Do IL-3/GM-CSF effect on the myofibroblastic differentiation of human adipose derived stromal cells?
Capsular contracture is an incurable complication after silicone-based implant surgery. Myofibroblast is the predominant cell in the contracted capsule. We hypothesized that human adipose derive stromal cells (hASCs) together with fibroblast may show a similar phenotypic characteristics of myofibroblast after the treatment of inflammatory cytokines in vitro. Interleukin 3 (IL-3) and granulocyte macrophage colony stimulating factor (GM-CSF) were treated in the culture of hASCs and HDFs. Lyn peptide inhibitor was applied as an inhibitor. The changes of cell surface markers (CD105, CD73, CD34, CD45, CD31, CD325 and CD146) were assessed. The expression of various cytokines related to wound contraction were tested such as TGF-β, α-SMA, HGF, FGF, ENT-1, and TSP-1. Myo-D, α-SMA, and glial fibrillary acidic protein (GFAP) were evaluated by blotting and immunocytochemical staining. The collagen-gel contraction assay was performed for the functional contraction of myofibroblastic phenotype. The expression of α-SMA, Myo-D and GFAP after the treatment of IL-3/GM-CSF showed similar results in hASCs and HDFs. Enhanced expression of TGF- β was observed in HDFs and the increase of ENT-1 and TSP-1 was significant in hASCs. Collagen-gel with HDFs contracted significantly within 24h after the treatment of IL-3/GM-CSF, and the contraction was inhibited by Lyn peptide inhibitor. But in hASCs, the gel-contraction was not significant. IL-3/ GM-CSF effected on the myofibroblastic differentiation of hASCs as well as it did on HDFs. But hASCs did not show the phenotypic gel-contraction within 24h.


Identification of a telomeric DNA-binding protein in Eimeria tenella.
Coccidiosis is considered to be a major problem for the poultry industry, and coccidiosis control is yet urgent. Due to the roles in telomere length regulation and end protection, telomere-binding proteins have been considered as a good target for drug design. In this work, a putative Gbp1p that is similar to telomeric DNA-binding protein Gbp (G-strand binding protein) of Cryptosporidium parvum, was searched in the database of Eimeria tenella. Sequence analysis indicated E.tenella Gbp1p (EtGbp1p) has significant sequence similarity to other eukaryotic Gbps in their RNA recognition motif (RRM) domains. Electrophoretic mobility shift assays (EMSAs) demonstrated recombinant EtGbp1p bound G-rich telomeric DNA, but not C-rich or double-stranded telomeric DNA sequences. Competition and antibody supershift assays confirmed the interaction of DNA-protein complex. Chromatin immunoprecipitation assays confirmed that EtGbp1p interacted with telomeric DNA in vivo. Collectively, these evidences suggest that EtGbp1p represents a G-rich single-stranded telomeric DNA-binding protein in E.tenella.


SU-E-J-192: Static Breath-Hold MRI Based Measurement of Change in Pulmonary Function Following a Course of Radiation Therapy.
Radiation Therapy (RT) induced pulmonary function change may depend on the location, underlying function of that lung prior to radiations, radiation dose/fractionation and other factors. We propose to evaluate the radiation induced pulmonary function change using static breath-hold MRI scans with vascular information and 3D deformable image registration which can provide pulmonary function relative to RT dose on a regional basis. A MRI scan pair near the end of inhale and near the end of exhale with breath hold were acquired for one lung cancer patient before RT and 6 months after RT. The patient was treated with SBRT with 55 Gy to PTVs in the right and the left lung respectively. B-spline based vesselness preserving image registration algorithm was applied to register the MRI pair for the calculation of local lung expansion as a measurement of regional pulmonary function (PF). The PF maps before RT and after RT were then mapped to the planning CT using the same algorithm tuned for MRI-CT registration. The pulmonary function change was calculated via the PF ratio between two MRI pairs. Strong spatial correlation was found between the irradiated lung region and the region with greatly decreased PF. Based on dose and PFC distribution, no strong determinant factor was found for PF lost in the left lung while the right lung shows that all the lung tissue receiving dose larger than 28 Gy will have a decreased PF. We demonstrated a method that uses static breath-hold MRI based lung imaging to evaluate radiation induced pulmonary function change which can be applied to study the dose and the pulmonary function change in a regional basis. This work is supported by NIH grant support 1R21CA144063.


Effect of emulsan on biodegradation of crude oil by pure and mixed bacterial cultures.
Crude oil was treated with purified emulsan, the heteropolysaccharide bioemulsifier produced by Acinetobacter calcoaceticus RAG-1. A mixed bacterial population as well as nine different pure cultures isolated from various sources was tested for biodegradation of emulsan-treated and untreated crude oil. Biodegradation was measured both quantitatively and qualitatively. Recovery of CO(2) from mineralized C-labeled substrates yielded quantitative data on degradation of specific compounds, and capillary gas chromatography of residual unlabeled oil yielded qualitative data on a broad spectrum of crude oil components. Biodegradation of linear alkanes and other saturated hydrocarbons, both by pure cultures and by the mixed population, was reduced some 50 to 90% after emulsan pretreatment. In addition, degradation of aromatic compounds by the mixed population was reduced some 90% in emulsan-treated oil. In sharp contrast, aromatic biodegradation by pure cultures was either unaffected or slightly stimulated by emulsification of the oil.


[¹⁸F]fluorothymidine-positron emission tomography in patients with locally advanced breast cancer under bevacizumab treatment: usefulness of different quantitative methods of tumor proliferation.
To investigate quantitative methods of tumor proliferation using 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT) PET in patients with breast cancer (BC), studied before and after one bevacizumab administration, and to correlate the [(18)F]FLT-PET uptake with the Ki67 index. Thirty patients with newly diagnosed, untreated BC underwent a [(18)F]FLT-PET before and 14 days after bevacizumab treatment. A dynamic scan centered over the tumor began simultaneously with the injection of [(18)F]FLT (385 ± 56 MBq). Image derived input functions were obtained using regions of interest drawn on the left ventricle (LV) and descending aorta (DA). Metabolite corrected blood curves were used as input functions to obtain the kinetic Ki constant using the Patlak graphical analysis (time interval 10-60 min after injection). Maximum SUV values were derived for the intervals 40-60 min (SUV40) and 50-60 min (SUV50). PET parameters were correlated with the Ki67 index obtained staining tumor biopsies. [(18)F]FLT uptake parameters decreased significantly (p<0.001) after treatment: SUV50=3.09 ± 1.21 vs 2.22 ± 0.96; SUV40=3.00 ± 1.18 vs 2.14 ± 0.95, Ki_LV(10-3)=52[22-116] vs 38[13-80] and Ki_DA(10-3)=49[15-129] vs 33[11-98]. Consistency interclass correlation coefficients within SUV and within Ki were high. Changes of SUV50 and Ki_DA between baseline PET and after one bevacizumab dose PET correlated with changes in Ki67 index (r-Pearson=0.35 and 0.26, p=0.06 and 0.16, respectively). [(18)F]FLT-PET is useful to demonstrate proliferative changes after a dose of bevacizumab in patients with BC. Quantification of tumor proliferation by means of SUV and Ki has shown similar results, but SUV50 obtained better results. A correlation between [(18)F]FLT changes and Ki67 index was observed.


Parallel diversifications of Cremastosperma and Mosannona (Annonaceae), tropical rainforest trees tracking Neogene upheaval of South America.
Much of the immense present day biological diversity of Neotropical rainforests originated from the Miocene onwards, a period of geological and ecological upheaval in South America. We assess the impact of the Andean orogeny, drainage of Lake Pebas and closure of the Panama isthmus on two clades of tropical trees (Cremastosperma, ca 31 spp.; and Mosannona, ca 14 spp.; both Annonaceae). Phylogenetic inference revealed similar patterns of geographically restricted clades and molecular dating showed diversifications in the different areas occurred in parallel, with timing consistent with Andean vicariance and Central American geodispersal. Ecological niche modelling approaches show phylogenetically conserved niche differentiation, particularly within Cremastosperma. Niche similarity and recent common ancestry of Amazon and Guianan Mosannona species contrast with dissimilar niches and more distant ancestry of Amazon, Venezuelan and Guianan species of Cremastosperma, suggesting that this element of the similar patterns of disjunct distributions in the two genera is instead a biogeographic parallelism, with differing origins. The results provide further independent evidence for the importance of the Andean orogeny, the drainage of Lake Pebas, and the formation of links between South and Central America in the evolutionary history of Neotropical lowland rainforest trees.


Preventive behaviours against radiation and related factors among general workers after Fukushima's nuclear disasters.
The nuclear power plant accidents in Fukushima resulted in a widespread release of radioactive substances in the Fukushima prefecture. To clarify what factors led to precautions among general workers who displayed preventive behaviours against radiation following the nuclear disasters in Fukushima. Descriptive study of preventive behaviours among general workers 3-5 months following the nuclear disasters. The subjects were 1394 regular workers who took part in radiation seminars conducted by the Fukushima Occupational Health Promotion Center between July and August 2011. Of 1217 responses, 1110 eligible responses were included in this study. This anonymous questionnaire survey was asking for characteristics and questions on preventive behaviours following the nuclear disasters. The authors assessed the contribution of each variable by a logistic regression analysis. Keeping track of environmental radiation levels and washing hands and gargling were significantly more frequent among female subjects, older age and workers residing up to approximately 80 km away from the power plants. Washing hands and gargling were also related with living with children. Wearing a mask when leaving home and buying bottled water were significantly more often observed with female subjects and workers residing up to 80 km. Refraining from going outdoors was positively associated with workers residing up to 80 km and workers living with children. These results provide information that may help with the targeting of health information after a nuclear disaster. This may contribute to determining an order of priority when distributing information after a nuclear disaster.


