Effects of transdermal clonidine treatment on withdrawal symptoms associated with smoking cessation. A randomized, controlled trial.
In a double-blind, randomized, placebo-controlled trial, we studied 40 cigarette smokers to determine the effects of one week of transdermal clonidine hydrochloride (Catapres-TTS No. 2) treatment on the withdrawal symptoms associated with smoking cessation. Subjects were instructed to maintain their usual cigarette intake during days 1 through 3 and cease smoking for days 4 through 6. All of the withdrawal symptoms measured (craving, irritability, anxiety, restlessness, difficulty concentrating, and hunger) significantly increased during the three days of smoking cessation in the placebo group. There was a 4.3-fold increase in craving, a 3.8-fold increase in irritability, a 3.7-fold increase in anxiety, and a 3.3-fold increase in restlessness in the placebo group compared with the transdermal clonidine group during the three days of smoking cessation. Impairment of concentration and hunger were not significantly diminished by transdermal clonidine treatment during smoking cessation. In addition, a trend was present in the transdermal clonidine group to spontaneously decrease the number of cigarettes smoked per day during the smoking period. Side effects were generally mild. We conclude that transdermal clonidine treatment ameliorates some of the short-term withdrawal symptoms, especially craving, associated with smoking cessation.


A cell-based biosensor for real-time detection of cardiotoxicity using lensfree imaging.
A portable and cost-effective real-time cardiotoxicity biosensor was developed using a CMOS imaging module extracted from a commercially available webcam. The detection system consists of a CMOS imaging module, a white LED and a pinhole. Real-time image processing was conducted by comparing reference and live frame images. To evaluate the engineered system, the effects of two different drugs, isoprenaline and doxorubicin, on the beating rate and beat-to-beat variations of ESC-derived cardiomyocytes were measured. The detection system was used to conclude that the beat-to-beat variability increased under treatment with both isoprenaline and doxorubicin. However, the beating rates increased upon the addition of isoprenaline but decreased for cultures supplemented with doxorubicin. Moreover, the response time for both the beating rates and the beat-to-beat variability of ESC-derived cardiomyocytes under treatment of isoprenaline was shorter than for doxorubicin, although the amount of isoprenaline used in the measurement was three orders of magnitude lower than that of doxorubicin. Given its ability to perform real-time cell monitoring in a simple and inexpensive manner, the proposed system may be useful for a range of cell-based biosensing applications.


Effect of temperature & salt concentration on salt tolerant nitrate-perchlorate reducing bacteria: Nitrate degradation kinetics.
The sustainability of nitrate-contaminated water treatment using ion-exchange processes can be achieved by regenerating the exhausted resin several times. Our previous study shows that the use of multi-cycle bioregeneration of resin enclosed in membrane is an effective and innovative regeneration method. In this research, the effects of two independent factors (temperature and salt concentration) on the biological denitrification rate were studied. The results of this research along with the experimental results of the previous study on the effect of the same factors on nitrate desorption rate from the resin allow the optimization of the bioregeneration process. The results of nitrate denitrification rate study show that the biodegradation rate at different temperature and salt concentration is independent of the initial nitrate concentration. At each specific salt concentration, the nitrate removal rate increased with increasing temperature with the average value of 0.001110 ± 0.0000647 mg-nitrate/mg-VSS.h.°C. However, the effect of different salt concentrations was dependent on the temperature; there is a significant interaction between salt concentration and temperature; within each group of temperatures, the nitrate degradation rate decreased with increasing the salt concentration. The temperature affected the tolerance to salinity and culture was less tolerant to high concentration of salt at low temperature. Evidenced by the difference between the minimum and maximum nitrate degradation rate being greater at lower temperature. At 35 °C, a 32% reduction in the nitrate degradation rate was observed while at 12 °C this reduction was 69%. This is the first published study to examine the interaction of salt concentration and temperature during biological denitrification.


Routine urine analysis in university candidates: is it worthwhile?
The study aimed to investigate the abnormalities in urine analysis in university candidates. A total of 247 students (150 males, 97 females) (mean age 20.08 years) had a medical check-up including urine analysis. In all, 38 urine samples had abnormalities (one or more abnormality/urinalysis). Pyuria was found in 20 students (8.1%), haematuria in 15 (6.1%), albuminuria in 12 (4.8%) and casts in 9 (3.6%). No glycosuria was found. Bacteria were found in 22 students (8.9%) and yeasts in two (0.8%). Urinalysis is warranted as a routine test in university students because of the percentage of abnormalities found and its importance in disease surveillance. However, it should not be a criterion for refusal by universities.


Computational Modeling Study of the Binding of Aging and Non-Aging Inhibitors with Neuropathy Target Esterase.
Neuropathy target esterase (NTE) is a serine hydrolase with phospholipase B activity, which is involved in maintaining the homeostasis of phospholipids. It can be inhibited by aging inhibitors such as some organophosphorus (OP) compounds, which leads to delayed neurotoxicity with distal degeneration of axons. However, the detailed binding conformation of aging and non-aging inhibitors with NTE is not known. In this study, new computational models were constructed by using MODELLER 10.3 and AlphaFold2 to further investigate the inhibition mechanism of aging and non-aging compounds using molecular docking. The results show that the non-aging compounds bind the hydrophobic pocket much deeper than aging compounds and form the hydrophobic interaction with Phe1066. Therefore, the unique binding conformation of non-aging compounds may prevent the aging reaction. These important differences of the binding conformations of aging and non-aging inhibitors with NTE may help explain their different inhibition mechanism and the protection of non-aging NTE inhibitors against delayed neuropathy.


Exploiting the Diversity of Saccharomycotina Yeasts To Engineer Biotin-Independent Growth of Saccharomyces cerevisiae.
Biotin, an important cofactor for carboxylases, is essential for all kingdoms of life. Since native biotin synthesis does not always suffice for fast growth and product formation, microbial cultivation in research and industry often requires supplementation of biotin. De novo biotin biosynthesis in yeasts is not fully understood, which hinders attempts to optimize the pathway in these industrially relevant microorganisms. Previous work based on laboratory evolution of Saccharomyces cerevisiae for biotin prototrophy identified Bio1, whose catalytic function remains unresolved, as a bottleneck in biotin synthesis. This study aimed at eliminating this bottleneck in the S. cerevisiae laboratory strain CEN.PK113-7D. A screening of 35 Saccharomycotina yeasts identified six species that grew fast without biotin supplementation. Overexpression of the S. cerevisiaeBIO1 (ScBIO1) ortholog isolated from one of these biotin prototrophs, Cyberlindnera fabianii, enabled fast growth of strain CEN.PK113-7D in biotin-free medium. Similar results were obtained by single overexpression of C. fabianii BIO1 (CfBIO1) in other laboratory and industrial S. cerevisiae strains. However, biotin prototrophy was restricted to aerobic conditions, probably reflecting the involvement of oxygen in the reaction catalyzed by the putative oxidoreductase CfBio1. In aerobic cultures on biotin-free medium, S. cerevisiae strains expressing CfBio1 showed a decreased susceptibility to contamination by biotin-auxotrophic S. cerevisiae This study illustrates how the vast Saccharomycotina genomic resources may be used to improve physiological characteristics of industrially relevant S. cerevisiaeIMPORTANCE The reported metabolic engineering strategy to enable optimal growth in the absence of biotin is of direct relevance for large-scale industrial applications of S. cerevisiae Important benefits of biotin prototrophy include cost reduction during the preparation of chemically defined industrial growth media as well as a lower susceptibility of biotin-prototrophic strains to contamination by auxotrophic microorganisms. The observed oxygen dependency of biotin synthesis by the engineered strains is relevant for further studies on the elucidation of fungal biotin biosynthesis pathways.


Reflections on physical activity intervention research in young people - dos, don'ts, and critical thoughts.
Physical activity has been associated with many benefits throughout the life course. As levels of physical activity appear to be insufficient in large populations, the development of effective interventions to promote or maintain activity levels in young people are therefore of key public health concern. Physical activity intervention research in young people is challenging, but this should not be a reason to continue conducting inferior quality evaluations. This paper highlights some of the key issues that require more careful and consistent consideration to enable future research to achieve meaningful impact. This paper critically evaluates, amongst others, current research practice regarding intervention development, targeting, active involvement of the target population, challenge of recruitment and retention, measurement and evaluation protocols, long-term follow-up, economic evaluation, process evaluation, and publication. It argues that funders and researchers should collaborate to ensure high quality long-term evaluations are prioritised and that a trial's success should be defined by its quality, not its achieved effect. The conduct and publication of well-designed evaluations of well-defined interventions is crucial to advance the field of youth physical activity promotion and make us better understand which intervention strategies may or may not work, why, and for whom.


Potential utility of rhIGF-1 in neuromuscular and/or degenerative disease.
Neuromuscular/neurodegenerative disorders, such as the death of spinal cord motor neurons in amyotrophic lateral sclerosis (ALS) or the degeneration of spinal cord motor neuron axons in certain peripheral neuropathies, present a unique opportunity for therapeutic intervention with neurotrophic proteins. We have found that in mixed rat embryonic spinal cord cultures or in purified motor neuron preparations, recombinant human insulin-like growth factor 1 (rhIGF-1) enhances the survival of motor neurons at EC50 concentrations of 2 nM, consistent with an interaction at the tyrosine kinase-coupled rhIGF-1 receptor. In a model of programmed cell death in ovo, administration of rhIGF-1 produces a marked survival of motor neurons. In a variety of models of predominantly motor neuron or nerve injury in rodents, administration of rhIGF-1 prevents the death of motor neurons in neonatal facial nerve lesions, attenuates the loss of cholinergic phenotype in adult hypoglossal nerve axotomy and hastens recovery from sciatic nerve crush in mice. In a genetic model of motor neuron compromise, the wobbler mouse, rhIGF-1 (1 mg/kg s.c. daily) delayed the deterioration of grip strength and provided for a more normal distribution of fibre types. In addition, rhIGF-1 (0.3-1.0 mg/kg s.c. daily) prevents the motor and/or sensory neuropathy in rodents caused by vincristine, cisplatinum or Taxol. These combined data indicate that rhIGF-1 has marked effects on the survival of compromised motor neurons and the maintenance of their axons and functional connections. They also suggest the potential utility of rhIGF-1 for the treatment of diseases such as ALS and certain neuropathies.


