Regulatory T cells ameliorate angiotensin II-induced cardiac damage.
Hypertensive target organ damage, especially cardiac hypertrophy with heart failure and arrhythmia, is a major source of morbidity and mortality. Angiotensin II, a major mediator of hypertension and cardiac damage, has proinflammatory properties. Inflammation and activation of the immune system play a pivotal role in pathogenesis of hypertensive target organ damage. However, the role of immunosuppressive CD4+CD25+ regulatory T (Treg) cells in the pathogenesis of hypertensive target organ damage is unexplored. We conducted adoptive transfer of Treg cells into angiotensin II-infused hypertensive mice. Treg cell recipients exhibited improved cardiac hypertrophy and less cardiac fibrosis despite sustained hypertension. Amelioration of cardiac morphology was accompanied by an improvement in arrhythmogenic electric remodeling, indicating the functional significance of the enhanced cardiac morphology. Delocalization of the connexin 43 gap junction protein is one of the major pathomechanisms in electric remodeling. Pronounced connexin 43 immunoreactivity was found at the lateral borders of cardiomyocytes in angiotensin II-treated mice. In contrast, connexin 43 was restricted to the intercalated disk regions in sham controls. Surprisingly, angiotensin II+Treg-treated mice showed normal connexin 43 gap junction protein localization. Adoptive Treg cell transfer resulted in a marked reduction in cardiac CD4+, CD8+, and CD69+ cell and macrophage infiltration. Immunosuppressive effects of transferred Treg cells ameliorated cardiac damage and accounted for the improved electric remodeling independently of blood pressure-lowering effects. Our results provide new insights into the pathogenesis of hypertensive cardiac damage and could therefore lead to new therapeutic approaches that involve manipulation of the immune system.


Sex determination: insights from the silkworm.
The sex-determining system differs considerably among organisms. Even among insect species, the genetic system for sexdetermination is highly diversified. In Drosophila melanogaster, somatic sexual differentiation is regulated by a well characterized genetic hierarchy X:A > Sxl > tra/tra2 > dsx and fru. This cascade seems to control sex determination in all Drosophila species and is partially conserved in another dipteran species, Ceratitis capitata: Cctra/Cctra-2 > Ccdsx and Ccfru. However, in the silkworm, Bombyx mori, femaleness is determined by the presence of a dominant feminizing factor on the W chromosome. Moreover, no sex-specific regulatory Sxl homolog has been isolated from B. mori. Also, no tra homolog has yet been found in the Bombyx genome. Despite such differences, dsx homolog of B. mori (Bmdsx) is implicated in the sex determination. Bmdsx produces alternatively spliced mRNA isoforms that encode sex specific transcription factors as observed in dsx. While the female-specific splicing of dsx is activated by splicing activators, Tra and Tra2, the female splicing of Bmdsx represents the default mode. Instead, a splicing inhibitor, BmPSI is involved in the regulation of male-specific splicing of Bmdsx. Since BmPSI does not exhibit any sequence relationship to known SR proteins, such as Tra and Tra2, the regulatory mechanism of sex-specific alternative splicing of Bmdsx is distinct from that of dsx.


Functional connectivity of reward processing in the brain.
Controversial results have been reported concerning the neural mechanisms involved in the processing of rewards and punishments. On the one hand, there is evidence suggesting that monetary gains and losses activate a similar fronto-subcortical network. On the other hand, results of recent studies imply that reward and punishment may engage distinct neural mechanisms. Using functional magnetic resonance imaging (fMRI) we investigated both regional and interregional functional connectivity patterns while participants performed a gambling task featuring unexpectedly high monetary gains and losses. Classical univariate statistical analysis showed that monetary gains and losses activated a similar fronto-striatal-limbic network, in which main activation peaks were observed bilaterally in the ventral striatum. Functional connectivity analysis showed similar responses for gain and loss conditions in the insular cortex, the amygdala, and the hippocampus that correlated with the activity observed in the seed region ventral striatum, with the connectivity to the amygdala appearing more pronounced after losses. Larger functional connectivity was found to the medial orbitofrontal cortex for negative outcomes. The fact that different functional patterns were obtained with both analyses suggests that the brain activations observed in the classical univariate approach identifies the involvement of different functional networks in the current task. These results stress the importance of studying functional connectivity in addition to standard fMRI analysis in reward-related studies.


Genetic Variability of Morphological, Flowering, and Biomass Quality Traits in Hemp (Cannabis sativa L.).
Hemp (Cannabis sativa L.) is a bast-fiber crop well-known for the great potential to produce sustainable fibers. Nevertheless, hemp fiber quality is a complex trait, and little is known about the phenotypic variability and heritability of fiber quality traits in hemp. The aim of this study is to gain insights into the variability in fiber quality within the hemp germplasm and to estimate the genetic components, environmental components, and genotype-by-environment (G×E) interactions on fiber quality traits in hemp. To investigate these parameters, a panel of 123 hemp accessions was phenotyped for 28 traits relevant to fiber quality at three locations in Europe, corresponding to climates of northern, central, and southern Europe. In general, hemp cultivated in northern latitudes showed a larger plant vigor while earlier flowering was characteristic of plants cultivated in southern latitudes. Extensive variability between accessions was observed for all traits. Most cell wall components (contents of monosaccharides derived from cellulose and hemicellulose; and lignin content), bast fiber content, and flowering traits revealed large genetic components with low G×E interactions and high broad-sense heritability values, making these traits suitable to maximize the genetic gains of fiber quality. In contrast, contents of pectin-related monosaccharides, most agronomic traits, and several fiber traits (fineness and decortication efficiency) showed low genetic components with large G×E interactions affecting the rankings across locations. These results suggest that pectin, agronomic traits, and fiber traits are unsuitable targets in breeding programs of hemp, as their large G×E interactions might lead to unexpected phenotypes in untested locations. Furthermore, all environmental effects on the 28 traits were statistically significant, suggesting a strong adaptive behavior of fiber quality in hemp to specific environments. The high variability in fiber quality observed in the hemp panel, the broad range in heritability, and adaptability among all traits prescribe positive prospects for the development of new hemp cultivars of excellent fiber quality.


Electron spin polarization-based integrated photonic devices.
The lack of optical isolators has limited the serial integration of components in the development of photonic integrated circuits. Isolators are inherently nonreciprocal and, as such, require nonreciprocal optical propagation. We propose a class of integrated photonic devices that make use of electrically-generated electron spin polarization in semiconductors to cause nonreciprocal TE/TM mode conversion. Active control over the non-reciprocal mode coupling rate allows for the design of electrically-controlled isolators, circulators, modulators and switches. We analyze the effects of waveguide birefringence and absorption loss as limiting factors to device performance.


A human centered GeoVisualization framework to facilitate visual exploration of telehealth data: a case study.
Public health data is typically organized by geospatial units. Routine geographic monitoring of health data enables an understanding of the spatial patterns of events in terms of causes and controls. GeoVisualization (GeoVis) allows users to see information hidden both visually and explicitly on a map. Despite the applicability of GeoVis in public health, it is still underused for visualizing public health data. The objective of this study is to examine the perception of telehealth users' to utilize GeoVis as a proof of concept to facilitate visual exploration of telehealth data in Brazil using principles of human centered approach and cognitive fit theory. A mixed methods approach combining qualitative and quantitative assessments was utilized in this cross sectional study conducted at the Telehealth Center of the Federal University of Pernambuco (NUTE-UFPE), Recife, Brazil. A convenient sample of 20 participants currently involved in NUTES was drawn during a period of Sep-Oct 2011. Data was gathered using previously tested questionnaire surveys and in-person interviews. Socio-demographic Information such as age, gender, prior education, familiarity with the use of computer and GeoVis was gathered. Other information gathered included participants' prior spatial analysis skills, level of motivation and use of GeoVis in telehealth. Audio recording was done for all interviews conducted in both English and Portuguese, and transcription of the audio content to English was done by a certified translator. Univariate analysis was performed and means and standard deviations were reported for the continuous variables and frequency distributions for the categorical variables. For the open-ended questions, we utilized a grounded theory to identify themes and their relationship as they emerge from the data. Analysis of the quantitative data was performed using SAS V9.1 and qualitative data was performed using NVivo9. The average age of participants was 28 years (SD=7), a majority of them were females and 100% were professionals with graduate degrees. The users had diverse backgrounds including nursing, computer science, biomedical informatics, statistics, dentistry, administration and engineering. The users had varied roles and responsibilities, used computers frequently but only 5% of them were familiar with GeoVis. Google maps were the most common GeoVis application that the users were familiar with. Despite having minimal spatial skills, there was a strong motivation and relevance among the telehealth users to use GeoVis to facilitate visual exploration of telehealth data for better informed decision making. Results also showed that of the 60% participants with no GeoVis familiarity; 33% had moderate to large data exploratory role, 83% had no spatial skills but 58% preferred analyzing both spatial and temporal dimensions of the data. Majority of the participants agreed to have maps as the first choice to represent the data as it will be able to display the events both in place and time. The results demonstrate a potentially growing need for the use of GeoVis applications to evaluate telehealth data. Understanding of user needs is essential to ensure that the technology is appropriately functional and will be useful to complete the tasks.


[Reduction of reconciliation errors in chronic pediatric patients through an educational strategy].
Medication reconciliation errors, also known as unintentional discrepancies, are frequent during admission, especially in chronic patients, and have an impact on safety. Educational interventions can be a reduction strategy. Quasi-experimental study, before-after design. Participants were chronic patients admitted into hospitalization services. Medication reconciliation was conducted at admission. The intervention consisted of a training to each prescribing physician with study contents and printed educational material. To study the association between intervention and change of frequency of unintentional discrepancies was made a logistic regression model, adjusting for selected variables. A sample of 54 patients was studied in each stage. In the first stage it was observed that 42.6% of patients had at least one unintentional discrepancy. After intervention the proportion of patients with at least one unintentional discrepancy decreased to 24.1% (p = 0.041). In both stages, omission was the main category of unintentional discrepancy. The significant reduction after the intervention is maintained by controlling for variables such as emergency admission and pre-admission service. Incidence of unintentional discrepancies in admission is high in chronic hospitalized patients and can be reduced through an educative strategy.


