- 0.01 microM to a peak of 1.3 +/- 0.1 microM by 20 s. Chelation of extracellular Ca2+ did not abolish either the secretory response to bombesin or the rise in [Ca2+]i, showing that Ca2+ influx was not required. Although the Ca2+ ionophore ionomycin (100 nM) mimicked the [Ca2+]i response to bombesin, it did not stimulate secretion. However, pretreating cells with ionomycin decreased the effects of bombesin on both [Ca2+]i and insulin release, suggesting that elevation of [Ca2+]i was instrumental in the secretory response to this peptide. To determine the role of the DAG produced upon bombesin stimulation, we examined the effects of another activator of protein kinase C, the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). TPA did not affect [Ca2+]i, but it increased insulin secretion after a 2 min lag. However, an immediate increase in secretion was observed when ionomycin was added simultaneously with TPA. These data indicate that the initial secretory burst induced by bombesin results from the synergistic action of the high [Ca2+]i produced by InsP3 and DAG-activated protein kinase C. However, activation of protein kinase C alone appears to be sufficient for a sustained secretory response.


Brain magnetic resonance imaging structural changes in a pedigree of asymptomatic progranulin mutation carriers.
Mutations in the progranulin (PGRN) gene have been recently demonstrated as a cause of frontotemporal lobar degeneration (FTLD) with ubiquitin-immunoreactive neuronal inclusion (FTD-U). Neuropathologic, clinical, and neuroimaging features associated with PGRN mutations have been carefully described. No studies on asymptomatic subjects carrying pathogenetic PGRN mutations are available yet. These would be crucial for establishing the timing of brain changes and bringing new insight into disease pathogenesis and disease course. The aim of this study was to evaluate structural brain morphology using diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) in asymptomatic carriers of PGRN delCACT mutation belonging to a four-generation FTLD pedigree (mean age, 37.0 +/- 12.0). The evaluation of the family proband presenting with progressive nonfluent aphasia at 53 years of age, revealed left frontotemporal hypoperfusion and atrophy. VBM analysis of gray and white matter reductions revealed no differences between asymptomatic carriers (n = 7) and controls (n = 15), and between no-carriers (n = 10) and controls (p < 0.001). DTI analysis revealed a reduction in fractional anisotropy in healthy PGRN mutation carriers in the left uncinate fasciculus, connecting the orbito-frontal regions to the temporal pole, and in the left inferior occipitofrontal fasciculus, connecting the parieto-occipital cortex to the dorsolateral frontal cortex (p < 0.001). No significant difference in fractional anisotropy between no-carriers and controls was found. Our data indicate loss of white matter integrity as an early preclinical feature in familial FTD that might antedate the onset of specific neurologic features. Alteration of fiber tracts within the perisylvian language network might represent the early hallmark of subsequent aphasia onset. The study of other pedigrees of asymptomatic PGRN mutation carriers is warranted.


Genetic and biochemical factors affecting the induction of bacteriophage lambda by N-nitroso compounds.
As part of our effort to validate a biochemical (prophage) induction assay (BIA) as a screening test for carcinogens, we have tested more than 100 N-nitroso compounds. An enzyme, beta-galactosidase, is induced as an indirect consequence of DNA damage to the host, as part of the 'SOS' response. Besides the obvious practical importance of detecting this class of carcinogen, there is the question of the mechanism by which these compounds work. Mutagenesis by one compound, N-methyl-N'-nitro-N-nitrosoguanidine, is known to proceed by both SOS (recA)-dependent and SOS-independent pathways. Mispairing due to O6 alkylation of guanine is thought to be responsible for the SOS-independent pathway; however, there has been little consideration of recA-dependent functions, of which phage induction is one. Although nitrosamides could be detected as phage inducers in our assay, N-nitrosamines in the presence of rat liver 9 000 X g supernatant usually gave no response. We found that the use of several mutant strains, particularly a lexA mutant, in combination with hamster liver 9 000 X g supernatant, allowed us to detect most N-nitrosamines reasonably well, in either a spot test or a quantitative tube assay. Induction in a lexA strain was most unexpected, since this mutation usually diminishes the expression of SOS functions induced by ultra-violet light. Because the genetic and biochemical conditions that favour phage induction are different from those that favour mutagenesis, it seems likely that the lesions in DNA leading to the two biological end-points are different.


Controlled Fragmentation of Single Molecules with Atomic Force Microscopy by Employing Doubly Charged States.
By atom manipulation we performed on-surface chemical reactions of a single molecule on a multilayer insulating film using noncontact atomic force microscopy. The single-electron sensitivity of atomic force microscopy allows us to follow the addition of single electrons to the molecule and the investigation of the reaction products. By performing a novel strategy based on long-lived doubly charged states a single molecule is fragmented. The fragmentation can be reverted by again changing the charge state of the system, characterizing a reversible reaction. The experimental results in addition to density-functional theory provide insight into the charge states of the different products and reaction pathways. Similar molecular systems could be used as charge-transfer units and to induce reversible chemical reactions.


Pearls and pitfalls in diagnosis of ovarian torsion.
Ovarian torsion is defined as partial or complete rotation of the ovarian vascular pedicle and causes obstruction to venous outflow and arterial inflow. Ovarian torsion is usually associated with a cyst or tumor, which is typically benign; the most common is mature cystic teratoma. Ultrasonography (US) is the primary imaging modality for evaluation of ovarian torsion. US features of ovarian torsion include a unilateral enlarged ovary, uniform peripheral cystic structures, a coexistent mass within the affected ovary, free pelvic fluid, lack of arterial or venous flow, and a twisted vascular pedicle. The presence of flow at color Doppler imaging does not allow exclusion of torsion but instead suggests that the ovary may be viable, especially if flow is present centrally. Absence of flow in the twisted vascular pedicle may indicate that the ovary is not viable. The role of computed tomography (CT) has expanded, and it is increasingly used in evaluation of abdominal pain. Common CT features of ovarian torsion include an enlarged ovary, uterine deviation to the twisted side, smooth wall thickening of the twisted adnexal cystic mass, fallopian tube thickening, peripheral cystic structures, and ascites. Understanding the imaging appearance of ovarian torsion will lead to conservative, ovary-sparing treatment.


