Readiness to change drinking behavior in female college students.
Motivational interviewing (MI) therapies are effective in reducing high-risk drinking in college populations. Although research supports efficacy of MI prevention strategies in reducing alcohol use, there are little data examining readiness to change (RTC), the underlying theoretical model of MI interventions. The purpose of the present study was to explore RTC variability and drinking behavior and whether MI increases RTC in an intervention group compared with controls. Two-hundred eighty-five first-year female college students participated in the study. Present analyses focused on those students who consumed alcohol in the month before the study (n = 182). RTC was measured using the Readiness to Change Ruler. Analyses were conducted using hierarchical linear modeling. There was significant variability in RTC: 71.86% of variance in RTC was between-person differences, and 28.14% was within-person differences. Higher RTC was associated with lower intentions to drink and future drinking behavior. However, in weeks in which students drank more, they experienced a decrease in RTC. Based on the significant cross-level interaction, the intervention group had significantly higher RTC than controls. These results provided partial support for our hypotheses. The overall theoretical construct of RTC varies both across and within individuals. These results also offer support for the utility of MI-based prevention strategies in increasing RTC within individuals. However, we did not consistently find that these changes related to drinking changes. Findings provide support for both the construct of RTC and utility of MI interventions in changing these beliefs in female college students.


Perspectives of family members participating in cultural assessment of psychiatric disorders: findings from the DSM-5 International Field Trial.
Despite the important roles families play in the lives of many individuals with mental illness across cultures, there is a dearth of data worldwide on how family members perceive the process of cultural assessment as well as to how to best include them. This study addresses this gap in our knowledge through analysis of data collected across six countries as part of a DSM-5 Field Trial of the Cultural Formulation Interview (CFI). At clinician discretion, individuals who accompanied patients to the clinic visit (i.e. patient companions) at the time the CFI was conducted were invited to participate in the cultural assessment and answer questions about their experience. The specific aims of this paper are (1) to describe patterns of participation of patient companions in the CFI across the six countries, and (2) to examine the comparative feasibility, acceptability, and clinical utility of the CFI from companion perspectives through analysis of both quantitative and qualitative data. Among the 321 patient interviews, only 86 (at four of 12 sites) included companions, all of whom were family members or other relatives. The utility, feasibility and acceptability of the CFI were rated favourably by relatives, supported by qualitative analyses of debriefing interviews. Cross-site differences in frequency of accompaniment merit further study.


Amateur boxing: physical and physiological attributes.
Boxing is one of the oldest combat sports. The aim of the current review is to critically analyze the amateur boxer's physical and physiological characteristics and to provide practical recommendations for training as well as new areas of scientific research. High-level male and female boxers show a propensity for low body fat levels. Although studies on boxer somatotypes are limited, the available information shows that elite-level male boxers are characterized by a higher proportion of mesomorphy with a well-developed muscle mass and a low body fat level. To help support the overall metabolic demands of a boxing match and to accelerate the recovery process between rounds, athletes of both sexes require a high level of cardiorespiratory fitness. International boxers show a high peak and mean anaerobic power output. Muscle strength in both the upper and lower limbs is paramount for a fighter's victory and is one of the keys to success in boxing. As boxing punches are brief actions and very dynamic, high-level boxing performance requires well-developed muscle power in both the upper and lower limbs. Albeit limited, the available studies reveal that isometric strength is linked to high-level boxing performance. Future investigations into the physical and physiological attributes of boxers are required to enrich the current data set and to help create a suitable training program.


Hepatic disposition of the acyl glucuronide1-O-gemfibrozil-beta-D-glucuronide: effects of dibromosulfophthalein on membrane transport and aglycone formation.
The liver plays an important role in the disposition of acyl glucuronides by determining their extent of formation, biliary excretion, and efflux into blood. Thus, both intrahepatic and extrahepatic exposure to these reactive polar conjugates depends on the efficiency of hepatic transport mechanisms, which may be shared with other nonbile acid organic anions. Using the isolated perfused rat liver preparation, the hepatic disposition of the acyl glucuronide, 1-O-gemfibrozil-beta-D-glucuronide, was examined in the presence of the organic anion dibromosulfophthalein (DBSP). Using a recirculating system, livers were perfused for 90 min with an erythrocyte-free perfusion medium containing 1% (w/v) albumin and 1-O-gemfibrozil-beta-D-glucuronide (3 microM) alone (n = 6) or with DBSP (200 microM, n = 7). The glucuronide was avidly taken up by the liver, excreted into bile, and hydrolyzed within the liver to its aglycone, gemfibrozil. DBSP significantly (P <.05) lowered the conjugate's mean hepatic clearance (8.98-5.17 ml/min), intrinsic clearance (44.0-17.7 ml/min), and fraction eliminated in bile (72. 8-48.7% of the dose), while increasing perfusate gemfibrozil concentrations (0.52-0.92 microM at 90 min). Furthermore, DBSP significantly (P <.05) lowered the ratio of intrahepatic to unbound perfusate concentrations of 1-O-gemfibrozil-beta-D-glucuronide (139. 0-35.0) and showed a trend to lower the ratio of bile to intrahepatic concentrations (111.3-76.2, P =.05). Thus, the study demonstrated that DBSP inhibited both the sinusoidal uptake and canalicular transport of 1-O-gemfibrozil-beta-D-glucuronide, suggesting that the hepatic membrane transport of acyl glucuronides is carrier mediated and shared with other organic anions.


STUB1 polyadenylation signal variant AACAAA does not affect polyadenylation but decreases STUB1 translation causing SCAR16.
We present three siblings afflicted with a disease characterized by cerebellar ataxia, cerebellar atrophy, pyramidal tract damage with increased lower limb tendon reflexes, and onset of 31 to 57 years, which is not typical for a known disease. In a region of shared homozygosity in patients, exome sequencing revealed novel homozygous c.*240T > C variant in the 3'UTR of STUB1, the gene responsible for autosomal recessive spinocerebellar ataxia 16 (SCAR16). In other genes, such an alteration of the evolutionarily highly conserved polyadenylation signal from AATAAA to AACAAA is known to highly impair polyadenylation. In contrast, RNA sequencing and quantification revealed that neither polyadenylation nor stability of STUB1 mRNA is affected. In silico analysis predicted that the secondary structure of the mRNA is altered. We propose that this change underlies the extremely low amounts of the encoded protein in patient leukocytes.


An outcome audit of the treatment of acute dentoalveolar infection: impact of penicillin resistance.
The aim of this audit was to measure the outcome of treatment of acute dentoalveolar infection and to determine if this was influenced by choice of antibiotic therapy or the presence of penicillin-resistance. A total of 112 patients with dentoalveolar infection were included in the audit. All patients underwent drainage, either incisional (n=105) or opening of the pulp chamber (n=7) supplemented with antibiotic therapy. A pus specimen was obtained from each patient for culture and susceptibility. Clinical signs and symptoms were recorded at the time of first presentation and re-evaluated after 48 or 72 h. A total of 104 (99%) of the patients who underwent incisional drainage exhibited improvement after 72 h. Signs and symptoms also improved in five of the seven patients who underwent drainage by opening of the root canal although the degree of improvement was less than that achieved by incisional drainage. Penicillin-resistant bacteria were found in 42 (38%) of the 112 patients in this study. Of the 65 patients who were given penicillin, 28 had penicillin-resistant bacteria. There was no statistical difference in the clinical outcome with regard to the antibiotic prescribed and the presence of penicillin-resistant bacteria. Strains of penicillin-resistant bacteria were isolated more frequently in patients who had previously received penicillin (p<0.05). Incisional drainage appeared to produce a more rapid improvement compared to drainage by opening of the root canal. The presence of penicillin-resistant bacteria did not adversely affect the outcome of treatment. The observations made support surgical drainage as the first principle of management and question the value of prescribing penicillin as part of treatment.


Premarital Screening and Genetic Counseling Program: Studies from an Endogamous Population.
Studies in Arab countries have shown a significant lack of knowledge of Premarital Screening and Genetic Counseling (PMSGC) Program. PMSGC can identify and modify, through prevention and management, some behavioral, medical, and other health risk factors known to impact pregnancy outcomes. The aim of this study was to explore the knowledge, attitudes, and practice of Qatari's toward the premarital screening program and shedding more light on a complex matter. A cross-sectional study based on Hospitals and Primary Health Care Centers. A total sample of 1246 participants was surveyed, and 873 participants (70.0%) expressed their consent to participate in the study during January 2013-May 2014. The questionnaire based on sociodemographic data and for responses, on the PMSGC program knowledge, attitude, and practice statements. In addition, questions were asked regarding the services, activities, and how to attract and motivate the PMSGC program. The mean age and standard deviation (SD) of the males' age were 30.4 ± 6.50 and the mean and SD of females' age were 31.08 ± 5.98. There were statistically significant differences between males and females with regard to age, educational status, occupation status, household income, consanguinity, body mass index, cigarette smoking, and Shisha smoking. There were no any statistically significant differences between males and females regarding sickle cell anemia and thalassemia, glucose-6-phosphate dehydrogenase deficiency cystic fibrosis, homocystinuria, HIV, and hepatitis. The response to the ''Why proceeding through high-risk marriage?'' by gender, males and females responded statistically significant differences (P = 0.019). The step-wise multivariate regression analyses as predictors for knowledge of PMSGC program revealed that age, educational level, the lack knowledge of genetics counseling, parental interventions for cousin marriage decision, positive test results affect and change marriage decision, religious impact, household income, consanguinity, hereditary diseases knowledge, occupational status, and love factors were considered as the main factors associated with the premarriage screening and genetics counseling after adjusting for age, gender, and other variables. The current study revealed that knowledge and attitude regarding PMSGC program were low in population. Motivation, enforcement, and implementation of program at the school and university educational campaigns are vital. Improved counseling and adding new topics for counseling on genetic, chronic, and mental illness; building healthy families; and reproduction and fertility are considered to be top priorities in community.


