A prospective randomized study of bovine carotid artery biologic graft and expanded polytetrafluoroethylene for permanent hemodialysis access.
Arteriovenous grafts (AVGs) remain reliable substitutes for permanent hemodialysis access in scenarios that preclude the placement of native arteriovenous fistulas (AVFs). The majority of AVGs are constructed of expanded polytetrafluoroethylene (ePTFE), which is relatively inexpensive and readily available, but synthetic AVGs have poor patency rates. On the other hand, biologic grafts confer an advantage by virtue of their inherent similarity to the native human vasculature. However, evidence to support the current preference of synthetic conduits over biologic grafts in clinical practice is scarce. The aim of this protocol is to propose a contemporary re-evaluation and comparison between ePTFE and bovine carotid artery (BCA) grafts. This prospective randomized controlled trial is being conducted at an academic hospital center. A total of 100 patients at least 18 years of age and undergoing AVG placement will be recruited and prospectively randomized into two parallel groups with a 1:1 allocation ratio. Patients eligible to receive AVF and those with a known allergic reaction or history of intolerance to any ePTFE or BCA component will not be included in the study. Moreover, patients with a recent active infection at the site of previous AVG placement and patients with a bleeding disorder, an active malignant disease, or a life expectancy <1 year or who refuse blood transfusion and pregnant women will be excluded. Patients will receive either BCA (experimental) or standard ePTFE grafts (control) in compliance with the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines for AVG creation. Primary end points include primary, primary assisted, secondary, and functional patency at 1 year and 2 years after graft placement. Secondary outcomes include complications (pseudoaneurysms, infections, and steal syndrome) and reintervention rates during the first and second postoperative years. Outcomes will be assessed and documented every 6 months. Once the study is completed, analysis of the data will be performed using univariate methods, and Kaplan-Meier and multivariate Cox proportional regression analyses will be employed to evaluate and to compare outcomes between BCA and ePTFE over time. The creation of a functional and durable dialysis vascular access is crucial in the treatment of patients with end-stage renal disease and is a challenging quest for vascular surgeons. The proposed study compares the outcomes of synthetic and biologic AVG options in patients who are poor candidates for a native AVF. This will help derive contemporary evidence and improve the care of vascular access patients.


Effect of crocetin from Gardenia jasminoides Ellis on sleep: a pilot study.
Crocetin is a pharmacologically active carotenoid compound of Gardenia jasminoides Ellis used as a traditional herbal medicine and natural colorant. The present pilot study investigated the effect of crocetin on sleep. The clinical trial comprised a double-blind, placebo-controlled, crossover trial of 21 healthy adult men with a mild sleep complaint. It included two intervention periods of 2 weeks each, separated by a 2-week washout period. We measured objective sleep quality using an actigraph, and assessed the subjective symptoms using St Mary's Hospital Sleep Questionnaire. Actigraph data showed that after administration of crocetin, the number of wakening episodes was reduced compared to that of the placebo (p=0.025). Subjective data from St Mary's Hospital Sleep Questionnaire showed that crocetin tended to improve the quality of sleep compared to sleep before its intake. Additionally, no side effects from crocetin intake were observed. The results suggest that crocetin may contribute to improving the quality of sleep.


[Determination of the catalytic activity of lipase by the continuous titration method].
Development of a standardized procedure for the titrimetric assay of lipase has been suggested. Comparative studies with triolein und olive oil were therefore undertaken. Optimal conditions, such as pH, substrate and glycocholate concentrations, etc. were determined for the assay with triolein. The results agree with those obtained earlier with olive oil as substrate. Experience with the quality of various reagents used since 1966 is reported. Problems of methodology are then discussed, especially the incomplete characterization and purity of the bile acid preparations, and their effects on the test conditions. A critical analysis shows that two point tests with modifications of the continuous titration cannot give reliable results. Haemolysis and its effect on catalytic activity of lipase are used to illustrate the consequences of the uncritical acceptance of data from the literature. Furthermore, the required sensitivity of the analytical equipment, operational errors, and the uncritical evaluation and interpretation of analytical data are discussed. The first experiments to be performed with the addition of colipase are described, and the question of whether this cofactor should be used routinely for test purposes is considered. The problem of whether lipoproteinlipase can be quantitatively inhibited is discussed. In view of the outlay on apparatus and the time required for the assay, continuous titration is definitely not suitable for routine screening purposes. On the other hand, simpler methods that give reproducible quantitative results have not yet been developed.


Single transcranial direct current stimulation in schizophrenia: Randomized, cross-over study of neurocognition, social cognition, ERPs, and side effects.
Over the last decades, the treatment of schizophrenia has shifted fundamentally from a focus on symptom reduction to a focus on recovery and improving aspects of functioning. In this study, we examined the effect of transcranial direct current stimulation (tDCS) on social cognitive and nonsocial neurocognitive functions, as well as on electroencephalogram (EEG) measures, in individuals with schizophrenia. Thirty-seven individuals with schizophrenia were administered one of three different tDCS conditions (cathodal, anodal, and sham) per visit over the course of three visits, with approximately one week between each visit. Order of conditions was randomized and counterbalanced across subjects. For the active conditions, the electrode was placed over the left dorsolateral prefrontal cortex with the reference electrode over right supraorbital cortex. Current intensity was 2 mA and was maintained for two 20-minute sessions, with a one hour break between the sessions. Assessments were conducted immediately following each session, in a counterbalanced order of administration. No systematic effects were found across the social and nonsocial cognitive domains, and no significant effects were detected on event-related potentials (ERPs). The very small effect sizes, further validated by post-hoc power analyses (large Critical Ns), demonstrated that these findings were not due to lack of statistical power. Except for mild local discomfort, no significant side effects were reported. Findings demonstrate the safety and ease of administration of this procedure, but suggest that a single dose of tDCS over these areas does not yield a therapeutic effect on cognition in schizophrenia. ClinicalTrials.gov NCT02539797.


Atomoxetine improved attention in children and adolescents with attention-deficit/hyperactivity disorder and dyslexia in a 16 week, acute, randomized, double-blind trial.
The purpose of this study was to evaluate atomoxetine treatment effects in attention-deficit/hyperactivity disorder (ADHD-only), attention-deficit/hyperactivity disorder with comorbid dyslexia (ADHD+D), or dyslexia only on ADHD core symptoms and on sluggish cognitive tempo (SCT), working memory, life performance, and self-concept. Children and adolescents (10-16 years of age) with ADHD+D (n=124), dyslexia-only (n=58), or ADHD-only (n=27) received atomoxetine (1.0-1.4 mg/kg/day) or placebo (ADHD-only subjects received atomoxetine) in a 16 week, acute, randomized, double-blind trial with a 16 week, open-label extension phase (atomoxetine treatment only). Changes from baseline were assessed to weeks 16 and 32 in ADHD Rating Scale-IV-Parent-Version:Investigator-Administered and Scored (ADHDRS-IV-Parent:Inv); ADHD Rating Scale-IV-Teacher-Version (ADHDRS-IV-Teacher-Version); Life Participation Scale-Child- or Parent-Rated Version (LPS); Kiddie-Sluggish Cognitive Tempo (K-SCT) Interview; Multidimensional Self Concept Scale (MSCS); and Working Memory Test Battery for Children (WMTB-C). At week 16, atomoxetine treatment resulted in significant (p<0.05) improvement from baseline in subjects with ADHD+D versus placebo on ADHDRS-IV-Parent:Inv Total (primary outcome) and subscales, ADHDRS-IV-Teacher-Version Inattentive subscale, K-SCT Interview Parent and Teacher subscales, and WMTB-C Central Executive component scores; in subjects with Dyslexia-only, atomoxetine versus placebo significantly improved K-SCT Youth subscale scores from baseline. At Week 32, atomoxetine-treated ADHD+D subjects significantly improved from baseline on all measures except MSCS Family subscale and WMTB-C Central Executive and Visuo-spatial Sketchpad component scores. The atomoxetine-treated dyslexia-only subjects significantly improved from baseline to week 32 on ADHDRS-IV-Parent:Inv Inattentive subscale, K-SCT Parent and Teacher subscales, and WMTB-C Phonological Loop and Central Executive component scores. The atomoxetine-treated ADHD-only subjects significantly improved from baseline to Week 32 on ADHDRS-Parent:Inv Total and subscales, ADHDRS-IV-Teacher-Version Hyperactive/Impulsive subscale, LPS Self-Control and Total, all K-SCT subscales, and MSCS Academic and Competence subscale scores. Atomoxetine treatment improved ADHD symptoms in subjects with ADHD+D and ADHD-only, but not in subjects with dyslexia-only without ADHD. This is the first study to report significant effects of any medication on SCT. This study was registered at: http://clinicaltrials.gov/ct2/home, NCT00607919.


Number of Days Required to Estimate Habitual Activity Using Wrist-Worn GENEActiv Accelerometer: A Cross-Sectional Study.
Objective methods like accelerometers are feasible for large studies and may quantify variability in day-to-day physical activity better than self-report. The variability between days suggests that day of the week cannot be ignored in the design and analysis of physical activity studies. The purpose of this paper is to investigate the optimal number of days needed to obtain reliable estimates of weekly habitual physical activity using the wrist-worn GENEActiv accelerometer. Data are from a subsample of the Mitchelstown cohort; 475 (44.6% males; mean aged 59.6±5.5 years) middle-aged Irish adults. Participants wore the wrist GENEActiv accelerometer for 7-consecutive days. Data were collected at 100Hz and summarised into a signal magnitude vector using 60s epochs. Each time interval was categorised according to intensity based on validated cut-offs. Spearman pairwise correlations determined the association between days of the week. Repeated measures ANOVA examined differences in average minutes across days. Intraclass correlations examined the proportion of variability between days, and Spearman-Brown formula estimated intra-class reliability coefficient associated with combinations of 1-7 days. Three hundred and ninety-seven adults (59.7±5.5yrs) had valid accelerometer data. Overall, men were most sedentary on weekends while women spent more time in sedentary behaviour on Sunday through Tuesday. Post hoc analysis found sedentary behaviour and light activity levels on Sunday to differ to all other days in the week. Analysis revealed greater than 1 day monitoring is necessary to achieve acceptable reliability. Monitoring frame duration for reliable estimates varied across intensity categories, (sedentary (3 days), light (2 days), moderate (2 days) and vigorous activity (6 days) and MVPA (2 days)). These findings provide knowledge into the behavioural variability in weekly activity patterns of middle-aged adults. Since Sunday differed from all other days in the week this suggests that day of the week cannot be overlooked in the design and analysis of physical activity studies and thus should be included in the study monitoring frames. Collectively our data suggest that six days monitoring, inclusive of Saturday and Sunday, are needed to reliably capture weekly habitual activity in all activity intensities using the wrist-worn GENEActiv accelerometer.


