Colonization of malaria vectors under semi-field conditions as a strategy for maintaining genetic and phenotypic similarity with wild populations.
Malaria still accounts for an estimated 207 million cases and 627,000 deaths worldwide each year. One proposed approach to complement existing malaria control methods is the release of genetically-modified (GM) and/or sterile male mosquitoes. As opposed to laboratory colonization, this requires realistic semi field systems to produce males that can compete for females in nature. This study investigated whether the establishment of a colony of the vector Anopheles arabiensis under more natural semi-field conditions can maintain higher levels of genetic diversity than achieved by laboratory colonization using traditional methods. Wild females of the African malaria vector An. arabiensis were collected from a village in southern Tanzania and used to establish new colonies under different conditions at the Ifakara Health Institute. Levels of genetic diversity and inbreeding were monitored in colonies of An. arabiensis that were simultaneously established in small cage colonies in the SFS and in a large semi-field (SFS) cage and compared with that observed in the original founder population. Phenotypic traits that determine their fitness (body size and energetic reserves) were measured at 10(th) generation and compared to founder wild population. In contrast to small cage colonies, the SFS population of An. arabiensis exhibited a higher degree of similarity to the founding field population through time in several ways: (i) the SFS colony maintained a significantly higher level of genetic variation than small cage colonies, (ii) the SFS colony had a lower degree of inbreeding than small cage colonies, and (iii) the mean and range of mosquito body size in the SFS colony was closer to that of the founding wild population than that of small cage colonies. Small cage colonies had significantly lower lipids and higher glycogen abundances than SFS and wild population. Colonization of An. arabiensis under semi-field conditions was associated with the retention of a higher degree of genetic diversity, reduced inbreeding and greater phenotypic similarity to the founding wild population than observed in small cage colonies. Thus, mosquitoes from such semi-field populations are expected to provide more realistic representation of mosquito ecology and physiology than those from small cage colonies.


Efficient continuous-time asymmetric Hopfield networks for memory retrieval.
A novel m energy functions method is adopted to analyze the retrieval property of continuous-time asymmetric Hopfield neural networks. Sufficient conditions for the local and global asymptotic stability of the network are proposed. Moreover, an efficient systematic procedure for designing asymmetric networks is proposed, and a given set of states can be assigned as locally asymptotically stable equilibrium points. Simulation examples show that the asymmetric network can act as an efficient associative memory, and it is almost free from spurious memory problem.


Heterologous DNA Uptake in Cultured Symbiodinium spp. Aided by Agrobacterium tumefaciens.
Plant-targeted pCB302 plasmids containing sequences encoding gfp fusions with a microtubule-binding domain; gfp with the fimbrin actin-binding domain 2; and gfp with AtRACK1C from Arabidopsis thaliana, all harbored in Agrobacterium tumefaciens, were used to assay heterologous expression on three different clades of the photosynthetic dinoflagellate, Symbiodinium. Accessibility to the resistant cell wall and through the plasma membrane of these dinoflagellates was gained after brief but vigorous shaking in the presence of glass beads and polyethylene glycol. A resistance gene to the herbicide Basta allowed appropriate selection of the cells expressing the hybrid proteins, which showed a characteristic green fluorescence, although they appeared to lose their photosynthetic pigments and did not further divide. Cell GFP expression frequency measured as green fluorescence emission yielded 839 per every 106 cells for Symbiodinium kawagutii, followed by 640 and 460 per every 106 cells for Symbiodinium microadriaticum and Symbiodinium sp. Mf11, respectively. Genomic PCR with specific primers amplified the AtRACK1C and gfp sequences after selection in all clades, thus revealing their presence in the cells. RT-PCR from RNA of S. kawagutii co-incubated with A. tumefaciens harboring each of the three vectors with their respective constructs, amplified products corresponding to the heterologous gfp sequence while no products were obtained from three distinct negative controls. The reported procedure shows that mild abrasion followed by co-incubation with A. tumefaciens harboring heterologous plasmids with CaMV35S and nos promoters can lead to expression of the encoded proteins into the Symbiodinium cells in culture. Despite the obvious drawbacks of the procedure, this is an important first step towards a stable transformation of Symbiodinium.


Individual contributions to babysitting in a cooperative mongoose, Suricata suricatta.
Evolutionary explanations of cooperative breeding based on kin selection have predicted that the individual contributions made by different helpers to rearing young should be correlated with their degree of kinship to the litter or brood they are raising. In the cooperative mongoose or meerkat, Suricata suricatta, helpers babysit pups at the natal burrow for the first month of pup life and frequent babysitters suffer substantial weight losses over the period of babysitting. Large differences in contributions exist between helpers, which are correlated with their age, sex and weight but not with their kinship to the young they are raising. Provision of food to some group members raises the contributions of individuals to babysitting. We discuss the implications of these results for evolutionary explanations of cooperative behaviour.


Comparison of thalamic populations in mammals and birds: expression of ErbB4 mRNA.
The expression of ErbB4 mRNA was examined in dorsal thalamic regions of chicks and rats. In rats, ErbB4 expression was observed in the habenular nuclei, the paraventricular nucleus, intermediodorsal nucleus, the central medial thalamic nucleus, the posterior nucleus, the parafascicular nucleus, the subparafascicular nucleus, the suprageniculate nucleus, the posterior limitans nucleus, the medial part of the medial geniculate nucleus, the peripeduncular nucleus, the posterior intralaminar nucleus, the lateral subparafascicular nucleus, the lateral posterior nucleus, and all ventral thalamic nuclei. In chicks, expression was observed in the subhabenular nucleus, the dorsomedialis posterior nucleus, the dorsointermedius posterior nucleus, the nucleus of the septomesencephalic tract, and areas surrounding the rotundus and ovoidalis nuclei, including the subrotundal and suprarotundal areas, and all ventral thalamic nuclei. Most cells within ovoidalis and rotundus were not labeled. The similar pattern of afferent and efferent projections originating from ErbB4-expressing regions of the mammalian and bird dorsal thalamus suggests that ErbB4 hybridizing cells may be derived from a single anlage that migrates into multiple thalamic regions. Most neurons in the rotundus and ovoidalis nuclei of chick may be homologous to unlabeled clusters of neurons intermingled with ErbB4-expressing cells of the mammalian posterior/intralaminar region.


Sympathetic neuronal survival induced by retinal trophic factors.
Neuronal survival in the vertebrate peripheral nervous system depends on neurotrophic factors available from target tissues. In an attempt to identify novel survival factors, we have studied the effect of secreted factors from retinal cells on the survival of chick sympathetic ganglion neurons. Embryonic day 10 sympathetic neurons undergo programmed cell death after 48 h without appropriate levels of nerve growth factor (NGF). Retina Conditioned Media (RCM) from explants of embryonic day 11 retinas maintained for 4 days in vitro supported 90% of E10 chick sympathetic neurons after 48 h. Conditioned medium from purified chick retinal Muller glial cells supported nearly 100% of E10 chick sympathetic neurons. Anti-NGF (1 microg/mL) blocked the survival effect of NGF, but did not block the trophic effect of RCM. Neither BDNF nor NT4 (0.1-50 ng/mL) supported E10 sympathetic neuron survival. Incubation of chimeric immunoglobulin-receptors TrkA, TrkB, or TrkC had no effect on RCM-induced sympathetic neuron survival. The survival effects were not blocked by anti-GDNF, anti-TGFbeta, and anti-CNTF and were not mimicked by FGFb (0.1-10 nM). LY294002 at 50 microM, but not PD098059 blocked sympathetic survival induced by RCM. Further, the combination of RCM and NGF did not result in an increase in neuronal survival compared with NGF alone (82% survival after 48 h). The secreted factor in RCM is retained in subfractions with a molecular weight above 100 kDa, binds to heparin, and is unaffected by dialysis, but is heat sensitive. Our results indicate the presence of a high-molecular weight retinal secreted factor that supports sympathetic neurons in culture.


Operator learning curve for transradial liver cancer embolization: implications for the initiation of a transradial access program.
We aimed to analyze transradial access (TRA) learning curve on patients undergoing hepatic chemoembolization, investigating the relationship between procedural volumes and various benchmarks of procedural success. We enrolled 60 consecutive patients who received two unilobar hepatic chemoembolizations within a 4-week interval performed by a single interventional radiologist, highly-trained in conventional transfemoral access (TFA) procedures, but without any previous practical experience in TRA procedures and with a preliminary 2-day theoretical training only. Consecutive patients were prospectively enrolled and analyzed in 3 groups: A (cases 1 to 20), B (cases 21 to 40), and C (cases 41 to 60). All patients underwent one hepatic chemoembolization using TRA and the other one using TFA in random order. All TFA procedures performed by the same operator in the same series of patients were considered as the control group. Primary endpoint was to analyze the relationship between TRA procedure operator experience and benchmarks of procedural success, to define the optimal procedural learning curve. Technical success was obtained in all patients, with a crossover rate (radial to femoral access) of 0%. An association between incremental TRA operator experience (in terms of performed procedures) and decrease of preparation, puncture, fluoroscopy, and total examination times was observed. Similarly, inverse associations between incremental TRA operator experience and contrast medium (CM) volumes (P < 0.001) and radiation dose (RD) values (in terms of RAK - Reference Air Kerma) (P < 0.001) were also observed. Compared with TFA, CM volumes and RD values were significantly higher only in group A (cases 1-20). Procedure success remained high in all TRA groups and no significant association between TRA incremental experience and postprocedural outcomes was found. Higher postprocedural complaints at the access route and more limitations in performing basic activities were recorded after TFA vs. TRA (P < 0.001). TRA catheterizations can be safely performed in patients treated for liver cancer embolization after a relatively short training in controlled conditions and with a better performance in comparison with TFA. Operator proficiency improves with greater TRA experience, with a threshold needed to overcome the learning curve represented by about 20 procedures.