Do students learn to be more conscientious at medical school?
Professionalism in medical students is not only difficult to define but difficult to teach and measure. As negative behaviour in medical students is associated with post-graduate disciplinary action it would be useful to have a model whereby unprofessional behaviour at the undergraduate level can easily be identified to permit appropriate intervention. We have previously developed a scalar measure of conscientiousness, the Conscientiousness Index (CI), which positively correlates to estimates of professional behaviour in undergraduate medical students. By comparing CI points awarded in year 1 and year 2 of study we were able to use the CI model to determine whether teaching and clinical exposure had any effect on students' conscientiousness. CI points were collected by administrative staff from 3 successive cohorts of students in years 1 and 2 of study. Points were awarded to students for activities such as submission of immunisation status and criminal record checks, submission of summative assignments by a specified date and attendance at compulsory teaching sessions. CI points were then converted to a percentage of maximal possible scores (CI %) to permit direct comparison between years 1 and 2 of study. CI % scores were generally high with each year of study for each cohort showing negatively skewed normal distributions with peaks > 89%. There was a high degree of correlation of CI % scores between year 1 and year 2 of study for each cohort alone and when cohort data was combined. When the change in CI % from year 1 to year 2 for all students was compared there was no significant difference in conscientiousness observed. We have provided evidence that use of a CI model in undergraduate medical students provides a reliable measure of conscientiousness that is easy to implement. Importantly this study shows that measurement of conscientiousness by the CI model in medical students does not change between years 1 and 2 study suggesting that it is a stable characteristic and not modified by teaching and clinical exposure.


Leaf-level water use efficiency determined by carbon isotope discrimination in rice seedlings: genetic variation associated with population structure and QTL mapping.
Increasing the water use efficiency (WUE) of our major crop species is an important target of agricultural research. Rice is a major water consumer in agriculture and it is also an attractive genetic model. We evaluated leaf-level WUE in young rice seedlings using carbon isotope discrimination (Delta(13)C) as an indicator of the trait. A survey of Delta(13)C was undertaken in 116 diverse germplasm accessions representing O. sativa, O. glaberrima and four wild Oryza species. O. sativa cultivars were classified into sub-populations based on SSR markers, and significant differences in Delta(13)C were observed among the five genetically defined groups. While individual accessions explained a greater proportion of the variation than did sub-population, indica rice varieties had the lowest Delta(13)C values overall, indicating superior WUE, while temperate japonica had the highest Delta(13)C. O sativa accessions had a similar or greater range of Delta(13)C values than wild Oryza species, while domesticated O. glaberrima had a narrower range. Correlation analysis identified leaf morphological and physiological traits that were significantly associated with Delta(13)C, including longer leaves, more drooping leaves, higher tillering ability, and lower leaf nitrogen content. These trait associations were investigated by quantitative trait locus (QTL) mapping using backcross inbred lines derived from a cross between Nipponbare (temperate japonica) and Kasalath (aus). Seven QTL for Delta(13)C were identified using composite interval analysis, located in five chromosomal regions. The QTL with the largest additive effect came from Kasalath and co-localized with QTL for leaf length, tiller number and nitrogen content.


[18FDG-PET and large vessel vasculitis: preliminary data on 25 patients].
To evaluate the predictive value of clinical and biochemical features when compared to 18FDG-PET in the diagnostic work-up of large vessel vasculitis (LVV). Twenty-five patients underwent 18FDG-PET for the clinical suspect of LVV. All of them presented history of systemic symptoms lasting >or=6 months and laboratoristic evidence of persistently high markers of inflammation. The patients were stratified according with: i) clinical manifestations, defined as presence of one or more ACR criteria for the classification of LVV; ii) laboratory investigations: Erythrocyte Sedimentation Rate (ESR) higher or lower than 50 mm/h, C-Reactive Protein (CRP) higher or lower than 2 mg/dl; iii) prednisone dose in the 4 weeks preceding PET examination. The total number of positive PET was higher in the group without clinical ACR criteria and in the group with inflammation markers under the established cut-off. The number of scans consistent with LVV was higher in the groups presenting one or more clinical criteria for LVV but in those with very high ESR and CRP. In all the cases differences between groups were not statistically significative. A clear cut negative correlation between steroid dose and number of scans suggestive for LVV has been observed. Diagnosis of LVV remains challenging, especially in patients presenting with a constellation of non-specific symptoms and laboratory findings. In this study, both clinical and biochemical features show low correlation with a vasculitic pattern of FDG uptake. In our experience 18FDG-PET represents an useful diagnostic tool in early stages of LVV and a powerful instrument to follow the treatment responses.


Meal-based intake assessment tool: relative validity when determining dietary intake of Fe and Zn and selected absorption modifiers in UK men.
A computer-based dietary assessment tool, the meal-based intake assessment tool (MBIAT), is described. In the current study, dietary intakes of Fe and Zn fractions (total Fe, non-haem Fe, haem Fe, meat Fe, total Zn) and dietary components that influence Fe and Zn absorption (vitamin C, phytate, Ca, grams of meat/fish/poultry, black tea equivalents, phytate:Zn molar ratio) were assessed. The relative validity of the MBIAT was determined in forty-eight UK men aged 40 years and over by comparing its results with those from weighed diet records collected over 12 d. There was good agreement between the MBIAT and the weighed diet records for median intakes of total, non-haem, haem and meat Fe, Zn, vitamin C, phytate, grams of meat/fish/poultry and phytate:Zn molar ratio. Correlations between the two methods ranged from 0.32 (for Ca) to 0.80 (for haem Fe), with 0.76 for total Fe and 0.75 for Zn. The percentage of participants classified by the MBIAT into the same/opposite weighed diet record quartiles ranged from 56/0 for Fe and 60/0 for Zn to 33/10 for Ca. The questionnaire also showed an acceptable level of agreement between repeat administrations (e.g. a correlation for total Fe of 0.74). In conclusion, the MBIAT is appropriate for assessing group dietary intakes of total Fe and Zn and their absorption modifiers in UK men aged 40 years and over.


An Unexpected Species Determined by X-ray Crystallography that May Represent an Intermediate in the Reaction Catalyzed by Quinolinate Synthase.
Quinolinic acid is a common intermediate in the biosynthesis of nicotinamide adenine dinucleotide and its derivatives in all organisms that synthesize the molecule de novo. In most prokaryotes, it is formed from the condensation of dihydroxyacetone phosphate (DHAP) and iminoaspartate (IA) by the action of quinolinate synthase (NadA). NadA contains a [4Fe-4S] cluster cofactor with a unique noncysteinyl-ligated iron ion (Fea), which is proposed to bind the hydroxyl group of an intermediate in its reaction to facilitate a dehydration step. However, direct evidence for this role in catalysis has yet to be provided, and the exact chemical mechanism that underlies this transformation remains elusive. Herein, we present a structure of NadA from Pyrococcus horikoshii (PhNadA) in complex with IA and show that a carboxylate group of the molecule is ligated to Fea of the iron-sulfur cluster, occupying the site to which DHAP has been proposed to bind during catalysis. When crystals of PhNadA in complex with IA are soaked briefly in DHAP before freezing, electron density for a new molecule is observed, which we suggest is related to an intermediate in the reaction. Similar, but slightly different, "intermediates" are observed when crystals of a PhNadA Glu198Gln variant are incubated with DHAP, oxaloacetate, and ammonium chloride, conditions under which IA is formed chemically. Continuous-wave and pulse electron paramagnetic resonance techniques are used to verify the binding mode of substrates and proposed intermediates in frozen solution.


Diaphragm rescue alone prevents heart dysfunction in dystrophic mice.
Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused, in most cases, by the complete absence of the 427 kDa cytoskeletal protein, dystrophin. There is no effective treatment, and affected individuals die from respiratory failure and cardiomyopathy by age 30. Here, we investigated whether cardiomyopathy could be prevented in animal models of DMD by increasing diaphragm utrophin or dystrophin expression and thereby restoring diaphragm function. In a transgenic mdx mouse, where utrophin was over expressed in the skeletal muscle and the diaphragm, but not in the heart, we found cardiac function, specifically right and left ventricular ejection fraction as measured using in vivo magnetic resonance imaging, was restored to wild-type levels. In mdx mice treated with a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) that resulted in high levels of dystrophin restoration in the skeletal muscle and the diaphragm only, cardiac function was also restored to wild-type levels. In dystrophin/utrophin-deficient double-knockout (dKO) mice, a more severely affected animal model of DMD, treatment with a PPMO again produced high levels of dystrophin only in the skeletal muscle and the diaphragm, and once more restored cardiac function to wild-type levels. In the dKO mouse, there was no difference in heart function between treatment of the diaphragm plus the heart and treatment of the diaphragm alone. Restoration of diaphragm and other respiratory muscle function, irrespective of the method used, was sufficient to prevent cardiomyopathy in dystrophic mice. This novel mechanism of treating respiratory muscles to prevent cardiomyopathy in dystrophic mice warrants further investigation for its implications on the need to directly treat the heart in DMD.


Examining 3-month test-retest reliability and reliable change using the Cambridge Neuropsychological Test Automated Battery.
The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a battery of computerized neuropsychological tests commonly used in Europe in neurology and psychiatry studies, including clinical trials. The purpose of this study was to investigate test-retest reliability and to develop reliable change indices and regression-based change formulas for using the CANTAB in research and practice involving repeated measurement. A sample of 75 healthy adults completed nine CANTAB tests, assessing three domains (i.e., visual learning and memory, executive function, and visual attention) twice over a 3-month period. Wilcoxon signed-rank tests showed significant practice effects for 6 of 14 outcome measures with effect sizes ranging from negligible to medium (Hedge's g: .15-.40; Cliff's delta: .09-.39). The Spatial Working Memory test, Attention Switching Task, and Rapid Visual Processing test were the only tests with scores of adequate test-retest reliability. For all outcome measures, Pearson's and Spearman's correlation coefficients ranged from .39 to .79. The measurement error surrounding difference scores was large, thus requiring large changes in performance (i.e., 1-2 SDs) in order to interpret a change score as reliable. In the regression equations, test scores from initial testing significantly predicted retest scores for all outcome measures. Age was a significant predictor in several of the equations, while education was a significant predictor in only two of the equations. The adjusted R2 values ranged between .19 and .67. The present study provides results enabling clinicians to make probabilistic statements about change in cognitive functions based on CANTAB test performances.