Disparities in Potentially Preventable Hospitalizations: Near-National Estimates for Hispanics.
To obtain near-national rates of potentially preventable hospitalization (PPH)-a marker of barriers to outpatient care access-for Hispanics; to examine their differences from other race-ethnic groups and by Hispanic national origin; and to identify key mediating factors. Data from all-payer inpatient discharge databases for 15 states accounting for 85 percent of Hispanics nationally. Combining counts of inpatient discharges with census population for adults aged 18 and older, we estimated age-sex-adjusted PPH rates. We examined county-level variation in race-ethnic disparities in these rates to identify the mediating role of area-level indicators of chronic condition prevalence, socioeconomic status (SES), health care access, acculturation, and provider availability. Age-sex-adjusted PPH rates were 13 percent higher among Hispanics (1,375 per 100,000 adults) and 111 percent higher among blacks (2,578) compared to whites (1,221). Among Hispanics, these rates were relatively higher in areas with predominantly Puerto Rican and Cuban Americans than in areas with Hispanics of other nationalities. Small area variation in chronic condition prevalence and SES fully accounted for the higher rates among Hispanics, but only partially among blacks. Hispanics and blacks face higher barriers to outpatient care access; the higher barriers among Hispanics (but not blacks) seem mediated by SES, lack of insurance, cost barriers, and limited provider availability.


Ageing and physical function in East African foragers and pastoralists.
Human lifespans are exceptionally long compared with those of other primates. A key element in exploring the evolution of human longevity is understanding how modern humans grow older. Our current understanding of common age-related changes in human health and function stems mostly from studies in industrialized societies, where older adulthood is often associated with an increased incidence of chronic diseases. However, individuals who engage in different lifestyles across industrialized and non-industrialized contexts may display variance in age-related changes in health and function. Here, we explore aspects of physical function in a non-industrialized context using three objective measures of physical function. We assessed physical activity levels, walking endurance and muscle strength in two East African populations: Hadza hunter-gatherers in Tanzania and Pokot pastoralists in Kenya. Both Hadza and Pokot participants displayed significant age-related differences in most, but not all, functional measures. Our results suggest that some age-related differences in physical function seen in industrialized contexts could be consistently experienced by most humans, while other age-related differences may vary across populations. Studies of ageing should expand to include a broad range of populations so we can create a more comprehensive understanding of how senescence varies across different lifestyle contexts. This article is part of the theme issue 'Evolution of the primate ageing process'.


OBSERVATIONS AND EXPERIMENTS ON THE SO-CALLED THYROID CARCINOMA OF BROOK TROUT (SALVELINUS FONTINALIS) AND ITS RELATION TO ORDINARY GOITRE.
Is this thyroid hyperplasia true carcinoma? In view of the facts that young fish are more affected than old fish, that iodin stops the hyperplasia and causes it to return to the colloid state, that removal of the fish from the ponds to the open brook also affects a cure, that the clinical incidence of tumors is directly related to the water supply, and that the severity of the disease as determined by histological examination is likewise directly related to the water supply, we cannot accept the prevailing opinion that the disease is true cancer. On the other hand, we believe that the disease as studied by us is an extreme illustration of endemic goitre, the end stage of which is cretinism. The opinion that it is cancer is based purely on anatomical studies-the essential fact being that the growing thyroid invades bone, muscle, etc. Such findings in mammalian tissues are strong evidence of malignancy, but this standard cannot be applied to fish thyroids for the reason that any growth of a widely and loosely distributed nonencapsulated gland would give the histological appearance of invasion of the surrounding tissues. The general views as to the cause of the disease may be divided into two groups: (I) infectious and (2) metabolic. Taking up the infectious theory, there are abundant grounds for such a view when one considers the flora of the tank. The very careful histological examinations by Hofer, Bonnet and Pick have yielded uniformly negative results. Direct infection cannot be excluded, but the fact that fish placed in the tail-race recover spontaneously, although living in the theoretically most polluted water, is not in harmony with our present conception of water-borne infection. Taking up the metabolic theory, the three factors of overfeeding, overcrowding and limited proportional water supply together with the many possibilities into which they are divisible seem to us to be in some way, still obscure, directly concerned with the development of the disease. It is not probable that a single substance, whether the result of food decomposition or of excretory products, excites the thyroid to its activity but rather that the thyroid reaction is the result of the activity of a great variety of these products.


Whole-body vibration training increases physical fitness measures without alteration of inflammatory markers in older adults.
This study investigated in older adults whether whole-body vibration (WBV) training results in significant increases of physical fitness measures without alterations in markers of inflammation. Sixteen volunteers completed a WBV programme 3 d.wk(-1) during 9 weeks. The programme consisted of lower and upper-body unloaded static and dynamic exercises. Training improved significantly several tests which evaluate physical fitness, such as 30-s chair stand, arm curl or chair sit and reach test. There was a significant increase in maximal voluntary isometric contraction (MVIC) between pre- and post-training conditions. Muscle power values, reached at 20, 40 and 60% MVIC, were also significantly greater after training. However, mRNA or protein levels for C-reactive protein, interleukin-6, interleukin-1β, tumour necrosis factor-α and interleukin-10 did not significantly differ from basal values. Our data confirm the usefulness of WBV training for counteracting the loss of muscle strength associated with sarcopenia in older adults and show that WBV training could be a safe training method which induces no inflammatory effects.


Mapping sleeping bees within their nest: spatial and temporal analysis of worker honey bee sleep.
Patterns of behavior within societies have long been visualized and interpreted using maps. Mapping the occurrence of sleep across individuals within a society could offer clues as to functional aspects of sleep. In spite of this, a detailed spatial analysis of sleep has never been conducted on an invertebrate society. We introduce the concept of mapping sleep across an insect society, and provide an empirical example, mapping sleep patterns within colonies of European honey bees (Apis mellifera L.). Honey bees face variables such as temperature and position of resources within their colony's nest that may impact their sleep. We mapped sleep behavior and temperature of worker bees and produced maps of their nest's comb contents as the colony grew and contents changed. By following marked bees, we discovered that individuals slept in many locations, but bees of different worker castes slept in different areas of the nest relative to position of the brood and surrounding temperature. Older worker bees generally slept outside cells, closer to the perimeter of the nest, in colder regions, and away from uncapped brood. Younger worker bees generally slept inside cells and closer to the center of the nest, and spent more time asleep than awake when surrounded by uncapped brood. The average surface temperature of sleeping foragers was lower than the surface temperature of their surroundings, offering a possible indicator of sleep for this caste. We propose mechanisms that could generate caste-dependent sleep patterns and discuss functional significance of these patterns.


Porphyromonas gingivalis (W83) Infection Induces Alzheimer's Disease-Like Pathophysiology in Obese and Diabetic Mice.
Periodontal disease(s) and metabolic illnesses negatively impact the quality of life and, eventually mental health. This study investigated the effect of Porphyromonas gingivalis (W83) oral infection on the development of Alzheimer's disease (AD) pathophysiology in a wild-type obese, diabetic (db/db) mouse model. The db/db mice were either orally infected with P. gingivalis and Fusobacterium nucleatum or sham infected for 16 weeks. The presence of amyloid-β (Aβ) and neurofibrillary tangles (NFTs) were assessed using a silver impregnation technique and subsequently by immunohistochemistry for tau and neuroinflammation. The mRNA abundance of a panel of 184 genes was performed using quantitative real-time PCR, and the differentially expressed genes were analyzed by Ingenuity Pathway Analysis. While no Aβ plaques and NFTs were evident by silver impregnation, immunohistochemistry (glial cell markers) of the P. gingivalis-infected mice tissue sections exhibited neuroinflammation in the form of reactive microglia and astrocytes. Anti-tau immunopositivity, in addition to cells, was prominent in thickened axons of hippocampal CA neurons. The mRNA abundance of crucial genes in the insulin signaling pathway (INSR, IGF1, IRS, IDE, PIK3R, SGK1, GYS, GSK3B, AKT1) were upregulated, potentially exacerbating insulin resistance in the brain by P. gingivalis oral infection. Increased mRNA abundance of several kinases, membrane receptors, transcription factors, and pro-inflammatory mediators indicated hyperactivation of intracellular cascades with potential for tau phosphorylation and Aβ release in the same infection group. P. gingivalis W83 infection of db/db mice provides a disease co-morbidity model with the potential to reproduce AD pathophysiology with induced periodontal disease.


Testosterone, ticks and travels: a test of the immunocompetence-handicap hypothesis in free-ranging male sand lizards.
The immunocompetence-handicap hypothesis suggests that androgen-dependent male characters constitute honest signals of mate and/or rival quality because of the imposed costs through immune suppression associated with elevated testosterone levels. We demonstrate in a field experiment that male sand lizards (Lacerta agilis) exposed to elevated testosterone suffered from increased mass loss and tick load compared to control males. Although the first of these two results could be due to an elevated basal metabolic rate from increased plasma testosterone levels, the increased parasite load was statistically independent of the loss in body condition and is likely to be due to compromised immune function. Testosterone-treated males showed greater mobility than control males, and greater mobility resulted in higher mating success. Our experiment thus lends support to the immunocompetence-handicap hypothesis, suggesting that male testosterone levels have been moderated by balancing selection for reproductive success and sustained immune function.


Experimental Constraints on Recycling of Potassium from Subducted Oceanic Crust
Petrological experiments on oceanic crust samples characterize the recycling of potassium from mid-ocean ridge basalts and sediments. Metasomatism could develop directly and continuously from subducted potassium-bearing crust from shallow levels to a maximum depth of 300 kilometers. Phengite (a potassium-rich mica) is the principal potassium host at subsolidus conditions. It transports potassium and water to depths of up to 300 kilometers and could yield over the entire depth range potassium-rich fluids or melts (depending on the specific geotherm), which are likely to constitute one of the primary metasomatic agents for generation of calc-alkaline magmas.