Relative contributions of optic flow, bearing, and splay angle information to lane keeping.
Heading from optic flow, bearing, and splay angle information can all be used for lane keeping on a straight path. Here we investigated the relative contributions of these three visual cues to accurate lane-keeping control in a novel way. The displays simulated observers steering a vehicle down a straight path defined by a pair of posts (providing bearing angles only) or a segment of lane edges (providing bearing and splay angles) at a fixed viewing distance, and the ground contained no flow, sparse flow, or dense flow. Observers used a joystick to control the vehicle's lateral movement to stay in the center of the lane while facing random perturbations to both the vehicle's lateral position and orientation. The lateral position perturbation affected the use of both splay and bearing angle cues, but the vehicle orientation perturbation only affected the use of bearing angles. We found that performance improved as more flow information was added to the scene regardless of the availability of bearing or splay angle information. In the presence of splay angles, observers would ignore bearing and rely mainly on splay angles for lane keeping.


Mobilizing physiotherapy knowledge: Understanding the best evidence and barriers to implementation of hydrotherapy for musculoskeletal disease.
To explore two linked strategies to highlight the best current available evidence for hydrotherapy and to explore the barriers and enablers to mobilizing this evidence into practice. Phase 1: The best published evidence for hydrotherapy was collated using a Critically Appraised Topic (CAT) methodology. The focus was the best available research evidence for hydrotherapy in musculoskeletal conditions (i.e. osteoarthritis (OA), juvenile idiopathic arthritis (JIA), rheumatoid arthritis (RA), ankylosing spondylitis (AS), and low back pain (LBP)). Once evaluated for quality, a summary of the evidence was produced in a Clinical Bottom Line (CBL). Phase 2: A Focus Group explored the: CBL, the barriers and facilitators of embedding the best evidence for hydrotherapy into practice. Phase 1: The CAT identified seven studies that indicated hydrotherapy had beneficial, although short term, effects for common musculoskeletal conditions. Phase 2: Six participants from primary, secondary care, private practice, and education discussed the evidence identified. They highlighted issues such as: understanding the value of hydrotherapy, an overuse of quantitative methodologies and the quality of existing research as being barriers to this knowledge being actively mobilized into clinical care. These two linked enquiries (CAT and Focus Group) identified the best evidence and the basis for discussion to explore barriers and facilitators of evidence use in practice. This gave an understanding of the reasons for the research to practice gap and thereby allows planning of knowledge mobilization strategies to reduce this.


Spontaneous action representation in smokers when watching movie characters smoke.
Do smokers simulate smoking when they see someone else smoke? For regular smokers, smoking is such a highly practiced motor skill that it often occurs automatically, without conscious awareness. Research on the brain basis of action observation has delineated a frontoparietal network that is commonly recruited when people observe, plan, or imitate actions. Here, we investigated whether this action observation network would be preferentially recruited in smokers when viewing complex smoking cues, such as those occurring in motion pictures. Seventeen right-handed smokers and 17 nonsmokers watched a popular movie while undergoing functional magnetic resonance imaging. Using a natural stimulus, such as a movie, allowed us to keep both smoking and nonsmoking participants naive to the goals of the experiment. Brain activity evoked by movie scenes of smoking was contrasted with nonsmoking control scenes that were matched for frequency and duration. Compared with nonsmokers, smokers showed greater activity in left anterior intraparietal sulcus and inferior frontal gyrus, regions involved in the simulation of contralateral hand-based gestures, when viewing smoking versus control scenes. These results demonstrate that smokers spontaneously represent the action of smoking when viewing others smoke, the consequence of which may make it more difficult to abstain from smoking.


A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in Pancreatic Cancer.
The p53 transcription factor is a critical barrier to pancreatic cancer progression. To unravel mechanisms of p53-mediated tumor suppression, which have remained elusive, we analyzed pancreatic cancer development in mice expressing p53 transcriptional activation domain (TAD) mutants. Surprisingly, the p5353,54 TAD2 mutant behaves as a "super-tumor suppressor," with an enhanced capacity to both suppress pancreatic cancer and transactivate select p53 target genes, including Ptpn14. Ptpn14 encodes a negative regulator of the Yap oncoprotein and is necessary and sufficient for pancreatic cancer suppression, like p53. We show that p53 deficiency promotes Yap signaling and that PTPN14 and TP53 mutations are mutually exclusive in human cancers. These studies uncover a p53-Ptpn14-Yap pathway that is integral to p53-mediated tumor suppression.


Aberrant expression of receptors for platelet-derived growth factor in an anaplastic thyroid carcinoma cell line.
Receptors for platelet-derived growth factor (PDGF) have previously only been found on cells of mesenchymal and glial origin. This study shows PDGF receptors on an anaplastic thyroid carcinoma cell line, C 643, that was found to express thyroglobulin mRNA, confirming its origin from thyroid epithelium. Northern blot analysis of poly(A)+ RNA hybridized with a human PDGF B-type receptor cDNA probe revealed a 5.4-kilobase transcript in the C 643 cells. The existence of receptor protein on the cell surface was shown by immunofluorescence microscopy with a PDGF receptor monoclonal antibody. Binding experiments with 125I-labeled dimeric forms of PDGF indicated that the cells contain B-, but not A-, type PDGF receptors. The addition of PDGF to C 643 membranes in the presence of [32P]ATP induced phosphorylation of the receptor. A polyclonal PDGF B-type receptor peptide antiserum was used to immunoprecipitate a receptor protein from metabolically labeled C 643 cells; the receptor was found to be 5-10 kDa larger than that in normal human fibroblasts. Removal of N-linked carbohydrates using endoglycosidase H resulted in deglycosylated receptor proteins of similar size in C 643 cells and fibroblasts, indicating differences in glycosylation patterns of the two receptor proteins. The aberrant expression of receptors might be crucial in tumor development by conferring a selective growth advantage to the cancer cells.


Enhanced dispersion compensation capability of angular elements based on beam expansion.
We demonstrate that beam size manipulation plays an important role in dispersion compensation. With expanded beam, the maximal negative group delay dispersion (GDD) provided by angular elements increases by an order of magnitude compared with original beam. Both calculation and experimental results show that a modest 2 x and 4 x expanded beams can improve dispersion compensation capability of prisms or acousto-optical deflectors: the restored minimal pulse width decreases by 50% and the corresponding distance between angular elements is shortened more than 70 cm. These findings will be helpful for designing dispersion compensation schemes for femtosecond pulse laser application systems such as multiphoton microscopy or laser micromachining.


[Evaluation of the technology employed in health care].
This report explains how and why to evaluate the technology employed in health care. This technology includes not only medicines, instruments, equipment, and procedures used directly on patients, but also the organizational models and support systems that make health care possible. During the various stages of a technology's life cycle, an assessment is made of several different characteristics, such as safety and effectiveness, clinical utility, economic impact, and effect on the organization and provision of services. Originally, the ways of assessing and testing technical methods were only of interest to manufactures and service providers. Today, however, the interested parties include legislators, government officials, health administrators, researchers, industrial managers, and, certainly, patients and their families. Therefore, health technology assessment is a highly important activity and its promotion is an element of PAHO's technical cooperation with the Member States.


Incidence, severity and correlates of bicycling injuries in a sample of cyclists in Queensland, Australia.
Bicycle injuries, particularly those resulting from single bicycle crashes, are underreported in both police and hospital records. Data on cyclist characteristics and crash circumstances are also often lacking. As a result, the ability to develop comprehensive injury prevention policies is hampered. The aim of this study was to examine the incidence, severity, cyclist characteristics, and crash circumstances associated with cycling injuries in a sample of cyclists in Queensland, Australia. A cross-sectional study of Queensland cyclists was conducted in 2009. Respondents (n=2056) completed an online survey about their cycling experiences, including cycling injuries. Logistic regression modelling was used to examine the associations between demographic and cycling behaviour variables with experiencing cycling injuries in the past year, and, separately, with serious cycling injuries requiring a trip to a hospital. Twenty-seven percent of respondents (n=545) reported injuries, and 6% (n=114) reported serious injuries. In multivariable modelling, reporting an injury was more likely for respondents who had cycled <5 years, compared to ≥ 10 years (p<0.005); cycled for competition (p=0.01); or experienced harassment from motor vehicle occupants (p<0.001). There were no gender differences in injury incidence, and respondents who cycled for transport did not have an increased risk of injury. Reporting a serious injury was more likely for those whose injury involved other road users (p<0.03). Along with environmental and behavioural approaches for reducing collisions and near-collisions with motor vehicles, interventions that improve the design and maintenance of cycling infrastructure, increase cyclists' skills, and encourage safe cycling behaviours and bicycle maintenance will also be important for reducing the overall incidence of cycling injuries.


An experimental test of well-described vegetation patterns across slope aspects using woodland herb transplants and manipulated abiotic drivers.
*The ubiquitous transition of plant communities across slope aspects is a well-described, but rarely tested, ecological dynamic. Aspect position is often used as a proxy for microclimate changes in moisture, light and temperature, but these abiotic drivers are seldom decoupled and very rarely manipulated across slope aspects. *To investigate the mechanisms and demographic stages driving the observed distribution patterns of two woodland herbs in the southeastern USA, seeds and adults were transplanted across north- and south-facing slopes, and moisture and light were experimentally manipulated. *Stage- and species-specific abiotic responses resulted in similar landscape-level patterning for Hexastylis arifolia and Hepatica nobilis, but the underlying abiotic drivers were unique. Adult rather than seed survival best explained the natural distributions across slope aspects, and Hexastylis arifolia was limited by higher temperature, whereas Hepatica nobilis was limited by lower soil moisture. *The stage- and species-specific responses indicated that the use of slope aspect to explain plant distributions not only obfuscates explanatory mechanisms, but probably undermines the portability of results. As abiotic drivers, not topographical proxies, are projected to shift with global climate change, distribution research requires direct abiotic data in association with key demographic stages rather than topographical proxies.