High burden stones: the role of SWL.
Percutaneous nephrolithotomy (PCNL), PCNL and Shock Wave Lithotripsy (SWL), SWL monotherapy and open surgery are nowadays the potential treatment alternatives for patients with staghorn stones. Several groups have proposed classification schemes to better define staghorn calculi dimensions taking into account size, morphology and composition of the stones. More recently the use of a CT imaging with three-dimensional reconstruction or of a coronal reconstruction of axial CT images was reported to obtain an accurate stone volume calculation. The difficulty in accurately assessing stone burden explains the wide range of reported stone-free rates for SWL monotherapy from 22 to 85%. A recent AUA guideline of the management of staghorn calculi stated that stone free rate is 78% for PCNL and 54% for SWL monotherapy and these values are similar to those reported in Segura guideline but the rate for combination treatment (PNL + SWL) is now lower (66% versus 81%) than in the previous guideline. This reduction is probably due to the fact that in the recent meta-analysis SWL was the last procedure and in the previous generally a sandwich therapy was performed with PCNL followed by a SWL and a secondary PCNL. Improved PCNL techniques with use offlexible nephroscopy and multitract PCNL allow to achieve complete stone clearance by PCNL alone. Complete removal of stone is crucial to eradicate infection and prevent further stone regrowth. Residual fragments may perpetuate postreatment infection and stone regrowth has been reported up to 78% in such patients after SWL monotherapy. In our previous experience (prior to 2000) we observed 45 pts with high burden stones: 31/45 pts (68%) underwent combined therapy PCNL and SWL with a successful rate of 65% (stone free and fragments < 4 mm). In our more recent experience ('03-'08) we treated 34 patients with high burden stones: we performed combined therapy PCNL and SWL in 11 pts (32%) with an overall success rate of 63%. PCNL was undertaken initially with the attempt to remove as much stone as possible with the aid offlexible nephroscopy and SWL was used only for residual stones because the passage, even of fragments < 4 mm, does not always occur in dilated renal cavities. SWL monotherapy should not be used for most patients and may be considered only in patients with small volume staghorn stones with normal collecting system.


If the Facts Were Not Untruths, Their Implications Were: Sponsorship Bias and Misleading Communication.
Sponsorship bias occurs when the financial interests of funders of scientific research influence claims made by scientists, especially in peer-reviewed publications. This article examines the relationship between sponsorship bias and misleading claims, understood as claims that are not necessarily false but which encourage those exposed to them to infer false conclusions. Misleading claims are relevant to how the term "bias" should be understood and thereby to evaluating a recent dispute about whether there is evidence of sponsorship bias in clinical research on statins. The concept of inferential asymmetry is introduced as an aid for understanding the relationship between misleading claims and sponsorship bias.


Neuroprotection of adult rat dorsal root ganglion neurons by combined hypothermia and alkalinization against prolonged ischemia.
Ischemia and ischemia-induced secondary events, such as acidosis and excessive activation of receptors by amino acids, trigger neuron death. The isolation and dissociation of dorsal root ganglion (DRG) involves time during which the neurons are ischemic due to being densely packed within the intact DRG and surrounded by a connective tissue coat. Thus, the longer the time between killing the host animal and when the DRG are dissociated, the longer the neurons are ischemic and exposed to ischemia-induced secondary causes of neuron death. It is well established that hypothermia and alkalinization each separately protect neurons from ischemia and ischemia-induced secondary causes of neuron death, but there are no data on the neuroprotection provided by simultaneous hypothermia and alkalinization. The present experiments were designed to determine the combination of hypothermic and alkaline conditions that yield the largest number of viable neurons dissociated from intact DRG maintained ischemic for up to 4 h. Hypothermia (20 degrees C>15 degrees C>37 degrees C) and alkalinization (pH 9.3>pH 8.3>pH 7.4) increased the yield of viable neurons compared with the yield from DRG maintained under physiological conditions. Hypothermia and alkalinization combined (20 degrees C/pH 9.3) provided the greatest neuroprotection with a yield of viable neurons after 1 h of ischemia 2.5-fold larger than that from DRG maintained under physiological conditions (37 degrees C/pH 7.6). Over 4 h of ischemia, the yield of viable neurons from DRG maintained under both hypothermic/alkaline and physiological conditions decreased in a linear manner, but those at 20 degrees C/pH 9.3 had a 4.5-fold greater yield of viable neurons than those at 37 degrees C/pH 7.6. Thus, combined hypothermia and alkalinization provide significantly greater protection against ischemia and ischemia-induced secondary causes of neuron death than either alone.


Relative stability of normal vs. inverse spinel for 3d transition metal oxides as lithium intercalation cathodes.
Spinel oxides represent an important class of cathode materials for Li-ion batteries. Two major variants of the spinel crystal structure are normal and inverse. The relative stability of normal and inverse ordering at different stages of lithiation has important consequences in lithium diffusivity, voltage, capacity retention and battery life. In this paper, we investigate the relative structural stability of normal and inverse structures of the 3d transition metal oxide spinels with first-principles DFT calculations. We have considered ternary spinel oxides LixM2O4 with M = Ti, V, Cr, Mn, Fe, Co and Ni in both lithiated (x = 1) and delithiated (x = 0) conditions. We find that for all lithiated spinels, the normal structure is preferred regardless of the metal. We observe that the normal structure for all these oxides has a lower size mismatch between octahedral cations compared to the inverse structure. With delithiation, many of the oxides undergo a change in stability with vanadium in particular, showing a tendency to occupy tetrahedral sites. We find that in the delithiated oxide, only vanadium ions can access a +5 oxidation state which prefers tetrahedral coordination. We have also calculated the average voltage of lithiation for these spinels. The calculated voltages agree well with the previously measured and calculated values, wherever available. For the yet to be characterized spinels, our calculation provides voltage values which can motivate further experimental attention. Lastly, we observe that all the normal spinel oxides of the 3d transition metal series have a driving force for a transformation to the non-spinel structure upon delithiation.


Characterization of acrylic polyamide plastic embolization particles in vitro and in human tissue sections by light microscopy, infrared microspectroscopy and scanning electron microscopy with energy dispersive X-ray analysis.
Vascular embolization is a well-established practice for the treatment of tumors and vascular lesions. Rounded beads (microspheres) of various materials (collagen, dextran and trisacryl-polymer-gelatin) were developed to solve problems encountered with earlier versions of embolic material. We performed histochemistry, Fourier transform infrared microspectroscopy and scanning electron microscopy with energy dispersive X-ray analysis on two uterine and one hepatic specimen with unidentified intravascular foreign material, and examined a reference embolization product for comparison. The hematoxylin and eosin stained tissue sections showed multiple foci with unidentified intravascular foreign material and fibrous obliteration of vessel lumens. Only one case had a clinical history of previous embolization but without specifying the material used. One case was submitted for identification of a 'parasite'. The material stained positively with Sirius red and mucicarmine, variably with Masson's trichrome stain and Movat pentachrome, and did not stain centrally with periodic acid Schiff with diastase. Infrared spectrophotometric analysis of the material from all three cases demonstrated the spectrum of acrylic polyamide plastic. A control sample of EmboGold exhibited infrared microspectroscopic spectra similar to the three tissue specimens. Analysis by scanning electron microscopy with energy dispersive X-ray analysis demonstrated some differences in elemental composition between the tissue sections and the selected reference material. To our knowledge, this is the first report of infrared spectrophotometric analysis with scanning electron microscopy with energy dispersive X-ray analysis of an acrylic polyamide plastic embolization product both in vitro and in human histologic tissue sections. In cases lacking appropriate clinical information, identification by these methods and/or a panel of special stains may assist pathologists unfamiliar with this material's light microscopic appearance.


Applying a Theory-Driven Framework to Guide Quality Improvement Efforts in Nursing Homes: The LOCK Model.
Implementing quality improvement (QI) programs in nursing homes continues to encounter significant challenges, despite recognized need. QI approaches provide nursing home staff with opportunities to collaborate on developing and testing strategies for improving care delivery. We present a theory-driven and user-friendly adaptable framework and facilitation package to overcome existing challenges and guide QI efforts in nursing homes. The framework is grounded in the foundational concepts of strengths-based learning, observation, relationship-based teams, efficiency, and organizational learning. We adapted these concepts to QI in the nursing home setting, creating the "LOCK" framework. The LOCK framework is currently being disseminated across the Veterans Health Administration. The LOCK framework has five tenets: (a) Look for the bright spots, (b) Observe, (c) Collaborate in huddles, (d) Keep it bite-sized, and (e) facilitation. Each tenet is described. We also present a case study documenting how a fictional nursing home can implement the LOCK framework as part of a QI effort to improve engagement between staff and residents. The case study describes sample observations, processes, and outcomes. We also discuss practical applications for nursing home staff, the adaptability of LOCK for different QI projects, the specific role of facilitation, and lessons learned. The proposed framework complements national efforts to improve quality of care and quality of life for nursing home residents and may be valuable across long-term care settings and QI project types.


Combining user logging with eye tracking for interactive and dynamic applications.
User evaluations of interactive and dynamic applications face various challenges related to the active nature of these displays. For example, users can often zoom and pan on digital products, and these interactions cause changes in the extent and/or level of detail of the stimulus. Therefore, in eye tracking studies, when a user's gaze is at a particular screen position (gaze position) over a period of time, the information contained in this particular position may have changed. Such digital activities are commonplace in modern life, yet it has been difficult to automatically compare the changing information at the viewed position, especially across many participants. Existing solutions typically involve tedious and time-consuming manual work. In this article, we propose a methodology that can overcome this problem. By combining eye tracking with user logging (mouse and keyboard actions) with cartographic products, we are able to accurately reference screen coordinates to geographic coordinates. This referencing approach allows researchers to know which geographic object (location or attribute) corresponds to the gaze coordinates at all times. We tested the proposed approach through two case studies, and discuss the advantages and disadvantages of the applied methodology. Furthermore, the applicability of the proposed approach is discussed with respect to other fields of research that use eye tracking-namely, marketing, sports and movement sciences, and experimental psychology. From these case studies and discussions, we conclude that combining eye tracking and user-logging data is an essential step forward in efficiently studying user behavior with interactive and static stimuli in multiple research fields.


