The development of viable and nutritive embryos in the direct developing gastropod Crepidula navicella.
Adelphophagy occurs when encapsulated embryos complete development by feeding on their developing siblings, which are known as nutritive embryos. Nutritive embryos are found in a variety of animal groups, and are especially common in some groups of marine invertebrates. Although they have evolved numerous times independently in the calyptraeid gastropods, adelphophagic development with nutritive embryos has not been described in detail. Using light microscopy and time-lapse imaging of laboratory-reared embryos, we describe the development of Crepidula navicella, a direct developer with nutritive embryos that cleave and gastrulate. Early stages of nutritive and viable embryos do not show any obvious morphological differences, but do show asynchrony in early cleavage among embryos from the same capsule. We discovered that two classes of nutritive embryos are produced; gastrula-like nutritive embryos, which arrest after gastrulation, and post-gastrula-like nutritive embryos that are more variable in morphology, and show evidence of minor differentiation. This study provides a framework for future research on the developmental and molecular mechanisms of nutritive embryo development of C. navicella, which will allow us to address the role of nutritive embryos in the origins of developmental polyphenisms. Careful description of the developmental sequence is necessary before adaptive hypotheses can be addressed, and comparisons with other taxa can be made. Understanding the different ways that embryos and their development are disrupted to produce nutritive embryos will provide important insights into the normal process of development.


Identification and characterization of Xenopus kctd15, an ectodermal gene repressed by the FGF pathway.
The FGF pathway regulates a variety of developmental processes in animals through activation and/or repression of numerous target genes. Here we have identified a Xenopus homolog of potassium channel tetramerization domain containing 15 (KCTD15) as an FGF-repressed gene. Kctd15 expression is first detected at the gastrula stage and gradually increases until the tadpole stage. Whole-mount in situ hybridization reveals that the spatial expression of kctd15 is tightly regulated during early embryogenesis. While kctd15 is uniformly expressed throughout the presumptive ectoderm at the early gastrula stage, its expression becomes restricted to the non-neural ectoderm and is excluded from the neural plate at the early neurula stage. At the mid-neurula stage, kctd15 shows a more restricted distribution pattern in regions that are located at the anterior, lateral or medial edge of the neural fold, including the preplacodal ectoderm, the craniofacial neural crest and the prospective roof plate. At the tailbud stage, kctd15 expression is mainly detected in neural crest- or placode-derived tissues that are located around the eye, including the mandibular arch, trigeminal ganglia and the olfactory placode. FGF represses kctd15 expression in ectodermal explants, and the inhibition of FGF receptor with a chemical compound dramatically expands the region expressing kctd15 in whole embryos. Dorsal depletion of kctd15 in Xenopus embryos leads to bent axes with reduced head structures, defective eyes and abnormal somites, while ventral depletion causes defects in ventral and caudal morphologies. These results suggest that kctd15 is an FGF-repressed ectodermal gene required for both dorsal and ventral development.


VIS30K: A Collection of Figures and Tables From IEEE Visualization Conference Publications.
We present the VIS30K dataset, a collection of 29,689 images that represents 30 years of figures and tables from each track of the IEEE Visualization conference series (Vis, SciVis, InfoVis, VAST). VIS30K's comprehensive coverage of the scientific literature in visualization not only reflects the progress of the field but also enables researchers to study the evolution of the state-of-the-art and to find relevant work based on graphical content. We describe the dataset and our semi-automatic collection process, which couples convolutional neural networks (CNN) with curation. Extracting figures and tables semi-automatically allows us to verify that no images are overlooked or extracted erroneously. To improve quality further, we engaged in a peer-search process for high-quality figures from early IEEE Visualization papers. With the resulting data, we also contribute VISImageNavigator (VIN, visimagenavigator.github.io), a web-based tool that facilitates searching and exploring VIS30K by author names, paper keywords, title and abstract, and years.


DNA Chimeras as Electrochemical Biosensors for Host-Guest Measurements in Blood.
Few sensing platforms have become ubiquitous to enable rapid and convenient measurements at the point-of-care. Those, however, are "one-off" technologies, meaning that they can only detect a single target and are hardly adaptable. In response, we plan to develop a sensing platform that can be extended to detect other classes of molecules and that affords rapid, convenient, continuous measurements directly in undiluted complex matrices. For this, we decided to rely on a host molecule that presents reversible interactions toward specific guest molecules to develop a new class of sensors that we coined "Electrochemical DNA-host chimeras". As a proof-of-concept for our sensor, we decided to use cyclobis(paraquat-p-phenylene) ("blue box") that we attached on an electrode-bound DNA to allow measurements of electron-rich guests such as dopamine and aspirin. Doing so allows to promote host-guest complex that could be quantified using blue box's electrochemistry. Because of this unique sensor architecture, we achieve, to our knowledge, the first reagentless, continuous and rapid (<5 min) host-guest measurements in undiluted whole blood. We envision that given the library of electroactive host molecules that this will allow the development of a sensing platform for measurements of several classes of molecules in complex matrices at the point-of-care.


The differential role of androgens in early human sex development.
Sexual development in humans is only partly understood at the molecular level. It is dependent on genetic control primarily induced by the sex chromosomal differences between males and females. This leads to the development of the gonads, whereby afterwards the differentiation of the apparent phenotype is controlled by hormone action. Sex steroids may exert permanent and temporary effects. Their organizational features of inducing permanent changes in phenotype occur through genetic control of downstream genes. In this, androgens are the key elements for the differentiation of male internal and external genitalia as well as other sexual organs and general body composition, acting through a single androgen receptor. The androgen receptor is a nuclear transcription factor modulating DNA transcription of respective target genes and thereby driving development and growth in a stringent manner. The specificity of androgen action seems to be a strictly time-controlled process with the androgen receptor acting in concert with different metabolites and an array of cofactors modulating the cellular response and thereby permanently altering the phenotype of any given individual. For every cell programmed by androgens, a specific 'androgen response index' must be proposed.


How can we help? From "sociology in" to "sociology of" bioethics.
Sociology and bioethics have an uneasy relationship. Bioethicists find sociology helpful for describing and analyzing ethical issues, but they are less enthusiastic when bioethics becomes the subject of sociological scrutiny. After review of different sociological approaches to bioethical topics -- descriptive, evaluative, and analytical -- I explain how bioethics will benefit by using the tools of sociology to answer its questions ("sociology in bioethics") and by allowing sociology to use bioethics to answer sociological questions ("sociology of bioethics").


Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: boron biodistribution study in a model of antigen-induced arthritis in rabbits.
Boron neutron capture synovectomy (BNCS) is explored for the treatment of rheumatoid arthritis (RA). The aim of the present study was to perform boron biodistribution studies in a model of antigen-induced arthritis (AIA) in female New Zealand rabbits, with the boron carriers boronophenylalanine (BPA) and sodium decahydrodecaborate (GB-10) to assess the potential feasibility of BNCS for RA. Rabbits in chronic phase of AIA were used for biodistribution studies employing the following protocols: intra-articular (ia) (a) BPA-f 0.14 M (0.7 mg (10)B), (b) GB-10 (5 mg (10)B), (c) GB-10 (50 mg (10)B) and intravenous (iv), (d) BPA-f 0.14 M (15.5 mg (10)B/kg), (e) GB-10 (50 mg (10)B/kg), and (f) BPA-f (15.5 mg (10)B/kg) + GB-10 (50 mg (10)B/kg). At different post-administration times (13-85 min for ia and 3 h for iv), samples of blood, pathological synovium (target tissue), cartilage, tendon, muscle, and skin were taken for boron measurement by inductively coupled plasma mass spectrometry. The intra-articular administration protocols at <40 min post-administration both for BPA-f and GB-10, and intravenous administration protocols for GB-10 and [GB-10 + BPA-f] exhibited therapeutically useful boron concentrations (>20 ppm) in the pathological synovium. Dosimetric estimations suggest that BNCS would be able to achieve a therapeutically useful dose in pathological synovium without exceeding the radiotolerance of normal tissues in the treatment volume, employing boron carriers approved for use in humans. Radiobiological in vivo studies will be necessary to determine the actual therapeutic efficacy of BNCS to treat RA in an experimental model.


[Role of free radicals in articular inflammatory process].
The authors review recent studies supporting the role of free radicals in the inflammatory articular process. More specifically, superoxide anion and its derived active species and nitric oxide are analyzed regarding their generation by the articular cells and tissues, their destructive activity n these specialized tissues. Likewise, effects of the inhibition of free radicals production or activity in the inflammatory process is also commented.


Sex-dependent diversity in ventral tegmental dopaminergic neurons and developmental programing: A molecular, cellular and behavioral analysis.
The knowledge that diverse populations of dopaminergic neurons within the ventral tegmental area (VTA) can be distinguished in terms of their molecular, electrophysiological and functional properties, as well as their differential projections to cortical and subcortical regions has significance for key brain functions, such as the regulation of motivation, working memory and sensorimotor control. Almost without exception, this understanding has evolved from landmark studies performed in the male sex. However, converging evidence from both clinical and pre-clinical studies illustrates that the structure and functioning of the VTA dopaminergic systems are intrinsically different in males and females. This may be driven by sex differences in the hormonal environment during adulthood ('activational' effects) and development (perinatal and/or pubertal 'organizational' effects), as well as genetic factors, especially the SRY gene on the Y chromosome in males, which is expressed in a sub-population of adult midbrain dopaminergic neurons. Stress and stress hormones, especially glucocorticoids, are important factors which interact with the VTA dopaminergic systems in order to achieve behavioral adaptation and enable the individual to cope with environmental change. Here, also, there is male/female diversity not only during adulthood, but also in early life when neurobiological programing by stress or glucocorticoid exposure differentially impacts dopaminergic developmental trajectories in male and female brains. This may have enduring consequences for individual resilience or susceptibility to pathophysiological change induced by stressors in later life, with potential translational significance for sex bias commonly found in disorders involving dysfunction of the mesocorticolimbic dopaminergic systems. These findings highlight the urgent need for a better understanding of the sexual dimorphism in the VTA if we are to improve strategies for the prevention and treatment of debilitating conditions which differentially affect men and women in their prevalence and nature, including schizophrenia, attention/deficit hyperactivity disorder, autism spectrum disorders, anxiety, depression and addiction.


