Enhanced depth imaging of the choroid in patients with neovascular age-related macular degeneration treated with anti-VEGF therapy versus untreated patients.
To compare the subfoveal choroidal thickness (SFCT) between patients with neovascular age-related macular degeneration (nAMD) who had multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents and those with treatment-naïve nAMD. This retrospective case-control study included 15 patients in group 1 (nAMD in one eye which had received at least three anti-VEGF injections and early AMD in the fellow eye) and 15 patients in group 2 (newly diagnosed nAMD in one eye which had not received any treatment and early AMD in the fellow eye). They underwent enhanced depth imaging optical coherence tomography (OCT), and two OCT readers manually measured the SFCT. Inter-ocular difference in SFCT (nAMD eye minus fellow eye) was calculated for each patient. The nAMD eyes in group 1 had received a median (range) of four (3-8) intravitreal injections of anti-VEGF agents, and the OCT scans were performed at a median (range) of 9 (4-17) months after the first injection. The median inter-ocular difference in SFCT in groups 1 and 2 were not significantly different (13.5 and 3.0 μm in groups 1 and 2 respectively, p=0.60). There was also no statistically significant difference in SFCT between nAMD and fellow eyes (p=0.16), although there was a trend for greater median SFCT in the nAMD eyes. The data from this small cohort suggests that no gross reduction in SFCT appears in nAMD patients after a time interval of at least 4 months between initiating repeated treatment with anti-VEGF therapy and OCT imaging. However, a study with a much larger sample size or longitudinal design is required to detect possible small fluctuations in SFCT in nAMD eyes receiving anti-VEGF therapy.


Post-dexamethasone cortisol as a predictor for the efficacy of electroconvulsive therapy in depressed inpatients.
Although several variables have been studied as a possible predictor for the efficacy of ECT, results regarding hypercortisolism have been inconsistent. This prospective study evaluates the relation between pre-treatment cortisol levels and the efficacy of ECT in a population of drug-free inpatients with severe major depression. At the inpatient depression unit, 18 patients meeting the DSM-IV criteria for depressive disorder, and with scores of at least 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D), were treated with bilateral ECT twice weekly. The HAM-D evaluated depression severity and was performed within 3 days prior to ECT, weekly during the course of ECT, and within 3 days after the last treatment. The outcome criterion was defined a priori as the change on the HAM-D score. Salivary cortisol was assessed within 3 days prior to ECT at two time points, followed by 0.5 mg dexamethasone ingestion. The following day, salivary cortisol was again assessed at two time points. The generalized linear model was used to assess the relation between salivary cortisol levels and reduction in HAM-D score as continuous variables. Higher levels of salivary cortisol at 9 AM after 0.5 mg dexamethasone ingestion are associated with a greater reduction in HAM-D score (B = -0.279, 95% CI: -0.557 to -0.01, s.e. = 0.13, p = 0.049; R square = 0.23; adjusted R square = 0.13). This study suggests that higher levels of post-dexamethasone salivary cortisol at 9 AM are predictive of ECT efficacy.


Acute sulfonylurea therapy at disease onset can cause permanent remission of KATP-induced diabetes.
Neonatal diabetes mellitus (NDM) can be caused by gain-of-function ATP-sensitive K(+) (K(ATP)) channel mutations. This realization has led to sulfonylurea therapy replacing insulin injections in many patients. In a murine model of K(ATP)-dependent NDM, hyperglycemia and consequent loss of β-cells are both avoided by chronic sulfonylurea treatment. Interestingly, K(ATP) mutations may underlie remitting-relapsing, transient, or permanent forms of the disease in different patients, but the reason for the different outcomes is unknown. To gain further insight into disease progression and outcome, we examined the effects of very early intervention by injecting NDM mice with high-dose glibenclamide for only 6 days, at the beginning of disease onset, then after the subsequent progression with measurements of blood glucose, islet function, and insulin sensitivity. Although ∼70% of mice developed severe diabetes after treatment cessation, ∼30% were essentially cured, maintaining near-normal blood glucose until killed. Another group of NDM mice was initiated on oral glibenclamide (in the drinking water), and the dose was titrated daily, to maintain blood glucose <200 mg/dL. In this case, ∼30% were also essentially cured; they were weaned from the drug after ∼4 weeks and again subsequently maintained near-normal blood glucose. These cured mice maintain normal insulin content and were more sensitive to insulin than control mice, a compensatory mechanism that together with basal insulin secretion may be sufficient to maintain near-normal glucose levels. At least in a subset of animals, early sulfonylurea treatment leads to permanent remission of NDM. These cured animals exhibit insulin-hypersensitivity. Although untreated NDM mice rapidly lose insulin content and progress to permanently extremely elevated blood glucose levels, early tight control of blood glucose may permit this insulin-hypersensitivity, in combination with maintained basal insulin secretion, to provide long-term remission.


Selected antioxidants and risk of hormone receptor-defined invasive breast cancers among postmenopausal women in the Women's Health Initiative Observational Study.
Few studies have evaluated carotenoids and vitamins C and E in association with the risk of breast cancers defined by estrogen receptor (ER) and progesterone receptor (PR) status. We examined the associations between dietary and supplemental intakes of these nutrients and risk of breast cancers jointly defined by both ER and PR status among postmenopausal women. Our investigation was conducted in the Women's Health Initiative Observational Study. After following 84 805 women for an average of 7.6 y, 2879 incident invasive breast cancer cases had been ascertained, of whom 2509 had receptor data. We used Cox proportional hazards models to assess the associations of interest. Dietary alpha-carotene (highest versus lowest quintile: RR = 0.83; 95% CL = 0.70, 0.99; P for trend = 0.019), beta-carotene (highest versus lowest quintile: RR = 0.78; 95% CL = 0.66, 0.94; P for trend = 0.021), and lycopene (highest versus lowest quintile: RR = 0.85; 95% CL = 0.73, 1.00; P for trend = 0.064) were inversely associated with risk of ER+PR+breast cancer, but not with other breast cancer groups jointly defined by ER and PR status. Total or supplemental beta-carotene and dietary intakes of lutein+zeaxanthin and beta-cryptoxanthin were not associated with breast cancers defined by ER and PR status. Vitamin E (regardless of source) and dietary vitamin C were not associated with breast cancer. However, total and supplemental vitamin C intake had weak positive associations with breast cancer overall. Dietary intake of certain carotenoids might be differentially associated with risk of invasive breast cancers jointly defined by ER and PR status among postmenopausal women.


Elevated expression of serine protease HtrA1 in preeclampsia and its role in trophoblast cell migration and invasion.
Aberrant expression of developmentally regulated genes during placental development could affect fetal growth and contribute to preeclampsia. Expression of serine protease HtrA1 is developmentally regulated with the highest expression in decidua capsularis, compared with ectoplacental cone, and with the highest expression during later stages of pregnancy, compared with early stages. This study was designed to determine the expression of HtrA1 in placental tissues from control and preeclamptic pregnancies and to determine the effect of HtrA1 expression in trophoblast cell migration and invasion. HtrA1 expression was assessed by immunohistochemistry in placentas from gestational age-matched preeclamptic and control pregnancies. HtrA1 expression in extravillous trophoblast cells, HTR-8/SVneo, was assessed by immunoblotting and immunofluorescence microscopy. Finally, the effect of ectopic expression of HtrA1 on cell migration and invasion was determined in HTR-8/SVneo cells. Higher expression of HtrA1 was detected in placental tissues collected from patients with early-onset preeclampsia, compared with those from gestational age-matched control samples. Moreover, ectopic expression of HtrA1 significantly attenuates HTR-8/SVneo cell migration and invasion. Higher expression of HtrA1 is associated with early-onset preeclampsia and may affect trophoblast cell migration and invasion.


A different approach to incarcerated and complicated rectal prolapse.
Rectal prolapse is an intussusception of the rectum through the anal canal. The extent of the prolapse varies from the rectal mucosa to the full thickness of the rectum and sigmoid colon. It usually appears after 50 years of age, with a female predominance of over 80-90% of cases. A rare case of incarcerated rectal prolapse with sigmoid colon perforation is reported. A different approach for large incarcerated rectal prolapse was used that can easily be performed in the emergency department in comorbid elderly patients. In emergent conditions, comorbid diseases of the patient increase the risk of mortality. Perineal resection allowed using loco-regional anesthesia. Perineal resection was safely applied and uncomplicated. Spinal anesthesia decreases the risk of operation and at same time allows correction of the main defect. After this operation there is no need for a second attempt. The patient was discharged seven days after the operation. The perineal resection technique used in this case has two distinctive features: it reconstructs the pathology as closely as possible to its original anatomical condition and allows the use of spinal anesthesia.


Evaluating the Accountable Health Communities Demonstration Project.
Despite substantial evidence documenting the social patterning of disease, relatively little information is available on how the health care system can best intervene on social determinants to impact individual and population health. Announced in January 2016, the Centers for Medicare and Medicaid Innovation's (CMMI) Accountable Health Communities (AHC) initiative provides an important opportunity to improve the evidence base around integrated social and medical care delivery. To maximize learning from this large-scale demonstration, comprehensive evaluation efforts should focus on effectiveness and implementation research by supporting local, regional, and national studies across a range of outcomes. Findings from this demonstration could transform how, when, and which patients' health-related social needs are addressed within the health care delivery system. Such findings would strongly complement other initiatives to address social factors outside of health care.


Endorsed and Anticipated Stigma Inventory (EASI): a tool for assessing beliefs about mental illness and mental health treatment among military personnel and veterans.
Many military personnel and veterans who would benefit from mental health treatment do not seek care, underscoring the need to identify factors that influence initiation and retention in mental health care. Both endorsed and anticipated mental health stigma may serve as principal barriers to treatment seeking. To date, most research on mental health stigma in military and veteran populations has relied on nonvalidated measures with limited content coverage and confounding in the assessment of different domains of mental health stigma. This article describes the development and psychometric evaluation of the Endorsed and Anticipated Stigma Inventory (EASI), which was designed to assess different dimensions of stigma-related beliefs about mental health among military and veteran populations. Findings based on a national sample of U.S. veterans deployed in support of Operation Enduring Freedom (OEF) in Afghanistan or Operation Iraqi Freedom (OIF) in Iraq suggest that the EASI is a psychometrically sound instrument. Specifically, results revealed evidence for the internal consistency reliability, content validity, convergent and discriminant validity, and discriminative validity of EASI scales. In addition, confirmatory factor analysis results supported the proposed factor structure for this inventory of scales.