Laboratory misdiagnosis of von Willebrand disease in post-menarchal females: A multi-center study.
Increased awareness of von Willebrand Disease (VWD) has led to more frequent diagnostic laboratory testing, which insurers often dictate be performed at a facility with off-site laboratory processing, instead of a coagulation facility with onsite processing. Off-site processing is more prone to preanalytical variables causing falsely low levels of von Willebrand Factor (VWF) due to the additional transport required. Our aim was to determine the percentage of discordance between off-site and onsite specimen processing for VWD in this multicenter, retrospective study. We enrolled females aged 12 to 50 years who had off-site specimen processing for VWF assays, and repeat testing performed at a consulting institution with onsite coagulation phlebotomy and processing. A total of 263 females from 17 institutions were included in the analysis. There were 251 subjects with both off-site and onsite VWF antigen (VWF:Ag) processing with 96 (38%) being low off-site and 56 (22%) low onsite; 223 subjects had VWF ristocetin co-factor (VWF:RCo), 122 (55%) were low off-site and 71 (32%) were low onsite. Similarly, 229 subjects had a Factor VIII (FVIII) assay, and 67 (29%) were low off-site with less than half, 29 (13%) confirmed low with onsite processing. Higher proportions of patients demonstrated low VWF:Ag, VWF:RCo, and/or FVIII with off-site processing compared to onsite (McNemar's test P-value <.0005, for all assays). These results emphasize the need to decrease delays from sample procurement to processing for VWF assays. The VWF assays should ideally be collected and processed at the same site under the guidance of a hematologist.


Estrogen and progestogen effect on venous thromboembolism in menopausal women.
Prior to 1996, the use of postmenopausal estrogen was not believed to increase the risk of venous thrombosis. Subsequent studies, particularly the prospective, randomized, double-blind, clinical trial of the Women's Health Initiative, have clearly shown an increase in the incidence and risk of venous thrombosis in postmenopausal women using conjugated equine estrogens with or without medroxyprogesterone acetate. The risk of venous thrombosis in postmenopausal women is also increased by obesity and age. Oral hormone therapy has been used principally for management of menopausal symptoms. Transdermal estrogens have not been used as extensively in the United States but have a significant use in Europe. Recent observational studies have indicated no increased risk of venous thrombosis with use of transdermal estrogens. Norpregnane derivatives have been associated with an increased risk of venous thrombosis, suggesting that progestins may contribute to the increased risk in postmenopausal women using estrogen plus progestin therapy.


Pattern recognition based on the correlated intensity fluctuations of thermal light.
Here we present a pattern recognition scheme based on the intensity correlation of thermal light. We prove theoretically that under spatially incoherent illumination the matched filtering technique can be realized in the ghost imaging field. Using the matched filtering technique, it is possible to distinguish an object from a preestablished set of objects through their ghost images, which are extracted by means of intensity correlation measurement. According to the pattern recognition scheme, we present a numerical simulation in which we can easily identify the character inserted into the object arm from a set of two characters through the position of the autocorrelation peak. This pattern recognition scheme opens up the possibility of performing coherent optical processing under spatially incoherent illumination.


Elevated serum vascular endothelial growth factor in patients with hormone-escaped prostate cancer.
To investigate the role of serum vascular endothelial growth factor (VEGF) in the assessment of patients with prostate cancer. Patients, subjects and methods Serum from 78 men was assayed for VEGF using a commercially available enzyme-linked immunosorbent assay kit. Forty-eight patients had a histopathological diagnosis of prostate cancer (16 local disease, 32 metastatic), nine had benign prostatic hyperplasia (BPH) and 21 were healthy controls. The mean serum VEGF level was significantly higher in patients with hormone-escaped prostate cancer than in all other groups (P </= 0. 02). There were no significant differences in serum VEGF levels among the other groups. In 18 patients with serial measurements there was no significant difference in serum VEGF level during either response to or escape from hormonal therapy. The significantly higher serum VEGF level in patients with hormone-escaped prostate cancer suggests a role in the pathogenesis of advanced disease. However, the lack of significant differences among the other groups and the failure to indicate either response to or escape from hormonal therapy suggests that serum VEGF in this setting is of limited use.


Putrescine-sensitive (artifactual) and insensitive (biosynthetic) S-adenosyl-L-methionine decarboxylase activities of Lathyrus sativus seedlings.
The crude extracts of 3-day-old etiolated seedlings of Lathyrus sativus contained two S-adenosyl-L-methionine decarboxylase activities. The artifactual putrescine-dependent activity was due to the H2O2 generated by diamine oxidase (EC 126.96.36.199) of this plant system and was inhibited by catalase. This observation was confirmed by using an electrophoretically and immunologically homogeneous preparation of L. sativus diamine oxidase. In the presence of putrescine, diamine oxidase, in addition to S-adenosylmethionine, decarboxylated L-lysine, L-arginine, L-ornithine, L-methionine and L-glutamic acid to varying degrees. The decarboxylation was not metal-ion dependent. The biosynthetic S-adenosylmethionine decarboxylase (EC 188.8.131.52) was detected after removing diamine oxidase specifically from the crude extracts by employing an immunoaffinity column. This Mg2+-dependent decarboxylase was not stimulated by putrescine or inhibited by catalase. The enzyme activity was inhibited by semicarbazide, 4-bromo-3-hydroxybenzoylamine dihydrogen phosphate and methylglyoxal-bis (guanylhydrazone). It was largely localized in the shoots of the etiolated seedlings and was purified 40-fold by employing a p-hydroxymercuribenzoate/AH-Sepharose affinity column, which also separated the decarboxylase activity from spermidine synthase.


Characterization of the influence of mediator complex in HIV-1 transcription.
HIV-1 exploits multiple host proteins during infection. siRNA-based screenings have identified new proteins implicated in different pathways of the viral cycle that participate in a broad range of cellular functions. The human Mediator complex (MED) is composed of 28 elements and represents a fundamental component of the transcription machinery, interacting with the RNA polymerase II enzyme and regulating its ability to express genes. Here, we provide an evaluation of the MED activity on HIV replication. Knockdown of 9 out of 28 human MED proteins significantly impaired viral replication without affecting cell viability, including MED6, MED7, MED11, MED14, MED21, MED26, MED27, MED28, and MED30. Impairment of viral replication by MED subunits was at a post-integration step. Inhibition of early HIV transcripts was observed by siRNA-mediated knockdown of MED6, MED7, MED11, MED14, and MED28, specifically affecting the transcription of the nascent viral mRNA transactivation-responsive element. In addition, MED14 and MED30 were shown to have special relevance during the formation of unspliced viral transcripts (p < 0.0005). Knockdown of the selected MED factors compromised HIV transcription induced by Tat, with the strongest inhibitory effect shown by siMED6 and siMED14 cells. Co-immunoprecipitation experiments suggested physical interaction between MED14 and HIV-1 Tat protein. A better understanding of the mechanisms and factors controlling HIV-1 transcription is key to addressing the development of new strategies required to inhibit HIV replication or reactivate HIV-1 from the latent reservoirs.


Perceptions of educational experience and inpatient workload among pediatric residents.
Education of residents in academic medical centers occurs as part of clinical care, but little is known about the relationship between clinical workload and educational experiences among pediatric residents. The goal of this study was to assess residents' perceptions of learning on inpatient services at a children's hospital in relation to perceived workload and actual patient census. This was a prospective cohort study of pediatric residents at 1 urban academic children's hospital. Surveys on educational experience were administered weekly to residents on 12 inpatient units from October 2010 to June 2011. Daily peak medical inpatient census data were collected, and Pearson correlations were performed. Mean weekly response rate was 25%. Perceived workload was correlated with weekly peak of patient census for interns (r = 0.66; P= .00) and senior residents (r = 0.73; P = .00). Many aspects of perceived learning were negatively correlated with perceived workload among interns and residents in "acute care" units. Activities beyond direct patient care (eg, attending conferences, independent reading) revealed more negative correlation than educational experience during rounds. Among seniors, scores of aspects of perceived learning did not correlate with workload. The study found mostly negative associations between high perceived workload and perceived learning, especially for interns. Results suggest varied impact of workload on perceived learning by training year. Although patient care is essential for resident education, higher workload may adversely affect learning opportunities for pediatric trainees. More research is needed to identify if generalizable thresholds of patient census and/or clinical workload cause declines in perceived or real education.


Novel Dietary Proteins Selectively Affect Intestinal Health In Vitro after Clostridium difficile-Secreted Toxin A Exposure.
Bacterial gastroenteritis forms a burden on a global scale, both socially and economically. The Gram-positive bacterium Clostridium difficile is an inducer of gastrointestinal bacterial infections, often triggered following disruption of the microbiota by broad-spectrum antibiotics to treat other conditions. The clinical manifestatiaons, e.g., diarrhea, are driven by its toxins secretion, toxin A (TcdA) and toxin B (TcdB). Current therapies are focused on discontinuing patient medication, including antibiotics. However, relapse rates upon therapy are high (20-25%). Here, eighteen dietary proteins were evaluated for their capacity to restore gut health upon C. difficile-derived TcdA exposure. We used bioengineered intestinal tubules to assess proteins for their beneficial effects by examining the epithelial barrier, cell viability, brush-border enzyme activity, IL-6 secretion, IL-8 secretion and nitric oxide (NO) levels upon TcdA challenge. TcdA effectively disrupted the epithelial barrier, increased mitochondrial activity, but did not affect alkaline phosphatase activity, IL-6, IL-8 and NO levels. Intervention with dietary proteins did not show a protective effect on epithelial barrier integrity or mitochondrial activity. However, bovine plasma and potato protein increased alkaline phosphatase activity, egg-white protein increased IL-6 and IL-8 release and wheat, lesser mealworm and yeast protein increased NO levels after TcdA exposure. Hence, dietary proteins can influence parameters involved in intestinal physiology and immune activation suggesting that supplementation with specific dietary proteins may be of benefit during C. difficile infections.