Presence of automated external defibrillators in North Carolina public middle schools.
Automated external defibrillators (AEDs) have been used in the school setting to successfully resuscitate students, staff, and visitors. All public high schools in North Carolina have an AED. However, the number of North Carolina public middle schools with an AED is unknown. The purpose of this study was to determine the presence of AEDs at public middle schools in North Carolina and to estimate the cost associated with providing an AED to all public middle schools currently without one. All 547 middle schools in North Carolina's 117 public school systems were surveyed in 2009 via e-mail, fax, and, when necessary, telephone about whether an AED was present on site. For middle schools without AEDs, we estimated the cost of purchase and for 1 year of maintenance. A total 66.6% of public middle schools responded to 1 of 3 survey mailings. The remaining schools were contacted by telephone, so that 100% were included in data collection. At the time of the survey, at least 1 AED was present in 334 schools (61.1%). Of the 213 schools without AEDs, 57 (26.8%) were in school systems in which some middle schools had AEDs, and 156 (73.2%) were in systems in which no middle school had an AED. On the basis of a start-up cost of $1,200 per AED, the cost of providing an AED to each school without one is approximately $255,600. These data are based on self-report, and we could not verify whether AEDs were functional. Cost estimates do not include charges for ongoing maintenance and staff training. Two hundred and thirteen North Carolina public middle schools (38.9%) do not have an AED on site.


The symptom structure of posttraumatic stress disorder and co-morbid depression among college students with childhood abuse experience: A network analysis.
Posttraumatic stress disorder (PTSD) and depression are highly co-morbid among individuals with childhood abuse history, while the mechanism of the co-morbidity is highly debated. This study sought to extent the work among college students with network analysis, which is a novel method that sees the co-morbidity from a symptom interacting perspective. Data was collected from 476 college students who were assessed to have childhood abuse history, PTSD and depression at the same time, using Childhood Trauma Questionnaire- Short Form, PTSD Checklist for DSM-5 and The Center for Epidemiological Studies Depression. We created a Graphical Gaussian Model (GGM) network to show associations between symptom pairs and a Directed Acyclic Graph (DAG) to estimate potential casual relationships among symptoms. The GGM network was reliably stable, feeling sad (Depression) and trouble experiencing positive feelings (PTSD) were the most central nodes. Trouble experiencing positive feelings and several negative affect symptoms, sleep problems and difficulty in concentrating were acting as important bridging nodes. The DAG network suggested the key triggering roles of exaggerated startle (PTSD) and several re-experiencing symptoms. The study used cross-sectional data and self-reported measures. Results from network analysis could be affected by scale factors and contain spurious correlations. In the childhood-abuse-related co-morbid structure, several negative affect symptoms both in PTSD and depression have pivotal roles, hyper-arousal symptoms and re-experiencing symptoms could trigger the co-morbid structure. Illustrating the strength and limitations of network analysis, this study help target the potentially influential symptoms for better clinical intervention.


Coacervation of poly-electrolytes in the presence of lipid bilayers: mutual alteration of structure and morphology.
Many intrinsically disordered peptides have been shown to undergo liquid-liquid phase separation and form complex coacervates, which play various regulatory roles in the cell. Recent experimental studies found that such phase separation processes may also occur at the lipid membrane surface and help organize biomolecules during signaling events; in some cases, phase separation of proteins at the membrane surface was also observed to lead to significant remodeling of the membrane morphology. The molecular mechanisms that govern the interactions between complex coacervates and lipid membranes and the impacts of such interactions on their structure and morphology, however, remain unclear. Here we study the coacervation of poly-glutamate (E30) and poly-lysine (K30) in the presence of lipid bilayers of different compositions. We carry out explicit-solvent coarse-grained molecular dynamics simulations by using the MARTINI (v3.0) force-field. We find that more than 20% anionic lipids are required for the coacervate to form stable contact with the bilayer. Upon wetting, the coacervate induces negative curvature to the bilayer and facilitates local lipid demixing, without any peptide insertion. The magnitude of negative curvature, extent of lipid demixing, and asphericity of the coacervate increase with the concentration of anionic lipids. Overall, we observe a decrease in the number of contacts among the polyelectrolytes as the droplet spreads over the bilayer. Therefore, unlike previous suggestions, interactions among polyelectrolytes do not constitute a driving force for the membrane bending upon wetting by the coacervate. Rather, analysis of interaction energy components suggests that bending of the membrane is favored by enhanced interactions between polyelectrolytes with lipids as well as with counterions. Kinetic studies reveal that, at the studied polyelectrolyte concentrations, the coacervate formation precedes bilayer wetting.


Immunoglobulin G4-related pathologic features in inflammatory neuropathies.
To evaluate the pathologic significance of immunoglobulin G4 (IgG4) in patients with inflammatory peripheral neuropathy. We clinicopathologically examined 149 consecutive patients with peripheral neuropathy who had clusters of inflammatory cells with or without vasculitis in sural nerve biopsy specimens and in whom we were able to assess the serum IgG4 levels. Elevation of serum IgG4 levels and infiltration of IgG4-positive plasma cells, which are currently defined as the diagnostic criteria for IgG4-related disease, were found in 35 and 29 patients, respectively. In the 44 patients exhibiting either elevated serum IgG4 levels or IgG4-positive cell infiltration, the diagnoses prior to the examination of IgG4 in serum and pathologic samples included microscopic polyangiitis (12 patients) and eosinophilic granulomatosis with polyangiitis, or Churg-Strauss syndrome (19 patients). Thirty-four patients (77%) had findings of vasculitis as indicated by the destruction or obstruction of the vessel walls. Sixteen (36%) of these patients had fibrinoid necrosis. Axonal degeneration without evidence of demyelination was observed irrespective of the presence of vasculitis. The extent of fibrosis, assessed as the fibrotic area in the epineurium, significantly correlated with the grade of IgG4-positive cell infiltration (p < 0.01). Elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells were observed in a subgroup of patients with inflammatory neuropathy, particularly in patients diagnosed with primary systemic vasculitis, including microscopic polyangiitis. Epineurial IgG4-positive plasma cell infiltration correlated with the extent of epineurial fibrosis.


Complication rates in the second and third trimester of spontaneous twin pregnancies and twin pregnancies after in vitro fertilization.
Most authors agree that the twin pregnancies have a higher risk of complications compared to singleton pregnancies. However, there is no unanimity as to whether the risk of complications in twin pregnancies resulting from in vitro fertilization is higher than in twin pregnancies resulting from spontaneous conception. The aim of this study was to estimate the frequency rates of complications in the second and third trimester of dichorionic-diamniotic twin pregnancies resulting from IVF (group I) compared to dichorionic-diamniotic and monochorionic-diamniotic twin pregnancies resulting from spontaneous conception (group II and III). The rate of cesarean section and cervical cerclage was significantly higher in the group I. Polyhydramnios occurred less frequently in group I than in group III. The discordant growth of fetuses occurred significantly more frequently in the group I. The frequency of other complications did not differ in the studied groups. The Apgar score was similar in the group I and II but significantly lower in the group III compared to the group I. 1) The frequency of complications in twin pregnancies after IVF is similar to those in the twin pregnancies conceived spontaneously. 2) In the twin pregnancies after IVF it is necessary to expect only a higher frequency of caesarean sections, cervical incompetence and a discordant growth of the twins when comparing with twin pregnancies conceived spontaneously. 3) In the twin pregnancies after IVF the intrauterine fetal demise and polyhydramnios occurred less frequently than in monochorionic-diamniotic pregnancies after spontaneous conception.


Neuromagnetic effects of pico-Tesla stimulation.
We used a double-blind experimental design to look for an effect of pico-Tesla magnetic stimulation in healthy subjects. Pico-Tesla stimulation is thought to increase the dominant frequency of 2-7 Hz oscillations in the human brain. We used magnetoencephalography to measure resting state brain activity. Each subject had two separate recording sessions consisting of three runs in between which they were given real or sham pT stimulation. We then tried to predict the real and sham stimulation sessions based on changes in the mean peak frequency in the 2-7 Hz band. Our predictions for these individual runs were 8 out of 14 at chance level (p = 0.39). After unblinding, we found no significant effect (p = 0.11) of an increase in the frequency range (2-7 Hz) across the subject group. Finally, we performed a Bayesian model comparison between the effect size predicted from previous clinical studies and a null model. Even though this study had a sensitivity advantage of at least one order of magnitude over previous work, we found the null model to be significantly (2000 times) more likely.


Heavy Hydrogen Doping into ZnO and the H/D Isotope Effect.
Hydrogen (H) can drastically change the physical properties of solids by the doping of host materials with minimum perturbation to the lattice because of its small size, quantum nature, and a variety of charged states from -1 (hydride, H-) to +1 (proton, H+). While the H-doping amount is limited under equilibrium conditions, H2+ ion irradiation at low temperature is a promising method for introducing a large amount of hydrogen into any material. Although the application of this method offers the potential for exploring unforeseen fascinating properties, the effects of nonequilibrium H doping at very low temperature below 10 K are largely underexplored and are not well understood. In this article, we report heavy H (D) doping into ZnO films by H2+ (D2+) irradiation at 7 K, which resulted in metallic conductivity and an isotope effect on the conductivity at 7 K. The H/D isotope effect is attributable to metastable H (D) trapping sites generated by the effect of irradiation. The isotope effect is decreased at low acceleration voltage. Furthermore, the subsequent thermal excursion induces a large irreversible decrease in resistivity, indicating the migration of H (D) from metastable trapping sites upon heating. This work provides a new strategy to control the physical properties of materials and to investigate the H (D) migration occurring with increasing temperature after excess H doping at very low temperature.


[Determination of human blood and urine progestins by the method of competitive protein binding on the basis of guinea pig transprogestin].
The use as a testing system of transprogestin or of progesterone-binding protein (obtained from a pregnant guinea pig) with a high specificity to progesterone and a number of its affiliated metabolites increased the sensitivity of the method considerably, permitting to determine progestins in the blood and urine of nonpregnant women (at various phases of the sexual cycle) and in men. Dynamics of the given progestins in the urine correlates with the changes of their blood level and permits complete and objective assessment of the ovarian and placental functions in women with various physiological conditions.


