Robust associations between the 20-item prosopagnosia index and the Cambridge Face Memory Test in the general population.
Developmental prosopagnosia (DP) is a neurodevelopmental condition, characterized by lifelong face recognition deficits. Leading research groups diagnose the condition using complementary computer-based tasks and self-report measures. In an attempt to standardize the reporting of self-report evidence, we recently developed the 20-item prosopagnosia index (PI20), a short questionnaire measure of prosopagnosic traits suitable for screening adult samples for DP. Strong correlations between scores on the PI20 and performance on the Cambridge Face Memory Test (CFMT) appeared to confirm that individuals possess sufficient insight into their face recognition ability to complete a self-report measure of prosopagnosic traits. However, the extent to which people have insight into their face recognition abilities remains contentious. A lingering concern is that feedback from formal testing, received prior to administration of the PI20, may have augmented the self-insight of some respondents in the original validation study. To determine whether the significant correlation with the CFMT was an artefact of previously delivered feedback, we sought to replicate the validation study in individuals with no history of formal testing. We report highly significant correlations in two independent samples drawn from the general population, confirming: (i) that a significant relationship exists between PI20 scores and performance on the CFMT, and (ii) that this is not dependent on the inclusion of individuals who have previously received feedback. These findings support the view that people have sufficient insight into their face recognition abilities to complete a self-report measure of prosopagnosic traits.


Women's intention to screen and willingness to vaccinate their daughters against cervical cancer - a cross sectional study in eastern Uganda.
The World Health Organization recommends cervical cancer screening and vaccination programmes as measures to combat cervical cancer. The uptake of these measures remains low in Uganda, most especially in rural areas. An understanding of the factors that influence women's decision to attend screening, and willingness to have their daughters vaccinated against cervical cancer is essential for any attempts to increase uptake of these services. This study assessed the factors associated with intention to screen for cervical cancer among women in eastern Uganda, and willingness to have their daughters vaccinated against the disease. This cross sectional study involved 900 females aged 25 to 49 years in Bugiri and Mayuge districts in eastern Uganda. Data were collected using a pretested semi-structured questionnaire, entered in Epidata version 3.02 and analysed in STATA version 12.0. Unadjusted and adjusted prevalence ratios (PR) were computed using a generalized linear model with Poisson family, and a log link with robust standard errors. Majority 819 (91.0%) of respondents stated that they intended to go for cervical cancer screening in the subsequent six months. Among them, 603 (73.6%) wanted to know their status, 256 (31.3%) thought it was important, 202 (24.7%) wanted to reduce their chances of getting the disease, and 20 (2.4%) had been told to do so by a health worker. Majority 813 (90.4%) of respondents were willing to vaccinate their daughters against cervical cancer. Higher income (adjusted PR = 1.11, 95% CI: 1.03-1.20), cervical cancer screening status (adjusted PR = 0.81, 95% CI: 0.67-0.99) and knowledge of at least one test for cervical cancer (adjusted PR = 0.92, 95% CI: 0.85-0.98) were significantly associated with intention to screen for cervical cancer. No socio-demographic characteristic was associated with willingness to vaccinate daughters among women. There is a very high intention to screen and willingness to vaccinate daughters against cervical cancer among women in eastern Uganda. To take advantage of this, there is need to avail opportunities for women to access cervical cancer screening and vaccinations particularly among rural communities.


DNA polymerase eta is a limiting factor for A:T mutations in Ig genes and contributes to antibody affinity maturation.
DNA polymerase eta (POLH) is required for the generation of A:T mutations during the somatic hypermutation of Ig genes in germinal center B cells. It remains unclear, however, whether POLH is a limiting factor for A:T mutations and how the absence of POLH might affect antibody affinity maturation. We found that the heterozygous Polh+/- mice exhibited a significant reduction in the frequency of A:T mutations in Ig genes, with each type of base substitutions at a level intermediate between the Polh+/+ and Polh(-/-) mice. These observations suggest that Polh is haplo-insufficient for the induction of A:T mutations in Ig genes. Intriguingly, there was also a reduction of C to T and G to A transitions in Polh+/- mice as compared with WT mice. Polh(-/-) mice produced decreased serum titers of high-affinity antibodies against a T-dependent antigen, which was associated with a significant reduction in the number of plasma cells secreting high-affinity antibodies. Analysis of the V region revealed that aa substitutions caused by A:T mutations were greatly reduced in Polh(-/-) mice. These results demonstrate that POLH is a limiting factor for A:T mutations and contributes to the efficient diversification of Ig genes and affinity maturation of antibodies.


Mechanistically Driven Development of an Iron Catalyst for Selective Syn-Dihydroxylation of Alkenes with Aqueous Hydrogen Peroxide.
Product release is the rate-determining step in the arene syn-dihydroxylation reaction taking place at Rieske oxygenase enzymes and is regarded as a difficult problem to be resolved in the design of iron catalysts for olefin syn-dihydroxylation with potential utility in organic synthesis. Toward this end, in this work a novel catalyst bearing a sterically encumbered tetradentate ligand based in the tpa (tpa = tris(2-methylpyridyl)amine) scaffold, [FeII(CF3SO3)2(5-tips3tpa)], 1 has been designed. The steric demand of the ligand was envisioned as a key element to support a high catalytic activity by isolating the metal center, preventing bimolecular decomposition paths and facilitating product release. In synergistic combination with a Lewis acid that helps sequestering the product, 1 provides good to excellent yields of diol products (up to 97% isolated yield), in short reaction times under mild experimental conditions using a slight excess (1.5 equiv) of aqueous hydrogen peroxide, from the oxidation of a broad range of olefins. Predictable site selective syn-dihydroxylation of diolefins is shown. The encumbered nature of the ligand also provides a unique tool that has been used in combination with isotopic analysis to define the nature of the active species and the mechanism of activation of H2O2. Furthermore, 1 is shown to be a competent synthetic tool for preparing O-labeled diols using water as oxygen source.


Oxidative damage to DNA and repair induced by Norwegian wood smoke particles in human A549 and THP-1 cell lines.
Genotoxic effects of traffic-generated particulate matter (PM) are well described, whereas little data are available on PM from combustion of biomass and wood, which contributes substantially to air pollution world wide. The aim of this study was to compare the genotoxicity of wood smoke particulate matter (WSPM), authentic traffic-generated particles, mineral PM and standard reference material (SRM2975) of diesel exhaust particles in human A549 lung epithelial and THP-1 monocytic cell lines. DNA damage was measured as strand breaks (SB) and formamidopyrimidine DNA glycosylase (FPG) sites by the comet assay, whereas cell cytotoxicity was determined as lactate dehydrogenase release. The exposure to WSPM generated SB and FPG sites in both cell lines at concentrations from 2.5 or 25 microg/ml, which were not cytotoxic. Compared to all other studied particles, WSPM generated greater responses in terms of both SB and FPG sites. Organic extracts of WSPM and SRM2975 elicited higher levels of SB than native and washed PM at 25 and 100 microg/ml, whereas assay saturation precluded reliable assessment of FPG sites. During a 6h post-exposure period, in which the medium with PM had been replaced by fresh medium, 60% of the DNA lesions generated by WSPM were removed. In conclusion, WSPM generated more DNA damage than traffic-generated PM per unit mass in human cell lines, possibly due to the high level of polycyclic aromatic hydrocarbons in WSPM. This suggests that exposure to WSPM might be more hazardous than PM collected from vehicle exhaust with respect to development of lung cancer.


Role of Astrocytes in the Pathophysiology of Lafora Disease and Other Glycogen Storage Disorders.
Lafora disease is a rare disorder caused by loss of function mutations in either the EPM2A or NHLRC1 gene. The initial symptoms of this condition are most commonly epileptic seizures, but the disease progresses rapidly with dementia, neuropsychiatric symptoms, and cognitive deterioration and has a fatal outcome within 5-10 years after onset. The hallmark of the disease is the accumulation of poorly branched glycogen in the form of aggregates known as Lafora bodies in the brain and other tissues. Several reports have demonstrated that the accumulation of this abnormal glycogen underlies all the pathologic traits of the disease. For decades, Lafora bodies were thought to accumulate exclusively in neurons. However, it was recently identified that most of these glycogen aggregates are present in astrocytes. Importantly, astrocytic Lafora bodies have been shown to contribute to pathology in Lafora disease. These results identify a primary role of astrocytes in the pathophysiology of Lafora disease and have important implications for other conditions in which glycogen abnormally accumulates in astrocytes, such as Adult Polyglucosan Body disease and the buildup of Corpora amylacea in aged brains.


Risk acceptance in multiple sclerosis patients on natalizumab treatment.
We aimed to investigate the ability of natalizumab (NTZ)-treated patients to assume treatment-associated risks and the factors involved in such risk acceptance. From a total of 185 patients, 114 patients on NTZ as of July 2011 carried out a comprehensive survey. We obtained disease severity perception scores, personality traits' scores, and risk-acceptance scores (RAS) so that higher RAS indicated higher risk acceptance. We recorded JC virus status (JCV+/-), prior immunosuppression, NTZ treatment duration, and clinical characteristics. NTZ patients were split into subgroups (A-E), depending on their individual PML risk. Some 22 MS patients on first-line drugs (DMD) acted as controls. No differences between treatment groups were observed in disease severity perception and personality traits. RAS were higher in NTZ than in DMD patients (p<0.01). Perception of the own disease as a more severe condition tended to predict higher RAS (p=0.07). Higher neuroticism scores predicted higher RAS in the NTZ group as a whole (p=0.04), and in high PML-risk subgroups (A-B) (p=0.02). In low PML-risk subgroups (C-E), higher RAS were associated with a JCV+ status (p=0.01). Neither disability scores nor pre-treatment relapse rate predicted RAS in either group. Risk acceptance is a multifactorial phenomenon, which might be partly explained by an adaptive process, in light of the higher risk acceptance amongst NTZ-treated patients and, especially, amongst those who are JCV seropositive but still have low PML risk, but which seems also intimately related to personality traits.