Cannabinoid agonists stimulate both receptor- and non-receptor-mediated signal transduction pathways in cells transfected with and expressing cannabinoid receptor clones.
The physiologic activity of (-)-delta 9-tetrahydrocannabinol, the most active component of marijuana, and of many synthetic cannabimimetics may be mediated either through receptor binding and functional coupling to specific signal transduction pathways or through nonspecific interaction with cell membrane components. The cloning of the human and rat cannabinoid receptors has provided the opportunity to investigate the binding properties and signal transduction pathways directly associated with these receptors. Cannabinoid receptor cDNA was transfected into and stably expressed in fibroblast cell lines that do not contain native cannabinoid receptors, thus allowing comparison with untransfected cells. Binding constants measured using [3H]CP55,940 indicated that the rat and human cloned cannabinoid receptors were similar to native cannabinoid receptors measured in brain and neural cell lines. The cloned receptors coupled to the inhibition of cAMP accumulation, as previously demonstrated. CP55,940 binding and inhibition of cAMP accumulation were absent in untransfected cells. Cannabinoid agonist-stimulated release of arachidonic acid and increase in intracellular calcium were observed in both transfected and untransfected cells. Stereoselectivity of cannabinoid agonists was demonstrated for binding and functional inhibition of cAMP accumulation, but not for the release of arachidonic acid and intracellular calcium. Therefore, cannabinoid agonists can stimulate signaling pathways through both receptor- and non-receptor-mediated pathways in the same cell.


Contributions of TRPV1, endovanilloids, and endoplasmic reticulum stress in lung cell death in vitro and lung injury.
Endogenous agonists of transient receptor potential vanilloid-1 (TRPV1) (endovanilloids) are implicated as mediators of lung injury during inflammation. This study tested the hypothesis that endovanilloids produced following lipopolysaccharide (LPS) treatment activate TRPV1 and cause endoplasmic reticulum stress/GADD153 expression in lung cells, representing a mechanistic component of lung injury. The TRPV1 agonist nonivamide induced GADD153 expression and caused cytotoxicity in immortalized and primary human bronchial, bronchiolar/alveolar, and microvascular endothelial cells, proportional to TRPV1 mRNA expression. In CF-1 mice, Trpv1 mRNA was most abundant in the alveoli, and intratracheal nonivamide treatment promoted Gadd153 expression in the alveolar region. Treatment of CF-1 mice with LPS increased Gadd153 in the lung, lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, and lung wet-to-dry weight ratio. Cotreating mice with LPS and the TRPV1 antagonist LJO-328 reduced Gadd153 induction and LDH in BAL but did not inhibit increases in lung wet-to-dry ratio. In Trpv1(-/-) mice treated with LPS, Gadd153 induction and LDH in BAL were reduced relative to wild-type mice, and the wet-to-dry weight ratios of lungs from both wild-type and Trpv1(-/-) mice decreased. Organic extracts of blood collected from LPS-treated mice were more cytotoxic to TRPV1-overexpressing cells compared with BEAS-2B cells and extracts from control mice, however, most pure endovanilloids did not produce cytotoxicity in a characteristic TRPV1-dependent manner. Collectively, these data indicate a role for TRPV1, and endogenous TRPV1 agonists, in ER stress and cytotoxicity in lung cells but demonstrate that ER stress and cytotoxicity are not essential for pulmonary edema.


Robustness and sensitivity of a blueprint for on-farm estimation of dairy cow energy balance.
Excessive negative energy balance (EB) has been associated with decreased reproductive performance and increased risk of lameness and metabolic diseases. On-farm, automated EB estimates for individual cows would enable dairy farmers to detect excessive negative EB early and act to minimize its extent and duration by altering feeding. Previously, we have shown that EB can be estimated from frequent measurements of body weight (BW) and body condition score (BCS) changes, referred to as EBbody. In this study, we investigated the robustness and sensitivity of the EBbody method to assess its genericity and on-farm applicability. We used 5 data sets with BW of lactating cows (name of data set in parenthesis): 65 Holstein cows in a French feeding trial (INRA); 6 Holstein cows in a British feeding trial (Friggens); 31 Holstein cows and 17 Jersey cows in a Danish feeding trial (DCRC); 140 Holstein cows in a British feeding trial (Scotland's Rural College, SRUC); and 1,592 Holstein cows on 9 Danish farms with milking robots (automatic milking system). We used the INRA and Friggens data sets to develop a dynamic formula to correct BW for increasing residual gut-fill (RGF) during early lactation. With the DCRC data, we tested the effect of smoothing parameters and weighing frequency on EBbody. Also, 2 robustness tests were performed using the SRUC data to test the effect of diet change on BW and the automatic milking system data to test the effect of farm on BW variation. Finally, we combined the results into a blueprint describing different ways to calculate EBbody depending on the purpose and on the availability of BCS. The dynamic RGF adjustment resulted in a lower empty BW during early lactation than that obtained with the previously used constant RGF. The double-exponential smoothing method used to correct for meal-related gut-fill was robust to choice of smoothing parameters. Cows should be weighed at least once every 4 d during early lactation to capture the duration of negative EBbody. Our EBbody method proved robust to diet changes. Finally, although cow BW varied significantly between farms, the quantile regression smoothing of BW did not bias the estimation of weight differences between herds. In conclusion, these results validate the applicability of the EBbody method to estimate EB across a range of farm conditions, and we provided a blueprint that enables the estimation of EBbody for individual cows on-farm using only frequent BW, in combination with BCS when available.


Discourses of illegality and exclusion: when water access matters.
This paper examines the politics and the underlying discourses of water provisioning and how residents of Korogocho and Viwandani slum settlements in Nairobi city cope with challenges relating to water access. We use qualitative data from 36 focus group discussions conducted in the two slums to unravel discourses regarding water provisioning in the rapidly growing slum settlements in African cities. Results show that the problems concerning water provisioning within Nairobi slums are less about water scarcity and more about unequal distribution and the marginalisation of slum areas in development plans. Poor water management, lack of equity-based policies and programmes, and other slum-specific features such as land-tenure systems and insecurity exacerbate water-supply problems within slum areas. It is hard to see how water supply in these communities can improve without the direct and active involvement of the government in infrastructural development and oversight of the water-supply actors. Innovative public-private partnerships in water provision and the harnessing of existing community efforts to improve the water supply would go a long way towards improving the water supply to the rapidly growing urban poor population in Africa.


Interface of culture, insecurity and HIV and AIDS: Lessons from displaced communities in Pader District, Northern Uganda.
Northern Uganda unlike other rural regions has registered high HIV prevalence rates comparable to those of urbanized Kampala and the central region. This could be due to the linkages of culture, insecurity and HIV. We explored community perceptions of HIV and AIDS as a problem and its inter-linkage with culture and insecurity in Pader District. A cross sectional qualitative study was conducted in four sub-counties of Pader District, Uganda between May and June 2008. Data for the study were collected through 12 focus group discussions (FGDs) held separately; 2 FGDs with men, 6 FGDs with women, and 4 FGDs with the youth (2 for each sex). In addition we conducted 15 key informant interviews with; 3 health workers, 4 community leaders at village and parish levels, 3 persons living with HIV and 5 district officials. Data were analysed using the content thematic approach. This process involved identification of the study themes and sub-themes following multiple reading of interview and discussion transcripts. Relevant quotations per thematic area were identified and have been used in the presentation of study findings. The struggles to meet the basic and survival needs by individuals and households overshadowed HIV as a major community problem. Conflict and risky sexual related cultural practices were perceived by communities as major drivers of HIV and AIDS in the district. Insecurity had led to congestion in the camps leading to moral decadence, rape and defilement, prostitution and poverty which increased vulnerability to HIV infection. The cultural drivers of HIV and AIDS were; widow inheritance, polygamy, early marriages, family expectations, silence about sex and alcoholism. Development partners including civil society organisations, central government, district administration, religious and cultural leaders as well as other stakeholders should mainstream HIV in all community development and livelihood interventions in the post conflict Pader district to curtail the likely escalation of the HIV epidemic. A comprehensive behaviour change communication strategy is urgently needed to address the negative cultural practices. Real progress in the region lies in advocacy and negotiation to realise lasting peace.


Optimizing surgical resection of the bleeding Meckel diverticulum in children.
Meckel diverticula containing gastric heterotopia predispose to local hyperacidity, mucosal ulceration, and gastrointestinal bleeding in children. Eradication of acid-producing oxyntic cells is performed by either of two surgical methods: segmental enterectomy including the diverticulum or diverticulectomy only. Retrospective review of all children having surgical resection of a Meckel diverticulum at a tertiary-referral children's hospital from 2002 to 2016 was performed. Demographic data, surgical method, pathological specimens, and outcomes were evaluated. 102 children underwent surgical resection of a Meckel diverticulum during the study period. 27 (26.5%) children presented with bleeding, of which 16 (59%) had diverticulectomy only, and 11 (41%) had segmental ileal resection. All Meckel diverticula in children presenting with bleeding contained gastric heterotopia, and resection margins were free of gastric mucosa. Histologically, 19 specimens showed microscopic features of ulceration, on average 2.95mm (SD 4.49) from the nearest gastric mucosa (range: 0-16mm). Mean length of hospitalization after ileal resection was 4.0days (SD 1.2) compared to 1.6days (SD 0.9) for diverticulectomy only (p<0.001), with no re-bleeding occurrences. In the operative management of children having a bleeding Meckel diverticulum, diverticulectomy-only completely eradicates gastric heterotopia without increased risk of continued bleeding or complications and significantly shortens hospitalization. Treatment Study: Level III.


A novel resource for studying function and dysfunction of α-synuclein: mouse lines for modulation of endogenous Snca gene expression.
Pathological modification of α-synuclein is believed to be an important event in pathogenesis of Parkinson's disease and several other neurodegenerative diseases. In normal cells this protein has been linked to many intracellular processes and pathways. However, neither normal function of α-synuclein in neuronal and certain other types of cells nor its exact role in the disease pathogenesis is well understood, which is largely due to limitations of animal models used for studying this protein. We produced and validated several novel mouse lines for manipulating expression of the endogenous Snca gene coding for α-synuclein. These include a line for conditional Cre-recombinase-driven inactivation of the gene; a line for conditional Flp-driven restoration of a neo-cassete-blocked α-synuclein expression; a new line with a "clean" constituent knockout of the gene as well as a line carrying this knockout locus and Rosa26-stop-lacZ reporter locus linked at the same mouse chromosome 6. Altogether these lines represent a set of new useful tools for studies of α-synuclein normal function and the role of this protein in disease pathogenesis.