Using data mining to explore complex clinical decisions: A study of hospitalization after a suicide attempt.
Medical education is moving toward developing guidelines using the evidence-based approach; however, controlled data are missing for answering complex treatment decisions such as those made during suicide attempts. A new set of statistical techniques called data mining (or machine learning) is being used by different industries to explore complex databases and can be used to explore large clinical databases. The study goal was to reanalyze, using data mining techniques, a published study of which variables predicted psychiatrists' decisions to hospitalize in 509 suicide attempters over the age of 18 years who were assessed in the emergency department. Patients were recruited for the study between 1996 and 1998. Traditional multivariate statistics were compared with data mining techniques to determine variables predicting hospitalization. Five analyses done by psychiatric researchers using traditional statistical techniques classified 72% to 88% of patients correctly. The model developed by researchers with no psychiatric knowledge and employing data mining techniques used 5 variables (drug consumption during the attempt, relief that the attempt was not effective, lack of family support, being a housewife, and family history of suicide attempts) and classified 99% of patients correctly (99% sensitivity and 100% specificity). This reanalysis of a published study fundamentally tries to make the point that these new multivariate techniques, called data mining, can be used to study large clinical databases in psychiatry. Data mining techniques may be used to explore important treatment questions and outcomes in large clinical databases and to help develop guidelines for problems where controlled data are difficult to obtain. New opportunities for good clinical research may be developed by using data mining analyses.


Chylomicron catabolism differs between Hooded and albino laboratory rats.
To extend previous reports that some aspects of lipid metabolism are different between Hooded and albino strains of laboratory rats, thoracic duct lymph chylomicrons were collected and their composition and metabolism were compared in this study. Chylomicrons from Hooded rats had more core components and fewer surface components than albino rats. After adding 1% cholesterol to the diet the ratio of cholesterol:phospholipid was higher in Hooded rat chylomicrons. Nascent lymph chylomicrons from Hooded rats contained less apolipoprotein A-IV, but after incubation with serum there was a gain of apolipoprotein A-IV and a loss of A-I from both types of chylomicron. The ratio of apoC to apoE was higher in Hooded than in albino rats. The metabolism of injected chylomicrons was slower in Hooded rats. Twenty minutes after a single injection, only 1-3% of chylomicron triacylglycerol and 8-13% of chylomicron cholesteryl ester remained in the plasma of albino rats, compared with 6-12% of triacylglycerol and 30-33% of cholesteryl ester in Hooded rats. At 30 min in the Hooded rats, the uptake of injected chylomicron cholesterol into the liver was decreased whereas uptake into other tissues, notably adipose tissue and muscle, was increased. During the steady intravenous injection of chylomicrons from the same strain, the fractional clearance rate of chylomicron triaclyglycerol was about three-fold faster in albino rats than in Hooded rats, and the fractional clearance rate of chylomicron cholesteryl ester was 70% faster in albino rats. When chylomicrons were allowed to circulate for 30 min after injection into functionally hepatectomized rats, with or without heparin, the remnant formation and chemical composition were similar in Hooded and albino rats. Hence the deficiency in chylomicron metabolism in Hooded rats was not due to an absolute impairment in the formation of remnants by the action of lipoprotein lipase in peripheral tissues, although our findings were most likely accounted for by some relative impairment of remnant formation in the Hooded strain. The deficiency in chylomicron metabolism correlated with an increased cholesterolemic response in Hooded rats compared with albino rats when 1% cholesterol was added to the diet.-Jeffery, F., and T. G. Redgrave. Chylomicron catabolism differs between Hooded and albino laboratory rats.


Use of palivizumab in infants and young children with severe respiratory disease: a Delphi study.
To achieve a consensus of opinion among an expert group of pediatric pulmonologists regarding the appropriateness of the off-label use of palivizumab for some pediatric patients with severe respiratory diseases. A two-round modified Delphi technique was used. A 43-item self-administered questionnaire grouped into seven clinical scenarios was developed. Level of agreement for each statement was ranked on a 0-9 scale with 0 being total disagreement and 9 total agreement. Consensus was sought through the feedback of information and iteration. The final responses were evaluated for median and interquartile range to determine which questions the group had reached consensus about, either affirmatively or negatively. Consensus was obtained for 24/43 statements (55.81%), including use of palivizumab for prevention of respiratory syncytial virus (RSV) infection in children with severe respiratory involvement due to neuromuscular disease, congenital or acquired immunodeficiency, storage disease, cystic fibrosis, diseases involving impaired ciliary clearance, patients operated on esophageal atresia and/or tracheoesophageal fistula, diaphragmatic hernia, bronchopulmonary malformations, severe tracheomalacia, lung transplant recipients and patients in the waiting list for lung transplant, patients oxygen-dependent for severe interstitial pulmonary disease and patients with severe pulmonary hypertension. Consensus against the use of palivizumab as prevention of RSV infection was also achieved in almost all the recurrent wheezing/asthma attacks situations. A set of indication for off-label uses of palivizumab in pediatric pulmonology was developed in accordance with the degree of professional consensus on which they were based. The applicability of the present results to clinical practice should be evaluated individually and reviewed periodically in the light of new emerging evidence. Further studies are needed to add evidence to the most frequent and clinically oriented scenarios that have shown higher levels of uncertainty.


