Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer.
New effective chemotherapy is needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC. Between January 1995 and April 1996, 414 patients with stage IIIB or IV NSCLC were randomized to received either a control arm of high-dose cisplatin (100 mg/m(2)) or a combination of paclitaxel (175 mg/m(2), 3-hour infusion) and cisplatin (80 mg/m(2)) every 21 days. Compared with the cisplatin-only arm, there was a 9% improvement (95% confidence interval, 0% to 19%) in overall response rate for the paclitaxel/cisplatin arm (17% v 26%, respectively; P=.028). Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm, respectively (P=.026). The study, however, failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm (8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm, P=.862). There was more hematotoxicity, peripheral neuropathy, and arthralgia/myalgia on the paclitaxel/cisplatin arm, whereas the high-dose cisplatin arm produced more ototoxicity, nausea, vomiting, and nephrotoxicity. Quality of life (QOL) was similar overall between the two arms. This large randomized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC. However, the paclitaxel/cisplatin combination did produce a better clinical response, resulting in an increased time to progression while providing a similar QOL.


Assessing the association of university stress and physiological reactivity with decision-making among students.
Compared with age-matched employees, university students report higher levels of chronic stress and this may affect their decision-making. The impact of chronic stress and physiological reactivity upon cognitive function is receiving more attention, but few studies have empirically assessed the associations of these variables concurrently. Our aim was to investigate if chronic student stress, as assessed by effort-reward imbalance (ERI) and overcommitment, and physiological reactivity, were related to decision-making. As measures of physiological reactivity, we collected salivary alpha-amylase (sAA) and continuously recorded heart rate variability (HRV) data from male students (n = 79) at pretest and immediately after some computerized decision-making tasks (simple and choice- reaction times). Our findings suggest that students who are higher in overcommitment and who are more physiologically reactive (sAA and HRV indices) at the pretest stage may be more "at-risk" of poor decision-making than others. If others can replicate our findings in more diverse samples, this will contribute to an evidence base for interventions targeted at reducing overcommitment, ERI, and dysregulated autonomic reactivity to improve decision-making.


How intensely nondaily smokers smoke in laboratory topography sessions correlates with cigarette smoking intensity in the field.
This study examines how well exposure in topography sessions correlates with exposure when smoking ad libitum in the field, by measuring material deposited on the filters of cigarettes smoked in the lab and in the field. The data were collected in a study of the effect of very low-nicotine-content versus normal-nicotine-content cigarettes in nondaily smokers. A total of 4,771 cigarette filters (323 from laboratory topography sessions, 4,448 from the field) from 123 nondaily smokers were analyzed. Optical scanning assessed density of deposits on cigarette filters, an indicator of smoke drawn through the cigarette and thus of exposure. Both during baseline, when participants smoked their own cigarettes, and during treatment, when smoking experimental cigarettes, lab and field exposure were well correlated (both rs = .62, p < .0001; r = .69, p < .0001, when analyzing all available data). Total puff volume also correlated with field exposure (p < .0001). In all analyses, exposure was slightly lower in the lab than in the field (p < .001). Exposure in laboratory topography sessions is a good indicator of exposure during ad libitum smoking in the field, both when smokers are smoking their own, varied, brands of cigarettes and when they are smoking uniform research cigarettes with very low or normal nicotine content. At least among nondaily smokers, topography measures of smokers' exposure are generalizable. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Calcipotriol inhibits proliferation of human keratinocytes by downregulating STAT1 and STAT3 signaling.
Psoriasis is an autoimmune disease, which is characterized by aberrantly high levels of inflammation, but the underlying pathogenic mechanisms are still not fully understood. Signal transducer and activator of transcription 1 (STAT1) and STAT3, and the downstream proteins suppressor of cytokine signaling 1 (SOCS1) and SOCS3, have been implicated in psoriasis disease progression. Calcipotriol, a synthetic derivative of vitamin D, has been used clinically to treat psoriasis, but the mechanism of action that underlies the beneficial effects of calcipotriol is still being explored. The objective of this study was to determine whether STAT1 and STAT3 signaling is involved in calcipotriol treatment. Using an in vitro immortal human keratinocyte cell line, HaCaT cells, as a psoriasis model, we examined the molecular signaling induced by calcipotriol treatment. We found that calcipotriol treatment or silencing of either STAT1 or STAT3 inhibited proliferation of HaCaT cells. Calcipotriol downregulated the expression of STAT1 and STAT3 at the messenger RNA (mRNA) and protein levels. The levels of phosphorylated STAT1 and STAT3 were also decreased, suggesting calcipotriol treatment inhibited STAT1 and STAT3 activation. Calcipotriol-mediated STAT inhibition was further substantiated by the downregulation of SOCS1 and SOCS3 at the mRNA and protein expression levels. Taken together, our results suggest a novel molecular mechanism for calcipotriol-mediated treatment effects in psoriasis.


Experimental intracerebral mass: time-related effects on local cerebral blood flow.
Cerebral blood flow (CBF) was measured at different times during the first 150 minutes following an experimental space-occupying lesion produced with a 50-microliter microballoon in rats. Local CBF was measured with the carbon-14-labeled iodoantipyrine quantitative autoradiographic technique. A region of local ischemia developed around the mass, while the remote effects of the mass were minimal. The focal ischemic lesion enlarged with time, and simulated removal of the lesion within this design did not alleviate the ischemia.


[Pregnancy, labor and the puerperium in women prisoners].
In 43 imprisoned women in Berlin, the authors investigated the situation in which imprisoned women find themselves when they are pregnant, with particular reference to pregnancy, delivery and puerperium. A control group of 172 women was examined parallel to this study. It was evident that the imprisoned women had significantly more complications with regard to the course of their pregnancy and delivery, including the condition of the newborn. An analysis of the individual data yielded, for the majority of the women, a worsening of their primarily poor social and mental condition, i.e. an aggravation caused by the imprisonment. It was the aim of this study to formulate, first of all, appropriate suggestions for lowering infantile and maternal morbidity in this risk group. One of the factors examined in this connection was a possible overall change in law enforcement (imprisonment) practice (for example, suspension of imprisonment according to paragraph 455/455a, 3 of the Federal German Code of Criminal Procedure, 1981, or rescission of imprisonment). Secondly, the authors recommend more intensive care during pregnancy and delivery, taking into account the experiences collected and presented in this article.


In situ localization of cell wall alpha-1,3-glucan in the fission yeast Schizosaccharomyces pombe.
The yeast cell walls of the budding yeast Saccharomyces cerevisiae are well studied and the results show the existence of a framework composed of beta-1,3-glucan. It is reported that the cell wall of the fission yeast Schizosaccharomyces pombe has different components and our analysis by 13C-nuclear magnetic resonance (NMR) spectroscopy also showed there is alpha-1,3-glucan in its cell wall. To refine our understanding of the architecture of the yeast cell wall, we re-examined the cell wall glucans of S. pombe by NMR spectroscopy and prepared antibody against alpha-1,3-glucan, which is a characteristic component of this yeast. By the competitive enzyme-linked immunosorbent assay (ELISA) system, specificity of the antibody was restricted to alpha-1,3-glucan, which did not take a highly ordered structure. We analysed the localization of the cell wall glucans by immunoelectron microscopy. Transmission electron microscope (TEM) images showed that most of the alpha-1,3-glucan was along the cell membrane and appeared to enclose the cytoplasm, supporting previous reports that this glucan is synthesized on the cell membrane.


Clinical significance of antibodies to a 68 kDa U1RNP polypeptide in connective tissue disease.
In a series of 163 patients with systemic lupus erythematosus (SLE) and/or systemic sclerosis and/or mixed connective tissue disease (MCTD), the presence of antibodies to a 68 kDa U1RNP associated polypeptide was more predictive for SLE (88%) than for MCTD (38-68%) using 3 different sets of proposed criteria for the latter condition. In all but one case studied serially the immunoblotting profile remained constant. In SLE recognition of the 68 kDa polypeptide identified a subset with increased vasoreactivity with Raynaud's phenomenon (96%, p less than 0.001) and swollen fingers (68%, p less than 0.001) whereas recognition of a 47 kDa La (SSB) polypeptide was associated with photosensitivity (72%, p less than 0.02), less renal involvement (p less than 0.05) and an older age of disease onset (46.6 years +/- 18.3 SD, p less than 0.002).


Tissue ablation with irreversible electroporation.
This study introduces a new method for minimally invasive treatment of cancer-the ablation of undesirable tissue through the use of irreversible electroporation. Electroporation is the permeabilization of the cell membrane due to an applied electric field. As a function of the field amplitude and duration, the permeabilization can be reversible or irreversible. Over the last decade, reversible electroporation has been intensively pursued as a very promising technique for the treatment of cancer. It is used in combination with cytotoxic drugs, such as bleomycin, in a technique known as electrochemotherapy. However, irreversible electroporation was completely ignored in cancer therapy. We show through mathematical analysis that irreversible electroporation can ablate substantial volumes of tissue, comparable to those achieved with other ablation techniques, without causing any detrimental thermal effects and without the need of adjuvant drugs. This study suggests that irreversible electroporation may become an important and innovative tool in the armamentarium of surgeons treating cancer.


Physiological effects of the presence and absence of gas vacuoles in the blue-green alga, Microcystis aeruginosa Kuetz. emend. Elenkin.
Physiological evidence was obtained for a light shielding role for gas vacuoles in Microcystis aeruginosa Kuetz. emend. Elenkin, by comparing photosynthetic oxygen evolution, growth behaviour and pigment composition of cells with intact or collapsed gas vacuoles. The oxygen evolution rates were strongly dependent on cell concentration, a maximum rate for cells with intact gas vacuoles occurring at about 1.4 X 10(9) cells/ml and for cells with collapsed gas vacuoles at about 2.5 X 10(9) cells/ml. By using light saturation curves for oxygen evolution, it was estimated that at low light intensities up to 30% of the photosynthetically useable light was shielded at a cell concentration of 6 X 10(8) cells/ml. Collapsing the gas vacuoles twice daily did not alter the initial growth rate of the cultures, but enabled them to reach a higher final cell density. Collapsing of gas vacuoles during growth for about four generations resulted in a lower level of all acetone soluble pigments with a greater relative reduction in carotenoids than in chlorophyll a. Collapse of the gas vacuoles does not alter the cell volume. Various optical interactions which could account for light shielding are discussed.