[Prenatal diagnosis of type II adenomatoid lung dysplasia].
Congenital adenomatoid malformation of the lung is a rare form of lung disease, characterised by excessive overgrowth of terminal respiratory elements. From the histological as well as the sonographical point of view it can be classified into 3 subtypes. The prognosis depends on the type and the associated malformations. We report on two cases of congenital adenomatoid malformation of the lung type II, diagnosed by ultrasound before the 23rd week of gestation. Criteria that may be useful in the prenatal diagnosis of this malformation are described, and the clinical management is discussed.


Identification of a Four Cancer Stem Cell-Related Gene Signature and Establishment of a Prognostic Nomogram Predicting Overall Survival of Pancreatic Adenocarcinoma.
Cancer stem cells (CSCs) are now being considered as the initial component in the development of pancreatic adenocarcinoma (PAAD). Our aim was to develop a CSCrelated signature to assess the prognosis of PAAD patients for the optimization of treatment. Differentially expressed genes (DEGs) between pancreatic tumor and normal tissue in the Cancer Genome Atlas (TCGA) were screened out, and the weighted gene correlation network analysis (WGCNA) was employed to identify the CSC-related gene sets. Then, univariate, Lasso Cox regression analyses and multivariate Cox regression were applied to construct a prognostic signature using the CSC-related genes. Its prognostic performance was validated in TCGA and ICGC cohorts. Furthermore, Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors in PAAD, and a prognostic nomogram was established. The Kaplan-Meier analysis, ROC curve and C-index indicated the good performance of the CSC-related signature at predicting overall survival (OS). Univariate Cox regression and multivariate Cox regression revealed that the CSC-related signature was an independent prognostic factor in PAAD. The nomogram was superior to the risk model and AJCC stage in predicting OS. In terms of mutation and tumor immunity, patients in the high-risk group had higher tumor mutation burden (TMB) scores than patients in the low-risk group, and the immune score and the ESTIMATE score were significantly lower in the high-risk group. Moreover, according to the results of principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA), the low-risk and high-risk groups displayed different stemness statuses based on the risk model. Our study identified four CSC-related gene signatures and established a prognostic nomogram that reliably predicts OS in PAAD. The findings may support new ideas for screening therapeutic targets to inhibit stem characteristics and the development of PAAD.


Overview of the Side-Effects of FDA- and/or EMA-Approved Targeted Therapies for the Treatment of Hematological Malignancies.
In the last decade there has been tremendous effort in offering better therapeutic management strategies to patients with hematologic malignancies. These efforts have ranged from biological to clinical approaches and resulted in the rapid development of new approaches. The main "problem" that comes with the high influx of newly approved drugs, which not only influences hematologists that frequently work with these drugs but also affects other healthcare professionals that work with hematologists in patient management, including intensive care unit (ICU) physicians, is they have to keep up within their specialty and, in addition, with the side-effects that can occur when encountering hematology-specific therapies. Nonetheless, there are few people that have an in-depth understanding of a specialty outside theirs. Thus, this manuscript offers an overview of the most common side-effects caused by therapies used in hematology nowadays, or that are currently being investigated in clinical trials, with the purpose to serve as an aid to other specialties. Nevertheless, because of the high amount of information on this subject, each chapter will offer an overview of the side-effects of a drug class with each reference of the section being intended as further reading.


Diffuse pulmonary hemosiderosis after exposure to pesticides. A case report.
This report describes the clinical, radiological, microscopical and ligandohistochemical findings in a 17-year-old woman who suffered from an acute onset of pulmonary hemosiderosis after inhalation of pesticides used for the cultivation of strawberries. She complained of headache, dyspnea, rhinitis, weakness and recurrent severe hemoptysis. Chest radiographs revealed bilateral patchy infiltrates, predominantly in the lower parts of both lungs. The consecutive severe anemia was treated by multiple blood transfusions which were repeated every 4-5 days. Open lung biopsies displayed signs of diffuse hemorrhage with hemosiderin-loaded macrophages, some hyaline membranes, focal fibroid deposits with intermingled histiocytes, mild interstitial fibrosis and focal intra-alveolar calcified bodies surrounded by foreign body giant cells. Analysis of endogenous lectins failed to demonstrate expression of binding capacities for maltose, fucose, mannose, lactose and sialic acid, Neither binding capacities for the macrophage-migration-inhibitory factor nor its presence, as analyzed by labeled sarcolectin, could be detected histochemically. The light microscopical findings are consistent with a longer-lasting diffuse pulmonary hemosiderosis; the presence of calcified bodies and foreign body giant cells (including the ligandohistochemical data) argues for a causal role of inhaled substances. The patient's clinical course improved after cyclophosphamide treatment, which restored her ability to work and released her from the need for recurrent blood transfusions.


Transduction by leukotriene B4 receptors of increases in cytosolic calcium in human polymorphonuclear leukocytes.
The uptake of Quin-2 by human polymorphonuclear (PMN) leukocytes permitted accurate fluorimetric quantification of the cytosolic concentration of intracellular calcium [( Ca+2]in), without altering the expression of the two subsets of leukotriene B4 (LTB4) receptors, as assessed by the binding of [3H]LTB4. Chemotactic concentrations of LTB4 elicited a rapid increase in [Ca+2]in, which reached a peak within 0.6 to 1 min and then decayed back to baseline levels by 6 to 10 min. The maximal increase and the half-maximal increase in [Ca+2]in were achieved by LTB4 at mean concentrations of 5 X 10(-10) M and 2 X 10(-10) M, respectively, where the binding of LTB4 to high-affinity receptors predominates. A rank order of potency of LTB4 greater than 5(S),12(S)-6-trans-LTB4 greater than 12(S)-LTB4 was established for the elicitation of increases in [Ca+2]in, which reflects the binding of the isomers to low-affinity receptors. PMN leukocytes were preincubated with 10(-8) M LTB4 to induce chemotactic deactivation, which eliminates the expression of high-affinity receptors without altering the expression of the low-affinity receptors for LTB4. LTB4 elicited an increase in [Ca+2]in in the deactivated PMN leukocytes with an EC50 of 3 X 10(-8) M, which is similar to the Kd for LTB4 binding to the low-affinity receptors. Two lines of cultured human leukemic cells, IM-9 and HL-60, did not bind LTB4 specifically and did not show any change in [Ca+2]in upon the addition of 3 X 10(-8) M LTB4. The HL-60 human promyelocytic leukemia cell line was induced to differentiate in 1% dimethyl sulfoxide to leukocytes with more mature myelocytic characteristics. Differentiated HL-60 cells expressed an average of 54,000 low-affinity receptors for LTB4 per cell with an average dissociation constant of 7.3 X 10(-8) M and concurrently developed the capacity to respond to LTB4 with an increase in [Ca+2]in. The binding of LTB4 to either high-affinity or low-affinity receptors appears to be sufficient to initiate an increase in [Ca+2]in in human PMN leukocytes and differentiated HL-60 cells. The specificity of LTB4 receptors in transducing maximum increases in [Ca+2]in is determined by the subset of receptors that predominate as a result of the concentration of LTB4 and the state of the responding cells.


[The predictive value of autoantibodies in disseminating lupus erythematosus and rheumatoid arthritis].
In some conditions e.g. osteoporosis, hypertension and hypercholesterolaemia, certain phenomena precede manifestation of the disease and preventive measures can be taken long before the disease presents itself. In the same way systemic lupus erythematosus (SLE) and rheumatoid arthritis can be explored. Recently, studies have been published on healthy blood donors, who later developed SLE or rheumatoid arthritis, and in whom specific autoantibodies could be demonstrated. In SLE the autoantibodies are not specific enough to develop preventive strategies, but in rheumatoid arthritis in particular there are specific antibodies against cyclic citrullinated peptides (anti-CCP-antibodies) which are very specific. A clinical trial has been initiated in which HLA-DR4-positive people with raised autoantibody concentrations are given 1-2 intramuscular injections of dexamethasone with the aim of halving the antibody concentration and in the long term lowering the incidence of rheumatoid arthritis.


Granulocyte colony-stimulating factor improves deficient in vitro neutrophil transendothelial migration in patients with advanced liver disease.
Bacterial infections are frequent complications in patients with liver cirrhosis. Cirrhotic patients present abnormalities in both innate and adaptive immune responses, including a deficient neutrophil recruitment to infected sites. The purpose of this study was to assess neutrophil-endothelium interactions in cirrhotic patients and evaluate the effects of G-CSF on this process. We studied neutrophil adhesion and transendothelial migration in 14 cirrhotic patients and 14 healthy controls. We also analyzed neutrophil expression of the adhesion molecules CD62L and CD11b in whole blood by flow cytometry. Cirrhotic patients expressed higher levels of CD11b than healthy controls, whereas CD62L expression was significantly lower, suggesting exposure of neutrophils to activating agents within the bloodstream. Neutrophils from cirrhotic patients showed increased adhesion to both resting and tumor necrosis factor alpha-stimulated microvascular endothelial cells and decreased transendothelial migration. Granulocyte colony-stimulating factor (G-CSF) (100 ng/ml) significantly enhanced neutrophil adhesion to microvascular endothelial cells in healthy controls but not in cirrhotic patients. G-CSF also significantly improved neutrophil transmigration in cirrhotic patients and healthy controls. In conclusion, cirrhotic patients exhibit increased neutrophil adhesion to microvascular endothelium and deficient transendothelial migration. G-CSF enhances neutrophil transendothelial migration in cirrhotic patients despite having no effect on neutrophil adhesion. Therefore, G-CSF may be able to increase neutrophil recruitment into infected sites in these patients.


Use of powdered egg yolk vs fresh egg yolk for the cryopreservation of ovine semen.
Egg yolk is a common additive to sperm cryopreservation diluents. Because of its animal origin, however, it also represents a potential risk of microbiological contamination in the diluent. This potential contamination can be avoided by using powdered egg yolk, instead of fresh egg yolk, as it is pasteurized. This study was conducted to determine ram sperm cryosurvival was affected by the type of egg yolk used (powdered egg yolk or fresh egg yolk) and by yolk concentration (10, 15 or 20%) in the diluent. Microbiological analyses were also performed to quantify the microbiological contamination in the diluents containing the two types of egg yolk. Sperm cryosurvival was determined by motility and morphology analyses after thawing. Motility parameters were assessed using a computer-assisted sperm analysis (CASA) system, and the percentage of sperm with a normal apical ridge was evaluated using a differential interference contrast microscope. No significant differences were observed between diluents in the percentage of sperm with normal apical ridge. However, higher percentages of total motile cells were observed for samples containing powdered egg yolk (69%) compared to samples containing fresh egg yolk (60%). However, sperm in diluents containing fresh egg yolk, exhibited higher values for average-path velocity, straight-line velocity and beat cross frequency and lower values for amplitude of lateral head displacement (p <0.05), compared to cells in diluents containing powdered egg yolk. Microbiological contamination was similar (<200 CFU/ml) in both diluents, and no bacterial growth was observed in either, when antibiotics were added. Therefore, powdered egg yolk can be effective used in diluents for the freezing of ram semen. However, the in vivo fertility of sperm frozen in diluents containing powdered egg yolk should be tested, as some motility parameters were different for sperm treated with powdered egg yolk compared to fresh egg yolk.