Dopamine D1 and D2 receptor immunoreactivities in the arcuate-median eminence complex and their link to the tubero-infundibular dopamine neurons.
Dopamine D1 and D2 receptor immunohistochemistry and Golgi techniques were used to study the structure of the adult rat arcuate-median eminence complex, and determine the distribution of the dopamine D1 and D2 receptor immunoreactivities therein, particularly in relation to the tubero-infundibular dopamine neurons. Punctate dopamine D1 and D2 receptor immunoreactivities, likely located on nerve terminals, were enriched in the lateral palisade zone built up of nerve terminals, while the densities were low to modest in the medial palisade zone. A codistribution of dopamine D1 receptor or dopamine D2 receptor immunoreactive puncta with tyrosine hydroxylase immunoreactive nerve terminals was demonstrated in the external layer. Dopamine D1 receptor but not dopamine D2 receptor immnunoreactivites nerve cell bodies were found in the ventromedial part of the arcuate nucleus and in the lateral part of the internal layer of the median eminence forming a continuous cell mass presumably representing neuropeptide Y immunoreactive nerve cell bodies. The major arcuate dopamine/ tyrosine hydroxylase nerve cell group was found in the dorsomedial part. A large number of tyrosine hydroxylase immunoreactive nerve cell bodies in this region demonstrated punctate dopamine D1 receptor immunoreactivity but only a few presented dopamine D2 receptor immunoreactivity which were mainly found in a substantial number of tyrosine hydroxylase cell bodies of the ventral periventricular hypothalamic nucleus, also belonging to the tubero-infundibular dopamine neurons. Structural evidence for projections of the arcuate nerve cells into the median eminence was also obtained. Distal axons formed horizontal axons in the internal layer issuing a variable number of collaterals classified into single or multiple strands located in the external layer increasing our understanding of the dopamine nerve terminal networks in this region. Dopamine D1 and D2 receptors may therefore directly and differentially modulate the activity and /or Dopamine synthesis of substantial numbers of tubero-infundibular dopamine neurons at the somatic and terminal level. The immunohistochemical work also gives support to the view that dopamine D1 receptors and/or dopamine D2 receptors in the lateral palisade zone by mediating dopamine volume transmission may contribute to the inhibition of luteinizing hormone releasing hormone release from nerve terminals in this region.


Laboratory animal science in China: current status and potential for adoption of Three R alternatives.
This paper aims to describe the development of laboratory animal science in China on the basis of historical evidence and recent national survey data, and to identify the problems facing the adoption of Three R alternatives. The authors undertook a national survey in 2006, by means of a questionnaire sent to 31 provinces, municipalities and autonomous regions, and also compared data from a variety of sources, including several national surveys and published papers. Laboratory animal science in China has developed rapidly over the past 30 years, as a result of a combination of economic, governmental and societal forces. More than 100,000 people work in the field of laboratory animal science, in 2,000 laboratory animal centres, institutes, universities, organisations, and companies. During the year of our survey, more than 19 million laboratory animals were produced from 320 licensed production facilities. Approximately 16 million laboratory animals were used in animal experiments, in 1530 facilities licensed for their use. The scale of the market for the supply and use of laboratory animals is huge, and thus it is very important to improve the level of adoption of these alternatives, in education, research and testing. For China, this presents a significant economic and technological opportunity in the field of biosciences research. The concept of the Three Rs first appeared in China in the 1980s, when the scale of laboratory animal sciences was starting to increase. In the 1990s, the Three Rs concept became commonly accepted among laboratory animal scientists, and began to appear in government documents. In the first decade of the 21st century, the Three Rs principles have become increasingly applied in our day-to-day work. But further time is still needed to achieve the full application of the Three Rs principles, especially the adoption of Three R alternatives. This paper describes the achievements in China relating to laboratory animal science, the use of Three R alternatives, and animal welfare, and shows that there is currently great potential for the adoption of alternatives. The information will help scientists and organisations around the world to gain better insight into the current state of laboratory animal science in China, and hopefully, will enable them to give advice on how we can improve the adoption of Three R alternatives in our country.


Egg consumption and carotid atherosclerosis in the Northern Manhattan study.
The evidence supporting recommendations to limit intake of cholesterol rich foods is inconclusive. We aimed to examine the association between egg consumption and carotid atherosclerosis phenotypes, and the association with clinical vascular events in a prospective, urban, multi-ethnic population. The Northern Manhattan Study is a population based cohort to determine stroke incidence, risk factors and prognosis. A sub-cohort of 1429 NOMAS participants with both carotid ultrasounds and comprehensive dietary information was evaluated (mean ± SD age of participants 65.80 ± 8.80, 40% male, 18% white, 20% black, 60% Hispanic). The association between egg consumption and carotid intima media thickness (cIMT) was assessed with linear regression. Logistic and quantile regression was used to examine the association between egg consumption and carotid plaque presence, thickness, and area. The relation between egg consumption and clinical vascular events (N = 2669) was examined with Cox models. The mean total cIMT was 0.91 ± 0.08 mm and 58% had carotid plaque present. Increasing egg consumption was inversely associated with cIMT, plaque presence, thickness, and area, in models adjusted for demographics, vascular risk factors and diet. For every additional egg consumed per week, the risk of plaque decreased by 11% (95% CI 3%-18%). No association was detected between egg consumption and risk of clinical vascular outcomes, over a mean follow up of 11 years and after adjustment for covariates. Frequency of egg consumption in the low to moderate range was inversely related to several markers of carotid atherosclerosis. No association with clinical vascular events, including stroke, was detected. Our findings do not support current vascular health guidelines suggesting the extreme limitation or avoidance of egg consumption due to its cholesterol content.


Regulation of the alginate biosynthesis gene algC in Pseudomonas aeruginosa during biofilm development in continuous culture.
Reporter gene technology was used to observe the regulation of the alginate biosynthesis gene, algC in a mucoid strain of Pseudomonas aeruginosa in developing and mature biofilms in continuous culture on Teflon and glass substrata. The plasmid pNZ63, carrying an algC-lacZ transcriptional fusion, was shown to not be diluted in continuous culture over a period of 25 days in the absence of selection pressure. Biofilm cells under bulk phase steady-state conditions demonstrated fluctuations in algC expression over a 16-day period, but no trend of increased or decreased expression over the time interval was indicated. In vivo detection of algC up-expression in developing biofilms was performed with a fluorogenic substrate for the plasmid-borne lacZ gene product (beta-galactosidase) by using microscopy coupled with image analysis. By this technique, cells were tracked over time and analyzed for algC activity. During the initial stages of biofilm development, cells already attached to a glass surface for at least 15 min exhibited up-expression of algC, detectable as the development of whole-cell fluorescence. However, initial cell attachment to the substratum appeared to be independent of algC promoter activity. Furthermore, cells not exhibiting algC up-expression were shown to be less capable of remaining at a glass surface under flowing conditions than were cells in which algC up-expression was detected.


Adaptive waveguide bends with homogeneous, nonmagnetic, and isotropic materials.
We propose a method for adaptive waveguide bends using homogeneous, nonmagnetic, and isotropic materials, which simplifies the parameters of the bends to the utmost extent. The proposed bend has an adaptive and compact shape because of all the flat boundaries. The nonmagnetic property is realized by selecting OB'/OC = 0.5. Only two nonmagnetic isotropic dielectrics are needed throughout, and the transmission is not sensitive to nonmagnetic isotropic dielectrics. Results validate and illustrate these functionalities, which make the bend much easier to fabricate and apply, owing to its simple parameters, compact shape, and versatility in connecting different waveguides.


Spirulina platensis protects against gentamicin-induced nephrotoxicity in rats.
The present study aimed to investigate the protective effect of Spirulina platensis (SP) on gentamicin sulphate (GS)-induced changes in the levels of lipid peroxidation and endogenous antioxidants in the kidney of rats. Sprague-Dawley rats were treated in separate groups as follows for 7 consecutive days: control (C), gentamicin sulphate (100 mg/kg i.p.) (GS), Spirulina platensis (1000 mg/kg orally) (SP) and Spirulina platensis (1000 mg/kg orally) plus gentamicin sulphate (100 mg/kg i.p.) (SP + GS). The degree of protection was evaluated by determining the effects of Spirulina platensis on malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPX) and nitric oxide (NO), and plasma creatinine and urea levels were estimated in kidney homogenates to evaluate antioxidant activity, and the kidney was histologically examined as well. Spirulina platensis elicited significant nephroprotective activity by decreasing lipid peroxidation (MDA) and elevated the levels of GSH, SOD, GPX, NO, creatinine and urea. Furthermore, these biochemical observations were supplemented by histological examination of the rat kidneys. In conclusion, the present study indicates a very important role of reactive oxygen species (ROS) and the relation to renal dysfunction and point to the therapeutic potential of Spirulina platensis in gentamicin sulphate induced nephrotoxicity.


Botulinum toxin for writer's cramp: a randomised, placebo-controlled trial and 1-year follow-up.
Botulinum toxin type A (BoNT-A) has become the treatment of choice for most types of focal dystonia. To investigate the efficacy of BoNT-A injections in patients with writer's cramp in a double-blind, randomised, placebo-controlled trial and to evaluate the follow-up results. Forty participants were randomised to treatment with either BoNT-A or placebo injections in two sessions. Trial duration was 12 weeks. The primary outcome measure was the patients' choice to continue with the treatment, despite its possible disadvantages. Secondary outcome measures included several clinical rating scales on the levels of impairment and disability. Assessments were made at baseline and 2 months (secondary outcomes) and 3 months (primary outcome). Duration of follow-up was 1 year. 39 patients completed the trial. Fourteen of 20 patients (70%) receiving BoNT-A reported a beneficial effect and chose to continue treatment, versus 6 of 19 patients (31.6%) in the placebo group (p = 0.03). The changes on most of the clinical rating scales were significantly in favour of BoNT-A. Side effects reported were hand weakness, which was mostly mild and always transient, and pain at the injection site. After 1 year, 20 of 39 patients were still under treatment with a positive effect. Treatment with BoNT-A injections led to a significantly greater improvement compared with placebo, according to patients' opinion and clinical assessment scales. Weakness in the hand is an important side effect of BoNT-A injections, but despite this disadvantage, most patients preferred to continue treatment. About 50% of our patients were still under treatment after 1 year.