Ethical observations on the choice of parenteral solvents. Choice of parenteral solvent....
The parenteral administration of insoluble drugs leads to the use of biologically active solvents inducing effects associated with ethical cause of concern including pain and pharmacological interactions. Selected vehicles currently used were ethically and scientifically reviewed. Our investigations allowed reinforcing the formulation decision tree with an ethical point of view. The last generation of cyclodextrin appears to be the safest solvent. Second choice could be lipidic emulsions, third choice being co-solvents, and finally non-ionic surfactants because of their hypersensitivity reactions. Screening tests including pH, osmolality measurements, cytotoxicity, and hemotoxicity, should allow to check the formulation tolerance before the animals' administration.


Hemodynamic effects of intravenous nicardipine in severely pre-eclamptic women with a hypertensive crisis.
Nicardipine permits rapid control of blood pressure in women with severe pre-eclampsia (PE) and hypertensive crisis. Our objective was to investigate its maternal and fetal hemodynamic effects. Ten severely pre-eclamptic pregnant women who required intravenous nicardipine for severe hypertension were included in this prospective observational trial. Maternal macrocirculation was assessed by transthoracic echocardiography. Maternal microcirculatory perfusion was examined sublingually with the sidestream dark field imaging technique. Fetal hemodynamics were assessed by Doppler examinations of the uteroplacental and fetal circulations. Maternal cardiac output, total vascular resistance, mitral E/A ratio and capillary heterogeneity index, uterine artery pulsatility index and fetal cerebroplacental ratio were considered primary outcomes. Paired measurements, obtained before administration of nicardipine infusion and after stabilization of blood pressure, were compared. Administration of nicardipine significantly reduced the mean arterial blood pressure (median difference, 26 mmHg; P = 0.002) and total vascular resistance (median difference, 791 dynes × s/cm(5) ; P = 0.002) in all included women. This induced a reflex tachycardia with consequent increase in cardiac output of 1.55 L/min (P = 0.004). There were no significant changes in the other determinants of maternal or fetal hemodynamic parameters. Nicardipine effectively reduces blood pressure through selective afterload reduction that triggers an increase in cardiac output, without affecting maternal diastolic function, or microcirculatory, uteroplacental or fetal perfusion. This hemodynamic response is uniform and predictable. Fetomaternal cardiovascular profiling can be achieved by combining transthoracic echocardiography with obstetric Doppler.


Harmonic admittance and dispersion equations--the theorem.
The harmonic admittance is known as a powerful tool for analyzing the excitation and propagation of surface acoustic waves (SAWs) in periodic electrode arrays. In particular, the dispersion relationships for open- and short-circuited systems are indicated, respectively, by the zeros and poles of the harmonic admittance. Here, we show that a strict reverse relationship also exists: the harmonic admittance of a periodic system of electrodes may always be expressed as the ratio of two determinants, which have been specifically constructed to describe the eigen-modes of the open- and short-circuited systems. There is no need to solve these equations to find the admittance. The existence of a connection between the excitation and propagation problems was recognized within the coupling-of-modes theory by Chen and Haus and was recently used to model surface transverse waves by Koskela et al., but a rigorous mathematical proof was only found later by Biryukov. Here, we reproduce this theorem in detail, give some examples of calculations based on this theorem, and compare the results with measured admittance curves.


Cross-talk between cellular stress, cell cycle and anticancer agents: mechanistic aspects.
Environmental conditions such as temperature, radiation, hypoxia, nutrients and drugs stimulate the adaptive sensory and signaling machinery of the cell. This stress response may influence cell cycle regulation, cellular differentiation, oncogenic transforma-tion, cell survival and apoptosis. The impact of the cytoprotective reprogramming in cancer pharmacology is presented by the recent extensive literature regarding the interplay between stress tolerance and anticancer drug effectiveness and resistance, relying on the dominating intrinsic pathways, which are simultaneously activated and regulate the death process either positively or negatively. This review presents the data that argue for the emergence of either common or specific mechanisms depending on the type, duration and severity of stress in all eukaryotic organisms from yeast to mammals. The understanding of the complexity and the balance between noxious and protective signal transduction pathways would contribute to a more explicit evaluation of the current therapeutic regiments and to the development of new leads targeting malignancy.


Absence of socioeconomic inequalities in access to good-quality breast cancer treatment within a population-wide screening programme in Turin (Italy).
Several studies suggest that population-based breast cancer screening programmes might help reduce social inequalities in breast cancer survival both by increasing early diagnosis and by improving access to effective treatments. To start disentangling the two effects, we evaluated social inequalities in quality of treatment of screen-detected breast cancer in the city of Turin (Italy). Combining data from the Audit System on Quality of Breast Cancer Treatment and the Turin Longitudinal Study, we analysed 2700 cases in the screening target age class 50-69 diagnosed in the period 1995-2008. We selected 10 indicators of the pathway of care, relative to timeliness and appropriateness of diagnosis and treatment, and three indicators of socioeconomic position: education, occupational status and housing characteristics. For each indicator of care, relative risks of failure were estimated by robust Poisson regression models, controlling for calendar period of diagnosis, size of tumour and activity volume of the surgery units. The principal predictor of failure of the good care indicators was the calendar period of diagnosis, with a general improvement with time in the quality of diagnosis and treatment, followed by size of the tumour and volume of activity. Socioeconomic indicators show only a marginal independent effect on timeliness indicators. The observed associations of quality indicators with socioeconomic characteristics are lower than expected, suggesting a possible role of the screening programme in reducing disparities in the access to good-quality treatments thanks to its capability to enter screen-detected women into a protected pathway of care.


Parsimony, not Bayesian analysis, recovers more stratigraphically congruent phylogenetic trees.
Reconstructing evolutionary histories requires accurate phylogenetic trees. Recent simulation studies suggest that probabilistic phylogenetic analyses of morphological data are more accurate than traditional parsimony techniques. Here, we use empirical data to compare Bayesian and parsimony phylogenies in terms of their congruence with the distribution of age ranges of the component taxa. Analysis of 167 independent morphological data matrices of fossil tetrapods finds that Bayesian trees exhibit significantly lower stratigraphic congruence than the equivalent parsimony trees. As such, taking stratigraphic data as an independent benchmark indicates that parsimony analyses are more accurate for phylogenetic reconstruction of morphological data. The discrepancy between simulated and empirical studies may result from historic data peaking practices or some complexities of empirical data as yet unaccounted for.


Nutrition in pediatric HIV infection: setting the research agenda. Nutrition and immune function II: maternal factors influencing transmission.
The risk of mother-to-child transmission of HIV ranges from 15-35 percent depending on the population under study (Fowler and Rogers 1996, Peckham and Gibb 1995). The recent finding that zidovudine treatment during pregnancy can reduce the risk of mother-to-child transmission of HIV by as much as two-thirds in some populations (CDC 1994, Connor et al. 1994), raises the question of which maternal, fetal, viral, immunologic, and placental factors play the greatest role in vertical transmission. It is clear that not only does the transmission rate vary dramatically by geographical distribution, but both the prevalence of infection and susceptibility of the uninfected may be higher in parts of the developing world. The transmission rate is significantly higher in the developing world presumably due to numerous factors including coinfection with other STD's, very little economic support for prevention, education, health maintenance or improving nutritional contributions to curb the spread of HIV. Furthermore, the strategies to reduce vertical transmission in industrialized countries are often not feasible in the developing world. Providing widescale availability of antivirals may not be feasible in areas where, to date, vitamin deficiencies often still exist. The healthcare budget in many of these developing countries cannot even pay for basic medical or prenatal services. The future directions in reducing the rate of mother-to-infant transmission must focus on strategies applicable to the developing world as well as industrialized countries. The vast majority of HIV in the pediatric age group is the result of vertical transmission of the virus. A number of maternal immunologic factors have been associated with vertical transmission. This paper offers a brief review of the extant knowledge with regard to the role of maternal factors in vertical transmission of HIV infection.


New power sharing control for inverter-dominated microgrid based on impedance match concept.
Power flow control is one of the most important issues for operating the inverter-dominated autonomous microgrid. A technical challenge is how to achieve the accurate active/reactive power sharing of inverters. P-F and Q-V droop control schemes have been widely used for power sharing in the past decades. But they suffer from the poor power sharing in the presence of unequal line impedance. In order to solve the problem, a comprehensive analysis of the power droop control is presented, and a new droop control based on the impedance match concept is proposed in this paper. In addition, the design guidelines of control coefficients and virtual impedance are provided. Finally, the performance evaluation is carried out, and the evaluation results verify the effectiveness of the proposed method.


Identification of pathogenic yeasts of the imperfect genus Candida by polymerase chain reaction fingerprinting.
With the increase in the number of immunocompromised hosts, the number of fungal pathogens has increased markedly. Identification and classification, especially of yeast species and strains, is often difficult when based solely on phenotypic characteristics. Since it became clear that different fungal pathogens require specific treatment strategies, there is a need for simple, rapid and reliable methods to identify fungal isolates. Polymerase chain reaction (PCR) fingerprinting was successfully applied here to identify yeast isolates. Microsatellite [(GTG)5; (GACA)4] and minisatellite [(5'GAGGGTGGCGGTTCT 3'), derived from the core-sequence of the phage M13] specific primers were used as single primers in the PCR to amplify hypervariable interrepeat DNA sequences from over 200 European, American and Australian clinical isolates within the genus Candida. Each species, represented by its type strain, could be identified by a specific multilocus pattern, allowing for the assignment of all the isolates to the appropriate species. Intra-species variation in the multilocus profiles was about 20% compared to inter-species variation, which was up to 80%. Anamorph-teleomorph pairs could be identified by highly homologous PCR fingerprint patterns. PCR fingerprinting was more discriminatory when compared with routinely used biochemical tests (Vitek YBC and API ID 32C). PCR fingerprinting has proven to be a powerful tool for the identification of medically important yeasts. It is rapid, sensitive, reliable, highly reproducible, stable in vitro and in vivo, and applicable to large scale experiments. Potential applications include: yeast taxonomy, epidemiology, environmental surveys, and improvement of the diagnosis of mycotic diseases.