Primulinasilaniae sp. nov. (Gesneriaceae) from the limestone area of Guizhou Province, China.
Primulinasilaniae X.X.Bai & F.Wen, a new species of Primulina Hance (Gesneriaceae) from the limestone area of Wangmo County, Guizhou Province, is described and illustrated. The new species is similar to P.spiradiclioides Z.B.Xin & F.Wen, but can be easily distinguished from the latter by a combination of characteristics, especially in the lateral veins of its leaf and floral shape and tube. At present, three populations in one locality of this new taxon were found, totaling about 600 mature individuals. According to the IUCN Red List Categories and Criteria (Version 3.1), the species is provisionally assessed as Vulnerable [VU D1].


Six-Month Evaluation of a Sodium Bicarbonate-Containing Toothpaste for Reduction of Established Gingivitis: A Randomized USA-Based Clinical Trial.
Short-term use of sodium bicarbonate (NaHCO3)-containing toothpaste reduces plaque and improves clinical measures of gingivitis. To examine this over a longer period, we compared efficacy and tolerability of twice-daily brushing for 24 weeks with 67% or 0% NaHCO3-containing toothpastes in USA-based participants with moderate gingivitis (Clinicaltrials.gov:NCT02207400). This was a six-month, randomized, examiner-blind, parallel-group, clinical trial. Investigators randomized adults with blood in expectorate after brushing and ≥ 20 gingival bleeding sites to 67% NaHCO3 (n = 123; n = 107 completed study) or 0% NaHCO3 (n = 123; n = 109 completed study) toothpastes. Primary efficacy variables included between-treatment differences in number of bleeding sites and Modified Gingival Index (MGI) score at 24 weeks. Secondary efficacy variables included Bleeding Index and Turesky modification of the Quigley-Hein Plaque Index (overall and interproximal sites) at six, 12, and 24 weeks. A subset of 50 participants underwent sampling to assess plaque microbiology over the course of treatment. Compared with the 0% NaHCO3 toothpaste, the 67% NaHCO3 toothpaste produced statistically significant improvements at Week 24 in number of bleeding sites (46.7% difference) and MGI (33.9% difference), and for all other endpoints (all p < 0.0001). There was no significant between-treatment difference in the proportion of participants harboring opportunistic pathogens. Products were generally well tolerated, with two and five treatment-related adverse events reported in the 67% and 0% NaHCO3 toothpaste groups, respectively. Gingival bleeding, gingivitis, and plaque indices were significantly improved at six, 12, and 24 weeks with twice-daily brushing with 67% NaHCO3-containing toothpaste in participants with moderate gingivitis.


Metabolism and elimination of oxazepam in B6C3F1 and Swiss-Webster mice.
The National Toxicology Program has recently determined oxazepam to be hepatocarcinogenic in mice. To aid in the assessment of the risks associated with human use of this drug, the metabolism and elimination of oxazepam in mice were exhaustively examined in B6C3F1 and Swiss-Webster mice. In this study males were given 25, 250, and 500 mg/kg by gavage, a range that includes doses found to be carcinogenic and noncarcinogenic in the National Toxicology Program bioassay. Metabolism of oxazepam by female mice of both strains was studied following administration of 500 mg/kg. More than 90% of the recovered activity was identified. Few strain differences were detected. Females of both strains metabolize oxazepam to a slightly greater extent than do males. Dose-dependent differences were detected, but they were usually nonlinear over the range examined. The routes of elimination in mice given a single dose of oxazepam were by order of importance: fecal > urinary > expired air. Pretreatment with dosed feed for 14 days (to model autoinduction in bioassay animals) resulted in a significant shift from the fecal to the urinary route of elimination, an approximately 2-fold increase in elimination of oxazepam glucuronide, and a significant decrease in excretion of unchanged oxazepam. Results of this study indicate that following constant exposure to oxazepam, mice metabolize and eliminate oxazepam in a manner more similar to that by humans than that by naive mice. This observation enhances the significance of data obtained in the bioassay and the extrapolation of that data to predict risks to human health.


Theranostic nanoparticles engineered for clinic and pharmaceutics.
Nanomedicine is the manipulation of human biological systems at the molecular level using nanoscale or nanostructured materials. Because nanoscale materials interact effectively with biological systems, the use of nanodiagnostics and nanotherapeutics may overcome many intractable health challenges. A variety of nanoparticles have been designed with modifiable functional surfaces and bioactive cores. The engineering of nanoparticles can result in several advantageous therapeutic and diagnostic properties including enhanced permeation and retention in the circulatory system, specific delivery of drugs to target sites, highly-efficient gene transfection, and enhanced medical imaging. These nanoscale materials offer the opportunity to detect chronic diseases early and to monitor the therapeutic effects of nanoformulated drugs used in the clinic. Many of these novel nanoparticles contain both drug(s) and imaging agent(s) within an individual nanoparticle for simultaneous disease diagnosis and therapy. Further integration of therapeutic compounds with diagnostic agents into theranostic nanoparticles would be highly beneficial. However, the unique physiochemical properties that make nanomaterials attractive for therapy and diagnosis may be also associated with potential health hazards. Our research has demonstrated that the biological response to nanomaterials is related to many factors including exposure levels, systemic accumulation and excretion profiles, tissue and organ distribution, and the age of the test subject. Therefore, when engineering new nanomaterials for clinical use, researchers need to consider these factors to minimize toxicity of nanoparticles in these applications. We have fabricated and evaluated nanomaterials such as cationic amphiphilic polymers and metallofullerenes that demonstrate both high efficiency and low toxicity in gene therapy and/or chemotherapy. In this Account, we describe the development of theranostic nanomaterials with low toxicity and illustrate their potential use as novel nanomedicines in translational research.


Sinonasal cancer in a worker exposed to chromium in an unusual industrial sector.
Occupational exposure to chromium is carcinogenic for human respiratory system. Due to the low incidence of sinonasal malignancies, there is still a paucity of evidence to confirm that chromium(VI) exposure is a cause of nasal cancer. To report on a sinonasal cancer (SNC) of rare occupational origin, increasing the awareness on epidemiological knowledge of occupational exposures to chromium compounds. We describe a case of a 64-year-old chrome plater who worked in the galvanic industry in the early 1970s. After a latency period of 39 years, he was diagnosed with sinonasal undifferentiated carcinoma (SNUC). A brief review of the literature was conducted. A thorough occupational history revealed a 4-year-long occupational exposure to chromium(VI) during a magnesium cylinder plating process involved in computer production. The patient underwent endoscopic endonasal removal of the SNUC. He is alive with no evidence of disease at 40-month follow-up. Our literature review identified 8 papers concerning 40 cases of chrome-induced sinonasal tumors. The maximum relative risk of SNC developing in chromium-exposed workers was 15.4. When dealing with patients diagnosed with SNC, the possibility of an underlying occupational risk is worth further investigation. Because chromium exposure is rare, and the incidence of SNUC is low, any information emerging on clinical and exposure-related aspects of SNCs in chrome plating workers can contribute to adding evidence on the possible causal relationship between chromium and sinonasal malignancies.


Urinary incontinence and its association with functional physical and cognitive health among female nursing home residents in Switzerland.
Specific knowledge of urinary incontinence (UI) and its interrelation with physical and cognitive health is essential to working towards prevention of UI and to improving quality of treatment and care. The purpose of this study was to determine the association between UI and the activities of daily living (ADL) hierarchy scale, the cognitive performance scale (CPS) and comorbid conditions. The cross-sectional retrospective analysis of 357 nursing homes in Switzerland was based on data of the Minimum Data Set of the Resident Assessment Instrument 2.0 (RAI-MDS). The analysis examined the effect of ADL hierarchy scale, CPS, joint motion and comorbidities on UI. Women ≥65 years were included (n = 44'811; January 2005 to September 2014) at the time of admission to a nursing home. Statistical analysis was done by means of descriptive statistics and logistic regression analysis. The prevalence of UI was 54.7%, the mean ADL hierarchy scale (± SD) 2.42 ± 3.26 (range = 0-6), the mean CPS 1.95 ± 1.67 (range = 0-6). There was a gradual increase in the odds ratio (OR) for UI depending on the ADL hierarchy scale, from the hierarchy scales of "supervised" to "total dependence" of 1.43 - 30.25. For CPS, the OR for UI from "borderline intact" to "very severe impairment" was 1.35 - 5.99. Considering the interaction between ADL and CPS, all ADL hierarchies remained significantly associated with UI, however for CPS this was the case only in the lower hierarchies. Of the 11 examined comorbid conditions, only diabetes mellitus (OR 1.19), dementia (OR 1.01) and arthrosis/arthritis (OR 1.53) were significantly associated with UI. The study indicated that impairment in ADL performance is strongly associated with UI, more than CPS performance and comorbidities. Physical more than cognitive training in order to improve or at least stabilize ADL performance could be a way to prevent or reduce the process of developing UI.


Increased plasma levels of interleukin-6 and interleukin-8 in beta-thalassaemia major.
Several immunological defects can be found in patients with beta-thalassaemia, among which the impairment of neurophil and macrophage phagocytic and killing functions and the production of some cytokines are the most important. It is known that interleukin-6 (IL-6) and interleukin-8 (IL-8) are important components of the pro-inflammatory response. The plasma levels of these cytokines may be relevant in the pathophysiology of beta-thalassaemia. To assess this hypothesis, the plasma IL-6 and IL-8 concentrations in patients with beta-thalassaemia, were investigated. Fourteen patients with thalassaemia major were studied by evaluating body iron status, iron supply for erythropoiesis, and plasma IL-6 and IL-8 levels, together with 12 age-matched healthy controls. The plasma levels of IL-6 and IL-8 were determined by enzyme-linked immunosorbent assay (ELISA). Patients with beta-thalassaemia were found to have higher IL-8 concentrations than normal controls (p < 0.001) and plasma IL-6 concentrations increased significantly in the beta-thalassaemic patients compared with control subjects (p = 0.01). Serum ferritin levels of beta-thalassaemic patients were significantly higher than those of control groups (p < 0.05). IL-8 levels correlated with ferritin levels (r = 0.694; p < 0.05) and the total number of transfusions (r = 0.64; p < 0.05). Plasma IL-6 levels in beta-thalassaemic patients did not correlate with any clinical, haematological or biochemical parameters. It was also found that plasma IL-8 levels in the patients who had blood transfusions over 100 times were significantly higher than those of under 100 times (p < 0.05), whereas there was no statistical difference for IL-6. Markedly increased plasma IL-6 and IL-8 levels were documented in patients with beta-thalassaemia. Increased production of IL-6 and IL-8 might have contributed to abnormalities in iron metabolism and it is probably due to overstimulation of macrophages. Before a clinical value can be ascribed to these changes in plasma cytokine levels in beta-thalassaemia, the follow-up samples of larger series of patients with 8-thalassaemia should be evaluated.


