Disordered Gambling Prevalence: Methodological Innovations in a General Danish Population Survey.
We study Danish adult gambling behavior with an emphasis on discovering patterns relevant to public health forecasting and economic welfare assessment of policy. Methodological innovations include measurement of formative in addition to reflective constructs, estimation of prospective risk for developing gambling disorder rather than risk of being falsely negatively diagnosed, analysis with attention to sample weights and correction for sample selection bias, estimation of the impact of trigger questions on prevalence estimates and sample characteristics, and distinguishing between total and marginal effects of risk-indicating factors. The most significant novelty in our design is that nobody was excluded on the basis of their response to a 'trigger' or 'gateway' question about previous gambling history. Our sample consists of 8405 adult Danes. We administered the Focal Adult Gambling Screen to all subjects and estimate prospective risk for disordered gambling. We find that 87.6% of the population is indicated for no detectable risk, 5.4% is indicated for early risk, 1.7% is indicated for intermediate risk, 2.6% is indicated for advanced risk, and 2.6% is indicated for disordered gambling. Correcting for sample weights and controlling for sample selection has a significant effect on prevalence rates. Although these estimates of the 'at risk' fraction of the population are significantly higher than conventionally reported, we infer a significant decrease in overall prevalence rates of detectable risk with these corrections, since gambling behavior is positively correlated with the decision to participate in gambling surveys. We also find that imposing a threshold gambling history leads to underestimation of the prevalence of gambling problems.


Coronary artery bypass surgery in a patient with symptomatic ventricular arrhythmia. A case presentation and review of the literature.
A 42-year-old White man suffered from recurrent symptomatic ventricular tachycardia but no angina pectoris. Cardiac catheterization demonstrated a normally contracting left ventricle and coronary angiography delineated significant atherosclerotic obstructions in the left circumflex (LC) coronary artery and the first diagonal branch of the left anterior descending (LAD) coronary artery. Coronary artery bypass graft (CABG) surgery was carried out on the anterolateral and mid-lateral branches of the LC coronary artery as well as the first diagonal branch of the LAD coronary artery. Frequent postoperative Holter monitoring as well as maximum-exercise stress testing has failed to show any recurrence of the ventricular arrhythmia, and the patient has remained asymptomatic and medical therapy has been discontinued. Some 30 months after operation left ventricular cine angiography demonstrated normal contractility. Selective coronary arteriography indicated that the CABG to the anterolateral branch of the LC coronary artery was occluded at its proximal aortic anastomosis. However, the CABGs to the midlateral branch of the LC and LAD coronary arteries were still patent. Repeat serial resting ECGs failed to show any evidence of postoperative myocardial infarction. It is concluded that CABG surgery was responsible for eliminating the episodes of life-threatening ventricular tachycardia, presumably by correcting myocardial ischaemia. The role of CABG surgery in the control of medically unresponsive and dangerous ventricular arrhythmias is reviewed.


Use of ab initio methods for the interpretation of the experimental IR reflectance spectra of crystalline compounds.
It is shown that ab initio simulation can be used as a powerful complementary tool in the interpretation of the experimental reflectance spectra R(ν) of crystalline compounds. Experimental frequencies and intensities are obtained from a best fit of R(ν) with a set of damped harmonic oscillators, whose number and initial position in frequency can dramatically influence the final results, as the parameters are strongly correlated. Computed ab initio values for frequencies and intensities are accurate enough to represent an excellent starting point for the best fit process. Moreover, at variance with respect to experiment, simulation permits to identify all the symmetry allowed modes, also when characterized by low intensity or when close to a very intense peak. Overall, simulation-aided analysis of experimental spectra prevents from classifying combination modes as fundamental modes and permits to discard artifacts due to superposition of bands, background, and noise. Finally, it allows to (almost) completely characterize the set of fundamental modes.


HIV sexual risk reduction interventions for women: a review.
AIDS has emerged as a serious public health threat for women. Reducing the risk for HIV infection among sexually active women requires the adoption of preventive strategies that effectively inhibit viral transmission. However, there is a paucity of published literature describing interventions targeted toward women and even fewer published reports evaluating their effectiveness. We conducted a search of HIV prevention interventions for women using the MEDLINE, ERIC and PSYCHLIT on-line computer database for the years January 1984-May 1995 to assess the effectiveness of interventions in increasing condom use during sexual intercourse. Interventions efficacious at increasing condom use applied a social psychological model of behavior to guide the development and implementation of the intervention, used randomized controlled designs to evaluate program efficacy, emphasized gender-related influences, were peer-led, and used multiple intervention sessions. While these findings are promising, methodologic limitations preclude any definitive assessment of programmatic efficacy. One challenge for future studies is to corroborate and extend these findings using rigorous methodologic research designs to evaluate programmatic efficacy, in particular, longer follow-up to assess stability of treatment effects over time. Another challenge is to understand the implications of previous research for the development of more gender-relevant interventions. The urgency of the HIV epidemic demands that the development and evaluation of HIV-prevention interventions tailored toward women remain a public health priority. Medical Subject Headings (MeSH): women, HIV/AIDS, interventions, prevention.


Reduced diabetes in btk-deficient nonobese diabetic mice and restoration of diabetes with provision of an anti-insulin IgH chain transgene.
Type 1 diabetes results from T cell-mediated destruction of insulin-producing beta cells. Although elimination of B lymphocytes has proven successful at preventing disease, modulation of B cell function as a means to prevent type 1 diabetes has not been investigated. The development, fate, and function of B lymphocytes depend upon BCR signaling, which is mediated in part by Bruton's tyrosine kinase (BTK). When introduced into NOD mice, btk deficiency only modestly reduces B cell numbers, but dramatically protects against diabetes. In NOD, btk deficiency mirrors changes in B cell subsets seen in other strains, but also improves B cell-related tolerance, as indicated by failure to generate insulin autoantibodies. Introduction of an anti-insulin BCR H chain transgene restores diabetes in btk-deficient NOD mice, indicating that btk-deficient B cells are functionally capable of promoting autoimmune diabetes if they have a critical autoimmune specificity. This suggests that the disease-protective effect of btk deficiency may reflect a lack of autoreactive specificities in the B cell repertoire. Thus, signaling via BTK can be modulated to improve B cell tolerance, and prevent T cell-mediated autoimmune diabetes.


Fungal survival during anaerobic digestion of organic household waste.
Anaerobic digestion of organic waste yields energy rich biogas and retains nutrients (N, P, K, S, etc.) in a stabilised residue. For the residue to be used as a soil fertiliser, it must be free from pollutants and harmful microorganisms. Fungal survival during sanitation and anaerobic treatment of source-separated organic household waste and during aerobic storage of the residue obtained was investigated. Decimal reduction times were determined for inoculated fungi (Aspergillus flavus and Aspergillus fumigatus, Penicillium roqueforti, Rhizomucor pusillus, Thermoascus crustaceus and Thermomyces lanuginosus). Several different fungal species were found after waste sanitation treatment (70 degrees C, 1 h), with Aspergillus species dominating in non-inoculated waste. Anaerobic waste degradation decreased the diversity of fungal species for processes run at both 37 and 55 degrees C, but not total fungal colony forming units. Fungi surviving the mesophilic anaerobic digestion were mainly thermotolerant Talaromyces and Paecilomyces species. T. crustaceus and T. lanuginosus were the only inoculated fungi to survive the thermophilic anaerobic degradation process. Aerobic storage of both types of anaerobic residues for one month significantly decreased fungal counts.


[Development and Psychometric Evaluation of the Transcultural Self-efficacy Scale for Nurses].
This methodological study was conducted to develop and psychometrically test the Transcultural Self-efficacy scale (TCSEscale) for nurses. Initial 41 items for the TCSE-scale were generated based on extensive literature reviews and in-depth interviews with 18 nurses who had experience in caring for foreign patients. Cultural Competence and Confidence model was used as a conceptual framework. Content validity was evaluated by an expert panel. Psychometric testing was performed with a convenience sample of 242 nurses recruited from four general hospitals in the Seoul metropolitan area and Gyeonggi-do province of South Korea. To evaluate the reliability of TCSE-scale, a test-retest reliability and an internal consistency reliability were analyzed. Construct validity, concurrent validity, criterion validity, convergent validity and discriminative validity were used to evaluate the validity. The 25-item TCSE-scale was found to have three subscales-Cognitive, Practical, and Affective domain-explaining 91.5% of the total variance. TCSE-scale also demonstrated a concurrent validity with the Cultural Competence Scale. Criterion-related validity was supported by known-group comparison. Reliability analysis showed an acceptable-to-high Cronbach's alpha-.88 in total, and subscales ranged from .76 to .87. The ICC was .90, indicating that the TCSE-scale has internal consistency and stability of reliability. This preliminary evaluation of the psychometric scale properties demonstrated an acceptable validity and reliability. The TCSE-scale is able to contribute to building up empirical and evidence based on data collection regarding the transcultural self-efficacy of clinical nurses. We suggest further testing of the applicability of TCSE-scale in different settings and community contexts.


Reef fishes in biodiversity hotspots are at greatest risk from loss of coral species.
Coral reef ecosystems are under a variety of threats from global change and anthropogenic disturbances that are reducing the number and type of coral species on reefs. Coral reefs support upwards of one third of all marine species of fish, so the loss of coral habitat may have substantial consequences to local fish diversity. We posit that the effects of habitat degradation will be most severe in coral regions with highest biodiversity of fishes due to greater specialization by fishes for particular coral habitats. Our novel approach to this important but untested hypothesis was to conduct the same field experiment at three geographic locations across the Indo-Pacific biodiversity gradient (Papua New Guinea; Great Barrier Reef, Australia; French Polynesia). Specifically, we experimentally explored whether the response of local fish communities to identical changes in diversity of habitat-providing corals was independent of the size of the regional species pool of fishes. We found that the proportional reduction (sensitivity) in fish biodiversity to loss of coral diversity was greater for regions with larger background species pools, reflecting variation in the degree of habitat specialization of fishes across the Indo-Pacific diversity gradient. This result implies that habitat-associated fish in diversity hotspots are at greater risk of local extinction to a given loss of habitat diversity compared to regions with lower species richness. This mechanism, related to the positive relationship between habitat specialization and regional biodiversity, and the elevated extinction risk this poses for biodiversity hotspots, may apply to species in other types of ecosystems.