Association of genetic variation within UBL5 with phenotypes of metabolic syndrome.
The BEACON gene was initially identified using the differential display polymerase chain reaction on hypothalamic mRNA samples collected from lean and obese Psammomys obesus, a polygenic animal model of obesity. Hypothalamic BEACON gene expression was positively correlated with percentage of body fat, and intracerebroventricular infusion of the Beacon protein resulted in a dose-dependent increase in food intake and body weight. The human homolog of BEACON, UBL5, is located on chromosome 19p in a region previously linked to quantitative traits related to obesity. Our previous studies showed a statistically significant association between UBL5 sequence variation and several obesity- and diabetes-related quantitative physiological measures in Asian Indian and Micronesian cohorts. Here we undertake a replication study in a Mexican American cohort where the original linkage signal was first detected. We exhaustively resequenced the complete gene plus the putative promoter region for genetic variation in 55 individuals and identified five single nucleotide polymorphisms (SNPs), one of which was novel. These SNPs were genotyped in a Mexican American cohort of 900 individuals from 40 families. Using a quantitative trait linkage disequilibrium test, we found significant associations between UBL5 genetic variants and waist-to-hip ratio (p = 0.027), and the circulating concentrations of insulin (p = 0.018) and total cholesterol (p = 0.023) in fasted individuals. These data are consistent with our earlier published studies and further support a functional role for the UBL5 gene in influencing physiological traits that underpin the development of metabolic syndrome.


Analysis of congenital hypomyelinating Egr2Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination.
Egr2 is a transcription factor required for peripheral nerve myelination in rodents, and mutations in Egr2 are associated with congenital hypomyelinating neuropathy (CHN) in humans. To further study its role in myelination, we generated mice harboring a hypomorphic Egr2 allele (Egr2Lo) that survive for up to 3 weeks postnatally, a period of active myelination in rodents. These Egr2Lo/Lo mice provided the opportunity to study the molecular effects of Egr2 deficiency on Schwann cell biology, an analysis that was not possible previously, because of the perinatal lethality of Egr2-null mice. Egr2Lo/Lo mice phenocopy CHN, as evidenced by the severe hypomyelination and increased numbers of proliferating Schwann cells of the peripheral nerves. Comparison of sciatic nerve gene expression profiles during development and after crush injury with those of Egr2Lo/Lo Schwann cells revealed that they are developmentally arrested, with down-regulation of myelination-related genes and up-regulation of genes associated with immature and promyelinating Schwann cells. One of the abnormally elevated genes in Egr2Lo/Lo Schwann cells, Sox2, encodes a transcription factor that is crucial for maintenance of neural stem cell pluripotency. Wild-type Schwann cells infected with Sox2 adenovirus or lentivirus inhibited expression of myelination-associated genes (e.g., myelin protein zero; Mpz), and failed to myelinate axons in vitro, but had an enhanced proliferative response to beta-neuregulin. The characterization of a mouse model of CHN has provided insight into Schwann cell differentiation and allowed the identification of Sox2 as a negative regulator of myelination.


Balancing conflicting mitigation and adaptation behaviours of urban residents under climate change and the urban heat island effect.
Under a warming climate and urban heat island effects, cooling behaviours are increasingly important for city dwellers. Cooling actions, especially air conditioning, receive increasing scrutiny in social science, as does engagement and communication on behaviours spanning adaptation and mitigation. In response, this paper evaluates the relation between residents' adaptation and mitigation behaviours around cooling in Fukuoka, Japan, and draws lessons for communication on encouraging adaptation and mitigation actions. A survey distributed to residents in six areas of Fukuoka, Japan, assessed perceptions of global warming and urban heat island effects, frequency of mitigation and adaptation behaviours, use of air conditioning, electricity bills and evaluation of green spaces. We observe a difference between respondents using air conditioning with an energy-saving (i.e. mitigation) focus, versus those using air conditioning with an adaptation (i.e. cooling) focus. We also note residents emphasising mitigation behaviours may use shade in parks or cooling centres as alternative cooling strategies, but that awareness of effective air conditioning use may be lacking. Our findings build on existing literature by reinforcing - in a subtropical context - the need to reconsider practices around air conditioner use; and illustrate the value of a breadth of messages to promote joint mitigation and adaptation actions.


Advancement of pediatric blood and marrow transplantation research in North America: priorities of the Pediatric Blood and Marrow Transplant Consortium.
Advances in pediatric bone marrow transplantation (BMT) are slowed by the small number of patients with a given disease who undergo transplantation, a lack of sufficient infrastructure to run early-phase oncology protocols and studies of rare nonmalignant disorders, and challenges associated with funding multi-institutional trials. Leadership of the Pediatric Blood and Marrow Transplant Consortium (PBMTC), a large pediatric BMT clinical trials network representing 77 active and 45 affiliated centers worldwide, met in April 2009 to develop strategic plans to address these issues. Key barriers, including infrastructure development and funding, along with scientific initiatives in malignant and nonmalignant disorders, cellular therapeutics, graft-versus-host disease, and supportive care were discussed. The PBMTC's agenda for approaching these issues will result in infrastructure and trials specific to pediatrics that will run through the PBMTC or its partners, the Blood and Marrow Transplant Clinical Trials Network and the Children's Oncology Group.


Spatial variation in egg size and egg number reflects trade-offs and bet-hedging in a freshwater fish.
1. Maternal reproductive investment is thought to reflect a trade-off between offspring size and fecundity, and models generally predict that mothers inhabiting adverse environments will produce fewer, larger offspring. More recently, the importance of environmental unpredictability in influencing maternal investment has been considered, with some models predicting that mothers should adopt a diversified bet-hedging strategy whilst others a conservative bet-hedging strategy. 2. We explore spatial egg size and fecundity patterns in the freshwater fish southern pygmy perch (Nannoperca australis) that inhabits a diversity of streams along gradients of environmental quality, variability and predictability. 3. Contrary to some predictions, N. australis populations inhabiting increasingly harsh streams produced more numerous and smaller eggs. Furthermore, within-female egg size variability increased as environments became more unpredictable. 4. We argue that in harsh environments or those prone to physical disturbance, sources of mortality are size independent with offspring size having only a minor influence on offspring fitness. Instead, maternal fitness is maximized by producing many small eggs, increasing the likelihood that some offspring will disperse to permanent water. We also provide empirical support for diversified bet-hedging as an adaptive strategy when future environmental quality is uncertain and suggest egg size may be a more appropriate fitness measure in stable environments characterized by size-dependent fitness. These results likely reflect spatial patterns of adaptive plasticity and bet-hedging in response to both predictable and unpredictable environmental variance and highlight the importance of considering both trait averages and variance. 5. Reproductive life-history traits can vary predictably along environmental gradients. Human activity, such as the hydrological modification of natural flow regimes, alters the form and magnitude of these gradients, and this can have both ecological and evolutionary implications for biota adapted to now non-existent natural environmental heterogeneity.


Generational differences in the physical activity of UK South Asians: a systematic review.
South Asians are some of the least active people in the UK, but we know very little about how physical activity varies within and between different UK South Asian groups. There is much socio-economic and cultural heterogeneity among UK Indians, Pakistanis and Bangladeshis, and the same approaches to increasing physical activity may not be appropriate for all people of these ethnic groups. We report on the variation in physical activity behaviour prevalence in quantitative studies and the variations in attitudes, motivations and barriers to physical activity among South Asians in qualitative papers. We performed systematic searches in MEDLINE, Embase and Psychinfo for papers written in English and published between 1990 and 2014. We also attempted to search literature not published in peer-review journals (the 'grey' literature). We reported data for the quantitative observational studies and synthesised themes from the qualitative literature according to age-group. We assessed the quality of studies using a National Institute of Health and Clinical Excellence tool. We included 29 quantitative papers and 17 qualitative papers. Thirteen papers reported on physical activity prevalence in South Asian children, with the majority comparing them to White British children. Four papers reported on adult second-generation South Asians and the rest reported on South Asian adults in general. Second-generation South Asians were more active than the first-generation but were still less active than the White British. There were no high quality qualitative studies on second-generation South Asian adults, but there were some studies on South Asian children. The adult studies indicated that the second-generation might have a more favourable attitude towards physical activity than the first-generation. There is clear variation in physical activity levels among UK South Asians. Second-generation South Asians appear to be more physically active than the first-generation, but still less active than the White British. More qualitative research is needed to understand why, but there are indications that second-generation South Asians have a more positive attitude towards physical activity than the first-generation. Different strategies to increase physical activity may be needed for different generations of UK South Asians.


Effort avoidance is not simply error avoidance.
Little is known about how effort is represented for different kinds of tasks. Recently, we suggested that it would help to establish empirical benchmarks for this problem. Accordingly, Feghhi and Rosenbaum (Journal of Experimental Psychology: Human Perception and Performance, 45:983-994, 2019) estimated how many additional digits to be memorized corresponded to navigating through a narrow gap versus a wide gap. The estimates were based on a study in which participants chose between walking paths with associated memory demands. We found that participants were equally willing to choose to walk through a narrow gap as to walk through a wide gap when the narrow-gap walk required memorization of 0.55 fewer digits on average than the wide-gap walk. In the present experiment, we sought to replicate and extend this previous finding in two ways: (1) by presenting the memory digits in auditory rather than visual form to test the hypothesis that participants used phonological recoding of the visually presented digits; and (2) by providing a new metric of the relative difficulty of navigation errors compared to recall errors. We provided 36 university students with two action/memorization options per trial and asked them to choose the easier option. Each option had varying degrees of physical demand (walking through a wide or narrow gap) and mental demand (memorizing 6, 7, or 8 digits). We expected performance to be comparable to what we observed earlier with visually presented digits to be memorized, and this prediction was confirmed. We also used a new metric to show that navigation errors were implicitly judged to be 17% more costly than recall errors. The fact that this percentage was not 0 indicates that reducing percent error was not the only basis for reducing effort.