A novel technique to initiate and investigate scroll waves in thin layers of the photosensitive Belousov-Zhabotinsky reaction.
While free scroll rings are non-stationary objects that either grow or contract with time, spatial confinement can have a large impact on their evolution reaching from significant lifetime extension (J.F. Totz, H. Engel, O. Steinbock, New J. Phys. 17, 093043 (2015)) up to formation of stable stationary and breathing pacemakers (A. Azhand, J.F. Totz, H. Engel, EPL 108, 10004 (2014)). Here, we explore the parameter range in which the interaction between an axis-symmetric scroll ring and a confining planar no-flux boundary can be studied experimentally in transparent gel layers supporting chemical wave propagation in the photosensitive variant of the Belousov-Zhabotinsky medium. Based on full three-dimensional simulations of the underlying modified complete Oregonator model for experimentally realistic parameters, we determine the conditions for successful initiation of scroll rings in a phase diagram spanned by the layer thickness and the applied light intensity. Furthermore, we discuss whether the illumination-induced excitability gradient due to Lambert-Beer's law as well as a possible inclination of the filament plane with respect to the no-flux boundary can destabilize the scroll ring.


Pituitary responsiveness to gonadotrophin-releasing and thyrotrophin-releasing hormones in children receiving phenobarbitone.
The effect of long-term treatment with phenobarbitone on pituitary responsiveness to gonadotrophin-releasing hormone and thyrotrophin-releasing hormone was studied in 20 boys being treated with the drug to prevent febrile convulsions. Baseline concentrations of luteinising and follicle-stimulating hormones were reduced as well as the responses of these hormones to stimulation with gonadotrophin-releasing hormone. Baseline prolactin concentrations were raised in comparison with those in normal children. The response of prolactin to thyrotrophin-releasing hormone, however, was impaired only in the children who had been receiving the drug for a long time. Phenobarbitone had no effect on the secretion of growth hormone. Further studies should be carried out to ascertain how long these effects on pituitary function last after phenobarbitone is withdrawn and whether this interference with pituitary function modifies the child's subsequent development.


Functionalized silica nanoparticles: a platform for fluorescence imaging at the cell and small animal levels.
Going in vivo, including living cells and the whole body, is very important for gaining a better understanding of the mystery of life and requires specialized imaging techniques. The diversity, composition, and temporal-spatial variation of life activities from cells to the whole body require the analysis techniques to be fast-response, noninvasive, highly sensitive, and stable, in situ and in real-time. Functionalized nanoparticle-based fluorescence imaging techniques have the potential to meet such needs through real-time and noninvasive visualization of biological events in vivo. Functionalized silica nanoparticles (SiNPs) doped with fluorescent dyes appear to be an ideal and flexible platform for developing fluorescence imaging techniques used in living cells and the whole body. We can select and incorporate different dyes inside the silica matrix either noncovalently or covalently. These form the functionalized hybrid SiNPs, which support multiplex labeling and ratiometric sensing in living systems. Since the silica matrix protects dyes from outside quenching and degrading factors, this enhances the photostability and biocompatibility of the SiNP-based probes. This makes them ideal for real-time and long-time tracking. One nanoparticle can encapsulate large numbers of dye molecules, which amplifies their optical signal and temporal-spatial resolution response. Integrating fluorescent dye-doped SiNPs with targeting ligands using various surface modification techniques can greatly improve selective recognition. Along with the endocytosis, functionalized SiNPs can be efficiently internalized into cells for noninvasive localization, assessment, and monitoring. These unique characteristics of functionalized SiNPs substantially support their applications in fluorescence imaging in vivo. In this Account, we summarize our efforts to develop functionalized dye-doped SiNPs for fluorescence imaging at the cell and small animal levels. We first discuss how to design and construct various functionalized dye-doped SiNPs. Then we describe their properties and imaging applications in cell surface receptor recognition, intracellular labeling, tracking, sensing, and controlled release. Additionally, we have demonstrated the promising application of dye-doped SiNPs as contrast imaging agents for in vivo fluorescence imaging in small animals. We expect these functionalized dye-doped SiNPs to open new opportunities for biological and medical research and applications.


Complement and hyper acute rejection.
Organ transplantation has been a major development in clinical medicine but its success has been marred by the immune system's capacity to respond to "non-self" cells and tissues. A full molecular understanding of this mechanism and the myriad triggers for immune rejection is yet to be elucidated. Consequently, immunosuppressive drugs remain the mainstay of post-transplant management; however, these interventions have side effects such as increased incidence of cancer, post-transplant lymphoproliferative disorders, susceptibility to infection if not managed appropriately and the inconvenience to the patient of lifelong treatment. Novel therapeutic approaches based on molecular understanding of immunological processes are thus needed in this field. The notion that factors influencing successful transplants might be of use as therapeutic approaches is both scientifically and medically appealing. Recent developments in the understanding of successful transplants are expected to provide new opportunities for safer transplantation. This article reviews the present understanding of the molecular basis of rejection and the role of complement in this process as well as the possibility of generating "intelligent" therapy that better target crucial components of hyper-acute rejections.


Measurement of renal perfusion and blood flow with fast computed tomography.
Fast computed tomography (CT) is one of the few methods available to measure cortical and medullary renal blood flow (RBF) directly. Because these measurements are complicated by passage of the contrast medium into extravascular compartments, we used the residual opacity following the vascular blush as an index to account for extravascular iohexol. Kidneys of anesthetized dogs were examined in situ by fast CT following intra-aortic injections of iohexol. Perfusion was analyzed during a control period and three subsequent periods in which RBF was reduced by 10%, 30%, and 50%. Cortical microvascular distribution volume changed from 19.7 +/- 2.8% to 19.8 +/- 1.7%, 15.3 +/- 1.2%, and 9.9 +/- 1.7%, respectively, without significant alterations in cortical mean transit time. Microvascular distribution volume was divided by mean transit time to determine tissue perfusion. Cortical perfusion changed from 3.8 +/- 0.7 to 3.9 +/- 0.6, 3.1 +/- 0.5, and 2.2 +/- 0.5 mL.min-1.mL tissue-1. Total cortical blood flow (cortical perfusion multiplied by cortical volume) decreased from 164 +/- 32 to 159 +/- 31, 117 +/- 20, and 86 +/- 22 mL/min, respectively. Medullary microvascular distribution volume, mean transit time, perfusion, and total blood flow remained unchanged. Fast CT-determined total RBFs (cortex plus medulla) were similar to simultaneous electromagnetic flow measurements. These results indicate that renal regional perfusion is more dependent on the microvascular distribution volume than mean transit time and that variations in renal tissue perfusion with reduction of RBF are more apparent in the cortex than in the medulla.


Therapeutic window of CA1 neuronal damage defined by an ultrashort-acting barbiturate after brain ischemia in gerbils.
Previous therapeutic studies on the prevention of selective vulnerability of neurons in the hippocampus have suggested that the critical period for induction of delayed neuronal injury occurs early during recirculation. To determine the onset and duration of this period, an ultrashort-acting barbiturate (methohexital) was infused into the left carotid artery of 47 gerbils after various times of recirculation following 10 minutes of bilateral forebrain ischemia. Neuronal density in the left CA1 sector was determined 7 days later by counting the number of surviving neurons per millimeter of pyramidal cell layer. In 16 saline-treated gerbils, less than 10% of the CA1 neurons survived the 10 minutes of ischemia. Postischemic carotid infusion of methohexital improved neuronal survival, the degree of improvement depending on the timing and duration of the methohexital infusion. When carried out during the initial 40 minutes of recirculation, methohexital infusion for 10 minutes increased the number of surviving neurons to approximately 60% of that in five sham-operated control gerbils. This increase was significant for infusions carried out between the 10th and 20th minutes (n = 6, p less than 0.05) and between the 30th and 40th minutes (n = 6, p less than 0.05) of recirculation. Methohexital infusion for 20 minutes increased neuronal survival to 95% and 73% of that in the controls when carried out between the 0th and 20th minutes (n = 5, p less than 0.005) and between the 20th and 40th minutes (n = 5, p less than 0.005) of recirculation, respectively. Protection was nonsignificant for 10- or 20-minute methohexital infusions carried out after the 40th minute of recirculation. Our results demonstrate that the pathologic processes leading to delayed neuronal injury in the CA1 sector are induced during the initial 40 minutes of recirculation and that barbiturates are able to reverse these processes only if given during this period.


Hair lead concentration in the Lebanese population: phase 1 results.
Phase 1 of this cross-sectional study aimed to compare hair lead concentrations and establish the determinants of hair lead levels in 149 occupationally exposed individuals versus 177 non-occupationally exposed controls in the Lebanese population. In addition to a standardized questionnaire, lead concentration was measured by atomic spectrophotometry. A 5-6-fold difference in hair lead concentration was found between occupationally exposed and non-exposed individuals (23.60 ppm versus 4.33 ppm). Professional exposure, particularly working in petrol refining and gasoline stations, had the highest correlation with lead exposure. In non-exposed individuals, male sex, non-Lebanese nationality and urban worksite correlated with higher hair lead concentration.


New steroidal aromatase inhibitors: suppression of estrogen-dependent breast cancer cell proliferation and induction of cell death.
Aromatase, the cytochrome P-450 enzyme (CYP19) responsible for estrogen biosynthesis, is an important target for the treatment of estrogen-dependent breast cancer. In fact, the use of synthetic aromatase inhibitors (AI), which induce suppression of estrogen synthesis, has shown to be an effective alternative to the classical tamoxifen for the treatment of postmenopausal patients with ER-positive breast cancer. New AIs obtained, in our laboratory, by modification of the A and D-rings of the natural substrate of aromatase, compounds 3a and 4a, showed previously to efficiently suppress aromatase activity in placental microsomes. In the present study we have investigated the effects of these compounds on cell proliferation, cell cycle progression and induction of cell death using the estrogen-dependent human breast cancer cell line stably transfected with the aromatase gene, MCF-7 aro cells. The new steroids inhibit hormone-dependent proliferation of MCF-7aro cells in a time and dose-dependent manner, causing cell cycle arrest in G0/G1 phase and inducing cell death with features of apoptosis and autophagic cell death. Our in vitro studies showed that the two steroidal AIs, 3a and 4a, are potent inhibitors of breast cancer cell proliferation. Moreover, it was also shown that the antiproliferative effects of these two steroids on MCF-7aro cells are mediated by disrupting cell cycle progression, through cell cycle arrest in G0/G1 phase and induction of cell death, being the dominant mechanism autophagic cell death. Our results are important for the elucidation of the cellular effects of steroidal AIs on breast cancer.