Impact of methamphetamine on regional metabolism and cerebral blood flow after traumatic brain injury.
Substance abuse is a frequent comorbid condition among patients with traumatic brain injury (TBI), but little is known about its potential additive or interactive effects on tissue injury or recovery from TBI. This study aims to evaluate changes in regional metabolism and cerebral perfusion in subjects who used methamphetamine (METH) prior to sustaining a TBI. We hypothesized that METH use would decrease pericontusional cerebral perfusion and markers of neuronal metabolism, in TBI patients compared to those without METH use. This is a single center prospective observational study. Adults with moderate and severe TBI were included. MRI scanning was performed on a 3 Tesla scanner. MP-RAGE and FLAIR sequences as well as Metabolite spectra of NAA and lactate in pericontusional and contralateral voxels identified on the MP-RAGE scans. A spiral-based FAIR sequence was used for the acquisition of cerebral blood flow (CBF) maps. Regional CBF images were analyzed using ImageJ open source software. Pericontusional and contralateral CBF, NAA, and lactate were assessed in the entire cohort and in the METH and non-METH groups. Seventeen subjects completed the MR studies. Analysis of entire cohort: pericontusional NAA concentrations (5.81 ± 2.0 mM/kg) were 12% lower compared to the contralateral NAA (6.98 ± 1.2 mM/kg; p = 0.03). Lactate concentrations and CBF were not significantly different between the two regions; however, regional CBF was equally reduced in the two regions. Subgroup analysis: 41% of subjects tested positive for METH. The mean age, Glasgow Coma Scale, and time to scan did not differ between groups. The two subject groups also had similar regional NAA and lactate. Pericontusional CBF was 60% lower in the METH users than the non-users, p = 0.04; contralateral CBF did not differ between the groups. This small study demonstrates that tissue metabolism is regionally heterogeneous after TBI and pericontusional perfusion was significantly reduced in the METH subgroup.


Coexistence of Physisorbed and Solvated HCl at Warm Ice Surfaces.
The interfacial ionization of strong acids is an essential factor of multiphase and heterogeneous chemistry in environmental science, cryospheric science, catalysis research and material science. Using near ambient pressure core level X-ray photoelectron spectroscopy, we directly detected a low surface coverage of adsorbed HCl at 253 K in both molecular and dissociated states. Depth profiles derived from XPS data indicate the results as physisorbed molecular HCl at the outermost ice surface and dissociation occurring upon solvation deeper in the interfacial region. Complementary X-ray absorption measurements confirm that the presence of Cl- ions induces significant changes to the hydrogen bonding network in the interfacial region. This study gives clear evidence for nonuniformity across the air-ice interface and questions the use of acid-base concepts in interfacial processes.


Predicting Where a Radiation Will Occur: Acoustic and Molecular Surveys Reveal Overlooked Diversity in Indian Ocean Island Crickets (Mogoplistinae: Ornebius).
Recent theory suggests that the geographic location of island radiations (local accumulation of species diversity due to cladogenesis) can be predicted based on island area and isolation. Crickets are a suitable group for testing these predictions, as they show both the ability to reach some of the most isolated islands in the world, and to speciate at small spatial scales. Despite substantial song variation between closely related species in many island cricket lineages worldwide, to date this characteristic has not received attention in the western Indian Ocean islands; existing species descriptions are based on morphology alone. Here we use a combination of acoustics and DNA sequencing to survey these islands for Ornebius crickets. We uncover a small but previously unknown radiation in the Mascarenes, constituting a three-fold increase in the Ornebius species diversity of this archipelago (from two to six species). A further new species is detected in the Comoros. Although double archipelago colonisation is the best explanation for species diversity in the Seychelles, in situ cladogenesis is the best explanation for the six species in the Mascarenes and two species of the Comoros. Whether the radiation of Mascarene Ornebius results from intra- or purely inter- island speciation cannot be determined on the basis of the phylogenetic data alone. However, the existence of genetic, song and ecological divergence at the intra-island scale is suggestive of an intra-island speciation scenario in which ecological and mating traits diverge hand-in-hand. Our results suggest that the geographic location of Ornebius radiations is partially but not fully explained by island area and isolation. A notable anomaly is Madagascar, where our surveys are consistent with existing accounts in finding no Ornebius species present. Possible explanations are discussed, invoking ecological differences between species and differences in environmental history between islands.


Children's television exposure and behavioral and social outcomes at 5.5 years: does timing of exposure matter?
The American Academy of Pediatrics recommends children > or = 2 years of age limit daily media exposure to < or = 1 to 2 hours and not have a television set in children's bedrooms. However, there are limited prospective studies to address how timing of media exposure influences children's health. Our goal was to examine relations among children's early, concurrent, and sustained television exposure and behavioral and social skills outcomes at 5.5 years. We analyzed data collected prospectively from the Healthy Steps for Young Children national evaluation. Television exposure was defined as > 2 hours of daily use (at 30-33 months and 5.5 years) and television in child's bedroom (at 5.5 years). At 5.5 years, outcomes were assessed by using the Child Behavior Checklist and social skills using the Social Skills Rating System. Linear regression was used to estimate the effect of television exposure on behavioral and social skills outcomes. Sixteen percent of parents reported that their child watched > 2 hours of television daily at 30 to 33 months only, 15% reported > 2 hours of television daily at 5.5 years only, and 20% reported > 2 hours of television daily at both times. Forty-one percent of the children had televisions in their bedrooms at 5.5 years. In adjusted analyses, sustained television viewing was associated with behavioral outcomes. Concurrent television exposure was associated with fewer social skills. For children with heavy television viewing only in early childhood, there was no consistent relation with behavioral or social skills outcomes. Having a television in the bedroom was associated with sleep problems and less emotional reactivity at 5.5 years but was not associated with social skills. Sustained exposure is a risk factor for behavioral problems, whereas early exposure that is subsequently reduced presents no additional risk. For social skills, concurrent exposure was more important than sustained or early exposure. Considering the timing of media exposure is vital for understanding the consequences of early experiences and informing prevention strategies.


Biomechanical analysis of the effect of congruence, depth and radius on the stability ratio of a simplistic 'ball-and-socket' joint model.
The bony shoulder stability ratio (BSSR) allows for quantification of the bony stabilisers in vivo. We aimed to biomechanically validate the BSSR, determine whether joint incongruence affects the stability ratio (SR) of a shoulder model, and determine the correct parameters (glenoid concavity versus humeral head radius) for calculation of the BSSR in vivo. Four polyethylene balls (radii: 19.1 mm to 38.1 mm) were used to mould four fitting sockets in four different depths (3.2 mm to 19.1mm). The SR was measured in biomechanical congruent and incongruent experimental series. The experimental SR of a congruent system was compared with the calculated SR based on the BSSR approach. Differences in SR between congruent and incongruent experimental conditions were quantified. Finally, the experimental SR was compared with either calculated SR based on the socket concavity or plastic ball radius. The experimental SR is comparable with the calculated SR (mean difference 10%, sd 8%; relative values). The experimental incongruence study observed almost no differences (2%, sd 2%). The calculated SR on the basis of the socket concavity radius is superior in predicting the experimental SR (mean difference 10%, sd 9%) compared with the calculated SR based on the plastic ball radius (mean difference 42%, sd 55%). The present biomechanical investigation confirmed the validity of the BSSR. Incongruence has no significant effect on the SR of a shoulder model. In the event of an incongruent system, the calculation of the BSSR on the basis of the glenoid concavity radius is recommended.Cite this article: L. Ernstbrunner, J-D. Werthel, T. Hatta, A. R. Thoreson, H. Resch, K-N. An, P. Moroder. Biomechanical analysis of the effect of congruence, depth and radius on the stability ratio of a simplistic 'ball-and-socket' joint model. Bone Joint Res 2016;5:453-460. DOI: 10.1302/2046-3758.510.BJR-2016-0078.R1.


Longitudinal study of influenza molecular viral shedding in Hutterite communities.
The nature of influenza viral shedding during naturally acquired infection is not well understood. A cohort study was conducted in Hutterite colonies in Alberta, Canada. Flocked nasal swabs were collected during 3 influenza seasons (2007-2008 to 2009-2010) from both symptomatic and asymptomatic individuals infected with influenza. Samples were tested by real-time reverse-transcription polymerase chain reaction for influenza A and influenza B, and the viral load (VL) was determined for influenza A positive samples. Eight hundred thirty-nine participants were included in the cohort; 25% (208) tested positive for influenza viruses. They experienced 238 episodes of viral shedding, of which 23 (10%) were not accompanied by symptoms. For seasonal and pandemic H1N1, VL peaked at or before onset of acute respiratory infection. For H3N2, VL peaked 2 days after the onset of acute respiratory infection, which corresponded to peaks in systemic and respiratory symptom scores. Although the duration of shedding was shorter for asymptomatic participants, the peak level of VL shedding was similar to that of symptomatic participants. Viral loads for children and adults revealed similar patterns. Molecular viral shedding values follow symptom scores, but timing of peak VL varies by subtype. Asymptomatic infections are infrequent.


Complete chloroplast genome sequence of Omani lime (Citrus aurantiifolia) and comparative analysis within the rosids.
The genus Citrus contains many economically important fruits that are grown worldwide for their high nutritional and medicinal value. Due to frequent hybridizations among species and cultivars, the exact number of natural species and the taxonomic relationships within this genus are unclear. To compare the differences between the Citrus chloroplast genomes and to develop useful genetic markers, we used a reference-assisted approach to assemble the complete chloroplast genome of Omani lime (C. aurantiifolia). The complete C. aurantiifolia chloroplast genome is 159,893 bp in length; the organization and gene content are similar to most of the rosids lineages characterized to date. Through comparison with the sweet orange (C. sinensis) chloroplast genome, we identified three intergenic regions and 94 simple sequence repeats (SSRs) that are potentially informative markers with resolution for interspecific relationships. These markers can be utilized to better understand the origin of cultivated Citrus. A comparison among 72 species belonging to 10 families of representative rosids lineages also provides new insights into their chloroplast genome evolution.