Androgen-induced oxidative stress in human LNCaP prostate cancer cells is associated with multiple mitochondrial modifications.
We investigated the role of androgen-induced oxidative stress in prostate cancer using the androgen-responsive LNCaP human prostate cancer cell line exposed to a 1-nM concentration of the synthetic androgen R1881 (which correlates with serum androgen levels). Such exposure, which decreases growth rate and increases oxidative stress in LNCaP cells, induced statistically significant mitochondrial changes. A 40% increase in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction, indicative of mitochondrial dehydrogenase activity, occurred 24 hr after androgen treatment. This change preceded 50-110% increases, 40-96 hr after R1881 exposure, in levels of cellular peroxides and hydroxyl radicals as measured by 2'7'-dicholorofluorescin diacetate (DCF) fluorescence. On the basis of electron microscopy measurements, R1881 treatment increased the area fraction of mitochondria per cell by approximately 100% at 72 hr. In agreement, mitochondrial mass at 96 hr, evaluated by the fluorescent dye nonyl acridine orange (NAO), was 80% higher in treated cells. R1881 exposure for 24 hr lowered the activities of electron transport system (ETS) complexes, I, II, and IV by 17-27% and ATP levels by 50%. The ETS inhibitors, rotenone and antimycin A, lowered androgen-induced DCF fluorescence readings to control levels thereby suggesting ETS involvement in androgen-induced oxidant production. Addition of alpha-tocopherol succinate abrogated R1881-induced elevations in MTT reduction. In sum, androgens may, directly or indirectly, contribute to oxidative stress in LNCaP cells by regulating mitochondrial number, activity, and oxidant production by mechanisms that are, at least in part, sensitive to an antioxidant.


Urinary excretion of amphetamine after termination of drug abuse.
Important issues in urinary drug testing are the variability between consecutive urine specimens, the duration of positive specimens after last intake, and the usefulness of creatinine concentration to correct for variability in urine concentration. These issues were addressed in the present study with amphetamine as the drug of abuse. Drug users who were starting their sentences in prison participated in the study. Urine specimens were collected 1 to 5 times per day. Screening was performed by EMIT d.a.u. (cutoff, 0.30 microgram/mL) and EMIT II (cutoff, 1.00 microgram/mL), and confirmation was performed with gas chromatography-mass spectrometry. Creatinine and pH were recorded. Amphetamine was demonstrated in seven subjects. The highest concentration was 135 micrograms/mL. The last positive-screened specimen was observed by EMIT d.a.u. after almost 9 days of imprisonment and by EMIT II after 3 days. Large concentration differences could be found between consecutive specimens, accompanied by considerable differences in creatinine and pH. The individual curves were generally smoother after creatinine correction of concentrations. As expected, urinary pH was observed to influence the excretion.


Cognitive impairment does not cause invalid performance: analyzing performance patterns among cognitively unimpaired, impaired, and noncredible participants across six performance validity tests.
Objective: Performance validity tests (PVTs) are essential in neuropsychological evaluations; however, it has been questioned how PVTs function in the context of cognitive impairment, and whether cognitive impairment alone is sufficient to cause PVT failure. Further, there is concern that some clinicians will disregard failed PVTs due to their perception that failures represent false-positive errors secondary to cognitive impairment. This study examined patterns associated with cognitively impaired versus noncredible performance across a battery of PVTs and neuropsychological tests. Additionally, the impact of VA service-connection and disability-seeking status on test validity was investigated. Method: A mixed-clinical sample of 103 veterans were administered six PVTs and neuropsychological tests. Performance was compared across three groups: valid-cognitively unimpaired, valid-cognitively impaired, and noncredible. Results: Significant PVT score differences and failure rates emerged across the three groups, with nonsignificant to small differences between valid-unimpaired and valid-impaired groups, and large differences between impaired and noncredible groups. In contrast, there were nonsignificant to small differences on neuropsychological tests between the valid-impaired and noncredible groups, indicating that impaired participants performed significantly better on PVTs despite comparable neurocognitive test scores. Service-connection rating itself was not associated with PVT failure, but an active disability claim to increase and/or establish service connection was associated with worse PVT performance. Conclusion: This study supports the use of multiple PVTs during evaluations of patients with varied cognitive abilities. Results indicated increased risk of PVT failure in patients who were seeking initiation/increase in service-connected payments, and shows that cognitive impairment does not cause PVT failure.


Management of selected patients with hyperprolactinaemia by partial hypophysectomy.
Results are reported in 35 patients with prolactinomas who underwent pituitary surgery within the past five years. After surgery prolactin concentrations became normal in 26 patients and symptoms were alleviated, and nine normal pregnancies were achieved in seven women, including all those who had complained of infertility. Normal prolactin concentrations were restored in 16 of 17 patients with tumours 5-19 mm in diameter but in only six of 11 with tumours less than or equal to 4 mm and four of seven with tumours greater than or equal to 20 mm. Normal prolactin concentrations were restored in all those with preoperative concentrations below 1000 mU/l but in none of those with concentrations above 10 000 mU/l. Although not all of the patients were followed up for five years, hyperprolactinaemia did not recur in any patient whose prolactin concentration had returned to normal six weeks after surgery. This included 16 patients with macroprolactinomas (greater than 10 mm in diameter), who were followed up for from two to five years. These data contrast strikingly with those reported by others at similar stages of follow up and show clearly that partial hypophysectomy offers an acceptable alternative treatment for selected patients with prolactinomas.


