Identification of animal glue and hen-egg yolk in paintings by use of enzyme-linked immunosorbent assay (ELISA).
We report the development of an indirect ELISA procedure for specific identification of chicken-egg yolk and animal glues in painting micro-samples. The results presented integrate previously published work on ELISA recognition of bovine β-casein and chicken ovalbumin in painting materials. The integrated final ELISA procedure-optimised for protein extraction, immuno-reagent concentrations, blocking solution, incubation time, and temperature-enables multiplex identification, in single samples, of proteinaceous materials, i.e. chicken-egg yolk and albumen, animal glues, and bovine milk and/or casein, mainly used by painters in the past. The procedure has been systematically tested on laboratory models of mural and easel paintings, both naturally and artificially aged, to assess possible inhibitory effects on the immuno-reaction caused by inorganic painting materials (pigments and substrates) and by protein degradation resulting from aging processes. Real samples from case studies, which had previously been investigated and characterised by spectroscopy and chromatography, were successfully studied by use of the developed ELISA procedure. The commercial availability of all the immuno-reagents used, the affordable analytical equipment, and the specificity, sensitivity, and rapidity of ELISA make this method very attractive to diagnostic laboratories in the field of cultural heritage science. Possible further developments to the analytical potential of this technique include improvement of antibody performance and inclusion of other classes of bio-molecules as analytical targets.


How to screen athletes for cardiovascular diseases.
The Italian screening protocol has adequate sensitivity and specificity for detection of potentially dangerous cardiovascular diseases, and substantially reduces mortality of young competitive athletes, mostly by preventing sudden cardiac death from cardiomyopathy. The results of the Italian preparticipation evaluation program have significant implications worldwide: this article addresses the efficacy and feasibility of preparticipation screening, essentially based on 12-lead ECG, as has been in practice in Italy for 25 years.


A priori design of new natural deep eutectic solvent for lutein recovery from microalgae.
Lutein is an important functional food ingredient. However, its recovery processes developed so far seem to fail in sustainability criteria, regarding the urgent need for improved extraction ability while maintaining stability. This work aimed to study the design and application of natural deep eutectic solvent (NADES) for lutein recovery from Scenedesmus sp with the aid of COSMO-RS. The performance of the novel fenchyl alcohol/thymol-based system was studied comprehensively under different extraction parameters. Furthermore, thermal, light and storage stability of lutein in NADES were investigated. It was found that lutein recovery from microalgae should be performed using equimolar hydrogen-bond acceptor/donor at 60 °C within 70 min. The NADES could increase lutein yield compared with the conventional methodology using organic solvents. Besides, it significantly enhanced the lutein stability under various conditions. Hydrogen bond and Van der Waals interaction play crucial roles during target processing, elucidated by theoretical calculations and nuclear magnetic resonance.


Course of antrum and body gastritis in pernicious anemia families.
The course of antrum and body gastritis was studied using an essentially linear multicompartmental model in pernicious anemia probands, their first-degree relatives, and controls consisting of a representative family sample of a large Finnish population. Our earlier dynamic approach showed that progression of body gastritis was virtually identical in a series followed up with biopsies and in cross-comparison analyses, indicating that cross-sectional data can be used for dynamic analyses at a population level. The collected data fitted a model which consisted of stepwise progression of body gastritis to severe atrophy, of corresponding progressive steps for antral gastritis, and of regression of the antral changes after the end-stage of the body process had been reached. In addition, acceleration of the progression of gastritis in older subjects had to be taken into account in the model construction. The main findings which characterized pernicious anemia probands and their close relatives were: (1) a rapid overall progression of body gastritis particularly after 50 years of age; (2) a very rapid progression of body atrophy in its final stages, which was unrelated to age; (3) the occurrence of juvenile severe body atrophy; and (4) the healing of antral gastritis which was most marked at the stage of superficial gastritis. These results may offer a dynamic explantation for the occurrence of severe body atrophy in association with a normal or slightly altered antral mucosa in pernicious anemia and the prepernicious anemia state.


Identifying families with complex needs after an initial child abuse investigation: A comparison of demographics and needs related to domestic violence, mental health, and substance use.
Families with complex needs related to domestic violence, mental health, and substance use have some of the worst child protective services (CPS) outcomes. Although many of these families are identified during a CPS investigation and subsequently referred to home-based postinvestigation services (HBPS), many are re-reported to CPS, so it is important to understand the postinvestigation experiences of this vulnerable group. Therefore, this study compared families with and without complex needs to understand their uniquedemographics, needs, and postinvestigation outcomes. The sample consisted of 2008 caregivers who received HBPS following an initial CPS investigation. The Family Assessment Form (FAF) was used to measure family functioning in eight domains using a 1-5 scale with higher ratings representing worse functioning. Complex needs were indicated by a mean FAF score of 3 or higher for either domestic violence, mental health, or substance use. Using Pearson chi-square analyses and two-sample t-tests, comparisons were made between families with (n=836) and without (n=1172) complex needs. Half of caregivers with complex needs had a history of abuse, 25% had three to five needs, and nearly half had six to eight needs; 90% of caregivers without complex needs had zero to two needs. Furthermore, caregivers with complex needs had higher mean scores for concrete, educational, and clinical needs. These findings highlight the importance of recognizing variation among families referred to HBPS and accurate screening to ensure that families with complex needs are offered and receive services matched to their unique characteristics and needs.


Temporal bone manifestation of primary extranodal Rosai-Dorfman disease: a case report.
Rosai-Dorfman disease is a rare benign histiocytic disorder characterized in most cases by painless cervical adenopathy. Less than 10% of extranodal cases involve bony lesions. Primary bone Rosai-Dorfman disease in the absence of nodal disease is extremely rare. A 48 year-old Caucasian male presented with progressive right-sided otalgia, tinnitus, vertigo, and hearing loss. A right temporal bone lytic lesion was detected on diagnostic imaging. Resection of the lesion and histopathological examination revealed Rosai-Dorfman disease. Rosai-Dorfman disease primary bone lesions are an atypical presentation of a rare disease. This is the second reported case of Rosai-Dorfman disease arising within the temporal bone. This case study reveals that Rosai-Dorfman disease should be considered for patients presenting with inflammatory/lytic lesions of the temporal bone, in cases where infection and malignancy have been excluded.


Mycobacterium tuberculosis antigen 85B and ESAT-6 expressed as a recombinant fusion protein in Mycobacterium smegmatis elicits cell-mediated immune response in a murine vaccination model.
In this study, we investigated the potential molecular and immunological differences of a recombinant fusion protein (Hybrid-1), comprising of the immunodominant antigens Ag85B and ESAT-6 from Mycobacterium tuberculosis, derived from two different expression systems, namely Mycobacterium smegmatis and Escherichia coli. The fusion protein was successfully expressed and purified from both bacterial hosts and analyzed for any host-dependent post-translational modifications that might affect the immunogenicity of the protein. We investigated the immunogenicity of Hybrid-1 expressed in the two host species in a murine vaccination model, together with a reference standard Hybrid-1 (expressed in E. coli) from the Statens Serum Institut. No evidence of any post-translation modification was found in the M. smegmatis-derived Hybrid-1 fusion protein, nor were there any significant differences in the T-cell responses obtained to the three antigens analyzed. In conclusion, the Hybrid-1 fusion protein was successfully expressed in a homologous expression system using M. smegmatis and this system is worth considering as a primary source for vaccination trials, as it provided protein of excellent yield, stability and free from lipopolysaccharide.


Thermal degradation in a trimodal poly(dimethylsiloxane) network studied by (1)H multiple quantum NMR.
Thermal degradation of a filled, cross-linked siloxane material synthesized from poly(dimethylsiloxane) chains of three different average molecular weights and with two different cross-linking species has been studied by (1)H multiple quantum (MQ) NMR methods. Multiple domains of polymer chains were detected by MQ NMR exhibiting residual dipolar coupling (<Omega(d)>) values of 200 and 600 Hz, corresponding to chains with high average molecular weight between cross-links and chains with low average molecular weight between cross-links or near the multifunctional cross-linking sites. Characterization of the <Omega(d)> values and changes in <Omega(d)> distributions present in the material were studied as a function of time at 250 degrees C and indicate significant time-dependent degradation. For the domains with low <Omega(d)>, a broadening in the distribution was observed with aging time. For the domain with high <Omega(d)>, increases in both the mean <Omega(d)> and the width in <Omega(d)> were observed with increasing aging time. Isothermal thermal gravimetric analysis reveals a 3% decrease in weight over 20 h of aging at 250 degrees C. Degraded samples also were analyzed by traditional solid-state (1)H NMR techniques, and off-gassing products were identified by solid-phase microextraction followed by gas chromatography-mass spectrometry. The results, which will be discussed here, suggest that thermal degradation proceeds by complex competition between oxidative chain scissioning and postcuring cross-linking that both contribute to embrittlement.


Combinatorial Clustering and the Beta Negative Binomial Process.
We develop a Bayesian nonparametric approach to a general family of latent class problems in which individuals can belong simultaneously to multiple classes and where each class can be exhibited multiple times by an individual. We introduce a combinatorial stochastic process known as the negative binomial process ( NBP ) as an infinite-dimensional prior appropriate for such problems. We show that the NBP is conjugate to the beta process, and we characterize the posterior distribution under the beta-negative binomial process ( BNBP) and hierarchical models based on the BNBP (the HBNBP). We study the asymptotic properties of the BNBP and develop a three-parameter extension of the BNBP that exhibits power-law behavior. We derive MCMC algorithms for posterior inference under the HBNBP , and we present experiments using these algorithms in the domains of image segmentation, object recognition, and document analysis.


Clinical advances in the management of severe nausea and vomiting during pregnancy.
The nutritional status of the woman with hyperemesis of pregnancy has been compromised by decreased food intake and increased nutrient loss. Depending on the severity of symptoms, interventions may begin with dietary and life-style alterations, proceed to oral nutritional supplementation or pharmacologic preparations, and continue on to intravenous vitamin-mineral therapy and either enteral tube feedings, parenteral nutrition, or both. These therapies, and the role of the nurse in initiating or supporting them, are described.