Lung volume measurements in wheezy infants: comparison of plethysmography and gas dilution.
The accuracy both of plethysmographic measurements of thoracic gas volume (TGV) and determinations of functional residual capacity (FRC) by gas dilution techniques in infants with obstructive lung disease is subject to continued dispute. We studied 25 wheezy infants and compared TGV derived from end-expiratory airway occlusions (TGVEE), corrected TGV after end-inspiratory airway occlusions (TGVEI), and FRC determined by nitrogen wash-out (FRCN2). Group mean TGVEE and TGVEI differed significantly (25.8 +/- 8.4 versus 24.6 +/- 7.1 ml.kg-1). TGVEE and FRCN2 did not differ significantly. TGVEE and TGVEI, as well as TGVEE and FRCN2, and TGVEI and FRCN2 data, respectively, showed lack of agreement. Based on 95% confidence intervals, calculated from TGVEE data, 14 of the 25 infants showed a significantly higher TGVEI than TGVEE; only one patient had a significantly lower TGVEI. Compared to FRCN1 data, TGVEE and TGVEI measurements yielded lower values in at least one third of our patients. The present study illustrates, that there is no gold standard for the measurement of lung volume in infants with airway obstruction.


[Single nucleotide polymorphisms (SNPs): functional implications of regulatory-SNP (rSNP) and structural RNA (srSNPs) in complex diseases].
Single nucleotide polymorphisms (SNPs) represent to the genetics variant most common founded in the human genome. These polymorphisms have a wide distribution and can found in any region of gene or mRNA, the SNPs that have functional implications on the levels of gene expression are called regulatory SNPs (rSNPs), while those that affect translation, splicing, efficiency to enhance or inhibit the alternative, mRNA stability and protein function (without altering its structure), they are called structural RNA SNPs (srSNPs). Several studies have identified to these polymorphisms associated with different common diseases e.g. hypertension, obesity, rheumatoid arthritis and coronary artery disease. The aim of this review is to discuss the functional implication of rSNPs and srSNPs in the common diseases.


IL-1R and Inflammasomes Mediate Early Pulmonary Protective Mechanisms in Respiratory Brucella Abortus Infection.
Brucella spp. infection is frequently acquired through contaminated aerosols. The role of interleukin-1 beta (IL-1β) in the early pulmonary response to respiratory Brucella infection is unknown. As shown here, IL-1β levels in lung homogenates and bronchoalveolar lavage fluid (BALF) of mice intratracheally inoculated with B. abortus were increased at 3 and 7 days p.i. At 7 days p.i., pulmonary CFU numbers were higher in IL-1 receptor (IL-1R) knockout (KO) mice than in wild type (WT) mice. At different times p.i. CFU in lungs and BALF were higher in mice lacking some inflammasome components (caspase-1, AIM2, NLRP3) than in WT mice. At 2 days p.i. pulmonary levels of IL-1β and CXCL1 (neutrophils chemoattractant) were lower in caspase-1/11 KO mice. At day 3 p.i., neutrophils counts in BALF were lower in caspase-1/11 KO mice than in WT mice. During in vitro infections, IL-1β secretion was lower in alveolar macrophages from caspase-1/11, NLRP3 or AIM2 KO mice than in WT controls. Similarly, IL-1β production by B. abortus-infected alveolar epithelial cells was reduced by pretreatment with a specific caspase-1 inhibitor. This study shows that IL-1R, probably through IL-1β action, and the NLRP3 and AIM2 inflammasomes are involved in pulmonary innate immune protective mechanisms against respiratory B. abortus infection.


Adenotonsillectomy improves neurocognitive function in children with obstructive sleep apnea syndrome.
To evaluate neurocognitive functions of children with obstructive sleep apnea syndrome (OSAS), before and after adenotonsillectomy, compared with healthy controls. Prospective study. Thirty-nine children with OSAS aged 5 to 9 years (mean age, 6.8 +/- 0.2 years) and 20 healthy children (mean age, 7.4 +/- 1.4 years) who served as controls, underwent a battery of neurocognitive tests containing process-oriented intelligence scales. Twenty-seven children in the OSAS group underwent follow-up neurocognitive testing 6 to 10 months after adenotonsillectomy. Fourteen children in the control group were also reevaluated 6 to 10 months after the first evaluation. Children with OSAS had lower scores compared with healthy children in some Kaufman Assessment Battery for Children (K-ABC) subtests and in the general scale Mental Processing Composite, indicating impaired neurocognitive function. No correlation was found between neurocognitive performance and OSAS severity. Six to 10 months after adenotonsillectomy, the children with OSAS demonstrated significant improvement in sleep characteristics, as well as in daytime behavior. Their neurocognitive performance improved considerably, reaching the level of the control group in the subtests Gestalt Closure, Triangles, Word Order, and the Matrix analogies, as well as in the K-ABC general scales, Sequential and Simultaneous Processing scales, and the Mental Processing Composite scale. The magnitude of the change expressed as effect sizes showed medium and large improvements in all 3 general scales of the K-ABC tests. Neurocognitive function is impaired in otherwise healthy children with OSAS. Most functions improve to the level of the control group, indicating that the impaired neurocognitive functions are mostly reversible, at least 3 to 10 months following adenotonsillectomy.


Collagen secretion and growth of mesangial cells require geranylgeranylpyrophosphate.
The mevalonate pathway is important for the biosynthesis of isoprenoids such as geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate, as well as cholesterol. It has been reported that treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor ameliorates glomerular injury in several experimental models of progressive glomerular disease. However, the effect of HMG-CoA reductase inhibitor on mesangial cell function has not been fully understood. This investigation was performed to elucidate the role of a mevalonate metabolite(s) in mesangial cell proliferation and extracellular matrix accumulation. Cycling or quiescent human mesangial cells were incubated in RPMI 1640 containing 10% heat-inactivated fetal calf serum (FCS) in the absence or presence of pravastatin, an inhibitor of HMG-CoA reductase, and mevalonate metabolites. Type IV collagen secretion, mRNA expression, and [3H]thymidine incorporation were measured. Cell cycle phases were monitored by flow cytometry. Pravastatin inhibited FCS-stimulated type IV collagen secretion (IC50 = 210 microM) and mRNA expression. Pravastatin also inhibited FCS-stimulated [3H]thymidine incorporation (IC50 = 430 microM). Analysis with flow cytometry revealed that pravastatin inhibited the G1 to S phase transition of FCS-stimulated mesangial cells. Mevalonate reversed these inhibitory effects of pravastatin completely. Among two major metabolites of mevalonate, GGPP and farnesylpyrophosphate, only GGPP reversed pravastatin-induced inhibition of type IV collagen secretion, DNA synthesis, and the G1 to S phase progression. These results suggest that GGPP plays critical roles for the type IV collagen secretion and G1 to S phase transition in FCS-stimulated human mesangial cells.


Application of an Online Combination Exercise Intervention to Improve Physical and Mental Health in Obese Children: A Single Arm Longitudinal Study.
Introduction: Childhood obesity has become a global public health concern in the past decade. The purpose of this study was to explore the effectiveness of an online combination exercise intervention in improving the physical and mental health of obese children. Methods: This study adopted a one-group pre-test and post-test research design. A total of 28 obese children from 6 elementary schools in Heze City, Shandong Province, China, were recruited. All participants received an 8-week online combination exercise intervention and were tested at a three-month follow-up. Participants were tested and surveyed regarding their demographic, feasibility, and obesity indicators using mental health and quality of life questionnaires. The data were statistically analyzed using a one-way analysis of variance with repeated measures. Results: A total of 26 obese children (Meanage = 10.15 years) completed the study. The retention rate was 92.9% for the entire trial (two obese children withdrew due to their inability to exercise) and no adverse events were reported. In addition, the obese children completed 25/32 (78.1%) of the online courses. After 8 weeks of the intervention, the changes in the body fat percentage of the obese children [mean difference (MD) = -3.126, p < 0.001, Cohen's d = -1.777], thinking dimension score (MD = 1.654, p < 0.001, Cohen's d = 0.603), total quality of life score (MD = 6.385, p < 0.05, Cohen's d = 0.610), and work attitude dimension score (MD = 1.346, p < 0.001, Cohen's d = 0.744) showed significant differences compared to the baseline. However, no significant differences were identified between the post-intervention and three-month follow-up measurements (p > 0.05), and we assumed that the intervention effect was maintained three months after the intervention. Conclusion: An online combination exercise intervention is a safe and feasible option to improve the mental health and quality of life of obese children and may have long-term health benefits.


Diverse molecular recognition properties of blood group A binding monoclonal antibodies.
Information about specificity and affinity is critical for use of carbohydrate-binding antibodies. Herein, we evaluated eight monoclonal antibodies to the blood group A (BG-A) antigen. Antibodies 87-G, 9A, HE-10, HE-24, HE-193, HE-195, T36 and Z2A were profiled on a glycan microarray to assess specificity, relative affinity and the influence of glycan density on recognition. Our studies highlight several noteworthy recognition properties. First, most antibodies bound GalNAcα1-3Gal and the BG-A trisaccharide nearly as well as larger BG-A oligosaccharides. Second, several antibodies only bound the BG-A trisaccharide when displayed on certain glycan chains. These first two points indicate that the carrier glycan chains primarily influence selectivity, rather than binding strength. Third, binding of some antibodies was highly dependent on glycan density, illustrating the importance of glycan presentation for recognition. Fourth, some antibodies recognized the tumor-associated Tn antigen, and one antibody only bound the variant composed of a GalNAc-alpha-linked to a serine residue. Collectively, these results provide new insights into the recognition properties of anti-BG-A antibodies.


