[What do the numbers tell us about the temporal evolution of Chagas' disease?]
Chagas disease remains highly prevalent in Chile, especially between the regions of Arica and Parinacota, and Coquimbo. Since 1999 it is considered that in Chile the vector transmission was interrupted. Under this premise, the epidemiological dynamics should be changing. We analyzed the evolution of the prevalence of Chagas' disease analyzing 64,995 xenodiagnosis performed in the laboratory of Parasitology of the Faculty of Medicine of the University of Chile between 1949 and 2014. The evolution of the mortalities and incidences from the databases of the Ministry of Health in the periods in which it was analyzed. The rates of domiciliary infestation and the number of vector insects sent to the Public Health Institute and its trypano-triatomine indices were also analyzed. The prevalence of Chagas' disease in inhabitants of risk areas remained stable in this period as well as mortality. The incidence rate shows a progressive increase with a tendency towards stabilization. A significant decrease in sampling effort was found, declining by two orders of magnitude, especially since 2000. The progressive increase in morbidity had no clear relation to the interruption of the vector chain nor to the greater diagnostic effort occurred in 2009, since it was evident from before. While home infestation declines, reports of intrusion of solitary individuals and wild foci of T. infestans have increased. Trypano-triatomine indices were maintained with high values in all vector species. This study shows a worrying situation, for while on the one hand the interruption of the vector transmission and improvement in the research systems is emphasized, the concern for this disease seems to be decreasing with less diagnostic efforts and lower education at the higher level, and by the other hand the numbers show that the problem if it is not increasing, at least maintains its careless historical magnitude.


Precursor-directed biosynthesis of micacocidin derivatives with activity against Mycoplasma pneumoniae.
Micacocidin is a promising natural product for the treatment of Mycoplasma pneumoniae infections. In the biosynthesis of this antibiotic, a fatty acid-AMP ligase (FAAL) activates the starter unit hexanoic acid as acyl-adenylate and forwards it to an iteratively acting polyketide synthase. Biochemical analysis of the FAAL revealed an extended substrate tolerance, thereby opening the door for the modification of a micacocidin residue that is barely accessible via semisynthesis. A total of six new analogues were generated by precursor-directed biosynthesis in this study and profiled against M. pneumoniae.


Spatial statistical modelling of capillary non-perfusion in the retina.
Manual grading of lesions in retinal images is relevant to clinical management and clinical trials, but it is time-consuming and expensive. Furthermore, it collects only limited information - such as lesion size or frequency. The spatial distribution of lesions is ignored, even though it may contribute to the overall clinical assessment of disease severity, and correspond to microvascular and physiological topography. Capillary non-perfusion (CNP) lesions are central to the pathogenesis of major causes of vision loss. Here we propose a novel method to analyse CNP using spatial statistical modelling. This quantifies the percentage of CNP-pixels in each of 48 sectors and then characterises the spatial distribution with goniometric functions. We applied our spatial approach to a set of images from patients with malarial retinopathy, and found it compares favourably with the raw percentage of CNP-pixels and also with manual grading. Furthermore, we were able to quantify a biological characteristic of macular CNP in malaria that had previously only been described subjectively: clustering at the temporal raphe. Microvascular location is likely to be biologically relevant to many diseases, and so our spatial approach may be applicable to a diverse range of pathological features in the retina and other organs.


Breast symptoms among women enrolled in a health maintenance organization: frequency, evaluation, and outcome.
Few data exist about visits to primary care clinicians for breast symptoms in the United States. To determine how often women present with breast symptoms, how these symptoms are evaluated, and how often cancer is diagnosed. Retrospective cohort study. Staff-model division of a large health maintenance organization (HMO) in New England. 2400 women who were 40 to 69 years of age as of 1 July 1983 and were continuously enrolled in the HMO until 30 June 1995. Information on all breast-related encounters from 1 July 1983 to 30 June 1993 was abstracted. Type of symptom, clinicians' findings and recommendations, and all subsequent evaluations were recorded. Cases of cancer diagnosed subsequent to the symptom were determined. Sixteen percent of the HMO population presented with a breast symptom during the 10-year period, for a rate of 22.8 presentations per 1000 person-years. Women younger than 50 years of age presented nearly twice as often as older women (P = 0.001). Women with breast symptoms had lower rates of screening than other women before presenting but higher rates of screening afterward (P < 0.001). Symptoms were evaluated beyond the initial visit in 66% of patients, and invasive procedures were performed in 27% of patients. Cancer was found in 6.2% of patients and 4.5% of episodes; rates of cancer detection varied significantly by type of symptom but not by patient age. Breast symptoms among women 40 to 70 years of age were common in this primary care practice. Evaluation beyond initial examinations was frequent, and invasive procedures were performed for 27% of patients. Cancer was diagnosed in more than 4% of episodes, indicating that follow-up of breast symptoms is important in primary care practices.


Enantiomeric specificity in a pheromone-kairomone system of two threatened saproxylic beetles, Osmoderma eremita and Elater ferrugineus.
The scarab beetle Osmoderma eremita and its larval predator, the click beetle Elater ferrugineus, are threatened saproxylic beetles regarded as indicators of the species-richness of insect fauna of hollow deciduous trees. Male O. eremita produce the pheromone (R)-(+)-gamma-decalactone to attract conspecific females, and this compound is also utilized by E. ferrugineus as a kairomone, presumably for detection of tree hollows containing prey. We have investigated enantiomeric specificity to gamma-decalactone in this pheromone-kairomone system by electrophysiological and field trapping experiments. In single-sensillum recordings from male and female O. eremita, which used the (R)-enantiomer and the racemic mixture of gamma-decalactone as odor stimuli, numerous olfactory receptor neurons (ORNs) responding to both stimuli were found. No neurons responded preferentially to the racemic mixture, showing that these beetles seem to lack receptors specific for the (S)-enantiomer. The enantiomeric specificity of ORNs was confirmed by gas chromatography-linked single-sensillum recordings where the two enantiomers in a racemic mixture were separated on a chiral column. Furthermore, in field experiments that used the (R)-enantiomer and the racemic mixture as lures, the attraction of O. eremita females corresponded to the amount of (R)-enantiomer released from lures with the (S)-enantiomer displaying no antagonistic effects. Trap catch data also suggested that the (S)-enantiomer is not a behavioral antagonist for E. ferrugineus. The odor-based system can be highly efficient in attracting the larval predator where trap catch in 1 yr almost equaled the total number of specimens collected in Sweden until 1993. Our study shows that racemic gamma-decalactone could be used for cost-effective monitoring of both beetles.


New criteria for the molecular identification of cereal grains associated with archaeological artefacts.
The domestication and transmission of cereals is one of the most fundamental components of early farming, but direct evidence of their use in early culinary practices and economies has remained frustratingly elusive. Using analysis of a well-preserved Early Bronze Age wooden container from Switzerland, we propose novel criteria for the identification of cereal residues. Using gas chromatography mass spectrometry (GC-MS), we identified compounds typically associated with plant products, including a series of phenolic lipids (alkylresorcinols) found only at appreciable concentration in wheat and rye bran. The value of these lipids as cereal grain biomarkers were independently corroborated by the presence of macrobotanical remains embedded in the deposit, and wheat and rye endosperm peptides extracted from residue. These findings demonstrate the utility of a lipid-based biomarker for wheat and rye bran and offer a methodological template for future investigations of wider range of archaeological contexts. Alkylresorcinols provide a new tool for residue analysis which can help explore the spread and exploitation of cereal grains, a fundamental component of the advent and spread of farming.


Cost effectiveness of zanamivir for the treatment of influenza in a high risk population in Australia.
To use data from a clinical trial of zanamivir, a new antiviral drug, to estimate the costs and effectiveness of alternative treatment strategies for a high-risk population in Australia visiting a physician for treatment of influenza or influenza-like illness within 36 hours of symptom onset. This was a modelling study using data from a randomised, double-blind, placebo-controlled trial with centres in Australia, New Zealand and South Africa. Cost data were taken from standard Australian sources. Efficacy data from the clinical trial were used to populate a computer model designed to estimate the costs and health outcomes associated with alternative treatments for influenza and influenza-like illness. Only patients who consulted the physician within 36 hours of symptom onset were included in this trial. Cost data were used to translate the clinical data into treatment cost estimates. Treatment with zanamivir for this high risk population results in an incremental cost of $A14.20 per day of symptoms avoided in the base case. The cost per quality-adjusted life-year (QALY) gained is $A11,715. The results are sensitive to several parameter values, including the influenza-positive rate and the impact of zanamivir on days to alleviate symptoms and hospitalisation. Influenza is costly for the high risk population who seek physician treatment. Treatment with zanamivir for this population is cost effective based on an $A78,000 per QALY benchmark. Zanamivir could be cost saving if it reduces the hospitalisation rate.


Effects of homelessness on the quality of life of persons with severe mental illness.
This study assessed the relationship between homelessness and specific quality-of-life problems for persons with severe and persistent mental illness. The objective and subjective quality of life of 106 homeless persons with severe mental illness who lived on the streets or in shelters in Baltimore was compared with that of 146 domiciled persons with severe mental illness who lived in the community. Objective and subjective quality of life of the homeless subjects was clearly worse than that of the domiciled group in the areas of living situation, family and social relations, employment, daily activities, and legal and safety problems. Homeless subjects were also less likely to have federal disability entitlements. Poorer quality of life is associated with homelessness among persons with severe mental illness. Their quality of life may be improved by efforts to increase their access to disability entitlements and treatment services and to help them develop supportive social networks.