Causes of death of patients with substance dependence: a record-linkage study in a psychiatric hospital in Taiwan.
The causes of death among a series of patients with substance dependence were investigated. A psychiatric teaching hospital in Taipei, Taiwan (Taipei City Psychiatric Center). A total of 1698 patients with various diagnostic categories of substance dependence, who had been admitted to TCPC for detoxification were followed-up from 1985 to 1996. A record-linkage study was performed using the patient's national identification number to link between TCPC chart records and the mortality file compiled by the National Department of Health. Risk factor analyses for mortality included socio-demographic data, clinical diagnosis and cause of death. A total of 141 patients died during the study period. Among them, 83 had a diagnosis of alcohol dependence, 41 of heroin dependence and the remaining 17 cases of sedative, glue or hallucinogen dependence. The annual mortality rate of patients with heroin dependence was 1.94%. Accidental death is the leading cause of death among patients with heroin dependence. However, the patients with alcohol dependence had a higher mortality risk than those with heroin dependence (relative hazard = 1.91, p < 0.001) in this study. The proportion of non-violent death was significantly higher among the patients with alcohol dependence than those with heroin dependence (p < 0.005). The causes of death among patients with substance dependence found in this Taiwanese series were very similar to those reported in the western literature. However, differences included the absence of death among heroin addicts due to HIV-related disease and a markedly high percentage of alcoholic patients who died of liver diseases.


Macrophage Phagocytosis and Allergen Avoidance in Children With Asthma.
Background and Objective: Airway macrophages perform the crucial functions of presenting antigens, clearing pathogens, and apoptotic cells. Macrophage phagocytosis is increased in adults with mild asthma and allergen exposure is known to activate macrophages. However, it is not clear whether the mechanism behind this is due to a primary defect or environmental factors such as allergen or lipopolysaccaride (LPS) exposure. Our aim was to assess the phagocytic function of airway macrophages in children with mild to moderate asthma after residence in a low allergen\LPS environment at high altitude. Methods: Sputum induction was performed in children with asthma at baseline and after residence for a 3 weeks' period at a high-altitude asthma center that has very low ambient allergen levels. The markers of eosinophilic inflammation (including percentage of macrophage cytoplasm with red hue) and phagocytosis of fluorescein isothiocyanate-labeled, heat-killed Staphylococcus aureus by airway macrophages was analyzed. Internalized bacteria were quantified using confocal microscopy. Results: The median bacterial count [mean (standard deviation)] per macrophage was significantly lower [39.55 (4.51) vs. 73.26 (39.42) (p = 0.006)] after residence at high altitude. No association was observed between markers of eosinophilic inflammation and bacterial phagocytosis. Conclusions: The results suggest that the mechanism behind the enhanced phagocytosis of bacteria in childhood asthma may be secondary to allergen or possibly LPS exposure.


Labor Pain in Different Dilatations of the Cervix and Apgar Scores Affected by Aromatherapy: A Systematic Review and Meta-analysis.
Labor pain (LP), as a physiological process, is known as one of the most severe pains. Aromatherapy is one of the methods to reduce LP in the first phase of labor. It is an important approach for enjoyable birth and decreases the severity of pain in today's society. Accordingly, this study aimed to systematically review the relieving effect of aromatherapy in LP and Apgar score. We used international databases such as EMBASE, Web of Science, Scopus, Google Scholar, PubMed, Cochrane Library, ProQuest, and clinicaltrials.gov to conduct a systematic search for all relevant articles. Cochran's Q-test and I2 statistic were applied to assess heterogeneity, a random-effects model was used to estimate the unstandardized mean difference (UMD), and a meta-regression method was utilized to investigate the factors affecting heterogeneity between studies. A total of 27 studies were included in the meta-analysis (sample size: 2,566). Overall, aromatherapy leads to relieving LP during delivery (UMD: 1.75; 95% CI: 1.13-2.37). Based on cervix dilation, aromatherapy significantly affects LP when cervix dilation is 8-10 cm (UMD: 6.18; 95% CI: 4.51-7.85) and 0-4 cm (UMD: 5.31; 95% CI: 3.74-6.87); but it had no effects on 1- and 5-min Apgar scores. No publication bias was observed (P=0.113). Mother's age, publication year, sample size, and cervix dilation had no significant effects on heterogeneity (P>0.05). Aromatherapy had a positive impact on relieving LP, and the greatest and least effect was witnessed in dilatation of 8-10 cm and 0-4 cm, respectively. Moreover, it had no effects on 1- and 5-min Apgar scores.


Productive lytic replication of a recombinant Kaposi's sarcoma-associated herpesvirus in efficient primary infection of primary human endothelial cells.
Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to the development of Kaposi's sarcoma (KS), a vascular spindle cell tumor primarily consisting of proliferating endothelial cells. Although KSHV has been shown to infect primary human endothelial cells and convert them into spindle shapes, KSHV infection is largely latent, and efforts to establish a highly efficient and sustainable infection system have been unsuccessful. A recombinant KSHV, BAC36, that has high primary-infection efficiency in 293 cells has been obtained (F. C. Zhou, Y. J. Zhang, J. H. Deng, X. P. Wang, H. Y. Pan, E. Hettler, and S. J. Gao, J. Virol. 76:6185-6196, 2002). BAC36 contains a green fluorescent protein cassette which can be used to conveniently monitor viral infection. Here, we describe the establishment of a KSHV lytic-replication-permissive infection cell model using BAC36 virions to infect primary human umbilical vein endothelial cell (HUVEC) cultures. BAC36 infection of HUVEC cultures has as high as 90% primary-infection efficiency and consists of two phases: a permissive phase, in which the cultures undergo active viral lytic replication, producing a large number of virions and concomitantly resulting in large-scale cell death, and a latent phase, in which the surviving cells from the permissive phase switch into latent infection, with a small number of cells undergoing spontaneous viral lytic replication, and proliferate into bundles of spindle cells with KS slit-like spaces. An assay for determining the KSHV titer in a virus preparation has also been developed. The cell model should be useful for examining KSHV infection and replication, as well as for understanding the development of KS.


Repeated traumatic brain injury affects composite cognitive function in piglets.
Cumulative effects of repetitive mild head injury in the pediatric population are unknown. We have developed a cognitive composite dysfunction score that correlates white matter injury severity in neonatal piglets with neurobehavioral assessments of executive function, memory, learning, and problem solving. Anesthetized 3- to 5-day-old piglets were subjected to single (n = 7), double one day apart (n = 7), and double one week apart (n = 7) moderate (190 rad/s) rapid non-impact axial rotations of the head and compared to instrumented shams (n = 7). Animals experiencing two head rotations one day apart had a significantly higher mortality rate (43%) compared to the other groups and had higher failures rates in visual-based problem solving compared to instrumented shams. White matter injury, assessed by beta-APP staining, was significantly higher in the double one week apart group compared to that with single injury and sham. Worsening performance on cognitive composite score correlated well with increasing severity of white matter axonal injury. In our immature large animal model of TBI, two head rotations produced poorer outcome as assessed by neuropathology and neurobehavioral functional outcomes compared to that with single rotations. More importantly, we have observed an increase in injury severity and mortality when the head rotations occur 24 h apart compared to 7 days apart. These observations have important clinical translation to infants subjected to repeated inflicted head trauma.


Current antiviral practice and course of Hepatitis B virus infection in inflammatory arthritis: a multicentric observational study (A + HBV study).
The reactivation of hepatitis B virus (HBV) infection is a well-known event in hepatitis B surface antigen (HbsAg)-positive patients receiving immunosuppressive therapy. The objective of this study was to assess the antiviral practice and course of HBV infection in inflammatory arthritis. Nineteen rheumatology centers participated in this retrospective study. HbsAg-positive patients who were taking disease-modifying antirheumatic drugs and who were being tested for HBV viral load at a minimum of two different time points were included. The case report form (CRF) consisted of demographic data, rheumatic diseases, treatment profiles, transaminase levels, viral hepatitis serological markers, and HBV viral load. The reactivation of HBV was defined as the abrupt rise in HBV replication by an increase in serum HBV DNA levels in a patient with a previously inactive HBV infection. In total, the data of 101 (female 50.5%) patients were included (76 patients with inactive HBV carriers and 25 patients with chronic HBV infection). The mean age of patients was 44±12 years, and the mean follow-up duration was 31±22 months. Of the 101 patients, 70 (69.3%) received antiviral treatment. HBV reactivation was detected in 13 of 76 (17.1%) patients with inactive HBV carriers. HBV reactivation was observed less frequently, not although significantly, in those patients receiving antiviral prophylaxis compared with those not receiving prophylaxis [5/41 (12.2%) vs. 8/33 (24.2%), p=0.17]. Forty-two patients (31 patients had inactive HBV carriers) were using anti-tumor necrosis factor agents. HBV reactivation was detected in 6 of the 31 (19.3%) patients. Twenty-five patients had chronic hepatitis, and five (20%) of them had not received antiviral prophylaxis. HBV viral loads were persistently elevated in 7 (28%) of 25 patients (three patients under and four patients not under antiviral treatment). HBV reactivation was observed in approximately 17% of patients under immunosuppressive treatments. HBV reactivation was more frequently observed in those who did not receive antiviral prophylaxis.


Natural protection against HIV-1 infection provided by HIV-2.
Significant differences have been observed in the rates of transmission and disease development in human immunodeficiency virus (HIV) types 1 and 2. Because many HIV-2-infected people remain asymptomatic for prolonged periods, the hypothesis that HIV-2 might protect against subsequent infection by HIV-1 was considered. During a 9-year period in Dakar, Senegal, the seroincidence of both HIV types was measured in a cohort of commercial sex workers. Despite a higher incidence of other sexually transmitted diseases (STDs), HIV-2-infected women had a lower incidence of HIV-1 than did HIV-seronegative women, with a relative risk of 0.32 (P = 0.008). An understanding of the cross-protective mechanisms involved may be directly relevant to HIV-1 vaccine development.