Caudalization by retinoic acid is correlated with inhibition of cell population growth and expansion of chick blastoderms cultured in vitro.
Full primitive streak stage chick embryos, cultured in vitro for 20 h in the presence of 10(-9) to 10(-7) moles of retinoic acid (retinol, all-trans), exhibit increasing extent of malformations. RA causes caudalization, suppression of telencephalon, formation of open and enlarged neural tube in the regions of midbrain, hindbrain and spinal cord, failure of fusion of heart tubes, and gives rise to winged or diffused, and even supernumerary somites. Extreme abnormalities include failure to form the head fold and foregut. Abnormal embryos were graded according to Rao and Chauhan (Teratology 4: 191-198, 1971), and we find that the larger the severity of malformation, the smaller the size of total cell population and blastoderm area. Concomitant to caudalization, retinoic acid suppresses the cell population growth.


Fast photogalvanic response of a Bi12SiO20 crystal.
A photoelectric response of a Bi12SiO20 crystal grown in an argon atmosphere on a linearly polarized light (which is referred to as the linear photogalvanic effect) is reported for the first time in the nanosecond-time domain. Optimal geometry for detection of the photo-induced current concerning the orientation of the polarization state of the incident light in respect to the crystallographic axes of a sample was determined considering both the natural optical activity and light absorption of sillenite crystals. Spectral dependence of the photogalvanic current was measured in the visible part (410 - 610 nm) of the spectrum. Temporal shape of light-induced electric-current pulses observed at different experimental conditions is discussed. Obtained results are believed to show that sillenite crystals are very prospective for development of different ultra-fast optoelectronics devices.


Translational research of photodynamic therapy with acridine orange which targets cancer acidity.
During the past 20 years, we have found that acridine orange (AO) selectively accumulates in musculoskeletal sarcomas in vivo or exerts selective cytocidal effects against sarcoma cells in vitro after illumination of the tumor cells with visible light or irradiation of the cells with low-dose X-rays. Based on the data obtained from basic research, we have employed reduction surgery followed by photo- or radiodynamic therapy using AO (AO-PDT & RDT) in 71 patients with musculoskeletal sarcomas, in an attempt to maintain excellent limb function in the patients. We have obtained good local control rates and remarkably better limb functions with this approach as compared to the results obtained with the conventional wide resection surgery. Our basic research demonstrated that AO accumulates densely in intracellular acidic vesicles, especially lysosomes, in an acidity-dependent manner. In cancer cells that proliferate under hypoxic conditions or with Warburg's effect, active glycolysis produces an enormous number of protons, which are released by the cells via proton pumps into the extracellular fluid or lysosomes to maintain a neutral pH of the cytosolic fluid. Cancer cells contain many strongly acidic lysosomes of large sizes; therefore, AO shows marked and prolonged accumulation in the acidic lysosomes of cancer cells. Photon energy excites the AO resulting in the production of activated oxygen species, which oxidize the fatty acids of the lysosomal membrane, resulting in the leakage of lysosomal enzymes and protons, followed by apoptosis of the cancer cells. Based on these observations, we conclude that AO-PDT & RDT target acidic vesicles, especially the lysosomes, in cancer cells, to exhibit selective anti-cancer cell activity. Therefore, it is suggested that AO excited by photon energy has excellent potential as an anticancer "Magic Bullet".


Epithelial disruption by proteases augments the responsiveness of porcine bronchial segments.
1. The effect of disruption to the epithelium of intact porcine bronchi was examined by comparing the responsiveness to agonists applied to the adventitial and luminal surfaces. The development of smooth muscle tone was measured as an increase in pressure in an isovolumic bronchial segment of approximately 2 mm i.d. The reactivity and sensitivity to acetylcholine (ACh) introduced intraluminally was greatly attenuated when compared with adventitial addition. 2. Luminal exposure to K+ and vanadate (VO3-) had little effect compared with strong responses obtained by adventitial application. 3. Intraluminal exposure to trypsin, chymotrypsin and elastase (1 mg/mL) selectively augmented both the sensitivity and the reactivity to the luminal addition of ACh, K+ and carbachol. 4. Mechanical removal of the epithelium produced a 716-fold increase in sensitivity to ACh introduced luminally but had no effect on ACh applied adventitially. 5. The inhibitory effects of luminally introduced isoprenaline on electrical field stimulation responses were also significantly potentiated in segments stripped of epithelium. 6. The evidence presented here indicates that the responsiveness of in vitro airways segments is highly influenced by the epithelial layer, which acts most prominently as a barrier inhibiting the penetration of luminally introduced agonists.


STUDIES ON MALARIAL PARASITES : VII. METHODS AND TECHNIQUES FOR CULTIVATION.
1. Methods of recovering adequate amounts of Plasmodium knowlesi from the monkey (Macaca, mulatta) for biochemical studies and in vitro cultivation are described. Concentrates of red blood cells parasitized with P. knowlesi can be obtained by differential sedimentation of parasitized blood because of physical and chemical changes produced by the parasites in the host cell and the plasma of the blood. 2. Two different techniques, the rocker-dilution and the rocker-perfusion methods, are described for the cultivation of malarial parasites. Details of the apparatus, assembly, and sterilization are given, as well as methods of counting and evaluating parasites. 3. In a series of 235 control experiments for 20 to 24 hours using three types of apparatus, the average rate of multiplication was 3.9. Each technique has specific value for studying the various aspects of metabolism, nutrition, and the action of antimalarial drugs.


Fecal near infrared spectroscopy to discriminate physiological status in giant pandas.
Giant panda (Ailuropoda melanoleuca) monitoring and research often require accurate estimates of population size and density. However, obtaining these estimates has been challenging. Innovative technologies, such as fecal near infrared reflectance spectroscopy (FNIRS), may be used to differentiate between sex, age class, and reproductive status as has been shown for several other species. The objective of this study was to determine if FNIRS could be similarly used for giant panda physiological discriminations. Based on samples from captive animals in four U.S. zoos, FNIRS calibrations correctly identified 78% of samples from adult males, 81% from adult females, 85% from adults, 89% from juveniles, 75% from pregnant and 70% from non-pregnant females. However, diet had an impact on the success of the calibrations. When diet was controlled for plant part such that "leaf only" feces were evaluated, FNIRS calibrations correctly identified 93% of samples from adult males and 95% from adult females. These data show that FNIRS has the potential to differentiate between the sex, age class, and reproductive status in the giant panda and may be applicable for surveying wild populations.


The quality of perioperative care: development of a tool for the perceptions of patients.
To find out how surgical hospital patients (n=874) perceived the quality of perioperative care they received in an operating department and in the recovery room. Patients' perceptions of the perioperative care have not been included systematically in the improvement of the care. Accordingly, there is no standardized, valid, and reliable instrument or system in common use that we could use for the evaluation. The nursing care in operating departments has an important role in modern health care, and therefore more research concerning perioperative care quality is needed urgently and the development of the measurement tool is urgent. The data were collected using a structured questionnaire in five operating departments in southern Finland during 1998. Physical activities (such as pain management and temperature maintenance) were rated as excellent, as were staff characteristics and the physical and social environment. The most critical comments were made with regard to supporting patient initiative, encouragement and educational activities. Patients stated they would have liked more information and it was felt that they should have been encouraged to ask more questions about unclear matters. Some of the patients said they had only very limited influence over their own care. The patients were very pleased with their care in the recovery room. There were only minor differences between the views of patients from different departments. Overall the quality of care was considered extremely good, but comparisons of different quality categories did reveal some problems. Although it has already proved to be a useful tool, the questionnaire needs to be developed and tested further.


Temperature dependence of rotational disorder in a non-standard amino acid from X-ray crystallography and molecular dynamics simulation.
The X-ray single-crystal structure of methyl 2-aminoisobutyrate hydrochloride (Me-AIB), a non-standard amino acid, is reported at 10, 30, 50, 70 and 100 K. Fourier maps indicate the presence of rotational disorder of the hydrogen atoms of the ester methyl group. To study this effect in detail, high resolution data were collected with synchrotron radiation. The non-spherical molecular electron density was predicted with invariom scattering factors and subtracted from the density obtained from a full multipole refinement. This allows disorder to be distinguished from the molecular electron density at each temperature. The disorder is reduced between 100 K and 30 K, but still detectable even at 10 K. Hence, difference densities can be applied for the purpose of electronic structure validation and have the advantage of an absence of noise over Fourier methods. Ultra-low temperature experiments are foreseen to be useful in reducing such kinds of disorder in ultra-high resolution protein crystallography. Molecular dynamics simulations of Me-AIB at temperatures between 10 and 100 K confirm the temperature dependence of the rotational motion of the methyl group seen experimentally. Modeling disorder in X-ray structure analysis will be an interesting future application of molecular dynamics simulations.


Early Parenting Intervention Effects on Brain Responses to Maternal Cues Among High-Risk Children.
Early adversity is correlated with increased risk for negative outcomes, including psychopathology and atypical neurodevelopment. The authors aimed to test the causal impact of an early parenting intervention (Attachment and Biobehavioral Catch-Up; ABC) on children's neural processing of parent cues and on psychosocial functioning in a longitudinal randomized clinical trial. Participants (N=68, mean age, 10.0 years [SD=0.8 years]) were 46 high-risk children whose parents were randomly assigned to receive either the ABC intervention (N=22) or a control intervention (N=24) while the children were infants, in addition to a comparison sample of low-risk children (N=22). During functional MRI scanning, children viewed pictures of their own mothers and of a stranger. Children in the ABC condition showed greater maternal cue-related activation than children in the control condition in clusters of brain regions, including the precuneus, the cingulate gyrus, and the hippocampus, regions commonly associated with social cognition. Additionally, greater activity in these regions was associated with fewer total behavior problems. There was an indirect effect of early intervention on middle childhood psychosocial functioning mediated through increased activity in brain regions in response to maternal cues. These results suggest that early parenting intervention (in this case the ABC intervention) can enhance brain regions supporting children's social cognitive development. In addition, the findings highlight these brain effects as a possible neural pathway through which ABC may prevent future behavior problems among high-risk children, yielding psychosocial benefits that endure through at least middle childhood without the need to intervene with the child directly.