Comparison of biting forces in different age and sex groups: a study of biting efficiency with mobile and non-mobile teeth.
This study aimed (1) to investigate the influences of sex, age and number of teeth on biting ability through a descriptive survey, and (2) to compare the biting ability between the subjects with and without mobile teeth in a case-control study. A total of 687 subjects cooperated in the descriptive survey. Each subject bit on a pressure detecting sheet with their maximum biting force. Three indices of biting ability: biting pressure (MPa), biting force (N) and occlusal contact area (mm2) were calculated from the impressed marks on the sheet using a high vision video processor system. These indices were correlated well with the number of teeth according to the multiple regression analysis. In the case-control study, matching procedures with sex, age and number of teeth were performed between the subjects with and without mobile teeth. No differences in the three indices were observed between the two well-balanced groups. The results showed that the number of teeth is most important to maintain biting ability, and that the presence of mobile teeth does not always reduce biting ability.


Pseudorabies virus glycoproteins gII and gp50 are essential for virus penetration.
Pseudorabies virus (PrV) glycoproteins gII and gp50 are major constituents of the viral envelope and targets of neutralizing monoclonal antibodies. Both are homologs of essential glycoproteins found in herpes simplex virus, gB (gII) and gD (gp50). We recently isolated a gII-negative PrV deletion mutant on complementing cell lines and established the essential character of gII for PrV replication (I. Rauh, F. Weiland, F. Fehler, G. Keil, and T.C. Mettenleiter, J. Virol. 65: 621-631, 1991). In this report, we describe the isolation of a gp50-negative PrV mutant after constructing cell lines that constitutively express gp50 and phenotypically complement the gp50 defect. Analysis of the gp50- mutant proved that gp50 is essential for PrV replication. Further studies showed that both gII and gp50 are required for viral penetration into target cells. The penetration defect in the gII and gp50 deletion mutants could be overcome by experimental polyethylene glycol-induced membrane fusion. Surprisingly, whereas gII proved to be essential for both penetration and cell-cell spread of the virus, gp50 was required only for penetration and appeared dispensable for direct cell-cell spread.


Validity of bioelectric impedance for body composition assessment in children.
Whole-body bioelectrical impedance analysis (BIA) was evaluated for its reliability and accuracy in estimating body composition in children. The hypothesis that the index, body height2 divided by resistance (RI), can accurately predict fat-free body mass (FFB) and percent fat (%FAT) in children was tested on 94 caucasian children 10-14 yr old. Criterion variables were FFB and %FAT estimated using multicomponent equations developed for children. BIA measurements (resistance and reactance) were found to be reliable. Prediction accuracy (standard error of the estimate, SEE) for FFB from RI alone was 2.6 kg and for %FAT from RI and body weight was 4.2%. For RI, anthropometric variables and reactance, the SEE improved to 1.9 kg FFB. For RI and anthropometric variables, the SEE was 3.3% FAT. For anthropometric variables alone, the SEE's were 2.1 kg FFB and 3.2% FAT. Adult FFB and %FAT prediction equations cross-validated with this sample resulted in SEE's similar to those for adult samples. We conclude that RI together with anthropometry is a reliable and an acceptably accurate method of estimating FFB mass and %FAT in children.


Oncolytic Viruses: Therapeutics With an Identity Crisis.
Oncolytic viruses (OV) are replicating viral therapeutics for the treatment of cancer and have been in laboratory development for about twenty years. Recently, the FDA approved Imlygic, a herpes virus based therapeutic for the treatment of melanoma and thus OVs have entered a new era where they are a weapon in the armament of the oncologist. OVs are unique therapeutics with multiple mechanisms of therapeutic activity. The exact path for their development and eventual uptake by pharmaceutical companies is somewhat clouded by an uncertain identity. Are they vaccines, tumour lysing therapeutics, inducers of innate immunity, gene therapy vectors, anti-vascular agents or all of the above? Should they be developed as stand-alone loco-regional therapeutics, systemically delivered tumour hunters or immune modulators best tested as combination therapeutics? We summarize data here supporting the idea, depending upon the virus, that OVs can be any or all of these things. Pursuing a "one-size fits all" approach is counter-productive to their clinical development and instead as a field we should build on the strengths of individual virus platforms.


Linking changes in antibiotic effluent concentrations to flow, removal and consumption in four different UK sewage treatment plants over four years.
The arrival and discharge of seven antibiotics were monitored at two trickling filter sewage treatment plants of 6000 and 11,000 population equivalents (PE) and two activated sludge plants of 33,000 and 162,000 PE in Southern England. The investigation consisted of 24 h composite samples taken on two separate days every summer from 2012 to 2015 and in the winter of 2015 (January) from influent and effluent. The average influent concentrations generally matched predictions based on England-wide prescription data for trimethoprim, sulfamethoxazole, azithromycin, oxytetracycline and levofloxacin (within 3-fold), but were 3-10 times less for clarithromycin, whilst tetracycline influent concentrations were 5-17 times greater than expected. Over the four years, effluent concentrations at a single sewage plant varied by up to 16-fold for clarithromycin, 10-fold for levofloxacin and sulfamethoxazole, 7-fold for oxytetracycline, 6-fold for tetracycline, 4-fold for azithromycin and 3-fold for trimethoprim. The study attempted to identify the principal reasons for this variation in effluent concentration. By measuring carbamazepine and using it as a conservative indicator of transport through the treatment process, it was found that flow and hence concentration could alter by up to 5-fold. Measuring influent and effluent concentrations allowed assessments to be made of removal efficiency. In the two activated sludge plants, antibiotic removal rates were similar for the tested antibiotics but could vary by several-fold at the trickling filter plants. However, for clarithromycin and levofloxacin the variations in effluent concentration were above that which could be explained by either flow and/or removal alone so here year on year changes in consumption are likely to have played a role.


Effects of lavender aroma on sleep quality in healthy Japanese students.
This single-blind randomized study investigated the effectiveness of lavender aroma on quality of sleep in healthy Japanese students. The data of seven participants (2 men, 5 women) in the intervention group and eight participants (3 men, 5 women) in the control group were analyzed (M age = 19.0 yr., SD = 0.9). The total procedure comprised 3 days for pre-intervention assessment, 5 days for the intervention, and 3 days for post-intervention assessment. Lavender exposure was compared with the absence of lavender (control). Information regarding the relaxing effect of aromas was provided to examine expectancy effects. Results showed that lavender aroma improved sleepiness at awakening after the intervention. Sex differences and daily variation in quality of sleep during the intervention period were not observed. The findings suggest that nighttime exposure to lavender aroma relieves sleepiness at awakening.


Double gradient ion chromatography using short monolithic columns modified with a long chained zwitterionic carboxybetaine surfactant.
The rapid separation of inorganic anions on short monolithic columns permanently coated with a long chained zwitterionic carboxybetaine-type surfactant is shown. The surfactant, N-dodecyl-N,N-(dimethylammonio)undecanoate (DDMAU), was used to coat 2.5, 5.0 and 10 cm long reversed-phase silica monoliths, resulting in a permanent zwitterionic exchange surface when used with aqueous based eluents. The unique structure of the surfactant results in a charge double layer structure on the surface of the stationary phase, with strong internal anionic and weak external cationic exchange groups. The dissociation of the weak external carboxylic acid group acts to shield the inner anionic exchange site, resulting in substantial effective capacity changes with eluent pH. Utilising this effect with the application of an eluent pH gradient, simultaneously combined with eluent flow-rate gradients, very rapid simultaneous separations of both weakly retained anions and strongly retained polarisable anions was possible, with up to 10-fold decreases in overall run times. Coating stability and retention times under isocratic and isofluentic eluent conditions were shown to be reproducible over >450 repeat injections, with peak efficiency values averaging 29,000 N/m for the 2.5 cm column and 42,000 N/m for the 10 cm monolithic column, again under isocratic elution conditions.


Development of 2-hour suicide intervention program among medical residents: first pilot trial.
Suicide is associated not only with primary psychiatric disorders but also with physical disorders. Physicians' education on suicide prevention contributes to reducing suicide. Therefore, medical residents, who contact patients daily and who eventually become primary physicians in each specialty, might be the most appropriate candidates for intervention. In this article, we introduce our newly developed suicide intervention program among medical residents. We developed a 2-hour suicide intervention program among medical residents, based on the Mental Health First Aid (MHFA), which had originally been developed for the public. The program contains a 1-hour lecture and a 1-hour role-play session. As the first pilot trial, we conducted the program among 44 first-year medical residents at a university hospital and evaluated its effectiveness. Changes in confidence, attitudes and behavior toward suicidal people were evaluated using self-reported questionnaires before, immediately after, and 6 months after the program. Participants' confidence and attitudes significantly improved after the program. The total mean score (standard deviation) of the Suicide Intervention Response Inventory improved from 18.4 (2.0) before the intervention to 19.4 (2.0) immediately after the intervention. However, the effectiveness was limited after 6 months. In the course of 6 months, the participants learned to apply the MHFA principles in their daily clinical practice. Our newly developed brief suicide intervention program demonstrating its effectiveness among medical residents should be modified in order to be more effective in the long term. The next trial with a control group ought to be conducted to evaluate our developed program.


Effectiveness of Mentha piperita in the Treatment of Infantile Colic: A Crossover Study.
Background. Infantile colic is a distressing and common condition for which there is no proven standard treatment. Objective. To compare the efficacy of Mentha piperita with simethicone in treatment for infantile colic. Methods. A double-blind crossover study was performed with 30 infants attending IMIP, Recife, Brazil. They were randomized to use Mentha piperita or simethicone in the treatment of infantile colic during 7 days with each drug. Primary outcomes were mother_s opinion about responses to the treatment, number of daily episodes of colic, and time spent crying, measured by a chronometer. Mann-Whitney and chi-square tests were used to compare the results. This study was previously approved by the Ethical Committee in Research at IMIP. Results. At baseline daily episodes of infantile colic was 3.9 (±1.1) and the mean crying time per day was 192 minutes (±51.6). At the end of the study daily episodes of colic fell to 1.6 (±0.6) and the crying duration decreased to 111 (±28) minutes. All mothers reported decrease of frequency and duration of the episodes of infantile colic and there were no differences between responses to Mentha piperita and simethicone. Conclusions. These findings suggest that Mentha piperita may be used to help control infantile colic. However, these results must be repeated by others studies.


Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2.
Oral estrogen administration attenuates the metabolic action of growth hormone (GH) in humans. To investigate the mechanism involved, we studied the effects of estrogen on GH signaling through Janus kinase (JAK)2 and the signal transducers and activators of transcription (STATs) in HEK293 cells stably expressing the GH receptor (293GHR), HuH7 (hepatoma) and T-47D (breast cancer) cells. 293GHR cells were transiently transfected with an estrogen receptor-alpha expression plasmid and luciferase reporters with binding elements for STAT3 and STAT5 or the beta-casein promoter. GH stimulated the reporter activities by four- to sixfold. Cotreatment with 17beta-estradiol (E(2)) resulted in a dose-dependent reduction in the response of all three reporters to GH to a maximum of 49-66% of control at 100 nM (P < 0.05). No reduction was seen when E(2) was added 1-2 h after GH treatment. Similar inhibitory effects were observed in HuH7 and T-47D cells. E(2) suppressed GH-induced JAK2 phosphorylation, an effect attenuated by actinomycin D, suggesting a requirement for gene expression. Next, we investigated the role of the suppressors of cytokine signaling (SOCS) in E(2) inhibition. E(2) increased the mRNA abundance of SOCS-2 but not SOCS-1 and SOCS-3 in HEK293 cells. The inhibitory effect of E(2) was absent in cells lacking SOCS-2 but not in those lacking SOCS-1 and SOCS-3. In conclusion, estrogen inhibits GH signaling, an action mediated by SOCS-2. This paper provides evidence for regulatory interaction between a sex steroid and the GHJAKSTAT pathway, in which SOCS-2 plays a central mechanistic role.


Decoding Episodic Retrieval Processes: Frontoparietal and Medial Temporal Lobe Contributions to Free Recall.
Neuroimaging studies of recognition memory have identified distinct patterns of cortical activity associated with two sets of cognitive processes: Recollective processes supporting retrieval of information specifying a probe item's original source are associated with the posterior hippocampus, ventral posterior parietal cortex, and medial pFC. Familiarity processes supporting the correct identification of previously studied probes (in the absence of a recollective response) are associated with activity in anterior medial temporal lobe (MTL) structures including the perirhinal cortex and anterior hippocampus, in addition to lateral prefrontal and dorsal posterior parietal cortex. Here, we address an open question in the cognitive neuroscientific literature: To what extent are these same neurocognitive processes engaged during an internally directed memory search task like free recall? We recorded fMRI activity while participants performed a series of free recall and source recognition trials, and we used a combination of univariate and multivariate analysis techniques to compare neural activation profiles across the two tasks. Univariate analyses showed that posterior MTL regions were commonly associated with recollective processes during source recognition and with free recall responses. Prefrontal and posterior parietal regions were commonly associated with familiarity processes and free recall responses, whereas anterior MTL regions were only associated with familiarity processes during recognition. In contrast with the univariate results, free recall activity patterns characterized using multivariate pattern analysis did not reliably match the neural patterns associated with recollective processes. However, these free recall patterns did reliably match patterns associated with familiarity processes, supporting theories of memory in which common cognitive mechanisms support both item recognition and free recall.


News Coverage of Cancer in Japanese Newspapers: A Content Analysis.
Newspapers could provide effective and comprehensive information about cancer to the public. The present study conducted a content analysis of cancer-related articles in Japanese newspapers published in 2011. In total, 5,314 articles were identified and subsequently coded. Coding variables included cancer type, the cancer continuum, and topic of articles mentioning cancer. Approximately half mentioned at least one specific type of cancer, with the focus mostly on lung, leukemia, and breast. Stomach and colon cancers, which have the highest morbidity, were relatively underreported. The continuum received little attention, and was mentioned in only 11% of articles. Treatment was the most frequently mentioned part of the continuum, with prevention and screening mentioned only rarely. The most frequently mentioned topic was social issues. The findings suggest that cancer-related articles were found regularly throughout the year, meaning that they might be one of the most important sources of cancer information. However, they are affected by social issues and there were some imbalances in both cancer type and continuum. Considering the influence of newspapers, it would be helpful for providing more effective and accurate information to the public if Japanese newspapers increased mentions of specific types of common cancers and the cancer continuum, especially prevention.


Self management of patients with mild COPD in primary care: randomised controlled trial.
To evaluate the effectiveness of telephone health coaching delivered by a nurse to support self management in a primary care population with mild symptoms of chronic obstructive pulmonary disease (COPD). Multicentre randomised controlled trial. 71 general practices in four areas of England. 577 patients with Medical Research Council dyspnoea scale scores of 1 or 2, recruited from primary care COPD registers with spirometry confirmed diagnosis. Patients were randomised to telephone health coaching (n=289) or usual care (n=288). Telephone health coaching intervention delivered by nurses, underpinned by Social Cognitive Theory. The coaching promoted accessing smoking cessation services, increasing physical activity, medication management, and action planning (4 sessions over 11 weeks; postal information at weeks 16 and 24). The nurses received two days of training. The usual care group received a leaflet about COPD. The primary outcome was health related quality of life at 12 months using the short version of the St George's Respiratory Questionnaire (SGRQ-C). The intervention was delivered with good fidelity: 86% of scheduled calls were delivered; 75% of patients received all four calls. 92% of patients were followed-up at six months and 89% at 12 months. There was no difference in SGRQ-C total score at 12 months (mean difference -1.3, 95% confidence interval -3.6 to 0.9, P=0.23). Compared with patients in the usual care group, at six months follow-up, the intervention group reported greater physical activity, more had received a care plan (44% v 30%), rescue packs of antibiotics (37% v 29%), and inhaler use technique check (68% v 55%). A new telephone health coaching intervention to promote behaviour change in primary care patients with mild symptoms of dyspnoea did lead to changes in self management activities, but did not improve health related quality of life. Current controlled trials ISRCTN 06710391.


Structure of the vacuolar-type ATPase from Saccharomyces cerevisiae at 11-Å resolution.
Vacuolar-type ATPases (V-type ATPases) in eukaryotic cells are large membrane protein complexes that acidify various intracellular compartments. The enzymes are regulated by dissociation of the V(1) and V(O) regions of the complex. Here we present the structure of the Saccharomyces cerevisiae V-type ATPase at 11-Å resolution by cryo-EM of protein particles in ice. The structure explains many cross-linking and protein interaction studies. Docking of crystal structures suggests that inhibition of ATPase activity by the dissociated V(1) region involves rearrangement of the N- and C-terminal domains of subunit H and also suggests how this inhibition is triggered upon dissociation. We provide support for this model by demonstrating that mutation of subunit H to increase the rigidity of the linker between its two domains decreases its ability to inhibit ATPase activity.


Exploiting protein cationization techniques in future drug development.
The development of a method for the efficient intracellular delivery of inherently non-permeable proteins is needed for manipulation of cellular phenotypes or the discovery of protein-based drugs. It has been demonstrated that proteins artificially cationized by chemical conjugation show efficient intracellular delivery via adsorptive-mediated endocytosis and then can exert their biological activity in cells. Studies have also revealed that cationic peptides known as cell-penetrating peptides (CPPs) provide a means to deliver molecules into mammalian cells. Although the internalization mechanisms remain controversial, it is now becoming clear that the main port of entry into cells by CPPs also involves adsorptive-mediated endocytosis rather than the direct penetration of the plasma membrane. As the mammalian cell membrane possesses an abundance of negatively charged glycoproteins and glycosphingolipids, cationization of proteins is a reasonable choice to endow them with the ability for intracellular delivery. Cationization of proteins is usually accompanied by drastic changes in protein properties, structure and biological activities. Recently developed sophisticated protein chemistry can minimize these side effects. Therefore, protein cationization techniques will hopefully prove to be powerful tools for innovative research and drug discovery. In this review, techniques for cationization of proteins and their intracellular delivery, as well as some of their potential therapeutic applications, are discussed.


Introduction to glycopathology: the concept, the tools and the perspectives.
Analyzing the flow of biological information is a fundamental challenge for basic sciences. The emerging results will then lend themselves to the development of new approaches for medical applications. Toward this end, the products of protein/lipid glycosylation deserve special attention. The covalent attachment of sugars to these carriers means much more than just a change of the carriers' physicochemical properties. In principle, the ubiquitous presence of glycoconjugates and the close inspection of the particular structural 'talents' of carbohydrates provide suggestive evidence for information coding by sugars. In fact, the theoretical number of 'words' (oligomers) formed by 'letters' (monosaccharides) is by far higher than by using nucleotides or amino acids. In other words, glycans harbor an unsurpassed coding capacity. The cyto- and histochemical detection of dynamic changes in the profile of cellular glycans (glycome, the equivalent of the proteome) by sugar receptors such as antibodies used as tools underscores the suitability of carbohydrates for such a task. The resulting staining patterns can be likened to a molecular fingerprint. By acting as ligand (counterreceptor) for endogenous receptors (tissue lectins), glycan epitopes become partners in a specific recognition pair, and the sugar-encoded information can then be translated into effects, e.g. in growth regulation. Of note, expression of both sides of such a pair, i.e. lectin and cognate glycan, can physiologically be orchestrated for optimal efficiency. Indeed, examples how to prevent autoimmune diseases by regulatory T cells and restrict carcinoma growth by a tumor suppressor attest occurrence of co-regulation. In consequence, these glycans have potential to establish a new class of functional biomarkers, and mapping presence of their receptors is warranted. In this review, the cyto- and histochemical methods, which contribute to explore information storage and transfer within the sugar code, are described. This introduction to the toolbox is flanked by illustrating the application of each type of tool in histopathology, with focus on adhesion/growth-regulating galectins. Together with an introduction to fundamental principles of the sugar code, the review is designed to guide into this field and to inspire respective research efforts. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1670639891114983.