Accumulation and clearance of orally administered erythromycin and its derivative, azithromycin, in juvenile fall chinook salmon Oncorhynchus tshawytscha.
Fall Chinook salmon Oncorhynchus tshawytscha were fed practical diets medicated with azithromycin (30 mg kg(-1) fish for 14 d) or erythromycin (100 mg kg(-1) fish for 28 d) either 1, 2, or 3 times beginning 14 d after initiation of exogenous feeding (February) and ending at smoltification (June). Average tissue concentrations of azithromycin increased from 19.0 microg g(-1) in fry to 44.9 microg g(-1) in smolts, and persisted in the tissues > 76 d after treatment ceased. Tissue concentrations of erythromycin were comparatively low, ranging from 0.2 microg g(-1) in fry to 10.4 microg g(-1) in smolts. Erythromycin was not detectable 21 d post-treatment. Neither antibiotic caused histopathologically significant lesions in the trunk kidney or other organ tissues. The high tissue concentrations and prolonged retention of azithromycin in Chinook may be factors that increase the efficacy of the antibiotic against Renibacterium salmoninarum, compared with erythromycin, particularly in early life history stages before covertly infected fish show clinical signs of disease.


Increased fundus autofluorescence associated with outer segment shortening in macular translocation model of neovascular age-related macular degeneration.
To report the frequency and origins of increased fundus autofluorescence (AF) in age-related macular degeneration using the model of macular translocation. In this retrospective observational case series, postoperative serial fundus AF images from 40 consecutive patients were examined. The origin of well-delineated increased AF changes was explored by examining simultaneous spectral-domain optical coherence tomography (SD-OCT) scans and coregistered microperimetry. AF images were taken between a mean of 13 and 36 months. Seven patients were excluded from analysis because of lack of postoperative AF imaging or extensive macular RPE atrophy. Of the remaining patients, 9 had masking pattern of foveal AF, 21 had small, round increased AF lesions in the fovea, and 3 had a near normal pattern of foveal hypo-AF. Parafoveal increased AF was seen in all 33 patients in 1 of 3 patterns: well-delineated homogenous increased AF patches (17), curvilinear increased AF bands (4), and speckled increased AF (12). Simultaneous SD-OCT showed loss of signal from the interface of the inner and outer segments of the photoreceptor cell layer with variable loss of outer nuclear layer thickness. Microperimetry showed subnormal retinal sensitivity in regions with increased AF. Parafoveal increased AF size remained stable for 2 to 5 years of follow-up. SD-OCT and microperimetry changes observed after translocation may be attributed to shortening of the outer segments. A corresponding reduction of visual pigment in the shortened outer segments may lead to an unmasking effect. Increased AF in some macular diseases may be attributed to unmasking of AF rather than to increased fluorophores within abnormal retina.


Prostate cancer progression and mortality: a review of diet and lifestyle factors.
To review and summarize evidence on the role of diet and lifestyle factors and prostate cancer progression, with a specific focus on habits after diagnosis and the risk of subsequent disease recurrence, progression, or death. Given the well-documented heterogeneity of prostate cancer and the long survivorship of the majority of diagnoses, our goal was to summarize and describe modifiable risk factors for clinically relevant prostate cancer. We focused where possible on epidemiologic studies of post-diagnostic habits and prostate cancer progression, defined as recurrence (e.g., PSA risk, secondary treatment), metastasis, or death. Where data were limited, we also describe evidence on risk factors and indicators of prostate cancer aggressiveness at diagnosis. A variety of dietary and lifestyle factors appear to affect prostate cancer progression. Several generally widely recommended lifestyle factors such as not smoking, maintaining a healthy body weight, and regular vigorous physical exercise also appear to affect prostate cancer progression. Several dietary factors, such as tomato sauce/lycopene, cruciferous vegetables, healthy sources of vegetable fats, and coffee, may also have a role in reducing risk of prostate cancer progression. Diet and lifestyle factors, in particular exercise and smoking cessation, may reduce the risk of prostate cancer progression and death. These promising findings warrant further investigation, as their overall impact might be large.


Cellular and molecular biology of ensheathing cells.
Ensheathing cells are the glial cells that envelop olfactory axons as they course from the olfactory epithelium to the bulb. They are derived from the olfactory placode and differ from the typical glia in terms of sharing the phenotypes of both astrocytes and Schwann cells. The aims of this study are to review (1) cellular characterisation of ensheathing cells in vivo and in vitro, (2) molecular insight into their growth promoting properties, and (3) their role in olfactory development and potential function as a therapeutic agent for nerve repair. Much of the characterisation of ensheathing cell property has developed from immunohistochemical studies that have been supplemented with new molecular methodologies in recent years. Many pieces of evidence clearly indicate that ensheathing cells actively produce growth-promoting molecules, which act in a paracrine and, in some cases, autocrine manner. However, a review of the available literature also suggests that there is a great deal that remains to be elucidated regarding the cell biology of ensheathing cells, for example, their rate of formation and turnover. In addition, the apparent antigenic heterogeneity as revealed by numerous in vitro studies warrants further analysis, particularly in view of the fact that in recent years these cells have been touted as a possible agent for central nerve repair. New molecular methodologies such as the microarray techniques will prove to be crucial for defining the unique characteristics of ensheathing cells.


Lipopolysaccharide increases alveolar type II cell number in fetal mouse lungs through Toll-like receptor 4 and NF-kappaB.
Chorioamnionitis is a major cause of preterm delivery. Infants exposed to inflammation in utero and then born preterm may have improved lung function in the immediate postnatal period. We developed a mouse model of chorioamnionitis to study the inflammatory signaling mechanisms that might influence fetal lung maturation. With this in vivo model, we found that Escherichia coli lipopolysaccharide (LPS) increased the number of alveolar type II cells in the fetal mouse lung. LPS also increased type II cell number in cultured fetal lung explants, suggesting that LPS could directly signal the fetal lung in the absence of maternal influences. Using immunostaining, we localized cells within the fetal mouse lung expressing the LPS receptor molecule Toll-like receptor 4 (TLR4). Similar to the signaling pathways in inflammatory cells, LPS activated NF-kappaB in fetal lung explants. Activation of the TLR4/NF-kappaB pathway appeared to be required, as LPS did not increase the number of type II cells in C.C3H-Tlr4(Lps-d) mice, a congenic strain containing a loss of function mutation in tlr4. In addition, the sesquiterpene lactone parthenolide inhibited NF-kappaB activation following LPS exposure and blocked the LPS-induced increase in type II cells. On the basis of these data from our mouse model of chorioamnionitis, it appears that LPS specifically activated the TLR4/NF-kappaB pathway, leading to increased type II cell maturation. These data implicate an important signaling mechanism in chorioamnionitis and suggest the TLR4/NF-kappaB pathway can influence lung development.


XRS2, a DNA repair gene of Saccharomyces cerevisiae, is needed for meiotic recombination.
The XRS2 gene of Saccharomyces cerevisiae has been previously identified as a DNA repair gene. In this communication, we show that XRS2 also encodes an essential meiotic function. Spore inviability of xrs2 strains is rescued by a spo13 mutation, but meiotic recombination (both gene conversion and crossing over) is highly depressed in spo13 xrs2 diploids. The xrs2 mutation suppresses spore inviability of a spo13 rad52 strain suggesting that XRS2 acts prior to RAD52 in the meiotic recombination pathway. In agreement with the genetic data, meiosis-specific double-strand breaks at the ARG4 meiotic recombination hotspot are not detected in xrs2 strains. Despite its effects on meiotic recombination, the xrs2 mutation does not prevent mitotic recombination events, including homologous integration of linear DNA, mating-type switching and radiation-induced gene conversion. Moreover, xrs2 strains display a mitotic hyper-rec phenotype. Haploid xrs2 cells fail to carry out G2-repair of gamma-induced lesions, whereas xrs2 diploids are able to perform some diploid-specific repair of these lesions. Meiotic and mitotic phenotypes of xrs2 cells are very similar to those of rad50 cells suggesting that XRS2 is involved in homologous recombination in a way analogous to that of RAD50.


Morpholino oligos: making sense of antisense?
Since morpholino oligos were first introduced as a means to inhibit gene function in embryos, in the Spring of 2000, they have been tested in a range of model organisms, including sea urchin, ascidian, zebrafish, frog, chick, and mouse. This review surveys the results of these studies and examines the successes and limitations of the approach for targeting maternal and zygotic gene function. The evidence so far suggests that, with careful controls, morpholinos provide a relatively simple and rapid method to study gene function.


Inulin, oligofructose and mineral metabolism - experimental data and mechanism.
Numerous investigations performed in animal models in the past 10 years have shown repeatedly that non-digestible oligosaccharides (NDO), such as inulin, oligofructose or transgalacto-oligosaccharides (TOS), stimulate mineral absorption, mainly calcium and magnesium. Long-term beneficial effects on bone health have been indicated by accumulation of bone mineral content in growing rats or prevention of bone loss in ovariectomized rats. However, bone mineral content or density are not necessarily associated with bone quality. In recent studies both oligofructose and calcium prevented loss of trabecular bone area induced by oestrogen deficiency, this, however, occurred at different trabecular shapes. The effects of NDO on mineral metabolism may be based on the enhancement of passive and active mineral transport across the intestinal epithelium, mediated by an increase in certain metabolites of the intestinal flora and a reduction of pH. The possible impact of short-chain fatty acids, butyrate in particular, and of polyamines on the stimulation of mineral absorption capacity, and the interaction of oligofructose and antibiotics is discussed.


Comparison of Growth Patterns of COVID-19 Cases through the ARIMA and Gompertz Models. Case Studies: Austria, Switzerland, and Israel.
On May 19, 2020, data confirmed that coronavirus 2019 disease (COVID-19) had spread worldwide, with more than 4.7 million infected people and more than 316,000 deaths. In this article, we carry out a comparison of the methods to calculate and forecast the growth of the pandemic using two statistical models: the autoregressive integrated moving average (ARIMA) and the Gompertz function growth model. The countries that have been chosen to verify the usefulness of these models are Austria, Switzerland, and Israel, which have a similar number of habitants. The investigation to check the accuracy of the models was carried out using data on confirmed, non-asymptomatic cases and confirmed deaths from the period February 21-May 19, 2020. We use the root mean squared error (RMSE), the mean absolute percentage error (MAPE), and the regression coefficient index R2 to check the accuracy of the models. The experimental results provide promising adjustment errors for both models (R2>0.99), with the ARIMA model being the best for infections and the Gompertz best for mortality. It has also been verified that countries are affected differently, which may be due to external factors that are difficult to measure quantitatively. These models provide a fast and effective system to check the growth of pandemics that can be useful for health systems and politicians so that appropriate measures are taken and countries' health care systems do not collapse.


Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters.
The extracellular matrix (ECM) is a major component of tumors and a significant contributor to cancer progression. In this study, we use proteomics to investigate the ECM of human mammary carcinoma xenografts and show that primary tumors of differing metastatic potential differ in ECM composition. Both tumor cells and stromal cells contribute to the tumor matrix and tumors of differing metastatic ability differ in both tumor- and stroma-derived ECM components. We define ECM signatures of poorly and highly metastatic mammary carcinomas and these signatures reveal up-regulation of signaling pathways including TGFβ and VEGF. We further demonstrate that several proteins characteristic of highly metastatic tumors (LTBP3, SNED1, EGLN1, and S100A2) play causal roles in metastasis, albeit at different steps. Finally we show that high expression of LTBP3 and SNED1 correlates with poor outcome for ER(-)/PR(-)breast cancer patients. This study thus identifies novel biomarkers that may serve as prognostic and diagnostic tools. DOI: http://dx.doi.org/10.7554/eLife.01308.001.


Occurrence and cytological mechanism of 2n pollen formation in a tetraploid accession of Ipomoea batatas (sweet potato).
We evaluated a 4x accession of Ipomoea batatas (L.) Lam. and four 2x accessions of Ipomoea triloba for 2n pollen production. Approximately 90% of the genotypes of accession 81.2 (I. batatas, 4x) produced 2n pollen with different frequencies. In contrast, none of the genotypes of I. triloba produced 2n pollen. The diameter of the 2n pollen was approximately 30% ((3) sqrt 2) larger than that of the n pollen, making it easy to identify, measure, and quantify. The correlation (r = 0.93**) between the frequency of giant pollen and the frequency of dyads and triads was highly significant, strongly suggesting that the giant pollen grains were 2n pollen. The 2n pollen producers presented either a parallel or tripolar spindle arrangement (Y shaped) at anaphase II instead of the normal 60 degrees crossed spindle orientation. These two abnormal spindle configurations produced dyads and triads, with different frequencies (13-67%), instead of tetrads. Occasionally a metaphase II spindle variation was found with a single fused spindle, which also forms a dyad. The correlation (r = 0.89**) between the frequency of 2n pollen and the frequency of parallel, fused, and tripolar spindle arrangements was also highly significant, suggesting that these abnormal spindle configurations are involved in the production of 2n pollen in I. batatas. When we evaluated the efficiency of 2n pollen in polyploidization using 4x x 4x (2n) crosses, all progenies were 4x, suggesting the existence of barriers to crossability between 4x genotypes and their 2n pollen-producer counterparts.


Circular scanning fluorescence correlation spectroscopy on membranes.
We discuss circular scanning Fluorescence Correlation Spectroscopy (sFCS) as a simple extension of standard FCS for accurate, robust and fast diffusion measurements on membranes. The implementation is based on a straightforward conversion of a conventional FCS instrument to a sFCS device by mounting a mirror onto a two-axis piezo scanner. The measurement volume is scanned in a circle with sub-micron radius, allowing the determination of diffusion coefficients and concentrations without any a priori knowledge of the size of the detection volume. This is highly important in measurements on two-dimensional surfaces, where the volume size, and therefore the quantitative outcome of the experiment, is determined by the relative position of the surface and the objective focus, a parameter difficult to control in practice. The technique is applied to diffusion measurements on model membrane systems: supported lipid bilayers and giant unilamellar vesicles. We show that the method is insensitive to membrane positioning and to disturbing processes on faster or slower time scales than diffusion, and yields accurate results even for fluctuating or drifting membranes. Its robustness, short measurement times, and small size of the probed area makes this technique particularly attractive for analyzing the properties of membranes and molecules diffusing and interacting within them.


Detection of ABCB5 tumour antigen-specific CD8+ T cells in melanoma patients and implications for immunotherapy.
ATP binding cassette subfamily B member 5 (ABCB5) has been identified as a tumour-initiating cell marker and is expressed in various malignancies, including melanoma. Moreover, treatment with anti-ABCB5 monoclonal antibodies has been shown to inhibit tumour growth in xenotransplantation models. Therefore, ABCB5 represents a potential target for cancer immunotherapy. However, cellular immune responses against ABCB5 in humans have not been described so far. Here, we investigated whether ABCB5-reactive T cells are present in human melanoma patients and tested the applicability of ABCB5-derived peptides for experimental induction of human T cell responses. Peripheral blood mononuclear cells (PBMNC) isolated from blood samples of melanoma patients (n = 40) were stimulated with ABCB5 peptides, followed by intracellular cytokine staining (ICS) for interferon (IFN)-γ and tumour necrosis factor (TNF)-α. To evaluate immunogenicity of ABCB5 peptides in naive healthy donors, CD8 T cells were co-cultured with ABCB5 antigen-loaded autologous dendritic cells (DC). ABCB5 reactivity in expanded T cells was assessed similarly by ICS. ABCB5-reactive CD8+ T cells were detected ex vivo in 19 of 29 patients, melanoma antigen recognised by T cells (MART-1)-reactive CD8+ T cells in six of 21 patients. In this small, heterogeneous cohort, reactivity against ABCB5 was significantly higher than against MART-1. It occurred significantly more often and independently of clinical characteristics. Reactivity against ABCB5 could be induced in 14 of 16 healthy donors in vitro by repeated stimulation with peptide-loaded autologous DC. As ABCB5-reactive CD8 T cells can be found in the peripheral blood of melanoma patients and an ABCB5-specific response can be induced in vitro in naive donors, ABCB5 could be a new target for immunotherapies in melanoma.


Seed Germination in Chenopodium album L: Relationships between Nitrate and the Effects of Plant Hormones.
Effects of ethylene, gibberellins, and kinetin on the germination of two lots of Chenopodium album L. seeds, collected from the field in 1982 and 1983, were studied in relation to the availability of nitrate. The experiments were conducted in darkness and at temperatures ranging from 12 to 32 degrees C. Ethylene induced over 75% germination in the 1983 seed but had little effect on the 1982 seed. Nitrate was only slightly promotive in either of the two seed lots. A combination of ethylene and nitrate, however, acted synergistically on 1982 seed, resulting in as much germination as that induced in 1983 seed by ethylene alone. In 1983 seed, a combination of ethylene and nitrate was only marginally more effective than ethylene. A similar relationship was observed in the effects of gibberellic acid(4+7) (GA(4+7)) and nitrate on seeds from the two lots. The 1982 seed, which responded synergistically to combinations of nitrate with ethylene or GA(4+7) was found to contain an extremely low endogenous level of nitrate as compared to 1983 seed. Thus, high levels of either endogenous or applied nitrate appeared to enhance the germination response to ethylene or GA(4+7).Kinetin had no effect on 1982 seed and only a small promotive effect on 1983 seed. There was no synergism between kinetin and nitrate in either of the seed lots.


A pilot study examining the effect of mindfulness-based stress reduction on symptoms of chronic mild traumatic brain injury/postconcussive syndrome.
To evaluate the effectiveness of the mindfulness-based stress reduction (MBSR) program tailored to individuals with mild traumatic brain injury (mTBI). A convenience sample recruited from clinical referrals over a 2-year period completed outcome measures pre- and posttreatment intervention. Post-acute brain injury rehabilitation center within a suburban medical facility. Twenty-two individuals with mTBI and a time postinjury more than 7 months. Eleven participants were men and 11 were women, ranging in age from 18 to 62 years. A 10-week group (with weekly 2-hour sessions) modeled after the MBSR program of Kabat-Zinn, but with modifications designed to facilitate implementation in a population of individuals with brain injury. (The treatment involved enhancement of attentional skills, in addition to increased awareness of internal and external experiences associated with the perspective change of acceptance and nonjudgmental attitude regarding those experiences). Perceived Quality of Life Scale, Perceived Self-Efficacy Scale, and the Neurobehavioral Symptom Inventory. Secondary measures included neuropsychological tests, a self-report problem-solving inventory, and a self-report measure of mindfulness. Clinically meaningful improvements were noted on measures of quality of life (Cohen d = 0.43) and perceived self-efficacy (Cohen d = 0.50) with smaller but still significant effects on measures of central executive aspects of working memory and regulation of attention. The MBSR program can be adapted for participants with mTBI. Improved performance on measures associated with improved quality of life and self-efficacy may be related to treatment directed at improving awareness and acceptance, thereby minimizing the catastrophic assessment of symptoms associated with mTBI and chronic disability. Additional research on the comparative effectiveness of the MBSR program for people with mTBI is warranted.


Can culture confirmation of gonococcal infection be improved in female subjects found to be positive by nucleic acid amplification tests in community clinics?
Use of nucleic acid amplification tests (NAATs), such as strand displacement assay (SDA, BD ProbeTec C trachomatis/N gonorrhoeae Amplified DNA Assay), for the detection of gonococcal infection in the community is controversial because of the possibility of false-positive results in low prevalence populations. To evaluate if culture confirmation of gonococcal infection can be improved for subjects found to be positive by BD ProbeTec in community clinics. Two cervical swabs were collected for culture to confirm NAAT positive results in women aged over 16 years-a majority of whom were <25 years and asymptomatic. One swab was urgently transported (UTP) and processed in the laboratory within 2 hours whereas the other swab (RTP) was stored at 4 degrees C, transported at room temperature and processed 4-72 hours after collection depending on the time and day of collection. Altogether, 56 subjects with NAAT positive results were recruited into the study. Nine (16.1%) subjects who were culture negative were excluded from final analysis due to prior antibiotic treatment (4/9) or the culture having been taken more than 1 month after the NAAT was positive (4/9) or an incorrect specimen being received (1/9). Overall, 41/47 (87.2%) NAAT positive subjects were confirmed by culture. In total, 40/47 (85.1%) UTP swabs and 27/47 (57.4%) RTP swabs were positive (p<0.05). This study shows that culture confirmation in NAAT positive subjects in a community gonococcus screening programme can be significantly improved by urgent transportation to and processing of specimens in the laboratory.