Connecting the Stimuli-Responsive Rheology of Biopolymer Hydrogels to Underlying Hydrogen-Bonding Interactions.
Many biopolymer hydrogels are environmentally responsive because they are held together by physical associations that depend on pH and temperature. Here, we investigate how the pH and temperature responses of the rheology of hyaluronan hydrogels are connected to the underlying molecular interactions. Hyaluronan is an essential structural biopolymer in the human body with many applications in biomedicine. Using two-dimensional infrared spectroscopy, we show that hyaluronan chains become connected by hydrogen bonds when the pH is changed from 7.0 to 2.5 and that the bond density at pH 2.5 is independent of temperature. Temperature-dependent rheology measurements show that because of this hydrogen bonding the stress relaxation at pH 2.5 is strongly slowed down in comparison to pH 7.0, consistent with the sticky reptation model of associative polymers. From the flow activation energy, we conclude that each polymer is cross-linked by multiple (5-15) hydrogen bonds to others, causing slow macroscopic stress relaxation, despite the short time scale of breaking and reformation of each individual hydrogen bond. Our findings can aid the design of stimuli-responsive hydrogels with tailored viscoelastic properties for biomedical applications.


Use of the Internet and ratings of information sources for medical decisions: results from the DECISIONS survey.
The rise in Internet use for seeking health information raises questions about the role the Internet may play in how patients make medical decisions. To examine Internet use and perceived importance of different sources of information by patients making 9 specific medical decisions covering prescription medication initiation, cancer screening, and elective surgery. National sample of US adults identified by random-digit dialing. Cross-sectional survey conducted between November 2006 and May 2007. The final sample comprised 2575 English-speaking US adults aged 40 y and older who had either undergone 1 of 9 medical procedures or tests or talked with a health care provider about doing so during the previous 2 y. Participants indicated if they or other family members used the Internet to seek information related to each of the specific medical decisions and rated how important the health care provider, the Internet (if used), family and friends, and the media (newspapers, magazines, and television) were in providing information to help make the medical decision. Use of the Internet for information related to specific decisions among adults 40 y and older was generally low (28%) but varied across decisions, from 17% for breast cancer screening to 48% for hip/knee replacement. Internet use was higher at younger ages, rising from 14% among those aged 70 y and older to 38% for those aged 40 to 49 y. Internet users consistently rated health care providers as the most influential source of information for medical decisions, followed by the Internet, family and friends, and media. Telephone surveys are limited by coverage and nonresponse. The authors excluded health-related Internet use not associated with the 9 target decisions. A minority of patients reported using the Internet to make specific common medical decisions, but use varied widely by type of decision. Perhaps reflecting perceived risk and uncertainty, use was lowest for screening decisions and highest for surgical decisions.


Interactions between assembly order and temperature can alter both short- and long-term community composition.
Both the order in which species arrive in a community, and environmental conditions, such as temperature, are known to affect community structure. Little is known, however, about the potential for, and occurrence of, interactions between assembly history and the environment. Of particular, interest may be the interaction between temperature and community assembly dynamics, especially in the light of predicted global climatic change and the fundamental processes that are governed, through metabolic rate, by an individual's environmental temperature. We present, to our knowledge, the first experimental exploration of how the influence of assembly history, temperature, and the interaction between the two alters the structure of communities of competitors, using small-scale protist microcosm communities where temperature and assembly order were manipulated factorially. In our experiment, the most important driver of long-term abundance was temperature but long-lasting assembly order effects influenced the relationship between temperature and abundance. Any advantage of early colonization proved to be short-lived, and there was rarely any long-term advantage to colonizing a habitat before other species. The results presented here suggest that environmental conditions shape community composition, but that occasionally temperature could interact with the stochastic nature of community assembly to significantly alter future community composition, especially where temperature change has been large. This could have important implications for the dynamics of both rare and invasive species.


Relaxed purifying selection and possibly high rate of adaptation in primate lineage-specific genes.
Genes in the same organism vary in the time since their evolutionary origin. Without horizontal gene transfer, young genes are necessarily restricted to a few closely related species, whereas old genes can be broadly distributed across the phylogeny. It has been shown that young genes evolve faster than old genes; however, the evolutionary forces responsible for this pattern remain obscure. Here, we classify human-chimp protein-coding genes into different age classes, according to the breath of their phylogenetic distribution. We estimate the strength of purifying selection and the rate of adaptive selection for genes in different age classes. We find that older genes carry fewer and less frequent nonsynonymous single-nucleotide polymorphisms than younger genes suggesting that older genes experience a stronger purifying selection at the protein-coding level. We infer the distribution of fitness effects of new deleterious mutations and find that older genes have proportionally more slightly deleterious mutations and fewer nearly neutral mutations than younger genes. To investigate the role of adaptive selection of genes in different age classes, we determine the selection coefficient (gamma = 2N(e)s) of genes using the MKPRF approach and estimate the ratio of the rate of adaptive nonsynonymous substitution to synonymous substitution (omega(A)) using the DoFE method. Although the proportion of positively selected genes (gamma > 0) is significantly higher in younger genes, we find no correlation between omega(A) and gene age. Collectively, these results provide strong evidence that younger genes are subject to weaker purifying selection and more tenuous evidence that they also undergo adaptive evolution more frequently.


AnaBench: a Web/CORBA-based workbench for biomolecular sequence analysis.
Sequence data analyses such as gene identification, structure modeling or phylogenetic tree inference involve a variety of bioinformatics software tools. Due to the heterogeneity of bioinformatics tools in usage and data requirements, scientists spend much effort on technical issues including data format, storage and management of input and output, and memorization of numerous parameters and multi-step analysis procedures. In this paper, we present the design and implementation of AnaBench, an interactive, Web-based bioinformatics Analysis workBench allowing streamlined data analysis. Our philosophy was to minimize the technical effort not only for the scientist who uses this environment to analyze data, but also for the administrator who manages and maintains the workbench. With new bioinformatics tools published daily, AnaBench permits easy incorporation of additional tools. This flexibility is achieved by employing a three-tier distributed architecture and recent technologies including CORBA middleware, Java, JDBC, and JSP. A CORBA server permits transparent access to a workbench management database, which stores information about the users, their data, as well as the description of all bioinformatics applications that can be launched from the workbench. AnaBench is an efficient and intuitive interactive bioinformatics environment, which offers scientists application-driven, data-driven and protocol-driven analysis approaches. The prototype of AnaBench, managed by a team at the Université de Montréal, is accessible on-line at: http://malawimonas.bcm.umontreal.ca:8091/anabench. Please contact the authors for details about setting up a local-network AnaBench site elsewhere.


Interference in the alcohol Stroop task with college student binge drinkers.
Heavy drinking among college students is associated with social, health, and legal problems. One factor that may contribute to heavy drinking is an attentional bias for alcohol-related cues, which can influence drinking automatically and without an individual's awareness. Using tests of alcohol-related attentional bias, such as the alcohol Stroop task, previous research has shown that alcohol dependent drinkers have greater attentional biases than non-dependent drinkers, but results for college student drinkers have been mixed. The present study examined alcohol Stroop task performance and its relationship to drinking levels and drinking-related problems among 84 college students during the 2009-2010 academic year with at least one binge drinking episode in the previous month. As hypothesized, results indicated that participants had greater attentional interference when alcohol words were presented compared to when neutral words were presented during the Stroop task, suggesting that the students in the sample displayed greater attentional biases for alcohol words compared to neutral words. Results showed that Stroop task responding did not vary by drinking frequency or drinking-related problems, but did vary by drinking intensity. Presentation of alcohol-related cues may cause heavier drinking college students to attend to these stimuli, which may increase the saliency of these cues and influence their likelihood of drinking. Implications for prevention and treatment efforts are discussed.


Anti-obesity Action of Fermented Barley Extracts with Lactobacillus plantarum dy-1 and Associated MicroRNA Expression in High-fat Diet-induced Obese Rats.
To further explore associated effects of Lactobacillus plantarum dy-1 (LFBE) on obesity and lipid metabolism at the gene expression level, the expression of microRNAs (miRNAs) was investigated in the liver of high-fat diet (HFD) induced obese rats. Three groups of animal models were established. Changes in miRNA expression in the liver of each group were analyzed by microarray and RT-qPCR, complemented by bioinformatics. Palmitateinduced hepatocellular carcinoma (HepG2) cells were used as a model to validate the test. LFBE treatment groups and HFD groups were observed to be distinctly different with respect to rates of increase in body weight and body fat percentage and triglyceride (TG) and total cholesterol (TC) levels in serum and liver. In addition, the LFBE group showed upregulation of ten miRNAs and downregulation of five miRNAs in the liver. Downregulation of miR-34a and miR-212 was observed in the livers of the LFBE group. Gene ontology and kyoto encyelopedia of geues and genomes (KEGG) pathway analysis showed that possible target genes of the deregulated miRNAs were significantly enriched in the adrenergic and HIF-1 signaling pathways. These results demonstrate that LFBE might regulate the expression of miRNAs in order to inhibit obesity and fatty liver.


