Patient-centred advice is effective in improving adherence to medicines.
To assess the effects of pharmacists giving advice to meet patients' needs after starting a new medicine for a chronic condition. A prospective health technology assessment including a randomised controlled trial of a pharmacist-delivered intervention to improve adherence using a centralised telephone service to patients at home in England. Patients were eligible for recruitment if they were receiving the first prescription for a newly prescribed medication for a chronic condition and were 75 or older or suffering from stroke, cardiovascular disease, asthma, diabetes or rheumatoid arthritis. Incidence of non-adherence, problems with the new medicine, beliefs about the new medicine, safety and usefulness of the interventions. Five hundred patients consented and were randomised. At 4-week follow-up, non-adherence was significantly lower in the intervention group compared to control (9% vs. 16%, P = 0.032). The number of patients reporting medicine-related problems was significantly lower in the intervention group compared to the control (23% vs. 34%, P = 0.021). Intervention group patients also had more positive beliefs about their new medicine, as shown by their higher score on the "necessity-concerns differential" (5.0 vs. 3.5, P = 0.007). The phone calls took a median of 12 min each. Most advice was judged by experts to be safe and helpful, and patients found it useful. Overall, these findings show benefits from pharmacists meeting patients' needs for information and advice on medicines, soon after starting treatment. While a substantially larger trial would be needed to confirm that the effect is real and sustained, these initial findings suggest the service may be safe and useful to patients.


Charge-free reverse wormlike micelles in nonaqueous media.
We report a facile method for the formation of charge-free reverse wormlike micelles in a nonionic surfactant/oil system without addition of water under ambient conditions. This route involves the addition of sucrose dioleate (SDO) to semidilute solutions of sucrose trioleate (STO) in hexadecane. A reverse wormlike micelle was possible to achieve only with ionic surfactants in which water and/or salts are fundamentally required to induce micellar growth so far. In this contribution, we have shown that less lipophilic nonionic surfactant SDO promotes one-dimensional growth to STO reverse micelles and leads to the formation of transient networks of viscoelastic reverse wormlike micelles. The zero-shear viscosity increases by ∼4 orders of magnitude, and it is the mixing fraction of SDO to STO that determines the viscosity growth. The structure and dynamics of the reverse micelles are confirmed by small-angle X-ray scattering (SAXS) and rheometry measurements.


Glucagon-like peptide-1 attenuates tumour necrosis factor-alpha-mediated induction of plasminogen [corrected] activator inhibitor-1 expression.
Glucagon-like peptide-1 (GLP-1) has been proposed as a target for treatment of type 2 diabetes. GLP-1 has also been demonstrated to improve endothelial cell dysfunction in diabetic patients. Elevated plasminogen activator inhibitor type-1 [corrected] (PAI-1) levels have been implicated in endothelial cell dysfunction. The effect of GLP-1 on PAI-1 expression in vascular endothelial cells has not been explored. In a spontaneously transformed human umbilical vein endothelial cell (HUVEC) line, C11-spontaneously transformed HUVEC (STH) and primary HUVEC cells, GLP-1 treatment, in the presence of a dipeptidyl peptidase IV inhibitor, attenuated induction of PAI-1 protein and mRNA expression by tumour necrosis factor-alpha (TNF-alpha). GLP-1 also inhibited the effect of TNF-alpha on a reporter gene construct harbouring the proximal PAI-1 promoter. In addition, GLP-1 attenuated TNF-alpha-mediated induction of Nur77 mRNA and TNF-alpha-mediated binding of nuclear proteins (NPs) to the PAI-1, Nur77, cis-acting response element nerve growth factor induced clone B response element (NBRE). GLP-1 treatment also inhibited TNF-alpha-mediated induction of Akt phosphorylation. Taken together, these observations suggest that GLP-1 inhibits TNF-alpha-mediated PAI-1 induction in vascular endothelial cells, and this effect may involve Akt-mediated signalling events and the modulation of Nur77 expression and NP binding to the PAI-1 NBRE.


Effects of velopharyngeal dysfunction on middle ear of repaired cleft palate patients.
Cleft palates are strongly associated with the development of otitis media due to the anatomic and functional defect of the soft palate musculature and the associated alterations of velopharyngeal muscle insertion on tubal cartilage, or even intrinsic alterations of the cartilage, which affects eustachian tube function. This study will assess velopharyngeal muscle adequacy after palatoplasty through videonasoendoscopy and verify if there is a correlation with otologic status. Transversal study. Otorhinolaryngology and cleft palate outpatient service of the Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil. Seventy-three patients with cleft palate or cleft lip and palate between the ages of 6 and 12 years who had already undergone palatoplasty. Videonasoendoscopy for evaluation of velopharyngeal function and videotoscopy to assess middle ear status. Severity scale for videonasoendoscopic and videotoscopic findings. There was no significant correlation between the videonasoendoscopic and the videotoscopic scores in the population studied. Intrinsic defects of the eustachian tube cartilage and of the insertion of the velopharyngeal muscles seem to contribute to the evolution of otitis media in patients with cleft palate, in addition to the actual defect of the soft palate. There was no correlation between the severity of the otoscopic findings and the degree of velopharyngeal dysfunction.


Crystallization Behavior of Solution-Processed CIGSe Thin Film Semiconductor by Stepwise Annealing Process.
CuIn(x)Ga1-xSe2 (CIGS) thin films were prepared by a solution-based CuInGa (CIG) precursor- selenization process. First, we investigated the effect of selenization temperature on the formation of polycrystalline CIGS and grain growth. The CIG precursor films were selenized using a two-step process to investigate the reaction of Se and CIG precursors during the formation of CIGS thin films. Depending on the temperature in the 1st step of the selenization process, the CIG precursor forms a different intermediate phase between the single phase to ternary phase such as Cu, Se, CuSe, InSe, and CuInSe2. In addition, the intermediate phase exerts a significant influence on the final phase obtained after the 2nd step of the selenization process, particularly with regard to characteristics such as polycrystalline structure and grain growth in the CIGS films. The photoelectron conversion efficiency of devices prepared using CIGS thin films was approximately 1.59-2.75%.


Piezoelectric control of needle-free transdermal drug delivery.
Transdermal drug delivery occurs primarily through hypodermic needle injections, which cause pain, require a trained administrator, and may contribute to the spread of disease. With the growing number of pharmaceutical therapies requiring transdermal delivery, an effective, safe, and simple needle-free alternative is needed. We present and characterize a needle-free jet injector that employs a piezoelectric actuator to accelerate a micron-scale stream of fluid (40-130 microm diameter) to velocities sufficient for skin penetration and drug delivery (50-160 m/s). Existing jet injectors, powered by compressed springs and gases, are not widely used due to painful injections and poor reliability in skin penetration depth and dose. In contrast, our device offers electronic control of the actuator expansion rate, resulting in direct control of jet velocity and thus the potential for more precise injections. We apply a simple fluid-dynamic model to predict the device response to actuator expansion. Further, we demonstrate that injection parameters including expelled volume, jet pressure, and penetration depth in soft materials vary with actuator expansion rate, but are highly coupled. Finally, we discuss how electronically-controlled jet injectors may enable the decoupling of injection parameters such as penetration depth and dose, improving the reliability of needle-free transdermal drug delivery.


Increase in urinary purines and pyrimidines in patients with methylmalonic aciduria combined with homocystinuria.
Methylmalonic aciduria combined with homocystinuria (MMA-HC) is the biochemical trait of a metabolic disorder resulting from impaired conversion of dietary cobalamin (cbl, or vitamin B12) to its two metabolically active forms. Effects on urinary purine and pyrimidine levels have not been described for this condition. Urine samples were collected from three patients with methylmalonic aciduria combined with homocystinuria and from 70 healthy subjects. Urinary purine and pyrimidine levels were quantitated by the use of LC/UV-Vis and LC/ESI/MS. Higher urine levels of pyrimidines were detected with both methods in patients compared to controls. Methylmalonic aciduria with homocystinuria is due to deficiency of the enzyme, cobalamin reductase. The enzyme defect leads to altered hepatic metabolism, which appears to modify circulating pyrimidine levels.


Context and implementation of advanced nursing practice in two countries: An exploratory qualitative comparative study.
The complexity and difficulties involved in the development and implementation of health innovations, such as advanced practice nursing roles, result in slow and sporadic international acceptance. To manage this complexity, it is advisable to deepen understanding of the context in which these innovation processes take place. However, there is little research specifically concerned with contextual factors that influence the implementation of advanced practice nursing roles. To integrate results and develop a comprehensive understanding of the contextual factors that influence the development and implementation of advanced practice nursing in two countries, Canada and Spain. The research method used was qualitative, descriptive, and explanatory. Different qualitative methods, a novel data-collection process, and perspectives from participants in various professional groups were used to triangulate the findings from both settings. Participants with diverse perspectives on practice, organization, and health and regulatory environments were engaged to participate in semistructured focus groups in Catalonia and individual interviews in Quebec. Data gathered were to provide information on a variety of context dimensions: understanding of advanced practice nursing; perceived needs to develop the role; and perceived barriers and facilitators present in the Catalan and Quebec contexts. Thematic analysis was carried out based on the theoretical proposals from the framework and triangulated for both sides. Thirty interviews were conducted in Quebec and 44 in Catalonia. Integration of findings reflected a vast predominance of convergent themes despite differences in context and population characteristics. The study identified common and divergent contextual factors in advanced practice development and implementation in these settings. The same perceived barriers and facilitators were prominent almost evenly across all groups, although organizational and environmental themes were the most coded and discussed during interviews. Understanding contextual factors will ultimately allow better understanding of complex phenomena in health care. Further reporting of contextual factors that influence the development and implementation of advanced practice nursing roles in other countries is required to compare innovative processes.