Cement kiln dusts as a selenium source in sheep rations.
Cement dust has been found to be a source of selenium when included in the rations of sheep. In the work reported, rations including 3% by weight of cement dusts were fed to sheep for 165 days. The dust were taken from 3 collectors located at progressively greater distances from the coal-fired end of the kiln. Selenium levels and blood and tissues of the animals fed the cement dusts increased significantly above those of the control sheep. No tissue abnormalities were observed in animals receiving any of the treatment rations. The source of selenium is believed to derive from its content of fly ash as a result of the coal combustion during cement manufacture.


The ubiquitin-proteasome system in positive-strand RNA virus infection.
Positive-stranded RNA viruses, like many other viruses, have evolved to exploit the host cellular machinery to their own advantage. In eukaryotic cells, the ubiquitin-proteasome system (UPS) that serves as the major intracellular pathway for protein degradation and modification plays a crucial role in the regulation of many fundamental cellular functions. A growing amount of evidence has suggested that the UPS can be utilized by positive-sense RNA viruses. The UPS eliminates excess viral proteins that prevent viral replication and modulates the function of viral proteins through post-translational modification mediated by ubiquitin or ubiquitin-like proteins. This review will discuss the current understanding of how positive RNA viruses have evolved various mechanisms to usurp the host UPS to modulate the function and stability of viral proteins. In addition to the pro-viral function, UPS-mediated viral protein degradation may also constitute a host defense process against some positive-stranded RNA viral infections. This issue will also be discussed in the current review.


Determination of four major saponins in the seeds of Aesculus chinensis Bunge using accelerated solvent extraction followed by high-performance liquid chromatography and electrospray-time of flight mass spectrometry.
A new method based on accelerated solvent extraction (ASE) followed by a reliable high-performance liquid chromatography-diode array detector (HPLC-DAD) and positive ion electrospray-time of flight mass spectrometry (ESI-TOF/MS) analysis has been developed for the characterization and quantification of four major saponins in extracts of the seeds of Aesculus chinensis Bunge (semen aesculi). The saponins escin Ia, escin Ib, isoescin Ia and isoescin Ib were extracted from seeds of A. chinesis Bunge via ASE, and the operational parameters of ASE were optimized, such as extraction solvent, extraction temperature, static extraction time and extraction cycles. The optimized procedure employed 70% MeOH as extraction solvent, 120 degrees C of extraction temperature, 7 min of static extraction time, 60% flush volume and the extraction recoveries of the four compounds were nearly to 100% for two cycles. The HPLC conditions are as follows: SinoChrom ODS BP C18 (4.6 mm x 200 mm, 5 microm) column, acetonitrile and 0.10% phosphoric acid solution as mobile phase, flow rate is 1.0 mL min(-1), detection length of UV is 203 nm, injection volume is 10 microL. The results indicated that the developed HPLC method is simple, sensitive and reliable for the determination of four major saponins in seeds of A. chinesis Bunge with a good linearity (r2 > 0.9994), precision (relative standard deviation (R.S.D.) < 1.5%) and the recovery ranges of 95.2-97.3%. The limits of detection (LOD) of the four compounds were in the range of 0.40-0.75 microg mL(-1). This assay can be readily utilized as a quality control method for semen aesculi and other related medicinal plants.


Adolescent executive cognitive functioning and trait impulsivity as predictors of young-adult risky drinking and alcohol-related problems.
Executive cognitive functioning (ECF) and trait impulsivity have long been implicated in risky drinking and alcohol-related problems. However, research on these constructs has developed independently. The present study tested whether two subdomains of adolescent ECF (updating and response inhibition) and adolescent trait impulsivity, considered separately and together, predicted young-adult risky drinking and alcohol-related problems. Data came from the Adolescent/Adult Family Development Project-a longitudinal study of the intergenerational transmission of alcohol use. Alcohol-naïve youth ages 11-17 (N = 249) completed three tasks tapping ECF subdomains of updating (letter-number sequencing, matrix span task) and inhibition (immediate memory task) and a self-reported measure of trait impulsivity (UPPS-P). Approximately 7 years later (ages 18-25), participants reported on their drinking behavior (maximum drinks in a day, heavy episodic drinking, alcohol-related problems). We tested whether adolescent ECF and trait impulsivity predicted young-adult drinking outcomes, separately and together. Results showed that poorer adolescent ECF (a latent factor) predicted more maximum drinks in a day (Incidence Rate Ratios [IRR] = 1.27, p = .001) but not young-adult heavy episodic drinking and alcohol-related problems. In contrast, adolescent trait impulsivity predicted all three outcomes: maximum drinks in a day (IRR = 1.34, p < .001), heavy episodic drinking (β = 0.27, p < .001), and alcohol-related problems in young adulthood (IRR = 1.60, p = .001). Results were similar when adolescent ECF and trait impulsivity were considered together in the same model. Findings suggest that adolescent trait impulsivity is a robust predictor of young-adult risky drinking and alcohol-related problems. Adolescent ECF, and specifically response inhibition, may add predictive value over and above trait impulsivity for some alcohol outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Sensitive acoustic vibration sensor using single-mode fiber tapers.
Optical fiber sensors are a good alternative to piezoelectric devices in electromagnetic sensitive environments. In this study, we reported a fiber acoustic sensor based on single-mode fiber (SMF) tapers. The fiber taper is used as the sensing arm in a Mach-Zehnder interferometer. Benefiting from their micrometer dimensions, fiber tapers have shown higher sensitivities to the acoustic vibrations than SMFs. Under the same conditions, the thinnest fiber taper in this report, with a diameter of 1.7 µm, shows a 20 dB improvement in the signal to noise ratio as compared to that of an SMF. This acoustic vibration sensor can detect the acoustic waves over the frequencies of 30 Hz-40 kHz, which is limited by the acoustic wave generator in experiments. We also discussed the phase changes of fiber tapers with different diameters under acoustic vibrations.


Trophic dynamics of scleractinian corals: stable isotope evidence.
Reef-building corals form symbioses with dinoflagellates from the diverse genus Symbiodinium. This symbiotic association has developed adaptations to acquire and share nutrients, which are essential for its survival and growth in nutrient-poor tropical waters. The host is thus able to prey on a wide range of organic food sources (heterotrophic nutrition) whereas the symbionts acquire most of the inorganic nutrients (autotrophic nutrition). However, nutrient fluxes between the two partners remain unclear, especially concerning heterotrophically acquired carbon and nitrogen. We combined physiological measurements and pulse-chase isotopic labeling of heterotrophic carbon and nitrogen, as well as autotrophic carbon to track nutrient fluxes in two coral species, Stylophora pistillata and Turbinaria reniformis, in symbiosis with Symbiodinium clades A, and C,D respectively. We showed a rapid acquisition, exchange and a long-term retention of heterotrophic nutrients within the symbiosis, whereas autotrophic nutrients were rapidly used to meet immediate metabolic needs. In addition, there was a higher retention of heterotrophic nitrogen compared with carbon, in agreement with the idea that tropical corals are nitrogen-limited. Finally, a coupling between auto- and heterotrophy was observed in the species S. pistillata, with a higher acquisition and retention of heterotrophic nutrients under low irradiance to compensate for a 50% reduction in autotrophic nutrient acquisition and translocation. Conversely, T. reniformis conserved an equivalent heterotrophic nutrient acquisition at both light levels because this coral species did not significantly reduce its rates of gross photosynthesis and autotrophic carbon acquisition between the two irradiances. These experiments advance the current understanding of the nutrient exchanges between the two partners of a symbiotic association, providing evidence of the complexity of the host-symbiont relationship.


[Linkage Between Promotion of Employment and Promotion of Health in the Community Setting - Results of the Pilot Project of the Federal Employment Agency and the Statutory Health Insurance].
The Federal Employment Agency and the Statutory Health Insurance (GKV) have put the link between the promotion of employment and of health to the test by making a joint approach aiming to reach unemployed persons with preventive health services and to maintain or improve their employability. Specialist case workers (Integrationsfachkräfte) of the job centres conducted health consultations, motivating unemployed persons and raising their awareness of their own health as well as enabling them to access health promotion services of health insurance funds on a voluntary basis. Three different approaches were tested: consultations either being offered by specialist case workers of the job centres, by contracted educational institutions or by the federal employment agency's own special services (Fachdienste). The pilot project was implemented locally in the community setting. The steering groups set up in the 6 pilot locations, consisting of representatives of the job centres and the health insurance funds as well as of further local players, were the key element of this project. The offers implemented were a success: The unemployed persons welcomed the consultations offered by job centres; the preventive health services specifically directed at unemployed persons that were provided by health insurance funds have proven successful, especially in terms of reducing stress and maintaining employability. Inclusion of the key points of this approach into the basic recommendations at federal level (Bundesrahmenempfehlungen) of the National Conference on Prevention of 19 February 2016 has created a basis for further advances and dissemination.


Reduced metabolic response of the aged rat brain to haloperidol.
Local cerebral glucose utilization (LCGU) was determined in 49 brain regions of 3-, 12-, 24-, and 33-month-old awake Fischer-344 rats, at 30 to 120 min after administration of the dopaminergic antagonist haloperidol (HAL) at 1 mg/kg (i.p.). The quantitative autoradiographic [14C]-2-deoxyglucose technique was employed. In 3-month rats, HAL produced statistically significant (p less than 0.05) reductions in LCGU in 63% of the brain regions examined, including those having dopaminergic as well as non-dopaminergic function. With increasing age, LCGU was progressively less affected by HAL. Significant declines in LCGU occurred in 21 to 23% of the observed regions in 12- and 24-month rats, and in 10% of the 49 regions in 33-month-old rats. The peak effects of HAL on LCGU occurred later in the 33-month- than in the 3-month-old rats (90 and 60 min after HAL, respectively). The behavioral effect (catalepsy) of HAL was less in old than in young rats. Age-related differences in the cerebral metabolic and behavioral responsivities of rats to HAL are not due to differences in brain concentrations of HAL, as higher concentrations are obtained in older animals (Kapetanovic, I.M., D.J. Sweeney, and S.I. Rapoport (1982) J. Pharmacol. Exp. Ther. 221: 434-438). The differences correlate with known age-dependent structural and biochemical deficits of the central dopaminergic system and indicate reduced functioning of that system in the rat brain after 12 months of age.