Lactococci and lactobacilli as mucosal delivery vectors for therapeutic proteins and DNA vaccines.
Food-grade Lactic Acid Bacteria (LAB) have been safely consumed for centuries by humans in fermented foods. Thus, they are good candidates to develop novel oral vectors, constituting attractive alternatives to attenuated pathogens, for mucosal delivery strategies. Herein, this review summarizes our research, up until now, on the use of LAB as mucosal delivery vectors for therapeutic proteins and DNA vaccines. Most of our work has been based on the model LAB Lactococcus lactis, for which we have developed efficient genetic tools, including expression signals and host strains, for the heterologous expression of therapeutic proteins such as antigens, cytokines and enzymes. Resulting recombinant lactococci strains have been tested successfully for their prophylactic and therapeutic effects in different animal models: i) against human papillomavirus type 16 (HPV-16)-induced tumors in mice, ii) to partially prevent a bovine β-lactoglobulin (BLG)-allergic reaction in mice and iii) to regulate body weight and food consumption in obese mice. Strikingly, all of these tools have been successfully transposed to the Lactobacillus genus, in recent years, within our laboratory. Notably, anti-oxidative Lactobacillus casei strains were constructed and tested in two chemically-induced colitis models. In parallel, we also developed a strategy based on the use of L. lactis to deliver DNA at the mucosal level, and were able to show that L. lactis is able to modulate the host response through DNA delivery. Today, we consider that all of our consistent data, together with those obtained by other groups, demonstrate and reinforce the interest of using LAB, particularly lactococci and lactobacilli strains, to develop novel therapeutic protein mucosal delivery vectors which should be tested now in human clinical trials.


Subcloning and expression of the Brucella abortus L7/L12 ribosomal gene and T-lymphocyte recognition of the recombinant protein.
The Brucella abortus L7/L12 ribosomal gene was amplified by PCR and subcloned into the prokaryotic expression vector pMAL-c2. Escherichia coli DH5 alpha was transformed with the pMAL-L7/L12 construct, and gene expression was induced by IPTG (isopropyl-beta-D-thiogalactopyranoside). The resulting fusion protein was purified by affinity chromatography and confirmed by Western blot (immunoblot) analysis using an anti-maltose-binding protein antibody. Additionally, purified recombinant L7/L12 protein induced T-lymphocyte proliferation of B. abortus-primed bovine peripheral blood mononuclear cells. Phenotypic analysis of the proliferating cell population demonstrated an increase in the percentage of CD4+ T lymphocytes when peripheral blood mononuclear cells were cultured with recombinant L7/L12 compared with cells cultured in medium alone. Subcloning and expression of a B. abortus gene encoding a previously demonstrated immunodominant protein for bovine lymphocytes are important steps in selecting Brucella proteins that have potential as a component of a genetically engineered candidate vaccine.


RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 3: Basic life support.
To systematically examine the evidence on basic life support (BLS) in veterinary CPR and to determine knowledge gaps. Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice. Relevant questions were answered on a worksheet template and reviewed by the Reassessment Campaign on Veterinary Resuscitation (RECOVER) BLS domain members, by the RECOVER committee and opened for comments by veterinary professionals for 30 days. Academia, referral practice, and general practice. Sixteen worksheets were prepared to evaluate techniques for chest compression and ventilation strategies as well as identification of cardiopulmonary arrest (CPA). Major recommendations arising from this evidence review include performing chest compressions at a rate of at least 100/min at a compression depth of one-third to half the width of the chest with minimal pauses, and early instigation of ventilation at a rate of 8-10 breaths/min in intubated patients, or using a 30:2 compression/ventilation ratio in nonintubated patients. Although veterinary clinical trials are lacking, much of the experimental literature on BLS utilized canine models. The major conclusions from this analysis of the literature are the importance of early identification of CPA, and immediate initiation of BLS in these patients. Many knowledge gaps exist, most importantly in our understanding of the optimal hand placement and technique for chest compressions, warranting coordinated future studies targeted at questions of relevance to differences between veterinary species and humans.


Increased soluble interleukin-1 type II receptor concentrations in postoperative patients and in patients with sepsis syndrome.
Plasma interleukin-1 (IL-1) activity is modulated in part through the simultaneous appearance of several inhibitors of IL-1 action, including interleukin-1 receptor antagonist (IL-1ra) and the soluble IL-1 type II receptor (IL-1RII). However, little is known concerning the plasma appearance of these inhibitors in patients following operative trauma or those with sepsis syndrome. In the present report, plasma IL-1beta, IL-1ra, and soluble IL-1RI and IL-1RII concentrations were evaluated in 118 patients with sepsis syndrome or after elective operative trauma. Plasma concentrations of IL-1ra increased significantly following elective operative repair of thoraco-abdominal and abdominal aortic aneurysms, and after bowel resection for inflammatory bowel disease, but did not increase after laparoscopic cholecystectomy. Plasma IL-1ra levels were also elevated in patients with sepsis syndrome. In contrast, soluble IL-1RII levels were only increased in patients after operative repair of thoraco-abdominal aortic aneurysms and in sepsis syndrome, whereas concentrations were unaffected by the other more modest surgical procedures. Plasma IL-1RI concentrations decreased in all postoperative patients in the first 24 hours after surgery. We conclude that both plasma IL-1ra and soluble IL-1RII concentrations often increase in sepsis and following some operative trauma. Less severe operative trauma increases the plasma concentration of only IL-1ra, whereas both IL-1ra and soluble IL-1RII are increased in patients with sepsis syndrome or following thoraco-abdominal aneurysm repair.


Usefulness of automated cell counter in detection of malaria in a cancer set up--our experience.
Malaria diagnosis presents a challenge to all laboratories. In malaria-endemic areas, there is a need for rapid, sensitive and cost-effective method to effectively screen all samples, especially when the workload is very high. Various hematology analyzers have been investigated for detection of malaria in the past. Here, we present our experience of malaria detection in a cancer hospital where a large number of complete blood count requests are received either before or during chemotherapy. Fever, being a very common symptom in cancer patients, causes a suspicion of malaria. This study was conducted to assess the usefulness of hematology cell counter, viz. WBC-DIFF and WBC/BASO scatter plots and the flaggings generated in malaria-positive cases. The occurrence of pseudoeosinophilia as reported by previous studies was also assessed. The parasitic index was determined and its correlation with the abnormalities found on the Hematology analyzer was also studied. Blood samples were collected from 80 out-patient department and inpatients with various solid as well as hematological malignancies, who presented with acute febrile illness during September 2010 and January 2012, and for whom complete blood cell analysis and peripheral smear for malaria parasite had been requested. Of the 80 patients who presented with fever and suspicion of malaria, 29 patients were positive for malaria and 10 cases were diagnosed incidentally by the findings on the cell counter and were confirmed by Giemsa-stained blood smears. The sensitivity and specificity of the abnormalities detected in the WBC-Diff channel in detecting malaria is 82% and 100% respectively. Using WBC-BASO channel abnormality for initial diagnosis the sensitivity and specificity is 50% and 92.5% respectively. The sensitivity and specificity with respect to pseudoeosinophilia is 18% and 100% respectively. The most common WBC and PLT flags were leukopenia, atypical lymphocytes, lymphopenia, WBC abnormal scattergram, platelet clumps, thrombocytopenia, platelet abnormal distribution flag. The instrument provides significantly valuable diagnostic parameters in detecting acute Plasmodium vivax malaria; however, it is not very useful for acute falciparum malaria infection. It is suggested that the laboratories using the hematology analyzers should be aware of such specific parameters, even in the absence of a clinical request.


Modeling the Self-Assembly of Nano Objects: Applications to Supramolecular Organic Monolayers Adsorbed on Metal Surfaces.
We present here the implementation of a code developed for the simulation of the self-assembly of nano objects (SANO). The code has the ability to predict the molecular self-assembly of different structural motifs by tuning the molecular building blocks as well as the metallic substrate. It consists in a two-dimensional grand canonical Monte Carlo (GCMC) approach developed to perform atomistic simulations of thousands of large organic molecules self-assembling on metal surfaces. By computing adsorption isotherms at room temperature and spanning over the characteristic submicrometric scales, we confront the robustness of the approach with three different well-known systems: ZnPcCl8 on Ag(111), CuPcF16 on Au(111), and PTBC on Ag(111). We retrieve respectively their square, oblique, and hexagonal supramolecular tilling. The code incorporates generalized force fields to describe the molecular interactions, which provides transferability to many organic building blocks and metal surfaces. Ultimately, the method is versatile and can be an interesting multiscale approach if one aims to bridge quantum level calculations to the experimental scales and within a treatment in temperature.


Neuropsychological findings in a sample of Operation Desert Storm veterans.
In response to ongoing complaints of memory, attention, and problem-solving difficulties among veterans of Operation Desert Storm and Shield (ODSS), a sample of 44 male veterans of ODSS underwent a comprehensive neuropsychological evaluation. Deficits relative to normative data were observed only on finger dexterity (Grooved Pegboard, bilaterally) and the Stroop Color and Word Test. Those with impaired Pegboard performance had lower performance on other tasks requiring psychomotor speed. Those with impaired Stroop had significantly lower motor and set-shifting performance. Scores of both impaired groups were higher on many clinical and supplemental scales of the MMPI. Despite subjective cognitive complaints reported in 39% of the overall sample, veterans with cognitive complaints differed from their peers primarily in greater psychological distress as depicted on the MMPI. The data are presented as preliminary clinical findings.


Association between language and spatial laterality and cognitive ability: an fMRI study.
The interaction between language and spatial laterality and its association with cognitive ability was explored in a group of 42 right-handers and 40 left-handers using functional magnetic resonance imaging. Cognitive ability measures including working memory, verbal comprehension and perceptual organisation were assessed using the Wechsler Adult Intelligence Scale (version III). Left-handers show lower working memory scores than right-handers. Increased rightward language laterality is also associated with decreased working memory performance, which we suggest is related to the involvement of the left inferior frontal gyrus in subvocal rehearsal during working memory tasks. The interaction between language and spatial laterality is associated with performance on verbal comprehension and perceptual organisation, such that when language and spatial laterality are dissociated between the hemispheres a significant increase in verbal comprehension and perceptual organisation performance is found. There is a decrease in performance on the verbal comprehension and perceptual organisation subtests when language and spatial processing are associated to the same hemisphere (i.e. both lateralised to the right hemisphere or both lateralised to the left). This interaction is interpreted in relation to the 'hemispheric crowding' hypothesis, which proposes increased cognitive ability when language and spatial laterality are dissociated.