Ca2+ Regulation of Cav3.3 T-type Ca2+ Channel Is Mediated by Calmodulin.
Calcium-dependent inactivation of high voltage-activated Ca2+ channels plays a crucial role in limiting rises in intracellular calcium (Ca2+i). A key mediator of these effects is calmodulin, which has been found to bind the C-terminus of the pore-forming α subunit. In contrast, little is known about how Ca2+i can regulate low voltage-activated T-type Ca2+ channels. Using whole cell patch clamp, we examined the biophysical properties of Ca2+ current through the three T-type Ca2+ channel isoforms, Cav3.1, Cav3.2, or Cav3.3, comparing internal solutions containing 27 nM and l μM free Ca2+ Both activation and inactivation kinetics of Cav3.3 current in l μM Ca2+i solution were more rapid than those in 27 nM Ca2+i solution. In addition, both activation and steady-state inactivation curves of Cav3.3 were negatively shifted in the higher Ca2+i solution. In contrast, the biophysical properties of Cav3.1 and Cav3.2 isoforms were not significantly different between the two internal solutions. Overexpression of CaM1234 (a calmodulin mutant that doesn't bind Ca2+) occluded the effects of l μM Ca2+i on Cav3.3, implying that CaM is involved in the Ca2+i regulation effects on Cav3.3. Yeast two-hybrid screening and co-immunoprecipitation experiments revealed a direct interaction of CaM with the carboxyl terminus of Cav3.3. Taken together, our results suggest that Cav3.3 T-type channel is potently regulated by Ca2+i via interaction of Ca2+/CaM with the carboxyl terminus of Cav3.3.


Tobacco cessation and youth: the feasibility of brief office interventions for adolescents.
The prevalence of tobacco use among adolescents remains high and the great majority of adult smokers begin smoking prior to the age of 18. While there have been a number of primary prevention projects in communities and schools, less attention has been given to smoking cessation for adolescents. This paper reviews the literature on the theory and practice of cessation as applicable to adolescents. The relevant literature was culled from a MEDLINE search and supplemented with secondary searches from those articles. There have been few studies on brief interventions for adolescent smoking cessation in health care settings. However, there are several models for smoking cessation that are either applicable to or designed for adolescents. Pharmacologic treatments are also beginning to be used. There is a great need for the development and evaluation of models for adolescent smoking cessation in health care settings. Recent developments, however, give cause for optimism in helping adolescent smokers in tobacco cessation.


The complete mitochondrial genome of Channa marulius (Perciformes: Channidae: Channa).
The traditional polymerase chain reaction method was employed to obtain the complete mitochondrial genome of Channa marulius from Pakistan. The mitogenome was determined to be 16,569 bp in length. It contains 13 protein-coding genes, 2 rRNAs and 22 tRNAs. This is the first report on the complete mitogenome sequence of C. marulius.


An in vitro effect of propolis on adult worms of Fasciola gigantica.
The effect of Siwa propolis on adult flukes was evaluated using scanning electron microcopy. It gave an overview of the surface architecture of the tegument of Fasciola gigantica apical cone. The base of the spines appeared to be "flaking off" and showed severe blebbing after 24h incubation with 10 micro/ml propolis. This swelling became so sever and the spines were barely visible, on increasing the concentration to 20 micro/ml. Besides, there were many large blebs on the apical cone, a number of which appeared to have burst, causing lesions and the tegument was marked by a number of pits caused by the loss of spines. With the higher concentration of 30 micro/ml, erosion of the surface had occurred to such extent that no tegument remained, only a mass of fibrous structures. The tegumental changes occurred following incubation in propolis were compared with those observed with triclabendazole (TCBZ) "Fasinex" because of its high efficacy against both mature and immature flukes.


Quasi-equilibria in reduced Liouville spaces.
The quasi-equilibrium behaviour of isolated nuclear spin systems in full and reduced Liouville spaces is discussed. We focus in particular on the reduced Liouville spaces used in the low-order correlations in Liouville space (LCL) simulation method, a restricted-spin-space approach to efficiently modelling the dynamics of large networks of strongly coupled spins. General numerical methods for the calculation of quasi-equilibrium expectation values of observables in Liouville space are presented. In particular, we treat the cases of a time-independent Hamiltonian, a time-periodic Hamiltonian (with and without stroboscopic sampling) and powder averaging. These quasi-equilibrium calculation methods are applied to the example case of spin diffusion in solid-state nuclear magnetic resonance. We show that there are marked differences between the quasi-equilibrium behaviour of spin systems in the full and reduced spaces. These differences are particularly interesting in the time-periodic-Hamiltonian case, where simulations carried out in the reduced space demonstrate ergodic behaviour even for small spins systems (as few as five homonuclei). The implications of this ergodic property on the success of the LCL method in modelling the dynamics of spin diffusion in magic-angle spinning experiments of powders is discussed.


N-glucuronidation catalyzed by UGT1A4 and UGT2B10 in human liver microsomes: Assay optimization and substrate identification.
N-glucuronidation is an important pathway for metabolism and disposition of tertiary amines in humans. This reaction is mainly catalyzed by the enzymes UGT1A4 and UGT2B10. However, the metabolic patterns of UGT1A4- and UGT2B10-mediated N-glucuronidation are not fully clear. In this study, we first optimized in vitro reaction conditions for N-glucuronidation by using specific substrates (i.e., trifluoperazine for UGT1A4, cotinine and amitriptyline for UGT2B10). Furthermore, we found that hepatic N-glucuronidation showed significant species differences. In addition, UGT1A4 and UGT2B10 were primarily responsible for N-glucuronidation of many tertiary amines, including asenapine, loxapine, clozapine, chlorpromazine, dothiepin, doxepin, mirtazapine, mianserin, chlorcyclizine, cyclizine, promethazine, cyclobenzaprine, imatinib, retrorsine, strychnine and brucine. In conclusion, this study provides an in vitro assay system for evaluating N-glucuronidation of amines. Also, UGT1A4- and UGT2B10-mediated N-glucuronidation might play significant roles in metabolism and detoxification of tertiary amines in humans.


QSAR study of phosphodiesterase inhibitory activity of imidazo[2,1-b]-quinazolines: active site analysis.
Published c-AMP phosphodiesterase inhibitory activities of 7-substituted-1,2,3,5-tetrahydro-2-oxoimidazo[2,1-b]quinazolines are used in a QSAR study to analyse a proposed model of the c-AMP PDE (type IV) active site. Based on the regression equations involving hydrophobic parameters and activities, additional subsites G1 and G2 are identified in the secondary binding region G, and steric hydrophobic tolerance at these subsites is discussed.


Analysis of phenolic constituents of biological interest in red wines by high-performance liquid chromatography.
We describe a reversed-phase HPLC method that uses gradient elution and diode array detection to determine four biologically active phenolic constituents of red wines: gallic acid, trans-resveratrol, quercetin and rutin. The method permits direct injection without sample pre-treatment. ODS Hypersil served as the stationary phase; the gradient was formed by acetic acid, methanol, and water. Each analysis required an equilibration period of 10 min and a run time of 50 min for completion. Previously, total phenols were analysed according to the Folin-Ciocalteu method, using gallic acid as the standard, and the results are given as gallic acid equivalent.


Two new variants of the lipocalin allergen Bos d 2.
Allergens from various sources have been shown to comprise several isoforms. In the present study, a series of chromatographic steps was carried out to separate the lipocalin allergen Bos d 2 isoforms present in cow dander. Subsequent HPLC-MS-MS analyses revealed two new Bos d 2 variants. In one of the proteins, tyrosine (Y83) was substituted by aspartic acid, and in the other protein valine (V102) was replaced by alanine. We propose the three Bos d 2 variants be named as Bos d 2.0101 (previously sequenced Bos d 2), Bos d 2.0102 and Bos d 2.0103. Our results suggest that molecular polymorphism is a common property among lipocalin allergens. Since allergen isoforms may show variation in their IgE binding and/or T-cell reactivity, all of the many allergen forms should be taken into account when planning preparations for immunotherapy.


Clustering of risk factors in parents of patients with type 1 diabetes and nephropathy.
To assess the impact of parental risk factors for diabetic nephropathy. This cross-sectional study included 2,355 type 1 diabetic patients from the FinnDiane (Finnish Diabetic Nephropathy) study. Diabetic nephropathy was defined as macroalbuminuria (urinary albumin excretion rate >200 microg/min or >300 mg/24 h) or end-stage renal disease. Information was available from 4,676 parents. Parental scores were calculated based on the number of various traits in the parents. Patients with diabetic nephropathy, compared with those without diabetic nephropathy, had a higher prevalence of maternal (41 vs. 35%, P = 0.046) and parental (62 vs. 55%, P = 0.044) hypertension, maternal stroke (7.6 vs. 5.1%, P = 0.044), and maternal (1.4 vs. 0.7%, P = 0.058) and parental (4.3 vs. 2.9%, P = 0.030) type 1 diabetes. If both, compared with none, of the parents had hypertension, the adjusted odds ratio (OR) for diabetic nephropathy in offspring was 1.56 (95% CI 1.13-2.15). The adjusted OR for diabetic nephropathy was 2.13 (1.36-3.33) for the parental hypertension-diabetes score (3-4 vs. 0 points) and 2.13 (1.37-3.33) for the parental hypertension-cardiovascular disease (CVD)-diabetes score (4-6 vs. 0 points). Fathers of patients with diabetic nephropathy, compared with those without diabetic nephropathy, had reduced overall survival (log-rank P = 0.04) and reduced cardiovascular survival (log-rank P = 0.03). A cluster of parental hypertension, CVD, and diabetes is associated with diabetic nephropathy in type 1 diabetes, as is paternal mortality.


Hippocampal dysfunction during aging II: deficits on the radial-arm maze.
Middle-aged and aged rats received dorsal hippocampal lesions before performance was evaluated on the radial-arm maze. The maze task contained simultaneous spatial working memory and visually cued reference memory components. Both middle-aged and aged rats that received lesions committed more errors of both types than sham-operated rats. Moreover, an age-related deficit was found for working and reference memory errors. After 14 sessions of training, a probe session revealed that: (a) middle-aged sham rats relied on spatial cues, (b) middle-aged lesioned rats employed the visual cues at the ends of the maze arms, (c) aged sham rats relied predominately on spatial information, (d) aged lesioned rats could not use spatial information or the visual cues at the ends of the maze arms. The additive effect of lesion and age suggests continued reliance on the hippocampus despite age-related deficits in its functioning. These data are suggestive of reduction in flexible cue utilization during aging, resulting paradoxically in more dependence on the hippocampus for aged rats than younger animals.


Molecular cytogenetic characterization of del(7q) in two uterine leiomyoma-derived cell lines.
Uterine leiomyoma cytogenetically exhibits at least six chromosomally abnormal subgroups. The largest subgroup is characterized by deletions of the long arm of chromosome 7. Few molecular and fluorescence in situ hybridization data are available that have aimed at a better definition of the lesion. Here, we report the results of a partial molecular cytogenetic characterization of two del(7q) chromosomes that were derived from cell lines established from two uterine leiomyomas with del(7)(q22q32). By using a large series of ordered 7q markers, we were able to identify the most proximal and the most distal conserved markers, which delineate the size of the deletion and which allow for a more targeted approach to the nature and function of genes that are possibly relevant for the pathogenesis of the disorder.