Latent Class Growth Trajectories of Letter Name Knowledge During Pre-Kindergarten and Kindergarten.
A major developmental task for young children in the United States involves the acquisition of knowledge about the letters in the English alphabet. In the current study, we examined the growth trajectories of children's letter name knowledge (LNK) during pre-kindergarten and kindergarten. A diverse sample of 1,015 children was drawn from the National Center for Early Development and Learning Multi-State Study of Pre-Kindergarten. Latent class growth analyses were used to identify three heterogeneous classes of children based on their LNK growth trajectories. Children's fall-of-pre-kindergarten language skills were associated with trajectory class membership, which in turn was associated with children's spring-of-kindergarten literacy skills. We also found that the association between children's fall-of-pre-kindergarten language skills and spring-of-kindergarten literacy skills was partially mediated by trajectory class membership. These findings point to the importance of LNK skill development as a marker variable to monitor and support children's emergent literacy development.


Inkjet-printed electrochemically reduced graphene oxide microelectrode as a platform for HT-2 mycotoxin immunoenzymatic biosensing.
The design and application of an inkjet-printed electrochemically reduced graphene oxide microelectrode for HT-2 mycotoxin immunoenzymatic biosensing is reported. A water-based graphene oxide ink was first formulated and single-drop line working microelectrodes were inkjet-printed onto poly(ethylene 2,6-naphthalate) substrates, with dimensions of 78 μm in width and 30 nm in height after solvent evaporation. The printed graphene oxide microelectrodes were electrochemically reduced and characterized by Raman and X-ray photoelectron spectroscopies in addition to microscopies. Through optimization of the electrochemical reduction parameters, differential pulse voltammetry were performed to examine the sensing of 1-naphthol (1-N), where it was revealed that reduction times had significant effects on electrode performance. The developed microelectrodes were then used as an immunoenzymatic biosensor for the detection of HT-2 mycotoxin based on carbodiimide linking of the microelectrode surface and HT-2 toxin antigen binding fragment of antibody (anti-HT2 (10) Fab). The HT-2 toxin and anti-HT2 (10) Fab reaction was reported by anti-HT2 immune complex single-chain variable fragment of antibody fused with alkaline phosphatase (anti-IC-HT2 scFv-ALP) which is able to produce an electroactive reporter - 1-N. The biosensor showed detection limit of 1.6 ng ∙ mL-1 and a linear dynamic range of 6.3 - 100.0 ng ∙ mL-1 within a 5 min incubation with 1-naphthyl phosphate (1-NP) substrate.


Urinary electrolytes, body weight, and blood pressure. Pooled cross-sectional results among four groups of adolescent females.
Results of blood pressures (BP) and urinary electrolyte excretion studies are reported among several groups of adolescent and young adult females, both black and white, who were initially examined in high school and restudied at home 3--4 years later. Pooling of the data from the several cross-sectional studies (n = 662) revealed a weak but statistically significant positive correlation systolic blood pressure (SBP) and the urinary sodium (Na) excretion rate. Three of four correlations between SBP and potassium (K) were of an inverse nature. Although not statistically significant in their own right, when coupled with the Na/K excretion ratio, which was significantly associated with SBP, a moderating role for K is suggested. The urinary Na, K, and creatinine (Cr) excretion rates were highly intercorrelated and were correlated with weight. As measured by R2 in a stepwise regression analysis, weight contributed approximately 3% to the BP variance, and the urinary electrolytes accounted for approximately 2% of the SBP variance. Statistically significant partial correlation coefficients between SBP and Na, and Na/K, remained after adjusting for body weight.


Novel Real-time Prediction of Liver Graft Function During Hypothermic Oxygenated Machine Perfusion Before Liver Transplantation.
The aim of this study was to determine the predictive value of machine perfusate analysis on graft outcome. Ex situ machine perfusion (MP) is gaining increasing interest to potentially repair injured organs and to assess organ function. In the field of liver transplantation, however, no studies exist on reliable prediction of graft function during MP. We have used hypothermic oxygenated perfusion (HOPE) for donation after circulatory death (DCD) or extended criteria donation after brain death (DBD) human liver grafts during the last 7 years. Our series includes 100 HOPE-treated liver-transplanted patients with an overall tumor-censored 5-year graft survival of 89%. We monitored 54 livers during HOPE in terms of fluorometric analysis of released mitochondrial flavin (flavin mononucleotide, FMN) in the machine perfusate. Real-time optical measurement of mitochondrial FMN release in machine perfusates of livers disclosed a strong correlation with lactate clearance and coagulation factors at day 1 and 2 after transplantation. Receiver-operating characteristic curve analysis revealed an area under the curve (AUROC) of 0.79 [95% confidence interval (CI), 0.62-0.97] for severe allograft dysfunction and for early graft loss (AUROC 0.93, 95% CI, 0.84-1.0). Assessment of flavin, a marker of mitochondrial complex I injury, in the perfusate provides a fast prediction of liver graft function and loss during ex situ MP before implantation. This finding may have high clinical relevance, as liver grafts from extended DBD or DCD donors carry considerable risks for recipients. On-line estimation of outcome before implantation would therefore substantially increase safe utilization of liver grafts.


Cucurbituril and Azide Cofunctionalized Graphene Oxide for Ultrasensitive Electro-Click Biosensing.
To achieve high selectivity and sensitivity simultaneously in an electrochemical biosensing platform, cucurbituril and azide cofunctionalized graphene oxide, a new functional nanomaterial that acts as a go-between to connect the recognition element with amplified signal architecture, is developed in this work. The cucurbituril and azide cofunctionalized graphene oxide features a high specific surface area with abundant levels of the two types of functional groups. Specifically, it emerges as a powerful tool to link recognition elements with simplicity, high yield, rapidity, and highly selective reactivity through azide-alkynyl click chemistry. Moreover, it possesses many host molecules to interact with guest molecules (also signal molecules)-grafted branched ethylene imine polymer, through which the detection sensitivity can be greatly improved. Together with electro-click technology, a highly controllable, selective, and sensitive biosensing platform can be easily created. For VEGF165 protein detection, the electro-click assay has high selectivity and sensitivity; a dynamic detection range from 10 fg mL-1 to 1 ng mL-1 with a detection limit of 8 fg mL-1 was achieved. The electro-click biosensing strategy based on cucurbituril and azide cofunctionalized graphene oxide would have great promise for other target analytes with a broad range of applications.


[Using cluster analysis for evaluation of sensitivity to antibiotics of pathogens isolated from women with genital inflammatory diseases].
The study was conducted to evaluate sensitivity to 44 antibiotics of pathogens isolated from 183 women with genital inflammatory diseases and to offer schemes of antibacterial treatment. The pathogens (66.8%) were in associations. The probability of isolation of main bacteria and sexually transmitted microorganisms in different associations was estimated in the work. Using the methods of clustering analysis all the tested antibiotics were divided into 3 groups, depending on their antimicrobial activity toward bacteria isolated both in monoculture and in associations. Furagin, cefotaxime, gentamicin, cefoperazon, ceftriaxon, ciprofloxacin, pefloxacin, as well as, cefazolin, zoxan, ofloxacin, and lomefloxacin were shown to be the most effective antibiotics in vitro. The least activity was diplayed by ectericid, chlorophillipt, and ampiox. These data should be considered when choosing the antibacterial treatment of genital inflammatory diseases.


Transcriptomic Profiling of Medial Temporal Lobe Epilepsy.
Epilepsy is one of the most prevalent neurological disorders affecting ~1% of the population. Medial temporal lobe epilepsy (MTLE) is the most frequent type of epilepsy observed in adults who do not respond to pharmacological treatment. The reason for intractability in these patients has not been systematically studied. Further, no markers are available that can predict the subset of patients who will not respond to pharmacotherapy. To identify potential biomarkers of epileptogenicity, we compared the mRNA profiles of surgically resected tissue from seizure zones with non-seizure zones from cases of intractable MTLE. We identified 413 genes that exhibited ≥2-fold change that were statistically significant across these two groups. Several of these differentially expressed genes have not been previously described in the context of MTLE including claudin 11 (CLDN11) and bone morphogenetic protein receptor, type IB (BMPR1B). In addition, we found significant downregulation of a subset of gamma-aminobutyric acid (GABA) associated genes. We also identified molecules such as BACH2 and ADAMTS15, which are already known to be associated with epilepsy. We validated one upregulated molecule, serine/threonine kinase 31 (STK31) and one downregulated molecule, SMARCA4, by immunohistochemical labeling of tissue sections. These molecules need to be further confirmed in large-scale studies to determine their potential use as diagnostic as well as prognostic markers in intractable MTLE.


A gerontology internship program for medical students.
Although the aged are the country's major users of medical care and social services, traditional medical school curricula devote little time to the aged and their social needs. This article reports on a community-based gerontology internship established for pre-clinical medical students to sensitize them to the needs of the elderly in the community. Students were assigned to community agencies servicing the elderly; working with elderly clients, they learned about needs and services. Students, agency staff and program faculty found the internship a meaningful, consciousness-raising experience, and an excellent vehicle for preparing future physicians to interact with and care for their aged patients.


[Quality of life of patients with metastatic breast or intestinal cancer, treated with anthroposophic medicine or with mainstream medicine, the latter with or without psycho-oncologic or supplementary anthroposophic therapy].
This project dealt with two subjects. On the one hand, the measurement of the quality of life of cancer patients which needed to be further refined in order to assess the usefulness and efficacy of a treatment by complementary medicine. On the other hand, it was important to know whether severely ill cancer patients treated in an anthroposophical clinic would differ from equally ill patients in a university hospital in terms of attitude towards their illness and in terms of clinical diagnosis. Finally, an attempt was made to demonstrate an improvement of quality of life in conventionally treated patients of the university hospital, who were offered an additional treatment either with a supportive-expressive group therapy or with an anthroposophical therapy. More than 500 patients participated in the study. There were marked sociodemographic and medical differences between the patients of the anthroposophical clinic and those of the university hospital. In addition, it seems that spiritually oriented and active, problem-oriented coping contribute a lot to the quality of life. It was not possible to truly compare the value of the two additional therapies offered to the patients at the university hospital because patient accrual was much slower than anticipated and many patients left the study too early for health reasons or death.