Chemokine Receptors CXCR3 and CCR6 and Their Ligands in the Liver and Blood of Patients with Chronic Hepatitis C.
We performed a comprehensive analysis of CCR6 and CXCR3 chemokine receptors and their ligands CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, and CXCL11/ITAC in the liver and blood of patients with chronic hepatitis C at different stages of the disease. TaqMan PCR was used to determine mRNA gene expression of chemokines and their receptors in liver specimens, xMAP multiplex analysis was performed to estimate the concentration of chemokines in blood plasma, and fl ow cytofluorometry was used to evaluate CCR6 and CXCR3 expression on peripheral blood lymphocyte populations. In the liver of patients with hepatitis C, mRNA expression of CXCL10, CCR6, and CXCR3 genes increases with fibrosis progression in the liver tissue. In the plasma, concentrations of all studied chemokines increased depending on the stage of liver fibrosis, CCR6 and CXCR3 expression was changed in various lymphocyte populations. Thus, chemokines are involved in the immunopathogenesis and fibrogenesis in chronic viral hepatitis C. The results suggest using these chemokines in the diagnosis and prognosis of the disease.


Anomalous origin of anterior choroidal artery.
We report a very rare case of anomalous origin of anterior choroidal artery. In our case anterior choroidal artery arises from internal carotid artery proximal to the posterior communicating artery.


The Structure of LiuC, a 3-Hydroxy-3-Methylglutaconyl CoA Dehydratase Involved in Isovaleryl-CoA Biosynthesis in Myxococcus xanthus, Reveals Insights into Specificity and Catalysis.
Myxobacteria are able to produce the important metabolite isovaleryl coenzyme A by a route other than leucine degradation. The first step into this pathway is mediated by LiuC, a member of the 3-methylglutaconyl CoA hydratases (MGCH). Here we present crystal structures refined to 2.05 and 1.1 Å of LiuC in the apo form and bound to coenzyme A, respectively. By using simulated annealing we modeled the enzyme substrate complex and identified residues potentially involved in substrate binding, specificity, and catalysis. The dehydration of 3-hydroxy-3-methylglutaconyl CoA to 3-methylglutaconyl CoA catalyzed by LiuC involves Glu112 and Glu132 and likely employs the typical crotonase acid-base mechanism. In this, Tyr231 and Arg69 are key players in positioning the substrate to enable catalysis. Surprisingly, LiuC shows higher sequence and structural similarity to human MGCH than to bacterial forms, although they convert the same substrate. This study provides structural insights into the alternative isovaleryl coenzyme A biosynthesis pathway and might open a path for biofuel research, as isovaleryl-CoA is a source for isobutene, a precursor for renewable fuels and chemicals.


Ascaris suum antigens incorporated into liposomes used to stimulate protection to migrating larvae.
Four- to 8-week-old SPF pigs were immunized, using antigens of Ascaris suum incorporated into liposomes, via intestinal cannula or orally. Avridine was also incorporated in the liposomes in one experiment and interleukin-2 (IL-2) injected into pigs in another experiment. A priming dose of embryonate eggs (80-470 eggs/pig) were given in four of six experiments. Compared to control animals, the greatest protection of pigs to migrating ascarid larvae from a challenge dose of 10,000 embryonated eggs occurred where pigs received (1) a priming dose of eggs plus second-stage ascarid larval wall incorporated into liposomes, with or without avridine or IL-2, or (2) a priming dose of eggs plus ascarid intestinal aminopeptidase incorporated into liposomes with IL-2. The degree of protection was not statistically significant due, in part, to the variability in the responses of animals in the same treatment groups and the small number of animals per group. In general, only low titers of specific serum antibodies were detected and specific antibodies were not detected in the intestinal washing.


Results of a pilot risk-based lung cancer screening study: outcomes and comparisons to a Medicare eligible cohort.
Risk-based lung cancer screening holds potential to detect more cancers and avert more cancer deaths than screening based on age and smoking history alone, but has not been widely assessed or implemented in the United States. The purpose of this study was to prospectively identify patients for lung cancer screening based on lung cancer risk using the PLCOm2012 model and to compare characteristics, risk profiles, and screening outcomes to a traditionally eligible screening cohort. Participants who had a 6 year lung cancer risk score ≥ 1.5% calculated by the PLCOm2012 model and were ineligible for screening under 2015 Medicare guidelines were recruited from a lung cancer screening clinic. After informed consent, participants completed shared decision-making counseling and underwent a low-dose CT (LDCT). Characteristics and screening outcomes of the study population were compared to the traditionally eligible Medicare cohort with Fisher's Exact, t-tests, or Brown Mood tests, as appropriate. From August 2016 to July 2019, the study completed 48 baseline LDCTs. 10% of LDCTs recommended further pulmonary nodule evaluation (Lung-RADs 3 or 4) with two early-stage lung cancers diagnosed in individuals that had quit smoking > 15 years prior. The study population was approximately 5 years older (p = 0.001) and had lower pack years (p = 0.002) than the Medicare cohort. Prospective application of risk-based screening identifies screening candidates who are similar to a traditionally eligible Medicare cohort and future research should focus on the impact of risk calculators on lung cancer outcomes and optimal usability in clinical environments. This study was retrospectively registered on clinicaltrials.gov (NCT03683940) on 09/25/2018.


Secretion of matrix metalloproteinase-9 by macrophages, in vitro, in response to Helicobacter pylori.
We have previously shown that matrix metalloproteinase-9 (MMP-9) activity is greatly enhanced within the active chronic inflammation of Helicobacter pylori infected individuals, of which a major fraction derives from macrophages in the tissue. Here, we have investigated the ability of macrophages to secrete MMPs in response to H. pylori. Human macrophages secrete MMP-9 in response to live and inactivated H. pylori, as well as to specific bacterial products. Protein kinase C, phosphatiolylinositol 3-kinase and calcium uptake channels all play a role in MMP-9 secretion, whereas neither tumour necrosis factor alpha, interleukin-8, nor interleukin-1beta autocrine stimulation appear to contribute. We conclude that human macrophages have the ability to react directly against several H. pylori derived factors, utilising several signalling pathways.


Human dietary exposure to polycyclic aromatic hydrocarbons: A review of the scientific literature.
Polycyclic aromatic hydrocarbons (PAHs) are a group of over 200 different organic compounds that are mainly formed as the result of pyrolytic processes. For the general population, a number of studies have shown that, as for other environmental organic contaminants, the major route of exposure to PAHs is through food consumption. In this paper, the scientific literature concerning the concentrations of PAHs in food and the human dietary intake of these compounds, is reviewed. Unexpectedly, we have detected a considerable lack of scientific papers for countries such as Australia, Canada, Germany, or Japan, among many others, which seems rather unusual given the important scientific and social interest on the knowledge of the health risks of human exposure to environmental pollutants. The data from countries for which the human dietary intake of PAHs is available, show important differences among them, which would be explained by a number of factors, being probably the most important, the different methodologies used in the respective surveys. Regarding the influence of cooking on the levels of PAHs in foodstuffs, and the consequent intake, we conclude that it depends, not only on the particular cooking process, but even more on the specific characteristics of the respective food items.


Cytotoxic agents for use in dermatology. I.
There are indications for the use of cytotoxic drugs in some dermatologic diseases. These drugs may be lifesaving for patients with diseases such as pemphigus, lymphomas, and vasculitis or they may merely offer an improved quality of life for patients who have diseases such as psoriasis, progressive systemic sclerosis, or sarcoidosis. In either set of circumstances, in the properly monitored patient cytotoxic drugs may be used safely and effectively, offering very few problems for the patient or the therapist. The dermatologist who is interested in offering his/her patients the best medical care possible will wish to become proficient in the use of cytotoxic drugs, just as he/she is proficient in the use of the tetracyclines, systemic corticosteroids, and other powerful, but useful, agents.


Easy and effective method to generate endotoxin-free chitosan particles for immunotoxicology and immunopharmacology studies.
The cationic biopolymer chitosan (CH) has emerged as a promising candidate adjuvant due to its safety profile and immunostimulatory properties. The presence of endotoxin contamination in biomaterials is generally underappreciated and can generate misleading results. It is important to establish a convenient methodology to obtain large amounts of high quality chitosan nanoparticles for biomedical applications. We developed an easy method to generate endotoxin-free chitosan and assessed its purity using the Limulus amebocyte lysate assay and by measuring dendritic cell activation. Purified chitosan-based formulations alone failed to induce production of the proinflammatory cytokines tumour necrosis factor alpha (TNF-α) and interleukin (IL)-6 in bone marrow-derived dendritic cells (BMDCs) generated from C57BL/6 mice, while maintaining its ability to promote IL-1β secretion in combination with the Toll-like receptor (TLR)-9 agonist, CpG. Moreover, BMDCs from C3H/HeN and TLR4-deficient mice, C3H/HeJ were stimulated with endotoxin-free chitosan-based formulations and no differences were observed in IL-6 and IL-1β secretion, excluding the involvement of TLR-4 in the immunomodulatory effects of chitosan. The developed method provides simple guidelines for the production of endotoxin-free chitosan, ideal for biomedical applications.


Biserial targeted feature projection based radial kernel regressive deep belief neural learning for covid-19 prediction.
Coronavirus disease 2019 (COVID-19) is a highly infectious viral disease caused by the novel SARS-CoV-2 virus. Different prediction techniques have been developed to predict the coronavirus disease's existence in patients. However, the accurate prediction was not improved and time consumption was not minimized. In order to address these existing problems, a novel technique called Biserial Targeted Feature Projection-based Radial Kernel Regressive Deep Belief Neural Learning (BTFP-RKRDBNL) is introduced to perform accurate disease prediction with lesser time consumption. The BTFP-RKRDBNL techniques perform disease prediction with the help of different layers such as two visible layers namely input and layer and two hidden layers. Initially, the features and data are collected from the dataset and transmitted to the input layer. The Point Biserial Correlative Target feature projection is used to select relevant features and other irrelevant features are removed with minimizing the disease prediction time. Then the relevant features are sent to the hidden layer 2. Next, Radial Kernel Regression is applied to analyze the training features and testing disease features to identify the disease with higher accuracy and a lesser false positive rate. Experimental analysis is planned to measure the prediction accuracy, sensitivity, and specificity, and prediction time for different numbers of patients. The result illustrates that the method increases the prediction accuracy, sensitivity, and specificity by 10, 6, and 21% and reduces the prediction time by 10% as compared to state-of-the-art works.


Fetal tissue transplantation, bone marrow transplantation and prospective gene therapy in severe immunodeficiencies and enzyme deficiencies.
The successful development of fetal tissue transplantation has resulted in therapeutical solutions for patients with a variety of diseases. Fetal liver transplants as well as bone marrow transplants, can completely cure patients with severe combined immunodeficiency disease. These transplants can also be applied to treat other types of immunodeficiency, hemopathies, and inborn errors of metabolism, in association with immunosuppressive therapy. Despite complete HLA incompatibility between transplanted stem cells and host cells, functional activities of donor-derived T-lymphocytes are not restricted. In severe forms of Di George syndrome, immunological reconstitution can be obtained by fetal thymus transplantation. It is expected that, in the near future, pure stem cell transplants and gene transplants will develop and will provide remarkable solutions for the therapy of a large number of diseases.


