Significantly Enhanced Separation using ZIF-8 Membranes by Partial Conversion of Calcined Layered Double Hydroxide Precursors.
Significantly enhanced H2 /CH4 (ca. 80) selectivity was realized by effective suppression of the framework flexibility of a prepared ZIF-8 membrane. Initially a ZnO buffer layer consisting of 20 nm-sized ZnO-nanoparticle aggregates was fabricated by controlled calcination of a ZnAl-NO3 layered double hydroxide membrane. Owing to its high chemical reactivity, the ZnO buffer layer was partially converted into a well-intergrown ZIF-8 membrane with a certain penetration depth upon solvothermal treatment with ligands. Our method may represent a new concept for the design of advanced MOF membranes with high selectivity.


Vaccination against influenza: UK health care workers not on-message.
Vaccination of health care workers against influenza is considered to be important as a means of protecting patients from nosocomial infection. Vaccine uptake rates have been reported to be no more than 40% and often between 20 and 30%. An evaluation of the performance of UK National Health Service trusts, following a governmental directive to implement vaccination during the winter of 2000-2001, has shown a poor uptake of vaccine. Reasons for accepting or declining vaccine are discussed. There is a need for global leadership on this issue to promote the value of vaccination and to change the behaviour of health care workers.


[Determination of sennoside A in rhubarb extracts by HPLC].
To determine sennoside A in rhubarb extracts by solvent extraction and SFE-CO2. Sennoside A was extracted by ultrasonic vibration. The analytical column was Allitima RP C18 (250 x 4.6 mm, 5 microm). The mobile phase consisted of 0.1% TFA-HCN (44:56). The flow rate was 1.0 ml/min. The UV detector wavelength was 280 nm and the reference wavelength was 600 nm. The column temperature was 25 degrees C. Considering the extracting rate of sennoside A, solvent extraction was better than SFE-CO2.


Unusual facio-upper arm band of a fetus mimicking amniotic band syndrome.
Amniotic band syndrome can lead to a wide spectrum of congenital abnormalities including orofacial and visceral defects. It is associated with malformations in truncal, craniofacial regions and the limbs, whereas it sometimes may imitate some genetic disorders. Here, we present an atypical case mimicking amniotic band syndrome with a facio-upper arm band that was having multiple fetal structural abnormalities including scoliosis, bilateral cleft lip and palate, upper limb abnormality, unilateral anophthalmia with contralateral microphthalmia, left hypertrophic kidney and severe ventriculomegaly.


Diagnosing acute appendicitis: are we overusing radiologic investigations?
Acute appendicitis is the most common emergency presenting to pediatric surgeons. With proper history and thorough physical examination, the diagnosis of the condition clinically should approach 90%. With the increasing ease of performing radiologic investigations because of technological advances, more ultrasound and computed tomography (CT) are used to help diagnosing appendicitis. The aim of this study is to review the trend of diagnosing appendicitis in a single center and discuss the implications. A retrospective analysis was carried out for all patients who were admitted with acute appendicitis between 1997 and 2007. The methods of diagnosis were divided into 3 groups as follows: clinical, ultrasound, and CT. The demographics and operative findings were noted. Statistical analysis was done using Fisher's Exact test and paired t test when appropriate. A value of P < .05 was considered to be statistically significant. During this period, a total of 254 patients (167 boys and 87 girls) were admitted with appendicitis. The average age at presentation was 12 years, and the mean duration of symptoms before presentation was 2 days. For 11 years, there was an initial rise of the use of ultrasound (10% in 1997 to a peak of 60% in 2005). This percentage decreased with a corresponding rise of the use of CT scan (0% in 1997 to 35% in 2007). There was no correlation found between the use of adjunct investigations and the severity of appendicitis found at operation, suggesting an overreliance of CT. It appears that there is an increasing trend in using radiologic investigations for the diagnosis of appendicitis for the past 11 years. With the association of cancer in later life and early radiation exposure well documented, it would be advisable to avoid the use of CT if possible.


Human mass balance study and metabolite profiling of 14C-niraparib, a novel poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor, in patients with advanced cancer.
Niraparib is an investigational oral, once daily, selective poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor. In the pivotal Phase 3 NOVA/ENGOT/OV16 study, niraparib met its primary endpoint of improving progression-free survival (PFS) for adult patients with recurrent, platinum sensitive, ovarian, fallopian tube, or primary peritoneal cancer in complete or partial response to platinum-based chemotherapy. Significant improvements in PFS were seen in all patient cohorts regardless of biomarker status. This study evaluates the absorption, metabolism and excretion (AME) of 14C-niraparib, administered to six patients as a single oral dose of 300 mg with a radioactivity of 100 μCi. Total radioactivity (TRA) in whole blood, plasma, urine and faeces was measured using liquid scintillation counting (LSC) to obtain the mass balance of niraparib. Moreover, metabolite profiling was performed on selected plasma, urine and faeces samples using liquid chromatography - tandem mass spectrometry (LC-MS/MS) coupled to off-line LSC. Mean TRA recovered over 504 h was 47.5% in urine and 38.8% in faeces, indicating that both renal and hepatic pathways are comparably involved in excretion of niraparib and its metabolites. The elimination of 14C-radioactivity was slow, with t1/2 in plasma on average 92.5 h. Oral absorption of 14C-niraparib was rapid, with niraparib concentrations peaking at 2.49 h, and reaching a mean maximum concentration of 540 ng/mL. Two major metabolites were found: the known metabolite M1 (amide hydrolysed niraparib) and the glucuronide of M1. Based on this study it was shown that niraparib undergoes hydrolytic, and conjugative metabolic conversions, with the oxidative pathway being minimal.


Anabolic-androgenic steroid use in the United States.
To estimate the size of the anabolic-androgenic steroid (AAS) user population in the United States, to examine characteristics of AAS users, and to explore the association between AAS use and the use of other illicit drugs as well as self-reported aggressive behaviors. A cross-sectional study using data from the 1991 National Household Survey on Drug Abuse. The survey covered the population aged 12 years and older living in households in the United States. The results of the survey were based on personal interviews combined with self-administered questionnaires from 32,594 respondents. These respondents were randomly selected by means of a stratified multistage area sample of the household population. Estimates based on data from the National Household Survey on Drug Abuse indicated that there are more than 1 million current or former AAS users in this country, with more than half of the lifetime user population being 26 years of age or older. More than 300,000 individuals used AAS in the past year. Males had higher levels of AAS use during their lifetime than females (0.9% and 0.1%, respectively; P < .01). The median age of first use of AAS for the study population was 18 years; for 12- to 17-year-olds, the median age of initiation was 15 years. Among 12- to 34-year-olds, AAS use was significantly and positively associated with the use of other illicit drugs (P < .05), cigarettes (12- to 17-year-olds only; P < .01), and alcohol (P < .01). Furthermore, AAS use is highly correlated with self-reported aggressive behavior (P < .01) and crimes against property (P < .01). These results indicate that AAS use impacts a large number of men and women from various racial and age groups across the nation. While causal inferences cannot be made regarding the associations between AAS use and use of other drugs as well as antisocial behavior, these findings should enhance our ability to profile the typical AAS user.


[Role of the intestinal MALT in pathogenesis of the IgA-nephropathy].
Modern view on pathogenesis of immunoglobulin (Ig)A-nephropathy and possible relation to intestinal MALT-system activity is presented in the article. Aberrant glycosylation of IgA and increased association of IgA-nephropathy with intestinal diseases or abnormal intestinal permeability are discussed in details. Based on supposed entero-renal pathogenesis of the disease future treatment modalities are considered. Relevant worlds literature is cited.


Influence of iron and copper oxides on polychlorinated diphenyl ether formation in heterogeneous reactions.
Polychlorinated diphenyl ether (PCDE) has attracted great attention recently as an important type of environmental pollutant. The influence of iron and copper oxides on formation of PCDEs was investigated using laboratory-scale flow reactors under air and under nitrogen at 350 °C, a temperature corresponding to the post-combustion zone of a municipal solid waste incinerator. The results show that the 2,2',3,4,4',5,5',6-otachlorodiphenyl ether (OCDE) formed from the condensation of pentachlorophenol (PCP) and 1,2,4,5-tetrachlorobenzene (Cl4Bz) is the predominant congener formed on the SiO2/Fe2O3 surface with and without oxygen. This indicated that HCl elimination between PCP and 1,2,4,5-Cl4Bz molecules formed 2,2',3,4,4',5,5',6-OCDE in the presence of Fe2O3. On the other hand, decachlorodiphenyl ether, nonachlorodiphenyl ether, and OCDE were the dominant products on the SiO2/CuO surface without oxygen, although the 2,2',3,4,4',5,5',6-OCDE was the dominant product on the SiO2/CuO surface with oxygen. Therefore, the presence of Fe2O3 and CuO influences the formation and homologue distribution of PCDEs, which shifted towards the lower chlorinated species. Fe2O3 can promote both the condensation and dechlorination reaction without oxygen. On the contrary, with oxygen, Fe2O3 suppresses the condensation of chlorobenzene and chlorophenol to form PCDEs and polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs). CuO can increase the formation of lower chlorinated PCDEs and PCDDs without oxygen. In conclusion, the different fly ash components have a major influence on PCDE emissions.


A Multi-Study Model-Based Evaluation of the Sequence of Imaging and Clinical Biomarker Changes in Huntington's Disease.
Understanding the order and progression of change in biomarkers of neurodegeneration is essential to detect the effects of pharmacological interventions on these biomarkers. In Huntington's disease (HD), motor, cognitive and MRI biomarkers are currently used in clinical trials of drug efficacy. Here for the first time we use directly compare data from three large observational studies of HD (total N = 532) using a probabilistic event-based model (EBM) to characterise the order in which motor, cognitive and MRI biomarkers become abnormal. We also investigate the impact of the genetic cause of HD, cytosine-adenine-guanine (CAG) repeat length, on progression through these stages. We find that EBM uncovers a broadly consistent order of events across all three studies; that EBM stage reflects clinical stage; and that EBM stage is related to age and genetic burden. Our findings indicate that measures of subcortical and white matter volume become abnormal prior to clinical and cognitive biomarkers. Importantly, CAG repeat length has a large impact on the timing of onset of each stage and progression through the stages, with a longer repeat length resulting in earlier onset and faster progression. Our results can be used to help design clinical trials of treatments for Huntington's disease, influencing the choice of biomarkers and the recruitment of participants.