Acute myocardial infarction: clinical characteristics, management and outcome in a university medical centre in a developing Middle Eastern country.
The management and outcome of acute myocardial infarction (AMI) have not been well studied in developing countries, although demographic data from the World Health Organization indicate that developing countries contribute a major share to the global burden of cardiovascular disease. To analyze the clinical characteristics, management and outcome of patients hospitalized with AMI in a university medical centre in a developing Middle Eastern country. The study population comprised all patients hospitalized with AMI at the American University of Beirut between January 1, 1997, and December 30, 1998. The medical records of the patients were reviewed to determine their clinical characteristics, the diagnostic and invasive procedures used during the hospitalization, and any in-hospital complications, including death. The population comprised 184 patients with a mean age of 60+/-13 years. Fifty-two per cent of the infarcts were anterior and 76% developed Q waves. Fifty-one per cent of the patients received thrombolytic therapy. At discharge, 80% of the patients were given acetylsalicylic acid, 35% were given beta-blockers, 34% were given angiotensin-converting enzyme inhibitors and 30% were given statins. Seventy-two per cent of the patients underwent coronary angiography, 23% underwent percutaneous transluminal coronary angioplasty and 13% had coronary artery bypass grafting. The in-hospital mortality was 13%. The predictors of in-hospital mortality were advanced age (over 60 years), diabetes, prior AMI, Killip class greater than I and ejection fraction less that 40%. In contrast, the predictors of coronary angiography were younger age (less than 60 years), absence of diabetes or no history of AMI, Killip class I and ejection fraction greater than 40%. Coronary angiography after AMI was performed more frequently than expected in a university medical centre in a developing country, and it seemed to be selectively used in the low- risk patients rather than the high-risk ones. Furthermore, the underuse of medical therapy with beta-blockers and statins was evident. These findings should prompt cardiac societies in these countries to initiate educational campaigns focusing on the cost-effectiveness of therapy in AMI to optimize the use of their limited resources.


Parallels in preschoolers' and adults' judgments about ownership rights and bodily rights.
Understanding ownership rights is necessary for socially appropriate behavior. We provide evidence that preschoolers' and adults' judgments of ownership rights are related to their judgments of bodily rights. Four-year-olds (n = 70) and adults (n = 89) evaluated the acceptability of harmless actions targeting owned property and body parts. At both ages, evaluations did not vary for owned property or body parts. Instead, evaluations were influenced by two other manipulations-whether the target belonged to the agent or another person, and whether that other person approved of the action. Moreover, these manipulations influenced judgments for owned objects and body parts in the same way: When the other person approved of the action, participants' judgments were positive regardless of who the target belonged to. In contrast, when that person disapproved, judgments depended on who the target belonged to. These findings show that young children grasp the importance of approval or consent for ownership rights and bodily rights, and likewise suggest that people's notions of ownership rights are related to their appreciation of bodily rights.


Determination of the antidepressants maprotiline and amoxapine, and their metabolites, in plasma by liquid chromatography.
Maprotiline, amoxapine, and their metabolites were determined in plasma by three separate procedures, each of which involves a three-step extraction followed by reversed-phase separations. Amoxapine, maprotiline, and N-desmethylmaprotiline can be measured with use of a conventional C-18 column with 10% carbon load, but analyses for 7- and 8-hydroxyamoxapines require a small (5-microns) particle size, high carbon load, 20% C-18 column with 0.2 mol/L phosphate as mobile phase. Within-run and day-to-day CVs were 5% and 8%, respectively. Peak-height ratios were linearly correlated with concentrations between 0 and 400 micrograms/L. Detection limits ranged from 1 to 3 ng. Interference studies indicated that nortriptyline co-elutes with maprotiline. Assays of patients' plasma showed substantial amounts of these drugs and most of their metabolites, but only trace amounts of 7-hydroxyamoxapine.


New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure.
Adipose tissue is central to the regulation of energy balance. Two functionally different types of fat are present in mammals: white adipose tissue, the primary site of triglyceride storage, and brown adipose tissue, which is specialized in energy expenditure and can counteract obesity. Factors that specify the developmental fate and function of white and brown adipose tissue remain poorly understood. Here we demonstrate that whereas some members of the family of bone morphogenetic proteins (BMPs) support white adipocyte differentiation, BMP7 singularly promotes differentiation of brown preadipocytes even in the absence of the normally required hormonal induction cocktail. BMP7 activates a full program of brown adipogenesis including induction of early regulators of brown fat fate PRDM16 (PR-domain-containing 16; ref. 4) and PGC-1alpha (peroxisome proliferator-activated receptor-gamma (PPARgamma) coactivator-1alpha; ref. 5), increased expression of the brown-fat-defining marker uncoupling protein 1 (UCP1) and adipogenic transcription factors PPARgamma and CCAAT/enhancer-binding proteins (C/EBPs), and induction of mitochondrial biogenesis via p38 mitogen-activated protein (MAP) kinase-(also known as Mapk14) and PGC-1-dependent pathways. Moreover, BMP7 triggers commitment of mesenchymal progenitor cells to a brown adipocyte lineage, and implantation of these cells into nude mice results in development of adipose tissue containing mostly brown adipocytes. Bmp7 knockout embryos show a marked paucity of brown fat and an almost complete absence of UCP1. Adenoviral-mediated expression of BMP7 in mice results in a significant increase in brown, but not white, fat mass and leads to an increase in energy expenditure and a reduction in weight gain. These data reveal an important role of BMP7 in promoting brown adipocyte differentiation and thermogenesis in vivo and in vitro, and provide a potential new therapeutic approach for the treatment of obesity.


Effectiveness of a training program for the management of risky alcohol use in primary care professionals based on motivational interviewing.
To assess the effectiveness of a training program for Primary Care (PC) professionals developed to increase knowledge, attitudes, and skills for managing patients with risky alcohol use and in the motivational interview. Multicenter, two-arm parallel, randomized, open-label controlled clinical trial. PC of the Andalusian Health Service. The study was completed by 80 healthcare professionals from 31 PC centers. In both experimental and control groups, a workshop on managing patients with risky alcohol consumption and the resolution of two videotaped clinical cases with standardized patients were conducted. The experimental group attended a workshop on motivational interviewing. Knowledge about managing risky alcohol use, clinical performance in patients with this health problem, and assessment of the motivational interview. Mean age was 39.50±13.06 - SD - (95% CI: 36.59-42.41); 71.3% (95% CI: 61.1-80.9%) were women. The average score of both groups in the knowledge questionnaire before the training program was 15.10±4.66, becoming 21.99±3.93 points after the training (95% CI: 5.70-7.92; p<0.001). The experimental group showed an average score of 18.53±13.23 before the intervention with the motivational interview and 28.33±11.86 after this intervention (p=0.002). In contrast, no significant variation was found in the score of the control group. A training program aimed at PC professionals designed to increase knowledge on how to manage risky alcohol use and acquire communication skills in motivational interviewing is effective.


The role played by oxidative stress in evoking the exercise pressor reflex in health and simulated peripheral artery disease.
Ligating the femoral artery of a rat for 72 h, a model for peripheral artery disease, causes an exaggerated exercise pressor reflex in response to muscle contraction. Likewise, the hindlimb muscles of rats with ligated femoral arteries show increased levels of reactive oxygen species. Infusion of tiron, a superoxide scavenger, attenuated the exaggerated pressor reflex and reduced reactive oxygen species production in rats with ligated femoral arteries. Conversely, we found no effect of tiron infusion on the pressor reflex in rats with patent femoral arteries. These results suggest a role of reactive oxygen species with respect to causing the exaggerated pressor response to contraction seen in rats with ligated arteries and peripheral artery disease. Contraction of muscle evokes the exercise pressor reflex (EPR), which is expressed partly by increases in heart rate and arterial pressure. Patients with peripheral artery disease (PAD) show an exaggerated EPR, sometimes report pain when walking and are at risk for cardiac arrthymias. Previous research suggested that reactive oxygen species (ROS) mediate the exaggerated EPR associated with PAD. To examine the effects of ROS on the EPR, we infused a superoxide scavenger, tiron, into the superficial epigastric artery of decerebrated rats. In some, we simulated PAD by ligating a femoral artery for 72 h before the experiment. The peak EPR in 'ligated' rats during saline infusion averaged 31 ± 4 mmHg, whereas the peak EPR in these rats during tiron infusion averaged 13 ± 2 mmHg (n = 12; P < 0.001); the attenuating effect of tiron on the EPR was partly reversed when saline was reinfused into the superficial epigastric artery (21 ± 2 mmHg; P < 0.01 vs. tiron). The peak EPR in 'ligated' rats was also attenuated (n = 7; P < 0.01) by infusion of gp91ds-tat, a peptide that blocks the activity of NAD(P)H oxidase. Tiron infusion had no effect on the EPR in rats with patent femoral arteries (n = 9). Western blots showed that the triceps surae muscles of 'ligated' rats expressed more Nox2 and p67phox, which are components of NADPH oxidase, compared to triceps surae muscles of 'freely perfused' rats. Tiron added to muscle homogenates reduced ROS production in vitro. The results of the present study provide further evidence indicating that ROS mediates the exaggeration of EPR in rats with simulated PAD.


Chronic cigarette smoking is associated with increased plasma circulating intercellular adhesion molecule 1 levels in young type 1 diabetic patients.
The purposes of this study were to compare plasma concentrations of circulating intercellular adhesion molecule 1 (cICAM-1), a marker of endothelial dysfunction, in nondiabetic subjects and type 1 diabetic patients and to evaluate whether chronic cigarette smoking had a deleterious effect on plasma cICAM-1 levels in type 1 diabetic patients. Plasma cICAM-1 concentrations were measured in 54 young type 1 diabetic patients without clinical macroangiopathy and in 20 healthy control subjects who were matched for age, sex, BMI, and smoking habit. Type 1 diabetic patients had significantly higher plasma levels of cICAM-1 than control subjects (280.4 +/- 59 vs. 224 +/- 53.6 ng/ml, respectively) (P < 0.001). After stratification by smoking status, diabetic smokers had values for age, sex, BMI, lipids, blood pressure, glycemic control, diabetes duration, and chronic complications of diabetes that were super-imposable on their nonsmoking counterparts. Nevertheless, plasma cICAM-1 levels were markedly elevated in type 1 diabetic smokers (321.4 +/- 64.2 vs. 257.3 +/- 41.5 ng/ml, respectively) (P < 0.001) in a dose-dependent fashion (P < 0.001 by analysis of variance when subjects were categorized by number of cigarettes smoked per day). Chronic cigarette smoking has a deleterious effect on plasma cICAM-1 levels in young type 1 diabetic patients, which further supports the clinical importance of discouraging the initiation of smoking and promoting its cessation in people with type 1 diabetes.