Evidence from autoimmune thyroiditis of skewed X-chromosome inactivation in female predisposition to autoimmunity.
The etiologic factors in the development of autoimmune thyroid diseases (AITDs) are not fully understood. We investigated the role of skewed X-chromosome inactivation (XCI) mosaicism in female predisposition to AITDs. One hundred and ten female AITDs patients (81 Hashimoto's thyroiditis (HT), 29 Graves' disease (GD)), and 160 female controls were analyzed for the androgen receptor locus by the HpaII/polymerase chain reaction assay to assess XCI patterns in DNA extracted from peripheral blood cells. In addition, thyroid biopsy, buccal mucosa, and hair follicle specimens were obtained from five patients whose blood revealed an extremely skewed pattern of XCI, and the analysis was repeated. Skewed XCI was observed in DNA from peripheral blood cells in 28 of 83 informative patients (34%) as compared with 10 of 124 informative controls (8%, P<0.0001). Extreme skewing was present in 16 patients (19%), but only in three controls (2.4%, P<0.0001). The buccal mucosa, and although less marked, the thyroid specimens also showed skewing. Analysis of two familial cases showed that only the affected individuals demonstrate skewed XCI patterns. Based on these results, skewed XCI mosaicism may play a significant role in the pathogenesis of AITDs.


Political institutions and their historical dynamics.
Traditionally, political scientists define political institutions deductively. This approach may prevent from discovery of existing institutions beyond the definitions. Here, a principal component analysis was used for an inductive extraction of dimensions in Polity IV data on the political institutions of all nations in the world the last two centuries. Three dimensions of institutions were revealed: core institutions of democracy, oligarchy, and despotism. We show that, historically and on a world scale, the dominance of the core institutions of despotism has first been replaced by a dominance of the core institutions of oligarchy, which in turn is now being followed by an increasing dominance by the core institutions of democracy. Nations do not take steps from despotic, to oligarchic and then to democratic institutions, however. Rather, nations hosting the core democracy institutions have succeeded in historically avoiding both the core institutions of despotism and those of oligarchy. On the other hand, some nations have not been influenced by any of these dimensions, while new institutional combinations are increasingly influencing others. We show that the extracted institutional dimensions do not correspond to the Polity scores for autocracy, "anocracy" and democracy, suggesting that changes in regime types occur at one level, while institutional dynamics work on another. Political regime types in that sense seem "canalized", i.e., underlying institutional architectures can and do vary, but to a considerable extent independently of regime types and their transitions. The inductive approach adds to the deductive regime type studies in that it produces results in line with modern studies of cultural evolution and memetic institutionalism in which institutions are the units of observation, not the nations that acts as host for them.


Synthetic applications of eosin Y in photoredox catalysis.
Eosin Y, a long known dye molecule, has recently been widely applied as a photoredox catalyst in organic synthesis. Low cost and good availability make eosin Y an attractive alternative to typical inorganic transition metal photocatalysts. We summarize the key photophysical properties of the dye and the recent synthetic applications in photoredox catalysis.


Immunochemical studies on the cross-reactivity between streptococcal and staphylococcal mucopeptide.
Particulate mucopeptides of Group A-variant streptococci and Staphylococcus aureus, solubilized by ultrasonic treatment, give a precipitin reaction with the sera of rabbits immunized with Group A-variant streptococci. gamma-G globulin antibodies have been recovered from these sera which react with the mucopeptides but not with the Group A-variant carbohydrate. The immunochemical basis for the cross-reactivity between the streptococcal and staphylococcal mucopeptides was investigated in detail. Three chemically different fractions have been isolated from enzymatic digests of staphylococcal mucopeptide and were employed as haptenic inhibitors of the precipitin reaction. A fraction consisting of the peptide moiety of mucopeptide was the strongest inhibitor, whereas the hexosamine-rich fraction was less effective. The third fraction, rich in glycine, was least effective. It is suggested that the immunologic cross-reactivity between streptococcal and staphylococcal mucopeptide is due to the fact that these two substances contain chemically similar tetrapeptides. The hexosamine polymer which is identical for both mucopeptides may also contribute to their cross-reactivity.


[The role of parasites and fungi in secondary infertility].
Parasite-host relationships can cause diminished or absent ability to conceive, ectopic pregnancy or pregnancy with undesired course. There are reports that some protozoa, helminths and fungi may impair women's reproductive capacity, causing deformities of genital tract, so that conception is impossible, or, if it does occur, normal implantation and development of placenta are impossible. Schistosoma haematobium may cause vulvar papule, swelling, tumors, irregular vaginal hemorrhage, tubular infertility and ectopic pregnancies. Patients with cirrhosis caused by schistosomas have gonadal dysfunction and schistosomiasis itself can lead to tubular infertility. Some authors found microfilaria of Mansonella perstans in follicular aspirates in patients with tubular adhesions. Chronic Entamoeba histolytica infection can cause pelvic pain and dyspareunia in some patients. Although Trichomonas vaginalis is a common cause of tubal inflammation, this protozoa affects semen quality and leads to secondary infertility. Soluble parasite extract of T. vaginalis can lead to impaired motility of 50% spermatozoa in vitro and affects semen quality by increased viscosity and amount of debris, or damage spermatozoid membrane. In enterobiosis, presence of adult worms and eggs in fallopian tube, can be followed by chronic salpingitis and tubal occlusion. Also in ascariosis, presence of adult forms and eggs can lead to acute colpitis. chronic endometritis, salpingitis or ovarian abscess. The consequence of fungal infections, such as colpitis and endometritis, caused by Candida albicans, may be infertility. Also, according to some reports, C. albicans leads to decreased spermatozoan motility. Hence parasites and fungi can cause infertility, we recommend examination of both partners in treatment of infertility.


MF Afragil® in the treatment of 34 menopause symptoms: a pilot study.
A combination of calcium, vitamin D3, lycopene , astaxantin and Citrus bioflavoid (MF Afragil®) was administered for a period of 8 weeks to 65 women to determine its effects in reducing signs/symptoms of climacteric status. Two groups of women were compared in a registry study (33 treated with MF Afragil® and 32 with no treatment). The climacteric condition was determined by using the 34-symptom questionnaire MSSQ, which was filled out at inclusion in the trial and after 8 weeks of treatment. The MSSQ signs/symptoms scores (Common Symptoms, Changes and Pains) of the two groups were comparable at inclusion, whereas after 8 weeks a significant reduction of many variables was found in the group treated with MF Afragil® and in the control group. Following the treatment with MF Afragil®, the total MSSQ score was reduced by more than 45%. There was a significant reduction in hot flashes, CNS symptoms (depression, anxiety and panic disorders), incontinence and joint pain, which are among the most frequent symptoms of climacteric status. Otsteoporosis was not analyzed due to the short period of treatment. MF Afragil® was found to be efficient in reducing climacteric symptoms following a short-term administration. More prolonged treatment and more cases are under analysis to also determine its effect on osteroporosis.


Determining the effectiveness of a vibrotactile balance prosthesis.
We present a quantitative method for characterizing the effectiveness of a balance prosthesis based on tactile vibrators. The balance prosthesis used an array of 12 tactile vibrators (tactors) placed on the anterior and posterior surfaces of the torso to provide body orientation feedback related to the angular position and velocity of anterior-posterior body sway. Body sway was evoked in subjects with normal sensory function and in vestibular loss subjects by rotating the support surface upon which a test subject stood with eyes closed. Tests were performed both with (tactor trials) and without (control trials) the prosthesis activated. Several amplitudes of support surface stimulation were presented with each stimulus following a pseudorandom motion profile. For each stimulus amplitude, a transfer function analysis characterized the amplitude (gain) and timing (phase) of body sway evoked by the support surface stimulus over a frequency range of 0.017 to 2.2 Hz. A comparison of transfer function results from the control trials of normal subjects with results from tactor trials of vestibular loss subjects provided a quantitative measure of the effectiveness of the balance prosthesis in substituting for missing vestibular information. Although this method was illustrated using a specific balance prosthesis, the method is general and could be applied to balance prostheses that utilize other technology.


Visual Function and Inner Retinal Structure in Relation to Birth Factors in Autosomal Dominant Optic Atrophy.
The extreme variation in expressivity of autosomal dominant optic atrophy (ADOA) is unexplained. It is present from early childhood, why there is reason to search for pre- and perinatal risk factors for poor vision in ADOA. The process of ganglion cell pruning in the fetus is of interest because mitochondria are involved in apoptosis. We hypothesized that suboptimal mitochondrial function makes the developing retina and optic nerve vulnerable to fetal stress in ADOA. We have examined visual function and inner retinal layer structure in relation to birth parameters in ADOA. The study included 142 participants with OPA1 ADOA, 62 unaffected first-degree relatives, and 90 unrelated control subjects. Outcome measures included best-corrected visual acuity, microperimetric sensitivity, nerve fiber layer (NFL) volume, and ganglion cell layer (GCL) volume. Descriptive parameters included birth weight, maternal age at birth, birth complications, and gestational age. Analysis was made using mixed modeling. The analysis showed a significant positive association between microperimetric sensitivity and longer gestational age in ADOA (0.5 dB/week, P = 0.017). Interaction analysis showed a significant different association between microperimetric sensitivity and gestational age between participants with ADOA and the control groups (P = 0.007) and a significant difference in association between NFL volume and birth weight (P = 0.04) and gestational age (P = 0.02) between variant types. The study suggests that gestational age and birth weight may affect the expressivity of ADOA. The results support that prospectively collected pre- and perinatal data should be included in future studies of the natural history of ADOA.


Treatment of spinal cord ependymomas by surgery with or without postoperative radiotherapy.
To evaluate the effectiveness of complete resection and postoperative radiotherapy in spinal cord ependymomas. We conducted a retrospective study over 20 patients (13 males and 7 females) with histologically confirmed spinal cord ependymomas between July 1985 and April 2001. Among them, 13 patients had ependymomas, 6 had myxopapillary ependymomas, and 1 had anaplastic ependymoma. All patients received radical surgery for tumor removal with 13 patients achieving complete resection and 7 incomplete resection due to technical difficulty. Among those with incomplete resection, 6 patients received postoperative radiotherapy to tumor bed and only one patient with anaplastic ependymoma received surgery alone. The total tumor dose ranged from 50 to 60 Gy. Among the 20 patients, 19 patients were alive and showed local control. The median survival time of all patients was 109 months, with 104 months in the complete resection alone group and 135 months in the incomplete resection with postoperative radiotherapy group. One patient with anaplastic ependymoma and no postoperative radiotherapy developed leptomeningeal seeding 9 months after surgery. Salvage therapy of radiotherapy and chemotherapy maintained normal neurological functions. The patient expired 34 months from the initial diagnosis due to progression of leptomeningeal seeding. Complete resection alone in spinal cord ependymoma can achieve excellent local control and survival. Patients should receive complete resection if technically possible. Postoperative radiotherapy is not recommended for complete resection. For incomplete resection, postoperative local radiotherapy is recommended and it can also achieve excellent local control and survival. Local radiotherapy with 50-60 Gy is effective and safe. Salvage radiotherapy improves quality of life for local recurrence or leptomeningeal seeding patients.