Cognitive stimulation by caregivers for people with dementia.
Cognitive stimulation (CS) is a psychological intervention for people with dementia aimed at maintaining cognitive functioning. CS provided by caregivers would allow long-term maintenance without greatly increasing demands on health services, but raises questions concerning treatment fidelity and acceptability, which were investigated in this study. Caregivers of home-living people with dementia were trained to provide CS activities to their relative with dementia. Recordings of intervention sessions and analysis of training manuals suggested adequate delivery of the intervention. Dyads continued with the activities after caregiver training had stopped. In addition, presentation of the activities without supervision from a health care professional had no detrimental effect on well-being in the caregiver or the person with dementia. The majority of caregivers indicated that, even though they experienced some burden from doing the activities with their relative, they themselves had also benefited from the intervention and intended to continue with some of the activities.


Prospective studies of the association between anticardiolipin antibody and outcome of pregnancy.
To investigate the association of anticardiolipin antibody with the genesis of spontaneous abortion, fetal growth restriction (FGR), and preeclampsia. Eight hundred sixty pregnant women constituted the study population. Anticardiolipin antibody was screened by enzyme-linked immunosorbent assay during the first trimester of pregnancy. The outcome of pregnancy in these women was analyzed prospectively, and the rate of occurrence of spontaneous abortion, preeclampsia, and FGR was compared in the anticardiolipin antibody-positive and -negative groups. Anticardiolipin antibody was positive in 60 of the 860 women (7.0%) and negative in 800 (93.0%). The rate of spontaneous abortions in the anticardiolipin antibody-positive group, 25.0%, was significantly higher than that in the anticardiolipin antibody-negative group, at 9.8% (P < .001; relative risk [RR] 2.56, 95% confidence interval (CI) 1.37-4.81). The rates of preeclampsia (11.7%) and FGR (11.7%) in the anticardiolipin antibody-positive group were also significantly higher than those in the -negative group (1.9 and 1.9%, respectively; for preeclampsia, P < .001; RR 6.22, 95% CI 2.43-16.0 and for FGR, P < .001; RR 6.22, 95% CI 2.43-16.0). Anticardiolipin antibody is associated with adverse outcomes of pregnancy such as spontaneous abortion, preeclampsia, and FGR.


Heavy metal enrichment characteristics in ash of municipal solid waste combustion in CO2/O2 atmosphere.
This paper investigated the behavior of six heavy metals (Cd, Pb, Cu, Cr, Ni and Zn) in the bottom ashes of recycled polyvinyl chloride pellets (PVC), wood sawdust (WS) and paper mixture (PM), representing the common components of municipal solid waste (MSW), obtained during combustion in CO2/O2 atmosphere in a lab-scale electrically heated tube furnace. Replacement of N2 by CO2 did not obviously change the shape of relative enrichment factor (RE) curves and subsequent order of heavy metals, but increased enrichment of these heavy metals in bottom ashes of WS, PM and PVC. The increment of O2 concentration in CO2/O2 atmosphere further increased RE values. It was only when the temperature was higher than or equal to 700°C that the increment of the combustion temperature reduced the RE values of heavy metals. The effect of temperature on heavy metals evaporation was the most pronounced for the medium volatile metal Pb, and the least for the low volatiles Cr and Ni. The effect of temperature was more pronounced for PVC ash than for WS and PM ashes. This paper contributes to the control of heavy metals during MSW incineration and management of MSW oxy-fuel residues.


Evolution of brain and language.
In this chapter evolutionary changes in the human brain that are relevant to language are reviewed. Most of what is known involves assessments of the relative sizes of brain regions. Overall brain size is associated with some key behavioral features relevant to language, including complexity of the social environment and the degree of conceptual complexity. Prefrontal cortical and temporal lobe areas relevant to language appear to have increased disproportionately. Areas relevant to language production and perception have changed less dramatically. The extent to which these changes were a consequence specifically of language versus other behavioral adaptations is a good question, but the process may best be viewed as a complex adaptive system, whereby cultural learning interacts with biology iteratively over time to produce language. Overall, language appears to have adapted to the human brain more so than the reverse.


Evaluation of surfactants as solubilizing agents in microsomal metabolism reactions with lipophilic substrates.
Solubilizing agents are routinely added when investigating the biotransformation of lipophilic substrates using hepatic microsomes. For highly lipophilic compounds, the concentration of solvent or surfactant necessary for dissolution can be detrimental to enzyme activity. This study evaluates the effect of 12 surfactants on microsomal metabolism and the ability of the same surfactants to improve the aqueous solubility of the pentabrominated diphenyl ether BDE-100, a lipophilic environmental contaminant previously found to be recalcitrant to in vitro metabolism. Of the surfactants investigated, Cremophor EL and Tween 80 displayed the best combination of increased BDE-100 solubility and minimal inhibition of microsomal metabolism. However, a comparison of the in vitro metabolism products of BDE-100 in the presence of the two surfactants revealed varying amounts of metabolites depending on the surfactant used.


Shopper marketing nutrition interventions.
Grocery stores represent a context in which a majority of people's food purchases occur. Considering the nutrition quality of the population's food intake has dramatically decreased, understanding how to improve food choice in the grocery store is paramount to healthier living. In this work, we detail the type of financial resources from which shoppers could draw (i.e., personal income and benefits from government food assistance programs to low income populations) and explain how these financial resources are allocated in the grocery store (i.e., planned, unplanned, error). Subsequently, we identify a conceptual framework for shopper marketing nutrition interventions that targets unplanned fruit and vegetable purchases (i.e., slack, or willingness to spend minus list items). Targeting slack for fresh fruit and vegetable purchases allows retailers to benefit economically (i.e., fruit and vegetables are higher margin) and allows shoppers to improve their nutrition without increasing their budgets (i.e., budget neutrality). We also provide preliminary evidence of what in-store marketing of fresh fruits and vegetables could entail by modifying grocery carts and grocery floors to provide information of what is common, normal, or appropriate fruit and vegetable purchases. In each example, fresh fruit and vegetable purchases increased and evidence suggested shopper budget neutrality. To provide context for these results, we detail measurement tools that can be used to measure shopper behaviors, purchases, and consumption patterns. Finally, we address theoretical, practical, and policy implications of shopper marketing nutrition interventions.


Repeatability and reproducibility of high concentration data in reversed-phase liquid chromatography. I. Overloaded band profiles on Kromasil-C18.
Single-component adsorption-isotherm data were acquired by frontal analysis (FA) for six low-molecular-mass compounds (phenol, aniline, caffeine, theophylline, ethylbenzene and propranolol) on one Kromasil-C18 column, using water-methanol solutions (between 70:30 and 20:80, v/v) as the mobile phase. Propranolol data were also acquired using an acetate buffer (0.2 M) instead of water. The data were modeled for best agreement between calculated and experimental overloaded band profiles. The adsorption energy distribution was also derived and used for the selection of the best isotherm model. Widely different isotherm models were found to model best the data obtained for these compounds, convex upward (i.e. Langmuirian), convex downward (i.e. anti-Langmuirian), and S-shaped isotherms. Using the same sample size for all columns (loading factor, Lf approximately 10%), overloaded band profiles were recorded on four different columns packed with the same batch of Kromasil-C18 and five other columns packed with different batches of Kromasil-C18. These experimental band profiles were compared to the profile calculated from the isotherm measured by FA on the first column. The repeatability as well as the column-to-column and the batch-to-batch reproducibilities of the band profiles are better than 4%.


Scientific papers presented at the European Congress of Radiology 2000: publication rates and characteristics during the period 2000-2004.
To determine the rate at which abstracts orally presented at the ECR 2000 were published between 2000-2004, and to identify predictive factors of publication and differences between abstracts and subsequently published papers. Specific search profiles were devised to retrieve items from the Medline database. From 1020 abstracts originating from 39 countries, 479 articles (publication rate 47%) were subsequently published in 139 Medline-indexed journals, most frequently in European Radiology (14%). Country of origin statistically (P<0.0001) influences the subsequent publication of the abstract, Germany having the highest number of presentations (n=343) and derived articles (publication rate 54%). Abstracts presented by authors from the USA (n=21) had the highest publication rate (76%). Most papers were published within the first 3 years after the meeting, as original articles and in English-language journals. Both the study sample size and the first author frequently changed. Chest and cardiac studies had the highest publication rates (56%, both). In summary, abstracts presented at the ECR 2000 had a high publication rate in Medline-indexed journals. Country of origin and subspecialty of presentation appeared to influence subsequent full publication. More articles were published in European Radiology than in other journal.


Effects of alternate day calorie restriction and exercise on cardio-metabolic risk factors in overweight and obese adults: an exploratory randomized controlled study.
It has been recognized that alternate day calorie restriction (ADCR) or exercise has positive effects on cardio-metabolic risk factors. It is unclear whether the combined effect of ADCR and exercise (aerobic + resistance training) influences risk. We investigated effects of an 8-week ADCR and exercise program (aerobic + resistance training) on cardio-metabolic risk factors in overweight and obese adults. This study randomized 45 overweight or obese but healthy adults (F = 26, M = 19; aged about 32 to 40 years) into 4 groups: ADCR (n = 13), exercise (n = 10), exercise plus ADCR (n = 12), and control (n = 10) for 8 weeks. Body composition, blood lipids profile, and insulin resistance were measured. The intention to treat (ITT) method was used to analyze all participants that were randomized. A total of 35 participants completed the trial (78%). Body weight, body mass index, waist circumference, fat mass and percent body fat were reduced in the exercise plus ADCR group (- 3.3 ± 2.4 kg, p < 0.01; - 1.3 ± 1.0 kg/m2, p < 0.01; - 4.1 ± 3.9 cm, p < 0.01; - 2.7 ± 2.0 kg, p < 0.01; - 2. 5 ± 2.2%, p < 0.01). Insulin, glucose, homeostasis model assessment insulin resistance and triglyceride (- 2.9 ± 4.1 μIU/ml, p < 0.05; - 10.9 ± 16.9 mg/dl, p < 0.05; - 0.9 ± 1.3, p < 0.05; - 43.8 ± 41.9 mg/dl, p < 0.01) decreased in the exercise plus ADCR group only. ADCR and exercise both proved to be beneficial, but the combined intervention was most effective at inducing beneficial changes in body weight, body composition, glucose, insulin, insulin resistance and triglyceride in overweight and obese adults. ClinicalTrials.gov: NCT03652532 , Registered August 28, 2018, 'retrospectively registered'.