Baseline Sensitivity of Monilinia fructicola from China to the DMI Fungicide SYP-Z048 and Analysis of DMI-Resistant Mutants.
Sterol 14α-demethylase inhibitors (DMIs) continue to be important in the management of brown rot of Monilinia spp. worldwide. In this study, the sensitivity of 100 Monilinia fructicola isolates from four unsprayed orchards and two packinghouses in Beijing, China, to the new DMI fungicide SYP-Z048 was evaluated and ranged from 0.003 to 0.039 and 0.016 to 0.047 μg/ml, respectively. Laboratory mutants resistant to SYP-Z048 were generated using UV irradiation but no mutants occurred spontaneously. Resistance was stable after 10 weekly consecutive transfers on fungicide-free medium. Three parameters, including growth rate, sporulation in vitro, and lesion area, were significantly different when sensitive isolates and resistant mutants were analyzed as groups. Mutants grew more slowly and developed significantly smaller lesions on detached fruit, and their sporulation ability in vitro was reduced. Cross resistance was found between SYP-Z048 and propiconazole (ρ = 0.82, P < 0.0001) but not between SYPZ048 and tridemorph, carbendazim, procymidone, azoxystrobin, or pyrimethanil. SYP-Z048 resistance in mutants exhibiting 50% mycelial growth inhibition values greater than 0.3 μg/ml was correlated with the presence of a mutation in the CYP51 gene that encodes the target protein for DMI fungicides. The mutation caused an amino acid change from tyrosine to phenylalanine at position 136 (Y136F). To our knowledge, this is the first baseline sensitivity of M. fructicola collected from China to a DMI fungicide. The inability of M. fructicola to generate spontaneous DMI-resistant mutants coupled with reduced fitness of Y136F mutants can explain why this target site mutation has not yet emerged as a DMI fungicide resistance determinant in M. fructicola field populations worldwide.


Testicular Cancer Awareness and Screening Practices: A Systematic Review.
To critically appraise empirical evidence gathered from studies that (a) explored men's knowledge, awareness, and attitudes toward testicular cancer (TC) and its screening; (b) addressed their testicular self-examination (TSE) practice; and/or (c) highlighted barriers and facilitators to this practice. . MEDLINE®, CINAHL®, and EMBASE®. . 25 articles met the inclusion criteria. Knowledge deficits regarding TC and its screening were seen. Participants who did not perform TSE often were uninformed about this practice. The majority of men perceived TC education as a positive step toward raising awareness about this malignancy. . Very few men were informed about TC and TSE. Future studies should include valid and reliable tools to assess TC knowledge and screening, address the means through which TC knowledge is delivered, explore the individual's experience with TC screening, and focus on TC awareness and screening among minority groups. . Although regular screening for TC is a controversial issue, nurses should encourage young men to seek medical attention in the event of discovering scrotal abnormalities.


Cytopathogenic mechanisms of Entamoeba histolytica.
Cinemicrography of Entamoeba histolytica destruction of Chinese hamster ovary (CHO) cells shows that ameba cytopathogenicity consists of separate components: a contact-dependent cytolethal effect, and phagocytosis. Cells not in contact with amebae remain intact. Quantitation of ameba destruction of CHO cells by applying the one-hit hypothesis confirms that the cytoethal effect of amebae is contact dependent. Studies with 111Indium oxine-labeled cells provide further evidence of extracellular killing by E. histolytica and indicate that > 94% of the target cells are killed before phagocytosis. When we examined for a cytotoxin release by E. histolytica, we found no effect on CHO cells with filtrates of amebae, and a nonspecific effect of cell rounding and release with sonicates of amebae. The ameba sonicate effect was time-dose dependent, was not cytolethal, was reversible, and was inhibited by alpha II macroglobulin. Cytochalasin B altered ameba motility and morphology, and monolayer experiments confirmed that cytochalasins A, B, or D inhibited CHO cell destruction by E. histolytica. Cytochalasin D also inhibited extracellular killing of CHO cells by amebae in pellets, apparently independent of effects on ameba motility or phagocytosis. Colchicine and vinblastine, alone or in combination with cytochalasin D, did not inhibit E. histolytica cytopathogenicity, which indicates that microtubule function is not required for target cell killing by amebae.


Type 2 diabetes after gestational diabetes: greater than fourfold risk among Indigenous compared with non-Indigenous Australian women.
Gestational diabetes is associated with a high risk of type 2 diabetes. However, progression rates among Indigenous women in Australia who experience high prevalence of gestational diabetes are unknown. This retrospective cohort study includes all births to women at a regional hospital in Far North Queensland, Australia, coded as having 'gestational diabetes' from 1 January 2004 to 31 December 2010 (1098 births) and receiving laboratory postpartum screening from 1 January 2004 to 31 December 2011 (n = 483 births). Women who did not receive postpartum screening were excluded from the denominator. Data were linked between hospital electronic records, routinely collected birth data and laboratories, with sample validation by reviews of medical records. Analysis was conducted using Cox-proportional regression models. Indigenous women had a greater than fourfold risk of developing type 2 diabetes within 8 years of having gestational diabetes, compared with non-Indigenous women (hazards ratio 4.55, 95% confidence interval 2.63-7.88, p < 0.0001). Among women receiving postpartum screening tests, by 3, 5 and 7 years postpartum, 21.9% (15.8-30.0%), 25.5% (18.6-34.3%) and 42.4% (29.6-58.0%) Indigenous women were diagnosed with type 2 diabetes after gestational diabetes, respectively, compared with 4.2% (2.5-7.2%), 5.7% (3.3-9.5%) and 13.5% (7.3-24.2%) non-Indigenous women. Multivariate analysis showed an increased risk of developing type 2 diabetes among women with an early pregnancy body mass index ≥25 kg/m(2) , only partially breastfeeding at hospital discharge and gestational diabetes diagnosis prior to 17 weeks gestation. This study demonstrates that, compared with non-Indigenous women, Indigenous Australian women have a greater than fourfold risk of developing type 2 diabetes after gestational diabetes. Strategies are urgently needed to reduce rates of type 2 diabetes by supporting a healthy weight and breastfeeding and to improve postpartum screening among Indigenous women with gestational diabetes. Copyright © 2015 John Wiley & Sons, Ltd.


Larval source management for malaria control in Africa: myths and reality.
As malaria declines in many African countries there is a growing realization that new interventions need to be added to the front-line vector control tools of long-lasting impregnated nets (LLINs) and indoor residual spraying (IRS) that target adult mosquitoes indoors. Larval source management (LSM) provides the dual benefits of not only reducing numbers of house-entering mosquitoes, but, importantly, also those that bite outdoors. Large-scale LSM was a highly effective method of malaria control in the first half of the twentieth century, but was largely disbanded in favour of IRS with DDT. Today LSM continues to be used in large-scale mosquito abatement programmes in North America and Europe, but has only recently been tested in a few trials of malaria control in contemporary Africa. The results from these trials show that hand-application of larvicides can reduce transmission by 70-90% in settings where mosquito larval habitats are defined but is largely ineffectual where habitats are so extensive that not all of them can be covered on foot, such as areas that experience substantial flooding. Importantly recent evidence shows that LSM can be an effective method of malaria control, especially when combined with LLINs. Nevertheless, there are a number of misconceptions or even myths that hamper the advocacy for LSM by leading international institutions and the uptake of LSM by Malaria Control Programmes. Many argue that LSM is not feasible in Africa due to the high number of small and temporary larval habitats for Anopheles gambiae that are difficult to find and treat promptly. Reference is often made to the Ross-Macdonald model to reinforce the view that larval control is ineffective. This paper challenges the notion that LSM cannot be successfully used for malaria control in African transmission settings by highlighting historical and recent successes, discussing its potential in an integrated vector management approach working towards malaria elimination and critically reviewing the most common arguments that are used against the adoption of LSM.


Liquid crystal spatial light modulator with very large phase modulation operating in high harmonic orders.
Unusually large phase modulation in a commercial liquid crystal spatial light modulator (LCSLM) is reported. Such a situation is obtained by illuminating with visible light a device designed to operate in the infrared range. The phase modulation range reaches 6π radians in the red region of the visible spectrum and 10π radians in the blue region. Excellent diffraction efficiency in high harmonic orders is demonstrated despite a concomitant and non-negligible Fabry-Perot interference effect. This type of SLM opens the possibility to implement diffractive elements with reduced chromatic dispersion or chromatic control.


Elevated reporting of unprotected anal intercourse and injecting drug use but no difference in HIV prevalence among Indigenous Australian men who have sex with men compared with their Anglo-Australian peers.
Although half of the HIV notifications among Aboriginal and Torres Strait Islander people ('Indigenous Australians') are attributed to homosexual transmission, there has been little research examining sexual and drug use risk practices among Indigenous Australian men who have sex with men (MSM). Respondents were Indigenous Australian (n=1278) and Anglo-Australian men (n=24002) participating in the routine cross-sectional Gay Community Periodic Surveys conducted in Australia from 2007 to 2011. Sociodemographic characteristics, sexual risk practices, drug use, HIV testing and HIV status of Indigenous and Anglo-Australian men were compared and evaluated to discover whether Indigenous status was independently associated with HIV risk practices. Although an equivalent proportion of Indigenous and Anglo-Australian men reported being HIV-positive (9.6%), Indigenous MSM were more likely to report unprotected anal intercourse with casual partners in the previous 6 months (27.9% v. 21.5%; Adjusted odds ratio (AOR)=1.29, 95% confidence interval (CI): 1.11-1.49). Indigenous men were more likely than Anglo-Australian men to report use of several specific drugs and twice as likely to report injecting drug use in the previous 6 months (8.8% v. 4.5%; AOR=1.43, 95% CI: 1.11-1.86). Despite a higher proportion of Indigenous men reporting sexual and drug use practices that increase the risk of HIV transmission, there were no differences in the HIV status of Indigenous and Anglo-Australian men. However, the elevated rates of risk practices suggest that Indigenous MSM should remain a focus for HIV prevention, care and support.