Estradiol increases cyclic adenosine monophosphate in rat pulmonary vascular smooth muscle cells by a nongenomic mechanism.
Estrogen, like other steroids, may induce rapid nongenomic cellular effects. We studied the effect on intracellular cAMP of short-term exposure (5 min) of cultured rat pulmonary vascular smooth muscle cells (VSMC) to estradiol 17 beta. At confluence, VSMC were incubated in phosphate buffer saline for 1 hr before exposure to different hormones. The reaction was stopped with 0.1 N HCl and cyclic adenosine monophosphate (cAMP) was measured by radioimmunoassay. The 5-min incubation with estradiol 17 beta (0.3-30 microM) significantly increased basal intracellular cAMP in a concentration-dependent manner. The stimulatory effect of estradiol on cAMP was time-dependent, increasing with prolonged exposure to the hormone, and was not affected by the protein synthesis inhibitor, actinomycin D (5 micrograms/ml), at 5 and 30 min. Comparable concentrations of testosterone or estradiol 17 alpha had no significant effect on cAMP. The estrogen receptor partial agonist, tamoxifen also significantly increased basal cAMP in a concentration-dependent manner, but inhibited the effect of estradiol. Furthermore, forskolin elicited a concentration-dependent increase in cAMP (396.6 +/- 53% at 10 microM concentration), which was significantly potentiated in presence of estradiol. The effect of estradiol is unlikely to be mediated by G-protein activation, because the G protein inhibitor, pertussis toxin (100 ng/ml), did not significantly affect estradiol-induced increase in cAMP. Removal of Ca++ from the incubation medium inhibited the stimulatory effect of estradiol 17 beta suggesting that estradiol may increase pulmonary VSMC cAMP via a Ca(++)-dependent pathway. We suggest that the effect of estradiol 17 beta in these experiments is nongenomic in nature, and is possibly mediated by direct interaction of the hormone with specific membrane binding sites.


Functional neural plasticity and associated changes in positive affect after compassion training.
The development of social emotions such as compassion is crucial for successful social interactions as well as for the maintenance of mental and physical health, especially when confronted with distressing life events. Yet, the neural mechanisms supporting the training of these emotions are poorly understood. To study affective plasticity in healthy adults, we measured functional neural and subjective responses to witnessing the distress of others in a newly developed task (Socio-affective Video Task). Participants' initial empathic responses to the task were accompanied by negative affect and activations in the anterior insula and anterior medial cingulate cortex--a core neural network underlying empathy for pain. Whereas participants reacted with negative affect before training, compassion training increased positive affective experiences, even in response to witnessing others in distress. On the neural level, we observed that, compared with a memory control group, compassion training elicited activity in a neural network including the medial orbitofrontal cortex, putamen, pallidum, and ventral tegmental area--brain regions previously associated with positive affect and affiliation. Taken together, these findings suggest that the deliberate cultivation of compassion offers a new coping strategy that fosters positive affect even when confronted with the distress of others.


Leucine-rich repeat kinase 2-linked Parkinson's disease: clinical and molecular findings.
Mutations in Leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of sporadic and familial late onset Parkinson's disease (PD). The G2019S common mutation has been identified about 1% of sporadic cases and 4-7% of familial cases. Over 50 variants have since been identified in LRRK2, and at least 7 of these are confirmed to be pathogenic. In addition to pathogenic mutations, several common polymorphisms in the LRRK2 gene (G2385R and R1628P) have been identified that may explain up to 10% of sporadic PD in Asian populations. LRRK2 is a large complex multidomain protein with 2,527-amino-acid and the molecular weight is 286 kDa. LRRK2 multidomain protein consists of a catalytic core domain, kinase domain and a number of putative protein-protein interaction domains. LRRK2 mutations found in PD families, including the G2019S and I2020T mutations show increased intrinsic kinase activity, when assessed with myelin basic protein as substrate. The modification of LRRK2 GTPase and kinase activity affecting residues in the ROC, COR and mitogen-activated protein kinase kinase kinases domains is believed to lead to neuronal cell death, but the pathways involved remain unclear. A number of in vivo models in C. elegans, D. melanogaster and mice have been developed to study the patho/physiological function of LRRK2. Based on current literature, a toxic gain of function in LRRK2 kinase activity is a possible pathophysiologic mechanism and thus inhibition of kinase activity in experimental models offers a potential therapeutic strategy for LRRK2-linked PD.


Quantitative analysis of DNA degradation in the dead body.
Postmortem degradation of DNA was quantitatively estimated. Brain, liver, kidney and muscle samples were obtained from sacrificed rats left at 20℃ or 4℃. The quantity of DNA was measured by real-time PCR using a primer set for a sequence in the Rsrc 1 gene. When the quantity of amplified DNA using 10ng Human Genomic DNA was defined as 100 RFU, the quantities in the brain, liver, kidney and skeletal muscle (each 2μg of dry weight) on the day of sacrifice were 253±11, 338±22, 556±14 and 531±12 Relative Fluorescence Units (RFU), respectively (mean±S.E., n=5). The quantity of amplified DNA decreased to below 10 RFU in 1-3 weeks in the liver, kidney and skeletal muscle at 20℃, while that in the brain was more than 10 RFU for six weeks, demonstrating the usefulness of the brain as a sample for DNA analysis of decaying corpses. It was suggested that quantifying the amplified DNA in the brain at 20℃ and in the liver at 4℃ as well as the ratio of the quantity of amplified DNA in the liver to the brain at 4℃ might be useful for diagnosing time of death. This study provides the first quantitative analysis of the postmortem progress of DNA degradation in the corpse.


Punica granatum (Pomegranate) activity in health promotion and cancer prevention.
Cancer has become one of the most fatal diseases in most countries. In spite of the medical care developing, cancer still remains a significant problem. The majority of the cancers are resistant to treatment. Thus, the research for novel, more efficient and less side effect treatment methods continues. Pomegranate contains strong antioxidant activity, with potential health interests. Research concern in pomegranate is increasing because of their anticancer potential due to possess rich in polyphenols. We highlight the pomegranate potential health benefits and mechanism of cancer progression inhibition. Pomegranate has indicated antiproliferative, anti-metastatic and anti-invasive effects on different cancer cell line in vitro, in vivo and clinical trial. The aim of this review is to evaluate functional properties and the medical benifits of pomegranate against various cancer diseases. In addition, pomegranate properties in in vitro and in vivo experimental human and animal clinical trials and its future use are explored. The available data suggest that Punica granatum (pomegranate) might be used in the control and potential therapeutic for some disease conditions and benefits human health status. This review summarizes in vitro, in vivo and clinical trial studies highlighting the pomegranate role in prevent and treatment of breast, prostate, lung, colon, skin and hepatocellular cell cancers.


Diagnoses and factors associated with medical evacuation and return to duty among nonmilitary personnel participating in military operations in Iraq and Afghanistan.
Nonmilitary personnel play an increasingly critical role in modern wars. Stark differences exist between the demographic characteristics, training and missions of military and nonmilitary members. We examined the differences in types of injury and rates of returning to duty among nonmilitary and military personnel participating in military operations in Iraq and Afghanistan. We collected data for nonmilitary personnel medically evacuated from military operations in Iraq and Afghanistan between 2004 and 2007. We compared injury categories and return-to-duty rates in this group with previously published data for military personnel and identified factors associated with return to duty. Of the 2155 medically evacuated nonmilitary personnel, 74.7% did not return to duty. War-related injuries in this group accounted for 25.6% of the evacuations, the most common causes being combat-related injuries (55.4%) and musculoskeletal/spinal injuries (22.9%). Among individuals with non-war-related injuries, musculoskeletal injuries accounted for 17.8% of evacuations. Diagnoses associated with the highest return-to-duty rates in the group of nonmilitary personnel were psychiatric diagnoses (15.6%) among those with war-related injuries and noncardiac chest or abdominal pain (44.0%) among those with non-war-related injuries. Compared with military personnel, nonmilitary personnel with war-related injuries were less likely to return to duty (4.4% v. 5.9%, p = 0.001) but more likely to return to duty after non-war-related injuries (32.5% v. 30.7%, p = 0.001). Compared with military personnel, nonmilitary personnel were more likely to be evacuated with non-war-related injuries but more likely to return to duty after such injuries. For evacuations because of war-related injuries, this trend was reversed.


Visual mismatch negativity elicited by facial expressions: new evidence from the equiprobable paradigm.
Converging evidence revealed that facial expressions are processed automatically. Recently, there is evidence that facial expressions might elicit the visual mismatch negativity (MMN), expression MMN (EMMN), reflecting that facial expression could be processed under non-attentional condition. In the present study, using a cross modality task we attempted to investigate whether there is a memory-comparison-based EMMN. 12 normal adults were instructed to simultaneously listen to a story and pay attention to a non-patterned white circle as a visual target interspersed among face stimuli. In the oddball block, the sad face was the deviant with a probability of 20% and the neutral face was the standard with a probability of 80%; in the control block, the identical sad face was presented with other four kinds of face stimuli with equal probability (20% for each). Electroencephalogram (EEG) was continuously recorded and ERPs (event-related potentials) in response to each kind of face stimuli were obtained. Oddball-EMMN in the oddball block was obtained by subtracting the ERPs elicited by the neutral faces (standard) from those by the sad faces (deviant), while controlled-EMMN was obtained by subtracting the ERPs elicited by the sad faces in the control block from those by the sad faces in the oddball block. Both EMMNs were measured and analyzed by ANOVAs (Analysis of Variance) with repeated measurements. sLORETA (standardized low-resolution brain electromagnetic tomography) was used to investigate the cortical generators of controlled-EMMN. Both the oddball-EMMN in deviant-standard comparison and the controlled-EMMN in deviant-control comparison were observed at occipital-temporal regions with right hemisphere predominance. The oddball-EMMN was bigger and earlier than the controlled-EMMN because, besides the memory-based comparison, the former included a difference of refractoriness due to the distinction of presented probability between the deviant and standard face stimuli. The source analysis of controlled-EMMN indicated a current source primarily involved in posterior areas including superior temporal gyrus, postcentral gyrus, inferior parietal lobule as well as the insula. The valid EMMN properly reflecting the memory-based comparison of facial expressions could be obtained, i.e., the controlled-EMMN.


Jejunoileal anastomosis following small intestinal resection in horses: seven cases (1999-2001).
To report the postoperative outcome in horses undergoing jejunoileal anastomosis performed with a 2-layer simple continuous technique. Retrospective study. 7 horses. Information regarding signalment, clinical signs, findings at surgery, and postoperative complications was obtained from medical records of horses that underwent exploratory ventral midline celiotomy, small intestinal resection, and jejunoileal anastomosis to correct various small intestinal strangulating lesions. Follow-up information was obtained via telephone conversations with owners or trainers. Six males and 1 female of various breeds aged 10 months to 27 years and weighing 312 to 785 kg (686.4 to 1,727 lb) were included. The most common complications were mild to moderate tachycardia and mild to moderate signs of abdominal pain. Two horses developed incisional infections and soft, fluctuant swelling at the incision site following resolution of the infection. Follow-up time ranged from 7 to 17 months after surgery. Owners reported no further colic episodes and no diet change necessary following surgery. All horses had returned to their intended level of use. Advantages to the jejunoileal technique include maintaining the normal ileocecal valve and a postoperative recovery period similar to that described following other small intestinal anastomoses. Jejunoileal anastomosis is a viable alternative to ileal bypass. This technique appears to result in a postoperative complication rate similar to that reported following jejunojejunostomy procedures.