Internet and Social Media Access Among Youth Experiencing Homelessness: Mixed-Methods Study.
Youth experiencing homelessness are at a risk for a variety of adverse outcomes. Given the widespread use of the internet and social media, these new technologies may be used to address their needs and for outreach purposes. However, little is known about how this group uses these resources. This study investigated how homeless adolescents use these technologies for general and health-related purposes, whether the scope of their use changes with housing status, and their interest in a website dedicated to youth experiencing homelessness. A convenience sample of youth aged 18 to 21 years was recruited from a youth-specific homeless shelter. All participants completed a 47-item survey, with 10 individuals completing a semistructured interview. Descriptive statistics, exact testing, logistic regression, and generalized estimating equation modeling was performed for quantitative data analysis. Interviews were transcribed verbatim, and NVivo 10 (QSR International) was employed to facilitate double coding and thematic analysis. A total of 87 participants completed the survey with a mean age of 19.4 (SD 1.1) years. While experiencing homelessness, 56% (49/87) accessed the internet at least once a day, with 86% (75/87) accessing once a week. Access to a smartphone was associated with a 3.03 greater odds of accessing the internet and was the most frequently used device (66% of participants, 57/87). While experiencing homelessness, subjects reported a 68% decreased odds in internet access frequency (odds ratio [OR] 0.32, P<.001), 75% decreased odds in spending greater amounts of time on the internet (OR 0.25, P<.001), and an 87% decreased odds of social media use (OR 0.13, P=.01). Ten participants completed the semistructured interview. Several themes were identified, including (1) changes in internet behaviors while experiencing homelessness, (2) health status as a major concern and reason for Internet use, and (3) interest in a website dedicated to youth experiencing homelessness. While experiencing homelessness, participants indicated their behaviors were more goal-oriented and less focused on leisure or entertainment activities. While homeless youth experience changes in the frequency, amount of time, and specific uses of the internet and social media, study participants were able to access the internet regularly. The internet was used to search health-related topics. Given the importance of smartphones in accessing the internet, mobile-optimized websites may be an effective method for reaching this group.


Photostability Can Be Significantly Modulated by Molecular Packing in Glasses.
While previous work has demonstrated that molecular packing in organic crystals can strongly influence photochemical stability, efforts to tune photostability in amorphous materials have shown much smaller effects. Here we show that physical vapor deposition can substantially improve the photostability of organic glasses. Disperse Orange 37 (DO37), an azobenzene derivative, is studied as a model system. Photostability is assessed through changes in the density and molecular orientation of glassy thin films during light irradiation. By optimizing the substrate temperature used for deposition, we can increase photostability by a factor of 50 relative to the liquid-cooled glass. Photostability correlates with glass density, with density increases of up to 1.3%. Coarse-grained molecular simulations, which mimic glass preparation and the photoisomerization reaction, also indicate that glasses with higher density have substantially increased photostability. These results provide insights that may assist in the design of organic photovoltaics and light-emission devices with longer lifetimes.


Simultaneous broadband light trapping and fill factor enhancement in crystalline silicon solar cells induced by Ag nanoparticles and nanoshells.
Crystalline silicon solar cells are predominant and occupying more than 89% of the global solar photovoltaic market. Despite the boom of the innovative solar technologies, few can provide a low-cost radical solution to dramatically boost the efficiency of crystalline silicon solar cells, which has reached plateau in the past ten years. Here, we present a novel strategy to simultaneously achieve dramatic enhancement in the short-circuit current and the fill factor through the integration of Ag plasmonic nanoparticles and nanoshells on the antireflection coating and the screen-printed fingers of monocrystalline silicon solar cells, respectively, by a single step and scalable modified electroless displacement method. As a consequence, up to 35.2% enhancement in the energy conversion efficiency has been achieved due to the plasmonic broadband light trapping and the significant reduction in the series resistance. More importantly, this method can further increase the efficiency of the best performing textured solar cells from 18.3% to 19.2%, producing the highest efficiency cells exceeding the state-of-the-art efficiency of the standard screen-printed solar cells. The dual functions of the Ag nanostructures, reported for the first time here, present a clear contrast to the previous works, where plasmonic nanostructures were integrated into solar cells to achieve the short-circuit current enhancement predominately. Our method offers a facile, cost-effective and scalable pathway for metallic nanostructures to be used to dramatically boost the overall efficiency of the optically thick crystalline silicon solar cells.


Role of traditional healers in eastern Uttar Pradesh.
Health is considered one of the basic needs of human beings and access to health services an undeniable right of every one. Improvement on human health front has not occurred equally every where and benefits have not percolated to every one. The rural population has least benefitted from the advancements of modern sciences. The health condition of rural areas is very poor. to achieve the goal of 'Health for all' the confidence and accumulated wisdom of traditional healers are to be used in proper direction. If proper facilities are provided to traditional healers they may help in easing pressure on overburdened clinics by treating minor, self limiting psychosomatic and certain other kinds of ailments in which traditional therapies are effective and appropriate.


Respiratory and Nitrogenase Activities of Soybean Nodules Formed by Hydrogen Uptake Negative (Hup) Mutant and Revertant Strains of Rhizobium japonicum Characterized by Protein Patterns.
Rates of respiratory CO(2) loss and nitrogenase activities of H(2) uptake-negative mutant strains and H(2) uptake-positive revertant strains of Rhizobium japonicum have been investigated. Two-dimensional gel protein patterns of bacteroids formed by inoculation of soybeans (Glycine max L.) with these two strains show that they are closely related and revealed only one obvious difference between them. On the basis of molecular weight standards, it was concluded that the missing protein spot in the H(2) uptake-negative mutant strain could be caused by a failure of the mutant to synthesize hydrogenase. Nodules formed by the H(2) uptake-negative mutant strain evolved respiratory CO(2) at a rate of about 10% higher than that of nodules formed by the H(2) uptake-positive revertant strain. During short-term experiments employed, rates of both C(2)H(2) reduction and (15)N(2) fixation varied considerably among replicate samples and no statistically significant differences between mutant and revertant strains were observed. It was observed that increasing the partial pressure of O(2) over nodules significantly decreased the proportion of nitrogenase electrons allocated to H(+).


Role of specific presynaptic calcium channel subtypes in isoflurane inhibition of synaptic vesicle exocytosis in rat hippocampal neurones.
P/Q- and N-type voltage-gated calcium channels (VGCC) are the principal subtypes mediating synaptic vesicle (SV) exocytosis. Both the degree of isoflurane inhibition of SV exocytosis and VGCC subtype expression vary between brain regions and neurotransmitter phenotype. We hypothesised that differences in VGCC subtype expression contribute to synapse-selective presynaptic effects of isoflurane. We used quantitative live-cell imaging to measure exocytosis in cultured rat hippocampal neurones after transfection of the fluorescent biosensor vGlut1-pHluorin. Selective inhibitors of P/Q- and N-type VGCCs were used to isolate subtype-specific effects of isoflurane. Inhibition of N-type channels by 1 μM ω-conotoxin GVIA reduced SV exocytosis to 81±5% of control (n=10). Residual exocytosis mediated by P/Q-type channels was further inhibited by isoflurane to 42±4% of control (n=10). The P/Q-type channel inhibitor ω-agatoxin IVA at 0.4 μM inhibited SV exocytosis to 29±3% of control (n=10). Residual exocytosis mediated by N-type channels was further inhibited by isoflurane to 17±3% of control (n=10). Analysis of isoflurane effects at the level of individual boutons revealed no difference in sensitivity to isoflurane between P/Q- or N-type channel-mediated SV exocytosis (P=0.35). There was no correlation between the effect of agatoxin (P=0.91) or conotoxin (P=0.15) and the effect of isoflurane on exocytosis. Sensitivity of SV exocytosis to isoflurane in rat hippocampal neurones is independent of the specific VGCC subtype coupled to exocytosis. The differential sensitivity of VGCC subtypes to isoflurane does not explain the observed neurotransmitter-selective effects of isoflurane in hippocampus.


Unimpaired thymic and peripheral T cell death in mice lacking the nuclear receptor NGFI-B (Nur77).
T cell hybridomas require the immediate-early gene NGFI-B (nur77) for T cell receptor (TCR)-mediated apoptosis, a model for negative selection of self-reactive T cells. TCR-mediated death was examined in mice bearing an NGFI-B loss-of-function mutation, either by administration of antibodies to CD3 (anti-CD3) or in two well-characterized transgenic models expressing self-reactive TCRs. Both the extent and the rate of thymocyte death were unimpaired. Anti-CD3-induced death was normal in CD4+ peripheral T cells, in which death is mediated predominantly by the Fas signaling pathway. Thus, no unique requirement for NGFI-B is observed for thymic or peripheral T cell death.


Factors influencing local ecological knowledge of forage resources: Ethnobotanical evidence from West Africa's savannas.
Recording local ecological knowledge (LEK) is a useful approach to understanding interactions of the complex social-ecological systems. In spite of the recent growing interest in LEK studies on the effects of climate and land use changes, livestock mobility decisions and other aspects of agro-pastoral systems, LEK on forage plants has still been vastly under-documented in the West African savannas. Using a study area ranging from northern Ghana to central Burkina Faso, we thus aimed at exploring how aridity and socio-demographic factors drive the distributional patterns of forage-related LEK among its holders. With stratified random sampling, we elicited LEK among 450 informants in 15 villages (seven in Ghana and eight in Burkina Faso) via free list tasks coupled with ethnobotanical walks and direct field observations. We performed generalized linear mixed-effects models (aridity- and ethnicity-based models) and robust model selection procedures. Our findings revealed that LEK for woody and herbaceous forage plants was strongly influenced by the ethnicity-based model, while aridity-based model performed better for LEK on overall forage resources and crop-related forage plants. We also found that climatic aridity had negative effect on the forage-related LEK across gender and age groups, while agro- and floristic diversity had positive effect on the body of LEK. About 135 species belonging to 95 genera and 52 families were cited. Our findings shed more light on how ethnicity and environmental harshness can markedly shape the body of LEK in the face of global climate change. Better understanding of such a place-based knowledge system is relevant for sustainable forage plants utilization and livestock production.