Suprabasal change and subsequent formation of disulfide-stabilized homo- and hetero-dimers of keratins during esophageal epithelial differentiation.
Rabbit esophageal epithelium, a parakeratinized stratified epithelium, synthesizes as one of its major differentiation products a keratin pair consisting of a basic K4 (59 kDa) and an acidic K13 (41 kDa) keratin. Although immunohistochemical staining data suggest that in esophageal epithelia of some other species these two keratins are suprabasally located, antigenic masking of the epitopes in the basal cells has not been ruled out. Using several well-characterized monoclonal antibodies including AE8, which specifically recognizes K13, coupled with biochemical analysis of keratins of basal and suprabasal cells isolated from confluent rabbit esophageal epithelial culture, we have obtained direct evidence that K4 and K13 keratins are largely absent in the undifferentiated basal cells, but are present in large amounts in suprabasal cells. We also show that in the cornified cell layers that are formed during the terminal stage of esophageal epithelial differentiation, K4 and K13 keratins become disulfide-crosslinked to form three different dimers. Two of them (110 kDa and 100 kDa) are heterodimers and consist of equimolar amounts of K4 and K13; they presumably represent isomers crosslinked via different cysteine residues. The third dimer (90 kDa) was found to be a homodimer of the acidic K13 keratin. Trypsinization experiment established that at least some of the disulfide crosslinks in the K4/K13 heterodimer must involve cysteine residues residing in the trypsin-resistant rod domains of keratins. Air-oxidation of in vitro reconstituted filaments reproduced the two heterodimers, which most likely involve the crosslinking between type I and type II keratins of different coiled coils. The formation of these disulfide-crosslinked keratin dimers, instead of higher molecular mass oligomers or polymers as occurring in the epidermis and hair, may contribute to the formation of cornified cells with a physical stability and rigidity that are optimal for esophageal function. Our data also suggest that interactions involved in the formation of homodimers, thought to be metastable and unimportant during the initial step of filament assembly (i.e. tetramer formation), may actually play an important role in stabilizing a higher order structure in mature keratin filaments.


Clonidine for sedation in the critically ill: a systematic review and meta-analysis (protocol).
Management and choice of sedation is important during critical illness in order to reduce patient suffering and to facilitate the delivery of care. Unfortunately, medications traditionally used for sedation in the intensive care unit (ICU) such as benzodiazepines and propofol are associated with significant unwanted effects. Clonidine is an alpha-2 selective adrenergic agonist that may have a role in optimizing current sedation practices in the pediatric and adult critically ill populations by potentially minimizing exposure to other sedative agents. We will search MEDLINE, EMBASE, CINAHL, ACPJC, the Cochrane trial registry, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), and clinicaltrials.gov for eligible observational studies and randomized controlled trials investigating the use of clonidine as an adjunctive or stand-alone sedative agent in patients requiring invasive mechanical ventilation. Our primary outcome is the duration of mechanical ventilation. Secondary outcomes include the following, listed by priority: duration of sedation infusions, dose of sedation used, level of sedation, incidence of withdrawal from other sedatives, delirium incidence, ICU and hospital length of stay, use and duration of non-invasive ventilation, and all-cause ICU and hospital mortality. We will also capture unwanted effects potentially associated with clonidine administration such as clinically significant hypotension or bradycardia, clonidine withdrawal, self-extubation, and the accidental removal of central intravenous lines and arterial lines. We will not apply any publication date, language, or journal restrictions. Two reviewers will independently screen and identify eligible studies using predefined eligibility criteria and then review full reports of all potentially relevant citations. A third reviewer will resolve disagreements if consensus cannot be achieved. We will use Review Manager (RevMan) to pool effect estimates from included studies across outcomes. We will present the results as relative risk (RR) with 95 % confidence intervals (CI) for dichotomous outcomes and as mean difference (MD) or standardized mean difference (SMD) for continuous outcomes with 95 % CI. We will assess the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The aim of this systematic review is to summarize the evidence on the efficacy and safety of clonidine as a sedative agent in the critically ill population. PROSPERO CRD42015019365.


Success with EASE: Who benefits from a STEM learning community?
During the past few decades, there has been a nationwide push to improve performance and persistence outcomes for STEM undergraduates. As part of this effort, recent research has emphasized the need for focus on not only improving the delivery of course content, but also addressing the social-psychological needs of students. One promising intervention type that has been proposed as a multifaceted way to address both cognitive and social-psychological aspects of the learning process is the learning community. Learning communities provide students with opportunities to build a strong support system in college and are generally associated with increased student engagement and integration with campus systems and cultures. In this study, we examine the impact of a learning community intervention for first-year biological sciences majors, the Enhanced Academic Success Experience (EASE) program. Incoming freshmen are assigned to EASE based on their SAT (or ACT equivalent) Math score, a metric demonstrated to be a key predictor of student success in the program. We find that enrollment in EASE is correlated with higher STEM course grades; an increase of 0.25 (on a 0-4 point scale) in cumulative first-year GPA; and gains in non-academic outcomes, such as measures of sense of belonging and academic integration. Further, these outcomes are more pronounced for particular subgroup populations. For example, whereas surveyed male students seemed to benefit academically from participating in a learning community, female students reported a greater sense of belonging in regard to the biological sciences major and reported higher values for behavioral indicators of academic integration. Lastly, we find that the EASE program is positively correlated with students' intention to stay in the biological sciences major. And, among the three race-oriented groups, this impact is most pronounced for under-represented students. In light of these findings, we discuss the potential of discipline-specific learning community programs to improve academic outcomes for students most at risk of leaving STEM majors, such as students underprepared for college level coursework.


Reliability of breath-alcohol analysis in individuals with gastroesophageal reflux disease.
Gastroesophageal reflux disease (GERD) is widespread in the population among all age groups and in both sexes. The reliability of breath alcohol analysis in subjects suffering from GERD is unknown. We investigated the relationship between breath-alcohol concentration (BrAC) and blood-alcohol concentration (BAC) in 5 male and 5 female subjects all suffering from severe gastroesophageal reflux disease and scheduled for antireflux surgery. Each subject served in two experiments in random order about 1-2 weeks apart. Both times they drank the same dose of ethanol (approximately 0.3 g/kg) as either beer, white wine, or vodka mixed with orange juice before venous blood and end-expired breath samples were obtained at 5-10 min intervals for 4 h. An attempt was made to provoke gastroesophageal reflux in one of the drinking experiments by applying an abdominal compression belt. Blood-ethanol concentration was determined by headspace gas chromatography and breath-ethanol was measured with an electrochemical instrument (Alcolmeter SD-400) or a quantitative infrared analyzer (Data-Master). During the absorption of alcohol, which occurred during the first 90 min after the start of drinking, BrAC (mg/210 L) tended to be the same or higher than venous BAC (mg/dL). In the post-peak phase, the BAC always exceeded BrAC. Four of the 10 subjects definitely experienced gastric reflux during the study although this did not result in widely deviant BrAC readings compared with BAC when sampling occurred at 5-min intervals. We conclude that the risk of alcohol erupting from the stomach into the mouth owing to gastric reflux and falsely increasing the result of an evidential breath-alcohol test is highly improbable.


Intercellular communication in plants: Evidence for a rapidly generated, bidirectionally transmitted wound signal.
Wounding (whether by excision, abrasion, or puncture) elicited rapid, massive, and enduring formation of polysomes in aged pea stems and other mature tissues. The response depended on temperature and severity of wounding but not on water uptake, and it occurred in tissues adjacent to, distant from, above, and below the site of injury. The kinetics of polysome formation were similar in tissues adjacent to or up to 150 mm distant from the point of injury. The wound-induced increases in protein-synthesizing capacity of the polysomes both in vivo and in vitro were much greater than the increases in rRNA and poly(A)(+)RNA. The results indicate that wounding evokes the almost immediate production of a wound signal that travels rapidly both acropetally and basipetally to stimulate the recruitment of preexisting ribosomes onto primarily preexisting mRNA, thence forming polysomes with greatly enhanced protein-synthesizing capacity.


Pandemic influenza H1N1 2009 in Thailand.
Developing a quantitative understanding of pandemic influenza dynamics in South-East Asia is important for informing future pandemic planning. Hence, transmission dynamics of influenza A/H1N1 were determined across space and time in Thailand. Dates of symptom onset were obtained for all daily laboratory-confirmed cases of influenza A/H1N1pdm in Thailand from 3 May 2009 to 26 December 2010 for four different geographic regions (Central, North, North-East, and South). These data were analysed using a probabilistic epidemic reconstruction, and estimates of the effective reproduction number, R(t), were derived by region and over time. Estimated R(t) values for the first wave peaked at 1.54 (95% CI: 1.42-1.71) in the Central region and 1.64 (95% CI: 1.38-1.92) in the North, whilst the corresponding values in the North-East and the South were 1.30 (95% CI: 1.17-1.46) and 1.39 (95% CI: 1.32-1.45) respectively. As the R(t) in the Central region fell below one, the value of R(t) in the rest of Thailand increased above one. R(t) was above one for 30 days continuously through the first wave in all regions of Thailand. During the second wave R(t) was only marginally above one in all regions except the South. In Thailand, the value of R(t) varied by region in the two pandemic waves. Higher R(t) estimates were found in Central and Northern regions in the first wave. Knowledge of regional variation in transmission potential is needed for predicting the course of future pandemics and for analysing the potential impact of control measures.


Nosocomial outbreak caused by Salmonella enterica serotype Livingstone producing CTX-M-27 extended-spectrum beta-lactamase in a neonatal unit in Sousse, Tunisia.
In this study, we report an outbreak of Salmonella enterica serotype Livingstone resistant to extended-spectrum cephalosporins that occurred in a neonatal ward of the maternity department of Farhat Hached Hospital, Sousse, Tunisia, in 2002. A total of 16 isolates were recovered from 16 babies hospitalized in the ward during the period 1 to 16 July. All these babies developed diarrhea, and three of them developed septicemia. All the isolates demonstrated resistance to ceftriaxone and ceftazidime due to the production of an extended-spectrum beta-lactamase (ESBL). The isolates were also resistant to aminoglycosides (kanamycin, tobramycin, netilmicin, gentamicin, and amikacin) and sulfamethoxazole-trimethoprim. DNA profiles were determined by pulsed-field gel electrophoresis using the XbaI and SpeI endonucleases and by ribotyping with PstI digestion. They yielded the same patterns, showing that the outbreak was caused by a single clone. The ESBL was identified as CTX-M-27 by sequencing of PCR products and by isoelectric focusing. The ESBL resistance was transferred by a 40-kb conjugative plasmid. The mobile insertion sequence ISEcp1 was found to be located upstream of bla(CTX-M-27) in the same position as that known for a bla(CTX-M-14) sequence. A new gene named dfrA21, encoding resistance to trimethoprim and carried by a 90-kb plasmid, was characterized. The dfrA21 gene was inserted as a single resistance cassette in a class I integron. The babies were treated with colistin, and all except two recovered. The outbreak came to an end when appropriate actions were taken: patient isolation, hand washing, and disinfection of the ward.