The journal of undergraduate neuroscience education: history, challenges, and future developments.
The 'JUNE and You' sessions presented at the July 2008 Undergraduate Neuroscience Education workshop, sponsored jointly by Faculty for Undergraduate Neuroscience (FUN) and Project Kaleidoscope (PKAL), featured background information about the history and mission of the Journal of Undergraduate Neuroscience Education (JUNE), followed by an informative discussion about the challenges facing JUNE, including new ideas for future developments. This article will highlight some of the information and ideas generated and shared at this conference. Critical discussion points included the need to keep members of FUN actively engaged in submitting and reviewing articles for JUNE. Ways in which authors, reviewers, and interested faculty members could best help in promoting the mission and vision of JUNE were discussed. Concerns about recent hackings into the JUNE website were also raised, and possible solutions and measures that can be taken to minimize this in the future were discussed. In addition, ideas for expanding the role of JUNE to provide a forum to evaluate new and emerging website information that is pertinent to undergraduate neuroscience education was discussed. Ideas for future developments of JUNE included revolving postings of articles as they are accepted, providing links to several related websites, and allowing updates for articles that have been previously published in JUNE. Finally, ideas for maintaining and expanding JUNE's stature as the resource for undergraduate neuroscience education included ensuring that JUNE is listed on important search vehicles, such as PubMed.


Skin prick test reactivity to foods in adult Malaysians with rhinitis.
The aim of the study was to determine the incidence of food and house dust mite (HDM) allergy in patients with nasal congestion and rhinorrhea attending the Otorhinolaryngology Clinic, National University of Malaysia, Kuala Lumpur. This was a prospective matched, controlled study of patients skin prick tested with commercial food and common aeroallergens. The participants were 148 Malaysian adults with symptoms of nasal congestion and rhinorrhea and 113 adult Malaysian control subjects without rhinitis symptoms. The skin prick test (SPT) was used to evaluate 11 foods common to the Malaysian diet and 3 HDM inhalants. Forty-eight percent of the patients with rhinitis had positive SPT results to foods, compared with 4.4% of control subjects (P < 0.05). The most commonly implicated foods were shrimp (48%) and rice (30%), which are common in the Malaysian diet. Seventy-two percent of rhinitis patients had positive SPT results to HDM, compared with 22.2% of control subjects (P < 0.05). Patients with rhinitis also had significantly more gastrointestinal problems than control subjects (P < 0.05). The incidences of HDM and food allergy are significantly greater in Malaysian adults with rhinitis symptoms than in control subjects without rhinitis. The effect of avoidance or immunotherapy awaits further study.


The Interleukin 6 Protein Level as well as a Genetic Variants, (rs1800795, rs1800797) Are Associated with Adverse Cardiovascular Outcomes within 10-Years Follow-Up.
Worldwide, cardiovascular disease (CVD) is the leading cause of premature death. The proinflammatory cytokine interleukin 6 (IL-6) is a essential marker of innate immunity that is considered to play an important proatherogenic role for cardiovascular disease. The aim of this study (substudy of ClinTrials.gov identifier: NCT01045070) was to evaluate IL-6 protein level and genetic variants (rs1800795, rs1800797) with respect to CV outcome (combined endpoint: myocardial infarction, stroke/transient ischemic attack, cardiac death, death according to stroke) among patients CVD within 10-years follow-up. Overall 1002 in-patients with CVD were included. IL-6 protein level was determined by electrochemiluminescence immunoassay (fasting, between 7 and 8 a.m.). Genetic analyses were carried out by single specific primer-polymerase chain reaction. In survival analyses, IL-6 protein levels of ≥6.4 pg/mL (log-rank test: p = 0.034; cox regression: p = 0.032, hazard ratio = 1.29) and CC genotype of rs1800795 (log-rank test: p < 0.001, cox regression: p < 0.001, hazard ratio = 1.72) and AA genotype of rs180797 (log-rank test: p = 0.002, cox regression: p < 0.001, hazard ratio = 1.62) were associated with a poorer CV prognosis considering combined CV endpoint. This study was the first to investigate both elevated IL-6 levels and genetic variants for their prognostic value for adverse CV outcomes in CVD patients within the 10-year follow-up period.


[Blood immunoglobulin E in acute pneumonia].
The program of examination of 209 patients suffering from acute pneumonias (AP) included identification of the etiologic agents and measurement of the blood serum concentrations of immunoglobulins E (IgE). Immunoglobulinemia E was detected in 106 patients (50.7%). That phenomenon was noted in all the patients with eosinophilic pneumonia. Immunoglobulinemia E occurred mostly in patients (p = 0.05-0.001) with an aggravated allergological anamnesis, in those with a history of obstructive bronchitis and in cases where antibacterial therapy had been administered for a long time. The concentration of IgE in blood serum was established to agree with the intensity of antibacterial chemotherapy.


A comparative study of the action of gamma-aminobutyric acid and piperazine on the lobster muscle fibre and the frog spinal cord.
1 The effects of gamma-aminobutyric acid (GABA) and piperazine were compared on two in vitro preparations, the lobster muscle fibre and the frog spinal cord. 2 Both GABA and piperazine increased the membrane conductance of single lobster muscle fibres without changing the membrane potential; sigmoidal log dose-conductance curves for these agents were obtained and a similar model expressed the receptor interaction of both substances. 3 The actions of GABA and piperazine on lobster muscle were antagonized by picrotoxin and were Cl-dependent. 4 In the frog spinal cord GABA depolarized the dorsal roots presumably by mimicking the activity of the transmitter depolarizing the primary afferents; sigmoidal log dose-response curves for GABA were obtained. 5 On the dorsal roots piperazine produced either depolarizations or biphasic responses; these were mainly indirect effects as was shown by experiments in the presence of tetrodotoxin (TTX). 6 The effects of GABA on the dorsal root (in TTX-treated cords) were antagonized by picrotoxin whereas those of piperazine were more resistant to this alkaloid. The GABA-induced responses appeared to be largely Na+-dependent while both Na+ and Cl- seemed to mediate the effects of piperazine. 7 It is proposed that piperazine has GABA-agonist activity on lobster muscle but little GABA-like activity on the frog spinal cord.


Individual differences in error-related frontal midline theta activity during visuomotor adaptation.
Post-feedback frontal midline EEG activity has been found to correlate with error magnitude during motor adaptation. However, the role of this neuronal activity remains to be elucidated. It has been hypothesized that post-feedback frontal midline activity may represent a prediction error, which in turn may be directly related to the adaptation process or to an unspecific orienting response. To address these hypotheses, we replicated a previous visuomotor adaptation experiment with very small perturbations, likely to invoke implicit adaptation, in a new group of 60 participants and combined it with EEG recordings. We found error-related peaks in the frontal midline electrodes in the time domain. However, these were best understood as modulations of frontal midline theta activity (FMT, 4-8 Hz). Trial-level differences in FMT correlated with error magnitude. This correlation was robust even for very small errors as well as in the absence of imposed perturbations, indicating that FMT does not depend on explicit or strategic re-aiming. Within participants, trial-level differences in FMT were not related to between-trial error corrections. Between participants, individual differences in FMT-error-sensitivity did not predict differences in adaptation rate. Taken together, these results imply that FMT does not drive implicit motor adaptation. Finally, individual differences in FMT-error-sensitivity negatively correlate to motor execution noise. This suggests that FMT reflects saliency: larger execution noise means a larger standard deviation of errors so that a fixed error magnitude is less salient. In conclusion, this study suggests that frontal midline theta activity represents a saliency signal and does not directly drive motor adaptation.


Assessment of tongue mechanical properties using different contraction tasks.
Inadequate upper airway (UA) dilator muscle function may play an important role in the pathophysiology of obstructive sleep apnea (OSA). To date, tongue mechanical properties have been assessed mainly using protrusion protocol with conflicting results. Performance during elevation tasks among patients with OSA remains unknown. This study aimed at assessing tongue muscle strength, strength stability, endurance time, fatigue indices, and total muscle work, using elevation and protrusion tasks with repetitive isometric fatiguing contractions in 12 normal plus mild, 17 moderate, and 11 severe patients with OSA, and to assess the influence of body mass index (BMI) and age. Endurance time was longer in protrusion than elevation task (P = 0.01). In both tasks, endurance time was negatively correlated with baseline value of strength coefficient of variation (P < 0.01). Compared with other groups, patients with moderate OSA had the lowest total muscle work for protrusion (P = 0.01) and shortest endurance time (P = 0.04), regardless of the type of task. Additionally, in patients with moderate-severe OSA, the total muscle work for both tasks was lower in nonobese compared with obese (P < 0.05). Total muscle work for protrusion was positively correlated with apnea hypopnea index (AHI) in obese subjects (P < 0.01). Endurance time was shorter (P < 0.01) and recovery time longer (P = 0.02) in the old compared with young subjects. In conclusion, the tongue is more prone to fatigue during the elevation task and in patients with moderate OSA. Obesity appeared to prevent alteration of tongue mechanical properties in patients with OSA. Baseline strength stability and endurance were related, illustrating the role of central neuromuscular output in tongue resistance to fatigue.NEW & NOTEWORTHY To our knowledge, this is the first study to assess and compare tongue function using both elevation and protrusion tasks with repetitive isometric fatiguing contractions in subjects with different OSA status. Tongue mechanical performance seemed to differ between protrusion and elevation tasks and depend on the severity of OSA.


Treatment of social phobia with antidepressants.
This article reviews evidence for the utility of antidepressant medications in the treatment of social phobia. Monoamine oxidase inhibitors (MAOIs) were the first antidepressants shown to be effective for social phobia, but dietary restrictions and a relatively high rate of adverse effects often relegate MAOIs to use after other treatments have been found ineffective. Reversible inhibitors of monoamine oxidase (RIMAs) hold promise as safer alternatives to MAOIs, but RIMAs may be less effective and are currently unavailable in the United States. Selective serotonin reuptake inhibitors (SSRIs), of which paroxetine has been the best studied in social phobia to date, have recently emerged as a first-line treatment for the generalized subtype of social phobia. The SSRIs are well tolerated and consistently have been shown to be efficacious in controlled trials.