A relative reward-strength algorithm for the hierarchical structure learning automata operating in the general nonstationary multiteacher environment.
A new learning algorithm for the hierarchical structure learning automata (HSLA) operating in the nonstationary multiteacher environment (NME) is proposed. The proposed algorithm is derived by extending the original relative reward-strength algorithm to be utilized in the HSLA operating in the general NME. It is shown that the proposed algorithm ensures convergence with probability 1 to the optimal path under a certain type of the NME. Several computer-simulation results, which have been carried out in order to compare the relative performance of the proposed algorithm in some NMEs against those of the two of the fastest algorithms today, confirm the effectiveness of the proposed algorithm.


Replacement of the methionine axial ligand to the primary electron acceptor A0 slows the A0- reoxidation dynamics in photosystem I.
The recent crystal structure of photosystem I (PSI) from Thermosynechococcus elongatus shows two nearly symmetric branches of electron transfer cofactors including the primary electron donor, P(700), and a sequence of electron acceptors, A, A(0) and A(1), bound to the PsaA and PsaB heterodimer. The central magnesium atoms of each of the putative primary electron acceptor chlorophylls, A(0), are unusually coordinated by the sulfur atom of methionine 688 of PsaA and 668 of PsaB, respectively. We [Ramesh et al. (2004a) Biochemistry 43:1369-1375] have shown that the replacement of either methionine with histidine in the PSI of the unicellular green alga Chlamydomonas reinhardtii resulted in accumulation of A(0)(-) (in 300-ps time scale), suggesting that both the PsaA and PsaB branches are active. This is in contrast to cyanobacterial PSI where studies with methionine-to-leucine mutants show that electron transfer occurs predominantly along the PsaA branch. In this contribution we report that the change of methionine to either leucine or serine leads to a similar accumulation of A(0)(-) on both the PsaA and the PsaB branch of PSI from C. reinhardtii, as we reported earlier for histidine mutants. More importantly, we further demonstrate that for all the mutants under study, accumulation of A(0)(-) is transient, and that reoxidation of A(0)(-) occurs within 1-2 ns, two orders of magnitude slower than in wild type PSI, most likely via slow electron transfer to A(1). This illustrates an indispensable role of methionine as an axial ligand to the primary acceptor A(0) in optimizing the rate of charge stabilization in PSI. A simple energetic model for this reaction is proposed. Our findings support the model of equivalent electron transfer along both cofactor branches in Photosystem I.


Evaluation of the BH3-only protein Puma as a direct Bak activator.
Interactions among Bcl-2 family proteins play critical roles in cellular life and death decisions. Previous studies have established the BH3-only proteins Bim, tBid, and Noxa as "direct activators" that are able to directly initiate the oligomerization and activation of Bak and/or Bax. Earlier studies of Puma have yielded equivocal results, with some concluding that it also acts as a direct activator and other studies suggesting that it acts solely as a sensitizer BH3-only protein. In the present study we examined the interaction of Puma BH3 domain or full-length protein with Bak by surface plasmon resonance, assessed Bak oligomerization status by cross-linking followed by immunoblotting, evaluated the ability of the Puma BH3 domain to induce Bak-mediated permeabilization of liposomes and mitochondria, and determined the effect of wild type and mutant Puma on cell viability in a variety of cellular contexts. Results of this analysis demonstrate high affinity (KD = 26 ± 5 nM) binding of the Puma BH3 domain to purified Bak ex vivo, leading to Bak homo-oligomerization and membrane permeabilization. Mutations in Puma that inhibit (L141E/M144E/L148E) or enhance (M144I/A145G) Puma BH3 binding to Bak also produce corresponding alterations in Bak oligomerization, Bak-mediated membrane permeabilization and, in a cellular context, Bak-mediated killing. Collectively, these results provide strong evidence that Puma, like Bim, Noxa, and tBid, is able to act as a direct Bak activator.


Comparison of Yacon (Smallanthus sonchifolius) Tuber with Commercialized Fructo-oligosaccharides (FOS) in Terms of Physiology, Fermentation Products and Intestinal Microbial Communities in Rats.
The yacon (Smallanthus sonchifolius) tuber was examined with regard to its prebiotic effects compared with commercialized fructo-oligosaccharides (FOS). A feed containing 10% yacon tuber, which is equivalent to 5% commercialized FOS in terms of the amount of fructo-oligosaccharides (GF2, GF3 and GF4), was administrated to rats for 28 days. The yacon diet changed the intestinal microbial communities beginning in the first week, resulting in a twofold greater concentration of cecal short-chain fatty acids (SCFAs). The SCFA composition differed, but the cecal pH in rats fed yacon tuber was equal to that in rats fed FOS. Serum triglycerides were lower in rats fed yacon compared with rats fed FOS and the control diet. Cecal size was greater with the yacon tuber diet compared with the control diet. The abundant fermentation in the intestines created a selective environment for the intestinal microbiota, which included Lactobacillus acidophilus, Bifidobacterium pseudolongum, Bifidobacterium animalis and Barnesiella spp. according to identification with culture-independent analysis, 16S rRNA gene PCR-DGGE combined with cloning and sequencing. Barnesiella spp. and B. pseudolongum were only found in the rats fed the yacon diet, while L. acidophilus and B. animalis were found in abundance in rats fed both the yacon and FOS diets. The genus Barnesiella has not previously been reported to be associated with yacon or FOS fermentation. We concluded that the physiological and microbiological effects of the yacon tuber were different from those of FOS. Differences in cecal size, blood triglycerides and microbial community profiles including their metabolites (SCFAs) between the yacon tuber and FOS were shown to be more greatly affected by the yacon tuber rather than FOS.


A model of Agrobacterium tumefaciens vacuum infiltration into harvested leaf tissue and subsequent in planta transgene transient expression.
Agrobacterium-mediated gene transfer, or agroinfiltration, can be a highly efficient method for transforming and inducing transient transgene expression in plant tissue. The technique uses the innate DNA secretion pathway of Agrobacterium tumefaciens to vector a particular plasmid-encoded segment of DNA from the bacteria to plant cells. Vacuum is often applied to plant tissue submerged in a suspension of A. tumefaciens to improve agroinfiltration. However, the effects of vacuum application on agroinfiltration and in planta transient transgene expression have not been well quantified. Here we show that vacuum application and release act to drive A. tumefaciens suspension into the interior of leaf tissue. Moreover, the amount of suspension that enters leaves can be predicted based on the vacuum intensity and duration. Furthermore, we show that transient expression levels of an agroinfiltrated reporter gene vary in response to the amount of A. tumefaciens vacuum infiltrated into leaf tissue, suggesting that vacuum infiltration conditions can be tailored to achieve optimal transient transgene expression levels after agroinfiltration.


Automaticity in atrioventricular valve leaflets of rabbit heart.
Microelectrode techniques were used to study the electrophysiological properties of pacemaker fibers in isolated atrioventricular valves of the rabbit heart. In spontaneously beating tricuspid and mitral valve preparations superfused with normal Tyrode solution, leading pacemaker activity was generated by fibers located on the valve leaflet. Impulse conduction from the automatic focus to atrial myocardium was slow, and in approximately 50% of preparations, exit block occurred. Valve pacemaker fibers had significantly different action potential characteristics compared with the primary pacemaker cells of the sinoatrial node. However, the activity of both pacemaker types was largely insensitive to tetrodotoxin but readily suppressed by verapamil. Endogenous neurotransmitters, released from postganglionic nerve endings in the vicinity of valve pacemaker fibers, exerted profound chrono- and dromotropic effects. Brief cholinergic stimuli strongly influenced valve pacemaker cycle length in a phase-dependent manner, qualitatively similar to that in the sinoatrial node. During overdrive of valve pacemaker fibers with external bipolar stimuli, locally released neurotransmitters modified automaticity and conduction which, under certain conditions, favored pacemaker escape. These data demonstrate that the atrioventricular valve leaflets contain cardiac fibers capable of generating spontaneous impulses and that intrinsic autonomic nerves may play a role in precipitating premature extrasystoles.


Removal of Methyl Red from Aqueous Solution Using Biochar Derived from Fennel Seeds.
In this study, fennel (Foeniculum vulgare) seeds were used as a precursor to obtain carbon adsorbents through physical activation with carbon dioxide and chemical activation by impregnating the precursor with sodium carbonate. The physical activation involved the carbonization of the precursor at a temperature of 600 °C for 60 min and activation at a temperature of 800 °C for 30 min with carbon dioxide. Chemical activation included impregnation of the precursor with sodium carbonate at a mass ratio of a precursor to activator of 1:2. The mixture was activated in a nitrogen atmosphere with a flow rate at a temperature of 700 °C for 45 min. The resulting biochar samples were washed with 5% hydrochloric acid and subsequently rinsed with boiling distilled water. The biochar adsorbents were characterized using low-temperature nitrogen adsorption-desorption isotherms, Boehm titration, and pH measurements of their aqueous extracts. The specific surface area of the obtained adsorbents ranged from 89 to 345 m2/g. Biochar adsorbents exhibit a predominance of acidic groups over basic groups on their surfaces. The sorption capacities of the obtained samples towards an aqueous solution of methyl red range from 26 to 135 mg/g. Based on adsorption studies, it was found that the adsorption of the dye on the obtained biochar materials follows a pseudo-second-order model. The Freundlich isotherm best describes the studied process, indicating the formation of a multilayer of adsorbate on the adsorbent surface. The efficacy of adsorption in aqueous solutions of methyl red was found to increase with the elevation of the process temperature. Moreover, thermodynamic studies have shown that the adsorption process is spontaneous and endothermic. Consequently, this work provides a description of the physicochemical parameters of two biochars obtained by physical and chemical activation of a little-studied precursor-fennel seeds-and studies on their potential use as adsorbents for contaminants from the aqueous phase.