Eye tracking technology in sports-related concussion: a systematic review and meta-analysis.
The development of objective quantitative tools for the assessment and monitoring of sports-related concussion is critical. Eye tracking is a novel tool that may provide suitable metrics. The aim of this review was to appraise current evidence for the use of eye tracking technology in sports-related concussion assessment and monitoring. A systematic literature review was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A search was run using Google Scholar, Microsoft Academic and PubMed for literature published between January 1980 and May 2018. Included were empirical research studies in English where at least 50% of the research participants were athletes, the participants were individuals with a diagnosis of concussion, and eye movements were measured using an eye tracking device. This systematic review integrates 21 publications on sports-related concussion and eye tracking technology, nine of which also qualified for the meta-analysis. Overall, the literature reported significant findings for variables in each of the four classes of eye tracking measurements (movement, position, count, and latency). Meta-comparison was made for seven variables for the acute concussions (the difference between the concussed and the control groups was significant for all of them) and one variable for the latent concussions (the difference was not significant). Most saccadic and pursuit deficits may be missed during clinical examination, and therefore eye tracking technology may be a useful and sensitive screening and monitoring tool for sports-related concussions. The inconsistencies between the eye movement metrics and methodology still make inferences challenging; however, using tasks that are closely related to brain areas involved in executive functions (such as memory-based saccade or antisaccade tasks) in the acute injury phase holds promise in differentiating between athletes who have a concussion compared to those who do not.


Safety of nonsteroidal anti-inflammatory drugs in patients with cardiovascular risk.
The review presents current information on the role of NSAIDs in the development of cardiovascular disasters. The development of non-desirable cardiovascular effects and an increase in cardiovascular risk with the administration of NSAIDs, most experts assess in terms of the antagonistic effect on the platelet-vascular homeostasis of metabolites of COX-thromboxane A2 and prostaglandin I2 (prostacyclin). All the presented reviews confirming an increase in the risk of MI complications in the administration of NSAIDs, indicate the class-specificity of this undesirable effect, not homogeneous for different representatives of the group. Important clinical aspects of prescribing NSAIDs for patients with low and moderate cardiovascular risk are the clinical features of the patient and the individual set of risk factors for CVD. Such pharmacokinetic characteristics of NSAIDs as a short half-life, a high degree of binding to blood plasma albumins are indicative of greater safety of NSAIDs, but the final decision must be made based on the accumulated data of clinical trials and meta-analyzes. Keywords: nonsteroidal anti-inflammatory drugs, cardiovascular diseases, cardiovascular risk, lornoxicam, diclofenac sodium, thrombo-elastogram, myocardial infarction, stroke.


Peak retrograde flow: a novel predictor of persistent, progressive and new onset asymmetry in adolescent varicocele.
The major indication for adolescent left varicocelectomy is testicular asymmetry. However, a period of observation is often recommended preoperatively to determine if the asymmetry resolves, persists or progresses. We investigated whether varicocele grade or the duplex Doppler ultrasound measurements of peak retrograde flow and mean vein diameter could be used as predictors of persistent, progressive or new onset asymmetry. Only patients with left varicoceles who had undergone at least 2 duplex Doppler ultrasounds without intervening surgery were included in the study. Grade of varicocele, peak retrograde flow and mean vein diameter were analyzed as possible determinants of catch-up growth, or persistent or new onset asymmetry. A total of 77 patients (mean age 14.3 years, range 9 to 20) were identified with a mean observation period of 13.2 months. Of the patients 50 (65%) had 10% or greater asymmetry at the first measurement. Of patients with initial 20% or greater asymmetry 71% had persistent or worsening asymmetry on followup evaluation. All 14 patients with the combination of an initial peak retrograde flow 38 cm per second or greater and 20% or greater asymmetry had progressive asymmetry on followup examination. Peak retrograde flow was the only significant parameter of predictive value for persistent or worsening asymmetry (p = 0.032). Peak retrograde flow can serve as a valuable tool in predicting persistent, progressive and new onset asymmetry. Varicoceles associated with a peak retrograde flow of 38 cm per second or greater and 20% or greater asymmetry should be considered for varicocelectomy at initial presentation. Patients with peak retrograde flow greater than 30 cm per second need to be monitored carefully. Those with peak retrograde flow less than 30 cm per second are less likely to require surgery.


Outcomes of total alloplastic replacement with periarticular autogenous fat grafting for management of reankylosis of the temporomandibular joint.
The purpose of this investigation was to review the subjective, objective, and quality of life outcomes in a group of temporomandibular joint (TMJ) reankylosis patients managed by total alloplastic replacement surgery with a patient fitted system augmented with periarticular autogenous fat grafts to prevent the reformation of heterotopic bone. A review of the literature regarding the use of autogenous fat as evidence for its efficacy in such cases is also presented. All 20 TMJ reankylosis patients (4 males, 16 females) who had undergone total TMJ replacement with the TMJ Concepts (Ventura, CA) Patient-Fitted Total TMJ Prosthesis System were studied. Thirteen patients had bilateral, 7 unilateral for a total of 33 joint replacements. All patients had autogenous fat harvested from the abdomen and grafted around the articulating portion of the prostheses at implantation. The patients' subjective variable outcomes of TMJ pain, mandibular function, diet consistency, quality of life since the reconstruction, and objective variable of maximal interincisal opening were obtained in a detailed questionnaire and follow-up phone calls. Analysis of the subjective outcomes data showed improvement in reported pain, increased jaw function, and diet consistency. Further, a significant number of these patients reported improvement in their quality of life after surgery. Analysis of the objective outcomes data showed a significant increase in the maximum interincisal opening postreplacement that was maintained. In the patients followed over the course of this study, total alloplastic replacement with a patient-fitted prosthesis seemed to provide a safe and effective management for reankylosis of the TMJ. Autogenous fat transplantation seems to be a useful adjunct as its use seems to minimize the recurrence of joint heterotopic calcification, consequently providing improved and consistent range of mandibular motion.


The Fear Survey Schedule as a measure of anxious arousal: evidence from ERPs.
Anxious arousal and anxious apprehension have been proposed to be two aspects of anxiety that are differentially lateralized. Two prior event-related potential (ERP) studies have found right-lateralized ERPs that correlate with scores on the Fear Survey Schedule (FSS) but not with the Spielberger State-Trait Anxiety Inventory (STAI) scores. This study attempts to replicate the findings of right-lateralization of FSS correlates using high-density ERPs (n=58). A spatial cueing task where emotional faces validly or invalidly cued targets was used. A right-lateralized posterior component (P296) greatest in amplitude for high FSS scores was found. This finding further supports the proposition that the FSS measures anxious arousal and that anxious arousal can be right-lateralized.


Water deprivation and subfornical organ activity in the pigeon a [14C]2-deoxyglucose study.
Following varying degrees of water deprivation (0, 24 and 72 h), functional activity in the subfornical organ (SFO) of pigeons was measured using the [14C]2-deoxyglucose method. Increasing levels of water deprivation produced a significant increase in glucose uptake in SFO. The magnitude of the effect was systematically correlated with morphologically defined SFO subdivisions.


Extending the boundaries of life: implications for practice.
Recent advances in medical technology are confounding traditional definitions of life and death and even of who is a person. This article considers the implications of these developments for social workers and presents a technique for helping clients make decisions in the face of ethical dilemmas created by new medical technologies.


Dexamethasone enhances the activity of rSP-C surfactant but not of exosurf in a rat model of the acute lung injury.
The possible enhancement of surfactant activity by pretreatment with a glucocorticosteroid (dexamethasone) was investigated in a rat lung lavage model of acute lung injury. Animals received a dose of dexamethasone (10 mg/kg i.p.) prior to the protein-free surfactant preparation Exosurf (pure phospholipids containing surfactant, Wellcome GmbH, Burgwedel, Germany) and a rSP-C based surfactant, respectively. Both surfactants were intratracheally instilled at doses of 25 and 100 mg phospholipids per kg body weight and were compared with pretreatment with dexamethasone at each dose level. These groups were also compared with untreated controls and to pretreatment with dexamethasone alone with respect to improvements in oxygenation, to inhibition of infiltration of polymorphonuclear neutrophil leukocytes (PMNL) and to influence formation of hyaline membranes. Dexamethasone alone had no influence on the reduced PaO(2) but reduced the infiltration of PMNL and the formation of hyaline membranes. Dexamethasone improved the oxygenation at both doses of rSP-C surfactant. At the low dose of rSP-C surfactant there were additional effects detectable with regard to histopathologic improvements. In contrast, dexamethasone had no additional effect on oxygenation and formation of hyaline membranes when combined with Exosurf. Only the infiltration of PMNL was decreased by combined treatment with dexamethasone and Exosurf. The effect was comparable to that of pretreatment with dexamethasone alone. In this animal model, pretreatment with dexamethasone showed additional effects on rSP-C surfactant that were superior to each treatment alone. From the comparison of rSP-C surfactant with the synthetic surfactant preparation Exosurf, we conclude that the activity of Exosurf cannot be improved substantially by additional pretreatment with drugs like glucocorticosteroids.


[Atypical corneal changes in Ehlers-Danlos syndrome].
An unusual case of corneal thinning is reported. Corneal thinning and many mesodermal tissue abnormalities corresponding to Ehlers-Danlos syndrome were observed.


Cardiac output measurement in critical care patients: Thoracic Electrical Bioimpedance versus thermodilution.
Thoracic Electrical Bioimpedance (TEB) is a method for measuring cardiac performance which is noninvasive, continuous, has minimal technical requirements, and no patient risk. We used a commercially available TEB device to measure cardiac output in patients with thermodilution catheters in place. We compared the cardiac output measurements for the two modalities. We also compared the average hospital cost for initial cardiac assessment using the two techniques. The mean difference between the two cardiac output measurements was small (0.23 +/- 0.56) and not affected by the magnitude of the cardiac output readings. There was a strong correlation between COTD and COTEB (r = 0.91) and the regression slope was 0.91 with a Y intercept of 0.76. Cost analysis demonstrated that the use of TEB was approximately $600 less than thermodilution. Thoracic electrical bioimpedance measurement of cardiac output may offer a valuable alternative to the invasive measurement of the thermodilution catheter.