N-(4-Bromo-phen-yl)-3,5-dinitro-benzamide.
The title mol-ecule, C(13)H(8)BrN(3)O(5), is slightly twisted, with the dihedral angle between the two benzene rings being 5.9 (1)°. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules into one-dimensional chains running along [101]. Further stabilization of the crystal structure is provided by π-π inter-actions [shortest centroid-centroid distance = 3.6467 (17) Å].


Muscimol and N,N-dimethylmuscimol: from a GABA agonist to a glycine antagonist.
By using molecular modeling methods, a molecular mechanism was identified which can explain how the incorporation of two methyl groups in place of two hydrogen atoms on the terminal nitrogen atom of muscimol can not only convert this potent agonist at GABAnergic receptors to an inactive molecule at these receptors, but also can convert this new derivative to an antagonist of glycine at glycinergic receptors. This insight into the molecular mechanism operative in the conversion of physiological function provides a basis for understanding how a single molecule may be able to act at both the GABA- and glycine-inhibitory receptors.


Pharmacotherapy of ovarian hyperstimulation syndrome.
One of the main objectives in assisted reproduction techiques (ART) is the maturation of multiple follicles and the recovery of multiple good quality oocytes. To realize this, it is necessary to interfere with the mechanisms of selection and follicular dominance, characteristic of spontaneous mono-ovulatory cycles, by administering gonadotrophins. In 12 - 20% of the stimulation cycles, the response to ovarian stimulation in terms of follicular development is higher than expected, with the onset of the so-called ovarian hyperstimulation syndrome (OHSS). This is considered to be an exaggerated response: an iatrogenic - possibly life-threatening - complication of ovarian stimulation. This review deals about reproductive, obstetric and gynecological aspects of OHSS. Understanding the pathophysiology of OHSS is the key to establishing a correct pharmacotherapy. However, the mechanisms underlying OHSS have not yet been completely clarified. Treatment of OHSS is empirical, so prevention is the most important aspect in its management. Several studies support the role of vascular endothelial growth factor in the development of OHSS in humans, so future studies about anti-angiogenetic molecules seem to be an important goal in ART. Methods to prevent OHSS.


Implantation-associated changes in bovine uterine expression of integrins and extracellular matrix.
Appropriate integrin expression appears to be necessary for successful implantation of human embryos and varies considerably among species. The present study was undertaken to determine the distributions of integrin subunits alpha(1), alpha(3), and alpha(6) as well as the extracellular matrix (ECM) components collagen IV and laminin in implanting bovine trophoblast and endometrium. Immunohistochemical staining of cryostat sections prepared from nonpregnant endometrium, of preattachment through to early villus development pregnant endometrium (Days 18, 21, 24, and 30), and of isolated trophoblast binucleate cells was performed. Trophoblast down-regulated the integrin alpha(1) subunit as attachment proceeded, whereas reactivity scores for alpha(6) antibody tended to increase from Day 18 through 24 and remained high. A subpopulation of trophoblast binucleate cells expressed the alpha(3) integrin subunit. Uterine epithelium constitutively expressed alpha(3) and alpha(6) integrin subunits, but the alpha(1) subunit was down-regulated as the luminal epithelium was modified. Collagen IV and laminin reactivity increased in the basal lamina and underlying subepithelial stroma as pregnancy proceeded. The results suggest that binucleate cell fusion with the maternal epithelium initiates integrin and ECM changes in the subepithelial stroma.


Investigation of solution chemistry effects on sorption behavior of Cu(II) on ZSM-5 zeolite.
The sorption of Cu(II) from an aqueous solution using ZSM-5 zeolite was investigated by batch technique under ambient conditions. Sorption was investigated as a function of pH, ionic strength, foreign ions, humic substances, and temperature. The results indicate that the sorption of Cu(II) on ZSM-5 zeolite is strongly dependent on pH. Sorption is dependent on ionic strength at low pH, but independent of ionic strength at high pH values. The presence of humic/fluvic acid (HA/FA) enhances the sorption of Cu(II) on ZSM-5 zeolite at low pH values, and reduces Cu(II) sorption at high pH values. Sorption isotherms were well simulated by the Langmuir model. Thermodynamic parameters (i.e., deltaH0, deltaS0 and deltaG0) for the sorption of Cu(II) were determined from temperature-dependent sorption isotherms at 293.15, 313.15, and 333.15 K, respectively. Results indicate that the sorption process of Cu(II) on ZSM-5 zeolite is spontaneous and endothermic.


Pulmonary Manifestations of Endocrine and Metabolic Diseases in Children.
Advances in technology, methodology, and deep phenotyping are increasingly driving the understanding of the pathologic basis of disease. Improvements in patient identification and treatment are impacting survival. This is true in endocrinology and inborn errors of metabolism, where disease-modifying therapies are developing. Inherent to this evolution is the increasing awareness of the respiratory manifestations of these rare diseases. This review updates clinicians, stratifying diseases spirometerically; pulmonary hypertension and diseases with a predisposition to recurrent pulmonary infection are discussed. This division is artificial; many diseases have multiple pathologic effects on respiration. This review does not cover the impact of obesity.


Erythrokeratolysis hiemalis--keratolytic winter erythema or 'Oudtshoorn Skin'. A new epidermal genodermatosis with its histological features.
A new autosomal, dominantly inherited epidermal disorder is described in which a spreading dissection of the stratum corneum with redness of the palms and soles occurs as a result of a centrifugal necrobiosis of the Malpighian layer below it. Iis is seen characteristically in winter. In extensive cases the limbs and trunk are affected with gyrate scaling erythemas.


Right Ventricular Angiogenesis is an Early Adaptive Response to Chronic Hypoxia-Induced Pulmonary Hypertension.
Myocardial angiogenesis is presumed to play a role in RV adaptation to PH, though definitive evidence and functional correlations are lacking. We aimed to use definitive methods to correlate RV angiogenesis, hypertrophy, and function in a murine PH model. Mice were exposed to CH for 21 days to induce PH and RV remodeling. We used unbiased stereology and flow cytometry to quantify angiogenesis and myocyte hypertrophy, and pressure-volume loops to measure RV function. Within seven days, RV-specific increases in total capillary length (10,576 ± 2574 cm vs. 6822 ± 1379 cm; p = 0.02), surface area (10 ± 3.3 cm(2) vs. 4.9 ± 1.5 cm(2) ; p = 0.01), and volume (0.0013 ± 0.0005 cm(3) vs. 0.0006 ± 0.0001 cm(3) ; p = 0.02) were observed, and RV EC proliferation increased nearly 10-fold. Continued exposure led to progressive RVH without additional angiogenesis. RV function was preserved, but activation of hypoxia-dependent gene expression was observed in both ventricles after 21 days. Early RV remodeling in CH-PH is associated with RV angiogenesis and preserved RV function. Continued CH-PH is associated with RVH but not angiogenesis, leading to biventricular activation of hypoxia-dependent gene expression.


Tumour and normal tissue radiosensitivity.
The place of personalized treatments is highly increasing in medical and radiation oncology. During the last decades, a huge number of assays have been developed to predict responses of normal tissues and tumours. These tests have not yet been included into daily clinical practice but the recent developments of radiation oncology are paving the way of personalized strategies including the risk of tumour recurrence and normal tissue reactions. Concerning tumor radiosensitivity prediction, no test are currently used, even if the radiosensitivity index and the genome-based model for adjusting radiotherapy dose assays seem the most promising with level II of evidence. Commercial developments are under progress. Concerning normal tissue radiosensitivity prediction, single nucleotide polymorphims of prostate cancer patients and radiation-induced CD8 T-lymphocyte apoptosis breast and prostate assays are of level I of evidence. They can be proposed before the beginning of radiotherapy in order to propose personalized treatments according to both risks of tumour and normal tissue radiosensitivity. Commercial developments are also under way.


Method to examine how geometry affects the release and retention of alpine touring boot-binding systems.
Develop a method to examine the effects of component geometry and force-deflection on the release process of Tech/Pin alpine touring (AT) ski boots and bindings. For seven AT boots, we measured the critical geometric dimensions of the metal inserts at the toe region of the boots. Binding geometry (including the pins and rocker arms) and the force-angular deflection curves of typical AT bindings were measured. A kinematic model was derived to predict the contact force between the metal inserts of the AT boots and the pins of the AT bindings, dependent on angular displacement of the binding rocker arms. By combining the kinematic model, the force-angular deflection curves, and moment equilibrium, we determined the force and binding rotation angle needed to release the AT boot in a direction normal to the ski. The metal AT boot insert geometry and AT binding pin geometry and dimensions can affect significantly the contact states and kinematics of release. Two load-deflection curves of similar peak loads can result in significantly different maximal forces and angles to release the binding, even when the geometry and dimensions of the binding pins and boot inserts remain unchanged. The geometry and dimensions of the binding (pins and rocker arm) and the boot inserts define the kinematics of the binding release. The model can be used to test the effects of varying parameters on the release and retention characteristics of Tech/Pin boot-binding systems to optimize the release and retention characteristics.


Thin endometrium in donor oocyte recipients: enigma or obstacle for implantation?
To evaluate the combined effect of endometrial thickness and anatomic uterine factors on clinical outcome in oocyte donation recipients. Retrospective analysis of oocyte donation cycles conducted between 2005 and 2010. Two private IVF centers. A total of 737 donor oocyte cycles. None. Clinical pregnancy and live birth rates. No statistically significant difference was found in clinical pregnancy rates and live birth rates in cycles with endometrial thickness <6 mm compared with those with endometrial thickness >10 mm. However, a relatively high rate of live births was found within a medium range of endometrial thickness (8.2-10 mm). All intrauterine adhesion cases occurred in cycles with thinner endometrium. No statistically significant difference was found in clinical pregnancy rates and live birth rates in cycles with endometrial thickness <6 mm compared with those with thickness >6 mm. A relatively high rate of live births was found within a medium range of endometrial thickness (9.1-10 mm).