The From The Heart study: a global survey of patient understanding of cholesterol management and cardiovascular risk, and physician-patient communication.
Cardiovascular disease (CVD) is the leading cause of mortality worldwide. A high level of low-density lipoprotein cholesterol (LDL-C) is a major CVD risk factor. Guidelines recommend effective cholesterol management and set LDL-C goals, yet deficiencies exist in physician implementation of these recommendations and in patient uptake of the advice. However, little is known of patient perceptions about CVD risk. Patients and physicians were randomly selected from ten countries to complete a confidential, semi-structured questionnaire. Response rates were 27% (n = 750) for physicians and 83% (n = 1547) for patients. Patients believed cancer (43%) to be a greater cause of mortality than heart attack or stroke (34%). Despite 77% of patients claiming to be satisfied with information on high cholesterol, only 26% were aware that heart attack was a possible consequence, and only 35% of patients thought they had achieved their cholesterol goals. Virtually all physicians (99%) claimed to inform patients of their cholesterol level, while 18% of patients reported that they were not informed. Although patients and physicians were selected at random, limitations of this survey relate typically to the reliability of physician and patient responses and the possibility that the survey population may not represent the overall population. A broad range of patients' backgrounds and a high response rate (83%) suggest these effects would be minimal in the patient population. The From The Heart study has shown surprisingly poor knowledge of CVD risk amongst patients with elevated cholesterol. This may contribute to poor concordance with recommendations and treatment.


The diagnosis and management of acute and chronic urticaria: 2014 update.
These parameters were developed by the Joint Task Force on Practice Parameters (JTFPP), representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology. The AAAAI and ACAAI have jointly accepted responsibility for establishing "The diagnosis and management of acute and chronic urticaria: 2014 update." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the JTFPP, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. The JTFPP understands that the cost of diagnostic tests and therapeutic agents is an important concern that might appropriately influence the work-up and treatment chosen for a given patient. The JTFPP recognizes that the emphasis of our primary recommendations regarding a medication might vary, for example, depending on third-party payer issues and product patent expiration dates. However, because a given test or agent's cost is so widely variable and there is a paucity of pharmacoeconomic data, the JTFPP generally does not consider cost when formulating practice parameter recommendations. In extraordinary circumstances, when the cost/benefit ratio of an intervention is prohibitive, as supported by pharmacoeconomic data, commentary might be provided. These parameters are not designed for use by pharmaceutical companies in drug promotion. The JTFPP is committed to ensuring that the practice parameters are based on the best scientific evidence that is free of commercial bias. To this end, the parameter development process includes multiple layers of rigorous review. These layers include the workgroup convened to draft the parameter, the task force reviewers, and peer review by members of each sponsoring society. Although the task force has the final responsibility for the content of the documents submitted for publication, each reviewer comment will be discussed, and reviewers will receive written responses to comments, when appropriate. To preserve the greatest transparency regarding potential conflicts of interest, all members of the JTFPP and the practice parameter workgroups will complete a standard potential conflict of interest disclosure form, which will be available for external review by the sponsoring organization and any other interested individual. In addition, before confirming the selection of a Work Group chairperson, the Joint Task Force will discuss and resolve all relevant potential conflicts of interest associated with this selection. Finally, all members of parameter workgroups will be provided a written statement regarding the importance of ensuring that the parameter development process is free of commercial bias. Practice parameters are available online at www.jcaai.org and www.allergyparameters.org.


Cell-free released components of Streptococcus sanguis inhibit human platelet aggregation.
To study the role of surface components in the selective binding and aggregation of platelet-rich plasma (PRP) by strains of viridans streptococci, we treated the binding, aggregation strain Streptococcus sanguis I 2017-78 by sonication or trypsinization. Morphologically identifiable electron-dense fibrils were released from the cell wall, apparently from an inner electron-dense layer, under conditions that left cells intact. These controlled conditions were determined to cause submaximal loss in adhesion to platelet ghosts and PRP aggregation by treated, washed S. sanguis. Soluble components were recovered from the controlled sonic or L-(tosylamido 2-phenyl)ethyl chloromethyl ketone-trypsin treatments. Each showed dose-response inhibition of aggregation when preincubated with PRP before challenge with fresh, untreated S. sanguis. The time to onset of PRP aggregation was inhibited by 50% with 0.2 mg of TPCK-trypsin peptides or 1.0 mg of the sonicate per ml per 2 X 10(8) platelets. Components of both preparations were immunologically cross-reactive, but lipoteichoic acid was not a major antigen of either. By weight, the TPCK-trypsin peptides were virtually all protein; the sonicate residues identified were about 50% protein and 7% hexose. Each was a complex mixture of components as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. More than 8 TPCK-trypsin peptides and 16 sonicate components were so identified. In contrast, at least four or five components from either preparation were recognized as surface determinants by a rabbit antiserum to whole homologous microbes. Platelet-binding ligands of S. sanguis could be among these determinants.


The nitrite transport protein NirC from Salmonella typhimurium is a nitrite/proton antiporter.
In anaerobically grown bacteria, transport of nitrite is catalyzed by an integral membrane protein of the form ate-nitrite transporter family, NirC, which in Salmonella typhimurium plays a critical role in intracellular virulence. We present a functional characterization of the S. typhimurium nitrite transporter StmNirC in native membrane vesicles as well as purified and reconstituted into proteoliposomes. Using an electrophysiological technique based on solid supported membranes, we show nitrite induced translocation of negative charges into proteoliposomes reconstituted with purified StmNirC. These data demonstrate the electrogenicity of StmNirC and its substrate specificity for nitrite. Monitoring changes in ΔpH on everted membrane vesicles containing overexpressed StmNirC using acridine orange as a pH indicator we demonstrate that StmNirC acts as a secondary active transporter. It promotes low affinity transport of nitrite coupled to H(+) antiport with a pH independent profile in the pH range from 6 to 8. In addition to nitrite also nitrate is transported by StmNirC, but with reduced flux and complete absence of proton antiport activity. Taken together, these data suggest a bispecific anion selectivity of StmNirC with an ion specific transport mode. This may play a role in regulating nitrite transport under physiological conditions.


Walking on treadmill with Rett syndrome-Effects on the autonomic nervous system.
People with Rett syndrome have deficient central autonomic control, which may interfere with walking. We have limited knowledge regarding the effects of exertion during physical activity in Rett syndrome. The aim was to investigate the autonomic responses during walking on a treadmill in Rett syndrome. Twenty-six females, 12 with Rett syndrome and 14 healthy females were included. All individuals started on the treadmill by standing still, followed by walking slowly with progressive speed until reaching maximum individual speed, which they kept for 6 min. Heart rate (HR), systolic (SBP), diastolic (DBP), mean arterial blood pressures (MAP), cardiac vagal tone (CVT), cardiac sensitivity to baroreflex (CSB), transcutaneous partial pressures of oxygen (pO2), carbon dioxide (pCO2), and breathing movements were recorded simultaneously and continuously. Autonomic responses were assessed by MAP, CSB and CVT during walking at 3 and 6 min. The changes in CSB and CVT in people with Rett syndrome compared to controls indicated more arousal, but only when the treadmill was started; as they continued walking, the arousal dropped to control level. People with Rett syndrome exhibited little changes in pCO2 whereas the controls showed increased values during walking. This suggests poor aerobic respiration in people with Rett syndrome during walking. Five people with Rett syndrome had Valsalva type of breathing at rest, three of those had normal breathing while walking on the treadmill while the remaining two started but soon stopped the Valsalva breathing during the walk. Our results show that individuals with Rett syndrome can walk for up to 6 min at their own maximum sustainable speed on a treadmill. Energy production may be low during walking in Rett syndrome, which could cause early tiredness. A treadmill can be used in people with Rett syndrome, but must be introduced slowly and should be individually tailored. We propose that walking promotes regular breathing in Rett syndrome.


Perspective on the interpretation of research and translation to clinical care with therapy-associated metastatic breast cancer progression as an example.
This commentary was written as a collaboration between the Board of the Metastasis Research Society and two patients with metastatic breast cancer. It was conceived in response to how preclinical scientific research is sometimes presented to non-scientists in a way that can cause stress and confusion. Translation of preclinical findings to the clinic requires overcoming multiple barriers. This is irrespective of whether the findings relate to exciting responses to new therapies or problematic effects of currently used therapies. It is important that these barriers are understood and acknowledged when research findings are summarized for mainstream reporting. To minimize confusion, patients should continue to rely on their oncology care team to help them interpret whether research findings presented in mainstream media have relevance for their individual care. Researchers, both bench and clinical, should work together where possible to increase options for patients with metastatic disease, which is still in desperate need of effective therapeutic approaches.


OH cleavage from tyrosine: debunking a myth.
During macromolecular X-ray crystallography experiments, protein crystals held at 100 K have been widely reported to exhibit reproducible bond scission events at doses on the order of several MGy. With the objective to mitigate the impact of radiation damage events on valid structure determination, it is essential to correctly understand the radiation chemistry mechanisms at play. OH-cleavage from tyrosine residues is regularly cited as amongst the most available damage pathways in protein crystals at 100 K, despite a lack of widespread reports of this phenomenon in protein crystal radiation damage studies. Furthermore, no clear mechanism for phenolic C-O bond cleavage in tyrosine has been reported, with the tyrosyl radical known to be relatively robust and long-lived in both aqueous solutions and the solid state. Here, the initial findings of Tyr -OH group damage in a myrosinase protein crystal have been reviewed. Consistent with that study, at increasing doses, clear electron density loss was detectable local to Tyr -OH groups. A systematic investigation performed on a range of protein crystal damage series deposited in the Protein Data Bank has established that Tyr -OH electron density loss is not generally a dominant damage pathway in protein crystals at 100 K. Full Tyr aromatic ring displacement is here proposed to account for instances of observable Tyr -OH electron density loss, with the original myrosinase data shown to be consistent with such a damage model. Systematic analysis of the effects of other environmental factors, including solvent accessibility and proximity to disulfide bonds or hydrogen bond interactions, is also presented. Residues in known active sites showed enhanced sensitivity to radiation-induced disordering, as has previously been reported.