Research preparedness paves the way to respond to pandemic H1N1 2009 influenza virus.
The international community has been preparing for an influenza pandemic because of the threat posed by H5N1 avian influenza. Over the past several years, Canada has dedicated funding to boost capacity for research, and public health and health care system readiness and response in the event of a pandemic. The current H1N1/09 influenza pandemic is now testing our readiness. From a research perspective, the present commentary discusses how have we prepared, along with the research gaps. We conclude that: sources of pandemics are not always predictable; investment in the past few years has paid off in a rapid response to pandemic H1N1/09 virus in Canada; and research to meet the challenges of infectious diseases has to be done on an ongoing long-term basis, and its funding has to be flexible, available and predictable to maintain capacity and expertise. In addition, new vaccine technologies are needed to develop and produce vaccines for public health emergencies in a timely fashion.


Degenerative dementia with proximal radial and lower vertical spatial neglect.
A 75 year-old man had a two-year history of progressive memory loss, trouble with finances and getting lost. On examination, he scored 16/30 in MoCA test, noticeably impaired on the attentional tasks. His screening bloodtests werenormal. Brain imaging revealed hippocampal atrophy and bilaterallarge areas of leukoaraiosis below posterior parietal lobes. On vertical line bisection he revealed a large upward bias and on radial bisection, a distal bias. Degeneration of his posterior parietal cortex may have caused both the leukoaraiosis and vertical-radial neglect. Unawareness of portions of space can be a source of disability and cause injury. Therefore, patients with degenerative dementia, especially those with similar patterns of leukoaraiosis or parietal degeneration should be tested for vertical and radial forms of spatial neglect.


Bidirectional reflectance distribution function effects in ladar-based reflection tomography.
Light reflection from a surface is described by the bidirectional reflectance distribution function (BRDF). In this paper, BRDF effects in reflection tomography are studied using modeled range-resolved reflection from well-characterized geometrical surfaces. It is demonstrated that BRDF effects can cause a darkening at the interior boundary of the reconstructed surface analogous to the well-known beam hardening artifact in x-ray transmission computed tomography (CT). This artifact arises from reduced reflection at glancing incidence angles to the surface. It is shown that a purely Lambertian surface without shadowed components is perfectly reconstructed from range-resolved measurements. This result is relevant to newly fabricated carbon nanotube materials. Shadowing is shown to cause crossed streak artifacts similar to limited-angle effects in CT reconstruction. In tomographic reconstruction, these effects can overwhelm highly diffuse components in proximity to specularly reflecting elements. Diffuse components can be recovered by specialized processing, such as reducing glints via thresholded measurements.


Malaria infected mosquitoes express enhanced attraction to human odor.
There is much evidence that some pathogens manipulate the behaviour of their mosquito hosts to enhance pathogen transmission. However, it is unknown whether this phenomenon exists in the interaction of Anopheles gambiae sensu stricto with the malaria parasite, Plasmodium falciparum--one of the most important interactions in the context of humanity, with malaria causing over 200 million human cases and over 770 thousand deaths each year. Here we demonstrate, for the first time, that infection with P. falciparum causes alterations in behavioural responses to host-derived olfactory stimuli in host-seeking female An. gambiae s.s. mosquitoes. In behavioural experiments we showed that P. falciparum-infected An. gambiae mosquitoes were significantly more attracted to human odors than uninfected mosquitoes. Both P. falciparum-infected and uninfected mosquitoes landed significantly more on a substrate emanating human skin odor compared to a clean substrate. However, significantly more infected mosquitoes landed and probed on a substrate emanating human skin odor than uninfected mosquitoes. This is the first demonstration of a change of An. gambiae behaviour in response to olfactory stimuli caused by infection with P. falciparum. The results of our study provide vital information that could be used to provide better predictions of how malaria is transmitted from human being to human being by An. gambiae s.s. females. Additionally, it highlights the urgent need to investigate this interaction further to determine the olfactory mechanisms that underlie the differential behavioural responses. In doing so, new attractive compounds could be identified which could be used to develop improved mosquito traps for surveillance or trapping programmes that may even specifically target P. falciparum-infected An. gambiae s.s. females.


Binocular open-view instrument to measure aberrations and pupillary dynamics.
We have designed and built a binocular Hartmann-Shack wave-front sensor using a single microlens array and camera for real-time aberration measurement of both eyes in an open-view configuration. Furthermore, the use of a long wavelength (1050 nm) laser diode makes the illumination source completely invisible, so that measurements can be unobtrusively performed while the subject stares at the visual world under realistic conditions. The setup provides a large dynamic range and simultaneous measurements of convergence, pupil size, accommodation, and aberrations. The open-view design not only offers the possibility of measuring the subject's ocular optics under natural conditions but also allows coupling the device with other existing vision testing instruments and setups, which increases its potential to become a powerful tool for different visual optics studies.


Bacterial diversity of a Carolina bay as determined by 16S rRNA gene analysis: confirmation of novel taxa.
Carolina bays are naturally occurring shallow elliptical depressions largely fed by rain and shallow ground water. To identify members of the domain Bacteria which inhibit such an environment, we used PCR to construct a library of 16S rRNA genes (16S rDNAs) cloned from DNA extracted from the sediments of Rainbow bay, located on the Savannah River Site, near Aiken, S.C. Oligonucleotides complementary to conserved regions of 16S rDNA were used as primers for PCR, and gel-purified PCR products were cloned into vector pGEM-T. Partial sequencing of the cloned 16S rDNAs revealed an extensive amount of phylogenetic diversity within this system. Of the 35 clones sequenced, 32 were affiliated with five bacterial groups: 11 clustered with the Proteobacteria division (including members of the alpha, beta, and delta subdivisions), 8 clustered with the Acidobacterium subdivision of the Fibrobacter division (as categorized by the Ribosomal Database Project's taxonomic scheme, version 5.0), 7 clustered with the Verrucomicrobium subdivision of the Planctomyces division, 3 clustered with the gram-positive bacteria (Clostridium and relatives subdivision), and 3 clustered with the green nonsulfur bacteria. One sequence branched very deeply from the Bacteria and was found not to be associated with any of the major divisions when phylogenetic trees were constructed. Two clones did not consistently cluster with specific groups and may be chimeric sequences. None of the clones exhibited an exact match to any of the 16S rDNA sequences deposited in the databases, suggesting that most of the bacteria in Rainbow Bay are novel species. In particular, the clones related to the Acidobacterium subdivision and the Verrucomicrobium subdivision confirm the presence of novel taxa discovered previously in other molecular surveys of this type.


Effect of capillary condensation on friction force and adhesion.
Friction force measurements have been conducted with a colloid probe on mica and silica (both hydrophilic and hydrophobized) after long (24 h) exposure to high-humidity air. Adhesion and friction measurements have also been performed on cellulose substrates. The long exposure to high humidity led to a large hysteresis between loading and unloading in the friction measurements with separation occurring at large negative applied loads. The large hysteresis in the friction-load relationship is attributed to a contact area hysteresis of the capillary condensate which built up during loading and did not evaporate during the unloading regime. The magnitude of the friction force varied dramatically between substrates and was lowest on the mica substrate and highest on the hydrophilic silica substrate, with the hydrophobized silica and cellulose being intermediate. The adhesion due to capillary forces on cellulose was small compared to that on the other substrates, due to the greater roughness of these surfaces.


A New Clip Generation for Microsurgical Treatment of Intracranial Aneurysms-The First Case Series.
Considerable effort has been made in order to reduce surgical invasiveness while maintaining optimal exploiting of the operative space in aneurysm surgery. One aspect of this evolution is represented by the Lazic (Peter Lazic GmbH, Tuttlingen, Germany) aneurysm clip system. The purpose of this study was to illustrate the new generation clip system in practiced aneurysm surgery. A retrospective analysis of all aneurysm surgeries in our departments between December 2015 and January 2018 using the new D-Clip system was performed. Evaluation included standardized retrospective review of the main surgeon, the nursing staff, as well as an analysis of surgical video documentation by objective reviewers. Forty-five patients with 50 intracranial aneurysms underwent surgical clipping using the D-Clip system. A total of 64 permanent and 19 temporary D-Clips were applied. Nine clips needed to be replaced. All aneurysms could be occluded totally. Surgeons considered handling and manoeuvrability of clip application as feasible and good in all cases (100%), even under impaired visibility circumstances (14%). Objective video analysis revealed comparable results. Nursing staff scored handling and practicability of D-Clips equivalent to the preceding L-Clip generation. There were no intraoperative complications. Surgery-related postoperative morbidity was 6.7%. The new D-Clip system combines an attenuated design for minimally invasive clipping procedures with traditional mechanisms of common clip systems. It therefore appears to be highly versatile in the context of variable different aneurysm morphologies and locations while maintaining high standard surgical safety and efficacy.


The HVEM network: new directions in targeting novel costimulatory/co-inhibitory molecules for cancer therapy.
The regulation of the immune system is controlled by many cell surface receptors. A prominent representative is the 'molecular switch' HVEM (herpes virus entry mediator) that can activate either proinflammatory or inhibitory signaling pathways. HVEM ligands belong to two distinct families: the TNF-related cytokines LIGHT and lymphotoxin-α, and the Ig-related membrane proteins BTLA and CD160. HVEM and its ligands have been involved in the pathogenesis of various autoimmune and inflammatory diseases, but recent reports indicate that this network may also be involved in tumor progression and resistance to immune response. Here we summarize the recent advances made regarding the knowledge on HVEM and its ligands in cancer cells, and their potential roles in tumor progression and escape to immune responses. Blockade or enhancement of these pathways may help improving cancer therapy.


Analysis of glyphosate and aminomethylphosphonic acid in leaves from Coffea arabica using high performance liquid chromatography with quadrupole mass spectrometry detection.
Glyphosate is a commonly applied herbicide in coffee plantations. Because of its non-selective mode of action it can damage the crop exposed through spray drift. Therefore, it is of interest to study glyphosate fate in coffee plants. The aim of this study was to develop an analytical method for accurate and precise quantification of glyphosate and its main metabolite aminomethylphosphonic acid (AMPA) at trace levels in coffee leaves using liquid chromatography with single-quadrupole mass spectrometry detection. The method is based on a two-step solid phase extraction (SPE) with an intermediate derivatization reaction using 9-fluorenylmethylchloroformate (FMOC). An isotope dilution method was used to account for matrix effects and to enhance the confidence in analyte identification. The limit of quantification (LOQ) for glyphosate and AMPA in coffee leaves was 41 and 111 μg kg(-1) dry weight, respectively. For the method optimization a design of experiments (DOE) approach was used. The sample clean-up procedure can be simplified for the analysis of less challenging matrices, for laboratories having a tandem mass spectrometry detector and for cases in which quantification limits above 0.1 mg kg(-1) are acceptable, which is often the case for glyphosate. The method is robust, possesses high identification confidence, while being suitable for most commercial and academic laboratories. All leaf samples from five coffee fields analyzed (n=21) contained glyphosate, while AMPA was absent. The simplified clean-up procedure was successfully validated for coffee leaves, rice, black beans and river water.