Coagulase-negative staphylococci: clinical, microbiological and molecular features to predict true bacteraemia.
Coagulase-negative staphylococci (CNS) are frequently isolated from blood cultures, where they may be only a contaminant or the cause of bacteraemia. Determining whether an isolate of CNS represents a true CNS bacteraemia is difficult, and there is no single criterion with sufficient specificity. The aim of this study was to assess those clinical, microbiological, pathogenic and genotypic features that characterize true CNS bacteraemia. Twenty patients having two or more blood cultures positive for CNS and 20 patients with only one positive blood culture were studied. Significant bacteraemia was defined according to clinical and laboratory criteria. Incubation time for blood cultures to become positive, macroscopic appearance of colonies, species determination, biotype, susceptibility to antimicrobials, PFGE pattern and adherence capacity were all studied. Clinical bacteraemia was present in 16/20 patients with two or more positive blood cultures and in 2/20 patients with only one positive blood culture. A significant difference was seen in the median time to positivity between the 18 clinical bacteraemias and 22 contaminations (23.6 versus 29.2 h; P = 0.04, Wilcoxon). There was also a significant difference between the two groups in the median absorbance of the slime test (1.36 versus 0.58; P = 0.005). All significant bacteraemias with two or more positive blood cultures had the same species identified, the same antimicrobial susceptibility pattern and the same PFGE pattern. In two patients with true bacteraemia with only one positive blood culture, the incubation time for the culture to turn positive was <24 h and the slime production absorbance was >2.5. The most useful parameters for the diagnosis of true CNS bacteraemia for patients with two positive blood cultures were incubation time until positive, species identification, antimicrobial susceptibility pattern, slime production and PFGE pattern. For patients with only one blood culture positive for CNS, the useful parameters for prediction of true bacteraemia were incubation time until positive and slime production, both of which are simple, low-cost tests.


Enhancing nursing research with children and families using a developmental science perspective.
Nursing scholarship on children and their families has increased rapidly over the past decades. This research focuses on infants, children, and adolescents and their families facing acute or chronic illness, as well as on promoting health and preventing disease in children. While the amount and scope of research in pediatric nursing has increased, the methods and theories used are diverse and are often not based on the most recent science in the broader fields of developmental research. Developmental science, which evolved over the past two decades into a new interdisciplinary framework for the study of human development, involves an integrated holistic, developmental, and systems-oriented perspective. According to this view, the individual functions and develops through dynamic and complex processes involving the integration of many systems within the individual, including mental, biological, and behavioral systems. In addition, individuals function and develop in a continuously ongoing, reciprocal process of interaction with their environment and, as such, have an influence on that environment. These nonlinear, dynamic processes demand complex conceptualizations and research designs if one is to truly understand human development, including health and illness. Key aspects of developmental science important in conceptualization, design, measurement, and data analysis are identified. By providing a framework for critiquing research and presenting recommendations for future research based on developmental science, we hope to move nursing research with children forward toward more developmentally sound knowledge of nursing practice.


A Genome-Wide Screen for Wortmannin-Resistant Mutants in Schizosaccharomyces pombe: The Phosphorylation-Impaired Mutants Are Resistant to Signaling Defect.
Complex human diseases such as metabolic disorders, cancer, neurodegenerative diseases, and mitochondrial dysfunctions arise from the biochemical or genetic defects in various cellular processes. Therefore, it is important to understand which metabolic processes are affected by which cellular impairment. Because genome-wide screening of mutant collections (haploid/diploid deletion library) provides important clues for the understanding of conserved biological processes and for finding potential target genes, we screened the haploid mutant collection of Schizosaccharomyces pombe with wortmannin that inhibits phosphatidylinositol-3-kinase signaling. Using genome-wide screening, we determined that 52 mutants were resistant to this chemical. When 52 genes that are deleted in these mutants were grouped in 41 different biological processes, we found that 37 of them have human orthologues and 4 genes were associated with human metabolic disorders. In addition, when we examined the pathways in which these 52 genes function, we determined that 9 genes were related to phosphorylation process. These results might provide new insights for better understanding of certain human diseases.


Polymyalgia rheumatica and rheumatoid arthritis of the elderly: a clinical, laboratory, and scintigraphic comparison.
Clinical, laboratory, and scintigraphic features of 16 patients with polymyalgia rheumatica and 23 patients matched for age presenting with classical or definite rheumatoid arthritis (American Rheumatism Association 1958 criteria) of the elderly were compared in order to define features that might distinguish between these two syndromes. The sensitivity of proposed diagnostic criteria for polymyalgia rheumatica was always higher in the group with polymyalgia rheumatica, though only significantly so for morning stiffness. A comparison of 27 different laboratory features showed few significant differences between the diseases, though correlation between laboratory variables within each of the disease groups differed, perhaps suggesting a fundamental pathogenetic difference between them. Scintigraphy of the shoulder joint proved of no value in differential diagnosis. It was concluded that polymyalgia rheumatica and rheumatoid arthritis of the elderly are probably discrete clinical entities. Bilateral upper arm tenderness, lack of positive rheumatoid factor, and a normal caeruloplasmin are the most valuable features for distinguishing polymyalgia rheumatica from rheumatoid arthritis of the elderly.


[Intrauterine infection and the preterm brain: dimensions of aetiology research].
Perinatal brain damage has a diverse and complex aetiology. Over the past decades, much progress has been made in this research field. In this article, I offer a discussion of seven dimensions of aetiological perinatal brain damage research: (1) hypoxia-ischaemia vs. inflammation; (2) "classic" vs. "remote" intrauterine infection; (3) focal vs. diffuse white matter damage; (4) maternal vs. foetal inflammatory response; (5) clinical vs. experimental data; (6) bacterial vs. viral infection; and (7) preterm vs. term delivery. Despite these complexities, it is hoped that obstetricians, neonatologists, and neuropaediatricians will agree on a perinatal neuroprotective strategy in the near future.


Accuracy, calibration and clinical performance of the new EuroSCORE II risk stratification system.
The European System for Cardiac Operative Risk Evaluation (EuroSCORE) has been used for many years since its introduction in 1999. Recently, a new EuroSCORE (EuroSCORE II) has been developed to update the previous version. The EuroSCORE II includes some different predictors and/or introduces a new classification of the already existing predictors. This study presents a validation series for the EuroSCORE II compared with the previous additive and the logistic EuroSCORE and with the Age, Creatinine and Ejection Fraction (ACEF) score. A total of 1090 consecutive adult patients operated on at our institution from September 2010 to October 2011 were admitted to this retrospective study. All the patients received a risk stratification based on the EuroSCORE II and the other scores considered. Accuracy, calibration and clinical performance of the various risk models were assessed. The accuracy of the EuroSCORE II was good (c-statistic 0.81) but not significantly higher than the other scores (range 0.78-0.8). Calibration at the Hosmer-Lemeshow statistic was good for all the scores; the difference between observed (3.75%) and predicted mortality in the overall population was not significant for the EuroSCORE II (3.1%) and the ACEF score (3.4%), whereas the additive EuroSCORE (5.8%) and the logistic EuroSCORE (7.3%) significantly overestimated the risk. In patients at low, mild moderate and high mortality risk, the EuroSCORE II provided a risk prediction not significantly different from the observed mortality rate, whereas in very high-risk patients (observed mortality rate 11%), it significantly underestimated (6.5%) the mortality risk. The accuracy of the EuroSCORE II was acceptable in isolated coronary surgery, and good or excellent in the other operations. The EuroSCORE II represents a useful update of the previous EuroSCORE version, with a much better clinical performance and the same good level of accuracy. It is possible that for the risk stratification of very high-risk patients, other factors (rare but associated with a mortality rate >50%) should be included in the future models.


[Nature of antigens antibodies to which are detected in the serum of schizophrenic patients].
The study was conducted by the immune absorption method. The serum activity before and after absorption was studied with the cytotoxic test and the fluorescent antibody method. The studies demonstrated that antibodies, detected in the blood serum of patients and normals differ not only qualitatively but also quantitatively. It was established as well that antibodies detected in normals may be completely absorbed by the brain and thymus of mice or by similar human tissues. In absorption of antibodies in patients by tissues of mice, the activity of the sera entirely disappears. On the contrary, the brain tissue and human thymocytes only insignificantly decrease the serum titres in patients.


High dose vitamin D3 empowers effects of subcutaneous immunotherapy in a grass pollen-driven mouse model of asthma.
Allergen-specific immunotherapy (AIT) has the potential to provide long-term protection against allergic diseases. However, efficacy of AIT is suboptimal, while application of high doses allergen has safety concerns. The use of adjuvants, like 1,25(OH)2VitD3 (VitD3), can improve efficacy of AIT. We have previously shown that low dose VitD3 can enhance suppression of airway inflammation, but not airway hyperresponsiveness in a grass pollen (GP)-subcutaneous immunotherapy (SCIT) mouse model of allergic asthma. We here aim to determine the optimal dose and formulation of VitD3 for the GP SCIT. GP-sensitized BALBc/ByJ mice received three SCIT injections of VitD3-GP (30, 100, and 300 ng or placebo). Separately, synthetic lipids, SAINT, was added to the VitD3-GP-SCIT formulation (300 nmol) and control groups. Subsequently, mice were challenged with intranasal GP, and airway hyperresponsiveness, GP-specific IgE, -IgG1, and -IgG2a, ear-swelling responses (ESR), eosinophils in broncho-alveolar lavage fluid and lung were measured. VitD3 supplementation of GP-SCIT dose-dependently induced significantly enhanced suppression of spIgE, inflammation and hyperresponsiveness, while neutralizing capacity was improved and ESR were reduced. Addition of VitD3 further decreased Th2 cytokine responses and innate cytokines to allergens in lung tissue by GP-SCIT. However, addition of synthetic lipids to the allergen/VitD3 mixes had no additional effect on VitD3-GP-SCIT. We find a clear, dose dependent effect of VitD3 on GP-SCIT-mediated suppression of allergic inflammation and airway hyperresponsiveness. In contrast, addition of synthetic lipids to the allergen/VitD3 mix had no therapeutic effect. These studies underscore the relevance of VitD3 as an adjuvant to improve clinical efficacy of SCIT treatment regimens.