Multivariate sexual selection on male song structure in wild populations of sagebrush crickets, Cyphoderris strepitans (Orthoptera: Haglidae).
While a number of studies have measured multivariate sexual selection acting on sexual signals in wild populations, few have confirmed these findings with experimental manipulation. Sagebrush crickets are ideally suited to such investigations because mating imposes an unambiguous phenotypic marker on males arising from nuptial feeding by females. We quantified sexual selection operating on male song by recording songs of virgin and mated males captured from three wild populations. To determine the extent to which selection on male song is influenced by female preference, we conducted a companion study in which we synthesized male songs and broadcast them to females in choice trials. Multivariate selection analysis revealed a saddle-shaped fitness surface, the highest peak of which corresponded to longer train and pulse durations, and longer intertrain intervals. Longer trains and pulses likely promote greater mate attraction, but selection for longer intertrain durations suggests that energetic constraints may necessitate "time outs". Playback trials confirmed the selection for longer train and pulse durations, and revealed significant stabilizing selection on dominant frequency, suggesting that the female auditory system is tightly tuned to the species-specific call frequency. Collectively, our results revealed a complex pattern of multivariate nonlinear selection characterized primarily by strong stabilizing and disruptive selection on male song traits.


Progress in DNA vaccine for prophylaxis and therapy of hepatitis B.
Increasing lines of evidence suggest that DNA vaccine is of interest to fight chronic hepatitis B virus (HBV) infection. We used the Pekin duck infected by duck HBV (DHBV), closely related to the human virus, which is an attractive model allowing study of protective and therapeutic effectiveness of DNA vaccines against hepatitis B. Immunisation with a plasmid encoding the DHBV large (L) envelope protein induced a strong, specific, highly neutralising and long-lasting anti-preS humoral response in uninfected ducks. Importantly, maternal antibodies elicited by such DNA immunisation were vertically transmitted and protected progeny against viral challenge. Therapeutic immunisation of chronic DHBV-carrier ducks with this plasmid DNA led to the dramatic and sustained decrease in viral replication and even to clearance of intrahepatic viral covalently close circular DNA (cccDNA) pool in some animals. Our recent combination therapy data showed even a more pronounced antiviral effect of DNA vaccine to DHBV envelope protein when associated with antiviral drug (lamivudine) treatment. Therefore, DNA-based vaccine appears as a promising new approach for prophylaxis and therapy of hepatitis B.


Measuring the phagocytic activity of cells.
Phagocytosis is a critical biological activity through which the host can protect itself from infectious and non-infectious environmental particles and remove unwanted host cells in order to maintain tissue homeostasis. Phagocytosis is an ancient, conserved process that is apparent in all multicellular organisms. The process of phagocytosis requires the recognition of ligands on particles by specific receptors expressed by the phagocyte that promote internalization via reorganization of cytoskeletal elements and directed formation of the phagosome. Subsequent phagosome-lysosome fusion delivers the contents for destruction and recycling in the acidic compartment. Significantly, receptor engagement and uptake can also trigger intracellular signaling pathways that initiate appropriate innate immune and pro-inflammatory or anti-inflammatory responses dependent upon the nature of the particle. The important benefits of phagocytosis to host survival are exemplified by the detrimental effects to health that occur when phagocytic efficiency is diminished. In an overview, we discuss the different experimental approaches or options that can be considered when investigating and determining the characteristics and quantification of phagocytic activity. These criteria will include choice of phagocytic cell type, selection, and method of labeling of particle for monitoring internalization, targeting of particles to specific receptors, and quantification of ingestion either at the single cell or at the population level. We provide two detailed examples of phagocytosis assays.


Forward-illumination light-extinction technique for soot measurement.
A forward-illumination light-extinction (FILE) soot volume fraction measurement technique was developed and tested. By using a camera and a point light source in front of the flame and a diffuser behind the flame, with this technique one can achieve a two-dimensional soot concentration measurement with only one window when one is studying confined combustion. The line-of-sight quantitative soot volume fraction is obtained by calculation of the reflected light intensity with or without the presence of soot cloud. Verification of this technique was accomplished by measurement of an axisymmetric ethylene diffusion flame. The field distribution obtained by Abel inversion is presented and matched well with previous point measurements. The FILE technique has high time resolution when a high-speed camera and a copper vapor laser are adopted. All these advantages of FILE make it suitable for line-of-sight integrated, two-dimensional soot distribution of transient combustion, e.g., in the case of in-cylinder Diesel combustion.


Structural basis of arginine asymmetrical dimethylation by PRMT6.
PRMT6 is a type I protein arginine methyltransferase, generating the asymmetric dimethylarginine mark on proteins such as histone H3R2. Asymmetric dimethylation of histone H3R2 by PRMT6 acts as a repressive mark that antagonizes trimethylation of H3 lysine 4 by the MLL histone H3K4 methyltransferase. PRMT6 is overexpressed in several cancer types, including prostate, bladder and lung cancers; therefore, it is of great interest to develop potent and selective inhibitors for PRMT6. Here, we report the synthesis of a potent bisubstrate inhibitor GMS [6'-methyleneamine sinefungin, an analog of sinefungin (SNF)], and the crystal structures of human PRMT6 in complex, respectively, with S-adenosyl-L-homocysteine (SAH) and the bisubstrate inhibitor GMS that shed light on the significantly improved inhibition effect of GMS on methylation activity of PRMT6 compared with SAH and an S-adenosyl-L-methionine competitive methyltransferase inhibitor SNF. In addition, we also crystallized PRMT6 in complex with SAH and a short arginine-containing peptide. Based on the structural information here and available in the PDB database, we proposed a mechanism that can rationalize the distinctive arginine methylation product specificity of different types of arginine methyltransferases and pinpoint the structural determinant of such a specificity.


Update on the treatment of diabetic retinopathy.
To describe the classification, clinical features, and evaluation of diabetic retinopathy and to review its conventional as well as most updated management. Literature search of Medline up to October 2006. Key words for the literature search were 'diabetic', 'retinopathy', 'treatment', 'laser photocoagulation', 'vitrectomy', 'corticosteroid', 'protein kinase C inhibitor', and 'VEGF inhibitor'. Original articles, review papers, and book chapters were reviewed. Diabetic retinopathy remains one of the leading causes of blindness worldwide. The duration of diabetes and severity of hyperglycaemia are the major risk factors. It progresses from non-proliferative diabetic retinopathy to proliferative diabetic retinopathy through various stages, and the accurate diagnosis of its stage is important. Strict metabolic control and tight blood pressure control can significantly reduce the risk of developing retinopathy and its progression, but are difficult to achieve in clinical practice. Laser photocoagulation and vitrectomy are effective in preventing severe visual loss from sight-threatening diabetic retinopathy and its complications, but both modalities have potential side-effects. Results from clinical trials for protein kinase C inhibitors, intravitreal steroid injections, anti-vascular endothelial growth factor agents, angiotensin converting enzyme inhibitors, and growth hormone inhibitors are promising. Evidence from past clinical trials does not support a role for anti-platelet agents, aldose reductase inhibitors, and advanced glycation end-products inhibitors. Strict metabolic control, tight blood pressure control, laser photocoagulation, and vitrectomy remain the conventional management of diabetic retinopathy. Further clinical trials exploring the role of protein kinase C inhibitors, intravitreal steroid, anti-vascular endothelial growth factor agents, angiotensin converting enzyme inhibitors, growth hormone, and other potential therapies for diabetic retinopathy are actively ongoing. In the near future, results from these clinical trials may lead to the introduction of additional treatments and a corresponding reduction in the frequency of visual loss due to diabetic retinopathy.


Insulin-like growth factor I messenger RNA and protein are expressed in the human lymph node and distinctly confined to subtypes of macrophages, antigen-presenting cells, lymphocytes and endothelial cells.
Insulin-like growth factor I (IGF-I) is a potent hormone that stimulates growth and differentiation and inhibits apoptosis in numerous tissues. Preliminary evidence suggests that IGF-I exerts differentiating, mitogenic and restoring activities in the immune system but the sites of synthesis of local IGF-I are unknown. Identification of these sites would allow the functional role of local IGF-I to be clarified. The presence of IGF-I in non-immune cells suggests that it acts as a trophic factor, while its occurrence in subtypes of lymphocytes or antigen-presenting cells indicates paracrine/autocrine direct regulatory involvement of IGF-I in the human immune response. The present study investigated the location of IGF-I messenger RNA and protein on archival human lymph node samples by in situ hybridization, immunohistochemistry and double immunofluorescence staining using an IGF-I probe and antisera specific for human IGF-I and CD3 (T lymphocytes), CD20 (B lymphocytes), CD68 (macrophages), CD21 (follicular dendritic cells), S100 (interdigitating dendritic cells) and podoplanin (fibroblastic reticular cells). Numerous cells within the B- and T-cell compartments expressed the IGF-I gene, and the majority of these cells were identified as macrophages. Solitary follicular dendritic cells exhibited IGF-I. A few T lymphocytes, and no B lymphocytes, contained IGF-I immunoreactive material. Furthermore, IGF-I immunoreactive cells outside the follicles that did not react with CD3, CD20, S100 or podoplanin markers were identified as high-endothelial venule (HEV) cells. From this we conclude that the main task of IGF-I in human non-tumoral lymph node may be autocrine and paracrine regulation of the differentiation, stimulation and survival of lymphocytes, antigen-presenting cells and macrophages and the differentiation and maintenance of HEV cells.