Comparative clinical study of doxycycline and minocycline.
Doxycycline and minocycline were given intravenously to patients with a serious underlying disease who presented a pulmonary infection or a wound infection. Both therapies were easy to administer and well tolerated. However they should not be used in the initial therapy since resistant strains may occur. The clinical and bacteriological effectiveness of doxycycline and minocycline were similar. In pneumococcal pulmonary infections, the rates of favorable clinical response to doxycycline and minocycline were 73% and 76% respectively. In infections caused by bacteroides sp.(mainly infections of wounds), doxycycline or minocycline resulted in a 75% rate of favorable clinical responses and in a 71% rate of favorable bacteriological responses. Adverse side effects were rare and of minor importance with the exception of bacteriological colonization by doxycycline-resistant or minocycline-resistant microorganisms. This complica-tion occurred in 39% of the patients who were treated with these drugs and resulted in clinical superinfection in 8% of the patients.


Analytical solution for compositional profile driven by gravitational segregation and diffusion.
An alternative analytical solution is presented, based on irreversible thermodynamics, that describes the equilibrium distribution of the components of a nonideal fluid mixture in a one-dimensional hydrostatic and isothermal system. In such a system, the vertical compositional profile of the fluid at equilibrium will be determined by the interaction of gravitational and chemical potentials. Our alternative analytical solution estimates this profile from the overall composition of the fluid. It is thus more general than the existing solution, which requires knowledge of the fluid composition at a given depth and assumes that the vertical compositional profile of this fluid is already at equilibrium. The solution is demonstrated by comparison against results obtained from previously published molecular dynamics simulations of segregation in a binary mixture and against numerical simulations of a real hydrocarbon reservoir system.


The assessment and characterization of the built-in internal photometer of primary diagnostic monitors.
The purpose of this work was to perform the initial evaluation of primary diagnostic monitor (PDM) characteristics following the implementation of New York City quality assurance (NYC QA) regulations on January 1, 2016, and compare the results of the QA measurements performed by an external photometer and the PDM manufacturer's built-in photometer. TG-18 and Society of Motion Picture and Television Engineers test patterns were used to evaluate monitor performance. Overall, 79 PDMs were included in the analysis. The verification of grayscale standard display function (GSDF) calibration, using a built-in photometer, showed that only 2 out of 79 PDMs failed calibration. However, the same measurements performed by the external luminance meter showed that 15 out of 79 monitors had failed GSDF calibration. Measurements of the PDMs maximum luminance (Lmax ), using an external photometer showed that 10 out of 53 PDMs calibrated for Lmax = 400 cd/m2 and 17 out of 26 PDMs calibrated for Lmax = 500 cd/m2 do not meet the manufacturer's recommended 10% tolerance limit for the target Lmax calibration. Two PDMs did not pass the Lmax ≥ 350 cd/m2 NYC QA regulations with Lmax = 331 cd/m2 and Lmax = 340 cd/m2 . All tested PDMs exceeded the minimum luminance ratio (LR) of 250:1 as required by NYC QA regulations. Measurements taken of Lmax and LR performed by a built-in photometer showed that none of the PDMs had failed the NYC QA regulations. All PDMs passed the luminance uniformity test with a maximum nonuniformity of 17% (according to NYC regulations it must be less than 30%). The luminance uniformity test could only be performed using an external photometer. The evaluation of 79 PDMs of various ages and models demonstrated up to 18% disagreement between luminance measurements performed by the manufacturer's built-in photometer when compared with those performed by an externally calibrated luminance meter. These disagreements were larger for older PDMs.


A reintroduction of environmental mite allergen control strategies for asthma treatment and the debate on their effectiveness.
Asthma affects three hundred million people worldwide. The effectiveness of house dust mite allergen control for asthma treatment is debatable. One aspect that has been little discussed in existing meta-analyses is the possible role of environmental strategies. Here, we reintroduce the previously defined strategies for mite allergen control and discuss their importance to the debate on clinical effectiveness. The strategy of concurrent bedroom interventions is related to the combined use of a priori defined interventions, while the strategy of exposure-based control relates to the treatment of relevant textiles after assessing exposure. The air purification strategy aims to purify the human breathing zone of airborne allergens. In Western European patient practice, the use of these strategies differs. A post hoc study of the dominant Cochrane review by Gøtzsche and Johansen (Cochrane Database of Systematic Reviews, 2008, Art. No: CD001187) appears to indicate that a majority of the underlying trials reported on the strategy of concurrent bedroom interventions, which were mainly executed in a minimal manner. Some trials have reported on the air purification strategy and may potentially alter the debate on effectiveness. No trial has reported on the strategy of exposure-based control. We therefore hypothesize that the absence of evidence for the effectiveness of mite allergen control for asthma treatment applies to the strategy of concurrent bedroom interventions. The evidence-based effectiveness of the exposure-based control strategy appears to be undetermined. The results of our post hoc reanalysis urge that future meta-analyses of mite allergen control should a priori define the environmental strategy under study. Future trials of mite allergen control are warranted to test the exposure-based strategy as well as the sparsely tested strategy of air purification.


Cadherin and Wnt signaling pathways as key regulators in diabetic nephropathy.
A recent meta-analysis of genome-wide linkage studies (GWLS) has identified multiple genetic regions suggestive of linkage with DN harboring hundreds of genes. Moving this number of genetic loci forward into biological insight is truly the next step. Here, we approach this challenge with a gene ontology (GO) analysis in order to yield biological and functional role to the genes, an over-representation test to find which GO terms are enriched in the gene list, pathway analysis, as well as protein network analysis. GO analysis was performed using protein analysis through evolutionary relationships (PANTHER) version 14.0 software and P-values less than 0.05 were considered statistically significant. GO analysis was followed by over-representation test for the identification of enriched terms. Statistical significance was calculated by Fisher's exact test and adjusted using the false discovery rate (FDR) for correction of multiple tests. Cytoscape with the relevant plugins was used for the construction of the protein network and clustering analysis. The GO analysis assign multiple GO terms to the genes regarding the molecular function, the biological process and the cellular component, protein class and pathway analysis. The findings of the over-representation test highlight the contribution of cell adhesion regarding the biological process, integral components of plasma membrane regarding the cellular component, chemokines and cytokines with regard to protein class, while the pathway analysis emphasizes the contribution of Wnt and cadherin signaling pathways. Our results suggest that a core feature of the pathogenesis of DN may be a disturbance in Wnt and cadherin signaling pathways, whereas the contribution of chemokines and cytokines need to be studied in additional studies.


Soy use and vasomotor symptoms: Soy Estrogen Alternative follow-up study.
To evaluate vasomotor symptoms and soy and hormone therapy use in women who had previously participated in the Soy Estrogen Alternative (SEA) study, a trial conducted to compare the effects of soy protein supplements containing differing levels of isoflavones on menopausal symptoms, chronic disease risk factors, and health-related quality of life in perimenopausal and postmenopausal women. Two years after the SEA study ended participants were recontacted to complete questionnaires to quantify their health status, medications, menopausal symptoms, and their use of hormone therapy and soy-based foods and supplements. Participants were also asked to record vasomotor symptoms for seven days. Surveys were collected from 182 of the 241 participants who had been enrolled in the SEA study (76% response rate). Women were 55 ± 2.8 years of age, well educated (80% more than high school), and 93% reported good to excellent health. All but six reported experiencing at least one menopausal symptom, and 56% reported one or more hot flashes on one or more days. Eighty-one women (45%) continued to use soy for menopausal symptom relief, and 58 (32%) were using hormone therapy. Women taking hormone therapy were experiencing fewer and less severe hot flashes than those who were not taking hormone therapy (P < 0.001); hot flash frequency and severity did not differ significantly between those who did and did not use soy, after controlling for hormone therapy use. Most participants reported they were still experiencing menopausal symptoms. Additionally, half of the most symptomatic women (not taking hormone therapy) were still consuming soy products for vasomotor symptoms.


Evolutionary dynamics in non-Markovian models of microbial populations.
In the past decade, great strides have been made to quantify the dynamics of single-cell growth and division in microbes. In order to make sense of the evolutionary history of these organisms, we must understand how features of single-cell growth and division influence evolutionary dynamics. This requires us to connect processes on the single-cell scale to population dynamics. Here, we consider a model of microbial growth in finite populations which explicitly incorporates the single-cell dynamics. We study the behavior of a mutant population in such a model and ask: can the evolutionary dynamics be coarse-grained so that the forces of natural selection and genetic drift can be expressed in terms of the long-term fitness? We show that it is in fact not possible, as there is no way to define a single fitness parameter (or reproductive rate) that defines the fate of an organism even in a constant environment. This is due to fluctuations in the population averaged division rate. As a result, various details of the single-cell dynamics affect the fate of a new mutant independently from how they affect the long-term growth rate of the mutant population. In particular, we show that in the case of neutral mutations, variability in generation times increases the rate of genetic drift, and in the case of beneficial mutations, variability decreases its fixation probability. Furthermore, we explain the source of the persistent division rate fluctuations and provide analytic solutions for the fixation probability as a multispecies generalization of the Euler-Lotka equation.


Cu-Au-Ag alloy nanoparticles incorporated silica films using a new three-layer deposition technique.
Formation of Au-Ag-Cu ternary alloy nanoparticles (NPs) is difficult mainly because the system Cu/Ag is immiscible. We present a new synthetic technique to generate such ternary alloy NPs in silica film matrix employing a three-layer (3L) coating design. In this methodology three successive coating layers were deposited on silica glass substrates from separately prepared Cu-, Au- and Ag-ion incorporated inorganic-organic hybrid silica sols by dipping method. The Au layer is kept in the middle because it is miscible with both the Ag and Cu. The 3L film assembly was subjected to UV- and heat-treatment at 450-750 degrees C in H2-N2 atmosphere. UV-treatment generates small Au and Ag NPs in the respective layers and Cu remains as Cu2+; subsequent heat-treatment in H2-N2 induces the formation of ternary alloy NPs by the interlayer diffusion of nanometals. The final heat-treated film (750 degrees C/H2-N2) shows single and sharp plasmon band centered at 480 nm in the UV-visible spectrum indicating the formation of alloy (solid solution) NPs. GIXRD study shows one set of diffraction peaks which are shifted towards higher angle with respect to the Au or Ag diffraction peaks. FESEM, GIXRD, HRTEM, and SAED analyses reveal that the alloy has a composition close to (Au + Ag)0.88Cu0.12. The EDS analyses using the nano probe attached with TEM confirm the presence of Au, Ag and Cu in all the alloy NPs.