MeCP2 post-translational modifications: a mechanism to control its involvement in synaptic plasticity and homeostasis?
Although Rett syndrome (RTT) represents one of the most frequent forms of severe intellectual disability in females worldwide, we still have an inadequate knowledge of the many roles played by MeCP2 (whose mutations are responsible for most cases of RTT) and their relevance for RTT pathobiology. Several studies support a role of MeCP2 in the regulation of synaptic plasticity and homeostasis. At the molecular level, MeCP2 is described as a repressor capable of inhibiting gene transcription through chromatin compaction. Indeed, it interacts with several chromatin remodeling factors, such as HDAC-containing complexes and ATRX. Other studies have inferred that MeCP2 functions also as an activator; a role in regulating mRNA splicing and in modulating protein synthesis has also been proposed. Further, MeCP2 avidly binds both 5-methyl- and 5-hydroxymethyl-cytosine. Recent evidence suggests that it is the highly disorganized structure of MeCP2, together with its post-translational modifications (PTMs) that generate and regulate this functional versatility. Indeed, several reports have demonstrated that differential phosphorylation of MeCP2 is a key mechanism by which the methyl binding protein modulates its affinity for its partners, gene expression and cellular adaptations to stimuli and neuronal plasticity. As logic consequence, generation of phospho-defective Mecp2 knock-in mice has permitted associating alterations in neuronal morphology, circuit formation, and mouse behavioral phenotypes with specific phosphorylation events. MeCP2 undergoes various other PTMs, including acetylation, ubiquitination and sumoylation, whose functional roles remain largely unexplored. These results, together with the genome-wide distribution of MeCP2 and its capability to substitute histone H1, recall the complex regulation of histones and suggest the relevance of quickly gaining a deeper comprehension of MeCP2 PTMs, the respective writers and readers and the consequent functional outcomes.


The start of a new school year: individual differences in salivary cortisol response in relation to child temperament.
Noon and evening salivary cortisol levels were examined in 70 elementary school children during the 1st week of a new school year. Samples were obtained on the 1st and 5th days of school and on weekend days. Delta cortisol scores were created to measure the change in children's levels on initial school days relative to weekend days. Temperament was assessed using Rothbart's Child Behavior Questionnaire, a parent report instrument. The three dimensions of surgency or extroversion, negative affectivity, and effortful control were examined. Positive correlations were obtained with Day 1 delta cortisol for negative affectivity and Day 5 delta cortisol for surgency. Contrary to the expectation that internalizing aspects of temperament (shyness, fearfulness) would be associated with larger increases in cortisol to the novelty and challenge of a new school year, these data indicate that larger increases in cortisol were observed in more extroverted children.


Internal medicine residents' perceptions of the Mini-Clinical Evaluation Exercise.
The mini-clinical evaluation exercise (mini-CEX) is a 30 minute observed clinical encounter which allows assessment of a resident's clinical competence with feedback on their performance. To assess residents' perceptions of the mini-CEX using qualitative methods. After introducing the mini-CEX into the University of British Columbia's Internal Medicine Residency Program, a one hour semi-structured focus group with voluntary first and second year residents was undertaken. The focus groups were conducted by an independent moderator, audio-taped, and transcribed verbatim. Using a phenomenological approach, the comments made by the focus group participants were read independently by the three authors and organized into major themes. The major themes included Education, Assessment and Exam Preparation. Residents described a conflict between the mini-CEX's role as a method of assessment and its utility as an educational tool. During initial mini-CEX encounters, they perceived the assessment format as anxiety-provoking. Over time, they felt that the mini-CEX provided insight into their clinical competence. Participants believed that the mini-CEX experience would benefit them in preparation and successful completion of their national specialty exam. Residents' perceptions of the mini-CEX reflected a tension between the tool's dual roles of assessment and education.


Comparison of volatile constituents, and antioxidant and antibacterial activities of the essential oils of Thymus caucasicus, T. kotschyanus and T. vulgaris.
A comparison of the chemical composition, and antioxidant and antibacterial activities of the essential oils obtained from the aerial parts of Thymus caucasicus, T. kotschyanus, and T vulgaris was carried out. The oils, obtained by hydrodistillation, were analyzed by GC and GC/MS. Twenty, 29 and 22 compounds representing 94.8%, 96.6% and 98.2% of the essential oils of T. caucasicus, T. kotschyanus and T. vulgaris, respectively, have been identified. The oil of T. caucasicus was characterized by 1,8-cineol (21.5%), thymol (12.6%), beta-fenchyl alcohol (8.7%), nerolidol (7.8%), terpinolene (7.2%), alpha-pinene (7.0%) and myrcene (6.8%). In the oil of T. kotschyanus, carvacrol (24.4%), beta-caryophyllene (14.5%), gamma-terpinene (12.4%), alpha-phellandrene (10.8%), p-cymene (9.8%) and thymol (6.8%) were the predominant compounds, whereas the main components of T. vulgaris oil were thymol (43.8%), p-cymene (15.2%), germacrene-D (11.7%), terpinolene (3.4%), carvacrol (3.2%), beta-caryophyllene (2.8%) and alpha-thujene (2.2%). In all three plants oil, hydrocarbon monoterpenes predominated over sesquiterpenes. Antioxidant activities were assessed by determining IC50 values in the DPPH radical scavenging assay. Antibacterial activity was determined by measuring minimum inhibitory concentration (MIC) using the broth dilution method. The essential oils of T. caucasicus, T. kotschyanus and T. vulgaris showed free radical scavenging and antibacterial activity.


Network Analysis of Different Exogenous Hormones on the Regulation of Deep Sowing Tolerance in Maize Seedlings.
The planting method of deep sowing can make the seeds make full use of water in deep soil, which is considered to be an effective way to respond to drought stress. However, deep sowing will affect the growth and development of maize (Zea mays L.) at seedling stage. To better understand the response of maize to deep sowing stress and the mechanism of exogenous hormones [Gibberellin (GA3), Brassinolide (BR), Strigolactone (SL)] alleviates the damaging effects of deep-sowing stress, the physiological and transcriptome expression profiles of seedlings of deep sowing sensitive inbred line Zi330 and the deep-tolerant inbred line Qi319 were compared under deep sowing stress and the conditions of exogenous hormones alleviates stress. The results showed that mesocotyl elongated significantly after both deep sowing stress and application of exogenous hormones, and its elongation was mainly through elongation and expansion of cell volume. Hormone assays revealed no significant changes in zeatin (ZT) content of the mesocotyl after deep sowing and exogenous hormone application. The endogenous GA3 and auxin (IAA) contents in the mesocotyl of the two inbred lines increased significantly after the addition of exogenous GA3, BR, and SL under deep sowing stress compared to deep sowing stress, while BR and SL decreased significantly. Transcriptome analysis showed that the deep seeding stress was alleviated by GA3, BR, and SLs, the differentially expressed genes (DEGs) mainly included cellulose synthase, expansin and glucanase, oxidase, lignin biosynthesis genes and so on. We also found that protein phosphatase 2C and GA receptor GID1 enhanced the ability of resist deep seeding stress in maize by participating in the abscisic acid (ABA) and the GA signaling pathway, respectively. In addition, we identified two gene modules that were significantly related to mesocotyl elongation, and identified some hub genes that were significantly related to mesocotyl elongation by WGCNA analysis. These genes were mainly involved in transcription regulation, hydrolase activity, protein binding and plasma membrane. Our results from this study may provide theoretical basis for determining the maize deep seeding tolerance and the mechanism by which exogenous hormones regulates deep seeding tolerance.


Tactile friction of topical formulations.
The tactile perception is essential for all types of topical formulations (cosmetic, pharmaceutical, medical device) and the possibility to predict the sensorial response by using instrumental methods instead of sensory testing would save time and cost at an early stage product development. Here, we report on an instrumental evaluation method using tactile friction measurements to estimate perceptual attributes of topical formulations. Friction was measured between an index finger and an artificial skin substrate after application of formulations using a force sensor. Both model formulations of liquid crystalline phase structures with significantly different tactile properties, as well as commercial pharmaceutical moisturizing creams being more tactile-similar, were investigated. Friction coefficients were calculated as the ratio of the friction force to the applied load. The structures of the model formulations and phase transitions as a result of water evaporation were identified using optical microscopy. The friction device could distinguish friction coefficients between the phase structures, as well as the commercial creams after spreading and absorption into the substrate. In addition, phase transitions resulting in alterations in the feel of the formulations could be detected. A correlation was established between skin hydration and friction coefficient, where hydrated skin gave rise to higher friction. Also a link between skin smoothening and finger friction was established for the commercial moisturizing creams, although further investigations are needed to analyse this and correlations with other sensorial attributes in more detail. The present investigation shows that tactile friction measurements have potential as an alternative or complement in the evaluation of perception of topical formulations.


Biosynthesis of compatible solutes in rhizobial strains isolated from Phaseolus vulgaris nodules in Tunisian fields.
Associated with appropriate crop and soil management, inoculation of legumes with microbial biofertilizers can improve food legume yield and soil fertility and reduce pollution by inorganic fertilizers. Rhizospheric bacteria are subjected to osmotic stress imposed by drought and/or NaCl, two abiotic constraints frequently found in semi-arid lands. Osmostress response in bacteria involves the accumulation of small organic compounds called compatible solutes. Whereas most studies on rhizobial osmoadaptation have focussed on the model species Sinorhizobium meliloti, little is known on the osmoadaptive mechanisms used by native rhizobia, which are good sources of inoculants. In this work, we investigated the synthesis and accumulations of compatible solutes by four rhizobial strains isolated from root nodules of Phaseolus vulgaris in Tunisia, as well as by the reference strain Rhizobium tropici CIAT 899T. The most NaCl-tolerant strain was A. tumefaciens 10c2, followed (in decreasing order) by R. tropici CIAT 899, R. leguminosarum bv. phaseoli 31c3, R. etli 12a3 and R. gallicum bv. phaseoli 8a3. 13C- and 1H-NMR analyses showed that all Rhizobium strains synthesized trehalose whereas A. tumefaciens 10c2 synthesized mannosucrose. Glutamate synthesis was also observed in R. tropici CIAT 899, R. leguminosarum bv. phaseoli 31c3 and A. tumefaciens 10c2. When added as a carbon source, mannitol was also accumulated by all strains. Accumulation of trehalose in R. tropici CIAT 899 and of mannosucrose in A. tumefaciens 10c2 was osmoregulated, suggesting their involvement in osmotolerance. The phylogenetic analysis of the otsA gene, encoding the trehalose-6-phosphate synthase, suggested the existence of lateral transfer events. In vivo 13C labeling experiments together with genomic analysis led us to propose the uptake and conversion pathways of different carbon sources into trehalose. Collaterally, the beta-1,2-cyclic glucan from R. tropici CIAT 899 was co-extracted with the cytoplasmic compatible solutes and its chemical structure was determined. The soil bacteria analyzed in this work accumulated mainly disaccharides in response to NaCl stress. We could not find a direct correlation between the trehalose content of the rhizobial strains and their osmotolerance, suggesting that additional osmoadaptive mechanism should be operating in the most NaCl-tolerant strain R. tropici CIAT 899.