The outcome of the surgical treatment of pelvic chondrosarcomas: a competing risk analysis of 58 tumours from a single centre.
Few studies dealing with chondrosarcoma of the pelvis are currently available. Different data about the overall survival and prognostic factors have been published but without a detailed analysis of surgery-related complications. We aimed to analyse the outcome of a series of pelvic chondrosarcomas treated at a single institution, with particular attention to the prognostic factors. Based on a competing risk model, our objective was to identify risk factors for the development of complications. In a retrospective single-centre study, 58 chondrosarcomas (26 patients alive, 32 patients dead) of the pelvis were reviewed. The mean follow-up was 13 years (one week to 23.1 years). A total of 26 patients (45%) were alive and 32 patients (55%) had died. Overall survival was 76%, 55% and 45% at one, five and ten years post-operatively, respectively. In a competing risk model the cumulative risk of the development of a surgery-related complication was 64% at six months and 69% at one year, post-operatively, respectively. Endoprosthetic reconstruction was a significant risk factor for the development of complications (p = 0.006). Complications were not significantly related to age or the location or grade of the tumour (p = 0.823, p = 0.976, p = 0.858). The development of complications did not have a negative effect on survival (p = 0.147). This is the first study with competing risk analysis of surgery-related complications in patients with a pelvic chondrosarcoma. The surgery in these patients remains prone to complications. Endoprosthetic reconstruction significantly increases the risk of the development of complications (p = 0.006). A competing risk model showed that the development of complications does not have a negative influence on overall survival (p = 0.147). An aggressive, surgical resection with the goal of achieving wide margins whenever possible remains the mainstay of treatment. Cite this article: Bone Joint J 2017;99-B:686-96.


Amyloid-directed assembly of nanostructures and functional devices for bionanoelectronics.
Amyloids have the potential to serve as useful building blocks for functional materials and bionanoelectronic devices because they possess precisely assembled fibrillar structures, tunable functionalities, excellent mechanical properties, and ultrastability over a wide range of harsh conditions. These attributes endow amyloids with the ability to direct one-dimensional (1D) and two-dimensional (2D) patterning of nanoparticles and to serve as templates for controlled growth of nanowires, nanotubes and hybrid architectures. When coupled with conductive objects or functionalized with particular molecules, peptides or protein domains, amyloids could become active components of biosensors and devices relevant to energy applications. Before the full potential of amyloids in future bionanoelectronics can be realized, however, key engineering breakthroughs will be required.


Hip and Knee Strengthening Is More Effective Than Knee Strengthening Alone for Reducing Pain and Improving Activity in Individuals With Patellofemoral Pain: A Systematic Review With Meta-analysis.
Study Design Systematic review with meta-analysis. Background The addition of hip strengthening to knee strengthening for persons with patellofemoral pain has the potential to optimize treatment effects. There is a need to systematically review and pool the current evidence in this area. Objective To examine the efficacy of hip strengthening, associated or not with knee strengthening, to increase strength, reduce pain, and improve activity in individuals with patellofemoral pain. Methods A systematic review of randomized and/or controlled trials was performed. Participants in the reviewed studies were individuals with patellofemoral pain, and the experimental intervention was hip and knee strengthening. Outcome data related to muscle strength, pain, and activity were extracted from the eligible trials and combined in a meta-analysis. Results The review included 14 trials involving 673 participants. Random-effects meta-analyses revealed that hip and knee strengthening decreased pain (mean difference, -3.3; 95% confidence interval [CI]: -5.6, -1.1) and improved activity (standardized mean difference, 1.4; 95% CI: 0.03, 2.8) compared to no training/placebo. In addition, hip and knee strengthening was superior to knee strengthening alone for decreasing pain (mean difference, -1.5; 95% CI: -2.3, -0.8) and improving activity (standardized mean difference, 0.7; 95% CI: 0.2, 1.3). Results were maintained beyond the intervention period. Meta-analyses showed no significant changes in strength for any of the interventions. Conclusion Hip and knee strengthening is effective and superior to knee strengthening alone for decreasing pain and improving activity in persons with patellofemoral pain; however, these outcomes were achieved without a concurrent change in strength. Level of Evidence Therapy, level 1a-. J Orthop Sports Phys Ther 2018;48(1):19-31. Epub 15 Oct 2017. doi:10.2519/jospt.2018.7365.


Role of bronchoalveolar lavage in immunocompromised patients with pneumonia treated with a broad spectrum antibiotic and antifungal regimen.
In a retrospective study the value of bronchoalveolar lavage (BAL) in the diagnosis of pneumonia was investigated in 95 immunocompromised patients suffering from haematological disorders and receiving a regimen of broad spectrum antibiotics and antifungal agents (BSAR). With the exception of four afebrile patients, all had fever, raised C reactive protein (CRP) levels, and new infiltrates visible on chest radiography. All patients underwent BAL to identify the organism causing the pneumonia and surveillance cultures were performed regularly for pathogens at different sites. Following classification of the isolates, patients with positive cultures were subdivided into two groups, pathogenic or contaminated. We investigated whether relevant pathogens were cultured only from the BAL fluid and whether they were susceptible to BSAR. Although 77 of the 95 patients were thrombocytopenic, bleeding during BAL occurred in only 15% of all patients. Ten days after the procedure the fever improved in 88% of patients, radiographic findings improved in 71%, and CRP levels improved in 75% of patients; 22% of patients died within 28 days. Pathologically relevant isolates were found in 65% of all patients. Respiratory pathogens were detected only in the BAL fluid of 29 of the 95 patients (35% Gram positive species, 40% Gram negative species, 11% Mycobacterium, 11% fungi, and 3% cytomegalovirus). In 16 of these 29 patients (55%) the pathogens cultured only from the BAL fluid were resistant to treatment. Pathogens detected only in the BAL fluid were not susceptible to a standard broad spectrum antibiotic and antifungal regimen including teicoplanin, ceftriaxon, tobramycin, and amphotericin B in 12 of the 29 patients (41%). Our data suggest that 12 patients were treated with broad spectrum antimicrobial agents which were not directed at the appropriate organism on in vitro sensitivity tests without BAL. BAL is a relatively safe procedure in the diagnosis of pneumonia, supplying important information in immunocompromised patients as well as in immunocompromised patients receiving BSAR.


Role of regulatory T cells in gastrointestinal inflammatory disease.
Regulatory T cells curb unwanted immune responses and regulate responses to microflora and it is now clear that regulatory T cells play an important role in a number of chronic inflammatory diseases of the gut. First, regulatory T cells are crucial in controlling immune responses to gastric autoantigens and thus preventing autoimmune gastritis and pernicious anemia. Second, regulatory T cells may modulate the response to Helicobacter pylori, thus affecting the ability of the immune system to clear the pathogen and mediate damage to the gastric mucosa. Finally, regulatory T cells play an important role in preventing damaging inflammatory responses to commensal organisms in the lower gut, thus guarding against inflammatory bowel diseases. In the present review, we examine the actions of regulatory T cells in the gut and conclude that further understanding of regulatory T cell biology may lead to new therapeutic approaches to chronic gastrointestinal disease.


Quantification of 18F-fluorocholine kinetics in patients with prostate cancer.
Choline kinase is upregulated in prostate cancer, resulting in increased (18)F-fluoromethylcholine uptake. This study used pharmacokinetic modeling to validate the use of simplified methods for quantification of (18)F-fluoromethylcholine uptake in a routine clinical setting. Forty-minute dynamic PET/CT scans were acquired after injection of 204 ± 9 MBq of (18)F-fluoromethylcholine, from 8 patients with histologically proven metastasized prostate cancer. Plasma input functions were obtained using continuous arterial blood-sampling as well as using image-derived methods. Manual arterial blood samples were used for calibration and correction for plasma-to-blood ratio and metabolites. Time-activity curves were derived from volumes of interest in all visually detectable lymph node metastases. (18)F-fluoromethylcholine kinetics were studied by nonlinear regression fitting of several single- and 2-tissue plasma input models to the time-activity curves. Model selection was based on the Akaike information criterion and measures of robustness. In addition, the performance of several simplified methods, such as standardized uptake value (SUV), was assessed. Best fits were obtained using an irreversible compartment model with blood volume parameter. Parent fractions were 0.12 ± 0.4 after 20 min, necessitating individual metabolite corrections. Correspondence between venous and arterial parent fractions was low as determined by the intraclass correlation coefficient (0.61). Results for image-derived input functions that were obtained from volumes of interest in blood-pool structures distant from tissues of high (18)F-fluoromethylcholine uptake yielded good correlation to those for the blood-sampling input functions (R(2) = 0.83). SUV showed poor correlation to parameters derived from full quantitative kinetic analysis (R(2) < 0.34). In contrast, lesion activity concentration normalized to the integral of the blood activity concentration over time (SUVAUC) showed good correlation (R(2) = 0.92 for metabolite-corrected plasma; 0.65 for whole-blood activity concentrations). SUV cannot be used to quantify (18)F-fluoromethylcholine uptake. A clinical compromise could be SUVAUC derived from 2 consecutive static PET scans, one centered on a large blood-pool structure during 0-30 min after injection to obtain the blood activity concentrations and the other a whole-body scan at 30 min after injection to obtain lymph node activity concentrations.


Receptors for Helix pomatia A haemagglutinin on leukaemic lymphocytes from patients with chronic lymphocytic leukaemia (CLL).
Blood lymphocytes from thirteen patients with CLL were studied for surface-bound Ig (SIg), Fc receptors (EA rosettes), receptors for sheep erythrocytes (E rosettes) and receptors for Helix pomatia A haemagglutinin (HP), a carbohydrate-binding protein with specificity for N-acetyl-D-galactosamine and related sugars. Fluorescein-labelled HP binds to subpopulations of human peripheral blood lymphocytes (PBL) treated with neuraminidase. In normal peripheral blood, HP binds to the T-lymphocytes while the majority of the B cells bearing surface-bound immunoglobulin do not have receptors for HP. In untreated CLL, HP binds to 90-100 percent of the neuraminidase-treated PBL. Almost all of the SI-G-POSITIVE CELLS IN CLL patients also have receptors for HP. Two groups of patients were found: in one the total fraction of SIg+ cells was less than or equal to 50 percent and about 30 percent of these lost their Ig during incubation at 37 degrees C. No such loss of SIg was revealed in the remaining patients where total SIg+ fraction was approximately 70 percent. These patients usually had higher blood lymphocyte counts, probably reflecting a more advanced disease. CLL patients in remission with low numbers of leukaemic cells also had low numbers of blood lymphocytes carrying both SIg and HP-receptors. It is concluded that leukaemic cells carry both HP receptors and SIg. Testing of this combination therefore provides a valuable new tool for monitoring patients with CLL.