Small molecular inhibitors for KRAS-mutant cancers.
Three rat sarcoma (RAS) gene isoforms, KRAS, NRAS, and HRAS, constitute the most mutated family of small GTPases in cancer. While the development of targeted immunotherapies has led to a substantial improvement in the overall survival of patients with non-KRAS-mutant cancer, patients with RAS-mutant cancers have an overall poorer prognosis owing to the high aggressiveness of RAS-mutant tumors. KRAS mutations are strongly implicated in lung, pancreatic, and colorectal cancers. However, RAS mutations exhibit diverse patterns of isoforms, substitutions, and positions in different types of cancers. Despite being considered "undruggable", recent advances in the use of allele-specific covalent inhibitors against the most common mutant form of RAS in non-small-cell lung cancer have led to the development of effective pharmacological interventions against RAS-mutant cancer. Sotorasib (AMG510) has been approved by the FDA as a second-line treatment for patients with KRAS-G12C mutant NSCLC who have received at least one prior systemic therapy. Other KRAS inhibitors are on the way to block KRAS-mutant cancers. In this review, we summarize the progress and promise of small-molecule inhibitors in clinical trials, including direct inhibitors of KRAS, pan-RAS inhibitors, inhibitors of RAS effector signaling, and immune checkpoint inhibitors or combinations with RAS inhibitors, to improve the prognosis of tumors with RAS mutations.


Dietetic guidelines: diet in secondary prevention of cardiovascular disease (first update, June 2003).
To update dietetic guidelines summarizing the systematic review evidence on dietary advice to prevent further events in people with existing cardiovascular disease (CVD) (secondary prevention). The Cochrane Library, MEDLINE and EMBASE were comprehensively searched to November 2002 for systematic reviews on aspects of diet and heart health. Reviews were included if they searched systematically for randomised controlled trials relating to diet and secondary prevention of CVD. Two members of the UK Heart Health and Thoracic Dietitians Group critically appraised each review. The quality and results of each review were discussed and summarized in a meeting of the whole group. Providing evidence-based dietary information (including increasing omega-3 fat intake) to all people who have had a myocardial infarction will save more lives than concentrating dietary advice on just those in need of weight loss or lipid lowering. The practice of prioritizing dietetic time in secondary prevention to those with raised lipids is out of date since the advent of statin therapy. However, effective dietary advice for those with angina, stroke, peripheral vascular disease or heart failure is less clear. There is good systematic review evidence that dietary advice to those with coronary heart disease can reduce mortality and morbidity as well as modify some risk factors. Dietary advice that does this most effectively should be prioritized.


DNA barcoding of clinically relevant Cunninghamella species.
Mucormycosis caused, in part, by representatives of the genus Cunninghamella is a severe infection with high mortality in patients with impaired immunity. Several species have been described in the literature as etiologic agents. A DNA barcoding study using ITS rDNA and tef-1α provided concordance of molecular data with conventional characters. The currently accepted Cunninghamella species were well supported in phylogenetic trees of both markers except for C. septata with ITS that clustered in the C. echinulata clade. Sequence variability was distinctly higher for the ITS than for tef-1α. Intraspecific ITS variability of some of the species exceeded that between some closely related species, but the marker remained applicable for species identification. The most variable species for both markers was C. echinulata. Cunninghamella bertholletiae is the main pathogenic species; infections by C. blakesleeana, C. echinulata, and C. elegans are highly exceptional.


Physiology and pharmacology of epileptiform activity induced by 4-aminopyridine in rat hippocampal slices.
1. Conventional intracellular and extracellular recording techniques were used to investigate the physiology and pharmacology of epileptiform bursts induced by 4-aminopyridine (4-AP, 50 microM) in the CA3 area of rat hippocampal slices maintained in vitro. 2. 4-AP-induced epileptiform bursts, consisting of a 25-to 80-ms depolarizing shift of the neuronal membrane associated with three to six fast action potentials, occurred at the frequency of 0.61 +/- 0.29 (SD)/s. The bursts were generated synchronously by CA3 neurons and were triggered by giant excitatory postsynaptic potentials (EPSPs). A second type of spontaneous activity consisting of a slow depolarization also occurred but at a lower rate (0.04 +/- 0.2/s). 3. The effects of 4-AP on EPSPs and inhibitory postsynaptic potentials (IPSPs) evoked by mossy fiber stimulation were studied on neurons impaled with a mixture of K acetate and 2(triethyl-amino)-N-(2,6-dimethylphenyl) acetamide (QX-314)-filled microelectrodes. After the addition of 4-AP, the EPSP became potentiated and was followed by the appearance of a giant EPSP. This giant EPSP completely obscured the early IPSP recorded under control conditions and inverted at -32 +/- 3.9 mV (n = 4), suggesting that both inhibitory and excitatory conductances were involved in its generation. IPSPs evoked by Schaffer collateral stimulation increased in amplitude and duration after 4-AP application. 4. The spontaneous field bursts and the stimulus-induced giant EPSP induced by 4-AP were not affected by N-methyl-D-aspartate (NMDA) receptor antagonists 3-3 (2-carboxy piperazine-4-yl) propyl-1-phosphonate (CPP) and DL-2-amino-5-phosphonovalerate (APV) but were blocked by quisqualate/kainate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX). CNQX also abolished the presence of small spontaneously occurring EPSPs, thereby disclosing the presence of bicuculline-sensitive (BMI, 20 microM) IPSPs. 5. Small, nonsynchronous EPSPs played an important role in the generation of 4-AP-induced epileptiform activity. 1) After the addition of 4-AP, small EPSPs appeared randomly on the baseline and then became clustered to produce a depolarizing envelope of irregular shape that progressively formed an epileptiform burst, 2) These small EPSPs were more numerous in the 100 ms period that preceded burst onset. 3) The frequency of occurrence of small EPSPs was positively correlated with the frequency of occurrence of synchronous bursts. 4) Small EPSPs and bursts were similarly decreased after the addition of different concentrations of CNQX (IC50 in both cases of approximately 1.2 microM).(ABSTRACT TRUNCATED AT 400 WORDS)


Preparation of optically anisotropic nanocomposites with oriented gold nanorods embedded in polyvinyl alcohol.
We demonstrated a simple but general method to prepare large-area flexible nanocomposites with oriented gold nanorods (GNRs) embedded in polyvinyl alcohol (PVA) film by directly introducing a GNR colloidal solution into a PVA aqueous solution and using solid-state drawing techniques. The optical property of the nanocomposite exhibits a strong dependence on the angle between the polarization of the incident light and the drawing direction of the nanocomposite film. The color of the composite film can be intelligently tuned and displays red and blue when the light polarization is switched parallel to and perpendicular to the drawing direction, respectively. These composite films have promise for application in a single electrooptical device.


[Effects of Yiqi Huayu Hutan decoction on pulmonary fibrosis in rats and its mechanism].
To investigate the effects of Yiqi Huayu Hutan decoction on pulmonary fibrosis of rats which induced by bleomycin. The rat model of pulmonary fibrosis was induced by intratracheal injection of bleomycin hydrochloride (5 mg/kg). Sixty SD rats were randomly divided into the normal group (group N), the model group (group M), the positive control group (group Y), group of low concentration (group LC), group of medium concentration (group MC) and group of high concentration of Yiqi Huayu Hutan decoction (group HC). After 4 weeks, the experimental groups were treated with low concentration decoction, medium concentration decoction and high concentration decoction respectively, and the Y group was treated with hydrocortisone acetate, the Group N and group M were treated with saline by intragastric administration. Twelve weeks later, rats were killed and the pathomorphism of pulmonary tissues of each group was observed by HE staining and Masson staining. Further, the expressions of transforming growth factor-β1(TGF-β1), Snail1, E-cadherin and Fibronectin in pulmonary tissues of each group were detected by qTR-PCR and Western blot. Compared with the model group, the collagen sediment in the interstitial was reduced in the experimental groups, especially in the group of medium concentration, which was observed by HE staining and Masson staining .Compared with the model group, the expressions of TGF-β1, Snail1 and Fibronectin protein in pulmonary tissues of the treatment groups were decreased in the experimental group, especially in the group of medium concentration, which were detected by qRT-PCR and Western blot. Yiqi Huayu Hutan decoction can significantly improve the pulmonary fibrosis which is induced by bleomycin, and the mechanism is related to the inhibition of the expression of TGF-β/Snail pathway of transcription TGF-β1.


Metamizole use among Hispanics in Miami: report of a survey conducted in a primary care setting.
Metamizole (dipyrone) is a myelotoxic, nonsteroidal anti-inflammatory agent that has been banned from the US market since 1979. However, dipyrone may be purchased in some areas of the US. We conducted a survey in a primary care setting in Miami, Florida to determine the prevalence of metamizole possession and use among Hispanics living in this area. Participants consisted of 137 Hispanic outpatients interviewed consecutively during a primary care visit in the month of February 2005. Metamizole was possessed by 28% of the surveyed population. The most common reasons for using dipyrone were pain (72%) and fever (24%). The vast majority of patients had purchased the medication in Latin America (95%), in most instances without a prescription (95%). Nineteen patients (13%) had used the medication during the previous year. Metamizole is available to Latino immigrants who reside in the US, despite the FDA ban imposed in 1977.