Phase-diversity wavefront sensing enhanced by a Fourier-based neural network.
Phase diversity wavefront sensing (PDWS) has been a successful approach to quantifying wavefront aberrations with only a few intensity measurements and nonlinear optimization. However, the inherent non-convexity of the inverse problem may lead to stagnation at a local minimum far from the true solution. Proper initialization of the nonlinear optimization is important to avoid local minima and improve wavefront retrieval accuracy. In this paper, we propose an effective neural network based on low-frequency coefficients in the Fourier domain to determine a better estimate of the unknown aberrations. By virtue of the proposed network, only a small amount of simulation data suffice for a robust training, two orders of magnitude less than those in existing work. Experimental results show that, when compared with some existing methods, our method achieves the highest accuracy while drastically reducing the training time to 1.4 min. The minimum, maximum, and mean values of the root mean square (RMS) residual errors for 800 aberrations are 0.017λ, 0.056λ, and 0.039λ, respectively, and 95% of the RMS residual errors are less than 0.05λ.


DISCOVERY AND VALIDATION OF GENES DRIVING DRUG-INTAKE AND RELATED BEHAVIORAL TRAITS IN MICE.
Substance use disorders (SUDs) are heritable disorders characterized by compulsive drug use, but the biological mechanisms driving addiction remain largely unknown. Genetic correlations reveal that predisposing drug-naïve phenotypes, including anxiety, depression, novelty preference, and sensation seeking, are predictive of drug-use phenotypes, implicating shared genetic mechanisms. Because of this relationship, high-throughput behavioral screening of predictive phenotypes in knockout (KO) mice allows efficient discovery of genes likely to be involved in drug use. We used this strategy in two rounds of screening in which we identified 33 drug-use candidate genes and ultimately validated the perturbation of 22 of these genes as causal drivers of substance intake. In our initial round of screening, we employed the two-bottle-choice paradigms to assess alcohol, methamphetamine, and nicotine intake. We identified 19 KO strains that were extreme responders on at least one predictive phenotype. Thirteen of the 19 gene deletions (68%) significantly affected alcohol use three methamphetamine use, and two both. In the second round of screening, we employed a multivariate approach to identify outliers and performed validation using methamphetamine two-bottle choice and ethanol drinking-in-the-dark protocols. We identified 15 KO strains that were extreme responders across the predisposing drug-naïve phenotypes. Eight of the 15 gene deletions (53%) significantly affected intake or preference for three alcohol, eight methamphetamine or three both (3). We observed multiple relations between predisposing behaviors and drug intake, revealing many distinct biobehavioral processes underlying these relationships. The set of mouse models identified in this study can be used to characterize these addiction-related processes further.


Molecular organization of the 20S proteasome gene family from Arabidopsis thaliana.
The 20S proteasome is the proteolytic complex in eukaryotes responsible for degrading short-lived and abnormal intracellular proteins, especially those targeted by ubiquitin conjugation. The 700-kD complex exists as a hollow cylinder comprising four stacked rings with the catalytic sites located in the lumen. The two outer rings and the two inner rings are composed of seven different alpha and beta polypeptides, respectively, giving an alpha7/beta7/beta7/alpha7 symmetric organization. Here we describe the molecular organization of the 20S proteasome from the plant Arabidopsis thaliana. From an analysis of a collection of cDNA and genomic clones, we identified a superfamily of 23 genes encoding all 14 of the Arabidopsis proteasome subunits, designated PAA-PAG and PBA-PBG for Proteasome Alpha and Beta subunits A-G, respectively. Four of the subunits likely are encoded by single genes, and the remaining subunits are encoded by families of at least 2 genes. Expression of the alpha and beta subunit genes appears to be coordinately regulated. Three of the nine Arabidopsis proteasome subunit genes tested, PAC1 (alpha3), PAE1 (alpha5) and PBC2 (beta3), could functionally replace their yeast orthologs, providing the first evidence for cross-species complementation of 20S subunit genes. Taken together, these results demonstrate that the 20S proteasome is structurally and functionally conserved among eukaryotes and suggest that the subunit arrangement of the Arabidopsis 20S proteasome is similar if not identical to that recently determined for the yeast complex.


Rigor mortis in an unusual position: Forensic considerations.
We report a case in which the dead body was found with rigor mortis in an unusual position. The dead body was lying on its back with limbs raised, defying gravity. Direction of the salivary stains on the face was also defying the gravity. We opined that the scene of occurrence of crime is unlikely to be the final place where the dead body was found. The clues were revealing a homicidal offence and an attempt to destroy the evidence. The forensic use of 'rigor mortis in an unusual position' is in furthering the investigations, and the scientific confirmation of two facts - the scene of death (occurrence) is different from the scene of disposal of dead body, and time gap between the two places.


BCG Signal Quality Assessment Based on Time-Series Imaging Methods.
This paper describes a signal quality classification method for arm ballistocardiogram (BCG), which has the potential for non-invasive and continuous blood pressure measurement. An advantage of the BCG signal for wearable devices is that it can easily be measured using accelerometers. However, the BCG signal is also susceptible to noise caused by motion artifacts. This distortion leads to errors in blood pressure estimation, thereby lowering the performance of blood pressure measurement based on BCG. In this study, to prevent such performance degradation, a binary classification model was created to distinguish between high-quality versus low-quality BCG signals. To estimate the most accurate model, four time-series imaging methods (recurrence plot, the Gramain angular summation field, the Gramain angular difference field, and the Markov transition field) were studied to convert the temporal BCG signal associated with each heartbeat into a 448 × 448 pixel image, and the image was classified using CNN models such as ResNet, SqueezeNet, DenseNet, and LeNet. A total of 9626 BCG beats were used for training, validation, and testing. The experimental results showed that the ResNet and SqueezeNet models with the Gramain angular difference field method achieved a binary classification accuracy of up to 87.5%.


Curcumin Mitigates Radiation-induced Lung Pneumonitis and Fibrosis in Rats.
Radiation-induced lung injury is one of the most prominent factors that interfere with chest cancer radiotherapy, and poses a great threat to patients exposed to total body irradiation. Upregulation of pro-oxidant enzymes is one of the main mechanisms through which the late effects of ionizing radiation on lung injury can be exerted. Interleukin (IL)-4 and IL-13 are two important cytokines that have been proposed to be involved in this process. Through stimulation of dual oxidase 1 and 2 (DUOX 1 & 2), they induce chronic oxidative stress in irradiated tissues. In this study, we evaluated the effects of curcumin treatment on the regulation of IL-4 and IL-13, DUOX1 & 2 genes as well as the pathological changes developed by this treatment. Twenty male Wistar rats were divided into four groups: radiation only; curcumin only; radiation +curcumin; and control group with neither pharmacotherapy nor radiation. Curcumin was administered for 4 and 6 consecutive days before and after irradiation, respectively. Also, the chest area was irradiated with 15 Gy using a cobalt-60 gamma rays source. All rats were sacrificed 67 days after irradiation, followed by the assessment of the levels of IL-4 and IL-13; the expression of IL- 4 receptor-a1 (IL4Ra1), IL13Ra2, DUOX1 and DUOX2, and finally the histopathological changes were evaluated. Radiation led to the increased level of IL-4, while the level of IL-13 showed no change. QPCR results showed the upregulation of IL4Ra1, DUOX1 and DUOX2 following lung irradiation. Histopathological evaluation also showed a remarkable increase in pneumonitis and fibrosis. Treatment with curcumin downregulated the expression of IL-4, IL4Ra1, DUOX1 & 2. Furthermore, it could mitigate pneumonitis and fibrosis following lung irradiation. The late effects of radiation- induced lung injury may be due to the upregulation of DUOX1 & 2 genes. Curcumin, through modulation of these genes, may contribute to the protection against ionizing radiation.


Sequential aeration of membrane-aerated biofilm reactors for high-rate autotrophic nitrogen removal: experimental demonstration.
One-stage autotrophic nitrogen (N) removal, requiring the simultaneous activity of aerobic and anaerobic ammonium oxidizing bacteria (AOB and AnAOB), can be obtained in spatially redox-stratified biofilms. However, previous experience with Membrane-Aerated Biofilm Reactors (MABRs) has revealed a difficulty in reducing the abundance and activity of nitrite oxidizing bacteria (NOB), which drastically lowers process efficiency. Here we show how sequential aeration is an effective strategy to attain autotrophic N removal in MABRs: Two separate MABRs, which displayed limited or no N removal under continuous aeration, could remove more than 5.5 g N/m(2)/day (at loads up to 8 g N/m(2)/day) by controlled variation of sequential aeration regimes. Daily averaged ratios of the surficial loads of O(2) (oxygen) to NH(4)(+) (ammonium) (L(O(2))/L(NH(4))) were close to 1.73 at this optimum. Real-time quantitative PCR based on 16S rRNA gene confirmed that sequential aeration, even at elevated average O(2) loads, stimulated the abundance of AnAOB and AOB and prevented the increase in NOB. Nitrous oxide (N(2)O) emissions were 100-fold lower compared to other anaerobic ammonium oxidation (Anammox)-nitritation systems. Hence, by applying periodic aeration to MABRs, one-stage autotrophic N removal biofilm reactors can be easily obtained, displaying very competitive removal rates, and negligible N(2)O emissions.


cDNA subtraction hybridization: a review and an application to neuroblastoma.
Recent advances in molecular biological techniques have increased our capability to distinguish the small differences in gene expression between subpopulations of cells found within specific tissues or tumor isolates. We use subtractive hybridization or subtractive cloning to generate information regarding genes that direct various aspects of mammalian embryonic development. The technique also is used to identify genes with specificity for particular tissues or cell types or those that regulate various processes in the cell. Also, subject to analysis is the aberrant expression of genes involved in tumorigenesis. Another use is analysis of subpopulations of cell types previously identified within individual solid tumors. We used subtractive cloning in the analysis of cell line subpopulations derived from the human pediatric tumor neuroblastoma. This has resulted in the identification of novel genes that may be useful in the study of this disease.