Differentiation of Jessner's Lymphocytic Infiltration of the Skin from Various Chronic Cutaneous Lupus Erythematosus Subtypes by Quantitative Computer-Aided Image Analysis.
The distinction between chronic cutaneous lupus erythematosus and Jessner's lymphocytic infiltration of the skin is still not clear. To investigate the difference between chronic cutaneous lupus erythematosus and Jessner's lymphocytic infiltration of the skin in an objective and quantitative manner. Clinical photographs were examined for erythema quantification using two erythema parameters (a* and erythema dose), and histological images were assessed by computer-aided image analysis. The difference between normal and erythematous skin was more prominent using erythema dose than a*, but no significant differences among the three diseases were observed. The correlation between inflammatory dermal cell infiltration and epidermal thickness, as well as that between erythema parameters and histopathological features, was not significant. This is the first attempt to use computer-aided image analysis for the differentiation of similar skin diseases. However, the differentiation between these diseases using quantitative computer-aided image analysis was still not possible.


Malignant lymphoma, Burkitt's type: histologic report of two cases in Italy.
Two cases of undifferentiated Burkitt's type malignant lymphoma with prevalent ovarian localization and observed in Italy are described histologically. Some brief considerations about the extra African diffusion of this lymphoma are pointed out.


Plant hormesis: Revising of the concepts of biostimulation, elicitation and their application in a sustainable agricultural production.
Current research in basic and applied knowledge of plant science has aimed to unravel the role of the interaction between environmental factors and the genome in the physiology of plants to confer the ability to overcome challenges in a climate change scenario. Evidence shows that factors causing environmental stress (stressors), whether of biological, chemical, or physical origin, induce eustressing or distressing effects in plants depending on the dose. The latter suggests the induction of the "hormesis" phenomenon. Sustainable crop production requires a better understanding of hormesis, its basic concepts, and the input variables to make its management feasible. This implies that acknowledging hormesis in plant research could allow specifying beneficial effects to effectively manage environmental stressors according to cultivation goals. Several factors have been useful in this regard, which at low doses show beneficial eustressing effects (biostimulant/elicitor), while at higher doses, they show distressing toxic effects. These insights highlight biostimulants/elicitors as tools to be included in integrated crop management strategies for reaching sustainability in plant science and agricultural studies. In addition, compelling evidence on the inheritance of elicited traits in plants unfolds the possibility of implementing stressors as a tool in plant breeding.


Peristaltic transport of a physiological fluid. Part - II. Flow in uniform geometry.
Using the model of peristaltic flow in non-uniform geometry, developed in the companion paper (Part I), results for uniform tube and channel are obtained in closed form. Comparison of analysis with other theories and the effect of viscosity variation are discussed in detail. Finally, quantitative comparison are made between theory and experiments of Weinberg et al. and Latham.


Effects of chronic exposure to benzalkonium chloride in Oncorhynchus mykiss: cholinergic neurotoxicity, oxidative stress, peroxidative damage and genotoxicity.
Benzalkonium chloride (BAC) is one of the most used conservatives in pharmaceutical preparations. However, its use is limited to a small set of external use formulations, due to its high toxicity. Benzalkonium chloride effects are related to the potential exertion of deleterious effects, mediated via oxidative stress and through interaction with membrane enzymes, leading to cellular damage. To address the ecotoxicity of this specific compound rainbow trouts were chronically exposed to BAC at environmental relevant concentrations (ranging from 0.100 to 1.050mg/L), and the biological response of cholinergic neurotoxicity, modulation of the antioxidant defense, phase II metabolism, lipid peroxidation and genotoxicity was studied. The obtained results showed a dual pattern of antioxidant response, with significant alterations in catalase activity (starting at 0.180mg/L), and lipid peroxidation, for intermediate (0.180 and 0.324mg/L) concentrations. No significant alterations occurred for glutathione-S-transferases activity. An unexpected increased of the acetylcholinesterase activity was also recorded for the individuals exposed to higher concentrations of BAC (starting at 0.180mg/L). Furthermore, exposure to BAC resulted in the establishment of genotoxic alterations, observable (for the specific case of the comet assay results) for all tested BAC concentrations. However, and considering that the oxidative response was not devisable, other mechanisms may be involved in the genotoxic effects reported here.


An unusual case of lightning injury: a melted silver necklace causing a full thickness linear burn.
An unusual case of lightning injury is shown. Flash-over current caused the fusion of a silver necklace producing a linear full thickness burn in the neck and chest with the silver welded throughout the wound.


Stability improvement of polyaniline nanocomposite immunosensor for early detection of insulin receptor antibody as biomarker of type 2 diabetes.
Polyaniline nanocomposite with controllable properties was used to design and fabricate a novel electrochemical immunosensor for the early detection of type 2 diabetes. Insulin receptor antibody is a powerful predictor of type 2 diabetes development in individuals. A systematic study was carried out to investigate the effects of different polyaniline layers and the Nafion layer on the morphological, chemical, and electrochemical properties of nanocomposite immunosensor, especially the stability. The bioengineered Nafion-Au nanoparticles-polyaniline/gold electrode demonstrated outstanding electrocatalytic performance in the detection of insulin receptor antibodies with a high sensitivity (136.21 µA.ng-1.ml.cm-2) in a linear range from 0.001 to 200 ng.ml-1 as well as a low detection limit of 1.827 pg.ml-1, response time within 10 min, remarkable selectivity, and significant stability of 80 days. Therefore, the developed immunosensor is a suitable nanocomposite platform for insulin receptor antibody level determination in human plasma.


A new antitumour substance, 7-oxabicyclo (2.2.1)-5-heptene-2,3-dicarboxylic anhydride.
7-Oxabicyclo(2.2.1)-5-heptene-2,3-dicarboxylic anhydride has been found to possess antitumour activity against Ehrlich ascites carcinoma cells. The tumour cells incubated with the drug showed a decrease in the viable counts and cell proliferation. These effects were confirmed by in vivo studies in Swiss albino mice. The compound has a direct cytotoxic effect on the tumour cells. Vacuolization and disruption of the cytoplasm accompanied by unequal nuclear division and scattered chromosomes were recorded. In addition, 250 and 10 mg/kg were found to be the MTD and MED respectively. A dose of 25 mg/kg injected i.p. for 5 consecutive days in the tumour-transplanted animals caused a significant increase in their survival period. The compound has been shown to have a significant inhibitory effect on the DNA and RNA biosynthesis of EAC cells after 3 hr of administration; the protein biosynthesis was less affected. Meanwhile, the cellular contents of these metabolites were significantly reduced.


Pneumococcal polysaccharide 23-valent vaccine: long-term persistence of circulating antibody and immunogenicity and safety after revaccination in adults.
Since publication of a 1997 review of the immunogenicity and safety data for pneumococcal polysaccharide vaccines (PPSVs), dozens of additional studies have been published, involving larger cohorts, longer observation periods, and more specific assays. Additionally, a 13-valent pneumococcal conjugate vaccine (PCV) has been licensed for adults. This paper reviews adult studies assessing antibody persistence for ≥ 3 years after pneumococcal vaccination, and adult studies of immunogenicity and safety after revaccination. This review emphasizes the currently registered PPSV23 formulations containing 25-μg polysaccharide per serotype, for which far more long-term data are available. Broadly, IgG and functional antibody levels after PPSV23 in adults persist above concentrations in unvaccinated adults for at least 5-10 years in most studies. The few exceptions involve populations of non-ambulatory adults or those with confounding host-factor issues. Revaccination with PPSV23 5-10 years after a previous dose consistently and substantially increases both IgG and functional antibody levels. There is an inverse association between circulating antibody level just before primary or revaccination and subsequent antibody increase. Although injection-site reactions (e.g., pain, swelling, redness) were reported more commonly after PPSV23 revaccination than after primary vaccination in most studies, these reactions typically resolved within 5 days. We interpret the contemporary literature as supporting pneumococcal revaccination as a means to sustain anti-pneumococcal antibodies at levels greater than among unvaccinated adults. PPSV23 is a broad-spectrum public-health tool to help prevent serious pneumococcal diseases across the adult lifespan.


Ureteral injuries due to external violence: 10 years' experience with 59 cases.
Fifty-nine cases of traumatic ureteral damage are presented. Gunshot wounds comprise the majority (52/59). Need for a high index of suspicion and aggressive diagnostic measures is stressed. The effects of missile velocity on the ureter are noted. Prompt operative management is advocated: choice of procedure depends on the location of the ureteral defect. Urinary complications occurred in 11/59 (19%). Four complications resulted from operative techniques no longer recommended. The death rate of 10% is related to the high incidence (57/59) of associated visceral and vascular injuries.


Over-expression of Her-2 in colorectal cancer tissue, but not in serum, constitutes an independent worse prognostic factor.
Currently, conflicting information exists regarding Her-2 over-expression and its clinicopathological implications in colorectal cancer (CRC). This study was undertaken to determine Her-2 over-expression in both serum and tumor tissue of CRC patients, and to assess its clinicopathological and targeted therapeutic implications. Ninety five CRC patients and sixty healthy controls were prospectively enrolled. Her-2 expression status in serum and CRC tissue were examined by chemiluminescent immunoassay and immunohistochemical staining, respectively. The results were confirmed using fluorescent in situ hybridization. Clinicopathological parameters were analyzed according to Her-2 expression status. Serum Her-2 levels were found to be increased in CRC patients as compared to those of healthy controls. However, serum Her-2 levels were not found to be significantly associated with prognostic parameters. Her-2 expression analysis of CRC tissues revealed Her-2 over-expression in 23 patients (25%), i.e., 13 patients (14%) showed moderate over-expression and 10 patients (11%) showed strong over-expression. The overall survival of patients negative for Her-2 expression was significantly better than that of patients positive for Her-2 expression (P=0.018). The disease-free survival of patients with Her-2 over-expression was significantly shorter than that of patients with no Her-2 expression (P=0.021). Her-2 over-expression in CRC tissue, but not in serum, acts as a significant independent worse prognostic factor. Assessment of Her-2 expression status may be valuable for the targeted therapeutic management of CRC.


Quality of Life, Burden of Disease, Co-morbidities, and Systemic Effects in Vitiligo Patients.
Vitiligo is a complex, systemic disease associated with many autoimmune and autoinflammatory conditions. Additionally, the cutaneous changes of vitiligo have significant effects on quality of life and self-esteem. Further efforts are needed to increase our understanding of vitiligo comorbidities as well as to increase awareness of the psychological effects of vitiligo.