Knocking out salicylate biosynthesis genes in Mycobacterium smegmatis induces hypersensitivity to p-aminosalicylate (PAS).
Because of the emergence of strains of Mycobacterium tuberculosis resistant to first-line antituberculosis agents, one of the second-line drugs, p-aminosalicylate (PAS), has regained importance in the treatment of tuberculosis. The mode of action of PAS, however, remains controversial as to whether it inhibits mycobactin or folate biosynthesis. To unravel this, we have studied the effect of PAS on wild-type Mycobacterium smegmatis and its mutants (gene knockouts of the salicylate pathway -trpE2, entC and entD). The wild type had no sensitivity to PAS (MIC>400 μg mL(-1) ), whereas the mutants were hypersensitive, with 1 μg mL(-1) inhibiting growth. The sulphonamides, trimethoprim and dapsone, had little effect on the growth of either the mutants or the wild type. In addition, PAS at 0.5 μg mL(-1) increased the accumulation of salicylate with the wild type and mutants. These results support our hypothesis that PAS targets the conversion of salicylate to mycobactin, thus preventing iron acquisition from the host.


A kinesin is present at unique sertoli/spermatid adherens junctions in rat and mouse testes.
During spermatogenesis, spermatids undergo a "down and up" translocation event in the seminiferous epithelium. This event has been proposed to result from the movement of ectoplasmic specializations, which are formed in Sertoli cells at sites of adhesion to spermatids, along adjacent microtubule tracts. To test the hypothesis that a kinesin is associated with ectoplasmic specializations, we generated antibodies to conserved kinesin sequences and detected kinesins on fixed frozen testis sections and fixed seminiferous epithelial fragments. The antibodies reacted with ectoplasmic specializations related to spermatids, in addition to reacting with other structures in the epithelium known to contain kinesins. At the electron microscopy level, the antibodies reacted with the cytoplasmic face of the endoplasmic reticulum component of ectoplasmic specializations. Based on mRNA transcript screens using mouse GeneChip arrays of testis and Sertoli cells, we identified KIF20 as a candidate kinesin at ectoplasmic specializations. Antibodies generated against a peptide sequence unique to this kinesin reacted at ectoplasmic specializations in testis sections and epithelial fragments, as well as with the endoplasmic reticulum component of ectoplasmic specializations when analyzed by electron microscopy. The antibody reacted on Western blots with full-length KIF20. On Western blots of testis lysates, the antibody reacted with a protein that is not present in other tissues and which migrates at a higher molecular weight than that predicted for KIF20. Our results demonstrate that a kinesin is associated with apical ectoplasmic specializations in Sertoli cells and that the motor may be an isoform of KIF20.


Bowing, kneeling and 'prostration': athlete's collapse patterns during sudden cardiac arrhythmia/arrest on the field of play.
Sudden cardiac arrest (SCA) on the field of play remains one of the most tragic and challenging events for a team physician. Even with robust regular preparticipation cardiac screening we cannot prevent all cases of SCA. Ability to recognise imminent cardiac arrest occurring on the field of play remains an important step in managing this condition without delay. You Tube was searched for video clips clearly depicting the sequence of an athlete's collapse of cardiac origin. A pattern of collapse was subsequently analysed. 13 cases were available for public viewing on You Tube and demonstrated the final position of collapse. 12 collapses had full video footage of athlete's fall. All athletes were men. 84.6% (11) cases were from football (soccer). 15.4% (2) of cases were from martial arts. In 10 out of 12 cardiac event cases (83.3%) bowing and/or kneeling were followed by decubitus position. 58.3% (7) of cases demonstrated bowing at the beginning of collapse. 58.3% (7) cases had kneeling as an element of collapse. 61.5% (8 out of 13 cases) of casualties adopted position of 'prostration' (ie, prone) as final stage of collapse. When on the field of play, in the absence of head injury, athletes displaying bowing and/or kneeling positions followed by collapse should be assumed to have a life-threatening cardiac event. Final position of 'prostration' was adopted in over half of cardiogenic collapses. A sports medicine professional should bear this in mind and target his/her assessment and treatment accordingly. When attending such casualties, a defibrillator must be taken to the collapsed player.


Solution NMR structure of the TatA component of the twin-arginine protein transport system from gram-positive bacterium Bacillus subtilis.
The twin-arginine transport (Tat) system translocates folded proteins across the bacterial cytoplasmic or chloroplast thylakoid membrane of plants. The Tat system in most Gram-positive bacteria consists of two essential components, the TatA and TatC proteins. TatA is considered to be a bifunctional subunit, which can form a protein-conducting channel by self-oligomerization and can also participate in substrate recognition. However, the molecular mechanism underlying protein translocation remains elusive. Herein, we report the solution structure of the TatA(d) protein from Bacillus subtilis by NMR spectroscopy, the first structure of the Tat system at atomic resolution. TatA(d) shows an L-shaped structure formed by a transmembrane helix and an amphipathic helix, while the C-terminal tail is largely unstructured. Our results strongly support the postulated topology of TatA(d) in which the transmembrane helix is inserted into the lipid bilayer while the amphipathic helix lies at the membrane-water interface. Moreover, the structure of TatA(d) revealed the structural importance of several conserved residues at the hinge region, thus shedding new light on further elucidation of the protein transport mechanism of the Tat system.


A turtle cognition research demonstration enhances visitor engagement and keeper-animal relationships.
Environmental enrichment techniques present animals with cognitive challenges while providing them opportunities to make choices and exert control over their environment. In this way, cognitive research and training is enriching to animals and can be used as a form of enrichment in zoos and aquariums. Cognitive research demonstrations also provide an opportunity to enhance visitor experience, as well as foster interactions between animals and keepers. We investigated how cognitive research sessions involving eastern box turtles (Terrapene carolina carolina) at Disney's Animal Kingdom® impacted both the rate of visitors coming to the exhibit and the amount of time they spent engaged. Further, we used a questionnaire to assess the impact of keeper participation in these sessions on their relationships with and perceptions of the turtles. While visitation rate to the exhibit was not impacted, cognitive research sessions held visitor attention for longer than keeper interpretation or at times during which no keepers or researchers were present. We also found that keepers that had worked with the turtles for longer and keepers that regularly participated in cognitive research sessions reported stronger bonds with the turtles. Our research suggests that use of cognitive research and training demonstrations for guest viewing in zoos and aquariums may enhance visitor learning opportunities by increasing the amount of time they spend at the exhibit. Our study also provides evidence that participation in such demonstrations by zoo and aquarium professionals can be related to improved keeper-animal bonds, potentially resulting in better husbandry and enhanced animal welfare.


Microarray-based detection and expression analysis of extracellular matrix proteins in drug‑resistant ovarian cancer cell lines.
Ovarian cancer is the most lethal gynecological malignancy. Multiple drug resistance (MDR) development leads to resistance of cancer cells to chemotherapy. Microarray methods can provide information regarding new candidate genes that can play a role in resistance to cytostatic drugs. Extracellular matrix (ECM) can influence drug resistance by inhibiting the penetration of the drug into cancer tissue as well as increased apoptosis resistance. In the present study, we report changes in the ECM and related gene expression pattern in methotrexate-, cisplatin-, doxorubicin-, vincristine-, topotecan- and paclitaxel-resistant variants of the W1 ovarian cancer cell line. The resistant variants of the W1 cell line were generated by stepwise selection of cells with an increasing concentration of the indicated drugs. Affymetrix GeneChip® Human Genome U219 Array Strips were used for hybridizations. Independent t-tests were used to determinate the statistical significance of results. Genes whose expression levels were higher than the assumed threshold (upregulated, >5-fold and downregulated, <5-fold) were visualized using the scatter plot method, selected and listed in the tables. Among the investigated genes, expression of 24 genes increased, expression of 14 genes decreased and expression of three genes increased or decreased depending on the cell line. Among the increased genes, expression of 10 increased very significantly, >20-fold. These genes were: ITGB1BP3, COL3A1, COL5A2, COL15A1, TGFBI, DCN, LUM, MATN2, POSTN and EGFL6. The expression of seven genes decreased very significantly: ITGA1, COL1A2, LAMA2, GPC3, KRT23, VIT and HMCN1. The expression pattern of ECM and related genes provided the preliminary view into the role of ECM components in cytostatic drug resistance of cancer cells. The exact role of the investigated genes in drug resistance requires further investigation.


Past, present and future of the surgery of the sympathetics.
Surgery of the autonomic nervous system has been used during more than a hundred years for different indications. The trend is in both parasympathetic and sympathetic surgery towards less invasive and more reversible methods. Thus in gastroenterology the bactericides have displaced vagotomies, and in sweating and blushing more and more sophisticated and atraumatic methods have emerged to displace sympathectomies. Even vagal stimulation has come forward to compete with sympathetic ablations in some indications, like depression. The side effects, and especially the late manifestation of some side effects have also raised ethical discussions of the justification of this kind of life quality or life style surgery. In this review, different indications and methods are discussed in the light of future needs and ethical demands.


Comparative NMR study of A(n)-bulge loops in DNA duplexes: intrahelical stacking of A, A-A, and A-A-A bulge loops.
We have prepared a series of deoxyoligonucleotide duplexes of the sequence d(G-C-A-T-C-G-X-G-C-T-A-C-G).d(C-G-T-A-G-C-C-G-A-T-G-C), in which X represents either one (A), two (A-A), or three (A-A-A) unpaired adenine basis. Using two-dimensional proton and phosphorus NMR spectroscopy, we have characterized conformational features of these bulge-loop duplexes in solution. We find that Watson-Crick hydrogen bonding is intact for all 12 base pairs, including the GC bases that flank the bulge loop. Observation of NOE connectivities in both H2O and D2O allows us to unambiguously localize all of the bulged adenine residues to intrahelical positions within the duplex. This is in contrast to an earlier model for multiple-base bulge loops in DNA [Bhattacharyya, A., & Lilley, D. M. J. (1989) Nucleic Acids Res. 17, 6821-6840], in which all but the most 5' bulged base are looped out into solution. We find that insertion of two or three bases into the duplex results in the disruption of specific sequential NOEs for the base step across from the bulge loop site on the opposite strand. This disruption is characterized by a partial shearing apart of these bases, such that certain sequential NOEs for this base step are preserved. We observe a downfield-shifted phosphorus resonance, which we assign in the A-A-A bulge duplex to the 3' side of the last bulged adenine residue. Proton and phosphorus chemical shift trends within the An-bulge duplex series indicate that there is an additive effect on the structural perturbations caused by additional unpaired bases within the bulge loop. This finding parallels previous observations [Bhattacharyya, A., & Lilley, D. M. J. (1989) Nucleic Acids Res. 17, 6821-6840; Hsieh, C.-H., & Griffith, J. D. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 4833-4837] on the magnitude of the induced bending of DNA duplexes by multiple-base bulge loops.