Examining the episodic-semantic interaction during future thinking - A reanalysis of external details.
While traditional analyses of autobiographical construction tend to focus on the 'internal' or episodic details of the narrative, contemporary studies employing fine-grained scoring measures reveal the 'external' component to contain important information relevant to the individual's life story. Here, we used the recently developed NExt scoring protocol to explore profiles of external details generated by patients with Alzheimer's disease (AD) (n = 11) and semantic dementia (SD) (n = 13) on a future thinking task. Overall, distinct NExt profiles were observed for future events in AD and SD. Specifically, AD patients provided significantly more Specific Episode external details compared with Controls. Using voxel-based morphometry, these increased external details within future narratives related to grey matter intensity in medial and lateral frontal regions in AD. By contrast, SD patients displayed an elevation of Specific Episode, Extended Episode, and General Semantic details during future simulation relative to Controls, which related to grey matter intensity of medial and lateral parietal regions. Our findings suggest that the compensatory external details generated during future simulation comprise an array of episodic and semantic details that vary in terms of specificity and self-relevance, which may be differentially affected depending on the locus of underlying neuropathology in dementia. Adopting a fine-grained approach to external details helps to characterise the interplay between episodic and semantic content during future stimulation and suggests potentially differential vulnerability and preservation of distinct components of the constructed narrative in clinical disorders.


Clinical features and analysis in 1385 Chinese patients with pituitary adenomas.
The prevalence of pituitary adenomas (PAs) is increasing as the development of imaging techniques. Few studies systematically documented the profile of these tumors in Chinese population. Our study is aimed to investigate the clinical features of PAs including the clinicopathologies, manifestations, and tumor recurrence. A retrospective analysis of clinic records of patients (median age, 39 years) with PAs was performed. A total of 1385 patients diagnosed and treated surgically at Tongji hospital, Hubei Province, China during the years 1987 through 2009 were identified that met our inclusion criteria and formed the study group. The distribution of each PA subtype was nonfunctioning pituitary adenomas (NFPA) occupying 40.0% of the total subjects, pure prolactin-secreting (PRL+) adenomas 18.6%, mixed adenomas 14.4%, growth hormone-secreting (GH+) adenomas 6.0%, follicle-stimulating hormone/luteinizing hormone-secreting (FSH/LH+) adenomas 5.9%, adrenocorticotropic hormone-secreting (ACTH+) adenomas 4.6%, and thyroid-stimulating hormone-secreting (TSH+) adenomas 0.6%. The most common initial symptoms were visual disturbances (N.=664), endocrine disturbances (N.=645), and headaches (N.=532). Patients who complained of endocrine disturbances mostly presented menstrual dysfunction in females whereas acromegaly in males. A total of 45 cases developed to recurrence, most of which occurred within 3 years after surgery. PRL+ adenoma showed the lowest frequency of recurrence (0.8%). Most adenomas were secretory PAs, with prolactinomas being the most common subtype. Visual defects, endocrine disorders, and headaches were the most common symptoms. Patients with PRL+ adenoma had the lowest chance to undertake recurrence. More clinical care and research activities are needed to improve the outcome of these patients.


Use of proteomics to demonstrate a hierarchical oxidative stress response to diesel exhaust particle chemicals in a macrophage cell line.
Epidemiological studies demonstrate an association between short term exposure to ambient particulate matter (PM) and cardiorespiratory morbidity and mortality. Although the biological mechanisms of these adverse effects are unknown, emerging data suggest a key role for oxidative stress. Ambient PM and diesel exhaust particles (DEP) contain redox cycling organic chemicals that induce pro-oxidative and pro-inflammatory effects in the lung. These responses are suppressed by N-acetylcysteine (NAC), which directly complexes to electrophilic DEP chemicals and exert additional antioxidant effects at the cellular level. A proteomics approach was used to study DEP-induced responses in the macrophage cell line, RAW 264.7. We demonstrate that in the dose range 10-100 microg/ml, organic DEP extracts induce a progressive decline in the cellular GSH/GSSG ratio, in parallel with a linear increase in newly expressed proteins on the two-dimensional gel. Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and electrospray ionization-liquid chromatography/mass spectrometry/mass spectrometry analysis, 32 newly induced/NAC-suppressed proteins were identified. These include antioxidant enzymes (e.g. heme oxygenase-1 and catalase), pro-inflammatory components (e.g. p38MAPK and Rel A), and products of intermediary metabolism that are regulated by oxidative stress. Heme oxygenase-1 was induced at low extract dose and with minimal decline in the GSH/GSSG ratio, whereas MAP kinase activation required a higher chemical dose and incremental levels of oxidative stress. Moreover, at extract doses >50 microg/ml, there is a steep decline in cellular viability. These data suggest that DEP induce a hierarchical oxidative stress response in which some of these proteins may serve as markers for oxidative stress during PM exposures.


Association between Mycobacterium avium subspecies paratuberculosis and lymph node size in New Zealand farmed deer (Cervus elaphus).
To develop and validate criteria for identification of abnormal lymph nodes (LN) at commercial slaughter, for the purpose of national surveillance for Mycobacterium avium subspecies paratuberculosis (Map) in New Zealand farmed deer. This included estimation of the predictive value of abnormal LN for Map infection; a standard circumference cut-point for measurement of abnormal LN; and identification of risk factors associated with increasing LN circumference. In Study 1, official assessors sampled 129 LN with macroscopically visible abnormalities (abnormal LN) from 76 deer herds between May and November 2007. LN samples were cultured for Map, with culture-negative LN further examined for typical histopathological changes. The predictive value of abnormal LN for Map infection was calculated and significance of herd location (North or South Island) assessed. In Study 2, the circumferences of 412 mesenteric LN (MLN) from 79 herds were measured between October 2007 and January 2009, with samples cultured for Map and examined for eight histopathological features. The minimum circumference of an abnormal MLN was defined, based on an arbitrary >95% specificity of a culture-positive Map diagnosis. Associations between the predictor variables Map culture status, carcase weight, animal age and gender, and histopathological features, and increasing MLN circumference were assessed using a linear mixed-effects model. Based solely on culture, the predictive value of abnormal LN for Map infection was 92.2 (95% CI: 86.2-96.2)% with no difference between the North and South Islands (p = 0.09). Inclusion of three culture-negative LN with histopathological changes typical of Map infection increased the predictive value estimate to 94.6 (95% CI: 89.2-97.3)%. The minimum circumference of an abnormal MLN was defined as 55 mm, with a sensitivity of Map detection at this cut-point of approximately 12%. Increasing MLN circumference was positively associated with the presence of moderate follicular hyperplasia (p < 0.01), focal granulomas (p < 0.01) and a synergistic interaction between focal granulomas and Map status (p = 0.03). Deer MLN with macroscopically visible abnormalities and/or a circumference of >55 mm have >95% likelihood of Map infection. However, sensitivity of Map diagnosis in MLN with circumference of >55 mm was 12%, indicating use of abnormal LN as a sole criterion in national surveillance for Map in slaughtered deer will underestimate animal-level prevalence.


A nodule on the scalp as the first sign of extranodal disease in medullary thyroid carcinoma.
Medullary carcinoma of the thyroid gland accounts for only 5-10% of thyroid carcinomas. Also, metastases to the skin of malignant tumors are infrequently (2-9% of patients). In the case herein reported in a 64-year old woman, a metastatic nodule on the scalp was the presenting clinical manifestation of a medullary thyroid carcinoma. A comprehensive review of the literature was conducted for similar cases using PubMed. Only 18 cases of cutaneous metastases of medullary thyroid carcinoma have been previously reported in the literature, but skin lesions were the presenting complaint of the thyroid neoplasm in only three.


Study on the Variation Law of the Main Mechanical Properties in the Processing of Longjing Tea.
Fresh tea leaves, both single bud and one leaf with a bud, were used as the test materials in this study. The variation in the main mechanical properties, such as texture and tensile properties, during the processing of Longjing tea was examined by using texture profile analysis (TPA) and stress-strain tensile tests. The plasticity showed a trend of first increasing and then decreasing during the processing, whereas the elasticity displayed the opposite tendency. The flexibility reached a maximum during the fixing stage and then slowly declined with a relatively small change. Initially, the maximum force dropped down and then gradually elevated later.Both the tensile strength and the fracture strain indicated an upward movement at the beginning and then a downfall afterward. The elastic modulus changed little before the final panning stage, then raised significantly. The correlation analysis revealed that the flexibility of tea leaves was highly positively correlated with water content. At water content of 30% and 50%, the plasticity and flexibility of tea leaves reached a clear peak and the maximum force was at a low level, which is suitable for the shaping of Longjing tea. The results also demonstrated that the main mechanical properties of different tender materials change differently during the processing. The research findings can provide parameters for optimizing the mechanical design and processing technology of Longjing tea.


Influence of O6 in mannosylations using benzylidene protected donors: stereoelectronic or conformational effects?
The stereoselective synthesis of β-mannosides and the underlying reaction mechanism have been thoroughly studied, and especially the benzylidene-protected mannosides have gained a lot of attention since the corresponding mannosyl triflates often give excellent selectivity. The hypothesis for the enhanced stereoselectivity has been that the benzylidene locks the molecule in a less reactive conformation with the O6 trans to the ring oxygen (O5), which would stabilize the formed α-triflate and subsequent give β-selectivity. In this work, the hypothesis is challenged by using the carbon analogue (C7) of the benzylidene-protected mannosyl donor, which is investigated in terms of diastereoselectivity and reactivity and by low-temperature NMR. In terms of diastereoselectivity, the C-7-analogue behaves similarly to the benzylidene-protected donor, but its low-temperature NMR reveals the formation of several reactive intermediate. One of the intermediates was found to be the β-oxosulfonium ion. The reactivity of the donor was found to be in between that of the "torsional" disarmed and an armed donor.


[Development of hearing, speech and language in congenitally deaf infants and children after cochlear implantation].
In Japan, universal newborn hearing screening has been partly introduced since 2000 in order to discover neonates with congenital deafness, and the average age at discovery was around five months; however, among infants who were not examined by the universal newborn hearing screening, the average age at discovery was around two years. After fitting hearing aids, congenitally deaf infants are educated in a preschool for speech and hearing. If hearing aids are not effective to develop hearing and speech, cochlear implant surgery is performed as modern technology. The outcome of hearing, speech and language after cochlear implantation was excellent. At the age of elementary school enrollment, most of their verbal IQ was considered to be the same as age-matched normal children. Cochlear implant is the most important treatment at present.