Foregut mucosal defects: an etiology of hyperamylasemia.
To evaluate a preliminary correlation of hyperamylasemia to upper gastrointestinal bleeding, total serum amylase and serum isoamylase profiles were determined in 50 patients with upper gastrointestinal bleeding. Etiologies of the bleeding were determined in 46 patients including gastritis or duodenitis in 25, gastric ulcers in 12, duodenal ulcers in 3, Mallory-Weiss tears in 3, gastric carcinoma in 2, and esophageal varices in 1. Gastritis or duodenitis was seen incidentally in 14 more patients. Hyperamylasemia was seen in 38 patients, most commonly being due to a rise of both nonpancreatic and pancreatic isoamylases (18 patients). In 13 patients it was due to an elevation of nonpancreatic amylase alone, and in 7 patients secondary to elevated pancreatic isoamylase alone. Acute pancreatitis raises only the pancreatic component and cannot explain the hyperamylasemia in most of these patients. Hyperamylasemia did not correlate to etiology of the bleeding; gastritis or duodenitis present in the majority of these patients appears to be the unifying factor. Since both nonpancreatic and pancreatic amylases are present in the duodenum and the stomach with pyloric reflux, reabsorption of intraluminal amylase across damaged mucosa is postulated as a mechanism to explain the observed isoamylase patterns. The possibility of decreased amylase clearance as an explanation is unlikely. An alternative central nervous system mechanism might be invoked. It is concluded that hyperamylasemia is a complex event which the use of isoamylase analysis is beginning to elucidate. The hyperamylasemia seen commonly in patients presenting with upper gastrointestinal bleeding does not imply the presence of acute pancreatitis.


Endothelial dysfunction and C-reactive protein predict the incidence of heart failure in hypertensive patients.
Endothelial dysfunction and heart failure are associated, but no prospective studies demonstrated that impaired endothelium-dependent vasodilation predicts incident heart failure. We designed this study to test whether endothelial dysfunction is associated with incident heart failure in a group of hypertensives. We enrolled 735 White never-treated hypertensive outpatients free from heart failure, diabetes, chronic kidney disease, and previous cardiovascular events. Endothelium-dependent vasodilation was investigated by intra-arterial infusion of acetylcholine, and laboratory determinations were obtained by standard procedures. During the follow-up [median 114 months (range 26-206)], there were 208 new cases of heart failure (3.1 events/100 patient-years). Dividing the study population in progressors and non-progressors, we observed that progressors were older, showed a higher prevalence of being female, and had a higher baseline heart rate, glucose, insulin, Homeostatic Model Assessment (HOMA), creatinine, and high-sensitivity C-reactive protein (hs-CRP) mean values, while estimated glomerular filtration rate and maximal acetylcholine-stimulated forearm blood flow were lower. In the multiple Cox regression analysis, female gender [hazard ratio (HR) = 1.454, 95% CI = 1.067-1.981], fasting glucose (HR = 1.186, 95% CI = 1.038-1.357), hs-CRP (HR = 1.162, 95% CI = 1.072-1.259), HOMA (HR = 1.124, 95% CI = 1.037-1.219), acetylcholine-stimulated forearm blood flow (HR = 0.779, 95% CI = 0.695-0.874), and estimated glomerular filtration rate (HR = 0.767, 95% CI = 0.693-0.849) maintained an independent association with the outcome. Successively, testing the interaction between forearm blood flow and hs-CRP, we observed that patients who have hs-CRP values above the median and forearm blood flow under the median show a higher risk of developing heart failure (HR = 7.699, 95% CI = 4.407-13.451). The present data demonstrate that an impaired endothelium-dependent vasodilation and hs-CRP predict development of incident heart failure in hypertensives.


Role of intestinal first-pass metabolism of baicalein in its absorption process.
The aim of the present study was to investigate the role of intestinal first-pass metabolism of baicalein (B) in its absorption process. The intestinal absorption of B was characterized using Caco-2 cell monolayer model and rat in situ single-pass intestinal perfusion model. In addition, preliminary metabolic kinetics of B was evaluated in both rat and human intestinal S9 fractions. B was well absorbed and extensively metabolized to baicalin (BG), baicalein-7-O-beta-glucuronide, in rat intestinal perfusion model, whereas less extent of metabolism was observed in the Caco-2 cell monolayer model. Moreover, BG generated in the intestinal epithelium during the absorption of B also rapidly transported to both the apical side (the apical chamber of Caco-2 model and the perfusate of the intestinal perfusion model) as well as the basolateral side of the small intestine (the basal chamber of Caco-2 model and the mesenteric vein of the intestinal perfusion model). From the preliminary metabolic studies, it was found that a higher loading dose of B resulted in a less extent of metabolism in intestine. In addition, the extent of metabolism of B was similar in jejunum and ileum when 50 microM of B was perfused through different sections of rat small intestine. The first-pass metabolism of B in small intestine may play an important role in its low oral bioavailability.


Postprandial serum gastrin levels in patients with combined hypergastrinaemia and hyperchlorhydria.
We have determined the serum gastrin response to a standard test meal in 13 unoperated patients with combined fasting hypergastrinaemia (more than 150 ng/l) and basal hypersecretion of gastric acid (BAO more than 10 mmol/h). In 10 of 11 patients with proved of presumptive Zollinger-Ellison syndrome the peak postprandial rise in serum gastrin concentration was less than 50 per cent of basal value. The integrated gastrin response to feeding ranged from 71-9 to 211-8 mug/lX 150 min. In 2 patients with proved hypergastrinaemia of antral origin, however, serum gastrin rose to 223 per cent and 255 per cent respectively of basal value after ingestion of the meal. The integrated postprandial serum gastrin responses in these patients were 66-8 and 22-0 mug/lX 150 min. Two patiets with Zollinger-Ellison syndrome and total gastrectomy showed peak serum gastrin levels after feeding of 174 and 255 per cent of basal concentration. The integrated postprandial gastrin secretions were 365 and 366 mug/l X 150 min respectively. It is concluded that the serum gastrin response to feeding, when expressed as percentage change, may be helpful in the differential diagnosis of unoperated patients with fasting hypergastrinaemia and basal gastric acid hypersecretion.


A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease.
The adiponutrin (PNPLA3) rs738409 polymorphism has been found to be associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in various cohorts. We further investigated the association of this polymorphism with non-alcoholic steatohepatitis (NASH) severity and with histological features of NAFLD. A total of 144 biopsy-proven NAFLD patients and 198 controls were genotyped for PNPLA3 gene polymorphism (rs738409 C>G). The biopsy specimens were histologically graded by a qualified pathologist. We observed an association of G allele with susceptibility to NAFLD in the pooled subjects (OR 2.34, 95% CI 1.69-3.24, p < 0.0001), and following stratification, in each of the three ethnic subgroups, namely Chinese, Indian and Malay (OR 1.94, 95% CI 1.12-3.37, p = 0.018; OR 3.51, 95% CI 1.69-7.26, p = 0.001 and OR 2.05, 95% CI 1.25-3.35, p = 0.005, respectively). The G allele is associated with susceptibility to NASH (OR 2.64, 95% CI 1.85-3.75, p < 0.0001), with NASH severity (OR 1.85, 95% CI 1.05-3.26, p = 0.035) and with presence of fibrosis (OR 1.95, 95% CI 1.17-3.26, p = 0.013) but not with simple steatosis nor with other histological parameters. Although the serum triglyceride level is significantly higher in NAFLD patients compared to controls, the G allele is associated with decreased level of triglycerides (p = 0.029) in the NAFLD patients. Overall, the rs738409 G allele is associated with severity of NASH and occurrence of fibrosis in patients with NAFLD.


Emergency department boarding times for patients admitted to intensive care unit: Patient and organizational influences.
Critically ill patients can be subject to prolonged stays in the emergency department following receipt of an order to admit to an intensive care unit. The purpose of this study was to explore patient and organizational influences on the duration of boarding times for intensive care bound patients. This exploratory descriptive study was situated in a Canadian hospital in northern Ontario. Through a six-month retrospective review of three data sources, information was collected pertaining to 16 patient and organizational variables detailing the emergency department boarding time of adults awaiting transfer to the intensive care unit. Data analysis involved descriptive and non-parametric methods. The majority of the 122 critically ill patients boarded in the ED were male, 55 years of age or older, arriving by ground ambulance on a weekday, and had an admitting diagnosis of trauma. The median boarding time was 34 min, with a range of 0-1549 min. Patients designated as most acute, intubated, and undergoing multiple diagnostic procedures had statistically significantly shorter boarding times. The study results provide a profile that may assist clinicians in understanding the complex and site-specific interplay of variables contributing to boarding of critically ill patients.


Effect of peripheral vasoconstriction on pulse oximetry.
We tested the hypothesis that peripheral vasodilation has an effect on arterial oxygen saturation measurements by pulse oximetry, independent of temperature. Study 1 compared finger arterial oxygen saturation values (SpO(2)), before and after peripheral vasoconstriction while temperature was kept constant. This was achieved by administering dexmedetomidine (peripheral vasoconstrictor) to 16 volunteers given general anesthesia. Study 2 compared SpO(2) before and after peripheral vasodilation (brachial plexus block) in a neurally denervated left hand and a neurally innervated right hand in ten awake volunteers. In both studies measurements were also made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmission through a finger (LTF), finger temperature and of hemodynamic variables. In Study 1, systolic blood pressure, SpO(2) and LTF values increased (vasoconstriction) during dexmedetomidine infusion, (P<0.0001 for all) while there were no changes in finger temperature. In Study 2, in the left hand (axillary block), temperature increased by 1.9 +/- 1.6 degrees C (P=0.004), SpO(2) decreased by 2.5 +/- 1.0 % (P<0.0001) and LTF values decreased (vasodilation) by 42 +/- 8 % (P<0.0001) after axillary block. Simultaneously, the axillary block did not induce any changes in temperature, SpO(2) or LTF values in the neurally innervated right hand. Our results demonstrate that finger pulse oximeter SpO(2) measurements can be affected by peripheral vascular tone independent of temperature. The mechanism for this effect remains speculative and unproven.


Glycosylation network mapping and site-specific glycan maturation in vivo.
Glycoprotein processing along a complex highly compartmentalized pathway is a hallmark of eukaryotic cells. We followed the kinetics of intracellular, site-specific glycan processing of a model protein with five distinct N-glycosylation sites and deduced a mathematical model of the secretory pathway that describes a complex set of processing reactions localized in defined intracellular compartments such as the endoplasmic reticulum the Golgi, or the lysosome. The model was able to accommodate site-specific N-glycan processing and we identified phosphorylated glycan structures of the mannose-6-phosphate pathway responsible for the lysosomal sorting of the glycoprotein. Importantly, our model protein can take different routes of the cellular secretory pathway, resulting in an increased glycan complexity of the secreted protein.