Impact of a new practice guideline on antibiotic use with pediatric tonsillectomy.
More than 500,000 children undergo tonsillectomy each year in the United States. Although prior studies suggest that most patients received perioperative antibiotics, practice varies across centers. In 2011, the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) published a practice guideline recommending against perioperative antibiotic use for pediatric tonsillectomy. The impact of this recommendation has not been thoroughly examined. To determine the impact of the AAO-HNS guideline on the use of perioperative antibiotics and patient outcomes for pediatric tonsillectomy. This was a quasi-experimental study including 9265 children who underwent routine tonsillectomy from January 2009 through August 2012 within a large pediatric health care network containing hospital-based and ambulatory surgical facilities. Data were collected from a shared electronic health record and validated through manual medical record review. We used an interrupted time series analysis with segmented logistic regression and a nonequivalent dependent variable (tympanoplasty) to assess acute changes and differences in trends over time relative to guideline publication. Publication of the AAO-HNS clinical practice guideline. The primary outcome was antibiotic administration on the day of surgery. Secondary outcomes included otolaryngology clinic encounters, emergency department encounters, hospital admissions, and surgical procedures for bleeding in the 30 days following tonsillectomy. Of 9265 tonsillectomies during the study period, 5359 met inclusion criteria. Immediately after guideline publication, perioperative antibiotic use dropped by 86.5% (P < .001) and was sustained throughout the postintervention period. Rates of otolaryngology clinic encounters, emergency department encounters, and hospital admissions did not change significantly over time. There was a small but statistically significant increase in surgical procedures for bleeding following the intervention from 1.35% (95% CI, 0.57%-2.14%) to 3.48% (95% CI, 1.85%-5.10%). AAO-HNS guideline publication decreased perioperative antibiotic use for pediatric tonsillectomy across a large pediatric health care network. Although there were no changes in otolaryngology clinic visits, emergency department visits, or admissions, we found a small but significant increase in surgery for bleeding following guideline publication. Additional studies are necessary to verify this unexpected association.


Antibacterial activity and mechanism of Ag-ZnO nanocomposite on S. aureus and GFP-expressing antibiotic resistant E. coli.
Emergence of multi-resistant organisms (MROs) leads to ineffective treatment with the currently available medications which pose a great threat to public health and food technology sectors. In this regard, there is an urgent need to strengthen the present therapies or to look over for other potential alternatives like use of "metal nanocomposites". Thus, the present study focuses on synthesis of silver-zinc oxide (Ag-ZnO) nanocomposites which will have a broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria. Ag-ZnO nanocomposites of varied molar ratios were synthesized by simple microwave assisted reactions in the absence of surfactants. The crystalline behavior, composition and morphological analysis of the prepared powders were evaluated by X-ray diffraction, infrared spectroscopy, field emission scanning electron microscopy (FE-SEM) and atomic absorption spectrophotometry (AAS). Particle size measurements were carried out by transmission electron microscopy (TEM). Staphylococcus aureus and recombinant green fluorescent protein (GFP) expressing antibiotic resistant Escherichia coli were selected as Gram-positive and Gram-negative model systems respectively and the bactericidal activity of Ag-ZnO nanocomposite was studied. The minimum inhibitory concentration (MIC) and minimum killing concentration (MKC) of the nanocomposite against the model systems were determined by visual turbidity analysis and optical density analysis. Qualitative and quantitative assessments of its antibacterial effects were performed by fluorescent microscopy, fluorescent spectroscopy and Gram staining measurements. Changes in cellular morphology were examined by atomic force microscopy (AFM), FE-SEM and TEM. Finally, on the basis of the present investigation and previously published reports, a plausible antibacterial mechanism of Ag-ZnO nanocomposites was proposed.


Specificity of Anti-Citrullinated Protein Antibodies to Citrullinated α-Enolase Peptides as a Function of Epitope Structure and Composition.
Rheumatoid arthritis (RA) is an autoimmune disease affecting approximately 1-2% of the world population. In addition to the first discovered serologic markers for RA, the rheumatoid factors (RFs), anti-citrullinated protein antibodies (ACPAs) are even more specific for the disease compared to RFs and are found in 70-80% of RA patient sera. RA etiopathogenesis still needs to be elucidated, as different factors are proposed to be involved, such as Epstein-Barr virus infection. Hence, understanding the interaction between ACPAs and their citrullinated peptide targets is relevant for a better knowledge of RA pathophysiology and for diagnostic purposes. In this study, a cohort of RA sera, healthy control sera and multiple sclerosis sera were screened for reactivity to a variety of citrullinated peptides originating from α-enolase, pro-filaggrin, proteoglycan and Epstein-Barr nuclear antigen-2 by enzyme-linked immunosorbent assay. ACPA reactivity to citrullinated α-enolase peptides was found to depend on peptide length and peptide conformation, favouring cyclic (disulfide bond) conformations for long peptides and linear peptides for truncated ones. Additional investigations about the optimal peptide conformation for ACPA detection, employing pro-filaggrin and EBNA-2 peptides, confirmed these findings, indicating a positive effect of cyclization of longer peptides of approximately 20 amino acids. Moreover, screening of the citrullinated peptides confirmed that ACPAs can be divided into two groups based on their reactivity. Approximately 90% of RA sera recognize several peptide targets, being defined as cross-reactive or overlapping reactivities, and whose reactivity to the citrullinated peptide is considered primarily to be backbone-dependent. In contrast, approximately 10% recognize a single target and are defined as nonoverlapping, primarily depending on the specific amino acid side-chains in the epitope for a stable interaction. Collectively, this study contributed to characterize epitope composition and structure for optimal ACPA reactivity and to obtain further knowledge about the cross-reactive nature of ACPAs.


Actin filaments and vasopressin-stimulated water flow in toad urinary bladder.
Vasopressin increases the water permeability of the apical membrane of the granular epithelial cells of the toad urinary bladder. Cytochalasin B inhibits this action of the hormone, indicating that microfilaments may play a role in the water permeability response. We have extended previous functional studies with cytochalasin B and have demonstrated that dihydrocytochalasin B, a more specific inhibitor of actin filament elongation, similarly diminishes the hydrosmotic response to vasopressin. Biochemical studies of isolated epithelial cells indicate that an actin-like protein accounts for about 10% of the soluble protein of the epithelium. Morphological studies of whole toad bladders incubated with heavy meromyosin conclusively demonstrate that actin is a component of the epithelial cells and that actin-containing filaments are associated with both plasma membranes and cytoplasmic organelle membranes. Taken together, these findings provide strong, albeit indirect, evidence that actin microfilaments play a functional role in the hormone-induced increase in water permeability in the toad urinary bladder.


Assessing physical activity in public parks in Brazil using systematic observation.
We assessed park use in Recife, Brazil, and differences in physical activity and occupation rates in public parks with and without the Academia da Cidade Program (ACP), which provides cost-free, supervised physical activity classes. We used the System for Observing Play and Recreation in Communities (SOPARC) in 128 targeted areas in 10 park sites (5 ACP sites, 5 non-ACP sites) to obtain data on the number of users and their physical activity levels and estimated age. Each area was assessed 4 times a day for 11 days over a 4-week period. A total of 32 974 people were observed during 5589 observation visits to target areas. People using ACP parks were more likely to be seen engaging in moderate-to-vigorous (64% vs 49%) and vigorous (25% vs 10%) physical activity. Relatively more participants in ACP sites than in non-ACP sites were females (45% vs 42% of park users) and older adults (14.7% vs 5.7% of park users). On the basis of systematic observation, ACP appears to be a useful strategy in promoting park use and physical activity among the population in Recife.


Environmental Tobacco Smoke Exposure during Pregnancy and Child Neurodevelopment.
The developing fetus is especially vulnerable to environmental toxicants, including tobacco constituents. The aim of this study was to assess the impact of environmental tobacco smoke (ETS) exposure during pregnancy on child neurodevelopment within the first two years of life. The study population consisted of 461 non-smoking pregnant women (saliva cotinine level <10 ng/mL). Maternal passive smoking was assessed based on the cotinine level in saliva analyzed by the use of high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-ESI + MS/MS) and by questionnaire data. The cotinine cut-off value for passive smoking was established at 1.5 ng/mL (sensitivity 63%, specificity 71%). Psychomotor development was assessed in children at the age of one- and two-years using the Bayley Scales of Infant and Toddler Development. Approximately 30% of the women were exposed to ETS during pregnancy. The multivariate linear regression model indicated that ETS exposure in the 1st and the 2nd trimesters of pregnancy were associated with decreasing child language functions at the age of one (β = -3.0, p = 0.03, and β = -4.1, p = 0.008, respectively), and two years (β = -3.8, p = 0.05, and β = -6.3, p = 0.005, respectively). A negative association was found for cotinine level ≥1.5 ng/mL in the 2nd trimester of pregnancy and child cognition at the age of 2 (β = -4.6, p = 0.05), as well as cotinine levels ≥1.5 ng/mL in all trimesters of pregnancy and child motor abilities at two years of age (β = -3.9, p = 0.06, β = -5.3, p = 0.02, and β = -4.2, p = 0.05, for the 1st, the 2nd, and the 3rd trimester of pregnancy, respectively; for the 1st trimester the effect was of borderline statistical significance). This study confirmed that ETS exposure during pregnancy can have a negative impact on child psychomotor development within the first two years of life and underscore the importance of public health interventions aiming at reducing this exposure.