Following in the footsteps of smallpox: can we achieve the global eradication of measles?
BACKGROUND: Although an effective measles vaccine has been available for almost 40 years, in 2000 there were about 30 million measles infections worldwide and 777,000 measles-related deaths. The history of smallpox suggests that achieving measles eradication depends on several factors; the biological characteristics of the organism; vaccine technology; surveillance and laboratory identification; effective delivery of vaccination programmes and international commitment to eradication. DISCUSSION: Like smallpox, measles virus has several biological characteristics that favour eradication. Humans are the only reservoir for the virus, which causes a visible illness and infection leading to life-long immunity. As the measles virus has only one genetic serotype which is relatively stable over time, the same basic vaccine can be used world-wide. Vaccination provides protection against measles infection for at least 15 years, although efficacy may be reduced due to host factors such as nutritional status. Measles vaccination may also confer other non-specific health benefits leading to reduced mortality. Accurate laboratory identification of measles cases enables enhanced surveillance to support elimination programmes. The "catch-up, keep-up, follow-up" vaccination programme implemented in the Americas has shown that measles elimination is possible using existing technologies. On 17th October 2003 the "Cape Town Measles Declaration" by the World Health Organisation and the United Nations Childrens Fund called on governments to intensify efforts to reduce measles mortality by supporting universal vaccination coverage and the development of more effective vaccination. SUMMARY: Although more difficult than for smallpox, recent experience in the Americas suggests that measles eradication is technically feasible. Growing international support to deliver these programmes means that measles, like smallpox, may very well become a curiosity of history.


Host defense impairments that may lead to respiratory infections.
Host defense mechanisms spaced along the respiratory tree and in the alveolar spaces effectively remove or contend with micro-organisms that enter the airways, so serious lung infections occur rarely in healthy people. Special circumstances, such as virgin exposure to a virulent microbe or a large innoculum of a pathogen, can result in illness, but usually routine surveillance host defenses are protective and suffice to keep colonizing airway flora in check. When pneumonia develops or recurrent sinopulmonary infection exists, however, some element of the normal defense apparatus may have failed or is inadequate. This review highlights several components of the apparatus, that is immunoglobulins IgG and IgA and the interaction of alveolar macrophages and lymphocytes, and examines deficiencies in their function that may result in infection. Along the conducting airways, poor mucociliary clearance and/or deficiencies in certain IgG subclass antibodies or destruction of IgA may predispose to sinopulmonary infections; these may be a manifestation of a hereditary disease. In pneumonia the alveolar macrophage is positioned as the central cell which must respond in several directions. This scavenger phagocyte first intercepts the microbe and either can kill or contain it or must call in some other phagocytic cell or inflammatory mediator(s) for assistance. Opsonic antibodies (IgG) and other nonimmune opsonins (complement and surfactant or fibronectin fragments) facilitate phagocytosis, but an absence of antibody may permit infection to develop with encapsulated bacteria (pneumococcus). Insufficient bone marrow reserves of PMNs or a paucity of chemotactic factors to attract them into the alveoli is a situation that may permit gram-negative bacilli and fungal organisms to flourish. Inability of immune T-lymphocytes to energize macrophages, through soluble cellular mediators that provide cell-mediated immunity and activation, makes containment of certain intracellular microbes impossible for these phagocytes (Legionella or mycobacteria). Likewise, concomitant infection of macrophages with viruses (human immunodeficiency virus, and cytomegalovirus or herpes viruses) plus an excessive T-lymphocyte suppressor cell influence may make P. carinii and common bacterial and fungal organisms difficult to contain in the lungs of AIDS patients. Consideration about what the lung host deficiency might be can make therapy more specific through immunization to develop special antibodies, replacement of certain immunoglobulins (IgG subclasses), or selective administration of cell mediators (gamma-interferon or interleukins).


The invasive proteome of glioblastoma revealed by laser-capture microdissection.
Glioblastomas are heterogeneous tumors composed of a necrotic and tumor core and an invasive periphery. Here, we performed a proteomics analysis of laser-capture micro-dissected glioblastoma core and invasive areas of patient-derived xenografts. Bioinformatics analysis identified enriched proteins in central and invasive tumor areas. Novel markers of invasion were identified, the genes proteolipid protein 1 (PLP1) and Dynamin-1 (DNM1), which were subsequently validated in tumors and by functional assays. In summary, our results identify new networks and molecules that may play an important role in glioblastoma development and may constitute potential novel therapeutic targets.


Enhancing the antimicrobial and antibiofilm effectiveness of silver nanoparticles prepared by green synthesis.
The use of polyphenol-rich plant extracts is well established for the green synthesis of silver nanoparticles (AgNPs). However, the size of the AgNPs varies substantially depending on the extract used and many researchers report sizes above 20 nm, which are not optimal for antimicrobial activity. Herein, using catechin as a model polyphenol, we have explored two techniques to improve its stabilising capacity and therefore decrease the subsequent AgNP size: cross-linking catechin with sodium tetraborate (borax); and preparation of a water soluble oligomer from catechin (polycat). The prepared AgNPs from the three stabilising systems, cat@AgNPs, cat-borax@AgNPs and polycat@AgNPs, were characterised by UV-Vis spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS). Cat-borax produced smaller AgNPs (18.4 nm) than catechin (42.3 nm) but the smallest particles were prepared with polycat (8.5 nm). Antimicrobial efficacy was assessed against Gram positive and Gram negative bacteria and was compared with 10 nm sodium citrate capped AgNPs (citrate@AgNPs). Polycat@AgNPs showed superior antimicrobial activity to cat@AgNPs and cat-borax@AgNPs as well as citrate@AgNPs, exhibiting MICs of only 1.25 μg mL-1 (Ag) for Pseudomonas aeruginosa and Acinetobacter baumannii. Polycat@AgNPs also demonstrated substantially enhanced antibiofilm activity. An Ag concentration of only 5 μg mL-1, was sufficient for a 99.9% reduction in biofilm cell viability and a 99.1% reduction in biofilm biomass with polycat@AgNPs. Uptake of polycat@AgNPs by bacteria was determined to be significantly higher than for citrate@AgNPs and tomographic and SEM images showed evidence of destruction of bacteria cells by polycat@AgNPs.


Typological review of environmental performance metrics (with illustrative examples for oil spill response).
An intensification of interest in environmental assessment during the last 2 decades has driven corporate efforts to better document environmental goals, improve environmental management systems, and increase awareness of the environmental and ecological effects of business operations. This trend has been motivated partly by regulatory requirements (such as the Toxics Release Inventory in the United States) and partly by the inclination of some large manufacturing firms to embrace a broader social and environmental mission characterized as "sustainability" or "ecoefficiency." Moreover, the importance of measurable objectives in the US government has been recognized at least since the Government Performance Results Act of 1993, which was intended to both improve the efficiency of government and the confidence of the American public in government managers. However, in management of environmental crises - such as catastrophic oil or chemical spills - development of measurable performance standards has lagged. Consequently, government spill managers are unable to define success in terms that are easily communicated to public and other stakeholder groups, and they could be disadvantaged in their efforts to deploy response resources with maximum efficiency. In this paper, we present a typological review of environmental assessment measures and summarize some of the current practices and strategic goals among federal agencies with regard to oil and chemical spills. A general approach to organizing metrics for oil spill response, restoration, and recovery is also presented. The results could improve planning efforts and communication among different federal, state, and local agencies and public or stakeholder groups involved in spill management.


Extended-spectrum beta-lactamases in Taiwan: epidemiology, detection, treatment and infection control.
Extended-spectrum beta-lactamases (ESBLs) efficiently hydrolyze extended-spectrum beta-lactams such as cefotaxime, ceftriaxone, ceftazidime, and aztreonam. ESBLs are most often plasmid-mediated. In Taiwan, the prevalence of ESBLs in bacteria has risen, ranging from 8.5 to 29.8% in Klebsiella pneumoniae and 1.5 to 16.7% in Escherichia coli isolates. The most prevalent types of ESBLs are SHV-5, SHV-12, CTX-M-3, and CTX-M-14 in isolates of K. pneumoniae and E. coli, with differences between institutions. SHV-12 and CTX-M-3 have been reported as the most common ESBLs in isolates of Enterobacter cloacae and Serratia marcescens, respectively. Molecular epidemiology studies suggest that the ESBL-encoding genes have been disseminated either by proliferation of epidemic strains or by transfer of plasmids carrying the resistance traits. The current ESBL screen guidelines of the Clinical and Laboratory Standards Institute (formerly National Committee for Clinical Laboratory Standards) are issued for E. coli, Klebsiella spp., and Proteus mirabilis. Owing to the lack of standard methods, it remains difficult to assure the presence of ESBL in an isolate co-harboring an AmpC beta-lactamase, particularly in cases where the latter is produced in larger amounts than the former. Empirical therapy with piperacillin-tazobactam to replace third-generation cephalosporins may help to reduce the occurrence of ESBLs in an institution with a high prevalence of ESBL producers. Carbapenems remain the drugs of choice for serious infections caused by ESBL-producing organisms. To retard the selection for carbapenem-resistant bacteria, 7-alpha-methoxy beta-lactams or fourth-generation cephalosporins can be therapeutic alternatives for mild-to-moderate infections provided that the pharmacokinetic and pharmacodynamic target can be easily achieved.


Challenges in designing a national surveillance program for inflammatory bowel disease in the United States.
This review describes the history of U.S. government funding for surveillance programs in inflammatory bowel diseases (IBD), provides current estimates of the incidence and prevalence of IBD in the United States, and enumerates a number of challenges faced by current and future IBD surveillance programs. A rationale for expanding the focus of IBD surveillance beyond counts of incidence and prevalence, to provide a greater understanding of the burden of IBD, disease etiology, and pathogenesis, is provided. Lessons learned from other countries are summarized, in addition to potential resources that may be used to optimize a new form of IBD surveillance in the United States. A consensus recommendation on the goals and available resources for a new model for disease surveillance are provided. This new model should focus on "surveillance of the burden of disease," including (1) natural history of disease and (2) outcomes and complications of the disease and/or treatments.