Mercury's exosphere: observations during MESSENGER's First Mercury flyby.
During MESSENGER's first Mercury flyby, the Mercury Atmospheric and Surface Composition Spectrometer measured Mercury's exospheric emissions, including those from the antisunward sodium tail, calcium and sodium close to the planet, and hydrogen at high altitudes on the dayside. Spatial variations indicate that multiple source and loss processes generate and maintain the exosphere. Energetic processes connected to the solar wind and magnetospheric interaction with the planet likely played an important role in determining the distributions of exospheric species during the flyby.


Cardiac arrest following an anaphylactic reaction to atracurium.
This report describes a life-threatening anaphylactic reaction in a 58-year-old woman who was scheduled for subacromial decompression of right shoulder joint. She had a modified rapid sequence induction using fentanyl 100 µg, propofol 150 mg and suxamethonium 100 mg. Following induction her blood pressure and pulse were stable. On return of spontaneous ventilation, she had intravenous administration of 30 mg of atracurium. Soon after, she developed profound bradycardia followed by a cardiac arrest. Cardiopulmonary resuscitation (CPR) commenced with 100% oxygen and intravenous administration of atropine 3 mg and epinephrine 1 mg. After 1 min of CPR she had the return of spontaneous circulation with a blood pressure of 160/100 mm Hg. Her sedation was maintained using minimal isoflurane until the return of spontaneous ventilation to avoid awareness. Surgery was postponed. Later she made an uneventful recovery. Her serum tryptase level was raised and a positive intradermal reaction to atracurium confirmed atracurium anaphylaxis.


A multicenter evaluation of lipid profiling with a compact analyzer (Miles Clinistat).
We evaluated the Clinistat Analyzer (Miles Inc., Diagnostics Division, Elkhart, IN) for measuring cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol at three medical centers. The system, based on multilayer film technology, uses precalibrated, dry film reagent disks. Ten microliters of serum is applied to the dry film reagent disk in the test procedure. For HDL-cholesterol measurement, serum is pretreated by precipitation with phosphotungstic acid and magnesium chloride. Total precision (CVs) of each of the three assays was less than or equal to 5%. The assay ranges were linear and satisfactory for clinical use. Patients' results compared well with established methods. No significant interferences were found with hemolysis, icterus, and lipemia.


Surface acoustic wave thermogravimetric measurements of thin polymer films.
The increased use of thin film polymers in microelectronic applications has resulted in the need to better understand their chemical, thermal, mechanical, and electrical properties. Of particular interest are changes in mass and viscoelasticity during curing of new high temperature polymers. A highly sensitive technique that can monitor mass and viscoelastic changes in thin polymer films during curing to high temperature is needed. In this work a surface acoustic wave (SAW) based system was developed that was capable of measuring the mass loss due to water outgassing during cure of thin polymer films in a temperature range of 20 to 400 degrees C. It also could measure the apparent glass transition temperature of acoustically thin films, and film resonance for acoustically thick films. The principle limitations of the system are the limited accuracy of temperature compensation and the limited ability to separate mass loss effects from viscoelastic effects.


Development of Water-Soluble Electrospun Fibers for the Oral Delivery of Cannabinoids.
Cannabidiol (CBD) and cannabigerol (CBG) are two active pharmaceutical ingredients, derived from cannabis plant. In the present study, CBD and CBG were formulated with polyvinyl(pyrrolidone) (PVP) and Eudragit L-100, using electrohydrodynamic atomization (electrospinning). The produced fibers were smooth and uniform in shape, with average fiber diameters in the range of 700-900 nm for PVP fibers and 1-5 μm for Eudragit L-100 fibers. The encapsulation efficiency for both CB and CBG was high (over 90%) for all formulations tested. Both in vitro release and disintegration tests of the formulations in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF) indicated the rapid disintegration and dissolution of the fibers and the subsequent rapid release of the drugs. The study concluded that the electrospinning process is a fast and efficient method to produce drug-loaded fibers suitable for the per os administration of cannabinoids.


[Thermal resistance of the spores of a Bac. stearothermophilus culture used for the preparation of bioindicators].
Thermostability of the spores of Bac. stearothermophilus in ampoules and capillaries in concentrations of 10(9), 10(8) and 10(6) cells per 1 ml of sodium chloride isotonic solution was determined at 119 to 124 degrees C with an interval of 1 degree C and an exposure time of 5, 10, 15, 20, 25, 30, 35 and 40 minutes. The results were used for plotting the survival curves. The time of the microbial death in the ampoules and capillaries at all the temperatures was the same and the ampoules were chosen as the bioindicator vehicle because of their availability and convenience in exploitation. The survival curves may be used for determination of the optimal sterilization conditions. The spore concentration of the thermostable culture in the bioindicator should be equal or exceed the level of the object microbial contamination. In the present study the concentration of the test microbe spores in the bioindicator was 10(6)--10(8) cells/ml.


Identification and quantification of phenolic compounds in grapes by HPLC-PDA-ESI-MS on a semimicro separation scale.
Reversed phase high performance liquid chromatography (RP-HPLC) on a semimicro separation scale was employed to develop a straightforward method for the simultaneous separation, identification, and quantification of phenolic compounds occurring in whole berries of Vitis vinifera, which comprise phenolic acids, flavonols, catechins, stilbenes, and anthocyanins. A C-18 narrow bore column of 150 x 2.0 mm I.D. and a semimicro photodiode array detector (PDA) cell of 2.5 microL, in conjunction with a mass spectrometry detector equipped with an electrospray ionization source (ESI-MS) to confirm peak identification, were employed. The C-18 narrow bore column was eluted by a multisegment gradient of increasing concentration of acetonitrile in water-formic acid solution that was optimized on the basis of the results of a study carried out to evaluate the influence of mobile phase composition and gradient shape on separation performance and detection sensitivity by ESI-MS. The identification of individual phenolic compounds was performed on the basis of their retention times and both UV-visible and mass spectra, acquired by a mass spectrometer (MS) equipped with an electrospray ionization (ESI) source, employed in conjunction with the PDA detector. Libraries comprising retention times, UV-visible, and mass spectra for major phenolic compounds expected in grape berries were made by subjecting solutions of each phenolic standard to the optimized RP-HPLC method. Quantification of individual compounds was performed by the external standard method using a six point regression graph of the UV-visible absorption data collected at the wavelength of maximum absorbance of each analyte determined by the PDA spectra. The RP-HPLC method was validated in terms of linearity of calibration graphs, limits of detection, limits of quantification, repeatability, and accuracy, which was evaluated by a recovery study. The developed method was successfully applied to identify the phenolic compounds occurring in the whole berries of nine red and one white grape of different varieties of Vitis vinifera, comprising some autochthonous varieties of south Italy such as Aglianico, Malvasia Nera, Uva di Troia, Negroamaro, Primitivo, and Susumaniello. Large differences in the content of phenolic compounds was found in the investigated grape varieties. As expected, only glycosilated flavonols were quantified, and the total amount of these compounds was higher in the whole berries of red grapes than in the white Moscato, where the most abundant phenolic compound was quercetin 3-O-glucoside. In almost all samples, the most and least abundant anthocyanins were malvidin 3-O-glucoside and cyanidin 3-O-glucoside, respectively, with the exception of Uva di Troia where the least abundant anthocyanin was delphinidin 3-O-glucoside.


Enteral naloxone for the treatment of opioid-induced constipation in the medical intensive care unit.
To determine the safety and efficacy of enteral naloxone for the treatment of opioid-induced constipation in the medical intensive care unit (MICU). This descriptive study included patients aged 18 to 89 years admitted to the MICU between July 1, 2007, and June 30, 2012, who received scheduled opioids and at least 1 dose of enteral naloxone. All data were obtained from electronic charting systems. Efficacy was assessed by evaluating time to bowel movement (BM), number of naloxone doses until BM, and ability to tolerate tube feeds after receipt of enteral naloxone. Safety was assessed by comparing opioid requirements, heart rates, and systolic blood pressures before and during naloxone treatment. Fifteen of the 16 patients included in the final analysis passed BMs during the study period. The median time to BM was 24.4 hours. The median number of naloxone doses received prior to passing a BM was 3. Seventy-eight percent of patients who were not receiving tube feeds at the time of naloxone administration received continuous tube feeds after naloxone initiation. No adverse effects associated with use of enteral naloxone were noted. Enteral naloxone appears safe for the treatment of opioid-induced constipation in the MICU. Enteral naloxone may be effective in treating opioid-induced constipation; however, further studies are warranted.


An Online Drug Abuse Prevention Program for Adolescent Girls: Posttest and 1-Year Outcomes.
Early adolescent girls' rates of drug use have matched, and in some instances, surpassed boys' rates. Though girls and boys share risk factors for drug use, girls also have gender-specific risks. Tailored interventions to prevent girls' drug use are warranted. This study developed and tested a web-based, drug abuse prevention program for adolescent girls. The nationwide sample of 13- and 14-year-old girls (N = 788) was recruited via Facebook ads. Enrolled girls were randomly assigned to the intervention or control condition. All girls completed pretest measures online. Following pretest, intervention girls interacted with the 9-session, gender-specific prevention program online. The program aimed to reduce girls' drug use and associated risk factors by improving their cognitive and behavioral skills around such areas as coping with stress, managing mood, maintaining a healthy body image, and refusing drug use offers. Girls in both conditions again completed measures at posttest and 1-year follow-up. At posttest, and compared to girls in the control condition, girls who received the intervention smoked fewer cigarettes and reported higher self-esteem, goal setting, media literacy, and self-efficacy. At 1-year follow-up, and compared to girls in the control condition, girls who received the intervention reported engaging in less binge drinking and cigarette smoking; girls assigned to the intervention condition also had higher alcohol, cigarette, and marijuana refusal skills, coping skills, and media literacy and lower rates of peer drug use. This study's findings support the use of tailored, online drug abuse prevention programming for early adolescent girls.