Pituitary centers of excellence.
Pituitary tumors and associated neuroendocrine disorders pose significant challenges in diagnostic and therapeutic management. Optimal care of the "pituitary patient" is best provided in a multidisciplinary collaborative environment that includes not only experienced pituitary practitioners in neurosurgery and endocrinology, but also in otorhinolaryngological surgery, radiation oncology, medical oncology, neuro-ophthalmology, diagnostic and interventional neuroradiology, and neuropathology. We provide the background and rationale for recognizing pituitary centers of excellence and suggest a voluntary verification process, similar to that used by the American College of Surgeons for Trauma Center verification. We propose that pituitary centers of excellence should fulfill 3 key missions: (1) provide comprehensive care and support to patients with pituitary disorders; (2) provide residency training, fellowship training, and/or continuing medical education in the management of pituitary and neuroendocrine disease; and (3) contribute to research in pituitary disorders. As this is a preliminary proposal, we recognize several issues that warrant further consideration including center and surgeon practice volume as well as oversight of the verification process.


Adenosine stimulates angiogenesis by up-regulating production of thrombospondin-1 by macrophages.
Increase of blood capillary density at the interface between normal and ischemic tissue after acute MI reduces infarct size and improves cardiac function. Cardiac injury triggers the production of the matricellular component TSP-1, but its role in angiogenesis is not clear, as both anti- and proangiogenic properties have been reported. It is unknown whether TSP-1 is modulated by other factors released during cardiac injury. Among these, Ado is a well-known promoter of angiogenesis. This study determined whether Ado modulates TSP-1 expression and the implication on angiogenesis. Ado dose dependently increased the production of TSP-1 by human macrophages. With the use of agonists and antagonists of AdoRs, coupled to RNA interference, we observed that this effect is mediated via A2AR and A2BR. The Ado effect was reproduced by cholera toxin (Gs protein activator) and forskolin (adenylate cyclase activator) and blocked by the PKA inhibitor H89. Conditioned medium from Ado-treated macrophages stimulated microvessel outgrowth from aortic ring explants by 400%, and induced vessel formation in matrigel plugs. Microvessel outgrowth and vessel formation were blocked completely by addition of anti-TSP-1 antibodies to conditioned medium. Chronic administration of Ado to rats after MI maintained long-term expression of TSP-1 in the infarct border zone, and this was associated with enhanced border-zone vascularization. Ado up-regulates TSP-1 production by macrophages, resulting in stimulation of angiogenesis. The mechanism involves A2AR and A2BR and is mediated through the cAMP/PKA pathway. This information may be important when designing Ado-based therapies of angiogenesis.


The stigma system: How sociopolitical domination, scapegoating, and stigma shape public health.
Stigma is a fundamental driver of adverse health outcomes. Although stigma is often studied at the individual level to focus on how stigma influences the mental and physical health of the stigmatized, considerable research has shown that stigma is multilevel and structural. This paper proposes a theoretical approach that synthesizes the literature on stigma with the literature on scapegoating and divide-and-rule as strategies that the wealthy and powerful use to maintain their power and wealth; the literatures on racial, gender, and other subordination; the literature on ideology and organization in sociopolitical systems; and the literature on resistance and rebellion against stigma, oppression and other forms of subordination. we develop a model of the "stigma system" as a dialectic of interacting and conflicting structures and processes. Understanding this system can help public health reorient stigma interventions to address the sources of stigma as well as the individual problems that stigma creates. On a broader level, this model can help those opposing stigma and its effects to develop alliances and strategies with which to oppose stigma and the processes that create it.


The effect of power asymmetries on cooperation and punishment in a prisoner's dilemma game.
Recent work has suggested that punishment is detrimental because punishment provokes retaliation, not cooperation, resulting in lower overall payoffs. These findings may stem from the unrealistic assumption that all players are equal: in reality individuals are expected to vary in the power with which they can punish defectors. Here, we allowed strong players to interact with weak players in an iterated prisoner's dilemma game with punishment. Defecting players were most likely to switch to cooperation if the partner cooperated: adding punishment yielded no additional benefit and, under some circumstances, increased the chance that the partner would both defect and retaliate against the punisher. Our findings show that, in a two-player game, cooperation begets cooperation and that punishment does not seem to yield any additional benefits. Further work should explore whether strong punishers might prevail in multi-player games.


Predictors of efficacy after stereotactic radiosurgery for medial temporal lobe epilepsy.
Stereotactic radiosurgery (RS) is a promising treatment for intractable medial temporal lobe epilepsy (MTLE). However, the basis of its efficacy is not well understood. Thirty patients with MTLE were prospectively randomized to receive 20 or 24 Gy 50% isodose RS centered at the amygdala, 2 cm of the anterior hippocampus, and the parahippocampal gyrus. Posttreatment MRI was evaluated quantitatively for abnormal T2 hyperintensity and contrast enhancement, mass effect, and qualitatively for spectroscopic and diffusion changes. MRI findings were analyzed for potential association with radiation dose and seizure remission (Engel Ib or better outcome). Despite highly standardized dose targeting, RS produced variable MRI alterations. In patients with multiple serial imaging, the appearance of vasogenic edema occurred approximately 9-12 months after RS and correlated with onset of seizure remission. Diffusion and spectroscopy-detected alterations were consistent with a mechanism of temporal lobe radiation injury mediated by local vascular insult and neuronal loss. The degree of these early alterations at the peak of radiographic response was dose-dependent and predicted long-term seizure remission in the third year of follow-up. Radiographic changes were not associated with neurocognitive impairments. Temporal lobe stereotactic radiosurgery resulted in significant seizure reduction in a delayed fashion which appeared to be well-correlated with structural and biochemical alterations observed on neuroimaging. Early detected changes may offer prognostic information for guiding management.


Relation between inhibition of platelet aggregation and clinical outcomes.
Despite a clinical trials experience in excess of 30,000 randomized patients, there is no definitive answer or agreement as to the relation between the level of inhibition of platelet aggregation and clinical outcome. Work with abciximab in the setting of percutaneous intervention would suggest that a level of platelet inhibition in excess of 80% provides the most favorable clinical benefit. Whether this applies to the small molecule inhibitors such as eptifibatide, tirofiban, and lamifiban is unknown and will require testing of the hypothesis in large-scale clinical trials. In the acute coronary syndromes, only the peptide and nonpeptide inhibitors have been studied independent of a need for percutaneous intervention. The level of platelet inhibition required to achieve maximal clinical benefit is unknown and awaits data from the large-scale unstable angina and myocardial infarction trials. Issues of combining heparin with GP IIb/IIIa inhibition and the platelet-altering effects of thrombolysis must be considered when examining what might be the optimal level of platelet inhibition that provides maximal efficacy while maintaining safety. Long-term therapy with the oral platelet inhibitors poses a particular challenge in determining an optimal level of treatment that renders clinical effectiveness while preserving safety. Large, ongoing clinical trials with these agents should provide insight into this question. Finally, given the complexity of using such potent therapies in any individual patient, there is a need for improved monitoring of the platelet inhibitory effect. Standard platelet aggregometry has its problems and limitations, as described, and is not a test that has wide-scale applicability. Whole blood aggregometry and other methods of rapidly assessing platelet function at the point of care have promise in this arena. In a clinical trial, such technology might allow better delineation of the population's pharmacodynamic response to an agent because it could be more widely applied and therefore more patients would be studied. In clinical practice, patients could be dosed individually so that a range of platelet inhibition could be achieved that was believed to provide optimal benefit and safety.