Integrating Behavioral Health and Primary Care: Consulting, Coordinating and Collaborating Among Professionals.
This paper sought to describe how clinicians from different backgrounds interact to deliver integrated behavioral and primary health care, and the contextual factors that shape such interactions. This was a comparative case study in which a multidisciplinary team used an immersion-crystallization approach to analyze data from observations of practice operations, interviews with practice members, and implementation diaries. The observed practices were drawn from 2 studies: Advancing Care Together, a demonstration project of 11 practices located in Colorado; and the Integration Workforce Study, consisting of 8 practices located across the United States. Primary care and behavioral health clinicians used 3 interpersonal strategies to work together in integrated settings: consulting, coordinating, and collaborating (3Cs). Consulting occurred when clinicians sought advice, validated care plans, or corroborated perceptions of a patient's needs with another professional. Coordinating involved 2 professionals working in a parallel or in a back-and-forth fashion to achieve a common patient care goal, while delivering care separately. Collaborating involved 2 or more professionals interacting in real time to discuss a patient's presenting symptoms, describe their views on treatment, and jointly develop a care plan. Collaborative behavior emerged when a patient's care or situation was complex or novel. We identified contextual factors shaping use of the 3Cs, including: time to plan patient care, staffing, employing brief therapeutic approaches, proximity of clinical team members, and electronic health record documenting behavior. Primary care and behavioral health clinicians, through their interactions, consult, coordinate, and collaborate with each other to solve patients' problems. Organizations can create integrated care environments that support these collaborations and health professions training programs should equip clinicians to execute all 3Cs routinely in practice.


Advancing predictive models for particulate formation in turbulent flames via massively parallel direct numerical simulations.
Combustion of fossil fuels is likely to continue for the near future due to the growing trends in energy consumption worldwide. The increase in efficiency and the reduction of pollutant emissions from combustion devices are pivotal to achieving meaningful levels of carbon abatement as part of the ongoing climate change efforts. Computational fluid dynamics featuring adequate combustion models will play an increasingly important role in the design of more efficient and cleaner industrial burners, internal combustion engines, and combustors for stationary power generation and aircraft propulsion. Today, turbulent combustion modelling is hindered severely by the lack of data that are accurate and sufficiently complete to assess and remedy model deficiencies effectively. In particular, the formation of pollutants is a complex, nonlinear and multi-scale process characterized by the interaction of molecular and turbulent mixing with a multitude of chemical reactions with disparate time scales. The use of direct numerical simulation (DNS) featuring a state of the art description of the underlying chemistry and physical processes has contributed greatly to combustion model development in recent years. In this paper, the analysis of the intricate evolution of soot formation in turbulent flames demonstrates how DNS databases are used to illuminate relevant physico-chemical mechanisms and to identify modelling needs.


Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men.
Ageing is thought to be associated with decreased vascular function partly due to oxidative stress. Resveratrol is a polyphenol, which in animal studies has been shown to decrease atherosclerosis, and improve cardiovascular health and physical capacity, in part through its effects on Sirtuin 1 signalling and through an improved antioxidant capacity. We tested the hypothesis that resveratrol supplementation enhances training-induced improvements in cardiovascular health parameters in aged men. Twenty-seven healthy physically inactive aged men (age: 65 ± 1 years; body mass index: 25.4 ± 0.7 kg m(-2); mean arterial pressure (MAP): 95.8 ± 2.2 mmHg; maximal oxygen uptake: 2488 ± 72 ml O2 min(-1)) were randomized into 8 weeks of either daily intake of either 250 mg trans-resveratrol (n = 14) or of placebo (n = 13) concomitant with high-intensity exercise training. Exercise training led to a 45% greater (P < 0.05) increase in maximal oxygen uptake in the placebo group than in the resveratrol group and to a decrease in MAP in the placebo group only (-4.8 ± 1.7 mmHg; P < 0.05). The interstitial level of vasodilator prostacyclin was lower in the resveratrol than in the placebo group after training (980 ± 90 vs. 1174 ± 121 pg ml(-1); P < 0.02) and muscle thromboxane synthase was higher in the resveratrol group after training (P < 0.05). Resveratrol administration also abolished the positive effects of exercise on low-density lipoprotein, total cholesterol/high-density lipoprotein ratio and triglyceride concentrations in blood (P < 0.05). Resveratrol did not alter the effect of exercise training on the atherosclerosis marker vascular cell adhesion molecule 1 (VCAM-1). Sirtuin 1 protein levels were not affected by resveratrol supplementation. These findings indicate that, whereas exercise training effectively improves several cardiovascular health parameters in aged men, concomitant resveratrol supplementation can blunt these effects.


Pharmacokinetic and Safety Evaluation of a Transscleral Sustained Unoprostone Release Device in Monkey Eyes.
We evaluate the ocular tissue distribution and retinal toxicity of unoprostone (UNO) during 12 months, after transscleral sustained-UNO administration using a drug delivery device in monkey eyes. The device consisted of a reservoir, controlled-release cover, and a drug formulation of photopolymerized polyethylene glycol dimethacrylate. Six mg UNO was loaded into the device (length, 17 mm; width, 4.4 mm; height, 1 mm). The concentrations of M1, a primary metabolite of UNO, in the retina, choroid, vitreous, lens, aqueous humor, iris, ciliary body, and plasma were determined by liquid chromatography-tandem mass spectrometry at 3, 6, and 12 months after implantation. Retinal toxicity was evaluated by electroretinography (ERG), optical coherence tomography (OCT), and IOP at preimplantation, and at 6, 9, and 12 months after implantation. Focal ERGs were performed at 9 and 12 months after implantation. M1 was detected in the choroid and retina with maximum peaks of 243.2 and 8.41 ng/g at 6 months, respectively. M1 in the ciliary body and iris was detected with maximum peaks of 7.66 and 10.4 ng/g at 6 and 12 months, respectively. Less than 1 ng/mL or ng/g of M1 was detected in the aqueous humor, vitreous, and lens. No changes were observed in retinal function as assessed by ERG, IOP, or macula thickness and retinal histology by OCT examinations during the 12-month period. No differences in focal ERG amplitudes, especially in the macula, were observed. The device provided intraocular sustained delivery of UNO for 12 months without producing severe retinal toxicity.


An update on the surgical treatment of malignant pineal region tumors.
Our current pineal region tumor series (n = 34) now spans 11 years and currently includes 15 patients with malignant pineal region tumors, only 3 of whom had pure germinomas. Complete gross microsurgical excision of well-encapsulated tumors was possible in 9 of 13 patients (69%) who underwent definitive surgical exploration. Subtotal excision only was possible in 2 of the other patients. In the remaining 2 patients who had pineal germinomas, a less aggressive subtotal excision was done because of the known radiosensitivity of this tumor. Four of the operative patients had a tumor of mixed histology with benign and malignant components, emphasizing the need for adequate tissue sampling (Table 20.2). Eleven of the 13 surgical patients received postoperative craniospinal radiation; a 6-month-old girl who had a gross total excision of a pineoblastoma was too young to be irradiated. Ten of the patients continue to do well up to 12 years postoperatively. In view of the fact that only 3 of the 15 patients had pure germinomas, these results appear to be better than those reported with shunting and radiotherapy. Only one of our surgical patients developed postoperative metastases, an embryonal cell tumor that spread to the spinal canal. In the 34 patients in this series with lesions of the pineal region, surgical exploration was associated with only one death (a patient with metastatic adenocarcinoma). As is common with the occipital transtentorial approach, a postoperative hemanopsia is common but usually transient. The wide exposure of this approach, however, may be responsible for the greater proportion of complete gross excisions of malignant pineal tumors using other approaches (24). We have also shown the importance of tumor markers and that germinomas are very sensitive to chemotherapy. Thus, microsurgery for pineal tumors provides a viable potential for complete gross tumor extirpation even with malignant lesions, and/or adequate tissue for diagnosis which is necessary in appropriate therapeutic planning for radiotherapy and/or chemotherapy. The traditional therapeutic approach of empiric radiotherapy without a tissue diagnosis for pineal lesions may no longer be acceptable.


Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression.
The epithelial Na(+) channel (ENaC) plays an essential role in the regulation of whole body Na(+) balance and blood pressure. The cell surface expression of this channel, a complex of three subunits (alpha, beta and gamma ENaC), has been shown to be regulated by hormones such as aldosterone and vasopressin and by intracellular signaling, including ubiquitylation and/or phosphorylation. However, the molecular mechanisms involving phosphorylation in the regulation of ENaC are unclear. Here we show by expression studies in Xenopus laevis oocytes that the aldosterone-induced Sgk1 kinase interacts with the ubiquitin protein ligase Nedd4-2 in a PY motif-dependent manner and phosphorylates Nedd4-2 on Ser444 and, to a lesser extent, Ser338. Such phosphorylation reduces the interaction between Nedd4-2 and ENaC, leading to elevated ENaC cell surface expression. These data show that phosphorylation of an enzyme involved in the ubiquitylation cascade (Nedd4-2) controls cell surface density of ENaC and propose a paradigm for the control of ion channels. Moreover, they suggest a novel and complete signaling cascade for aldosterone-dependent regulation of ENaC.


GlycoFish: a database of zebrafish N-linked glycoproteins identified using SPEG method coupled with LC/MS.
Zebrafish (Danio rerio) is a model organism that is used to study the mechanisms and pathways of human disorders. Many dysfunctions in neurological, development, and neuromuscular systems are due to glycosylation deficiencies, but the glycoproteins involved in zebrafish embryonic development have not been established. In this study, a mass spectrometry-based glycoproteomic characterization of zebrafish embryos was performed to identify the N-linked glycoproteins and N-linked glycosylation sites. To increase the number of glycopeptides, proteins from zebrafish were digested with two different proteases--chymotrypsin and trypsin--into peptides of different length. The N-glycosylated peptides of zebrafish were then captured by the solid-phase extraction of N-linked glycopeptides (SPEG) method and the peptides were identified with an LTQ OrbiTrap Velos mass spectrometer. From 265 unique glycopeptides, including 269 consensus NXT/S glycosites, we identified 169 different N-glycosylated proteins. The identified glycoproteins were highly abundant in proteins belonging to the transporter, cell adhesion, and ion channel/ion binding categories, which are important to embryonic, organ, and central nervous system development. This proteomics data will expand our knowledge about glycoproteins in zebrafish and may be used to elucidate the role that glycosylation plays in cellular processes and disease. The glycoprotein data are available through the GlycoFish database (http://betenbaugh.jhu.edu/GlycoFish) introduced in this paper.