The relationship between alanerv(®) consumption and erythrocytes' redox status in post-acute stroke patients undergoing rehabilitation.
Stroke is a pathological condition associated with a redox imbalance. Both the acute and the post-acute phases after a stroke are characterized by a pro-oxidant state, which could be corrected through antioxidant supplementation. The aim of the present study was to evaluate the effect of the ALAnerv(®) upon the redox status of erythrocytes. For this pilot study were enrolled 28 post-acute stroke patients. They were randomly divided into a control group [(-) ALA] and a study group [(+) ALA]. Patients were hospitalized for a period of two weeks. Blood samples were taken at the beginning and at the end of this period. Patients from (+) ALA group received the nutritional supplement ALAnerv(®). Catalase, SOD, GPx, GRed and GT activities were assessed on erythrocytes' lysates. Also, the total antioxidant capacity as well as the concentration of total thiols were evaluated. During the study period only SOD (1393.48 ± 69.14 U/g Hb vs. 1514.06 ± 60.80) and GRed (4.47 ± 0.37 U/g Hb vs. 5.06 ± 0.24) significantly increased in (+) ALA group. Catalase (173.70 ± 14.62 k/g Hb vs. 123.41 ± 8.71) and GT (5.55 ± 0.26 U/g Hb vs. 4.95 ± 0.23) activities significantly decreased during the study period. Multiple regression indicated that only SOD, GT and GRed activities were influenced by the ALAnerv(®) consumption. There was no significant increase if the total thiols concentration. ALAnerv(®) consumption could be associated with a correction of the erythrocytes' redox status. There is a need to investigate if administration of ALAnerv(®) over a longer time period could have a more significant influence on the erythrocytes' antioxidant system.


Small transrectal ultrasound volume predicts clinically significant Gleason score upgrading after radical prostatectomy: results from the SEARCH database.
Needle biopsy Gleason scores are often upgraded after pathological examination of the prostate following radical prostatectomy. It has been suggested that larger prostates would be associated with a greater risk of upgrading since a smaller percentage of the gland is sampled and, thus, the highest grade disease would more likely be missed, assuming an equal number of cores is taken from similar locations. We examined the likelihood of clinically relevant upgrading after radical prostatectomy as a function of transrectal ultrasound volume. We examined the association between transrectal ultrasound volume and upgrading (higher Gleason score category in the radical prostatectomy specimen than in the biopsy) in 586 men treated with radical prostatectomy between 1995 and 2006 in the SEARCH database who underwent at least a sextant biopsy using multivariate logistic regression. Transrectal ultrasound volume was categorized as 20 or less (in 71), 21 to 40 (in 334), 41 to 60 (in 123) and greater than 60 cm(3) (in 58). Gleason score was examined as a categorical variable of 2-6, 3 + 4 and 4 + 3 or greater. Overall 138 cases (24%) were upgraded, 80 (14%) were downgraded, and 368 (62%) had identical biopsy and pathological Gleason sum groups. Larger transrectal ultrasound volume was significantly associated with decreased likelihood of upgrading (p trend <0.001). For transrectal ultrasound volumes greater than 60, 41 to 60, 21 to 40 and 20 cm(3) or less, the estimated multivariate adjusted probability of upgrading was 12.6%, 27.5%, 36.4% and 45.5% for Gleason 2-6 tumors, and 6.1%, 8.5%, 18.9% and 20.9% for Gleason 3 + 4 tumors, respectively. Larger transrectal ultrasound volumes were at decreased risk for clinically significant upgrading after radical prostatectomy. This fact should be kept in mind when deciding on treatment decisions for men with apparently low grade prostate cancer on biopsy.


Animal vocal sequences: not the Markov chains we thought they were.
Many animals produce vocal sequences that appear complex. Most researchers assume that these sequences are well characterized as Markov chains (i.e. that the probability of a particular vocal element can be calculated from the history of only a finite number of preceding elements). However, this assumption has never been explicitly tested. Furthermore, it is unclear how language could evolve in a single step from a Markovian origin, as is frequently assumed, as no intermediate forms have been found between animal communication and human language. Here, we assess whether animal taxa produce vocal sequences that are better described by Markov chains, or by non-Markovian dynamics such as the 'renewal process' (RP), characterized by a strong tendency to repeat elements. We examined vocal sequences of seven taxa: Bengalese finches Lonchura striata domestica, Carolina chickadees Poecile carolinensis, free-tailed bats Tadarida brasiliensis, rock hyraxes Procavia capensis, pilot whales Globicephala macrorhynchus, killer whales Orcinus orca and orangutans Pongo spp. The vocal systems of most of these species are more consistent with a non-Markovian RP than with the Markovian models traditionally assumed. Our data suggest that non-Markovian vocal sequences may be more common than Markov sequences, which must be taken into account when evaluating alternative hypotheses for the evolution of signalling complexity, and perhaps human language origins.


Twentieth anniversary of the European Union health mandate: taking stock of perceived achievements, failures and missed opportunities - a qualitative study.
The European Union (EU) health mandate was initially defined in the Maastricht Treaty in 1992. The twentieth anniversary of the Treaty offers a unique opportunity to take stock of EU health actions by giving an overview of influential public health related EU-level policy outputs and a summary of policy outputs or actions perceived as an achievement, a failure or a missed opportunity. Semi-structured expert interviews (N = 20) were conducted focusing on EU-level actions that were relevant for health. Respondents were asked to name EU policies or actions that they perceived as an achievement, a failure or a missed opportunity. A directed content analysis approach was used to identify expert perceptions on achievements, failures and missed opportunities in the interviews. Additionally, a nominal group technique was applied to identify influential and public health relevant EU-level policy outputs. The ranking of influential policy outputs resulted in top positions of adjudications and legislations, agencies, European Commission (EC) programmes and strategies, official networks, cooperative structures and exchange efforts, the work on health determinants and uptake of scientific knowledge. The assessment of EU health policies as being an achievement, a failure or a missed opportunity was often characterized by diverging respondent views. Recurring topics that emerged were the Directorate General for Health and Consumers (DG SANCO), EU agencies, life style factors, internal market provisions as well as the EU Directive on patients' rights in cross-border healthcare. Among these recurring topics, expert perceptions on the establishment of DG SANCO, EU public health agencies, and successes in tobacco control were dominated by aspects of achievements. The implementation status of the Health in All Policy approach was perceived as a missed opportunity. When comparing the emerging themes from the interviews conducted with the responsibilities defined in the EU health mandate, one can identify that these responsibilities were only partly fulfilled or acknowledged by the respondents. In general, the EU is a recognized public health player in Europe which over the past two decades, has begun to develop competencies in supporting, coordinating and supplementing member state health actions. However, the assurance of health protection in other European policies seems to require further development.


Sphingosine 1-phosphate signaling pathway in inner ear biology. New therapeutic strategies for hearing loss?
Hearing loss is one of the most prevalent conditions around the world, in particular among people over 60 years old. Thus, an increase of this affection is predicted as result of the aging process in our population. In this context, it is important to further explore the function of molecular targets involved in the biology of inner ear sensory cells to better individuate new candidates for therapeutic application. One of the main causes of deafness resides into the premature death of hair cells and auditory neurons. In this regard, neurotrophins and growth factors such as insulin like growth factor are known to be beneficial by favoring the survival of these cells. An elevated number of published data in the last 20 years have individuated sphingolipids not only as structural components of biological membranes but also as critical regulators of key biological processes, including cell survival. Ceramide, formed by catabolism of sphingomyelin (SM) and other complex sphingolipids, is a strong inducer of apoptotic pathway, whereas sphingosine 1-phosphate (S1P), generated by cleavage of ceramide to sphingosine and phosphorylation catalyzed by two distinct sphingosine kinase (SK) enzymes, stimulates cell survival. Interestingly S1P, by acting as intracellular mediator or as ligand of a family of five distinct S1P receptors (S1P1-S1P5), is a very powerful bioactive sphingolipid, capable of triggering also other diverse cellular responses such as cell migration, proliferation and differentiation, and is critically involved in the development and homeostasis of several organs and tissues. Although new interesting data have become available, the information on S1P pathway and other sphingolipids in the biology of the inner ear is limited. Nonetheless, there are several lines of evidence implicating these signaling molecules during neurogenesis in other cell populations. In this review, we discuss the role of S1P during inner ear development, also as guidance for future studies.


Cancer stem cells: progress and challenges in lung cancer.
The identification of a subpopulation of tumor cells with stem cell-like characteristics first in hematological malignancies and later in solid tumors has emerged into a novel field of cancer research. It has been proposed that this aberrant population of cells now called "cancer stem cells" (CSCs) drives tumor initiation, progression, metastasis, recurrence, and drug resistance. CSCs have been shown to have the capacity of self-renewal and multipotency. Adopting strategies from the field of stem cell research has aided in identification, localization, and targeting of CSCs in many tumors. Despite the huge progress in other solid tumors such as brain, breast, and colon cancers no substantial advancements have been made in lung cancer. This is most likely due to the current rudimentary understanding of lung stem cell hierarchy and heterogeneous nature of lung disease. In this review, we will discuss the most recent findings related to identification of normal lung stem cells and CSCs, pathways involved in regulating the development of CSCs, and the importance of the stem cell niche in development and maintenance of CSCs. Additionally, we will examine the development and feasibility of novel CSC-targeted therapeutic strategies aimed at eradicating lung CSCs.


Interleukin-4 stimulates papillary thyroid cancer cell survival: implications in patients with thyroid cancer and concomitant Graves' disease.
IL-4, a pleiotropic cytokine mainly produced by activated helper T lymphocytes type 2 (Th2), is known to protect thyroid cells from autoimmune damage. Acting via its receptors (IL-4Ralpha), IL-4 has antiproliferative and apoptotic effects in many malignancies. Its effect in thyroid cancer is unknown. We found that surgical specimens of thyroid carcinomas express both IL-4Ralpha and IL-4 in the majority of cases. Thyroid glands affected by Graves' disease also express IL-4. We also studied a panel of eight thyroid cancer cell lines from different histotypes and found that thyroid cancer cells express high levels of IL-4Ralpha although they do not express IL-4. We then compared the biological effects of IL-4 in TPC-1, a thyroid cancer cell line, and in MCF-7 breast cancer cells. IL-4 very weakly stimulated thyroid cancer cell proliferation, but it was very effective in protecting thyroid cancer cells from apoptosis induced by staurosporin. The protective effect of IL-4 was similar in magnitude to that of IGF-I and was associated with up-regulation of the antiapoptotic molecule Bcl-2 and weak down-regulation of the proapoptotic molecule Bax. Moreover, IL-4 slightly potentiated the survival effect of IGF-I. In contrast, IL-4 reduced growth and induced apoptosis in MCF-7 cells. Taken together, these findings suggest that thyroid cancer cells receive significant protection from apoptosis by IL-4 produced in the thyroid gland by activated T lymphocytes when concomitant Graves' disease is present.