Nurse-driven protocols and the prevention of catheter-associated urinary tract infections: A systematic review.
Catheter-associated urinary tract infections (CAUTIs) are one of the most common hospital-acquired conditions and no longer reimbursable from Medicare as of 2008. Nurse-driven protocols (NDPs), which provide a medically approved rubric for professional nurses to make autonomous care decisions, can facilitate appropriate catheter use and timely removal, as advised in the Centers for Disease Control and Prevention's 2009 CAUTI prevention guidelines. However, little attempt has been made to systematically evaluate their effect on clinical outcomes. A systematic review of studies published in the United States since 2006 was performed, following guidelines from the Institute of Medicine. Sources included CINAHL, Medline, professional agencies, hand-searching, and expert consultation. Clinical predictors and prevalence of CAUTI were examined and synthesized qualitatively; heterogeneity of outcomes made a statistical meta-analysis inappropriate. Twenty-nine studies were found eligible for inclusion. All used a case-control (pre-post) approach, and all reported reductions in clinical predictors of CAUTI, particularly indwelling-urinary catheter utilization and CAUTI rates. However, the number of CAUTIs remained unchanged in 1 study. A formal quality assessment revealed a high risk of bias; included studies met an average of 4.9 out of 11 quality indicators. Specifically, many did not use standardized measures. NDPs appear to have a positive impact on the clinical predictors and prevalence of CAUTI. However, this review identified need for improving the study design of quality improvement projects conducted within the patient care setting.


Occurrence of Blastocystis in Patients with Clostridioides difficile Infection.
Clostridiodes difficile comprises a public-health threat that has been understudied in Colombia. Hypervirulent strains of C. difficile harbor multiple toxins, can be easily spread, and can have their onset of disease within healthcare facilities (HCFO) and the community (CO). Studies have shown that a disrupted microbiota (e.g., dysbiosis) may allow C. difficile infection (CDI). It has been suggested that dysbiosis prevents colonization by the anaerobic eukaryote Blastocystis, possibly due to an increase in luminal oxygen tension. No study has found co-occurrence of CDI and Blastocystis. Therefore, we aimed to determine the frequencies of C. difficile and Blastocystis infection/colonization in 220 diarrheal fecal samples. Molecular detection by PCR for both microorganisms was performed, with descriptive analyses of four variables (CDI detection, determination of C. difficile toxigenic profiles, Blastocystis detection, and patient site of onset). We demonstrate a significant association between the presence of Blastocystis and CDI, with coinfection found in 61 patients, and show a high frequency of CDI among both HCFO and CO groups. Our results of coinfection frequencies could support hypotheses that suggest Blastocystis can adapt to dysbiosis and oxidative stress. Further, the presence of toxigenic C. difficile occurring outside healthcare facilities shown here raises the alarm for community wide spread.


Influence of the metabolic state during lactation on milk production in modern sows.
Selection for prolificacy in sows has resulted in higher metabolic demands during lactation. In addition, modern sows have an increased genetic merit for leanness. Consequently, sow metabolism during lactation has changed, possibly affecting milk production and litter weight gain. The aim of this study was to investigate the effect of lactational feed intake on milk production and relations between mobilization of body tissues (adipose tissue or skeletal muscle) and milk production in modern sows with a different lactational feed intake. A total of 36 primiparous sows were used, which were either full-fed (6.5 kg/day) or restricted-fed (3.25 kg/day) during the last 2 weeks of a 24-day lactation. Restricted-fed sows had a lower milk fat percentage at weaning and a lower litter weight gain and estimated milk fat and protein production in the last week of lactation. Next, several relations between sow body condition (loss) and milk production variables were identified. Sow BW, loin muscle depth and backfat depth at parturition were positively related to milk fat production in the last week of lactation. In addition, milk fat production was related to the backfat depth loss while milk protein production was related to the loin muscle depth loss during lactation. Backfat depth and loin muscle depth at parturition were positively related to lactational backfat depth loss or muscle depth loss, respectively. Together, results suggest that sows which have more available resources during lactation, either from a higher amount of body tissues at parturition or from an increased feed intake during lactation, direct more energy toward milk production to support a higher litter weight gain. In addition, results show that the type of milk nutrients that sows produce (i.e. milk fat or milk protein) is highly related to the type of body tissues that are mobilized during lactation. Interestingly, relations between sow body condition and milk production were all independent of feed level during lactation. Sow management strategies to increase milk production and litter growth in modern sows may focus on improving sow body condition at the start of lactation or increasing feed intake during lactation.


Trypanosoma cruzi infection in dogs along the US-Mexico border: R0 changes with vector species composition.
Infection with Trypanosoma cruzi, etiological agent of Chagas disease, is common in US government working dogs along the US-Mexico border. This 3145 km long border comprises four states: Texas (TX), New Mexico (NM), Arizona (AZ) and California (CA) with diverse ecosystems and several triatomine (a.k.a., kissing bug) species, primary vectors of T. cruzi in this region. The kissing bug (Heteroptera: Reduviidae) community ranging from CA to TX includes Triatoma protracta (Uhler), Triatoma recurva (Stål) and Triatoma rubida (Uhler) and becomes dominated by Triatoma gerstaeckeri Stål in TX. Here, we ask if T. cruzi infection dynamics in dogs varies along this border region, potentially reflecting changes in vector species and their vectorial capacity. Using reversible catalytic models of infection, where seropositivity can be lost, we estimated an R0 (Estimate ± S.E.) of 1.192 ± 0.084 for TX and NM. In contrast, seropositivity decayed to zero as dogs aged in AZ and CA. These results suggest that dogs are likely infected by T. cruzi during their training in western TX, with a force of infection large enough for keeping R0 above 1, i.e., the disease endemically established, in TX and NM. In AZ and CA, a lower force of infection, probably associated with different vector species communities and associated vectorial capacity and/or different lineages of T. cruzi, results in dogs decreasing their seropositivity with age.


[The importance of collagen in the biological value of meat].
Rat experiments showed that increases in the levels of collagen from 6.1 to 15.5% of the total content of meat proteins enhanced the growth and weight indices of animals. The differences in the biological value of the above quantity of collagen for man and rats were attributable to different physiological requirements for the quality of protein. Therefore, the findings in man are in agreement with those in rats.


Posterior deltoid shoulder tightness and greater contralateral lower limb muscle strength are associated with swimmers' shoulder pain.
To identify factors associated with shoulder pain in swimmers based on elastic muscle modulus, joint range of motion, and isometric muscle strength. Cohort study. Forty-eight competitive swimmers without shoulder pain (age: 18-28 years; men: 29) were followed-up for 6 months. Baseline measurements of the elastic modulus of the pectoralis minor, supraspinatus, infraspinatus, posterior deltoid, and pectoralis minor muscles were obtained using shear wave elastography. Range of motion and isometric strength were measured using a goniometer and a hand-held dynamometer, respectively. A questionnaire was administered weekly for 6 months to determine shoulder pain occurrence. Each item was compared between shoulders with and without pain at baseline. For participants with shoulder pain exceeding 2 weeks, shear wave elastography and range of motion at baseline (pre pain) and during follow-up (post pain) were compared. Of 46 swimmers followed-up for 6 months, 20 reported shoulder pain. 14 swimmers with pain were evaluated twice. Participants with shoulder pain during follow-up had significantly higher posterior deltoid and pectoralis minor stiffness at baseline and high lower extremity isometric muscle strength contralateral to the shoulder with pain compared to those without pain (p < 0.05). Swimmers with pain exceeding 2 weeks exhibited no differences in ultrasound shear wave elastography and range of motion at baseline and after pain onset. Posterior deltoid and pectoralis minor muscle stiffness, and high isometric lower extremity strength contralateral to the shoulder with pain may be associated with shoulder pain development, thereby indicating the importance of maintaining posterior deltoid and pectoralis minor muscle flexibility during conditioning.


Rapid enumeration of active Legionella pneumophila in freshwater environments by the microcolony method combined with direct fluorescent antibody staining.
In this study, a microcolony technique was combined with direct fluorescent antibody staining for the specific detection and enumeration of Legionella pneumophila in freshwater samples with growth activity. This method allowed the detection of active L. pneumophila (within 48 h) in 91 bath water samples collected from 30 bathing facilities, with similar sensitivity of a conventional plate-counting method. These results suggest that the microcolony method combined with fluorescent antibody staining could be useful as a monitoring technique for the prevention of Legionnaires' disease through the early detection of L. pneumophila in freshwater.


Prognostic Value of Intraplaque Neovascularization Detected by Carotid Contrast-Enhanced Ultrasound in Patients Undergoing Stress Echocardiography.
Stress echocardiography (SE) is used for diagnosis and risk stratification of patients with known or suspected coronary artery disease (CAD). Contrast-enhanced ultrasound (CEUS) detects carotid intraplaque neovascularization (IPN). The aim of this study was to test the hypothesis that combining SE with carotid CEUS in patients with known or suspected CAD might provide incremental prognostic value beyond clinical risk factors and either test alone for the occurrence of cardiovascular events. One hundred eighty-five patients (mean age, 69 ± 8 years; 79% men) with known or suspected CAD referred for SE and found to have carotid plaque on screening were recruited for carotid CEUS imaging. IPN was graded by presence and location within plaque. Patients were followed for cardiovascular events (CVEs) including cardiac death, myocardial infarction, unstable angina, and transient ischemic attack or stroke. A subset of patients (n = 27) underwent carotid magnetic resonance imaging within 1 month of CEUS; carotid plaque was assessed for lipid-rich necrotic core, loose matrix, and presence of intraplaque hemorrhage. Sixty-nine patients had abnormal findings on SE. IPN was identified in 112 patients; 52 patients had IPN localized to plaque shoulder (IPNS). Plaques with IPNS had larger lipid-rich necrotic cores and were more likely to have intraplaque hemorrhage. During follow-up (median, 31 months), 26 CVEs occurred. Multivariate Cox proportional-hazard analysis showed IPN and IPNS to be predictors of CVEs (hazard ratios, 3.34 [95% CI, 1.25-8.93; P = .02] and 4.88 [95% CI, 1.77-13.49; P = .002], respectively). The presence of IPNS increased the likelihood of CVEs beyond SE and history of CAD (χ2 = 9.0, P = .02). Carotid IPN detected by CEUS and localized to plaque shoulder was an independent predictor of CVEs in patients referred for SE.


Automatic on-line fermentation headspace gas analysis using a computer-controlled gas chromatograph.
A computer-controlled headspace gas chromatograph was used to monitor the progress of ethanol production from both aerobic batch and anaerobic continuous fermentations. Using an automatic, electropneumatic sampling system, aliquots of fermentation headspace gas were injected directly onto the column for quantitative ethanol determinations every six minutes. A sample volume of 1 mL permitted liquid ethanol concentrations from 2 to 100 g/L to be measured with better than 3% standard deviation on five repeated injections. Provided fermenter liquid temperature and ionic strength were maintained constant, the signal-tohyphen;concentration ratio remained linear to 80 g/L ethanol. This quantitative gas chromatographic (GC) method is suitable for accurate, precise analysis of multiple solvent fermentations, and is limited only by the elution rate and separating capacity of the GC column.