Root of the Tree: The Significance, Evolution, and Origins of the Ribosome.
The ribosome is an ancient molecular fossil that provides a telescope to the origins of life. Made from RNA and protein, the ribosome translates mRNA to coded protein in all living systems. Universality, economy, centrality and antiquity are ingrained in translation. The translation machinery dominates the set of genes that are shared as orthologues across the tree of life. The lineage of the translation system defines the universal tree of life. The function of a ribosome is to build ribosomes; to accomplish this task, ribosomes make ribosomal proteins, polymerases, enzymes, and signaling proteins. Every coded protein ever produced by life on Earth has passed through the exit tunnel, which is the birth canal of biology. During the root phase of the tree of life, before the last common ancestor of life (LUCA), exit tunnel evolution is dominant and unremitting. Protein folding coevolved with evolution of the exit tunnel. The ribosome shows that protein folding initiated with intrinsic disorder, supported through a short, primitive exit tunnel. Folding progressed to thermodynamically stable β-structures and then to kinetically trapped α-structures. The latter were enabled by a long, mature exit tunnel that partially offset the general thermodynamic tendency of all polypeptides to form β-sheets. RNA chaperoned the evolution of protein folding from the very beginning. The universal common core of the ribosome, with a mass of nearly 2 million Daltons, was finalized by LUCA. The ribosome entered stasis after LUCA and remained in that state for billions of years. Bacterial ribosomes never left stasis. Archaeal ribosomes have remained near stasis, except for the superphylum Asgard, which has accreted rRNA post LUCA. Eukaryotic ribosomes in some lineages appear to be logarithmically accreting rRNA over the last billion years. Ribosomal expansion in Asgard and Eukarya has been incremental and iterative, without substantial remodeling of pre-existing basal structures. The ribosome preserves information on its history.


Transitional care services: a quality and safety process improvement program in neurosurgery.
OBJECTIVE Readmissions increasingly serve as a metric of hospital performance, inviting quality improvement initiatives in both medicine and surgery. However, few readmission reduction programs have targeted surgical patient populations. The objective of this study was to establish a transitional care program (TCP) with the goal of decreasing length of stay (LOS), improving discharge efficiency, and reducing readmissions of neurosurgical patients by optimizing patient education and postdischarge surveillance. METHODS Patients undergoing elective cranial or spinal neurosurgery performed by one of 5 participating surgeons at a quaternary care hospital were enrolled into a multifaceted intervention. A preadmission overview and establishment of an anticipated discharge date were both intended to set patient expectations for a shorter hospitalization. At discharge, in-hospital prescription filling was provided to facilitate medication compliance. Extended discharge appointments with a neurosurgery TCP-trained nurse emphasized postoperative activity, medications, incisional care, nutrition, signs that merit return to medical attention, and follow-up appointments. Finally, patients received a surveillance phone call 48 hours after discharge. Eligible patients omitted due to staff limitations were selected as controls. Patients were matched by sex, age, and operation type-key confounding variables-with control patients, who were eligible patients treated at the same time period but not enrolled in the TCP due to staff limitation. Multivariable logistic regression evaluated the association of TCP enrollment with discharge time and readmission, and linear regression with LOS. Covariates included matching criteria and Charlson Comorbidity Index scores. RESULTS Between 2013 and 2015, 416 patients were enrolled in the program and matched to a control. The median patient age was 55 years (interquartile range 44.5-65 years); 58.4% were male. The majority of enrolled patients underwent spine surgery (59.4%, compared with 40.6% undergoing cranial surgery). Hospitalizations averaged 62.1 hours for TCP patients versus 79.6 hours for controls (a 16.40% reduction, 95% CI 9.30%-23.49%; p < 0.001). The intervention was associated with a higher proportion of morning discharges, which was intended to free beds for afternoon admissions and improve patient flow (OR 3.13, 95% CI 2.27-4.30; p < 0.001), and decreased 30-day readmissions (2.5% vs 5.8%; OR 2.43, 95% CI 1.14-5.27; p = 0.02). CONCLUSIONS This neurosurgical TCP was associated with a significantly shorter LOS, earlier discharge, and reduced 30-day readmission after elective neurosurgery. These results underscore the importance of patient education and surveillance after hospital discharge.


Not working 3 years after breast cancer: predictors in a population-based study.
Little is known about factors increasing likelihood of not working among breast cancer survivors compared with women in the general population. A population-based retrospective cohort study was conducted in Quebec, Canada, based on the consecutive series of working women aged younger than 60 years when first treated for breast cancer (identified through the Quebec Tumor Registry), and on a group of randomly selected similar women, living in Quebec, who were working at the time of survivors' diagnoses, but who were without cancer (identified through provincial health care files). Data came from a telephone interview, 3 years after diagnosis for 646 survivors (73% of those eligible) or during a similar period for 890 comparison women (51%). Slightly more survivors were not working 3 years after diagnosis compared with women never diagnosed with cancer (21% and 15%, respectively). Older age (for survivors and comparison women, relative risk [RR] = 4.62, P < .0001 and RR = 4.98, P < .0001, respectively) and union membership (RR = 1.88, P = .0003 and RR = 1.40, P = .06, respectively) increased the likelihood of not working at the end of follow-up. In addition, income less than 20,000 dollars compared with > or = 50,000 dollars was associated with not working only among survivors (RR = 3.18; P = .0008). Adjuvant treatments did not predict work cessation, but any new cancer event during follow-up did (RR = 2.14; P < .0001). Although reassuring that adjuvant treatments did not appear to play a role in survivors' not working, other aspects of the cancer experience might nonetheless have influenced the decision to reduce work effort after breast cancer.


Silent Victims in the Public Eye: Socially Vulnerable EU Citizens' Exposure to Crime and Its Consequences.
This study used thematic analysis to explore 28 socially vulnerable European Union (EU) citizens who support themselves by begging in public spaces in Malmö, Sweden, their exposure to crime, and the consequences of victimization. The analysis revolved around the following themes: daily harassment in public spaces, multiple motives for victimization, strategies to combat victimization, and consequences of victimization. The participants described that they lived in a constant state of stress, due to their marginalized life situation and a fear of becoming victimized in public spaces while begging. Study participants claimed that it was not their ethnicity but rather the activity of begging and their overall vulnerable life situation together with a label as "non-Swedish" that motivate offenders to commit attacks against them. The discussion concludes by presenting a number of policy implications.


Comparison of growth characteristics of in vitro cultured granulosa cells from geese follicles at different developmental stages.
Granulosa cells (GCs) are essential components of follicles and are involved in regulating the process of follicles development. However, comparative studies on GCs isolated from different staged follicles have not been conducted in goose. The aim of the present study was to identify the growth characteristics of goose GCs from pre-hierarchical (6-10 mm) and hierarchical (F4-F2, F1) follicles. Our results showed that the three cohorts of cells had different tolerance to collagenase and had noticeable morphological differences. The F1 granulosa layers were fully digested by 0.1% collagenase, while higher concentration (0.3%) was used for both F4-F2 and pre-hierarchical granulosa layers. In the state of suspension, the diameter of F1 individual cell was larger than the other two cohorts. However, after adhering to the culture plate, cells of F1 just had changes in the diameter accompanied by small bright spots, while both pre-hierarchical and F4-F2 GCs proliferated rapidly with spreading and irregularly shaped voids. Furthermore, all attached cells could be stained by the follicle-stimulating hormone receptor antibody. Analyses of both growth curve and the mRNA expression profiles of genes related to cellular proliferation, apoptosis, and steroidogenesis suggested that three cohorts of in vitro cultured GCs had different physiological viability and functions. Taken together, the present study not only revealed differences of the growth characteristics among three cohorts of goose GCs from pre-hierarchical, F4-F2 and F1 follicles, but also optimized the in vitro culture system of geese different staged GCs.


T1- and T2-weighted Magnetic Resonance Dual Contrast by Single Core Truncated Cubic Iron Oxide Nanoparticles with Abrupt Cellular Internalization and Immune Evasion.
Conventional T1- or T2-weighted single mode contrast-enhanced magnetic resonance imaging (MRI) may produce false results. Thereby, there is a need to develop dual contrast agents, T1- and T2-weighted, for more accurate MRI imaging. The dual contrast agents should possess high magnetic resonance (MR) relaxivities, targeted tumor linking, and minimum recognition by the immune system. We have developed nitrodopamine-PEG grafted single core truncated cubic iron oxide nanoparticles (ND-PEG-tNCIOs) capable of producing marked dual contrasts in MRI with enhanced longitudinal and transverse relaxivities of 32 ± 1.29 and 791 ± 38.39 mM-1 s-1, respectively. Furthermore, the ND-PEG-tNCIOs show excellent colloidal stability in physiological buffers and higher cellular internalization in cancerous cells than in phagocytic cells, indicating the immune evasive capability of the nanoparticles. These findings indicate that tNCIOs are strong candidates for dual contrast MRI imaging, which is vital for noninvasive real-time detection of nascent cancer cells in vivo and for monitoring stem cells transplants.


Crystallin Alpha-B Overexpression as a Possible Marker of Reactive Astrogliosis in Human Cerebral Contusions.
The pathophysiology of traumatic brain injury (TBI) has not yet been fully elucidated. Crystallin alpha-B (CRYAB) is a molecular chaperone that apparently tries to stabilize the rapid thickening of the intermediate filaments of glial fibrillary acidic protein (GFAP) during the process of reactive astrogliosis in response to TBI. Previous analyses of the gene expression profile in human brain contusion tissue showed us an exacerbated CRYAB overexpression. Here, we used 3, 3'-diaminobenzidine (DAB) immunohistochemistry and immunofluorescence to verify CRYAB overexpression and to describe its expression and distribution in samples of contused cortical tissue derived from emergency decompressive surgery after severe TBI. The histological expression of CRYAB was mainly seen in subcortical white matter astrocytes of injured tissue. Most of the cells that overexpressed GFAP in the analyzed tissue also overexpressed CRYAB, a finding corroborated by the co-localization of the two markers. The only difference was the presence of a few pyramidal neurons that expressed CRYAB in layer V of the cerebral cortex. The selective vulnerability of layer V of the cerebral cortex during TBI could explain the expression of CRYAB in neurons of this cortical layer. Our results indicate a parallel behavior in the cellular expression of CRYAB and GFAP during the subacute response to TBI. These results lead us to postulate CRYAB as a possible marker of reactive astrogliosis in contused cortical tissue.