Quantitative characterization of the inhibitory effects of salt, humic acid, and heavy metals on the recovery of waterborne norovirus by electropositive filters.
The virus adsorption-elution technique (VIRADEL) using electropositively charged filters is used frequently for recovering enteric viruses from water. The filter-absorbed virus is typically eluted, concentrated, and subsequently detected by culture or molecular methods. Human norovirus (HuNoV), one of the most important waterborne pathogens, cannot be cultivated by conventional culture methods and is typically detected using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. However, it is plausible that various inhibitors could be concentrated simultaneously during the VIRADEL process and affect RT-PCR assays. In this study, we evaluated the effect of typical inhibitors, including humic acid, heavy metals, and salt, on the recovery of norovirus by two different electropositive filters: 1MDS and Nanoceram. Known amounts of HuNoV and murine norovirus were inoculated in 1 L of surface water containing various concentrations of humic acid, heavy metals (cadmium and lead), or NaCl. Our results indicate that the presence of heavy metals or salt significantly reduced the recovery of virus from the electropositive filters. Thus, care should be taken when analyzing waterborne norovirus using electropositive filters in environments with high concentrations of heavy metal inhibitors or salts.


Maximum reproductive lifespan correlates with CD33rSIGLEC gene number: Implications for NADPH oxidase-derived reactive oxygen species in aging.
Humans and orcas are among the very rare species that have a prolonged post-reproductive lifespan (PRLS), during which the aging process continues. Reactive oxygen species (ROS) derived from mitochondria and from the NADPH oxidase (NOX) enzymes of innate immune cells are known to contribute to aging, with the former thought to be dominant. CD33-related-Siglecs are immune receptors that recognize self-associated-molecular-patterns and modulate NOX-derived-ROS. We herewith demonstrate a strong correlation of lifespan with CD33rSIGLEC gene number in 26 species, independent of body weight or phylogeny. The correlation is stronger when considering total CD33rSIGLEC gene number rather than those encoding inhibitory and activating subsets, suggesting that lifetime balancing of ROS is important. Combining independent lines of evidence including the short half-life and spontaneous activation of neutrophils, we calculate that even without inter-current inflammation, a major source of lifetime ROS exposure may actually be neutrophil NOX-derived. However, genomes of human supercentenarians (>110 years) do not harbor a significantly higher number of functional CD33rSIGLEC genes. Instead, lifespan correlation with CD33rSIGLEC gene number was markedly strengthened by excluding the post-reproductive lifespan of humans and orcas (R2 = 0.83; P < .0001). Thus, CD33rSIGLEC modulation of ROS likely contributes to maximum reproductive lifespan, but other unknown mechanisms could be important to PRLS.


First Report of Lasiodiplodia theobromae Causing Stem Canker of Jatropha curcas in Malaysia.
Physic nut (Jatropha curcas L.) is an important biofuel crop worldwide. Although it has been reported to be resistant to pests and diseases (1), stem cankers have been observed on this plant at several locations in Peninsular Malaysia since early February 2008. Necrotic lesions on branches appear as scars with vascular discoloration in the tissue below the lesion. The affected area is brownish and sunken in appearance. Disease incidence of these symptomatic nonwoody plants can reach up to 80% in a plantation. Forty-eight samples of symptomatic branches collected from six locations (University Farm, Setiu, Gemenceh, Pulau Carey, Port Dickson, and Kuala Selangor) were surface sterilized in 10% bleach, rinsed twice with sterile distilled water, air dried on filter paper, and plated on water agar. After 4 days, fungal colonies on the agar were transferred to potato dextrose agar (PDA) and incubated at 25°C. Twenty-seven single-spore fungal cultures obtained from all locations produced white, aerial mycelium that became dull gray after a week in culture. Pycnidia from 30-day-old pure cultures produced dark brown, oval conidia that were two celled, thin walled, and oval shape with longitudinal striations. The average size of the conidia was 23.63 × 12.72 μm with a length/width ratio of 1.86. On the basis of conidial morphology, these cultures were identified as Lasiodiplodia theobromae. To confirm the identity of the isolates, the internal transcribed spacer (ITS) region was amplified with ITS1/ITS4 primers and sequenced. The sequences were deposited in GenBank (Accession Nos. HM466951, HM466953, HM466957, GU228527, HM466959, and GU219983). Sequences from the 27 isolates were 99 to 100% identical to two L. theobromae accessions in GenBank (Nos. HM008598 and HM999905). Hence, both morphological and molecular characteristics confirmed the isolates as L. theobromae. Pathogenicity tests were performed in the glasshouse with 2-month-old J. curcas seedlings. Each plant was wound inoculated by removing the bark on a branch to a depth of 2 mm with a 10-mm cork borer. Inoculation was conducted by inserting a 10-mm-diameter PDA plug of mycelium into the wound and wrapping the inoculation site with wetted, cotton wool and Parafilm. Control plants were treated with plugs of sterile PDA. Each isolate had four replicates and two controls. After 6 days of incubation, all inoculated plants produced sunken, necrotic lesions with vascular discoloration. Leaves were wilted and yellow above the point of inoculation on branches. The control plants remained symptomless. The pathogen was successfully reisolated from lesions on inoculated branches. L. theobromae has been reported to cause cankers and dieback in a wide range of hosts and is common in tropical and subtropical regions of the world (2,3). To our knowledge, this is the first report of stem canker associated with L. theobromae on J. curcas in Malaysia. References: (1) S. Chitra and S. K. Dhyani. Curr. Sci. 91:162, 2006. (2) S. Mohali et al. For. Pathol. 35:385, 2005. (3) E. Punithalingam. Page 519 in: CMI Descriptions of Pathogenic Fungi and Bacteria. Commonwealth Mycological Institute, Kew, Surrey, UK. 1976.


Homogeneous Water Oxidation by Half-Sandwich Iridium(III) N-Heterocyclic Carbene Complexes with Pendant Hydroxy and Amino Groups.
Herein, we report three IrIII Cp* complexes with hydroxy- or amino-functionalized N-heterocyclic carbene (NHC) ligands that catalyze efficient water oxidation induced by addition of ceric ammonium nitrate (CAN). The pendant hydroxy or amino groups are very important for activity, and the complexes with heteroatom-functionalized NHC ligands show up to 15 times higher rates of oxygen evolution in CAN-induced water oxidation than a reference IrIII Cp* complex without heteroatom functionalization. The formation of molecular high-valent Ir intermediates that are presumably involved in the rate-determining step for water oxidation is established by UV/Vis spectroscopy and ESI-MS under turnover conditions. The hydroxy groups on the NHC ligands, as well as chloride ligands on the iridium center are proposed to structurally stabilize the high-valent species, and thereby improve the catalytic activity. The IrIII complex with a hydroxy-functionalized NHC shows the highest catalytic activity with a TON of 2500 obtained in 3 h and with >90 % yield relative to the amount of oxidant used.


Comparative assessment of fluorescent proteins for in vivo imaging in an animal model system.
Fluorescent protein tags are fundamental tools used to visualize gene products and analyze their dynamics in vivo. Recent advances in genome editing have expedited the precise insertion of fluorescent protein tags into the genomes of diverse organisms. These advances expand the potential of in vivo imaging experiments and facilitate experimentation with new, bright, photostable fluorescent proteins. Most quantitative comparisons of the brightness and photostability of different fluorescent proteins have been made in vitro, removed from biological variables that govern their performance in cells or organisms. To address the gap, we quantitatively assessed fluorescent protein properties in vivo in an animal model system. We generated transgenic Caenorhabditis elegans strains expressing green, yellow, or red fluorescent proteins in embryos and imaged embryos expressing different fluorescent proteins under the same conditions for direct comparison. We found that mNeonGreen was not as bright in vivo as predicted based on in vitro data but is a better tag than GFP for specific kinds of experiments, and we report on optimal red fluorescent proteins. These results identify ideal fluorescent proteins for imaging in vivo in C. elegans embryos and suggest good candidate fluorescent proteins to test in other animal model systems for in vivo imaging experiments.


An exploratory pilot study of childhood injuries on cattle farms in Jalisco, Mexico.
Childhood agricultural injuries have been a concern in the United States for many years. Much research has been performed on the cause and prevention of such injuries. The North American Guidelines for Children's Agricultural Tasks (NAGCAT) have been developed in the United States to address the common agricultural tasks and injuries sustained by children. Data are lacking concerning the common agricultural tasks and injuries of children working on Mexican farms. The goal of the study was to determine if the NAGCAT guidelines developed for the United States may be applicable to children in Jalisco, Mexico. Interviews of local physicians were performed regarding their perception of common childhood agricultural injuries. Interviews about common childhood agricultural tasks and injuries were performed at 27 farms through the help of a local cooperative. Work practices at these farms were also observed. Emergency department records were reviewed for childhood agricultural injuries. Surveys of local cattle farms revealed the most common childhood agricultural tasks were feeding animals, milking cows, and cleaning corrals. Through the same cattle farm interviews, the most common childhood agricultural injuries included being kicked by an animal, scorpion bites, cuts, and falls. Physician interviews revealed machinery, poisonings, cuts, and lacerations as the most common injuries. Due to the lack of adequate documentation, the emergency department medical record review was not useful. The NAGCAT guidelines address many of the common tasks and injuries in the Tepatitlán area, including animal care, operating machinery, and cleaning corrals. There are other common injuries in the Tepatitlán area such as scorpion bites for which no NAGCAT guidelines currently exist but for which guidelines could be developed. Once translated to Spanish and adjusted for cultural relevancy, the NAGCAT guidelines would address many of the common agricultural tasks and injuries of children in Jalisco, Mexico.