Examining explanations for the link between bullying perpetration and physical dating violence perpetration: Do they vary by bullying victimization?
This short-term longitudinal study examined whether the association between bullying perpetration and later physical dating violence perpetration and mediators of that association (via anger, depression, anxiety, and social status), varied depending on level of bullying victimization. Differences have been noted between those who bully but are not victims of bullying, and those who are both bullies and victims. These differences may influence dating violence risk and the explanations for why bullying leads to dating violence. Data were from dating adolescents in three rural counties who completed self-administered questionnaires in the fall semester of grades 8-10 and again in the spring semester. The sample (N = 2,414) was 44.08% male and 61.31% white. Bullying perpetration in the fall semester predicted physical dating violence perpetration in the spring semester when there was no bullying victimization, but not when there was any bullying victimization. Bullying perpetration was positively associated with anger at all levels of bullying victimization and with social status when there was no or low amounts of victimization; it was negatively associated with social status at high levels of victimization. Bullying victimization was positively associated with anger, depression, and anxiety at all levels of bullying perpetration. Anger mediated the association between bullying perpetration and dating violence, regardless of level of victimization; depression, anxiety, and social status did not mediate the association at any level of bullying victimization. The findings have implications for dating violence prevention efforts and for future research on the link between bullying and dating violence.


Rhizobium phaseoli symbiotic mutants with transposon Tn5 insertions.
Rhizobium phaseoli CFN42 DNA was mutated by random insertion of Tn5 from suicide plasmid pJB4JI to obtain independently arising strains that were defective in symbiosis with Phaseolus vulgaris but grew normally outside the plant. When these mutants were incubated with the plant, one did not initiate visible nodule tissue (Nod-), seven led to slow nodule development (Ndv), and two led to superficially normal early nodule development but lacked symbiotic nitrogenase activity (Sna-). The Nod- mutant lacked the large transmissible indigenous plasmid pCFN42d that has homology to Klebsiella pneumoniae nitrogenase (nif) genes. The other mutants had normal plasmid content. In the two Sna- mutants and one Ndv mutant, Tn5 had inserted into plasmid pCFN42d outside the region of nif homology. The insertions of the other Ndv mutants were apparently in the chromosome. They were not in plasmids detected on agarose gels, and, in contrast to insertions on indigenous plasmids, they were transmitted in crosses to wild-type strain CFN42 at the same frequency as auxotrophic markers and with the same enhancement of transmission by conjugation plasmid R68.45. In these Ndv mutants the Tn5 insertions were the same as or very closely linked to mutations causing the Ndv phenotype. However, in two mutants with Tn5 insertions on plasmid pCFN42d, an additional mutation on the same plasmid, rather than Tn5, was responsible for the Sna- or Ndv phenotype. When plasmid pJB4JI was transferred to two other R. phaseoli strains, analysis of symbiotic mutants was complicated by Tn5-containing deleted forms of pJB4JI that were stably maintained.


Pesticide exposure and diabetes mellitus in a semi-urban Nepali population: a cross-sectional study.
Epidemiological studies suggest exposure to pesticides to be related to risk of diabetes mellitus. The objective of the present study was to assess the association between pesticide use and diabetes mellitus in a semi-urban population in Nepal. We conducted a nested cross-sectional study on pesticides and diabetes mellitus in a population-based cohort from the former Lekhnath Municipality, Nepal. 2643 persons were invited, and 2310 persons participated (response rate 87.4%). All participants were tested for fasting plasma glucose. Diabetes mellitus was defined as either fasting plasma glucose (FPG) ≥ 7.0 mmol/L (126 mg/dL) or self-reported diagnosis of diabetes mellitus. Exposure to pesticides was determined by questionnaire. For the exposed persons, three exposure metrics (years of exposure, weeks of exposure per year and hours of exposure per week) were categorized and used to model exposure-response relationships. Although 62% of participants reported to be exposed to pesticides, the frequency and intensity of pesticide usage was low. Contrary to our hypothesis, we found lower odds of diabetes mellitus among persons reporting any pesticide use compared to those reporting no use of pesticides-adjusted odds ratio with 95% CI = 0.68 [0.52; 0.90]. However, we found no clear exposure-response relationships between pesticide exposure and neither diabetes mellitus nor FPG, and few and inconsistent associations were seen between pesticide exposure and symptoms of acute pesticide intoxication. The apparently lower odds of diabetes mellitus among pesticide-exposed persons in this population are probably due to residual confounding. Our results do not seem to support an association between pesticide exposure and diabetes mellitus in this low-exposed population dominated by subsistence farmers, although results should be interpreted with caution in light of the study limitations.


Determinants of the decline in mortality from acute stroke in England: linked national database study of 795 869 adults.
To study trends in stroke mortality rates, event rates, and case fatality, and to explain the extent to which the reduction in stroke mortality rates was influenced by changes in stroke event rates or case fatality. Population based study. Person linked routine hospital and mortality data, England. 795 869 adults aged 20 and older who were admitted to hospital with acute stroke or died from stroke. Stroke mortality rates, stroke event rates (stroke admission or stroke death without admission), and case fatality within 30 days after stroke. Between 2001 and 2010 stroke mortality rates decreased by 55%, stroke event rates by 20%, and case fatality by 40%. The study population included 358 599 (45%) men and 437 270 (55%) women. Average annual change in mortality rate was -6.0% (95% confidence interval -6.2% to -5.8%) in men and -6.1% (-6.3% to -6.0%) in women, in stroke event rate was -1.3% (-1.4% to -1.2%) in men and -2.1% (-2.2 to -2.0) in women, and in case fatality was -4.7% (-4.9% to -4.5%) in men and -4.4% (-4.5% to -4.2%) in women. Mortality and case fatality but not event rate declined in all age groups: the stroke event rate decreased in older people but increased by 2% each year in adults aged 35 to 54 years. Of the total decline in mortality rates, 71% was attributed to the decline in case fatality (78% in men and 66% in women) and the remainder to the reduction in stroke event rates. The contribution of the two factors varied between age groups. Whereas the reduction in mortality rates in people younger than 55 years was due to the reduction in case fatality, in the oldest age group (≥85 years) reductions in case fatality and event rates contributed nearly equally. Declines in case fatality, probably driven by improvements in stroke care, contributed more than declines in event rates to the overall reduction in stroke mortality. Mortality reduction in men and women younger than 55 was solely a result of a decrease in case fatality, whereas stroke event rates increased in the age group 35 to 54 years. The increase in stroke event rates in young adults is a concern. This suggests that stroke prevention needs to be strengthened to reduce the occurrence of stroke in people younger than 55 years.


Admixture of a recombinant vaccinia virus containing the gene for the costimulatory molecule B7 and a recombinant vaccinia virus containing a tumor-associated antigen gene results in enhanced specific T-cell responses and antitumor immunity.
At least two signals are required for the activation of naive T cells by antigen-bearing target cells: an antigen-specific signal, delivered through the T-cell receptor, and a costimulatory signal delivered through the T-cell surface molecule CD28 by its natural ligand B7-1. The immunological benefit of coexpression of B7 with target antigen has been demonstrated with the use of several retroviral systems to transfect antigen-bearing cells. Although engineering recombinant constructs with genes for two or more antigens can mediate the dual expression of those antigens, disadvantages of this approach include the time for construction of each desirable combination and the inability to control differential expression levels of each gene product. An alternative approach would utilize separate constructs that could be admixed appropriately before administration. In this report we describe the functional consequences of the admixture of recombinant vaccinia murine B7-1 (rV-B7) to recombinant vaccinia expressing the human carcinoembryonic antigen gene (rV-CEA). Coinfection of cells resulted in high levels of cell surface expression of both the CEA and B7 molecules. Immunization of mice with various ratios (1:3, 1:1, 3:1) of rV-CEA and rV-B7 demonstrated that an admixture of rV-CEA and rV-B7 at a 3:1 ratio resulted in the generation of optimal CEA-specific T-cell responses. Next, we examined the efficacy of this admixture on antitumor activity. Typically, injection of murine carcinoma cells expressing CEA leads to the death of the host. One immunization of C57BL/6 mice with rV-CEA:rV-B7 (3:1) resulted in no tumor establishment. In contrast, administration of rV-CEA or rV-B7 alone had little or no antitumor effects. These studies demonstrate the advantages of the use of recombinant vaccinia viruses to deliver B7 molecules in combination with a tumor-associated antigen. The availability of the rV-B7 single construct and the ability to alter the B7 ratio could also have potential utility when coinfecting rV-B7 with recombinant vaccinia viruses containing genes for infectious agents or other tumor-associated antigen genes.