Lewy bodies in progressive supranuclear palsy represent an independent disease process.
Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy characterized by Parkinsonism, vertical gaze palsy, and early falls. Lewy bodies (LBs) are detected in approximately 10% of PSP cases, but there is little information on the relationship of LBs to tau pathology. We determined the frequency of LBs in a large series of autopsy-confirmed cases of PSP and studied the density and distribution of LBs, including Parkinson disease stage, in cases with LBs (PSP/LBD). PSP/LBD was compared with pure LB disease (LBD), including assessment of neuronal loss in key brainstem nuclei. Immunohistochemistry for alpha-synuclein revealed LBs in 31 of 290 PSP cases (11%). One case had multiple system atrophy in addition to PSP and was excluded from further study along with 2 PSP/LBD cases with concurrent Alzheimer disease. The 29 cases of PSP/LBD were compared with 30 cases of PSP and 24 cases of LBD. The age, sex, brain weight, Braak neurofibrillary tangle (NFT) stage, as well as counts of NFTs and senile plaques were not different among PSP, LBD, and PSP/LBD, but disease duration was longer in LBD. The Parkinson disease stage was similar, but the density of LBs in most subcortical nuclei tended to be greater in LBD than in PSP/LBD. In contrast, substantia nigra neuronal loss was greater in PSP/LBD than both PSP and LBD. Double immunostaining demonstrated alpha-synuclein and tau in different neurons with few exceptions. The findings suggest that LBs in PSP are similar in distribution to those in LBD and independent of tau pathology. The greater density of LBs in LBD compared with PSP/LBD may be the result of longer disease duration in LBD, whereas greater neuronal loss in the substantia nigra in PSP/LBD may be the result of vulnerability of this brain region to both disease processes.


Primary replacement of the humeral head in iatrogenically displaced fracture-dislocations of the shoulder: a report about six cases.
Dislocation of the shoulder is a common injury and may be associated with a variety of complications. We report six cases of primary replacement of the humeral head where closed reduction of a shoulder dislocation associated with an undisplaced fracture of the humeral neck led to displacement of the neck fracture. All dislocations examined were anterior with a displaced greater tubercle fracture. The patients had undergone closed reduction at other medical centres and were referred to us because of iatrogenically displaced fracture-dislocations of the shoulder. Three were women and three were men with a mean age of 52.8 years (range 38-72). Primary replacement of the humeral head was done in an average of 9.3 days (range 2-30 days) following the injury. The average follow-up period was 30.2 months (range 12-55 months). Postoperative pain, active range of motion and function were evaluated with the American Shoulder and Elbow Surgeons Criteria. The forward flexion averaged 124 degrees, active external rotation averaged 29 degrees and internal rotation (achieved movement) to the second lumbar vertebra. Because of the high risk of avascular necrosis and severe collapse of the humeral head, we conclude that the primary replacement of the humeral head is the superior treatment option in iatrogenically displaced fracture dislocations of the shoulder.


Retroviral insertional mutagenesis of a herpesvirus: a Marek's disease virus mutant attenuated for oncogenicity but not for immunosuppression or in vivo replication.
Our earlier studies have shown that retrovirus insertion into herpesvirus is an efficient process that engenders recombinant herpesviruses with altered biological properties. The RM1 clone is derived from the JM strain of Marek's disease virus (MDV) through retrovirus insertional mutagenesis and contains sequences of reticuloendotheliosis virus inserted at the junction of the internal repeat and unique short regions of the genome. In previous studies, the RM1 clone appeared attenuated for oncogenicity but caused marked atrophy of the thymic lobes. The present studies represent a detailed analysis of the biological characteristics of the RM1 clone in order to better understand mechanisms of oncogenicity and gene function of MDV. RM1 was almost fully attenuated for oncogenicity but retained other in vivo properties of virulent viruses such as thymic and bursal atrophy, early immunosuppression, early cytolytic infection followed by efficient replication, and contact spread--all normally absent in attenuated strains. This suggests that, for serotype 1 MDV, oncogenicity is not tightly linked with immunodepression or viral replication and that these properties may be controlled by different genes or mechanisms. The mutation was stable through serial passage of the virus in chickens as determined by molecular analysis. None of the mutant viruses demonstrated expansion of the 132-bp repeat region of the genome, indicating that such expansion is not required for attenuation. Chickens vaccinated with RM1 clones were protected against challenge with virulent MDV, and levels of protection exceeded those of other attenuated serotype 1 vaccine viruses. Thus, attenuation by selective mutation may be an advantageous strategy for development of serotype 1 Marek's disease vaccines.


The cell cycle program of polypeptide labeling in Chlamydomonas reinhardtii.
The cell cycle program of polypeptide labeling in syndhronous cultures of wild-type Chlamydomonas reinhardtii was analyzed by pulse-labeling cells with 35SO4 = or [3H]arginine at different cell cycle stages. Nearly 100 labeled membrane and soluble polypeptides were resolved and studied using one-dimensional sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The labeling experiments produced the following results. (a) Total 35SO4 = and [3H]arginine incorporation rates varied independently throughout the cell cycle. 35SO4 = incorporation was highest in the mid-light phase, while [3H]arginine incorporation peaked in the dark phase just before cell division. (b) The relative labeling rate for 20 of 100 polypeptides showed significant fluctuations (3-12 fold) during the cell cycle. The remaining polypeptides were labeled at a rate commensurate with total 35SO4 = or [3H]arginine incorporation. The polypeptides that showed significant fluctuations in relative labeling rates served as markers to identify cell cycle stages. (c) The effects of illumination conditions on the apparent cell cycle stage-specific labeling of polypeptides were tested. Shifting light-grown asynchronous cells to the dark had an immediate and pronounced effect on the pattern of polypeptide labeling, but shifting dark-phase syndhronous cells to the light had little effect. The apparent cell cycle variations in the labeling of ribulose 1,5-biphosphate (RUBP)-carboxylase were strongly influenced by illumination effects. (d) Pulse-chase experiments with light-grown asynchronous cells revealed little turnover or inter-conversion of labeled polypeptides within one cell generation, meaning that major polypeptides, whether labeled in a stage-specific manner or not, do not appear transiently in the cell cycle of actively dividing, light-grown cells. The cell cycle program of labeling was used to analyze effects of a temperature-sensitive cycle blocked (cb) mutant. A synchronous culture of ts10001 was shifted to restrictive temperature before its block point to prevent it from dividing. The mutant continued its cell cycle program of polypeptide labeling for over a cell generation, despite its inability to divide.


Adrenaline and extracellular ATP switch between two modes of acid extrusion in the guinea-pig ventricular myocyte.
1. Intracellular pH (pHi) was recorded in isolated guinea-pig ventricular myocytes using the pH-sensitive fluoroprobe, carboxy-SNARF-1 (carboxy-seminaphthorhodafluor). 2. Addition and removal of 10 mM NH4Cl was used to induce an intracellular acid load in a myocyte perfused with HCO3(-)-buffered solution containing amiloride. Under these conditions, subsequent pHi recovery is known to rely upon Na(+)-HCO3- co-transport into the cell. The application of 0.5-5 microM adrenaline resulted in an inhibition of this pHi recovery. 3. In HEPES-buffered solution, where acid extrusion is mediated primarily by Na(+)-H+ antiport, pHi recovery from an acid load was stimulated by the application of adrenaline. 4. In HCO3-/CO2-buffered solution (no amiloride), when both acid-aquivalent extruders are activated by an intracellular acidification, adrenaline was found to slow pHi recovery. 5. When both carriers were inhibited in Na(+)-free, HCO3(-)-buffered medium, adrenaline had no effect on pHi, ruling out any effect of the catecholamine on background acid loading. 6. The voltage clamp technique was used to test if the inhibitory effect of adrenaline on amiloride-resistant, HCO3(-)-dependent pHi recovery was due to an efflux of HCO3- ions through catecholamine-activated anion channels. During pHi recovery, membrane depolarization, sufficient to reverse the electrochemical driving force acting on HCO3-, had no effect upon pHi recovery rate. 7. The above results show that adrenaline has direct but opposite effects on Na(+)-HCO3- co-transport and Na(+)-H+ antiport. In the presence of this agonist, the pHi dependence of Na(+)-HCO3- symport was shifted to the left along the pHi axis by 0.13 +/- 0.03 units (n = 4) whereas that for Na(+)-H+ antiport was shifted in the opposite direction by only 0.07 +/- 0.01 units (n = 3). Following an acid load, the net effect of adrenaline under physiological conditions was, therefore, a slowing of pHi recovery. 8. The application of extracellular ATP (ATPo, 10-50 microM) mimicked the effects of adrenaline on both Na(+)-H+ exchange and Na(+)-HCO3- symport. 9. Adenosine (50 microM) and ADP (50 microM) did not induce any inhibition of Na(+)-HCO3- symport, suggesting that the inhibition induced by ATP was not mediated through P1 or P2-purinergic receptors. 10. We conclude that Na(+)-H+ antiport and Na(+)-HCO3- symport are both coupled to adrenaline and ATPo receptors. Activation of these receptors switches acid-equivalent extrusion from a situation dependent on both HCO3- and H+ ions to one nearly exclusively dependent upon H+.


Plasma glucose and insulin responses to mixed meals: impaired fasting glucose re-visited.
In individuals with varying glucose tolerance, glucose and insulin comparisons are usually made based on response to oral glucose challenge. However, an oral glucose tolerance test may not reflect daylong glucose and insulin excursions in response to meals. To better understand individuals with impaired fasting glucose (IFG), we compared insulin action as well as plasma glucose and insulin responses to mixed meals in individuals with normal fasting glucose (NFG; n = 141) and IFG (n = 148) concentrations. Insulin action was quantified by determining steady-state plasma glucose (SSPG) concentrations during the insulin suppression test. Plasma glucose and insulin concentrations were measured before and hourly after two mixed meals. SSPG concentrations were significantly higher in the IFG group (11.8 ± 3.6 vs. 9.1 ± 3.8 mmol/l). Mean hourly daylong glucose (6.4 ± 0.07 vs. 5.5 ± 0.04 mmol/l) and insulin (390 ± 20 vs. 279 ± 15 pmol/l) concentrations were also higher in those with IFG (p < 0.001). Daylong incremental meal-stimulated glucose response, however, was comparable (p = 0.77) in the two groups, whereas the incremental insulin response was 44% higher in the IFG group. Although individuals are currently defined as having IFG based on fasting plasma glucose concentration, our data show that these individuals with IFG also are insulin resistant and have higher daylong insulin concentrations.