Gating function of isoleucine-116 in TM-3 (position III:16/3.40) for the activity state of the CC-chemokine receptor 5 (CCR5).
A conserved amino acid within a protein family indicates a significance of the residue. In the centre of transmembrane helix (TM)-5, position V:13/5.47, an aromatic amino acid is conserved among class A 7TM receptors. However, in 37% of chemokine receptors - a subgroup of 7TM receptors - it is a leucine indicating an altered function. Here, we describe the significance of this position and its possible interaction with TM-3 for CCR5 activity. The effects of [L203F]-CCR5 in TM-5 (position V:13/5.47), [I116A]-CCR5 in TM-3 (III:16/3.40) and [L203F;G286F]-CCR5 (V:13/5.47;VII:09/7.42) were determined in G-protein- and β-arrestin-coupled signalling. Computational modelling monitored changes in amino acid conformation. [L203F]-CCR5 increased the basal level of G-protein coupling (20-70% of Emax ) and β-arrestin recruitment (50% of Emax ) with a threefold increase in agonist potency. In silico, [I116A]-CCR5 switched χ1-angle in [L203F]-CCR5. Furthermore, [I116A]-CCR5 was constitutively active to a similar degree as [L203F]-CCR5. Tyr(244) in TM-6 (VI:09/6.44) moved towards TM-5 in silico, consistent with its previously shown function for CCR5 activation. On [L203F;G286F]-CCR5 the antagonist aplaviroc was converted to a superagonist. The results imply that an aromatic amino acid in the centre of TM-5 controls the level of receptor activity. Furthermore, Ile(116) acts as a gate for the movement of Tyr(244) towards TM-5 in the active state, a mechanism proposed previously for the β2 -adrenoceptor. The results provide an understanding of chemokine receptor function and thereby information for the development of biased and non-biased antagonists and inverse agonists.


Association between physical fitness and musculoskeletal health in firefighters.
Introduction: Firefighters are often placed in situations that require high levels of physical exertion, leading to significant strain on firefighters' musculoskeletal system, predisposing them to musculoskeletal discomfort (MSD) and/or musculoskeletal injury (MSI). Physical fitness programs are often recommended and justified, in part, to prevent injuries. The aim of this study was to determine the association between physical fitness and musculoskeletal health (MSH) in firefighters. Methods: A total of 308 full-time firefighters took part in the study conducted in Cape Town, South Africa. Physical fitness tests encompassed a non-exercise estimation for cardiorespiratory fitness, grip and leg strength for upper and lower body strength, push-ups and sit-ups for muscular endurance, and sit-and-reach for flexibility. The Nordic Musculoskeletal Questionnaire and Cornell Musculoskeletal Discomfort Questionnaire were used to determine MSIs and MSD, respectively. A p-value <0.05 indicated statistical significance. Results: Every one-unit increase in AbVO2max, push-ups, sit-ups, and sit-and-reach decreased the odds of firefighters reporting MSIs by 5% (p = 0.005), 3% (p = 0.017), 3% (p = 0.006), and 3% (p = 0.034), respectively. Every one repetition increase in push-up capacity increased the odds of firefighters reporting neck, elbow and forearm, wrist and hand, and thigh discomfort by 3% (p = 0.039), 4% (p = 0.031), 5% (p = 0.002), and 5%` (p = 0.007), respectively. Every one repetition increase in sit-up capacity increased the odds of firefighters reporting upper back discomfort and thigh discomfort by 5% (p = 0.045) and 7% (p = 0.013), respectively. Conclusion: Maintenance of physical fitness is likely beneficial in reducing MSIs, which, however, may increase the feeling of MSD in firefighters. In addition, it may be noticed that there is an ideal level of physical fitness that is conducive to the reduction of MSIs and should be studied further.


Defining Recommendations to Guide User Interface Design: Multimethod Approach.
For the development of digital solutions, different aspects of user interface design must be taken into consideration. Different technologies, interaction paradigms, user characteristics and needs, and interface design components are some of the aspects that designers and developers should pay attention to when designing a solution. Many user interface design recommendations for different digital solutions and user profiles are found in the literature, but these recommendations have numerous similarities, contradictions, and different levels of detail. A detailed critical analysis is needed that compares, evaluates, and validates existing recommendations and allows the definition of a practical set of recommendations. This study aimed to analyze and synthesize existing user interface design recommendations and propose a practical set of recommendations that guide the development of different technologies. Based on previous studies, a set of recommendations on user interface design was generated following 4 steps: (1) interview with user interface design experts; (2) analysis of the experts' feedback and drafting of a set of recommendations; (3) reanalysis of the shorter list of recommendations by a group of experts; and (4) refining and finalizing the list. The findings allowed us to define a set of 174 recommendations divided into 12 categories, according to usability principles, and organized into 2 levels of hierarchy: generic (69 recommendations) and specific (105 recommendations). This study shows that user interface design recommendations can be divided according to usability principles and organized into levels of detail. Moreover, this study reveals that some recommendations, as they address different technologies and interaction paradigms, need further work.


Reaction norms with bifurcations shaped by evolution.
Two versions of a model for the evolution of seasonal polyphenism investigate the evolution of reaction norm bifurcation and branching. The first version is without a specific submodel for morphological development and the second has an explicit developmental map. Version 1 is evolutionarily relatively unconstrained: (i) reaction norms are specified by matrices containing the probabilities of occurrence of environment-phenotype combinations, (ii) all conceivable reaction norm matrices are reachable through a sequence of mutations, and (iii) small as well as large mutational effects occur. This version is used to find the evolutionarily stable strategy favoured by the population ecology that is characterized by stabilizing viability selection with a cyclically fluctuating selection optimum. When the strength of selection is large and when the lag between initiation of development and selection on mature phenotype is not a multiple of half the period of the environmental cycle, a branching reaction norm evolves. In the second model version, branching reaction norms occur for certain parameter combinations of the developmental submodel, but the evolution of this pattern is often constrained. The evolutionary trajectory becomes trapped in a local selective optimum for the parameters of the developmental system. Substantial developmental noise evolves, but mutations that produce a selectively advantageous branching pattern do not occur from there.


Expression, intracellular targeting and purification of HIV Nef variants in tobacco cells.
Plants may represent excellent alternatives to classical heterologous protein expression systems, especially for the production of biopharmaceuticals and vaccine components. Modern vaccines are becoming increasingly complex, with the incorporation of multiple antigens. Approaches towards developing an HIV vaccine appear to confirm this, with a combination of candidate antigens. Among these, HIV-Nef is considered a promising target for vaccine development because immune responses directed against this viral protein could help to control the initial steps of viral infection and to reduce viral loads and spreading. Two isoforms of Nef protein can be found in cells: a full-length N-terminal myristoylated form (p27, 27 kDa) and a truncated form (p25, 25 kDa). Here we report the expression and purification of HIV Nef from transgenic tobacco. We designed constructs to direct the expression of p25 and p27 Nef to either the cytosol or the secretory pathway. We tested these constructs by transient expression in tobacco protoplasts. Cytosolic Nef polypeptides are correctly synthesised and are stable. The same is not true for Nef polypeptides targeted to the secretory pathway by virtue of a signal peptide. We therefore generated transgenic plants expressing cytosolic, full length or truncated Nef. Expression levels were variable, but in some lines they averaged 0.7% of total soluble proteins. Hexahistidine-tagged Nef was easily purified from transgenic tissue in a one-step procedure. We have shown that transient expression can help to rapidly determine the best cellular compartment for accumulation of a recombinant protein. We have successfully expressed HIV Nef polypeptides in the cytosol of transgenic tobacco plants. The proteins can easily be purified from transgenic tissue.


Application of a quartz crystal microbalance to evaluate biodegradability of starch by Bacillus subtilis.
Biodegradation of solution-cast starch films by Bacillus subtilis was monitored using a quartz crystal microbalance (QCM). A starch film was formed on the crystal by solution casting and exposed to the Bacillus subtilis culture in a bioreactor. The high sensitivity of the QCM could monitor small weight changes of the starch films on the crystal in the initial stages of biodegradation by secreted exo-enzymes of the bacterium. The feasibility of this approach as a means of quantification and characterisation of biodegradability of different polymeric materials by selected organisms is discussed.


Frequency and Significance of Coinfection in Patients with COVID-19 at Hospital Admission.
Objective Viral pneumonia is not rare in community-acquired pneumonia (CAP). Mixed or secondary pneumonia (coinfection) can be seen in viral pneumonia; however, its frequency in coronavirus disease 2019 (COVID-19) has only been investigated in a few studies of short duration, and its significance has not been fully elucidated. We investigated the frequency and significance of co-infection in patients with COVID-19 over a 1-year study period. Methods Coinfection was investigated via multiplex polymerase chain reaction (PCR), culture of respiratory samples, rapid diagnostic tests, and paired sera. We used logistic regression analysis to analyze the effect of coinfection on severity at admission and Cox proportional-hazards model analysis to analyze the effect of coinfection on need for high-flow nasal cannula, invasive mandatory ventilation use, and death, respectively. Patients We retrospectively investigated 298 patients who suffered CAP due to severe acute respiratory syndrome coronavirus-2 infection diagnosed by PCR and were admitted to our institution from February 2020 to January 2021. Results Primary viral pneumonia, and mixed viral and bacterial pneumonia, accounted for 90.3% and 9.7%, respectively, of COVID-19-associated CAP, with viral coinfection found in 30.5% of patients with primary viral pneumonia. Influenza virus was the most common (9.4%). Multivariable analysis showed coinfection not to be an independent factor of severity on admission, need for high-flow nasal cannula or invasive mandatory ventilation, and mortality. Conclusion Viral coinfection was common in COVID-19-associated CAP. Severity on admission, need for high-flow oxygen therapy or invasive mandatory ventilation, and mortality were not affected by coinfection.