Effect of interleukin-1beta and dehydroepiandrosterone on the expression of lumican and fibromodulin in fibroblast-like synovial cells of the human temporomandibular joint.
Several epidemiological studies have reported that temporomandibular disorders (TMDs) are more prevalent in women than in men. It has recently been proposed that sex hormones such as estrogen, testosterone and dehydroepiandrosterone (DHEA) are involved with the pathogenesis of TMDs. Although studies have investigated the relationship between estrogen and testosterone and the restoration of TMDs, the relationship between DHEA and TMDs is unknown. The synovial tissue of the temporomandibular joint (TMJ) is made up of connective tissue with an extracellular matrix (ECM) composed of collagen and proteoglycan. One proteoglycan family, comprised of small leucine-rich repeat proteoglycans (SLRPs), was found to be involved in collagen fibril formation and interaction. In recent years, the participation of SLRPs such as lumican and fibromodulin in the internal derangement of TMJ has been suggested. Although these SLRPs may contribute to the restoration of the synovium, their effect is still unclear. The purpose of this study was to investigate the effect of DHEA, a sex hormone, on the expression of lumican and fibromodulin in human temporomandibular specimens and in cultured human TMJ fibroblast-like synovial cells in the presence or absence of the pro-inflammatory cytokine interleukin-1beta (IL-1beta). In the in vivo study, both normal and osteoarthritic (OA) human temporomandibular synovial tissues were immunohistochemically examined. In the in vitro study, five fibroblast-like synoviocyte (FLS) cell lines were established from human TMJ synovial tissue of patients with osteoarthritis. The subcultured cells were then incubated for 3, 6, 12 or 24 h with/without IL-1beta (1 ng/mL) in the presence or absence of DHEA (10 μM). The gene expression of lumican and fibromodulin was examined using the real-time polymerase chain reaction (PCR) and their protein expression was examined using immunofluorescent staining. We demonstrated that the expression of lumican significantly differs from that of fibromodulin in synovial tissue in OA and furthermore, that IL-1beta induced a significant increase in lumican mRNA and immunofluorescent staining in FLS compared to cells without IL-1beta. DHEA plus IL-1beta induced a significant increase in fibromodulin, but not in lumican mRNA, compared to DHEA alone, IL-1beta alone and in the absence of DHEA and IL-1beta. In immunofluorescent staining, weaker fibromodulin staining of FLS cells was observed in cells cultured in the absence of both DHEA and IL-1beta compared to fibromodulin staining of cells cultured with DHEA alone, with DHEA plus IL-1beta, or with IL-1beta alone. These results indicate that DHEA may have a protective effect on synovial tissue in TMJ by enhancing fibromodulin formation after IL-1beta induced inflammation. DHEA enhancement of fibromodulin expression may also exert a protective effect against the hyperplasia of fibrous tissue that TGF-beta1 induces. In addition lumican and fibromodulin are differentially expressed under different cell stimulation conditions and lumican and fibromodulin may promote regeneration of the TMJ after degeneration and deformation induced by IL-1beta.


An Adaptable Human-Like Gait Pattern Generator Derived From a Lower Limb Exoskeleton.
Walking rehabilitation processes include many repetitions of the same physical movements in order to replicate, as close as possible, the normal gait trajectories, and kinematics of all leg joints. In these conventional therapies, the therapist's ability to discover patient's limitations-and gradually reduce them-is key to the success of the therapy. Lower-limb robotic exoskeletons have strong deficiencies in this respect as compared to an experienced therapist. Most of the currently available robotic solutions are not able to properly adapt their trajectories to the biomechanical limitations of the patient. With this in mind, much research and development is still required in order to improve artificial human-like walking patterns sufficiently for valuable clinical use. The work herein reported develops and presents a method to acquire and saliently analyze subject-specific gait data while the subject dons a passive lower-limb exoskeleton. Furthermore, the method can generate adjustable, yet subject-specific, kinematic gait trajectories useful in programming controllers for future robotic rehabilitation protocols. A human-user study with ten healthy subjects provides the experimental setup to validate the proposed method. The experimental protocol consists in capturing kinematic data while subjects walk, with the donned H2 lower-limb exoskeleton, across three experimental conditions: walking with three different pre-determined step lengths marked on a lane. The captured ankle trajectories in the sagittal plane were found by normalizing all trials of each test from one heel strike to the next heel strike independent of the specific gait features of each individual. Prior literature suggests analyzing gait in phases. A preliminary data analysis, however, suggests that there exist six key events of the gait cycle, events that can adequately characterize gait for the purposes required of robotic rehabilitation including gait analysis and reference trajectory generation. Defining the ankle as an end effector and the hip as the origin of the coordinate frame and basing the linear regression calculations only on the six key events, i.e., Heel Strike, Toe Off, Pre-Swing, Initial Swing, Mid-Swing, and Terminal Swing, it is possible to generate a new calculated ankle trajectory with an arbitrary step length. The Leave-One-Out Cross Validation algorithm was used to estimate the fitting error of the calculated trajectory vs. the characteristic captured trajectory per subject, showing a fidelity average value of 95.2, 96.1, and 97.2%, respectively, for each step-length trial including all subjects. This research presents method to capture ankle trajectories from subjects and generate human-like ankle trajectories that could be scaled and computed on-line, could be adjusted to different gait scenarios, and could be used not only to generate reference trajectories for gait controllers, but also as an accurate and salient benchmark to test the human likeness of gait trajectories employed by existing robotic exoskeletal devices.


Fine-needle aspiration biopsy diagnosis of gastrointestinal stromal tumors using morphology, immunocytochemistry, and mutational analysis of c-kit.
Differentiating gastrointestinal stromal tumors (GISTs) from other intramural mesenchymal tumors of the GI tract on fine-needle aspiration biopsies (FNABs) is difficult. Recent studies have shown that GISTs are immunophenotypically and genetically distinct. GISTs exhibit consistent immunohistochemical expression of CD-117 (KIT) and often express activating mutations of this protooncogene. The aim of the current study was to employ immunocytochemistry and mutational analysis of the c-kit gene to aid in the diagnosis of GISTs on FNAB. Five endoscopic ultrasound-guided FNABs of gastrointestinal spindle cell neoplasms performed at the Veterans Affairs Medical Center (VAMC) in Portland, Oregon, from 1998-1999 were reviewed. A panel of immunocytochemical stains was performed on each cellblock including CD-117 (KIT), smooth muscle actin (SMA), desmin, S-100, and CD34. Genomic DNA (gDNA) was extracted, and amplification of exons 9, 11, 13 and 17 of c-kit was performed by polymerase chain reaction (PCR) on CD-117 (KIT) and CD34 positive cases. Direct sequencing of amplicons identified the mutations. Five patients were diagnosed with GISTs based on morphology and immunocytochemical positivity for CD-117 and CD34. PCR analysis of c-kit exon 11 revealed three cases with novel-sized PCR bands in addition to the expected wild-type-sized PCR product. Amplicons from these cases contained an in-frame deletion mutation. One of the two cases with wild-type-;sized exon 11 amplicons was found to be heterozygous for a point mutation producing an amino acid substitution (W557R). No mutations in exon 9, 11, 13, or 17 of c-kit were found in the remaining case. Ancillary techniques such as immunocytochemistry and c-kit gene mutational analysis may aid in the diagnosis of GISTs on FNABs.


Disentangling the drivers of reduced long-distance seed dispersal by birds in an experimentally fragmented landscape.
Seed dispersal is a crucial component of plant population dynamics. Human landscape modifications, such as habitat destruction and fragmentation, can alter the abundance of fruiting plants and animal dispersers, foraging rates, vector movement, and the composition of the disperser community, all of which can singly or in concert affect seed dispersal. Here, we quantify and tease apart the effects of landscape configuration, namely, fragmentation of primary forest and the composition of the surrounding forest matrix, on individual components of seed dispersal of Heliconia acuminata, an Amazonian understory herb. First we identified the effects of landscape configuration on the abundance of fruiting plants and six bird disperser species. Although highly variable in space and time, densities of fruiting plants were similar in continuous forest and fragments. However, the two largest-bodied avian dispersers were less common or absent in small fragments. Second, we determined whether fragmentation affected foraging rates. Fruit removal rates were similar and very high across the landscape, suggesting that Heliconia fruits are a key resource for small frugivores in this landscape. Third, we used radiotelemetry and statistical models to quantify how landscape configuration influences vector movement patterns. Bird dispersers flew farther and faster, and perched longer in primary relative to secondary forests. One species also altered its movement direction in response to habitat boundaries between primary and secondary forests. Finally, we parameterized a simulation model linking data on fruit density and disperser abundance and behavior with empirical estimates of seed retention times to generate seed dispersal patterns in two hypothetical landscapes. Despite clear changes in bird movement in response to landscape configuration, our simulations demonstrate that these differences had negligible effects on dispersal distances. However, small fragments had reduced densities of Turdus albicollis, the largest-bodied disperser and the only one to both regurgitate and defecate seeds. This change in Turdus abundance acted together with lower numbers of fruiting plants in small fragments to decrease the probability of long-distance dispersal events from small patches. These findings emphasize the importance of foraging style for seed dispersal and highlight the primacy of habitat size relative to spatial configuration in preserving biotic interactions.


Response to Comment on "Dynamic Shifts of Limited Working Memory Resources in Human Vision"
Cowan & Rouder suggest that a modification to the four-slot model of visual working memory fits the available data better than our distributed resource model. However their comparisons of statistical fit are biased in favour of the slot model. Here we compare the predictions of the two models and present further evidence against the division of visual memory into slots.


Illness and injury in athletes during the competition period at the London 2012 Paralympic Games: development and implementation of a web-based surveillance system (WEB-IISS) for team medical staff.
In this study we describe (1) the implementation of a novel web-based injury and illness surveillance system (WEB-IISS) for use by a team of physicians at multisport events and (2) the incidence and characteristics of injuries and illness in athletes during the London 2012 Paralympic Games. Overall, 3565 athletes from 160 of the 164 participating countries were followed daily over a 14-day period, consisting of a precompetition period (3 days), and a competition period (11 days) (49 910 athlete-days). Daily injury and illness data were obtained from teams with their own medical support (78 teams, 3329 athletes) via the WEB-IISS, and without their own medical support through the London Organising Committee of the Olympic Games and Paralympic Games database (82 teams and 236 athletes). There were no differences between incidence rates (IR) of injury and illness, or between the precompetition and competition periods. The IR of injury during the competition period was 12.1/1000 athlete-days, with an incidence proportion (IP) of 11.6% (95% CI 11.0% to 13.3%). Upper limb injuries (35%), particularly of the shoulder (17%) were most common. The IR of illness during the competition period was 12.8/1000 athlete-days (95% CI 12.18 to 1421), with an IP of 10.2%. The IP was highest in the respiratory system (27.4%), skin (18.3%) and the gastrointestinal (14.5%) systems. During the competition period, the IR and IP of illness and injury at the Games were similar and comparable to the observed rates in other elite competitions. In Paralympic athletes, the IP of upper limb injuries is higher than that of lower limb injuries and non-respiratory illnesses are more common.