Role of TGF beta s and BMPs as signals controlling the position of the digits and the areas of interdigital cell death in the developing chick limb autopod.
The establishment of the digital rays and the interdigital spaces in the developing limb autopod is accompanied by the occurrence of corresponding domains of expression of TGF beta s and BMPs. This study analyzes whether these coincident events are functionally correlated. The experiments consisted of local administration of TGF beta-1, TGF beta-2 or BMP-4 by means of heparin or Affi-gel blue beads to the chick limb autopod in the stages preceding the onset of interdigital cell death. When beads bearing either TGF beta-1 or -2 were implanted in the interdigits, the mesodermal cells were diverted from the death program forming ectopic cartilages or extra digits in a dose- and stage-dependent fashion. This change in the interdigital phenotype was preceded by a precocious ectopic expression of ck-erg gene around the bead accompanied by down-regulation of bmp-4, msx-1 and msx-2 gene expression. When BMP-beads were implanted in the interdigital spaces, programmed cell death and the freeing of the digits were both accelerated. Implantation of beads bearing BMP-4 at the tip of the growing digits was followed by digit bifurcation, accompanied by the formation of an ectopic area of cell death resembling an extra interdigit, both morphologically and molecularly. The death-inducing effect of the BMP beads and the chondrogenic-inducing effect of the TGF beta beads were antagonized by the implantation of an additional bead preabsorbed with FGF-2, which constitutes a signal characteristic of the progress zone. It is concluded that the spatial distribution of digital rays and interdigital spaces might be controlled by a patterned distribution of TGF beta s and BMPs in the mesoderm subjacent to the progress zone.


Cross-cultural adaptation and validation of the European Heart Failure Self-Care Behavior Scale for Brazilian Portuguese.
To adapt and validate a Brazilian Portuguese version of the European Heart Failure Self-Care Behavior Scale. The cross-cultural adaptation (translation, synthesis, back-translation, expert committee review, and pretesting) and validation (assessment of face validity, content validity, and internal consistency reliability) were carried out in accordance with the literature. The European Heart Failure Self-Care Behavior Scale assesses key components of self-care: recognition of the signs and symptoms of decompensated heart failure (HF) and decision-making when these signs and symptoms arise. It comprises 12 items (range 12-60, where lower scores indicate better self-care). The sample comprised 124 HF patients with a mean age of 62.3 ± 12 years. The Cronbach's Alpha internal consistency was 0.70 and the intraclass correlation coefficient for reproducibility was 0.87. Face and content validity, internal consistency and reproducibility have lended validity and reliability for the use of the instrument in Brazil.


Mapping QTL for drought stress-induced premature senescence and maturity in cowpea [Vigna unguiculata (L.) Walp.].
Cowpea is an important crop for subsistence farmers in arid regions of Africa, Asia, and South America. Efforts to develop cultivars with improved productivity under drought conditions are constrained by lack of molecular markers associated with drought tolerance. Here, we report the mapping of 12 quantitative trait loci (QTL) associated with seedling drought tolerance and maturity in a cowpea recombinant inbred (RIL) population. One hundred and twenty-seven F(8) RILs developed from a cross between IT93K503-1 and CB46 were screened with 62 EcoR1 and Mse1 primer combinations to generate 306 amplified fragment length polymorphisms for use in genetic linkage mapping. The same population was phenotyped for maintenance of stem greenness (stg) and recovery dry weight (rdw) after drought stress in six greenhouse experiments. In field experiments conducted over 3 years, visual ratings and dry weights were used to phenotype drought stress-induced premature senescence in the RIL population. Kruskall-Wallis and multiple-QTL model mapping analysis were used to identify QTL associated with drought response phenotypes. Observed QTL were highly reproducible between stg and rdw under greenhouse conditions. Field studies confirmed all ten drought-response QTL observed under greenhouse conditions. Regions harboring drought-related QTL were observed on linkage groups 1, 2, 3, 5, 6, 7, 9, and 10 accounting for between 4.7 and 24.2% of the phenotypic variance (R(2)). Further, two QTL for maturity (R(2) = 14.4-28.9% and R(2) = 11.7-25.2%) mapped on linkage groups 7 and 8 separately from drought-related QTL. These results provide a platform for identification of genetic determinants of seedling drought tolerance in cowpea.


Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135.
In order to investigate the in vivo dopamine (DA) stimulant properties of selected 3rd generation Spice/K2 cannabinoids, BB-22, 5F-PB-22, 5F-AKB-48 and STS-135, their in vitro affinity and agonist potency at native rat and mice CB1 receptors was studied. The compounds bind with high affinity to CB1 receptors in rat cerebral cortex homogenates and stimulate CB1-induced [(35)S]GTPγS binding with high potency and efficacy. BB-22 and 5F-PB-22 showed the lowest Ki of binding to CB1 receptors (0.11 and 0.13 nM), i.e., 30 and 26 times lower respectively than that of JWH-018 (3.38 nM), and a potency (EC50, 2.9 and 3.7 nM, respectively) and efficacy (Emax, 217% and 203%, respectively) as CB1 agonists higher than JWH-018 (EC50, 20.2 nM; Emax, 163%). 5F-AKB-48 and STS-135 had higher Ki for CB1 binding, higher EC50 and lower Emax as CB1 agonists than BB-22 and 5F-PB-22 but still comparatively more favourable than JWH-018. The agonist properties of all the compounds were abolished or drastically reduced by the CB1 antagonist/inverse agonist AM251 (0.1 μM). No activation of G-protein was observed in CB1-KO mice. BB-22 (0.003-0.01 mg/kg i.v.) increased dialysate DA in the accumbens shell but not in the core or in the medial prefrontal cortex, with a bell shaped dose-response curve and an effect at 0.01 mg/kg and a biphasic time-course. Systemic AM251 (1.0 mg/kg i.p.) completely prevented the stimulant effect of BB-22 on dialysate DA in the NAc shell. All the other compounds increased dialysate DA in the NAc shell at doses consistent with their in vitro affinity for CB1 receptors (5F-PB-22, 0.01 mg/kg; 5F-AKB-48, 0.1 mg/kg; STS-135, 0.15 mg/kg i.v.). 3rd generation cannabinoids can be even more potent and super-high CB1 receptor agonists compared to JWH-018. Future research will try to establish if these properties can explain the high toxicity and lethality associated with these compounds.


Dopaminergic Contributions to Vocal Learning.
Although the brain relies on auditory information to calibrate vocal behavior, the neural substrates of vocal learning remain unclear. Here we demonstrate that lesions of the dopaminergic inputs to a basal ganglia nucleus in a songbird species (Bengalese finches, Lonchura striata var. domestica) greatly reduced the magnitude of vocal learning driven by disruptive auditory feedback in a negative reinforcement task. These lesions produced no measureable effects on the quality of vocal performance or the amount of song produced. Our results suggest that dopaminergic inputs to the basal ganglia selectively mediate reinforcement-driven vocal plasticity. In contrast, dopaminergic lesions produced no measurable effects on the birds' ability to restore song acoustics to baseline following the cessation of reinforcement training, suggesting that different forms of vocal plasticity may use different neural mechanisms. During skill learning, the brain relies on sensory feedback to improve motor performance. However, the neural basis of sensorimotor learning is poorly understood. Here, we investigate the role of the neurotransmitter dopamine in regulating vocal learning in the Bengalese finch, a songbird with an extremely precise singing behavior that can nevertheless be reshaped dramatically by auditory feedback. Our findings show that reduction of dopamine inputs to a region of the songbird basal ganglia greatly impairs vocal learning but has no detectable effect on vocal performance. These results suggest a specific role for dopamine in regulating vocal plasticity.


IgG and IgG4 antibodies in subjects with irritable bowel syndrome: a case control study in the general population.
Patients with Irritable Bowel Syndrome (IBS) often relate their symptoms to the intake of food and modify their diet. IgE-mediated food allergy is uncommon in IBS, but the role of IgG-mediated food hypersensitivity remains inconclusive. The primary aim of this study was to compare food- and yeast-specific IgG and IgG4 antibodies in subjects with and without IBS. This was a case control study in the general population for which subjects completed questionnaires about abdominal complaints and their intake of common food items. Blood samples were collected, and food- and yeast-specific IgG and IgG4 antibodies were measured. Antibodies were measured in mg/L. We included 269 subjects with IBS and 277 control subjects. After correction for subject characteristics and diet, there were no significant differences with regard to food- and yeast-specific IgG and IgG4 antibodies between subjects with IBS and controls. Lower values of IgG antibodies against egg (OR 0.99 (0.98 to 1.00), p = 0.002) and beef (OR 0.75 (0.60 to 0.94), p = 0.012) and higher values of IgG antibodies against chicken (OR 1.14 (1.03 to 1.27), p = 0.009) were associated with more severe symptoms. Our findings suggest that IgG-and IgG4-mediated food and yeast hypersensitivity in IBS is unlikely. IgG antibodies against food and yeast may reflect the diet.


Crystallographic evaluation of internal motion of human alpha-lactalbumin refined by full-matrix least-squares method.
The low temperature form of human alpha-lactalbumin (HAL) was crystallized from a 2H2O solution and its structure was refined to the R value of 0.119 at 1.15 A resolution by the full-matrix least-squares method. Average estimated standard deviations of atomic parameters for non-hydrogen atoms were 0.038 A for coordinates and 0.044 A2 for anisotropic temperature factors (Uij). The magnitude of equivalent isotropic temperature factors (Ueqv) was highly correlated with the distance from the molecular centroid and fitted to a quadratic equation as a function of atomic coordinates. The atomic thermal motion was rather isotropic in the core region and the anisotropy increased towards the molecular surface. The statistical analysis revealed the out-of-plane motion of main-chain oxygen atoms, indicating that peptide groups are in rotational vibration around a Calpha.Calpha axis. The TLS model, which describes the rigid-body motion in terms of translation, libration, and screw motions, was adopted for the evaluation of the molecular motion and the TLS parameters were determined by the least-squares fit to Uij. The reproduced Ueqvcal from the TLS parameters was in fair agreement with observed Ueqv, but differences were found in regions of residues, 5-22, 44-48, 70-75, and 121-123, where Ueqv was larger than Ueqvcal because of large local motions. To evaluate the internal motion of HAL, the contribution of the rigid-body motion was determined to be 42.4 % of Ueqv in magnitude, which was the highest estimation to satisfy the condition that the Uijint tensors of the internal motion have positive eigen values. The internal motion represented with atomic thermal ellipsoids clearly showed local motions different from those observed in chicken-type lysozymes which have a backbone structure very similar to HAL. The result indicates that the internal motion is closely related to biological function of proteins.