Rolipram inhibits leukocyte-endothelial cell interactions in vivo through P- and E-selectin downregulation.
1. Rolipram, a selective phosphodiesterase (PDE) type 4 inhibitor, was used to characterize leukocyte recruitment mechanisms in models of acute and subacute inflammation. Intravital microscopy within the rat mesenteric microcirculation was employed. 2. Mesentery superfusion with PAF (0.1 microM) induced a significant increase in leukocyte rolling flux, adhesion and emigration at 60 min. Rolipram pretreatment, markedly inhibited these parameters by 100, 95 and 95% respectively. 3. Similar effects were observed when the mesentery was superfused with LPS (1 microg ml(-1)) for the same time period and these leukocyte parameters were nearly abrogated by rolipram pretreatment. 4. LPS exposure of the mesentery for 4 h caused a greater increase in leukocyte rolling flux, adhesion and emigration which were inhibited by rolipram administration by 51, 71 and 81% respectively. 5. Immunohistochemistry revealed a significant increase in P-selectin expression after 60 min superfusion with PAF which was attenuated by rolipram. 6. LPS exposure of the mesentery for 4 h caused a significant increase in P- and E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression. Rolipram pretreatment down-regulated both P- and E-selectin expression but had no effect on ICAM-1 and VCAM-1 expression. 7. Significant increases in plasma cyclic AMP levels were detected at 4.5 h after rolipram administration. 8. In conclusion, we have demonstrated that rolipram is a potent in vivo inhibitor of leukocyte-endothelial cell interactions. The effects observed are mediated through endothelial P- and E-selectin downregulation. Therefore, selective PDE-4 inhibitors may be useful in the control of different inflammatory disorders.


Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element.
Systematic study of bones' responses to loading requires simple non-invasive models in appropriate experimental animals where the applied load is controllable and the changes in bone quantifiable. Herein, we validate a model for applying axial loads, non-invasively to murine tibiae. This allows the effects of mechanical loading in both cancellous and cortical bone to be determined within a single bone in which genetic, neuronal and functional influences can also be readily manipulated. Using female C57Bl/J6 mice, peak strains at the tibial mid-shaft were measured during walking (<300 micro epsilon tension) and jumping (<600 micro epsilon compression) with single longitudinally oriented strain gauges attached to the bone's lateral and medial surfaces. Identically positioned gauges were also used to determine, for calibration, the strains engendered by external applied compressive tibial loading between the flexed knee and ankle ex vivo. Applied loads between 5 and 13 N produced strains of 1150-2000 micro epsilon on the lateral surface, and in vivo repetitions of these loads on alternate days for 2 weeks produced significant load magnitude-related increases in cortical bone formation that were similar in mice at 8, 12 and 20 weeks of age. Micro-CT scans showed that loading significantly increases trabecular bone volume in 8 week old mice, but modifies trabecular organization with decreases in trabecular bone volume in 12 and 20 week old mice. This model for loading the tibia has several advantages over other approaches, including scope to study the effects of loading in cancellous as well as cortical bone, against a background of either disuse or of treatment with osteotropic agents within a single bone in normal, mutant and transgenic mice.


Nonpeptidergic circuits feel your pain.
Pain consists of both a sensory component and an affective component. In this issue of Neuron, Braz and colleagues genetically targeted the transneuronal tract tracer wheat germ agglutinin (WGA) to nonpeptidergic nociceptive neurons. They found that these neurons give rise to a specialized multisynaptic circuit that links pain signals in the periphery to limbic/affective regions of the brain.


Continuous lavage in (chemical) corneal lesions.
In a small number of patients with severe chemical corneal damage and in a few patients with corneal ulcers, continuous lavage of the conjunctival sac with a mixture of the patient's own serum, tissue culture fluid and various medicaments was carried out with great success.


[Molecular diagnostics and molecular tumor board in uro-oncology : Precision medicine using the example of metastatic castration-resistant prostate cancer].
Novel approaches to molecular tumor profiling evaluate DNA, RNA and protein alterations to create a detailed molecular map that enables precise and personalized treatment decisions. As the field of molecular profiling is constantly evolving, the training and networking of doctors is of decisive importance. Through the establishment of precision medicine with precision oncological consultations supported by interdisciplinary molecular tumor boards, many patients with difficult to treat tumor diseases can be advised and treated. Many pathophysiological relationships in progressive tumors can be elucidated resulting in new therapeutic options for the profiled patients; however, understanding the complex mutational profiles remains a very demanding task that requires a suitably trained and committed team that should be in close contact with the scientific advancements in precision oncology.


Generalized path integral method for Elliott-Yafet spin relaxations in quantum wells and narrow wires.
We generalized the semiclassical path integral method originally used in the D'yakonov-Perel' mechanism to study the spin relaxation of the Elliott-Yafet mechanism in low-dimensional systems. In quantum wells, the spin properties calculated by this method confirmed the experimental results. In two-dimensional narrow wires, size and impurity effects on the Elliott-Yafet relaxation were predicted, including the wire-width-dependent relaxation time, the polarization evolution on the sample boundaries, and the relaxation behavior during the diffusive-ballistic transition. These properties were compared with those of the D'yakonov-Perel' relaxation calculated under similar conditions. For ballistic narrow wires, we derived an exact relation between the Elliott-Yafet relaxation time and the wire width, which confirmed the above simulations.


Identification of two functional nuclear localization signals mediating nuclear import of liver receptor homologue-1.
Liver receptor homologue-1 (LRH-1) is a member of the nuclear receptor superfamily. We characterized two functional nuclear localization signals (NLSs) in LRH-1. NLS1 (residues 117-168) overlaps the second zinc finger in the DNA binding domain. Mutagenesis showed that the zinc finger structure and two basic clusters on either side of the zinc finger loop are critical for nuclear import of NLS1. NLS2 (residues 169-204) is located in the Ftz-F1 box that contains a bipartite signal. In full-length LRH-1, mutation of either NLS1 or NLS2 had no effect on nuclear localization, but disruption of both NLS1 and NLS2 resulted in the cytoplasmic accumulation of LRH-1. Either NLS1 or NLS2 alone was sufficient to target LRH-1 to the nucleus. Both NLS1 and NLS2 mediate nuclear transport by a mechanism involving importin α/β. Finally, we showed that three crucial basic clusters in the NLSs are involved in the DNA binding and transcriptional activities of LRH-1.


Patterns in home care use in Manitoba.
Administrative home care data from the Manitoba Support Services Payroll (MSSP) system for fiscal years 1995/1996 to 1998/1999 were utilized to study home care client characteristics and changes in home care use over time. Patterns in home care access and use after hospitalization, before admission to a nursing home, and before death were examined. The study found that the majority of home care clients were female, aged 65 and over, and not married. The proportion of Manitobans using home care increased slowly, but significantly, over the 4 years. The greatest increases were found among the older age groups. The average number of days that clients received home care before death or before admission to a nursing home was stable over time, while a significant increase over time in home care use after hospitalization was experienced. These findings can be useful to regional health authorities for planning and budgeting.


Depression in cultural context: "Chinese somatization," revisited.
We have presented a view of culture and mental health that builds on work in cultural psychiatry, anthropology, and cultural psychology, and applied it to research on culture and depression. In particular, we have returned to the well-known topic of Chinese somatization. A culture–mind–brain approach to these questions helps us think about them in a way that points toward new research. We have applied this approach to thinking about a single set of questions, relevant to a single (DSM-based) diagnosis, in a single cultural group. The potential, however, is to rethink how we conceptualize mental health in ways consistent with cultural psychiatry's general perspective over the past several decades, while incorporating rather than rejecting the many recent advances in brain and behavior sciences. In so doing, we gain a more expanded and nuanced view of the global landscape of mental health, accompanied by a more expanded and nuanced view of individual patients.


Cardiac allograft preservation using donor-shed blood supplemented with L-arginine.
Despite improved preservation techniques, myocardial and endothelial dysfunction persists after cardiac transplantation. L-arginine has been shown to decrease endothelial injury in several models of ischemia and reperfusion. We assessed the effects of L-arginine on allograft preservation in a porcine model of cardiac transplantation. Orthotopic cardiac transplants were performed in Yorkshire pigs. Hearts were randomly arrested with high potassium cardioplegia with or without L-arginine at a dose of 2.5 mmol/liter (LARGlow) and 5.0 mmol/liter. Donor-shed blood was collected at the time of organ harvest and intermittently perfused throughout the storage period. Coronary endothelial function was assessed at baseline and after reperfusion by measuring the change in coronary blood flow after exposure to acetylcholine or nitroglycerin. Pressure-volume relationships before and after transplant were evaluated with conductance catheter measurements. Myocardial biopsy specimens were assessed for inflammatory markers of cellular injury. High-dose L-arginine uniformly resulted in ischemic contracture in all hearts, and there was no return of function in any hearts after storage. The low-dose L-arginine group had a greater ability to wean off cardiopulmonary bypass and displayed improved recovery of left ventricular function. Control animals had a 26% reduction in coronary flow compared with 13% for LARGlow. LARGlow resulted in decreased release of inflammatory cytokines compared with control. Low-dose L-arginine preserves myocardial and endothelial function and decreases endothelial injury when it is used as a supplement to intermittent donor blood perfusion. In contrast, high-dose L-arginine resulted in severe endothelial injury and an inability to recover ventricular function after 5 hours of global ischemia.


Reflex seizures and reflex epilepsies: old models for understanding mechanisms of epileptogenesis.
Reflex seizures and epilepsies represent an ancient human model to understand basic mechanisms of epilepsy. The increase of light stimulation makes this issue extremely actual and interesting. In addition, a lot of observations show the frequent occurrence of provoked seizures in malformations of cortical development and in recently defined conditions such as familial or sporadic lateral temporal epilepsy. Advances in morphological and functional neuroimaging techniques, and the possibility of their fusion with EEG (e.g., fMRI-EEG co-registration) offer a unique non-invasive opportunity to investigate cortical areas and brain networks involved in cerebral functions and in epileptic discharges.


Syringopleural shunt for refractory syringomyelia: how I do it.
Surgical treatment of syringomyelia is directed at the reconstruction of the subarachnoid space and restoration normal cerebrospinal fluid flow. Direct intervention on the syrinx is a rescue procedure and should be offered to patients with refractory syringomyelia. We provide an overview on indications and technique of syringopleural shunt (SPS). The procedure involves the connection of syrinx with the pleural space using a lumboperitoneal shunt. The occurrence of a negative pressure inside the pleural compartment offers an appropriate gradient for drainage from the syrinx. The SPS allows for a safe and effective treatment of persistent syringomyelia when management of the underlying cause does not yield substantial improvement.