Defective proliferative capacity and accelerated telomeric loss of hematopoietic progenitor cells in rheumatoid arthritis.
In rheumatoid arthritis (RA), telomeres of lymphoid and myeloid cells are age-inappropriately shortened, suggesting excessive turnover of hematopoietic precursor cells (HPCs). The purpose of this study was to examine the functional competence (proliferative capacity, maintenance of telomeric reserve) of CD34+ HPCs in RA. Frequencies of peripheral blood CD34+,CD45+ HPCs from 63 rheumatoid factor-positive RA patients and 48 controls matched for age, sex, and ethnicity were measured by flow cytometry. Proliferative burst, cell cycle dynamics, and induction of lineage-restricted receptors were tested in purified CD34+ HPCs after stimulation with early hematopoietins. Telomere sequences were quantified by real-time polymerase chain reaction. HPC functions were correlated with the duration, activity, and severity of RA as well as its treatment. In healthy donors, CD34+ HPCs accounted for 0.05% of nucleated cells; their numbers were strictly age dependent and declined at a rate of 1.3% per year. In RA patients, CD34+ HPC frequencies were age-independently reduced to 0.03%. Upon growth factor stimulation, control HPCs passed through 5 replication cycles over 4 days. In contrast, RA-derived HPCs completed only 3 generations. Telomeres of RA CD34+ HPCs were age-inappropriately shortened by 1,600 bp. All HPC defects were independent of disease duration, disease activity, and smoking status, and were present to the same degree in untreated patients. In RA, circulating bone marrow-derived progenitor cells were diminished, and concentrations stagnated at levels typical of those in old control subjects. HPCs from RA patients displayed growth factor nonresponsiveness and sluggish cell cycle progression; marked telomere shortening indicated proliferative stress-induced senescence. Defective HPC function independent of disease activity markers suggests bone marrow failure as a potential pathogenic factor in RA.


Acceptance and tolerability of an adjuvanted nH1N1 vaccine in HIV-infected patients in the Cologne-Bonn cohort.
To evaluate the acceptance and tolerability of the nH1N1 2009 vaccine in HIV-positive individuals. 758 patients were included in this prospective study. Different study populations were formed: The Tolerability Study Group consists of HIV-infected patients who visited three outpatient clinics (Cologne, Bonn, Freiburg) during a predefined time period. Patients were offered nH1N1 vaccination. Those accepting were administered a standard dose AS03 adjuvant nH1N1 vaccine. Questionnaires to report side effects occurring within 7 days after immunization were handed out. In a substudy conducted during the same time period, acceptance towards immunization was recorded. This Acceptance Study Group consists of all HIV-infected patients visiting the Cologne clinic. They were offered vaccination. In case of refusal, motivation was recorded. In the Tolerability Study Group, a total of 475 patient diaries returned in the three study centres could be evaluated, 119 of those (25%) reported no side effects. Distribution of symptoms was as follows: Pain 285/475 patients (60%), swelling 96 (20%), redness 54 (11%), fever 48/475 (10%), muscle/joint ache 173 (36%), headache 127 (27%), and fatigue 210 (44%). Association of side effects with clinical data was calculated for patients in Cologne and Bonn. Incidence of side effects was significantly associated with CDC stages A, B compared to C, and with a detectable viral load (>50 copies/mL). No correlation was noted for CD4 cell count, age, gender or ethnicity. - In the Acceptance Study Group, 538 HIV-infected patients were offered vaccination, 402 (75%) accepted, while 136 (25%) rejected. Main reasons for rejection were: Negative media coverage (35%), indecisiveness with preference to wait until a later date (23%), influenza not seen as personal threat (19%) and scepticism towards immunization in general (10%). A total of 622 HIV-infected patients were vaccinated against nH1N1-influenza in the three study centres. No severe adverse events were reported. The tolerability was in most parts comparable to general population. Acceptance rate towards influenza vaccination was high (75%). Those refusing the immunization mentioned negative media coverage as the major influence on their decision.


Elucidating ultrafast electron dynamics at surfaces using extreme ultraviolet (XUV) reflection-absorption spectroscopy.
Here we review the recent development of extreme ultraviolet reflection-absorption (XUV-RA) spectroscopy. This method combines the benefits of X-ray absorption spectroscopy, such as element, oxidation, and spin state specificity, with surface sensitivity and ultrafast time resolution, having a probe depth of only a few nm and an instrument response less than 100 fs. Using this technique we investigated the ultrafast electron dynamics at a hematite (α-Fe2O3) surface. Surface electron trapping and small polaron formation both occur in 660 fs following photoexcitation. These kinetics are independent of surface morphology indicating that electron trapping is not mediated by defects. Instead, small polaron formation is proposed as the likely driving force for surface electron trapping. We also show that in Fe2O3, Co3O4, and NiO, band gap excitation promotes electron transfer from O 2p valence band states to metal 3d conduction band states. In addition to detecting the photoexcited electron at the metal M2,3-edge, the valence band hole is directly observed as transient signal at the O L1-edge. The size of the resulting charge transfer exciton is on the order of a single metal-oxygen bond length. Spectral shifts at the O L1-edge correlate with metal-oxygen bond covalency, confirming the relationship between valence band hybridization and the overpotential for water oxidation. These examples demonstrate the unique ability to measure ultrafast electron dynamics with element and chemical state resolution using XUV-RA spectroscopy. Accordingly, this method is poised to play an important role to reveal chemical details of previously unseen surface electron dynamics.


[Spatial distribution of elderly individuals in a medium-sized city in São Paulo State, Brazil, according to key socio-demographic and morbidity characteristics].
Geographic Information Systems serve as important public health tools for analyzing population disease distribution and thus for identifying individuals with chronic non-communicable diseases. The current study performed a spatial analysis of the distribution of the population 60 years and older in the city of Botucatu, São Paulo State, Brazil, studying the socio-demographic profile and the presence of diabetes mellitus and arterial hypertension. Data were analyzed from 468 elderly individuals from a population survey conducted in 2001-2002. Elders with the highest socioeconomic status live in the census tracts with the highest social strata, as proven statistically by spatial analysis techniques for income and schooling. No spatial distribution pattern was found for elderly individuals with hypertension and diabetes, who were located heterogeneously on the map. The study suggests the use of geoprocessing techniques for digital mapping of areas covered by primary health care units, aimed at better monitoring of the distribution of elderly individuals with chronic diseases and their care by health professionals.


Rare somatic cells from human breast tissue exhibit extensive lineage plasticity.
We identified cell surface markers associated with repression of p16(INK4a)/cyclin-dependent kinase inhibitor 2A(CDKN2A), a critical determinant in the acquisition of a plastic state. These cell surface markers allowed direct isolation of rare cells from healthy human breast tissue that exhibit extensive lineage plasticity. This subpopulation is poised to transcribe plasticity markers, OCT3/4, SOX2, and NANOG, at levels similar to those measured in human embryonic stem cells and to acquire a plastic state sensitive to environmental programming. In vitro, in vivo, and teratoma assays demonstrated that either a directly sorted (uncultured) or a single-cell (clonogenic) cell population from primary tissue can differentiate into functional derivatives of each germ layer, ectodermal, endodermal, and mesodermal. In contrast to other cells that express OCT3/4, SOX2, and NANOG, these human endogenous plastic somatic cells are mortal, express low telomerase activity, expand for an extensive but finite number of population doublings, and maintain a diploid karyotype before arresting in G1.


A randomized controlled trial of very early rehabilitation in speech after stroke.
The efficacy of rehabilitation therapy for aphasia caused by stroke is uncertain. The Very Early Rehabilitation of Speech (VERSE) trial aims to determine if intensive prescribed aphasia therapy (VERSE) is more effective and cost saving than non-prescribed, intensive (usual care-plus) and non-intensive usual care (UC) therapy when started within 15 days of stroke onset and continued daily over four weeks. We hypothesize that aphasia therapy when started very early after stroke and delivered daily could enhance recovery of communication compared with UC. A total of 246 participants (82 per arm) will provide 80% power to detect a 4.4% improvement on aphasia quotient between VERSE and UC plus at a significance level of α = 0.05. Acute-care hospitals and accompanying rehabilitation services throughout Australia, 2014-2017. Three-arm, prospective, randomized, parallel group, open-label, blinded endpoint assessment (PROBE) trial. Acute stroke in previous 14 days and aphasia diagnosed by aphasia quotient (AQ) of the Western Aphasia Battery (WAB). Computer-generated blocked randomization procedure stratified by aphasia severity according to Western Aphasia Battery, to one of three arms. All participants receive UC-usual ward-based aphasia therapy. Arm 1: UC-no additional therapy; Arm 2: UC-plus usual ward-based therapy; Arm 3: VERSE therapy-a prescribed and structured aphasia therapy program. Arms 2 and 3 receive a total of 20 additional sessions (45-60 min, provided daily) of aphasia therapy. The additional intervention must be provided before day 50 post stroke. The aphasia quotient of Western Aphasia Battery at 12 weeks post stroke. Secondary outcomes include discourse measures, the Stroke and Aphasia Quality of Life Scale-39 and the Aphasia Depression Rating Scale at 12 and 26 weeks. Incremental cost-effectiveness ratios at 26 weeks will be reported. This trial is designed to test whether the intensive and prescribed VERSE intervention is effective in promoting maximum recovery and preventing costly health complications in a vulnerable population of survivors of stroke. It will also provide novel, prospective, aphasia specific cost-effectiveness data to guide future policy development for this population.