Arabidopsis DXO1 possesses deNADding and exonuclease activities and its mutation affects defense-related and photosynthetic gene expression.
RNA capping and decapping tightly coordinate with transcription, translation, and RNA decay to regulate gene expression. Proteins in the DXO/Rai1 family have been implicated in mRNA decapping and decay, and mammalian DXO was recently found to also function as a decapping enzyme for NAD+ -capped RNAs (NAD-RNA). The Arabidopsis genome contains a single gene encoding a DXO/Rai1 protein, AtDXO1. Here we show that AtDXO1 possesses both NAD-RNA decapping activity and 5'-3' exonuclease activity but does not hydrolyze the m7 G cap. The atdxo1 mutation increased the stability of NAD-RNAs and led to pleiotropic phenotypes, including severe growth retardation, pale color, and multiple developmental defects. Transcriptome profiling analysis showed that the atdxo1 mutation resulted in upregulation of defense-related genes but downregulation of photosynthesis-related genes. The autoimmunity phenotype of the mutant could be suppressed by either eds1 or npr1 mutation. However, the various phenotypes associated with the atdxo1 mutant could be complemented by an enzymatically inactive AtDXO1. The atdxo1 mutation apparently enhances post-transcriptional gene silencing by elevating levels of siRNAs. Our study indicates that AtDXO1 regulates gene expression in various biological and physiological processes through its pleiotropic molecular functions in mediating RNA processing and decay.


[Total endoprosthesis of the knee joint].
The results of conduction of 7 operations endoprosthetics of the knee joint using AGC-system of the "Biomet" concern are adduced. Details of operative procedure are enlightened, clinical cases and immediate results of operation are adduced.


Combination of hypercholesterolemia and hypertension augments renal function abnormalities.
Hypercholesterolemia and hypertension are both risk factors for end-stage renal disease. This study was designed to examine whether their coexistence augmented impairment in renal function and redox status. Regional renal hemodynamics and function in response to vasoactive challenges with acetylcholine or sodium nitroprusside were quantified by using electron-beam computed tomography in pigs after 12 weeks of either a normal (n=10) or hypercholesterolemic (n=10) diet, renovascular hypertension (n=7), or combined hypercholesterolemia+hypertension (n=6). The hypercholesterolemic and hypercholesterolemic+hypertensive groups had significantly increased serum cholesterol levels, whereas in the hypertensive and hypercholesterolemic+hypertensive groups, mean arterial pressure was significantly elevated compared with the group fed a normal diet. Basal regional renal perfusion and glomerular filtration rates were similar among the groups. In response to acetylcholine, cortical perfusion increased in normal animals (15.6+/-4.7%, P=0.002) but not in hypercholesterolemic or hypertensive animals (8.0+/-7.4% and 8.2+/-5.9%, respectively; P>0.05). Moreover, in the hypercholesterolemic+hypertensive group, cortical perfusion response was further attenuated (2.5+/-4.8%, P=0.02) and significantly different from the group fed a normal diet (P<0.05). The response to sodium nitroprusside followed a similar pattern, and the impairment was augmented in the hypercholesterolemic+hypertensive group. The functional abnormalities in hypercholesterolemia or hypertension were associated with a decrease in systemic and/or renal tissue levels of oxygen radical scavengers that was again accentuated in hypercholesterolemia+hypertension. These results demonstrate that concurrent hypercholesterolemia and hypertension have a greater detrimental effect on renal perfusion responses compared with hypercholesterolemia or hypertension alone, associated with a marked pro-oxidant shift in redox status. These effects may potentially augment renal functional impairment and play a role in the initiation and progression of renal injury in hypertension and atherosclerosis.


Pollinator specificity drives strong prepollination reproductive isolation in sympatric sexually deceptive orchids.
Few studies have quantified the full range of pre- and postzygotic barriers that limit introgression between closely related plant species. Here, we assess the strength of four isolating mechanisms operating between two morphologically similar and very closely related sympatric orchid taxa, Chiloglottis valida and C. aff. jeanesii. Each taxon sexually attracts its specific wasp pollinator via distinct floral volatile chemistry. Behavioral experiments with flowers and synthetic versions of their floral volatiles confirmed that very strong pollinator isolation is mediated by floral odor chemistry. However, artificially placing flowers of the two taxa in contact proximity revealed the potential for rare interspecific pollination. Although we found hybrid vigor in F1 hybrids produced by hand-crossing, genetic analysis at both nuclear and chloroplast loci showed significant and moderate-to-strong genetic differentiation between taxa. A Bayesian clustering method for the detection of introgression at nuclear loci failed to find any evidence for hybridization across 571 unique genotypes at one site of sympatry. Rather than inhibiting gene flow, postpollination barriers surveyed here show no contribution to overall reproductive isolation. This demonstrates the primacy of pollinators in maintaining species boundaries in these orchids, which display one of the strongest known examples of prepollination floral isolation.


Buprenorphine use in pregnant opioid users: a critical review.
Pregnancy in opioid users poses a number of problems to treating physicians. Most guidelines recommend maintenance treatment to manage opioid addiction in pregnancy, with methadone being the gold standard. More recently, buprenorphine has been discussed as an alternate medication. The use and efficacy of buprenorphine in pregnancy is still controversial. This article reviews the current database on the basis of a detailed and critical literature search performed in MEDLINE (206 counts). Most of the relevant studies (randomised clinical trials and one national cohort sample) were published in the last 2 years and mainly compared buprenorphine with methadone. Some studies are related to maternal outcomes, others to foetal, neonatal or older child outcomes. With respect to maternal outcomes, most studies suggest that buprenorphine has similar effects to methadone. Very few data from small studies discuss an effect of buprenorphine on neurodevelopment of the foetus. Neonatal abstinence syndrome is common in infants of both buprenorphine- and methadone-maintained mothers. As regards neonatal outcomes, buprenorphine has the same clinical outcome as methadone, although some newer studies suggest that it causes fewer withdrawal symptoms. Since hardly any studies have investigated the combination of buprenorphine with naloxone (which has been suggested to possibly have teratogenic effects) in pregnant women, a switch to buprenorphine monotherapy is recommended in women who become pregnant while receiving the combination product. These novel findings indicate that buprenorphine is emerging as a first-line treatment for pregnant opioid users.


Functional, nutritional and social factors associated with mobility limitations in the elderly: a systematic review.
To systematically review the prevalence and incidence of mobility limitations in the elderly people and their associated factors. Articles in the electronic literature were searched via PubMed, Scopus,,Lilacs, SciELO, PAHO, MedCarib, Repidisca, Wholis, IBCES, PEDro, Medline and Bireme (2012-2016). The instrument STROBE was used to analyze the quality of the work and the PRISMA recommendation was used to structure the review. Nine studies were included. The prevalence of mobility limitations ranged from 58.1 to 93.2% and the incidence ranged from 23 to 53.7%. Studies provided evidence of association of mobility limitations in the elderly population with high BMI, low 25-hydroxy vitamin D, sarcopenia, fragility, chronic pain, functional dependence, advanced age in women, low hip flexion, sedentary lifestyle, and social support difficulties. Mobility limitations in the elderly had high prevalence and incidence, and there was evidence of association with nutritional, functional and social factors.


Next generation media monitoring: Global coverage of electronic nicotine delivery systems (electronic cigarettes) on Bing, Google and Twitter, 2013-2018.
News media monitoring is an important scientific tool. By treating news reporters as data collectors and their reports as qualitative accounts of a fast changing public health landscape, researchers can glean many valuable insights. Yet, there have been surprisingly few innovations in public health media monitoring, with nearly all studies relying on labor-intensive content analyses limited to a small number of media reports. We propose to advance this subfield by using scalable machine learning. In potentially the largest contemporary public health media monitoring study to date, we systematically characterize global news reports surrounding electronic cigarettes or electronic nicotine delivery systems (ENDS) using natural language processing techniques. News reports including ENDS terms (e.g., "electronic cigarettes") from over 100,000 sources (all sources archived on Google News or Bing News, as well as all news articles shared on Twitter) were monitored for 1 January 2013 through 31 July 2018. The geographic and subject (e.g., prevalence, bans, quitting, warnings, marketing, prices, age, flavor and industry) foci of news articles, their popularity among readers who share news on social media, and the sentiment behind news articles were assessed algorithmically. Globally there were 86,872 ENDS news reports with coverage increasing from 8 (standard deviation [SD] = 8) stories per day in 2013 to 75 (SD = 56) stories per day during 2018. The focus of ENDS news spanned 148 nations, with the plurality focusing on the United States (34% of all news). Potentially overlooked hotspots of ENDS media activity included China, Egypt, Russia, Ukraine, and Paraguay. The most common subject was warnings about ENDS (18%), followed by bans on using ENDS (13%) and ENDS prices (9%). Flavor and age restrictions were the least covered news subjects (~1% each). Among different subject foci, reports on quitting cigarettes using ENDS had the highest probability of scoring in the top three deciles of popularity rankings. Moreover, ENDS news on quitting and prices had a more positive sentiment on average than news with other subject foci. Public health leaders can use these trends to stay abreast of how ENDS are portrayed in the media, and potentially how the public perceives ENDS. Because our analytical strategies are updated in near real time, we aim to make media monitoring part of standard practice to support evidence-based tobacco control in the future.


The role of the PET scan in the management of sarcoidosis.
It is important to gain knowledge and understanding about the appropriate use of PET scan in the management of sarcoidosis patients. This means that, in view of the radiation dose and costs, defining appropriate indications for PET scanning in sarcoidosis patients is vital. PET has been shown to be a very sensitive technique for the assessment of inflammatory activity in sarcoidosis by detecting and quantifying the degree of inflammatory and granulomatous reactions that occur in the lungs and elsewhere in the body. PET is not indicated in the standard workup, but can be of great value to complement more routinely used techniques. On the basis of the current findings, PET offers added value in sarcoidosis patients with unexplained persistent disabling symptoms. PET appears especially helpful in those persistently symptomatic patients without serological signs of inflammatory activity, in patients with radiologic signs of fibrosis and in the detection of active cardiac sarcoidosis. The use of PET to assess the extent of disease can uncover a suitable location for biopsy to obtain histological evidence for the diagnosis or to explain the (mainly extrathoracic) symptoms. Furthermore, the detection of unexpected organ involvement may offer prognostic value.