Implementing a Disaster Preparedness Curriculum for Medical Students.
Training in disaster medicine and preparedness is minimal or absent in the curricula of many medical schools in the United States. Despite a 2003 joint recommendation by the Association of American Medical Colleges and the Centers for Disease Control and Prevention, few medical schools require disaster training for medical students. The challenges of including disaster training in an already rigorous medical school curriculum are significant. We evaluated medical students' experiences with mandatory disaster training during a 2-year period in a medical university setting. Disaster training has been mandatory at Thomas Jefferson University since 2002 and requires all first-year medical students to attend lectures, undergo practical skills simulation training, and participate in the hospital's interdisciplinary disaster exercise. Medical students were encouraged to complete a survey after each component of the required training. Twenty-three survey questions focused on assessing students' experiences and opinions of the training, including evaluation of the disaster exercise. Students provided ratings on a 5-point Likert scale (5 = strongly agree, 1 = strongly disagree). A total of 503 medical students participated in the disaster preparedness curriculum during the course of 2 years. Survey response rates were high for each portion of the training: lectures (91%), skills sessions (84%), and disaster exercise (100%). Students believed that disaster preparedness should remain part of the medical school curriculum (rating 4.58/5). The disaster lectures were considered valuable (rating 4.26/5) and practical skills sessions should continue to be part of the first-year curriculum (4.97/5). Students also believed that participation in the disaster exercise allowed them to better understand the difficulties faced in a real disaster situation (4.2/5). Our mandatory disaster preparedness training course was successfully integrated into the first-year curriculum >10 years ago and has been well received by students without compromising the existing university curriculum. Integrating interdisciplinary teams and course components important to other education stakeholders may help other schools overcome obstacles to implementing disaster medicine training. Future education research should focus on developing interdisciplinary education to help disseminate disaster medicine topics across all 4 years of medical school.


Reflection and transmission of an incident solitary wave at an interface of a binary complex plasma in a microgravity condition.
Theoretical results are given in the present paper, which can well explain the experimental observations performed under microgravity conditions in the PK-3 Plus Laboratory on board the International Space Station about the propagation of a solitary wave across an interface in a binary complex plasma. By using the traditional reductive perturbation method and the continuity conditions of both the electric potential and the momentum at the interface, we obtain the equivalent "initial conditions" for both the transmitted wave and the reflected waves from the incident wave. Then we obtain the numbers of the reflected and the transmitted solitary waves as well as all the wave amplitudes by using the inverse scattering method. The ripples of both reflection and transmission have also been given by using the Fourier series. The number of the reflected and the transmitted solitary waves produced by interface, as well as all the solitary wave amplitudes, depend on the system parameters such as the number density, electric charge, mass of the dust particles, and the effective temperature in both regions. The analytical results agree with observations in the experiments.


Cardiovascular effects of tiapamil (Ro 11-1781), a new calcium-entry blocker.
We studied the hemodynamic effects of the new calcium antagonist tiapamil (Ro 11-1781) in anesthetized open-chest dogs and compared them with those of verapamil. Increasing doses of tiapamil injected intravenously caused the following hemodynamic effects: increase in coronary flow and decrease in coronary vascular resistance, followed by decreases in heart rate, blood pressure, and total peripheral resistance. Tiapamil did not depress myocardial contractility over a rather wide dose range, while verapamil did. Tiapamil was more effective in increasing coronary flow than verapamil. Cardiac autonomic denervation did not modify the tiapamil-induced decrease in coronary vascular resistance and did not cause tiapamil to display negative inotropism. Both tiapamil and verapamil reduced the extent of S-T segment elevation in the epicardial electrocardiogram produced by transient occlusion of the left anterior descending coronary artery. Neither drug had this effect when heart rate was kept constant by atrial pacing. In contrast to nitroglycerin, tiapamil dilated small but not large coronary arteries. Tiapamil raised PO2 relatively more in the subendocardial than in the subepicardial layers of the myocardium. The hemodynamic and electrocardiographic effects of tiapamil were not changed by diphenylhydantoin and disopyramide or by pindolol, a beta-adrenoceptor blocking agent with intrinsic sympathomimetic activity. However, the decreases in heart rate and blood pressure in response to propranolol were enhanced by tiapamil.


Cardiopulmonary bypass management and acute kidney injury in 118 Jehovah's Witness patients: a retrospective propensity-matched multicentre cohort from 30,942 patients.
Patients refusing blood products in cardiac surgery present challenges for cardiopulmonary bypass. Accurate detail of the modifiable factors of cardiopulmonary bypass relating to acute kidney injury is previously unreported in this patient population. A total of 118 adult Jehovah's Witness patients refusing transfusion were propensity matched to 118 adult patients accepting transfusion from the 30,942 patients in the Australian and New Zealand Collaborative Perfusion Registry. The primary endpoint was acute kidney injury. Intraoperative and bypass management characteristics were also compared between early (2007-2012) and late (2013-2018) cohorts along with the acceptance or refusal of transfusion. In patients accepting transfusion, 49% received a blood product. In patients refusing transfusion, acute kidney injury was lower (8% vs. 22%; p = 0.003) cell salvage use was higher (70% vs. 22%; p < 0.001), as was use of haemofiltration (8% vs. 4%; p = 0.03) and tranexamic acid in the early period (87% vs. 62%, p = 0.004) but not late (100% vs. 97%; p = 0.15). There was no difference in modifiable cardiopulmonary bypass factors (mean arterial pressure, minimum oxygen delivery (DO2i), retrograde autologous prime, circuit prime volume) between the two groups; however, prime volume decreased and DO2i increased over time for both. Patients refusing transfusion had lower postoperative blood loss (p = 0.02) and shorter postoperative length of stay (p < 0.001) with no difference in morbidity (p = 0.46) or mortality (p = 0.68). Refusal of transfusion in patients undergoing cardiopulmonary bypass was associated with reduced acute kidney injury, hospital stay and postoperative blood loss, while not impacting mortality.


Oceanisphaera sediminis sp. nov., isolated from marine sediment.
Two strains, designated TW92(T) and TW93, were isolated from marine sediment collected from the south coast of Korea. Cells of both strains were Gram-staining-negative, coccus-shaped, aerobic, motile and catalase- and oxidase-positive. Strain TW92(T) grew optimally in the presence of 2 % (w/v) NaCl (range 1-5%) while strain TW93 grew optimally in the presence of 1% (w/v) NaCl (range 0-12%), and both strains had an optimal growth temperature of 30 °C (range 4-37 °C). Strains TW92(T) and TW93 had the same optimum pH (pH 7), but differed in their ability to grow at pH 10. Phylogenetic analysis based on 16S rRNA gene sequence similarity showed that strains TW92(T) and TW93 were most closely related to Oceanisphaera donghaensis BL1(T), with 98.8% and 98.7% similarity, respectively. Pairwise similarity between the 16S rRNA gene sequences of strains TW92(T) and TW93 was 99.9%. The major fatty acids of both strains were summed features 3 (comprising C(16:1)ω7c/iso-C(15) 2-OH), C(16:0) and C(18:1)ω7c. Both strains possessed the ubiquinone Q-8 as the predominant respiratory quinone and phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol as the polar lipids. The genomic DNA G+C contents of strains TW92(T) and TW93 were 58.5 and 59.6 mol%, respectively. Genomic relatedness values based on DNA-DNA hybridization of strains TW92(T) and TW93 with related species were below 47% and 31%, respectively. DNA-DNA hybridization values between strains TW92(T) and TW93 were above 85%. On the basis of a taxonomic study using polyphasic analysis, it is proposed that the two isolates represent a novel species, Oceanisphaera sediminis sp. nov., with strain TW92(T) (=KACC 15117(T)=JCM 17329(T)) as the type strain and strain TW93 (=KACC 15118=JCM 17330) as an additional strain.


Changes on Hepatitis C virus genotype distribution in Western Turkey: Evaluation of twelve-year data.
Hepatitis C virus (HCV) prevalence is 1% in Turkey with genotype 1 being the predominant type traditionally. However unique geographical location of Turkey and increasing human migration in the region influences the epidemiology of the infection. The aim of this study was to determine the changes in distribution of HCV genotypes and risk factors. In this retrospective single-center study, HCV genotyping results of 558 patients were evaluated in between 2005 and 2016.Three different HCV genotyping assays were used during the 12-year study period;restriction fragment length polymorphism (RFLP), Abbott Real Time HCV Genotype II and Bosphore HCV genotyping kit. The most prevalent HCV genotype was genotype 1 detected in 88.4% of the patients followed by genotype 3 (5.2%),genotype 4 (2.9%),genotype 2 (2.1%), mixed genotypes (1.1%) and genotype 5 (0.3%).Genotype 1a showed an increasing prevalence.There were 19 patients (3.4%) either of foreign nationalities or Turkish citizens living abroad. Genotype 3 was the most common type among these patients which 10.3% had intravenous drug use history.Syrian migrant population differed in terms of HCV genotypes.Genotype 5 detected in two Syrian patients, which is the first report of HCV type 5 in Western Turkey. Among the HCV genotype 4 infected patients, 31.3% were Syrians. Our study showed that although genotype 1b dominance continues, the distribution and prevalence of HCV genotypes are changing in our region mainly due to migration and increase in the frequency of patients with non-traditional risk factors such as intravenous drug use. Monitoring the epidemiology of HCV genotypes may provide guidance in treatment decisions.


Phase-Amplitude Coupling of Neural Oscillations Can Be Effectively Probed with Concurrent TMS-EEG.
Despite the widespread use of transcranial magnetic stimulation (TMS), knowledge of its neurophysiological mode of action is still incomplete. Recently, TMS has been proposed to synchronise neural oscillators and to thereby increase the detectability of corresponding oscillations at the population level. As oscillations in the human brain are known to interact within nested hierarchies via phase-amplitude coupling, TMS might also be able to increase the macroscopic detectability of such coupling. In a concurrent TMS-electroencephalography study, we therefore examined the technique's influence on theta-gamma, alpha-gamma, and beta-gamma phase-amplitude coupling by delivering single-pulse TMS (sTMS) and repetitive TMS (rTMS) over the left motor cortex and right visual cortex of healthy participants. The rTMS pulse trains were of 5 Hz, 11 Hz, and 23 Hz for the three coupling variations, respectively. Relative to sham stimulation, all conditions showed transient but significant increases in phase-amplitude coupling at the stimulation site. In addition, we observed enhanced coupling over various other cortical sites, with a more extensive propagation during rTMS than during sTMS. By indicating that scalp-recorded phase-amplitude coupling can be effectively probed with TMS, these findings open the door to the technique's application in manipulative dissections of such coupling during human cognition and behaviour in healthy and pathological conditions.


Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate.
To evaluate the efficacy and safety of repeated administration of infliximab plus methotrexate (MTX) over a 2-year period in patients with rheumatoid arthritis (RA) who previously experienced an incomplete response to MTX. Four hundred twenty-eight patients were randomly assigned to receive MTX plus placebo or infliximab at a dose of 3 or 10 mg/kg plus MTX for 54 weeks, with an additional year of followup. The protocol was later amended to allow for continued treatment during the second year. Of 259 patients who entered the second year of treatment, 216 continued to receive infliximab plus MTX for 102 weeks. Ninety-four of these 259 patients experienced a gap in therapy of >8 weeks before continuing therapy. Infusions were administered at weeks 0, 2, and 6, followed by treatment every 4 weeks or every 8 weeks (alternating with placebo infusions in the interim 4-week visits) at a dose of 3 or 10 mg/kg for a total of 102 weeks (including the gap in therapy). For safety and efficacy assessments, data on the patients who were randomized to receive treatment, irrespective of whether treatment was administered for 102 weeks, were evaluated using all actual observations available. The efficacy measures included the Health Assessment Questionnaire (HAQ) (physical function), Short Form 36 health survey (SF-36) (health-related quality of life), total radiographic scores (structural damage), and the American College of Rheumatology 20% improvement criteria (ACR20) (signs and symptoms). The infliximab plus MTX regimens resulted in significantly greater improvement in HAQ scores (P < or = 0.006) and SF-36 physical component summary scores (P < or = 0.011) compared with the MTX-only group. There also was stability in the SF-36 mental component summary score among patients who received the infliximab plus MTX regimens. Median changes from baseline to week 102 in the total radiographic score were 4.25 for patients who received the MTX-only regimen and 0.50 for patients who received the infliximab plus MTX regimen. The proportion of patients achieving an ACR20 response at week 102 varied from 40% to 48% for the infliximab plus MTX groups compared with 16% for the MTX-only group. Throughout 102 weeks of therapy, infliximab plus MTX provided significant, clinically relevant improvement in physical function and quality of life, accompanied by inhibition of progressive joint damage and sustained improvement in the signs and symptoms of RA among patients who previously had an incomplete response to MTX alone.


Induction of meandering functional reentrant wave front in isolated human atrial tissues.
The purpose of this study was to test the hypothesis that a single meandering functional reentrant wave front can result in rapid and irregular electrogram activity in human atrial tissues. The study used the explanted hearts of five human cardiac transplant recipients. Three right and two left atrial tissue samples, 3.4+/-0.3 mm thick, were excised and trimmed to 3.5x3.0 cm. The isolated atrium was placed endocardial surface down in a chamber with a 477 bipolar recording electrode array built into the bottom of the tissue bath. The interelectrode distance was 1.6 mm. The tissue was constantly superfused with 36.5 degrees C oxygenated Tyrode's solution at a rate of 10 mL/min. After eight baseline stimuli (S1) delivered at 400- or 600-ms cycle length from the edge of the tissue, a single premature stimulus (S2) was given at the center of the tissue to induce reentry. A total of nine episodes of reentry were induced with S1-S2 coupling intervals of 232+/-29 ms (range, 190 to 290 ms) and an S2 strength of 10+/-3 mA (range, 5 to 15 mA). In all samples, a single meandering reentrant wave front was induced, causing irregular and rapid bipolar electrogram activity. These wave fronts had a mean cycle length of 229+/-45 ms (160 to 290 ms) and persisted for 1.1+/-0.3 seconds (0.6 seconds to 2.5 seconds), or 5.2+/-1.4 (3 to 9) cycles, before spontaneous termination. A single meandering functional reentrant wave front can be induced in human atrial tissues and produce rapid and irregular electrical activity.


The severe acute respiratory syndrome due to coronavirus 2 (SARS-CoV-2) infection and the climacteric woman.
The severe acute respiratory syndrome due to coronavirus 2 (SARS-CoV-2) infection has affected millions of individuals worldwide, causing high mortality rates and severe physical sequelae, with a negative impact on society, economy, health care, lifestyle and personal relationships. Studies have confirmed this infection has sex and age differences in terms of disease severity and immune response, with a particular relationship with the anti-Müllerian hormone, a marker of aging, and estradiol, a marker of ovarian function. Postmenopausal women seem to present a more severe infection as compared to premenopausal ones. Estradiol protects the vascular system, mediating with the renin-angiotensin-aldosterone system, whereas testosterone enhances the levels of angiotensin-converting enzyme and the transmembrane protease serine-type 2, thus delaying viral clearance in men as compared to women. This new infection will stay among us, transforming our social, economic and daily lifestyle, and hence medical and health care as well as the use of menopause hormone therapy will need redefining, considering both preventive and curative perspectives.


[Hemorrhagic fever with renal syndrome: historical aspects].
A mysterious disease was first reported from Korea when it had been observed during late spring 1951 in UN Forces operating in the central area close to the 38th parallel. The disease showed distinctive features which included high fever, low blood pressure, hemorrhagic tendency and acute renal failure. Historically it was apparently a similar disease to a clinical entity designated as Epidemic hemorrhagic fever in Manchuria or Hemorrhagic nephrosonephritis in Far Eastern Russia. After Lee Ho-Wang succeeded in demonstrating Hantaan virus which caused hemorrhagic fever with renal syndrome (HFRS), many studies has revealed various biological and epidemiological aspects of the disease. But the origin of the disease in Korea still remains unknown. This article tests some hypotheses which explain the origin of the disease and reviews the relation between the Korean War and HFRS. It is concluded that the emerging of HFRS would be closely related with the establishment of the munitions supply network in early 1951 in Chinese troop.


Models of care for post-treatment follow-up of adult cancer survivors: a systematic review and quality appraisal of the evidence.
The impact of cancer and cancer treatment on the long-term health and quality of life of survivors is substantial, leading to questions about the most appropriate configuration of services and models of care for follow-up of post-primary treatment survivors. A systematic review and quality appraisal of the health literature for structure of services and models of follow-up care for post-treatment survivors was identified through a search of guideline sources and empirical databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Library, CINAHL, and EBSCO from 1999 through December 2009. Ten practice guidelines and nine randomized controlled trials comprised the evidence base for models of care for adult cancer survivors. Although the evidence base was rated as low quality, nurse-led and primary care physician models of follow-up care were equivalent for detecting recurrence. Consensus also suggests that cancer survivors may benefit from coordinated transition planning that includes the provision of survivorship care plans as part of standard care. Realignment of models of care is identified as a health system priority to meet the supportive care and surveillance needs of a burgeoning survivor population. Further research is needed to evaluate the efficacy of models of care in a broader population of cancer survivors with differing needs and risks. While the evidence is limited, there is research that may be used to guide the configuration of health care services and planning.


Effect of a single injection of gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) on testicular blood flow measured by color doppler ultrasonography in male Shiba goats.
Although color Doppler ultrasonography has been used to evaluate testicular blood flow in many species, very little has been done in goat. Eight male Shiba goats were exposed to a single intramuscular injection of either gonadotropin-releasing hormone (GnRH group; 1 µg/kg BW) or human chorionic gonadotropin (hCG group; 25 IU/kg BW). Plasma testosterone (T), estradiol (E2) and inhibin (INH) were measured just before (0 hr) and at different intervals post injection by radioimmunoassay. Testis volume (TV) and Doppler indices, such as resistive index (RI) and pulsatility index (PI) of the supratesticular artery, were measured by B-mode and color Doppler ultrasonography, respectively. The results indicated an increase in testicular blood flow in both groups, as RI and PI decreased significantly (P<0.05), but this increase was significant higher and earlier in hCG group (1 hr) than in the GnRH group (2 hr). A high correlation was found for RI and PI with both T (RI, r= -0.862; PI, r= -0.707) and INH in the GnRH group (RI, r=0.661; PI, r=0.701). However, a significant (P<0.05) correlation was found between E2 and both RI (r= -0.610) and PI (r= -0.763) in hCG group. In addition, TV significantly increased and was highly correlated with RI in both groups (GnRH, r= -0.718; hCG, r= -0.779). In conclusion, hCG and GnRH may improve testicular blood flow and TV in Shiba goats.


Service provision trends among Australian private general dental practitioners: 1983/84 to 1998/99.
To investigate time trends in service provision. Four cross-sectional surveys across a 15-year period. Australian private general practice. A random sample of dentists. Dentists were surveyed by mailed questionnaire in 1983, 1988, 1993 and 1998 (response rates 71%-75%). Data were weighted to provide representative estimates for the age by sex distribution of private general practitioners in 1983, 1988, 1993 and 1998. Services per visit, annual services per dentist, annual services per patient. Total services per visit increased over the study period from 1.78 to 2.14 (Poisson regression; p < 0.05). However the annual number of services provided per dentist did not vary significantly, reflecting a trend among dentists to supply fewer patient visits per year. The annual number of services provided per patient increased over the period from 3.47 to 5.22 (OLS regression; p < 0.05), reflecting both the increased service rate per visit and increased numbers of visits by patients. Dentists provided less restorative, prosthodontic and extraction services per year, but more endodontic and crown and bridge services. The pattern of annual care received per patient also included more endodontic and crown and bridge services but differed from the dentist pattern through increased service rates over the study period in areas such as restorative, diagnostic and preventive. While dentists are providing a similar number of services annually, the content of their workload has changed to include less emphasis on removal and replacement of teeth and more effort on maintenance and retention of natural dentitions.


Loss of complement receptor type 1 (CR1) on ageing of erythrocytes. Studies of proteolytic release of the receptor.
Complement receptor type 1 (CR1) is a glycoprotein of Mr about 250 000 present on erythrocytes and other cell types. CR1 acts as a cofactor in the factor I-mediated breakdown of complement fragment C3b to form iC3b. Using an assay of cofactor activity, a wide variation in mean CR1 levels between erythrocytes from individual donors is observed. CR1 levels also decrease on ageing of erythrocytes in vivo, and again the rate of loss is widely variable between individuals. However, variable loss of CR1 during ageing of erythrocytes is likely to make only a minor contribution to the observed variation in mean CR1 levels. CR1 is very sensitive to proteolysis, and random proteolytic removal of CR1 from erythrocytes is likely to be an important factor in loss of CR1 on ageing of red cells in vivo. In vitro, mild trypsin treatment, plasmin or thrombin digestion of erythrocytes results in the loss of the factor I cofactor activity from the cell surface, and appearance of this activity in the supernatant. We conclude that an active fragment of CR1 is released from the cell surface on proteolysis. Subsequent prolonged trypsin treatment destroys most of the activity of this fragment. Proteolytic removal of CR1 from red cells may account not only for loss on ageing of cells, but also for the acquired CR1 deficiencies observed by others in systemic lupus erythematosus.