Preoperative versus postoperative adjuvant radiotherapy for surgically curable carcinoma of the rectum and distal sigmoid colon.
From January 1979 to October 1986, 86 patients with surgically resectable adenocarcinoma of the rectum or rectosigmoid were treated with adjuvant radiotherapy consisting of preoperative 2,400 cGy (22 patients), preoperative 4,000 cGy (14 patients), "sandwich" technique (27 patients), and postoperative irradiation (23 patients). Average follow-up was 42.9 months. The local recurrence rate was 4.5%, 9.1%, 7.4%, and 34.8%, respectively. The distant metastasis rate was 18.2%, 18.2%, 7.4%, and 30.4%, respectively. Preoperative radiotherapy with adequate surgical resection appears more effective in reducing the incidence of local recurrence.


Self-Assembly of Large Gold Nanoparticles for Surface-Enhanced Raman Spectroscopy.
Performance of portable technologies from mobile phones to electric vehicles is currently limited by the energy density and lifetime of lithium batteries. Expanding the limits of battery technology requires in situ detection of trace components at electrode-electrolyte interphases. Surface-enhance Raman spectroscopy could satisfy this need if a robust and reproducible substrate were available. Gold nanoparticles (Au NPs) larger than 20 nm diameter are expected to greatly enhance Raman intensity if they can be assembled into ordered monolayers. A three-phase self-assembly method is presented that successfully results in ordered Au NP monolayers for particle diameters ranging from 13 to 90 nm. The monolayer structure and Raman enhancement factors (EFs) are reported for a model analyte, rhodamine, as well as the best performing polymer electrolyte salt, lithium bis(trifluoromethane)sulfonimide. Experimental EFs for the most part correlate with predictions based on monolayer geometry and with numerical simulations that identify local electromagnetic field enhancements. The EFs for the best performing Au NP monolayer are between 106 and 108 and give quantitative signal response when analyte concentration is changed.


Inspiratory on-switch evoked by stimulation of mesencephalic structures: a patterned response.
The effects of brief tetanic electrical stimulation (50 to 100 ms) of the mesencephalic central gray matter and reticular formation on the inspiratory "on-switch" mechanism were studied during expiration (E phase) in cats anaesthetized with urethan-chloralose. Stimulation during the E phase evoked powerful effects on the phrenic nerve discharge comprising (1) a primary response (Prim. R.) during the train; (2) a patterned response (Patt. R.) resembling that of the normal inspiratory (I) phase and lasting 170 to 1,000 ms. The patterned response corresponded to activation of the inspiratory on-switch (E-I switching) and appeared either immediately after the Prim. R. or within a latent period of 100 ms. The primary response was always obtained during the E phase whatever the stimulation intensity (0.1-1.0 mA). The patterned response was a function (a) of the stimulus time: the later the stimulus in the E phase, the longer the duration of the response; (b) of the stimulus intensity: with 1.0 mA current strength the response was obtained throughout the E phase; with weaker stimuli (0.4 to 0.5 mA) the response was always evoked by trains delivered early (0-300 ms) or late (1,000-1,800 ms) in the E phase; while it occurred irregularly to stimulation in the middle (300-1,000 ms) of the E phase. These results indicate that: (a) the system which promotes inspiration is progressively rather than abruptly depressed at the beginning of expiration, followed by a progressive inspiratory-promoting facilitation at the end of expiration; (b) the patterned response, mostly independent of the stimulus parameter, is not stereotyped and displays considerable plasticity.


MR imaging of renal neoplasms.
MR imaging has many advantages over other modalities in the detection and staging of renal neoplasms, because of its intrinsic high soft tissue contrast, direct multiplanar imaging capabilities, and the availability of a non-nephrotoxic, renally excreted contrast agent. The ongoing refinement of breath-hold imaging sequences will probably broaden the use of MR techniques in imaging renal neoplasms.


Mood Disorders and Down Syndrome.
Even clinical neuropsychiatrists who do not focus on mental illness and mental retardation may be intrigued by the subject of mood disorders in persons with Down syndrome. This article reviews the following subjects in persons with Down syndrome: epidemiology of major depression and bipolar disorder; clinical symptoms including "psychotoform," differential diagnosis of mood disorders, comorbid diagnoses, and treatment.


Results of clinical trials with ciprofloxacin in Italy.
The Authors report about the results of 23 clinical trials carried out in Italy with oral formulations of BAY o 9867 (ciprofloxacin) in the treatment of infections in various sites of the body. Altogether 644 patients were evaluated for therapeutic efficacy; positive clinical results were obtained in 95 to 100% of the treated patients, according to the site of the infection. The bacteriological examinations performed on 575 cases show eradication in 89.22%, eradication with relapse or reinfection in 2.26%, and persistence in 6.09%. Adverse reactions were observed in 38 out of 646 patients (5.89%); none of them, however, were severe or irreversible.


[Late results after nerve transplantation on the upper extremities].
The purpose of this retrospective study was to determine the influence of the type of injury, the time elapsed after the injury, the blood supply to the operation area, the size of the graft, and the applied treatment method on the late results. In the study period from 1985 through 2000, nerve transplantations had been performed in 281 patients. There were 204 men and 77 women. Reconstructions were applied on the median nerve in 59 patients, ulnar nerve in 48, median and ulnar nerves in 23, radial nerve in ten, and digital nerves in 141 patients. 188 patients presented for late follow-up (66.9%). Evaluation was made according to the Highet scheme. In patients with median nerve transplantation M(3) or better results were seen in 69%, with M(3) being 45.2%. S(3) or better was observed in 64.3%, with S(3) being 47.6%. In patients after ulnar nerve transplantation M(3) or better result was achieved in 56.8%, M(3) being 19%. S(3) or better result was seen in 32.4%, S(3) being 27%. In patients who underwent median and ulnar nerve transplantations M(3) or better result was seen in 36.8%, M(3) being 26.3%. S(3) was in 42.1%, while S(4) did not occur. In patients after radial nerve transplantation M(3) or better effect resulted in 87.5%, M(3) being 12.5%. In patients with digital nerve transplantation S(3) or better result occurred in 57.4 %, S(3) being 47.6%. The best result can be achieved with nerve suturing, performed as an optimum from all aspects. However, as far as the surgical technique is concerned, results of using interfascicular grafts are more advantageous than epineural nerve suture based on compromises. In ideal circumstances, transplantation of a nerve graft less than 2 cm is of the same value as a good primary suture. If a nerve graft is longer than 2 cm, and negative local factors are accumulating due to the type of injury, late results will gradually deteriorating. The final outcome definitely depends on the patient's age and the time elapsed from the injury to the operation.


Institutional violence and humanization in health: notes to debate.
This paper starts from humanization policies and the academic debate around them to reflect about institutional violence inside health services. Based on research on scientific publications in Collective Health, it was observed that violence in relationships between health professionals and users - which is at the core of the humanization's debate - is conceptualized as an excessive power in exercise of professional authority. Using Hannah Arendt thinking as theoretical contributions regarding the concepts of 'authority', 'power' and 'violence', our objective is to define and rethink these phenomena. Melting these reflections with the history of institutionalization of health in Brazil, and especially the changes in medical work during the twentieth century, we conclude that the problem of institutional violence on health services is not based on excess of authority and power of professionals, but rather in its opposite. When there is a vacuum of professional authority, and relationships between people do not happen through power relations, there is space for the phenomenon of violence.


An immunofluorescent study of alpha-fetoprotein. I. Its ontogenic development in human conceptus.
A development of alpha-fetoprotein-producing tissues was investigated in 52 cases of human conceptuses ranging from 2 to 7 months in gestation by a fluorescent antibody technique. It is synthesized in endodermal cells of the yolk sac, hepatocytes including the cells of large bile canaliculi, and some gland epithelial cells of the stomach, while its accumulation also occurs in mesenchymal cells of the yolk sac and Kupffer cells of the liver. A mode of its localization in individual tissues was described and possible explanation on the origin of its producers was discussed.


Together I Can! Joint Attention Boosts 3- to 4-Year-Olds' Performance in a Verbal False-Belief Test.
Effects of joint attention were addressed on 3- to 4-year-olds' performance in a verbal false-Belief Test (FBT), featuring the experimenter as co-watcher rather than narrator. In two experiments, children (N = 183) watched a filmed-FBT jointly with a test leader, disjointed from a test leader, or alone. Children attending jointly with a test leader were more likely to pass the FBT compared with normative data and to spontaneously recall information indicating false-belief understanding, suggesting that joint attention strengthens the plausibility of the FBT and renders plot-critical information more salient. In a third experiment (N = 59), results were replicated using a typical, image-based FBT. Overall findings highlight the profound impact of experimenter as social context in verbal FBTs, and link recall of specific story features to false-belief understanding.


Point-of-care ultrasound detection of acute scaphoid fracture.
In cases of traumatic wrist pain, emergency physicians must maintain a high index of suspicion for scaphoid fractures due to their potential for serious complications. A growing body of literature supports the use of point-of-care ultrasonography by emergency physicians in the evaluation of potential fractures. We report a case of a pediatric scaphoid fracture that was initially not visualized on x-ray and was subsequently detected using point-of-care ultrasound in the ED.


Bloodstream and non-invasive isolates of Candida glabrata have similar population structures and fluconazole susceptibilities.
We have compared multilocus sequence typing (MLST) and fluconazole susceptibility profiles of Candida glabrata bloodstream isolates obtained during active, population-based surveillance to those obtained from non-sterile sites of individuals with no evidence of fungal disease (i.e., non-invasive isolates) in the same US city during an overlapping time period. In each of the two populations, different proportions of the same six major sequence types (STs) encompassed 82% of the isolates. One ST was more prevalent in the candidemia population and two other STs were more prevalent in the non-invasive population, but the overall allelic frequencies within the groups suggested little, if any, genotypic diversity between them. Fluconazole susceptibility profiles of isolates from the patients in the two groups were not significantly different and were not associated with a particular sequence type. Our results support the hypothesis that C. glabrata strains causing bloodstream infections are genetically indistinguishable from those normally residing in/on the host, suggesting that relative pathogenicity may be closely tied to commensalism.