Proteome analysis during chondrocyte differentiation in a new chondrogenesis model using human umbilical cord stroma mesenchymal stem cells.
Umbilical cord stroma mesenchymal stem cells were differentiated toward chondrocyte-like cells using a new in vitro model that consists of the random formation of spheroids in a medium supplemented with fetal bovine serum on a nonadherent surface. The medium was changed after 2 days to one specific for the induction of chondrocyte differentiation. We assessed this model using reverse transcriptase-polymerase chain reaction, flow cytometry, immunohistochemistry, and secretome analyses. The purpose of this study was to determine which proteins were differentially expressed during chondrogenesis. Differential gel electrophoresis analysis was performed, followed by matrix-assisted laser desorption/ionization mass spectrometry protein identification. A total of 97 spots were modulated during the chondrogenesis process, 54 of these spots were identified as 39 different proteins and 15 were isoforms. Of the 39 different proteins identified 15 were down-regulated, 21 were up-regulated, and 3 were up- and down-regulated during the chondrogenesis process. Using Pathway Studio 7.0 software, our results showed that the major cell functions modulated during chondrogenesis were cellular differentiation, proliferation, and migration. Five proteins involved in cartilage extracellular matrix metabolism found during the differential gel electrophoresis study were confirmed using Western blot. The results indicate that our in vitro chondrogenesis model is an efficient and rapid technique for obtaining cells similar to chondrocytes that express proteins characteristic of the cartilage extracellular matrix. These chondrocyte-like cells could prove useful for future cell therapy treatment of cartilage pathologies.


Ultrasound-assisted synthesis of poly(MMA-co-BA)/ZnO nanocomposites with enhanced physical properties.
The present study reports synthesis and characterization of poly(MMA-co-BA)/ZnO nanocomposites using ultrasound-assisted in-situ emulsion polymerization. Methyl methacrylate (MMA) was copolymerized with butyl acrylate (BA), for enhanced ductility of copolymer matrix, in presence of nanoscale ZnO particles. Ultrasound generated strong micro-turbulence in reaction mixture, which resulted in higher encapsulation and uniform dispersion of ZnO (in native form - without surface modification) in polymer matrix, as compared to mechanical stirring. The nanocomposites were characterized for physical properties and structural morphology using standard techniques such as XRD, FTIR, particle size analysis, UV-Visible spectroscopy, electrical conductivity, TGA, DSC, FE-SEM and TEM. Copolymerization of MMA and BA (in presence of ZnO) followed second order kinetics. Thermal stability (T10%=324.9°C) and glass transition temperature (Tg=67.8°C) of poly(MMA-co-BA)/ZnO nanocomposites showed significant enhancement (35.1°C for 1wt% ZnO and 15.7°C for 4wt% ZnO, respectively), as compared to pristine poly(MMA-co-BA). poly(MMA-co-BA)/ZnO (5wt%) nanocomposites possessed the highest electrical conductivity of 0.192μS/cm and peak UV absorptivity of 0.55 at 372nm. Solution rheological study of nanocomposites revealed enhancement in viscosity with increasing ZnO loading. Maximum viscosity of 0.01Pa-s was obtained for 5wt% ZnO loading.


Next-generation phylogeography resolves post-glacial colonization patterns in a widespread carnivore, the red fox (Vulpes vulpes), in Europe.
Carnivores tend to exhibit a lack of (or less pronounced) genetic structure at continental scales in both a geographic and temporal sense and this can confound the identification of post-glacial colonization patterns in this group. In this study we used genome-wide data (using genotyping by sequencing [GBS]) to reconstruct the phylogeographic history of a widespread carnivore, the red fox (Vulpes vulpes), by investigating broad-scale patterns of genomic variation, differentiation and admixture amongst contemporary populations in Europe. Using 15,003 single nucleotide polymorphisms (SNPs) from 524 individuals allowed us to identify the importance of refugial regions for the red fox in terms of endemism (e.g., Iberia). In addition, we tested multiple post-glacial recolonization scenarios of previously glaciated regions during the Last Glacial Maximum using an Approximate Bayesian Computation (ABC) approach that were unresolved from previous studies. This allowed us to identify the role of admixture from multiple source population post-Younger Dryas in the case of Scandinavia and ancient land-bridges in the colonization of the British Isles. A natural colonization of Ireland was deemed more likely than an ancient human-mediated introduction as has previously been proposed and potentially points to a larger mammalian community on the island in the early post-glacial period. Using genome-wide data has allowed us to tease apart broad-scale patterns of structure and diversity in a widespread carnivore in Europe that was not evident from using more limited marker sets and provides a foundation for next-generation phylogeographic studies in other non-model species.


High-performance and stable organic transistors and circuits with patterned polypyrrole electrodes.
High performance p-/n-type transistors and complementary inverter circuits are demonstrated using patterned polypyrrole (PPY) as pure electrodes. Strikingly, these devices show good stability under continuous operation and long-term storage conditions. Furthermore, PPY electrodes also exhibit good applicability in solution-processed and flexible devices. All these results indicate the great potential of PPY electrodes in solution-processed, all-organic, flexible, transparent, and low-power electronics.


Defining "smoker": college student attitudes and related smoking characteristics.
Less than half of college students who have smoked in the past month identify themselves as smokers. Thus, we examined (a) how college students define the term "smoker" and (b) how this definition impacts smoking behavior and attitudes. We conducted 12 focus groups with a total of 73 college student smokers drawn from survey participants at two colleges in Minnesota (a two-year technical college and a four-year university). Each group was homogenous in terms of gender and school (two-year, four-year). The majority (56.2%) were female, 49.3% attended a 2-year college, and 32.9% were regular smokers (smoked > or = 25 of the last 30 days). Participants described a "smoker" in terms of (a) smoking frequency, ranging from smoking infrequently to smoking daily; (b) contextual factors, such that smoking alone indicates being a smoker rather than smoking at parties; (c) time since initiation; (d) whether one purchases cigarettes, such that "smokers" buy cigarettes while nonsmokers borrow them; (e) addiction and being able to quit without great effort; (f) whether smoking is habitual; and (g) personality and physical characteristic. These beliefs had implications on experiences in quitting smoking, motivation to quit, and perceived barriers. Many participants indicated confidence in being able to quit but believed that they were not "smokers" and thus did not need to quit. College students use a broad range of criteria to define who is a smoker. These criteria impact how motivated students are to quit smoking and their perception of needing to "quit smoking."


[Clinical and morphological findings in a case of malignant hyperthermia (author's transl)].
A 32-year-old man survived malignant hyperthermia which developed in conjunction with laparotomy. Muscles biopsy indicated acute necrosis of muscle fibers as well as changes consistent with a latent myopathy. Clinical, laboratory and morphological studies of the relatives revealed familial subclinical myopathy. The hyperthermia resulting from the anaesthesia is thought to be casually related to the myopathy, and members of the family have been warned against this potential risk.


Isometric Stretch Alters Vascular Reactivity of Mouse Aortic Segments.
Most vaso-reactive studies in mouse aortic segments are performed in isometric conditions and at an optimal preload, which is the preload corresponding to a maximal contraction by non-receptor or receptor-mediated stimulation. In general, this optimal preload ranges from about 1.2 to 8.0 mN/mm, which according to Laplace's law roughly correlates with transmural pressures of 10-65 mmHg. For physiologic transmural pressures around 100 mmHg, preloads of 15.0 mN/mm should be implemented. The present study aimed to compare vascular reactivity of 2 mm mouse (C57Bl6) aortic segments preloaded at optimal (8.0 mN/mm) vs. (patho) physiological (10.0-32.5 mN/mm) preload. Voltage-dependent contractions of aortic segments, induced by increasing extracellular K+, and contractions by α1-adrenergic stimulation with phenylephrine (PE) were studied at these preloads in the absence and presence of L-NAME to inhibit basal release of NO from endothelial cells (EC). In the absence of basal NO release and with higher than optimal preload, contractions evoked by depolarization or PE were attenuated, whereas in the presence of basal release of NO PE-, but not depolarization-induced contractions were preload-independent. Phasic contractions by PE, as measured in the absence of external Ca2+, were decreased at higher than optimal preload suggestive for a lower contractile SR Ca2+ content at physiological preload. Further, in the presence of external Ca2+, contractions by Ca2+ influx via voltage-dependent Ca2+ channels were preload-independent, whereas non-selective cation channel-mediated contractions were increased. The latter contractions were very sensitive to the basal release of NO, which itself seemed to be preload-independent. Relaxation by endogenous NO (acetylcholine) of aortic segments pre-contracted with PE was preload-independent, whereas relaxation by exogenous NO (diethylamine NONOate) displayed higher sensitivity at high preload. Results indicated that stretching aortic segments to higher than optimal preload depolarizes the SMC and causes Ca2+ unloading of the contractile SR, making them extremely sensitive to small changes in the basal release of NO from EC as can occur in hypertension or arterial stiffening.


Rhodococcus jostii sp. nov., isolated from a medieval grave.
The taxonomic position of a bacterial strain isolated from the femur of the remains of Jost Lucemburský, margrave in Moravia, Brno (Czech Republic), was investigated by phenotypic, chemotaxonomic and molecular taxonomic methods. The chemotaxonomic characteristics, including the cell-wall amino acid and sugar compositions, the quinone system and the fatty acid profile, were in good agreement with those of the genus Rhodococcus. The G+C content of the DNA was 67.4 mol%. Comparative 16S rRNA gene sequencing demonstrated that the unknown strain represents a distinct line of descent within the genus Rhodococcus. The nearest relatives of the bacterium were Rhodococcus opacus and Rhodococcus percolatus. The unknown bacterium was readily distinguished from these species by using phenotypic methods. On the basis of phylogenetic and phenotypic evidence, it is proposed that the unknown bacterium be classified as Rhodococcus jostii sp. nov. The type strain is strain IFO 16295T (= CCM 4760T).


Exercise in the treatment of childhood obesity.
Research on exercise in the treatment of childhood obesity is reviewed. The role of activity or sedentary behaviors in the development of obesity is discussed, with a conceptual model for understanding choice of being sedentary or active presented. Research that assesses the effects of exercise alone and diet plus exercise on child weight control are reviewed, as well as new research on modifying access to sedentary behaviors. Treatment research suggests exercise alone is not sufficient, with the combination of diet plus exercise more effective for long-term than short-term changes. Finally, suggestions for new research are presented.