Immuno-genomic analysis reveals eosinophilic feature and favorable prognosis of female non-smoking esophageal squamous cell carcinomas.
Most of esophageal squamous cell carcinoma (ESCC) develop in smoking males in Japan, but the genomic etiology and immunological characteristics of rare non-smoking female ECSS remain unclear. To elucidate the genomic and immunological features of ESCC in non-smoking females, we analyzed whole-genome or transcriptome sequencing data from 94 ESCCs, including 20 rare non-smoking female cases. In addition, 31,611 immune cells were extracted from four ESCC tissues and subject to single-cell RNA-seq. We compared their immuno-genomic and microbiome profiles between non-smoking female and smoking ESCCs. Non-smoking females showed much better prognosis. Whole-genome sequencing analysis showed no significant differences in driver genes or copy number alterations depending on smoking status. The mutational signatures specifically observed in non-smoking females ESCC could be attributed to aging. Immune profiling from RNA-seq revealed that ESCC in non-smoking females had high tumor microenvironment signatures and a high abundance of eosinophils with a favorable prognosis. Single-cell RNA-sequencing of intratumor immune cells revealed gender differences of eosinophils and their activation in female cases. ESCCs in non-smoking females have age-related mutational signatures and gender-specific tumor immune environment with eosinophils, which is likely to contribute to their favorable prognosis.


Bacterial flagellar microhydrodynamics: Laminar flow over complex flagellar filaments, analog archimedean screws and cylinders, and its perturbations.
The flagellar filament, the bacterial organelle of motility, is the smallest rotary propeller known. It consists of 1), a basal body (part of which is the proton driven rotary motor), 2), a hook (universal joint-allowing for off-axial transmission of rotary motion), and 3), a filament (propeller-a long, rigid, supercoiled helical assembly allowing for the conversion of rotary motion into linear thrust). Helically perturbed (so-called "complex") filaments have a coarse surface composed of deep grooves and ridges following the three-start helical lines. These surface structures, reminiscent of a turbine or Archimedean screw, originate from symmetry reduction along the six-start helical lines due to dimerization of the flagellin monomers from which the filament self assembles. Using high-resolution electron microscopy and helical image reconstruction methods, we calculated three-dimensional density maps of the complex filament of Rhizobium lupini H13-3 and determined its surface pattern and boundaries. The helical symmetry of the filament allows viewing it as a stack of identical slices spaced axially and rotated by constant increments. Here we use the closed outlines of these slices to explore, in two dimensions, the hydrodynamic effect of the turbine-like boundaries of the flagellar filament. In particular, we try to determine if, and under what conditions, transitions from laminar to turbulent flow (or perturbations of the laminar flow) may occur on or near the surface of the bacterial propeller. To address these questions, we apply the boundary element method in a manner allowing the handling of convoluted boundaries. We tested the method on several simple, well-characterized cylindrical structures before applying it to real, highly convoluted biological surfaces and to simplified mechanical analogs. Our results indicate that under extreme structural and functional conditions, and at low Reynolds numbers, a deviation from laminar flow might occur on the flagellar surface. These transitions, and the conditions enabling them, may affect flagellar polymorphism and the formation and dispersion of flagellar bundles-factors important in the chemotactic response.


Open-source image reconstruction of super-resolution structured illumination microscopy data in ImageJ.
Super-resolved structured illumination microscopy (SR-SIM) is an important tool for fluorescence microscopy. SR-SIM microscopes perform multiple image acquisitions with varying illumination patterns, and reconstruct them to a super-resolved image. In its most frequent, linear implementation, SR-SIM doubles the spatial resolution. The reconstruction is performed numerically on the acquired wide-field image data, and thus relies on a software implementation of specific SR-SIM image reconstruction algorithms. We present fairSIM, an easy-to-use plugin that provides SR-SIM reconstructions for a wide range of SR-SIM platforms directly within ImageJ. For research groups developing their own implementations of super-resolution structured illumination microscopy, fairSIM takes away the hurdle of generating yet another implementation of the reconstruction algorithm. For users of commercial microscopes, it offers an additional, in-depth analysis option for their data independent of specific operating systems. As a modular, open-source solution, fairSIM can easily be adapted, automated and extended as the field of SR-SIM progresses.


Capacity planning for a different future.
As NHS waiting lists in England top three million,(1) the highest figure since waiting list 'targets' were created, estates teams have a key role to play in ensuring that infrastructure is best placed to meet demand. Working across Europe, operator of mobile healthcare facilities, Vanguard Healthcare Solutions, claims to have 'a unique insight' into the variety of estates policies and solutions being adopted by our European neighbors. Here Rob van Liefland, European representative, takes a look at the situation in Belgium and the Netherlands, and considers how the UK compares.


The v-rel oncogene encodes a cell-specific transcriptional activator of certain promoters.
Transformation by the v-rel oncogene of avian reticuloendotheliosis virus strain T (Rev-T) is primarily cell-specific. While v-rel efficiently transforms chicken spleen and bone marrow stem cells in vitro and induces rapid lethal lymphomas in young birds, it does not rapidly transform chicken embryo fibroblasts. The nuclear localization of the v-rel gene product in non-transformed fibroblasts along with its ability to function as a transforming protein in the nucleus of chicken spleen cells suggests that p59v-rel might belong to the family of nuclear oncoproteins and thus may express an immortalizing function in fibroblasts. To gain insight into the specificity of cell transformation by the v-rel oncogene, we determined whether v-rel could immortalize primary rat fibroblasts. Our experiments have shown that, unlike other nuclear oncoproteins, p59v-rel did not immortalize primary rat embryo fibroblasts. However p59v-rel was able to cooperate in a synergistic way with the polyomavirus middle T protein in inducing efficient transformation of established rat fibroblasts by increasing the steady-state level of middle T RNA, indicating that p59v-rel might function as a transactivator. Cotransfection of cells from different species with the v-rel gene along with constructs expressing the chloramphenicol acetyl transferase gene under the control of different promoters revealed that p59v-rel is a cell-specific transcriptional transactivator of certain promoters. Moreover, the extent of cell-specific transactivation by v-rel correlated with its toxic effect in these same cells.