Patterns of deliveries in a Brazilian birth cohort: almost universal cesarean sections for the better-off.
To describe the patterns of deliveries in a birth cohort and to compare vaginal and cesarean section deliveries. All children born to mothers from the urban area of Pelotas, Brazil, in 2004, were recruited for a birth cohort study. Mothers were contacted and interviewed during their hospital stay when extensive information on the gestation, the birth and the newborn, along with maternal health history and family characteristics was collected. Maternal characteristics and childbirth care financing - either private or public healthcare (SUS) patients - were the main factors investigated along with a description of C-sections distribution according to day of the week and delivery time. Standard descriptive techniques, Χ² tests for comparing proportions and Poisson regression to explore the independent effect of C-section predictors were the methods used. The overall C-section rate was 45%, 36% among SUS and 81% among private patients, where 35% of C-sections were reported elective. C-sections were more frequent on Tuesdays and Wednesdays, reducing by about a third on Sundays, while normal deliveries had a uniform distribution along the week. Delivery time for C-sections was markedly different among public and private patients. Maternal schooling was positively associated with C-section among SUS patients, but not among private patients. C-sections were almost universal among the wealthier mothers, and strongly related to maternal education among SUS patients. The patterns we describe are compatible with the idea that C-sections are largely done to suit the doctor's schedule. Drastic action is called for to change the current situation.


To be understood: Transitioning to adult life for people with Autism Spectrum Disorder.
The purpose of this study was to explore the viewpoints of parents of young people with Autism Spectrum Disorder (ASD) in relation to their child's transition to adulthood. Data were collected during four structured focus groups with 19 parents of young people with ASD with average to high intellectual capacities. Condensed meaning units were identified and checked during focus groups, and were subsequently linked to the International Classification of Functioning, Disability and Health (ICF). Three major themes emerged: to be understood, to understand the world and to succeed. The ICF domains of activity and participation and environmental factors emerged as having the greatest potential to influence transition outcomes. Policies and services should focus on strengths to maximise participation in higher education, employment and independent living amongst young people with ASD. Interventions targeting environmental factors could be effective in improving participation in adult life. Person-centred and individualised approaches could further complement this approach supporting the transition to adulthood for people with ASD, ultimately improving outcomes in adulthood.


The aversive effect of electromagnetic radiation on foraging bats: a possible means of discouraging bats from approaching wind turbines.
Large numbers of bats are killed by collisions with wind turbines and there is at present no accepted method of reducing or preventing this mortality. Following our demonstration that bat activity is reduced in the vicinity of large air traffic control and weather radars, we tested the hypothesis that an electromagnetic signal from a small portable radar can act as a deterrent to foraging bats. From June to September 2007 bat activity was compared at 20 foraging sites in northeast Scotland during experimental trials (radar switched on) and control trials (no radar signal). Starting 45 minutes after sunset, bat activity was recorded for a period of 30 minutes during each trial and the order of trials were alternated between nights. From July to September 2008 aerial insects at 16 of these sites were sampled using two miniature light-suction traps. At each site one of the traps was exposed to a radar signal and the other functioned as a control. Bat activity and foraging effort per unit time were significantly reduced during experimental trials when the radar antenna was fixed to produce a unidirectional signal therefore maximising exposure of foraging bats to the radar beam. However, although bat activity was significantly reduced during such trials, the radar had no significant effect on the abundance of insects captured by the traps.


Adult hippocampal neurogenesis and memory interference.
Rats, subjected to low-dose irradiation that suppressed hippocampal neurogenesis, or a sham treatment, were administered a visual discrimination task under conditions of high, or low interference. Half of the rats engaged in running activity and the other half did not. In the non-runners, there was no effect of irradiation on learning, or remembering the discrimination response under low interference, but irradiation treatment increased their susceptibility to interference, resulting in loss of memory for the previously learned discrimination. Irradiated rats that engaged in running activity exhibited increased neuronal growth and protection from memory impairment. The results, which show that hippocampal cells generated in adulthood play a role in differentiating between conflicting, context-dependent memories, provide further evidence of the importance of neurogenesis in hippocampus-sensitive memory tasks. The results are consistent with computational models of hippocampal function that specify a central role for neurogenesis in the modulation of interfering influences during learning and memory.


The effects of acupuncture on pregnancy outcomes of in vitro fertilization: a systematic review and meta-analysis.
The effects of acupuncture on in vitro fertilization (IVF) outcomes remain controversial. And the variation in participant, interventions, outcomes studied, and trial design may relate to the efficacy of adjuvant acupuncture. We searched digital databases for relevant studies, including Embase, PubMed, Cochrane Library and some Chinese databases up to December 2018, for randomized controlled trials (RCTs) evaluating the effects of acupuncture on women undergoing IVF. We included studies with intervention groups using needling, and control groups consisting of no acupuncture or sham (placebo) acupuncture. Primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR). Meta-regression and subgroup analysis were conducted on the basis of eight pre-specified covariates to investigate the variances of the effects of adjuvant acupuncture on pregnancy rates and the sources of heterogeneity. Twenty-seven studies with 6116 participants were included. The pooled clinical pregnancy rate (CPR) from all of acupuncture groups was significantly greater than that of control groups (RR 1.21, 95% CI: 1.07-1.38), whereas the pooled live birth rate (LBR) was not. Meta-regression subgroup analysis showed a more significant benefit of acupuncture for repeated IVF cycle proportion (number of women with a history of prior unsuccessful IVF attempt divided by number of women included in each trial) ≥ 50% group (CPR: RR 1.60, 95% CI: 1.28-2.00; LBR: RR 1.42, 95% CI: 1.05-1.92), and this covariate explained most of the heterogeneity (CPR and LBR: adjusted R2 = 100 and 87.90%). Similar results were found between CPR and number of acupuncture treatments (CPR: p = 0.002, adjusted R2 = 51.90%), but not LBR. Our analysis finds a benefit of acupuncture for IVF outcomes in women with a history of unsuccessful IVF attempt, and number of acupuncture treatments is a potential influential factor. Given the poor reporting and methodological flaws of existing studies, studies with larger scales and better methodologies are needed to verify these findings.


A disconnected policy network: The UK's response to the Sierra Leone Ebola epidemic.
This paper investigates whether the inclusion of social scientists in the UK policy network that responded to the Ebola crisis in Sierra Leone (2013-16) was a transformational moment in the use of interdisciplinary research. In contrast to the existing literature, that relies heavily on qualitative accounts of the epidemic and ethnography, this study tests the dynamics of the connections between critical actors with quantitative network analysis. This novel approach explores how individuals are embedded in social relationships and how this may affect the production and use of evidence. The meso-level analysis, conducted between March and June 2019, is based on the traces of individuals' engagement found in secondary sources. Source material includes policy and strategy documents, committee papers, meeting minutes and personal correspondence. Social network analysis software, UCINet, was used to analyse the data and Netdraw for the visualisation of the network. Far from being one cohesive community of experts and government officials, the network of 134 people was weakly held together by a handful of super-connectors. Social scientists' poor connections to the government embedded biomedical community may explain why they were most successful when they framed their expertise in terms of widely accepted concepts. The whole network was geographically and racially almost entirely isolated from those affected by or directly responding to the crisis in West Africa. Nonetheless, the case was made for interdisciplinarity and the value of social science in emergency preparedness and response. The challenge now is moving from the rhetoric to action on complex infectious disease outbreaks in ways that value all perspectives equally.


Current developments and future trends in solid-phase microextraction techniques for pharmaceutical and biomedical analyses.
Sample preparation is important for the isolation and concentration of desired trace components from complex matrices. Sample preparation is the most labor-intensive and error-prone process in analytical methodology, and greatly influences the reliable and accurate determination of analytes. The integration of sample preparation with various analytical instruments is most conveniently achieved by using microextraction techniques and/or microdevices. Solid-phase microextraction (SPME) is both simple and effective, enabling miniaturization, automation and high-throughput performance. Moreover, SPME has reduced analysis times, as well as the costs of solvents and disposal. This review describes current developments and future trends in novel SPME techniques, including fiber SPME, in-tube SPME and related new microextraction techniques. Especially innovative SPME approaches, including multi-well high-throughput sampling, ligand-receptor binding study for pharmacokinetics, direct in vivo sampling, chip-based microfluidic system, and new sampling techniques using intelligent carbon nanotube and temperature-response polymer in pharmaceutical and biomedical analysis are focused items.


Inhibin B: are modified ranges needed for orchiectomised testicular cancer patients?
Inhibin B is a gonadal hormone that downregulates the pituitary production of follicle-stimulating hormone (FSH). In recent years, inhibin B has proved to be an excellent marker of spermatogenesis and even a predictive factor for the recovery of fertility in patients undergoing orchiectomy and antineoplastic treatments. We propose to study inhibin B levels in orchiectomised testicular cancer patients, in order to identify a minimum value representative of normal semen quality. This retrospective study evaluates hormonal and semen parameters of 290 normozoospermic patients attending the Laboratory of Seminology - Sperm Bank "Loredana Gandini" (Rome, Italy) for cryopreservation of seminal fluid following a diagnosis of testicular cancer (TC group) and 117 healthy, normozoospermic men as a control group (CTR group). The percentile distribution of gonadotropin and inhibin B values in the TC and CTR groups was analyzed. There was a statistically significant difference between the two groups in the levels of all hormones (P ≤ 0.001) and in all semen parameters (P < 0.05). About 20% of TC patients revealed inhibin B levels below the 5th percentile of CTR group, despite normozoospermia, and 31.4% had normal spermatogenesis in the presence of FSH values >95th percentile of CTR group. Orchiectomised patients for testicular cancer presented inhibin B levels lower than healthy patients, despite normozoospermia. Our study revealed the poor sensitivity of the current inhibin B reference range when applied to monorchidic patients, suggesting the need to establish more representative ranges to enable more appropriate counseling in relation to the patient's new endocrine condition.