Intestinal Transcriptome Analysis Reveals Soy Derivative-Linked Changes in Atlantic Salmon.
Intestinal inflammation in farmed fish is a non-infectious disease that deserves attention because it is a major issue linked to carnivorous fishes. The current norm is to formulate feeds based on plant-derived substances, and the ingredients that have antinutritional factors are known to cause intestinal inflammation in fishes such as Atlantic salmon. Hence, we studied inflammatory responses in the distal intestine of Atlantic salmon that received a feed rich in soybean derivatives, employing histology, transcriptomic and flow cytometry techniques. The fish fed on soy products had altered intestinal morphology as well as upregulated inflammation-associated genes and aberrated ion transport-linked genes. The enriched pathways for the upregulated genes were among others taurine and hypotaurine metabolism, drug metabolism-cytochrome P450 and steroid biosynthesis. The enriched gene ontology terms belonged to transmembrane transporter- and channel-activities. Furthermore, soybean products altered the immune cell counts; lymphocyte-like cell populations were significantly higher in the whole blood of fish fed soy products than those of control fish. Interestingly, the transcriptome of the head kidney did not reveal any differential gene expression, unlike the observations in the distal intestine. The present study demonstrated that soybean derivatives could evoke marked changes in intestinal transport mechanisms and metabolic pathways, and these responses are likely to have a significant impact on the intestine of Atlantic salmon. Hence, soybean-induced enteritis in Atlantic salmon is an ideal model to investigate the inflammatory responses at the cellular and molecular levels.


Glutamine-induced signaling pathways via amino acid receptors in enteroendocrine L cell lines.
Glucagon-like peptide-1 (GLP-1), secreted by gastrointestinal enteroendocrine L cells, induces insulin secretion and is important for glucose homeostasis. GLP-1 secretion is induced by various luminal nutrients, including amino acids. Intracellular Ca2+ and cAMP dynamics play an important role in GLP-1 secretion regulation; however, several aspects of the underlying mechanism of amino acid-induced GLP-1 secretion are not well characterized. We investigated the mechanisms underlying the L-glutamine-induced increase in Ca2+ and cAMP intracellular concentrations ([Ca2+]i and [cAMP]i, respectively) in murine enteroendocrine L cell line GLUTag cells. Application of L-glutamine to cells under low extracellular [Na+] conditions, which inhibited the function of the sodium-coupled L-glutamine transporter, did not induce an increase in [Ca2+]i. Application of G protein-coupled receptor family C group 6 member A and calcium-sensing receptor antagonist showed little effect on [Ca2+]i and [cAMP]i; however, taste receptor type 1 member 3 (TAS1R3) antagonist suppressed the increase in [cAMP]i. To elucidate the function of TAS1R3, which forms a heterodimeric umami receptor with taste receptor type 1 member 1 (TAS1R1), we generated TAS1R1 and TAS1R3 mutant GLUTag cells using the CRISPR/Cas9 system. TAS1R1 mutant GLUTag cells exhibited L-glutamine-induced increase in [cAMP]i, whereas some TAS1R3 mutant GLUTag cells did not exhibit L-glutamine-induced increase in [cAMP]i and GLP-1 secretion. These findings suggest that TAS1R3 is important for L-glutamine-induced increase in [cAMP]i and GLP-1 secretion. Thus, TAS1R3 may be coupled with Gs and related to cAMP regulation.


Novel bacterial lineages associated with boreal moss species.
Mosses are critical components of boreal ecosystems where they typically account for a large proportion of net primary productivity and harbour diverse bacterial communities that can be the major source of biologically-fixed nitrogen in these ecosystems. Despite their ecological importance, we have limited understanding of how microbial communities vary across boreal moss species and the extent to which local site conditions may influence the composition of these bacterial communities. We used marker gene sequencing to analyze bacterial communities associated with seven boreal moss species collected near Fairbanks, AK, USA. We found that host identity was more important than site in determining bacterial community composition and that mosses harbour diverse lineages of potential N2 -fixers as well as an abundance of novel taxa assigned to understudied bacterial phyla (including candidate phylum WPS-2). We performed shotgun metagenomic sequencing to assemble genomes from the WPS-2 candidate phylum and found that these moss-associated bacteria are likely anoxygenic phototrophs capable of carbon fixation via RuBisCo with an ability to utilize byproducts of photorespiration from hosts via a glyoxylate shunt. These results give new insights into the metabolic capabilities of understudied bacterial lineages that associate with mosses and the importance of plant hosts in shaping their microbiomes.


5-azacitidine efficacy and safety in patients aged >65 years with myelodysplastic syndromes outside clinical trials.
The efficacy and safety of azacitidine in elderly patients (aged >65 years) with myelodysplastic syndromes (MDS) treated outside clinical trials are reported. Thirty-eight patients with MDS received azacitidine (75 mg/m(2), schedule 5+2 +2): seven patients were classified as having refractory cytopenia with multilineage dysplasia (RCMD), nine patients with refractory anemia with excess of blasts (RAEB) type 1, 18 patients with RAEB type 2 and four patients with chronic myelomonocytic leukemia type 2 (CMML-2). According to International Working Group (IWG) 2006 criteria, after the first four cycles we detected complete remission in seven patients (CR, 18%), improvement of bone marrow dysplasia and reduction of blast percentage in seven patients (partial response, 18%), stable disease in 20 patients (53%) and progression to acute leukemia in four patients (10%). Median overall survival for all patients treated was 16.4 months. Only mild non-hematologic toxicity was detected (grade 1-2 nausea and pruritus), whereas 55% of patients experienced hematologic side effects (25% grade 3-4 thrombocytopenia and 30% grade 3-4 neutropenia). Our results suggest that advanced age should not preclude effective treatment with azacitidine in non-selected elderly patients wih MDS.


Cloning, characterization, and functional expression of acs, the gene which encodes acetyl coenzyme A synthetase in Escherichia coli.
Acetyl coenzyme A synthetase (Acs) activates acetate to acetyl coenzyme A through an acetyladenylate intermediate; two other enzymes, acetate kinase (Ack) and phosphotransacetylase (Pta), activate acetate through an acetyl phosphate intermediate. We subcloned acs, the Escherichia coli open reading frame purported to encode Acs (F. R. Blattner, V. Burland, G. Plunkett III, H. J. Sofia, and D. L. Daniels, Nucleic Acids Res. 21:5408-5417, 1993). We constructed a mutant allele, delta acs::Km, with the central 0.72-kb BclI-BclI portion of acs deleted, and recombined it into the chromosome. Whereas wild-type cells grew well on acetate across a wide range of concentrations (2.5 to 50 mM), those deleted for acs grew poorly on low concentrations (< or = 10 mM), those deleted for ackA and pta (which encode Ack and Pta, respectively) grew poorly on high concentrations (> or = 25 mM), and those deleted for acs, ackA, and pta did not grow on acetate at any concentration tested. Expression of acs from a multicopy plasmid restored growth to cells deleted for all three genes. Relative to wild-type cells, those deleted for acs did not activate acetate as well, those deleted for ackA and pta displayed even less activity, and those deleted for all three genes did not activate acetate at any concentration tested. Induction of acs resulted in expression of a 72-kDa protein, as predicted by the reported sequence. This protein immunoreacted with antiserum raised against purified Acs isolated from an unrelated species, Methanothrix soehngenii. The purified E. coli Acs then was used to raise anti-E. coli Acs antiserum, which immunoreacted with a 72-kDa protein expressed by wild-type cells but not by those deleted for acs. When purified in the presence, but not in the absence, of coenzyme A, the E. coli enzyme activated acetate across a wide range of concentrations in a coenzyme A-dependent manner. On the basis of these and other observations, we conclude that this open reading frame encodes the acetate-activating enzyme, Acs.


Factors affecting short-term precision of musculoskeletal measures using peripheral quantitative computed tomography (pQCT).
Few studies have investigated factors influencing the precision of peripheral quantitative computed tomography (pQCT) measures. This study found time between repeat scans and subject anthropometric characteristics to influence short-term precision of pQCT-derived measures in the lower leg. These findings have implications for both investigators and clinicians utilizing pQCT outcomes. Peripheral quantitative computed tomography (pQCT) is increasingly being used to investigate musculoskeletal changes associated with age, disease and/or intervention. Precision of pQCT measures is of paramount importance in this endeavor. This study aimed to establish the short-term precision of pQCT-derived musculoskeletal measures of the lower leg and investigate factors influencing this precision. Thirty healthy subjects had a series of six pQCT scans of the lower leg (66% of tibial length proximal from its distal end) performed on two separate days by two different testers. The influences of different testers, time between repeat scans, and subject anthropometric characteristics on precision were explored. Overall precision error (root mean square) increased from bone (<1%) to muscle (<1.5%) to fat (3%). The two testers were equally precise in performing pQCT measures; however, precision error increased when repeat scans were repeated 1 week apart as opposed to on the same day. Subject anthropometric characteristics influenced precision errors with the general finding being that an increase in subject size was associated with less precise pQCT measures. pQCT is a relatively precise technique for the assessment of bone and muscle, but precision is influenced by time between repeat scans and subject anthropometric characteristics. Investigators and clinicians need to be aware of these factors influencing pQCT outcomes as they may influence statistical power in clinical studies and the characterization of change in individual patients.


Real-time visualization of human prolactin alternate promoter usage in vivo using a double-transgenic rat model.
We have generated a humanized double-reporter transgenic rat for whole-body in vivo imaging of endocrine gene expression, using the human prolactin (PRL) gene locus as a physiologically important endocrine model system. The approach combines the advantages of bacterial artificial chromosome recombineering to report appropriate regulation of gene expression by distant elements, with double reporter activity for the study of highly dynamic promoter regulation in vivo and ex vivo. We show first that this rat transgenic model allows quantitative in vivo imaging of gene expression in the pituitary gland, allowing the study of pulsatile dynamic activity of the PRL promoter in normal endocrine cells in different physiological states. Using the dual reporters in combination, dramatic and unexpected changes in PRL expression were observed after inflammatory challenge. Expression of PRL was shown by RT-PCR to be driven by activation of the alternative upstream extrapituitary promoter and flow cytometry analysis pointed at diverse immune cells expressing the reporter gene. These studies demonstrate the effective use of this type of model for molecular physiology and illustrate the potential for providing novel insight into human gene expression using a heterologous system.