Color technology is not necessary for rich and efficient color language.
The evolution of basic color terms in language is claimed to be stimulated by technological development, involving technological control of color or exposure to artificially colored objects. Accordingly, technologically "simple" non-industrialized societies are expected to have poor lexicalization of color, i.e., only rudimentary lexica of 2, 3 or 4 basic color terms, with unnamed gaps in the color space. While it may indeed be the case that technology stimulates lexical growth of color terms, it is sometimes considered a sine qua non for color salience and lexicalization. We provide novel evidence that this overlooks the role of the natural environment, and people's engagement with the environment, in the evolution of color vocabulary. We introduce the Maniq-nomadic hunter-gatherers with no color technology, but who have a basic color lexicon of 6 or 7 terms, thus of the same order as large languages like Vietnamese and Hausa, and who routinely talk about color. We examine color language in Maniq and compare it to available data in other languages to demonstrate it has remarkably high consensual color term usage, on a par with English, and high coding efficiency. This shows colors can matter even for non-industrialized societies, suggesting technology is not necessary for color language. Instead, factors such as perceptual prominence of color in natural environments, its practical usefulness across communicative contexts, and symbolic importance can all stimulate elaboration of color language.


Faster Detection of Poliomyelitis Outbreaks to Support Polio Eradication.
As the global eradication of poliomyelitis approaches the final stages, prompt detection of new outbreaks is critical to enable a fast and effective outbreak response. Surveillance relies on reporting of acute flaccid paralysis (AFP) cases and laboratory confirmation through isolation of poliovirus from stool. However, delayed sample collection and testing can delay outbreak detection. We investigated whether weekly testing for clusters of AFP by location and time, using the Kulldorff scan statistic, could provide an early warning for outbreaks in 20 countries. A mixed-effects regression model was used to predict background rates of nonpolio AFP at the district level. In Tajikistan and Congo, testing for AFP clusters would have resulted in an outbreak warning 39 and 11 days, respectively, before official confirmation of large outbreaks. This method has relatively high specificity and could be integrated into the current polio information system to support rapid outbreak response activities.


Evaluation and management of the cardiac amyloidosis.
Cardiac amyloidosis describes clinically significant involvement of the heart by amyloid deposition, which may or may not be associated with involvement of other organs. The purpose of this review is to summarize the current state of evidence for the effective evaluation and management of cardiac amyloidosis. Acquired systemic amyloidosis occurs in more than 10 per million person-years in the U.S. population. Although no single noninvasive test or abnormality is pathognomonic of cardiac amyloid, case-control studies indicate that echocardiographic evidence of left ventricular wall thickening, biatrial enlargement, and increased echogenicity in conjunction with reduced electrocardiographic voltages is strongly suggestive of cardiac amyloidosis. Furthermore, newer echocardiographic techniques such as strain and strain rate imaging can demonstrate impairment in longitudinal function before ejection fraction becomes abnormal. Recent observational studies also suggest that cardiovascular magnetic resonance imaging yields characteristic findings in amyloidosis, offering promise for the early detection of cardiac involvement, and the presence of detectable cardiac troponin and elevated B-type natriuretic peptide in serum of affected patients portends an adverse prognosis. Management strategies for cardiac amyloid are largely based on nonrandomized single-center studies. One of the few published randomized studies shows the superiority of oral prednisolone and melphalan compared with colchicine in systemic AL amyloidosis. Intermediate-dose infusional chemotherapy regimes (such as vincristine, adriamycin, and dexamethasone) and high-dose chemotherapy with peripheral stem cell rescue have been used widely, but treatment-related mortality remains substantial with chemotherapy. Recent studies also indicate promising strategies to stabilize the native structures of amyloidogenic proteins; inhibit fibril formation; and disrupt established deposits using antibodies, synthetic peptides, and small-molecule drugs.


Different Chemical Structures and Physiological/Pathological Roles of Cyclooxygenases.
This review describes cyclooxygenase (COX), which synthesizes prostanoids that play an important role in living things. The authors conducted a national and international literature review on the subject. The COX enzyme uses arachidonic acid to form prostanoids, which play a role in several physiological and pathological conditions. This enzyme has different isoforms, mainly COX-1 and COX-2. The constitutive isoform is COX-1, while COX-2 is the inducible isoform. Both are expressed in different tissues and at different levels, but they may also coexist within the same tissue. Both isoforms show essentially the same mode of action, but their substrates and inhibitors may differ. The COX-1 isoform, which plays a role in the continuation of physiological events, has an increased expression level in various carcinomas, and the COX-2 isoform, which is increased in inflammatory conditions, is typically expressed at low physiological levels in some tissues such as the brain, kidney, and uterus. In addition to investigating the efficacies of the COX-1 and COX-2 isoforms, the discovery of potential new COX enzymes and their effect continues. This review also looks at the roles of the COX enzyme in certain physiological and pathological conditions.


Deep brain stimulation for obsessive-compulsive disorders: long-term analysis of quality of life.
To evaluate the long-term effects of deep brain stimulation (DBS) on quality of life (QOL) in therapy-refractory obsessive-compulsive disorder (OCD) patients. 16 patients who met Diagnostic and Statistical Manual of Mental Disorders (4th ed) (DSM-IV) criteria for OCD and were considered therapy-refractory were treated with DBS. Patients were assessed 1 month before device implantation (T0), at 8 months of active stimulation (T1) and at 3-5 years of active stimulation (T2). QOL was measured with the WHO Quality of Life Scale-Brief Version (WHOQOL-BREF) that covers physical, psychological, social and environmental domains. The study was conducted between April 2005 and January 2011 at the Academic Medical Center, Amsterdam, The Netherlands. At T1 and T2, we found significant improvement (p<0.05) in the general score and in the physical, psychological and environmental domains of WHOQOL-BREF. Between T1 and T2, the physical and psychological domains improved further (p<0.05). At T2, the general score improved by a total of 90%, the physical and psychological domains both improved by 39.5% and the environmental domain improved by 16%. The social domain did not change between baseline and follow-up assessments. In line with symptom improvement, patient's QOL improved in the general score and in three of the four WHOQOL-BREF domains. This suggests that the improvement caused by DBS is not limited to symptom reduction alone, but also has a positive influence on patients' perception of their physical, psychological, environmental and global QOL. http://isrctn.org identifier: ISRCTN23255677.


Internalization of near-infrared fluorescent dyes within isolated leukocyte populations.
Scientists have expressed continued interest in the development of microsensor technology that can indicate toxicity that occurs within a cell after a chemical challenge. One of the more useful approaches of microsensor technology is the application of fluorescent spectroscopy to indicate early-stage injury with optimal specificity and decreased background interference. If the toxicity is detected during the early onset period of injury, then the probability for therapeutic recovery is promising. There has been increasing interest in the use of infrared (IR) and near infrared (NIR) dyes as biological microsensors due to their fluorescent spectral characteristics. Three of the most essential characteristics are the ability to minimize background interference by extraneous biological matrices, to exhibit optimal molar absorptivity and quantum yields, to maintain chronic cellular homeostasis. Therefore, the present study was developed to determine if selected NIR dyes would distribute within isolated neutrophil populations without altering normal cellular homeostasis using fluorescent wavelength analysis. The results demonstrate that selected NIR dyes undergo internalization within target cell populations while maintaining cell viability and homeostasis. In addition, these dyes demonstrate changes in absorbance and fluorescence analysis after the immune cells were challenged with a stimulant. Moreover, critical cellular functions, such as degranulation and superoxide production were not compromised by the internalization of the NIR dyes. These data suggest that selected NIR dyes can undergo intracellular uptake within neutrophil cultures without altering the normal functional capabilities of the targeted cell population.


Stage I serous papillary carcinoma of the endometrium.
From 1973 to 1987, 16 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage I serous papillary endometrial carcinoma were evaluated and treated at the University of Kentucky Medical Center (Lexington, KY). All patients were 60 years of age or older, and all were postmenopausal. Patients were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and paraaortic lymph node sampling, and 38% were noted to have more extensive disease than appreciated clinically. Nine patients were given adjuvant postoperative radiation. Seven patients (44%) developed recurrent cancer with liver, lung, and upper abdomen being the most common sites of spread. Prognosis was most directly related to the presence of lymph vascular space invasion and the depth of myometrial penetration. No patient with serous papillary carcinoma confined to the endometrium developed recurrent cancer. In contrast, the recurrence rate of patients having myometrial invasion was 70% (P less than 0.03). Hormonal therapy was of limited value in the treatment of recurrent disease. This data suggests the need for adjuvant systemic therapy in the treatment of patients with Stage I serous papillary carcinoma of the endometrium who have myometrial invasion.


A qualitative assessment of the acceptability of hepatitis C remote self-testing and self-sampling amongst people who use drugs in London, UK.
Hepatitis C (HCV) diagnosis and care is a major challenge for people who use illicit drugs, and is characterised by low rates of testing and treatment engagement globally. New approaches to fostering engagement are needed. We explored the acceptability of remote forms of HCV testing including self-testing and self-sampling among people who use drugs in London, UK. A qualitative rapid assessment was undertaken with people who use drugs and stakeholders in London, UK. Focus groups were held with men who have sex with men engaged in drug use, people who currently inject drugs and people who formerly injected drugs (22 participants across the 3 focus groups). Stakeholders participated in semi-structured interviews (n = 5). We used a thematic analysis to report significant themes in participants' responses. We report an overarching theme of 'tension' in how participants responded to the acceptability of remote testing. This tension is evident across four separate sub-themes we explore. First, choice and control, with some valuing the autonomy and privacy remote testing could support. Second, the ease of use of self testing linked to its immediate result and saliva sample was preferred over the delayed result from a self administered blood sample tested in a laboratory. Third, many respondents described the need to embed remote testing within a supportive care pathway. Fourth, were concerns over managing a positive result, and its different meanings, in isolation. The concept of remote HCV testing is acceptable to some people who use drugs in London, although tensions with lived experience of drug use and health system access limit its relevance. Future development of remote testing must respond to concerns raised in order for acceptable implementation to take place.