Measuring perceptions related to e-cigarettes: Important principles and next steps to enhance study validity.
Measuring perceptions associated with e-cigarette use can provide valuable information to help explain why youth and adults initiate and continue to use e-cigarettes. However, given the complexity of e-cigarette devices and their continuing evolution, measures of perceptions of this product have varied greatly. Our goal, as members of the working group on e-cigarette measurement within the Tobacco Centers of Regulatory Science (TCORS) network, is to provide guidance to researchers developing surveys concerning e-cigarette perceptions. We surveyed the 14 TCORS sites and received and reviewed 371 e-cigarette perception items from seven sites. We categorized the items based on types of perceptions asked, and identified measurement approaches that could enhance data validity and approaches that researchers may consider avoiding. The committee provides suggestions in four areas: (1) perceptions of benefits, (2) harm perceptions, (3) addiction perceptions, and (4) perceptions of social norms. Across these 4 areas, the most appropriate way to assess e-cigarette perceptions depends largely on study aims. The type and number of items used to examine e-cigarette perceptions will also vary depending on respondents' e-cigarette experience (i.e., user vs. non-user), level of experience (e.g., experimental vs. established), type of e-cigarette device (e.g., cig-a-like, mod), and age. Continuous formative work is critical to adequately capture perceptions in response to the rapidly changing e-cigarette landscape. Most important, it is imperative to consider the unique perceptual aspects of e-cigarettes, building on the conventional cigarette literature as appropriate, but not relying on existing conventional cigarette perception items without adjustment.


Pathway of ADP-stimulated ADP release and dissociation of tethered kinesin from microtubules. Implications for the extent of processivity.
Kinesin binds to microtubules with half-site ADP release to form a tethered intermediate with one attached head without nucleotide and one tethered head that retains its bound ADP. For DKH405 containing amino acid residues 1-405 of Drosophila kinesin, release of the remaining ADP from the tethered head is slow (0.05 s(-1)), but release is accelerated by added ADP or ATP. The maximum rate of ADP-stimulated dissociation of tethered DKH405 from the microtubule is approximately 12 s(-1) as determined by turbidity. Parallel measurements of ADP-stimulated release of 2'(3')-O-(N-methylanthraniloyl)-ADP (mantADP) from the tethered intermediate by fluorescence indicate that the reaction is biphasic with a fast phase that occurs at a rate that is similar to dissociation. The rate of the slow phase is dependent on the concentrations of salt and microtubules and is equal in each case to the rate for bimolecular stimulation of ADP release by microtubules as measured independently. These results are consistent with a scheme in which the fast phase, with approximately one-third of the total amplitude change, is due to ADP-stimulated release of mantADP from the tethered intermediate at approximately 6 s(-1). This direct release of mantADP continues until terminated by dissociation of DKH405 from the microtubule at approximately 12 s(-1). The majority of the amplitude change thus occurs through bimolecular recombination of DKH405.mantADP with microtubules following initial dissociation. Analysis of a simple scheme indicates that hydrolysis of ATP at the attached head before the tethered head can release its ADP and become tightly bound may be the principal limitation to processivity.


R1617Q epilepsy mutation slows NaV 1.6 sodium channel inactivation and increases the persistent current and neuronal firing.
A human NaV 1.6 construct was established to study the biophysical consequences of the R1617Q mutation on NaV 1.6 identified in patients with unclassified epileptic encephalopathy and severe intellectual disability. The R1617Q mutation disrupts the inactivation process of the channel, and more specifically, slows the current decay, increases the persistent sodium current that was blocked by tetrodotoxin and riluzole, and disrupts the inactivation voltage-dependence and increases the kinetics of recovery. In native hippocampal neurons, the R1617Q mutation exhibited a significant increase in action potentials triggered in response to stimulation and a significant increase in the number of neurons that exhibited spontaneous activity compared to neurons expressing WT channels that were inhibited by riluzole. The abnormally persistent current activity caused by the disruption of the channel inactivation process in NaV 1.6/R1617Q may result in epileptic encephalopathy in patients. The voltage-gated sodium channel NaV 1.6 is the most abundantly expressed sodium channel isoform in the central nervous system. It plays a critical role in saltatory and continuous conduction. Although over 40 NaV 1.6 mutations have been linked to epileptic encephalopathy, only a few have been functionally analysed. In the present study, we characterized a NaV 1.6 mutation (R1617Q) identified in patients with epileptic encephalopathy and intellectual disability. R1617Q substitutes an arginine for a glutamine in the S4 segment of domain IV, which plays a major role in coupling the activation and inactivation of sodium channels. We used patch-clamp to show that R1617Q is a gain-of-function mutation. It is typified by slower inactivation kinetics and a loss of inactivation of voltage-dependence, which result in a 2.5-fold increase in the window current. In addition, sodium currents exhibited an enhanced rate of recovery from inactivation, most likely due to the destabilization of the inactivation state. The alterations in the fast inactivation caused a significant increase in the persistent sodium current. Overexpression of R1617Q in rat hippocampal neurons resulted in an increase in action potential firing activity that was inhibited by riluzole, consistent with the gain-of-function observed. We conclude that the R1617Q mutation causes neuronal hyperexcitability and may result in epileptic encephalopathy.


Examining the surface evolution of LaTiOxNy an oxynitride solar water splitting photocatalyst.
LaTiOxNy oxynitride thin films are employed to study the surface modifications at the solid-liquid interface that occur during photoelectrocatalytic water splitting. Neutron reflectometry and grazing incidence x-ray absorption spectroscopy were utilised to distinguish between the surface and bulk signals, with a surface sensitivity of 3 nm. Here we show, contrary to what is typically assumed, that the A cations are active sites that undergo oxidation at the surface as a consequence of the water splitting process. Whereas, the B cations undergo local disordering with the valence state remaining unchanged. This surface modification reduces the overall water splitting efficiency, but is suppressed when the oxynitride thin films are decorated with a co-catalyst. With this example we present the possibilities of surface sensitive studies using techniques capable of operando measurements in water, opening up new opportunities for applications to other materials and for surface sensitive, operando studies of the water splitting process.


The schizophrenia-rheumatoid arthritis connection: infectious, immune, or both?
Schizophrenia and rheumatoid arthritis share an impressive number of similarities. Both are chronic, relapsing diseases of unknown etiology. Both became prominent in the early 19th century and have prevalences of approximately 1% in North America and Europe. Both run in families, have pairwise concordance rates of approximately 30% among monozygotic twins, and are more common among individuals born in urban areas. For both diseases, studies have reported greater exposure to cats in childhood than in controls. Both diseases have been associated with similar class II HLA antigens. Both have also been suspected of having infectious etiology, with similar agents--retroviruses, herpesviruses including EBV, and Toxoplasma gondii--having been associated in some cases. Since there is also a well-documented inverse correlation between these two diseases, it is possible that they share a common infectious and/or immune etiology and that once a person gets one of the diseases then they are relatively immune to the other.


Effects of 'target' plant species body size on neighbourhood species richness and composition in old-field vegetation.
Competition is generally regarded as an important force in organizing the structure of vegetation, and evidence from several experimental studies of species mixtures suggests that larger mature plant size elicits a competitive advantage. However, these findings are at odds with the fact that large and small plant species generally coexist, and relatively smaller species are more common in virtually all plant communities. Here, we use replicates of ten relatively large old-field plant species to explore the competitive impact of target individual size on their surrounding neighbourhoods compared to nearby neighbourhoods of the same size that are not centred by a large target individual. While target individuals of the largest of our test species, Centaurea jacea L., had a strong impact on neighbouring species, in general, target species size was a weak predictor of the number of other resident species growing within its immediate neighbourhood, as well as the number of resident species that were reproductive. Thus, the presence of a large competitor did not restrict the ability of neighbouring species to reproduce. Lastly, target species size did not have any impact on the species size structure of neighbouring species; i.e. they did not restrict smaller, supposedly poorer competitors, from growing and reproducing close by. Taken together, these results provide no support for a size-advantage in competition restricting local species richness or the ability of small species to coexist and successfully reproduce in the immediate neighbourhood of a large species.


Cost-comparativeness of proton versus photon therapy.
Proton beam radiotherapy (PBT) offers great promise in the treatment of a wide variety of cancers owing to the sharp drop-off in radiation dose at a defined point, known as the Bragg peak, beyond which there is no appreciable dose. However, it is also well-understood that PBT is associated with large economic costs, including both capital investment and operating costs. From a medical as well as societal perspective, therefore, it is important to be aware of the economic implications of new technologies such as PBT, and to evaluate the cost effectiveness based on different clinical and treatment scenarios. This review examines PBT from a health economics perspective, evaluating both the design and results of costeffectiveness (CE) studies that have been performed previously. We further examine several salient variables that can affect CE of PBT, including patient, tumor, treatment, and logistical factors. We discuss the implication of technological advances on PBT delivery, and its impact on overall healthcare delivery costs. Additionally, we evaluate the status of economic analyses for PBT and discuss the role of ongoing and future CE studies in better defining the economic role of PBT as part of modern cancer therapy.


Densitometric assay of nanogram quantities of proteoglycans precipitated on nitrocellulose membrane with Safranin O.
Proteoglycan (PG) and glycosaminoglycan (GAG) samples corresponding to a minimum of 10 ng of uronic acid were reliably quantified as precipitates with the cationic dye Safranin O, collected by vacuum-aided filtration onto a cellulose acetate/nitrate membrane in a standard 96-well dot assay apparatus. The reflectances of the precipitation dots were measured by automatic densitometric scanning of the membrane sheets. Standard GAGs produced reflectance values which were related to the number of anionic groups per unit disaccharide; hyaluronate and keratan sulfate gave lower values while heparin yielded values higher than those of chondroitin sulfates. The presence of 8 M urea, 1% Triton X-100, 30% sucrose, 0.02% NaN3, or mixtures of proteinase inhibitors and various buffers did not markedly influence the reflectances, while 4 M guanidinium chloride and 3 M CsCl reduced the sensitivity of the assay to 30-50 ng. Samples containing sodium dodecyl sulfate (SDS) were not applicable because SDS precipitated with Safranin O. Proteins showed virtually no response, while nucleic acids gave significant although smaller reflectances than GAGs. Owing to its marked sensitivity and convenience the method is particularly suitable for the detection of PGs during their preparative purification and fractionation as well as in various analytical assays.