Pharmacological treatment for psychotic depression.
Evidence is limited regarding the most effective pharmacological treatment for psychotic depression: monotherapy with an antidepressant, monotherapy with an antipsychotic, another treatment (e.g. mifepristone), or combination of an antidepressant plus an antipsychotic. This is an update of a review first published in 2005 and last updated in 2015. 1. To compare the clinical efficacy of pharmacological treatments for patients with an acute psychotic depression: antidepressant monotherapy, antipsychotic monotherapy, mifepristone monotherapy, and the combination of an antidepressant plus an antipsychotic versus placebo and/or each other. 2. To assess whether differences in response to treatment in the current episode are related to non-response to prior treatment. A search of the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR); Ovid MEDLINE (1950-); Embase (1974-); and PsycINFO (1960-) was conducted on 21 February 2020. Reference lists of all included studies and related reviews were screened and key study authors contacted. All randomised controlled trials (RCTs) that included participants with acute major depression with psychotic features, as well as RCTs consisting of participants with acute major depression with or without psychotic features, that reported separately on the subgroup of participants with psychotic features. Two review authors independently extracted data and assessed risk of bias in the included studies, according to criteria from the Cochrane Handbook for Systematic Reviews of Interventions. Data were entered into RevMan 5.1. We used intention-to-treat data. Primary outcomes were clinical response for efficacy and overall dropout rate for harm/tolerance. Secondary outcome were remission of depression, change from baseline severity score, quality of life, and dropout rate due to adverse effects. For dichotomous efficacy outcomes (i.e. response and overall dropout), risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Regarding the primary outcome of harm, only overall dropout rates were available for all studies. If the study did not report any of the response criteria as defined above, remission as defined here could be used as an alternative. For continuously distributed outcomes, it was not possible to extract data from the RCTs. MAIN RESULTS: The search identified 3947 abstracts, but only 12 RCTs with a total of 929 participants could be included in the review. Because of clinical heterogeneity, few meta-analyses were possible. The main outcome was reduction in severity (response) of depression, not of psychosis. For depression response, we found no evidence of a difference between antidepressant and placebo (RR 8.40, 95% CI 0.50 to 142.27; participants = 27, studies = 1; very low-certainty evidence) or between antipsychotic and placebo (RR 1.13, 95% CI 0.74 to 1.73; participants = 201, studies = 2; very low-certainty evidence). Furthermore, we found no evidence of a difference in overall dropouts with antidepressant (RR 1.24, 95% CI 0.34 to 4.51; participants = 27, studies = 1; very low-certainty evidence) or antipsychotic monotherapy (RR 0.79, 95% CI 0.57 to 1.08; participants = 201, studies = 2; very low-certainty evidence). No evidence suggests a difference in depression response (RR 2.09, 95% CI 0.64 to 6.82; participants = 36, studies = 1; very low-certainty evidence) or overall dropouts (RR 1.79, 95% CI 0.18 to 18.02; participants = 36, studies = 1; very low-certainty evidence) between antidepressant and antipsychotic. For depression response, low- to very low-certainty evidence suggests that the combination of an antidepressant plus an antipsychotic may be more effective than antipsychotic monotherapy (RR 1.83, 95% CI 1.40 to 2.38; participants = 447, studies = 4), more effective than antidepressant monotherapy (RR 1.42, 95% CI 1.11 to 1.80; participants = 245, studies = 5), and more effective than placebo (RR 1.86, 95% CI 1.23 to 2.82; participants = 148, studies = 2). Very low-certainty evidence suggests no difference in overall dropouts between the combination of an antidepressant plus an antipsychotic versus antipsychotic monotherapy (RR 0.79, 95% CI 0.63 to 1.01; participants = 447, studies = 4), antidepressant monotherapy (RR 0.91, 95% CI 0.55 to 1.50; participants = 245, studies = 5), or placebo alone (RR 0.75, 95% CI 0.48 to 1.18; participants = 148, studies = 2). No study measured change in depression severity from baseline, quality of life, or dropouts due to adverse events. We found no RCTs with mifepristone that fulfilled our inclusion criteria. Risk of bias is considerable: we noted differences between studies with regards to diagnosis, uncertainties around randomisation and allocation concealment, treatment interventions (pharmacological differences between various antidepressants and antipsychotics), and outcome criteria. Psychotic depression is heavily under-studied, limiting confidence in the conclusions drawn. Some evidence indicates that combination therapy with an antidepressant plus an antipsychotic is more effective than either treatment alone or placebo. Evidence is limited for treatment with an antidepressant alone or with an antipsychotic alone. Evidence for efficacy of mifepristone is lacking.


Communication technology access, use, and preferences among primary care patients: from the Residency Research Network of Texas (RRNeT).
The digital revolution is changing the manner in which patients communicate with their health care providers, yet many patients still lack access to communication technology. We conducted this study to evaluate access to, use of, and preferences for using communication technology among a predominantly low-income patient population. We determined whether access, use, and preferences were associated with type of health insurance, sex, age, and ethnicity. In 2011, medical student researchers administered questionnaires to patients of randomly selected physicians within 9 primary care clinics in the Residency Research Network of Texas. Surveys addressed access to and use of cell phones and home computers and preferences for communicating with health care providers. In this sample of 533 patients (77% response rate), 448 (84%) owned a cell phone and 325 (62%) owned computers. Only 48% reported conducting Internet searches, sending and receiving E-mails, and looking up health information on the Internet. Older individuals, those in government sponsored insurance programs, and individuals from racial/ethnic minority groups had the lowest levels of technology adoption. In addition, more than 60% of patients preferred not to send and receive health information over the Internet, by instant messaging, or by text messaging. Many patients in this sample did not seek health information electronically nor did they want to communicate electronically with their physicians. This finding raises concerns about the vision of the patient-centered medical home to enhance the doctor-patient relationship through communication technology. Our patients represent some of the more vulnerable populations in the United States and, as such, deserve attention from health care policymakers who are promoting widespread use of communication technology.


A cost-benefit analysis of peer coaching for overhead lift use in the long-term care sector in Canada.
To evaluate whether a peer-coaching programme for patient lift use in British Columbia, Canada, was effective and cost-beneficial. We used monthly panel data from 15 long-term care facilities from 2004 to 2011 to estimate the number of patient-handling injuries averted by the peer-coaching programme using a generalised estimating equation model. Facilities that had not yet introduced the programme served as concurrent controls. Accepted lost-time claim counts related to patient handling were the outcome of interest with a denominator of full-time equivalents of nursing staff. A cost-benefit approach was used to estimate the net monetary gains at the system level. The coaching programme was found to be associated with a reduction in the injury rate of 34% during the programme and 56% after the programme concluded with an estimated 62 lost-time injury claims averted. 2 other factors were associated with changes in injury rates: larger facilities had a lower injury rate, and the more care hours per bed the lower the injury rate. We calculated monetary benefits to the system of $748 431 and costs of $894 000 (both in 2006 Canadian dollars) with a benefit-to-cost ratio of 0.84. The benefit-to-cost ratio was -0.05 in the worst case scenario and 2.31 in the best case scenario. The largest cost item was peer coaches' time. A simulation of the programme continuing for 5 years with the same coaching intensity would result in a benefit-to-cost ratio of 0.63. A peer-coaching programme to increase effective use of overhead lifts prevented additional patient-handling injuries but added modest incremental cost to the system.


Molecular characterization and geological microenvironment of a microbial community inhabiting weathered receding shale cliffs.
Shales play an important role in many earth system processes including coastal erosion, and they form the foundations of many engineering structures. The geobiology of the interior of pyrite-containing receding shale cliffs on the coast of northeast England was examined. The surface of the weathered shales was characterised by a thin layer of disordered authigenic iron oxyhydroxides and localised acicular, platy and aggregated gypsum, which was characterised by Raman spectroscopy, XAS and SEM. These chemical changes are likely to play an important role in causing rock weakening along fractures at the micron scale, which ultimately lead to coastal retreat at the larger scale. The surface of the shale hosts a novel, low-diversity microbial community. The bacterial community was dominated by Proteobacteria, with phylotypes closely associating with Methylocella and other members of the γ-subdivision. The second largest phylogenetic group corresponded to Nitrospira. The archaeal 16S rRNA phylotypes were dominated by a single group of sequences that matched phylotypes reported from South African gold mines and possessed ammonia monooxygenase (amoA) genes. Both the phylogenetic and the mineral data show that acidic microenvironments play an important role in shale weathering, but the shale has a higher microbial diversity than previously described pyritic acid mine drainage sites. The presence of a potentially biogeochemically active microbial population on the rock surface suggests that microorganisms may contribute to early events of shale degradation and coastal erosion.


Social learning and human mate preferences: a potential mechanism for generating and maintaining between-population diversity in attraction.
Inspired by studies demonstrating mate-choice copying effects in non-human species, recent studies of attractiveness judgements suggest that social learning also influences human preferences. In the first part of our article, we review evidence for social learning effects on preferences in humans and other animals. In the second part, we present new empirical evidence that social learning not only influences the attractiveness of specific individuals, but can also generalize to judgements of previously unseen individuals possessing similar physical traits. The different conditions represent different populations and, once a preference arises in a population, social learning can lead to the spread of preferences within that population. In the final part of our article, we discuss the theoretical basis for, and possible impact of, biases in social learning whereby individuals may preferentially copy the choices of those with high status or better access to critical information about potential mates. Such biases could mean that the choices of a select few individuals carry the greatest weight, rapidly generating agreement in preferences within a population. Collectively, these issues suggest that social learning mechanisms encourage the spread of preferences for certain traits once they arise within a population and so may explain certain cross-cultural differences.


Strong Influence of Coadsorbate Interaction on CO Desorption Dynamics on Ru(0001) Probed by Ultrafast X-Ray Spectroscopy and Ab Initio Simulations.
We show that coadsorbed oxygen atoms have a dramatic influence on the CO desorption dynamics from Ru(0001). In contrast to the precursor-mediated desorption mechanism on Ru(0001), the presence of surface oxygen modifies the electronic structure of Ru atoms such that CO desorption occurs predominantly via the direct pathway. This phenomenon is directly observed in an ultrafast pump-probe experiment using a soft x-ray free-electron laser to monitor the dynamic evolution of the valence electronic structure of the surface species. This is supported with the potential of mean force along the CO desorption path obtained from density-functional theory calculations. Charge density distribution and frozen-orbital analysis suggest that the oxygen-induced reduction of the Pauli repulsion, and consequent increase of the dative interaction between the CO 5σ and the charged Ru atom, is the electronic origin of the distinct desorption dynamics. Ab initio molecular dynamics simulations of CO desorption from Ru(0001) and oxygen-coadsorbed Ru(0001) provide further insights into the surface bond-breaking process.


Socio-demographic and clinical aspects of rheumatoid arthritis.
To determine the socio-demographic profiles and some clinical aspects of patients with rheumatoid arthritis (RA). Prospective, cross-sectional study. Ambulatory out- patient clinics of Kenyatta National Hospital (KNH), a public national and referral hospital. Out of 180 patients interviewed and examined, 60 met American College of Rheumatology (ACR) diagnostic criteria of RA. Of the 60 patients recruited 52 (87%) were females with male: female ratio of 1: 6.5. The mean age of patients was 41.38(+/- 16.8) years. There were two peaks of age of occurrence, 20-29 and 40-49 years. In 75% of the study patients, one or more of metacarpophalangeal joints of the hand were involved in the disease. Other frequently involved sites were--wrists, elbows, knees, ankles and glenohumeral joints of shoulders in a symmetrical manner. Serum rheumatoid factor was positive in 78.9% while rheumatoid nodules were present in 13.3% of the study patients. A large majority of patients (88%) had active disease with 18% having mild disease, 38% moderate activity and 32% having severe disease. Only 12% of patients had disease in remission. Forty six point seven per cent (46.7%) of the study patients were on at least one Disease Modifying anti Rheumatic Drugs (DMARD) from a selection of methotrexate, sulphasalazine, hydroxychloroquine and leflunamide. The most frequent drug combination was methotrexate plus prednisolone at 30% of the study population; while 66.7% were on oral prednisolone with 25% of the study patients taking only Non-Steroidal anti Inflammatory Drugs (NSAIDS). A large majority of ambulatory patients with RA had active disease. Most of them were sub-optimally treated, especially the use of DMARDS. About two thirds were on oral steroids. Sub-optimal therapy in relatively young patients, peak 20-29 and 40-49 years is likely to impact negatively on their disease control and quality of life.