Search for Allergens from the Pollen Proteome of Sunflower (Helianthus annuus L.): A Major Sensitizer for Respiratory Allergy Patients.
Respiratory allergy triggered by pollen allergens is increasing at an alarming rate worldwide. Sunflower pollen is thought to be an important source of inhalant allergens. Present study aims to identify the prevalence of sunflower pollinosis among the Indian allergic population and characterizes the pollen allergens using immuno-proteomic tools. Clinico-immunological tests were performed to understand the prevalence of sensitivity towards sunflower pollen among the atopic population. Sera from selected sunflower positive patients were used as probe to detect the IgE-reactive proteins from the one and two dimensional electrophoretic separated proteome of sunflower pollen. The antigenic nature of the sugar moiety of the glycoallergens was studied by meta-periodate modification of IgE-immunoblot. Finally, these allergens were identified by mass-spectrometry. Prevalence of sunflower pollen sensitization was observed among 21% of the pollen allergic population and associated with elevated level of specific IgE and histamine in the sera of these patients. Immunoscreening of sunflower pollen proteome with patient sera detected seven IgE-reactive proteins with varying molecular weight and pI. Hierarchical clustering of 2D-immunoblot data highlighted three allergens characterized by a more frequent immuno-reactivity and increased levels of IgE antibodies in the sera of susceptible patients. These allergens were considered as the major allergens of sunflower pollen and were found to have their glycan moiety critical for inducing IgE response. Homology driven search of MS/MS data of these IgE-reactive proteins identified seven previously unreported allergens from sunflower pollen. Three major allergenic proteins were identified as two pectate lyases and a cysteine protease. Novelty of the present report is the identification of a panel of seven sunflower pollen allergens for the first time at immuno-biochemical and proteomic level, which substantiated the clinical evidence of sunflower allergy. Further purification and recombinant expression of these allergens will improve component-resolved diagnosis and therapy of pollen allergy.


Alterations in arthropod and neuronal exosomes reduce virus transmission and replication in recipient cells.
Targeting the modes of pathogen shedding/transmission via exosomes or extracellular vesicles has been envisioned as the best approach to control vector-borne diseases. This study is focused on altering exosomes stability to affect the pathogen transmission from infected to naïve recipient cells. In this study, neuronal or arthropod exosomes were treated at different temperatures or with different salts or pH conditions to analyze their ability and efficiency in the transmission of tick-borne Langat virus (LGTV) from infected to naïve recipient cells. Quantitative real-time PCR (qRT-PCR) and immunoblotting analyses revealed that treatment of neuronal or tick exosomes at warmer temperatures of 37 °C or 23 °C, respectively, or with sulfate salts such as Magnesium or Ammonium sulfates or with highly alkaline pH of 9 or 11.5, dramatically reduced transmission of LGTV via infectious exosomes (human or tick cells-derived) to human neuronal (SH-SY5Y) cells or skin keratinocytes (HaCaT cells), respectively. Overall, this study suggests that exosome-mediated viral transmission of vector-borne pathogens to the vertebrate host or the viral dissemination and replication within or between the mammalian host can be reduced by altering the ability of exosomes with basic changes in temperatures, salts or pH conditions.


Choleretic effect of vasoactive intestinal peptide.
Vasoactive intestinal peptide, VIP, was administered intravenously as 10-minute infusions, dosage 0.05 and 0.5 mug/kg/min, to anaesthetized dogs provided with common duct fistulas. When VIP was given to fasting animals, the output of bile, sodium and amylase increased significantly, the bile output by approximately 200% of the control. The biliary concentration of sodium was constant, while that of amylase decreased. When VIP was given to animals, which were fed before the experiment, the bile output was essentially unaffected. The two doses used gave equal peak responses, but the duration of the effect was doubled or trebled following the highest dosage.


Determination of nutrient mass balance in turkeys.
Retention and excretion of phosphorus and nitrogen were determined for turkeys fed 2 diets at 3 ages, via mass balance based on the nutrient content of consumed feed, carcasses, and litter. The 2 diets consisted of an industry diet (IND) and a low phosphorus + 600 U of phytase/kg (LP) diet. A subsample of birds was weighed and killed at 12, 15, and 18 wk of age for nutrient retention (via whole carcasses) and excretion (via litter). Diet did not affect BW or feed intake from 12 to 18 wk of age. The mass of phosphorus excreted from 0 to 12, 0 to 15, and 0 to 18 wk of age was 37, 46, and 40% greater for birds fed the IND diets compared with birds fed the LP diets. Phosphorus retained as the percentage of phosphorus consumed was greater at 12, 15, and 18 wk for birds fed the LP diets (67.0, 63.8, and 53.8%) than for birds fed the IND diets (47.3, 44.0, and 32.8%). The difference between the mass of phosphorus excreted, as calculated from litter, compared with feed intake minus carcass retention was less than 5% at 18 wk. The nitrogen retained averaged 90.7, 136.7, and 184.2 g/bird, whereas nitrogen excreted averaged 377.6, 620.7, and 921.8 g/bird at 12, 15, and 18 wk of age, respectively. Additionally, with an 18-wk average litter DM of 78.0%, the unaccounted for nitrogen at 18 wk was 427 and 405 g/bird for birds fed the IND and LP diets, respectively (40 and 37% of excreted nitrogen).


Portrait of inequality.
America's children are stalked by race- and income-based inequities that demand our attention. Health care reform efforts that respect the needs of the entire child can diminish these inequities. Six prescriptions will help: universal early childhood education; comprehensive health and family life education; parental support; reinforcement of male responsibility; comprehensive school-based clinics; and opportunities for higher education.


Biosynthesis of the Plant Coumarin Osthole by Engineered Saccharomyces cerevisiae.
Osthole is a coumarin compound found in the traditional Chinese medicine Cnidium monnieri. Extensive studies have shown that osthole exhibits many medicinal properties, and recently, researchers have found that it possesses potent airway-relaxation activity by inhibiting phosphodiesterase 4D activity, making it a potential novel bronchodilator that does not target β2-adrenoceptors for asthma treatment. Here, we report the complete biosynthesis of osthole in engineered yeast. We created an umbelliferone (UMB)-producing strain by reconstituting the complete UMB pathway in yeast. We found that coumarin synthase (COSY) is essential for the conversion of 2',4'-dihydroxycinnamoyl-CoA into UMB in yeast; this conversion has been treated as a spontaneous step in previously reported UMB-producing microbials. By introducing downstream prenyltransferase and methyltransferase genes and addressing problems such as protein expression and cofactor supply to fulfill the downstream steps, complete biosynthesis of osthole was achieved. Finally, through metabolic engineering, to ensure precursor supply, and the debugging of rate-limited steps, the osthole titer reached 108.10 mg/L in shake flasks and 255.1 mg/L in fed-batch fermentation. Our study is the first to produce osthole using engineered microbes, providing a blueprint for the supply of plant-derived osthole via microbial fermentation, which will remove the barriers of resource limitations for osthole-based drug development.


Ex vivo induction of regulatory T cells from conventional CD4+ T cells is sensitive to substrate rigidity.
The immune system maintains a balance between protection and tolerance. Regulatory T cells (Tregs) function as a vital tolerance mechanism in the immune system to suppress effector immune cells. Additionally, Tregs can be utilized as a form of immunotherapy for autoimmune disorders. As T cells have previously been shown to exhibit sensitivity to the rigidity of an activating substrate upon activation via IL-2 secretion, we herein explore the previously unknown effect of substrate rigidity on the induction of Tregs from conventional naïve mouse CD4+ T cells. Substrates with modulatable rigidities ranging from a hundred kilopascals to a few megapascals were fabricated via poly(dimethylsiloxane). We found that there was a significant increase in Treg induction at lower substrate rigidities (i.e., E ~ 100 kPa) compared to higher rigidity levels (i.e., E ~ 3 MPa). To confirm that this significant difference in induction rate was truly related to T-cell mechanosensing, we administered compound Y-27632 to inhibit myosin contractility. In the presence of Y-27632, the myosin-based contractility was disrupted and, as a result, the difference in Treg induction caused by the substrate rigidity was abrogated. This study demonstrates that mechanosensing is involved in Treg induction and raises questions about the underlying molecular mechanisms involved in this process. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3001-3008, 2018.


Who owns implicit attitudes? Testing a metacognitive perspective.
Metacognitive inferences about ownership for one's implicit attitudes have the power to turn implicit bias into explicit prejudice. In Study 1, participants were assigned to construe their implicit attitudes toward gay men as belonging to themselves (owned) or as unrelated to the self (disowned). Construing one's implicit responses as owned led to greater implicit-explicit attitude correspondence. In Study 2, we measured ownership for implicit attitudes as well as self-esteem. We predicted that ownership inferences would dictate explicit attitudes to the degree that people had positive views of the self. Indeed, higher ownership for implicit bias was associated with greater implicit-explicit attitude correspondence, and this effect was driven by participants high in self-esteem. Finally, in Study 3, we manipulated inferences of ownership and measured self-esteem. Metacognitions of ownership affected implicit-explicit attitude correspondence but only among those with relatively high self-esteem. We conclude that subjective inferences about implicit bias affect explicit prejudice.


Kidney tubular epithelium is restored without replacement with bone marrow-derived cells during repair after ischemic injury.
The kidney has the ability to restore the structural and functional integrity of the proximal tubule, which undergoes extensive epithelial cell death after prolonged exposure to ischemia. In order to study the role that adult bone marrow-derived stem cells might play in kidney remodeling after injury, we employed a murine model of ischemia/reperfusion (I/R) injury in which the degree of injury, dysfunction, repair, tubular cell proliferation and functional recovery have been characterized [Park KM, et al, J Biol Chem 276:11870-11876, 2001]. We generated chimeric mice using marrow from mice expressing the bacterial LacZ gene, or the enhanced green fluorescence protein (eGFP) gene, or from male mice transplanted into female mice. The establishment of chimerism was confirmed at 6 weeks following transplantation in each case. I/R injury was induced in chimeric mice by occluding the renal arteries and veins with microaneurysm clamps for 30 minutes. After functional recovery in the eGFP chimeras, although there were many interstitial cells, no tubular cells were derived from bone marrow cells. In the bacterial beta-galactosidase (beta-gal) chimeric mice we found evidence of mammalian (endogenous) beta-gal by 5-bomo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining, but not bacterial beta-gal in tubule cells. Detection of the Y chromosome by fluorescence in situ hybridization (FISH) in the postischemic kidneys of gender-mismatched chimeras revealed Y chromosome positivity only in the nuclei of interstitial cells, when scrutinized by deconvolution microscopy. In our model of I/R injury there was a large amount of proliferation of surviving, injured tubular cells indicating that the injured tubule is repopulated by daughter cells of surviving tubular cells. Analysis of the phenotype of interstitial and vascular cells following I/R injury revealed small numbers of peritubular endothelial cells to be derived from bone marrow cells that may serve in the repair process.