Spatial Compartmentalization of the Microbiome between the Lumen and Crypts Is Lost in the Murine Cecum following the Process of Surgery, Including Overnight Fasting and Exposure to Antibiotics.
The cecum is a unique region in the mammalian intestinal tract in which the microbiome is localized to two compartments, the lumen and the crypts. The microbiome within crypts is particularly important as it is in direct contact with lining epithelial cells including stem cells. Here, we analyzed the microbiome in cecum of mice using multiple techniques including metagenomics. The lumen microbiome comprised Firmicutes and Bacteroidetes whereas the crypts were dominated by Proteobacteria and Deferribacteres, and the mucus comprised a mixture of these 4 phyla. The lumen microbial functional potential comprised mainly carbon metabolism, while the crypt microbiome was enriched for genes encoding stress resistance. In order to determine how this structure, assembly, and function are altered under provocative conditions, we exposed mice to overnight starvation (S), antibiotics (A), and a major surgical injury (partial hepatectomy [H]), as occurs with major surgery in humans. We have previously demonstrated that the combined effect of this "SAH" treatment leads to a major disturbance of the cecal microbiota at the bottom of crypts in a manner that disrupts crypt cell homeostasis. Here, we applied the SAH conditions and observed a loss of compartmentalization in both composition and function of the cecal microbiome associated with major shifts in local physicochemical cues including decrease of hypoxia, increase of pH, and loss of butyrate production. Taken together, these studies demonstrated a defined order, structure, and function of the cecal microbiome that can be disrupted under provocative conditions such as major surgery and its attendant exposures.IMPORTANCE The proximal colon and cecum are two intestinal regions in which the microbiome localizes to two spatially distinct compartments, the lumen and crypts. The differences in composition and function of luminal and crypt microbiome in the cecum and the effect of physiological stress on their compartmentalization remain poorly characterized. Here, we characterized the composition and function of the lumen-, mucus-, and crypt-associated microbiome in the cecum of mice. We observed a highly ordered microbial architecture within the cecum whose assembly and function become markedly disrupted when provoked by physiological stress such as surgery and its attendant preoperative treatments (i.e., overnight fasting and antibiotics). Major shifts in local physicochemical cues including a decrease in hypoxia levels, an increase in pH, and a loss of butyrate production were associated with the loss of compositional and functional compartmentalization of the cecal microbiome.


Enhanced binding of the hypoxic cell marker [3H]fluoromisonidazole in ischemic myocardium.
The 2-nitroimidazole fluoromisonidazole is metabolically trapped in viable hypoxic cells in inverse proportion to PO2. This attribute suggests that [18F]fluoromisonidazole may be useful for imaging hypoxic tissue using positron emission tomography. To examine this potential, we studied the pharmacokinetics and biodistribution of [3H]fluoromisonidazole in six open chest dogs. In two normal dogs, plasma and urine samples were collected over a 4-hr period following i.v. injection of the drug. In four animals, regional myocardial ischemia was produced 2 hr prior to drug injection by occlusion of the circumflex coronary artery and maintained during the 4-hr sampling period. In all animals, postmortem samples of myocardium and other organs were obtained and tissue, plasma, and urine tritium activity were determined by liquid scintillation counting. In areas of reduced flow, [3H]fluoromisonidazole accumulated in myocardium in inverse proportion to myocardial blood flow measured by microspheres, indicating enhanced binding in hypoxic tissues. Maximum tissue concentrations in ischemic myocardium were two- to three-fold greater than in normal myocardium and plasma. Plasma clearance data indicate the drug is rapidly distributed into the total-body water, clears from the body with a half-life of 275 +/- 50 min, and undergoes minimal metabolism by 4 hr. We conclude [18F]fluoromisonidazole may be a suitable agent for radionuclide imaging of hypoxic myocardium.


Strengthening public health laboratory capacity in Thailand for International Health Regulations (IHR) (2005).
Thailand conducted a national laboratory assessment of core capacities related to the International Health Regulations (IHR) (2005), and thereby established a baseline to measure future progress. The assessment was limited to public laboratories found within the Thai Bureau of Quality and Safety of Food, National Institute of Health and regional medical science centres. The World Health Organization (WHO) laboratory assessment tool was adapted to Thailand through a participatory approach. This adapted version employed a specific scoring matrix and comprised 16 modules with a quantitative output. Two teams jointly performed the on-site assessments in December 2010 over a two-week period, in 17 public health laboratories in Thailand. The assessment focused on the capacity to identify and accurately detect pathogens mentioned in Annex 2 of the IHR (2005) in a timely manner, as well as other public health priority pathogens for Thailand. Performance of quality management, budget and finance, data management and communications was considered strong (>90%); premises quality, specimen collection, biosafety, public health functions, supplies management and equipment availability were judged as very good (>70% but ≤90%); while microbiological capacity, staffing, training and supervision, and information technology needed improvement (>60% but ≤70%). This assessment is a major step in Thailand towards development of an optimized and standardized national laboratory network for the detection and reporting of infectious disease that would be compliant with IHR (2005). The participatory strategy employed to adapt an international tool to the Thai context can also serve as a model for use by other countries in the Region. The participatory approach probably ensured better quality and ownership of the results, while providing critical information to help decision-makers determine where best to invest finite resources.


Optimal control design of pulse shapes as analytic functions.
Representing NMR pulse shapes by analytic functions is widely employed in procedures for optimizing performance. Insights concerning pulse dynamics can be applied to the choice of appropriate functions that target specific performance criteria, focusing the solution search and reducing the space of possible pulse shapes that must be considered to a manageable level. Optimal control theory can accommodate significantly larger parameter spaces and has been able to tackle problems of much larger scope than more traditional optimization methods. However, its numerically generated pulses, as currently constructed, do not readily incorporate the capabilities of particular functional forms, and the pulses are not guaranteed to vary smoothly in time, which can be a problem for faithful implementation on older hardware. An optimal control methodology is derived for generating pulse shapes as simple parameterized functions. It combines the benefits of analytic and numerical protocols in a single powerful algorithm that both complements and enhances existing optimization strategies.


Cadmium inhibits the electron transfer chain and induces reactive oxygen species.
Recent research indicates that cadmium (Cd) induces oxidative damage in cells; however, the mechanism of the oxidative stress induced by this metal is unclear. We investigated the effects of Cd on the individual complexes of the electron transfer chain (ETC) and on the stimulation of reactive oxygen species (ROS) production in mitochondria. The activity of complexes II (succinate:ubiquinone oxidoreductase) and III (ubiquinol:cytochrome c oxidoreductase) of mitochondrial ETC from liver, brain, and heart showed greater inhibition by Cd than the other complexes. Cd stimulated ROS production in the mitochondria of all three tissues mentioned above. The effect of various electron donors (NADH, succinate, and 2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinol) on ROS production was tested separately in the presence and in the absence of Cd. ESR showed that complex III might be the only site of ROS production induced by Cd. The results of kinetic studies and electron turnover experiments suggest that Cd may bind between semiubiquinone and cytochrome b566 of the Q0 site of cytochrome b of complex III, resulting in accumulation of semiubiquinones at the Q0 site. The semiubiquinones, being unstable, are prone to transfer one electron to molecular oxygen to form superoxide, providing a possible mechanism for Cd-induced generation of ROS in mitochondria.


Investigating State Restriction in Fluorescent Protein FRET Using Time-Resolved Fluorescence and Anisotropy.
Most fluorescent proteins exhibit multiexponential fluorescence decays, indicating a heterogeneous excited state population. FRET between fluorescent proteins should therefore involve multiple energy transfer pathways. We recently demonstrated the FRET pathways between EGFP and mCherry (mC), upon the dimerization of 3-phosphoinositide dependent protein kinase 1 (PDK1), to be highly restricted. A mechanism for FRET restriction based on a highly unfavorable κ2 orientation factor arising from differences in donor-acceptor transition dipole moment angles in a far from coplanar and near static interaction geometry was proposed. Here this is tested via FRET to mC arising from the association of glutathione (GSH) and glutathione S-transferase (GST) with an intrinsically homogeneous and more mobile donor Oregon Green 488 (OG). A new analysis of the acceptor window intensity, based on the turnover point of the sensitized fluorescence, is combined with donor window intensity and anisotropy measurements which show that unrestricted FRET to mC takes place. However, a long-lived anisotropy decay component in the donor window reveals a GST-GSH population in which FRET does not occur, explaining previous discrepancies between quantitative FRET measurements of GST-GSH association and their accepted values. This reinforces the importance of the local donor-acceptor environment in mediating energy transfer and the need to perform spectrally resolved intensity and anisotropy decay measurements in the accurate quantification of fluorescent protein FRET.


Efficient conversion of aromatic amines into azides: a one-pot synthesis of triazole linkages.
[reaction: see text] An efficient and improved procedure for the preparation of aromatic azides and their application in the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition ("click reaction") is described. The synthesis of aromatic azides from the corresponding amines is accomplished under mild conditions with tert-butyl nitrite and azidotrimethylsilane. 1,4-Disubstituted 1,2,3-triazoles were obtained in excellent yields from a variety of aromatic amines without the need for isolation of the azide intermediates.


Screening for Causative Mutations of Major Prolificacy Genes in Iranian Fat-Tailed Sheep.
The presence of different missense mutations in sheep breeds have shown that the bone morphogenetic protein receptor 1B (BMPR1B), bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) genes play a vital role in ovulation rate and prolificacy in ewes. Therefore, the present study aims to investigate BMPR1B, BMP15 and GDF9 gene mutations in prolific ewes of Iranian fat-tailed Lori-Bakhtiari sheep. In the present experimental study, genomic DNA was extracted from whole blood of 10 prolific Lori-Bakhtiari ewes with at least two twinning records in the first four parities to identify point mutations of the BMPR1B, BMP15 and GDF9 genes, using DNA sequencing. The results obtained from DNA sequencing showed a new synonymous mutation (g.66496G>A) in exon 8 of the BMPR1B gene, without any amino acid change. Sequencing of the BMP15 gene revealed a deletion of 3 bp (g.656_658delTTC) in exon 1, leading to an amino acid deletion (p.Leu19del). Four single nucleotide polymorphisms (G1:g.2118G>A, G2:g.3451T>C, G3:g.3457A>G and G4:g.3701G>A), were detected in exons 1 and 2 of the GDF9 gene, two of which caused amino acid substitutions (G1: p.87Arg>His and G4: p.241Glu>Lys). These amino acid alterations are proposed to have a benign impact on structure and function of the GDF9 polypeptide sequence. Three major prolificacy genes (BMPR1B, BMP15 and GDF9) were polymorphic in Lori-Bakhtiari sheep, although none of the major causative mutation was detected in this sheep type. Further studies using high throughput methods such as genome-wide association study (GWAS) and evaluation of other candidate genes are necessary in the future.