Prevalence, impact and cultural context of psychotic experiences among ethnic minority youth.
The risk for psychotic disorders is increased for many ethnic minority groups and may develop in early childhood. This study investigated whether the prevalence of psychotic experiences (PE) with high impact is higher among ethnic minority youth compared to majority youth and examined the significance of these PE. A school-based study assessed a large community sample of 1545 ethnic minority and majority children in The Netherlands (mean age 12.98 ± 1.81 years). The Dutch (n = 702, 45.4%), Moroccan-Dutch (n = 400, 25.9%) and Turkish-Dutch (n = 170, 11.0%) ethnic groups could be studied separately. Self-report questionnaires on PE, impact and cultural context were administered. Prevalence of PE with high impact was 3.1% in Dutch, 9.5% in Moroccan-Dutch and 7.1% in Turkish-Dutch youth. Compared to Dutch youth, odds ratios were 3.0 [95% confidence interval (CI) 1.7-5.1] for Moroccan-Dutch youth and 2.2 (95% CI 1.1-4.6) for Turkish-Dutch youth. Differences were not explained by cultural or religious differences. The increased risk for psychotic disorders in ethnic minorities may already be detectable in childhood, since PE with high impact were more common among ethnic minority youth compared to majority youth. The additional measurement of impact of PE appears to be a valid approach to identify those children at risk to develop psychotic or other more common psychiatric disorders.


The effect of shoe type and fatigue on strike index and spatiotemporal parameters of running.
We aimed to observe differences in running style parameters and the stride-to-stride coefficient of variation and correlative patterns using detrended fluctuation analysis (DFA) between conventional and first-time minimalistic shoe use. We also aimed to study the effect of fatigue on these parameters. 26 recreational runners were tested using a pressure insole device on a treadmill whilst wearing conventional (CONV) and minimalistic (MIN) shoes. They then performed a prolonged running bout simulating a fatiguing training session, before being tested a second time in both shoe types. Average values of strike index (initial ground contact point on the footsole expressed as a percentage of total sole length) were not significantly different between CONV [25.7±14.6% (unfatigued), 23.1±11.1% (fatigued)] and MIN [28.9±19.1% (unfatigued), 26.7±17.6% (fatigued)] (p=0.501). The fatigued state also yielded a similar strike index compared to the unfatigued state (p=0.661). An overall trend in decreased inter-stride correlative patterns of strike index was observed in MIN compared to CONV (p=0.075). No differences in contact time, flight time, stride time, duty factor, stride length and stride frequency were found between shoe types. A trend in reduced flight time (p=0.078) and therefore increased duty factor (p=0.053) was observed due to fatigue. We conclude that in recreational runners, no meaningful, acute adaptation in running style occurs as a result of first-time MIN use. Similarly, runners were able to maintain their running style after a prolonged running bout.


Development and application of a quantitative real-time PCR for the diagnosis of Surra in water buffaloes.
Trypanosoma evansi (T. evansi) causes the disease called Surra in domestic animals, which is of great economic importance in South Asian countries. In order to improve the diagnosis of Surra, we endeavored to develop a real-time PCR assay for the detection and quantification of parasites in water buffaloes using specific primers for the T. evansi Rode Trypanozoon antigen type (RoTat) 1.2 Variable Surface Glycoprotein (VSG) gene, which is a known diverse DNA region in trypanosomes. The quantitative detection limit of the assay was 10(2) trypanosomes per mL of blood, and the identity of the amplicon was confirmed in all assays by melting curve analysis. To evaluate the clinical applicability of this procedure, detection and estimation of parasitemia in blood samples obtained from water buffaloes and horses were conducted. T. evansi was detected in 17/607 (2.8%) blood samples, with parasitemia levels ranging from >10(1) to 10(7) parasites per mL of blood. Interestingly, out of the 17 PCR positive animals, 3 had previously received trypanocidal treatment and 1 had abortion history. These data indicate that real-time PCR for the estimation of putative parasitemia levels is a quantitatively and objectively applicable technique for clinical diagnosis of Surra, and could help to understand disease stage and risk of transmission of T. evansi.


Disparities in Caregivers' Experiences at the Dentist With Their Young Child.
To understand the experiences of diverse families when taking their young children to the dentist and to document their prevalence. An exploratory sequential design was used. First, 4 focus groups (N = 33) comprised of low-income female caregivers of children under 6 years of age were conducted in English and Spanish. Discussions centered around facilitators and barriers to taking children to the dentist. Themes derived from the groups were then used to create a survey that was given to 1184 caregivers in English, Spanish, or Vietnamese. Thematic coding of focus groups found little support for typically reported barriers to pediatric oral health care utilization (eg, transportation, cost, knowledge); instead, caregivers reported negative experiences (eg, restraint, separation) as barriers. In the surveys, 66% of caregivers reported being separated from their children, 25% reported that their children were restrained (53.7% for cleanings), 26% of children were given sedating medication for cleanings, and 22% of the caregivers reported experiences that made them not want to return to the dentist. The prevalence of these experiences differed significantly among Latino, Asian, and Caucasian families and for annual incomes under or above $50,000. Families with lower incomes and/or from ethnic and linguistic minority groups were more likely to report negative experiences at the dentist than higher income and Caucasian families. These data document the high prevalence of negative experiences and suggest ethnic, financial, and linguistic disparities in the quality of experiences. More research is needed on the role of dentists in facilitating or hindering oral health care utilization among diverse families.


How Can Decision Making Be Improved?
The optimal moment to address the question of how to improve human decision making has arrived. Thanks to 50 years of research by judgment and decision-making scholars, psychologists have developed a detailed picture of the ways in which human judgment is bounded. This article argues that the time has come to focus attention on the search for strategies that will improve bounded judgment because decision-making errors are costly and are growing more costly, decision makers are receptive, and academic insights are sure to follow from research on improvement. In addition to calling for research on improvement strategies, this article organizes the existing literature pertaining to improvement strategies and highlights promising directions for future research.


Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection.
A simple treatment regimen that is effective in a broad range of patients who are chronically infected with the hepatitis C virus (HCV) remains an unmet medical need. We conducted a phase 3, double-blind, placebo-controlled study involving untreated and previously treated patients with chronic HCV genotype 1, 2, 4, 5, or 6 infection, including those with compensated cirrhosis. Patients with HCV genotype 1, 2, 4, or 6 were randomly assigned in a 5:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir in a once-daily, fixed-dose combination tablet or matching placebo for 12 weeks. Because of the low prevalence of genotype 5 in the study regions, patients with genotype 5 did not undergo randomization but were assigned to the sofosbuvir-velpatasvir group. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. Of the 624 patients who received treatment with sofosbuvir-velpatasvir, 34% had HCV genotype 1a, 19% genotype 1b, 17% genotype 2, 19% genotype 4, 6% genotype 5, and 7% genotype 6. A total of 8% of patients were black, 19% had cirrhosis, and 32% had been previously treated for HCV. The rate of sustained virologic response among patients receiving sofosbuvir-velpatasvir was 99% (95% confidence interval, 98 to >99). Two patients receiving sofosbuvir-velpatasvir, both with HCV genotype 1, had a virologic relapse. None of the 116 patients receiving placebo had a sustained virologic response. Serious adverse events were reported in 15 patients (2%) in the sofosbuvir-velpatasvir group and none in the placebo group. Once-daily sofosbuvir-velpatasvir for 12 weeks provided high rates of sustained virologic response among both previously treated and untreated patients infected with HCV genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT02201940.).


The role of p21 in regulating mammalian regeneration.
The MRL (Murphy Roths Large) mouse has provided a unique model of adult mammalian regeneration as multiple tissues show this important phenotype. Furthermore, the healing employs a blastema-like structure similar to that seen in amphibian regenerating tissue. Cells from the MRL mouse display DNA damage, cell cycle G2/M arrest, and a reduced level of p21CIP1/WAF. A functional role for p21 was confirmed when tissue injury in an adult p21-/- mouse showed a healing phenotype that matched the MRL mouse, with the replacement of tissues, including cartilage, and with hair follicle formation and a lack of scarring. Since the major canonical function of p21 is part of the p53/p21 axis, we explored the consequences of p53 deletion. A regenerative response was not seen in a p53-/- mouse and the elimination of p53 from the MRL background had no negative effect on the regeneration of the MRL.p53-/- mouse. An exploration of other knockout mice to identify p21-dependent, p53-independent regulatory pathways involved in the regenerative response revealed another significant finding showing that elimination of transforming growth factor-β1 displayed a healing response as well. These results are discussed in terms of their effect on senescence and differentiation.


Curcumin modulates efflux mediated by yeast ABC multidrug transporters and is synergistic with antifungals.
Curcumin (CUR), a natural product of turmeric, from rhizomes of Curcuma longa, is a known agent of reversal of drug resistance phenotypes in cancer cells overexpressing ATP-binding cassette (ABC) transporters, viz., ABCB1, ABCG2, and ABCC1. In the present study, we evaluated whether CUR could also modulate multidrug transporters of yeasts that belong either to the ABC family or to the major facilitator superfamily (MFS). The effect of CUR on multidrug transporter proteins was demonstrated by examining rhodamine 6G (R6G) efflux in Saccharomyces cerevisiae cells overexpressing the Candida albicans ABC transporters Cdr1p and Cdr2p (CaCdr1p and CaCdr2p, respectively) and the MFS transporters CaMdr1p and S. cerevisiae Pdr5p. CUR decreased the extracellular concentration of R6G in ABC transporter-expressing cells but had no effect on methotrexate efflux mediated through the MFS transporter CaMdr1p. CUR competitively inhibited R6G efflux and the photolabeling of CaCdr1p by [(125)I]iodoarylazidoprazosin, a drug analogue of the substrate prazosin (50% inhibitory concentration, 14.2 microM). Notably, the mutant variants of CaCdr1p that displayed abrogated efflux of R6G also showed reduced modulation by CUR. Drug susceptibility testing of ABC protein-expressing cells by spot assays and checkerboard tests revealed that CUR was selectively synergistic with drug substrates such as R6G, ketoconazole, itraconazole, and miconazole but not with fluconazole, voriconazole, anisomycin, cycloheximide, or FK520. Taken together, our results provide the first evidence that CUR modulates only ABC multidrug transporters and could be exploited in combination with certain conventional antifungal drugs to reverse multidrug resistance in Candida cells.