Cellular transformation by adenovirus type 5 is influenced by the viral DNA polymerase.
Early region 2B (E2B) of the group C adenoviruses encodes a number of proteins, including the 140-kilodalton DNA polymerase, which plays a role in the initiation of viral DNA replication. Temperature-sensitive (ts) mutants with mutations mapping to E2B are conditionally defective for both DNA replication in human cells and transformation of rat cells. Nucleotide sequence analysis shows that the E2B mutant ts36 possesses a single point mutation specific to the viral DNA polymerase; this transition of a C to a T at position 7623 changes leucine residue 249 in the polymerase to a phenylalanine. A wild-type (ts+) revertant possesses a codon specifying the original leucine at position 249. Phenotypic analysis of revertant and wild-type viruses derived by marker rescue from ts36 shows that these variants are wild type for both viral DNA replication and transformation. Thus, the single point mutation in the polymerase gene of ts36 is responsible for both defects.


The Metabolites of the Dietary Flavonoid Quercetin Possess Potent Antithrombotic Activity, and Interact with Aspirin to Enhance Antiplatelet Effects.
Quercetin, a dietary flavonoid, has been reported to possess antiplatelet activity. However, its extensive metabolism following ingestion has resulted in difficulty elucidating precise mechanisms of action. In this study, we aimed to characterize the antiplatelet mechanisms of two methylated metabolites of quercetin-isorhamnetin and tamarixetin-and explore potential interactions with aspirin. Isorhamnetin and tamarixetin inhibited human platelet aggregation, and suppressed activatory processes including granule secretion, integrin αIIbβ3 function, calcium mobilization, and spleen tyrosine kinase (Syk)/linker for activation of T cells (LAT) phosphorylation downstream of glycoprotein VI with similar potency to quercetin. All three flavonoids attenuated thrombus formation in an in vitro microfluidic model, and isoquercetin, a 3-O-glucoside of quercetin, inhibited thrombosis in a murine laser injury model. Isorhamnetin, tamarixetin, and quercetin enhanced the antiplatelet effects of aspirin more-than-additively in a plate-based aggregometry assay, reducing aspirin IC 50 values by an order of magnitude, with this synergy maintained in a whole blood test of platelet function. Our data provide mechanistic evidence for the antiplatelet activity of two quercetin metabolites, isorhamnetin and tamarixetin, and suggest a potential antithrombotic role for these flavonoids. In combination with their interactions with aspirin, this may represent a novel avenue of investigation for the development of new antithrombotic strategies and management of current therapies.


Inverse scattering approach based on the field equivalence principle: inversion without a priori information on incident fields.
An inverse scattering approach based on the field equivalence principle is developed for reconstructing the parameters of the medium of a scattering object. A problem equivalent to the original scattering problem but internal to the measurement surface is set up. The equivalent surface currents determined by the measured total-field data rigorously yield the incident fields in the region under test, so the approach does not require explicit knowledge of the incident fields. Taking into account the fact that the equivalent surface currents produce a null field external to the surface, a functional of the medium's parameters is introduced, and a genetic algorithm is applied to minimization of the functional. Numerical simulations for imaging defects in a known dielectric cylinder from only total-field data measured on an observation surface are performed to illustrate the efficacy of the proposed inversion method.


Effect of seepage conditions on chemical attenuation of arsenic by soils across an abandoned mine site.
The effect of seepage velocity on the As leaching/adsorption by soils collected from abandoned mine sites was evaluated under batch equilibrium and different seepage settings. The breakthrough curves (BTCs) of As leaching from the mine soil column initially displayed the peak export and gradually leveled off over the leaching experiment. A similar As peak was observed after a flow interruption period. Adsorption by downgradient soils was clearly nonlinear, as Freundlich N was <1. In the BTCs of the layered columns, where downgradient soils were overloaded above the mine soil, the extended lag period of As appearance and lower steady-state As concentration observed for slow seepage velocity supported the idea of kinetically limited As attenuation driven by soil adsorption. The perturbation of As concentration was insignificant when the intra-column As concentration gradient was higher. The As concentration drop and time to recovery were greater for less adsorptive soil and fast seepage velocity. Desorption of As from soils retrieved from both batch adsorption and column experiment demonstrate hysteric behavior. The results of this work demonstrated that the risk of As leaching from an abandoned mine site can be greatly attenuated by intermediate downgradient soils via chemical adsorption, which tends to be kinetically limited and energetically hysteric (i.e., non-identical energy pathway).


Becoming pure: identifying generational classes of admixed individuals within lesser and greater scaup populations.
Estimating the frequency of hybridization is important to understand its evolutionary consequences and its effects on conservation efforts. In this study, we examined the extent of hybridization in two sister species of ducks that hybridize. We used mitochondrial control region sequences and 3589 double-digest restriction-associated DNA sequences (ddRADseq) to identify admixture between wild lesser scaup (Aythya affinis) and greater scaup (A. marila). Among 111 individuals, we found one introgressed mitochondrial DNA haplotype in lesser scaup and four in greater scaup. Likewise, based on the site-frequency spectrum from autosomal DNA, gene flow was asymmetrical, with higher rates from lesser into greater scaup. However, using ddRADseq nuclear DNA, all individuals were assigned to their respective species with >0.95 posterior assignment probability. To examine the power for detecting admixture, we simulated a breeding experiment in which empirical data were used to create F1 hybrids and nine generations (F2-F10) of backcrossing. F1 hybrids and F2, F3 and most F4 backcrosses were clearly distinguishable from pure individuals, but evidence of admixed histories was effectively lost after the fourth generation. Thus, we conclude that low interspecific assignment probabilities (0.011-0.043) for two lesser and nineteen greater scaup were consistent with admixed histories beyond the F3 generation. These results indicate that the propensity of these species to hybridize in the wild is low and largely asymmetric. When applied to species-specific cases, our approach offers powerful utility for examining concerns of hybridization in conservation efforts, especially for determining the generational time until admixed histories are effectively lost through backcrossing.


Real-time monitoring of railway traffic using slope-assisted Brillouin distributed sensors.
The application of a Brillouin distributed sensor for the monitoring of railway traffic is presented in this work. The field test is performed on the Italian regional line San Severo-Peschici, operated by Ferrovie del Gargano. A single-mode optical fiber sensor was attached along a rail length of about 60 m. The strain associated with train passage was acquired along the monitored rail length at 31 Hz acquisition rate and 1 m spatial resolution. The data acquired by the sensor demonstrates its capability of retrieving useful information in railway traffic monitoring, such as train identification, axle counting, speed detection, and dynamic load calculation.


Mesenchymal Stem Cells Increase Hippocampal Neurogenesis and Neuronal Differentiation by Enhancing the Wnt Signaling Pathway in an Alzheimer's Disease Model.
Neurogenesis in the subgranular zone of the hippocampal dentate gyrus may act as an endogenous repair mechanism in Alzheimer's disease (AD), and the Wnt signaling pathway has been suggested to closely modulate neurogenesis in amyloid-β (Aβ)-related AD models. The present study investigated whether mesenchymal stem cells (MSCs) would modulate hippocampal neurogenesis via modulation of the Wnt signaling pathway in a model of AD. In Aβ-treated neuronal progenitor cells (NPCs), the coculture with MSCs increased significantly the expression of Ki-67, GFAP, SOX2, nestin, and HuD compared to Aβ treatment alone. In addition, MSC treatment in Aβ-treated NPCs enhanced the expression of β-catenin and Ngn1 compared to Aβ treatment alone. MSC treatment in Aβ-treated animals significantly increased the number of BrdU-ir cells in the hippocampus at 2 and 4 weeks compared to Aβ treatment alone. In addition, quantitative analysis showed that the number of BrdU and HuD double-positive cells in the dentate gyrus was significantly higher in the MSC-treated group than in controls or after Aβ treatment alone. These results demonstrate that MSC administration significantly augments hippocampal neurogenesis and enhances the differentiation of NPCs into mature neurons in AD models by augmenting the Wnt signaling pathway. The use of MSCs to modulate endogenous adult neurogenesis may have a significant impact on future strategies for AD treatment.


Six-day selenium supplementation led to either UVA-photoprotection or toxic effects in human fibroblasts depending on the chemical form and dose of Se.
Selenium (Se) is an essential trace element with a narrow safety zone and unclear effects on skin photoageing. The aim of this work was to investigate the photoageing properties of sodium selenite or selenomethionine (SeMet) after a long term (6 days) Se supplementation in normal human skin fibroblasts (NHSF) subjected to ultraviolet-A (UVA) irradiation inducing 30% cell death. The uptake, toxicity and antioxidant effects of sodium selenite and SeMet were compared to better understand their photoageing properties. SeMet uptake was better than sodium selenite and their uptake by fibroblasts was not via an actively transport process. Sodium selenite induced a higher toxicity than SeMet. At 5 μM, sodium selenite inhibited cell proliferation associated with a blockage in the G2 phase and induced DNA fragmentation leading to caspase-3-dependent apoptosis cell death. At low doses (<1 μM), SeMet and sodium selenite induced glutathione peroxidase-1 (GPX1) activity and selenoproteinW1 (SEPW1) transcript expression but metalloproteinase (MMP)-1 was only induced by sodium selenite. SeMet and sodium selenite did not protect NHSFs from UVA-induced cell death. However, SeMet decreased malondialdehyde (MDA) and protected NHSFs from UVA-induced MMP1 and MMP3. We then observed a large difference in terms of photoprotection according to selenium forms. SeMet may be a potential agent for the prevention and treatment of skin photoageing.