Polymorphism of the apolipoprotein B gene and blood lipid concentrations in Japanese and Caucasian population samples.
To examine whether a racial difference in apolipoprotein B (Apo B) gene polymorphism between Japanese and American Caucasians corresponds with the lower blood cholesterol concentrations in Japanese than in Americans, we examined the EcoRI polymorphism of the Apo B gene for 271 nonsmoking men and women aged 47-69 years in two population-based samples: rural Japanese living in Akita and Caucasians living in Minneapolis-St. Paul, Minnesota, USA. Mean values of serum cholesterol concentrations were significantly lower in Japanese than in Caucasians for both men and women (difference = 25-26 mg/dl). An allele-specific polymerase chain reaction was conducted to examine the Eco RI cutting site at the 12669 cDNA position of the Apo B gene. The allele R2 (absence of the cutting site) has been associated with lower cholesterol concentrations in two previous studies. The frequency of the R2 allele was 6% for Japanese and 17% for Caucasians (P < 0.001), and this race difference in allele frequency was identical for men and women. After controlling for age, body mass index, alcohol intake, and for women, menopausal status and hormone replacement therapy, the adjusted mean (SE) cholesterol level among Japanese was 204 (3) mg/dl for genotype R1R1 and 185 (7) mg/dl for genotype R1R2 or R2R2 combined (P = 0.01). The respective mean values among Caucasians were 224(5) mg/dl and 232(7) mg/dl (P = 0.36). The polymorphism had a similar effect on total cholesterol concentrations for both men and women. The observed lower prevalence of the R2 allele in Japanese than in Caucasians indicates that this variation in the Apo B gene does not explain the racial difference in blood cholesterol concentrations.


Muscle spindle activity in man during standing.
In standing human subjects, muscle spindle activity was recorded from peroneal nerve fascicles innervating anterior compartment muscles. Provided that the receptor-bearing muscle remained relaxed, the basal activity and responses to stretch seen in multi-unit and single unit afferent recordings were stable and not altered by eye-closures of assistance to balance. The discharge frequencies of single afferent fibres were similar to those recorded at comparable muscle lengths in relaxed reclining subjects. By analogy to findings in reclining subjects, these results suggest that, during standing, the background fusimotor drive to relaxed muscles is neglibible. Backward body sway can induce a sway-stabilizing reflex contraction in the muscles of the anterior compartment. Such reflex contractions were accompanied by increased muscle spindle activity, the intensity of which appeared to be related to the intensity of the skeletomotor contraction. When balance was assisted by holding a support, swaying movements of similar or greater amplitude and velocity did not produce reflex activity, and the spindle response was of low frequency. It is concluded that the sway-stabilizing reflex contraction operates in alpha-gamma linkage, and that these contractions are not generated by segmental stretch reflex pathways.


Serum amylase and macroamylase in patients with systemic lupus erythematosus.
We measured serum amylase and macroamylase activity in 25 patients with systemic lupus erythematosus (SLE) and 15 controls. The mean (+/- SD) for SLE was greater than for the controls (161 +/- 71.8 versus 116 +/- 38.8 units/dl). Five patients (20%) had elevated amylase and 6 (25%) had a macroamylase present. None of the controls had amylase elevation or macroamylase. None of the patients had abdominal pain and there was no observable correlation of amylase activity with disease activity, drugs, or renal function. Elevation of serum amylase in SLE without pancreatitis is frequent, as is the presence of macroamylase. Autoantibodies to this serum enzyme may be frequent in SLE.


Organ-confined prostate carcinoma radiation brachytherapy compared with external either photon- or hadron-beam radiation therapy. Just a short up-to-date.
Both low dose rate (LDR) permanent either 1251 or 103Pd seed implant and high dose rate (HDR) 1921r temporary implant are an excellent way to release high dose of ionizing radiations to cancerous lesions while significantly sparing the surrounding healthy tissues. Therefore, the radiation brachytherapy, among the established treatment options of organ-confined prostate carcinoma--interstitial radiofrequency, high intensity focused ultrasound, cryotherapy--has gained large acceptance in the last decades. The LDR permanent interstitial radioactive seed implantation is often used as monotherapy for low risk prostate carcinoma whereas the HDR temporary implant may useful to treat intermediate-to-high risk prostate tumors as a radiation boost to combined external beam radiation therapy (EBRT). On the other hand, with recent refinement of EBRT techniques--either three-dimensional conformal- or intensity-modulated radiotherapy, cyber-knife radiosurgery with even 4D-high resolution image-guided tracking--high doses of X-rays may be precisely delivered to prostate malignant lesions without increasing toxicity for surrounding normal structures. Also hadron therapy is an increasingly successful technique that allows the release of effective energy of protons (H+), neutrons or carbon ions (6(12)C) to the limited extent of the cancerous target site, thus destroying malignant lesion with millimetric precision--just as bloodless surgery--while less damaging the neighbouring healthy tissues. Looking to the near future, even more effective oncotherapy modality appears to be the use of antiprotons because of their highly confined energy deposition at well defined body dept around the annihilation point in contact with protons of the ordinary matter, so targeting only a very limited body volume.


Impact of the C-N status on the amino acid profile in tobacco source leaves.
This paper investigates the influence of the carbon (C) and nitrogen (N) status on the amino acid profile in tobacco source leaves. Treatments used included growing plants at different light intensities, using an antisense RBCS (small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase) construct to inhibit Rubisco activity, growing plants on 12 or 0.5 mM nitrate, comparing wild-types with genotypes that have small and large decreases in nitrate reductase (NIA) activity, and sampling plants at different times during the diurnal cycle. This combination of experiments provides information on how amino acid levels respond to several inputs including the C and N status, nitrate, excess light and light-dark transitions. The data set was analysed using principal component analysis, regression analysis and by normalizing the level of each individual amino acid on the total amino acid pool. Most amino acids show a downward trend when the C or the N status is decreased, and rise during day and fall at night during the diurnal cycle. However, individual amino acids often showed deviating responses. Furthermore, no evidence was found for feedback inhibition of minor amino acid synthesis, either within or between pathways, when 18 individual amino acids were supplied to detached leaves. Results indicate that regulation of amino acid metabolism, for example by the C and N status, leads to qualitatively similar responses of many amino acids, but homeostatic mechanisms involving feedback inhibition within or between individual amino acid biosynthesis pathways are not stringent. All of the above inputs affect the level of phenylalanine, an amino acid that is also the substrate for an important sector of secondary metabolism. The levels of glutamate were remarkably constant, indicating that unknown mechanisms stabilize the concentration of this key central amino acid. Analyses of metabolite levels and feeding experiments indicated that 2-oxoglutarate plays an important role in regulating glutamate levels. Glutamate was the most effective inhibitor of NIA activity when 18 individual amino acids were supplied to detached leaves. Feeding glutamate, and other downstream amino acids, led to an increase of glutamine, indicating glutamate exerts feedback regulation on ammonium metabolism.


Femoral anteversion. A clinical assessment of idiopathic intoeing gait in children.
Hip rotation in extension and flexion was studied in 23 patients with idiopathic intoeing gait. In extension all the hips had markedly increased medial rotation and limited lateral rotation, fulfilling the criteria of excessive femoral anteversion. In flexion, however, rotation varied widely; in one group of patients medial rotation remained greater than lateral, but in the second group lateral rotation was equal to or greater than medial. CT scans showed that the hips in the first group were significantly more anteverted than those in the second. Clearly measurement of hip rotation in extension alone does not provide a dependable indication of femoral anteversion in children with intoeing gait; rotation in flexion also needs to be measured.


An approach to the study of analyzability and analyses: the course of forty consecutive cases selected for supervised analysis.
The cases of 40 consecutive patients, accepted for supervised psychoanalysis at the Treatment Center of The New York Psychoanalytic Institute, are reviewed. The process of the initial evaluation is examined as well as the nature of the patient group, the characteristics of the treatment, outcome, and follow-up data. A survey of a group of 42 patients from the private practice of a group of graduate analysts during the same period of time is also reported. Both studies are discussed in relation to methodological issues, and an approach is suggested for the study of assessment of analyzability and analyses through a systematic prospective study of analytic treatments conducted by experienced analysts.


Cheyne-Stokes respiration in patients with congestive heart failure.
Cheyne-Stokes Respiration (CSR) is a breathing pattern characterised by rhythmic oscillation of tidal volume with regularly recurring periods of hyperpnoea, hypopnoea and apnoea. CSR is no longer solely regarded as a symptom of severe congestive heart failure (CHF), but has been recognised as an independent risk factor for worsening heart failure and reduced survival in patients with CHF. CSR is associated with frequent awakening that fragment sleep and with concomitant sympathetic activation both of which may worsen CHF. Cheyne-Stokes Respiration is very common in patients with severe CHF and its prevalence may have been underestimated in the past due to technical limitations that precluded respiratory monitoring outside sleep laboratories. Since treatment of CSR appears to be beneficial and safe, patients at risk should be promptly diagnosed and treated. Treatment of CSR has been demonstrated to improve left ventricular ejection fraction and potentially prolongs survival in patients with severe CHF. This article briefly summarises the current knowledge of the patho-physiology, prevalence and therapy of Cheyne-Stokes respiration.


Hypopharyngeal amyloidosis: A case report.
Hypopharyngeal amyloidosis is rare. Management depends on etiology. We report a case of hypopharyngeal amyloidosis and review the characteristics of this exceptional pathology. A 60-year-old woman with a history of diabetes and chronic cervicalgia consulted for dysphagia and deteriorated general health status, which had been evolving for 2 months. Clinical examination found two ulcerations of the lateral edge of the tongue and right pyriform sinus salivary stasis. Panendoscopy found regular swelling of the posterior wall of the hypopharynx and cervical esophagus. The pyriform sinuses and larynx were normal. Cervical CT and MRI showed thickening of the posterior wall of the hypopharynx. Biopsy found amorphous acellular eosinophil interstitial deposits, shown to be amyloid on Congo red staining, leading to a diagnosis of amyloidosis. Etiological assessment pointed to myeloma. The patient was managed by chemotherapy associating melphalan and prednisone. Evolution at 12 months' follow-up was good. Localized amyloidosis is a rare lesion of the superior aerodigestive tract, predominating in the larynx. Hypopharyngeal involvement is exceptional. Diagnosis is histological. Management depends on etiology. Local treatment is exceptional other than in case of complication. Systemic forms with associated myeloma are of poor prognosis.