Drug Use among Street Children in Tehran, Iran: A Qualitative Study.
Globally, children who work and live on the streets are at higher risk of undesired behavioral health outcomes, including increased drug use and abuse. Considering the rapid growth of this population in Iran and the lack of program planning that is partly due to a scarcity of research-based information, this study was conducted in 2013 to investigate drug use among street children in Tehran. With a qualitative design, we conducted a Rapid Assessment and Response Survey of street children in Tehran, 2012-2013. Data were also obtained from 10 focus group discussions with street children using semi-structured questionnaires and 27 in-depth interviews with key informants in governmental, non-governmental, and international organizations. The variation in age at first use, type of drugs, and pattern of drug use were found based on ethnicity. Consuming of Alcohol was reported to be more among an ethnic group. Drug use problems were commonly described among families of street children. Children whose parents had drug-use problems described using drugs earlier than other children. Informants reported that families with drug-related problems used children for procurement of drugs. Children themselves described using drugs to cope with stress, and to reduce physical and psychological stressors and problems, such as fatigue, sadness, and pressure, resulting from frequent failures in life. These results suggest that intervention and prevention programs dealing with drug use of street children in Iran should include family and peers when addressing drug use by street children.


Co-occurring lower respiratory symptoms and posttraumatic stress disorder 5 to 6 years after the World Trade Center terrorist attack.
We have described the epidemiology of co-occurring lower respiratory symptoms (LRS) and probable posttraumatic stress disorder (PTSD) 5 to 6 years after exposure to the 9/11 disaster. We analyzed residents, office workers, and passersby (n = 16,363) in the World Trade Center Health Registry. Using multivariable logistic regression, we examined patterns of reported respiratory symptoms, treatment sought for symptoms, diagnosed respiratory conditions, mental health comorbidities, quality of life, and unmet health care needs in relation to comorbidity. Among individuals with either LRS or PTSD, 24.6% had both conditions. The odds of comorbidity was significantly higher among those with more severe 9/11 exposures. Independent of 9/11 exposures, participants with LRS had 4 times the odds of those without it of meeting criteria for PTSD, and those with PTSD had 4 times the odds of those without it of meeting criteria for LRS. Participants with comorbidity had worse quality of life and more unmet mental health care needs than did all other outcome groups. Respiratory and mental illness are closely linked in individuals exposed to 9/11 and should be considered jointly in public health outreach and treatment programs.


Pyramids: a platform for designing multifunctional plasmonic particles.
This Account explores nanofabricated pyramids, a new class of nanoparticles with tunable optical properties at visible and near-infrared wavelengths. This system is ideally suited for designing multifunctional plasmonic materials for use in diagnostics, imaging, sensing, and therapeutics. The nanofabrication scheme that we developed (called PEEL) for these asymmetric metal particles is extremely versatile and offers several advantages over synthetic methodologies. The PEEL approach yields pyramids with variable sizes, thicknesses, and multimetal compositions, as well as blunt or ultrasharp tips or no tips. In addition, we have prepared pyramids with site-specific chemical and biological functionality on different portions of the pyramids. This is an important design feature for biological applications, as suggested by the generation of amphiphilic gold pyramids functionalized with alkanethiols on the hydrophobic portions and DNA on the hydrophilic portions. The optical characteristics of these pyramids depend on particle orientation, wavevector direction, and polarization direction and can be tuned. Using the multipolar surface plasmon resonances of large (>250 nm) pyramids, imaging and spectral identification of pyramid orientation in condensed media was possible. We were also able to direct pyramids to assemble into one- and two-dimensional arrays with interesting optical properties. Furthermore, modification of the PEEL fabrication scheme allowed the production of multimaterial pyramidal structures with complex attributes, highlighting the power of this platform for exacting nanometer-scale control over particle structure and composition.


Use of selective inhibitors and chromogenic substrates to differentiate bacteria based on toluene oxygenase activity.
In whole-cell studies, two alkynes, 1-pentyne and phenylacetylene, were selective, irreversible inhibitors of monooxygenase enzymes in catabolic pathways that permit growth of bacteria on toluene. 1-Pentyne selectively inhibited growth of Burkholderia cepacia G4 (toluene 2-monooxygenase [T2MO] pathway) and B. pickettii PKO1 (toluene 3-monooxygenase [T3MO] pathway) on toluene, but did not inhibit growth of bacteria expressing other pathways. In further studies with strain G4, chromogenic transformation of alpha,alpha,alpha-Trifluoro-m-cresol (TFC) was irreversibly inhibited by 1-pentyne, but the presence of phenol prevented this inhibition. Transformation of catechol by G4 was unaffected by 1-pentyne. With respect to the various pathways and bacteria tested, phenylacetylene selectively inhibited growth of Pseudomonas mendocina KR1 (toluene 4-monooxygenase [T4MO] pathway) on toluene, but not on p-cresol. An Escherichia coli transformant expressing T4MO transformed indole or naphthalene in chromogenic reactions, but not after exposure to phenylacetylene. The naphthalene reaction remained diminished in phenylacetylene-treated cells relative to untreated cells after phenylacetylene was removed, indicating irreversible inhibition.These techniques were used to differentiate toluene-degrading isolates from an aquifer. Based on data generated with these indicators and inhibitors, along with results from Biolog analysis for sole carbon source oxidation, the groundwater isolates were assigned to eight separate groups, some of which apparently differ in their mode of toluene catabolism.


The influence of early sexual debut and sexual violence on adolescent pregnancy: a matched case-control study in Jamaica.
Contraceptive knowledge and use at first sex have increased over time among Jamaican adolescents, yet high unintended pregnancy rates persist. More information on risk factors for adolescent pregnancy is needed to inform programs. Structured interviews were conducted with 15-17-year-old females-250 who were currently pregnant and 500 sexually experienced, but never-pregnant, neighborhood-matched controls. Bivariate and multivariate analyses were used to examine associations between adolescent pregnancy and early sexual debut, sexual coercion or violence and sexual risk-taking behaviors. Greater proportions of pregnant youth than of their never-pregnant peers reported having had first sex by age 14 (54% vs. 41%), a first sexual partner who was five or more years older (33% vs. 20%) or multiple partners (63% vs. 50%); a greater proportion of never-pregnant youth had used contraceptives at first sex (88% vs. 80%). Almost half (49%) of all young women reported ever having experienced sexual coercion or violence. Compared with controls, pregnant youth had greater odds of having had an older partner at first sex and believing contraception is a woman's responsibility (odds ratios, 1.3 and 2.1, respectively), and had lower odds of ever having experienced sexual violence and thinking that it is important to protect oneself against pregnancy (0.5 and 0.2, respectively). An interaction between early sexual debut and multiple partners was found. Having had multiple partners was associated with pregnancy only for youth with early sexual debut. Encouraging adolescents to delay sexual debut and reduce their number of sexual partners may help prevent unintended pregnancies. Experiences of sexual coercion and violence were common among both groups, highlighting the need to address gender-based violence at the community level.


Chemical and toxicological evaluation of transformation products during advanced oxidation processes.
The entry of pharmaceuticals into the water cycle from sewage treatment plants is of growing concern because environmental effects are evident at trace levels. Ozonation, UV- and UV/H(2)O(2)-treatment were tested as an additional step in waste water treatment because they have been proven to be effective in eliminating aqueous organic contaminants. The pharmaceuticals carbamazepine, ciprofloxacin, diclofenac, metoprolol and sulfamethoxazole as well as the personal care products galaxolide and tonalide were investigated in terms of degradation efficiency and by-product formation in consideration of toxic effects. The substances were largely removed from treatment plant effluent by ozonation, UV- and UV/H(2)O(2)-treatment. Transformation products were detected in all tested treatment processes. Accompanying analysis showed no genotoxic, cytotoxic or estrogenic potential for the investigated compounds after oxidative treatment of real waste waters. The results indicate that by-product formation from ozonation and advanced oxidation processes does not have any negative environmental impact.


Influence of reduced feed ration on Lepeophtheirus salmonis infestation and inflammatory gene expression in juvenile pink salmon.
The effect of reduced feed ration on infestation levels with the sea louse Lepeophtheirus salmonis and gene expression in juvenile pink salmon Oncorhynchus gorbuscha was tested in three laboratory trials. Body weight was significantly lower among fish on the reduced ration for 27, 34, or 65 d than fish on the full ration. Neither the prevalence nor the abundance of L. salmonis differed between fish on full and reduced rations at any time in any trial. In trial 2, sea louse rejection was delayed among fish on reduced rations; however, the parasite was ultimately rejected from all fish in this trial regardless of ration. Proinflammatory gene expression in salmon exposed to L. salmonis was modulated by reduced rations. There was a reduction in the expression of interleukin-8 in pink salmon on reduced rations 7 d after exposure but not 14 d after exposure. In contrast, the 7-d expression of interleukin-1 beta (IL-1beta) was reduced in exposed pink salmon regardless of ration. By day 14, however, expression of IL-1beta was increased in association with reduced rations among exposed salmon. Similarly, the expression of tumor necrosis factor alpha (TNFalpha) was increased 14 d after exposure among salmon on a reduced ration. There was no evidence that short-duration exposure of otherwise healthy juvenile pink salmon to a reduced ration affected susceptibility to L. salmonis. The expression data do not suggest an obvious mechanism of louse rejection; rather, they indicate that a more comprehensive suite of inflammatory pathways should be surveyed to better understand the early pink salmon response to L. salmonis.