IkappaB kinase-2-independent and -dependent inflammation in airway disease models: relevance of IKK-2 inhibition to the clinic.
Nuclear factor kappaB (NF-kappaB) is a transcription factor believed to be central in the expression of numerous inflammatory genes and the pathogenesis of many respiratory diseases. We have previously demonstrated increased NF-kappaB pathway activation in a steroid-sensitive animal model of lipopolysaccharide (LPS)-driven airway inflammation. It is noteworthy that this phenomenon was not observed in a steroid-insensitive model of elastase-induced inflammation in the rat. The aim of this study was to gather further evidence to suggest that these similar profiles of neutrophilic inflammation can be NF-kappaB-dependent or -independent by determining the impact of an IkappaB kinase-2 (IKK-2) inhibitor, 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1). In the LPS model, TPCA-1 blocked the increase in NF-kappaB DNA binding, a marker of NF-kappaB pathway activation. This inhibition was associated with a reduction in inflammatory mediator release [tumor necrosis factor alpha (TNFalpha)/interleukin-1beta (IL-1beta)/matrix metalloproteinase-9 (MMP-9)] and lung inflammatory cell burden (neutrophilia/eosinophilia). These data were paralleled with a steroid and in human cell based assays. In the elastase-driven inflammation model, in which our group has previously failed to measure an increase in NF-kappaB DNA binding, neither TPCA-1 nor the steroid, affected mediator release (IL-1beta/MMP-9) or cellular burden (neutrophilia/lymphomononuclear cells). This is the first study to examine the effect of an IKK-2 inhibitor in well validated models that mimic aspects of the inflammatory lesion evident in diseases such as COPD. In conclusion, we have demonstrated that animal models with similar profiles of airway inflammation can be IKK-2 inhibitor/steroid-sensitive or -insensitive. If both profiles of inflammation exist in the clinic, then this finding is extremely exciting and may lead to greater understanding of disease pathology and the discovery of novel anti-inflammatory targets.


Knowledge About COVID-19 in Brazil: Cross-Sectional Web-Based Study.
COVID-19 is a highly transmissible illness caused by SARS-CoV-2. The disease has affected more than 200 countries, and the measures that have been implemented to combat its spread, as there is still no vaccine or definitive medication, have been based on supportive interventions and drug repositioning. Brazil, the largest country in South America, has had more than 140,000 recorded deaths and is one of the most affected countries. Despite the extensive quantity of scientifically recognized information, there are still conflicting discussions on how best to face the disease and the virus, especially with regard to social distancing, preventive methods, and the use of medications. The main purpose of this study is to evaluate the Brazilian population's basic knowledge about COVID-19 to demonstrate how Brazilians are managing to identify scientifically proven information. A cross-sectional study design was used. An original online questionnaire survey was administered from June 16 to August 21, 2020, across all five different geopolitical regions of the country (ie, the North, Northeast, Center-West, Southeast, and South). The questionnaire was comprised of questions about basic aspects of COVID-19, such as the related symptoms, conduct that should be followed when suspected of infection, risk groups, prevention, transmission, and social distancing. The wrong questionnaire response alternatives were taken from the fake news combat website of the Brazilian Ministry of Health. Participants (aged ≥18 years) were recruited through social networking platforms, including Facebook, WhatsApp, and Twitter. The mean distributions, frequencies, and similarities or dissimilarities between the responses for the different variables of the study were evaluated. The significance level for all statistical tests was less than .05. A total of 4180 valid responses representative of all the states and regions of Brazil were recorded. Most respondents had good knowledge about COVID-19, getting an average of 86.59% of the total score with regard to the basic aspects of the disease. The region, education level, age, sex, and social condition had a significant association (P<.001) with knowledge about the disease, which meant that women, the young, those with higher education levels, nonrecipients of social assistance, and more economically and socially developed regions had more correct answers. Overall, Brazilians with social media access have a good level of basic knowledge about COVID-19 but with differences depending on the analyzed subgroup. Due to the limitation of the platform used in carrying out the study, care should be taken when generalizing the study findings to populations with less education or who are not used to accessing social networking platforms.


Prevalence of mcr-1 in Escherichia coli and Klebsiella pneumoniae recovered from bloodstream infections in China: a multicentre longitudinal study.
Polymyxin antibiotics are used as last-resort therapies to treat infections caused by multidrug-resistant Gram-negative bacteria. The plasmid-mediated colistin resistance determinant MCR-1 has been identified in Enterobacteriaceae in China. We did this study to investigate the prevalence of the mcr-1 gene in clinical isolates from patients with bloodstream infections in China. Clinical isolates of Escherichia coli and Klebsiella pneumoniae were collected from patients with bloodstream infections at 28 hospitals in China, then screened for colistin resistance by broth microdilution and for the presence of the mcr-1 gene by PCR amplification. We subjected mcr-1-positive isolates to genotyping, susceptibility testing, and clinical data analysis. We established the genetic location of mcr-1 with Southern blot hybridisation, and we analysed plasmids containing mcr-1 with filter mating, electroporation, and DNA sequencing. 2066 isolates, consisting of 1495 E coli isolates and 571 K pneumoniae isolates were collected. Of the 1495 E coli isolates, 20 (1%) were mcr-1-positive, whereas we detected only one (<1%) mcr-1-positive isolate among the 571 K pneumoniae isolates. All mcr-1-positive E coli and K pneumoniae isolates were resistant to colistin, with minimum inhibitory concentrations values in the range of 4-32 mg/L, except for one E coli isolate that had a minimum inhibitory concentration less than or equal to 0·06 mg/L. All 21 mcr-1-positive isolates were susceptible to tigecycline and 20 isolates (95%) were susceptible to the carbapenem and β-lactamase inhibitor combination piperacillin and tazobactam. One mcr-1-positive E coli isolate also produced NDM-5, which confers resistance to beta-lactam antibiotics. The 21 mcr-1-positive isolates were clonally diverse and carried mcr-1 on two types of plasmids, a 33 kb IncX4 plasmid and a 61 kb Inc12 plasmid. The 30 day mortality of the patients with bloodstream infections caused by mcr-1-positive isolates was zero. mcr-1-positive isolates from bloodstream infections were rare, sporadic, and remained susceptible to many antimicrobial agents. E coli, rather than K pneumoniae, was the main host of the mcr-1 gene. Further studies are needed to clarify the clinical impact of this novel resistance gene. National Natural Science Foundation of China.


Diffusely Adherent Escherichia coli Strains Isolated from Healthy Carriers Suppress Cytokine Secretions of Epithelial Cells Stimulated by Inflammatory Substances.
Diarrheagenicity of diffusely adherent Escherichia coli (DAEC) remains controversial. Previously, we found that motile DAEC strains isolated from diarrheal patients induced high levels of interleukin 8 (IL-8) secretion via Toll-like receptor 5 (TLR5). However, DAEC strains from healthy carriers hardly induced IL-8 secretion, irrespective of their possessing flagella. In this study, we demonstrated that SK1144, a DAEC strain from a healthy carrier, suppressed IL-8 and IL-6 secretion from human epithelial cell lines. Suppression of IL-8 in human embryonic kidney (HEK293) cells that were transformed to express TLR5 was observed not only upon inflammatory stimulation by flagellin but also in response to tumor necrosis factor alpha (TNF-α) and phorbol myristate acetate (PMA), despite the fact that the TNF-α- and PMA-induced inflammatory pathways reportedly are not TLR5 mediated. SK1144 neither decreased IL-8 transcript accumulation nor increased intracellular retention of IL-8. No suppression was observed when the bacteria were cultured in Transwell cups above the epithelial cells; however, a nonadherent bacterial mutant (lacking the afimbrial adhesin gene) still inhibited IL-8 secretion. Direct contact between the bacteria and epithelial cells was necessary, but diffuse adhesion was dispensable for the inhibitory effects. Infection in the presence of chloramphenicol did not suppress cytokine release by the epithelial cells, suggesting that suppression depended on effectors synthesized de novo Inflammatory suppression was attenuated with infection by a bacterial mutant deleted for hcp (encoding a component of a type VI secretion system). In conclusion, DAEC strains from healthy carriers impede epithelial cell cytokine secretion, possibly by interfering with translation via the type VI secretion system.


Identification of pharmacological chaperones for Gaucher disease and characterization of their effects on beta-glucocerebrosidase by hydrogen/deuterium exchange mass spectrometry.
Point mutations in beta-glucocerebrosidase (GCase) can result in a deficiency of both GCase activity and protein in lysosomes thereby causing Gaucher Disease (GD). Enzyme inhibitors such as isofagomine, acting as pharmacological chaperones (PCs), increase these levels by binding and stabilizing the native form of the enzyme in the endoplasmic reticulum (ER), and allow increased lysosomal transport of the enzyme. A high-throughput screen of the 50,000-compound Maybridge library identified two, non-carbohydrate-based inhibitory molecules, a 2,4-diamino-5-substituted quinazoline (IC(50) 5 microM) and a 5-substituted pyridinyl-2-furamide (IC(50) 8 microM). They raised the levels of functional GCase 1.5-2.5-fold in N370S or F213I GD fibroblasts. Immunofluorescence confirmed that treated GD fibroblasts had decreased levels of GCase in their ER and increased levels in lysosomes. Changes in protein dynamics, monitored by hydrogen/deuterium-exchange mass spectrometry, identified a domain III active-site loop (residues 243-249) as being significantly stabilized upon binding of isofagomine or either of these two new compounds; this suggests a common mechanism for PC enhancement of intracellular transport.


Mechanisms of site-specific photochemistry following core-shell ionization of chemically inequivalent carbon atoms in acetaldehyde (ethanal).
Site-specific fragmentation upon 1s photoionisation of acetaldehyde has been studied using synchrotron radiation and a multi-electron-ion coincidence technique based on a magnetic bottle. Experimental evidence is presented that bond rupture occurs with highest probability in the vicinity of the initial charge localisation and possible mechanisms are discussed. We find that a significant contribution to site-specific photochemistry is made by different fragmentation patterns of individual quantum states populated at identical ionisation energies.