Vomiting as an ictal manifestation of epileptic seizures and syndromes.
Twenty-four out of 900 adult and children patients with epilepsy, were found to have vomiting during an ictus. All the 24 patients were children before puberty with a similar clinical pattern consisting of partial seizures which were mainly nocturnal. Ictal vomiting was always concurrent with other epileptic manifestations, more often deviation of the eyes and impairment of consciousness. The initial part of the ictus was short or prolonged for hours with frequent "marching" to hemi-convulsions and generalised seizures. Seventeen of the 24 children suffered from benign childhood epilepsies (BCE) with complete remission in long follow-up. A significantly higher association was found between ictal vomiting and the syndrome of BCE with occipital spikes (p less than 0.001) but not with centro-temporal spikes (p less than 0.2). The recognition of this association may have important theoretical implications. On clinical grounds, it may prevent unnecessary investigations and undue concern.


Patient attitudes, behaviours, and other factors considered by doctors when estimating cancer patients' anxiety and desire for information.
The aim was to describe the patient attitudes, behaviours, and other factors, considered by doctors when estimating cancer patients' worry about how the disease may develop and the desire for information about the disease and its treatment. Data was gathered through semi-structured interviews with 19 doctors regarding 29 patients within endocrine oncology and haematology care, and the data were analysed by content analysis. The doctors considered the patients' verbal expressions, verbal behaviours, questions, body language, and facial expressions together with their own professional knowledge and experience, when estimating the patients' worry and desire for information. The doctors also considered contextual factors, patients' demographical factors, and medical situation when estimating the patients' worry, and also when estimating the patients' desire for information. The findings illustrate that estimating patients' worry and desire for information is a multifaceted and complex task, and that doctors consider not only the patients' verbal and nonverbal cues, but also factors, such as their own professional knowledge and experience, contextual factors, and patients' demographical variables. The findings should be communicated to doctors who meet cancer patients in medical consultations in order to illuminate the complexity of the medical consultation. The awareness of potentially important patient cues and other factors may aid doctors in their efforts to gain insight about their patients' emotions and informational needs.


Individually Dispersed Wood-Based Cellulose Nanocrystals.
Good dispersion of cellulose nanocrystals (CNCs) in the polymer matrix is one of the key factors to obtaining good properties in the resulting nanocomposites. However, the preparation of individually dispersed CNCs in solvents or in polymer matrices has been a challenge. In this study, individually dispersed wood-based CNCs have been successfully prepared in solvents, including dimethylformamide (DMF), H2O, and a mixture of H2O/DMF, by sonication of moisture-containing CNCs. The CNCs dispersions were characterized by dynamic light scattering (DLS). It is found that CNCs containing above about 3.8 wt % moisture is critical for achieving individually dispersed CNC in solvents. Hydrodynamic radius (Rh) of CNCs is smaller in H2O/DMF co-solvent mixture than that in pure DMF or in pure H2O under same sonication treatment conditions. Experimental results have been corroborated using molecular simulation study.


Homebirth and the future child.
Debate around homebirth typically focuses on the risk of maternal and perinatal mortality and morbidity--the primary focus is on deaths. There is little discussion on the risk of long-term disability to the future child. We argue that maternal and perinatal mortality are truly tragic outcomes, but focusing disproportionately on them overshadows the importance of harm to a future child created by avoidable, foreseeable disability. The interests of future children are of great moral importance. Both professionals and pregnant women have an ethical obligation to minimize risk of long-term harm to the future child; harm to people who will exist is a clear and uncontroversial morally relevant harm. The medical literature does not currently adequately address the risk of long-term disability, which is at least as relevant as other outcomes. The choice of place of elective birth (home, hospital or other) may only be justified if it does not expose the future child to an unreasonable increased risk of avoidable disability. Doctors' duty of care for the life of the pregnant woman and her fetus may be overridden by the woman's choices. But further research is required to document the prevalence of long term avoidable disability associated with different birth place choices. Couples should be informed of this risk and doctors should attempt to dissuade couples when they elect a place of birth that puts the health and well-being of the future child at risk.


Homocysteine levels in aqueous humor and plasma of patients with primary open-angle glaucoma.
We determined homocysteine (Hcy) levels in aqueous humor (AH) and plasma and their association with B-vitamin levels in patients with primary open-angle glaucoma (POAG) and controls. Both AH Hcy and plasma Hcy levels were significantly increased in POAG, and elevation of AH Hcy and plasma Hcy was a significant risk factor for POAG. In contrast to controls, neither plasma nor AH Hcy of POAG patients demonstrated a significant association with important non-genetic determinants of elevated Hcy such as low B-vitamin levels, increasing age and caffeine consumption. Considering that Hcy is a neurotoxin that induces apoptotic retinal ganglion cell death via stimulation of the N-methyl-D-asparate (NMDA) receptor, increased Hcy concentrations in AH and plasma might contribute to the optic nerve damage in POAG.


Long-read sequencing of nascent RNA reveals coupling among RNA processing events.
Pre-mRNA splicing is accomplished by the spliceosome, a megadalton complex that assembles de novo on each intron. Because spliceosome assembly and catalysis occur cotranscriptionally, we hypothesized that introns are removed in the order of their transcription in genomes dominated by constitutive splicing. Remarkably little is known about splicing order and the regulatory potential of nascent transcript remodeling by splicing, due to the limitations of existing methods that focus on analysis of mature splicing products (mRNAs) rather than substrates and intermediates. Here, we overcome this obstacle through long-read RNA sequencing of nascent, multi-intron transcripts in the fission yeast Schizosaccharomyces pombe Most multi-intron transcripts were fully spliced, consistent with rapid cotranscriptional splicing. However, an unexpectedly high proportion of transcripts were either fully spliced or fully unspliced, suggesting that splicing of any given intron is dependent on the splicing status of other introns in the transcript. Supporting this, mild inhibition of splicing by a temperature-sensitive mutation in prp2, the homolog of vertebrate U2AF65, increased the frequency of fully unspliced transcripts. Importantly, fully unspliced transcripts displayed transcriptional read-through at the polyA site and were degraded cotranscriptionally by the nuclear exosome. Finally, we show that cellular mRNA levels were reduced in genes with a high number of unspliced nascent transcripts during caffeine treatment, showing regulatory significance of cotranscriptional splicing. Therefore, overall splicing of individual nascent transcripts, 3' end formation, and mRNA half-life depend on the splicing status of neighboring introns, suggesting crosstalk among spliceosomes and the polyA cleavage machinery during transcription elongation.


Health care reform: looking back to go ahead.
Health was a prominent policy issue in the 1972 Australian federal government elections, and the policy of the new Labor Government at that time emphasised the regional approach to health service delivery, including community-based services and preventive health programs, in close cooperation with the states. The Hospitals and Health Services Commission Act 1973 (Cwlth) was passed in December 1973 and members of the new Commission were appointed in April 1974. The Commission had broad-ranging functions and powers that had major influences on national health policy development in Australia. Major accomplishments of the Commission included the Community Health Program, which incorporated: the Hospitals Development Program, health services planning and research, a review of the School of Public Health and Tropical Medicine at the University of Sydney, diagnostic services, rehabilitation, Aboriginal health, rural health, health transport, nursing personnel, health careers and occupational health, many of which were long-neglected areas of public health. The National Health and Hospitals Reform Commission established by the Rudd Labor Government in February, 2008, while welcome, is an investigative body, whereas the Hospitals and Health Services Commission was responsible for both health policy development and implementation.


Interaction of blood lead and delta-aminolevulinic acid dehydratase genotype on markers of heme synthesis and sperm production in lead smelter workers.
The gene that encodes gamma-aminolevulinic acid dehydratase (ALAD) has a polymorphism that may modify lead toxicokinetics and ultimately influence individual susceptibility to lead poisoning. To evaluate the effect of the ALAD polymorphism on lead-mediated outcomes, a cross-sectional study of male employees from a lead-zinc smelter compared associations between blood lead concentration and markers of heme synthesis and semen quality with respect to ALAD genotype. Male employees were recruited via postal questionnaire to donate blood and urine for analysis of blood lead, zinc protoporphyrin (ZPP), urinary coproporphyrin (CPU), and ALAD genotype, and semen samples for semen analysis. Of the 134 workers who had ALAD genotypes completed, 114 (85%) were ALAD1-1 (ALAD1) and 20 (15%) were ALAD1-2 (ALAD2). The mean blood lead concentrations for ALAD1 and ALAD2 were 23.1 and 28.4 microg/dl (p = 0.08), respectively. ZPP/heme ratios were higher in ALAD1 workers (68.6 vs. 57.8 micromol/ml; p = 0.14), and the slope of the blood lead ZPP linear relationship was greater for ALAD1 (2.83 vs. 1.50, p = 0.06). No linear relationship between CPU and blood lead concentration was observed for either ALAD1 or ALAD2. The associations of blood lead concentration with ZPP, CPU, sperm count, and sperm concentration were more evident in workers with the ALAD1 genotype and blood lead concentrations >/= 40 microg/dl. The ALAD genetic polymorphism appears to modify the association between blood lead concentration and ZPP. However, consistent modification of effects were not found for CPU, sperm count, or sperm concentration.


A cortical representation of the local visual environment.
Medial temporal brain regions such as the hippocampal formation and parahippocampal cortex have been generally implicated in navigation and visual memory. However, the specific function of each of these regions is not yet clear. Here we present evidence that a particular area within human parahippocampal cortex is involved in a critical component of navigation: perceiving the local visual environment. This region, which we name the 'parahippocampal place area' (PPA), responds selectively and automatically in functional magnetic resonance imaging (fMRI) to passively viewed scenes, but only weakly to single objects and not at all to faces. The critical factor for this activation appears to be the presence in the stimulus of information about the layout of local space. The response in the PPA to scenes with spatial layout but no discrete objects (empty rooms) is as strong as the response to complex meaningful scenes containing multiple objects (the same rooms furnished) and over twice as strong as the response to arrays of multiple objects without three-dimensional spatial context (the furniture from these rooms on a blank background). This response is reduced if the surfaces in the scene are rearranged so that they no longer define a coherent space. We propose that the PPA represents places by encoding the geometry of the local environment.