Impact of human bocavirus on children and their families.
This study was planned to investigate the prevalence and clinical features of the illnesses associated with human bocavirus (hBoV) in children with acute disease. We prospectively enrolled all subjects aged less than 15 years attending an emergency room in Milan, Italy, on Wednesdays and Sundays between 1 November 2004 and 31 March 2005 for any acute medical reason, excluding surgical diseases and trauma. Nasopharyngeal swabs were collected at admission to detect hBoV; influenza A and B viruses; respiratory syncytial virus; human metapneumovirus; parainfluenza viruses 1, 2, 3, and 4; rhinovirus; adenovirus; and coronaviruses 229E, OC43, NL63, and HKU1 by real-time PCR. Among the 1,332 enrolled children, hBoV was the fifth most frequently detected virus (7.4%). The rate of hBoV coinfections with other viruses was significantly higher than for the other viruses (50.5% versus 27.5%; P < 0.0001). Eighty-nine of the 99 hBoV-positive children (89.9%) had a respiratory tract infection, and 10 (10.1%) had gastroenteritis. hBoV coinfections had a significantly greater clinical and socioeconomic impact on the infected children and their households than hBoV infection alone. In conclusion, these findings show that the role of hBoV infection alone seems marginal in children attending an emergency room for acute disease; its clinical and socioeconomic importance becomes relevant only when it is associated with other viruses.


Effects of Qi-therapy on blood pressure, pain and psychological symptoms in the elderly: a randomized controlled pilot trial.
Recently, we reported that Qi-therapy may be beneficial in reducing negative psychological symptoms and increasing melatonin levels, neutrophil function and natural killer cell cytotoxicity in young subjects. However, there is little scientific evidence of its efficacy in elderly subjects. Therefore, this study was designed to investigate the effects of Qi-therapy on anxiety, depression, fatigue, pain and blood pressure in elderly subjects. Ninety-four elderly subjects were randomly assigned to either Qi-therapy (n=47) or mimic therapy (n=47) groups. Both groups received a 10-min intervention period once using similar procedures. The Qi-therapy group exhibited greater reduction in anxiety, depression, fatigue, pain level and blood pressure compared to the placebo group; the difference in anxiety was significant (P=0.014). These results suggest that even a brief application of Qi-therapy may exert a positive psychological and physiological effect. However, further research is necessary in order to fully understand the long-term impact of Qi-therapy on psychological health and the cardiovascular system.


Distinction of endocervical and endometrial adenocarcinomas: immunohistochemical p16 expression correlated with human papillomavirus (HPV) DNA detection.
Determining the origin of uterine adenocarcinomas can be difficult in biopsy and curettage specimens because the morphologic spectrum of endocervical and endometrial adenocarcinomas overlaps. In hysterectomy specimens, the primary site is often equivocal for tumors that involve the lower uterine segment and endocervix and lack identifiable precursor lesions. Most endocervical adenocarcinomas (ECAs) contain high-risk human papillomavirus (HPV) DNA, whereas endometrial adenocarcinomas (EMAs) rarely do. p16 is an inhibitor ofcyclin-dependent kinases, and overexpression of p16 has been observed in cervical intraepithelial lesions and invasive carcinomas associated with high-risk HPV types. We evaluated the utility of immunohistochemistry for p16 in the distinction of ECAs and EMAs. p16 expression was assessed in 24 unequivocal EMAs and 19 unequivocal ECAs and correlated with HPV DNA detection by in situ hybridization and polymerase chain reaction. These assays were then used to assist in the classification of four lower uterine segment/upper endocervical adenocarcinomas (LUS/EC-A) of equivocal origin. p16 expression was moderate-strong and diffuse in 18 ECAs (median 90% of tumor cells positive, range 90%-100%), and weak and diffuse in one. Fourteen of these were positive for HPV DNA, whereas 5 lacked detectable HPV DNA by in situ hybridization; one of these 5 was positive by polymerase chain reaction. In contrast, EMAs displayed weaker staining with patchy distribution (median 30% of tumor cells positive, range 5%-70%) and none contained HPV DNA by in situ hybridization. Two LUS/EC-As, which were positive for HPV, exhibited strong, diffuse p16 expression, consistent with endocervical origin of the tumors. The remaining 2 LUS/EC-As showed patchy p16 staining and did not contain detectable HPV DNA, consistent with the endometrial origin of the tumors. The p16 expression pattern can distinguish ECAs from EMAs. Compared with HPV DNA detection by in situ hybridization, p16 immunohistochemistry appears to be a more sensitive and easier to perform method for distinguishing ECAs from EMAs, can be used to assist in the classification of LUS/EC-As of equivocal origin, and should be evaluated for its utility in the prospective classification of uterine adenocarcinomas in curettage specimens prior to hysterectomy.


The Discodermia calyx toxin calyculin a enhances cyclin D1 phosphorylation and degradation, and arrests cell cycle progression in human breast cancer cells.
Cyclin D1 is a key regulator of the cell cycle that is over expressed in more than half of breast cancer patients. The levels of cyclin D1 are controlled primarily through post-translational mechanisms and phosphorylation of cyclin D1 at T286 induces its proteasomal degradation. To date, no studies have explored the involvement of phosphatases in this process. Here we treated human breast cancer cells with the structurally distinct toxins calyculin A, okadaic acid, and cantharidin, which are known to inhibit Ser/Thr phosphatases of the PPP family. At low nanomolar concentrations calyculin A induced T286 phosphorylation and degradation of cyclin D1 via the proteosome in MDA-MB-468 and MDA-MB-231 cells. Cyclin D1 degradation also was dose-dependently induced by okadaic acid and catharidin, implicating a negative regulatory role for type-2A phosphatases. These effects occurred without increasing phosphorylation of p70S6K, cyclin D3, or myosin light chain that were used as endogenous reporters of cellular PP2A and PP1 activity. A reverse phase phosphoprotein array analysis revealed increased phosphorylation of only 6 out of 33 Ser/Thr phosphosites, indicating selective inhibition of phosphatases by calyculin A. Calyculin A treatment induced cell cycle arrest in MDA-MB-468 and MCF-7 breast cancer cells. These findings suggest that a specific pool of type-2A phosphatase is inhibited by calyculin A leading to the degradation of cyclin D1 in human breast cancer cells. The results highlight the utility of toxins as pharmacological probes and points to the T286 cyclin D1 phosphatase inhibited by calyculin A as a possible target for chemotherapy to treat triple negative breast cancer.