Dreaming of toilets: using photovoice to explore knowledge, attitudes and practices around water-health linkages in rural Kenya.
As part of a knowledge, attitudes, practices and empowerment (KAPE) project implemented by the United Nations University Institute for Water, Environment and Health (UNU-INWEH) in the Lake Victoria Basin, this paper reports findings from a photovoice study with women in Usoma, a lakeshore community in Western Kenya. Drawing on ecosocial and political ecology theory, findings reveal that access to water, perceptions and practices were shaped by ecological and broader structural factors. Further, collective actions to improve access were constrained by institutional and economic structures, thus (re)enforcing inequalities.


Crystal cell rupture after injury in Drosophila requires the JNK pathway, small GTPases and the TNF homolog Eiger.
The prophenoloxidase-activating cascade is a key component of arthropod immunity. Drosophila prophenoloxidase is stored in crystal cells, a specialized class of blood cells from which it is released through cell rupture. Within minutes after bleeding, prophenoloxidase is activated leading to visible melanization of the clot matrix. Using crystal cell rupture and melanization as readouts to screen mutants in signal transduction pathways, we show that prophenoloxidase release requires Jun N-terminal kinase, small Rho GTPases and Eiger, the Drosophila homolog of tumor necrosis factor. We also provide evidence that in addition to microbial products, endogenous signals from dying hemocytes contribute to triggering and/or assembly of the prophenoloxidase-activating cascade, and that this process can be inhibited in vitro and in vivo using the viral apoptotic inhibitor p35. Our results provide a more comprehensive view of immune signal transduction pathways, with implications for immune reactions where cell death is used as a terminal mode of cell activation.


Locally advanced asymptomatic papillary thyroid cancer presenting with retropharyngeal lymph node metastasis symptoms.
Papillary thyroid cancer (PTC) rarely metastasizes to the retropharyngeal lymph nodes. Managing patients with locally advanced primary PTC and metastasis located in distant anatomical areas is challenging. Herein, we report a 56-year-old patient with locally advanced asymptomatic PTC, who presented with obstructive airway symptoms due to the metastatic retropharyngeal lymph node. The patient underwent simultaneous total thyroidectomy, central lymph node dissection, en bloc resection of strap muscle and left laryngeal nerve via cervical approach and transoral resection of the metastatic retropharyngeal lymph node. Metastatic PTC should be included in the differential diagnosis of a retropharyngeal masses. Simultaneous total thyroidectomy of the primary thyroid cancer via a cervical approach and transoral resection of an isolated retropharyngeal metastasis is safe and feasible.


National Standards for Public Involvement in Research: missing the forest for the trees.
Biomedical research funding bodies across Europe and North America increasingly encourage-and, in some cases, require-investigators to involve members of the public in funded research. Yet there remains a striking lack of clarity about what 'good' or 'successful' public involvement looks like. In an effort to provide guidance to investigators and research organisations, representatives of several key research funding bodies in the UK recently came together to develop the National Standards for Public Involvement in Research. The Standards have critical implications for the future of biomedical research in the UK and in other countries as researchers and funders abroad look to the Standards as a model for their own policy development. We assess the Standards and find that despite offering useful suggestions for dealing with practical challenges associated with public involvement, the Standards fail to address fundamental questions about when, why and with whom public involvement should be undertaken in the first place. We show that presented without this justificatory context, many of the recommendations in the Standards are, at best, fragments that require substantial elaboration by those looking to apply the Standards in their own work and, at worst, subject to potentially harmful misapplication by well-meaning investigators. As funding bodies increasingly push for public involvement in research, the key lesson of our analysis is that future recommendations about how public involvement should be conducted cannot be coherently formulated without a clear sense of the underlying goals and rationales for public involvement.


Pathogenicity, Virulence, and Vegetative Compatibility Grouping of Verticillium Isolates from Spinach Seed.
In 2005, Verticillium dahliae was first reported to be pathogenic to spinach seed crops in the Pacific Northwest, with symptoms only developing after initiation of the reproductive stage of plant growth, and to be prevalent on commercial spinach seed lots produced in Denmark, The Netherlands, and the United States. In this study, the genetic diversity, pathogenicity, and virulence were examined for a collection of isolates of Verticillium spp. from spinach as well as other hosts (alfalfa, cotton, lettuce, mint, peppermint, potato, radish, and tomato) from various countries and from different vegetative compatibility groups (VCGs). Of a total of 210 isolates of V. dahliae obtained from spinach seed produced in Denmark, the Netherlands, New Zealand, or the United States, 128 were assigned to VCG 4B (89% of 91 U.S. isolates, 86% of 42 isolates from the Netherlands, 19% of 43 Denmark isolates, and 8% of 13 New Zealand isolates), 65 to VCG 2B (92% of the New Zealand isolates, 79% of the Denmark isolates, 14% of the Netherlands isolates, and 9% of the U.S. isolates), and 3 to VCG 2A (2% of each of the Denmark and U.S. isolates, and 0% of the Netherlands and New Zealand isolates); 14 isolates could not be assigned to a VCG. Although little variation in the sequence of the internal transcribed spacer (ITS) region of ribosomal DNA was observed among isolates within each Verticillium sp., the ITS region readily differentiated isolates of the species V. dahliae, V. tricorpus, and Gibellulopsis nigrescens (formerly V. nigrescens) obtained from spinach seed. Greenhouse pathogenicity assays on spinach, cotton, lettuce, and tomato plants using isolates of V. dahliae (n = 29 to 34 isolates), V. tricorpus (n = 3), G. nigrescens (n = 2), and V. albo-atrum (n = 1) originally obtained from these hosts as well as from alfalfa, mint, peppermint, potato, and radish, revealed a wide range in virulence among the isolates. Isolates of V. tricorpus and G. nigrescens recovered from spinach seed and an isolate of V. albo-atrum from alfalfa were not pathogenic on spinach. In addition, isolates of V. dahliae from mint and peppermint were not pathogenic or only weakly virulent on the hosts evaluated. Although there was a wide range in virulence among the isolates of V. dahliae tested, all of the V. dahliae isolates caused Verticillium wilt symptoms on spinach, lettuce, tomato, and cotton. None of the isolates of V. dahliae showed host specificity. These results indicate that Verticillium and related species associated with spinach seed display substantial variability in virulence and pathogenicity to spinach and other plants but the V. dahliae isolates were restricted to three VCGs.


Maintaining functional independence in elderly adults: the roles of health status and financial resources in predicting home modifications and use of mobility equipment.
We investigated whether health status (i.e., need characteristics) and financial resources (i.e., enabling characteristics) were important predictors of two types of functional adaptations among elderly adults: home modifications such as putting nonslip tape on rugs or installing more telephones and use of equipment for mobility or activities of daily living (ADLs) such as canes or walkers. Participants were identified from the National Survey of Self-Care and Aging (n = 3,485), a nationally representative sample of noninstitutionalized U.S. adults aged 65 and older. Need and enabling characteristics were used to predict home modifications and equipment use in multinomial logistic analysis, controlling for predisposing characteristics. Although several health-status (need) variables had significant, direct effects on functional adaptations, the effects of ADL limitations were diminished at higher levels of impairment. Among the financial (enabling) variables, subjective income measures and supplemental insurance had significant, direct effects on functional adaptations. Promotion of functional adaptations among elderly people may benefit from both a proactive approach that targets elders with few limitations and a consideration of financial factors in addition to health status.


Qualitative and quantitative effects of harmonic echocardiographic imaging on endocardial edge definition and side-lobe artifacts.
Harmonic imaging is a new ultrasonographic technique that is designed to improve image quality by exploiting the spontaneous generation of higher frequencies as ultrasound propagates through tissue. We studied 51 difficult-to-image patients with blinded side-by-side cineloop evaluation of endocardial border definition by harmonic versus fundamental imaging. In addition, quantitative intensities from cavity versus wall were compared for harmonic versus fundamental imaging. Harmonic imaging improved left ventricular endocardial border delineation over fundamental imaging (superior: harmonic = 71.1%, fundamental = 18.7%; similar: 10.2%; P <.001). Quantitative analysis of 100 wall/cavity combinations demonstrated brighter wall segments and more strikingly darker cavities during harmonic imaging (cavity intensity on a 0 to 255 scale: fundamental = 15.6 +/- 8.6; harmonic = 6.0 +/- 5.3; P <.0001), which led to enhanced contrast between the wall and cavity (1.89 versus 1.19, P <.0001). Harmonic imaging reduces side-lobe artifacts, resulting in a darker cavity and brighter walls, thereby improving image contrast and endocardial delineation.


Repellency of citronella for head lice: double-blind randomized trial of efficacy and safety.
Head lice move easily from head to head. The lack of safe, effective repellents leads to reinfestation. To test the efficacy of a slow-release citronella formulation as a repellent against the head louse. During 4 months in 2003 a randomized, placebo-controlled double-blind clinical study was conducted in four elementary schools; 103 children were treated with the test formulation and 95 with a placebo. A significant difference was observed during the second examination 2 months later, when 12.0% of the children treated with the test repellent and 50.5% of those treated with placebo were infested with lice. A significant difference was also observed at the third examination 2 months later, when 12.4% of the children treated with the test repellent and 33.7% treated with placebo were infested. Overall, there were significant differences between those treated with the repellent and those treated with the placebo (15.4% and 55.1% respectively, P < 0.0001). Side effects were observed in 4.4% of children who disliked the odor of the formulation, and an additional 1.0% who complained of a slight itching and burning sensation. Use of an effective repellent could significantly lower the incidence of reinfestations, which would lower expenditure on lice control, including pediculicides, combs and products for nit removal, and the time spent on treatment and removal of the nits.