Decision-making Impairments in Primary Angle-closure Glaucoma Patients.
Primary angle-closure glaucoma (PACG) is a common eye disease and a common cause of blindness. Inappropriate medical decisions severely affect the prognosis. This study investigated decision-making under risk in PACG patients. Thirty patients with first acute attack of PACG before surgery and thirty healthy controls were included in the study. Decision-making under risk was evaluated with the game of dice task (GDT). The results of Eysenck Personality Questionnaire (EPQ) and GDT between PACG patients and healthy controls were compared. Risky decisions in PACG patients were more than those in healthy controls as measured by mean score of GDT (12.47 ± 5.72 vs. 4.33 ± 3.30, P< 0.001). Higher neuroticism score in EPQ was found in PACG patients compared to healthy controls (14.97 ± 3.93 vs. 9.90 ± 4.49, P< 0.001). Neuroticism scores in EPQ were associated with decision-making performance (r = 0.417, P = 0.001). Neuroticism positively correlated with risky decisions. Decision-making might be influenced by neuroticism. Future studies will show whether therapy compliance will be improved by emotional management and psychological intervention in PACG patients.


Ferric Sulfate and Proline Enhance Heavy-Metal Tolerance of Halophilic/Halotolerant Soil Microorganisms and Their Bioremediation Potential for Spilled-Oil Under Multiple Stresses.
The aim of this study was to explore the heavy-metal resistance and hydrocarbonoclastic potential of microorganisms in a hypersaline soil. For this, hydrocarbonoclastic microorganisms were counted on a mineral medium with oil vapor as a sole carbon source in the presence of increasing concentrations of ZnSO4, HgCl2, CdSO4, PbNO3, CuSO4, and Na2HAsO4. The colony-forming units counted decreased in number from about 150 g-1 on the heavy-metal-free medium to zero units on media with 40-100 mg l-1 of HgCl2, CdSO4, PbNO3, or Na2HAsO4. On media with CuSO4 or ZnSO4 on the other hand, numbers increased first reaching maxima on media with 50 mg l-1 CuSO4 and 90 mg l-1 ZnSO4. Higher concentrations reduced the numbers, which however, still remained considerable. Pure microbial isolates in cultures tolerated 200-1600 mg l-1 of HgCl2, CdSO4, PbNO3, CuSO4, and Na2HAsO4 in the absence of crude oil. In the presence of oil vapor, the isolates tolerated much lower concentrations of the heavy metals, only 10-80 mg l-1. The addition of 10 Fe2(SO4)3 and 200 mg l-1 proline (by up to two- to threefold) enhanced the tolerance of several isolates to heavy metals, and consequently their potential for oil biodegradation in their presence. The results are useful in designing bioremediation technologies for oil spilled in hypersaline areas.


ASF1 binds to a heterodimer of histones H3 and H4: a two-step mechanism for the assembly of the H3-H4 heterotetramer on DNA.
The first step in the formation of the nucleosome is commonly assumed to be the deposition of a histone H3-H4 heterotetramer onto DNA. Antisilencing function 1 (ASF1) is a major histone H3-H4 chaperone that deposits histones H3 and H4 onto DNA. With a goal of understanding the mechanism of deposition of histones H3 and H4 onto DNA, we have determined the stoichiometry of the Asf1-H3-H4 complex. We have established that a single molecule of Asf1 binds to an H3-H4 heterodimer using gel filtration, amino acid, reversed-phase chromatography, and analytical ultracentrifugation analyses. We demonstrate that Asf1 blocks formation of the H3-H4 heterotetramer by a mechanism that likely involves occlusion of the H3-H3 dimerization interface.


Frequency of Familial Mediterranean Fever Gene Mutation in Patients Presenting With Joint Pain and Diagnosed With Acute Rheumatic Fever.
Introduction Acute rheumatic fever (ARF) is a non-suppurative systemic inflammatory disease that manifests 1-5 weeks following a Group A beta-hemolytic streptococcal infection. On the other hand, familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized as an autosomal recessive disease, with affected individuals having pathogenic mutations in the Mediterranean fever gene (MEFV) gene located on the short arm of chromosome 16. FMF and ARF have overlapping symptoms and signs, and both disorders are common in Turkey. In ARF, the target organ is the heart, while in FMF, the target organ is the kidney; both organs can benefit from prophylactic measures. Our study aims to determine the frequency of the FMF gene mutation in patients with ARF in Turkey and detect any overlapping conditions. Method Patients who were diagnosed with a first-attack ARF between May 2015 and May 2018 were retrospectively screened. Patients who underwent MEFV gene analysis considering FMF in the differential diagnosis were included in the study. Results In this study, no statistical difference was found between the presence of MEFV gene mutations, carditis, high anti-streptolysin-O antibody (ASO) levels, and the groups with monoarthritis, polyarthritis, and polyarthralgia (p >0.05). Conclusions In conclusion, patients with ARF should be evaluated for FMF to avoid irreversible complications.


Assessment of a novel scanner-supported system for processing of child health and immunization data in Uganda.
Electronic data capturing has the potential to improve data quality and user-friendliness compared to manually processed, paper-based documentation systems. The MyChild system uses an innovative approach to process immunization data by employing detachable vouchers integrated into a vaccination booklet which are then scanned and converted into individual-level health data. The aim was to evaluate the MyChild data capturing system by assessing the proportion of correctly processed vouchers and to compare the user-friendliness in term of time spent on documentation and health worker experiences with the standard health information system at health facilities in Uganda. We used a mixed method approach. Documented data were manually copied and compared to processed health records to calculate the proportion of correctly registered vouchers. To compare time spend on documentation we did a continuous observational time-motion study and analyzed data using a Mann-Whitney U test. Semi-structured interviews were conducted to assess health workers' experiences and analyzed using conventional content analysis. Data was collected in 14 health facilities in two districts in Uganda using different systems. The MyChild system processed 97% (224 of 231) of the vouchers correctly. Recording using the MyChild system increased time spend on documentation of vaccination follow-up visits by 24 s compared to the standard system (02:25 vs. 02:01 min/child, Mann-Whitney U = 6293, n1 = 115, n2 = 151, p < 0.001 two-tailed, Z = - 3.861, r = 0.186). However, high variance between health centers using the same health information system suggests that documentation time differences can be attributed to other factors than the way information was processed. Health workers perceived both health management information systems as predominantly functional and easy to use, while the MyChild system achieved a higher level of satisfaction. The MyChild system electronically processes individual-level immunization data correctly without increasing significantly time spent on recording and is appreciated by health providers making it a potential solution to overcome shortcomings of present paper-based health information systems in health centers.


On being genetically "irresponsible".
New genetic technologies continue to emerge that allow us to control the genetic endowment of future children. Increasingly the claim is made that it is morally "irresponsible" for parents to fail to use such technologies when they know their possible children are at risk for a serious genetic disorder. We believe such charges are often unwarrented. Our goal in this article is to offer a careful conceptual analysis of the language of irresponsibility in an effort to encourage more care in its use. Two of our more important sub-claims are: (1) A fair judgement of genetic irresponsibility necessarily requires a thick background description of the specific reproductive choice; and (2) there is no necessary connection between an act's being morally wrong and its being irresponsible. These are distinct judgments requiring distinct justification.


Comparing Outcomes of 45 Xen Implantation ab Interno with Closed Conjunctiva to ab Externo with Open Conjunctiva Approaches.
Ab externo with open conjunctiva placement may lead to improved gelatin stent (XEN® Gel Stent; Allergan™) success rate compared to ab interno with closed conjunctiva because it conferred more favorable results for intraocular pressure and medication burden reduction based on our complete and qualified success criteria. To compare outcomes of a gelatin stent (XEN® 45 Gel Stent; XGS; Allergan™) placed either ab interno with closed conjunctiva (AIC) or ab externo with open conjunctiva (AEO) with or without cataract surgery in patients with glaucoma. Retrospective, nonrandomized comparative study of 85 eyes from 85 glaucoma patients who received XGS placed either AIC (N=32) or AEO (N=53) with or without cataract surgery between July 2018 and January 2022 at Massachusetts Eye and Ear. Patients were included if they were≥18 years of age and had at least 30 days of follow-up without any disqualifying event. Baseline demographics were similar between both groups, except for the glaucoma type. Both AIC and AEO procedures resulted in significant patterns of IOP and medication reduction from baseline up to 1 year. At POY1, mean IOP was reduced to 11.34±4 mmHg on 1.29±1.34 medications after AEO, and 13.70±3.32 mmHg on 2±1.81 medications after AIC. The average IOP reduction was significantly greater in the AEO group at all postoperative timepoints beyond POW2. There were significant differences in the survival curves of AEO and AIC groups under both the complete success criteria and the qualified success criteria. Under the complete success criteria, the cumulative probability of survival at POY1 was 28.5% in the AEO group and 3.8% in the AIC group. Under the qualified success criteria, the cumulative probability of survival at POY1 was 60.3% in the AEO group and 21.9% in the AIC group. In our study, we demonstrate that both placements reduce IOP and medication from baseline, with AEO placement having more favorable IOP and medication results, in addition to improved success rates compared to AIC placement.


Timing of débridement of open fractures.
Although débridement within 6 to 8 hours of injury seems nearly universally accepted, the data supporting this recommendation are lacking. Most studies indicate that, in the context of modern antibiotic treatment, early débridement is not an independent predictor of decreased risk of infection. Achieving early débridement may pose unjustified risks to patient safety. Given the numerous factors that influence timing of surgical débridement in trauma centers, a prospective randomized trial of emergent versus urgent débridement is not feasible. However, a prospective longitudinal study could yield valuable data.