Multiple fusiform cerebral aneurysms - case report.
A true aneurysym is a dilation of arterial lumen as a consequence of congenital or acquired abnormalities leading to a reduction of mechanical resistance of vascular wall, most commonly caused by its defected structure in the form of absence or weakening of the muscular and/or elastic layer. From the pathophysiological point of view, cerebral aneurysms can be classified as 'saccular' - most commonly occurring, and 'other types', including fusiform/dolichoectatic, dissecting, serpentine, posttraumatic, mycotic and giant aneurysms with or without intra-aneurysmal thrombosis. We present a rare case of a patient with multiple fusiform dilations of cerebral vessels and giant fusiform aneurysm in supraclinoid segment of the internal carotid artery. The patient presented to hospital because of sudden, severe vertigo with nausea, impaired balance and disturbed vision. Vascular anomalies were detected on CT scanning without contrast. The diagnostic work-up was complemented by CT angiography, MRI and cerebral angiography. Aneurysm located within the intracranial arteries is one of the most common vascular defects of the brain. The number, size and location of aneurysms are highly variable. Aneurysms can have either supra- or infratentorial location, affecting a single or multiple arteries within one or both brain hemispheres. There is often a correlation between the location of the aneurysm and its etiology, as in case of so-called mirror-image aneurysms. Symmetrically located aneurysms may indicate a defect in vascular structure. Asymmetric location, as in the patient described above, is more likely due to acquired causes, mainly atherosclerosis, but also septic emboli or blood disorders.


Ab initio computation for solid-state 31P NMR of inorganic phosphates: revisiting X-ray structures.
The complete 31P NMR chemical shift tensors for 22 inorganic phosphates obtained from ab initio computation are found to correspond closely to experimentally obtained parameters. Further improvement was found when structures determined by diffraction were geometry optimized. Besides aiding in spectral assignment, the cases where correspondence is significantly improved upon geometry optimization point to the crystal structures requiring correction.


Compliance with guidelines for management of dental school patients susceptible to infective endocarditis.
The purpose of the investigation was to determine the extent to which the 1984 American Heart Association prophylaxis guidelines were adopted in a sample of dental school patients and to determine whether implementation strategies resulted in change in the management of patients at risk for infective endocarditis (IE). Dental records of 330 patients requiring medical consultation on the basis of a heart problem identified in the medical history questionnaire were reviewed. One hundred fifty-four patients required IE prophylaxis according to their physicians. Only 11 percent of IE-susceptible patient charts showed documentation of correct prophylaxis for every appointment at which a bacteremia was possible. Only 35 percent of patients receiving prophylaxis after December 1984 were covered according to the new American Heart Association guidelines.


Online measures of looking and learning in infancy.
Infants in laboratory settings look longer at events that violate their expectations, learn better about objects that behave unexpectedly, and match utterances to the objects that likely elicited them. The paradigms revealing these behaviors have become cornerstones of research on preverbal cognition. However, little is known about whether these canonical behaviors are observed outside laboratory settings. Here, we describe a series of online protocols that replicate classic laboratory findings, detailing our methods throughout. In Experiment 1a, 15-month-old infants (N = 24) looked longer at an online support event culminating in an Unexpected outcome (i.e., appearing to defy gravity) than an Expected outcome. Infants did not, however, show the same success with an online solidity event. In Experiment 1b, 15-month-old infants (N = 24) showed surprise-induced learning following online events-they were better able to learn a novel object's label when the object had behaved unexpectedly compared to when it behaved expectedly. Finally, in Experiment 2, 16-month-old infants (N = 20) who heard a valenced utterance ("Yum!") showed preferential looking to the object most likely to have generated that utterance. Together, these results suggest that, with some adjustments, online testing is a feasible and promising approach for infant cognition research.


[Complex intensive care for acute gastroduodenal hemorrhages in patients after operations on the heart and vessels].
The purpose of the study was to define the most effective principles of intensive care for acute gastroduodenal hemorrhages in patients undergoing operations on the heart and vessels. The outcomes of 13,345 operations on the heart and vessels, performed at the A. N. Bakulev Research Center of Cardiovascular Surgery, Russian Academy of Medical Sciences, were analyzed. Gastroduodenal hemorrhages were diagnosed in 114 patients, which amounted to 0.8% of the total number of operated patients. In the vast majority (86.8%) patients, gastroduodenal hemorrhages occurred after surgery under extracorporeal circulation. The results of medical and surgical treatment were analyzed. The medical treatment for gastroduodenal hemorrhages included intensive drug therapy and endoscopic hemostasis. The comprehensive and intensive approach to performing antiulcer therapy (concomitant use of the antisecretory agents: proton pump inhibitors, gastric protectors, and reparative agents) could reduce the incidence of recurrent bleeding and the timing of epithelization of gastrointestinal mucosal defects. Analyzing the results of the treatments has indicated that the efficiency of conservative measures significantly exceeds the beneficial effect of the treatment of gastroduodenal bleedings, including urgent abdominal surgical interventions. Emergency surgical interventions for gastroduodenal hemorrhages in cardiosurgical patients deteriorate the postoperative period and lead to an increase in postoperative morbidity, which determines the expediency of their performance only when conservative measures are ineffective. An algorithm of tactical actions has been developed for gastroduodenal hemorrhages occurring after operations on the heart and vessels.