Color, context, and cognitive style: variations in color knowledge retrieval as a function of task and subject variables.
Neuroimaging tests of sensorimotor theories of semantic memory hinge on the extent to which similar activation patterns are observed during perception and retrieval of objects or object properties. The present study was motivated by the hypothesis that some of the seeming discrepancies across studies reflect flexibility in the systems responsible for conceptual and perceptual processing of color. Specifically, we test the hypothesis that retrieval of color knowledge can be influenced by both context (a task variable) and individual differences in cognitive style (a subject variable). In Experiment 1, we provide fMRI evidence for differential activity during color knowledge retrieval by having subjects perform a verbal task, in which context encouraged subjects to retrieve more- or less-detailed information about the colors of named common objects in a blocked experimental design. In the left fusiform, we found more activity during retrieval of more- versus less-detailed color knowledge. We also assessed preference for verbal or visual cognitive style, finding that brain activity in the left lingual gyrus significantly correlated with preference for a visual cognitive style. We replicated many of these effects in Experiment 2, in which stimuli were presented more quickly, in a random order, and in the auditory modality. This illustration of some of the factors that can influence color knowledge retrieval leads to the conclusion that tests of conceptual and perceptual overlap must consider variation in both of these processes.


Branch retinal artery occlusion caused by toxoplasmosis in an adolescent.
Branch retinal artery occlusion (BRAO), while not uncommon in elderly patient populations, is rare in children and adolescents. We report a case of a BRAO secondary to toxoplasmosis in this demographic. A previously healthy 17-year-old male developed a unilateral BRAO in conjunction with inflammation and increased intraocular pressure. Family history was positive for cerebrovascular accidents in multiple family members at relatively young ages. The patient had a hypercoagulable workup as well as a cardiovascular workup which were both normal. A rheumatologic workup was unremarkable. By 3 weeks, a patch of retinitis was more easily distinguished from the BRAO and the diagnosis of ocular toxoplasmosis was made. Treatment was started with prednisone and azithromycin with subsequent improvement in vision. Toxoplasma antibody levels were elevated for IgG and negative for IgM, IgA, and IgE. The etiology of the BRAO was attributed to ocular toxoplasmosis. Vascular occlusions are rare in toxoplasmosis. This is the third case report of a BRAO in a patient in the pediatric population. The diagnosis of ocular toxoplasmosis should be considered in young patients with retinal artery occlusions associated with inflammation.


Toxic time bombs: Frequent detection of anticoagulant rodenticides in urban reptiles at multiple trophic levels.
Anticoagulant rodenticides (ARs) are regularly used around the world to control pest mammals. Second-generation anticoagulant rodenticides (SGARs) are highly persistent in biological tissue and have a high potential for bioaccumulation and biomagnification. Consequently, exposure and poisoning of non-target organisms has been frequently documented, especially in countries with unregulated AR sales and usage. Most of this research has focussed on rodent-predators, usually raptors and predatory mammals, although exposure has also been documented in invertebrates and insectivorous fauna. Few studies have explored non-target exposure in reptiles, despite species sharing similar trophic positions and dietary preferences to other exposed fauna. We tested three abundant urban reptile species in Perth, Western Australia that differ in diet and trophic tiers for multiple AR exposure, the dugite Pseudonaja affinis (rodent-predator), the bobtail Tiliqua rugosa (omnivore) and the tiger snake Notechis scutatus occidentalis (frog-predator). We found frequent exposure in all three species (91% in dugites, 60% in bobtails and 45% in tiger snakes). Mean combined liver concentrations of ARs of exposed individuals were 0.178 mg/kg in dugites, 0.040 mg/kg in bobtails and 0.009 mg/kg in tiger snakes. High exposure frequency and liver concentration was expected for the dugite. Exposure in the other species is more surprising and implies widespread AR contamination of the food web. We discuss the likelihood of global AR exposure of urban reptiles, highlight the potential for reptiles to be important vectors of ARs in the food web and highlight implications for humans consuming wild reptiles.


Beneficial effects of paeoniflorin on osteoporosis induced by high-carbohydrate, high-fat diet-associated hyperlipidemia in vivo.
Osteoporosis is linked to reduced bone mineral density (BMD) as a major risk factor for fragility fractures. Recent studies indicated an association between BMD and abnormally elevated lipid levels in blood as common indicators for hyperlipidemia. In this study, we assessed the protective effect of paeoniflorin, a phytochemical compound with multiple pharmacological activities, against hyperlipidemia-induced osteoporosis in rats fed a high-carbohydrate, high-fat diet (HCHF). The special diet-fed rats were subjected to an 8-week treatment with either paeoniflorin (20 mg/kg, daily) or vehicle. The control group received a normal diet during the entire study. At study conclusion, serum markers of lipid metabolism and bone turnover were measured. Bone strength was assessed by biomechanical testing, and femurs were scanned using micro-computed tomography to analyze trabecular and cortical bone structure. Interestingly, paeoniflorin controlled the serum lipid profile by significantly decreasing HCHF-induced high levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol. Paeoniflorin significantly improved trabecular and cortical parameters as well as femur length and width that were negatively affected by HCHF diet. Biomechanical strength testing showed that femurs of HCHF diet-fed rats endured significantly lower force but higher displacement and strain than those of control rats, whereas paeoniflorin reversed the negative effects. Moreover, paeoniflorin rescued osteoblast differentiation and cell spreading activities along with bone turnover markers. In conclusion, HCHF-induced hyperlipidemia caused adverse effects on the bone that were rescued by paeoniflorin treatment.


Magnetic field effect on the free induction decay of hydroxyl radicals (OH) in the terahertz region.
The effect of an external longitudinal magnetic field on the optical free induction decay from a free radical is observed for the first time. The experiments were performed on a rotational transition of the hydroxyl radical, OH (2Π3/2(J = 1) ← 2Π3/2(J = 0) at 83.8 cm-1), using a terahertz free electron laser. In contrast to the results of the experiments with a stable paramagnetic molecule, NO, the observed effect of an external magnetic field on the free induction decay from hydroxyl radicals is more complicated. A longitudinal magnetic field leads to the rotation of the polarization plane of the FID radiation and to an additional modulation of the signal intensity. The angle of the rotation of the plane of polarization is large, in agreement with the theoretical predictions. The observed FID kinetics in the time domain are in semi-quantitative agreement with the modeling. This observation opens an opportunity for the selective detection of weak signals of short-lived reactive paramagnetic free radicals from overwhelming signals that originate from stable non-paramagnetic species by polarization discrimination.


Secreted nuclear protein DEK regulates hematopoiesis through CXCR2 signaling.
The nuclear protein DEK is an endogenous DNA-binding chromatin factor regulating hematopoiesis. DEK is one of only 2 known secreted nuclear chromatin factors, but whether and how extracellular DEK regulates hematopoiesis is not known. We demonstrated that extracellular DEK greatly enhanced ex vivo expansion of cytokine-stimulated human and mouse hematopoietic stem cells (HSCs) and regulated HSC and hematopoietic progenitor cell (HPC) numbers in vivo and in vitro as determined both phenotypically (by flow cytometry) and functionally (through transplantation and colony formation assays). Recombinant DEK increased long-term HSC numbers and decreased HPC numbers through a mechanism mediated by the CXC chemokine receptor CXCR2 and heparan sulfate proteoglycans (HSPGs) (as determined utilizing Cxcr2-/- mice, blocking CXCR2 antibodies, and 3 different HSPG inhibitors) that was associated with enhanced phosphorylation of ERK1/2, AKT, and p38 MAPK. To determine whether extracellular DEK required nuclear function to regulate hematopoiesis, we utilized 2 mutant forms of DEK: one that lacked its nuclear translocation signal and one that lacked DNA-binding ability. Both altered HSC and HPC numbers in vivo or in vitro, suggesting the nuclear function of DEK is not required. Thus, DEK acts as a hematopoietic cytokine, with the potential for clinical applicability.


The pilA regulatory gene modulates the pilus-mediated adhesion of Neisseria meningitidis by controlling the transcription of pilC1.
Adherence to eukaryotic cells is essential in the pathogenesis of Neisseria meningitidis. Pilus-mediated adhesion has been shown to play an essential role in this process. Pilin, the pilus major subunit, and two pilus associated proteins, PilC1 and PilC2, are key components in meningococcal adhesiveness. Phase and/or antigenic variation of these molecules are the only identified means by which N. meningitidis modulates pilus-mediated adhesion. PilA/PilB is a pleiotropic regulatory system first characterized in Neisseria gonorrhoeae where it controls pilin gene transcription. Similar alleles are found in N. meningitidis. To address the role of this regulatory pathway in N. meningitidis, we engineered a meningococcal pilA mutant strain and analysed the consequences of this mutation on pilus-mediated adhesion using epithelial Hec-1-B cells. This mutation resulted in a threefold reduction in adhesiveness. As no change in the amount of pilin nor in pilin gene mRNA was detected, we compared the expression of the pilC genes in both pilA and parental strains. Two transcriptional fusions pilC1-lacZ and pilC2-lacZ were constructed. A threefold reduction in beta-galactosidase activity was observed in the pilA mutant strain harbouring the pilC1-lacZ fusion. No effect of the pilA mutation on beta-galactosidase activity was observed in the strain carrying the pilC2-lacZ fusion. Gel retardation experiments confirmed that the PilA protein binds to the promoter region of pilC1 but not of pilC2. Taken together, these data demonstrate that PilA modulates meningococcal adhesiveness via the transcription of pilC1. Thus, in addition to phase variation, a more co-ordinate and responsive system may allow a fine adaptation of adhesiveness of meningococci to various environmental signals.


Evaluating the mechanical response of novel synthetic femurs for representing osteoporotic bone.
Osteoporosis is a disease prevalent in older adults, characterized by high porosity in bone and subsequent decrease in fracture resistance. This demographic is also the population that most frequently receives devices such as hip implants. However, high porosity complicates surgery and reduces the fixation and effectiveness of orthopaedic devices, which are typically designed using cadaveric specimens from the general population. Synthetic bones are also used in the design of such devices but need to represent the properties of the patient population. Thus, the mechanical response of two iterations of novel synthetic femurs were evaluated for their ability to represent osteoporotic cadaveric specimens and were tested and compared against cadaveric specimens across four loading modes. The first iteration had reduced density and wall thickness compared to standard models and was typically too rigid or too stiff to be a feasible alternative to cadaveric specimens. The second iteration, with similarly reduced wall thickness and further reduced density, was quite representative, with no statistical differences identified against the cadaveric specimens in any loading mode, except in screw pullout. Such a model can provide a foundation for the development of orthopaedic devices better suited to osteoporotic bone, potentially improving surgical outcomes, reducing medical expense, and improving quality of life for patients.