Interaction between diabetes specialist nurses and patients during group sessions about self-management in type 2 diabetes.
The aim of this study was to explore the interaction between diabetes specialist nurses (DSNs) and patients with type 2 diabetes (T2D) during group sessions about self-management. Ten DSNs and 44 patients were observed during group sessions about self-management, and thereafter the observations were analyzed using qualitative content analysis. The interaction was characterized by three themes: becoming empowered, approaching each other from different perspectives, and struggling for authority. The interaction was not a linear process, but rather a dynamic process with distinct episodes that characterized the content of the sessions. It is important to achieve an interaction that is patient-centered, where the DSN is aware of each patient's individual needs and avoids responding to patients in a normative way. A satisfying interaction may strengthen patients' self-management, and also may strengthen the DSNs in their professional performance. Authority struggles between patients and DSNs could be a prerequisite for patients to become autonomous and decisive in self-management. DSNs might benefit from an increased awareness about this issue, because they can better support patients if they do not perceive authority struggles as threats to their professional role.


Obesity: An independent protective factor for localized renal cell carcinoma in a systemic inflammation state.
To explore the prognostic value of obesity (measured by BMI) on RCC in a systemic inflammation state. Clinicopathological and hematological data of 540 surgically treated Chinese localized RCC patients between 2005 and 2010 were retrospectively collected. Found by receiver operating characteristic (ROC) curve for cancer-specific survival (CSS), the optimal cutoff values of neutrophil-lymphocyte ratio (NLR, an indicator of systemic inflammation state) and BMI were 2.12 and 23.32, respectively. Survival curves were drawn using Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of BMI in localized RCC patients with different NLR. Overall, 36 patients died with a median follow-up of 70 months. Median overall survival (OS) was 66 months and the 5-year OS rate was 92.7%. In the multivariate analysis of total patients, higher BMI was an independent protective factor for CSS in total patients (p=0.048). While in systemic inflammation subgroup (high NLR subgroup) patients, higher BMI (obesity) turned out to be an independent protective factor for both CSS (p=0.025) and RFS (p=0.048). In localized RCC patients, obesity was an independent protective factor for CSS and RFS in a systemic inflammation state. Available at. https://www.intbrazjurol.com.br/pdf/aop/2019-0228OA.pdf.


Effects of CPAP therapy withdrawal on exhaled breath pattern in obstructive sleep apnoea.
Obstructive sleep apnoea (OSA) is highly prevalent and associated with cardiovascular and metabolic changes. OSA is usually diagnosed by polysomnography which is time-consuming and provides little information on the patient's phenotype thus limiting a personalised treatment approach. Exhaled breath contains information on metabolism which can be analysed by mass spectrometry within minutes. The objective of this study was to identify a breath profile in OSA recurrence by use of secondary-electrospray-ionization-mass spectrometry (SESI-MS). Patients with OSA effectively treated with CPAP were randomised to either withdraw treatment (subtherapeutic CPAP) or continue therapeutic CPAP for 2 weeks. Exhaled breath analysis by untargeted SESI-MS was performed at baseline and 2 weeks after randomisation. The primary outcome was the change in exhaled molecular breath pattern. 30 patients with OSA were randomised and 26 completed the trial according to the protocol. CPAP withdrawal led to a recurrence of OSA (mean difference in change of oxygen desaturation index between groups +30.3/h; 95% CI 19.8/h,40.7/h, p<0.001) which was accompanied by a significant change in 62 exhaled features (16 metabolites identified). The panel of discriminating mass-spectral features allowed differentiation between treated and untreated OSA with a sensitivity of 92.9% and a specificity of 84.6%. Exhaled breath analysis by SESI-MS allows rapid and accurate detection of OSA recurrence. The technique has the potential to characterise an individual's metabolic response to OSA and thus makes a comprehensible phenotyping of OSA possible. NCT02050425 (registered at ClinicalTrials.gov).


A 'hot-spot' mutation alters the mechanical properties of keratin filament networks.
Keratins 5 and 14 polymerize to form the intermediate filament network in the progenitor basal cells of many stratified epithelia including epidermis, where it provides crucial mechanical support. Inherited mutations in K5 or K14 result in epidermolysis bullosa simplex (EBS), a skin-fragility disorder. The impact that such mutations exert on the intrinsic mechanical properties of K5/K14 filaments is unknown. Here we show, by using differential interference contrast microscopy, that a 'hot-spot' mutation in K14 greatly reduces the ability of reconstituted mutant filaments to bundle under crosslinking conditions. Rheological assays measure similar small-deformation mechanical responses for crosslinked solutions of wild-type and mutant keratins. The mutation, however, markedly reduces the resilience of crosslinked networks against large deformations. Single-particle tracking, which probes the local organization of filament networks, shows that the mutant polymer exhibits highly heterogeneous structures compared to those of wild-type filaments. Our results indicate that the fragility of epithelial cells expressing mutant keratin may result from an impaired ability of keratin polymers to be crosslinked into a functional network.


ProCommunity: procalcitonin use in real-world US community hospital settings.
Procalcitonin (PCT) is a biomarker that may help providers optimize antibiotic (AB) therapy. Numerous clinical trials have demonstrated the utility of PCT-guided decision algorithms in treating lower respiratory tract infections and sepsis, but evidence from real-world studies is limited. This study sought to evaluate the effects of PCT on select clinical outcomes in community hospitals. An observational, retrospective, case-control study was conducted. Hospitals from a large US hospital system were categorized into "treatment" and "control" hospitals. Treatment hospitals were those with in-house PCT testing, a pharmacy team tasked with PCT testing follow-up and results in the patient's electronic medical records alongside a recommendation on AB treatment. Control hospitals either did not have PCT testing available in house or sent out tests to a laboratory or neighboring facility. Patients from treatment hospitals were matched 1:1 to patients from control hospitals based on admission diagnosis code, sex, age and whether an intensive care unit admission was observed. Clinical outcomes included number of days of AB treatment, length of stay, 30 day readmissions, mortality and acute kidney injury. Comparisons were conducted using multivariable regressions accounting for clustering at the hospital level. Patients from treatment hospitals had significantly shorter hospital stays (-0.68 days, 95% CI: -1.26, -0.09; p = .02). A reduction in days of AB treatment (-1.50 days, 95% CI: -3.27, 0.27; p = .10) was observed, but did not reach statistical significance. These findings suggest that PCT, along with specific treatment recommendations, may lead to shortened hospital stays with no adverse outcome on patient safety.


Negative Air Ions and Their Effects on Human Health and Air Quality Improvement.
Negative air ions (NAIs) have been discovered for more than 100 years and are widely used for air cleaning. Here, we have carried out a comprehensive reviewing on the effects of NAIs on humans/animals, and microorganisms, and plant development. The presence of NAIs is credited for increasing psychological health, productivity, and overall well-being but without consistent or reliable evidence in therapeutic effects and with controversy in anti-microorganisms. Reports also showed that NAIs could help people in relieving symptoms of allergies to dust, mold spores, and other allergens. Particulate matter (PM) is a major air pollutant that affects human health. Experimental data showed that NAIs could be used to high-efficiently remove PM. Finally, we have reviewed the plant-based NAI release system under the pulsed electric field (PEF) stimulation. This is a new NAI generation system which releases a huge amount of NAIs under the PEF treatment. The system may be used to freshen indoor air and reduce PM concentration in addition to enriching oxygen content and indoor decoration at home, school, hospital, airport, and other indoor areas.


Internal conversion versus intersystem crossing: what drives the gas phase dynamics of cyclic α,β-enones?
We investigate the competition between intersystem crossing (ISC) and internal conversion (IC) as nonradiative relaxation pathways in cyclic α,β-unsaturated enones following excitation to their lowest lying (1)ππ* state, by means of time-resolved photoelectron spectroscopy and ab initio computation. Upon excitation, the (1)ππ* state of 2-cyclopentenone decays to the lowest lying (1)nπ* state within 120 ± 20 fs. Within 1.2 ± 0.2 ps, the molecule subsequently decays to the triplet manifold and the singlet ground state, with quantum yields of 0.35 and 0.65, respectively. The corresponding dynamics in modified derivatives, obtained by selective methylation, show a decrease in both IC and ISC rates, with the quantum yields of ISC varying between 0.35 and 0.08. The rapid rates of ISC are explained by a large spin orbit coupling of 45-60 cm(-1) over an extended region of near degeneracy between the singlet and triplet state. Furthermore, the rate of IC is depressed by the existence of a well-defined minimum on the (1)nπ* potential energy surface. The nonadiabatic pathways evinced by the present results highlight the fact that these molecular systems conceptually represent "intermediate cases" between ultrafast dynamics mediated by vibrational motions at conical intersections versus those by statistical decay mechanisms.


Effect of Early Limited Formula on Breastfeeding Duration in the First Year of Life: A Randomized Clinical Trial.
Breastfeeding through 6 and 12 months are 2 goals of the Centers for Disease Control and Prevention Healthy People 2020 initiative, but the 6-month goal is met for only 52% of US infants and the 12-month goal for 30% of US infants. To determine whether structured, short-term formula supplementation for at-risk neonates affects the proportion still breastfeeding at 6 and 12 months. This randomized clinical trial conducted at 2 US academic medical centers enrolled 164 exclusively breastfeeding mother-infant dyads of mothers who were not yet producing copious milk and infants who were 24 to 72 hours old with newborn weight loss at or above the 75th percentile for age. Participants were enrolled from January 2015 through September 2016. Early Limited Formula (ELF), a structured formula supplementation protocol (10 mL formula fed after each breastfeeding until mothers produced copious milk), compared with control dyads, who continued exclusive breastfeeding and received a safety teaching intervention. The study's primary outcome was any breastfeeding at 6 months. Secondary outcomes included age at breastfeeding cessation and any breastfeeding at 12 months. All outcomes were assessed by maternal phone survey. Eighty-two newborns were randomized to ELF and 82 to the control group. Mean (SD) maternal age was 31.4 (5.9) years, and 114 (69.5%) self-identified as non-Hispanic white; 20 (12.2%), Hispanic; 17 (10.4%), Asian; 5 (3.0%), non-Hispanic black; and 7 (4.3%), other. Compared with controls, mothers randomized to ELF were less likely to be married (n = 53 [64.6%] vs n = 66 [80.5%]; P = .03) and had shorter mean (SD) intended duration of breastfeeding (8.6 [3.4] vs 9.9 [4.4] months; P = .049). Median (interquartile range) duration of breastfeeding in the cohort was 9 (6-12) months. At 6 months, 47 (65%) infants randomized to ELF were breastfeeding, compared with 60 (77%) of the control infants (absolute difference, -12%; 95% CI, -26% to 3%; P = .12). At 12 months, 21 of the 71 ELF infants available for analysis (29.6%) were breastfeeding, compared with 37 of the available 77 (48.1%) control infants (risk difference, -18%; 95% CI, -34% to -3%). Marital status and intended breastfeeding duration were both associated with breastfeeding duration; models adjusting for these found a hazard ratio for time-to-event of breastfeeding cessation through 12 months of 0.74 (95% CI, 0.48-1.14) for ELF infants compared with infants in the control group. In this cohort with high breastfeeding prevalence, ELF was not associated with any improvement in breastfeeding duration. Future research should examine the effect of ELF in populations at higher risk of early cessation. ClinicalTrials.gov identifier: NCT02313181.