[Detecting HB-1 Expression Level in Bone Marrow of Acute Leukemia Patients by Real-Time Fluorescence Quantitative RT-PCR].
To investigate the expression level of HB-1 gene in patients with acute lymphoblastic leukemia (ALL) and the significance of HB-1 gene in monitoring of minimal residual disease (MRD). The method of real-time fluorescence quantitative RT-PCR (Taqman probe) was established to detect the expression levels of HB-1 gene; then the sensitivity, specificity and repeatability of this assay were evaluated and verified. The HB-1 gene expression levels in bone marrow of 183 cases of ALL, 70 cases of acute myeloid leukemias (AML), 52 cases of non-malignant hematologic diseases and 24 healthy hematopoietic stem cell donors were detected. The correlation of HB-1 level with diagnosis and relapse was analyzed by detecting bone marrow samples of 33 B-ALL. The sensitivity of this assay reached the 10-4 level. The coefficient of variation for inter-batch and inter-tube of HB-1 were 6.79% and 4.80%, respectively. It was found that HB-1 gene specifically expressed in acute B lymphoblastic leukemia. The median expression levels of HB-1 gene in newly diagnosed and relapsed B-ALL patients were statistically significantly higher than those in ALL in complete remission(CR), newly diagnosed T-ALL, newly diagnosed AML, non-malignant hematologic diseases, and healthy hematopoietic stem cell donors(33.0% vs 0.68%, 0.07%, 0.02%, 0.58% and 0, respectively) (P<0.01). No statistical differences were found between newly diagnosed T-ALL, newly diagnosed AML, non-malignant hematologic diseases and healthy donors (P>0.05). The expression level of HB-1 gene declined sharply when B-ALL patients reached complete remission (0-7.99%, with median level 0.68%), but increased when relapsed (7.69%, 8.08% and 484.0% in 3 relapsed samples), which was in accordance with results of flow cytometry. HB-1 gene specifically expressed in acute B lymphoblastic leukemia cells. The established real-time fluorescence quantitative RT-PCR assay shows good sensitivity, specificity and repeatability, thus, can be used as a biological marker in the clinical detection, monitoring MRD and predicting of early relapse for B-ALL patients.


[Clinical use of a micromanipulator system: preliminary clinical experience in middle ear surgery].
Nowadays all procedures in tympanoplasty are performed using conventional instrumentation without any mechatronic based manipulators. A micromanipulator system (MMS) holds microinstruments and transmits the surgeon's hand movements to a monitor, thus, improving precision and ergonomics. Using the Cartesian principle, a telemanipulator with three linear degrees of freedom controlled with a joystick was designed. The three axes are powered by a servomotor. The manipulator is equipped with a sterilizable instrument holder, which is placed on a sterile covered system. On this instrument holder, sterile surgical instruments can be clipped and can be easily changed during surgery. In the scope of this study, the MMS was used to perform a tympanoplasty III in 20 patients. A workflow expert protocol, a video of the surgery, and a questionnaire completed by all surgeons were evaluated. Clinical use of the MMS 2.0 was performed in all 20 patients as planned. A partial/total ossicular replacement prosthesis (PORP/TORP) was used in all cases with the MMS as planned. Significantly more time was necessary not only to prepare for surgery but also to prepare the equipment intraoperatively, and the incision to suture time was longer. The number of intraoperative changes of instruments decreased by 24%. The frequency of contact between the instrument and the prosthesis was significantly decreased. All questionnaires indicated that further improvement of the MMS is needed. The manipulator MMS 2.0 was successfully used in the clinical setting for the first time. The tool offers great potential for middle ear surgery (e.g., tympanoplasty III, stapes surgery and cochlear implant insertion). The principal of telemanipulation (master-slave) could be transferred to middle ear surgery. However, numerous technical improvements are still required.


Transcriptional analysis of the 16S rRNA gene of the rrnD gene set of Streptomyces coelicolor A3(2).
The nucleotide sequence of 2.5 kb of the Streptomyces coelicolor A3(2) rRNA gene set rrnD, extending from upstream of the 16S rRNA gene to the putative 5' end of the 23S rRNA gene, has been determined (Baylis and Bibb, 1987; this paper). In addition to locating the 5' end of the 16S rRNA gene, nuclease S1 mapping identified seven RNA 5' end-points upstream of the 16S rRNA gene; four of these were coincident with transcriptional initiation points for S. coelicolor A3(2) RNA polymerase in vitro and were consequently regarded as in vivo transcription start points for promoters p1 to p4. One end-point identified by nuclease S1 mapping localized a putative processing site analogous to those found upstream of 16S rRNA genes in other eubacteria. Sequence motifs similar to those discovered in low G+C Gram-positive bacteria were found associated with two of the promoters and the processing site. A probable protein coding region was observed upstream of the promoter region.


[Study of gastric secretion in rats with ligation of the pylorus according to the Shay and Dai methods].
A comparative study of gastric secretion in rats with pyloric ligature according to either Shays' or Dais' methods was carried on, studying in both groups gastic acid and peptic secretions, mucous pepsinogen, and Na+, K+, and Cl-. The acid-peptic output as well as gastric Pu/g were greater in Dais' method. There were no changes regarding mucous pepsinogen when comparing both methods. Cl- and Na+ determinations showed minimal changes, whereas K+ showed no difference in both methods. We explain these modifications based on the difference in the secreted volume, since the acid concentration and Pu/ml are practically the same when comparing both methods.


Further evidence for the involvement of base and base sequence in the antigenic determination of thermally denatured DNA.
The antigenic determinant of thermally denatured salmon sperm (ss) DNA was extensively investigated with a radioimmunoassay technique using the ssDNA immune system. It was demonstrated that mixed sequences of purines and pyrimidines play a key role in the antigenic determination of DNA. On the other hand, the importance of the bases in the manifestation of DNA antigenicity was demonstrated by using brominated, methylated and/or ultraviolet irradiated ssDNA preparations.


Locomotion mode identification for lower limbs using neuromuscular and joint kinematic signals.
Recent development in lower limb prosthetics has seen an emergence of powered prosthesis that have the capability to operate in different locomotion modes. However, these devices cannot transition seamlessly between modes such as level walking, stair ascent and descent and up slope and down slope walking. They require some form of user input that defines the human intent. The purpose of this study was to develop a locomotion mode detection system and evaluate its performance for different sensor configurations and to study the effect of locomotion mode detection with and without electromyography (EMG) signals while using kinematic data from hip joint of non-dominant/impaired limb and an accelerometer. Data was collected from four able bodied subjects that completed two circuits that contained standing, level-walking, ramp ascent and descent and stair ascent and descent. By using only the kinematic data from the hip joint and accelerometer data the system was able to identify the transitions, stance and swing phases with similar performance as compared to using only EMG and accelerometer data. However, significant improvement in classification error was observed when EMG, kinematic and accelerometer data were used together to identify the locomotion modes. The higher recognition rates when using the kinematic data along with EMG shows that the joint kinematics could be beneficial in intent recognition systems of locomotion modes.


First description of giant Archaea (Thaumarchaeota) associated with putative bacterial ectosymbionts in a sulfidic marine habitat.
Archaea may be involved in global energy cycles, and are known for their ability to interact with eukaryotic species (sponges, corals and ascidians) or as archaeal-bacterial consortia. The recently proposed phylum Thaumarchaeota may represent the deepest branching lineage in the archaeal phylogeny emerging before the divergence between Euryarchaeota and Crenarchaeota. Here we report the first characterization of two marine thaumarchaeal species from shallow waters that consist of multiple giant cells. One species is coated with sulfur-oxidizing γ-Proteobacteria. These new uncultured thaumarchaeal species are able to live in the sulfide-rich environments of a tropical mangrove swamp, either on living tissues such as roots or on various kinds of materials such as stones, sunken woods, etc. These archaea and archaea/bacteria associations have been studied using light microscopy, transmission electron microscopy and scanning electron microscopy. Species identification of archaeons and the putative bacterial symbiont have been assessed by 16S small subunit ribosomal RNA analysis. The sulfur-oxidizing ability of the bacteria has been assessed by genetic investigation on alpha-subunit of the adenosine-5'-phosphosulfate reductase/oxidase's (AprA). Species identifications have been confirmed by fluorescence in situ hybridization using specific probes designed in this study. In this article, we describe two new giant archaeal species that form the biggest archaeal filaments ever observed. One of these species is covered by a specific biofilm of sulfur-oxidizing γ-Proteobacteria. This study highlights an unexpected morphological and genetic diversity of the phylum Thaumarchaeota.


Life and death on the waiting list for coronary bypass surgery.
To assess the baseline characteristics of patients referred for isolated coronary bypass surgery (CABG), waiting times for coronary bypass surgery and clinical events while waiting for coronary bypass surgery. To compare the New Zealand priority scoring system with a previously validated Ontario urgency score. Outcomes in a consecutive case series of 88 patients referred from Christchurch Hospital for coronary bypass surgery between July 1 and December 31 1993 were compared with a previous Christchurch case series and a contemporary Canadian case series. Patients were stratified according to both Ontario and New Zealand priority scores. Of 88 patients, one patient died prior to surgery, 79 had undergone coronary bypass surgery (with three deaths), and eight were still waiting as at December 31 1995. Twenty five percent of patients had left main disease, another 60% had multivessel disease that included the proximal left anterior descending coronary artery and 64% had angina at rest or on minimal exertion. The median waiting time was 92 days (inter-quartile range 20-234), 8 (6-12) days in the 23 patients who underwent surgery as in-hospital cases, and 181 (83-295) in those who waited at home. Patients with left main disease waited a median of 41 (11-205) days. While waiting at home one patient died, one patient suffered a myocardial infarction, and 17 patients were readmitted with unstable angina. Readmissions were not predicted by New Zealand or Ontario priority scores, nor by clinical variables. Thresholds for referral are very similar, but waiting times for coronary bypass surgery are far longer in New Zealand than Canada. The long waiting times are a considerable cost to both patients and government. Priority scores facilitate comparison between countries but they may not predict readmission to hospital while on a long waiting list.