Redox metals and oxidative abnormalities in human prion diseases.
Prion diseases are characterized by the accumulation of diffuse and aggregated plaques of protease-resistant prion protein (PrP) in the brains of affected individuals and animals. Whereas prion diseases in animals appear to be almost exclusively transmitted by infection, human prion diseases most often occur sporadically and, to a lesser extent, by inheritance or infection. In the sporadic cases (sporadic Creutzfeld-Jakob disease, sCJD), PrP-containing plaques are infrequent, whereas in transmitted (variant CJD) and inherited (Gerstmann-Straussler-Scheinker Syndrome) cases, plaques are a usual feature. In the current study, representative cases from each of the classes of human prion disease were analyzed for the presence of markers of oxidative damage that have been found in other neurodegenerative diseases. Interestingly, we found that the pattern of deposition of PrP, amyloid-beta, and redox active metals was distinct for the various prion diseases. Whereas 8-hydroxyguanosine has been shown to be increased in sCJD, and inducible NOS is increased in scrapie-infected mice, well-studied markers of oxidative damage that accumulate in the lesions of other neurodegenerative diseases (such as Alzheimer's disease, progressive supranuclear palsy, and Parkinson's disease), such as heme oxygenase-1 and lipid peroxidation, were not found around PrP deposits or in vulnerable neurons. These findings suggest an important distinction in prion-related oxidative stress, indicating that different neurodegenerative pathways are involved in different prion diseases.


Differential outcomes of type A dissection with malperfusion according to affected organ system.
The management of malperfusion in patients with acute Stanford type A aortic dissection is controversial. We sought to determine the rate of resolution of malperfusion following primary repair of the dissection and to identify anatomic sites of malperfusion that may require additional management. We reviewed the hospital records of patients who presented to our institution with acute type A aortic dissection. Patient demographics, operative details and post-operative course were retrospectively extracted from our institutional electronic database. Depending upon the anatomic site, malperfusion was identified by a combination of radiographic and clinical definitions. Data were analyzed using standard univariable and multivariable methods. Between 1997-2013, 101 patients underwent repair of an acute type A dissection. Thirty-day mortality was 14.9% (15/101); there were five intraoperative deaths. There was no difference in 30-day mortality between patients with or without malperfusion (15.4% vs. 14.7%, P=0.93). Twenty-five patients (24.7%), who survived surgery, presented with 31 sites of malperfusion. Anatomic sites included extremities [14], renal [10], cerebral [5] and intestinal [2]. Of these 31 sites, malperfusion resolved in 18 (58.1%) with primary aortic repair. Renal malperfusion resolved radiographically in 80.0%, with no difference in the incidence of insufficiency (44.0% vs. 35.2%; P=0.44) or dialysis (20.0% vs. 15.5%; P=0.61) between malperfusion and non-malperfusion patients. Extremity malperfusion resolved postoperatively in six out of 14 patients. Of the remaining eight, concomitant revascularization was performed in four, one had an amputation and three required postoperative interventions. Advanced patient age (OR: 1.06, 95% CI: 1.01-1.12, P=0.02) was an independent predictor of 30-day mortality, while preoperative malperfusion was not (OR: 0.77, 95% CI: 0.18-3.31, P=0.73). Malperfusion complicating acute type A dissection can be managed in many patients by aortic replacement alone with low overall mortality. Most cases of renal and cerebral malperfusion resolved following aortic surgery. Revascularization was frequently necessary in patients with extremity malperfusion. Patients presenting with intestinal ischemia had very poor outcomes. A patient-specific approach is recommended in such complex patients.


A nano flow cytometer for single lipid vesicle analysis.
We present a nanofluidic device for fluorescence-based detection and characterization of small lipid vesicles on a single particle basis. The device works like a nano flow cytometer where individual vesicles are visualized by fluorescence microscopy while passing through parallel nanochannels in a pressure-driven flow. An experiment requires less than 20 μl sample volume to quantify both the vesicle content and the fluorescence signals emitted by individual vesicles. We show that the device can be used to accurately count the number of fluorescent synthetic lipid vesicles down to a vesicle concentration of 170 fM. We also show that the size-distribution of the vesicles can be resolved from their fluorescence intensity distribution after calibration. We demonstrate the applicability of the assay in two different examples. In the first, we use the nanofluidic device to determine the particle concentration in a sample containing cell-derived extracellular vesicles labelled with a lipophilic dye. In the second, we demonstrate that dual-color detection can be used to probe peptide binding to synthetic lipid vesicles; we identify a positive membrane-curvature sensing behavior of an arginine enriched version of the Antennapedia homeodomain peptide penetratin. Altogether, these results illustrate the potential of this nanofluidic-based methodology for characterization and quantification of small biological vesicles and their interactors without ensemble averaging. The device is therefore likely to find use as a quantitative analytical tool in a variety of fields ranging from diagnostics to fundamental biology research. Moreover, our results have potential to facilitate further development of automated lab-on-a-chip devices for vesicle analysis.


The neonatal airway.
Safe and effective management of the neonatal airway requires knowledge, teamwork, preparation and experience. At baseline, the neonatal airway can present significant challenges to experienced neonatologists and paediatric anaesthesiologists, and increased difficulty can be due to anatomical abnormalities, physiological instability or increased situational stress. Neonatal airway obstruction is under recognised, and should be considered an emergency until the diagnosis and physiological implications are understood. When multiple types of difficulties are present or there are multiple levels of anatomical obstruction, the challenge increases exponentially. In these situations, preparation, multi-disciplinary teamwork and a consistent hospital-wide approach will help to reduce errors and morbidity.


Simulation and analysis of pollen coronas.
By numerical simulation of light scattering by birch and pine pollen grains, we create color plates of coronas with vertical elliptical shapes and strong brightenings, respectively. The shape of the pollen is modeled by the union of n ellipsoids. The Fraunhofer integral is solved by the use of the fast Hartley transform. The sensitivity of the patterns to pollen orientation, Sun elevation, and pollen shape and size is discussed. Good agreement is obtained with amazing photographs made by a Finnish network of amateur astonomers, in the case of strong vertical orientation of the pollen axis.


Allergy-associated FcRbeta is a molecular amplifier of IgE- and IgG-mediated in vivo responses.
A role for the Fc receptor beta chain (FcRbeta) in the pathogenesis of allergy has been suggested by genetic studies. FcRbeta is a subunit common to the high-affinity IgE (FcepsilonRI) and low-affinity IgG (FcgammaRIII) receptors, both of which contribute to the initiation of allergic reactions. Current in vitro data suggest that FcRbeta can function as either a positive or negative regulator, leaving a mechanistic explanation for its association with the development of atopy unclear. To address this controversy, we have generated novel mouse models relevant to human Fc receptor function. Analysis of FcepsilonRI- and FcgammaRIII-dependent responses in these mice provides unequivocal genetic evidence that FcRbeta functions as an amplifier of early and late mast cell responses and, remarkably, in vivo anaphylactic responses.


Laparoscopic treatment of congenital choledochal cyst and hepaticojejunostomy with extracorporeal Roux-en-Y anastomosis: technical aspects and early experience with three cases.
Choledochal cyst (CDC) is a congenital dilatation of the extra and/or intrahepatic bile ducts and it is a rare condition in western countries. Classical treatment consists of cyst excision and hepaticojejunostomy. The first case of a laparoscopic CDC excision was described in 1995 and since that time an increasing number of institutions have adopted this technique, with good success. We describe our early experience of 3 cases of CDC treated with laparoscopic approach. We used a 10 mm umbilical port for the camera, and four 3-5 mm operative ports. We performed the laparoscopic removal of the cyst and gallbladder, videoassisted preparation of the Roux-en-Y loop and laparoscopic hepaticjejunostomy. No post-operative complications occurred. Laparoscopic excision of CDCs has been supposed to give better observation, a better cosmetic result, potentially less postoperative pain, and a shorter recovery. The main argument for performing an extracorporeal anastomosis is that it decreases the operative time. We recommend caution to prevent injury to the pancreatic duct and biliary structures during dissection and anastomosis. Lifelong surveillance is mandatory, even after resection of the choledochal cyst.


Characteristics of emergency services personnel related to peritraumatic dissociation during critical incident exposure.
The aim of this study was to identify characteristics of emergency services personnel related to acute dissociative responses at the time of critical incident exposure, a phenomenon designated "peritraumatic dissociation." The authors studied 157 rescue workers who responded to the Nimitz Freeway collapse during the 1989 Loma Prieta earthquake in the San Francisco Bay Area as well as 201 rescue workers who were not involved in that disaster. Demographics, level of critical incident exposure, perceived threat at the time of exposure, personality attributes (assessed by the Hogan Personality Inventory), coping strategies (assessed by the Ways of Coping Questionnaire), and locus of control were related to subjects' scores on the Peritraumatic Dissociative Experiences Questionnaire. According to univariate tests, the subjects with clinically meaningful levels of peritraumatic dissociation were younger; reported greater exposure to critical incident stress; felt greater perceived threat; had lower scores on the adjustment, identify, ambition, and prudence scales of the Hogan Personality Inventory; had higher scores on measures of coping by means of escape-avoidance, self-control, and active problem solving; and had greater externality in locus of control. Linear modeling with multiple logistic regression analyses indicated that greater feelings of perceived threat, coping by means of escape-avoidance, and coping by means of self-control were associated with a greater likelihood of being in the peritraumatic dissociation group, above and beyond age and exposure to stress. Rescue workers who are shy, inhibited, uncertain about their identity, or reluctant to take leadership roles, who have global cognitive styles, who believe their fate is determined by factors beyond their control, and who cope with critical incident trauma by emotional suppression and wishful thinking are at higher risk for acute dissociative responses to trauma and subsequent posttraumatic stress disorder.