Protein kinase Calpha activates c-Src and induces podosome formation via AFAP-110.
We report that the actin filament-associated protein AFAP-110 is required to mediate protein kinase Calpha (PKCalpha) activation of the nonreceptor tyrosine kinase c-Src and the subsequent formation of podosomes. Immunofluorescence analysis demonstrated that activation of PKCalpha by phorbol 12-myristate 13-acetate (PMA), or ectopic expression of constitutively activated PKCalpha, directs AFAP-110 to colocalize with and bind to the c-Src SH3 domain, resulting in activation of the tyrosine kinase. Activation of c-Src then directs the formation of podosomes, which contain cortactin, AFAP-110, actin, and c-Src. In a cell line (CaOV3) that has very little or no detectable AFAP-110, PMA treatment was unable to activate c-Src or effect podosome formation. Ectopic expression of AFAP-110 in CaOV3 cells rescued PKCalpha-mediated activation of c-Src and elevated tyrosine phosphorylation levels and subsequent formation of podosomes. Neither expression of activated PKCalpha nor treatment with PMA was able to induce these changes in CAOV3 cells expressing mutant forms of AFAP-110 that are unable to bind to, or colocalize with, c-Src. We hypothesize that one major function of AFAP-110 is to relay signals from PKCalpha that direct the activation of c-Src and the formation of podosomes.


[Osteonecrosis of the jaws].
Medication-related osteonecrosis of the jaw is a disease where there is necrotic bone exposed or that can be explored by means of a fistula in the maxillofacial region. It has been associated with the use Biphosphonates and denosumab for osteoporosis. Although its etiology is unclear, it may be related to a decrease in bone turnover produced by these drugs, rendering the bone more prone to generate cell necrosis during invasive dental procedures, especially in the posterior region of the jaw. There is no consensus about the prevention and treatment of this condition. The aim of this paper is to present a review of the literature with the main characteristics of osteonecrosis of the jaws associated with drugs, together with a proposal for prevention and treatment for these patients.


Effects of nurse-led lower extremity strength training on knee function recovery in patients who underwent total knee replacement.
To examine the effects of lower extremity muscle strength training on knee function recovery and quality of life in patients who underwent total knee replacement. Patients with knee osteoarthritis after surgery experience decreased knee function that impacts their quality of life. However, patients typically lack a long-term, home-based and continuous leg exercise training method and rarely have studies explored the effects of exercise training on knee function recovery and quality of life. A experimental and longitudinal study design. The simple randomised sampling (based on patients' admission priority order) was used to collect participant data. Outcome measurements included the Knee Injury and Osteoarthritis Outcome Score. Participants were randomised to receive and starting lower extremity muscle strength training before surgery (training group, n = 100) or to receive usual care (nontraining group, n = 100). Data were collected and followed up with the patients before surgery (T1) and at 2 weeks (T2), 1 month (T3), 2 months (T4) and 3 months (T5) after discharge. The Knee Injury and Osteoarthritis Outcome Score subscale scores showed that both groups of patients experienced knee function and quality of life decreases 2 weeks after total knee replacement, but all subscale scores gradually increased from the first month to the third month after total knee replacement. Both groups and times were significantly different, but the training group's knee function and quality of life recovered earlier and better than the nontraining group does. This study confirmed that lower extremity muscle strength training helps to improve quality of life and knee function in patients who undergo total knee replacement. Healthcare staff should include this training in presurgical nursing care and in patients' discharge plans as a continuous, daily rehabilitation activity at home. When patients are diagnosed with knee osteoarthritis and undergo surgery, a presurgical exercise education and discussion of knee function rehabilitation should be part of standard care.


Ultrastructural study of a perineurioma with ribosome-lamella complexes.
The participation of the perineurial cell in peripheral nerve tumors is the subject of much debate. The case of a 75-year-old female with a soft tissue tumor on her left shoulder is presented. The tumor had histological, ultrastructural, and immunohistochemical characteristics of a pure perineurial cell neoplasm. Ultrastructurally, distinctive ribosome-lamella complexes were found in the cytoplasm of the perineurial cells. This may be the first time that these structures have been described in perineurioma.


[Relation between ouabain-insensitive differential sodium flux and sodium concentrations in solution].
The dependence of net sodium ion flux on the external sodium concentration was studied under the inhibition of the sodium pump. A steady state balance of sodium ion fluxes occurred at external sodium concentration differing from the calculated one, therefore the existence of a non-diffusion component of sodium ion flux was evident. It was shown that the non-diffusion ouabain-insensitive sodium ion flux consisted of the sodium efflux not connected with chlorine efflux or potassium influx, and the sodium influx connected, perhaps, with potassium efflux.


A carbon nanohorn-porphyrin supramolecular assembly for photoinduced electron-transfer processes.
A supramolecular assembly of zinc porphyrin-carbon nanohorns (CNHs) was constructed in a polar solvent. An ammonium cation was covalently connected to the CNH through a spacer (sp) (CNH-sp-NH(3)(+)) and bound to a crown ether linked to a zinc porphyrin (Crown-ZnP). Nanohybrids CNH-sp-NH(3)(+);Crown-ZnP and CNH-sp-NH(3)(+) were characterized by several techniques, such as high-resolution transmission electron microscopy, thermogravimetric analysis, X-ray photoelectron spectroscopy, and Raman spectroscopy. The photoinduced electron-transfer processes of the nanohybrids have been confirmed by using time-resolved absorption and fluorescence measurements by combining the steady-state spectral data. Fluorescence quenching of the ZnP unit by CNH-sp-NH(3)(+) has been observed, therefore, photoinduced charge separation through the excited singlet state of the ZnP unit is suggested for the hybrid material, CNH-sp-NH(3)(+);Crown-ZnP. As transient absorption spectral experiments reveal the formation of the radical cation of the ZnP unit, electron generation is suggested as a counterpart of the charge-separation on the CNHs; such an electron on the CNHs is further confirmed by migrating to the hexylviologen dication (HV(2+)). Accumulation of the electron captured from HV(*+) is observed as electron pooling in solution in the presence of a hole-shifting reagent. Photovoltaic performance with moderate efficiency is confirmed for CNH-sp-NH(3)(+);Crown-ZnP deposited onto nanostructured SnO(2) films.


Pharmacotherapeutic strategies for patients treated for depression in UK primary care: a database analysis.
To investigate long-term patterns of antidepressant treatment in patients in primary care in the UK, and to assess their healthcare resource use and disease outcomes. A retrospective longitudinal cohort study was conducted using the Clinical Practice Research Datalink. The study population comprised patients aged ≥18 years with depression receiving a prescription for antidepressant monotherapy between 1 January 2006 and 31 December 2011 with no antidepressants within the preceding 6 months. Recovery was defined by timing of antidepressant prescriptions (≥6 months without treatment). Treatment lines and strategies (switching, combining, augmenting and resuming medication) were analyzed. Healthcare resource use for the different treatment strategies and periods of no therapy was assessed. Data from 123,662 patients (287,564 treatment lines) were analyzed. Switching and resumption of treatment were more frequent than other strategies. Recovery was highest with first-line monotherapy (45% of patients), while as a second-line strategy switching was more successful (43%) than combination or augmentation. In subsequent lines of treatment, switching was associated with successively lower rates of recovery (31% in the third line and 24% from the fourth line onwards). Similar rates were observed for resumption. Healthcare resource use was greater during antidepressant use than treatment-free periods. Augmentation was associated with the highest proportions of patients with a psychiatrist referral, psychologist referral and psychiatric hospitalization. This study provides extensive real-world information on the prescribing patterns and treatment outcomes for a large cohort of patients treated for depression with antidepressants in primary care. Switching is more frequently used than augmentation or combination treatment, with decreasing effectiveness across successive lines. Key limitations of the study were: (i) risk of selection bias due to the use of inclusion criteria based on depression diagnoses recorded by the practitioner; and (ii) reliance on prescribing patterns as proxies for clinical outcomes, such as recovery.


Survival outcomes of twin-twin transfusion syndrome stage I: a systematic review of literature.
To review literature about treatment of twin-twin transfusion syndrome (TTTS) stage I. A search in PubMed, EMBASE, Medline, and reference lists was performed. Inclusion criteria were TTTS diagnosed with standard criteria and classified with Quintero staging and survival rates (SR) stratified for stage and first-choice treatment. Outcomes were SR and progression to advanced stages. Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. Seven articles pooled 262 twin sets treated with amnioreduction (16%), conservative management (22%), and laser therapy (62%). The overall SR was 77% after amnioreduction, 86% in the conservative management group, and 85% in the laser therapy group. Progression rate occurred in 30%, 15%, and 0%, respectively. Outcomes were similar between laser therapy as first- versus second-choice treatment. Because most studies were observational and not comparative, a meta-analysis was not performed. Conservative management of TTTS stage I is a reasonable option until randomized clinical trials are presented.


On the psychodynamics of collecting.
The urge to collect is a ubiquitous phenomenon which has anthropological, sociobiological and individual psychodynamic roots, but occurs far more frequently among men than women. The author examines the reasons for this gender difference and defines systematic collecting to distinguish it from addictive, obsessive and messy collecting, and from related phenomena such as perversion. The mode of collecting and choice of object are important indicators as to the unconscious psychodynamics of a collector and offer opportunity to describe his structural level. Collecting ranges across a broad spectrum, from an ego-syntonic integrated mode, i.e. sublimation, to a neurotic defence against pre-oedipal or oedipal traumas and conflicts. Alongside this drive-theoretical approach, object and Kleinian theory are also applied to the understanding of collecting. Collecting represents a specific form of object relating and way of handling primary loss trauma, which is different from addiction, compulsion, or perversion. Under certain circumstances collecting can also result in a successful Gestalt or way of life. The paper concludes with a case study showing how collecting develops from a pre-oedipal to a more integrated oedipal mode during the course of the analysis, which is reflected in changes in the transference.


Perfusion imaging.
Measurement of tissue perfusion is important for the functional assessment of organs in vivo. Here we report the use of 1H NMR imaging to generate perfusion maps in the rat brain at 4.7 T. Blood water flowing to the brain is saturated in the neck region with a slice-selective saturation imaging sequence, creating an endogenous tracer in the form of proximally saturated spins. Because proton T1 times are relatively long, particularly at high field strengths, saturated spins exchange with bulk water in the brain and a steady state is created where the regional concentration of saturated spins is determined by the regional blood flow and regional T1. Distal saturation applied equidistantly outside the brain serves as a control for effects of the saturation pulses. Average cerebral blood flow in normocapnic rat brain under halothane anesthesia was determined to be 105 +/- 16 cc.100 g-1.min-1 (mean +/- SEM, n = 3), in good agreement with values reported in the literature, and was sensitive to increases in arterial pCO2. This technique allows regional perfusion maps to be measured noninvasively, with the resolution of 1H MRI, and should be readily applicable to human studies.