The core competencies for mental, neurological, and substance use disorder care in sub-Saharan Africa.
The 2010 Global Burden of Disease Study points to a changing landscape in which non-communicable diseases, such as mental, neurological, and substance use (MNS) disorders, account for an increasing proportion of premature mortality and disability globally. Despite evidence of the need for care, a remarkable deficit of providers for MNS disorder service delivery persists in sub-Saharan Africa. This critical workforce can be developed from a range of non-specialist and specialist health workers who have access to evidence-based interventions, whose roles, and the associated tasks, are articulated and clearly delineated, and who are equipped to master and maintain the competencies associated with providing MNS disorder care. In 2012, the Neuroscience Forum of the Institute of Medicine convened a meeting of key stakeholders in Kampala, Uganda, to discuss a set of candidate core competencies for the delivery of mental health and neurological care, focusing specifically on depression, psychosis, epilepsy, and alcohol use disorders. This article discusses the candidate core competencies for non-specialist health workers and the complexities of implementing core competencies in low- and middle-income country settings. Sub-Saharan Africa, however, has the potential to implement novel training initiatives through university networks and through structured processes that engage ministries of health. Finally, we outline challenges associated with implementing competencies in order to sustain a workforce capable of delivering quality services for people with MNS disorders.


Interventions shown to aid executive function development in children 4 to 12 years old.
To be successful takes creativity, flexibility, self-control, and discipline. Central to all those are executive functions, including mentally playing with ideas, giving a considered rather than an impulsive response, and staying focused. Diverse activities have been shown to improve children's executive functions: computerized training, noncomputerized games, aerobics, martial arts, yoga, mindfulness, and school curricula. All successful programs involve repeated practice and progressively increase the challenge to executive functions. Children with worse executive functions benefit most from these activities; thus, early executive-function training may avert widening achievement gaps later. To improve executive functions, focusing narrowly on them may not be as effective as also addressing emotional and social development (as do curricula that improve executive functions) and physical development (shown by positive effects of aerobics, martial arts, and yoga).


Estimation of genetic parameters for hip dysplasia in Czech Labrador Retrievers.
The objective of this study was to estimate the genetic parameters, genetic trends and breeding values using linear model (LM) and threshold model (TM) for the development of hip dysplasia (HD) in Labrador Retrievers in the Czech Republic (n = 3151). The right and left hip joints were evaluated separately using the Fédération Cynologique Internationale scoring system. Four linear and four TMs were tested for the correct estimation of genetic parameters. All the tested models utilized fixed effects of sex, assessor, year of birth, regression of age at evaluation, random direct genetic effects and the effect of the animals' permanent environments. The models differed in the inclusion of the following effects: fixed effects of regression of inbreeding coefficient, random maternal effect and random effect of the maternal permanent environment. Compared to the TM, the LM provided lower coefficients of direct (0.25-0.29 versus 0.26-0.35) and maternal heritability (0.01-0.02 versus 0.03-0.05), repeatability (0.76-0.77 versus 0.78-0.83) and of the correlation between direct and maternal effects (-0.55 to -0.21 versus -0.80 to -0.27). In the tested models, no statistical significance was found for fixed regression of inbreeding coefficients or for the random effect of the permanent maternal environment. In spite of the similarity of the LM and TM results, the TM is recommended as the more suitable model for estimating genetic parameters and subsequent breeding values for HD in Labrador Retrievers in the Czech Republic.


Alterations in blood viscosity in horses competing in cross country jumping.
Packed cell volume and plasma total protein (TP), serum albumin (Alb) and globulin (Glb), and plasma ionized calcium (PCa) concentrations, blood viscosity (BV), and plasma viscosity (PV) were measured in 42 horses at rest and after the cross country jumping phase of a horse trial competition. The BV and PV were determined at 6 shear rates (230, 115, 46, 23, 11.5, 5.75 s-1), using a digital rotational cone and plate microviscometer. A paired t-test was used to determine differences between PCV, TP, Alb, Glb and PCa values at rest and after exercise. The PCV, TP, Alb, and Glb values increased (P < 0.05) in horses after exercise. The PCa concentration decreased (P < 0.05) in horses after exercise. Mean BV and PV in the 42 horses at rest and after exercise were fitted to an asymptotic function. Significant (P < 0.05) correlation at all shear rates was seen between BV at rest and PCV, TP, Alb, Glb, and PCa values at rest; and between BV after exercise and PCV, TP, Alb, Glb, and PCa values after exercise. Significant correlation was not seen between PV at rest and TP, Alb, Glb, and PCa at rest, or between PV after exercise and TP, Alb, Glb, and PCa concentrations after exercise at any shear rate.


Analysis of Inpatient Falls After Total Knee Arthroplasty in Patients With Continuous Femoral Nerve Block.
Continuous femoral nerve block (cFNB) is thought to increase the risk of falls after total knee arthroplasty (TKA). Previous studies have failed to consider the timing of cFNB removal in relation to inpatient falls. We investigated all inpatient falls after TKA over a 3-year period using our institutional safety report database. Ninety-five falls were reported from a total of 3745 patients. The frequency of falls after TKA persisted at a similar rate despite removal of cFNB and likely regression of femoral nerve block. Other modifiable risk factors may play a more prominent role in falls risk after TKA.


Study of Microbial Interaction Formed by "Candida krusei" and "Candida glabrata": "In Vitro" and "In Vivo" Studies.
Recently, the non-albicans Candida species have become recognized as an important source of infection and oral colonization by association of different species in a large number of immunosuppressed patients. The objective of this study was to evaluate the interactions between C. krusei and C. glabrata in biofilms formed in vitro and their ability to colonize the oral cavity of mouse model. Monospecies and mixed biofilms were developed of each strain, on 96-well microtiter plates for 48 h. These biofilms were analyzed by counting colony-forming units (CFU/mL) and by determining cell viability, using the XTT hydroxide colorimetric assay. For the in vivo study, twenty-four mice received topical applications of monospecie or mixed suspensions of each strain. After 48 h, yeasts were recovered from the mice and quantified by CFU/mL count. In the biofilm assays, the results for the CFU/mL count and the XTT assay showed that the two species studied were capable of forming high levels of in vitro monospecie biofilm. In mixed biofilm, the CFU of C. krusei increased (p=0.0001) and C. glabrata decreased (p=0.0001). The metabolic activity observed in XTT assay of mixed biofilm was significantly reduced compared with a single C. glabrata biofilm (p=0.0001). Agreeing with CFU in vitro count, C. glabrata CFU/mL values recovered from oral cavity of mice were statistically higher in the group with single infection (p=0.0001) than the group with mixed infection. We concluded that C. krusei inhibits C. glabrata and takes advantage to colonize the oral cavity and to form biofilms.


A Review on Breathing Behaviors of Metal-Organic-Frameworks (MOFs) for Gas Adsorption.
Metal-organic frameworks (MOFs) are a new class of microporous materials that possess framework flexibility, large surface areas, "tailor-made" framework functionalities, and tunable pore sizes. These features empower MOFs superior performances and broader application spectra than those of zeolites and phosphine-based molecular sieves. In parallel with designing new structures and new chemistry of MOFs, the observation of unique breathing behaviors upon adsorption of gases or solvents stimulates their potential applications as host materials in gas storage for renewable energy. This has attracted intense research energy to understand the causes at the atomic level, using in situ X-ray diffraction, calorimetry, Fourier transform infrared spectroscopy, and molecular dynamics simulations. This article is developed in the following order: first to introduce the definition of MOFs and the observation of their framework flexibility. Second, synthesis routes of MOFs are summarized with the emphasis on the hydrothermal synthesis, owing to the environmental-benign and economically availability of water. Third, MOFs exhibiting breathing behaviors are summarized, followed by rationales from thermodynamic viewpoint. Subsequently, effects of various functionalities on breathing behaviors are appraised, including using post-synthetic modification routes. Finally, possible framework spatial requirements of MOFs for yielding breathing behaviors are highlighted as the design strategies for new syntheses.


Shedding light on the different behavior of ionic and nonionic surfactants in emulsion polymerization: from atomistic simulations to experimental observations.
Although surfactants are known to play a vital role in polymerization reactions carried out in dispersed media, many aspects of their use are poorly understood, perhaps none more so than the vastly different action of ionic and nonionic surfactants in emulsion polymerization. In this work, we combine experimental measurements of emulsion polymerization of styrene with atomistic molecular dynamics simulations to better understand the behavior of surfactants at monomer/polymer-water interfaces. In a batch emulsion polymerization of styrene, the nonionic surfactant Disponil AFX 1080 leads to two nucleation periods, in contrast to the behavior observed for the ionic surfactant SDS. This can be explained by the absorption of the nonionic surfactant into the organic phase at the early stages of the polymerization reaction which is then released as the reaction progresses. Indeed, we find that the partition coefficient of the surfactant between the organic phase and water increases with the amount of monomer in the former, and preferential partitioning is detected to organic phases containing at least 55% styrene. Results from molecular dynamics simulations confirm that spontaneous dissolution of the non-ionic surfactant into a styrene-rich organic phase occurs above a critical concentration of the surfactant adsorbed at the interface. Above this critical concentration, a linear correlation between the amount of surfactant adsorbed at the interface and that absorbed inside the organic phase is observed. To facilitate this absorption into a completely hydrophobic medium, water molecules accompany the intruding surfactants. Similar simulations but with the ionic surfactant instead did not result in any absorption of the surfactant into a neat styrene phase, likely because of its strongly hydrophilic head group. The unusual partitioning behavior of nonionic surfactants explains a number of observable features of emulsion polymerization reactions which use nonionic surfactants and should help with future development of processes for improved control over polymerization.


Raynaud syndrome.
Raynaud syndrome (RS) was first described by the French physician Maurice Raynaud in 1862 with the characteristic tricolor change featuring pallor (ischemic phase), cyanosis (deoxygenation phase), and erythema (reperfusion phase) induced by cold or stress. Although the underlying pathophysiological mechanism is unclear, alterations in activity of the peripheral adrenoceptor have been implicated, specifically an enhanced smooth muscle contraction due to overexpression or hyperactivity of postsynaptic alpha 2 receptors. There are 2 ways that RS can appear clinically; isolated, formerly referred as Raynaud disease or now primary RS and in association with other conditions, usually connective tissue disorders (eg, Sjögren syndrome, systemic lupus erythematosus, scleroderma, and rheumatoid arthritis), frequently called Raynaud phenomenon or secondary RS. The estimated prevalence in the general population is 3%-5%, with a higher prevalence in women than in men. The diagnosis is mainly clinical, based on patient descriptions of skin changes. Upper extremity pulse-volume recording is used to rule out proximal arterial obstruction. The differentiation between a vasospastic vs and obstructive mechanism is made using digital pressures and photoplethysmography, where an obstructive mechanism has decreased pressures and blunted waveforms. Cold challenge testing, such as ice water immersion with temperature recovery, is highly sensitive but lack specificity. Serologic screening (antinuclear antibody and rheumatoid factor) is advocated to rule out associated connective tissue disorders. Most patients with RS can be managed conservatively, with avoidance of cold exposure or hand warming. For those in whom conservative management is inadequate, a number of pharmacologic and surgical therapies have been used. Owing to lack of complete understanding of the underlying pathophysiology, targeted therapy has not been possible; rather, therapy has been focused on the use of general vasodilation strategies. In this review, the diagnosis, natural history, and current medical and invasive therapy are summarized.