Novel combinations in the treatment of hypertension.
Not uncommonly the effective treatment of hypertension requires multi-drug therapy. Multi-drug combinations that dominate clinical practice typically include a thiazide-type diuretic together with either an angiotensin-converting enzyme inhibitor, or an angiotensin-receptor blocker, or a beta-blocker. On the other hand, there are several medication choices that provide incremental blood pressure reduction but all too often go under-appreciated as to their effectiveness. Such drug combinations include within class switching of diuretics, combining a thiazide-type diuretic with a calcium-channel blocker, utilizing 2 calcium-channel blockers from different classes, giving an ACE inhibitor together with an angiotensin-receptor blocker, adding an aldosterone receptor antagonist to any of several other drug classes, as well as adding nitrate therapy to any of several other drug classes. Such novel pharmacologic approaches offer useful options for treatment in the otherwise difficult to control hypertensive patient.


Distributed bees algorithm parameters optimization for a cost efficient target allocation in swarms of robots.
Swarms of robots can use their sensing abilities to explore unknown environments and deploy on sites of interest. In this task, a large number of robots is more effective than a single unit because of their ability to quickly cover the area. However, the coordination of large teams of robots is not an easy problem, especially when the resources for the deployment are limited. In this paper, the distributed bees algorithm (DBA), previously proposed by the authors, is optimized and applied to distributed target allocation in swarms of robots. Improved target allocation in terms of deployment cost efficiency is achieved through optimization of the DBA's control parameters by means of a genetic algorithm. Experimental results show that with the optimized set of parameters, the deployment cost measured as the average distance traveled by the robots is reduced. The cost-efficient deployment is in some cases achieved at the expense of increased robots' distribution error. Nevertheless, the proposed approach allows the swarm to adapt to the operating conditions when available resources are scarce.


Airborne micro-organisms and prevalence of byssinotic symptoms in cotton mills.
The concentration of airborne microbes, their endotoxins and the prevalence of byssinotic symptoms among workers were measured in the cardrooms of seven cotton spinning, a wool spinning and two cotton waste mills and in a dusty workroom of a group of five willowing mills, a tea-packing plant and a pipe tobacco factory. The concentration of microbes cultured on endoagar plates were found to correlate with byssinosis prevalence (r greater than 0.95, P less than 0.001). The concentration of nutrient agar microbes correlated with prevalence less well (r greater than 0.77, P less than 0.01) and that of fungi and endotoxins not at all.


Parallel Headspace Extraction onto Etched Sorbent Sheets Prior to Ambient-Ionization Mass Spectrometry for Automated, Trace-Level Volatile Analyses.
Headspace (HS) extraction and preconcentration of volatiles by solid-phase microextraction (SPME) can improve the sensitivity and selectivity of ambient ionization-mass spectrometry approaches like direct analysis in real time (DART), but previous approaches to HS-SPME-DART-MS have been challenging to automate. This report describes the production of inexpensive, reusable solid-phase mesh-enhanced sorption from headspace (SPMESH) sheets by laser-etching mesh patterns into poly(dimethylsiloxane) (PDMS) sheets. Parallel headspace extraction of volatiles from multiple samples can be achieved by positioning the SPMESH sheets over multiwell plates and then attaching to a positioning stage for automated DART-MS quantitation. Using three representative odorants (3-isobutyl-2-methoxypyrazine, linalool, and methyl anthranilate), we achieved μg/L-ng/L detection limits with SPMESH-DART-MS, with the DART-MS step requiring only 17 min for 24 samples. Acceptable repeatability (24% or less day-to-day variation) and excellent recovery from a grape matrix (99-106%) could be achieved. Through use of a Teflon gasket and stainless steel spacers, cross-contamination between the headspaces of adjacent wells could be limited to roughly 1%. Optimum SPMESH extraction and desorption parameters were determined by response surface methodology. In summary, sheet-based SPMESH provides a sensitive, readily automated approach for coupling with DART-MS and achieving high-throughput trace-level volatile analyses.


Evaluation of the efficacy of topically administered imidacloprid + pyriproxyfen and orally administered spinosad against cat fleas (Ctenocephalides felis): Impact of treated dogs on flea life stages in a simulated home environment.
Cat fleas, Ctenocephalides felis, are one of the most common ectoparasites infesting dogs and their environments. This study evaluated the efficacy of imidacloprid + pyriproxyfen (PPF) (Advantage® II for Dogs) and spinosad (Comfortis®) against established C. felis populations in dogs' simulated home environments. Thirty Beagle dogs were randomly assigned to three groups of 10 dogs each and treated twice (Study Days 0 and 28) with imidacloprid + PPF, spinosad tablets, or a negative control (untreated). Dogs were housed individually in controlled simulated home environments capable of supporting the flea life cycle. Flea infestations were established in these environments by infesting each dog with 100 adult cat fleas on Study Days -21, -16 and 1. The impact of the treatments on fleas in the dogs' environments were assessed by collecting floor mat samples from each simulated home environment, incubating them for 32 days, and counting the number of emerging adult fleas. On Study Days 7, 14, 21, 28, 35, 42, 49 and 56, after collection of the cocoa matting samples, each dog was infested with an additional 5 ± 1 fleas to maintain the environmental infestations. Flea comb counts on dogs were conducted on Study Days 0 (pretreatment) and 63. From Study Days 7-28, flea infestations in the imidacloprid + PPF environments were significantly lower (p < 0.03) than those in the spinosad environments. Following the second treatment, flea infestations in all the imidacloprid + PPF environments fell to zero for the remainder of the study. In contrast, flea infestations persisted in some of the spinosad environments through the study's end.On Study Day 63 all 10 dogs treated with imidacloprid + PPF were flea free, while only one of the 10 spinosad treated dogs was flea free. Flea counts on the other 9 spinosad treated dogs ranged from 3 to 46 fleas/dog (geometric mean = 8.6). A mean of 405 adult fleas/animal were recovered from the control dogs on Study Day 63. Flea infestations in environments of dogs treated with imidacloprid + PPF declined more rapidly than in those containing dogs treated with spinosad. Flea infestations were completely eliminated by Study Day 56 in environments of dogs treated with imidacloprid + PPF, but persisted through the study's end in some of environments of dogs treated with spinosad.


Effects of simvastatin and fenofibrate on butyrylcholinesterase activity in the brain, plasma, and liver of normolipidemic and hyperlipidemic rats.
The study objective was to test the hypothesis that simvastatin and fenofibrate should cause an increase in butyrylcholinesterase (BuChE) activity not only in the plasma and liver but also in the brain of normolipidemic and hyperlipidemic rats. Catalytic enzyme activity was measured using acetylthiocholine (ATCh) and butyrylthiocholine (BTCh) as substrates. Normolipidemic and hyperlipidemic rats were divided in four groups receiving 50 mg/kg of simvastatin a day or 30 mg/kg of fenofibrate a day for three weeks and three control groups receiving saline. Simvastatin and fenofibrate caused an increase in brain BuChE activity in both normo- and hyperlipidemic rats regardless of the substrate. The increase with BTCh as substrate was significant and practically the same in normolipidemic and hyperlipidemic rats after simvastatin treatment (14-17% vs controls). Simvastatin and fenofibrate also increased liver and plasma BuChE activity in both normolipidemic and hyperlipidemic rats regardless of the substrate. In most cases the increase was significant. Considering the important role of BuChE in cholinergic transmission as well as its pharmacological function, it is necessary to continue investigations of the effects of lipid-lowering drugs on BuChE activity.


Photorhabdus luminescens subsp. noenieputensis subsp. nov., a symbiotic bacterium associated with a novel Heterorhabditis species related to Heterorhabditis indica.
The bacterial symbiont AM7(T), isolated from a novel entomopathogenic nematode species of the genus Heterorhabditis, displays the main phenotypic traits of the genus Photorhabdus and is highly pathogenic to Galleria mellonella. Phylogenetic analysis based on a multigene approach (16S rRNA, recA, gyrB, dnaN, gltX and infB) confirmed the classification of isolate AM7(T) within the species Photorhabdus luminescens and revealed its close relatedness to Photorhabdus luminescens subsp. caribbeanensis, P. luminescens subsp. akhurstii and P. luminescens subsp. hainanensis. The five concatenated protein-encoding sequences (4197 nt) of strain AM7(T) revealed 95.8, 95.4 and 94.9 % nucleotide identity to sequences of P. luminescens subsp. caribbeanensis HG29(T), P. luminescens subsp. akhurstii FRG04(T) and P. luminescens subsp. hainanensis C8404(T), respectively. These identity values are less than the threshold of 97 % proposed for classification within one of the existing subspecies of P. luminescens. Unlike other strains described for P. luminescens, strain AM7(T) produces acid from adonitol, sorbitol and xylitol, assimilates xylitol and has no lipase activity on medium containing Tween 20 or 60. Strain AM7(T) is differentiated from P. luminescens subsp. caribbeanensis by the assimilation of N-acetylglucosamine and the absence of haemolytic activity. Unlike P. luminescens subsp. akhurstii, strain AM7(T) does not assimilate mannitol, and it is distinguished from P. luminescens subsp. hainanensis by the assimilation of trehalose and citrate, the inability to produce indole from tryptophan and the presence of acetoin production and urease activity. Strain AM7(T) ( = ATCC BAA-2407(T) = DSM 25462(T)) belongs to a novel subspecies, and is proposed as the type strain of Photorhabdus luminescens subsp. noenieputensis sp. nov.


Bicarbonate ion transport: a mechanism for the acidification of urine in the turtle.
The uricotelic turtle Pseudemys scripta acidifies the urine to a pH as low as 4 in the urinary bladder. Data in this report show that the mechanism of acidification in this bladder is the transport of bicarbonate ion from lumen to serosa, and that the temperature to which the turtles are adapted prior to the in vitro experiment largely determines the direction of the transmural carbon dioxide gradient observed. This temperature effect also serves to reconcile apparently disparate data that were previously reported. A new technique for the direct determination of the partial pressure of carbon dioxide was employed.


[Pemphigus vulgaris and benign cicatricial mucous membrane pemphigoid in the upper respiratory tract and esophagus].
Pemphigus vulgaris and benign cicatricial membrane pemphigoid are both autoimmune, blistering, dermatologic diseases characterised clinically by tense bullae on skin or on mucous membranes. Both diseases are rare, but very serious, associated with a high death rate (pemphigus) or high morbidity with cicatricial mucosal lesions (pemphigoid) if untreated. These diseases are discussed and two case stories mentioned where the primary focus was in the upper aerodigestive tract, which is very seldom. The otolaryngologist can make an important contribution to the early recognition, diagnosis, and management of these diseases. The biopsy must undergo immunofluorescence examination.