A link between inflammation and thrombosis in atherosclerotic cardiovascular diseases: Clinical and therapeutic implications.
The association between thrombosis and acute coronary syndromes is well established. Inflammation and activation of innate and adaptive immunity are another important factor implicated in atherosclerosis. However, the exact interactions between thrombosis and inflammation in atherosclerosis are less well understood. Accumulating data suggest a firm interaction between these two key pathophysiologic processes. Pro-inflammatory cytokines, such as tumor necrosis factor α, interleukin-6 and interleukin-1, have been implicated in the thrombotic cascade following plaque rupture and myocardial infarction. Furthermore, cell adhesion molecules accelerate not only atheromatosis but also thrombosis formation while activated platelets are able to trigger leukocyte adhesion and accumulation. Additionally, tissue factor, thrombin, and activated coagulation factors induce the release of pro-inflammatory cytokines such as prostaglandin and C reactive protein, which may further induce von Willebrand factor secretion. Treatments targeting immune activation (i.e. interleukin-1 inhibitors, colchicine, statins, etc.) may also beneficially modulate platelet activation while common anti-thrombotic therapies appear to attenuate the inflammatory process. Taken together in the context of cardiovascular diseases, thrombosis and inflammation should be studied and managed as a common entity under the concept of thrombo-inflammation.


Out of society? Retirement affects perceived social exclusion in Germany.
Perceived social exclusion (PSE) depends on individual access to resources (e.g. income and social networks) and recognition of a social status. Working provides individuals with both resources and a social status. This situation leaves the non-working population at a severe social disadvantage, which might partly be remedied by retirement. We expected to find differential effects on PSE when individuals retire. For individuals working until retirement the transition might be mostly associated with a loss of resources (leading to an increase in PSE) and for individuals not working before retirement the transition might be more strongly associated with an increase in social status (leading to a decrease in PSE). We used longitudinal data from the German Panel Study of Labor Market and Social Security (PASS) to estimate fixed effects panel regression models for 790 men and women experiencing the transition to retirement (4110 observations). Models were estimated separately for retired persons who worked or did not work prior to retirement. At retirement those working prior to the transition reported lower levels of PSE than those not working. As expected retirement increased PSE for those previously working and for those not previously working retirement decreased PSE in the short term. Both effects remained stable after compensating for resource changes due to retirement. Retirement reduced the differences in PSE between previously working and non-working groups. For those previously working retirement seemed to depict a loss of social acceptance whereas for those previously not working retirement seemed to indicate a reduction of stigmatization. The previous effect of the labor market, however, continued to affect individuals in retirement for a long time.


Uptake of gentamicin by vestibular efferent neurons and superior olivary complex after transtympanic administration in guinea pigs.
Transtympanic administration of gentamicin is a widely accepted and effective approach for treating patients with intractable vertigo. Previous studies have demonstrated the uptake, distribution and effects of gentamicin in peripheral vestibular and cochlear structures after transtympanic injection. However, little is known about whether transtympanically administered gentamicin is trafficked into more central auditory and vestibular structures and its effect on these structures. In this study, we used immunofluorescence to determine the distribution of gentamicin within the auditory and vestibular brainstem. We observed gentamicin immunolabeling bilaterally in the vestibular efferent neurons, and in the superior olivary complex, and ipsilaterally in the cochlear nucleus 24h after transtympanic administration of gentamicin, and that the drug could still be detected in these locations 30 days after injection. In contrast, no gentamicin labeling was detected in the vestibular nuclear complex. In the vestibular efferent neurons and superior olivary complex, gentamicin labeling was detected in the cytoplasm and cell processes, while in the cochlear nucleus gentamicin is mainly localized outside and adjacent to the cell bodies of neurons. Nerve fibers in cochlear nucleus, root of eighth nerve, as well as descending pathways from the superior olivary complex, are also immunolabeled with gentamicin continuously. Based on these data, we hypothesize that retrograde axonal transport of gentamicin is responsible for the distribution of gentamicin in these efferent nuclei including vestibular efferent neurons and superior olivary complex and anterograde axonal transport into the ipsilateral cochlear nucleus.


The impact of electronic cigarettes on the paediatric population.
To review the impact of electronic cigarettes (e-cigarettes) on children. Five electronic databases were searched through 31 December 2013. Studies in English that included data for children younger than 18 years of age were included. In addition, relevant data from articles identified during searches of the e-cigarette literature, relevant state survey data and paediatric voluntary adverse event reports submitted to the US Food and Drug Administration (FDA) were reviewed and included. Use of e-cigarettes by youth is increasing and is not limited to traditional cigarette smokers. Data regarding the reasons for youth e-cigarette initiation and ongoing use are limited. The effects of e-cigarette marketing and the availability of flavoured e-liquids on youth use are unknown. The abuse liability of e-cigarettes in youth is also not known. Unintentional exposures to e-cigarettes and e-liquids have been reported in children. The number of e-cigarette-related reports received by poison centres is increasing. No data are available on secondhand and thirdhand e-cigarette aerosol exposures in children. Data on the impact of e-cigarettes on children are extremely limited. The available data indicate that youth awareness is high and use is increasing rapidly. The extent to which e-cigarette use in youth will result in nicotine dependence and subsequent use of other tobacco products is unknown. e-cigarettes present risks of unintentional nicotine exposure and are potential choking hazards. A greater understanding of the impact of e-cigarettes on children is needed and will be important in the evaluation of the effects of these products on the public health.


The association between parental imprisonment and the mental health of Palestinian adolescents.
Since 1967, the Palestinian Occupied Territories are marked by a protracted political conflict. During this conflict, about one fifth of the Palestinian population has been detained; a considerable part of them having children outside prison. Although parental detention negatively impacts children's psychological well-being, little is known about this impact within contexts of protracted armed conflict. Therefore, this study aimed at gaining insight into the impact of parental detention onto adolescents' psychological well-being. Of 314 (11- to 18-year old) Palestinian adolescents who took part, the fathers of 204 adolescents were detained in Israeli prisons. The adolescents completed two self-report questionnaires: the UCLA-PTSD-Reaction Index, investigating symptoms of posttraumatic stress, and the Strengths and Difficulties Questionnaire, looking at overall psychological problems. Several hierarchical regression analyses investigated mental health differences between both the groups, and possible associations between sociodemographic characteristics and the witnessing of the father's arrest, and the mental health outcomes. Parental detention largely impacted adolescents' mental health, with one fifth to two thirds of the adolescents reporting considerable mental health problems. Witnessing the arrest of the father even increased this risk considerably. Above, girls, younger adolescents, participants living in refugee camps, and those living with extended families also reported higher scores on both questionnaires. Detention of fathers in the context of protracted armed conflicts has a large impact on adolescents' mental health. Besides an overall plea to end armed conflicts as fast as possible, the study also delineates considerable implications for the support and care for these adolescents and their families.


Global tests for multiple binary outcomes.
The applied statistician often encounters the need to compare two or more groups with respect to more than one outcome or response. Several options are generally available, including reducing the dimension of the problem by averaging or summarizing the outcomes, using Bonferroni or other adjustments for multiple comparisons, or applying a global test based on a suitable multivariate model. For normally distributed data, it is well established that global tests tend to be significantly more sensitive than other procedures. While global tests have also been proposed for multiple binary outcomes, their properties have not been well studied nor have they been widely discussed in the context of clustered data. In this paper, we derive a class of quasi-likelihood score tests for multiple binary outcomes, and show that special cases of this class correspond to other tests that have been proposed. We discuss extensions to allow for clustered data, and compare the results to the simple approach of collapsing the data to a single binary outcome, indicating the presence or absence of at least one response. The asymptotic relative efficiencies of the tests are shown to depend not only on the correlation between the outcomes, but also on the response probabilities. Although global tests based on a multivariate model are generally recommended, our findings suggest that a test based on the collapsed data can maintain surprisingly high efficiency, especially when the outcomes of interest are rare. Data from several developmental toxicity studies illustrate our results.


Maintenance of real objects and their verbal designations in working memory.
The present study investigated the neural correlates of working memory maintenance for real objects in contrast to their verbal designations. For this purpose we employed a delayed match-to-sample task using functional magnetic resonance imaging. The conjunction of load effects for objects and for words revealed a common bilateral network with main foci in the ventrolateral prefrontal cortex and the intraparietal sulcus. Load effect for objects in comparison to load effect for words revealed stronger activation of bilateral precuneus, which suggests the use of mental imagery of objects and object features. The opposite comparison load words versus load objects showed premotor and auditory areas to be activated in association with phonological rehearsal. The bilateral common activation indicates overlapping codes for real-world objects and their verbal designations. Importantly, there is also a dissociation between maintenance of words and objects, which indicates that phonological rehearsal and mental imagery are employed to different degrees.


Impact of patient and hospital-level risk factors on extended length of stay following spinal fusion for adolescent idiopathic scoliosis.
Health policy changes have led to increased emphasis on value-based care to improve resource utilization and reduce inpatient hospital length of stay (LOS). Recently, LOS has become a major determinant of quality of care and resource utilization. For adolescent idiopathic scoliosis (AIS), the determinants of extended LOS after elective posterior spinal fusion (PSF) remain relatively unknown. In the present study, the authors investigated the impact of patient and hospital-level risk factors on extended LOS following elective PSF surgery (≥ 4 levels) for AIS. The Kids' Inpatient Database (KID) was queried for the year 2012. Adolescent patients (age range 10-17 years) with AIS undergoing elective PSF (≥ 4 levels) were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Extended hospital LOS was defined as greater than the 75th percentile for the entire cohort (> 6 days), and patients were dichotomized as having normal LOS or extended LOS. Patient demographics, comorbidities, complications, LOS, discharge disposition, and total cost were recorded. A multivariate logistic regression model was used to determine the odds ratio for risk-adjusted LOS. The primary outcome was the degree to which patient comorbidities or postoperative complications correlated with extended LOS. Comorbidities were overall significantly higher in the extended-LOS cohort than the normal-LOS cohort. Patients with extended LOS had a significantly greater proportion of blood transfusion (p < 0.001) and ≥ 9 vertebral levels fused (p < 0.001). The overall complication rates were greater in the extended-LOS cohort (20.3% [normal-LOS group] vs 43.5% [extended-LOS group]; p < 0.001). On average, the extended-LOS cohort incurred $18,916 more in total cost than the normal-LOS group ($54,697 ± $24,217 vs $73,613 ± $38,689, respectively; p < 0.001) and had more patients discharged to locations other than home (p < 0.001) than did patients in the normal-LOS cohort. On multivariate logistic regression, several risk factors were associated with extended LOS, including female sex, obesity, hypertension, fluid electrolyte disorder, paralysis, blood transfusion, ≥ 9 vertebrae fused, dural injury, and nerve cord injury. The odds ratio for extended LOS was 1.95 (95% CI 1.50-2.52) for patients with 1 complication and 5.43 (95% CI 3.35-8.71) for patients with > 1 complication. The authors' study using the KID demonstrates that patient comorbidities and intra- and postoperative complications all contribute to extended LOS after spinal fusion for AIS. Identifying multimodality interventions focused on reducing LOS, bettering patient outcomes, and lowering healthcare costs are necessary to improve the overall value of care for patients undergoing spinal fusion for AIS.