Oral contraceptive use and breast cancer risk among African-American women.
Recent epidemiologic studies, most of them in predominantly White populations, have suggested that long duration of oral contraceptive (OC) use may increase the risk of breast cancer at young ages. We assessed the relationship of OC use to the risk of breast cancer in African-American women aged 25 to 59 years, using interview data from a multipurpose hospital-based case-control study. Five hundred and twenty-four cases hospitalized for invasive breast cancer were compared with 1,021 controls with nonmalignant conditions unrelated to OC use. Relative risks (RR) and 95 percent confidence intervals (CI) were estimated relative to a reference category of use for less than 12 months; potential confounders were controlled by multiple logistic regression analysis. Among women under age 45, three or more years of OC use was associated with an increased risk of breast cancer: the RR estimate was 2.8 (CI = 1.5-5.0) for three to four years of use, and declined to 1.5 (CI = 08.3.0) for 10 or more years of use. Recency and timing of use did not explain the observed association. Among women aged 45 to 59, OC use was associated with little or no increase in risk: the RR estimate for three or more years of use was 1.3 (CI = 0.7-2.4). The findings add to the evidence from studies of White women and a recent study of Black women which have suggested an increased risk of breast cancer at young ages for moderate or long duration use of OCs.


Amphipathic antimicrobial peptides--from biophysics to therapeutics?
Amphipathic peptides are accommodated within the diffuse gradient of polarity that characterizes the interfacial regions of phospholipid bilayer membranes. Interfacial membrane interactions are key to the diverse biological functions and activities of these peptides, which encompass a large class of antimicrobial peptides, including the helical peptides magainin, melittin, and RTA3 derived from the commensal bacterium Streptococcus mitis. For these peptides in vitro efficacy (high antimicrobial activity with minimal mammalian cell toxicity, equivalent to high potential therapeutic index; PTI), can be broadly understood in relation to the thermodynamics of interfacial binding and membrane disruption in membranes having surface charges that correspond to bacterial and mammalian cell membranes, respectively. Peptides with disrupted amphipathicity resulting from a positively charged amino acid residue on the non-polar helix face, can have greatly enhanced PTI, although a balance of amphipathicity, hydrophobicity and positive charge is required for retention of high antimicrobial activity. These observations are illustrated with recent examples from the literature, and studies on RTA3 and magainin analogues from our laboratories. Despite the identification and optimisation of peptides with very good PTI, a focus on addressing toxicity upon systemic administration and poor in vivo efficacy is likely to be required to translate growing understanding of the relationships between peptide interfacial activity and effects on cells, into novel systemic therapeutics.


Binaural masking effects in bone-conducted noise.
When pure tones are masked by bone-conducted noise presented at the midline of the forehead, it is possible that binaural unmasking may occur due to the interaural phase relations of the noise. To study this possibility, the amount of masking produced in bone-conducted noise, in correlated air-conducted noise, and in monaural noise was determined using narrow bands of noise centered at 240, 500, 910, and 1900 Hz as markers and a block up-down two-interval forced choice procedure. The subjects were four women under 30 years of age with 10 dB HTL or better (ANSI, 1969) for the frequencies tested. The amount of unmasking (the masking-level difference) was determined by subtracting the masking levels obtained under each noise condition at each frequency from those obtained in the comparable monaural noise-monaural signal condition. Levels of binaural unmasking obtained in correlated air-conducted noise agreed with those in previously reported experiments. Comparable binaural unmasking effects were demonstrated for midline presentation of bone-conducted noise. Some clinical implications of the findings are discussed.


A human Mad protein acting as a BMP-regulated transcriptional activator.
The TGF-beta/activin/BMP cytokine family signals through serine/threonine kinase receptors, but how the receptors transduce the signal is unknown. The Mad (Mothers against decapentaplegic) gene from Drosophila and the related Sma genes from Caenorhabditis elegans have been genetically implicated in signalling by members of the bone-morphogenetic-protein (BMP) subfamily. We have cloned Smad1, a human homologue of Mad and Sma. Microinjection of Smad1 messenger RNA into Xenopus embryo animal caps mimics the mesoderm-ventralizing effects of BMP4. Smad1 moves into the nucleus in response to BMP4. Smad1 has transcriptional activity when fused to a heterologous DNA-binding domain, and this activity is increased by BMP4 acting through BMP-receptor types I and II. The transactivating activity resides in the conserved carboxy-terminal domain of Smad1 and is disrupted by a nonsense mutation that corresponds to null mutations found in Mad and in the related gene DPC4, a candidate tumour-suppressor gene in human pancreatic cancer. Additionally, we show that DPC4 contains a transcriptional activation domain. The results suggests that the Smad proteins are a new class of transcription factors that mediate responses to the TGF-beta family.


Redescription of the orb-weaving spider Gasteracantha geminata (Fabricius, 1798) (Araneae, Araneidae).
The orb-weaving spider genus Gasteracantha Sundevall, 1833 (Araneidae) is notable for its pronounced sexual size dimorphism. Gasteracantha females are characterized by having a highly sclerotized "spiny" abdomen varying in relative size and number of spines, as well as abdomen dorsally and ventrally provided with varying numbers of sigillae (Cambridge 1879). The genus currently includes 70 described species and 31 subspecies (World Spider Catalog 2014). The Oriental species Gasteracantha geminata (Fabricius, 1798) was originally described from Ramnad (now known as Ramanathapuram) in Tamilnadu State of Southern India based on an unspecified number of female specimen(s). The female of this species has been described and illustrated several times by various authors. Its male is only known from the description of Simon (1895). Simon's original description of the male of G. geminata was supported by two simple but beautiful and informative illustrations: a retrolateral view of the cephalothorax and a dorsal view of the abdomen (Simon 1895, figs. 886, 887). However we lack a clear and detailed description of the male genitalia. The present paper provides detailed redescription of G. geminata and illustrations of the male pedipalp.


The regulation of autophagy in porcine blastocysts: Regulation of PARylation-mediated autophagy via mammalian target of rapamycin complex 1 (mTORC1) signaling.
Poly(ADP-ribosyl)ation (PARylation) acts as a modulator of selective autophagic degradation of ubiquitinated aggregates for cellular quality control, functioning in pro-survival role. It was reported previously that the inhibition of PARylation resulted in autophagy defects leading accumulation of ubiquitinated aggregates SQSTM1/p62 and apoptosis in porcine blastocysts. Thus, this study aims to investigate the mechanism between PARylation and autophagy in porcine blastocysts. In vitro produced (IVP) embryos were treated with 3-aminobenzamide (3ABA, poly (ADP-ribose) polymerase inhibitor) and/or rapamycin (RAPA, an mTORC1 inhibitor) during blastocyst formation. Then, these treated blastocysts were analyzed by real-time PCR, immunocytochemistry and TUNEL Assay. We found that the 3ABA treatment increased mTORC1 downstream target, phosphorylation of thr389 p70S6K (p-p70S6K-thr389), suggesting an increase in mTORC1 activity. Co-treatment with rapamycin (RAPA), mTORC1 inhibitor, restored the 3ABA-induced autophagy defects to those of the controls by normalizing mTORC1 activity. Moreover, autophagy induction, with only RAPA treatment, increased the rate of blastocyst development (70.05 ± 0.93 vs. 50.61 ± 3.49%), total cell number (58.48 ± 2.94 vs. 49.58 ± 2.43) and blastomere survival, but decreased the accumulation of SQSTM1/p62 aggregates. In summary, mTORC1 signaling is a key mechanism of PARylation-autophagy and its inhibition improved developmental ability and embryo quality by promoting selective autophagic degradation of ubiquitinated aggregates in porcine blastocysts. Therefore, these findings have significant implications for understanding the importance of autophagy regulation for successful in vitro production of porcine embryos.


Heterobimetallic chalcogenidometallate strands: synthesis, structure, magnetism, and conductivity.
Two salts with one-dimensional, SiS(2)-type telluridostannate chain anions {[MSnTe(4)](2-)}(n), Rb(2)[HgSnTe(4)] (2) and (NMe(4))(2)[MnSnTe(4)] (3), were prepared by the reactions of [SnTe](4-) anions with Hg(2+) or Mn(2+) ions in solution. We present the crystal structures of 2 and 3, as well as the magnetic properties of the previously reported Cs(+) analogue Cs(2)[MnSnTe(4)] (1).


Ileal duplication causing recurrent intussusception.
Intestinal duplications are rare congenital lesions that can develop anywhere along the alimentary tract. Symptoms usually appear during the first year of life and are varied. Diagnosis is difficult to achieve, and surgery is required for treatment. Here the case of a 6-month-old male with history of recurrent intussusception is reported. Surgery was indicated, and an ileal duplication was found. Intestinal duplication is discussed based on its epidemiology, clinical presentation, diagnosis, and treatment.


Evaluation of Abortion Stigma in the Workforce: Development of the Revised Abortion Providers Stigma Scale.
We report on the development of a scale measuring abortion providers' experiences of stigma. Using previous measures, qualitative data, and expert review, we created a 49-item question pool. We administered questions to 315 abortion providers before participation in the Providers Share Workshop. We explored the factor structure and item quality using exploratory factor analysis. We assessed reliability using Cronbach's alpha. To test construct validity, we calculated Pearson's correlation coefficients between the stigma scales, the Maslach Burnout Inventory, and the K10 measure of psychological distress. We used Stata SE/12.0 for analyses. Factor analysis revealed a 35-item, five-factor model: worries about disclosure, internalized states, social judgment, social isolation, and discrimination (Cronbach's alphas 0.79-0.94). Our stigma measure was correlated with psychological distress (r = 0.40; p < .001), and with Maslach Burnout Inventory's emotional exhaustion (r = 0.27; p < .001), and depersonalization (0.23; p < .001) subscales, and was inversely correlated with Maslach Burnout Inventory's personal accomplishment subscale (r = -0.15; p < .05). Psychometric analysis of this scale reveals that it is a reliable and valid tool for measuring stigma in abortion providers, and may be helpful in evaluating stigma reduction programs.


Effect of dose fractionation of daunorubicin on survival of leukemic cells.
Mice bearing transplanted AKR leukemia received daunorubicin either as a single dose or as four equally divided doses (0.2 mg/mouse; four times) with the time interval between the divided doses varying from 12 to 36 hr; survival of leukemia colony-forming cells was then assayed. When daunorubicin was administered in any of the fractionated schedules, the dose-survival curve was exponential with a shoulder region demonstrable. As expected, there was significantly less cell killing for the fractionated schedule than for a comparable accumulated single dose; however, with administration of the fourth dose for any interval studied, the increment in cell killing was so large that it was quite similar to that resulting from a single 0.8-mg/mouse dose. We examined the time course of cell killing for the 24-hr fractionation schedule and found greater killing than expected after each subsequent dose with the most pronounced increase occurring after the fourth dose. Possible mechanisms for this effect are discussed.