Community curation of bioinformatics software and data resources.
The corpus of bioinformatics resources is huge and expanding rapidly, presenting life scientists with a growing challenge in selecting tools that fit the desired purpose. To address this, the European Infrastructure for Biological Information is supporting a systematic approach towards a comprehensive registry of tools and databases for all domains of bioinformatics, provided under a single portal (https://bio.tools). We describe here the practical means by which scientific communities, including individual developers and projects, through major service providers and research infrastructures, can describe their own bioinformatics resources and share these via bio.tools.


Plastic changes underlying vestibular compensation in the guinea-pig persist in isolated, in vitro whole brain preparations.
Vestibular compensation for the postural and oculomotor deficits induced by unilateral labyrinthectomy is a model of post-lesional plasticity in the central nervous system. Just after the removal of one labyrinth, the deafferented, ipsilateral vestibular nucleus neurons are almost silent, and the discharge of the contralateral vestibular nucleus neurons is increased. The associated static disorders disappear in a few days, as normal activity is restored in both vestibular nuclei. In this study, we searched for traces of vestibular compensation in isolated whole brains taken from adult guinea-pigs. The electrophysiological responses evoked in control brains were compared to those evoked in brains taken from animals that had previously been labyrinthectomized. Guinea-pigs compensated for an initial labyrinthectomy within three days. In vivo, subsequent deafferentation of vestibular nucleus neurons on the intact side triggered "Bechterew's phenomenon": a new postural and oculomotor syndrome appeared, similar to the one induced by the first lesion, but directed to the newly deafferented side. These disturbances would be caused by the new imbalance between the discharges of neurons in the two vestibular nuclei triggered by the second deafferentation. Experiments were designed to search for a similar imbalance in vitro in brains taken from labyrinthectomized animals, where the intact vestibular nerve is cut during the dissection. Isolated whole brains were obtained from young guinea-pigs at various times (one to seven days) following an initial labyrinthectomy. An imbalance between the resting activities of medial vestibular nucleus neurons on both sides of the brainstem was revealed in brains taken more than three days after the lesion: their discharge was higher on the compensated, initially lesioned side than on the newly deafferented side. In some cases, an oscillatory pattern of discharge, reminiscent of the spontaneous nystagmus associated in vivo with Bechterew's syndrome, appeared in both abducens nerves. These data demonstrate that most of the changes underlying vestibular compensation persist, and can thus be investigated in the isolated whole brain preparation. Brains removed only one day after the lesion displayed normal commissural responses and symmetric spinal inputs to vestibular nucleus neurons. However, an unusually large proportion of the neurons recorded on both sides of the preparation had very irregular spontaneous discharge rates. These data suggest that the first stages of vestibular compensation might be associated with transient changes in the membrane properties of vestibular nucleus neurons. Brains taken from compensated animals displayed a significant, bilateral decrease of the inhibitory commissural responses evoked in the medial vestibular nucleus by single-shock stimulation of the contralateral vestibular nerve. The sensitivity of abducens motoneurons on the initially lesioned, compensated side to synaptic activation from the contralesional vestibular nucleus neurons was also decreased. Both changes may explain the long-term, bilateral decrease of vestibular-related reflexes observed following unilateral labyrinthectomy. Spinal inputs to vestibular nucleus neurons became progressively asymmetric: their efficacy was increased on the lesioned side and decreased on the intact one. This last modification may support a functional substitution of the deficient, vestibular-related synergies involved in gaze and posture stabilization by neck-related reflexes.


Comparison of trimethoprim-sulfamethoxazole, cephadroxil and cefprozil as prophylaxis for recurrent urinary tract infections in children.
The aim of this study was to compare the efficacy of prophylactic trimethoprim-sulfamethoxazole (TMP/SMZ), cefprozil and cephadroxil treatments in children who have recurrent urinary tract infection, but no urinary tract pathology. After acute urinary tract infections (UTIs) were treated, the patients were divided into 3 groups randomly and TMP/SMZ was given to 21 patients, cephadroxil was given to 25 patients and cefprozil was given to 34 patients for 3 months--one dose at night. All patients were followed for 6 months following prophylaxis. The frequency of symptomatic UTIs among groups during prophylaxis was not statistically different, however the number of symptomatic UTIs in the cephadroxil group was lower than the other groups. Asymptomatic bacteriuria episodes were detected in TMP/SMZ and cefprozil groups, whereas no asymptomatic bacteriuria episodes were seen in the cephadroxil group. The number of patients with symptomatic UTI during the follow-up period was not different between groups, however all the asymptomatic bacteriuria episodes were encountered in the cefprozil group. In conclusion, in this study cephadroxil was found to be slightly superior to TMP/SMZ and cefprozil in preventing asymptomatic bacteriuria episodes and symptomatic UTIs in children with recurrent UTI and normal urinary tract system.


Corrigendum to: Metabolomic characterisation of the functional division of nitrogen metabolism in variegated leaves.
Many horticultural and natural plant species have variegated leaves, that is, patchy leaves with green and non-green or white areas. Specific studies on the metabolism of variegated leaves are scarce and although white (non-green) areas have been assumed to play the role of a 'nitrogen store', there is no specific studies showing the analysis of nitrogenous metabolites and the dynamics of nitrogen assimilation. Here, we examined the metabolism of variegated leaves of Pelargonium × hortorum. We show that white areas have a larger N : C ratio, more amino acids, with a clear accumulation of arginine. Metabolomic analyses revealed clear differences in the chemical composition, suggesting contrasted metabolic commitments such as an enhancement of alkaloid biosynthesis in white areas. Using isotopic labelling followed by nuclear magnetic resonance or liquid chromatography/mass spectrometry, we further showed that in addition to glutamine, tyrosine and tryptophan, N metabolism forms ornithine in green area and huge amounts of arginine in white areas. Fine isotopic measurements with isotope ratio mass spectrometry indicated that white and green areas exchange nitrogenous molecules but nitrogen export from green areas is quantitatively much more important. The biological significance of the metabolic exchange between leaf areas is briefly discussed.