Carotenoids in fruits of different persimmon cultivars.
Carotenoids in the peel and the flesh of persimmon fruit were identified, and the contents of carotenoids in the fleshes of 46 different persimmon cultivars were analyzed. The results indicated that 31 specific carotenoids were detected in both cultivars of persimmons, among which nine specific carotenoids were characterized. β-cryptoxanthin was the most abundant carotenoid among all individual components in both the peel and the flesh, accounting for about 20-30% of the total carotenoids in both cultivars. The contents of total carotenoids in the fleshes of different persimmon cultivars were between 194.61 µg/100g FW and 1,566.30 µg/100g FW. Zeaxanthin was also the most abundant in all persimmon fleshes besides β-cryptoxanthin, and the total amount of these two components accounted for 37.84-85.11% of the total carotenoids. The RE values in the fleshes of different cultivars also differed greatly. Besides, the stage of maturation was also important factor which could influence the carotenoid content and RE value in the fleshes.


Metabolic profiling study of yang deficiency syndrome in hepatocellular carcinoma by h1 NMR and pattern recognition.
This study proposes a (1)H NMR-based metabonomic approach to explore the biochemical characteristics of Yang deficiency syndrome in hepatocellular carcinoma (HCC) based on serum metabolic profiling. Serum samples from 21 cases of Yang deficiency syndrome HCC patients (YDS-HCC) and 21 cases of non-Yang deficiency syndrome HCC patients (NYDS-HCC) were analyzed using (1)H NMR spectroscopy and partial least squares discriminant analysis (PLS-DA) was applied to visualize the variation patterns in metabolic profiling of sera from different groups. The differential metabolites were identified and the biochemical characteristics were analyzed. We found that the intensities of six metabolites (LDL/VLDL, isoleucine, lactate, lipids, choline, and glucose/sugars) in serum of Yang deficiency syndrome patients were lower than those of non-Yang deficiency syndrome patients. It implies that multiple metabolisms, mainly including lipid, amino acid, and energy metabolisms, are unbalanced or weakened in Yang deficiency syndrome patients with HCC. The decreased intensities of metabolites including LDL/VLDL, isoleucine, lactate, lipids, choline, and glucose/sugars in serum may be the distinctive metabolic variations of Yang deficiency syndrome patients with HCC. And these metabolites may be potential biomarkers for diagnosis of Yang deficiency syndrome in HCC.


Decreased proliferation of pituitary cells of streptozotocin-induced diabetic rats in response to estradiol-17-beta.
Insulin is involved in the proliferation of fibroblasts, hepatocytes and certain other lines of cultured cells. In the present study an attempt was made to clarify the role of insulin in the proliferation of rat pituitary cells. Adult male rats of the Wistar/Tw strain were given intraperitoneal injections of streptozotocin (STZ) at a dose of 32.5 mg/kg. STZ-treated rats developed high blood glucose levels and low serum insulin levels. Proliferation of cells was examined by monitoring the cell uptake of bromodeoxyuridine (BrdU). Estradiol-17 beta (50 micrograms) was given to stimulate the proliferation of pituitary cells. The number of BrdU-containing cells was lower in STZ-treated rats than in controls. The responsiveness to estrogen in terms of cell proliferation was lower in STZ-treated rats than in controls. Treatment of STZ-treated rats with insulin increased the number of BrdU-containing cells and restored the responsiveness to estrogen. Insulin stimulated the proliferation of prolactin-secreting cells and growth hormone-secreting cells in estrogen-treated rats. These results suggest that insulin is necessary for the proliferation of pituitary cells.


Can health care providers recognise a fibromyalgia personality?
To determine if experienced health care providers (HCPs) can recognise patients with fibromyalgia (FM) based on a limited set of personality items, exploring the existence of a FM personality. From the 240-item NEO-PI-R personality questionnaire, 8 HCPs from two different countries each selected 20 items they considered most discriminative of FM personality. Then, evaluating the scores on these items of 129 female patients with FM and 127 female controls, each HCP rated the probability of FM for each individual on a 0-10 scale. Personality characteristics (domains and facets) of selected items were determined. Scores of patients with FM and controls on the eight 20-item sets, and HCPs' estimates of each individual's probability of FM were analysed for their discriminative value. The eight 20-item sets discriminated for FM, with areas under the receiver operating characteristic curve ranging from 0.71-0.81. The estimated probabilities for FM showed, in general, percentages of correct classifications above 50%, with rising correct percentages for higher estimated probabilities. The most often chosen and discriminatory items were predominantly of the domain neuroticism (all with higher scores in FM), followed by some items of the facet trust (lower scores in FM). HCPs can, based on a limited set of items from a personality questionnaire, distinguish patients with FM from controls with a statistically significant probability. The HCPs' expectation that personality in FM patients is associated with higher levels for aspects of neuroticism (proneness to psychological distress) and lower scores for aspects of trust, proved to be correct.


Chemical profile and biological activities of Veronica thymoides subsp. pseudocinerea.
In Turkey, Veronica species (Plantaginaceae) have been used as a diuretic and for wound healing in traditional medicine. To examine the fatty acid and essential oil profiles, the antioxidant, anticholinesterase, antimicrobial, and DNA damage effects of Veronica thymoides P.H. Davis subsp. pseudocinerea M.A. Fischer as a potential source of natural active compounds. GC/MS was used to analyze essential oil and fatty acid obtained from whole plant. The antioxidant activity was evaluated by the β-carotene-linoleic acid test system, DPPH-free and ABTS cation radicals scavenging, and cupric reducing antioxidant capacity assays. The anticholinesterase and antimicrobial activities were determined by Ellman and broth macrodillution methods, respectively. The effect of the methanol extract on DNA cleavage was investigated. Hexatriacontene (21.0%) was found to be the main constituent in essential oil, and linoleic acid (25.2%) and palmitic acid (20.6%) in fatty acid. Methanol extract demonstrated the best IC50 values in lipid peroxidation (49.81 ± 0.31 µg/ml) and DPPH-free radical scavenging activity (15.32 ± 0.17 µg/ml). Methanol and water extracts possessed strong ABTS cation radical scavenging activity with IC50 values 9.15 ± 0.28 and 8.90 ± 0.1 µg/ml, respectively. The acetone extract exhibited moderate butyrylcholinesterase inhibitory activity. The highest antimicrobial activity was determined in methanol extract against Escherichia coli with 31.25 µg/ml MIC value. Inhibition of methanol extract on plasmid DNA cleavage by OH radicals was found to be 93.32% at 500 µg/ml. The methanol extract having strong antioxidant and DNA damage effects could be investigated phytochemically to find natural active compounds.


1991 Muriel Driver lecture. The environment: a focus for occupational therapy.
Individuals in Canada with a disability encounter environmental constraints that limit their active participation in the daily life of our communities. Fundamental inequities in participation and integration continue to exist and there is a need for a concerted effort to eliminate these disabling environments. Several factors, including the built environment, societal production of space, classification of individuals based on norms, the perception of disability as deviance, the power of health disciplines and bureaucracy are examined to determine their contribution to the creation of these disabling environments. Recent modifications to occupational therapy theory and practice, while meaningful, have not fully explored ways in which disabling environments limit occupation. Prevailing ideas about occupation and the environment are examined for their contribution to solving these environmental problems. Principles which can assist occupational therapy intervention directed at changing disabling environments are described. The intent is to define methods of changing disabling environments, based on the desires and active participation of people with disabilities


The safety of amodiaquine use in pregnant women.
Few antimalarial drugs have been evaluated extensively in pregnancy because of fears over toxicity. However, increasing Plasmodium falciparum resistance to chloroquine and sulfadoxine-pyrimethamine makes finding alternative antimalarials that are safe and effective in pregnancy a priority. There is a renewed interest in amodiaquine as a potential candidate, particularly as a partner drug in artemisinin-based combination therapy. The available data suggest that, at standard dosages, amodiaquine is not teratogenic and that the adverse events associated with taking amodiaquine in pregnancy are not greater than those associated with falciparum malaria in pregnancy. Thus, amodiaquine in combination with other antimalarial drugs may be useful for malaria treatment in pregnancy, but inadequate data on its safety and pharmacokinetics in pregnancy limits its deployment for intermittent preventive treatment in pregnancy.


An Agathokakological Tale of Δ9-THC: Exploration of Possible Biological Targets.
Δ9-Tetrahydrocannabinol (Δ9-THC), the active phytocannabinoid in cannabis, is virtually an adjunct to the endogenous endocannabinoid signaling system. By interacting with G-proteincoupled receptors CB1 and CB2, Δ9-THC affects peripheral and central circulation by lowering sympathetic activity, altering gene expression, cell proliferation, and differentiation, decreasing leukocyte migration, modulating neurotransmitter release, thereby modulating cardiovascular functioning, tumorigenesis, immune responses, behavioral and locomotory activities. Δ9-THC effectively suppresses chemotherapy-induced vomiting, retards malignant tumor growth, inhibits metastasis, and promotes apoptosis. Other mechanisms involved are targeting cell cycle at the G2-M phase in human breast cancer, downregulation of E2F transcription factor 1 (E2F1) in human glioblastoma multiforme, and stimulation of ER stress-induced autophagy. Δ9-THC also plays a role in ameliorating neuroinflammation, excitotoxicity, neuroplasticity, trauma, and stroke and is associated with reliving childhood epilepsy, brain trauma, and neurodegenerative diseases. Δ9-THC via CB1 receptors affects nociception, emotion, memory, and reduces neuronal excitability and excitotoxicity in epilepsy. It also increases renal blood flow, reduces intraocular pressure via a sympathetic pathway, and modulates hormonal release, thereby decreasing the reproductive function and increasing glucose metabolism. Versatile medical marijuana has stimulated abundant research demonstrating substantial therapeutic promise, suggesting the possibilities of first-in-class drugs in diverse therapeutic segments. This review represents the current pharmacological status of the phytocannabinoid, Δ9-THC, and synthetic analogs in cancer, cardiovascular, and neurodegenerative disorders.