Effects of oxygen on Propionibacterium shermanii grown in continuous culture.
Growth yields, enzyme activities, cytochrome concentrations and the rates of product formation were determined in Propionibacterium shermanii cultures grown in a chemostat with lactate as the energy source at various concentrations of oxygen. Oxygen was toxic when its partial pressure in the inflowing gas was just sufficient to give measurable dissolved oxygen concentration in the culture, when it inhibited lactate oxidation and NADH oxidase activity. Below this oxygen concentration, P. shermanii behaved as a facultative anaerobe. The adaptation from anaerobic metabolism to aerobic metabolism, however, was complex. Low partial pressures of oxygen led to decreased cytochrome and membrane-bound dehydrogenase activities and molar growth yield. Above an oxygen partial pressure of 42 mmHg in the inflowing gas stream, these changes were reversed, leading to an aerobic type of metabolism. At the highest subtoxic concentration of oxygen used (330 mmHg in the input gas), lactate was oxidized mainly to acetate and carbon dioxide and the rate of propionate formation was very low. The high molar growth yield obtained under these conditions suggested that lactate and NADH oxidation via the cytochrome electron transport system was coupled to ATP synthesis.


Are Adolescent Religious Attendance/Spirituality Associated with Family Characteristics?
The family environment is associated with religiosity and spirituality as well as many aspects of adolescent lives, including their health behaviour. Therefore, the aim of this study was to assess family environment associations with adolescent religious attendance (RA), i.e., weekly participation in religious services, and spirituality in a highly secular country. A nationally representative sample (n = 4182, 14.4 ± 1.1 years, 48.6% boys) of Czech adolescents participated in the 2014 Health Behaviour in School-aged Children cross-sectional study. RA, spirituality and the family environment, i.e., family communication, perceived emotional support, and parental monitoring, were measured. Higher adolescent RA was associated with lower self-reported easiness of communication with mother (odds ratio (OR) = 0.68; 99% confidence interval (99% CI) = 0.47-0.99; p < 0.01). In contrast, spiritual respondents were more likely to report both easier communication with their father (OR per standard deviation (SD) change = 1.12, 99% CI 1.02-1.23; p < 0.01) and mother (OR per SD change = 1.38 (1.23-1.55); p < 0.001) and higher perceived emotional support (OR per SD change = 1.73 (1.55-1.92); p < 0.001). Parents of respondents who attended religious services at least once a week, as well as parents of spiritual respondents, were generally more likely to monitor adolescent behaviour. Thus, this study provides information for parents, mental health workers, and pastoral carers. Further research should assess the association of a lower easiness of family communication with dissonances in adolescent-parent religiosity/spirituality and with higher parental monitoring.


Thermal robustness of magnetic tunnel junctions with perpendicular shape anisotropy.
The concept of Perpendicular Shape Anisotropy STT-MRAM (PSA-STT-MRAM) has been recently proposed as a solution to enable the downsize scalability of STT-MRAM devices beyond the sub-20 nm technology node. For conventional p-STT-MRAM devices with sub-20 nm diameters, the perpendicular anisotropy arising from the MgO/CoFeB interface becomes too weak to ensure thermal stability of the storage layer. In addition, this interfacial anisotropy rapidly decreases with increasing temperature which constitutes a drawback in applications with a large range of operating temperatures. Here, we show that by using a PSA based storage layer, the source of anisotropy is much more robust against thermal fluctuations than the interfacial anisotropy, which allows considerable reduction of the temperature dependence of the coercivity. From a practical point of view, this is very interesting for applications having to operate on a wide range of temperatures (e.g. automotive -40 °C/+150 °C).


Pharmacological approach to chronic visceral pain. Focus on oxycodone controlled release: an open multicentric study.
Visceral pain is a significant issue for patients, and the importance of treating pain is underestimated. New opioid formulations, the primary treatment option for moderate-to-severe pain, have been shown to be effective, but no studies have been conducted to address the efficacy of these agents for visceral pain. This study was conducted to determine the incidence of visceral pain in patients with uncontrolled moderate-to-severe pain, and to evaluate the efficacy of controlled-release (CR) oxycodone in this context. s: In this multicenter, prospective, observational study, 967 of 980 evaluated patients were included, 350 (36.2%) of whom presented mainly visceral pain. In most cases (57.0%), patients had experienced pain for < or = 3 months, and the majority (94.9%) were cancer patients. Pain was uncontrolled in 340 (97.1%) patients, and was rated as severe in >2/3 of patients (mean numerical rating scale (NRS) value 7.04 +/- 1.68). Patients with uncontrolled pain were given oxycodone CR; all completed the 15-day study and no patient was switched to an alternative opioid. Oxycodone CR was associated with significant reductions in mean NRS value at day 3, 7 and 15 (final mean NRS 2.37 +/- 1.59) and the proportion of patients experiencing severe pain had decreased by the end of the study to 1.5%. The SF-12 questionnaire showed significant improvements in quality of life in all domains, and oxycodone CR was well tolerated. Oxycodone CR appears to be a very well tolerated and effective treatment for patients with visceral pain.


Structural and functional evidence of high specificity of Cbf5 for ACA trinucleotide.
Cbf5 is the catalytic subunit of the H/ACA small nucleolar/Cajal body ribonucleoprotein particles (RNPs) responsible for site specific isomerization of uridine in ribosomal and small nuclear RNA. Recent evidence from studies on archaeal Cbf5 suggests its second functional role in modifying tRNA U55 independent of guide RNA. In order to act both as a stand-alone and a RNP pseudouridine synthase, Cbf5 must differentiate features in H/ACA RNA from those in tRNA or rRNA. Most H/ACA RNAs contain a hallmark ACA trinucleotide downstream of the H/ACA motif. Here we challenged an archaeal Cbf5 (in the form of a ternary complex with its accessory proteins Nop10 and Gar1) with T-stem-loop RNAs with or without ACA trinucleotide in the stem. Although these substrates were previously shown to be substrates for the bacterial stand-alone pseudouridine synthase TruB, the Cbf5-Nop10-Gar1 complex was only able to modify those without ACA trinucleotide. A crystal structure of Cbf5-Nop10-Gar1 trimer bound with an ACA-containing T-stem-loop revealed that the ACA trinucleotide detracted Cbf5 from the stand-alone binding mode, thereby suggesting that the H/ACA RNP-associated function of Cbf5 likely supersedes its stand-alone function.


Disturbed cardiac mitochondrial and cytosolic calcium handling in a metabolic risk-related rat model of heart failure with preserved ejection fraction.
Calcium ions play a pivotal role in matching energy supply and demand in cardiac muscle. Mitochondrial calcium concentration is lower in animal models of heart failure with reduced ejection fraction (HFrEF), but limited information is available about mitochondrial calcium handling in heart failure with preserved ejection fraction (HFpEF). We assessed mitochondrial Ca2+ handling in intact cardiomyocytes from Zucker/fatty Spontaneously hypertensive F1 hybrid (ZSF1)-lean (control) and ZSF1-obese rats, a metabolic risk-related model of HFpEF. A mitochondrially targeted Ca2+ indicator (MitoCam) was expressed in cultured adult rat cardiomyocytes. Cytosolic and mitochondrial Ca2+ transients were measured at different stimulation frequencies. Mitochondrial respiration and swelling, and expression of key proteins were determined ex vivo. At rest, mitochondrial Ca2+ concentration in ZSF1-obese was larger than in ZSF1-lean. The diastolic and systolic mitochondrial Ca2+ concentrations increased with stimulation frequency, but the steady-state levels were larger in ZSF1-obese. The half-widths of the contractile responses, the resting cytosolic Ca2+ concentration and the decay half-times of the cytosolic Ca2+ transients were higher in ZSF1-obese, likely because of a lower SERCA2a/phospholamban ratio. Mitochondrial respiration was lower, particularly with nicotinamide adenine dinucleotide (NADH) (complex I) substrates, and mitochondrial swelling was larger in ZSF1-obese. The free mitochondrial calcium concentration is higher in HFpEF owing to alterations in mitochondrial and cytosolic Ca2+ handling. This coupling between cytosolic and mitochondrial Ca2+ levels may compensate for myocardial ATP supply in vivo under conditions of mild mitochondrial dysfunction. However, if mitochondrial Ca2+ concentration is sustainedly increased, it might trigger mitochondrial permeability transition pore opening.


Evaluation of General Practice Pharmacists: Study Protocol to Assess Interprofessional Collaboration and Team Effectiveness.
The inclusion of pharmacists into general practices has expanded in Australia. However, there is a paucity of research examining interprofessional collaboration and team effectiveness after including a pharmacist into the general practice team in primary or community care. This is a protocol for a cross-national comparative mixed-methods study to (i) investigate interprofessional collaboration and team effectiveness within the general practice team after employing pharmacists in general practices in the Australian Capital Territory (ACT) and (ii) to compare interprofessional collaboration and team effectiveness of pharmacists in general practice across Australia with international sites. The first objective will be addressed through a multiphase sequential explanatory mixed-method design, using surveys and semi-structured interviews. The study will recruit general practice pharmacists, general practitioners, and other health professionals from eight general practices in the ACT. Quantitative and qualitative results will be merged during interpretation to provide complementary perspectives of interprofessional collaboration. Secondly, a quantitative descriptive design will compare findings on interprofessional collaboration (professional interactions, relationship initiation, exchange characteristics, and commitment to collaboration) and team effectiveness of general practice pharmacists in Australia with international sites from Canada and the United Kingdom. The results of the study will be used to provide recommendations on how to best implement the role of general practice pharmacists across Australia.


Articulatory-to-acoustic relations in response to speaking rate and loudness manipulations.
In this investigation, the authors determined the strength of association between tongue kinematic and speech acoustics changes in response to speaking rate and loudness manipulations. Performance changes in the kinematic and acoustic domains were measured using two aspects of speech production presumably affecting speech clarity: phonetic specification and variability. Tongue movements for the vowels /ia/ were recorded in 10 healthy adults during habitual, fast, slow, and loud speech using three-dimensional electromagnetic articulography. To determine articulatory-to-acoustic relations for phonetic specification, the authors correlated changes in lingual displacement with changes in acoustic vowel distance. To determine articulatory-to-acoustic relations for phonetic variability, the authors correlated changes in lingual movement variability with changes in formant movement variability. A significant positive linear association was found for kinematic and acoustic specification but not for kinematic and acoustic variability. Several significant speaking task effects were also observed. Lingual displacement is a good predictor of acoustic vowel distance in healthy talkers. The weak association between kinematic and acoustic variability raises questions regarding the effects of articulatory variability on speech clarity and intelligibility, particularly in individuals with motor speech disorders.