The implication of mediators for enhancement of laccase oxidation of sulfonamide antibiotics.
In this study, the transformation of sulfonamide antibiotics (SAs, 50 mg L(-1)) was investigated in systems consisting of a fungal laccase (6 IU) and six mediators (1mM). The results illustrate that the laccase had limited effect on the removal of sulfadimethoxine and sulfamonomethoxine. However, laccase oxidation with the mediators (LMS) led to significant declines of the SAs. Two mediators, 2-2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) and violuric acid, provided the fastest transformations of SAs in LMS, with t(1/2)s of 1.8-4.1 min; slower transformations in syringaldehyde and 4-hydroxybenzyl alcohol, with t(1/2)s of 19.0-131 min; and the slowest or no significant decline in 4-hydroxyacetophenone and 4-cyanophenol, with t(1/2)s > 330 min. The decline of the re-added SAs in LMS was slower than that of the first addition. De-aniline and oxidative coupling are the two detectable pathways for the transformation of SAs. The results indicated that some mediators enhanced laccase oxidation of the SAs.


Synthetic studies toward aryl-(4-aryl-4H-[1,2,4]triazole-3-yl)-amine from 1,3-diarylthiourea as urea mimetics.
A thiophile-promoted synthesis of disubstituted 4H-[1,2,4]triazole-3-yl-amines as urea mimetics from the corresponding 1,3-disubstituted thioureas has been studied, and the scope and limitations of this reaction are presented. The reaction proceeds through the formation of a carbodiimide, followed by a sequential addition--dehydration with acyl hydrazides. 1,3-Branched dialkylthioureas result in the formation of the corresponding ureas. The electronic and steric effects of the substitution on the phenyl rings of the 1,3-diarylthioureas play an important role in the formation of the intermediary carbodiimde and the direction of the subsequent ring closure of the N-acyl hydrazide adduct.


Cognitive reserve and persistent post-concussion symptoms--A prospective mild traumatic brain injury (mTBI) cohort study.
Having three or more persisting (i.e. > 3 months) post-concussion symptoms (PCS) affects a significant number of patients after a mild traumatic brain injury (mTBI). A common complaint is cognitive deficits. However, several meta-analyses have found no evidence of long-term cognitive impairment in mTBI patients. The study sought to answer two questions: first, is there a difference in cognitive performance between PCS and recovered mTBI patients? Second, is lower cognitive reserve a risk factor for developing PCS? Prospective inception cohort study. One hundred and twenty-two adult patients were recruited from emergency departments within 24 hours of an mTBI. Three months post-injury, participants completed the Rivermead Post Concussion Symptoms Questionnaire and a neuropsychological assessment. A healthy control group (n = 35) were recruited. The estimate of cognitive reserve was based upon sub-test Information from Wechsler Adult Intelligence Scale and international classifications of educational level and occupational skill level. mTBI patients showed reduced memory performance. Patients with lower cognitive reserve were 4.14-times more likely to suffer from PCS. mTBI may be linked to subtle executive memory deficits. Lower cognitive reserve appears to be a risk factor for PCS and indicates individual vulnerabilities.


Management of Preterm Premature Rupture of Membranes: A Comparison of Inpatient and Outpatient Care.
We sought to evaluate the safety of outpatient management of pregnancy complicated by preterm premature rupture of membranes (PPROM). We performed a retrospective cohort study of women with PPROM and a latency period of at least one week in one provincial health region between January 2007 and December 2012. We evaluated pregnancy outcomes for 133 women whose cases were managed using specialized community care and compared these with outcomes of a similar group of 122 women whose cases were managed entirely in the hospital. The primary outcome measured was the difference in the latency period between the two groups. For categorical variable outcomes, data were analyzed using chi-square tests, and continuous variable outcomes were compared using t tests. The median latency period for inpatients was 11 days compared with 18 days for patients in the community (P < 0.001). The most common reason for delivery was spontaneous labour (57% of inpatients and 50% of outpatients). Rates of stillbirth and neonatal mortality were similar between the two groups (3% in the inpatient group and 4% in the outpatient group). Precipitous vaginal delivery of a preterm breech infant was associated with mortality. Umbilical cord pH was < 7.10 in 5% of the inpatient group and 3% of the outpatient group. Median Apgar scores were slightly higher among the outpatient group. The safety of outpatient management of appropriately selected patients with PPROM is comparable with the safety of in-hospital management. Patients with PPROM and a fetus in breech presentation may not be appropriate for outpatient management, especially prior to 28 weeks' gestation. The decision to manage a patient with PPROM on an outpatient basis must be made after careful evaluation, with a thorough discussion of the risks and benefits and with serial reassessment of patient suitability.


Consistent topography and amplitude symmetry are more typical than morphology of epileptiform discharges in genetic generalized epilepsy.
To provide a quantitative evaluation of typical electroencephalographic (EEG) abnormalities in genetic generalized epilepsy (GGE). We prospectively performed 24-h ambulatory EEG recordings in a cohort of patients with GGE. The diagnosis was established according to the International League Against Epilepsy criteria. Details of all epileptiform discharges across the 24-h time scale were entered into an electronic database. We carried out descriptive statistics to provide a quantitative breakdown of typical EEG abnormalities. A total of 6923 epileptiform discharges from 105 abnormal 24-h ambulatory EEGs were analyzed. 96% of discharges were symmetric in amplitude with fronto-central maximum topographically. Only 24% of the paroxysms had typical morphology while 43% were regular. Photoparoxysmal response, eye-closure sensitivity and hyperventilation-induced generalized paroxysms were less common in around 10%, whereas occipital intermittent rhythmic delta activity was very rare (2%). Our results indicate that generalized discharges with symmetric amplitude and fronto-central maxima are the most consistent findings in GGE, and other features are observed less frequently. Epileptiform discharges displaying highly consistent amplitude symmetry coupled with fronto-central topography should provoke consideration of GGE. Recognition of variations from typical abnormalities is important to avoid the risk of misdiagnosis and delayed diagnosis.


Prevalence of syphilis and chlamydia trachomatis infection among female sex workers in Jiangsu, China: Results from a multicenter cross-sectional and venue-based study.
Female sex workers (FSWs) are considered highly vulnerable to sexually transmitted infections (STIs), but available data on the prevalence of STIs among FSWs in China is limited at a provincial level. This study aimed to evaluate the prevalence of STIs and risk factors among FSWs in Jiangsu, China. We conducted a multicenter cross-sectional study in seven cities of Jiangsu to investigate the prevalence and risk factors associated with HIV and other STIs. Blood and urine were collected to test for HIV, syphilis, Hepatitis C (HCV), Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections. We enrolled 3,580 FSWs. The overall prevalence of bacterial STIs was 6.2% (5.4%-7.0%). The prevalence of HIV, syphilis infection, HCV, NG and CT were 0.1% (95%CI, 0.0-0.2), 1.8% (95%CI, 1.4-2.3), 0.3% (95%CI, 0.1-0.5), 0.3% (95%CI, 0.2-0.5) and 4.3% (95%CI, 3.6-5.0), respectively. Most FSWs (85.6%) reported consistent condom use with clients in the past month. Only 10.6% of FSWs reported group sex, and 68.3% self-reported HIV testing in the previous year. According to the multivariable model, having group sex in the past year (aOR, 2.521, 95%CI: 1.366-4.651) and HIV infection (aOR, 26.260, 95%CI: 2.432-283.563) were associated with a higher risk of syphilis infection. Migrants (aOR, 1.669, 95%CI: 1.163-2.395), having a history of STIs in the past year (aOR, 4.601, 95%CI: 1.003-21.118), and NG infection (aOR, 38.549, 95%CI: 11.214-132.514) were associated with a higher risk of CT infection. On the contrary, FSWs aged older than 25 were associated with lower risk of syphilis infection (25-34: aOR, 0.339, 95%CI: 0.151-0.763) and CT infection (25-34: aOR, 0.503, 95%CI: 0.316-0.802; ≥35: aOR, 0.578, 95%CI: 0.362-0.925). This study's prevalence rates of syphilis and CT infections show the need to promote comprehensive STIs control and prevention strategies, including behavioral intervention and STIs screening, especially in younger high-risk populations. With the increasing coverage of HIV testing, integrating other STIs screening with HIV testing may be a reasonable way to implement comprehensive STIs control and prevention.


Suppression of cancer proliferation and metastasis by a versatile nanomedicine integrating photodynamic therapy, photothermal therapy, and enzyme inhibition.
Cancer therapeutics are varied and target diverse processes in cancer progression. Photodynamic therapy (PDT), photothermal therapy (PTT), and the inhibition of pro-cancer proteases are non-invasive anticancer therapeutics that attract increasing attentions for their enhanced specificities and milder systemic toxicities compared to traditional therapeutics. These modalities offer advantages to compensate for the shortcomings of their counterparts. For instance, PDT or PTT efficiently eliminates locally confined tumor cells while exhibiting no effect on metastatic tumor cells. In contrast, the inhibition of pro-cancer proteases systemically suppresses the proliferation and metastasis of cancer cells but does not eradicate existing cancer cells. To synergize these therapeutics, we hereby report a versatile nanoparticle that integrates the effects of PDT, PTT, and enzyme-inhibition. This nanoparticle (CIKP-NP) was synthesized by covalently or non-covalently modifying a photothermal nanoparticle with a photosensitizer, a pro-cancer protease inhibitor, and an albumin-binding molecule. After confirming the PDT, PTT, albumin-binding, and enzyme-inhibition properties at the molecular level, we demonstrated that CIKP-NP killed tumor cells through PDT or PTT and suppressed tumor cell invasion through enzyme-inhibition. In addition, through a breast cancer xenograft mouse model, we demonstrated that CIKP-NP suppressed tumor growth by PDT or PTT effect. Notably, the synergism of PDT and PTT significantly enhanced its anticancer efficiency. Furthermore, CIKP-NP significantly suppressed cancer metastasis in a lung metastatic mouse model. Last, biodistribution and the in vivo retention of CIKP-NP confirmed the tumor-targeting property. Beyond demonstrating the anti-tumor and anti-metastatic efficacy of CIKP-NP, our study also suggests a new strategy to synergize multiple anticancer therapeutics.