To what extent can we explain time trade-off values from other information about respondents?
The time trade-off (TTO) is one of the most widely used health state valuation methods and was recently used to develop a set of values for the EQ-5D descriptive system from 3000 members of the UK general population. However, there is currently very little understanding of precisely what determines responses to TTO questions. The data that were used to generate this set of values are ideal for addressing this question since they contain a plethora of information relating to the respondents and their cognition during the TTO exercise. A particularly useful characteristic of this dataset is the existence of visual analogue scale (VAS) valuations on the same states for the same respondents. The results suggest that age, sex and marital status are the most important respondent characteristics determining health state valuations. The VAS valuations were found to add very little to the explanatory power of the models.


Seasonal Differences and Grazing Pressure Alter the Fate of Gold Nanoparticles in a Microcosm Experiment.
Gold nanoparticles (AuNPs) are used as models to track and predict NP fates and effects in ecosystems. Previous work found that aquatic macrophytes and their associated biofilm primarily drove the fate of AuNPs within aquatic ecosystems and that seasonality was an important abiotic factor in the fate of AuNPs. Therefore, the present work aims to study if grazers, by feeding on these interfaces, modify the AuNP fate and if this is altered by seasonal fluctuations. Microcosms were dosed with 44.8 μg/L of AuNP weekly for 4 weeks and maintained in environmental chambers simulating Spring and Fall light and temperature conditions. We discovered that seasonal changes and the presence of grazers significantly altered the fate of Au. Higher temperatures in the warmer season increased dissolved organic carbon (DOC) content in the water column, leading to stabilization of Au in the water column. Additionally, snail grazing on biofilm growing on the Egeria densa surface led to a transfer of Au from macrophytes to the organic matter above the sediments. These results demonstrate that climate and grazers significantly impacted the fate of Au from AuNPs, highlighting the role that grazers might have in a large and biologically more complex ecosystem.


[Validating an instrument for measuring the perceived quality of services received by people using hospitals in Colombia].
Validating an instrument for measuring the perceived quality of services received by people using hospitals forming part of the Colombian Ministry of Social Protection's restructuring, redesigning and modernisation programme for health-service providing networks. Sánchez and Echeverri's guidelines for validating health quality measurement scales were followed due to the lack of a valid instrument for doing this in Colombia. Conceptual synthesis led to identifying a structure of constituent indicators, domains and sub-domains regarding the perception of health service quality. A list of reactions (having a scale for categorising the replies) was analysed according to the validity of appearance, construct, criteria and utility as criteria for sensitivity and usefulness. Successive revisions and three rounds of field-trials led to producing PECASUSS, an acronym given to the instrument for measuring users' perception of health service quality (Percepción de Calidad Según Usuarios de Servicios de Salud). The guidelines effectively orientated the validation of the instrument required for measuring the perceived quality of health services received by people using hospitals forming part of the programme.


Low-dose radiation and leukemia.
We investigated the effect of diagnostic and low-level therapeutic radiation (less than 300 rads to the bone marrow) on the development of leukemia. During this study, 138 patients with leukemia (representing all known incidence cases of leukemia in residents of Olmsted County, Minnesota, between 1955 and 1974) were each matched with two controls, and the lifelong experiences of both groups with regard to diagnostic and therapeutic radiation were ascertained. No statistically significant increase was found in the risk of developing leukemia after radiation doses of 0 to 300 rads (3 Gy) to the bone marrow when these amounts were administered in small doses over long periods of time, as in routine medical care.


Orbital frontal cortex ablations of rock squirrels (Spermophilus variegatus) disinhibit innate antisnake behavior.
The antisnake behavior of rock squirrels (Spermophilus variegatus) was examined to determine the role of the orbital frontal cortex in regulating physiological arousal and behavioral excitability during encounters with a rattlesnake predator. Rock squirrels with orbital frontal cortex ablations and sham-surgery control squirrels were presented with a caged rattlesnake pre- and postsurgery. Orbital frontal cortex ablations had no substantial effect on the expression of gross motor behavior in dealing with the rattlesnake, but they augmented the speed of snake recognition and clearly disinhibited sympathetic arousal as manifested by increased tail piloerection and tail-flagging activity, which is a specific antisnake behavior. Natural selection from snakes has probably shaped the neural organization of the orbital frontal cortex to afford adaptive behavioral flexibility during snake encounters.


Plasma level of homocysteine is inversely-associated with the development of collateral circulation in patients with single-vessel coronary artery disease.
Homocysteine induces endothelial injury and inhibits endothelial cell proliferation, which is a key role in angiogenesis. The purpose of this study was to investigate whether the plasma level of homocysteine is associated with the development of collaterals in patients with single-vessel coronary artery disease (CAD). Among a series of 105 male patients with angiographic estimation, 49 with single-vessel CAD were intensively investigated. Development of collaterals was classified by Rentrop's method. Univariate and multivariate analyses revealed that hyperhomocysteinemia negatively affected the development of collaterals (p=0.0015 and 0.0011, odds ratio 0.69, 95% confidence interval 0.52-0.90), whereas the duration of angina and percent stenosis evaluated by quantitative coronary angiography had a positive affect. Moreover, the level of homocysteine in the group with poorly developed collaterals (n=7, Rentrop class 0 and 1) was significantly higher than that in the group with well-developed collaterals (n=12, Rentrop class 2 and 3) of the patients with single-vessel disease showing total occlusion (p=0.034). This study clearly demonstrates that the plasma level of homocysteine is independently and inversely associated with the development of collateral circulation in CAD patients. Homocysteine might be a new undesirable aspect of ischemic heart disease through its inhibition of collateral development.


Squamous cell carcinoma of the prostate.
A primary squamous cell carcinoma occurring in the prostate is described. Local irradition, systemic anticancer chemotherapy using bleomycin and intraarterial administration of cis-platinum were done. Twenty-one months after the initial diagnosis there is no sign of tumor progression.


[A gene-chip image grid localization method based on profiles of image].
Automatic gene-chip image grid localization is an essential task for gene-chip image analysis. Now an method based on profiles of gene-chip image is proposed. Using the differences between two profiles after filtration by arithmetic mean method, we can easily find the local grayscale minimum between two probe spots, then the probe spots are automatically located. The experiments show that the new approach correctly locates the probes while giving protection against noise affection robustly. Grid location


Assembly characteristics of flagellar cap protein HAP2 of Salmonella: decamer and pentamer in the pH-sensitive equilibrium.
The cap of the bacterial flagellum is an oligomeric assembly of HAP2 protein (also called FliD), tightly attached to the tip of the flagellar filament. Flagellar growth does not occur in fliD-deficient mutants because flagellin monomers transported through the central channel of the flagellum leak out without polymerizing at the distal end. The structure of the cap complex is not known yet. An in vitro assembly of HAP2 proteins was found to have a pentagonal shape, while its molecular mass corresponded roughly to that of a dodecamer. To characterize the structure and assembly behavior of the complex formed in vitro in more detail, the stoichiometry of the complex and the association equilibrium have been studied. Crosslinking experiments now clearly show that the HAP2 complex is decameric. The assembly equilibrium is mainly between the monomer and decamer with a minor population of intermediate oligomers involved, and is highly dependent on the solution pH as well as the salt concentration: the fraction of the decamer sharply rises as the pH decreases from 8.5 to 8.0; the physiological concentration of salt partially suppresses the decamer formation. A preferential crosslinking within a pentameric unit together with a bipolar feature of the complex particle observed by electron microscopy suggests that the decamer is a bipolar pair of pentamers. Because of the polar nature of the filament cap structure, the pentamer is suggested to be the cap complex with its decamer forming surface involved in interactions with the filament.


Benchmarking of fluorescence cameras through the use of a composite phantom.
Fluorescence molecular imaging (FMI) has shown potential to detect and delineate cancer during surgery or diagnostic endoscopy. Recent progress on imaging systems has allowed sensitive detection of fluorescent agents even in video rate mode. However, lack of standardization in fluorescence imaging challenges the clinical application of FMI, since the use of different systems may lead to different results from a given study, even when using the same fluorescent agent. In this work, we investigate the use of a composite fluorescence phantom, employed as an FMI standard, to offer a comprehensive method for validation and standardization of the performance of different imaging systems. To exclude user interaction, all phantom features are automatically extracted from the acquired epi-illumination color and fluorescence images, using appropriately constructed templates. These features are then employed to characterize the performance and compare different cameras to each other. The proposed method could serve as a framework toward the calibration and benchmarking of FMI systems, to facilitate their clinical translation.


A gene from chromosome 4p16.3 with similarity to a superfamily of transporter proteins.
We have previously used exon amplification to identify the ADD1 gene in cosmid Y24 from the Huntington's disease (HD) region of 4p16.3. The same technique has now yielded a second gene from this cosmid. This gene appears to encode a novel member of a superfamily of transporter proteins that includes active and passive transporters in a number of species. The predicted protein of 455 amino acids displays sequence similarity with the E. coli tetracycline resistance efflux protein encoded by cloning vector pBR322, and with a number of related transporters. This gene should open a route to isolating additional mammalian members of this growing superfamily.


Involvement of Subcortical Brain Structures During Olfactory Stimulation in Multiple Chemical Sensitivity.
Multiple chemical sensitivity (MCS) patients usually react to odour compounds and the majority of neuroimaging studies assessed, especially at the cortical level, many olfactory-related correlates. The purpose of the present study was to depict sub-cortical metabolic changes during a neutral (NC) and pure (OC) olfactory stimulation by using a recently validated (18)F-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computer tomography procedure in 26 MCS and 11 healthy (HC) resting subjects undergoing a battery of clinical tests. Twelve subcortical volumes of interest were identified by the automated anatomical labeling library and normalized to thalamus FDG uptake. In both groups, when comparing OC to NC, the within-subjects ANOVA demonstrated a relative decreased metabolism in bilateral putamen and hippocampus and a relative increased metabolism in bilateral amygdala, olfactory cortex (OLF), caudate and pallidum. The between-groups ANOVA demonstrated in MCS a significant higher metabolism in bilateral OLF during NC. As in HC subjects negative correlations were found in OC between FDG uptake in bilateral amygdala and hippocampus and odor pleasantness scale, the latter positively correlated with MCS subjects' bilateral putamen FDG uptake in OC. Besides FDG uptake resemblances in both groups were found, for the first time a relative higher metabolism increase in OLF in MCS subjects at rest with respect to HC was found. When merging this aspect to the different subcortical FDG uptake correlations patterns in the two groups, the present study demonstrated to describe a peculiar metabolic index of behavioral and neurological aspects of MCS complaints.