Skill mastery in public CPR classes.
Effectiveness of CPR performance on a manikin was evaluated immediately after training in public CPR classes by trained independent observers using validated measures and procedures. An instrumented manikin was used to assess critical skills thought to be related to survival following out-of-hospital cardiac arrest (compressions and ventilations), applying standards of the American Heart Association. The 226 subjects were enrolled in CPR classes offered to the public by the American Red Cross and the American Heart Association. Fifty percent of subjects performed 2% or fewer compressions correctly (the most common error being insufficient depth), and 50% performed 10% or fewer of ventilations correctly (the most common error being insufficient volume). Sixty-five percent failed to achieve a compression rate of 80 to 100/min. Forty-five percent of subjects failed to open the airway prior to a breathing check, 50% failed to adequately assess breathing, and 53% did not perform an adequate pulse check. Nearly half of all subjects made at least four errors in assessment and sequencing of skills. According to published criteria, trainee performance of CPR is poor. Failure in critical skills may contribute to poor survival rate following out-of-hospital cardiac arrest. CPR training programs must be developed with attention to learner outcomes.


Prehospital airway procedures performed in trauma patients by ground forces in Afghanistan.
Airway management is of critical importance in combat trauma patients. Airway compromise is the second leading cause of potentially survivable death on the battlefield and accounts for approximately 1 in 10 preventable deaths. Reports from the Iraq and Afghanistan wars indicate 4% to 7% incidence of airway interventions on casualties transported to combat hospitals. The goal of this study was to describe airway management in the prehospital combat setting and document airway devices used on the battlefield. This study is a retrospective review of casualties that required a prehospital lifesaving airway intervention during combat operations in Afghanistan. We obtained data from the Prehospital Trauma Registry that was linked to the Department of Defense Trauma Registry for outcome data for the time period between January 2013 and September 2014. Seven hundred five total trauma patients were included, 16.9% required a prehospital airway management procedure. There were 132 total airway procedures performed, including 83 (63.4%) endotracheal intubations and 26 (19.8%) nasopharyngeal airway placements. Combat medics were involved in 48 (36.4%) of airway cases and medical officers in 73 (55.3%). Most (94.2%) patients underwent airway procedures due to battle injuries caused by explosion or gunshot wounds. Casualties requiring airway management were more severely injured and less likely to survive as indicated by Injury Severity Score, responsiveness level, Glascow Coma Scale, and outcome. Percentages of airway interventions more than tripled from previous reports from the wars in Afghanistan and Iraq. These changes are significant, and further study is needed to determine the causes. Casualties requiring airway interventions sustained more severe injuries and experienced lower survival than patients who did not undergo an airway procedure, findings suggested in previous reports. Prognostic and epidemiological study, level III.


Chronic Hepatitis C virus infection in Swiss primary care practices: low case loads-high barriers to treatment?
The primary care physician (PCP) diagnoses chronic Hepatitis C virus (HCV) infection in most patients. He serves as gatekeeper and plays a key role in counselling and treatment guidance. To calculate the approximate HCV caseload per practice and characterize PCPs management of the disease; in particular, to determine antiviral treatment rates and reasons for PCPs for withholding treatment. The ultimate objective was to identify potentially modifiable barriers to treatment. A confidential self-administered questionnaire centred on the above-mentioned questions was distributed to 2371 Swiss primary care physicians. All respondents of the main questionnaire received an additional small questionnaire focussed on the initial disease workup. Descriptive statistics were used to describe questionnaire responses and PCP demographics. The response rate was 53.1%. Of all participating PCPs (n = 1084), 86.2% reported having patients with chronic HCV, with an average number of 4 patients per practice; 18.6% (n = 142) of PCPs did not monitor their chronic HCV patients. Two-thirds (66.8%) of the sample chronic HCV patient population (n = 4626) never received antiviral therapy. The main reasons given by PCPs for withholding treatment were HCV-specialist advice, patient preference, normal liver enzymes and patient related factors like substance abuse or psychiatric co morbidity. Most PCPs follow patients with chronic hepatitis C, but practice caseloads are low, which may account for insecurity in managing this complex disease.


Women's responses to nausea and vomiting in pregnancy.
To explore women's experiences of nausea and vomiting in pregnancy. secondary (thematic) analysis of data collected by narrative interviews for two wider studies about antenatal screening and about pregnancy for the DIPEx website (www.dipex.org). A maximum variation sample was recruited throughout the UK. Data from the 73 women interviewed have been analysed. Interviews took place between October 2003 and December 2004, mostly in the home. sickness is considered a typical and almost inevitable feature of pregnancy. Against this backdrop, a new framework for understanding women's responses to nausea and vomiting in pregnancy, and the meanings they attach to it, is suggested: nausea and vomiting as something to be expected, survived, resisted, resented, and acknowledged by others. The concepts of loss of self and biographical disruption from the field of chronic illness seem to resonate with the women's experiences, and may perhaps be extended to transient as well as chronic health conditions. People's experiences of their bodies in health as well as illness need to be more widely studied. Many women would appreciate greater acknowledgement of the distress nausea and vomiting in pregnancy causes them, information about remedies and strategies other women have found helpful, and reassurance. Expressions of empathy by health-care professionals are frequently lacking and particularly desired.


Myocardial perfusion imaging with adenosine triphosphate predicts the rate of cardiovascular events.
Adenosine triphosphate (ATP) has effects similar to adenosine, including a very short half-life, with the advantage of a much lower cost. Our aim was to evaluate whether myocardial single photon emission computed tomography (SPECT) with ATP can predict the rate of hard events. We studied 299 patients (188 men; mean age, 64 +/- 10 years) with known or suspected coronary disease with thallium 201 SPECT during ATP infusion and at rest. Perfusion defects were divided into the following: absent/mild reversible, moderate/severe reversible, and mixed/fixed. During a maximum follow-up of 87 months (mean, 32.7 +/- 20.3 months), the rate of cardiovascular events was studied. The prognostic value of different variables that can influence survival was calculated with the Cox proportional hazards model. The total number of cardiovascular events was 115 (43 hard events). The annual rate of hard events according to type of perfusion defect was 3.44% (95% confidence interval [CI], 2.12-5.26) for absent/mild reversible, 6.06% (95% CI, 2.23-13.20) for moderate/severe reversible, and 15.12% (95% CI, 8.64-24.55) for mixed/fixed. In the Cox model the variables that significantly predicted hard events were age greater than 55 years (P = .0293), diabetes (P = .0036), and severe perfusion defects (P = .0008). ATP can be used for pharmacologic stress testing. SPECT with ATP has a stronger correlation with the rate of hard events than clinical variables.


Effect of conjugated and unconjugated hyperbilirubinaemia on the plasma 25-hydroxy-vitamin D response to ultraviolet radiation in the rat.
1. Vitamin D deficiency was induced in anicteric Wistar rats, Wistar rats before common bile-duct ligation was performed and Gunn rats with unconjugated hyperbilirubinaemia. 2. The effect of ultraviolet radiation on plasma concentrations of 25-hydroxy-vitamin D was studied in a group of control anicteric Wistar rats (n = 11), Wistar rats 8 days after common bile-duct ligation (n = 7) with conjugated hyperbilirubinaemia and in Gunn rats (n = 11). 3. The plasma 25-hydroxy-vitamin D response to ultraviolet radiation was similar in the three groups. 4. It is suggested that neither conjugated nor unconjugated hyperbilirubinaemia prevent cutaneous vitamin D3 synthesis or 25-hydroxylation in the rat.


Investigation of gene expression and genetic simultaneous control associated with erectile dysfunction and diabetes.
Diabetes can cause some diseases or abnormalities. One of the disorders caused by diabetes may be erectile dysfunction (ED). ED is sexual dysfunction characterized by the inability to establish or maintain an erect penis during sexual activity and is a common problem of men with chronic type 2 diabetes. These processes, disorders and diseases are highly influenced by the genetics of individuals. In this study, the relationship between genes and diabetes and ED has been explored by a system biology approach. For this purpose, the samples from ten control and diabetic-ED rats were collected. After a search in Gene Expression Omnibus (GEO), series with accession number GSE2457 comprising of 5 normal and 5 diabetic-ED rats were selected. Raw CEL files of these samples were normalized with robust multi-array average (RMA) expression measure method by using the linear models for microarray data (LIMMA) R package. The extracted probe IDs were transformed into 10451 unique and validated official gene symbols. Then, differentially expressed genes (DEGs) were identified between control and normal penile mucosa by employing the LIMMA R package. DEGs were classified by utilizing KEGG to underlying pathways by Enrichr. The expression values of DEGs were used to construct a gene regulatory network (GRN), by the GENEI3 R package. To analyze the topology of constructed GRNs, betweenness centrality was calculated. Genes with higher betweenness centrality scores were then identified, through the CytoNCA. We then took the commonality of DEGs genes and high-top ranking genes from CytoNCA via a predicted interaction network using GeneMANIA as the most likely important genes in erectile dysfunction. Among the 374 DEGs studied, 146 DEGs showed up-regulation and 228 DEGs displayed down-regulation expression in diabetic-ED rats. According to the Volcano plot, the dpp4, LOC102553868, Ndufa412, Oxct1, Atp2b3 and Zfp91 gene down-regulated and Lpl, Retsat, B4galt1 and Pdk4 genes up-regulated in ED and diabetic rats. Furthermore, genes like dpp4 acted as hubs in the inferred GRN.