Immunological relationships between phocid and canine distemper virus studied with monoclonal antibodies.
The immunological relationships between distemper viruses, isolated from a seal and mink in Denmark and from a dog in Greenland, were investigated with 39 previously developed monoclonal antibodies (MAbs) directed against four major structural proteins of canine distemper virus (CDV). They were also investigated with 16 newly developed MAbs directed against the fusion (F) and large glycoprotein (named H in analogy with measles virus) of phocid distemper virus (PDV) isolated from a harbour seal (Phoca vitulina). These MAbs were reacted with the three different isolated viruses and with the LEC strain of measles virus, in ELISA and immunofluorescence tests. In addition, immunoprecipitation tests were carried out with some of the cross-reacting antibodies. All 55 MAbs reacted identically with distemper virus isolated from seals or mink. When the MAbs produced against CDV were tested, 37 of 39 antibodies reacted with a virus isolated from a sled dog diseased in an outbreak of distemper in Greenland prior to the epizootic among seals in the North Sea. Of the 39 antibodies, 25 reacted with PDV and distemper virus isolated from mink. Of these antibodies, only three of the nine antibodies directed against the H protein of CDV cross-reacted with PDV and distemper virus from mink. Eleven MAbs, reacting with six epitopes of the H protein of PDV, were produced. All 11 antibodies reacted with distemper virus from mink, two of the antibodies reacted with CDV and none reacted with measles virus. All five antibodies reacting with three different epitopes of the F protein of PDV reacted with distemper virus from mink and CDV. Of these five antibodies three, directed against two epitopes, reacted with measles virus. Of the two envelope proteins, the H protein shows pronounced immunological differences between PDV and CDV. In contrast, immunologically the F protein appears to be well conserved among morbilliviruses. It is concluded that the virus causing the epizootic in seals in the North Sea in 1988 may have infected mink on land, or, alternatively, the virus in the sea may have originated from virus-infected mink.


Comparison of free-hand fluoroscopic guidance and electromagnetic navigation in distal locking of femoral intramedullary nails.
Although the method has been used widely, one of the greatest challenges for intramedullary nailing is to position the distal locking screw. A new technology, the electromagnetic navigation system, is a radiation-free way to locate the position of the drill bit and provide 3-dimensional real-time feedback of location and orientation of the drill bit relative to the locking holes. The purpose of our study was to evaluate the reliability and efficiency of the free-hand technique compared to the new electromagnetic navigation system. Fifty-four patients with femoral fracture who needed treatment with intramedullary nails were divided into 2 groups. One group including 26 patients underwent distal locking using the standard free-hand method, whereas the electromagnetic navigation system was used with the other 29 patients. Intraoperative fluoroscopy exposure times, screw insertion times, and healing times were recorded; these parameters were used for comparison between the 2 groups. There were 17 males and 9 females who had femoral intramedullary nails using the free-hand technique, whereas 21 males and 8 females received intramedullary nails using the electromagnetic navigation system. The mean time of distal locking was 19.5 ± 6.0 minutes in the free-hand (FH) group, whereas the time was 6.1 ± 1.4 minutes in the electromagnetic (ET) group. The exposure time for the FH group was 26.8 ± 13.3 seconds and 2.2 ± 1.1 seconds for the ET group. Healing time proved to be comparable in the FH and ET groups (16.4 ± 3.7 weeks vs 15.1 ± 2.8 weeks). Under the premise of achieving the same effect, the electromagnetic navigation system has the advantage of less distal locking time and less radiation dose.


Pyrophosphoryl derivatives of 1-(2-deoxy-3-O-phosphono-methyl-beta- and -alpha-D-erythro-pentofuranosyl)thymine: synthesis and substrate properties towards some DNA polymerases.
The synthesis of 1-(2-deoxy-3-O-phosphonomethyl-beta-D-erythropentofuranosyl)thymine (17) and its alpha-anomer 18 is described. Attempts to prepare 1-[2-deoxy-3-O-(pyrophosphoryl)phosphonomethyl-beta-D-erythro-pentofuranosyl]thymine (19) by an activation of the respective phosphonate 17 with 1,1'-carbonyldiimidazole (Im2CO) resulted in the quantitative formation of the corresponding pyrophosphonate derivative 21 (Scheme 2). Activation of inorganic pyrophosphate with Im2CO followed by the condensation with the phosphonates 17 and 18 afforded the desired analogues of nucleoside triphosphate 19 (35%) and its alpha-anomer 20 (27%) along with the respective pyrophosphonate derivatives 21 (37%) and 24 (38%) (Scheme 3). It was found that compounds 19 and 20 display (i) no substrate properties toward calf thymus terminal deoxynucleotidyl transferase (TDT) and AMV reverse transcriptase, and (ii) moderate substrate activity with E. coli DNA polymerase I (Klenow fragment).


Pteridines as a new marker to detect human T cells activated by allogeneic or modified self major histocompatibility complex (MHC) determinants.
Evidence is presented that activation of T cells by allogeneic or modified autologous cells leads to the specific production of two distinct molecular compounds of the PT class. One of these two PT has previously been identified as neopterin. The structure of the other is still under investigation. This conclusion was based on the following findings: a) In vitro both PT were produced by T cells proliferating in response to HLA incompatible allogeneic or to autologous EB-virus-transformed or TNP-haptenized cells. b) In vitro stimulation of T cells with mitogenic lectins or protein antigens, of macrophages with zymosan-complement, of B cells with PWM or EB-virus, and of NK effector cells with tumor targets failed to induce comparable release of these PT. c) In vivo increased amounts of both PT were excreted via the urine during allograft rejection and viral infections. It thus appears that the production of these PT is primarily a feature of activated T cells involved in the control of self integrity.


Economic choices reveal probability distortion in macaque monkeys.
Economic choices are largely determined by two principal elements, reward value (utility) and probability. Although nonlinear utility functions have been acknowledged for centuries, nonlinear probability weighting (probability distortion) was only recently recognized as a ubiquitous aspect of real-world choice behavior. Even when outcome probabilities are known and acknowledged, human decision makers often overweight low probability outcomes and underweight high probability outcomes. Whereas recent studies measured utility functions and their corresponding neural correlates in monkeys, it is not known whether monkeys distort probability in a manner similar to humans. Therefore, we investigated economic choices in macaque monkeys for evidence of probability distortion. We trained two monkeys to predict reward from probabilistic gambles with constant outcome values (0.5 ml or nothing). The probability of winning was conveyed using explicit visual cues (sector stimuli). Choices between the gambles revealed that the monkeys used the explicit probability information to make meaningful decisions. Using these cues, we measured probability distortion from choices between the gambles and safe rewards. Parametric modeling of the choices revealed classic probability weighting functions with inverted-S shape. Therefore, the animals overweighted low probability rewards and underweighted high probability rewards. Empirical investigation of the behavior verified that the choices were best explained by a combination of nonlinear value and nonlinear probability distortion. Together, these results suggest that probability distortion may reflect evolutionarily preserved neuronal processing.


Public reporting drove quality gains at nursing homes.
Public reporting of the quality of care delivered in hospitals and nursing homes is thought to foster improvements in care. When information is available, consumers may choose high-quality providers. That choice, in turn, may stimulate providers to improve quality as a way to attract a larger share of the market. However, these assumptions have gone largely untested. We examined short-stay care provided at 8,137 nursing homes after the Nursing Home Compare public reporting requirements went into effect in 2002. We found that quality improved both because consumers chose higher-quality nursing homes and because providers improved the care they delivered. These findings support the continued use of public reporting to improve quality.


Comparative analysis of whole-transcriptome RNA expression of lung tissue of Chinese soft-shell turtle infected by Trionyx sinensis Hemorrhagic Syndrome Virus.
Trionyx sinensis Hemorrhagic Syndrome Virus (TSHSV), the first aquatic arterivirus identified in China, causes severe mortality to T. sinensis. In this study, we sought to determine the functions of T. sinensis mRNAs and non-coding RNAs (ncRNAs) that were differentially expressed (DE) over different periods of TSHSV infection of T. sinensis lung. We used RT-qPCR to validate the sequencing results of select RNAs, confirming their reliable and referable nature. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict multiple biological functions and signaling pathways in various comparison groups (1-day versus mock, 3-day versus 1-day, and 5-day versus 3-day). Multiple types of differentially expressed RNA, including mRNA, lncRNA, circRNA, and miRNA, were associated with cardiac dysfunction, coagulation abnormalities, and arachidonic acid metabolism at day 1. Pre-inflammatory cytokines and inflammatory factors such as PLA2G4A, cPLA2, γ-GGT1, TNFRSF14, TCP11L2, PTER CYP2J2 and LTC4S, were noticeably regulated at the same time. On day 3, multiple GO terms and KEGG pathways were implicated, including those related to virus defense, apoptosis, pyroptosis, and inflammatory response. Notably, key genes such as RSAD2, TRIM39, STAT4, CASP1, CASP14, MYD88, CXCL3, CARD11, ZBP1, and ROBO4 exhibited significant regulation. The lncRNAs and circRNAs that targeted the genes involved in viral recognition (TLR5), apoptosis (CARD11), pyroptosis (ZBP1), inflammatory processes (NEK7, RASGRP4, and SELE) and angiogenesis (ROBO4) exhibited significant regulation. Significantly regulated miRNAs were primarily linked to genes involved in apoptosis (Let-7f-3p, miR-1260a, miR-455-3p), and inflammation (miR-146a, miR-125a, miR-17a, miR-301b, and miR-30a-3p). The findings could advance our understanding of the host immunological response to TSHSV and offer new ideas for developing effective strategies to prevent infection of T. sinensis.


Biomechanics and tissue engineering.
Development of artificial scaffold for musculo-skeletal applications, especially in load-bearing situations, requires the consideration of biomechanical aspects for its integrity and its function. However, the biomechanical loading could also be used to favour tissue formation through mechano-transduction phenomena. Design of scaffold could take advantages of this intrinsic mechanical loading.