Safety and efficacy of a feed additive consisting of Limosilactobacillus reuteri (formerly Lactobacillus reuteri) DSM 32264 as a feed additive for cats (NBF Lanes s.r.l.).
Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the efficacy of a product consisting of Limosilactobacillus reuteri (formerly Lactobacillus reuteri) DSM 32264 as a zootechnical additive for cats. The additive is a preparation of viable cells of L. reuteri DSM 32264 and it has not been previously authorised as a feed additive in the European Union. The additive is intended for use in complete feed for cats at a minimum inclusion level of 6 × 109 colony forming units (CFU) per animal and day. In a previous opinion, the FEEDAP Panel could not conclude on the efficacy of L. reuteri DSM 32264 for cats. The applicant has provided supplementary information to support the efficacy of the additive for cats. Based on the data provided, the FEEDAP Panel concluded that L. reuteri DSM 32264 has the potential to improve faecal consistency by reducing the moisture content of stools from cats receiving the additive at 1 × 1010 CFU/kg feed. However, the Panel had some reservations on the effects in the moisture content, which if maintained overtime, might cast doubts on the benefits on the long-term use of the additive since it could lead to constipation.


Malaria epidemics in India: Role of climatic condition and control measures.
Malaria is a major public health problem in India, which is the second most populous country in the world. This study aimed to investigate the impact of climatic parameters and malaria control efforts implemented by the Indian national malaria control program on malaria epidemics between January of 2009 and December of 2015. A chi-squared test was used to study the correlation of all implemented control methods with occurrence of epidemics within 30, 45, 60 and 90 days and in the same district, 50, 100 and 200 km distance radiuses. The effect of each control method on probability of epidemics was also measured, and the effects of district population, season, and incidence of malaria parasite types were evaluated using logistic regression models. Fever survey was found to be effective for decreasing the odds of epidemics within 45, 60 and 90 days in 100 km. Anti-larval activity was also effective within 30, 45 and 60 days in 200 km. Winter had negative effects on odds ratio while summer and fall were more likely to trigger epidemics. These results contribute to understanding the role of climate variability and control efforts performed in India.


Attractive but Toxic: Emerging Roles of Glycosidically Bound Volatiles and Glycosyltransferases Involved in Their Formation.
Plants emit an overabundance of volatile compounds, which act in their producers either as appreciated attractants to lure beneficial animals or as repellent toxins to deter pests in a species-specific and concentration-dependent manner. Plants have evolved solutions to provide sufficient volatiles without poisoning themselves. Uridine-diphosphate sugar-dependent glycosyltransferases (UGTs) acting on volatiles is one important part of this sophisticated system, which balances the levels of bioactive metabolites and prepares them for cellular and long-distance transport and storage but enables the remobilization of disarmed toxins for the benefit of plant protection. This review provides an overview of the research history of glycosidically bound volatiles (GBVs), a relatively new group of plant secondary metabolites, and discusses the role of UGTs in the production of GBVs for plant protection.


Unaltered retinal dopamine levels in a C57BL/6 mouse model of form-deprivation myopia.
Retinal dopamine has been long implicated in the signaling pathway regulating eye growth, as evidenced by its reduced levels in myopic eyes in various species. We examined whether and how retinal dopamine levels were changed in a C57BL/6 mouse model of experimental myopia. Form-deprivation myopia (FDM) was induced in C57BL/6 mice by wearing monocular occluder for 4 weeks. Refractive errors were measured using an infrared photorefractor. Retinal dopamine/DOPAC and vitreal DOPAC levels were assessed by high-performance liquid chromatography (HPLC). Extracellular dopamine concentrations were examined by Western blot analysis of dopamine transporter (DAT) expression levels. The intactness of retinal dopaminergic system was evaluated by counting tyrosine hydroxylase (TH) immunoreactive cells, measuring the areas occupied by processes of these cells, and quantifying retinal TH expression at both protein and transcription levels. Form-deprivation myopia was successfully induced in C57BL/6 mice with the refractive status of deprived eyes being significantly different from fellow eyes. Unlike most of the previous results obtained in other myopic animal models, however, no significant changes in retinal dopamine, DOPAC, DAT, and vitreal DOPAC levels were detected in deprived eyes, either in the daytime or at night. Furthermore, neither the number of dopaminergic amacrine cells, the area size occupied by the processes of these cells, nor retinal TH expression, were altered in deprived eyes. The retinal dopamine system remains intact in C57BL/6 mice with FDM, and retinal dopamine levels are not associated with the development of FDM in this mouse strain.


The Effect of Aromatherapy on Elderly Persons With Dry Skin: A Randomized Controlled Trial.
Dry skin, which is one of the most frequent dermatological problems seen in the elderly population, is an important problem that increases with aging. This study was conducted as a randomized controlled experimental trial to determine the effect of aromatherapy, applied to elderly persons residing in a nursing home in a city center, on dry skin. Elderly persons were grouped into a control group (20 elderly persons), an olive oil group (20 elderly persons), and an aromatherapy group (20 elderly persons). When examining between-measurements differences of the groups in the study, skin moisture levels of the elderly individuals in the aromatherapy group increased in all zones, arm, leg, back, and chest, at measurements of the second and fourth weeks compared with the first measurements. This improvement was determined to be higher after the second week. Skin moisture levels of elderly persons in the olive oil group were determined to significantly increase at the arm zone in the fourth week and at the back zone in the second and fourth weeks compared with the first measurements. Skin moisture levels of elderly persons in the control group, on the contrary, did not change in the second and fourth weeks compared with the first measurements and their dry skin continued at the same level. The intervention performed in this manner in the present study can be used in the clinical practice as an effective nursing intervention to reducing dry skin among elderly persons.


Fracture surgery of the extremities with the intra-operative use of 3D-RX: a randomized multicenter trial (EF3X-trial).
Posttraumatic osteoarthritis can develop after an intra-articular extremity fracture, leading to pain and loss of function. According to international guidelines, anatomical reduction and fixation are the basis for an optimal functional result. In order to achieve this during fracture surgery, an optimal view on the position of the bone fragments and fixation material is a necessity. The currently used 2D-fluoroscopy does not provide sufficient insight, in particular in cases with complex anatomy or subtle injury, and even an 18-26% suboptimal fracture reduction is reported for the ankle and foot. More intra-operative information is therefore needed.Recently the 3D-RX-system was developed, which provides conventional 2D-fluoroscopic images as well as a 3D-reconstruction of bony structures. This modality provides more information, which consequently leads to extra corrections in 18-30% of the fracture operations. However, the effect of the extra corrections on the quality of the anatomical fracture reduction and fixation as well as on patient relevant outcomes has never been investigated.The objective of this study protocol is to investigate the effectiveness of the intra-operative use of the 3D-RX-system as compared to the conventional 2D-fluoroscopy in patients with traumatic intra-articular fractures of the wrist, ankle and calcaneus. The effectiveness will be assessed in two different areas: 1) the quality of fracture reduction and fixation, based on the current golden standard, Computed Tomography. 2) The patient-relevant outcomes like functional outcome range of motion and pain. In addition, the diagnostic accuracy of the 3D-RX-scan will be determined in a clinical setting and a cost-effectiveness as well as a cost-utility analysis will be performed. In this protocol for an international multicenter randomized clinical trial, adult patients (age > 17 years) with a traumatic intra-articular fracture of the wrist, ankle or calcaneus eligible for surgery will be subjected to additional intra-operative 3D-RX. In half of the patients the surgeon will be blinded to these results, in the other half the surgeon may use the 3D-RX results to further optimize fracture reduction. In both randomization groups a CT-scan will be performed postoperatively. Based on these CT-scans the quality of fracture reduction and fixation will be determined. During the follow-up visits after hospital discharge at 6 and 12 weeks and 1 year postoperatively the patient relevant outcomes will be determined by joint specific, health economic and quality of life questionnaires. In addition a follow up study will be performed to determine the patient relevant outcomes and prevalence of posttraumatic osteoarthritis at 2 and 5 years postoperatively. The results of the study will provide more information on the effectiveness of the intra-operative use of 3D-imaging during surgical treatment of intra-articular fractures of the wrist, ankle and calcaneus. A randomized design in which patients will be allocated to a treatment arm during surgery will be used because of its high methodological quality and the ability to detect incongruences in the reduction and/or fixation that occur intra-operatively in the blinded arm of the 3D-RX. An alternative, pragmatic design could be to randomize before the start of the surgery, then two surgical strategies would be compared. This resembles clinical practice better, but introduces more bias and does not allow the assessment of incongruences that would have been detected by 3D-RX in the blinded arm. Dutch Trial Register NTR 1902.


Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis.
Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression.


Surface-induced patterns from evaporating droplets of aqueous carbon nanotube dispersions.
Evaporation of aqueous droplets of carbon nanotubes (CNTs) coated with a physisorbed layer of humic acid (HA) on a partially hydrophilic substrate induces the formation of a film of CNTs. Here, we investigate the role that the global geometry of the substrate surfaces has on the structure of the CNT film. On a flat mica or silica surface, the evaporation of a convex droplet of the CNT dispersion induces the well-known "coffee ring", while evaporation of a concave droplet (capillary meniscus) of the CNT dispersion in a wedge of two planar mica sheets or between two crossed-cylinder sheets induces a large area (>mm(2)) of textured or patterned films characterized by different short- and long-range orientational and positional ordering of the CNTs. The resulting patterns appear to be determined by two competing or cooperative sedimentation mechanisms: (1) capillary forces between CNTs giving micrometer-sized filaments parallel to the boundary line of the evaporating droplet and (2) fingering instability at the boundary line of the evaporating droplet and subsequent pinning of CNTs on the surface giving micrometer-sized filaments of CNTs perpendicular to this boundary line. The interplay between substrate surface geometry and sedimentation mechanisms gives an extra control parameter for manipulating patterns of self-assembling nanoparticles at substrate surfaces.