Serglycin as a potential biomarker for glioma: association of serglycin expression, extent of mast cell recruitment and glioblastoma progression.
Serglycin is an intracellular proteoglycan with a unique ability to adopt highly divergent structures by glycosylation with variable types of glycosaminoglycans (GAGs) when expressed by different cell types. Serglycin is overexpressed in aggressive cancers suggesting its protumorigenic role. In this study, we explored the expression of serglycin in human glioma and its correlation with survival and immune cell infiltration. We demonstrate that serglycin is expressed in glioma and that increased expression predicts poor survival of patients. Analysis of serglycin expression in a large cohort of low- and high-grade human glioma samples reveals that its expression is grade dependent and is positively correlated with mast cell (MC) infiltration. Moreover, serglycin expression in patient-derived glioma cells is significantly increased upon MC co-culture. This is also accompanied by increased expression of CXCL12, CXCL10, as well as markers of cancer progression, including CD44, ZEB1 and vimentin.In conclusion, these findings indicate the importance of infiltrating MCs in glioma by modulating signaling cascades involving serglycin, CD44 and ZEB1. The present investigation reveals serglycin as a potential prognostic marker for glioma and demonstrates an association with the extent of MC recruitment and glioma progression, uncovering potential future therapeutic opportunities for patients.


Regenerating descending axons preferentially reroute to the gray matter in the presence of a general macrophage/microglial reaction caudal to a spinal transection in adult zebrafish.
We analyzed pathway choices of regenerating, mostly supraspinal, descending axons in the spinal cord of adult zebrafish and the cellular changes in the spinal cord caudal to a lesion site after complete spinal transection. Anterograde tracing (by application of the tracer rostral to the spinal lesion site) showed that significantly more descending axons (74%) regenerated in the spinal gray matter of the caudal spinal cord than would be expected from random growth. Retrograde tracing (by application of the tracer caudal to the spinal lesion site) showed that, rostral to the lesion, most of these axons (80%) extended into the major white matter tracts. Thus, ventral descending tracts often were devoid of labeled axons caudal to a spinal lesion but contained many axons rostral to the lesion in the same animals, indicating a pathway switch of descending axons from the white matter to the gray matter. Ascending axons of spinal neurons were not observed regrowing to the rostral tracer application site; therefore, they most likely did not contribute to the axonal populations analyzed. A macrophage/microglia response within 2 days of spinal cord transection, along with phagocytosis of myelin, was observed caudal to the transection by immunohistochemistry and electron microscopy. Nevertheless, caudal to the lesion, descending tracts in the white matter were filled with myelin debris during the time of axonal regrowth, at least up to 6 weeks postlesion. We suggest that the spontaneous regeneration of axons of supraspinal origin after spinal cord transection in adult zebrafish may be due in part to the axons' ability to negotiate novel pathways in the spinal cord gray matter.


Sufficient statistics as a generalization of binning in spectral X-ray imaging.
It is well known that the energy dependence of X-ray attenuation can be used to characterize materials. Yet, even with energy discriminating photon counting X-ray detectors, it is still unclear how to best form energy dependent measurements for spectral imaging. Common ideas include binning photon counts based on their energies and detectors with both photon counting and energy integrating electronics. These approaches can be generalized to energy weighted measurements, which we prove can form a sufficient statistic for spectral X-ray imaging if the weights used, which we term μ-weights, are basis attenuation functions that can also be used for material decomposition. To study the performance of these different methods, we evaluate the Cramér-Rao lower bound (CRLB) of material estimates in the presence of quantum noise. We found that the choice of binning and weighting schemes can greatly affect the performance of material decomposition. Even with optimized thresholds, binning condenses information but incurs penalties to decomposition precision and is not robust to changes in the source spectrum or object size, although this can be mitigated by adding more bins or removing photons of certain energies from the spectrum. On the other hand, because μ-weighted measurements form a sufficient statistic for spectral imaging, the CRLB of the material decomposition estimates is identical to the quantum noise limited performance of a system with complete energy information of all photons. Finally, we show that μ-weights lead to increased conspicuity over other methods in a simulated calcium contrast experiment.


Inhibition of Manual Movements at Speech Arrest Sites in the Posterior Inferior Frontal Lobe.
Intraoperative stimulation of the posterior inferior frontal lobe (IFL) induces speech arrest, which is often interpreted as demonstration of essential language function. However, prior reports have described "negative motor areas" in the IFL, sites where stimulation halts ongoing limb motor activity. To investigate the spatial and functional relationship between IFL speech arrest areas and negative motor areas (NMAs). In this retrospective cohort study, intraoperative stimulation mapping was performed to localize speech and motor function, as well as arrest of hand movement, hand posture, and guitar playing in a set of patients undergoing awake craniotomy for dominant hemisphere pathologies. The incidence and localization of speech arrest and motor inhibition was analyzed. Eleven patients underwent intraoperative localization of speech arrest sites and inhibitory motor areas. A total of 17 speech arrest sites were identified in the dominant frontal lobe, and, of these, 5 sites (29.4%) were also identified as NMAs. Speech arrest and arrest of guitar playing was also evoked by a single IFL site in 1 subject. Inferior frontal gyrus speech arrest sites do not function solely in speech production. These findings provide further evidence for the complexity of language organization, and suggest the need for refined mapping strategies that discern between language-specific sites and inhibitory motor areas.