The NIEHS Xenopus maternal EST project: interim analysis of the first 13,879 ESTs from unfertilized eggs.
The sequencing of expressed sequence tags (ESTs) from Xenopus laevis has lagged behind efforts on many other common experimental organisms and man, partly because of the pseudotetraploid nature of the Xenopus genome. Nonetheless, large collections of Xenopus ESTs would be useful in gene discovery, oligonucleotide-based knockout studies, gene chip analyses of normal and perturbed development, mapping studies in the related diploid frog X. tropicalis, and for other reasons. We have created a normalized library of cDNAs from unfertilized Xenopus eggs. These cells contain all of the information necessary for the first several cell divisions in the early embryo, as well as much of the information needed for embryonic pattern formation and cell fate determination. To date, we have successfully sequenced 13,879 ESTs out of 16,607 attempts (83.6% success rate), with an average sequence read length of 508 bp. Using a fragment assembly program, these ESTs were assembled into 8,985 'contigs' comprised of up to 11 ESTs each. When these contigs were used to search publicly available databases, 46.2% bore no relationship to protein or DNA sequences in the database at the significance level of 1e-6. Examination of a sample of 100 of the assembled contigs revealed that most ( approximately 87%) were comprised of two apparent allelic variants. Expression profiles of 16 of the most prominent contigs showed that 12 exhibited some degree of zygotic expression. These findings have implications for sequence-specific applications for Xenopus ESTs, particularly the use of allele-specific oligonucleotides for knockout studies, differential hybridization techniques such as gene chip analysis, and the establishment of accurate nomenclature and databases for this species.


Extracellular Adenosine Production by ecto-5'-Nucleotidase (CD73) Enhances Radiation-Induced Lung Fibrosis.
Radiation-induced pulmonary fibrosis is a severe side effect of thoracic irradiation, but its pathogenesis remains poorly understood and no effective treatment is available. In this study, we investigated the role of the extracellular adenosine as generated by the ecto-5'-nucleotidase CD73 in fibrosis development after thoracic irradiation. Exposure of wild-type C57BL/6 mice to a single dose (15 Gray) of whole thorax irradiation triggered a progressive increase in CD73 activity in the lung between 3 and 30 weeks postirradiation. In parallel, adenosine levels in bronchoalveolar lavage fluid (BALF) were increased by approximately 3-fold. Histologic evidence of lung fibrosis was observed by 25 weeks after irradiation. Conversely, CD73-deficient mice failed to accumulate adenosine in BALF and exhibited significantly less radiation-induced lung fibrosis (P < 0.010). Furthermore, treatment of wild-type mice with pegylated adenosine deaminase or CD73 antibodies also significantly reduced radiation-induced lung fibrosis. Taken together, our findings demonstrate that CD73 potentiates radiation-induced lung fibrosis, suggesting that existing pharmacologic strategies for modulating adenosine may be effective in limiting lung toxicities associated with the treatment of thoracic malignancies. Cancer Res; 76(10); 3045-56. ©2016 AACR.


Microbial enrichment and gene functional categories revealed on the walls of a spent fuel pool of a nuclear power plant.
Microorganisms developing in the liner of the spent fuel pool (SFP) and the fuel transfer channel (FTC) of a Nuclear Power Plant (NPP) can form high radiation resistant biofilms and cause corrosion. Due to difficulties and limitations to obtain large samples from SFP and FTC, cotton swabs were used to collect the biofilm from the wall of these installations. Molecular characterization was performed using massively parallel sequencing to obtain a taxonomic and functional gene classification. Also, samples from the drainage system were evaluated because microorganisms may travel over the 12-meter column of the pool water of the Brazilian Nuclear Power Plant (Angra1), which has been functioning since 1985. Regardless of the treatment of the pool water, our data reveal the unexpected presence of Fungi (Basidiomycota and Ascomycota) as the main contaminators of the SFP and FTC. Ustilaginomycetes (Basidiomycota) was the major class contributor (70%) in the SFP and FTC reflecting the little diversity in these sites; nevertheless, Proteobacteria, Actinobacteria, Firmicutes (Bacilli) were present in small proportions. Mapping total reads against six fungal reference genomes indicate that there is, in fact, a high abundance of fungal sequences in samples collected from SFP and FTC. Analysis of the ribosomal internal transcribed spacer (ITS) 1 and 2 regions and the protein found in the mitochondria of eukaryotic cells, cytochrome b (cytb) grouped our sample fungi in the clade 7 as Ustilago and Pseudozyma. In contrast, in the drainage system, Alphaproteobacteria were present in high abundances (55%). The presence of Sphingopyxis, Mesorhizobium, Erythrobacter, Sphingomonas, Novosphingobium, Sphingobium, Chelativorans, Oceanicaulis, Acidovorax, and Cyanobacteria was observed. Based on genomic annotation data, the assessment of the biological function found a higher proportion of protein-coding sequences related to respiration and protein metabolism in SFP and FTC samples. The knowledge of this biological inventory present in the system may contribute to further studies of potential microorganisms that might be useful for bioremediation of nuclear waste.


Lower than expected hepatitis B virus infection prevalence among first generation Koreans in the U.S.: results of HBV screening in the Southern California Inland Empire.
Hepatitis B virus (HBV) infection is prevalent in Asian immigrants in the USA. California's Inland Empire region has a population of approximately four million, including an estimated 19,000 first generation Koreans. Our aim was to screen these adult individuals to establish HBV serological diagnoses, educate, and establish linkage to care. A community-based program was conducted in Korean churches from 11/2009 to 2/2010. Subjects were asked to complete a HBV background related questionnaire, provided with HBV education, and tested for serum HBsAg, HBsAb and HBcAb. HBsAg positive subjects were tested for HBV quantitative DNA, HBeAg and HBeAb, counseled and directed to healthcare providers. Subjects unexposed to HBV were invited to attend a HBV vaccination clinic. A total of 973 first generation Koreans were screened, aged 52.3y (18-93y), M/F: 384/589. Most (75%) had a higher than high school education and were from Seoul (62.2%). By questionnaire, 24.7% stated they had been vaccinated against HBV. The serological diagnoses were: HBV infected (3.0%), immune due to natural infection (35.7%), susceptible (20.1%), immune due to vaccination (40.3%), and other (0.9%). Men had a higher infection prevalence (4.9% vs. 1.7%, p = 0.004) and a lower vaccination rate (34.6% vs. 44.0%, p = 0.004) compared to women. Self-reports of immunization status were incorrect for 35.1% of subjects. This large screening study in first generation Koreans in Southern California demonstrates: 1) a lower than expected HBV prevalence (3%), 2) a continued need for vaccination, and 3) a need for screening despite a reported history of vaccination.


Ischemic complications of surgery for anterior choroidal artery aneurysms.
Anterior choroidal artery (AChA) aneurysms account for 4% of all intracranial aneurysms. The surgical approach is similar to that for other supraclinoid carotid artery lesions, but surgery may involve a higher risk of debilitating ischemic complications because of the critical territory supplied by the AChA. Between 1968 and 1999, 51 AChA aneurysms in 50 patients were treated using craniotomy and clipping at the Mayo Clinic. There were 22 men (44%) and 28 women (56%) whose average age was 53 years (range 27-79 years). Twenty-four AChA aneurysms (47%) had hemorrhaged; nine patients (18%) had subarachnoid hemorrhage from another aneurysm. Three AChA aneurysms (6%) were associated with symptoms other than rupture. Forty-one patients (82%) achieved a Glasgow Outcome Scale (GOS) score of 4 or 5 at long-term follow up. The surgical mortality rate was 4%, and major surgical morbidity (GOS < or = 3) was 10%. Eight patients (16%) had clinically and computerized tomography-demonstrated AChA territory infarcts. Five of these strokes manifested in a delayed fashion 6 to 36 hours after the operation, and progressed from mild to complete deficit over hours. In 41 patients the aneurysm arose from the internal carotid artery adjacent to the AChA, and in nine patients the aneurysm arose directly from the origin of the AChA itself; four of these nine patients had postoperative infarction. Surgical treatment of AChA aneurysms involves a significant risk of debilitating ischemic complications. Most postoperative strokes occur in a delayed fashion, offering a potential therapeutic window. Patients with aneurysms arising from the AChA itself have an extremely high risk for postoperative stroke.


Accuracy of frozen section for lymph node metastasis in patients undergoing radical hysterectomy for carcinoma of the cervix.
The efficacy of frozen section in detecting metastases in pelvic and or periaortic lymph nodes during radical hysterectomy is unknown. The finding of positive nodes may result in termination of the operative procedure. In this study, we attempted to determine the accuracy of frozen sections in this situation. Intraoperative pathology consultation records were examined for 127 patients undergoing surgical exploration for radical hysterectomy between 1977 and 1992. Microscopic slides of lymph nodes were reviewed for accuracy. Metastasis diameters were measured and blocks cut five close microtome levels deeper. In 19 cases (15%) positive nodes were documented on permanent section, with metastases ranging in size from less than 1 to 19 mm. Thirteen cases of node metastasis were diagnosed at frozen section. All were suspicious to the pathologist on palpation and gross inspection after bisection. Six cases were missed by sampling error on frozen section; in 4, metastases were smaller than 1 mm; in 1, between 2 and 3 mm; and in 1, 19 mm. The sensitivity was 68%, the false-negative rate was 32%, and the specificity was 100%. No cases were false positive at frozen section. The frequency of nodal metastasis and detection rate by frozen section did not differ significantly between carcinoma types. No micrometastases (< 2 mm) were detected by frozen section. All micrometastases were no longer present within five microtome levels. Frozen section diagnosis of pelvic node metastasis is a highly specific procedure which should alter intraoperative management of early-stage cervical cancer.