Endogenous patterns of mechanical stress are required for branching morphogenesis.
Spatial patterning of cell behaviors establishes the regional differences within tissues that collectively develop branched organs into their characteristic treelike shapes. Here we show that the pattern of branching morphogenesis of three-dimensional (3D) engineered epithelial tissues is controlled in part by gradients of endogenous mechanical stress. We used microfabrication to build model mammary epithelial tissues of defined geometry that branched in a stereotyped pattern when induced with growth factors. Branches initiated from sites of high mechanical stress within the tissues, as predicted numerically and measured directly using 3D traction force microscopy. Branch sites were defined by activation of focal adhesion kinase (FAK), inhibition of which disrupted morphogenesis. Stress, FAK activation, and branching were all altered by manipulating cellular contractility, matrix stiffness, intercellular cohesion and tissue geometry. These data suggest that the pattern and magnitude of mechanical stress across epithelial tissues cooperate with biochemical signals to specify branching pattern.


Altered retrieval of melodic information in congenital amusia: insights from dynamic causal modeling of MEG data.
Congenital amusia is a neuro-developmental disorder that primarily manifests as a difficulty in the perception and memory of pitch-based materials, including music. Recent findings have shown that the amusic brain exhibits altered functioning of a fronto-temporal network during pitch perception and short-term memory. Within this network, during the encoding of melodies, a decreased right backward frontal-to-temporal connectivity was reported in amusia, along with an abnormal connectivity within and between auditory cortices. The present study investigated whether connectivity patterns between these regions were affected during the short-term memory retrieval of melodies. Amusics and controls had to indicate whether sequences of six tones that were presented in pairs were the same or different. When melodies were different only one tone changed in the second melody. Brain responses to the changed tone in "Different" trials and to its equivalent (original) tone in "Same" trials were compared between groups using Dynamic Causal Modeling (DCM). DCM results confirmed that congenital amusia is characterized by an altered effective connectivity within and between the two auditory cortices during sound processing. Furthermore, right temporal-to-frontal message passing was altered in comparison to controls, with notably an increase in "Same" trials. An additional analysis in control participants emphasized that the detection of an unexpected event in the typically functioning brain is supported by right fronto-temporal connections. The results can be interpreted in a predictive coding framework as reflecting an abnormal prediction error sent by temporal auditory regions towards frontal areas in the amusic brain.


A Host-Pathogen Interaction Screen Identifies ada2 as a Mediator of Candida glabrata Defenses Against Reactive Oxygen Species.
Candida glabrata (C. glabrata) forms part of the normal human gut microbiota but can cause life-threatening invasive infections in immune-compromised individuals. C. glabrata displays high resistance to common azole antifungals, which necessitates new treatments. In this investigation, we identified five C. glabrata deletion mutants (∆ada2, ∆bas1, ∆hir3, ∆ino2 and ∆met31) from a library of 196 transcription factor mutants that were unable to grow and activate an immune response in Drosophila larvae. This highlighted the importance of these transcription factors in C. glabrata infectivity. Further ex vivo investigation into these mutants revealed the requirement of C. glabrata ADA2 for oxidative stress tolerance. We confirmed this observation in vivo whereby growth of the C. glabrata Δada2 strain was permitted only in flies with suppressed production of reactive oxygen species (ROS). Conversely, overexpression of ADA2 promoted C. glabrata replication in infected wild type larvae resulting in larval killing. We propose that ADA2 orchestrates the response of C. glabrata against ROS-mediated immune defenses during infection. With the need to find alternative antifungal treatment for C. glabrata infections, genes required for survival in the host environment, such as ADA2, provide promising potential targets.


Detection of cytomegalovirus by ELISA in urine samples is inhibited by beta 2 microglobulin.
During development of an enzyme immunoassay for the detection of cytomegalovirus (CMV) we previously discovered that virus found naturally in urine specimens could not be captured onto the solid phase by CMV-specific monoclonal antibodies, whereas these same antibodies could capture CMV from cell culture supernatants. We now report that urine from normal CMV-seronegative individuals contains a substance of molecular weight 11-12,000 daltons that inhibits the ELISA detection of cell culture-grown CMV. The addition of a known urinary protein of this molecular weight, beta 2 microglobulin (beta 2m; 11,700 daltons), inhibited the detection of cell culture-grown CMV in the ELISA over the concentration range found in clinical urine samples. In contrast, another low molecular weight urinary protein, lysozyme, had no inhibitory effect. beta 2m caused inhibition only when added to the virus preparation and not to the antibody-capture stage. We conclude that beta 2m in urine prevents the detection of CMV by ELISA by binding to the virus and masking its antigenic determinants and we calculate that of the order of 10(5) molecules of beta 2m bind to each particle of cell culture-grown CMV. We postulate that CMV in fresh urine specimens is similarly coated with beta 2m, accounting for the failure to detect it by ELISA.


Spatiotemporal endothelial cell - pericyte association in tumors as shown by high resolution 4D intravital imaging.
Endothelial cells and pericytes are integral cellular components of the vasculature with distinct interactive functionalities. To study dynamic interactions between these two cells we created two transgenic animal lines. A truncated eNOS (endothelial nitric oxide synthase) construct was used as a GFP tag for endothelial cell evaluation and an inducible Cre-lox recombination, under control of the Pdgfrb (platelet derived growth factor receptor beta) promoter, was created for pericyte assessment. Also, eNOStag-GFP animals were crossed with the already established Cspg4-DsRed mice expressing DsRed fluorescent protein in pericytes. For intravital imaging we used tumors implanted in the dorsal skinfold of these transgenic animals. This setup allowed us to study time and space dependent complexities, such as distribution, morphology, motility, and association between both vascular cell types in all angiogenetic stages, without the need for additional labeling. Moreover, as fluorescence was still clearly detectable after fixation, it is possible to perform comparative histology following intravital evaluation. These transgenic mouse lines form an excellent model to capture collective and individual cellular and subcellular endothelial cell - pericyte dynamics and will help answer key questions on the cellular and molecular relationship between these two cells.


An insight into the sialotranscriptome of the West Nile mosquito vector, Culex tarsalis.
Saliva of adult female mosquitoes help sugar and blood feeding by providing enzymes and polypeptides that help sugar digestion, control microbial growth and counteract their vertebrate host hemostasis and inflammation. Mosquito saliva also potentiates the transmission of vector borne pathogens, including arboviruses. Culex tarsalis is a bird feeding mosquito vector of West Nile Virus closely related to C. quinquefasciatus, a mosquito relatively recently adapted to feed on humans, and the only mosquito of the genus Culex to have its sialotranscriptome so far described. A total of 1,753 clones randomly selected from an adult female C. tarsalis salivary glands (SG) cDNA library were sequenced and used to assemble a database that yielded 809 clusters of related sequences, 675 of which were singletons. Primer extension experiments were performed in selected clones to further extend sequence coverage, allowing for the identification of 283 protein sequences, 80 of which code for putative secreted proteins. Comparison of the C. tarsalis sialotranscriptome with that of C. quinquefasciatus reveals accelerated evolution of salivary proteins as compared to housekeeping proteins. The average amino acid identity among salivary proteins is 70.1%, while that for housekeeping proteins is 91.2% (P < 0.05), and the codon volatility of secreted proteins is significantly higher than those of housekeeping proteins. Several protein families previously found exclusive of mosquitoes, including only in the Aedes genus have been identified in C. tarsalis. Interestingly, a protein family so far unique to C. quinquefasciatus, with 30 genes, is also found in C. tarsalis, indicating it was not a specific C. quinquefasciatus acquisition in its evolution to optimize mammal blood feeding.


Relationship between COX-2 specific inhibitors and hypertension.
There is controversy whether cyclooxygenase-2 (COX-2) specific inhibitors are associated with elevations in blood pressure requiring treatment in typical clinical practice. We examined the risk of new onset hypertension in a retrospective case-control study involving 17 844 subjects aged > or =65 years from 2 US states. Multivariable logistic models were examined to assess the relative risk of new onset hypertension requiring treatment in patients who used celecoxib or rofecoxib compared with patients taking either the other COX-2 specific inhibitor, a nonspecific NSAID, or no NSAID. During the 1999 to 2000 study period, 3915 patients were diagnosed and began treatment for hypertension; 4 controls were selected for every case. In no model was celecoxib significantly associated with the development of hypertension. Rofecoxib users were at a significantly increased relative risk of new onset hypertension compared with patients taking celecoxib (odds ratio [OR] 1.6; 95% confidence interval [CI], 1.2 to 2.1), taking a nonspecific NSAID (OR 1.4; 95% CI, 1.1 to 1.9), or taking no NSAID (OR 1.6; 95% CI, 1.3 to 2.0). There were no clear dosage or duration effects. In patients with a history of chronic renal disease, liver disease, or congestive heart failure, the relative risk of new onset hypertension was twice as high in those taking rofecoxib compared with celecoxib (OR 2.1; 95% CI, 1.0 to 4.3). In this retrospective case-control study of patients aged > or =65 years, rofecoxib use was associated with an increased relative risk of new onset hypertension; this was not seen in patients taking celecoxib.